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obesity is an alarming public health problem and its prevalence is increasing worldwide ( 1 ) . gastritis is inflammation of the lining of the stomach due to several causes , including h. pylori infection , which is caused by gram negative bacteria that affect the gastric mucosa ( 2 ) . the prevalence of h. pylori in obesity and its possible impact on sleeve gastrectomy , which is used as therapeutic option for morbid obesity , require additional evaluation . the aim of this study was to show the prevalence of chronic gastritis in morbidly - obese patients who were subjected to sleeve gastrectomy , with focus on h. pylori - related gastritis to demonstrate any influence of chronic gastritis in the surgical procedure or its post - operative course . this retrospective study was conducted for all sleeve gastrectomy procedures performed for morbid obesity in king abdulaziz university hospital ( kauh ) in jeddah , saudi arabia , from march 2014 to april 2015 . epidemiological data for each patient including age , gender , and bmi , were collected on a data sheet . pre - operative preparation included a complete blood workup , abdominal ultrasound , and upper gastro - intestinal endoscopy . vertical sleeve gastrectomy was performed by a skilled , well - trained , laparoscopic surgery team . specimens were sent to histopathology to rule out any pathological finding and to diagnose gastritis and for h. pylori special stain . the mean operative time and particular attention was given to post - operative complications , with reference to their relationship with chronic gastritis . in - patient medications were only intra - venous fluids and proton - pump inhibitor ; the latter was prescribed as a home medication for two weeks after discharge from the hospital . patients were instructed to come to the out - patient clinic for follow - up at intervals of one week , three months , six months , and one year . regarding research ethics , approval for the study this retrospective study included 106 morbidly obese patients who were admitted in kauh through the out - patient clinic from march 2014 to april 2015 . the ages ranged from 18 to 67 with a mean of 34 . seventy females and 36 males were involved in the study , i.e. , 66 and 34% females and males , respectively . the histopathology report showed 35 cases out 106 ( 33.01% ) had evident chronic gastritis , and nine of them were confirmed to have h. pylori , accounting for 25.7% of chronic gastritis cases , 8.5% ) from all cases . the lamina propria of the gastric mucosa diagnosed with chronic gastritis showed increased plasma cells with lymphocytes and a few lymphoid follicles . the presence of neutrophils in the glandular or surface epithelial layer was a sign of activity . helicobacter pylori bacteria , if present , were accentuated by cresyl fast violet ( cfv ) stain . the mucosa harboring h. pylori contained lymphoid follicles with germinal centers in their lamina propria . the age of those cases with chronic gastritis , including the cases of h. pylori - related gastritis , ranged from 21 to 55 , and the mean age was 38 . the mean bmi of gastritis cases was 40.75 kg / m , and the mean bmi for the whole group who had sleeve gastrectomy was almost the same of the bmi of the patients who had chronic gastritis with a p - value of 0.55 . the mean operative time was one hour and 20 minutes for all cases , including the gastritis cases , and the mean hospital stay was 23 days for all of the patients . five cases developed post - operative complications ( three with leaks , two with strictures ) , but none of them was found to have gastritis . the gender distribution of chronic gastritis and h. pylori are presented in tables 1 , 2 . obesity has become a major concern among physicians due to its large influence in metabolic , gastrointestinal , and hepatic diseases and due to its being an epidemic disorder in some countries ( 4 ) . in the study in ( 4 ) , the female - to - male ratio was 1.5 : 1 , and this ratio suggests that women in the u.a.e have a higher prevalence of obesity than men ( 5 ) . our study showed the female - to - male ratio to be 2:1 , further indicating a greater prevalence among females . the pathophysiology of obesity is affected by environmental and host agents , making the pathophysiology of obesity multifactorial ( 1 ) . the various factors involved in the process include diet , in the lack of physical activity , the use of drugs , and genetic and neurophysiological factors . the development of obesity is affected by two important gastro - intestinal hormones , i.e. , leptin and ghrelin , which are involved in the dysregulation of the mechanisms that control food intake . ghrelin is secreted by the gastric mucosa and is thought to regulate eating behavior and weight balance . this can occur gradually ( chronic gastritis ) or it may happen abruptly ( acute gastritis ) . indicated that several studies of morbid obese patients have indicated that obesity is related to the high incidence of endoscopic and histologic gastritis . thirty - three percent of our patients ( 35 out of 106 ) were proved to have chronic gastritis . warren and marshall in 1982 ( 7 ) first described helicobacter pylori as gram negative , spiral - shaped bacteria . they stated that it s the main route of infection was feco - oral ( 8) , and it is considered to be one of the main causes of gastritis . the prevalence of infection is higher in developing countries ( > 80% ) than it is in developed countries ( 2040% ) ( 8) . there is still considerable debate concerning the prevalence of h. pylori infection in morbidly obese patients . the patients who were scheduled for bariatric surgery had a pre - operative prevalence of h. pylori that ranged from 8.7% to 85.5% ( 9 , 10 ) . h. pylori was identified in 5.2% of all cases and in 33.3% of cases of gastritis in raees et al.s study ( 11 ) , while , in our study , it was illustrated that h. pylori was found in 9/106 ( 8.5% ) of all cases , 9/35 ( 25.71% ) of gastritis cases , representing very similar results . there are two main reasons for the high concern about h. pylori infection in obesity , i.e. , ( 1 ) its possible relationship with bmi and ( 2 ) its acting as a negative factor in limiting access to bariatric surgery . the effects of h. pylori on the production of gastric ghrelin still are controversial . in obese patients , h. pylori diminishes the density of gastric ghrelin - positive cells , which are associated with some authors , such as osawa , have claimed that the h. pylori infection protects against obesity by decreasing secretion of ghrelin ( 12 ) . however , other recent studies have failed to identify a relationship between h. pylori infection and reduced bmi ( caraboti et al . indicated that obesity can alter innate and adaptive immunity and that the immunological impairment was related to the grade of obesity , thereby producing less maturation of monocytes into macrophages and reducing the polymorphonuclear bactericidal capacity , which promote the development of gastritis ( 13 ) . that there is a protective role of infection towards obesity seems apparent due to the significant increase in bmi after the successful elimination of h. pylori . the increased incidence and severity of infection observed in obese patients , due to their decreased immunity seem to counter the argument that h. pylori infection has a protective role ( 14 ) . the probable explanation of these inconsistent results could be the pattern of h. pylori - related gastritis . gastric extension , which generally starts with enteritis and progresses to pan - gastritis , alters the effect of h. pylori infection . also , the occurrence of atrophy reduces the secretory activity , which subsequently decreases the production of ghrelin ( 15 ) . serology , which is used to diagnose h. pylori infection in most of studies , has a low diagnostic accuracy , but it is useful for excluding h. pylori infection . positive serology should be confirmed by a test for active infection , such as the stool antigen assay , which has a sensitivity of 94% and a specificity of 92% . also , the urea breath test ( ubt ) can be used , and it has a sensitivity of 88%95% and specificity of 95%100% . histological examination has excellent sensitivity and specificity , and it was used successfully in our study to diagnose h. pylori infection . according to raees et al . , candidates for the surgery should undergo a rigorous pre - operative evaluation , including double contrast upper gastrointestinal radiographic series . our preoperative protocol followed the european guidelines , which specify upper gastrointestinal endoscopy before bariatric surgery to treat any lesions , including h. pylori infection . this is due to the fact that such lesions may cause post - operative complications ( 16 ) . however , patients schedule to undergo sleeve gastrectomy are presumed to have no significant gastric pathology . even so , eradication should decrease the risk of gastro - duodenal peptic lesions in the gastro - jejunostomy site after gastric bypass ( 17 ) . laparoscopic sleeve gastrectomy has been advocated as a multipurpose restrictive procedure for obese patients ( 18 ) with low incidence of complications ( 19 ) . the existing infection might represent a confounding and limiting factor in bariatric surgery due to the high incidence of post - operative symptoms and/or lesions in non - eradicated patients . our study did not show any relationship between chronic gastritis and the post - operative outcome , since laparoscopic sleeve gastrectomy entails gastric resection with pylorus preservation . in theory , this antral resection removes the habitat of h. pylori bacteria , thereby eradicating them without medical therapy , which is a cost - effective approach ( 20 , 21 ) . obesity , a condition that is occurring with high incidence worldwide , has significant adverse impacts on public health . chronic gastritis showed increased prevalence in obesity , more particularly h. pylori - related gastritis . it was clearly confirmed in our study that 33.01% of the patients who had sleeve gastrectomy also had chronic gastritis with a high incidence ( 8.5% ) of h. pylori - related gastritis , which indicated that obesity is a risk factor for chronic gastritis and h. pylori infection . pre - operative investigations and eradication of infection are necessary , because the stomach is presumed to be free of pathogens even if the outcome is not affected . further studies are necessary to obtain clinical results at long - term follow - up .

introductionobesity is a condition that has significant impact on public health . recent exciting studies have linked chronic gastritis and h. pylori infection to obesity . chronic gastritis has shown increased prevalence in obesity , more particularly h. pylori - related gastritis . this study aimed to determine the prevalence of chronic gastritis in morbidly obese patients who were subjected to sleeve gastrectomy , with focus on h. pylori - related gastritis . the aim was to demonstrate any influence on chronic gastritis of the surgical procedure or its post - operative course.methodsone hundred six morbidly obese patients were subjected to vertical sleeve gastrectomy in king abdulaziz university hospital ( kauh ) from march 2014 to april 2015 . after full pre - operative preparation , sleeve gastrectomy was carried out , followed by histological examination of the specimen to view the chronic gastritis and h. pylori - related cases . all epidemiological data of the patients , including age , gender , body mass index ( bmi ) , as well as mean operative time , length of hospital stay , and post - operative complications were documented and analyzed by ibm - spss version 22.resultsfemale patients presented the higher prevalence , i.e. , 66% among the group of patients with sleeve resection , while 33% had chronic gastritis and 8.5% had h. pylori - related gastritis.conclusionthis study highlights the high prevalence of chronic gastritis in morbidly obese patients with reference to the high incidence of h. pylori - related gastritis among them , however no relationship was found between this infection and the post - operative outcome .

the study area was selected because , although most bovines in zambzia province are vaccinated , no vaccination of small ruminants had been performed and the local veterinary service had identified this province as a potential high - risk area for rvfv . the farms were selected based on willingness of farmers and overlap with the regions investigated by fafetine et al . ( 11 ) . both female and male animals were sampled , and the animals were categorised into three age groups ( 06 months , 612 months and > 12 months ) , see table 1 for further details . serum was separated from the whole blood and was stored at + 4c until tested . a map of mozambique , highlighting zambzia province and displaying the three areas ( mopeia ( a ) , nicoadala ( b ) and quelimane ( c ) ) where the sampling has occurred . details of the seroprevalence of rvfv in goat and sheep populations sampled in 2013 in zambzia , mozambique for each species , the overall data have been grouped according to the sex and age of the sampled animals . the 368 serum samples were analysed using the i d screen rift valley fever competition multi - species elisa ( id - vet ) according to the manufacturer 's instruction . optical reading was performed at 450 nm , and the cut - off values suggested by the manufacturer were followed . the seroprevalence was calculated , with a 95% confidence interval , using the modified wald method ( 14 ) . the seroprevalence was compared between species , gender and age using a chi - square test . the study area was selected because , although most bovines in zambzia province are vaccinated , no vaccination of small ruminants had been performed and the local veterinary service had identified this province as a potential high - risk area for rvfv . the farms were selected based on willingness of farmers and overlap with the regions investigated by fafetine et al . ( 11 ) . both female and male animals were sampled , and the animals were categorised into three age groups ( 06 months , 612 months and > 12 months ) , see table 1 for further details . serum was separated from the whole blood and was stored at + 4c until tested . a map of mozambique , highlighting zambzia province and displaying the three areas ( mopeia ( a ) , nicoadala ( b ) and quelimane ( c ) ) where the sampling has occurred . details of the seroprevalence of rvfv in goat and sheep populations sampled in 2013 in zambzia , mozambique for each species , the overall data have been grouped according to the sex and age of the sampled animals . the 368 serum samples were analysed using the i d screen rift valley fever competition multi - species elisa ( id - vet ) according to the manufacturer 's instruction . optical reading was performed at 450 nm , and the cut - off values suggested by the manufacturer were followed . the seroprevalence was calculated , with a 95% confidence interval , using the modified wald method ( 14 ) . the seroprevalence was compared between species , gender and age using a chi - square test . in total , 368 ruminants ( 187 goat and 181 sheep ) were sampled in the three districts ( table 1 ) . most of the samples were from adult animals ( > 12 months ) but animals < 12 months were also sampled . antibodies specific for rvfv were detected in animals from all localities included in this study ( table 2 ) . one hundred twenty - seven of the 368 analysed serum samples ( 37.5% ; 95% ci 29.839.5 ) were positive for rvfv antibodies . the overall seroprevalence in sheep was significantly higher than in goats ( p<0.001 ) , with 44.2 and 25.1% seropositive animals , respectively ( table 1 ) . no statistically significant difference in seroprevalence was observed between gender for sheep or goats . however , adult animals ( > 12 months ) had a higher seroprevalence than younger animals ( p<0.001 ) . the seroprevalence for both goat and sheep varied between districts and between individual localities ( excluding places with < 30 animals sampled ) , with a seroprevalence range of 7.540.6% for goats and 19.790.9% for sheep . the seroprevalence of rvfv in goat and sheep sampled in different localities in the three districts mopeia , nicoadala and quelimane in connection to the sampling activities , the animal keepers were asked about animal health and mortality on their farm . all the farms had experienced death of animals during the sampling year ; however , the deaths did not appear to be associated with typical rvf symptoms . in this study , we show that rvfv is circulating during inter - epidemic periods in the zambzia province in both goats and sheep . the overall seroprevalence in 2013 was 44.2 and 25.1% for sheep and goat , respectively . why the seroprevalence is different in goat and sheep , sometimes even on the same farm , is not known ; however , it could be that one species is more susceptible than the other , which would be supported by the fact that in this study we consistently found a higher seroprevalence in sheep than goats . the possible difference in susceptibility could be due to a number of unidentified factors , such as host genetic background and differences in animal management , but more studies are needed to elucidate this . the highest seroprevalence for both goat and sheep was observed in adult animals ( > 12 months ) . the higher seroprevalence in adult animals was expected as they have been exposed to the risk of infection for a longer period . for goats , the youngest animals ( 06 months ) had a higher seroprevalence ( 20.7% ) than goats between 6 and 12 months of age ( 7.3% ) . the reason for this could be that maternal immunity can last up to 6 months of age . a previous study by fafetine et al . ( 11 ) investigated serum samples collected in 2007 and 2010 from sheep and goats in the same regions as those included in this study . together , the data show that the overall seroprevalence in zambzia province varies between years . in 2007 , the seroprevalence in goat and sheep , respectively , was 21.2 and 35.8% ; in 2010 , it was 11.6 and 9.2% ; and in 2013 , it was 25.1 and 44.2% . one reason could be precipitation because high rainfall is an important risk factor of rvf . in 2013 , the average monthly precipitation from january to april was 333 mm , compared to 114 mm in 2010 and 210 mm in 2007 ( instituto nacional de metreologica , maputo mozambique , 2013 ) . increased rain could lead to a rise in seroprevalence through an increased vector population . ( 11 ) used an elisa detecting only igg antibodies , whereas , in this study , we used an elisa detecting both igg and igm antibodies . also , although the same region in zambzia was studied in both studies , it was not always possible to sample exactly the same farms . the seropositivity in livestock during inter - epidemic periods has been investigated in other counties . ( 15 ) showed that in the kilombero river valley , tanzania , the overall prevalence in livestock ( cattle , sheep and goat ) born after the rvfv outbreak in 2006/07 ( 15 ) was 5.55% , much lower than observed in this study . the reason for this is not known , but factors such as closeness to fresh water or dambos during the dry period , the presence of containers or tires on the farm that could serve as mosquito breeding grounds , possible effects of vaccination of cattle in the area for transmission of rvfv to small ruminants , the size of the herds , closeness to wild fauna and possible wildlife reservoirs could play a role in the transmission of rvfv . in summary , the high level of rvfv seroprevalence in small ruminants in zambzia suggests viral circulation , even without reports of clinical signs in susceptible hosts . therefore , it is important to monitor the rvfv circulation in mozambique for the early detection of epidemic occurrence of disease and prevention of transmission to humans . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

backgroundthe rift valley fever virus ( rvfv ) is a vector - borne virus that causes disease in ruminants , but it can also infect humans . in humans , the infection can be asymptomatic but can also lead to illness , ranging from a mild disease with fever , headache and muscle pain to a severe disease with encephalitis and haemorrhagic fever . in rare cases , death can occur . in infected animals , influenza - like symptoms can occur , and abortion and mortality in young animals are indicative of rvfv infection . since the initial outbreak in kenya in the 1930s , the virus has become endemic to most of sub - saharan africa . in 2000 , the virus appeared in yemen and saudi arabia ; this was the first outbreak of rvf outside of africa . rift valley fever epidemics are often connected to heavy rainfall , leading to an increased vector population and spread of the virus to animals and/or humans . however , the virus needs to be maintained during the inter - epidemic periods . in this study , we investigated the circulation of rvfv in small ruminants ( goats and sheep ) in zambzia , mozambique , an area with a close vector / wildlife / livestock / human interface.materials and methodsbetween september and october 2013 , 181 sheep and 187 goat blood samples were collected from eight localities in the central region of zambzia , mozambique . the samples were analysed for the presence of antibodies against rvfv using a commercial competitive elisa.results and discussionthe overall seroprevalence was higher in sheep ( 44.2% ) than goats ( 25.1% ) ; however , there was a high variation in seroprevalence between different localities . the data indicate an increased seroprevalence for sheep compared to 2010 , when a similar study was conducted in this region and in overlapping villages . no noticeable health problems in the herds were reported.conclusionsthis study shows an inter - epidemic circulation of rvfv in small ruminants in zambzia , mozambique . neither outbreaks of rvf nor typical clinical signs of rvfv have been reported in the investigated herds , indicating subclinical infection .

the issue of child sex selection and gender preferences is as old as human life . it seems that the historical tendency to determine the sex of the child is rooted in religious , economic , cultural - social and medical issues . until recently , sex selection seemed impossible , but modern medical technologies in the area of reproduction and genetics such as pre - implantation genetic diagnosis ( pgd ) , introduce some assured methods for the couples regarding embryo sex selection before embryo transfer to uterus . currently , the reasons for using child sex selection technology can be categorized into three groups : a ) preventing from the birth of babies with severe sex - linked diseases , b ) choosing the gender of the baby to balance the child sex combination in the family and c ) the freeness to choose the gender of the baby ( 1 , 2 ) . when sex selection is used for medical care , a small number of ethical issues are mentioned . problems usually arise when these methods are used in non - medical cases ( 3 , 4 ) . the sex selection technologies may cause gender discrimination or the gender imbalance in community ( 57 ) . the most countries , including european ones , accepted the prohibition of sex selection except in medical cases . furthermore , they concluded that there is not enough acceptable reason to prohibit sex selection in case of social causes such as family balancing ( 811 ) . the decline in fertility in modern societies makes sex determination technology essential to prevent the repeated pregnancies ( 12 ) . if couples have one or two children , they may be more inclined towards sex selection in order to have children of the preferred sex , or both sexes . investigating the causes of the couples tendency to embryo sex selection before transfer to the uterus , especially in non - medical cases are very important factors for consideration . social and ethical reasons of the tendency toward this attitude need to be assessed ; moreover , the relation between this determination and the parents demographic and social - economic situation should be examined ( 3 ) . many institutions in europe , including the uk department of health , was studied the various aspects of the ethical , legal and social reasons for non - medical sex selection of embryos ( 13 , 14 ) . sex selection is carried out through pgd technique in some leading clinics in iran . although sex selection through pgd is allowed by religious scholars in iran but its application is limited ( 15 ) . like many asian countries , there are some gender preferences in iran , and women with daughter are more likely to have an abortion . in a small - scale study of sheykhi ( 2012 ) , 11.1% of women underwent induced abortion after sex determination ( 12 ) . as induced abortion is illegal in iran except in certain medical conditions ( 16 ) , the sex selection demands more attention . the main objectives of the present study were evaluating the gender preferences and the attitudes of couples towards sex selection , and also determination of the factors affecting attitudes in using this method in iran . this cross - sectional study was conducted in tehran , iran in 2010 - 2011 . participants were 100 women aged 18 - 45 years who were referred to avicenna fertility clinic for sex selection . single child families ( families formed of parents and a child ) were chosen because the parents desire to have a second child or a baby of the other gender was more likely . the questions were designed by the researchers at the experts panel with focus on available scientific documents . to determine the validity of the questionnaire , the viewpoints of professors specialized in these issues were obtained . then inappropriate questions were excluded and the questionnaires were answered by 30 women referred to avicenna fertility center in the pilot phase of the study . based on the results of the pilot phase , some modifications were made in the questionnaire . each likert - type question was scored from 1 to 5 ( score 3 was a borderline score for each question ) . attitudes toward gender preferences , religious values , ownership of body components and body products were assessed quantitatively by calculating the total marks obtained by each variable . the gender preferences section based on the importance of the role of the son or daughter from the perspective of parents included 5 questions with borderline score of 15 . the gender based preferences section based on the importance of the role of the son or daughter from the perspective of the community included 13 questions with borderline score of 39 . the religious values section included 12 items with borderline score of 36 , ownership of body components section included 8 questions with borderline score of 24 and body products section included 6 questions with borderline score of 18 . in body ownership section , the first item was the rights and control of the body owner over the components and parts of his body and the second item was the rights and control of the body owner over the products of its body . for religious values , moreover , answers were developed from a range of favorable response to undesirable and from 5 to 1 point . in gender preference section , the scores below the grade boundary indicate the positive attitude of respondents to male gender . scores above the grade boundary for religious values , ownership of body components and body products , indicate the positive attitude of respondents to embryo sex selection . the results of the variables including parents satisfaction with sex composition of children and familiarity with various methods of embryo sex selection were examined based on the frequency of each answer . the mean age of women recruited in the present study was 35.5 years ( sd = 4.6 ) and their marriage duration was 15 years ( sd = 5 ) . the demographic data including ethnicity , religion and level of education of participants are listed in table 1 . most of participants had no prior experience of sex selection ( 82% ) ; and agreed to have embryo sex selection experience ( 93% ) . the parental gender preferences and the gender preferences based on the importance of the role of the son or daughter from the perspective of the community , religious values , ownership and possession of body parts and body products are summarized in table 2 . based on the mean scores reported in the method , the parental gender preferences and the gender preferences based on the importance of the role of the son or daughter from the perspective of the community were toward the male sex ( 55.5% male,15.5% female and 28.5% no tendency ) . participants had a more positive attitude toward sex selection in terms of religious values , ownership of body part and body products . demographic characteristics of women parental gender preferences , gender preferences , religious values , ownership of body parts , body products in relation to ethnicity and the education level of women and their spouses the values related to satisfaction with sex composition of children , awareness about sex selection methods and the importance of sex selection were not statistically significant based on women 's ethnicity ( p = 0.623 , p = 0.302 , p = 0.560 ) and their spouses ( p = 0.095 , p = 0.110 , p = 0.502 ) . thevalues related to agreements with sex determination with medical or non - medical reasons in women ( p = 0.186 , p = 0.970 ) and spouses ( p = 0.576 , p = 0.180 ) were not statistically significant . values regarding satisfaction with sex composition of children , awareness about sex determination techniques , the importance of sex selection in general , in terms of women 's education level ( p = 0.791 , p = 0.126 , p = 0.876 ) and their spouses ( p = 0.745 , p= 0.303 , p = 0.092 ) were not statistically significant . values regarding agreement with embryo sex selection with medical and non - medical reasons in terms of women 's level of education ( p = 0.05 , p= 0.001 ) and with medical reasons in terms of spouses level of education were statistically significant ( p = 0.001 ) but the difference was not significant due to non - medical reason and spouses level of education ( p = 0.286 ) . regression analysis showed that higher levels of education affect sex selection with medical reasons . with higher education level , the average score for sex selection with medical reasons increased . the score was 0.21 for women and 0.24 for men . also with higher education level , the average score for sex selection with non - medical reasons increased 0.24 for women . in other words , level of education has positive effect on agreements with sex selection . satisfaction with sex composition of children , familiarity with various methods of embryo sex determination and agreements with embryo sex determination according to medical and non - medical reasons are summarized in table 3 . a significant percentage of the participants were satisfied with their existing children 's gender composition . majority of participants had moderate knowledge about different methods of sex selection and agreed with medical sex selection reasons and non - medical sex selection in order to balance the family . in this research , participants were referred for sex selection and consequently most of them ( 93% ) agreed to have the experience of embryo sex determination . in examining the parental gender preferences and the general gender preferences in participants , the tendency was toward the male sex . son preference is an important issue that has a significant impact on the risk of female birth and can change the reproductive behavior of couples . performed a study in pakistan on gender preference issues and evaluated the demand of pregnant women for sex selection of embryos before transfer to the uterus . demand for boys was so high in some classes that may have caused gender imbalances . study of statham in england , 58% and 82% of respondents did not have any gender preferences , respectively ( 17 , 18 ) . although in the present study , results revealed the tendency to male sex , the tendency was not so strong . therefore , it seems unlikely that this selection is subject to conditions such as gender discrimination and will result in gender composition changes of the population in future . tendency for abortion has been more in women with daughter ( 26.51% ) in the study of sheykhi ( 2012 ) in iran ( 12 ) . as son preference is a significant predictor for induced abortions in women ( 19 , 20 ) and induced abortion is illegal in iran except in certain medical conditions ( 16 ) , then it seems that allocating enough resources for sex selection services can reduce the incidence of illegal induced abortion in iran . in the present study , participants consent to embryo sex determination to balance the sex composition of their children has won a high percentage . in other words , most people would employ sex selection to have a balanced two - child family and balancing has more influence on the desire to sex selection than the male preference ( 21 , 22 ) . furthermore , it can be inferred from the results that agreement of people to embryo sex determination with non - medical reasons in the present study was for balancing the sex composition of their children and not for sex discrimination which is especially common in some asian countries . similarly , in a study that was conducted on 809 couples during 18 months in england , it was revealed that the aim of majority of the clients for using sex determination techniques was to have a balanced family , and 95% of couples went to the center only for this reason , to have a balanced family ( 23 ) . in a study conducted by jain ( 2005 ) , it was shown that infertile women seriously wanted to choose the sex of their fetus , especially those who had no children or who had children of the same sex ( 3 ) . in the study of himmel et al . ( 2008 ) in germany , a positive attitude towards sex selection was more likely in infertile people if the respondents had a preference for either a boy or a girl and/or had an unbalanced family ( 24 ) . preference for having at least one child of each sex is a common pattern of parental gender preferences in many different social , economic and cultural contexts ( 25 ) . although the participants in this study were referred to the center for sex selection , they were satisfied with the sex composition of their existing children . it means that family balancing is more important than having a child with special sex composition . the hypothesis that parents religious values and their idea about ownership of body components may influence their attitude about sex selection was evaluated and based on the findings of the present study , it could be claimed that respondents had a positive attitude toward sex selection with respect to religious values , ownership of body parts and body products . higher education levels resulted in more agreements to embryo sex selection with medical and non - medical reasons . similarly , in the study of kippen ( 2006 ) in australia , respondents with bachelor degree or above were more likely to agree with this technology ( 26 ) . in the study of gleicher and barad in usa ( 2007 ) , chinese , arab / muslim and asian - indian couples preferred male children more than female ( 27 ) . however , sex selection in terms of different ethnicities was not significant in the present study . in examining parental gender preferences and gender preferences , tendency was toward the male sex but it was not so strong . most participants agreed to have the experience of sex selection and wanted to use this technique for gender balance in the family . only women 's level of education had positive effect on agreements to embryo sex selection with medical and non - medical reasons . the participants were satisfied with their existing child sex composition , although they were referred to the center for sex selection . in fact , providing sex selection services to iranian couples seeking family balancing is unlikely to result in some conditions such as gender discrimination or severe sex imbalance . it seems that allocating enough resources for sex selection services can reduce the incidence of illegal induced abortion in iran .

backgroundgender preference is prevalent in some communities and using medical techniques to choose the baby 's sex may cause the gender discrimination and gender imbalance in communities . therefore , evaluating the gender preferences and attitudes towards using sex selection technologies seems to be necessary.methodsthis cross - sectional study was conducted in avicenna fertility center . participants were 100 women with one child who were referred for sex selection . data were collected through self - developed questionnaires . the questions were designed by the researchers at the experts panel . to determine the validity of the questionnaire , the viewpoints of professors specialized in these issues were obtained . the statistical analysis of the data was performed using spss software ( version 11.5 ) , and p < 0.05 was considered significant.resultstendency toward the male was more than female sex ( 55.5% male , 15.5% female and 28.5% no tendency ) . majority of participants agreed with sex selection with medical reason and sex selection in order to balance the family . women 's level of education had positive effect on agreements to fetal sex selection with medical and non - medical reasons ( p < 0.001).conclusionalthough gender preferences were toward the male sex but this preference was not very strong . most participants agreed with non - medical sex selection for balancing the sex composition of their children . it does n't seem that non - medical sex selection for family balancing causes severe sex imbalance in iran .

this study was carried out in strict accordance with the guidelines of the german animal protection law ( tierschg ) . all procedures including housing , treatment , and sacrifice by cervical dislocation following isoflurane anesthesia were performed as authorized by and were reported to the responsible state office regierung von oberbayern ( munich , germany ) per standard legal procedure ( references 55.2.1.5425322611 and 55.2154253211114 ) . card9 ( card9 ) and ascdeficient ( asc ) mice have been described previously 7 , 27 . rpmi1640 medium ( invitrogen ) and dmem ( invitrogen ) were supplemented with 10% v / v fcs ( hyclone ) , 3 mm lglutamine , 100 u / ml of penicillin , and 100 g / ml of streptomycin ( all from sigmaaldrich ) . cpg 1826 and curdlan were purchased from invivogen and wako chemicals ( richmond , usa ) . the b16f10 murine melanoma cell line expressing full length chicken ova ( here referred to as b16.ova ) was cultured in complete dmem medium supplemented with 400 g / ml g418 ( from sigmaaldrich ) . bm cells were harvested from murine femur and tibia and erythrocytes were lysed with ammonium chloride buffer ( bd biosciences , heidelberg , germany ) . bmdcs were generated by culturing bm cells in complete rpmi medium supplemented with 20 ng / ml gmcsf ( from immunotools , friesoythe , germay ) . on days 6 to 7 cd8 t cells from oti splenocytes were purified with magnetic beads according to the manufacturer 's protocol ( miltenyi biotech , bergisch gladbach ) . for in vitro stimulation assays , cells were cultured in complete rpmi . dcs were stimulated with curdlan ( 50 g / ml ) , cpg 1826 ( 0.075 m ) , or pam3csk4 ( 1 g / ml ) , if not stated otherwise . for coculture experiments , 10 purified , cfselabeled cd8 oti t cells were cultured in the presence of 25 000 stimulated dcs . cell supernatants were analyzed for cytokine secretion by elisa ( bd , r&d systems , or ebioscience ) according to the manufacturer 's protocol . the fixable viability dye efluor 506 ( ebioscience ) was used to stain and exclude dead cells . the itag mhci murine tetramers detecting siinfeklspecific cd8 t cells were from mbl ( woburn , ma ) . for intracellular cytokine staining the foxp3 transcription factor fixation / permeabilization kit ( ebioscience ) was used . data were acquired on a facscanto ii ( bd biosciences ) and analyzed using flowjo software ( treestar ) . cells were gated as follows : dcs : singlets > viability dye > cd11c > cd86 ( mfi ) . t cells : singlets > viability dye > cd3 > cd8 > cfse ( proliferating ) + ifn. in vivo cytotoxicity was evaluated 4 days after the final treatment as described previously 12 . in brief , splenocytes from nave syngenic donor mice were pulsed with siinfekl peptide at different concentrations ( 0 and 200 nm ) for 3045 min at 37c . these two populations were then stained with different concentrations of celltracker violet ( ctv , 0.1 and 5 m ) , washed , mixed in a 1:1 ratio , and were injected i.v . the next day , animals were sacrificed and the target cell frequency in the ln draining the initial vaccination site was determined by flow cytometry as follows : singlets > viability dye > ctv versus ctv . specific killing was calculated using the formula 100 ( 1 % / % ) as described 12 . wt or card9 mice were injected s.c . in the right flank with 100 g ova together with 25 g cpg 1826 or 100 g curdlan . one week later , the frequency of agspecific cd8 t cells in the peripheral blood was analyzed with siinfeklh2 kb tetramers . subsequently , mice were injected s.c . with 1 10 b16.ova cells in the left flank and tumor growth was monitored continuously . according to standard legal procedure ( responsible state office regierung von oberbayern ) treatment with anticd8 ( clone 2.43 ) or antink1.1 ( clone pk136 , both from bioxcell ) depleting antibodies was initiated 2 days prior to vaccination ( 100 g i.p . ) and was repeated twice weekly ( 50 g i.p . ) . for rechallenge experiments , fourteen days later , mice were sacrificed and macroscopically visible , superficial pulmonary pseudometastases were counted . all data are presented as mean + sem if not stated otherwise . for multiple statistical comparison of a data set , the oneway anova test with bonferroni posttest was used . significance was set at pvalues p < 0.05 , p < 0.01 , and p < 0.001 and was then indicated with asterisks ( * , * * , and * * * ) . all statistical calculations were performed using graphpad prism ( graphpad software , san diego , usa ) . this study was carried out in strict accordance with the guidelines of the german animal protection law ( tierschg ) . all procedures including housing , treatment , and sacrifice by cervical dislocation following isoflurane anesthesia were performed as authorized by and were reported to the responsible state office regierung von oberbayern ( munich , germany ) per standard legal procedure ( references 55.2.1.5425322611 and 55.2154253211114 ) . card9 ( card9 ) and ascdeficient ( asc ) mice have been described previously 7 , 27 . rpmi1640 medium ( invitrogen ) and dmem ( invitrogen ) were supplemented with 10% v / v fcs ( hyclone ) , 3 mm lglutamine , 100 u / ml of penicillin , and 100 g / ml of streptomycin ( all from sigmaaldrich ) . cpg 1826 and curdlan were purchased from invivogen and wako chemicals ( richmond , usa ) . the b16f10 murine melanoma cell line expressing full length chicken ova ( here referred to as b16.ova ) was cultured in complete dmem medium supplemented with 400 g / ml g418 ( from sigmaaldrich ) . bm cells were harvested from murine femur and tibia and erythrocytes were lysed with ammonium chloride buffer ( bd biosciences , heidelberg , germany ) . bmdcs were generated by culturing bm cells in complete rpmi medium supplemented with 20 ng / ml gmcsf ( from immunotools , friesoythe , germay ) . on days 6 to 7 cd8 t cells from oti splenocytes were purified with magnetic beads according to the manufacturer 's protocol ( miltenyi biotech , bergisch gladbach ) . for in vitro stimulation assays , cells were cultured in complete rpmi . dcs were stimulated with curdlan ( 50 g / ml ) , cpg 1826 ( 0.075 m ) , or pam3csk4 ( 1 g / ml ) , if not stated otherwise . for coculture experiments , 10 purified , cfselabeled cd8 oti t cells were cultured in the presence of 25 000 stimulated dcs . cell supernatants were analyzed for cytokine secretion by elisa ( bd , r&d systems , or ebioscience ) according to the manufacturer 's protocol . the fixable viability dye efluor 506 ( ebioscience ) was used to stain and exclude dead cells . the itag mhci murine tetramers detecting siinfeklspecific cd8 t cells were from mbl ( woburn , ma ) . for intracellular cytokine staining the foxp3 transcription factor fixation / permeabilization kit ( ebioscience ) was used . data were acquired on a facscanto ii ( bd biosciences ) and analyzed using flowjo software ( treestar ) . cells were gated as follows : dcs : singlets > viability dye > cd11c > cd86 ( mfi ) . t cells : singlets > viability dye > cd3 > cd8 > cfse ( proliferating ) + ifn. in vivo cytotoxicity was evaluated 4 days after the final treatment as described previously 12 . in brief , splenocytes from nave syngenic donor mice were pulsed with siinfekl peptide at different concentrations ( 0 and 200 nm ) for 3045 min at 37c . these two populations were then stained with different concentrations of celltracker violet ( ctv , 0.1 and 5 m ) , washed , mixed in a 1:1 ratio , and were injected i.v . the next day , animals were sacrificed and the target cell frequency in the ln draining the initial vaccination site was determined by flow cytometry as follows : singlets > viability dye > ctv versus ctv . specific killing was calculated using the formula 100 ( 1 % / % ) as described 12 . wt or card9 mice were injected s.c . in the right flank with 100 g ova together with 25 g cpg 1826 or 100 g curdlan . one week later , the frequency of agspecific cd8 t cells in the peripheral blood was analyzed with siinfeklh2 kb tetramers . subsequently , mice were injected s.c . with 1 10 b16.ova cells in the left flank and tumor growth was monitored continuously . according to standard legal procedure ( responsible state office regierung von oberbayern ) treatment with anticd8 ( clone 2.43 ) or antink1.1 ( clone pk136 , both from bioxcell ) depleting antibodies was initiated 2 days prior to vaccination ( 100 g i.p . ) and was repeated twice weekly ( 50 g i.p . ) . for rechallenge experiments , mice were injected i.v . with 5 10 b16.ova cells on day 28 after initial tumor induction . fourteen days later , mice were sacrificed and macroscopically visible , superficial pulmonary pseudometastases were counted . all data are presented as mean + sem if not stated otherwise . for multiple statistical comparison of a data set , the oneway anova test with bonferroni posttest was used . significance was set at pvalues p < 0.05 , p < 0.01 , and p < 0.001 and was then indicated with asterisks ( * , * * , and * * * ) . all statistical calculations were performed using graphpad prism ( graphpad software , san diego , usa ) . supporting information figure 1 : bmdcs from wt , card9 supporting information figure 2 : wt and card9deficient supporting information figure 3 : wt mice were vaccinated with ova click here for additional data file .

activation of the ctype lectin receptor dectin1 by glucans triggers multiple signals within dcs that result in activation of innate immunity . while these mechanisms can potently prime cd8 + cytotoxic tcell ( ctl ) responses without additional adjuvants , the dectin1 effector pathways that control ctl induction remain unclear . here we demonstrate that dectin1induced ctl crosspriming in mice does not require inflammasome activation but strictly depends on the adapter protein card9 in vitro . in vivo , dectin1mediated card9 activation after vaccination drives both expansion and activation of agspecific ctls , resulting in longlasting ctl responses that are sufficient to protect mice from tumor challenge . this dectin1induced antitumor immune response was independent of nk cell function and completely abrogated in card9deficient mice . thus , our results demonstrate that dectin1triggered card9 signaling but not inflammasome activation can potently crossprime agspecific ctls , suggesting that this pathway would be a candidate for immunotherapy and vaccine development .

andropause is a condition of decreasing testosterone in men that usually begins to occur at about 40 years of age . many men also find it difficult to acknowledge there may be a problem by refusing to even talk about the symptoms . ignorance and fear of the andropause condition abounds in the general public and even among health professionals . over 10,000 articles on climacteric ( or menopause ) for women can be found but relatively less has been conducted on the male equivalent . attaining knowledge regarding andropause will help the caregivers and gerontologists to achieve the ultimate goal of a dignified healthy ageing and maintain the highest quality of life . thus , it 's adding life to years and not simply years to life while ignorance about andropause persists , having an instrument turns out to be a necessity . the study was investigated to the standards of massq ( 2012 ) within male older adults to introduce a relevant criterion . about 382 men with age range of 50 - 80 and with the mean age of 65.3 2.32 were sampled with the cluster - ratio sampling method from the eight cities of khuzestan province in southwestern iran ( n = 228784 aged persons in the province ) [ appendix 1 ] . the massq questionnaire mainly consists of a 25-item disability / symptom scale regarding andropause that was investigated by authors and literature reviews . each item in the disability / symptom scale has five response options from 1 = none to 5 = extremely severe . if the 25 items are completed , a scale score ranging from 25 ( no symptoms ) to 125 ( most severe symptoms ) can be calculated . the questionnaire was translated into persian from its english version by three instructors and an english language expert . the four translated versions were compared by the authors , and the researchers developed a common persian text from them . afterward , the persian version of the massq was translated back into english by an english language expert who had not seen the original english text and by a linguist . the english statements of the questionnaire that had been translated from persian into english were compared with the original version , and any necessary revisions were made as well . from the eight cities of khuzestan province in southwestern iran , that is , ahwaz , behbahan , dezful , shoushtar , abadan , mah - shahr , masjid soleiman , and ramhormoz , about 400 aged men responded to the iranian version of the massq . of the 400 responders , 382 had responded to all of the 25 items used in the massq and were included in the analysis . the mean age of the samples was 65.3 2.32 ( range : 54 - 86 ) years . the questionnaire was translated into persian from its english version by three instructors and an english language expert . the four translated versions were compared by the authors , and the researchers developed a common persian text from them . afterward , the persian version of the massq was translated back into english by an english language expert who had not seen the original english text and by a linguist . the english statements of the questionnaire that had been translated from persian into english were compared with the original version , and any necessary revisions were made as well . from the eight cities of khuzestan province in southwestern iran , that is , ahwaz , behbahan , dezful , shoushtar , abadan , mah - shahr , masjid soleiman , and ramhormoz , about 400 aged men responded to the iranian version of the massq . of the 400 responders , 382 had responded to all of the 25 items used in the massq and were included in the analysis . the mean age of the samples was 65.3 2.32 ( range : 54 - 86 ) years . coefficients of cronbach 's alpha ( = 0.89 ) , split - half ( 0.91 ) , convergent validity ( 0.72 ) , divergent validity ( -0.32 ) criterion validity ( 0.67 ) were estimated , which were significant at p < 0.01 . the exploratory factor analysis demonstrated that the 25-items of massq for aged samples are organized into four factors ( factor 1 : sexual , factor 2 : somatic , factor 3 : psychic , and factor 4 : behavioral ) which clarify 83% of the scale 's variance . second - order confirmatory factor analysis pointed out that the factors were well matched up onto a principal factor . according to the table 1 , the rotated factor matrix pattern of varimax for the massq 's subscale questions was considered . varimax - rotated factors matrix of the massq consequently , the four - factor model was appropriate for the data and the fit index techniques for adjusting the scale . the indexes of the model 's goodness of fit refer to the integrity of the four - factor model with data . the root mean square error of approximation ( rmsea ) and standardized root mean residual ( srmr ) must be less than 0.05 that indicate to good models . the model pointed out the goodness of fit of the model in the study ( agfi = 0.92 , gfi = 0.91 , rmsea = 0.006 , ifi = 0.94 , nfi = 0.91 , cfi = 0.97 ) . as closer measure to 1 in the normed fit index ( nfi ) , the comparative fit index ( cfi ) , goodness - of - fit statistic ( gfi ) , the incremental fit index ( ifi ) , and the adjusted goodness of fit index ( agfi ) , they refer to the goodness and fit of model . the aim of the study is to look for the relevant instrument regarding common symptoms of an aged - related issue called andropause within aged males in the iranian social context , even the issue still is challengeable . so , the andropause symptoms self - assessment questionnaire ( massq , 2012 ) was used and evaluated . the results stated to the well - adjusted reliability and validity of massq and usefulness of it in the relevant studies as well . therefore , future researchers should not limit themselves to the western scales but should also consider specific cultural factors . additionally , it is suggested that in future studies , the female menopause symptoms self - assessment questionnaire , which are compatible with iran 's native culture , be conducted and evaluated as well . validity and reliability in the aged male community of the iranian society and it can be employed to measure andropause symptoms . it is applicable by gerontologists for the future studies as well as to the geriatrics in their diagnostics . ethical matters , for example , plagiarism , uninformed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , and so on , have been totally observed by the authors . ethical matters , for example , plagiarism , uninformed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , and so on , have been totally observed by the authors .

background : andropause is a condition of decreasing testosterone in men that usually begins to occur at about 40 years of age . many men find it difficult to acknowledge there may be a problem by refusing to even talk about the symptoms.aims:the study was conducted to the standards of massq ( 2012 ) within male older adults to introduce a relevant criterion.materials and methods : about 382 men with age range of 50 - 80 and with the mean age of 65.3 2.32 were sampled with the cluster - ratio sampling method from the eight cities of khuzestan province in southwestern iran . the aged samples replied to the 25 items of massq.results:coefficients of cronbach 's alpha ( = 0.89 ) , split - half ( 0.91 ) , convergent validity ( 0.72 ) , divergent validity ( 0.32 ) , and criterion validity ( 0.67 ) were estimated , which were significant at p < 0.01 . the exploratory factor analysis demonstrated that the 25-items of massq for aged samples are organized into four factors ( sexual , somatic , psychic , and behavioral ) which clarify 79% of the scale 's variance . second - order confirmatory factor analysis pointed out that the factors are well - matched up onto a principal factor . consequently , the four - factor model was well appropriate for the data by the fit index techniques for adjusting the scale [ adjusted goodness of fit index = 0.92 , goodness - of - fit statistic = 0.91 , root mean square error of approximation = 0.006 , incremental fit index = 0.94 , normed fit index = 0.91 , comparative fit index = 0.97].conclusions : the results pointed to the well - adjusted reliability and validity of massq and its usefulness for the relevant studies as well .

the pathologic causes of hyperparathyroidism can be divided into single adenoma of the parathyroid ( 89% ) , multiple hyperplasia of the parathyroid ( 6% ) , and parathyroid carcinoma ( 0.1 to 4% ) . the diagnosis of parathyroid carcinoma is made by first referring to serum calcium or intact parathyroid hormone ( ipth ) levels , then locating the enlarged parathyroid with ultrasonography , scintigraphy , or computed tomography and confirming the parathyroid tumor with fine needle aspiration biopsy . however , if asymptomatic , most parathyroid tumors are adhered to the thyroid gland , and therefore , making the distinction between parathyroid and thyroid tumor is difficult under ultrasonography , and the differential diagnosis is also difficult with cytologic findings alone without clinical signs . stated that vesicle formation and presence of colloid or macrophages suggests thyroid lesions . however , studies on numerous parathyroid lesions have reported that the amount of colloid , vesicular structures , and presence or absence of macrophages , do not greatly help in distinguishing thyroid tumors from parathyroid tumors . for this reason , the criteria for diagnosis of parathyroid carcinoma include 1 ) direct invasion into neighboring organs , such as thyroid gland , neck muscles , nerve , and esophagus , 2 ) distant metastasis to lung or liver , 3 ) cervical lymph node metastasis , and 4 ) histological findings including fibrosis , trabecular growth , necrosis , and nuclear atypia ( pleomorphism , large nuclei , macronucleoli , mitosis ) . the recurrence of parathyroid carcinoma occurs within 2 to 3 years after removal , but the disease - free survival period is known to vary greatly from case to case . therefore , various studies have attempted subgrouping to classify high - risk and low - risk categories , histologically to reflect variable prognosis of the carcinoma . among such studies , the study by bondeson et al . argues that macronucleoli , necrosis , and mitotic activity in excess of 5 per 50 high - power fields reflect bad prognosis . in addition , a report by kameyama and takami argues that the criteria suggested by bondeson et al . did not reflect the patients ' prognosisappropriately and classified parathyroid carcinoma into either minimally invasive or widely invasive carcinoma , similar to the classification of follicular carcinoma . serum calcium levels typically returns to normal within 24 to 48 hours after excision of the parathyroid gland due to primary hyperparathyroidism , but hypocalcemia occurs in 10 to 30% of the cases . this is known to be due to the time required for normal parathyroid glands to recover their sensitivity to calcium after surgery , which takes several days . however , persistent hypocalcemia requires differential diagnosis of hypoparathyroidism due to surgery , concomitant hypomagnesemia , and hungry bone syndrome . in other words , after the excision of the parathyroid gland due to primary hyperparathyrodism of any cause , serum ipth levels normalize and serum calcium and phosphate rapidly migrate to the bone , leading to hypocalcemia . this syndrome is known as hungry bone syndrome , known to occur in about 12.6% of operations on the parathyroid gland . we experienced 1 case of minimally invasive parathyroid cancer accompanied by postoperative hungry bone syndrome , and attempt to report this case along with a review of related literatures . a 29-year - old female without any notable past history visited for further evaluation of elevated alkaline phosphatase ( alp ) and a mass was found at the lower right thyroid gland during a regular checkup . a relatively firm mass of about 3 2 cm was found at the right anterior portion of the neck upon examination . the mass was movable , and there was no palpable lymph node . a clinical laboratory study performed before the operation resulted in the following : blood urea nitrogen 6.3 mg / dl , creatinine 0.8 mg / dl , serum calcium 11.1 mg / dl , phosphorous 2.1 mg / dl , alp 1,072 u / l , and ipth 1,476 pg / dl . a round , hypoechogenic mass sized about 2 1.7 3 cm with well - defined margin separate from the right lower thyroid gland was observed under ultrasonography , and accompanied by signs of increased blood flow ( fig . some lymph nodes appearing to be positive reactive changes were observed inferior to the mass at level vi of right neck . fine needle aspiration revealed hurthle cell change of cell clusters , implying the possibility of hurthle cell neoplasm of the thyroid gland or a parathyroid neoplasm . the immunohistochemistry resultsshowed ipth and the clinical pattern confirmed the suspicion of parathyroid tumor , and therefore , a diagnosis of parathyroid tumor was made ( fig . sincecytologic study alone was unable to determine the benign or malignant nature of the tumor , a need for a frozen section of the specimen upon surgical excision was suggested . imaging studies showed enhancement upon contrast injection , making the determination of the exact nature of the tumor more difficult ( fig . the right lower parathyroid gland did not show any direct invasion to neighboring organs on surgical examination , and a round shaped mass of about 3 2 cm with a smooth capsule easily separable from the thyroid gland and the surrounding muscles was found . a right lower parathyroidectomy was performed , and an excisional biopsy of the surrounding lymph nodes was also performed simultaneously for frozen - sectionevaluation . the pathologic result of the frozen section reported high possibility of benign parathyroidoma , and examination of the excised lymph nodes revealed reactive hyperplasia . therefore , no further operation was performed . the serum ipth level immediately after the excision was 199.7 pg / dl , which became 18.54 pg / dl 1 hour later and 43.84 pg / dl 3 hours later . positive chevostek sign was observed , but the patient did not show any spasmodic muscle contraction . serum calcium , phosphorous , and ipth at this period was measured to be 7.2 mg / dl , 1.9 mg / dl , and 102.5 pg / ml , respectively . intravenous calcium chloride solution and 4 tablets of oral calcium agent ( dicamax 1000 tab , dalim biotech , seoul , korea ) divided into 2 doses twice a day , were concomitantly administered thereafter . the serum calcium level was maintained at below normal value despite a continuous supply of calcium , and serum calcium and ipth 8 days after operation was 7.1 mg / dl and 226.1 pg / dl , respectively . dicamax1000 tab was replaced by healthcal tab ( dong wha pharm co. , seoul , korea ) , with a daily dosage of 6 tablets divided into 3 doses three times a day . the patient was discharged 18 days after operation since she did not show any particular symptoms , and laboratory study performed 174 days after surgery reported ipth at 65.73 pg / dl , alp at 172 u / l , serum calcium level at 9.1 mg / dl , and phosphorous at 4.3 mg / dl ( fig . healthcal tab was replaced by dicamax 1000 tab with daily dose of 2 tablets divided into 2 doses twice a day . the final pathologic diagnosis of the patient was minimally invasive parathyroid carcinoma , and no metastasis to surrounding lymph nodes was found ( fig . various studies describe cytologic findings that distinguish parathyroid lesions from thyroid lesions , but the distinguishing points vary from paper to paper , and are sometimes even contradictory [ 4 - 6,12 ] . in short , there is no single cytologic finding that can definitively diagnose a parathyroid lesion as of yet . there have been reports of mixing fine needle - aspirated samples of parathyroid with liquid and measuring the concentration of parathyroid hormone of the solution being helpful in making the diagnosis in such cases . in the case of this patient , the clinical signs clearly pointed toward parathyroid tumor , and the measurement of parathyroid hormone levels in fine - needle aspirated samples is thought to help in making the diagnosis in cases of asymptomatic parathyroid tumors . it is especially of major importance to distinguish hungry bone syndrome from surgical hypoparathyroidism in order to start early the appropriate treatment given for a long period . therefore , we could establishthe cause of hypocalcemia in this patient as hungry bone syndrome . hungry bone syndrome was first reported in 1948 after studying patients who showed hypocalcemia , muscle spasm , and hypophosphatemia after receiving parathyroidectomy . extensive remineralization of the bone , reflecting deposition of calcium and phosphate within the bone parenchyme , was discovered upon bone tissue biopsy , and this finding was named ' hungry bone syndrome ' . the treatment of hungry bone syndrome usually involves supplementation of inadequate minerals . intravenous or oral calcium agents are administered in cases of hypocalcemia , and intravenous or oral magnesium agents are supplied in cases of hypomagnesemia as well . this patient similarly showed hypocalcemia and hypomagnesemia , and therefore , she received supplementary minerals , and a normalized serum calcium level was achieved14 days after operation . braiser and nussbaum suggested relatively large tumor size , blood urea nitrogen , alp , osteitisfibrosacystica , and old age as risk factors that may cause hungry bone syndrome in patients with primary hyperparathyroidism who receiveparathyroidectomy . when taking into consideration the tumor size and preoperative alp level , it is thought that the possibility of occurrence of hungry bone syndrome after operation in this patient could have been predicted beforehand . in addition , it is thought that radiographic studies , such as osteitisfibrosacystica , that observe the changes in bone related to hungry bone syndrome may have needed to be performed in more detail . mizrachi et al . stated that of all patients with primary hyperparathyroidism due to parathyroid adenoma , 25% experience a postoperative rise of ipth and that patients with preoperative ipth greater than 225 pg / ml can be predicted to maintain high levels of ipth after operation . mittendorf and mchenry recorded that this postoperative increase of pth is due to remineralization of the bone , and stated that most postoperative increases of ipth dropped to normal levels after an average of 16 months . since this patient recorded preoperative ipth greater than 225 pg / ml , a persistent elevation in postoperative ipth could be predicted , and a nearly normal level was recorded after about 6 months of follow - up study . the cause of primary hyperparathyroidism in this case was parathyroid carcinoma , which prompted the possibility of metastatic lesions in distant areas and caused much concern ; however , both preoperative and postoperative imaging studies revealed no abnormal findings , so close follow - up monitoring is thought to be needed . in this patient , a focal , very limited capsular invasion and invasion into one small vessel was histologically observed , which prompted the diagnosis of minimally invasive parathyroid carcinoma according to the aforementioned report by kameyama and takami . their report also stated that all of 12 patients who had no recurrence had minimally invasive parathyroid carcinoma . examination of preoperative laboratory results related to postoperative hungry bone syndrome can help in predicting the possibility of hungry bone syndrome . there is a high possibility that a postoperative increase of ipth may be caused by remineralization of the bone associated with hungry bone syndrome ; also , close follow - up monitoring , including blood tests and imaging studies , is thought to be warranted even in minimally invasive parathyroid carcinomas that are reported to show good prognosis . a case of hungry bone syndrome , accompanied by persisting hypocalcemia and elevated ipth after operation on postoperatively diagnosed minimally invasive parathyroid carcinoma has been reported as such .

the prognosis of parathyroid carcinoma varies significantly between numerous studies . therefore , many attempts have been made to grade the degree of parathyroid carcinoma , and recently , classifying parathyroid carcinomas into either minimally invasive or widely invasive carcinoma- similar to follicular carcinoma of the thyroid- has led to a more reliable prediction of the prognosis . hungry bone syndrome can occur if parathyroidectomy is performed due to primary hyperparathyroidism regardless of the cause of the disease . hungry bone syndrome is characterized by postoperative a hypocalcemic state due to remineralization of various minerals , including calcium , of the bone ; this syndrome requires a long - term supplementation of calcium . the authors aim to report , along with a review of related literatures , 1 case of a 29-year - old female patient diagnosed with minimally invasive parathyroid carcinoma who fell into hungry bone syndrome after parathyroidectomy .

toxic epidermal necrolysis ( ten ) -like rash of lupus , a rare entity , is clinically indistinguishable from drug - induced ten . toxic epidermal necrolysis ( ten ) is a common , yet one of the most dreaded dermatological emergencies . ten - like rash of lupus , which is clinically indistinguishable from drug - induced ten , is a rare entity , with less than 50 cases reported worldwide . unless there is a high index of suspicion , the subtle features of le , complemented with investigative findings like hematological abnormalities , proteinuria , high positive antinuclear antibody ( ana ) titer , and so on can be easily overlooked in a sick patient presenting with vesiculobullous lesions with peeling of skin , screaming for urgent management . we came across a 45-year - old female , who presented in emergency with a history of an insidious - onset peeling of skin , vesiculobullous lesions , and oral ulceration , which developed over the previous 10 days , without any acute primordial signs or symptoms [ figure 1 ] . she gave a history of fever on and off with pain in multiple joints for two years for which she had been taking diclofenac and naproxen almost on a daily basis , without developing any systemic or cutaneous adverse effect , making these two drugs unlikely culprits . she also reported a history suggestive of photosensitivity and painless oral ulcers over the previous two years . routine hematological and biochemical investigations revealed anemia [ hemoglobin ( hb ) : 7 gm% ] with a positivity for direct coomb 's test , hypoproteinemia ( 5.5 gm% ) , and proteinuria ( 3 + ) . ana and anti - dsdna ( dsdna : double - stranded deoxyribonucleic acid ) were positive ( ana titer by immunoflorescence 1:1280 , homogenous and peripheral ; anti - dsdna titer 1:640 ) . the patient was put on systemic steroids , namely , prednisolone , with a dose of 1.5 mg / kg / day once daily , till clinical improvement , both cutaneous and systemic , was apparent . this was about a week later , following which the oral steroid was slowly tapered . the active vesiculobullous lesion healed completely over two weeks , revealing the previously inapparent malar and discoid rash of lupus over the face [ figure 2 ] . skin biopsy from a discoid lesion over the forehead revealed epidermal atrophy , interface dermatitis , follicular plugging , and basal cell degeneration , suggesting discoid lupus erythematosus [ figure 3 ] . direct immunofluorescence ( dif ) showed immunoglobulin g ( igg ) and complement 3 ( c3 ) deposits at the dermo - epidermal junction . sheet - like desquamation over back ( a ) , chest ( b ) , and hemorrhagic crusting over lips ( c ) well - defined , discoid plaques over the nose ( a ) , forehead ( b ) , and right foot ( c ) ( a ) histology showing basal cell vacuolization ( h and e , 10 ) ; ( b ) epidermal atrophy , follicular plugging , interface dermatitis , dermal edema ( h and e stain , 10 ) vesiculobullous lesions occurring in the setting of le were classified by sontheimer as ten - like acute cutaneous leten - like subacute cutaneous leten occurring in systemic lupus erythematosus ( sle ) patients not having conventional le - specific skin lesionsvesiculobullous changes occurring at the active border of advancing annular subacute cutaneous levesiculobullous chronic cutaneous le . ten - like acute cutaneous le ten - like subacute cutaneous le ten occurring in systemic lupus erythematosus ( sle ) patients not having conventional le - specific skin lesions vesiculobullous changes occurring at the active border of advancing annular subacute cutaneous le vesiculobullous chronic cutaneous le . the first three entities , which are associated with an exacerbation of activity of the underlying lupus , clinically mimic drug - induced ten , but differ widely in terms of etiopathogenesis . it has been proposed that exaggerated keratinocyte apoptosis due to increase in fas expression may underlie many of the major manifestations of le , including cutaneous lesions as seen in our patient . differentiating ten - like lesions of le from drug - induced ten can be a challenge because ten is known to occur with increased frequency in connective tissue disease . moreover , patients of sle are often on chronic medication which further increases the risk of drug - induced ten histopathological findings are almost identical ( full - thickness epithelial necrosis and sparse superficial lymphocytic infiltrate ) both respond well to steroids . however , the points which favor ten - like rash of le over drug - induced ten are lack of evidence of ingestion of high - risk drugs photodistribution of ten - like lesions subacute presentation over weeks recent exacerbation of sle history of painless oral ulcer associated malar or discoid rash distinctive serologic profile , including a strongly positive ana and positive anti - dsdna , suggestive of underlying connective tissue disease however , these differences are largely subjective and theoretical . lately , a unifying concept of acute syndrome of apoptotic pan - epidermolysis ( asap) has been proposed by ting et al . in 2004 . it encompasses all the life - threatening clinical situations of massive epidermal cleavage resulting from a hyperacute apoptotic injury , which may be drug induced or due to other causes like le , acute graft versus host disease , pseudoporphyria , and so on . acute syndrome of apoptotic pan - epidermolysis ( asap) is a unifying concept that encompasses all the life - threatening clinical situations of massive epidermal cleavage resulting from a hyperacute apoptotic injury .

for most dermatologists , the challenge posed by toxic epidermal necrolysis ( ten ) lies not in its diagnosis , but in pulling the patient out of this life - threatening condition . however , when a patient presents with a ten - like picture in the background of lupus erythematosus ( le ) , it becomes difficult to decide whether the eruption is drug induced or a manifestation of lupus itself .

in 1997 , nozaki et al . ( 1 ) described subdiaphragmatic intrasellar meningiomas that originated from the sellar turcica ; two of which only originated from the floor of the sellar turcica . since then , only one case of intrasellar meningioma from the sellar floor has been reported in the english literature ( 2 ) . the pituitary gland is reported to be covered by two distinct structures : the capsule and dura ( 3 ) . although meningiomas can originate from anywhere in the sella turcica , subglandular meningiomas are extremely rare ( 1 ) . we report a case of subglandular meningioma probably originating from the floor of the sella turcica along with a review of the pituitary fossa anatomy . the imaging revealed an intrasellar mass measuring approximately 1.8 1.7 cm with a slightly upward bulge , homogenous isointense signals on t1- and t2-weighted images , and a focal inhomogenous signal on t2-weighted images ( fig . on contrast - enhanced t1-weighted images , the lower portion of the sellar mass was greatly enhanced , and the upper portion , lesser enhanced ( fig . initially the upper portion was thought to be a pituitary adenoma and the lower portion , normal pituitary gland . when an endonasal transsphenoidal operation was performed to remove the tumor , a bulging tumor on the sellar floor the normal pituitary gland was elevated and shifted to the left anterolateral side by the mass . after the tumor was removed , the diaphragma sellae was identified at the top of the sellar turcica . on histological examination , the low - lying intrasellar lesion was confirmed as a meningioma , while above it was the normal pituitary gland ( fig . in 1969 , hardy and robert ( 4 ) described a separate type of intrasellar meningioma originating from the inferior aspect of the diaphragma sellae . in 1985 , al - mefty et al . ( 5 ) proposed that diaphragmatic meningiomas and a tuberculum sellae meningiomas were separate entities . in 1995 , kinjo et al . ( 6 ) classified diaphragm sellae tumors according to their site of origin from the diaphragm : type a originated from the upper leaf of the diaphragma sellae anterior to the pituitary stalk ; type b from the upper leaf of the diaphragma sellae posterior to the pituitary stalk ; and type c from the inferior leaf of the diaphragma sellae . in 1997 , nozaki et al . ( 1 ) summarized observations in the literature on 18 operatively confirmed pure subdiaphragmatic intrasellar meningiomas originating from the dura of the sella turcica . they included type c diaphragma sellae meningiomas according to kinjo 's classification and intrasellar meningiomas from the other side of the sella , such as the floor and anterior or lateral wall . they established the origin of 9 meningiomas ; 6 from the inferior leaf of the diaphragma sellae ( the same as type c diaphragma sellae meningiomas ) , 2 from the floor of the sella turcica , and only one from the anterior wall of the sella turcica . one further example from the floor of the sella has been reported since then ( 2 ) . to the best of our knowledge , only three cases of intrasellar meningiomas originating from the floor of sella turcica have been reported . it is important to differentiate a diaphragm sellae meningioma from a pituitary macroadenoma because they require different surgical approaches . ( 7 ) emphasized that , most of the intra- and suprasellar macroadenomas could be approached by the transsphenoidal route , while diaphragma sellae meningiomas might require a craniotomy . for diaphragma sellae meningiomas , the transcranial - transsphenoidal approach is preferred for a type c meningioma and the cranio - orbital approach for type a and type b meningiomas ( 6 ) . on the other hand , the transsphenoidal approach is advocated for all subdiaphragmatic meningiomas ( 8) , or should be tried first , irrespective of whether the lesion is a meningioma or a pituitary adenoma ; even if it has a small suprasellar extension ( 2 ) . according to cappabianca et al . ( 7 ) , it is essential for the diagnosis of type c meningiomas that the diaphragma sellae be displaced upwards with the normal pituitary gland visible below . our case also showed upward bulging of the complex of the diaphragma sellae and pituitary gland , with the meningioma located below the pituitary gland with a broad - based attachment to the sellar floor . the pituitary gland is reported to be covered by two distinct structures ; a capsule and the dura in the pituitary fossa ( 3 ) . at each inferolateral edge of the pituitary fossa , the thick dura of the inferior wall splits into two thinner layers that form a y shape . one of the arms of the y forming the lateral wall of the pituitary fossa is directed superiorly , while the other arm continues as the sphenoidal part of the medial wall of the cavernous sinus and extends to the lateral limit of the sinus ( 3 ) . it is difficult to differentiate intrasellar meningiomas from intrasellar tumors , which can include pituitary adenoma , pituicytomas , intrasellar germinomas , craniopharyngiomas , aneurysms , and metastases . calcifications are a feature of intrasellar meningiomas , craniopharyngiomas , and aneurysms , but they are not typical features of adenomas . necrotic or cystic changes can be found in most types of intrasellar tumors except for meningiomas . meanwhile , imaging findings on the angioarchitecture of aneurysms allow them to be differentiated from other tumorous lesions . the intrasellar mass in our case was treated by the transsphenoidal approach because our preoperative diagnosis was a pituitary adenoma . during the operation , the lower part of the intrasellar mass was found to be subglandular meningioma following a frozen biopsy , which was successfully removed , while leaving intact normal pituitary gland in the upper part of the intrasellar mass . in conclusion , they probably originate from the dura in the sellar floor , while most intrasellar meningiomas that are located in the subdiaphragmatic and supraglandular area originate from the diaphragma sellae . we report a case of intrasellar and subglandular meningioma along with a review of the literature .

most intrasellar meningiomas are located in the subdiaphragmatic and supraglandular region because they originate from the diaphragma sellae . subglandular meningiomas located under the pituitary gland are extremely rare . intrasellar meningiomas in the subdiaphragmatic and subglandular region probably originate from the dura in the sellar floor . we report a case of a subglandular meningioma along with a review of the literature .

histologically , there is an increase in collagen fibers as well as hyaline degeneration within the lamina propria [ 13 ] . the pathogenesis of myringosclerosis is complex and can not be explained by any single factor , but associated factors include otitis media with effusion treated with myringotomy and tympanostomy tubes [ 5 , 6 ] . myringosclerosis caused by insertion of the tympanostomy tubes is not known to affect the hearing threshold . myringosclerosis is considered a healed inflammation or a particular form of scar tissue following recurrent otitis media . thus , removing the myringosclerosis over a perforated whole tympanic membrane might influence the grafting success . in japan , simple underlay myringoplasty with fibrin glue is a well - established procedure because of its high success rate and low risk of sensorineural hearing loss [ 911 ] . the aim of our study is to demonstrate the surgical management of myringosclerosis over a perforated whole tympanic membrane using simple underlay myringoplasty . we present our operative procedure of simple underlay myringoplasty with myringosclerosis ( figure 1(a ) ) over the whole tympanic membrane under general anesthesia . the indications for surgery include hearing improvement after closure of the perforation by paper patch , dry ear at operation , and wide / straight external ear canal . first , the edge of the perforation is removed with a fine pick through an ear speculum to create a vascular bed ( figure 1(b ) ) . secondly , myringosclerotic deposits at the edge of the perforation are removed from the lamina propria , while preserving the epidermis and the mucosal layer as much as possible ( figure 1(c ) ) . it is impossible to remove the myringosclerotic deposits all at once from the lamina propria at the edge of the perforation . the myringosclerotic deposits are removed from the lamina propria on all sides of the perforation stepwise with a fine pick , straight microforceps , curved right microforceps , curved left microforceps , and microscissors . although myringosclerosis still remains in the anterior superior and posterior superior quadrants , no myringosclerosis is observed at the edge of the perforation . finally , fascia obtained from the retroauricular region is fixed as an underlay with a few drops of fibrin glue ( figure 1(d ) ) . an endoscope is employed for patients in whom the margin of the perforation of the tympanic membrane is invisible with the operating microscope due to a curved external auditory canal . a portion of the remaining fascia is kept in a deep freezer to be used for repairing any perforation in the postoperative course . the main points of the surgical technique are presented again with schematic drawings . at the edge of the perforation , the epidermis not only covers the edge , but also extends beneath the tympanic membrane . after removal of the epidermis which extends to the mucous layer , the myringosclerotic deposits are removed from the lamina propria , while preserving the epidermis and the mucous layer as much as possible . after several months , the tympanic membrane is intact despite the remaining myringosclerosis in the anterior superior and posterior quadrants ( figure 1(e ) ) . closure of the perforation was successful in 10 ( 91% ) of the 11 patients . failure of the graft occurred in one patient who underwent a revision procedure using her stored fascia in the outpatient clinic with a successful outcome . the air conduction hearing level postoperatively was significantly improved as compared with that of preoperative level ( figure 2 ) . the air - bone gap was also significantly ( one - way anova ) reduced after surgery ( figure 3 ) . hearing gain after operation was 12.4 8.7 db ( mean standard deviation ) . all patients gave their written informed consent , and the study was approved by the ethics committee of juntendo university faculty of medicine . myringosclerosis is the term used to describe hyalinization and calcification of the connective tissue layer in the lamina propria of the tympanic membrane . an increased oxygen concentration in the atmosphere of the ear is associated with the increased development of myringosclerosis in a traumatized tympanic membrane , and administration of oxygen free radical scavengers reduces the occurrence of myringosclerosis in rat . myringosclerosis over the whole tympanic membrane may severely impair mobility of the tympanic membrane and induce a mild to moderate hearing loss . the present study describes the surgical management of myringosclerosis over a whole perforated tympanic membrane using simple underlay myringoplasty . a previous study showed no significant difference in the success rate of myringoplasty between the myringosclerotic and the nonmyringosclerotic groups . on the other hand , appropriate freshening of the perforation edges , with removal of sclerotic plaque , results in a high rate of successful closure of a perforated tympanic membrane with coexisting myringosclerosis . since both blood vessels and myringosclerosis are situated in the lamina propria of the tympanic membrane , blood supply to the graft may be blocked when myringosclerosis exists over a perforated tympanic membrane . when myringosclerosis is situated at the edge of a perforation , this induces tears in the residual tympanic membrane and a large perforation , which is technically more difficult to close if the myringosclerosis is removed together with epidermal and mucous layers . our surgical technique , which preserves the epidermal layer and mucous layer as much as possible , does not create a larger perforation . in japan , simple underlay myringoplasty with fibrin glue is a routine procedure with good results [ 911 ] . therefore , removal of myringosclerosis at the edge of the perforation might be a beneficial technique for simple underlay myringoplasty in terms of the success rate and postoperative hearing threshold , especially when myringosclerosis extends over the entire tympanic membrane . however , there are no data to confirm that it improves either graft success or improves hearing thresholds because of no control group with myringosclerosis treated with underlaying technique without removal of plaque , with which they could have compared the results . in conclusion , despite the small number of cases and having no control group , removal of myringosclerosis at the edge of a perforation is expected to improve graft success and a better - looking graft for simple underlay myringoplasty , especially when myringosclerosis extends over the entire tympanic membrane .

the aim of our study is to demonstrate the surgical management of myringosclerosis over a perforated whole tympanic membrane using simple underlay myringoplasty . simple underlay myringoplasty with fibrin glue was performed in 11 ears with myringosclerosis over the entire tympanic membrane . the patients were one male and ten females and their mean age was 61.8 years ( range , 4073 yr ) . surgical success was defined as an intact tympanic membrane 12 months after surgery . closure of the perforation was successful in 10 ( 91% ) of the 11 patients . failure of the graft occurred in one patient who then underwent a revision procedure using her stored fascia in the outpatient clinic with a successful outcome . the overall success rate was 100% . although this study included a small number of cases , removal of myringosclerosis at the edge of a perforation is a beneficial technique for simple underlay myringoplasty in terms of the success rate and postoperative hearing threshold , especially when myringosclerosis extends over the entire tympanic membrane .

the au nanowires were fabricated by electrodeposition into nanoporous alumina templates in a three - electrode set up 30 . a thick cu layer ( ~ 2 m ) sputtered at the back of the template served as the working electrode , ag / agcl served as a reference electrode , and a pt mesh served as counter electrode . a dc voltage of 1v with reference to the ag / agcl was applied on the working electrode to reduce au ions in the solution into au metal inside the nanopores of the template . the size of the nanopores defined the diameter of the nanowires , whereas the length of the nanowires was controlled by the amount of total electrical charge passing through the circuit . after the electrodeposition , the nanowires were released in a 2 m naoh solution followed by two cycles of sonication and centrifugation in ethanol and deionized ( di ) water . the nanowires were then dispersed and re - suspended in solutions such as di water . the suspended au nanowires were conjugated with tnf protein ( invitrogen ) by hydrophobic interaction . first , the au nanowire surface was functionalized and made hydrophobic by incubation in 5 mm 1-dodecanethiol ( 98% , alfa aesar inc . ) after centrifugation and resuspension twice in ethanol , once in di water , and once in phosphate buffered saline ( pbs ) , the nanowires were incubated in 10ng / ml tnf in pbs solution for 34 hours at 4c . the excess tnf on the nanowires and in solution was washed away by the pbs solution . protein adsorption was measured using nanowires prepared in a similar fashion , but incubated in a solution of tnf labeled with rhodamine ( labeling kit from thermo fisher scientific ) . detailed procedures for device fabrication and operation for manipulating nanowires can be found in our previous work 10 . in brief , the microelectrodes used to manipulate nanowires were fabricated by standard photolithography . a thin chromium ( cr ) layer ( typically 20 nanometers thick ) was first deposited on a glass substrate as the adhesion layer , followed by the deposition of a gold ( au ) layer of 120 nanometers . s1813 photoresist was used to transfer the electrode patterns onto a transparent mask ( cad / art services , inc . ) after the development of the photoresist , the cr / au layers were etched by their respective chemical etchants . electric voltages were applied to these microelectrodes through custom designed circuits , which controlled the duration and sequence of the applied electric fields . a slab of polydimethylsiloxane ( sylgard 184 , corning ) with ~5 mm holes was placed over the glass to form a well to enable cell culture in the nanowire manipulating area . finally , the area was coated with 10g / ml of fibronectin ( sigma ) for cell adhesion . we simulated nf-b activation dynamics using the consensus version of our computational model of the tnf - nf-b signaling pathway 22 . the backbone of this version is our original model of the pathway 21 augmented with ib- and ib-mediated negative feedback 31 and a coarse - grained description of tnf - induced ikk activation 14 . consensus model is capable of recapitulating a wide variety of nf-b dynamics in wildtype cells and cells deficient in one or more ib isoforms in response to various durations of tnf stimulation 14 , 21 , 31 , 32 . as a control , we simulated nf-b dynamics in response to a step input of 10ng / ml tnf . to simulate stimulation by tnf - coated nanowires , we considered tnf inputs of the form c(t ) = u(t ) cos [ 1 exp(t / tos ) ] ( supplementary fig . 2 ) or c(t ) = u(t ) cos exp(t / tos ) ( fig . 4a , 4b ) , where u(t ) is the unit step function , the variable cos respectively reflects the limiting or initial concentration , and tos reflects the rate of desorption 14 . matlab r2006a ( mathworks ) code is available upon request . to quantitatively compare simulations and experiment , as shown in fig . 4a and 4b , we determined the scaling factor to convert the experimental unit for nf-b activity ( normalized intensity , fig . the scaling factor value of 0.73m gave the best least squares fit between the simulated and experimentally measured nf-b response to a step input of 10ng / ml tnf ( orange curve and red squares , respectively , in fig . next , we scaled the nf-b response to tnf - coated nanowire as measured in a transfected hela cell into the simulated units ( magenta circles in fig . finally , by varying the values of cos and tos in a grid - like fashion , we determined that the values of cos = 0.25 ng / ml and tos = 2.00 hrs gave the global best fit in the least squares sense to the experimental time - course . additional methods ( calculation of stokes diameter , tnf desportion kinetics , cell culture , immunocytochemistry , microscopy , and image analysis ) can be found in the supplementary information . the au nanowires were fabricated by electrodeposition into nanoporous alumina templates in a three - electrode set up 30 . a thick cu layer ( ~ 2 m ) sputtered at the back of the template served as the working electrode , ag / agcl served as a reference electrode , and a pt mesh served as counter electrode . a dc voltage of 1v with reference to the ag / agcl was applied on the working electrode to reduce au ions in the solution into au metal inside the nanopores of the template . the size of the nanopores defined the diameter of the nanowires , whereas the length of the nanowires was controlled by the amount of total electrical charge passing through the circuit . after the electrodeposition , the nanowires were released in a 2 m naoh solution followed by two cycles of sonication and centrifugation in ethanol and deionized ( di ) water . the nanowires were then dispersed and re - suspended in solutions such as di water . the suspended au nanowires were conjugated with tnf protein ( invitrogen ) by hydrophobic interaction . first , the au nanowire surface was functionalized and made hydrophobic by incubation in 5 mm 1-dodecanethiol ( 98% , alfa aesar inc . ) after centrifugation and resuspension twice in ethanol , once in di water , and once in phosphate buffered saline ( pbs ) , the nanowires were incubated in 10ng / ml tnf in pbs solution for 34 hours at 4c . the excess tnf on the nanowires and in solution was washed away by the pbs solution . protein adsorption was measured using nanowires prepared in a similar fashion , but incubated in a solution of tnf labeled with rhodamine ( labeling kit from thermo fisher scientific ) . detailed procedures for device fabrication and operation for manipulating nanowires can be found in our previous work 10 . in brief , the microelectrodes used to manipulate nanowires were fabricated by standard photolithography . a thin chromium ( cr ) layer ( typically 20 nanometers thick ) was first deposited on a glass substrate as the adhesion layer , followed by the deposition of a gold ( au ) layer of 120 nanometers . s1813 photoresist was used to transfer the electrode patterns onto a transparent mask ( cad / art services , inc . ) electric voltages were applied to these microelectrodes through custom designed circuits , which controlled the duration and sequence of the applied electric fields . a slab of polydimethylsiloxane ( sylgard 184 , corning ) with ~5 mm holes was placed over the glass to form a well to enable cell culture in the nanowire manipulating area . finally , the area was coated with 10g / ml of fibronectin ( sigma ) for cell adhesion . we simulated nf-b activation dynamics using the consensus version of our computational model of the tnf - nf-b signaling pathway 22 . the backbone of this version is our original model of the pathway 21 augmented with ib- and ib-mediated negative feedback 31 and a coarse - grained description of tnf - induced ikk activation 14 . consensus model is capable of recapitulating a wide variety of nf-b dynamics in wildtype cells and cells deficient in one or more ib isoforms in response to various durations of tnf stimulation 14 , 21 , 31 , 32 . as a control , we simulated nf-b dynamics in response to a step input of 10ng / ml tnf . to simulate stimulation by tnf - coated nanowires , we considered tnf inputs of the form c(t ) = u(t ) cos [ 1 exp(t / tos ) ] ( supplementary fig . 2 ) or c(t ) = u(t ) cos exp(t / tos ) ( fig . 4a , 4b ) , where u(t ) is the unit step function , the variable cos respectively reflects the limiting or initial concentration , and tos reflects the rate of desorption 14 . matlab r2006a ( mathworks ) code is available upon request . to quantitatively compare simulations and experiment , as shown in fig . 4a and 4b , we determined the scaling factor to convert the experimental unit for nf-b activity ( normalized intensity , fig . the scaling factor value of 0.73m gave the best least squares fit between the simulated and experimentally measured nf-b response to a step input of 10ng / ml tnf ( orange curve and red squares , respectively , in fig . next , we scaled the nf-b response to tnf - coated nanowire as measured in a transfected hela cell into the simulated units ( magenta circles in fig . finally , by varying the values of cos and tos in a grid - like fashion , we determined that the values of cos = 0.25 ng / ml and tos = 2.00 hrs gave the global best fit in the least squares sense to the experimental time - course . additional methods ( calculation of stokes diameter , tnf desportion kinetics , cell culture , immunocytochemistry , microscopy , and image analysis ) can be found in the supplementary information .

precise delivery of molecular doses of biologically active chemicals to a pre - specified single cell among many , or a specific sub - cellular location , is still a largely unmet challenge hampering our understanding of cell biology . overcoming this could allow unprecedented levels of cell manipulation and targeted intervention . here , we show that gold nanowires conjugated with cytokine , such as tumour necrosis factor - alpha ( tnf ) , can be transported along any prescribed trajectory or orientation using electrophoretic and dielectrophoretic forces to a specific location with subcellular resolution . the nanowire , 6 m long and 300 nm in diameter , delivered the cytokine and activated canonical nuclear factor - kappab signaling in a single cell . combined computational modeling and experimentation indicated that cell stimulation was highly localized to the nanowire vicinity . this targeted delivery method has profound implications for controlling signaling events on the single cell level .

the eye has a special relationship with the immune system , known as immune privilege . the term was coined in the 1940s by sir peter medawar , who noticed that foreign tissue grafts placed in the anterior chamber ( ac ) of the eye were not rejected . while the concept of immune privilege is simple , research into its nature has revealed its highly complex character , which is still incompletely understood ( reviewed in ) . multiple mechanisms combine to maintain immune privilege : ( a ) physical barriers ( efficient blood - retina barrier and lack of efferent lymphatics ) prevent free entry and exit of cells , and even larger molecules , into and out of the eye . the integrity of the blood - retinal barrier is routinely measured in the clinic by the fluorescein test and provides a widely accepted measure of ocular health nevertheless , the concept of sequestration of the eye from the immune system has recently been debated , mostly on the basis of the phenomenon known as anterior chamber - associated immune deviation ( acaid ) . ( b ) the inhibitory ocular microenvironment , composed of cell - bound and soluble immunosuppressive factors within the eye , inhibits the activity of immune - competent cells . the soluble factors include transforming growth factor - beta ( tgf- ) ( which can also be membrane - bound ) , neuropeptides such as alpha - melanocyte - stimulating hormone ( -msh ) , vasoactive intestinal peptide , and others . ocular resident cells directly inhibit immune cells ( at least in culture ) by secreting soluble factors and by contact - dependent mechanisms . retinal glial mller cells were the first to be identified , but their inhibitory surface molecules were not characterized . the pigmented epithelia of the retina ( rpe ) and the iris / ciliary body ( ipe ) not only inhibit t cells , but also induce them to become t regulatory ( treg ) cells . surface - bound molecules involved in these processes include cd86 [ which engages cytotoxic t lymphocyte antigen 4 ( ctla-4 ) on t cells ] , fasl , thrombospondin , and galectins . the classic example is acaid , a unique and highly orchestrated immune response to antigens injected into the ac . it involves migration from the eye to the spleen of f4/80 antigen - presenting cells that interact with invariant natural killer t cells and b cells and culminates in elicitation of systemic regulatory immunity through induction of cd4 afferent and cd8 efferent treg cells ( reviewed in ) . proteins and even cells or cellular fragments were shown to pass from the ac directly into the blood through a highly porous structure known as the trabecular meshwork . while some regard this as negating the concept of ocular antigen sequestration , elicitation of acaid requires puncturing of the eye with a needle and perturbation of ocular integrity . it is therefore likely that acaid is more representative of a response to trauma rather than of a mechanism of tolerance to tissue - specific antigens contained in the healthy eye . a less controversial example is post - recovery tolerance , in which spleen cells from mice that have recovered from experimental autoimmune uveitis ( eau ) contain regulatory activity , whose generation is dependent on the presence of eye [ 7 - 9 ] . this type of tolerance was shown to involve the melanocortin pathway and can not be induced in melanocortin-5 receptor knockout mouse , but whether it is -msh from the eye that is involved has not been determined . corneal allografts are up to 90% successful without tissue matching and without systemic immunosuppressive therapy . on the downside , however , ocular immune privilege may leave the eye vulnerable to autoimmunity by impeding peripheral tolerance to eye - specific antigens sequestered behind the blood - retinal barrier . while some effects of neuropeptides that help maintain the immunoinhibitory ocular microenvironment may be exerted directly on lymphoid cells , neuropeptides may also regulate production of tgf- within the eye . a recent study demonstrated that immune privilege of the eye , as evaluated by rejection of allogeneic tumor cells , development of acaid , and maintenance of high tgf- levels in aqueous humor , was lost following removal of functional sympathetic fibers . thus , although some neuropeptides in ocular fluids might be produced by ocular cells themselves , sympathetic innervation of the eye is critical for maintenance of the above - mentioned manifestations of immune privilege . this could stem from the observed effects on tgf- as there is no evidence from previous studies for direct effects of neuropeptides on acaid and related phenomena . recent studies addressing local regulation by pigmented ocular epithelia identified previously unrecognized molecular pathways by which they mediate t - cell suppression and their conversion to treg cells . ligands for the t - cell inhibitory receptor programmed death-1 ( pd-1 ) were detected on human as well as mouse rpe cells . both the human arpe-19 line and primary human rpe express both pd - l1 and pd - l2 , and expression on primary human rpe was enhanced by interferon - gamma ( ifn- ) . in murine rpe , pd - l1 was below detection in primary cells but was induced by ifn-. pd - l1 expression was functionally relevant and negatively regulated cytokine production by t cells . this could be reversed by blocking antibodies to pd - l1 or by pd-1 deficiency . rpe cells also were found to constitutively produce ctla-2 , a cathepsin l ( cathl ) inhibitor . cd4 t cells exposed to ctla-2-expressing rpe cells or to recombinant ctla-2 converted to cd25foxp3 treg cells . importantly , this pathway was functional also in vivo and provided protection from autoimmune uveitis in the mouse eau model , as demonstrated using anti - ctla-2 antibodies and ctla-2-deficient mice . ctla-2 directly lowers cathl activity in t cells and also promotes activation of tgf- by facilitating treg conversion . thus , pd-1 pathway may function in suppression of the th1 responses and ctla-2 may additionally convert t cells that slipped through the pd-1 pathway into treg cells . in contrast , the t cell inhibitory activity of human ipe was shown to be driven by a contact - mediated tgf--dependent mechanism that could be reversed by tgf2-sirna ( short interfering rna ) or anti - tgf- antibodies . the elaborate and highly redundant nature of mechanisms comprising ocular immune privilege seems undisputed . if things are so good , then why are they so bad ? it seems unreasonable that in the face of immune privilege and in the absence of physical trauma , the eye remains vulnerable to autoimmune uveitis in both its clinical and experimental forms . as amply demonstrated by experimental models of induced uveitis , privilege is easily broken by even small numbers of activated t - effector cells that have been primed in the periphery or adoptively transferred . why are they not inactivated or converted to treg cells by the ocular microenvironment but allowed to induce destructive inflammation ? furthermore , spontaneous uveitis develops when there is increased frequency of retina - specific t cells , such as in mice lacking the transcription factor aire ( autoimmune regulator ) which do not delete retina - specific cells in the thymus or in mice expressing a foreign protein in the retina and having t cells that carry the specific t - cell receptor . if retinal antigens are indeed sequestered , where are the t cells being primed ? and if they are not sequestered , why has privilege not resulted in systemic tolerance ? it would seem that the concept of immune privilege needs to be further studied , refined , and perhaps revised .

the eye attempts to limit local immune and inflammatory responses to preserve vision . this phenomenon , known as ocular immune privilege , is mediated by a combination of local and systemic mechanisms . while immune privilege is believed to protect the eye from day - to - day inflammatory insults , it is not absolute and its mechanisms are still incompletely understood .

a 19-year - old male presented to our medical clinic in mid-2009 with complaints of acne , hair loss , and difficulty in getting up from sitting position with evidence of proximal muscle weakness . he had been recently diagnosed with dermatomyositis based on his clinical features of elevated creatine kinase levels , typical skin changes , and electromyography ( emg ) pattern consistent with dermatomyositis . his medications at the time included prednisone , methotrexate , folate , and vitamin d. he was sexually active with both male and female partners with inconsistent use of condoms . subsequently , he had multiple clinic visits between 2010 and 2011 for complaints of sore throat , fever , chills , anal pain , anal itching , and anal discharge . during this time , he was treated for oral candidiasis , scabies infestation , syphilis , and condyloma acuminata . he refused hiv testing , claiming that he was tested negative elsewhere . in early 2012 , he consented for hiv testing . hiv elisa and western blot were positive , with a cd4 + cell count of 182 cells/l and hiv rna copies of 1,337,310 copies / ml on diagnosis . after initiation of haart his cd4 + count gradually increased to 346 cells/l and hiv-1 rna copies decreased to 462 copies / ml within 2 months . at this time , he started having frequent flares of dermatomyositis . his dermatomyositis had been fairly well controlled on prednisone and methotrexate before initiation of haart . he was switched to a combination of prednisone and azathioprine , then with mycophenolate mofetil , all with poor response . in june 2013 , he was started on monthly intravenous immunoglobulins ( ivig ) , to which he initially had a fair response but ultimately required reintroduction of methotrexate and increased doses of prednisone to control the dermatomyositis flares . despite this regimen , he had another dermatomyositis flare in 2014 . in mid-2015 , he presented to the emergency department with complains of diffuse muscle pain , chest pain , and shortness of breath on exertion . his active medications were prednisone 60 mg daily , methotrexate 40 mg once a week , ivig once a month , and atripla . on physical examination , he had mild heliotrope rash on eyes , chest wall tenderness , neck , and proximal muscle weakness on both upper and lower limbs . critical laboratory findings included creatine kinase of 1,145 iu / l , aspartate transaminase of 400 iu / l , and alanine transaminase of 220 iu / l . because of the refractoriness of therapy , a muscle biopsy was done which confirmed the clinical diagnosis of dermatomyositis ( fig . he was treated with intravenous methylprednisolone at stress doses with prompt improvement in overall muscle strength . he continues to take haart and follows up in infectious disease clinic . at the time of this report , the patient 's latest helper cd4 counts was 320 cells / mcl and hiv-1 ultrasensitive rna < 20 copies / ml 02/8/2016 . ( a ) muscle biopsy showing small fibers in the perifascicular portion of the biopsy ( right side ) with normal sized fibers in the central portion of the fascicle ( left side ) . ( b ) a distorted frozen section shows small round mononuclear inflammatory cells in the upper right quadrant of the picture . it then infects the cd4 + t cells leading to their apoptosis and thus uncoupling of cd8 + t cells ( ctls ) activation through the type 1 t helper cells ( th1 ) pathway ( 11 ) . it infects ctls directly as well and alters the function of the memory and effector ctls , which is a critical blow to the antiviral defense mechanism of the body . despite this , the host is usually able to mount a seemingly effective immune response to hiv infection as is seen with the clearance of viremia and partial recovery of the cd4 t cell numbers . however , hiv is not completely eradicated as its reservoir has already been established in the monocyte / macrophage cell lines ( 11 ) . as viral replication occurs at this stage , cd4 counts begin to drop again and there is an inversion of the cd4:cd8 ratio . the differentiation of the remaining cd4 cells is persistently moved from the strong antiviral th1 arm to the b - cell activating th2 arm ( 11 ) . in addition , there exists the homology between some hiv-1 epitopes and some regions on t and b lymphocytes which may induce molecular mimicry . as a result of this mimicry , hiv also targets the regulatory t cells ( treg ) that are critical in peripheral tolerance of naive t cells and prevent autoimmunity . b cell activation through the th2 pathway and dysfunction of treg provides the perfect milieu for the development of autoimmune diseases . this could be the reason why th1 response - mediated autoimmune diseases such as rheumatoid arthritis are seen infrequently and undergo remission / stabilization in hiv infection , while immune complex - mediated illnesses such as vasculitis and cd8 cell - mediated illnesses such as diffuse infiltrative lymphocytic syndrome or reactive arthritis are seen much more frequently in hiv patients ( 13 ) . with progression of hiv infection , both cd4 and cd8 numbers drop and there is profound immunodeficiency that would preclude emergence of any autoimmune diseases . ultimately , with restoration of immunity from haart , a resurgence of autoimmune diseases is seen in the subsequent period . the different stages of autoimmune diseases as a function of natural history of hiv infection has been proposed by zandman - goddard and shoenfeld , as in table 1 ( 12 ) . this is followed by complement activation and formation of membrane attack complex ( mac ) . mac mediated injury to endothelium , leads to downstream muscle ischemia and micronecrosis that appears as microinfarcts and inflammation on muscle biopsy . complement deposition on endothelium also leads to cytokine release and recruitment of macrophages , b and t lymphocytes from the blood into the perimysial spaces . hiv patients have all the above mechanisms at play potentially providing the milieu for development of dermatomyositis . hiv patients have been shown to have autoantibodies which have special predilection toward vascular endothelial components of endomysial blood vessels and capillaries ( 14 ) . products of complement activation have been detected in the plasma of adult hiv patients , suggesting the presence of chronic low - grade complement activation . hiv can also have direct cytotoxic effect on the endothelial wall , which through molecular mimicry could lead potentiate formation of autoantibodies . although our patient 's hiv diagnosis was confirmed 3 years after the clinical diagnosis of dermatomyositis , he had sexual risk factors and multiple opportunistic and syphilis infection during this time , which suggests that he likely was already infected with hiv before his dermatomyositis symptoms manifested . if indeed our patient tested negative for hiv as he claimed in 2009 , it is not far - fetched to wonder if he developed dermatomyositis during the seroconversion phase of his hiv illness . haart leads to immune reconstitution in hiv and has changed hiv from a rapidly fatal illness to a chronic medical condition . at the same time , immune reconstitution may produce emergence and flare of new autoimmune phenomenon in these patients with hiv . the autoimmune conditions in hiv patients on haart are often refractory to treatment and management is fraught with multiple relapses as seen in our patient . however , there exists a risk of opportunistic infection at these doses of steroids , more so in patients with hiv and low cd4 counts . as a precaution , we started our patient on pneumocystis jiroveci pneumonia ( pjp ) prophylaxis despite his cd4 counts being > 200 cells / mcl ( 260 cells / mcl on 05/21/15 ) . because our patient was refractory to steroids and immunosuppressants , he was advised to follow up for rituximab therapy . physicians should be aware of the possibility of an underlying hiv infection precipitating an autoimmune phenomenon such as dermatomyositis , especially in patient with risk factors for hiv . treatment remains a huge challenge , as immune reconstitution can potentially worsen the course of autoimmune phenomenon . m.c . : conception and design , analysis and interpretation of literature , involved in drafting the manuscript and revising it critically for important intellectual content . also gave the final approval of the version to be published . : conception and design , analysis and interpretation of iterature , involved in drafting the manuscript and revising it critically for important intellectual content . also gave the final approval of the version to be published . : analysis and interpretation of literature , involved in drafting the manuscript and revising it critically for important intellectual content . also gave the final approval of the version to be published . : conception and design , involved in drafting the manuscript and revising it critically for important intellectual content . also gave the final approval of the version to be published . : conception and design , involved in drafting the manuscript and revising it critically for important intellectual content . conception and design , involved in drafting the manuscript and revising it critically for important intellectual content . also gave the final approval of the version to be published . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

hiv has been linked to several autoimmune disorders since its emergence in the 1980s . by affecting different cells and pathways in the immune system , hiv induces the development of certain autoimmune diseases while prohibiting the emergence of others . dermatomyositis has been rarely described in patients with hiv . we present a case of dermatomyositis in a patient with hiv and explore the pathogenesis of autoimmune disorders in hiv focusing on dermatomyositis .

a 52-year - old male was admitted to medical ward for the management of a severe headache and raised blood pressure . subsequently , he suffered a seizure and developed an irrelevant speech for which a psychiatric consultation was sought . history revealed alcohol consumption from the age of 22 years . by the age of 45 years , he had features of alcohol dependence in the form of craving , tolerance , loss of control , withdrawal discomfort , the primacy of alcohol use , and sociooccupational deterioration . he consumed around 750 ml of rum daily . before 2 days admission , he abruptly stopped drinking after repeated pleading by family members . he had been detected to have hypertension in 2007 and diabetes mellitus ( type ii ) along with dyslipidemia in 2008 . he is educated up to 9 class and has been employed for last 26 years . he had tachycardia , raised blood pressure , bilateral coarse digital tremors , and diaphoresis . he was disoriented and had vivid visual and auditory hallucinations along with secondary delusions of persecution . a diagnosis of alcohol dependence syndrome ( complicated withdrawal with seizures and delirium ) was made , and the patient was treated with chlordiazepoxide in tapering doses , thiamine supplementation and parenteral haloperidol for behavioral control . his response to treatment was tardy and though his orientation improved he had difficulty in comprehending instructions even a week later . mini- mental state examination ( mmse ) score improved from 12 at admission to 26 . however , he remained dull and was unable to participate in routine neurocognitive evaluation even a fortnight after admission . laboratory investigations alcohol withdrawal scale and mini - mental state examination scores contrast enhanced magnetic resonance imaging ( mri ) brain done then , revealed a nonenhancing area of altered signal intensity in central pons suggestive of cpm [ figure 1 ] . brain spect showed hypoperfusion of frontal lobes ( l > r ) but yielded no further information about the pons [ figure 2 ] . electroencephalogram showed no abnormality . by the 3 week , cognitive functions started improving , and he was co - operative . evaluation of lifetime drinking history yielded total alcohol consumption of 496.61 kg over 30 years , with an average drinking day consumption of 80.35 g / day . repeated after 8 weeks brain , spect showed improvement in frontal lobe perfusion [ figure 3 ] . detailed neuropsychological evaluation done at 2 , 6 , and 10 weeks of admission is depicted in table 3 . even though there was relative improvement in scores on neuropsychological evaluation in the 6 and 10 week , cognitive deficits remained . contrast enhanced magnetic resonance imaging of brain ill - defined area of altered signal intensity in central pons ( 7.0 mm 6.7 mm 8.1 mm ) . ( c ) on magnetic resonance imaging diffusion there is true restriction of diffusion on diffusion weighted imaging and apparent diffusion coefficient map initial brain single photon emission computed tomography hypoperfusion in frontal lobes ( left hypoperfusion [ 15.96% ] > right hypoperfusion [ 20.87% ] ) repeat brain single photon emission computed tomography ( 8 weeks later ) . perfusion in frontal lobes ( left [ 17.91% ] , right [ 22.24% ] ) is better than in previous scan neuropsychological evaluation various mechanisms have been proposed for the development of osmotic demyelination following chronic alcohol use . oligodendroglia are particularly susceptible to dehydration and volume changes due to their physically tight alignment in the basis pontis . during rapid correction of hyponatremia , intracellular electrolyte corrections are swift , but the brain is unable to correct the loss of organic osmolytes quickly enough , resulting in cellular dehydration , damage to the myelin sheath , and oligodendrocyte degeneration . the process of maintaining an iso - osmolar environment with respect to the serum is energy consuming . if the patient is malnourished , as is typically the case in alcohol dependence , the cells may lack sufficient energy reserve to maintain the na / k atpase pump activity and to synthesize organic osmoles . alcohol - associated thiamine deficiency may exacerbate the problem because it decreases brain glucose uptake . this energy supply demand imbalance results in a pro - apoptotic drive . in this patient , no hyponatremia was detected , though he had been initially treated with intravenous ringer 's lactate in the medical ward for dehydration . after a protracted alcohol withdrawal , he manifested significant impairment in all cognitive domains which improved partially and gradually thereafter . nicols et al . found that two - thirds of patients of active chronic alcoholism exhibited frontal lobe impairment demonstrated by neuropsychological testing and spect , independent of brain atrophy . reported that decreased blood flow in the inferior frontal gyrus assessed by spect was associated with executive function deficits which were related to relapse in detoxified alcohol - dependent individuals . they should be investigated using neuroimaging and caution should be exercised while correcting their fluid and electrolyte imbalances .

osmotic demyelination syndrome includes central pontine myelinolysis and extrapontine myelinolysis . this condition has been described in cases of chronic alcohol dependence syndrome and in rapid correction of hyponatremia . though we frequently see patients with alcohol dependence syndrome presenting with complicated withdrawal , central pontine myelinolysis remains largely undetected and under - reported in literature . we present here a case of protracted delirium tremens where mri brain revealed central pontine myelinolysis . subsequently cognitive assessment revealed significant dysfunction and brain spect showed hypo - perfusion of the frontal lobes . osmotic demyelination syndrome should be suspected in protracted delirium tremens .

the crispr / cas system is one of several defense systems that prokaryotes can use to prevent invasion by foreign genetic elements ( for a more detailed description see recent reviews ) . the function and significance of this system was only recently discovered , and it differs from other known defense systems because it is heritable , can adapt to new invaders and it is sequence specific . the system uses a set of proteins and short rna molecules , termed cas proteins and crrna , respectively . the crrnas are processed from a longer pre - crrna that is encoded in the crispr locus , a peculiar series of short , directly repeated sequences between which are unique spacer sequences ( fig . 1 ) . the latter sequences originate from previous ( and unsuccessful ) invading elements , which were degraded . thus the crispr locus is a memory of previously encountered invaders to which the cell has adapted and is immune . the pre - crrna is encoded in the crispr locus , which consists of repeat ( in black ) and spacer sequences ( colored ) . in some cases the repeat sequences are able to fold into stem loop structures . crispr locus transcription starts from the leader region ( black arrow ) yielding the pre - crrna , which is subsequently processed to generate the crrnas . immune defense proceeds in three stages : ( 1 ) adaptation , ( 2 ) expression and ( 3 ) interference . in the first stage , the nucleic acid of the invading element enters the cell , and is immediately recognized as a foreign element . a piece of the invader dna , termed protospacer , is selected and then integrated into the crispr locus as a new spacer ( fig . 2 ) . note that the sequence is called protospacer as long as it is still part of the invader . selection as a new spacer depends on the presence of a certain neighboring sequence , the protospacer adjacent motif ( pam ) . the invading foreign nucleic acid is recognized by cas proteins and a piece of the invader dna ( termed the protospacer , shown in red ) is selected to be integrated as a new spacer into the crispr locus . a prerequisite to be selected as a new spacer is the presence of the pam sequence ( shown in light blue ) adjacent to the protospacer . in haloferax the pam sequence has to be located upstream of the protospacer sequence ( directly 5 to it ) . this motif is not only important for spacer selection but also for accurately targeting the defense reaction . in the second stage of the defense reaction , the crispr locus is expressed , generating a pre - crrna which is subsequently processed to short crrnas , each of which is specific for a single invader ( fig . 1 ) . together with the cas proteins , this crrna recognizes the invader in the third stage of the defense reaction . the spacer sequence of the crrna base pairs with the invader sequence from which it was derived , rendering the defense sequence specific . the crispr / cas system of haloferax consists of eight cas proteins and three crispr rnas , and phylogenetically they belong to the type i - b group of crispr / cas systems . we could show that all three crispr rnas are constitutively expressed and processed , indicating that although the strain has been in the laboratory for more than 30 y and probably did not encounter any invaders during that time , the defense system has remained active . comparison of the spacer sequences of the three haloferax crispr loci to sequences deposited in the public sequence databases showed only two matches . one spacer matched to the haloferax genome within an annotated open - reading frame ( hvo_0372 ) encoding a protein of unknown function . the 5 part of the spacer was identical to the genomic sequence , but the 3 part showed nine mismatches , which is probably sufficient to prevent autoimmune targeting by the crispr / cas system . the second spacer was similar to an environmental sequence recovered from a salt lake in australia ( lake tyrrell ) and differed at only four positions , distributed along the sequence . the 5 part of the sequence matches perfectly , and in e. coli it has been shown that a perfect match in the 5 sequence ( termed the seed sequence ) is essential for recognition and target degradation . it is likely then , that invading elements containing this sequence would be targeted by the crispr / cas system . the low number of spacer matches to known sequences probably reflects that relatively few haloarchaeal viruses have been isolated and sequenced . another factor is that the ds2 strain was isolated from the dead sea in 1974 . viral populations would have changed in the 40 y since , making it unlikely that the original matching sequences would now be common enough to have been recovered and sequenced . to investigate the haloferax defense system , we developed a plasmid invader system similar to the one described for sulfolobus . the invader plasmid contained a piece of invader dna , and an adjacent motif marking the dna as invader the so - called pam sequence . as invader dna , we chose a spacer sequence included in the haloferax crispr loci , and this was cloned into a haloferax shuttle vector ( fig . the pam sequences used by haloferax ( or by other haloarchaea ) were not known before this study , and it was also unknown if they are located upstream or downstream of the protospacer . so we tested all possible di- and trinucleotide combinations ( pam sequences are generally 25 nucleotides long ) ( fig . in addition , the plasmid contained a marker gene allowing growth without uracil , so only cells carrying the plasmid are able to grow on selective media . if the defense mechanism is active against the plasmid , then it is destroyed ( together with the selection marker ) and such cells can not grow on selective medium , which results in a severe ( about 100-fold ) reduction of transformation efficiency . using this approach six different trinucleotide sequences were identified that were active in triggering the defense response , which is currently the highest number of pams identified for a single crispr repeat group . in addition , we could show that this motif has to be located upstream of the protospacer sequence to activate the defense reaction ( fig . figure 3 . an artificial invader for haloferax . to challenge the haloferax defense system , we generated an artificial invader consisting of a spacer sequence ( from one of the haloferax crispr loci , shown in red ) and an adjacent sequence with all possible two- and three - nucleotide combinations as potential pam sequences ( shown in light blue ) . these were cloned into a haloferax plasmid vector that also carried a selection marker pyre2 ( which makes growth of the pyre2-haloferax recipient strain independent of supplied uracil ) . ( a ) initial experiments were performed with potential pam sequences up- and downstream of the spacer sequence . ( b ) pam localization experiments showed that the pam sequence is only required upstream of the spacer sequence and thus we positioned pam sequences upstream only . while the majority of cells challenged with these six types of invader plasmids were unable to grow without uracil , a low level of background colonies were observed . when examples of these were analyzed , the majority was found to have mutations in , or complete deletions of the cas gene cluster , thereby inactivating the defense system and allowing the cell to maintain the plasmid . to gain more insight into the pam sequences used for adaptation , we searched for other haloarchaea for which recent metagenomic data were available . we used the spacer sequences encoded in the haloquadratum walsbyi crispr loci to look for matches in the databases . eight matches were found and the pam sequences obtained for them were in seven cases ttc , which is identical to one of the six pam sequences we found experimentally for haloferax . walsbyi contains a crispr / cas type i - b system , with crispr repeat sequences that are very similar to those of haloferax ( fig . further comparison with other haloarchaea showed that those that are available in the crispr database ( crispr.u-psud.fr/crispr/ , july 2012 ) and which encode cas proteins all belong to the type i - b crispr / cas group . blast searches with the haloferax repeat sequence show that in 20 of the 32 haloarchaeal genomes currently deposited in the nbci database ( www.ncbi.nlm.nih.gov/sutils/genom_table.cgi , august 2012 ) and in the jgi img database ( http://www.jgi.doe.gov/ ) , the repeat sequence is well conserved , with only one to five mismatches between the repeats from the different haloarchaeal organisms ( fig . 4 ) . have been reported to be connected to the repeat sequence and to the crispr / cas type it is reasonable to expect that these haloarchaeal sequences require the same pam sequence . volcanii chromosomally encoded crispr locus c differs from the other two crispr loci ( p1 and p2 ) by one nucleotide . the repeat sequence of the chromosomally encoded crispr locus ( locus c ) from hfx . volcanii was compared ( blastn ) with the haloarchaeal genomes deposited in the ncbi database ( www.ncbi.nlm.nih.gov/sutils/genom_table.cgi , august 2012 ) and to the jgi img database ( http://www.jgi.doe.gov/ ) . in 20 of the 32 additionally available genomes at least one crispr locus was found where the repeat was conserved , with only one to five mismatches . all of the repeat sequences shown are part of putative crispr loci that contained multiple repeats , and were positively identified as crispr loci by the crispr finder algorithm at ( http://crispr.u-psud.fr/ ) . whether all of these loci represent intact and functional crispr / cas systems is yet to be determined . distant , a cas gene cluster is only found elsewhere in the genome , and is adjacent to another crispr locus with a different repeat sequence . unknown , the genome sequence remains in numerous contigs , and it is not known if a cas gene cluster is nearby to the crispr locus containing this repeat sequence . after the identification of cas gene clusters their proximity to the crispr locus was determined by homology searches ( e.g. , the cas gene finder option at crispr finder ) , followed by manual inspection of the annotated genome sequence . classification of cas gene clusters was done according to makarova et al.cas gene clusters are considered near when they are adjacent to the crispr locus and distant if found elsewhere in the genome ( where they were usually adjacent to another crispr locus with a different repeat sequence ) . sulfurifontis remains in numerous contigs , so the proximity of cas genes to this locus is currently unknown . in our study we analyzed the requirements for the crispr / cas defense reaction and identified six different pam sequences that were able to trigger this reaction . such a high number of permissible pam sequences could be advantageous when defending against related invading elements , as it tolerates individual mutations as well as clonal divergence , making the system more broadly effective . this makes sense because the prokaryotic defense mechanism will remain active against virus mutants that otherwise could avoid immune recognition . in contrast , the few data we collected in silico concerning pam motifs for haloquadratum walsbyi revealed only two pam motifs . since hqr . volcanii have very similar repeat sequences and belong to the same crispr / cas type they might have similar pam requirements . taken together , the evidence suggests that the adaptation step is more restrictive in terms of its pam requirements compared with the interference step . in streptococcus thermophilus ( crispr / cas type ii ) , a similar recognition of several different pam sequences on invader plasmids was observed . the pam requirements of crispr / cas type iii systems have not yet been reported , but it has been shown in staphylococcus epidermidis , that the protospacer adjacent sequence of this system must be different from the repeat sequence located upstream of the spacer in the crispr locus , so ensuring differentiation between self dna ( crispr locus ) and the foreign genetic element . a clearer picture of how this immune reaction operates will be revealed as more data are collected , from all of the known crispr / cas systems .

prokaryotes have developed several strategies to defend themselves against foreign genetic elements . one of those defense mechanisms is the recently identified crispr / cas system , which is used by approximately half of all bacterial and almost all archaeal organisms . the crispr / cas system differs from the other defense strategies because it is adaptive , hereditary and it recognizes the invader by a sequence specific mechanism . to identify the invading foreign nucleic acid , a crrna that matches the invader dna is required , as well as a short sequence motif called protospacer adjacent motif ( pam ) . we recently identified the pam sequences for the halophilic archaeon haloferax volcanii , and found that several motifs were active in triggering the defense reaction . in contrast , selection of protospacers from the invader seems to be based on fewer pam sequences , as evidenced by comparative sequence data . this suggests that the selection of protospacers has stricter requirements than the defense reaction . comparison of crispr - repeat sequences carried by sequenced haloarchaea revealed that in more than half of the species , the repeat sequence is conserved and that they have the same crispr / cas type .

differential diagnoses for the relatively rare nasopharyngeal cysts include tornwaldt s disease , rathke s cleft cyst , intra - adenoid cyst , branchial cysts , and pseudocysts.1 here we report a case in which the presence of nasopharyngeal cysts was indicated as hampering nasal continuous positive airway pressure ( ncpap ) treatment of refractory obstructive sleep apnea syndrome ( osas ) . nasopharyngeal cysts are comparatively rare , and most do not exhibit themselves but are found incidentally . however , various symptoms , such as nasal congestion , apnea , and hearing loss , may be exhibited depending on the developing site due to increasing cyst diameter.1 diagnosis is often difficult and is comprehensively determined by the site of occurrence , characteristics of the cyst surface , and tissue findings . tornwaldt s disease , rathke s cleft cyst , pharyngeal tonsil central fossa cyst , branchial cysts , and pseudocysts are raised as differential diagnosis.2 the frequency of occurrence of nasopharyngeal cysts has not been previously mentioned , but in one report it was observed that this occurs in 1.4%3.3% cases of tornwaldt s disease by autopsy.3 moreover , according pathophysiological findings , nasopharyngeal cysts can be classified as congenital when occurring in the pharyngeal bursa vestigial remnant or rathke s pouch , or as acquired as a result of infection or surgery.4 we recently encountered a case that suggested nasopharyngeal cysts as the cause of treatment - resistant osas . here , we report it including bibliographic considerations . a woman in her 50s was referred to the otorhinolaryngology department , kyorin university , with the chief complaint of nasal congestion and pharyngeal discomfort . her weight and height were 70.0 kg and 153 cm , respectively , with a bmi of 29.9 kg / m . the patient had been experiencing nasal congestion for approximately 20 years , but had opted against seeking treatment . a local internist diagnosed the patient with sas in june 2010 , and initiated ncpap therapy . consequently , the patient experienced exacerbation of her nasal congestion , and chose to visit a local otolaryngologist . a tumor lesion was discovered in the patient s nasopharynx , and the doctor referred her to our department . the initial clinical findings following nasopharyngeal fiberscopy included the presence of an oval tumor with a grooved surface in the nasopharynx , which was not associated with the eustachian orifice ( fig . the results of laboratory blood analyses revealed no evidence of an inflammatory reaction . in order to examine the cause of the hypertension , serum levels of thyroid - stimulating hormone ( tsh ) , free thyroxine , free tri - iodothyronine , epinephrine , norepinephrine , dopamine , aldosterone , and renin were analyzed . cytological results of an aspiration biopsy indicated ciliated columnar epithelial cells with mildly enlarged nuclei . a culture of the cyst contents resulted in the detection of coagulase - negative staphylococci of 1 + , and staphylococcus aureus ( mssa ) of 1 + . noncontrast computed tomography ( ct ) imaging findings included the detection of a partially fluid - filled cystic lesion in the nasopharynx that had its base on the median part . a cystic lesion was detected by magnetic resonance imaging ( mri ) , the contents of which were hypointense and relatively hyperintense on the t1- and t2-weighted images , respectively ( fig . extirpation of the lesion was performed under general anesthesia . because no clear contents of the tumor lesion could be aspirated by centesis , the anterior wall of the tumor was dissected by forceps to allow removal of the contents . after debridement using a ktp laser to control the bleeding , the cyst was totally extirpated . the histopathological findings following hematoxylin eosin ( h&e ) staining included the detection of lymphoid tissue accompanied by expansion of the crypt , as well as inflammatory cell infiltration and follicular hyperplasia ( fig . the expression of cd4 , cd8 , cd20 , bcl-2 , and ckae1ae3 was evaluated using immunohistochemistry , and the results indicated the presence of cd20-positive b cells in the follicles , cd4-positive helper t cells in the interfollicular region , and cytokeratin in the lymphoepithelial symbiosis aspect of the crypt . also , the expression of cd8 and bcl-2 was detected , which indicated continued immune function of the pharyngeal tonsils in an individual over the age of 50 ( fig . 3c , d , e , f , and g ) . nonetheless , the association with the sacculation was unclear . thirty - three months following the operation , the patient s nasal congestion disappeared and she was able to get sound sleep . in addition , the patient s systolic blood pressure improved from 140160 to 120140 mmhg . however , her body weight and bmi increased to 72.3 kg and 30.9 kg / m , respectively . a polysomnography ( psg ) showed an apnea hypopnea index ( ahi ) of 26.6 before the operation . . however , ahi was still 26.4 , and we could not see any improvement . nasopharyngeal cysts are comparatively rare , and most do not exhibit themselves but are found incidentally . however , various symptoms , such as nasal congestion , apnea , and hearing loss , may show up depending on the developing site due to increasing cyst diameter.1 diagnosis is often difficult and comprehensively determined by the occurring site , characteristics of the cyst surface , and tissue findings.2 differential diagnoses for nasopharyngeal cysts include rathke s cleft cysts , pseudocysts , tornwaldt s disease , branchial cysts , intra - adenoid cyst , abscesses , and retention cysts ( table 1).2 a rathke s cleft cyst is a benign growth in the rathke s pouch , which is the opening of the craniopharyngeal duct to the pharynx during the embryonic period . rathke s cleft cyst is usually completely occluded by the second month of embryonic development . in most cases , the site of development is localized to the intrasellar region of the sella turcica , or the intrasellar and suprasellar regions , of which the latter accounts for 70% . further , the development of a rathke s cleft cyst in the suprasellar region is rare . ct findings have shown low attenuation areas in a majority of the cysts and capsular enhancement in nearly half of the cysts . however , calcification of the cysts is rare . mri findings have indicated that two - thirds of the cysts are hyperintensive , while the remaining one - third are hypointensive on the t1-weighted image , whereas about 50% are hyperintensive on t2-weighted images . however , many cases are asymptomatic , and the overall incidence is approximately 0.4%.5 pseudocysts are caused by brain hernias , teratomas , and meningiomas that escape from the persistent craniopharyngeal duct . pseudocysts can be differentiated from other cysts by using diagnostic imaging to confirm the contents . tornwaldt s disease is characterized by the presence of inflammation or an abscess of the embryonic remnant cyst in the area between the front end of the notochord and the nasopharyngeal epithelium between the bilateral anterior vertebral muscles on the posterior median nasopharyngeal wall . according to previous reports , tornwaldt s disease is more prevalent in individuals aged between 20 and 30 years , with overall incidence ranging from 0.2% to 5.0%.3 the lesion is located on the medial aspect of the nasopharynx and has a smooth surface . ct scans of the lesion reveal high attenuation areas because the cyst s contents often include blood and an elevated protein concentration . the lesion is hyperintensive on t1- and t2-weighted mri images , but gd contrast agents show no contrast effect . histopathologically , the lesion is covered with a respiratory epithelium without lymphoid tissue , and ranges in size from 2 to 30 mm in diameter.2 branchial cysts develop from remnants of the second branchial groove and are usually unilateral but occasionally bilateral . the difference between branchial cysts and other nasopharyngeal cysts bailey classified the cysts into four types based on the relative position of the cyst : sternocleidomastoid muscle , internal jugular vein , jugular vein , and the pharynx . among the different classes of branchial cysts , type iv is designated as a nasopharyngeal cyst.6 histopathologically , the lesions exhibit lymphocytic infiltration and the formation of lymph follicles . further , the lesion is hypointensive and hyperintensive on the t1-and t2-weighted mri images , respectively , but gd contrast agents show no contrast effect . intra - adenoid cysts are caused by mechanical or inflammatory occlusion of an embryonic groove ( central fossa ) on the pharyngeal tonsil before lymphoid tissues appear . histopathologically , crypts possess lymphoid tissue , and are characterized by columnar as well as squamous and columnar epithelium . in mri without contrast , the crypts appear hypointensive and hyperintensive on the t1- and t2-weighted images , respectively , whereas gd contrast agents exhibit no contrast . nevertheless , in many cases the intra - adenoid cysts are difficult to distinguish from tornwaldt s disease . for that reason , tornwaldt s syndrome , including intra - adenoid cyst and tornwaldt s disease , was proposed in a previous report.7 different types of nasopharyngeal cysts can be ascertained from the site of their development ( fig . 4 ) . rathke s cleft cysts are located in the cranial area . beneath them are intra - adenoid cysts , followed by tornwaldt s disease , and branchial cysts are located in the lowermost area among them . the cysts are characterized by their development on the medial wall of the nasopharynx , except for branchial cysts which develop on the lateral wall . in the present case , because the lesion was nasopharyngeal and cystic , and the contents were hypointensive on the t1- weighted mri images and relatively hyperintensive on the t2-weighted images , we ruled out rathke s cleft cysts . branchial cysts were also excluded because the basal portion of the cyst was located on the median of the nasopharynx , and a grooved surface was present according to the nasopharyngeal fiberscopy and ct findings . pseudocysts , tornwaldt s disease , and retention cysts were eventually ruled out because , according to the histopathological findings , the lesion possessed lymphoid tissue with follicular hyperplasia . therefore , we diagnosed the lesions as crypts in the nasopharynx . regarding the relationship between sas and nasopharyngeal tumors , the latter are detected at a rate that is approximately four times more frequent in sas patients than in the general population . furthermore , according to a previous report , a tumor or cystic disease causes complications in the upper respiratory tract in 0.24% of sas patients.8 as a clinical condition of hypertension accompanying sleep apnea , sympathetic nerve stimulation due to hypoxemia is considered to be related,9 but no abnormality was observed in the preoperative serum hormone concentration ( e and en ) . however , since blood pressure decreased postoperatively , a cystectomy was performed for ncpap function , and this is thought to have contributed to a decrease in blood pressure . however , sas was caused not only by obstructions but also by a central nervous system factor . in addition , ahi unfortunately did not improve in our patient because there was no change in her body weight . investigation of a possible nasopharyngeal lesion is considered particularly useful for the ncpap treatment of refractory osas . we treated a case in which a cyst occupied the nasopharyngeal space and caused nasal congestion . histopathologically , the cyst was located on the median of the nasopharyngeal space and showed hyperplasia of lymph follicles . therefore , we diagnosed it as an intra - adenoid cyst , which resulted in continued immune function of the pharyngeal tonsils in an individual over the age of 50 . finally , the presence of a nasopharyngeal cystic disease was determined as the cause that hampered ncpap treatment of refractory osas .

a woman in her 50s was referred to our department with the chief complaint of nasal congestion and pharyngeal discomfort . the patient had been diagnosed with sleep apnea at the department of internal medicine , and had undergone nasal continuous positive airway pressure ( ncpap ) therapy , but her response to the treatment was poor . a cystic lesion occupying the nasopharynx , which was detected by nasopharyngeal fiberscopy , computed tomography , and magnetic resonance imaging , was thought to be the cause of the nasal congestion , pharyngeal discomfort , and obstructive sleep apnea syndrome ( osas ) . consequently , the patient underwent extirpation of the lesion under general anesthesia for the purpose of obtaining a definitive diagnosis as well as for treatment of the nasopharyngeal tumor . the diagnosis of intra - adenoid cyst was eventually made based on the pathological findings , which revealed lymphoid tissue accompanied by expansion of the crypt , as well as inflammatory cell infiltration with follicular hyperplasia . after the operation , the patient reported subjective improvement of her symptoms , and began to respond to the ncpap therapy for her sleep apnea syndrome . nasopharyngeal cysts , in particular adult intra - adenoid cyst , are relatively rare . the outcomes of the current case indicated that the presence of a nasopharyngeal cystic disease was hampering the ncpap treatment of refractory osas .

the advent of effective chemotherapy has made limb salvage an oncologically safe option for a large majority of bone tumors without compromising long term survival . the femur is the commonest site for primary bone tumors , and rarely , the extent of tumor may necessitate resection of the complete femur to achieve adequate oncologic clearance . options include total femoral prostheses ( tfp ) , allografts , and rotationplasty.16 few reports in literature address the use of tfp exclusively for bone sarcomas . most of these describe the functional results with expensive internationally available prostheses.25 in a resource challenged population , the cost of prostheses can occasionally be a limiting factor to limb salvage , especially in cases of malignant tumors where the prognosis is guarded.7 we present our experience with indigenously manufactured low cost total femoral prosthesis ( tfp ) for oncologic outcomes and implant survival after resection and replacement of the total femur . nine patients were operated between december 2003 and june 2009 for resection and tfp implantation . endoprosthetic reconstruction after resection was achieved with a modular total femur prosthesis using an indigenously manufactured fixed hinge tfp ( tmh - nice / restor , sushrut - adler mediequip pvt . ltd . , devrukh , india www.sushrut.com/restor.htm ) in eight cases and an expandable howmedica modular resection system ( hmrs ) prosthesis in one case . the eight cases in which the indigenously manufactured tfp was implanted were analyzed in this case series . there were four males and four females with a mean age of 32 years ( range 1372 years ) . all except one were done as a limb salvage procedure for a primary or recurrent malignant bone tumor . case 7 was for revision of a broken proximal femur replacement , originally done for a malignant bone tumor [ table 1 ] . the diagnosis included osteogenic sarcoma ( n=5 ) , ewing 's sarcoma ( n=1 ) , and chondrosarcoma ( n=2 ) . the primary goal of surgery was limb preservation with complete excision of the tumor while retaining adequate muscle for satisfactory residual function . surgery involved disarticulation of the hip and knee with enbloc excision of the entire femur and surrounding muscles involved with the tumor while preserving the neurovascular bundle . the indigenously manufactured modular total femur system comprises a trochanteric component , a central resection segment , and a distal femoral component , designed to lock into each other with a customized self - locking taper . the central resection segments are available in various sizes to match the length of the patient 's femur . restoration of length was based on preoperative radiological assessment and reconfirmed intraoperatively by measurement of the resected specimen [ figure 1 ] . ( a ) preoperative t1-weighted mri showing involvement of the entire femur in a case of ewing 's sarcoma . ( c ) radiograph demonstrating restoration of limb length after total femur prosthesis to further reinforce hip stability and prevent dislocation , the residual hip capsule was sutured around the neck of the prosthesis . in cases where the capsule was deficient , it was reinforced with a polypropylene mesh ( prolene johnson and johnson , ethicon division , aurangabad , india ) that was anchored to the acetabulum and extended to form a sleeve around the proximal part of the prosthesis.8 only glutei were either sutured directly to the prosthesis and/or sutured to the polypropylene mesh . progressive mobilization using a walker or crutches was started within the first few postoperative days and patients gradually progressed to ambulation without the use of supports . patients were instructed to restrict hip flexion to 60 for the first 6 weeks while encouraging active quadriceps exercises to regain knee extension . patients were asked to followup every 3 months for the first 2 years and six monthly subsequently . functional status was assessed at the time of last followup using the musculoskeletal tumor society ( msts ) scoring system.9 this was based on the analysis of six factors ( pain , use of supports for ambulation , walking ability , functional activities , gait , and emotional acceptance ) . for each of the six factors , values of 05 were assigned based on established criteria . the result was expressed as a sum total with a maximum score of 30 and as a percentage of the expected normal function for the patient . survival of the implant was analyzed with the starting point defined as the date of implantation of the endoprosthesis and the endpoint being removal ( whatever the cause ) . patients were censored for statistical analysis ( observation stopped before the event occurred ) if removal had not occurred at the time the patient was last assessed . the mean followup was 33 months ( 972 months ) for all patients ( n=8 ) and 40 months ( 2472 months ) in survivors ( n= 5 ) . 8 patients analysed , 1 lost to follow up , 2 dead , 5 alive and were available for followup . there was one case of infection which developed after 7 months in a patient who had the tfp implanted after excision of a recurrence around an earlier distal femoral prosthesis . repeated wound lavage failed to control the infection and a hip disarticulation was finally performed ( case 1 ) . it occurred in a 72-year - old male who had a large open biopsy elsewhere . his biopsy diagnosis was chondrosarcoma which was revised to chondroblastic osteosarcoma after evaluation of the excised femur . another patient ( case 1 ) who had the tfp implanted after excision of a recurrence around an earlier distal femoral prosthesis eventually succumbed to distant metastasis . thus , five of the seven patients available for follow up are currently alive . the msts score for patients evaluated at their last followup ranged from 21 to 25 with a mean of 24 ( 80% ) . all the patients were independent ambulators and none of them required a support for walking . there was one case of infection which developed after 7 months in a patient who had the tfp implanted after excision of a recurrence around an earlier distal femoral prosthesis . repeated wound lavage failed to control the infection and a hip disarticulation was finally performed ( case 1 ) . it occurred in a 72-year - old male who had a large open biopsy elsewhere . his biopsy diagnosis was chondrosarcoma which was revised to chondroblastic osteosarcoma after evaluation of the excised femur . another patient ( case 1 ) who had the tfp implanted after excision of a recurrence around an earlier distal femoral prosthesis eventually succumbed to distant metastasis . the msts score for patients evaluated at their last followup ranged from 21 to 25 with a mean of 24 ( 80% ) . all the patients were independent ambulators and none of them required a support for walking . reconstructing large defects after resection of a tumor has always been challenging . in the past , most patients with extended sarcomas of the femur had an amputation with poor function.3 the advent of better imaging modalities , effective chemotherapy , better understanding of anatomy with continuous refinement in surgical techniques , and advances in prosthesis design and materials have all played a part in increasing the incidence of limb salvage surgery . limb salvage should not compromise patient survival while ensuring that patients are able to resume near - normal function as soon as possible.5 the prostheses used must also demonstrate good long term survival . when evaluating a reconstruction technique , various factors need to be considered including its complications , functional outcome , and durability . in resource - challenged populations , cost too often plays a role in the decision making.10 in most cases of tumors involving the femur , adequate resection may be possible with retention of enough bone either proximally or distally to seat an intramedullary stem for a distal femoral or proximal femoral prosthesis . occasionally , for oncologic reasons , entire femoral resection may be necessary or the residual bone stump after proximal / distal femoral resection may be too short to adequately seat a stable intramedullary stem . hip dislocation is a common complication reported after total femur replacement.24611 a combination of various factors can contribute to this . these include lack of functional abductor musculature , resection of the joint capsule , acetabular resurfacing , and use of a rotating hinge design at the knee since rotation at the knee can lead to hip dislocation.25 in our series , we did not have any dislocation . this can be attributed to the use of a fixed hinge prosthesis , using a bipolar head in all cases , and reinforcing the residual hip capsule with a polypropylene mesh in cases where the capsule was deficient . the incidence of local recurrence is a reflection of adequate oncologic clearance and the effectiveness of chemotherapy.12 we had one local recurrence occurring in a case of osteosarcoma , who had an open biopsy at a non oncology center and received no chemotherapy . having identified definite adverse contributing factors in this case , we believe that limb salvage with a tfp is an oncologically sound procedure in appropriately selected cases . local control rates are similar to those described for limb salvage procedures at other sites.7 the survival of the implant was 88% , with removal as the endpoint . the average functional score ( 80% ) in our study as evaluated by the msts scoring system is encouraging when compared with other series describing the use of tfp [ table 2].246 one case ( case 8) currently has 3 cm shortening and is managing with a shoe raise . patients reported very good psychological acceptance after limb salvage with the tfp despite having a poor gait which is primarily due to the lack of good abductor muscle attachment . this is significant as the prostheses used for limb salvage were low - cost , locally manufactured devices costing approximately us $ 2000 ( international prosthesis costs approximately us $ 18,000 ) . thus , due to cost constraints , we are unable to offer conventional limb salvage to some young children requiring total femur excision and do a rotationplasty instead.13 our study is limited by its small numbers , but the uncommon use of tfp for bone sarcomas would necessitate results from various centers being pooled to reach meaningful conclusions.4 though late local recurrence is uncommon , the incidence of implant related complications can be expected to increase with a longer followup.12 in spite of these shortcomings , we believe that this study does add to the existing literature on use of massive implants in limb salvage , especially the use of tfp in appropriately indicated patients with malignant bone tumors . the successful use of locally manufactured megaprostheses demonstrates that cost constraints need no longer be an insurmountable barrier for the use of limb salvage implants in resource - challenged populations .

background : the extent of tumor may necessitate resection of the complete femur rarely to achieve adequate oncologic clearance in bone sarcomas . we present our experience with reconstruction in such cases using an indigenously manufactured , low - cost , total femoral prosthesis ( tfp ) . we assessed the complications of the procedure , the oncologic and functional outcomes , and implant survival.materials and methods : eight patients ( four males and four females ) with a mean age of 32 years , operated between december 2003 and june 2009 , had a tfp implanted . the diagnosis included osteogenic sarcoma ( 5 ) , ewing 's sarcoma ( 1 ) , and chondrosarcoma ( 2 ) . mean followup was 33 months ( 972 months ) for all and 40 months ( 2472 months ) in survivors . they were evaluated by musculoskeletal tumor society score , implant survival as well as patient survival.results:there was one local recurrence and five of seven patients are currently alive at the time of last followup . the musculoskeletal tumor society score for patients ranged from 21 to 25 with a mean of 24 ( 80% ) . the implant survival was 88% at 5 years with only one tfp needing removal because of infection.conclusions:a tfp in appropriately indicated patients with malignant bone tumors is oncologically safe . a locally manufactured , cost - effective implant provided consistent and predictable results after excision of the total femur with good functional outcomes .

a 52-year - old thai woman presented with asymptomatic annular erythematous plaques on the forehead and both cheeks that persisted for 2 years . dermatologic examination showed few discrete annular erythematous plaques on her forehead and both cheeks , 15 cm in diameter . there were solar lentigines and telangiectasias on the malar area , nose , and forehead as shown in fig . 1 and fig the routine histopathology demonstrated nodular and interstitial inflammatory cell infiltrate of histiocytes intermingled with some lymphocytes in the dermis as shown in fig . elastic stain showed elastotic material phagoticized by multinucleated cells and marked decrease of elastic tissue in some foci of the affected dermis ( fig . 4 ) . according to the clinical and histopathological findings , the dermatologic diagnosis was actinic granuloma ( ag ) . complete blood count , liver enzyme , fasting blood glucose , and glycated hemoglobin were within normal range . the patient 's dermatologic condition was treated with prednisolone 15 mg / day for 6 weeks with a good response currently , she has been treated with hydroxychloroquine ( 200 mg / day ) , topical 0.1% mometasone furoate cream , broad spectrum sunscreen , and sun avoidance with partial improvement . it was also termed annular elastolytic giant cell granuloma , atypical necrobiosis lipoidica of the face and scalp , miescher 's granuloma of the face , and granuloma multiforme [ 1 , 2 , 3 , 4 ] . ultraviolet ( uv ) radiation , especially uva , and heat are recognized as causal factors , by changing the antigenicity of elastic fibers . the immune response mediated by helper t cells to degenerated elastic tissue the typical cutaneous lesion of ag is an initially smooth , elevated , nonscaly , erythematous papule which centrifugally extends to an annular plaque with central clearing . they are usually distributed on chronically sun - exposed areas such as the face , neck , upper back , forearms , and dorsum of the hands . apart from the skin , conjunctival involvement has been reported in a few cases [ 6 , 7 ] . there are some reports on the association between ag and internal diseases such as hematologic and solid malignancy , monoclonal gammopathy , temporal arteritis , erythema nodosum , and x - linked dominant protoporphyria [ 8 , 9 , 10 , 11 ] . diabetes mellitus has been found in about 3740% of patient with ag , and may be caused by injury of elastic fiber from hyperglycemic state . as for the renal condition , focal segmental glomerulosclerosis has been described in association with various granulomatous diseases ( e.g. , sarcoidosis , wegener 's granulomatosis , churg - strauss syndrome , and kimura 's disease ) [ 13 , 14 , 15 , 16 ] . these include granuloma annulare , erythema annulare centrifugum , annular lichen planus , secondary syphilis , necrobiosis lipoidica , tinea corporis , and tuberculoid leprosy . the best method to obtain a precise histopathology is an elliptical biopsy across the annular rim and stained with elastic van gieson to demonstrate the three zones of elastic tissue change . in the first zone , solar elastosis is identified in the surrounding unaffected skin . in the second zone , a granulomatous reaction consisting of histiocytes and foreign - body type multinucleated cells is seen , with engulfment of elastotic fibers , representing the annular rim . in the third zone , an absence of elastic tissue in the superficial dermis is found in the center of the plaque . due to aesthetic concern in our case topical corticosteroids , intralesional corticosteroids , systemic corticosteroids , topical calcineurin inhibitors , phototherapy and photochemotherapy ( narrowband uvb , puva , re - puva ) have been used with some benefit [ 18 , 19 , 20 ] . cyclosporine a , dapsone , pentoxifylline , isotretinoin , and acitretin have been reported to be effective in some cases [ 21 , 22 , 23 ] . there are a few case reports with positive results from antimalarial therapy ( chloroquine and hydroxychloroquine ) . to prevent the development of new lesions , patients should be instructed to avoid sun exposure and regularly use sunscreen . our patient had good response to a short course of low - dose prednisolone . however , rapid relapse occurred after the treatment was discontinued . currently , she has been treated with hydroxychloroquine ( 200 mg / day ) , topical 0.1% mometasone furoate cream , broad spectrum sunscreen , and sun avoidance with partial improvement . to the best of our knowledge , the correlation between ag and focal segmental glomerulosclerosis is still unidentified , further investigation is needed to establish the relationship between these two conditions . the authors declare no conflicts of interest . there was no funding for this work .

actinic granuloma is an uncommon granulomatous disease , characterized by annular erythematous plaque with central clearing predominately located on sun - damaged skin . the pathogenesis is not well understood , ultraviolet radiation is recognized as precipitating factor . we report a case of a 52-year - old woman who presented with asymptomatic annular erythematous plaques on the forehead and both cheeks persisting for 2 years . the clinical presentation and histopathologic findings support the diagnosis of actinic granuloma . during that period of time , she also developed focal segmental glomerulosclerosis . the association between actinic granuloma and focal segmental glomerulosclerosis needs to be clarified by further studies .

aging of the population is a worldwide phenomenon that is accompanied by a series of modifications to several physiological parameters , such as a progressive increase in fat mass and a decrease in lean body mass.1 however , these alterations are not linear and must be constantly monitored.24 in elderly individuals , changes in body composition result in the prevalence of overweight and obesity combined with a loss of muscle mass and strength ; this has recently been defined as sarcopenic obesity.57 sarcopenic obesity is associated with functional limitations and increased mortality.8 among the consequences of obesity in elderly individuals are increased risk of cardiometabolic complications , physical incapacity , sexual dysfunction , urinary incontinence , depression , type 2 diabetes , arthritis , decreased cognitive function , dementia , and compromised health - related quality of life.912 apart from this , the loss of muscle mass associated with the aging process results in muscle weakness , increased fall risk , and fat infiltration in the skeletal muscle.13,14 in this sense sarcopenia is defined as a decline in muscle mass associated with spinal shortening and a decrease in muscle strength and functionality.5,15 these deleterious effects seem to result from a complex interaction of innervation disturbances , decreased hormonal levels , and increased inflammatory mediators during aging.1,16,17 the reduction in muscle mass and strength is responsible for the decrease in mobility , decreased functional capacity , and increase in dependency ; there are also economic and social costs.4,6,14 the impact of sarcopenic obesity on the health of older individuals is poorly understood . thus , the present study aimed to investigate the associations between body composition profile and sarcopenia prevalence in elderly sedentary brazilian women . our initial hypothesis was that a proper diagnosis of sarcopenic obesity would be independent of the nutritional state . this transversal and analytical study consisted of 272 elderly women from a local community located in the federal district , brazil . participants were not specifically representative of the brazilian population and were recruited on a voluntary basis from the local community from posters and lectures about the study . individuals visited the laboratory on two occasions . on the first visit they completed an anamnesis form and physical activity questionnaire and the following day they were subjected to dual - energy x - ray absorptiometry ( dxa ) analysis . inclusion criteria were age 60 years , sedentary females , and completion of all anthropometric testing . individuals with inflammatory , rheumatic , or autoimmune conditions or use of medications ( beta blockers and metformin ) that could modulate body composition were excluded . the local ethics committee for human research of the catholic university of brasilia approved the methodology of the present study , and all participants signed an informed consent document . the procedures were in accordance with guidelines for experimentation with human participants . additionally , the study met the ethical standards proposed by the international journal of sports medicine.18 the determination of body composition was completed using dxa ( general electric - ge model 8548 bx1l , year 2005 , lunar dpx type , software encore 2005 ; rommelsdorf , germany ) . the appendicular fat - free mass ( affm ) was determined by the sum of the fat - free mass from the lower and upper body . sarcopenic obesity was determined by body composition measured by the dxa method according to oliveira et al.19 individuals with residual values 3.4 were classified as presenting an inadequate ffm in reference to the body surface . the identification of sarcopenia was based on the values proposed by baumgartner et al,3 which define female individuals as sarcopenic with an affm < 5.45 kg / m . body fat percentage values were distributed according to the recommendations of the national institute of diabetes and digestive and kidney diseases,20 assuming a cut - off point of 32% for women . obesity levels determined by bmi ( body mass / height ) followed the proposal of lipschitz,21 assuming a cut - off point of 27 kg / m for women . based on differences between individuals aged 60 to 69 years and those above 70 years , the participants were divided into two age groups . smirnov normality test and a homoscedasticity test ( mauchly ) were used to test the normal distribution of the data . whitney test for variables with two levels , and kruskal wallis test for variables with more than two levels . the statistical package for the social sciences ( [ spss ] v.19 ; ibm corporation , armonk , ny ) was used for analyses . the determination of body composition was completed using dxa ( general electric - ge model 8548 bx1l , year 2005 , lunar dpx type , software encore 2005 ; rommelsdorf , germany ) . the appendicular fat - free mass ( affm ) was determined by the sum of the fat - free mass from the lower and upper body . sarcopenic obesity was determined by body composition measured by the dxa method according to oliveira et al.19 individuals with residual values 3.4 were classified as presenting an inadequate ffm in reference to the body surface . the identification of sarcopenia was based on the values proposed by baumgartner et al,3 which define female individuals as sarcopenic with an affm < 5.45 kg / m . body fat percentage values were distributed according to the recommendations of the national institute of diabetes and digestive and kidney diseases,20 assuming a cut - off point of 32% for women . obesity levels determined by bmi ( body mass / height ) followed the proposal of lipschitz,21 assuming a cut - off point of 27 kg / m for women . based on differences between individuals aged 60 to 69 years and those above 70 years smirnov normality test and a homoscedasticity test ( mauchly ) were used to test the normal distribution of the data . whitney test for variables with two levels , and kruskal wallis test for variables with more than two levels . the statistical package for the social sciences ( [ spss ] v.19 ; ibm corporation , armonk , ny ) was used for analyses . characterization of the nutritional state by bmi revealed that 65.1% ( n = 177 ) were eutrophic , while all women were classified as obese by dxa ( n = 272 ) with different degrees of severity ; most of them exhibited morbid obesity ( table 2 ) . the majority of women ( 61.76% ) were classified as morbid obesity , while 34.2% ( n = 93 ) presented sarcopenic obesity . among this group women between 60 to 69 years exhibited a higher body fat percentage ( p = 0.004 ) and obesity determined by body composition ( p = 0.001 ) measured by dxa as compared with women above 70 years , according to the classification of the national institute of diabetes and digestive and kidney diseases.20 there was no statistically significant difference between age groups in the parameters determined by bmi ( p = 0.07 ) , sarcopenic obesity ( p = 0.40 ) , or sarcopenia ( p = 0.40 ) . thirty - nine percent of the eutrophic elderly women determined by bmi exhibited sarcopenic obesity , while 23.1% of those classified with mild and moderate obesity by dxa presented sarcopenic obesity ( table 3 ) . there was no association with sarcopenic obesity independent of obesity severity determined by dxa ( table 3 ) . however , there was a negative association between sarcopenia and sarcopenic obesity , hence most of the elderly women with sarcopenia did not present sarcopenic obesity ( table 3 ) . independent of obesity or eutrophy , there was an association between sarcopenia and bmi ( table 4 ) . apart from this , there was an association between sarcopenia and obesity determined by dxa , and as obesity increased in severity the prevalence of sarcopenia increased ( table 4 ) . the combination of sarcopenia and obesity ( known as sarcopenic obesity ) is an important public health problem that induces fragility in the elderly.2,22,23 the current incidence of sarcopenic obesity in elderly brazilian women suggests it plays a role as an important negative factor that counteracts a successful aging process . in comparison , an elderly mexican population showed a higher incidence of sarcopenic obesity ( 48%)3 compared with our results . the reduction in muscle mass ( sarcopenia ) that accompanies the normal aging process is also associated with increments in fat mass . with the concurrent increment in elderly people as reported by the brazilian institute of geography and statistics24 and the prevalence of sarcopenic obesity in brazilians , a higher fragility could be expected in this population.25,26 our results suggest the necessity of proper diagnosis of sarcopenic obesity independent of the nutritional state , such as muscle cross - sectional area , because the eutrophic status or the different obesity levels do not influence the diagnosis of sarcopenic obesity . our study indicates that a sedentary lifestyle may be an additional risk factor for both overweight and obesity , highlighting the concurrent muscular force loss as previously suggested.27 this is in accordance with previous literature.28 the diagnosis for obesity requires the utilization of various methods because bmi has been suggested to be inappropriate for this purpose in the elderly.10 moreover , the current results suggest some discrepancies between bmi and dxa methods regarding the nutritional status of participants . thus , eutrophic elderly women as determined by bmi were classified as obese with various severity levels with the employment of dxa , confirming the previous observations of pahor et al.29 in this regard , bmi has demonstrated some limitations because of the concurrent lean body mass loss and fat mass gain observed in the elderly.10 furthermore , all participants of the present study exhibited various levels of obesity , thus confirming the findings of previous studies in brazilian populations . 30,31 although bmi has been widely used in population studies , this method considers only height and body mass . on the other hand adipose tissue is currently recognized as an important metabolic and hormonal secretory organ with more than 50 product molecules identified.1 subsequently , when there is an increase in adipose tissue , the impact of these molecules is also augmented , thus favoring the development of insulin resistance , type ii diabetes , atherosclerosis , and metabolic syndrome and therefore impacting the health of older individuals.8,32,33 with the current results it was possible to verify an overestimation of muscle mass as a consequence of not taking into account the true differences in water , bone mass , and ffm , as the elderly have demonstrated an excessive extracellular fluid accumulation.29 this syndrome is associated with a progressive loss of muscle force and mass with subsequent lower physical capacity and quality of life , and hence the current results should be considered for further interventions in this population . the premise is based on the fact that individuals with high fat mass also demonstrate a high ffm . therefore , individuals with high fat mass and subsequently high ffm would not be diagnosed as sarcopenic , independently of its influence on total body mass or functional capacity . in order to adjust ffm with fat mass , newman et al34 proposed a method based on the residuals of a regression equation that predicts affm from fat mass and height ; this was helpful in the diagnosis of sarcopenic obesity in the current study . the limitations of the present study are the reduced number of participants and lack of additional measures , such as calf circumference and other metabolic parameters , that would certainly be of interest . in summary , the present study observed a critical relationship between sarcopenia and obesity in an elderly female population . the combination of sarcopenic obesity may have a dynamic negative impact on the aging process in the elderly , and thus the ability to correctly diagnose this condition becomes important . further studies are needed for the diagnosis of sarcopenic obesity as well for understanding its etiology and clinical impact , specifically in the elderly population of developing countries where public health systems are not prepared for the demands of this population sector .

the aim of the present study was to investigate the prevalence of sarcopenic obesity and its association with obesity and sarcopenia in elderly brazilian women . two hundred and seventy - two sedentary women with a mean age of 66.75 5.38 years were recruited for participation in this study . obesity was determined by both body mass index and dual - energy x - ray absorptiometry ( dxa ) evaluations . sarcopenic obesity diagnosis was established from the ratio between fat - free mass and body surface area as obtained by dxa . there was no association of obesity with sarcopenic obesity ( p = 0.424 ) . in contrast , sarcopenia was significantly related to sarcopenic obesity ( p < 0.001 ) , although most of the elderly women with sarcopenia ( n = 171 ) did not exhibit sarcopenic obesity . these results highlight the importance of diagnosing sarcopenic obesity as elderly women exhibiting sarcopenia could be either eutrophic or obese .

pancreatic neuroendocrine tumors ( pnets ) represent a relatively uncommon form of malignancy with an incidence of 0.43 cases per 100,000 in the usa . at diagnosis , nearly 70% of patients have metastatic disease , of which 85% will have liver metastases . management options for pnets metastatic to the liver include surgical , ablative , cytotoxic , and radioisotope approaches . unfortunately , due to the scarcity of these tumors there is a paucity of randomized trials to guide optimal therapy sequencing . the north american neuro - endocrine tumor society and european neuroendocrine tumor society both support the use of radioembolization for progressive or symptomatic liver metastasis [ 3 , 4 ] . to date , yttrium-90 ( y ) therapy has appeared safe ; however , there is no randomized controlled trial assessing toxicities . we present the case of a woman undergoing y therapy for metastatic pnet to the liver who developed liver enzyme elevation and subsequent cirrhosis following treatment . there are only 3 other reported de novo cases of cirrhosis following y administration , with only 1 demonstrating confirmatory pathology [ 6 , 7 , 8 ] . ultrasonography and computed tomography ( ct ) of the abdomen revealed a 9.5 8.6 10.5 cm , heterogeneous , hypervascular mass adjacent to the spleen and abutting the stomach wall and tail of the pancreas . fine - needle aspiration guided by endoscopic ultrasound revealed cytologic evidence of a neuroendocrine tumor . the patient proceeded to a distal pancreatectomy , splenectomy , wedge resection of the stomach , and partial resection of the left adrenal gland . pathology demonstrated a 13-cm , well - differentiated neuroendocrine tumor of the pancreas with perineural invasion , but no vascular invasion and negative margins . it was found to be adherent to both the spleen and the stomach , but did not invade either . it had a mitotic rate of 2 mitoses / high - power field and a ki-67 index of < 2% . two months postoperatively , the patient was found to have 4 subcentimeter hypervascular lesions in the liver which were in octreotide scan negative . over the following 9 months , the patient developed 8 new lesions , while the original lesions increased to a maximum size of 1.2 cm . therapy with octreotide lar 20 mg intramuscularly once monthly was initiated but discontinued after 9 months due to progressive hepatic disease . a ct scan of the liver performed 3 months after embolization demonstrated a mixed tumor response with the overall impression of progressive disease and development of new liver metastasis . the patient was presented with the option of systemic therapy with everolimus , shown in phase iii trials to improve progression - free survival in patients with well - differentiated pnets . due to the absence of extrahepatic metastasis , liver - directed therapy with y embolization was also offered , which the patient chose to proceed with . prior to y treatment , there was no radiologic evidence of cirrhosis and the liver enzymes were within normal ranges ( ast 24 u / l [ normal range ( n ) 1038 < 50 u / l ] , alkaline phosphatase 156 u / l [ n 50200 u / l ] , total bilirubin 5 mol / l [ n 018 mol / l ] ) . she had a technetium-99 macroaggregate albumin planning spect ct demonstrating multiple focal regions of increased activity in the left and right lobes of the liver which corresponded to the patient 's known metastases . radioembolization with 3.5 gbq of y theraspheres was administered to the right hepatic artery , delivering a total dose of 140 gy to the right lobe of the liver , and 1.8 gbq of y theraspheres was delivered through the left hepatic artery with a dosing of 140 gy to the left lobe of the liver on the same day . over the following 3 months , the patient developed abdominal pain and nausea and was found to have elevated liver enzymes , in a pattern suggesting damage to the biliary tree ( ast 52 u / l , alt 86 u / l , alkaline phosphatase 405 u / l , ggt 604 u / l , total bilirubin 5 ct scanning of the abdomen demonstrated generalized mottling of the liver , compatible with postembolization edema with a substantial decrease in tumor burden and 2 significant lesions remaining . the patient 's liver enzymes remained elevated over the following 6 months until she developed significant right upper quadrant pain . ct 9 months after y treatment revealed a very inhomogeneous liver texture and a large biloma traversing segments 5 and 8 of the liver , measuring 8.5 6.5 5.5 cm . this was initially noted 10 months after y treatment and was slightly progressive on the 14-month scan ( fig . 1 ) . imaging also demonstrated multiple subcentimeter right hepatic lesions raising concern for metastatic disease , some of which had not previously been seen . due to radiographic evidence of progressive disease , everolimus 10 mg once daily was initiated , and the patient continued on this for 36 months with stabilization of the disease . her liver enzymes remained unchanged over this time , with elevated hepatobiliary enzymes and borderline - elevated hepatocellular enzymes . at 25 months after initiation of everolimus therapy , progressive disease was noted in 2 solitary hepatic lesions and was treated with radiofrequency ablation . due to disease control in the remainder of the hepatic parenchyma , everolimus was resumed after radiofrequency ablation . thirty - five months after initiation of everolimus therapy , radiographic note was made of the advanced cirrhotic appearance of the liver ( fig . 1 ) and the increase in size of a left hepatic lesion . there was no evidence of portal hypertension . due to the radiographic evidence of progressive disease and the cirrhotic appearance of the liver , everolimus therapy was interrupted and a liver biopsy to further characterize the nature of the parenchymal disease was performed . a single 18-gauge core was obtained from the left lobe of the liver in order to avoid the biloma involving the right lobe . the biopsy demonstrated large fibrotic bands in keeping with cirrhosis with mildly active steatohepatitis ( approx . the patient had not been started on any other new medications , did not drink alcohol excessively , performed no high - risk activities for viral hepatitis , and had no family history of liver disease . serology was nonreactive for hbsag , hbcab , and hepatitis c virus , and the patient had immunity to hepatitis b virus . her antinuclear antibody was equivocal , and her anti - smooth muscle antibody and antimitochondrial antibody were negative . given the chronologic association of y administration with liver enzyme elevation , with the exclusion of other causes of cirrhosis , the diagnosis of y - induced cirrhosis was made . she has not suffered any cirrhosis - associated complications and is currently child - turcotte - pugh class a. to date , y - related cirrhosis has only been reported in 3 cases [ 6 , 7 , 8 ] . a prior systematic review assessing outcomes following y radioembolization identified grade 3 and higher adverse events in 012.9% of patients . in their review , the authors were able to identify 1 episode of cirrhosis and 3 episodes of hepatic failure . the 1 cirrhotic patient identified was seen by saxena et al . , who described a patient with cirrhosis and ascites 6 months after treatment with grade 3 elevation of serum alkaline phosphatase and grade 2 elevations of alt and bilirubin . other reported cases of cirrhosis come from case reports by brock et al . and ayav et al . brock et al . described a patient with metastatic breast cancer with bone and liver metastases who received y. the patient had a good response to treatment at 4 weeks , but 3 months later developed ct imaging findings consistent with cirrhosis and portal hypertension . described a 39-year - old man who received y for colon carcinoma metastatic to the liver . four months after administration , the patient was found to have signs of portal hypertension and had a biopsy consistent with cirrhosis . the timeline of initial hepatic changes seen with our patient closely resembles these previous reports , with a subacute onset of irregular echotexture and cirrhosis occurring several months following treatment with y [ 6 , 7 , 8 ] . y microspheres deliver focused radiotherapy to metastases in the liver while sparing viable hepatic tissue , due to the predominant arterial supply of hepatic metastases as compared to the predominantly portal venous blood supply of normal liver parenchyma . an assessment of explanted livers following y treatment showed no fibrosis > 1 cm from tumor borders . the case of our patient adds to 3 previously reported cases that demonstrate cirrhosis as a potential long - term complication of y treatment . an increasingly long median life expectancy is observed with pnets , with a 5-year overall survival of patients with low - grade tumors of 75% . therapies with a significant rate of long - term toxicities should therefore be avoided early in the course of therapy among patients with advanced disease . the notion that y therapy may lead to cirrhosis is supported by radiographic studies assessing volume changes and signs of portal hypertension following y treatment . in a series of 17 patients treated with y , a mean decrease in liver volume of 11.8% and a mean increase in splenic volume of 27.9% were noted , accompanied by increases in portal vein diameter . in another series of 45 patients , liver volumes were shown to decrease in lobes treated with radioembolization by up to 45% at 12 months after treatment . the difficulty with utilizing volume changes and liver texture to define outcomes following y administration lies in differentiating normal radiographic changes following radioembolization from true cirrhosis . in the current case report , imaging was reported as being consistent with prior radioembolization throughout many of the reports , with a progressive worsening noted over time . while differentiating this from cirrhosis is very difficult , the differential for these radiographic changes needs to include cirrhosis . the only other agent that could be chronologically associated with cirrhosis in our patient is everolimus ; however , this was started after radiographic changes had already been seen in the liver . in addition , early preclinical work suggests that inhibition of the mtor pathway with mtor inhibitors may be antifibrotic . there is , however , 1 case report of steatohepatitis following administration of everolimus . while our patient did not have steatosis severe enough to be considered solely responsible for the observed cirrhosis , it is possible that she suffered an initial insult from y administration and had impaired hepatic regeneration subsequently due to everolimus - induced steatosis , thus causing accelerated progression to cirrhosis she developed a large biloma 10 months following y treatment . in a 327-patient retrospective review by atassi et al . in contrast to normal hepatocytes , intrahepatic bile ducts lack a dual blood supply and are fed by intrahepatic arteries . biloma development is thought to develop following peripheral bile duct necrosis , resulting in biliary drainage into surrounding tissue . this case report adds to a growing body of evidence that y treatment may cause serious damage to the biliary tree , and it is clinically important because it demonstrates pathology confirming that a long - term outcome of y administration may be cirrhosis . this long - term risk needs to be considered when sequencing therapy for patients who have a high rate of 5-year survival and who have other systemic and ablative treatment options .

backgroundmanagement options for pancreatic neuroendocrine tumors ( pnets ) metastatic to the liver include surgical , ablative , cytotoxic , and radioisotope approaches . one potential local treatment option includes selective internal radiotherapy utilizing yttrium-90 ( 90y ) microspheres . 90y has also been used in the treatment of hepatocellular carcinoma and tumors metastatic to the liver . it appears to be well tolerated ; however , there is no randomized controlled trial reporting long - term toxicities . previous retrospective reports have described biliary damage as a potential complication of therapy with 90y and chemoembolization ; however , the long - term sequelae of 90y treatment are poorly understood.case presentationwe present the case of a 65-year - old caucasian woman who suffered biliary damage following 90y administration for metastatic pnets and subsequently developed cirrhosis . given the timeline of her various treatments and the lack of any other identifiable etiology for her cirrhosis , we believe this to be a potential long - term complication of 90y therapy.conclusionthis case provides pathologic confirmation of cirrhosis as a potential long - term sequela of 90y treatment . this long - term risk needs to be considered when sequencing therapy for patients with neuroendocrine tumors who have a good prognosis . there are now several other systemic and ablative treatment options available to these patients , and long - term complications must be considered during treatment .

the principal theory of laser refractive surgery is that the optical power of the eye can be changed by modifying the corneal curvature . laser in situ keratomileusis ( lasik ) is performed to correct myopia and myopic astigmatism by ablating the corneal tissue and flattening the central anterior corneal curvature . the subsequent increase in the corneal radius lowers the dioptric power of the cornea and allows accurate correction of myopic defects . although laser in situ keratomileusis ( lasik ) has been shown to be safe and effective for the treatment of myopia [ 3 , 4 ] , greater outcome variability has been reported in eyes with higher degrees of myopia . many factors have been investigated to find what influences the predictability of lasik including patient age , optical zone diameter , epithelial hyperplasia , and preoperative keratometry ( k ) . the question of whether the preoperative k power influences outcomes in myopic patients has been studied somewhat in patients undergoing photorefractive keratometry ( prk ) procedures and more in hyperopic lasik , and the findings are contradictory . therefore , we tried to deduct the effect of both pre- and postoperative keratometry on moderate to high myopic patients undergoing lasik since the literature is unclear regarding their influence . the case records of 812 consecutive eyes of 420 patients with moderate and high myopia 6 d were retrospectively analyzed . lasik was done at sohag laser center , egypt , from january 2010 to november 2013 . data obtained from the case records included patient age , spherical equivalent ( se ) refraction ( pre- and postoperative ) , corrected distance visual acuity ( cdva ) ( pre- and postoperative ) , and keratometry ( pre- and postoperative ) and details of intraoperative complications . exclusion criteria were ( 1 ) eyes with spherical equivalence > 12 d , ( 2 ) eyes with follow - up of less than 6 months , ( 3 ) eyes with intraoperative complications , ( 4 ) eyes with preoperative cdva < 0.3 , ( 5 ) eyes that needed undercorrection due to thin corneas not permitting total correction , and ( 6 ) eyes with previous ocular surgeries . rabinowitz criteria [ 911 ] were applied meticulously to screen for keratoconus and exclude risk factors . corneal keratometry ( k ) was measured in the flat and steep axes using a scheimpflug topography system ( sirius , cso , italy ) . change in k ( k ) was calculated as preoperative minus postoperative average k. visual acuity was recorded using logmar . one refractive eye surgeon ( em ) operated on the patients using the same nomogram for all treatments . the minimum residual stromal bed was planned to be 280 m with emmetropia being the goal in all cases . superior hinged lamellar flaps were created with a moria m2 microkeratome using a 90 m single use head and 9.0 mm ring . laser ablation was performed using the visx star s4 ir , creating a 6.5 mm optical zone with 8.0 mm blend zone with centration over the center of the pupil . following noncustomized ablation , the flap was replaced and the patients then received fluoroquinolone qid for 7 days and prednisolone acetate 1% drops qid for 7 days and then tapering over 3 weeks . for the purpose of analysis , patients were divided into three groups based on the degree of preoperative myopia : group 1 , 6 d to 7.9 d ; group 2 , 8 to 9.9 d ; and group 3 , 10 to 12 d. the reported refractive values correspond to spectacle plane . the refractive outcome among the different myopic groups was further stratified by pre- and postoperative keratometry . means were compared using the unpaired t - test ( 2-tailed ) , while nonparametric data were analyzed using the chi - square test . trends in data were tested using an analysis of variance , and the relationship between preoperative keratometry and postoperative refraction was studied by linear regression . the demographics of the 420 patients ( 155 men , 265 women ) and the three groups which are stratified according to the degree of preoperative myopia are reported in table 1 . no statistically significant difference existed between the 3 myopic matched cohort groups in mean age ( p = 0.26 ) . the data was further stratified according to the mean preoperative keratometry ( k ) power into 3 subdivisions : ( 1 ) k < 42 d , ( 2 ) k = 4245.9 d , and ( 3 ) k > 46 d. there was a statistically significant difference in postoperative spherical equivalence in both groups , 2 and 3 , when the corneal power was less than 42 d and more than 46 d ( p = 0.032 and p = 0.015 , resp . ) ( figure 1(a ) ) and the same applies to the corrected distance visual acuity ( table 2 ) . in patients with similar preoperative myopia , greater undercorrection was noted in eyes with preoperative keratometry < 42 d. although this was seen in all myopia subgroups , the difference was greatest in those with higher preoperative myopia ( se of 10.0 to 12 d ) ( p = 0.015 ) . in table 3 , the postoperative corneal powers were divided into three subdivisions : ( 1 ) k < 35 d , ( 2 ) k = 3538.9 d , and ( 3 ) k > 39 d. there was a statistically significant difference in postoperative spherical equivalence and corrected distance visual acuity in all groups of myopia when the corneal power was less than 35 d and more than 38 d. in patients with similar preoperative myopia , greater undercorrection was noted in eyes with postoperative keratometry < 35 d than in eyes with steeper corneas ( keratometry > 39 d ) ( figure 1(b ) ) . the results showed that the larger the change in the keratometry between pre- and postoperative keratometric readings is , the more the postoperative spherical equivalence was affected . the postoperative se was more when k was higher in all groups of myopia as shown in table 4 . the results of spearman correlation coefficient between the degree of pre- and postoperative keratometry and the q - factor ( pre- and postoperative ) revealed a correlation coefficient of 0.90 and 0.96 , respectively , indicating a high correlation between the 2 variables ; that is , the change in corneal asphericity increased with the degree of corneal curvature ( figure 2 ) . the precision of refractive surgery for the correction of myopia has improved with the advent of lasik , particularly for high myopia . however , marked variability in refractive outcomes still exists among individual patients [ 3 , 5 ] . this study analyzed the relationship between preoperative and postoperative keratometry to postoperative spherical equivalence and corrected distance visual acuity in a cohort of 812 eyes having lasik by a single surgeon , using a standardized treatment protocol for all patients . to the best of our knowledge , this is the first study to address the effect of both pre- and postoperative keratometry in cases of moderate and high myopia in a large group of patients . the relationship between preoperative keratometry ( k ) and visual outcomes in laser - assisted in situ keratomileusis ( lasik ) has been studied in myopia as well as in hyperopia . we noted a trend toward greater undercorrection in patients with keratometry < 43.5 d than in those with keratometry > 46 d in all myopia groups . the possibility of undercorrection resulting from treating flatter corneas with a standard protocol has been described in a neural network model . also , the loss of ablation efficiency at nonnormal incidence may explain many of the current findings : considering the loss of efficiency in a pure myopia profile , the profile shrinks , steepening the average slope and then slightly increasing the myopic power of the profile as well as inducing spherical aberrations [ 1316 ] . rao et al . reported increased undercorrection in eyes with preoperative se of 10.0 to 11.9 d and in eyes with flat corneas compared with steeper corneas . perez - santonja et al . also reported a tendency toward undercorrection in eyes with flatter corneas that had received lasik for the correction of high myopia of 8.00 to 20.00 d , while christiansen et al . studied moderately myopic eyes undergoing lasik and their results suggested that flatter corneas have better visual outcomes than those with steeper corneas which disagreed with the previous studies as well as ours . prospectively examined 6-month follow - up data and found an increased incidence of loss of bscva with eyes that had preoperative k > 44.0 d. esquenazi and mendoza found that undercorrection occurred more frequently in eyes with preoperative k > 45.0 d. another study of the effect of keratometry on refractive outcome was carried out by de benito - llopis et al . in lasek cases on 1180 eyes and found that there is a weak positive correlation between preoperative keratometry and postoperative se , mostly in the subgroup with steeper corneas and when the preoperative refractive error was higher . yet they did not find a tendency toward undercorrection in flatter corneas , as some studies of lasik have concluded . blaker and hersh , and varssano et al . yielded the same results in prk patients as well . they found that flat , rather than steep , preoperative corneal keratometry led to greater regression and vision undercorrection . the differences between the results of surface ablation and lasik may be due to the fact that creating a stromal flap could be a confounding factor in lasik . flattening of the central cornea can result from cutting the peripheral stroma due to interlamellar forces [ 25 , 26 ] . in non - femto - assisted lasik , the microkeratome produces a meniscus shaped flap that is thinner in the center and thicker in the periphery [ 27 , 28 ] . the preoperative corneal curvature seems to affect the profile of the stromal flap , while surface laser ablation alters only the corneal curvature , thus avoiding this potential confounding factor . another factor that might explain why the studies of prk patients found no relationship between these 2 factors is the aggressive stromal healing response and epithelial remodeling in surface ablation . so , with less healing response in lasik , any relationship between preoperative keratometry and final refraction may be more evident . rao et al . suggest that because the change in corneal curvature is responsible for correcting myopia , more ablation might be required in a flatter cornea than a steeper cornea to produce a similar amount of effective change . stark et al . also suggest that the laser beam incises less perpendicularly the surface in the midperiphery of steep corneas than of flatter ones , which may cause a loss of ablative efficiency away from the corneal apex in steep corneas . this can result in deeper central ablation and shallower paracentral ablation leading to slightly greater myopic correction in steep corneas than in flat corneas . as regards the effect of postoperative keratometry on refractive state , jin et al . found no association between postoperative k greater than 49.0 d and poor visual acuity in hyperopes . cobo - soriano et al . also found that postoperative k did not affect outcomes and that postoperative k greater than 48.0 d had no effect on visual outcomes . supported the conclusion that rather than dependence on the preoperative or postoperative k values , the outcomes of hyperopic lasik are dependent on intraoperative changes in k. cobo - soriano et al . as well found an association between k changes greater than 4.0 d and poor outcomes . as regards corneal asphericity , holladay et al . found a high average rise in the q - factor after refractive surgery , which declined over 6 months to a value that was still higher than the presurgery level . investigated the asphericity change after wavefront - guided lasik in 177 myopic eyes and found that there is a change in the direction of a more oblate profile which is in agreement with our results as well . several studies revealed that corneal vertex centration resulted in less ocular aberrations and changes in asphericity . because of the smaller angle between corneal vertex and pupil center associated with myopes compared with hyperopes , centration problems are less apparent [ 36 , 37 ] . however , pupillary offset larger than 250 m seems to be sufficiently large to be responsible for differences in ocular aberrations , yet not large enough to correlate this difference in ocular aberrations with functional vision [ 3840 ] . we classified the myopic eyes into 3 groups to avoid masking the underlying relationship between keratometry and refractive outcome if it has been analyzed all in one group as the level of preoperative ametropia was proved to strongly affect the final outcome [ 3 , 5 , 17 ] . we understand that longer follow - up periods were warranted to shed light on the long term postoperative effects . in conclusion , our data revealed the occurrence of greater undercorrection after lasik in eyes with flatter preoperative keratometry and postoperative keratometry as well . analysis of large group of patients allowed us to conclude that the effect of preoperative keratometry on the final refractive outcome appeared greater in eyes with higher myopia , and these differences were clinically significant in eyes with myopia greater than 10.0 d. preoperative and postoperative keratometry appeared to influence the corneal asphericity as well . lasik nomograms integrating corneal curvature would lead to better outcomes particularly in eyes with high myopia .

purpose . to evaluate the effect of preoperative and postoperative keratometry on the refractive outcome after laser in situ keratomileusis ( lasik ) for moderate and high myopia . methods . records of 812 eyes ( 420 patients ) with myopia 6 d who had lasik at sohag laser center , egypt , from january 2010 to november 2013 , were retrospectively analyzed . main outcome measures were postoperative corrected distance visual acuity ( cdva ) , postoperative spherical equivalence , and postoperative q factor . results . lasik was performed in 812 eyes ( mean age 21.8 5.2 years ) . patients were grouped according to the degree of preoperative myopia into three groups : group 1 , 6 d to 7.9 d ; group 2 , 8 to 9.9 d ; and group 3 , 10 to 12 d. the refractive outcome among the different myopia groups was stratified by pre- and postoperative keratometry . a trend toward greater undercorrection was noted in eyes with preoperative keratometry < 43.5 d compared with those with steeper keratometry > 46 d in all myopia groups . the undercorrection was also noted in postoperative keratometry groups < 35 d. conclusions . preoperative and postoperative keratometry appeared to influence the refractive outcome especially in high myopic eyes .

schizophrenia is a chronic disease characterized by diverse and varied picture of the clinical course . it is undoubtedly the most serious and most debilitating mental illness , which is one of the first ten causes of disability among the young and the elderly . the risk over a lifetime reaches 1% regardless of geographical areas and cultural regions in the world . in the course of the disease all aspects of human functioning before illness are changing . the incidence is equal in both sexes , but men usually suffer at an earlier age , women in later life . in poland , schizophrenia affects about 400 thousand people . in the province of lublin in 2008 , the number of patients with schizophrenia was 6674 , and the number of newly registered cases of the disease was equal to 1225 . the fact of occurrence of chronic illness and the phenomenon of stigmatisation that is associated with the attitude of the society toward the mentally ill people often makes it impossible for them to start their own family . among those remaining in the formal marriages or informal relationships the occurrence of the disease usually worsens the relationship with their spouse or partner , with children and other family members . the patient is unable to perform their previous roles , their system of values is changed , and needs and life plans are also different . the patients start to break contact with other people , isolation , loss of interest , and emotional ties occur . the difficulties of patients are not limited to episodes of illness , but also concern the period between them . in accordance with many consequences that schizophrenia brings for individual and social functioning of ill people , their assessment of quality of their lives seems to be interesting . often , however , their use is associated with deterioration in quality of life of patients , it becomes a reason for giving up the treatment , which in turn is equal to its ineffectiveness . initially , this type of analysis was carried out mainly in the field of oncology . then researchers drew attention to the concept of quality of life also in other fields of medicine . patients with chronic diseases like diabetes or epilepsy were tested . in the case of the mentally ill patients , there were doubts whether the lack of access , presence of psychotic symptoms can affect the patient 's assessment of their quality of life and whether that assessment is reliable . despite all the doubts about the credibility and reliability of assessment of the quality of life conducted by patients themselves , for several years till now the subjective assessment of a patients with schizophrenia is taken increasingly into account and is considered to be the most important . it is fair to say that the assessment of quality of life of patients is one of the most important components of modern medical diagnosis and prognosis and allows for more targeted therapeutic intervention , expressing subjective approach to the patient , in order to meet their real needs . the main objective of the study was to assess the prevalence and severity of anxiety and depression as well as the impact analysis of level of anxiety and depression on quality of life of people with schizophrenia . before we started the implementation of the present study , this research project was reported to the bioethical committee of the medical university in lublin . after receiving a positive review for the presented project of the clinical trial with the no . ke-0254/142/2008 , we began to collect the research material . in the study conducted from july 2009 to april 2010 the group of patients with schizophrenia from community psychiatric centres in lublin province ( environmental self - help homes , charitable society for aid to the sick misericordia " and the care and educational facility misericordia " , daily department of the neuropsychiatric hospital in lublin , department of psychiatric rehabilitation at the neuropsychiatric hospital in lublin and occupational therapy workshops ) was involved . the criteria for inclusion of people with schizophrenia to the study were the following : written consent to participate in the study , diagnosis of schizophrenia according to icd-10 , age from 18 to 65 years , at least one hospitalization in the closed ward , no evidence of cns damage , the lack of addictions , and contact with the family . among 180 distributed questionnaires , 122 were received . 7 questionnaires were improperly filled by people with schizophrenia , and therefore they were excluded from the study . we analyzed 115 correctly completed questionnaires , consisting of a set of methods for patients with schizophrenia . a set of methods for people with schizophrenia consisted of five scales : author 's questionnaire , the quality of life scale , a standardized whoqol - bref instrument , anxiety and depression scale , a standardized hads instrument ( hospital anxiety and depression scale ) , author 's questionnaire was developed for the patient based on knowledge and experience of the author and the available literature . whoqol - bref scale is a research tool designed for the cognitive and clinical purposes . bref version ( the short one ) whoqol was constructed on the basis of whoqol-100 . it is used to measure satisfaction with life of people in the general population and in people suffering from various diseases . whoqol - bref consists of 26 questions and allows to obtain the profile of the quality of life in four domains : physical , psychological , social relationships , and environmental . the score reflects the areas of individual perceptions of quality of life in these areas . it is the scale of satisfactory reliability and validity , and its usefulness in studies of people with mental disorders has been documented by many works , both in poland and in the world . anxiety and depression scale , hospital anxiety and depression scale ( hads ) , was constructed in 1983 by rp zigmonda and snaith . it consists of two separate subscales , one evaluates anxiety ( hads - a ) and the second one depression ( hads - d ) . each of the subscales contains 7 statements about the current state of the test person . there are 4 variants of answers ; each variant is indicated by a different numerical value ( from 0 to 3 ) . counting is a simple summation of all values for the marked answers , separately for questions about anxiety , and separately for questions about depression . the anxiety scale measures the general anxiety , unfocused on a particular situation , and describes the mood of fear , anxiety , and lack of relaxation . the average level of anxiety was 9.53 ( sd = 3.63 ) and depression 7.58 ( sd = 4.09 ) ( figure 1 ) . mild anxiety disorders occurred in every second ( 43.48% ) , moderate in every fourth ( 25.22% ) , and severe in every tenth ( 9.57% ) test person . mild depressive disorders occurred in every third ( 33.043% ) , moderate in every eighth ( 13.04% ) test person , and severe in only six ( 5.22% ) respondents . a correlation between the quality of life of tested patients with schizophrenia and the occurrence of anxiety and depression disorders in these patients was tested . in the study group we looked for correlations between the results in two general questions and areas of quality of life as well as anxiety and depression disorders . a strong negative correlation was observed between the severity of both anxiety disorders and depression and the values obtained in the overall perception of quality of life , in the general health situation as well as in all areas of quality of life , which means that the more severe anxiety and depressive disorders , the lower values observed in all tested components of quality of life ( table 1 ) . it is worth noting that the strongest correlations were observed between the level of anxiety and depressive disorders and psychological field ( table 2 ) . respondents in the case of severe anxiety or depression got the lowest scores in all areas of quality of life , while in those without any depressive disorder were observed the highest scores in all areas ( table 3 ) . it is assumed that depressive disorders occur in 60%75% of people with schizophrenia . during the first episode and reactivation of psychosis the frequency rate of depressive disorders ranges from 65% to 80% , and during the remission period from 4% to 20% . all the studies published so far provide evidence that depression and anxiety are strong predictors of quality of life in schizophrenia [ 818 ] . as well as the impact of depression on quality of life of people with schizophrenia seems to be a stronger predictor than psychotic symptoms . found that anxiety and depression measured by the scale of bprs ( brief psychiatric rating scale ) , independently of each other and of other symptoms of schizophrenia , correlate mostly with the subjective quality of life . similar conclusions are reached by bechdolf et al . in 2003 in their study on a group of 66 people with schizophrenia ; in their case depression most strongly correlated with subjective quality of life of patients . the work of grna et al . demonstrated that people with schizophrenia with accompanying depression received lower scores in two questions , both general and in all areas of quality of life measured by whoqol - bref scale compared to those without depression . the largest disparity occurred in the field of psychology . in the the work in china from 2008 the level of depression measured using the hamilton depression rating scale strongly negatively correlated with all domains of quality of life scale whoqol - bref , anxiety measured using bprs scale only with the field of psychology . similar results were obtained by the author in his earlier work from 2007 . anxiety and depression strongly correlated with overall quality of life and with all areas of whoqol - bref scale . researchers from portugal in 2008 came to similar conclusions : the level of depression as measured by the hamilton depression rating scale strongly negatively correlated with the field of psychological and physical scale whoqol - bref . additionally , it also appears that those patients with concomitant depression are more aware of the consequences of their disease and treatment efficacy . depressive symptoms can occur as a consequence of the realization of loss , humiliation , shame , and an expression of blame because of their mental state . correlations between the severity of anxiety disorders and depression and the values obtained in the overall perception of quality of life , in the general health condition as well as in all areas of quality of life , were pointed out which means that the more severe anxiety and depressive disorders , the lower values were observed in all tested components of quality of life . it is worth noting that the strongest correlations were observed between the level of anxiety and depressive disorders and psychological field including elements of the subscales : appearance , negative feelings , positive feelings , self - esteem , spirituality / religion / personal faith , and thinking / learning / memory / concentration . the study of quality of life of the mentally ill people should be conducted on a continuous basis in order to explore the current factors influencing the improvement of their mental and physical welfare . moderate and severe anxiety disorders occurred among 34.79% of people with schizophrenia , while moderate and severe depressive disorders in 18.26% of people with schizophrenia . these individuals require consultation with a psychologist or psychiatrist and consideration of implementation of appropriate pharmacological or psychotherapeutic interactions . efforts should be made to compensate these disorders , because the more severe anxiety and depressive disorders , the worse the values observed in all areas of quality of life . it is necessary to promote prohealthy mental lifestyle and encourage participation in the preventive activities in mental illness , particularly in the eastern region of poland . the quality of life of people with schizophrenia and their families is one of the major subjects that are currently being considered in both theory and practice . the need to ensure the quality of life results from the fact that life and human health are the highest value .

schizophrenia is the most severe and most debilitating mental illness , which is one of the first ten causes of disability in youth and elderly people . regarding many consequences that schizophrenia brings for individual and social functioning of ill people , their assessment of the quality of their lives seems to be interesting . the aim of this study is to evaluate the incidence and severity of anxiety and depression as well as analysis of the impact level of anxiety and depression on life quality of people with schizophrenia . a group of patients with schizophrenia from psychiatric centers was involved in a study . a set of methods , included : author 's questionnaire , the quality of life scale whoqol - bref , and the hospital anxiety and depression scale ( hads ) . anxiety disorders occurred in more than 78% of respondents , while depressive disorders in more than half of respondents . the more severe anxiety and depressive disorders , the lower values were observed in all tested components of quality of life . the study of quality of life of the mentally ill patients should be conducted on a continuous basis in order to explore the current factors influencing the improvement of their psychophysical welfare . it is necessary to promote prohealthy mental lifestyle .

diabetes mellitus represents an extreme disturbance in glucose metabolism with severe hyperglycemia and insulin deficiency . diabetes mellitus is the fifth most common chronic condition and the sixth most frequent cause of death among the elderly . tissue repair is affected and dysfunction of the oral mucosa occurs due to alterations in salivary flow and constituents , changes in nutrition and reduced immune defenses leading to changes in microbial oral flora and a greater tendency to infections . as a result , xerostomia ; candidiasis ; increased incidence of dental caries , gingivitis and periodontitis ; periapical abscess ; parotid enlargement and burning mouth syndrome are prevalent in diabetics . therefore , early diagnosis of the diabetes mellitus is an important aspect of health care . glycogen fails to stain with conventional hematoxylin solutions and only stains weakly , if at all , with eosin . diastase is the commonly employed form of glycogen digestion enzyme as it is easy to use , stable and comparatively cheap . the aim of our study was to study the effects of diastase enzyme on the glycogen content of the epithelial cells of mucosa of normal and diabetic patients in exfoliative cytology and to compare the staining quality in mucosa of normal and diabetic patients using hematoxylin and eosin ( h and e ) stain ; papanicolaou ( pap ) stain , periodic acid schiff ( pas ) and pas - diastase ( pas - d ) stains , respectively . it is a case - control study involving a total of 20 subjects ( 10 cases and 10 controls ) . diagnosed cases of diabetes were selected . the method used to estimate the values of blood sugar levels ( bsl ) ( fasting and postprandial [ pp ] ) was glucose oxidase method . patients with habits ( tobacco chewing and smoking ) , other systemic diseases / malignancies / taking medications other than the diabetic medications were excluded . smears were taken from the mucosa of normal ( control ) and diabetic ( study ) patients using a wooden spatula and transferred onto clean glass slides . the glass slides ( 40 ) were then immediately fixed in 95% ethyl alcohol and stained using h and e ( 10 slides ) , pap ( 10 slides ) , pas ( 10 slides ) and pas - d ( 10 slides ) stains for both the groups . for pas - d , the slides were first incubated in diastase solution at 37c for 1-h , washed and then stained with pas stain . the staining quality in the cells and their glycogen content was studied in both the groups and then compared . it is used to detect both hypoglycemia and hyperglycemia and helps in diagnosis of diabetes . glucose oxidase is an enzyme highly specific for glucose and does not react with blood saccharides . the principle used in pas - d stain was that diastase ( or -amylase ) acts on glycogen to depolymerize it into smaller sugar units , maltose and glucose , that are washed out of the section . glycogen will be stained magenta on pas [ figure 1 ] stained slide and will be absent on the pas - d [ figure 2 ] stained slide because of glycogen digestion by the diastase enzyme . photomicrograph of buccal exfoliated cells ( pas stain , 400 ) photomicrograph of buccal exfoliated cells ( pas - d stain , 400 ) on comparison of the mean and standard deviation values during fasting and pp , we found that high bsls were seen in the study group as compared to that of the control group [ table 1 ] . by applying student 's unpaired t - test , there was a highly significant difference between mean values of bsl when compared to control versus study group ( i.e. , p < 0.01 ) . also , it was seen that the mean values of bsl both fasting and pp was more in the study group as compared to the control group [ table 2 ] . by applying student 's unpaired t - test , there was a highly significant difference between mean values of bsl when compared to fasting versus pp in both control and study group ( i.e. , p < 0.01 ) [ table 3 ] . mean and standard deviation values of blood sugar level in control and study group comparison of mean values of blood sugar level in control and study group comparison of mean values of both fasting and post - prandial blood sugar levels in control and study group the study group exhibited nuclear changes such as binucleation [ figure 3 ] , decreased cytoplasmic / nuclear ratio , nuclear enlargement [ figure 4 ] and enucleation [ figure 5 ] in pap stained slides as compared to that of control group . photomicrograph of exfoliated cells exhibiting binucleation ( h&e stain , 400 ) photomicrograph of exfoliated cells exhibiting nuclear enlargement ( pas stain , 400 ) photomicrograph of exfoliated cells exhibiting enucleation ( h&e stain , 400 ) diabetes mellitus , a complex metabolic disorder , is a syndrome characterized by abnormalities in carbohydrates , lipid and protein metabolism that results either from a profound or an absolute deficiency of insulin ( type i ) or from target tissue resistance to its cellular metabolic effects ( type ii ) . although many of the pathological processes affecting the oral mucosa are clinically distinguishable , most lesions require a definitive diagnosis before the appropriate therapy may be commenced . the most accepted clinical technique for the diagnosis of lesions of the oral mucosa is an incisional or excisional biopsy . in specific clinical conditions , such as diabetes , a great many invasive techniques lose viability as a result of variations in blood glucose and the disease itself . in these cases a cytologic smear is an advantageous diagnostic procedure because it is noninvasive , relatively painless , inexpensive and requires a minimum of technical skill . it is useful when a patient refuses to have a biopsy performed or when medically compromised patients would be exposed to unnecessary surgical risks and anxious patients can be reassured quickly about the nature of oral mucosal changes , especially when a fear of cancer or a family history of cancer accounts for their apprehension . in a study developed in sudan , the oral cytologic analysis is proposed as a useful early diagnostic method for epithelial atypia and therefore also for malignant oral lesions . in our study , we compared the slides of h and e , pap , pas , pas - d in both control and study group and found that the cells in the study group exhibited binucleation , decreased cytoplasmic / nuclear ratio , nuclear enlargement , enucleation and inflammation as compared to that of control group , which is similar to the findings of jajarm et al . alberti et al . who also found that diabetes mellitus can produce alterations in oral epithelial cells , detectable by microscopy and cytomorphometry , which can be used in evaluation of this disease . our study evaluated whether diabetes diagnosis can be made by analysis of the glycogen content of the oral epithelial cells in diabetics . we compared the mean values of bsl in control and study group and found that mean values of bsl fasting and pp is more in study group as compared control group which is highly significant with a p < 0.01 . because of the increased glucose in diabetics , their epithelial cells showed less staining when stained with pas - d , since glycogen is digested by the diastase enzyme treatment prior to pas staining . in our study , the oral smears obtained from diabetic and control groups contained cellular representatives of all the epithelial strata , from nonkeratinized cells to the completely keratinized ones . these patients presented cellular alterations , both quantitative and qualitative , at all differentiation levels . we found that nuclear changes were significantly higher in the diabetic group than in the control group that was similar to the findings of jajarm et al . decreased cellular turnover might be a secondary reaction to ischemia caused by atherosclerosis in diabetic patients . thus as a result of ischemia , cellular turnover would decrease and limited production of young cells would mean that the majority of cells are old or aged . we found a significant increase in inflammation in the diabetic group in comparison with the control group . this might result from decreased salivary flow in diabetes , due to hypofunction of the salivary glands secondary to adverse hormonal , microvascular and neuronal changes . conner et al . , reported a decrease in the salivary flow of diabetic patients , probably related to systemic dehydration ( polyuria ) , medicament interference ( diuretics ) and/or membranopathy of the ducts . from our study , we can say that exfoliative cytology is useful as an additional tool to aid in the diagnosis of diabetes mellitus . furthermore , studies with greater sample size and comparison to other conditions causing similar cytomorphometric changes are needed to determine the predictive value of this method . thus , from our study , it can be said that exfoliative cytology can be used as a tool for diagnosis as well as for screening the patients for diabetes using pas - d stain . however , larger sample size studies should be performed to come to a definite conclusion .

background : diabetes mellitus is the fifth most common chronic condition and the sixth most frequent cause of death among the elderly . the objective of this research was to develop a new method for diabetes diagnosis by analysis of the glycogen content of the oral epithelial cells.materials and methods : ten control subjects and ten diabetic patients ( study group ) were taken , four oral smears for both control and study group from the buccal mucosa were taken and stained with hematoxylin and eosin stain , papanicolaou ( pap ) stain , periodic acid schiff ( pas ) stain and pas - diastase ( pas - d ) stain.results:the results showed that in the diabetic group : ( i ) the epithelial cells stained with pap stain exhibited figures of binucleation and occasional karyorrhexis , ( ii ) the epithelial cells treated with pas - d showed that glycogen containing cells did not take up the stain as compared to the other cells.conclusion:the results associated with clinical and histological observations suggest that diabetes mellitus can produce alterations of oral epithelial cells as well as in their glycogen content .

urogenital infections ( ugis ) are prevalent during pregnancy and are recognized as an important cause of premature labor . normal cervicovaginal flora plays a crucial role in the defense against the growth and ascension of pathogens . lactobacilli exercises a local defense mechanism due to its production of lactic acid and hydrogen peroxide . during pregnancy , an imbalance in the vaginal flora favors the colonization of the urogenital system by microorganisms , which can complicate a pregnancy . bacterial vaginosis ( bv ) , vulvovaginal candidiasis ( vc ) , and trichomoniasis are responsible for 90% of cases of infectious vulvovaginitis , which can lead to gynecological and obstetrical complications such as pelvic inflammatory disease , postabortion endometritis , chorioamnionitis , and premature labor [ 3 , 4 ] . the most common infection among women in preterm labor ( ptl ) and preterm delivery ( ptd ) is bv . during pregnancy , normal vaginal microbiota , which consists primarily of lactobacilli , is substituted by anaerobic bacteria such as gardnerella vaginalis and mycoplasma homini , resulting in a significant reduction in lactobacilli and increased ph ( greater than 4.5 ) [ 57 ] . vaginal candidiasis ( vc ) is an infection of the vulva and vagina that is caused by various species of candida , a commensal fungus of the digestive and vaginal mucosae that can become pathogenic under specific conditions such as pregnancy [ 8 , 9 ] . studies have shown that trichomoniasis is associated with the premature rupture of membranes , premature delivery , low birth weight , postpartum endometritis , stillbirth , and neonatal death . the presence of pathogenic bacteria in the bladder of pregnant women is associated with the mass colonization of the inferior genital tract and the presence of chorioamnionitis , even when the infection is subclinical . in the early 1970s , group b streptococcus ( gbs ) was recognized as an important cause of neonatal morbidity and mortality in the united states and was determined to be responsible for meningitis and sepsis in newborns , both in its early form in the first seven days of life and in its later form from the seventh to the ninetieth day of life . due to the high risk of death , preventive measures against gbs moreover , many studies have demonstrated the importance of adequate maternal diagnosis and treatment for the reduction of the vertical transmission of bgs and early - onset neonatal sepsis . in mothers colonized by gbs during pregnancy , . revealed that the prevalence of vaginal and anorectal gbs colonization was 14.9% in pregnant women in the third trimester . conducted a study in campinas , sp and demonstrated that the rate of maternal colonization was 27.6% . in the aforementioned study , 30% of these women also suffered from preterm membrane rupture , and 25% went into ptl . adequate diagnosis and treatment of urogenital infections during the prenatal period is necessary ; however , the prevalence of infections during labor must be studied , and the importance of these infections in determining the outcome of pregnancy and the health of the newborns must be evaluated . the present study involved 94 pregnant women admitted to the inpatient maternity clinic of the federal university of rio grande do norte ( ufrn ) in natal , brazil , between january and june of 2009 . two groups were created : the preterm labor group ( ptl ) , which consisted of 49 patients with a gestation period less than 36.6 weeks ( confirmed by the date of last menstruation and/or ultrasound in the first trimester or by the capurro index ) and the full - term labor group ( ftl ) , which included 45 patients with a gestation period between 37 and 42 weeks . all of the women were personally interviewed by one of the researchers , and they were included in the study after signing documentation of informed consent . each patient underwent a gynecological exam , and urinary , vaginal , and perianal samples were taken for microbiological study . the isolated bacteria were identified based on biochemical tests carried out on a microscan automation apparatus . bv was identified according to the amsel criteria , and vc was diagnosed by analyzing vaginal smears . vaginal trichomoniasis was diagnosed via direct microscopic examination , and the presence of gbs was determined by obtaining rectal and vaginal cultures ( todd - hewitt medium ) . data were collected and condensed into a database and were analyzed using statistics 6.1 and spss 13 . a descriptive analysis of the data was completed by constructing bivariate frequency tables , and the following variables were crossed : type of birth , full - term or preterm labor , various sociodemographic factors , the presence of a ugi , and statistics such as the average and standard deviation . to identify differences among the variables , pearson 's chi - square test with yates ' corrections and the mann - whitney u test were used . the prerequisites for each test were considered continuously , and a significance level of 5% was adopted for all tests . this study was approved by the ethics committee of the medicine faculty of the state university of campinas . the results of the sociodemographic analysis demonstrated that among the 49 ptl women , 79.6% were caucasian , 95.9% were married ( with a fixed partner ) , 10.2% were smokers , and the average age was 25 years old . among the 45 ftl women , 75.6% were caucasian , 97.8% were married , 2.2% were smokers , and the average age was 24 years old . no statistically significant differences in the sociodemographic variables were observed between the groups ( tables 1 and 2 ) . of the 49 women in the ptl group , 24 had general infections ( 49.0% ) . among the urogenital infections detected in the ptl group , urinary tract infections ( utis ) were the most prevalent ( 36.7% ) , followed by bacterial vaginosis ( 34.7% ) . in the ftl group , the most common infections in the ftl group were bacterial vaginosis and candidiasis ( 28.9% for both ) . ugis during pregnancy are an important cause of ptl ; thus , preventative measures must be taken during the prenatal period . the prevention of prenatal ugis is often impossible because ugis generally present a multifactorial or unknown etiology . in particular , an association between premature labor and infection at the end of gestation ( 3436 weeks of gestation ) is fairly uncommon . microbiota that inhabit the vagina play an important role in the spread of illnesses and the maintenance of a healthy genital tract . the correlation between ugis and the possibility of infection in the newborn is high ; thus , as a first step toward the understanding of infection in newborns , it is imperative to determine the prevalence of colonization in pregnant women . in the present study , the highest rate of vaginal infection was observed in the ftl group ( 53.3% ) ; the rate of infection in the ptl group was 49.0% . trichomoniasis is also associated with genital infection ; however , in the present study , its presence was insignificant , and only one ( 01 ) case was identified in each group . in the last few decades , the number of cases of trichomoniasis has decreased due to adequate treatment and improved health conditions of the population . in the current study , high rates of bacterial vaginosis were observed in both groups ; 34.7% of women in the ptl group and 28.9% of women in the ftl group had bacterial vaginosis . infections that induce premature labor occur very early in pregnancy and are undetected until childbirth [ 17 , 18 ] . the results of the present study can not confirm that ptl is associated with the presence of infection . significant differences in the prevalence of gbs were not observed between ptl ( 6.1% ) and ftl women ( 15.6% ) , which is in agreement with the results obtained by other researchers , who demonstrated that gbs colonization occurred in 535% of women during pregnancy . the rate of gbs colonization is dependent on sociocultural and geographical variables , the site and time of sampling , and the bacteriological methodology used to identify gbs . benchetrit et al . conducted a study in porto alegre and were the first to analyze gbs colonization in pregnant women in brazil . in the aforementioned study , 86 women were evaluated , and the colonization rate was equal to 26% . in the city of londrina , parana , simes et al . studied candida albicans and found a prevalence of 19.3% for vaginal candidiasis in normal pregnant women in the third trimester . in the present study , candida albicans was identified in 20.4% of ptl women and 28.99% of ftl women ; there was significant difference between the two groups . the frequency and severity of utis during pregnancy have been established for more than a century . although it is accepted that utis cause relatively common problems during pregnancy , several questions concerning this subject remain controversial and have become a motive for clinical investigations . to reduce the rate of urinary infection and related complications during pregnancy , several measures at different points of obstetric assistance must be conducted . urine cultures must be obtained during prenatal followup to diagnose and treat cases of asymptomatic bacteriuria , the most effective antimicrobial treatment must be used , close medical care should be arranged for high - risk prenatal cases , and the treatment of maternal and perinatal complications in hospitals with adequate conditions must be guaranteed . in the current study , a high percentage of utis was observed in both groups ; 36.7% and 22.2% of ptl and ftl mothers , respectively , had a uti . these results are worrisome because of possible complications during pregnancy and labor as well as serious consequences for the newborn . our results failed to show an association between sociodemographic variables and the prevalence of ugi . despite the fact that several risk factors can affect the occurrence of ugis , such as maternal age , conjugal status , race , and smoking , significant correlations between risk factors and ugi prevalence were not observed in the present study . due to the fact that ugis cause premature labor and are often asymptomatic , early screening and treatment are necessary to reduce mortality and morbidity resulting from premature labor and birth .

urogenital infections are extremely prevalent during pregnancy and are an important cause of premature labor . however , the prevalence of urogenital infections during childbirth is not well known . objective . identify urogenital infections present at the beginning of labor in both full - term and preterm pregnancies . study design . ninety - four women were admitted to the inpatient maternity clinic of the federal university of rio grande do norte ( ufrn ) . in total , 49 women in preterm labor and 45 women in full - term labor were included in the study , and samples of urinary , vaginal , and perianal material were collected for microbiological analysis . results . the prevalences of general infections in the preterm labor group and the full - term labor group were 49.0% and 53.3% ( p = 0.8300 ) , respectively . urogenital infections in the preterm and full - term labor groups included urinary tract infection in 36.7% and 22.2% of women , vaginal candidiasis in 20.4% and 28.9% of women , bacterial vaginosis in 34.7% and 28.9% of women , and group b streptococcus in 6.1% and 15.6% of women , respectively . conclusions . urogenital infections were prevalent in women in preterm labor and full - term labor ; however , significant differences between the groups were not observed .

the most common hospital - acquired infection is catheter - associated urinary tract infection ( cauti ) accounting for almost 40% of all the nosocomial infections . the single most important predisposing factor for cauti is the insertion of urinary catheter . urinary ( foley ) catheters are used very frequently in hospitalized patients , and almost 25% of them undergo urinary catheterization during their stay in the hospital . the frequency of urinary catheterization in intensive care unit ( icu ) can range as high as 100% . catheter - associated urinary tract infection produces substantial morbidity in hospitalized patients including discomfort , fever , malaise and unnecessary antibiotic use , which may become an important source of antibiotic resistant organisms . further , the catheterized urinary tract acts as a reservoir for the dissemination of these drug resistant organisms to other patients . there are increased chances of catheter blockage , urinary tract stones and even increased risk of malignancy of the urinary tract following cauti . if it gets complicated by bacteremia , it increases the cost of care tremendously besides increasing the mortality in these hospitalized patients . most doctors and nurses are unfamiliar with the indication of catheterization and further there is no defined management plan to monitor the presence of unnecessary catheter . since the number of catheter days in icu setting is more , the frequency of cauti is expected to be higher . but many studies have shown similar rates of cauti in the icu and non icu patients . this shows that all hospitalized patients including non icu patients are an important group for surveillance and prevention of cauti . many studies have shown that single most important modifiable risk factor for decreasing the incidence of cauti is reducing unnecessary catheter use . preventive measures such as catheter reminders for removing the catheter as soon as possible restrict the number of catheter days and thus lead to decreased incidence of cauti . training the health care personnel and introducing the prevention of cauti as a high priority in hospitals is strongly associated with decreased incidence of cauti . there are limited studies from india , which have assessed the knowledge of health care personnel regarding indication for catheterization and methods to prevent cauti . the present study was planned to assess the knowledge of various health care personnel regarding indication for catheterization and measures to prevent cauti . the study also assessed the attitude of health care provider ( hcp ) regarding cauti . the questions regarding the indication for catheterization and measures for prevention of cauti were taken as per centers for disease control ( cdc ) guidelines . the content of the questionnaire was given independently to all the authors for assessing the simplicity of questions , clarity of language , accuracy and adequacy of questions for the purpose of the study . the survey covered demographic details of the respondents including age , sex , qualification , designation years of experience in health care setup after obtaining graduation and area of posting . the contents of the questionnaire were designed to assess the knowledge of the health care professionals regarding indication for catheter use ( 10 questions ) and the methods of preventing cauti ( 15 questions ) in a catheterized patient . knowledge regarding indication for catheter insertion was assessed by asking the respondents to grade their answers on a 4 point scale ( 4 : almost always indicated , 3 : sometimes indicated , 2 : rarely indicated , 1 : never indicated ) they were given 10 situations in which they had to grade their answers [ table 1 ] . demographic details of the study group ( n=154 ; 49 : doctors ; 105 : nurses ) knowledge regarding the methods to prevent cauti included 15 methods [ table 2 ] . the respondents had to grade their answers on a 4 point scale ( 4 : large effect , 3 : moderate effect , 2 : some effect , 1 : no effect ) . the answers for both the indication and prevention of cauti were compared with the cdc guidelines . for evaluating the indication for catheterization , the response almost , always and sometimes indicated , was taken as appropriate for the indication and the response of rarely and not indicated was taken as appropriate for nonindication . for evaluating the preventive measures , the response of large effect and moderate effect were taken as effective , and that of some effect or no effect were taken as noneffective . frequency of respondents having identified the indications correctly there were 10 questions to assess the attitude and the answers had to be given as whether they agree or disagree with the statements . this was not compared with any reference , and the format of the questionnaire was designed to be used for this study . the data were compiled and analyzed using spss for windows version 12.0 . various statistical test used were simple frequency table , chi - square test , fischer 's exact t - test for significance and univariate analysis for testing the correlation . the data were compiled and analyzed using spss for windows version 12.0 . various statistical test used were simple frequency table , chi - square test , fischer 's exact t - test for significance and univariate analysis for testing the correlation . the data were compiled and analyzed using spss for windows version 12.0 . various statistical test used were simple frequency table , chi - square test , fischer 's exact t - test for significance and univariate analysis for testing the correlation . in the present study , 154 health care personnel ( doctors = 49 and nurses = 105 ) out of the 180 participants completed a questionnaire and were included in the study . the mean age of the study group was 31.9 years ( range : 2359 ) and the mean years of experience was 7.94 years ( range : 136 ) . though doctors had significantly higher knowledge as compared to nurses regarding various indications for catheterization , more than half of the doctors could not identify important indications such as urethral stricture or in patients receiving large volume infusions during surgery [ table 2 ] . more than one - third of the respondents identified urine output monitoring in a mobile patient or even obtaining a urine sample for culture sensitivity as a valid indication for catheterization [ table 2 ] . most respondents could not correctly identify noneffective measures such as bladder irrigation or twice daily meatal care . in general , the hcp could not differentiate the effective measures from noneffective ones [ table 3 ] . number of doctors and nurses correctly identifying methods to prevent cauti doctors had significantly better knowledge than nurses regarding the indications of catheterization and preventive measures for cauti [ table 4 ] . hcp posted in high - risk areas such as icus had significantly better knowledge than the hcp posted in wards regarding various indications , but there was no difference in their awareness in respect to preventive measures [ table 4 ] . univariate predictors of indications of catheterization most of the hcp felt that including prevention of cauti as a high priority in the hospitals and use of renewal reminders would definitely help in preventing cauti . more than 90% of the hcp also felt that education regarding basic catheter care would also help prevent cauti [ table 5 ] . almost 40% of the nurses and 25% of the doctors felt that catheters could be inserted even for nursing convenience . nearly , 10% of the respondents showed hopelessness regarding prevention of cauti [ table 5 ] . urinary catheters once inserted in the hospitalized patients tend to remain in place even after the indication for its use ends . this leads to cauti being one of the most common health care associated infection . the most important preventive measure for decreasing the incidence of cauti is limiting catheter use . this is possible only if the hcp has adequate knowledge regarding the appropriate indications for inserting urinary catheters . we assessed the knowledge of doctors and nurses regarding indication for catheterization to help manage the problem of inappropriate catheterization and cauti . overall the knowledge of doctors was significantly better than nurses in identifying the indications for catheterization ( p < 0.05 ) . since in our facility doctors decide on the catheterization protocol , they would be more aware regarding the indications . educating nurses regarding indications for catheterization will help prevent cauti as they could remind the doctors on removing catheters as soon as the indication for catheterization ends . this finding is consistent with other observers in that nurse 's daily determination for the need of catheter in a patient helps reduce the incidence of cauti . almost 79% of the nurses and 12% of the doctors justified the use of catheters for nursing care of incontinent patients . almost one - third of the respondents justified the use of catheters for routinely obtaining urine samples for culture and sensitivity testing and for urine output monitoring even in mobile patients . it would be worthwhile educating both doctors and nurses regarding the various indications for catheterization as this can keep a check on unnecessary catheter use . knowledge regarding various preventive measures was also suboptimal in the study group . the health care personnel could not identify the preventive measures , which are less effective or noneffective . being over cautious is better than being ignorant but this lack of knowledge regarding preventive measures may lead to wastage of time on unimportant issues at the cost of truly effective measures . a complete knowledge regarding all effective preventive measures would help them prioritize the care of the urinary catheters . almost 77% ( 119/154 ) of the hcp felt that regular bacteriological monitoring is effective for prevention of cauti . this causes increased costs of treatment for the patients in addition to increasing sample load in the laboratories . almost 45% ( 68/154 ) of the hcp felt that prophylactic antimicrobials for 3 days can prevent cauti . this is ineffective besides exposing the patients to unnecessary antibiotics and selecting out on antibiotic resistant organisms . in spite of the fact that nurses are involved with routine catheter care in our setup , more than one - third of the nurses did not know that the urinary collection bag should be below the level of the bladder and it should be emptied regularly to allow unobstructed urine flow . these seemingly simple measures can have a major effect in the prevention of cauti . almost 25% ( 38/154 ) of the hcp felt that isolation of the patient helps in preventing cauti . if they follow this practice , it will lead to emotional , social stress in the patients . thus , appropriate knowledge regarding all preventive measure would save on cost and time and would help in more efficient patient care . the knowledge regarding the correct preventive measures can be imparted through educational training and reinforcement thereafter . in our study , females were more aware regarding the indications and preventive measures . we also observed that experience had no effect on awareness levels , and knowledge in one domain did not affect the awareness levels in another domain . the study again reiterates the finding that educating the hcp regarding indications and preventive measures will help them do evidence - based practice . more than 95% of the hcp felt that hospitals focusing on prevention of cauti as a high priority and use of urinary catheter reminders would help in preventing cauti . despite this , most of the hospitals in india have not implemented any defined strategy for prevention of cauti . the finding is in agreement with other observers and even in many developed nations many hospitals do not have any protocol to monitor the number of catheterization and duration of catheterization . most of the hcp also felt the need for education regarding basic catheter care for prevention of cauti . thus , despite the need being felt for these measures , the implementation was lacking at various levels including organizational levels . this hopelessness can be improved by educating them and showing them the definite evidences of prevention of cauti following appropriate preventive measures . multifaceted interventions in the form of routine educational trainings to hcp regarding cauti and its prevention , implementation of catheter reminder system to discontinue unnecessary catheters , changes in the hospital policies would definitely help in reducing unnecessary catheter use , decrease the number of catheter days , and thus reduce the incidence of cauti . surveillance of the incidence of cauti on a regular basis in all the hospitals would be desirable to initiate preventive measures as early as required . catheter - associated urinary tract infection is one of the most common health care associated infections . it is largely preventable if indications for catheterization , methods for catheter care and other preventive measures are followed diligently . in the present study , it was seen that though doctors had significantly better awareness than nursing staff regarding reasons for urinary catheter indication and preventive measures , yet it was suboptimal and had a lot of scope of improvement . further , it was observed that cauti was not thought of as a serious problem . all the health care personnel including the doctors should have regular training regarding prevention of cauti , and all efforts should be made by hospital authorities to include prevention of cauti in its high priority list . surveillance of the incidence of cauti would also be helpful in recording the improvement observed as a result of these education based and administrative interventions .

background and aims : catheter - associated urinary tract infection ( cauti ) is one of the most common health care acquired infection encountered in clinical practice . the present study was planned to assess the knowledge and attitude of health care providers regarding the indications for catheterization and methods of preventing cauti.methods:a prospective questionnaire - based survey was done from march 2011 to august 2011 . a structured questionnaire comprising of 41 items related to demographic details of the respondents , their knowledge regarding indications for catheterization and methods of preventing cauti was given to 54 doctors and 105 nurses . the response was evaluated for statistical correlation using a computer software.results:the mean years of experience of the respondents in the health care setup was 6.8 years . only 57% of the respondents could identify all the measures for prevention of cauti . the knowledge regarding the indication for catheterization though suboptimal was significantly better amongst the doctors as compared to nurses.conclusion:the knowledge regarding indication and preventive measures was suboptimal in our study group . there is a tremendous scope of improvement in catheterization practices in our hospital and education induced intervention would be the most appropriate effort toward reducing the incidence of cauti .

microbiological confirmation of bacterial infection is rarely achieved in children with acute lower - respiratory - tract infections ( alrtis ) because of the inability to obtain material from the infection site ( ie , the lung ) . treatment is , therefore , mostly empirical , which irrevocably leads to overtreatment and sometimes undertreatment . sputum induction with nebulized hypertonic saline can help adequately produce sputum in children who are otherwise unable to do so . sputum induction is routinely used to obtain samples for microbial cultures in pediatric illnesses such as cystic fibrosis and tuberculosis . it may also be useful in establishing a causative diagnosis of alrti in otherwise healthy children . the purpose of this study was to determine the effectiveness of sputum induction in obtaining good quality sputum in children with clinically suspected alrti in the everyday , busy general hospital setting . a prospective study in 2 large regional hospitals ( jeroen bosch hospital and mxima medical centre ) in the netherlands was conducted between october 2009 and october 2011 . children aged 6 months to 18 years presenting with suspected alrti were eligible for inclusion . suspected alrti was a clinical diagnosis of the attending physician , with tachypnea and 1 of the following symptoms : dyspnea , fever , cough , and/or abdominal pain . exclusion criteria for participation were a recent severe asthma exacerbation , oxygen saturation 92% , anatomical airway abnormalities , and the use of -blockers or diuretics blood inflammation parameters ( ie , leukocyte count and c - reactive protein [ crp ] level ) , blood culture , and chest x - ray were performed before initiation of the study procedure as part of routine diagnostics . sputum induction was performed with hypertonic saline ( nacl 5.8% ) inhalation using a nebulizing device with oxygen flow . when a patient was unable to expectorate sputum after induction , a sterile suction catheter was used to obtain secretions from the oropharynx . specimens were considered of good quality if < 25 squamous epithelial cells and > 25 leukocytes were present per low - power field ( 10x lens objective ) . sputum samples were cultured for 48 hours using routine microbiological procedures . a concomitant nasopharyngeal lavage sample was also obtained and used for routine bacterial culture . also , infection with influenza a , influenza b , respiratory syncytial virus ( rsv ) , and human metapneumovirus ( hmpv ) was routinely investigated by polymerase chain reaction on nasopharyngeal specimens , if considered necessary by the treating physician , taking into account anticipated seasonal circulation . continuous data were first analyzed for normality using stem - and - leaf plots and quantile - quantile plots , after which either a t - test or mann - whitney u test for nonparametric data was performed . to assess the agreement between sputum and nasopharyngeal bacterial cultures , a simple coefficient was calculated . spss ( version 22.0 ; ibm corp , armonk , ny ) was used for all statistical analyses . a prospective study in 2 large regional hospitals ( jeroen bosch hospital and mxima medical centre ) in the netherlands was conducted between october 2009 and october 2011 . children aged 6 months to 18 years presenting with suspected alrti were eligible for inclusion . suspected alrti was a clinical diagnosis of the attending physician , with tachypnea and 1 of the following symptoms : dyspnea , fever , cough , and/or abdominal pain . exclusion criteria for participation were a recent severe asthma exacerbation , oxygen saturation 92% , anatomical airway abnormalities , and the use of -blockers or diuretics blood inflammation parameters ( ie , leukocyte count and c - reactive protein [ crp ] level ) , blood culture , and chest x - ray were performed before initiation of the study procedure as part of routine diagnostics . sputum induction was performed with hypertonic saline ( nacl 5.8% ) inhalation using a nebulizing device with oxygen flow . when a patient was unable to expectorate sputum after induction , a sterile suction catheter was used to obtain secretions from the oropharynx . specimens were considered of good quality if < 25 squamous epithelial cells and > 25 leukocytes were present per low - power field ( 10x lens objective ) . sputum samples were cultured for 48 hours using routine microbiological procedures . a concomitant nasopharyngeal lavage sample was also obtained and used for routine bacterial culture . also , infection with influenza a , influenza b , respiratory syncytial virus ( rsv ) , and human metapneumovirus ( hmpv ) was routinely investigated by polymerase chain reaction on nasopharyngeal specimens , if considered necessary by the treating physician , taking into account anticipated seasonal circulation . continuous data were first analyzed for normality using stem - and - leaf plots and quantile - quantile plots , after which either a t - test or mann - whitney u test for nonparametric data was performed . to assess the agreement between sputum and nasopharyngeal bacterial cultures , a simple coefficient was calculated . spss ( version 22.0 ; ibm corp , armonk , ny ) was used for all statistical analyses . informed consent was obtained for 126 patients with suspected alrti , but 28 patients ( 22% ) did not complete the study procedure and were excluded in the analysis of the microbiological sputum data ( figure 1 ) . in 3 patients , the final study group consisted of 98 patients , with a median age of 2.6 years ( range = 0.5 - 16.8 years ) . the study and drop - out groups were not significantly different in terms of age ( p = .694 ) , sex ( p = .365 ) , leukocyte count ( p = .725 ) , crp level ( p = .444 ) , or radiological diagnosis ( p = .289 ) . flow diagram of the study group and sputum samples . in 89/98 ( 91% ) patients , only 4 patients were unable to produce sputum after completing the induction procedure ; 5 samples were of poor quality and were , therefore , not processed ( figure 1 ) . mild adverse reactions were reported in 6 patients : cough ( n = 3 ) , vomiting ( n = 1 ) , wheezing ( n = 1 ) , transiently decreased oxygen saturation ( n = 1 ) , and mild epistaxis ( n = 1 ) . no treatment was needed for the adverse reactions ; no serious adverse events were reported . bacterial pathogens were isolated in 22/89 sputum cultures ( 25% ) ; 13 samples grew only 1 pathogen : haemophillus influenzae ( n = 8) , streptococcus pneumoniae ( n = 1 ) , staphylococcus aureus ( n = 2 ) , moraxella catarrhalis ( n = 1 ) , sphingomonas paucimobilis ( n = 1 ) . in 9 samples , 2 bacterial pathogens were isolated : h influenzae + m catarrhalis ( n = 3 ) , h influenzae + streptococcus pneumoniae ( n = 5 ) , and streptococcus pyogenes + pseudomonas aeruginosa ( n = 1 ) . the detection of bacteria in sputum samples was similar in patients with and without radiologically confirmed pneumonia ( 24% vs 27% , p = .483 ) . when comparing the detection of bacteria in sputum cultures with their concomitant nasopharyngeal bacterial cultures ( n = 76 ) , different pathogens were frequently found . in 15 sputum samples , a bacterial pathogen was also found in the concomitant nasopharyngeal culture ; 19 nasopharyngeal cultures yielded bacterial pathogens that were not found in concomitant sputum cultures . in 6 sputum samples , the bacterial pathogen was only detected in sputum and not in the concomitant nasopharyngeal aspirate : moraxella catarrhalis ( n = 3 ) , haemophilus influenzae ( n = 4 ) , and sphingomonas paucimobilis ( n = 1 ) . no significant associations between the sputum and nasopharyngeal bacterial yield were found , with the exception of haemophilus influenzae ( = 0.538 ) . viral ( co)infections ( rsv , hmpv , influenza a , and influenza b ) were found in 35/75 ( 47% ) nasopharyngeal specimens . the viral presence did not differ between the bacterial sputum culture positive and negative groups ( p = .484 ) or between the children with and without radiologically confirmed pneumonia ( p = .87 ) . this study shows that good quality sputum samples could be obtained by an induced sputum collection procedure in our everyday , busy general hospital setting in 91% of children with clinically suspected alrti . our success rate is significantly higher than previously reported , using similar definitions of sputum quality . bacterial pathogens were found in 25% of induced sputum samples . not unexpectedly , haemophilus influenzae , streptococcus pneumoniae , and moraxella catarrhalis were found most frequently . in 29% of positive sputum cultures , the bacterial pathogen was found only in sputum and not in the concomitant nasopharyngeal aspirate culture , suggesting its origin from the lower respiratory tract . these findings support our hypothesis that sputum induction is useful to support etiological diagnoses in every day practice because its yield is significantly higher when compared with blood culture or acute phase serology . the relatively low percentage of bacterial pathogens detected from induced sputum samples is probably a result of the fact that many alrtis were in fact viral infections , as is common in young children . induced sputum not only identifies bacterial pathogens but can also help exclude bacterial infections and , thus , reduce overtreatment with antibiotics when comparing our results with those of a similar study performed by mermond et al , there is a difference in bacterial sputum yield ( 25% vs 50% ) . however , their good quality sputum yield was significantly lower than ours ( 91% vs 25% ) , which was attributed by the authors to methodological problems . another study by lahti et al found evidence for a bacterial infection from induced sputum in 79% of cases but only included patients with radiologically confirmed pneumonia . in our cohort , we found no difference between the presence of common viral and/or bacterial pathogens and radiological diagnosis . because the use of radiology for the diagnosis of alrtis has been a major point of discussion , study inclusion based on clinical suspicion of alrti probably gives a more realistic reflection of everyday practice . even though we found no significant difference in baseline characteristics between the groups , the drop - out percentage after inclusion ( 22% ) is a limitation of our study , but is similar to that in the study by lahti et al , a study that is currently seen as a justification of sputum induction in alrtis . another limitation of our study is that we can not rule out the possibility that , occasionally , the induced sputum did not reflect the etiology of the alrti because we did not compare the induced sputum cultures with material retrieved directly from the lungs by bronchoalveolar lavage or thoracocentesis , which would obviously have been unethical to perform in these non critically ill children . the majority of bacteria found in sputum cultures were also present in the concomitant nasopharyngeal cultures . this could either mean that the sputum sample was contaminated while passing the upper - respiratory tract during expectoration or that an invasive infection by a colonizing bacterial pathogen had taken place , which is a known phenomenon in respiratory tract infections . it is likely that many bacteria cultured from induced sputum during an acute respiratory tract infection play a causative role . in conclusion , we found that sputum induction in children with suspected alrtis in a general hospital setting provides good quality sputum in most cases , with infrequent and only mild adverse events . it can be a useful tool for the general pediatrician to promote pathogen - based treatment of alrtis in everyday clinical practice . iyb contributed to the conception and design ; contributed to acquisition , analysis , and interpretation of data ; drafted the manuscript ; gave final approval ; and agrees to be accountable for all aspects of work ensuring integrity and accuracy . mm contributed to the acquisition and interpretation of data ; critically revised the manuscript ; gave final approval ; and agrees to be accountable for all aspects of work ensuring integrity and accuracy . rvg contributed to acquisition of data ; critically revised the analysis and first drafts of the manuscript ; could not give final approval ( deceased ) . mhvl contributed to acquisition and interpretation of data ; critically revised the manuscript ; gave final approval ; and agrees to be accountable for all aspects of work ensuring integrity and accuracy . mh contributed to analysis of data ; critically revised the manuscript ; gave final approval ; and agrees to be accountable for all aspects of work ensuring integrity and accuracy . aw contributed to the conception and design ; contributed to interpretation ; critically revised the manuscript ; gave final approval ; and agrees to be accountable for all aspects of work ensuring integrity and accuracy . pcw contributed to the conception and design ; contributed to interpretation ; critically revised the manuscript ; gave final approval ; and agrees to be accountable for all aspects of work ensuring integrity and accuracy . edv contributed to the conception and design ; contributed to acquisition , analysis , and interpretation of data ; codrafted the manuscript ; critically revised the manuscript ; gave final approval ; and agrees to be accountable for all aspects of work ensuring integrity and accuracy .

we prospectively studied the feasibility and effectiveness of sputum induction in obtaining good quality sputum and its subsequent bacterial yield in children with clinically suspected acute lower - respiratory - tract infection ( alrti ) . good quality sputum was collected in 89/98 ( 91% ) patients . sputum cultures revealed 1 bacterial pathogens in 22 cases ( 25% ) . adverse events were infrequent and mild ( 6% ) . sputum induction is feasible in young children and leads to an increased number of etiological diagnoses of alrti .

the two most common forms of senile dementia , alzheimer s disease ( ad ) and vascular dementia ( vad ) , share many of the same clinical signs and symptoms . both diseases are characterized by cognitive decline , functional deterioration and neuropsychiatric symptoms that may present as behavioral alterations.1 vascular disease risk factors such as hypertension , diabetes mellitus , obesity , hypercholesterolemia and vascular changes in the white matter of the brain may not only be present in vascular dementia , but also in alzheimer s disease.2,3 these shared features always cause difficulties for the differential diagnosis of these two diseases , especially for the insidious onset of subcortical vascular dementia ( svad ) due to small - vessel disease , which leads to lacunar infarcts and the demyelination of white matter and deep subcortical gray and white matter . although it is generally accepted that episodic memory impairment , dyscalculia , agnosia , apraxia , and aphasia are more prominent in ad and that executive / attentional processing , semantic memory and visuospatial / perceptual function are more impaired in vascular dementia , especially in patients with svad , there is a lack of a uniformly identified cognitive , clinical , imaging and pathological profile typical of svad.4,5 ideomotor limb apraxia , which is the most common subtype of apraxia , is the disturbance of planning and the execution of motor activity without any dysfunction of the motor or sensory nervous system or the lack of understanding and motivation.6 dysfunction has been conventionally localized on the left fronto - parieto - temporal cortex , which has been implicated in processing movements of relatively high complexity , planning and sequencing movements . bihemispheric lesions of the deep white matter , the commissural tracts or the basal ganglia have also been reported as a cause of ideomotor apraxia.710 these reports suggest that an interruption in the association or commissural tracts of relative cortical areas can also cause the symptom of ideomotor apraxia . it is still accepted as a diagnostically indicative sign for alzheimer s disease.11 a small study reported that the frequency of apraxia in mild cognitive impairment patients was not different from that of the age - matched healthy population . retrospective analyses have shown that only mci patients who subsequently proceeded to a clinical diagnosis of ad were significantly slower than controls in completing sequential movement tasks despite unimpaired performance.12 these results suggested that the absence of apraxia can be one of the clinical indicators for differentiating mci from the other types of dementia . in this study , we hypothesized that presence of apraxia may be an indicator to differentiate svad and mci patients from mild to moderate ad patients and we investigated the difference in ideomotor apraxia frequency amongst ad , svad and mci patients and the relationship between the dementia severity and the presence of ideomotor apraxia in each group of cognitive disease patients . the patients data were retrospectively gathered from two neurodegenerative diseases units ( eskiehir osmangazi university medical faculty and marmara university medical faculty neurology clinics ) , which were participating in the turkuaz alzheimer working ( ta ) group . this turkish web - based dementia registry includes neuropsyhiatric and cognitive scales that are commonly used for dementia assessment and is currently being used in 18 dementia referral centers across turkey.13 in this registry , patients are recorded with their detailed neuropsychiatric assessments including the neuropsychiatric inventory ( npi ) . ninety - six consecutive ad , 72 subcortical svad and 84 mci patients were recruited from the web - based data of the two centers . the ad diagnosis was based on the dsm iv - tr and ninds - adrda criteria.11 svad patients met the criteria for vascular dementia also proposed by the dsm iv - tr and ninds - airen . all of the patients showed at least two of the following focal neurological symptoms or signs : facial palsy , dysarthria , dysphagia , pathologic laughing or crying , weakness or sensory loss of limbs , hyperactive deep tendon reflexes , extensor plantar responses , rigidity of limbs , axial rigidity , bradykinesia , hemiplegic gait , stooped posture , short - step gait , festinating gait , shuffling gait , decreased arm swing while walking , and multi - step turning . these changes were defined by high signal intensity ( hsi ) on t2-weighted or flair images corresponding to grade 3 of the fazekas criteria.14 brain mri scans confirmed the absence of structural lesions such as intracranial hemorrhage , tumor , traumatic brain injury , or hydrocephalus . the diagnosis of mci was consistent with the criteria proposed by petersen and colleagues.15 all of the ad patients were in the mild to moderate stage of the disease according to the global deterioration scale / functional assessment staging system.16 apraxia was examined using the apraxia screening test of tulia ( ast ) , which has high diagnostic accuracy ( 95% sensitivity and 100% specificity ) in stroke.17 the ast requires the performance of 12 gestures in two domains : ( 1 ) imitation including one meaningless gesture , one intransitive ( communicative ) gesture and five transitive ( tool - related ) gestures and ( 2 ) pantomime including two intransitive gestures and three transitive gestures . the performance was dichotomously ( fail : 0 , pass : 1 ) scored by the investigators immediately after the patient s performance . the scoring method is described in detail elsewhere.17 a validated turkish version of the mini - mental status examination ( mmse ) was used to evaluate the cognitive status.18 the clinical dementia rating scale was applied to all of the patients for staging the severity of the dementia.19 spss 15 ( spss inc , chicago , il , usa ) was used for statistical analyses . continuous variables were expressed as mean sd and were compared between the patients with and without prior stress tests using the one - way anova test with the post - hoc tukey test . categorical variables were expressed as frequency percentages and were compared between the groups using the chi - square test or the fisher exact test as appropriate.20 statistically significant level was accepted as 0.05 and it was two - sided . no significant differences were found between the ad and svad groups for each demographic group . there were no significant differences amongst the three groups in terms of sex ratio and age . compared to the ad and svad groups , the mci group had significantly higher mmse scores and lower disease duration and cdr ( p < 0.001 , for each variable ) ( table 1 ) . although mmse and cdr scores were better in the svad group than in the ad group , the difference was found to be insignificant ( p > 0.05 , for each variable ) . apraxia was significantly more frequent in ad disease patients ( 32.3% , n = 31 ) than both svad ( 16.7% , n = 12 ) ( x = 4.787 at df = 1 , p = 0.0287 ) and mci ( 4.8% , n = 4 ) ( x = 18.778 at df = 1 , p < 0.005 ) patients . the frequency of apraxia was also significantly higher in svad patients than the mci patients ( x = 6.545 at df = 1 , p = 0.0105 ) . when we compared the groups according to the apraxia scores , we observed that ad patients had significantly lower apraxia scores than both of the svad and mci patients ( odds ratio : 5.04 [ 95% confidence interval { ci } : 1.8411.73 ] , p < 0.05 and odds ratio : 4.17 [ 95% ci : 2.679.87 ] , p < 0.001 , respectively ) . in addition , a significant difference was found between the svad and mci patients in terms of apraxia scores ( odds ratio : 3.12 [ % 95 ci : 1.125.71 ] , p < 0.05 ) ( figure 2 ) . although a large number of studies have revealed many aspects of the pathophysiology of ad , no strongly specific biological or laboratory markers for this disease have been detected . this paucity is a possible reason for low diagnostic accuracy , especially in the early stages of the disease in which the disease is often confused with other forms of dementia , particularly vascular dementia.21,22 with the lack of a specific diagnostic marker , the diagnosis is still based primarily on clinical findings . the disease progression over time leads to involvement of other cognitive domains in addition to memory , including visuospatial function and praxis , language , and executive skills.23 in our study with ad and svad patients with similar disease duration and dementia severity scores , apraxia seems to be a significant differential marker between these diseases , but it must be noted that svad patients can also have significant ideomotor apraxia . therefore , apraxia , unaccompanied by other signs of dementia , is a weak differential diagnosis parameter for ad and svad . although apraxia is accepted as one of the diagnostic clinical variables for ad , there are a few studies about its diagnostic value.2428 in one of the early studies , kramer et al25 investigated the frequency of apraxia with agnosia and aphasia in groups of cortical ( probable ad ) dementias and a heterogeneous group of subcortical dementias ( parkinson s disease and normal pressure hydrocephalus ) ; they reported that only aphasia had been significantly more frequent in cortical dementias and had a very low diagnostic sensitivity , specificity and total predictive value for all three symptoms . these authors concluded that cortical and subcortical dementias can not be reliably dissociated on the basis of apraxia , aphasia or agnosia . in a similar recent report assessing the occurrence of ideomotor apraxia in ad and huntington disease patients , the authors concluded that ideomotor apraxia was a common sign in both groups of patients . furthermore , they reported that significantly more huntington disease patients had been classified as apraxic according to the hands and finger imitation and pantomimic subtypes than ad patients.26 however , our study found that apraxia was more frequent in ad than the svad patients . this inconsistency between our results and those of the other subcortical dementia studies could be the result of the difference in the pathogenesis and lesion localization of neurodegenerative and vascular subcortical dementias . for example , in huntington disease , prominent heterogeneously cortical dysfunction overlapping with the brain areas of praxis function , even in early stages of the disease , can be a different pathological process from svad.2931 as the authors of the huntington disease study concluded , the cortical degeneration during the disease process may contribute highly to the development of apraxia.26 previous studies have reported that thalamic and basal ganglia vascular lesions were more associated with apraxia.32 however , our svad group had heterogeneous subcortical lesion localization , and the basal ganglia lesions were not separately investigated in the present study . this approach could be the reason for the difference between our results and those of previous neurodegenerative dementia studies . significantly lower apraxia scores in ad patients than in svad patients with similar disease duration may suggest that praxis function is affected earlier and more severely in the neurodegenerative process . without any pathologically proven diagnosis , however , our study is insufficient to make this conclusion . in our study , the frequency of apraxia in svad patients ( 16.7% ) was significantly higher than in mci ( 4.8% ) patients . although there is insufficient data in the literature , the frequency of apraxia in subcortical stroke patients was reported to be 33.3% by a previous study.33 the authors of that study used a different apraxia test , the movement imitation test , to assess the patients , and they included all of the stroke patients regardless of the presence of dementia.34 this methodological difference could explain the frequency disparity between our results and those of that study . these findings may suggest a methodological problem in the assessment methods for apraxia or the difference between the assessed groups of patients between the studies . for example , apraxia is a well - recognized diagnostic sign in ad , but the exact frequency is still controversial . the frequency has a wide range , from 33% to 77%.35,36 the assessment tests used in the studies , the stage of illness , disease severity , and the psychological status of patients can influence the results we used a screening test called the apraxia screening of tulia ( ast ) that comprises 12 items extracted from the more comprehensive test of upper limb apraxia , tulia by item reduction analysis.17 the ast is a simple bedside test that was previously validated for stroke and parkinson s disease patients with high clinimetric standards.17,37 the validation for both vascular and neurodegenerative disease patients was the reason for selecting this test for our study . although a high diagnostic sensitivity and specificity for the presence of apraxia in stroke and parkinson s disease patients have been reported , the reliability of this test in dementia may be questionable . reliable results of screening for apraxia in multiple sclerosis have been reported in a recent study.38 however , it must be kept in mind that this test is only a fast screening test and does not allow for the subclassification of limb apraxia . this can also be a limitation for our results , but it should be noted that all the data have been recorded by specialists in cognitive disorders . besides the study gives data only from the turkish population and the results absence of a control group that could give information about the apraxia in a normal population , may be another limitation for the study . but we believe that the significant difference for mci patients seems to be an apperant indicator . in this study , we investigated the frequency and severity of ideomotor apraxia amongst three different cognitive problems ( ad , svad and mci ) in addition to whether it is a good clinical marker to differentiate these diseases . although ideomotor apraxia was observed more commonly and was more severe in the ad patients than in the svad and mci patients , this significant difference was also observed between the svad and mci patients . these results suggest that , contrary to widespread belief , it is not completely accurate to state that apraxia and cortical dementias are associated but do not include subcortical dementias . however , the significant difference between both of the dementia groups and mci patients suggests that the absence of apraxia can only be a predictor for the diagnosis of mci and that apraxia can be an additional supporting sign for the existing diagnostic criteria .

although ideomotor limb apraxia is considered to be a typical sign of cortical pathologies such as alzheimer s disease ( ad ) , it has been also reported in subcortical neurodegenerative diseases and vascular lesions . we aimed to investigate the difference between ad , subcortical vascular dementia ( svad ) and mild cognitive impairment ( mci ) patients by means of ideomotor limb apraxia frequency and severity . ninety - six ad , 72 svad , and 84 mci patients were assessed with the mini - mental status examination ( mmse ) , clinical dementia rating ( cdr ) and the apraxia screening test of tulia ( ast ) . apraxia was significantly more frequent in the ad patients ( 32.3% ) than in both of the svad ( 16.7% ) and mci ( 4.8% ) patients . the frequency of apraxia was also significantly higher in svad patients than in mci patients . ad patients had significantly lower apraxia scores than both svad and mci patients . in addition , a significant difference was found between svad and mci patients in terms of apraxia scores . these results suggest that the widespread belief of the association between apraxia and cortical dementias is not exactly correct . the significant difference between both of the dementia groups and the mci patients suggests that the absence of apraxia can be an indicator for mci diagnosis .

ewing s sarcomas is a rare primitive neuroectodermal tumour ( pnet ) which has an annual incidence of 2.9 /million population in usa 1jeffery toretsky et al ( 2008 ) they are very uncommon in african and asian population . it is commonly associated with reciprocal translocation between chromosome 11 and 12 t ( 11:12 ) or less frequently the t(21;22)(q22;ql 2 ) translocation . it is highly aggressive tumor which is pas- and cd99 ( mic2)-positive relatively few variant translocations have been reported in primary ewing s sarcomas ( es ) . we are hereby presenting a case of extra skeletal soft tissue ewing s sarcoma with unusual translocation of chromosome t ( 4 , 22 ) ( q35 , q12 ) . patient presented to us in advanced stage with pulmonary metastasis and lower limb neurological deficit . relatively few variant translocations have been reported in primary ewing s sarcomas ( es ) . to date , 13 variants of the ews fusion gene have been described in literature . they are extremely rare , representing altogether < 1% of the cases 23we are reporting a case of a variant simple translocation of chromosome t ( 4 ; 22 ) ( q35;1 2 ) . in our exhaustive literature search we could find only one case of complex translocation which was identified in a dysmorphic 15-year - old girl , t ( 4:11 ; 22)(q21 ; q24 ; q12 ) reported by squire jet al ( 1993 ) . this type of translocation is extremely rare and has not been reported in the literature so far . clinical presentation was initial indolent but later at the time patient presented to our institute he had developed pulmonary metastases and paraplegia due to involvement of spine . our case report will provide new insight about rare translocation types in ewing s sarcoma and understand their clinical behavior of ewing s sarcoma with such type of translocation . ewing sarcoma ( es)/primitive neuroectodermal tumor ( pnet ) of bone is the second most common primary malignant bone cancer in children and adolescents , the extra skeletal variety has been reported in adults . it is commonly associated with reciprocal translocation between chromosome 11 and 12 t ( 11:12 ) or less frequently the t ( 21;22)(q22;ql 2 ) translocation . the median age at the time of diagnosis is 15 years and there is a male predilection of 1.5/11 . the demonstration of translocation by karyotype analysis with short term culture and metaphase spreads is labor intensive , time consuming and requires fresh tissue specimen . hence the advent of florescence insitu hybridization technique and reverse transcriptase polymerase chain reaction helps in rapid diagnosis of translocations . 1 ) presented to our hospital with history of swelling in right distal thigh associated and dull aching pain which started after a trivial trauma about three years back . he was seen by his primary care physician who has diagnosed the condition as soft tissue tumor for which patient underwent 4 cycles of chemotherapy followed by resection of tumor . patient remained asymptomatic in the subsequent year but unfortunately developed recurrence of swelling in same region that gradually increased in size . when he presented to our institution with the swelling over right distal thigh ( fig . 2 ) he had developed low backache and complete weakness of both lower limbs . at the time of examination patient had a large irregular shaped swelling measuring about 352520 cm at distal half of right thigh(fig . the skin over swelling appeared shiny and stretched shiny with engorged veins movements of knee was restricted . x ray pelvis and spine showed multiple lytic skeletal metastases . chest x ray ( fig . the core needle biopsy from tumor under microscope revealed tumor cells predominantly arranged in sheets , cells round to oval with centrally placed hyper chromatic nucleus and scanty cytoplasm , rosettes seen at places ( fig . 7 ) showed variant translocation karyotype 46 , xy , t ( 4 , 22 ) ( q35 , q12 ) . since the patient presented to us in an advanced state it was decided to start palliative treatment . clinical photo of patient with swelling over distal aspect of right thigh swelling measuring almost 352520 , skin appears stretched and dilated veins are vible . previous surgery scar x ray of right femur showing soft tissue mass with irregeular perisosteal reaction ap and lateral view of spine showing pathological compression fracture d11(kyphosis ) with widespread mets microscopy showing tumor cells predominantly arranged in sheets , cells round to oval with centrally placed hyperchromatic nucleus and scanty cytoplasm , rosettes seen at places cytogenetics showing variant translocation 46,xy , t(4,22 ) ( q35,q12 ) immunohistocytochemistry positive for cd99 tumors with the type 1 transcript ( ews - fly1 ) are associated with a better prognosis than those with other transcripts . the common genetic alteration in es is a translocation between the ews gene on chromosome 22 and various genes of the ets family of transcription factors . alternatively , chromosome 22 is found as partner in 10% of the cases . to date , 13 variants of the ews fusion gene have been described , involving many chromosomes : 2 , 6,7,9,11,12 17 and 22 . previously only one case of complex translocation was identified in a dysmorphic 15- year - old girl , t ( 4 ; 11 ; 22 ) ( q21 ; q24 ; q12 ) . our patient was initially treated somewhere outside by the time he presented to our institute he had a irregular swelling over right distal thigh , restricted movements of knee , feeble peripheral pulse and pure motor deficit . what is unusual about this case is from the time patient noticed the swelling and was treated by his primary care physician the tumor behaved indolent . patient has lost the details about the details of chemotherapy before surgical excision of tumor and unfortunately could not be obtained . the earliest symptom is pain associated with swelling which progressed to form large tumors in soft tissues . imaging modalities like x ray , ct , mri , isotope scan will help in diagnosis and detecting distant metastasis . the definitive diagnosis is made by biopsy , providing sufficient material for conventional histology , immune histochemistry and molecular biology . es is a small blue round - cell tumor , pas- and cd99 ( mic2)-positive . apart from various prognostic factors recently it has been reported that the type of ews / flil fusion transcript is prognostically relevant , as patients with the type l ews / flil fusion transcript appear to have increased disease - free survival over that of patients with other fusion transcript types 6 . ewing s sarcoma is a rare primary malignant bone tumor which is often indistinguishable from primary neuroectodermal tumors by histopathology . clinically both these type of tumors behave same hence the clinical management remains the same with adjuvant chemotherapy , excision and radiotherapy being the cornerstone of treatment . karyotype and insitu hybridization helps to detect the type of chromosomal translocation which can predict the overall prognosis of the tumor . we have reported a very unusual variant simple translocation of chromosome t ( 4 ; 22 ) ( q35 ; 12 ) . this patient had widespread metastasis with a complete paraplegia due to involvement of spinal cord . since patient presented in grade 4 stage at the time of presentation to our institute this type of translocation further study is required to evaluate the prognosis of ewing s sarcoma in patients with this type of unusual translocation . it is imperative to conduct appropriate immunohistocytochemistry to confirm this type of translocation when patient presents with unusual clinical presentation .

introduction : ewing s sarcomas is a rare primitive neuroectodermal tumour ( pnet ) which has an annual incidence of 2.9 /million population in usa 1jeffery toretsky et al ( 2008 ) they are very uncommon in african and asian population . it is commonly associated with reciprocal translocation between chromosome 11 and 12 t ( 11:12 ) or less frequently the t(21;22)(q22;ql 2 ) translocation . it is highly aggressive tumor which is pas- and cd99 ( mic2)-positive relatively few variant translocations have been reported in primary ewing s sarcomas ( es).case report : we are hereby presenting a case of extra skeletal soft tissue ewing s sarcoma with unusual translocation of chromosome t ( 4 , 22 ) ( q35 , q12 ) . patient presented to us in advanced stage with pulmonary metastasis and lower limb neurological deficit . relatively few variant translocations have been reported in primary ewing s sarcomas ( es ) . to date , 13 variants of the ews fusion gene have been described in literature . they are extremely rare , representing altogether < 1% of the cases 23we are reporting a case of a variant simple translocation of chromosome t ( 4 ; 22 ) ( q35;1 2 ) . in our exhaustive literature search we could find only one case of complex translocation which was identified in a dysmorphic 15-year - old girl , t ( 4:11 ; 22)(q21 ; q24 ; q12 ) reported by squire jet al ( 1993).conclusion : this type of translocation is extremely rare and has not been reported in the literature so far . clinical presentation was initial indolent but later at the time patient presented to our institute he had developed pulmonary metastases and paraplegia due to involvement of spine . our case report will provide new insight about rare translocation types in ewing s sarcoma and understand their clinical behavior of ewing s sarcoma with such type of translocation .

a 60-year - old man has been in your intensive care unit with septic shock for 5 days and he has required a norepinephrine infusion for the entire time . frank v ritacca , carmine simone and randy wax despite advances in providing care for patients with septic shock , mortality rates remain unacceptably high . exogenous corticosteroids have potent anti - inflammatory effects and their use for modulation of the host response in septic shock has been debated for decades . two meta - analyses have suggested that high - dose steroids are not beneficial in patients with septic shock . we believe there are recent data showing that low - dose corticosteroids hasten discontinuation of vasopressors in refractory septic shock , and may improve outcome . demonstration of an intact hypothalamic - pituitary - adrenal axis response has been associated with reduced mortality in septic shock . corticosteroids can regulate the synthesis and function of catecholamines and their receptors , which in turn control vascular tone and organ perfusion . proinflammatory cytokines released in sepsis alter steroid responsiveness , leading to the deleterious effects of catecholamine dysfunction and refractory hypotension . downregulation of catecholamine receptors occurs with prolonged use of exogenous catecholamines and this may be reversed with administration of low - dose steroids . restoring endogenous regulation of vasomotor tone would be desirable to preserve regional regulation of perfusion . three recent clinical trials have provided encouraging results for the use of corticosteroids in septic shock ( table 1 ) . patients were treated with corticosteroids at lower doses and for a longer interval than in previous trials . showed that patients receiving low - dose steroids had a significantly higher rate of shock reversal ( stable blood pressure without fluid boluses or vasopressors ) . the treatment effect was present irrespective of hypothalamic - pituitary - adrenal axis function as measured by an adrenocorticotrophic hormone ( acth ) stimulation test . briegel et al . similarly found that low - dose corticosteroids could hasten independence from vasopressor support . although no mortality benefits were found , increased rates of shock reversal may imply decreased resource use ( e.g. shorter length of stay in the intensive care unit ) and complications ( e.g. catheter - related infections ) . data published in abstract form from a multicenter trial testing low - dose corticosteroid and mineralocorticoid support led to a relative risk reduction of almost 30% in patients with septic shock . the survival benefit of combination therapy was significant only in patients with blunted response to acth stimulation . however , this may be due to a smaller number of patients in the normal response group . finally , one retrospective study suggests that low - dose corticosteroids may reduce post - traumatic stress disorder and improve health - related quality of life in survivors of septic shock . although exciting developments in targeted drug therapy for sepsis have occurred recently , supportive care remains key to maximizing survival in patients . even if subsequent studies do not confirm a mortality reduction , ' fewer days of vasopressor dependence ' may itself be an important outcome . given that the patient described for this debate appears to have been adequately treated for infection , repair of sepsis - induced dysregulation of vasomotor tone using low - dose corticosteroids is reasonable and appropriate . katherine g craig and keith r walley the debate surrounding the use of corticosteroids in septic patients has continued for over 30 years . two meta - analyses in the mid-1990s seemed to put an end to the controversy . the conclusions drawn from these works were that corticosteroids provided no benefit to patients with septic shock and that corticosteroids may actually cause harm , as evidenced by a slight increase in overall mortality . the debate has recently been re - opened by several small , prospective , randomized , placebo - controlled trials . a study by bollaert et al . , in which septic patients requiring catecholamines were randomized to receive hydrocortisone ( 100 mg intravenously three times a day for 5 days ) or placebo , found a significant reduction in the time it took to reverse shock , and a trend towards improved survival . while the results of this trial were impressive , care must be taken not to overinterpret the results ; it was a small clinical trial with only about 20 patients in each arm , and there was a relatively high mortality rate in the placebo arm ( 63% ) for patients with septic shock . in a similar small trial by briegel et al . , septic shock patients were randomized to receive either a placebo or hydrocortisone ( 100 mg intravenous bolus ) , followed by continuous infusion until septic shock resolved . the length of time for which vasopressor support was required was significantly reduced , and measures such as mean arterial pressure and systemic vascular resistance index were increased in patients treated with steroids . in addition , there were trends toward earlier reversal of organ dysfunction . it may be germane to recognize that all benefit of immunomodulatory therapy in adequately powered , randomized , controlled trials is confined to the most severely ill . this does not fit with the patient described in the aforementioned scenario . in view of conflicting older , yet strong , evidence ( that high - dose steroids are not beneficial ) and newer , yet preliminary , studies ( that suggest low - dose steroids are beneficial ) , the question becomes one of whether steroid - induced reversal of vasopressor support confers any outcome benefits . the patient described in the present scenario is improving in all aspects of organ failure , but remains catecholamine dependent . a thorough examination and review of his management needs to be conducted to ensure no reversible cause of hypotension can be determined . there is ongoing debate in the literature as to the usefulness of this corticotropin stimulation test in so - called ' relative adrenal insufficient ' patients , although it may be of prognostic significance . a recent study by schroeder et al . found low basal plasma cortisol levels and diminished responses to corticotropin - releasing hormone in patients that died of septic shock as compared with those who survived . , however , found an elevated basal cortisol level ( 34 g / dl ) and a poor response to corticotropin ( e.g. 9 g / dl elevation at 30 or 60 min ) to be a predictor of the poorest survival in patients with sepsis . at this point in time there is not sufficient evidence to guide clinical practice . we therefore do not advocate use of steroids in this clinically improving patient without another indication . we must be cautious in our enthusiasm to try new therapies as history provides many examples of promising small clinical trials that have not held up to the test of time and larger , multicentered trials . in view of conflicting older , yet strong , evidence ( that high - dose steroids are not beneficial ) and newer , yet preliminary , studies ( that suggest low - dose steroids are beneficial ) , the question becomes one of whether steroid - induced reversal of vasopressor support confers any outcome benefits . the patient described in the present scenario is improving in all aspects of organ failure , but remains catecholamine dependent . a thorough examination and review of his management there is ongoing debate in the literature as to the usefulness of this corticotropin stimulation test in so - called ' relative adrenal insufficient ' patients , although it may be of prognostic significance . a recent study by schroeder et al . found low basal plasma cortisol levels and diminished responses to corticotropin - releasing hormone in patients that died of septic shock as compared with those who survived . , however , found an elevated basal cortisol level ( 34 g / dl ) and a poor response to corticotropin ( e.g. 9 g / dl elevation at 30 or 60 min ) to be a predictor of the poorest survival in patients with sepsis . at this point in time there is not sufficient evidence to guide clinical practice . we therefore do not advocate use of steroids in this clinically improving patient without another indication . we must be cautious in our enthusiasm to try new therapies as history provides many examples of promising small clinical trials that have not held up to the test of time and larger , multicentered trials . frank v ritacca , carmine simone and randy wax applying data from trials using high - dose steroids is inappropriate and leads to therapeutic nihilism . life - saving therapy , such as low - dose beta - blockers in severe cardiomyopathy , met similar resistance because of poor experiences with identical drugs given in higher doses . a normal corticotropin stimulation test result can not exclude benefit of low - dose corticosteroids . although this patient is not ' most severely ill ' , catecholamine receptor effects may be more important than the immunomodulatory effects of this therapy . katherine g craig and keith r walley while the foundations of the pro / con debates are remarkably similar , the resulting recommendations are not . dr ritacca and colleagues suggest that " appropriate supplementation of corticosteroids [ be ] part of the regimen of supportive care " . first , with the level of evidence currently available it must be recognized that the use of steroids in sepsis , while promising , is still experimental , and should not be given the same status as routine measures of supportive care . second , even if a physician makes a conscious decision to try steroids , there are again no data to suggest a dose or timing for ' appropriate supplementation ' . we urge restraint and recognition of the potential adverse side effects of , and lack of clear evidence for , steroid therapy in sepsis .

decision - making in the intensive care unit is often very difficult . although we are encouraged to make evidence - based decisions , this may be difficult for a number of reasons . to begin with , evidence may not exist to answer the clinical question . second , when there is evidence it may not be applicable to the patient in question or the clinician may be reluctant to apply it to the patient based on a number of secondary issues such as costs , premorbid condition or possible complications . finally , emotions are often highly charged when caring for patients that have a significant chance of death , and care - givers as well as families are frequently prepared to take chances on a therapy whose benefit is not entirely clear . steroid use in septic shock is an example of a therapy that makes some sense but has conflicting support in the literature . in this issue of critical care forum , the two sides of this often heated debate are brought to the forefront in an interesting format .

bedding can be effectively used as a floor covering to absorb moisture and provide a soft surface . some studies have used the preference test to investigate the bedding preference in horses and ponies [ 3 , 4 , 6 ] . these studies have reported that the animals preferred straw over shavings and paper as the material for bedding . in japan , rice straw has frequently been used as bedding , and in some cases , used straw bedding is often reused after drying in the sunshine . ( 2004 ) reported that drying the bedding in sunshine was not sufficient to completely clean it from urine ammonia . moreover , rice straw has been unobtainable in japan and imported from foreign countries , and the law relating to excreta of livestock was proclaimed . therefore , it is required to use a new reusable material for bedding . in this study , the husk and fiber of coconuts , which are wasted during the production of coconut milk , oil , etc . from coconut , were used as bedding materials . we investigated the effect of these bedding materials and that of the commonly used bedding materials , namely , straw and sawdust , on the welfare of stable horses by observing their resting behavior . twenty horses ranging from 3 to 21 years of age were used at the equine research institute of the japan racing association , utsunomiya , japan . the breeds of horses were thoroughbred ( n=8 ) , anglo - arab ( n=3 ) , selle francais ( n=3 ) , thoroughbred mixed breed ( n=2 ) , and dutch warmblood , haflinger , hannover , and westfalen ( n=1 each ) . the horses were kept individually in box stall which floor was concrete ( 2.6 m 3.6 m ) . they were ridden from 7:00 to 9:00 or were turned out into a pasture or a paddock from 09:00 to 13:00 . each horse received a pelleted concentrate and oat mixture and cut alfalfa hay at 05:30 and 15:30 , and long timothy hay at 12:00 as a maintenance ration . the following 4 types of bedding materials were used : straw , sawdust , coconut husk ( husk ) , and coconut fiber ( fiber ) . the husk was made of crushed coconut husk and the fiber bedding was prepared with husk bedding covered with fiber from coconut husk . three weeks before the behavioral observation , the bedding was changed to the experimental bedding . five horses were allocated to each bedding condition . in every bedding condition , the box stalls were cleaned and their faeces were removed once daily . dirty straw was replaced with new straw daily , and the other beddings were replaced with new bedding once a week . the behavior of each horse was recorded by video camera for 3 days and was continuously sampled from 17:00 to 05:00 . the box stalls were illuminated during the observation period . the total duration ( minutes per a day ) , the number of bouts ( times per a day ) , the mean and the maximum duration of bouts ( minutes ) in standing rest , sternal lying , and lateral lying were calculated . the data in each behavioral category were analysed with the kruskal - wallis test , and a post hoc steel - dwass test was used to investigate the differences among beddings . twenty horses ranging from 3 to 21 years of age were used at the equine research institute of the japan racing association , utsunomiya , japan . the breeds of horses were thoroughbred ( n=8 ) , anglo - arab ( n=3 ) , selle francais ( n=3 ) , thoroughbred mixed breed ( n=2 ) , and dutch warmblood , haflinger , hannover , and westfalen ( n=1 each ) . the horses were kept individually in box stall which floor was concrete ( 2.6 m 3.6 m ) . they were ridden from 7:00 to 9:00 or were turned out into a pasture or a paddock from 09:00 to 13:00 . each horse received a pelleted concentrate and oat mixture and cut alfalfa hay at 05:30 and 15:30 , and long timothy hay at 12:00 as a maintenance ration . the following 4 types of bedding materials were used : straw , sawdust , coconut husk ( husk ) , and coconut fiber ( fiber ) . the husk was made of crushed coconut husk and the fiber bedding was prepared with husk bedding covered with fiber from coconut husk . three weeks before the behavioral observation , the bedding was changed to the experimental bedding . five horses were allocated to each bedding condition . in every bedding condition , the box stalls were cleaned and their faeces were removed once daily . dirty straw was replaced with new straw daily , and the other beddings were replaced with new bedding once a week . the behavior of each horse was recorded by video camera for 3 days and was continuously sampled from 17:00 to 05:00 . the box stalls were illuminated during the observation period . the total duration ( minutes per a day ) , the number of bouts ( times per a day ) , the mean and the maximum duration of bouts ( minutes ) in standing rest , sternal lying , and lateral lying were calculated . the data in each behavioral category were analysed with the kruskal - wallis test , and a post hoc steel - dwass test was used to investigate the differences among beddings . there was no significant difference among beddings in the standing rest and the sternal lying ( tables 1 and 2table 1.effects of bedding materials on the standing rest in stabled horsebedding materialsstrawsawdusthuskfibertotal duration ( minutes)381.6 88.7437.8 75.7409.8 75.7443.8 151.2number of bout20.7 4.824.1 4.926.8 9.816.7 5.8mean duration of bout ( minutes)18.4 11.818.2 3.715.3 7.526.6 8.5maximum duration ( minutes)93.0 59.0116.4 78.5102.8 43.393.9 husk was made of crushed coconut husk and fiber was prepared with husk bedding covered with fiber from coconut husk.table 2.effects of bedding materials on the sternal lying in stabled horsebedding materialsstrawsawdusthuskfibertotal duration ( minutes)38.6 33.119.4 20.169.6 39.419.1 28.4number of bout2.8 2.61.7 1.56.1 3.61.7 1.4mean duration of bout ( minutes)13.8 7.911.6 5.811.3 4.811.0 8.3maximum duration ( minutes)31.5 27.913.6 9.828.7 10.213.4 husk was made of crushed coconut husk and fiber was prepared with husk bedding covered with fiber from coconut husk . ) . significant differences in the total duration , the number of bouts , and the mean and the maximum duration of bouts in the lateral lying were observed among beddings ( p<0.05 ) . the values of the means of the total duration , the number of bouts , and the mean and the maximum duration of bouts in the lateral lying when husk was used as bedding were greater than those when sawdust were used as bedding ( p<0.05 , table 3table 3.effects of bedding materials on the lateral lying in stabled horsebedding materialsstrawsawdusthuskfibertotal duration ( minutes)4.0 5.60.02 0.0510.1 10.91.5 2.5number of bout1.6 1.80.1 0.153.4 0.90.3 0.5mean duration of bout ( minutes)2.5 1.10.3 0.013.0 0.94.4 2.5maximum duration ( minutes)4.4 3.90.07 0.155.1 2.23.8 husk was made of crushed coconut husk and fiber was prepared with husk bedding covered with fiber from coconut husk . numbers with different letters are statistically different ( a , b : p<0.05 ) . ) . husk was made of crushed coconut husk and fiber was prepared with husk bedding covered with fiber from coconut husk . husk was made of crushed coconut husk and fiber was prepared with husk bedding covered with fiber from coconut husk . husk was made of crushed coconut husk and fiber was prepared with husk bedding covered with fiber from coconut husk . numbers with different letters are statistically different ( a , b : p<0.05 ) . resting behavior when husk and fiber bedding were used was not different from that in straw treatment . the resting behavior indicates that these new bedding materials would be as usable as straw . however , lateral lying was observed less frequently with sawdust , which is a commonly used bedding material , than when husk was used as bedding . the lateral lying is said to be related to sleeping , which is a positive indicator of welfare in stabled horses . it is also reported that horses preferred straw bedding over shavings in the preference tests . the less frequent observation of the lateral lying with sawdust indicates that sawdust used as bedding material decrease the welfare of stabled horses . in this study , replacing dirty bedding with new bedding of sawdust was performed once a week although faeces in stalls were removed once a day . moreover , it is said that the sleeping behavior was related to learning and memory ( review , ) . therefore , further investigations on the effect of bedding material and the method of cleaning the bedding on the horses welfare and learning are required . however , in animal welfare , we focus on the physical and mental health of the animals with reference to the 5 freedoms. the concept of 5 freedoms are ( 1 ) freedom from hunger and thirst ; ( 2 ) freedom from discomfort ; ( 3 ) freedom from pain , injury , or disease ; ( 4 ) freedom to express normal behavior ; and ( 5 ) freedom from fear and distress . bedding material is related to the freedom from discomfort in terms of moisture , soft surface , and air ammonia , freedom from pain , injury , or disease in terms of hoof disease and skin conditions , and the effect of bedding materials on the welfare of stabled horses should be evaluated not only based on the resting behavior but also based on the water content in bedding , airborne ammonia ( e.g. ) , and hoof condition . moreover , the use of beddings should be evaluated in terms of management and costs for the applied purpose .

the objective of this study was to investigate the effect of straw , sawdust , coconut husk ( husk ) , and coconut fiber ( fiber ) on the welfare of stable horses by observing their resting behavior . twenty horses with ages ranging from 3 to 21 years were used at the equine research institute of the japan racing association , utsunomiya , japan . five horses were allocated to each bedding condition . the behavior of each horse was recorded by video camera for 3 days and was continuously sampled from 17:00 to 05:00 . the total duration , the number of bouts , and the mean and the maximum duration of bouts in standing rest , sternal lying , and lateral lying were calculated and analysed by the kruskal - wallis test and post hoc steel - dwass test . there was no difference in the standing rest and the sternal lying among beddings . significant differences were observed in these values in the lateral lying among the different beddings ( p<0.05 ) . the values of the means of the total duration , the number of bouts , and the mean and the maximum duration of bout in the lateral lying were greater when husk was used as the bedding material than when sawdust were used ( p<0.05 ) . the results of the observations show that the new bedding materials would be as usable as straw . however , lateral lying was observed less frequently when sawdust were used as bedding ; this indicates that use of sawdust as bedding material will decrease the welfare of stabled horses .

intravenous thrombolytic therapy when given within 4.5 h from symptom onset remains the mainstay of treatment for ischemic stroke patients . while intravenous tissue plasminogen activator ( iv tpa ) has been shown to be effective in improving outcome , the most feared complication is symptomatic intracerebral hemorrhage ( sich ) , which occurs in up to 7 percent of patients and significantly increases mortality and morbidity . standard management of post thrombolysis intracerebral hemorrhage includes replacement of coagulation factors with cryoprecipitate and platelets , as suggested by the american heart association , which is based on small case series and expert opinion and the efficacy of such treatment is unknown . thus there exists heterogeneity in clinical practice with respect to the strategies implemented in the management of sich . the lack of consensus on how to manage sich as well as continued poor outcomes despite treatment should create a driving force in the stroke community to investigate effectiveness and rapidity of other potential treatment options . we report a 68-year old right handed hispanic woman with a history of diabetes mellitus type ii , hypertension , hyperlipidemia , and two prior strokes with residual right hemiparesis , who presented with sudden onset vertigo , slurred speech , and blurred vision . the first stroke was a left putamen intracerebral hemorrhage with minimal residual right hemiparesis that occurred over 20 years prior to admission . the second stroke was a cryptogenic stroke that occurred around 5 years prior to admission for which she was outside the time window of thrombolytic therapy and was maintained on aspirin 81 mg daily . her initial exam showed dysarthria , left sided sensory loss , skew deviation with upgaze vertical nystagmus , mild right hemiparesis , and an nihss score of 4 . initial head computed tomography ( ct ) ( figure 1a ) showed evidence of prior strokes and no acute hemorrhage . since she had a new fixed and potentially disabling neurological deficit and she was within the 4.5 h window , decision was made to administer thrombolytic therapy . an hour after the iv tpa infusion was complete , she complained of an acute severe headache without a change in neurological exam and repeat ct head showed right temporal ich with a subdural component ( figure 1b ) . two hours after the completion of this treatment , she became somnolent and had new left hemiparesis . ct head was repeated that showed ich expansion and new intraventricular hemorrhage ( figure 1c ) . in the next 3 h head ct at that point showed further expansion of ich and intraventricular hemorrhage ( figure 1d ) . the decision was made to administer recombinant factor viia ( 50 mcg / kg ) and she was subsequently taken to the operating room with successful clot evacuation . postoperatively , her exam slowly improved and she was back to her baseline neurological exam on post - operative day 3 ( figure 1e ) . alteplase converts plasminogen to plasmin , which in turn converts fibrin into the fibrin split products causing thrombolysis . it also causes a reduction in fibrinogen the degree of which is associated with sich . using cryoprecipitate ( factor viii and fibrinogen ) , in post thrombolysis sich increases fibrinogen levels , enhances fibrin formation and may potentially stabilize the clot thus reducing the risk of further hemorrhage . however , a study from get with the guidelines data showed that around 40 percent of patients with post thrombolysis sich have continued bleeding despite cryoprecipitate treatment . the lack of efficacy may be due to delays in diagnosis and treatment , insufficient dosing of cryoprecipitate to replenish fibrinogen , or lack of augmentation with rapid acting factors that help convert fibrinogen into fibrin . to our knowledge , this is the first case reporting the use of recombinant factor viia along with cryoprecipitate and platelets in the treatment of symptomatic ich following intravenous thrombolysis . activated factor viia has been studied in spontaneous intracerebral hemorrhage and has been shown to reduce hematoma growth with no effect on mortality and morbidity however . activated factor viia , which has a relatively quick time of onset and is an extrinsic and intrinsic pathway activator , may further enhance clot stability and potentially reduce the risk of hematoma expansion , which is likely what happened with our patient . although recombinant factor viia carries a risk of thrombosis and is relatively expensive , its use in this patient population may potentially alter the course of the disease and improve outcome . randomized studies may be considered to compare the outcome of patients with post thrombolysis sich when rapid reversal agents such as recombinant factor viia or prothrombin complex concentrate are added to the standard treatment or given in isolation .

symptomatic intracerebral hemorrhage ( sich ) occurs in up to 7% of stroke patients treated with thrombolytic therapy . there are limited data on the effectiveness of the reversal agents used for intravenous tissue plasminogen activator related intracranial bleeds . we report a patient with sich following intravenous thrombolysis whose intracerebral hemorrhage continued to expand despite treatment with platelets and cryoprecipitate , needing recombinant factor viia use for stabilization before surgical evacuation . factor viia along with routine reversal agents following intravenous thrombolysis related sich may further enhance clot stability and reduce the risk of hematoma expansion . it could be a bridge to definitive surgical management in those patients .

primary amenorrhea is the absence of menstruation and secondary sexual characteristics in phenotypic women aged 14 years or older . common hormonal cause of primary amenorrhea includes pituitary dysfunction , chronic systemic disease , and absent ovarian function . gonadal failure in genetically xx individuals is ovarian failure ; when this occurs at any time before onset of sexual maturation , there will be primary amenorrhea and incomplete breast development . xy individuals with gonadal failure will have female genitalia because mullerian inhibiting factor and testosterone will not be produced . gonadal tumors occur in up to 25% of women with a y chromosome ; unlike complete androgen insensitivity , these gonads do not secrete hormones and should be removed at the time of diagnosis . the incidence of the chromosomal abnormality ( ca ) in live births is around 90 per 10,000 . included in the incidence are the numerical ( monosomy / trisomy / mosaicism ) as well as the structural ( translocation / isochromosome / deletion / duplication / ring ) ca . 233 women with primary amenorrhea who were referred to cytogenetic unit , children hospital , mansoura university , egypt from july 2008 to december 2010 . for all patients , steroidal hormonal assay were setup according to elisa technique,[810 ] and chromosomal cultures were setup according to g- banding , about 1 ml of blood was mixed with 5 ml of rpmi medium , 1 ml of fetal bovine serum , 0.1 g / ml of phytohemagglutinin ( pha ) and was incubated at 37c . after 72 hour of incubation , the colcimid ( 1 mg / ml ) was added and incubated for another 1.5 hour . the cells were then harvested by hypotonic treatment ( 1.5 hour with 0.075 m kcl at 37c ) , fixed and washed thrice with fixative solution ( methanol and acetic acid in a ratio of 3:1 ) , and then metaphases were spread and stained using standard g - banding technique . for each case , 50 spread metaphases were analyzed with cytovision system . fluorescence in situ hybridization ( fish ) technique was carried out in some of cases to more evaluation according to technique of . 10 l of the x , y centromeric probe were applied to the target area , and the cover slip was applied to the slide immediately . the cover slip was sealed with rubber cement , and the slide was placed on hot plate at 72c for 2 minutes . the slide was placed in a warmed humidified box , and the box was placed at 37c in an incubator overnight . the cover slip was removed from slide , and it was immersed in 70 ml of the 0.4 x ssc/0.3% np-40 in a coplin jar at a 731c water bath for 2 minutes . then , the slide was immersed in 70 ml of the 2 x ssc/0.1% np-40 in coplin jar at 25c for 2 minutes . the slide was air - dried in the dark , and 10 l of dapi ii counter stain were applied to the target area of slide , and the cover slip was applied to the each slide . 233 patients with primary amenorrhea were referred from different parts of egypt to cytogenetic laboratory of genetic unit , children hospital mansoura university , from july 2008 to december 2010 . ( 1 ) the numerical abnormalities of the x chromosome were detected in 23 ( 50% ) . ( 2 ) structural abnormalities of the x chromosome were detected in 11 ( 23.91% ) . ( 4 ) male karyotype 46 , xy was presented in 2 ( 4.35% ) , [ table 1 ] . the two patients with association of chromosome y was confirmed by fish [ figure 1 ] , and the presence of deletion of long arm of chromosome x in 3 patients was confirmed , using fish [ figure 2 ] . classification of chromosomal abnormalities of patients with primary amenorrhea interphase and metaphase from fish analysis showing one x chromosome and one y chromosome of female confirming the testicular feminization syndrome ( xy ) metaphase from fish analysis showing one x chromosome and short arm of another x of female confirming the form x , xq in table 2 , follicle stimulating hormone ( fsh ) and luteinizing hormone ( lh ) mean levels in sera of females with primary amenorrhea , whether they have numerical , structural , or mosaicism chromosomal abnormalities , were significantly higher than those of the control group ( p<0.05 ) . but , estradiol ( e2 ) mean levels in sera of them were significantly lower than those of the control group ( p<0.05 ) . 20.63% of chromosomal abnormalities in primary amenorrhea of present study compared with those in various study conducted between 1983 and 2010 [ table 3 ] . chromosome abnormalities in primary amenorrhea in various study and compared with present study genes essential for gonadal function are located on the proximal part of xp , the long arm of x proximal to xq13 and/or the long arm of x distal to xq26 . large deletion of xq with breakpoints at or proximal to q13 are expected to produce gonadal dysgenesis with primary amenorrhea , half of the patients with such deletions have turner`s syndrome . that explained the cause of our two patients with deletion of xq have primary amenorrhea , but have not feature of turner syndrome , whereas other three patients who have deletion of xp have primary amenorrhea and all the features of turner syndrome . ten et al . found one patient with primary amenorrhea and 47 , xxx had mental retardation and the cause of that , an extra x , can slow down embryonic cell development in a special way . similar to that , there were mental retardation in two of our patients with karyotype of 47 , xxx . xy individuals with gonadal failure will have female genitalia because mullerian inhibiting factor and testosterone will not be produced . gonadal tumors occur in up to 25% of women with a y chromosome ; unlike complete androgen insensitivity , these gonads do not secrete hormones and should be removed at the time of diagnosis . in our study , we diagnosed two patients of primary amenorrhea as testicular feminization syndrome ( xy ) using fish technique . the molecular cytogenetic technique , fish , accurately delineate the nature and origin of marker chromosomes in primary amenorrhea patients , which is difficult by conventional cytogenetics . as similar to that , in present study , the presence of deletion of long arm of chromosome x in 2 patients was confirmed , using fish , which is very difficult by conventional cytogenetic where short arm of the x chromosome is similar to the y chromosome . ten et al . found that , serum follicle stimulating hormones and luteinizing hormones were always increased in primary amenorrhea patients with chromosomal abnormalities . the present study showed that karyotype and fish are necessary to detect the causes of primary amenorrhea . this study also revealed the incidence of chromosomal abnormalities in women with primary amenorrhea in egypt is similar to that reported in previous literatures .

background : primary amenorrhea is defined as the absence of menstruation and secondary sexual characteristics in phenotypic women aged 14 years or older . hormonal disorders are main causes of primary amenorrhea . common hormonal cause of primary amenorrhea includes pituitary dysfunction and absent ovarian function . the aim of this study was to estimate the incidence and types of chromosomal abnormalities in patients with primary amenorrhea in egypt.materials and methods : chromosomal analysis and hormonal assay were carried out on 223 patients with primary amenorrhea that were referred from different parts of egypt to cytogenetic laboratory of genetic unit , children hospital mansoura university , from july 2008 to december 2010 . fish technique was carried out in some of cases to more evaluation.results:the frequency of chromosomal abnormalities was 46 ( 20.63% ) in primary amenorrhea patients . the chromosomal abnormalities can be classified into four main types . ( 1 ) the numerical abnormalities of the x chromosome were detected in 23 ( 50 % ) . ( 2 ) structural abnormalities of the x chromosome were detected in 11 ( 23.91% ) . ( 3 ) mosaicism of x chromosome was found in 10 ( 21.74% ) . ( 4 ) male karyotype 46 , xy was presented in 2 ( 4.35%).conclusion : the present study showed that karyotype and fish are necessary to detect the causes of primary amenorrhea . this study also revealed the incidence of chromosomal abnormalities in women with primary amenorrhea in egypt is similar to that reported in previous literatures .

the 2-year survival of patients starting rrt has progressively increased for cohorts from 2001 to 2006 , measured either as overall survival for patients starting rrt ( to 82.2% for the cohort starting in 2006 reported in the era - edta registry 2012 report ) , on dialysis ( 79.7% ) or receiving living - related kidney transplantation ( 98.3% ) ( figure 1 ) [ 13 ] . in contrast , 2-year survival for cadaveric kidney transplantation remains stable at 96.096.1% for cohorts starting from 2003 to 2006 pointing to a plateau that would need novel approaches to be surpassed . these data are in agreement with other registries reporting increasing overall survival of patients starting rrt in the last decade [ 47 ] . similar improvements were observed for 5-year survival , pointing to an overall improvement in the standard of care , unlike the us situation in the 1990s , in which progressive increases in survival at 12 and 24 months were associated with decreasing survival at 5 years [ 4 , 8 ] . drop in longer - term survival and whether a similar phenomenon occurred outside this country still need detailed studies , in search of lessons that might be learned and applied to improve the current standard of care . on the dark side , data point to persistent inequalities between european citizens in incidence and prevalence of rrt and in access to transplantation . living in greece , belgium ( both french- and dutch - speaking ) or portugal ( the gbp countries ) is associated with higher chances of initiating rrt than living in other european countries . very high incidence of rrt was also reported in israel and georgia in 2012 and in turkey in 2011 and 2010 . the adjusted rrt incidence for gbp countries was 188 , 201 - 174 and 220 pmp in 2012 , respectively ( although portugal data are unadjusted ) . this compares with 122 , 114 and 97 pmp in the netherlands or spanish regions ( galicia , castilla - leon ) bordering portugal ( figure 2a ) . moreover , these differences persist when prevalence is examined ( figure 2c ) , although prevalence / incidence values are lower for high incidence countries ( figure 3 ) . one potential explanation is more stringent patient selection in low incidence countries , although better on - rrt care may also contribute . in lower income countries , the low incidence of rrt may represent lack of access to needed healthcare ( e.g. montenegro 26 pmp ) . however , how can the high incidence and prevalence of rrt in the gbp countries be explained ? do gbp citizens have access to rrt techniques that are denied to citizens in other high income countries , e.g. adjusted incidence of rrt 100 pmp in scotland and 77 pmp in finland ? are there local genetic or environmental factors that favour progression of ckd and have not been tackled by public health authorities ? are there perverse incentives or forces that favour ckd progression or initiation of rrt ? or it is just a matter of reporting methods or of nephrologist beliefs regarding the timing of initiation of rrt when hard evidence is lacking ? unravelling the underlying reasons for the observed inequalities is an urgent research need : only when the causes are known can corrective measures be applied . table 1.potential causes of differences in rrt incidence and prevalencevery concerning overuse of rrt denial of access to rrt financial incentives to initiate rrtconcerning different incidence or progression of ckd public health system fails to prevent development of ckd healthcare system structure or access results in suboptimal ckd care different views on the relative value of rrt versus conservative management of esrdother different data reporting methods refusal of rrt by an informed population when rrt is offered potential causes of differences in rrt incidence and prevalence several countries with low incidence and prevalence of rrt have higher incomes than countries with higher prevalence ( figure 4a ) . the differences do not appear to depend on a better public health system or success in preventing ckd progression in those countries with high income . thus , some countries with higher income and low rrt incidence start rrt at a median younger age than countries which have both lower income and higher incidence of rrt . in this regard , low overall incidence and prevalence of rrt is frequently associated with low incidence and prevalence of rrt in those aged > 75 years ( figures 2b , d and 4c ) . thus , the age pattern is consistent with denial of rrt to the elderly , refusal of rrt by the elderly or different criteria for indicating conservative treatment versus rrt in younger or elderly patients in countries with low rrt incidence . in these high income countries , low rrt incidence in the elderly does not appear to depend on economic constraints , as is the case in low income countries . the low rrt incidence may be based on the genuine belief that conservative treatment is the best option for elderly patients with esrd [ 9 , 10 ] . in this regard , there is an urgent need for hard evidence on the relative merits of conservative treatment versus rrt in the elderly as well as on the optimal timing of rrt start . if indeed conservative management has clear advantages , then in some countries overdialysis might be an issue . in this regard , a recent survey of nephrologists from 11 european countries disclosed very different practices regarding start of rrt in uncomplicated relatively young ( 60-year - old ) patients : the estimated glomerular filtration rates ( egfrs ) at which rrt would be started by different nephrologists ranged from 5 to 20 ml / min/1.73 m and this was the most important parameter to initiate rrt in such a patient for a majority of nephrologists . obviously , starting at an egfr of 5 or 20 ml / min/1.73 m may have a great impact on the incidence of rrt . if the same range would be applied to those over 75 years of age ( which was not the subject of the study ) , it would mean the difference between initiating and never initiating rrt for a great number of patients . interestingly , nephrologists from countries with a high incidence of rrt more often believed that starting at a gfr > 10.5 ml / min/1.73 m is always beneficial compared with respondents from low incidence countries ( 18 versus 6% ) . furthermore , the target egfr was higher for nephrologists working at for - profit centres . further information is needed about the gfr at initiation of rrt in different countries as well as on the use of and acceptance by patients and doctors and outcomes of conservative management of esrd in the elderly . the fact that differences in prevalence are lower than differences in incidence is concordant with prevalence / incidence value data ( figure 3 ) and can be interpreted as a high rate of patient loss in some high incidence countries . whether these shorter periods on rrt in some countries with a high incidence of rrt result in improved patient quality of life and are indeed appreciated by the patient there are additional hypotheses potentially explaining the lower incidence of rrt coupled to a younger mean age at start of rrt in some high income countries . patients may be dying earlier from cardiovascular disease and , thus , not living long enough to need rrt . however , life expectancy does not differ much between countries selected for this commentary , except for low income montenegro ( figure 4b ) . public health may also impact the incidence and prevalence of ckd and , thus , of esrd . factors potentially involved include the presence of toxins in the environment or food ( i.e. the exposome , as an example , aristolochic nephropathy ) , over - the - counter medication policies ( allowing unrestricted access to nephrotoxic drugs ) or country - level policies regarding salt or phosphate content in the diet . in addition , the healthcare system may also impact , as an example , whether there is universal unrestricted access to healthcare or to nephrologists . the percentage of patients on rrt who have a functioning kidney graft ranges from 7% in bosnia and herzegovina to 60% in norway , finland and iceland . also worrisome is the fact that rrt epidemiology data from some countries big and small ( e.g. germany , ireland , hungary and italy , among others ) at the core of europe are not available , as it was the case for 2011 and , except for some parts of italy , for 2010 [ 13 ] . this virtual black - out makes comparison with other european countries difficult that could improve the standard of care and to detect pockets of substandard care or endemic ckd hotspots . in summary , the era - edta registry continues to provide a wealth of data on the epidemiology of rrt . key points of this year 's report include ( i ) the improving outcomes for patients on rrt , with exception of recipients of cadaveric donor kidneys , ( ii ) the persistence of inequalities in rrt incidence and prevalence and transplantation availability in different european countries that may hide ckd hotspots , substandard ckd care , overuse of rrt or lack of access to needed rrt ; and ( iii ) a preoccupying lack of data from key countries . there is an urgent need to study the factors underlying the inequalities in rrt incidence and prevalence and to identify and correct potential substandard care for some european citizens . renal replacement therapy in europe : a summary of the 2012 era edta registry annual report .

the 2012 era - edta registry annual report contains both good news and bad news . on the bright side , the 2-year survival of patients starting renal replacement therapy ( rrt ) for chronic kidney disease ( ckd ) , on dialysis or receiving a living - related kidney transplantation , has progressively increased to 82.2 , 79.7 and 98.3% , respectively , whereas for cadaveric kidney transplantation it remains stable ( 96.096.1% ) . on the dark side , inequalities persist between european citizens in access to renal transplantation and in incidence and prevalence of rrt . living in greece , belgium ( french- or dutch - speaking ) or portugal ( the gbp countries ) is associated with higher chances of initiating rrt than living in other european countries . the adjusted rrt incidence for gbp countries was 188 , 201 - 174 and 220 * ( * unadjusted ) pmp in 2012 , respectively ( versus 122 , 114 and 97 pmp in the netherlands or two spanish regions bordering portugal ) . in lower income countries , a low rrt incidence may represent lack of access to needed healthcare ( e.g. montenegro 26 pmp ) . however , how can the high incidence and prevalence of rrt in the gbp countries be explained ? do gbp citizens have access to rrt that is denied , rejected or considered unnecessary in other high income countries ? does the gbp healthcare system fail to prevent progression of ckd ? do local genetic or environmental factors favour ckd progression ? unravelling the underlying reasons is an urgent research need : only an understanding of the causes will allow correction of the problem . unavailability of data from some large countries ( e.g. germany and italy ) is not helpful .

' mesotherapy ' is a non - surgical , minimally invasive method of drug delivery that consists of multiple intradermal or subcutaneous injections of a mixture of compounds ' melange ' in minute doses . it has gained disrepute because of inadequate scientific evidence to prove its efficacy . in spite of this , many new substances such as platelet - rich plasma ( prp ) , peptides , growth factors and collagen are finding their way to enter the field of mesotherapy . since small amounts of material have to be injected by multiple pricks rapidly over a large area , mesogun is used . mesogun is a motor - driven equipment that can be used to rapidly deliver the chemicals into the skin and subcutis . however , most mesoguns are expensive and tend to waste material due to dripping from the needle postulated to be due to rapid withdrawal [ figure 1 ] . while this may not be significant in financial terms when inexpensive substances are injected , products such as prp or meso solutions for injection which are either expensive or too precious should not be wasted . the cause for dripping is possibly due to lack of minimal recoil , following the injection by the motor - driven plunger . on searching the web , we found a syringe with a spring attached to the piston which would provide the recoil needed to prevent dripping . since these syringes are not freely available , we modified the available disposable syringe to rapidly deliver small quantity of material into the skin , similar to a mesogun . a 5 ml syringe or an insulin syringe is taken and the piston is removed from the body and a spring which is sterilised using ethylene oxide is inserted onto the piston which is inserted back into the body of the syringe [ figure 2 ] . the material to be injected is drawn into the syringe and the regular needle is replaced with the meso needle . the specifics of the spring provided for the purpose of duplication and standardisation used are as follows : wastage of injectable material from mesogun spring - loaded 5 cc syringes length 37 mm , thickness 1.21 mm , pitch 4 mm , outer diameter 15 mm , inner diameter 12.6 mm , spring constant ( k ) = 1300 n / m . length 71.30 mm , thickness 0.75 mm , spring outer diameter 5.7 mm , spring inner diameter 4.58 mm , spring constant ( k ) = 890 n / m . spring constant ( k ) is calculated as follows : the spring constant of a spring represents the force required to deform it by a certain amount . as most springs obey hooke 's law , the spring constant k is treated as a constant characteristic operational parameter for the spring . in the case of helical coiled springs , it represents the force required to extend ( or compress ) the spring by a certain length . experimentally , it is measured by fixing it at one end and applying a force ' f ' on the other end , along its axis , causing it to extend by a length x. the spring constant is then calculated by the formula : f is expressed in newton and x is in metres . small quantities of material can be injected by first piercing the needle into the tissue , pressing the piston using the thumb and removing the thumb which results in the recoil of the piston ; the syringe is withdrawn from the skin , following which the next site is injected [ video 1 ] . before disposal of the syringe , the spring can be removed and retained for reuse after sterilisation . the approximate cost of the spring - loaded syringe would be 30 inr for the 5 cc syringe and 26 inr for the 1 cc syringe . thus the modified spring loaded syringe can be an efficient , cost effective method of drug delivery for mesotherapy and intralesional injections . length 37 mm , thickness 1.21 mm , pitch 4 mm , outer diameter 15 mm , inner diameter 12.6 mm , spring constant ( k ) = 1300 n / m . length 71.30 mm , thickness 0.75 mm , spring outer diameter 5.7 mm , spring inner diameter 4.58 mm , spring constant ( k ) = 890 n / m . spring constant ( k ) is calculated as follows : the spring constant of a spring represents the force required to deform it by a certain amount . as most springs obey hooke 's law , the spring constant k is treated as a constant characteristic operational parameter for the spring . in the case of helical coiled springs , it represents the force required to extend ( or compress ) the spring by a certain length . experimentally , it is measured by fixing it at one end and applying a force ' f ' on the other end , along its axis , causing it to extend by a length x. the spring constant is then calculated by the formula : f is expressed in newton and x is in metres . small quantities of material can be injected by first piercing the needle into the tissue , pressing the piston using the thumb and removing the thumb which results in the recoil of the piston ; the syringe is withdrawn from the skin , following which the next site is injected [ video 1 ] . before disposal of the syringe , the spring can be removed and retained for reuse after sterilisation . the approximate cost of the spring - loaded syringe would be 30 inr for the 5 cc syringe and 26 inr for the 1 cc syringe . thus the modified spring loaded syringe can be an efficient , cost effective method of drug delivery for mesotherapy and intralesional injections .

mesotherapy refers to multiple injections of small quantity of the drug over a large area . the mesoguns available are expensive and the motor - driven models tends to waste the expensive material to be injected since the plunger stops after injecting without recoil . we searched for a less expensive device which would inject like the mesogun and still not waste the solution . on searching the web , we identified a spring - loaded syringe . we describe the assembly and use of this inexpensive syringe for delivering multiple injections with minimal wastage .

since its first full description some 70 years ago , cystic fibrosis has been the focus of considerable clinical and scientific research . we now know cystic fibrosis to be a common genetic disease , in which the mutation underpinning cf results in altered ion transport . while this impacts multiple body systems , most clinical concern arises over the airways and the chronic infections that typically develop there . through these infections and the resulting host response , lung damage occurs that is key to morbidity and mortality in this patient group . a decade ago , diagnostic microbiology was focused on the culture - based detection of a small set of bacterial and fungal species that were considered of clinical significance . from 2003 onward , however , a series of studies showed through culture - independent analysis that a complex mix of bacteria ( 1 ) , fungi ( 2 , 3 ) , and viruses ( 4 ) form the airway microbiota of an individual chronically infected with cf . recent studies on the chronically infected airways have shown associations between the bacterial microbiota of sputum and a range of clinical parameters over time ( 5 , 6 ) . a continued research effort is now needed to better understand how these data can inform the process of improving the health of cf patients ( 7 ) . abnormal mucus production in the small intestine is thought to contribute to gastrointestinal ( gi ) symptoms of malabsorption and obstruction . evidence that the fecal microbiota of cf patients differs from those of individuals without cf also exists ( 8) . combining these points , it is possible that altered microbiotas may have important negative effects on the growth , development , and physiology of a child with cf . to date , then , work in this field has focused primarily on the airway microbiota and most typically on that in patients that are chronically colonized . this is , in part at least , due to the need to better understand the microbiota and the impact of antibiotic therapies that have been key to improving well - being and extending life . this emphasis on the airway microbiotas of chronically infected cf patients , however , misses important questions on how the microbiotas in the airways and gut assemble . is this a stochastic process , or do founding members determine the microbiota composition at these and other body sites in later life ? does this explain differences in health outcomes , and could this lead to directed interventions to steer the microbiota in directions beneficial to the host ? to start to answer these questions , we need to look at cf at earlier stages . a number of studies have reported on the airway microbiota of young individuals with cf ( 911 ) . in their study , madan et al . ( 12 ) looked still further back by examining neonates with cf , something that is itself enabled by diagnostic advances in next - generation high - throughput sequencing technologies , and tracked patients through the first 21 months of life . in that paper , gut and respiratory were used to describe the samples taken . while this is fair although this is a commonly used strategy , studies have shown that the composition of fecal microbiota differs from that of the microbiota associated with biopsy samples ( 13 ) . also used oropharyngeal swabbing to characterize the airway microbiota . here , a more direct sampling of the lung itself would be more helpful , but as the authors comment , the processes needed to sample the lower airways , e.g. , bronchoalveolar lavage , are invasive . as the authors also discuss , there is evidence to suggest that there is a correlation between the species present in the oropharynx and the lower airways . the exact relationship is , however , not clear , and this is an area that needs more detailed research . with these caveats in mind , so as to avoid confusion , the terms gut and respiratory are used in this commentary . it should be stressed , though , that the collection of clinical samples that the team assembled is unique and represents a strength of the work . the culture - independent 16s rrna gene 454 pyrosequencing method used to study the bacterial genera that were present over time was similar to that employed in previous studies . here , though , it is essential to highlight the importance of statistical methodologies , such as intraclass correlation coefficient analysis and recursive partitioned mixed modeling , as tools for interpreting this class of data . the combination of such tools with pyrosequencing approaches is another marked strength of the work . the first observation was that overall , a relatively limited set of eight genera was common , including streptococcus , prevotella , and veillonella in respiratory samples and bacteroides , bifidobacterium , and veillonella in gut samples . the presence of the genera veillonella and prevotella in respiratory samples is consistent with findings that report the same anaerobic genera in many chronically colonized cf patients . this identification of key groups of bacteria here presents an opportunity to make comparisons with those reported in analogous studies outside this clinical context . for example , comparisons with studies focusing on the respiratory or gastrointestinal tracts of non - cf individuals could allow the extent to which microbiota composition reflects the underlying physiological changes that are associated with this condition to be determined . the authors also determined that interindividual consistency was greater for respiratory than for gut microbiotas . overall , too , while this study found that microbiotas fell into two clusters one comprising respiratory samples and the other gut samples this small group of genera was common to both . this concept of identifying core , as opposed to transient , microbiota membership within a metacommunity has been used before in a study of cf ( 14 ) . reflecting the unique longitudinal nature of the data set , some of the most interesting findings came through a comparison of the genus - level data over time . by tracking the temporal dynamics of the microbiota , the authors identified a significant increase in bacterial diversity over time , with the fastest increase being detected among the respiratory samples . not only is this of potential importance , as the authors state , in relation to disease severity ( 15 ) , but there may also be implications for immunodevelopment , as set out in the biodiversity hypothesis ( 16 ) . in the study by madan et al . ( 12 ) , the same genera that were seen to increase in the gut were also found to increase in respiratory samples . also , certain genera were found to be present early in the neonatal gut and then later in the respiratory samples as well ; i.e. , gut colonization presages their appearance in the respiratory tract . again , the authors were able to show significant links for the cluster patterns of bacterial genera in respiratory samples , such as associations with breastfeeding and the introduction of solid foods into the diet of the child . with regard to study limitations , the caveats set out above emphasize the need to exercise caution when interpreting the presence of species as being it might be interesting to reconsider aspects of the findings in relation to the means of sampling ; oropharyngeal swabs contact the epithelial surface directly , whereas fecal samples are by their nature a ( variable ) mix of food and cellular contributions of a variety of sources . as the authors state , clear limitations also include the number of cf patients monitored and the frequency of sample collection . at this point , however , it is important to credit the authors for their ability to involve and maintain the commitment to the study of the parents in the program . the contributions of this study to future directions of work in this field are likely to be seen as particularly important . the authors propose interventional studies in terms of diet or probiotics as attractive longer - term options . while the debate that this will generate is in itself welcome , there is much to be done to first reinforce and then extend what is presented in this paper . cf clinicians are concerned about the acquisition of certain species , such as pseudomonas aeruginosa , which are associated with a range of poor clinical outcomes . studies of why key species such as this colonize cf patients at different ages are warranted is this linked to the composition of the microbiota at time of colonization ? as for studies in later cf , it is also important to consider other components of the microbiota in parallel through , for example , metagenomics - based analysis . microbiota studies need to be tied more specifically to clinical outcome , with concepts of mechanism being needed as much as intervention . clearly , then , there is a need for a set of long - term studies that link microbiota with clinical outcome . to some extent , the importance of this study is in its initiation of work in this area , with more questions emerging than perhaps might have been hypothesized originally . it is important to reflect that for many years following the full description of the condition in the late 1930s , this study would not have been possible life expectancy then was still 6 months on average . while the advances made in cf should not be underestimated , we need to continue to move forward . this needs support in order to develop , but the promise of clinical benefit that microbiota studies will allow is great . the paper by madan et al . initiates activity in microbiota research in neonatal cf and is to be commended as such .

abstractrecent studies have greatly extended our understanding of the microbiota present in and on the human body . here , advanced sequencing strategies have provided unprecedented analytical power . the important implications that the emerging data have for human health emphasize the need to intensify research in this area ( d. a. relman , nature 486:194 - 195 , 2012 ) . it is already clear from these studies that the microbiotas characterized in different body locations of healthy individuals are both complex and diverse ( the human microbiome project consortium , nature 486:215 - 221 ) . these studies also provide a point of contrast for investigations that aim to characterize the microbiota present in disease conditions . in this regard , madan et al . ( mbio 3(4):e00251 - 12 , 2012 ) monitored the development over time of microbiota in the oropharynges and feces of neonates with cystic fibrosis and explored the potential for interactions between these complex microbial systems .

with the increase in international travels and multiracial communities in the united states , non - rubella immune ( nri ) pregnant women as well as nonimmune individuals are at risk of rubella infection . a study in 1988 suggested that between 7.5 and 17.4% of pregnant women in the united states lack immunity to rubella . similarly , a prevalence rate of 15.1% among pregnant women was reported in 1999 by investigators in michigan . in addition , a rate of 9.1% was found among women who attended prenatal care at lejeune nc in 2004 . in view of the recent report of two adult cases of rubella infection in the united states , the importance of identifying populations at risk for rubella infection can not be over emphasized . this may result in miscarriage , fetal death , or severe anomalies in the infant with crs . infection during the first trimester of pregnancy is associated with worst outcomes and development of multiple organ anomalies associated with crs . some of the effects of crs may not be apparent at birth and may manifest as a chronic disease capable of producing ongoing organ damage throughout the life of an infected child . although the prevalence of crs and adult rubella infection declined remarkably following the introduction of rubella vaccine in 1969 in the united states [ 8 , 9 ] , the disease is still endemic in many developing countries . in many developing countries such as sub - saharan africa , there is no existing national vaccination program against rubella , and surveillance data is limited [ 10 , 11 ] . these developing countries are responsible for most of the estimated 238,000 global cases of children born annually with crs . in the united states , the last major epidemic of the disease resulted in about 12.5 million cases of infection , 20 000 cases of crs and 11,000 fetal deaths . sporadic cases of the disease still occur in the united states [ 14 , 15 ] because of lack of universal immunization , primary and secondary vaccine failure and reinfections [ 16 , 17 ] . some sporadic cases in the united states have led to the association of race with rubella infection . for instance , rangel and colleagues reported outbreak of rubella infection in a hispanic community in north carolina . in addition , another outbreak was reported in meat processing plants that employed many hispanics and other foreign nationals in kansas and nebraska . similarly , plotinsky and colleagues reported a case of crs in an infant born to a liberian refugee living in new hampshire . furthermore , during 1997 to 1999 , 81% of reported crs cases were hispanics and 92% of the infants were born to foreign mothers . apart from the numerous medical consequences of the disease [ 2124 ] , the economic cost of the disease is also enormous . identification and protection of nri women of child bearing age against rubella will prevent crs and its associated morbidity , mortality , and economic health burden . the objectives of this study were to evaluate the prevalence and distribution of nri among pregnant women who attended multiracial high - risk prenatal clinic in 2007 . findings from the study may provide the rationale for targeted public health intervention that may prevent reemergence of rubella . this is a retrospective , chart review study involving pregnant women who attended high - risk prenatal clinic in northwestern iowa in 2007 . this study was part of a routine evaluation of prenatal care in the clinic and approved by sioux city institutional review board , iowa , united states . the clinic serves a diverse population of low - income and multiracial groups including a large hispanic population , non - hispanic whites , native americans , african americans , asians , and african immigrants living in the tri - state area of nebraska , iowa , and south dakota . during their initial prenatal visit , all patients gave blood samples for routine prenatal laboratory screening . rubella screening was conducted by evaluating serum rubella igg antibody titer using enzyme linked immunosorbent assay ( elisa ) ( wampole laboratories , princeton , nj ) as described previously . individuals with equivocal results and those with no rubella igg antibody were regarded as nonimmune . single researcher extracted the data in microsoft excel ( microsoft corp . , redmond , wa ) for analysis . prevalence rate in the study population was calculated by dividing the number of nri women with the total number of women screened during the study period . these include less than 20 years of age , or adolescent , 2029 years of age and 30 or more years of age . nri prevalence rates in these age groups were calculated by dividing the number of nri in the age group by the total number of women screened in that age group . furthermore , we evaluated the prevalence rates in four major study populations , namely , hispanics , whites , native americans , and african americans . data was analyzed using sigma stat software ( jandel scientific , san rafael , ca ) . statistical significance was established using chi square or fisher 's exact test . to control for possible differences in age distribution across race / ethnic groups , race / ethnic group was the primary explanatory variable , and whites were selected as the reference category for comparison purposes . age was added to the unadjusted logistic model to determine the relationship between race / ethnicity and the presence or absence of rubella immunity while holding constant the influence of age . non - hispanic population comprised of whites or caucasians ( 180 ) , african americans ( 34 ) , native americans ( 52 ) , asians ( 21 ) , and others ( 7 ) . the asians , biracial ( 3 ) , and africans from somalia ( 4 ) were in the group classified as women aged 2029 years of age constituted the highest number of subjects and accounted for 57.9% of the study population . adolescents and women 30 or more years of age accounted for 18.4% and 23.7% of the study population , respectively . the prevalence rate among native americans was highest at 17.3% , compared to whites 7.3% , blacks 5.9% , and hispanics 4.6% ( see figure 1 ) . in the study population , prevalence rate among adolescents was 10.2% compared to 6.2% and 5.9% among women aged 2029 and 30 or more years of age , respectively ( see figure 2 ) . analysis of the trend in three major racial groups demonstrated a high rate among native american teenagers at 18.2% compared to whites and hispanics at 10.8% and 8.5% , respectively . in women aged 2029 years of age , the rate among native americans was 11.5% compared to 7.4% and 3.2% of whites and hispanics , respectively . among older women ( 30 years or more ) , the prevalence rate among native americans was 26.7% compared to 0% and 4.9% of whites and hispanics , respectively . the overall trend in nri in the three main racial groups demonstrated persistence of nri at a higher rate among native americans compared to whites and hispanics ( see figure 3 ) . crude and adjusted multivariate analysis demonstrated that native americans were more than two and a half times more likely not to have rubella immunity than whites ( or 2.7 ; 95% ci : 1.1 , 6.6 ) . once we control for suspected differences in age distribution , the association remained ( or 2.7 ; 95% ci : 1.1 , 6.7 ) . this study evaluated nri among women attending high - risk prenatal care in iowa , united states . the prevalence rate of nri demonstrated in this study appeared lower compared to previous studies in 1988 ( 7.5%17.4% ) , 1999 ( 15.4% ) , and 2004 ( 9.1% ) . one of the important findings of this study is the presence of comparatively higher nri among adolescents in the study population ( see figure 2 ) . this finding supports rubella booster vaccination for nonpregnant women such as high school female teenagers . secondly , booster vaccination may also prevent undiagnosed cases of rubella that resulted in congenital anomalies and first trimester loss of pregnancy . since there is no effective treatment of infection during pregnancy that will prevent crs , protecting women before pregnancy is therefore an attractive public health intervention against crs . another important implication of this study is the finding of significant prevalence of nri across all age groups among the native american women . compared to whites , native americans are more likely to be non - immune to rubella . this finding calls for further studies and evaluation of mmr vaccination programs existing in native american communities . replication of the findings in this study may warrant public health interventions aimed at protecting these communities from rubella epidemic . despite the important findings of this study , it should be seen as a pilot study because of the imbalance in the study population . however , the study may provide the basis for evaluation of longevity of immunity derived from rubella vaccine currently administered to children in the united states as part of mmr vaccine . similarly , this paper may provide the rationale for further studies in native american communities targeted at elucidating factors that foster decreased immunity to rubella .

since the introduction of the rubella vaccine in 1969 , prevalence of congenital rubella syndrome ( crs ) has greatly declined in the united states . however , reports of sporadic adult cases of the disease and frequent identification of non - rubella immune ( nri ) women in prenatal units may result in outbreak of crs in susceptible communities . identifying populations with high rates of nri will assist in evidence - based public health intervention that may prevent epidemic of crs in the united states . method . this is a retrospective , cross - sectional study involving chart audit of rubella screening results of 642 women who attended a high - risk prenatal care at a northwestern iowa clinic between january 1 and december 31 , 2007 . results . nri was found in 6.9% of the study population . the highest prevalence rate of 10.2% was found among adolescents . nri was highest among native american women at 17.3% , compared to whites 7.3% , african americans 5.9% , and hispanics 4.6% . multivariate analysis demonstrated that native americans were 2.5 times more likely to be nri compared to whites ( or 2.7 ; 95% ci : 1.1 , 6.6 ) . conclusion . this study demonstrated higher rate of non - rubella immunity among adolescent pregnant women and supports rubella booster immunization for all non - pregnant teenage women . the observed high rate of nri among native americans may require further studies and evaluation of rubella vaccination programs in tribal communities .

due to the nature of the job , physical therapists provide medical services in close relationships with patients1 , 2 . the turnover of physical therapists is a major loss in quality improvement of health services and rehabilitation related to human resources3 . currently , medical services are moving from healthcare provider - centered to patient - centered and hospitals are also converting into patient - centered healthcare systems4 . in addition , hospital organizations are recognizing recruitment , training , and retraining for healthcare providers in each specialized field5 . to provide good quality health services , healthcare providers beliefs in significantly contributing to patient care and their own work satisfaction emotional labor refers to the idea of suppressing and limiting emotions to satisfy hospitals changing patient - centered goals and patients feelings6 , 7 . stress caused by excessive emotional labor has a negative effect on workers commitment to the organization and satisfaction toward the job9 , 10 , resulting in work - related stress ( ws ) . the work environment ( we ) of human service workers has also been presented as a major factor in turnovers11 . if an organization member leaves the organization due to turnover , ensuring good quality staffing is threatened ; large amounts of money are spent in the selection and training of new staff , finally resulting in loss to the organization12 . additionally , new employees are highly likely to make mistakes or cause accidents compared to employees with experience . employee replacement costs are also much higher than the costs of actually recruiting , hiring , and training new staff12 ; therefore , this has negative effects on the overall health and economic sectors . byun13 said in her previous research that promoting efficient task execution and reducing turnovers by reducing ws and increasing job satisfaction are very important . for the efficient management of internal employees , it is necessary to accurately identify job satisfaction and ws and analyze their correlations with turnovers . examining similar research on the correlation between a variety of factors in the workplace and turnovers within medical institutions , radiological technologists showed higher job satisfaction with higher annual income and lower working years and showed higher turnovers depending on the number of working years , wages , and night watch duty14 . age , characteristics of medical institutions in which they are working , and job satisfaction are related to turnover of occupational therapists15 . for nurses , excellent nursing is dependent on job satisfaction enabling them to handle work positively and efficiently ; higher job satisfaction reduces turnovers16 . the reality is that studies related to physical therapists include studies on ws17 , research on working conditions and job satisfaction18 , empowerment and job satisfaction , research on organizational commitment19 , etc . however , the number is remarkably small compared to studies targeting other health service workers and the data on turnover intention ( ti ) itself as well as studies that analyze the relationship between ti and we and ws of physical therapists are very rare . therefore , by investigating the effect of ws and we on physical therapists and turnover , this study can provide basic data for reducing the turnover of physical therapists and seeking effective human resource and organizational management measures in the future . the study participants were 241 physical therapists currently working in medical institutions who were directly visited during the three months from january to march 2014 for questionnaire distribution and collection . five questionnaires were miswritten due to error or insufficient survey answer contents ; 236 questionnaires were examined statistically . those who fully comprehended the study procedure and voluntarily agreed to participate were selected as participants . the ti measurement tool used seven questions ; for turnover factors , four questions modified and used by gang20 were modified and reconstructed for this study . , this study used the questionnaire consisting of 15 questions after modifying and complementing the method used by byun13 . the we measurement tool was reconstructed for this study based on the survey tool reconstructed by lim21 . each question on the measurement tool was based on a likert scale from 1 ( not at all ) to 5 ( strongly agree ) points and higher scores meant better we . cronbach s alpha values in a previous and the present study were more than 0.700 . spss 18.0 was used for the collected data and the analysis method is as follows . ti , ws , and we of the participants were obtained as means and standard deviations . the data were analyzed using cronbach s alpha coefficient to verify the reliability of questionnaire internal consistencies . the correlation between ti , ws , and we used correlation analysis through pearson s correlation coefficient and linear regression analysis to determine the impact of ws and we on ti2 . there were 106 males ( 44.9% ) and 130 females ( 55.1% ) . for age , 155 were less than 30 years old ( 65.7% ) and 81 were older than 30 years ( 34.3% ) . most were single ( n=190 , 80.5% ) ; 46 were married ( 19.5% ) . there were 104 college graduates ( 44.1% ) , 88 university graduates ( 37.3% ) , and 44 graduate students or higher ( 18.6% ) . most were hopeful ( n=198 , 83.9%).this was the first job for 113 ( 47.9% ) . in career tenure , 56 had less than one year ( 23.7% ) , 99 had 14 years ( 41.9% ) , 42 had 59 years ( 17.8% ) , and 39 had more than 10 years ( 16.5% ) . in current hospital tenure , 79 had less than 1 year ( 33.5% ) , 125 had 13 years ( 53.0% ) , and 32 had more than four years ( 13.6% ) . sixty people had less than 1.5 million monthly income ( 25.4% ) , 98 had 1.52 million ( 41.5% ) , 57 had 22.5 million ( 24.2% ) , and 21 had more than 2.5 million ( 8.9% ) . the total ti mean of participants was 3.09 0.78 ; for ws , 3.31 0.56 ; and for we , 3.25 0.46 . ti and ws ( r=0.531 , p<0.01 ) had a statistically significant positive correlation and ti and we ( r=0.511 , p<0.01 ) had a statistically significant negative correlation . ws ( =0.415 ) had a significant positive impact and we ( =0.387 ) had a significant negative impact on ti ( p<0.01 ) ( table 1table 1.impact of work environment and work related stress of study subjects on the turnover intentionvariablestwork related stress0.4157.929work environment0.3877.395r=0.419 , adjust r=0.414 , f=83.848 ( * p<0.001 ) ) . the effects of physical therapy appear through emotional and cognitive interactions in the relationship with patients . in this process , emotional labor of a physical therapist affects both the therapist and the patient . however , therapists who have previously adapted to the healthcare system have emphasized only ability and have neglected the emotional aspect22 . accordingly , psychological factors may burden poor we and reduced job involvement and job satisfaction levels9 , 10 . to provide the best care services to patients , physical therapists should continue to have a smooth interactive relationship with patients , constantly watch the patient condition , and find the optimum treatment in this process . thus , physical therapists satisfaction with their job and working with responsibility are essential elements in increasing treatment efficiency as well as cementing the relationship with patients8 . in this study , the correlations between ti , ws , and we were analyzed ; there was a statistically significant positive correlation between ti and ws . ti and we had a statistically significant negative correlation ; results of a study21 targeting 290 nurses support the results of this paper . the results of regression analysis on physical therapists ti by ws showed a positive explanatory power of 41.5% ( r=0.415 ) ; the size of the influence ( =0.415 ) shows that higher ws leads to relatively higher ti . lim s study targeting 248 nursing teachers showed 53.6% explanatory power ( r=0.536 ) and influence of =0.540 ; ws also affected ti in other occupations , highly supporting the results of this study19 . however , heo s study , targeting 353 nurses obtained only 12% explanatory power ( influence =0.36 ) showing relatively low support for the results of this study24 . on the other hand , satisfaction with we showed a negative explanatory power of 41.5% of ti ( r=0.415 ) and the size of the influence was =0.387 , indicating that low satisfaction with we leads to relatively high ti . other research results include explanatory power of 52.1% ( r=0.521 ) , and influence of =0.229 ( working environment ) , =0.382 ( self - development ) , and =0.263 ( working facilities ) in lee s study targeting 236 golf course employees25 ; explanatory power of 53.6% ( r=0.536 ) and influence of =0.141(relationship with superintendent ) and =0.118 ( compensation adequacy ) in lim s study targeting nursing teachers21 ; and explanatory power of 36% ( r=0.360 ) and influence of =0.228 in sin s study targeting local hospital nurses23 . thus , we affected ti in other occupations , showing high support for the results of this study . according to the results of this study , the higher the ws , the higher the ti , and the better the we , the lower the ti . in particular , ws had a greater impact on ti than we . this is similar to the results of lim21 and jeongs26 studies in which ws had the most significant impact on ti . therefore , ws becomes the direct cause of turnovers and if not solved , leads to turnovers . thus , it is essential to reduce the ws of physical therapists and improve the we ; ways to reduce turnovers should be sought through this . the limitation of this study is that it can not be generalized to all physical therapists due to its potential selection bias ; physical therapists in daejeon ( chungcheong ) , physical therapists working in rehabilitation hospitals , and young physical therapists were surveyed . further , the correlations between various stress factors and we affecting ti could not be clearly identified because survey questions were not segmented . in conclusion , future research including national physical therapists , all medical institutions , and participants of various ages needs to be conducted . the root cause can be found and solved when correlations of each factor are identified more clearly through the segmentation of the survey questions .

[ purpose ] this study was conducted to provide basic data for solutions to reduce the turnover rate of physical therapists . it should help create efficient personnel and organization management by exploring the impact of the work environment and work - related stress on turnover intention and analyzing the correlation between them . [ subjects and methods ] a survey was conducted with 236 physical therapists working at medical institutions in the daejeon and chungcheong areas . for the analysis on the collected data , correlational and linear regression analyses were conducted using the spss 18.0 program and cronbach s alpha coefficient . [ results ] the results showed a statistically significant positive correlation between turnover intention and work - related stress but a statistically significant negative correlation respectively between turnover intention and work environment . work - related stress ( =0.415 ) had a significant positive impact on turnover intention and work environment ( =0.387 ) had a significant negative impact on turnover intention . [ conclusion ] to increase satisfaction level with the profession as well as the workplace for physical therapists , improvement of the work environment was the most necessary primary improvement .

numbers were maintained at about this level for a further five years since when there has been a consistent reduction in the mule population . in 2009 the numbers of mules in the country were at their lowest recorded , the actual number being about 51,500 . the reason for mules maintaining their numbers for a longer period than donkeys whose numbers started to decline rapidly from the early 1970s were able to do is not known . mules are the least numerous equine in turkey representing 11.1 % of the total complement of this group compared to the 38.6 % of horses and the 50.3 % of donkeys . mules are found principally in four more or less mountainous and discrete areas of turkey ( fig . these are ; ( 1 ) southeast and east turkey below the southeast taurus mountains in the sirnak , mardin , hakkari and van in provinces close to the national border with syria , iraq and iran where they are owned almost exclusively by kurds ; ( 2 ) southern turkey in the hilly and mountainous areas of the middle taurus mountains in mersin ( formerly iel ) province where they are mostly owned by the pastoral and seminomadic yoruk people ; ( 3 ) western turkey south of the sea of marmara and east of the mediterranean sea and around mount temnus in balikesir province where once again the main owners are the yoruks ; and ( 4 ) north - central turkey south of the black sea and in the northern foothills of the canik mountains in ordu province . mules are not bred in the country but imported from neighbouring iraq and iran ( interviews with owners and key informants by orhan yilmaz ) . these imports are technically illegal in that there is very little to no formal transfer of place nor owner when the animals enter turkey . in the southeast in sirnak , mardin and hakkari province has borders with both iraq and iran but it is only iraq that provides mules to turkey here . in these provinces all the mules in the mersin area are imported from iraq to turkey and first transit through the east / southeast concentration area before being brought to mersin . rather more surprising is the apparent fact that mules in balikesir also originate from far - away iraq and are then transported to the far northwest of turkey . ordu province appears to be unique in turkey in that it is the only concentration area of mules in which in the twenty - first century they are actually bred . the home tract of the canik is north - central anatolia close to the black sea mainly in the canik mountains after which the horse type is named . it is a very sure footed horse well adapted to the hilly and mountainous areas that are its home and thus probably an ideal progenitor for mules . mules were used by both the ottoman and the western armies in the first world war ( 19141918 ) . little is known of their actual use by the ottomans but there is considerable information on their employment by the western allies . elements of the indian army and the australian and new zealand army corps ( anzac ) made great use of mules at the battles around gallipoli in the summer and autumn of 1915 . there was also a zion mule corps which had been raised in egypt expressly for the dardanelles expedition from jewish refugees from syria and was thought to be the first entirely jewish unit to enter battle for almost two thousand years . the indian mule corps manned largely by sikhs who refused to take leave because they thought their replacements would not take good care of their mules comprised eight troops of 96 mules each that carried ammunition , medical supplies and signalling equipment . it was said that horse or motor transport would not have been able to face the difficulties of anzac . there were 1889 mules at anzac cove in 1915 of which at least 296 were killed and 599 wounded . it is noteworthy that mules in modern turkey are mainly found in what might be considered classic country for this hardy and sure - footed species . in these mountainous areas roads are few and far between or non existent , so motor vehicles are largely precluded and horses have insufficient strength , stamina and agility to work here . this preponderance of mules in more difficult terrain is to be expected from their locations in other countries such as upland nepal , in high altitude natural - resource - poor areas of central mexico and in lesotho where mules are used at altitudes and in forestry conditions not suitable for wheeled transport . another particularity of mules in turkey is their association with minority groups such as kurds and yoruk ( fig . kurd woman with pack mule . in the kurdish areas of east and southeast turkey mules are largely used in cross - border trade , much of which is illegal . the main commodities transported are oil products originating in iran and cigarettes from iraq . animals are often turned loose outside turkey and left without attendants to return alone to their own homes . although the national borders are patrolled by the army there seems to be some tacit acceptance of smuggling . the reasons for this could be related to the european union accession process and also to a belief on the part of the authorities that further oppression of the kurds will lead to greater separatist activity and terrorism . the rocky areas of the southeast taurus mountains in which mersin province is located are largely unsuitable for agriculture but are well wooded . the local yoruk people have maintained their seminomadic and pastoral existence and use their mules here for transporting wood and other forest products to supplement their incomes and contribute to improved livelihoods . although balikesir in the northwest has some hilly and mountain areas the environment here is less demanding than in mersin and the mediterranean influence allows cultivation of olives . in addition to transport of wood and forest products the yoruk people also hire out their mules to local cultivators for carrying olives and olive oil . the canik mountains of ordu province are blessed with better soils than many other parts of turkey . hazel ( cob ) nuts are a major agricultural output from this area and their transport is one of the major activities of mules . others are used by cattle and sheep breeders who transume to the mountains to carry camp gear and other small necessities . many mules in turkey are used to advanced ages . in one study in the southeast of the country 24 % of mules were aged more than 10 years and some were still being used at upwards of 30 years . use to advanced ages is common in other countries : in morocco , for example , 54 % of mules slaughtered for meat were 1015 years of age and 19 % were older than 15 years . in a study of 236 mules in four provinces of east and southeast turkey the anova and students t - test functions of the minitab programme were used to analyze data . average withers height was 130.6 0.49 cm ( 12 hands 3 ) . these results were very similar to those found in an earlier study of the morphometry of turkish mules where withers height was determined as 130.4 cm . withers height was not affected by sex ( although males appeared slightly larger ) , age or coat colour but was by province of location ( table 1table 1.descriptive statistics of some phenotypic traits of turkish mules ) . all measured traits were affected by the province variable but there were no other significant differences in traits due to sex , age or coat colour . the lack of difference in mensuration due to age is indicative of early maturity of mules for body size . turkish mules appear to be larger than english ones which average about 120 cm at the withers ( faith burden , personal communication , 12 july 2011 ) . other common colours are white ( 23.7 % ) and black ( 16.5 % ) with chestnut ( 7.6 % ) and grey ( 7.6 % ) being less common and dun ( buckskin ) ( 0.8 % ) and cream ( isabelline ) ( 0.8 % ) being seen occasionally . the back stripe and shoulder cross of the parent donkey is maintained in some mules ( fig . they have been used in war and in agricultural and transport operations as both riding and pack animals . they have lost much of their former value , having been replaced by mechanical and electrical power in many areas . they still retain some importance in hilly and mountainous areas and especially for resource poor minority groups . downward pressure on numbers ( the mule population of 51,500 animals in 2009 was less than one - sixth of the 324,000 head present in the country in 1977 ) will continue and this , combined with the restricted and fragmented geographical distribution of the species within the country , will exert a negative effect on a part of turkey s national heritage and domestic animal biodiversity . as part of the country s historical and cultural heritage , however , their breeding should be encouraged and supported .

mules are known to have been used as carriage and riding animals in mesopotamia and anatolia as early as the beginning of the second millennium bc but may have been first bred in anatolia in the third century bc . they have thus contributed to turkey s cultural , social and economic heritage for more than 4,000 years and were an ancient component of its guild of domestic animals and overall biodiversity . once bred country - wide most mules are now introduced illegally to the southeast and east from iraq and iran . mules are now bred only in one small area in north - central turkey close to the black sea . the major role as a pack animal has been usurped since the mid - twentieth century by increasing use of motor transport and numbers have declined rapidly since the early 1980s . in 2009 about 51,500 mules remained in turkey , mainly distributed in discrete areas in the extreme southeast , the centre - south , the northwest and the centre - north . in the southeast the main role is in cross - border trade ( much of it described as smuggling ) whereas in other areas mules are used in support of pastoral and farming operations . mules in turkey are of various colours but are generally large and strong compared to those found in many other countries . pressure on numbers will continue and will exert a negative effect on a part of turkey s national heritage and domestic animal biodiversity .

atrial fibrillation and heart failure are emerging and co - existing cardiovascular disease epidemics of the new millennium . atrial fibrillation , present in 10 - 40% of patients with heart failure , is associated with adverse clinical consequences , including excess risk of death , hemodynamic decompensation , exacerbation of heart failure , impaired functional capacity , and risk of stroke [ 1 - 7 ] . the adverse impact of atrial fibrillation in heart failure has been attributed to the presence of irregular and/or excessive ventricular rates , lack of atrial contribution to ventricular filling , and the toxicity of therapies prescribed to control rate , to control rhythm , and to reduce the risk of stroke . in addition to anticoagulation , rate control [ drugs or atrioventricular ( av ) junctional ablation ] is probably the only option for permanent atrial fibrillation , but the optimal strategy for managing paroxysmal and persistent atrial fibrillation in heart failure remains uncertain . given adverse prognostic implications and postulated hemodynamic consequences , aggressive re - establishment and maintenance of sinus rhythm with antiarrhythmic drugs and/or ablation has been advocated , and frequently attempted , in the hope of achieving better outcomes . on the other hand , interventions to attempt to maintain sinus rhythm may be ineffective , temporary , and potentially toxic . available data show no benefit for a routine rhythm - control strategy for management of atrial fibrillation [ 9 - 11 ] but only a small minority of the patients enrolled had systolic dysfunction . a recent prospective , multicenter , randomized clinical trial , termed the atrial fibrillation and congestive heart failure ( af - chf ) trial , confirms this same finding in the heart failure population . the af - chf trial randomized 1,376 patients with paroxysmal or persistent atrial fibrillation , a left ventricular ejection fraction < 35% , and new york heart association ( nyha ) functional class iii or iv heart failure , to a rate - control strategy ( using beta - blockers and/or digoxin with av junctional ablation if drugs were ineffective ) or a rhythm - control approach ( amiodarone along with electrical cardioversion as needed ) . the rhythm - control group was associated with a substantial increase in sinus rhythm but no obvious benefit was seen during the 37 19-month follow - up . death from cardiovascular causes , adjusted for baseline differences , was the same in both groups . secondary outcomes , including death from any cause , stroke , and worsening heart failure , were also similar in both groups . it is unclear whether a better therapy to maintain sinus rhythm would have had a better outcome . given the currently reported success rates of atrial fibrillation ablation , it is unlikely that ablation would be better than the rhythm - control strategy ( that is , amiodarone ) used in the af - chf trial . in regard to pharmacologic therapy to maintain sinus rhythm , amiodarone appears to be the most potent . only amiodarone and dofetilide have been shown to have a neutral effect on survival when compared to placebo [ 4,14 - 17 ] , but these drugs may have long - term toxicity . dronedarone , a congener of amiodarone ( with its multichannel - blocking abilities , but without its iodine - related moiety ) , seemed appealing in this regard . the recently reported anti - arrhythmic trial with dronedarone in moderate to severe congestive heart failure evaluating morbidity decrease ( andromeda ) , compared dronedarone with placebo in atrial fibrillation patients who had heart failure and a left ventricular ejection fraction < 35% . the study was terminated prematurely after enrolling 627 patients ( 310 taking dronedarone and 317 taking placebo ) over a 7-month period ( median follow - up of 2 months ) as mortality was significantly increased in the dronedarone arm ( 8.1 versus 3.8% in the placebo arm ) . this excess mortality was predominantly due to deaths from worsening heart failure and was greatest in patients with the most severe left ventricular dysfunction . treatment with dronedarone was the most powerful predictor of death after adjustment for other risk factors . this study dealt a blow at efforts to develop a safe and effective antiarrhythmic drug to use for atrial fibrillation in heart failure . although previous studies indicate that atrial fibrillation is independently associated with increased mortality in heart failure , in reality , atrial fibrillation may simply be a marker of poor prognosis , as these heart failure patients may be more ill . thus , the rhythm by itself may not need treatment except to manage adverse consequences - that is , exacerbation of heart failure and risk of thromboembolism - in selected patients . adjunctive therapies , including angiotensin - converting enzyme inhibitors ( aceis ) , angiotensin receptor blockers ( arbs ) , statins , and omega-3 fatty acids , may also help prevent atrial fibrillation in heart failure patients . modulation of the renin - angiotensin system by aceis has been shown to attenuate arrhythmogenic atrial structural remodeling in experimental models of heart failure . a meta - analysis of randomized clinical trials showed that use of both aceis and arbs significantly reduced ( relative risk reduction = 44% ) the incidence of atrial fibrillation in patients with systolic heart failure . both statins and omega-3 fatty acids have been thought to have favorable effects on atrial structural remodeling in heart failure , but the exact mechanisms as well as the magnitude of their beneficial effects remain unclear . it is time to rethink the widely held belief that restoration and maintenance of sinus rhythm using antiarrhythmics and serial electrical cardioversions benefits patients with systolic dysfunction and heart failure . a strategy aimed at sinus rhythm does not improve cardiovascular and all - cause mortality , risk of stroke , and worsening of heart failure . instead , it can result in repeated cardioversions , hospitalization from drug - related side effects , and even increased mortality , as shown with the use of dronedarone . whether invasive attempts at rhythm control , such as by ablation , will improve outcomes , remains to be seen . at present , rate control with appropriate anticoagulation should be considered as the primary strategy to manage atrial fibrillation in patients with heart failure . beta - blockers with or without digoxin should be first - line rate - control agents but multiple drug combinations and even av junctional ablation may be needed . in regard to anticoagulation rhythm control should only be pursued in those highly symptomatic heart failure patients who have rapid uncontrolled atrial fibrillation that fails to respond to standard rate - control therapy and for selected patients who are shown to have worsening heart failure symptoms and/or poor quality of life attributable to atrial fibrillation , despite adequate rate control .

atrial fibrillation , a common problem in patients with heart failure , is associated with increased mortality and morbidity . pharmacological as well as invasive management and the endpoints of such management are complex . recent randomized trials indicate that a rate - control strategy , along with anticoagulation treatment with warfarin , when appropriate , has a similar outcome in terms of mortality and morbidity as rhythm control , and could , therefore , be considered as the primary management strategy for atrial fibrillation in patients with heart failure .

to begin this procedure , we ensure that all scuva components have sufficient battery power , recording tape ( for the high - definition or hd video camera ) , and function properly . depending on the flows to be measured , select video camera resolution and frame rates that yield best results for digital particle image velocimetry ( dpiv ) . prepare the laser and camera housings for use by cleaning the o - ring grooves and o - rings with a clean towel or wipe . spread manufacturer provided o - ring grease evenly on the o - rings and replace them in the housing grooves . in addition , clean the laser and camera housing apertures to prevent laser sheet deformation and marks on the camera housing lens . check the o - ring seals by placing both empty housings in a tub full of water . weighted objects will need to be placed on top of the housings to submerge them since the housings float when empty . after 5 to 10 minutes , remove the housings from the tub and towel dry the outside . check whether there is any moisture inside the housings . also consider using disposable , paper moisture strips during the pressure test to indicate whether there is moisture in the housings after the test . after the housings pass the pressure test , place scuva components inside the housings . ensure that the lights are oriented in such a way that they illuminate the area directly ahead of the camera and operator , and do not interfere with maintaining grip on handles and operation of camera controls . in a low light environment , ensure that the laser beam is properly aligned relative to the optical lens installed in the laser housing . when properly aligned , the laser / lens combination will create a vertical sheet of light that is oriented perpendicular to the camera housing . for safety , use a temperature - sensitive sheet of paper to determine laser sheet orientation . using scuva attachments and the rigid , extendable arm , connect the laser housing and the camera housing to each other . ensure that the housings are firmly attached and that the housings can not rotate with respect to each other . it is critical that the laser sheet remains oriented perpendicular to the camera s field of view throughout the measurement . due to the current capabilities of scuva , measurement dives can only be conducted in low - light locations or at nighttime to prevent natural light interference with the laser sheet . the camera housing has a built - in electronic moisture sensor that provides visual warnings ( flashing led lights ) in case of moisture in the camera housing . once attached to the apparatus , release scuva to determine the buoyancy characteristics of the device . depending on the buoyancy characteristics , attach buoyancy foam or lead weights to one or both housings to ensure neutral buoyancy and prevent rotation of the apparatus in water . position the laser using the extendable arm sufficiently far from the diver to minimize measurement of diver - induced flows . any measurements of diver - induced flows near the target introduce error and are not used for subsequent analysis . adjust the camera zoom until the field of view frames the target and surrounding fluid . while keeping the apparatus stationary , focus the video camera on the laser sheet until particles appear sharp and in focus . once the laser sheet plane is in focus , switch the camera to the manual focus mode . this will prevent the camera from refocusing on any objects that appear in the field of view during measurement , resulting in blurred particles in the laser sheet . to calibrate scuva , place an object with known dimensions in the laser sheet within the video camera 's field of view . after the dive , an image will be extracted from this video sequence to determine a calibration constant that converts the field of view size from units of pixels to cm . if at any time the operator adjusts the field of view size be re - position the extendable arm or changing the camera zoom during the dive , steps 12 and 13 will need to be repeated . the environmental bulk flow properties need to be determined . if present , the current direction will dictate apparatus and diver positioning relative to the target during measurements . the direction of bulk flow surrounding the target can be inferred by observing bubbles exhaled from the diver and noting their lateral motion . in addition to bubbles , a small quantity of fluorescent dye ( i.e. , fluorescein ) can be released to determine the current direction . since diver - generated flow can be a source of dpiv measurement error , the diver should not be located upstream of the target . in addition , the laser sheet should be positioned parallel to the direction of current so as to maximize particle residence time within the laser sheet , thereby minimizing dpiv errors . however , if no current or bulk flow is present , diver and scuva positioning relative to the target are unrestricted . if attempting to record the flow surrounding a moving target first predict the location of the target , and then position scuva to the predicted location while remaining motionless . as the target moves through the camera s field of view , if the target is motionless , frame the target and surrounding fluid in the video camera s field of view and begin recording while remaining motionless . the operator should refrain from rotational and out - of - plane motions during video recording since these motions result in erroneous dpiv results . therefore , measurements collected during rotational and out - of - plane diver motions will not be used for further data analysis . once video collection is complete , turn off all components of scuva and restore the laser arm to its retracted position . remove scuva from the water and detach the camera and laser housings from the arm . rinse or soak the apparatus in fresh water before drying to prevent rusting of the apparatus . once the housings are dried , remove components from the housings , and recharge and replace batteries if needed for another dive . connect the video camera to a computer and extract video from the hd tape by using a hd video software package ( i.e. , adobe premiere pro or imovie ) . after the video is extracted , determine the range of video to be converted into a series of images for dpiv analysis . ensure that the pixel aspect ratios and extracted image sizes match the hd video settings . these images are imported to a dpiv processing program ( i.e. , davis or matpiv ) . after proper selection of calibration constant and image capture parameters , which are prompted from the dpiv software package , velocity fields can be generated from consecutive particle images . additional post - processing steps , depending on the quality and types of measurements , can also be applied . when the protocol is done correctly , the particle images surrounding the target will be sharp and easy to distinguish . using the particle fields captured in situ by scuva s video camera ( figure 1a ) and a dpiv processing software package , velocity fields of flow surrounding the target ( figure 1b ) vectors in the velocity field indicate magnitude and direction of the local flow velocity . if sufficient video is collected to provide a time series of images , a time series of velocity fields can also be determined . figure 1 measured in situ particle fields ( a ) surrounding aurelia labiata . corresponding velocity field ( b ) with yellow vectors indicating flow direction and magnitude . red arrow in a indicates a region of high reflectivity , which results in saturation of the image , making it difficult to distinguish between particles and the target . red arrow in b indicates a region of streaking that results when the flow rate is not sampled at a high enough frequency . when the protocol is done correctly , the particle images surrounding the target will be sharp and easy to distinguish . using the particle fields captured in situ by scuva s video camera ( figure 1a ) and a dpiv processing software package , velocity fields of flow surrounding the target ( figure 1b ) will be revealed . vectors in the velocity field indicate magnitude and direction of the local flow velocity . if sufficient video is collected to provide a time series of images , a time series of velocity fields can also be determined . figure 1 measured in situ particle fields ( a ) surrounding aurelia labiata . corresponding velocity field ( b ) with yellow vectors indicating flow direction and magnitude . red arrow in a indicates a region of high reflectivity , which results in saturation of the image , making it difficult to distinguish between particles and the target . red arrow in b indicates a region of streaking that results when the flow rate is not sampled at a high enough frequency . a potential constraint in the field is the need for particles in the flow , which are necessary to implement digital particle image velocimetry ( dpiv ) . in coastal water , suspended particulate matter exhibits sizes on the order of 10 m in diameter and concentrations between 0.002 and 10 per mm . additional studies using a submersible holocamera for particle detection confirm sufficient presence of seeding particles to perform dpiv in ocean water . during open sea and coastal ocean diving , we have found that particle densities and sizes are not a constraint for conducting in situ dpiv . aside from particle densities and sizes , qualitatively , if a region within an interrogation window has greater particle concentrations than another , the velocity magnitude generated by the dpiv analysis will be biased towards the region with higher particle concentrations . we found thatcle concentrations are relatively constant during particle concentrations are relatively constant during dives where the diver is suspended in the middle of the water column . however , particle fields in benthic environments have the potential for inhomogeneity due to resuspension of particles by environmental or diver - induced flows near the sea floor . care must be taken to minimize disruption of particles during measurements in benthic environments . to the authors ' knowledge , a formal analysis of errors generated by inhomogeneous particle concentration fields has not been conducted in either laboratory or field conditions , and should be a subject for further consideration in a separate publication . several different issues should be considered when preparing and conducting in situ experiments using the protocol . while recording , the operator is instructed to remain stationary and refrain from all out - of - plane and rotational motion . this request is simple in theory but difficult in practice , and these measurements require advanced diving skill to be completed successfully . out - of plane and rotational motions of the operator result in erroneous dpiv data . however , in - plane motions can be corrected by using in - house software . it is recommended to the operator to practice buoyancy control for several dives before using scuva to maximize measurement efficiency . besides buoyancy considerations flows that travel out - of - plane relative to the laser sheet will not yield reliable dpiv results , and the operator should orient scuva to capture these flows most effectively . in addition , the position of the diver relative to the target must be selected so as to minimize diver - induced flow in the measurements . diver - induced flow introduces error to the target flow , and measurements that include diver effects should not be used for further analysis . in the event that the target has a highly reflective surface , the fluid region surrounding the target will be strongly illuminated , making it difficult to distinguish nearby individual particles from surrounding fluid ( region indicated by red arrow , figure 2a ) . filters or polarizers can be added to the laser or camera housings to reduce the intensity of the laser light captured by the video camera sensor . if this is not possible due to logistical constraints and limited access to equipment , post - processing of images using in - house software can provide sufficient correction by subtracting from the images the elevated pixel intensities near the target . another consideration that affects the quality of dpiv data is whether particle streaks are present . if particle fields have regions of streaking ( indicated by red arrow , figure 2b ) , the video camera is recording at a frame rate too low to resolve these high velocities . by increasing the frame rate , , this results in a reduction of light reaching the video camera sensor and makes the particle field look dimmer . if the video camera has the ability to manually set aperture settings , increase the aperture setting to prevent dimming of the particle field . determining the optimal device settings may require multiple dives with scuva before successful data collection .

the ability to directly measure velocity fields in a fluid environment is necessary to provide empirical data for studies in fields as diverse as oceanography , ecology , biology , and fluid mechanics . field measurements introduce practical challenges such as environmental conditions , animal availability , and the need for field - compatible measurement techniques . to avoid these challenges , scientists typically use controlled laboratory environments to study animal - fluid interactions . however , it is reasonable to question whether one can extrapolate natural behavior ( i.e. , that which occurs in the field ) from laboratory measurements . therefore , in situ quantitative flow measurements are needed to accurately describe animal swimming in their natural environment.we designed a self - contained , portable device that operates independent of any connection to the surface , and can provide quantitative measurements of the flow field surrounding an animal . this apparatus , a self - contained underwater velocimetry apparatus ( scuva ) , can be operated by a single scuba diver in depths up to 40 m. due to the added complexity inherent of field conditions , additional considerations and preparation are required when compared to laboratory measurements . these considerations include , but are not limited to , operator motion , predicting position of swimming targets , available natural suspended particulate , and orientation of scuva relative to the flow of interest . the following protocol is intended to address these common field challenges and to maximize measurement success .

visual imagery is the ability to generate percept - like images in the absence of retinal input and is therefore a vivid demonstration of retrieving pictorial information from memory . psychophysical and brain imaging studies have demonstrated functional similarities between visual perception and visual imagery to the extent that common mechanisms appear to be activated by both [ 1 - 4 ] . numerous neuroimaging studies have shown that visual imagery , like visual perception , evokes activation in occipito - parietal and occipito - temporal visual association areas . in some studies , the primary visual cortex was activated during imagery , suggesting that the generation of mental images may involve sensory representations at the earlier processing stages in the visual pathway . studies of patients with brain damage have demonstrated a dissociation of visual - object and visual - spatial imagery , indicating that different parts of the visual system mediate where and what imagery , a dissociation that parallels the two anatomically distinct visual systems proposed for visual perception . single - unit recordings in epileptic patients revealed that neurons in the human medial temporal lobe fired selectively during both visual perception and visual imagery , suggesting that the neurons activated during storage of incoming visual input are later reactivated during the mnemonic retrieval . although many studies have focused on the overlap and similarities between perception and imagery , the subjective experiences of imagining and seeing are clearly very different . the intriguing case study of ck , a patient with severe visual agnosia who can not recognize objects but can draw them with considerable details from memory , suggests that visual imagery can be dissociated from visual perception . it has also been shown that during visual imagery , deactivation in auditory cortex is negatively correlated with activation in visual cortex and with the score of subjective vividness of visual imagery , suggesting that in order to generate vivid mental images , the brain needs to filter out irrelevant sensory information . functional magnetic resonance imaging ( fmri ) studies have reported that within the ventral pathway , faces and other objects , such as outdoor scenes , houses , animals , and tools , have distinct representations . in particular , it has been shown that faces , houses , and chairs evoke highly consistent patterns of neural responses in occipital and temporal cortices . similar activation is observed in extrastriate cortex during visual and tactile recognition of faces and man - made objects in sighted subjects and during tactile recognition in blind subjects , suggesting that more abstract features of object form are represented in the visual ventral stream . inspired by the consistent topology of the response to faces , houses , and chairs , a series of studies were conducted to investigate whether visual imagery of these objects would evoke content - related activation within the same ventral regions that are activated during perception . content - related activation during imagery was found in temporal cortex ( e.g. , imagery of faces activated the lateral fusiform gyrus , whereas imagery of houses activated the medial fusiform gyrus ) , but this activity was restricted to small subsets of the regions that were activated during perception . moreover , visual imagery of faces and objects evoked activity in parietal and frontal cortex , suggesting that content - related activation during imagery is mediated by the retrieval of face and object representations from long - term memory and their maintenance in the mind s eye . analysis of effective connectivity revealed that during visual perception , category - selective patterns of activation in extrastriate cortex are mediated by content - sensitive forward connections from early visual areas . in contrast , during visual imagery , category - selective activation is mediated by content - sensitive backward connections from prefrontal cortex , suggesting that neuronal interactions between occipito - temporal , parietal , and frontal regions are task- and stimulus - dependent . additionally , non - selective , top - down processes , originating in superior parietal areas , contribute to the generation of mental images , regardless of their content , and their maintenance through visual imagery . similar findings were reported in a study of motion imagery , which found activation in a network composed of motion - sensitive regions ( human middle temporal / v5 complex ) and prefrontal areas ( frontal eye field and brodmann area [ ba ] 9/46 ) . it therefore seems that mental imagery is a dynamic cognitive function that engages distributed cortical networks activated during the allocation of attention and retrieval from memory . interestingly , recent studies of art perception have shown that when confronted with abstract and indeterminate paintings , viewers use mental imagery and contextual associations to understand the content of these art compositions . these novel findings indicate that visual imagery is an essential cognitive ability required not only for anticipating and retrieving information from memory but , importantly , for comprehending the world around us . functional magnetic resonance imaging ( fmri ) studies have reported that within the ventral pathway , faces and other objects , such as outdoor scenes , houses , animals , and tools , have distinct representations . in particular , it has been shown that faces , houses , and chairs evoke highly consistent patterns of neural responses in occipital and temporal cortices . similar activation is observed in extrastriate cortex during visual and tactile recognition of faces and man - made objects in sighted subjects and during tactile recognition in blind subjects , suggesting that more abstract features of object form are represented in the visual ventral stream . inspired by the consistent topology of the response to faces , houses , and chairs , a series of studies were conducted to investigate whether visual imagery of these objects would evoke content - related activation within the same ventral regions that are activated during perception . content - related activation during imagery was found in temporal cortex ( e.g. , imagery of faces activated the lateral fusiform gyrus , whereas imagery of houses activated the medial fusiform gyrus ) , but this activity was restricted to small subsets of the regions that were activated during perception . moreover , visual imagery of faces and objects evoked activity in parietal and frontal cortex , suggesting that content - related activation during imagery is mediated by the retrieval of face and object representations from long - term memory and their maintenance in the mind s eye . analysis of effective connectivity revealed that during visual perception , category - selective patterns of activation in extrastriate cortex are mediated by content - sensitive forward connections from early visual areas . in contrast , during visual imagery , category - selective activation is mediated by content - sensitive backward connections from prefrontal cortex , suggesting that neuronal interactions between occipito - temporal , parietal , and frontal regions are task- and stimulus - dependent . additionally , non - selective , top - down processes , originating in superior parietal areas , contribute to the generation of mental images , regardless of their content , and their maintenance through visual imagery . similar findings were reported in a study of motion imagery , which found activation in a network composed of motion - sensitive regions ( human middle temporal / v5 complex ) and prefrontal areas ( frontal eye field and brodmann area [ ba ] 9/46 ) . it therefore seems that mental imagery is a dynamic cognitive function that engages distributed cortical networks activated during the allocation of attention and retrieval from memory . interestingly , recent studies of art perception have shown that when confronted with abstract and indeterminate paintings , viewers use mental imagery and contextual associations to understand the content of these art compositions . these novel findings indicate that visual imagery is an essential cognitive ability required not only for anticipating and retrieving information from memory but , importantly , for comprehending the world around us . recent studies in vegetative state patients have discovered normal patterns of activation in their brain during mental imagery . when a young woman in a vegetative state was asked to imagine playing tennis or to navigate her way around her house , significant activity was observed in her brain , similar to the activity in the brain of healthy volunteers performing the same tasks ( figure 1 ) . these surprising findings suggest that vegetative state patients retain the ability to understand verbal instructions and to carry out mental tasks in response to those instructions , namely to exhibit willed , voluntary behavior in the absence of any overt action . mental imagery can therefore be used as a neural proxy for behavior in order to assess the degree of consciousness in non - communicative brain - damaged patients and perhaps predict their recovery . a recent study has shown that the precuneus , which mediates memory - related imagery , is also activated during hypnosis , suggesting that such a state of enhanced self - monitoring is achieved by control of motor responses by internal representations . thus , understanding the neural mechanisms of mental imagery could have far - reaching implications for understanding conscious awareness and its various disorders . yes responses ) and imagining moving from room to room in the home ( to convey no responses ) . the similar patterns of neural activation suggest that some patients in a vegetative or minimally conscious state have activity that reflects awareness and cognition . adapted from monti et al recent studies in vegetative state patients have discovered normal patterns of activation in their brain during mental imagery . when a young woman in a vegetative state was asked to imagine playing tennis or to navigate her way around her house , significant activity was observed in her brain , similar to the activity in the brain of healthy volunteers performing the same tasks ( figure 1 ) . these surprising findings suggest that vegetative state patients retain the ability to understand verbal instructions and to carry out mental tasks in response to those instructions , namely to exhibit willed , voluntary behavior in the absence of any overt action . mental imagery can therefore be used as a neural proxy for behavior in order to assess the degree of consciousness in non - communicative brain - damaged patients and perhaps predict their recovery . a recent study has shown that the precuneus , which mediates memory - related imagery , is also activated during hypnosis , suggesting that such a state of enhanced self - monitoring is achieved by control of motor responses by internal representations . thus , understanding the neural mechanisms of mental imagery could have far - reaching implications for understanding conscious awareness and its various disorders . yes responses ) and imagining moving from room to room in the home ( to convey no responses ) . the similar patterns of neural activation suggest that some patients in a vegetative or minimally conscious state have activity that reflects awareness and cognition . adapted from monti et al recent developments in deciphering the mental chronometry and functional and effective connectivity during spatial imagery suggest hierarchical temporal dynamics within the imagery network . the use of classifiers for decoding mental states and predictive coding models would enable additional insights into the neural mechanisms of both perception and mental imagery . understanding the neuronal interactions among visual , parietal , and prefrontal regions has far - reaching clinical implications , reinforced by the fact that vegetative state patients show healthy patterns of brain activation during mental imagery which reflect will and intention , the hallmark of conscious awareness . identifying residual cognitive function in such patients by means of fmri and electroencephalogram can be used not only for diagnosis and prognosis but perhaps also as a form of communication with patients who lack speech or the motor act of expression . hopefully , in the near future , combining cutting - edge analytic techniques will enable clinicians to make accurate predictions about the recovery of non - communicative brain - damaged patients .

with the advent of functional brain imaging techniques and recent developments in the analysis of cortical connectivity , the focus of mental imagery studies has shifted from a semi - modular approach to an integrated cortical network perspective . functional magnetic resonance imaging studies of visual imagery of faces and objects show that activation of content - specific representations stored in the ventral visual stream is top - down - modulated by parietal and frontal regions . recent findings in patients with conscious awareness disorders reveal that mental imagery can be used to map patterns of residual cognitive function in their brain and to provide diagnostic and prognostic indicators .

anterior crossbite is a major esthetic and functional anomaly which has to be corrected at the onset in primary as well as mixed dentition to allow the normal development of occlusion . it is the lingual positioning of the maxillary anterior teeth in relation to the mandibular anterior teeth or lingo - occlusion of upper incisors or reverse over jet . etiological factors include trauma , supernumerary teeth , crowding , lip biting , over - retained , necrotic or pulpless primary tooth or root , delayed exfoliation of the primary incisors , and odontomas . functional crossbite or pseudo class 3 results from an early dental interference that forces the mandible to a more forward position to obtain maximum intercuspation . anterior and posterior crossbites in the early mixed dentition are believed to be transferred from the primary to the permanent dentition and can have long - term effects on the growth and development of the teeth and jaws . early treatment is directed with the following objectives : to prevent dysplastic growth of both dental and skeletal componentsto prevent excessive , abnormal wear of labial surface of maxillary and mandibular incisorsto avoid periodontal problems in mandibular incisors because of traumato alleviate functional posterior crossbite that can develop from cuspal interferences and mandibular shift that happens to accommodate the crossbiteto prevent habits such as bruxism resulting from improper occlusion , andearly treatment can re - establish proper muscle balance , thus prevents jaw muscles adjusting to the habitual posture of the mandible . to prevent dysplastic growth of both dental and skeletal components to prevent excessive , abnormal wear of labial surface of maxillary and mandibular incisors to avoid periodontal problems in mandibular incisors because of trauma to alleviate functional posterior crossbite that can develop from cuspal interferences and mandibular shift that happens to accommodate the crossbite to prevent habits such as bruxism resulting from improper occlusion , and early treatment can re - establish proper muscle balance , thus prevents jaw muscles adjusting to the habitual posture of the mandible . several orthodontic and nonorthodontic treatment options are available . nonorthodontic options include tongue blades , composite inclined planes , reversed stainless steel crowns , abnormally bulky restorations , and extractions followed by prosthetic replacement in older populations . other less common options include selective recontouring of teeth , surgically repositioning teeth , and segmental osteotomy of the affected teeth . orthodontic options include various removable acrylic appliances and fixed appliances with lingual springs and expansion screws . the name invisalign ( align technology , inc . , san jose , ca , usa ) has given rise to various other similar techniques such as clear align and clear bite . kesling in 1946 described the concept of using a series of thermoplastic positioners to move teeth . align technology in 1997 introduced clear aligner technology . over the years , it has evolved and can correct many irregularities which were not possible with earlier appliances . basically , all these appliances use a series of clear aligners and move teeth in a series of 0.251 mm at a time and are worn from 7 to 14 days per tray according to different manufactures . initially , it was fabricated on stone casts which has given way to thermoforming and three - dimensional printing . the major drawbacks of clear aligners are the phenomenal costs and some limitations in tooth movement . when applying this science to anterior crossbite correction , it had the following limitations . the tray being thin ( 0.5 mm sheet ) can not open the bite when done in maxillary arch alone . if both arches are done in some cases , it can be manageduse of thicker sheets is not possible to overcome this , as thicker sheets will not have elasticity and will impart larger forces . the tray being thin ( 0.5 mm sheet ) can not open the bite when done in maxillary arch alone . if both arches are done in some cases , it can be managed use of thicker sheets is not possible to overcome this , as thicker sheets will not have elasticity and will impart larger forces . the solution is to sufficiently fabricate thin posterior bite plane in cold cure acrylic , finish it , and place it on the master cast and clear tray is fabricated over it . this case report documents a case of an anterior crossbite which was successfully corrected using modified clear tray aligners , which can be fabricated in our clinical setting . an 8-year - old girl reported to the department of pedodontics and preventive dentistry , with a complaint of irregular tooth in the upper arch . family history and health history were not significant and no known allergies were reported . on examination , there was a space deficiency of 2 mm mesiodistally for the tooth to get corrected . one was used as a study cast and the other three were marked as i , ii , and iii . a plan cut [ figure 1b ] was made to separate the tooth to be moved from the base , one at a time [ figure 1c ] . initially , the maxillary right central incisor was moved 0.5 mm distally and fixed with wax . then , the maxillary left central incisor was cut and moved 0.5 mm anteriorly and fixed with wax . later , the maxillary left lateral incisor was moved 0.5 mm distally and fixed with wax . model number two and three were cut and the tooth was moved to 1 mm and 1.5 mm so that each model will move the tooth 0.5 mm in a succession . all the models were finished using modeling wax to fill all the spaces created with cutting and moving the tooth . plan for tooth movement ( a ) , v cut for separation ( b ) , separated tooth ( c ) , and teeth repositioned with wax ( d ) from these master casts , new impressions were made and models were prepared to serve as working casts . the acrylic was extended occlusally and about 1 - 1.5 mm buccolingually so that it will form an undercut and will lock into the tray material . this is placed on the cast and clear tray material of 0.5 mm was fabricated using thermoforming machine with vacuum . the bite plane gets nicely locked into the tray and will not be accidently dislodged when in use [ figure 2b ] . the excess material were cut and finished and kept in marked packets to be given to the patient . all the models should be preserved till the end of the treatment so as to make any corrections during the treatment . posterior bite plane constructed ( a ) , bite plane within the aligner ( b ) , and models with tooth reposition ( c ) if a tray can not be inserted with moderate pressure , it means that the tooth has been moved in excess . in that case , another model can be created by pushing back the tooth slightly in the master cast , a working cast is prepared and another tray is created . thus , even if the tooth is moved in excess and the tray is not fitting , it is possible to correct it at any stage . the appliance has to be in position as much time as possible , except during meal time or consuming warm or hot liquids . the trays should be brushed gently along with the tooth brushing , twice a day . initially , the tray will be slightly tight on insertion , and light pressure should be used to seat it fully onto the teeth . the pain experienced during the initial few hours to a day or two will be due to the tooth movement . if the pain persists , if the tray can not be seated or the edges of the tray bruise the soft tissues , report to your dentist at the earliest and get the trays adjusted . the tray should be used for 7 days and progress to new set in the series . the appliance has to be in position as much time as possible , except during meal time or consuming warm or hot liquids . the trays should be brushed gently along with the tooth brushing , twice a day . initially , the tray will be slightly tight on insertion , and light pressure should be used to seat it fully onto the teeth . the pain experienced during the initial few hours to a day or two will be due to the tooth movement . if the pain persists , if the tray can not be seated or the edges of the tray bruise the soft tissues , report to your dentist at the earliest and get the trays adjusted . the tray should be used for 7 days and progress to new set in the series . after the first tray was used , the child experienced difficulty in inserting the second tray . to correct this problem , this was done by softening the wax in between the teeth with a warm wax knife and moving the incisor 0.25 mm behind so that it is positioned in between numbers 1 and 2 . then , the cast was finished , an impression was made of the corrected master cast , and a new working model was prepared . this was labeled 1a and the original number 2 model will become number 2b [ figure 2c ] . four clear trays were used to correct the crossbite successfully over a period of 4 weeks time figure 3a d , with the pre- and post - treatment pictures show an esthetically acceptable result [ figure 4a and b ] . different aligners used for correction of the crossbite ( a - d ) preoperative ( a ) and postoperative ( b ) view of the maxillary anterior teeth a desire for cosmetic solution in search of comfortable and well - designed appliances than the bulkier ones has led to newer treatment modalities . transparent aligners are useful in space maintenance , space regaining , correction of crowding and spacing . they can also be used for arch expansion or constriction , anterior and posterior crossbite correction , and mild skeletal class 3 corrections . if more than three teeth require correction , it requires considerable expertise as it is easy to lose the track of the direction and distance , when the tooth is moved . if additional tooth movements such as extrusion or rotation are necessary , a small composite resin build - up ( button ) of 1 mm on the facial surface of the tooth should be made before the initial impression in the first appointment and will remain on the child 's teeth till the end of the treatment . this facilitates the tray to lock on to this button and will not allow the tray to slip , and in turn enables better tooth movement . otherwise , the tooth will not move appropriately to the desired position during extrusion or rotations . ideal forces vary from 35 to 60 g for tipping and 70 - 120 g for translation . hahn et al . recorded 282 - 542 g of force being applied for 1.51 mm of movement done . in comparison , invisalign uses 0.25 mm of movement per tray and uses new plastic called smart track , which is more resilient . drake et al . reported that though bodily protraction of the target tooth was programed during the fabrication of aligners , uncontrolled tipping resulted . duong and kuo compared the load deflection rates of nickel - titanium ( niti ) and stainless steel wires of 0.017 0.017 with 0.030 mm polyurethane material in vitro and found that the load deflection of the polyurethane was greater than the niti wire but less than the stainless steel wire . krishnan and davidovitch reported that the tooth targeted by clear aligner did not undergo the classic cycle of tooth movement as there is some amount of distortion of tray after wearing it for 1 - 2 days resulting in orthodontic forces tapering off . hence , even if slightly higher force is applied , it will not harm the tooth as the force will start diminishing after a day . use of thin sheets of 0.5 mm will result in optimal force applied to the teeth . care should be taken not to move the tooth more than 0.5 mm per tray as it will result in more force applied to the tooth as well as difficulty in insertion of the tray . esthetics and convenience has already emerged as the important factors in the acceptance of treatment as children have become very conscious of their appearance with the orthodontic appliances . modified tray aligners can be easily fabricated in clinic setting , which makes it very affordable . these aligners are transparent , comfortable , and easily tolerated and have only minimal or no speech disturbance

anterior crossbite results from the abnormal axial inclination of one or more anterior teeth . it is a major esthetic and functional anomaly which has to be corrected in the primary and early mixed dentition period to allow the normal development of maxilla and mandible as well as the occlusion . several treatment options are available to correct the problem . a unique appliance , modified transparent tray aligners was used to correct the anterior crossbite in an 8-year - old child . the clinical presentation , fabrication of the appliance , and the outcome are discussed .

the incidence of diffuse large b cell lymphoma ( dlbcl ) increases with age , with approximately 40% of patients aged over 70 years . combination chemotherapy has improved the prognosis of dlbcl ; before the rituximab era the standard treatment included cyclophosphamide , doxorubicin , vincristine , and prednisolone ( chop ) . while chop has improved the treatment outcome , many studies have shown that elderly patients with dlbcl had a low survival rate because of poor performance status , comorbidity or reduced dose of doxorubicin . whether dlbcl in elderly patients is associated with a specific genetic abnormality or histologic characteristic is not yet clear . have a decreased ability to tolerate treatment and are more vulnerable to the toxic effects of chemotherapy such as doxorubicin than younger dlbcl patients . dose reduction of doxorubicin may lead to different survival rates between young and old patients . rituximab , a chimeric monoclonal antibody against the cd20 protein has demonstrable efficacy in dlbcl patients . several studies have indicated that the addition of rituximab to chop ( r - chop ) increased cure rates by 10%-15% in elderly patients , hence r - chop has become the new standard treatment . dose intensity of doxorubicin ( did ) was important before the rituximab era ; however , few studies on proper did are found in the literature . to the best of our knowledge , few studies analyzing the effect of doxorubicin dose on treatment outcomes in elderly dlbcl patients in the rituximab era have been reported . the purpose of this study was to analyze the treatment outcomes of elderly patients who were treated with r - chop according to the did . we conducted a single center retrospective analysis of dlbcl patients treated with r - chop at the seoul national university hospital between december 2003 and october 2011 . inclusion criteria were ( 1 ) pathologically confirmed dlbcl patients according to world health organization criteria by specialized hematopathologists ( y.k.j . and c.w.k . ) ; ( 2 ) patients who received first - line therapy with r - chop . full dose r - chop consisted of 375 mg / m rituximab , 750 mg / m cyclophosphamide , 50 mg / m doxorubicin and 1.4 mg / m vincristine on day 1 , and 100 mg oral prednisolone on days 1 - 5 of each cycle . the combination treatment was repeated at 3-week intervals . patients who received radiotherapy , surgery , and chemotherapy other than r - chop were excluded . the dose intensity of the agent was calculated by dividing the total received dose by the number of weeks of treatment . the standard did was 16.7 mg / m / wk . all study patients received over 6.7 mg / m / wk of doxorubicin ( 40% dose reduction from standard dose ) . the chi - square test was used to compare the percentage between two groups by age or did . survival analysis was performed using the kaplan - meier method and tested using the log - rank test . overall survival ( os ) was defined as the time from diagnosis until death or the last follow - up . progression - free survival ( pfs ) was defined as the time from first day of treatment until disease progression . the study protocol was approved by the institutional review board ( irb ) of the seoul national university hospital ( irb no . we conducted a single center retrospective analysis of dlbcl patients treated with r - chop at the seoul national university hospital between december 2003 and october 2011 . inclusion criteria were ( 1 ) pathologically confirmed dlbcl patients according to world health organization criteria by specialized hematopathologists ( y.k.j . and c.w.k . ) ; ( 2 ) patients who received first - line therapy with r - chop . full dose r - chop consisted of 375 mg / m rituximab , 750 mg / m cyclophosphamide , 50 mg / m doxorubicin and 1.4 mg / m vincristine on day 1 , and 100 mg oral prednisolone on days 1 - 5 of each cycle . the combination treatment was repeated at 3-week intervals . patients who received radiotherapy , surgery , and chemotherapy other than r - chop were excluded . the dose intensity of the agent was calculated by dividing the total received dose by the number of weeks of treatment . the standard did was 16.7 mg / m / wk . all study patients received over 6.7 mg / m / wk of doxorubicin ( 40% dose reduction from standard dose ) . the chi - square test was used to compare the percentage between two groups by age or did . survival analysis was performed using the kaplan - meier method and tested using the log - rank test . overall survival ( os ) was defined as the time from diagnosis until death or the last follow - up . progression - free survival ( pfs ) was defined as the time from first day of treatment until disease progression . the study protocol was approved by the institutional review board ( irb ) of the seoul national university hospital ( irb no . of the 433 patients , 83 ( 19.2% ) were aged 70 years and 350 ( 80.8% ) were younger than 70 years . there were no significant differences between the two groups , except for performance status ( eastern cooperative oncology group [ ecog ] 0 - 1 vs. ecog 2 or more ) , international prognostic index ( ipi ) , and bone marrow involvement . os of the patients with dlbcl who received r - chop was analyzed according to age group . age - specific 2-year os rate was decreased with age in patients aged 70 years , below 70% ( fig . approximately 53% of elderly patients received doxorubicin at 11.7 mg / m / wk < did 15.0 mg / m / wk ( table 2 ) . twenty - four patients ( aged 70 ) used prophylactic granulocyte - colony stimulating factors , 87.5% of them received did 10 mg / m / wk . we analyzed treatment outcomes according to did in the two age groups as shown in table 3 and fig . 2 . did did not have an effect on complete remission ( cr ) rate , disease progression and death rate in patients aged 70 years , however significant differences were observed in the younger than 70 year age group . two - year pfs and os showed significant difference according to doxorubicin dose intensity ( did 10 mg / m / wk and did > 10 mg / m / wk ) in the young and elderly patients groups . the difference of survival was more significant in younger patients ( figs . 3 and 4 ) . survival outcomes in elderly dlbcl patients remained with no significant difference when did was over 10 mg / m / wk . we utilized univariate and multivariate analyses to determine the effect of prognostic factors ( b symptom , ann arbor stage , performance status , lactate dehydrogenase [ ldh ] level , number of extranodal sites , ipi score , bone marrow involvement , bulky tumor , and did ) on treatment outcome . performance status , b symptom , ipi score , ldh level , and ann arbor stage , did were identified as significant prognostic factors in univariate analysis . performance status was the only prognostic factor associated with poor survival rate in multivariate analysis ( table 4 ) . causes of death in elderly patients are shown in table 5 . disease progression and treatment related mortality such as sepsis and bleeding of the 433 patients , 83 ( 19.2% ) were aged 70 years and 350 ( 80.8% ) were younger than 70 years . there were no significant differences between the two groups , except for performance status ( eastern cooperative oncology group [ ecog ] 0 - 1 vs. ecog 2 or more ) , international prognostic index ( ipi ) , and bone marrow involvement . os of the patients with dlbcl who received r - chop was analyzed according to age group . age - specific 2-year os rate was decreased with age in patients aged 70 years , below 70% ( fig . approximately 53% of elderly patients received doxorubicin at 11.7 mg / m / wk < did 15.0 mg / m / wk ( table 2 ) . twenty - four patients ( aged 70 ) used prophylactic granulocyte - colony stimulating factors , 87.5% of them received did 10 mg / m / wk . we analyzed treatment outcomes according to did in the two age groups as shown in table 3 and fig . 2 . did did not have an effect on complete remission ( cr ) rate , disease progression and death rate in patients aged 70 years , however significant differences were observed in the younger than 70 year age group . two - year pfs and os showed significant difference according to doxorubicin dose intensity ( did 10 mg / m / wk and did > 10 mg / m / wk ) in the young and elderly patients groups . 3 and 4 ) . survival outcomes in elderly dlbcl patients remained with no significant difference when did was over 10 mg / m / wk . we utilized univariate and multivariate analyses to determine the effect of prognostic factors ( b symptom , ann arbor stage , performance status , lactate dehydrogenase [ ldh ] level , number of extranodal sites , ipi score , bone marrow involvement , bulky tumor , and did ) on treatment outcome . performance status , b symptom , ipi score , ldh level , and ann arbor stage , did were identified as significant prognostic factors in univariate analysis . performance status was the only prognostic factor associated with poor survival rate in multivariate analysis ( table 4 ) . causes of death in elderly patients are shown in table 5 . disease progression and treatment related mortality such as sepsis and bleeding significantly shorter survival was observed for did 10 mg / m / wk than for did > 10 mg / m / wk in elderly patients with dlbcl . when more than 10 mg / m / wk of doxorubicin was administered , no significant differences were observed in treatment outcomes according to did ( 2-year os rate , 75.0% ; 10.0 mg / m / wk < did 11.7 mg / m / wk [ 60%-70% of standard did ] , 66.7% ; 15.0 mg / m / wk < did 16.7 mg / m / wk [ 90%-100% of standard did ] ; p=0.815 ) . each subgroup divided by 1.7 mg / m / wk of did showed insignificant difference in pfs and os . cr rate and disease progression rate were similar regardless of did ; however , survival outcomes improved with more than 10 mg / m / wk of doxorubicin in patients aged 70 years . patients younger than 70 showed significant difference in cr rate , disease progression rate , and treatment outcomes by did . the reason for this finding was assumed to be the small number of expired patients ( n=46 ) . performance status was an independent prognostic factor in multivariative analysis , and the elderly patients had a poorer performance status than young patients , which was in agreement with past studies . a previous study which analyzed treatment outcomes according to did before the rituximab era reported that patients with did 10 mg / m / wk had better treatment outcomes than did < 10 mg / m / wk in elderly patients with dlbcl . a recent study showed that low - dose chop ( mini - chop ) plus rituximab was effective and safe in dlbcl patients aged 80 years . our study showed that did can be reduced ; however , maintenance of did 10 mg / m / wk was necessary in elderly dlbcl patients in the rituximab era . a recent study showed that elderly dlbcl with chop or r - chop had an increased risk of cardiovascular disease , such as congestive heart failure , cardiomyopathy and acute myocardial infarction . several studies were conducted with additional alternate anti - cancer drugs such as bleomycin , and pixantrone , to reduce the myocardial damage of doxorubicin - based chemotherapy in elderly patients . however , they were less effective or no more beneficial than chop [ 19 - 22 ] . it is thus important to determine the tolerable dose of doxorubicin that achieves comparable treatment outcomes . first , it was a retrospective , single center study on a small patient population . several studies evaluating the effect of age on prognosis showed that > 70 years was a significant adverse factor . as life expectancy increases , a consensus on the definition of elderly is necessary and follow - up study is needed . however the strength of our study lay in the comparison of treatment outcomes according to did in several subgroups . did was required at a minimum of 10 mg / m per week in elderly patients with dlbcl in the rituximab era . despite improved survival outcomes by the introduction of rituximab , maintenance of did was still important to the treatment of elderly dlbcl patients .

purposethe dose intensity of doxorubicin ( did ) is important to the survival of diffuse large b cell lymphoma ( dlbcl ) patients . however , due to expected toxicities , most elderly patients can not receive full doses of anthracyclines . the purpose of this study was to evaluate the effect of did on the survival of elderly dlbcl patients ( age 70 years ) in the rituximab era.materials and methodswe analyzed 433 dlbcl patients who were treated with r - chop between december 2003 and october 2011 at the seoul national university hospital . of these patients , 19.2% were aged 70 years . we analyzed the survival outcomes according to did.resultssignificantly poorer overall survival ( os ) was observed for patients aged 70 years ( 2-year os rate : 59.9% vs. 84.2% ; p < 0.001 ) . did 10 mg / m2/wk had a significant effect on the os and progression - free survival ( pfs ) in elderly patients ( 2-year os rate : 40.0% in did 10 mg / m2/wk vs. 62.6% in did > 10 mg / m2/wk ; p=0.031 ; 2-year pfs : 35.0% vs. 65.7% ; p=0.036 ) . the os on each 1.7 mg / m2/wk doxorubicin increment above 10 mg / m2/wk in elderly patients was not significant among the groups ( 2-year os rate : 75.0% in did 10.0 - 11.7 mg / m2/wk vs. 66.7% in did 15.0 - 16.7 mg / m2/wk ; p=0.859 ) . treatment related mortality was not related to did . conclusiondid can be reduced up to 10 mg / m2/wk in elderly dlbcl patients in the rituximab era . maintenance of did > 10 mg / m2/wk and judicious selection of elderly patients who are tolerant to did is necessary .

carbon nanotube ( cnt ) have many potential applications in nanobiological devices and nanomechanical systems because of excellent mechanical properties , chemical and thermal stability , and hollow geometry [ 1 - 4 ] . in addition , the cnt is ultralight and is highly sensitive to its environment changes . therefore , many researchers have explored the potential of using cnt as nanomechanical resonators in atomic - scale mass sensor [ 5 - 7 ] . for example , chiu et al . utilized the detection of shifts in the resonance frequency of the nanotubes to measure nanotube resonator vibration characteristics . the atomic - scale mass sensing with a resonator is based on the fact that the resonant frequency is sensitive to the attached mass . in addition , the shift in resonant frequency is associated with the location of attached mass . to analyze the effects of adsorbed mass and its location on the resonant frequency of cnt , the continuum models based on beam as well as shell was used . studied the nanomechanical mass detection using nonlinear oscillators based on continuum elastic model and obtained that nonlinear oscillation leads to the unique resonant frequency shift due to mass adsorption , quite different from that in harmonic oscillation . chowdhury et al . presented an equivalent approximation model to analyze frequency shift of a single - walled carbon nanotube ( swcnt ) due to an attached particle fixed at a location . it is more useful for a mass sensor to simultaneously detect the mass and position of the attached particle . in this letter , frequency shift of carbon - nanotube - based sensor with an attached mass is studied using nonlocal elasticity theory , which is a modified classical elasticity theory . this theory with long - range interactions is often applied to analyze the vibration behaviour of cnt [ 11 - 13 ] . in addition , the effects of nonlocal parameter , attached mass and its location on the frequency shift of a cantilevered swcnt are analyzed . a schematic diagram of a swcnt with an attached mass m located at c from the fixed end is described as a cantilever beam as depicted in fig . 1 . the swcnt with length l has an equivalent bending rigidity ei , the volume density , the cross - sectional area a , and transverse displacement y depend on the spatial coordinate x and time t. based on nonlocal elasticity theory , the governing equation of transverse vibration for the swcnt can be expressed as where e0a is the nonlocal parameter , and it is used to modify the classical elasticity theory and is limited to apply to a device on the nanometer scale . a cantilevered nanotube - based mass sensor with an attached mass the harmonic solution of the governing equation can be assumed as where is the angular frequency . by introducing the dimensionless parameters x = x / l , and substituting eq . 2 into eq . 1 , one obtain the corresponding boundary conditions are where m = m/al and = c / l are the dimensionless mass and position of the attached mass , respectively ; w1 and w2 are the dimensionless transverse displacements on the left and right sides of the attached mass , respectively . the boundary conditions given by eq . 5 correspond to conditions of zero displacement and the zero slope at fixed end ( x = 0 ) , eqs . 6 and 7 are zero moment and the zero shear force at free end ( x = 1 ) , respectively . eqs . 8 , 9 , 10 and 11 are the compatibility conditions at the location of the attached mass . 12 and 13 into eqs . 5 , 6 , 7 , 8 , 9 , 10 and 11 , we can obtain the following matrix form : therefore , the characteristic equation is given by where is the determinant of the matrix according to dimensionless variables given in eq . 4 , the frequency is meanwhile , the dimensionless sensitivity m can be obtained from the following equation : while neglecting the nonlocal effect ( = 0 ) , and assuming the attached mass at free end ( = 1 ) , the frequency equation for a cantilevered swcnt with attached mass can be reduced . then the frequency expressed in dimensionless wave number k can be obtained by solving the following equation : furthermore , neglecting the attached mass ( m = 0 ) , the dimensionless wave number k can be obtained from the above frequency equation expressed in dimensionless wave number k for the free vibration of a cantilever beam can also be found in the textbook about vibration . based on nonlocal elasticity theory , we have derived the frequency equation to analyze the effects of nonlocal parameter , e0a / l , attached mass and its location , c / l , on the frequency shift of carbon - nanotube - based mass sensor . according to the equation , the relationship between the dimensionless frequency shift and dimensionless added mass on the cantilever mass sensor for mode 1 with c / l = 1 and e0a / l = 0 is obtained and shown in fig . the dimensionless frequency shift is defined as the ratio of the difference between the fundamental frequency of a nanotube with and without attached mass , to that without attached mass , f0 . to compare with a previous study , we use the same normalized mass as described in ref . , where the value of parameter is 140/33 . it can be seen that the comparison of the two results shows good agreement . however , the previous work that assumes a fixed location of attached mass ( i.e. , c / l = 1 ) ; and it is only a special case of this study . in addition , the nonlocal effect was not taken into account in their analysis ( i.e. , e0a / l = 0 ) . the relationship between the dimensionless frequency shift and dimensionless added mass on the mass sensor for mode 1 with c / l = 1 and e0a / l = 0 conventional continuum mechanics theories assume that the stress at a point is a function of strain at that point in local elasticity . material behaviors predicted by such a local theory are assumed to be scale - independence in the constitutive law . when the continuum elasticity theory is applied to the analysis of the nano - scale structures , it is found to be inadequate because of ignoring the small scale effect . for improving this situation , the theory assumes that the stress at a given point is a function of strain at every point in the body . accordingly , the small scale effect can be taken into account in the constitutive equation . figure 3 depicts the effect of nonlocal parameter on the frequency shift of the cantilever sensor with attached mass for c / l = 1 . it can be seen that the frequency shift of the sensor increases with increasing the attached mass . based on the nonlocal elasticity theory , long - range interactions are taken account in the analysis that makes the sensor stiffer . therefore , it can be found that increasing the nonlocal parameter increases the frequency shift . the trend is obvious when the attached mass is small compared with that of the sensor . the effect of nonlocal parameter on the frequency shift of the sensor with attached mass for c / l = 1 in addition , the location of attached mass can influence on the changes in frequency of the mass sensor . figure 4 illustrates the effect of location of attached mass , c / l , on the frequency shift of the cantilever mass sensor for e0a / l = 0.3 . it can be seen that the effect of the location of attached mass on the frequency shift of the mass sensor is significant . this is because the frequency of the sensor with the attached mass decreases with increasing the particle mass . increasing the value of c / l is equivalent to an increase of the particle mass at the same location . the effect of location of attached mass on the frequency shift of the sensor for e0a / l = 0.3 it is important to know the sensitivity of the mass sensor . the sensitivity of the sensor is defined as the ratio of the variation of the frequency shift to the variation of the attached mass . figure 5 shows the effect of location of attached mass on the sensitivity of the sensor for e0a / l = 0.3 . it can be seen from fig . in addition , it can be observed that the sensitivity of the sensor is strongly dependent on the location of attached mass , c / l . the sensitivity of the sensor quickly drops as the value of c / l decreased . this is because the frequency shift decreases with decreasing the value of c / l . the effect of location of attached mass on the sensitivity of the sensor for e0a / l = 0.3 in this letter , the frequency shift and sensitivity of carbon - nanotube - based sensor with an attached mass was studied using nonlocal elasticity theory . the relationship equation between the frequency shift of the sensor and the attached mass was derived analytically . when the nonlocal effect was not taken into account , the result was compared with the previous study , which adopted a simplified method and obtained an approximate result . according to this study , the result showed that increasing the nonlocal parameter obviously decreased the frequency shift of the sensor when the attached mass was small compared with that of the sensor . the value of frequency shift was larger when the location of the attached mass was closer to the free end . in addition , a high sensitivity of the sensor was revealed when the attached mass was small . however , the sensitivity quickly dropped as the location of the attached mass was closed to the fixed end . the authors wish to thank the national science council of the republic of china in taiwan for providing financial support for this study under projects nsc 99 - 2221-e-168 - 019 and nsc 99 - 2221-e-168 - 031 . this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited . this article is distributed under the terms of the creative commons attribution noncommercial license which permits any noncommercial use , distribution , and reproduction in any medium , provided the original author(s ) and source are credited .

the frequency equation of carbon - nanotube - based cantilever sensor with an attached mass is derived analytically using nonlocal elasticity theory . according to the equation , the relationship between the frequency shift of the sensor and the attached mass can be obtained . when the nonlocal effect is not taken into account , the variation of frequency shift with the attached mass on the sensor is compared with the previous study . according to this study , the result shows that the frequency shift of the sensor increases with increasing the attached mass . when the attached mass is small compared with that of the sensor , the nonlocal effect is obvious and increasing nonlocal parameter decreases the frequency shift of the sensor . in addition , when the location of the attached mass is closer to the free end , the frequency shift is more significant and that makes the sensor reveal more sensitive . when the attached mass is small , a high sensitivity is obtained .

tuberculosis ( tb ) is a major global health problem , and can be a multisystemic disease . tuberculosis of the ribs usually presents with rib destruction and soft tissue mass of the chest wall , which is called tubercular abscess of the chest wall ( tacw ) or cold abscess of the chest wall . the isolated involvement of caries rib without caries spine has rarely been described in previous literature . cases of parenchymal tuberculosis and tubercular lymphadenitis with simultaneous caries rib and tacw have not been reported so far to the best of our knowledge . an 18-year - old female student referred to jss hospital , city of mysore , state of karnataka , south india with chief complaints of cough with white mucoid sputum since two months , swelling over the back on the left side since one and a half months , and weight loss since one month . there was no history of fever , breathlessness , chest pain or hemoptysis and no history of contact with a case of tuberculosis . on examination , the patient was moderately built and nourished with weight of 46 kg , height of 153 cm and body mass index ( bmi ) of 19.5 , pulse rate of 110/min , blood pressure of 110/80 mmhg . she had right posterior cervical lymphadenopathy with a node , which was single , non tender , mobile , firm in consistency , and measuring 32 cm . local examination revealed a swelling in the left side of the chest on the posterior aspect in infrascapular region ( figure 1 ) . the swelling , measuring about 1010 cm in size , was non tender , soft in consistency with no local rise of temperature . the swelling was also fluctuant and irreducible , had no cough impulse , and was situated in the subcutaneous plane . respiratory system examination revealed dullness in the left infra - axillary area with reduced intensity of breath sounds . a swelling in left infrascapular region the patient s hemoglobin was 9.5 gm% , and the smear of her peripheral blood showed normocytic normochromic anemia . plain chest radiograph showed non - homogenous opacity in the left lower zone with blunting of left costo - phrenic angle ( figure 2 ) . it also showed asymmetry of the soft tissue shadow on the left side of the chest with mediastinal lymphadenopathy . initial chest x - ray showing non - homogenous opacity in the left lower zone with blunting of left costo - phrenic angle . computed tomography ( ct ) of the thorax showed features suggestive of pulmonary tuberculosis in the left lower lobe ( figures 3 and 4 ) . the ct also showed destruction and pathological fracture of the left sixth rib with a collection of low density fluid in the left pleural cavity , left side of the chest wall and the region inferior to left breast , which were suggestive of cold abscess . a few paratracheal and retrocaval lymph nodes were also seen . computed tomography of the thorax . fine needle aspiration cytology ( fnac ) from the chest wall swelling showed smears positive for acid - fast bacilli . sputum analysis revealed acid fast bacilli in all three samples . patient was scheduled to receive anti tubercular therapy ( category i ) with four drugs including isoniazid , rifampicin , ethambutol and pyrazinamide on the fifth day after admission . repeat plain radiograph of the chest after two weeks of treatment showed clearance of the shadows and mediastinal lymphadenopathy ( figure 5 ) . tuberculosis is a major global health problem , and any organ system can be involved . tuberculosis of the chest wall accounts for 1 - 5% of all cases of musculoskeletal tb . the disease may also involve lymph nodes including mediastinal , mesenteric or cervical , and visceral lesions . computed tomography of the thorax . it also shows features suggestive of destruction and pathological fracture of the left sixth rib with low density fluid collection in the left pleural cavity , left side of the chest wall and the region inferior to left breast suggestive of cold abscess chest x - ray after two weeks of treatment with antituberclosis drugs . it shows clearance of the shadows and mediastinal lymphadenopathy depending on the predominant clinical or pathologic feature , there are many terminologies such as caries rib or cold abscess , etc for tacw . but all the terms come under the same disease entity i.e , tuberculous abscess of the chest wall with or without rib involvement . it has been postulated that tb of bone results from lymphatic or hematogenous dissemination of bacilli from a source of primary infection in lungs . combined effects of pressure necrosis by granulation tissue and the direct action of invading bacilli result in bone erosion in tb . it has been hypothesized that infection of lymph nodes in the chest wall is a result of pleuritis due to invasion of the tubercle bacilli . cold abscesses of chest wall are extraparenchymal collections consisting of caseous material from the necrosed lymph nodes . these can track through the chest wall to form visible swellings on the surface without redness or tenderness . sternum , costochondral junctions , rib shafts , costovertebral joints and vertebrae can be involved in tuberculous abscesses of the chest wall . involvement of intrathoracic lymph nodes with relatively lesser involvement of lung parenchyma and pleura can also occur . computed tomography is necessary for assessing tuberculous chest wall lesions , as it elucidates the nature and extent of soft tissue collections , intrathoracic adenopathy and bone erosion . our patient , a young immunocompetent lady , had a posterior chest wall tuberculous abscess / cold abscess , which was due to caries rib . fine needle aspiration cytology from the abscess showed smears positive for acid - fast bacilli . our patient also had sputum positive pulmonary tuberculosis and tubercular lymphadenitis of neck and mediastinum . therefore , an optimal treatment strategy is controversial . though anti tubercular therapy ( extended course ) is the cornerstone of the treatment of tuberculous abscess of the chest wall the occurrence of caries rib and cold abscess of the chest wall with concomitant pulmonary tuberculosis and tubercular lymphadenitis of neck and mediastinum has rarely been described in an immunocompetent individual . the rarity of our case lies in the fact that the patient was immunocompetent with cold abscess due to caries rib and rare association of pulmonary tuberculosis and tubercular lymphadenitis of neck and mediastinum . parietal chest wall tb is rare , and tb of the rib still rarer . computed tomography is necessary for assessing tuberculous chest wall lesions . anti tubercular therapy ( extended course ) is the cornerstone of the treatment of tuberculous abscess of the chest wall and surgical treatment also plays a vital role .

musculoskeletal tuberculosis accounts for 1 - 2% of all types of tuberculosis . tubercular abscess of the chest wall accounts for 1 - 5% of all cases of musculoskeletal tuberculosis . herein , we report a case of tubercular abscess of the chest wall . the occurrence of caries rib and cold abscess of the chest wall with concomitant pulmonary tuberculosis , and tubercular lymphadenitis of neck and mediastinum has rarely been described in an immunocompetent individual . the rarity of our case lies in the fact that the patient was immunocompetent with cold abscess due to caries rib , with rare association of pulmonary tuberculosis and tubercular lymphadenitis of neck and mediastinum .

gardner described a syndrome consisting of hereditary intestinal polyposis with osteomas and multiple cutaneous and subcutaneous lesions in 1953.1 this syndrome has since been modified by the addition of other features such as osteomas , supernumerary teeth , dental abnormalities , fibrous dysplasia of the skull , fibromas , desmoid tumours , epidermoid cysts and a number of malignant tumors.24 the most important feature of the gardner s syndrome is the association of multiple colonic polyps ( familial adenomatous polyposis coli - fap ) with sebaceous cysts and jaw osteomas . the significance of this dominantly inherited condition to the dentist is that the colonic polyps usually undergo malignant change by the fourth decade and the extra - intestinal lesions may be apparent before those in the bowel.5 although these are often subclinical oral manifestations could be diagnostical . as such , early detection of multiple jaw osteomas and/or multiple sebaceous cysts ( particularly on the scalp ) may lead to appropriate further investigation and treatment which might be life saving . as the syndrome is genetically inherited , diagnosis of this condition also has implications for other family members.5,6 skeletal abnormalities , the most common of which are osteomas , are an essential component of gardner syndrome . the benign tumours are characterized by slow , continuous growth,4 and occur most frequently in the mandible , the outer cortex of the skull and the paranasal sinuses . the angle of the mandible is a particularly diagnostic site.7 the osteomas may be either exostoses , often referred to as peripheral osteomas , or endostoses , which are detectable only radiographically . the radiographic appearance of either type is a localized radiopaque lesion with a sharp border . another type of lesion has been described , which appears as a large and diffuse radiopaque cotton wool - like area in either jaw , and is referred to as a widespread radiopaque lesion.8 dental abnormalities are present in around 30% of patients with gardner syndrome , and may include supernumerary teeth , compound odontomas , hypodontia , abnormal tooth morphology and impacted or unerupted teeth . the highest incidence of dental abnormalities is found in patients with multiple osteomas , but dental changes may be determined in the absence of skeletal lesions , and the dental anomalies are not secondary to bony changes.9 the principal cutaneous lesions in gardner syndrome are multiple epidermoid cysts , present in around 50%65% of patients . the cysts arise prior to puberty and occur primarily on the face , scalp and extremities.10 desmoid tumors may occur in the skin of the anterior abdominal wall or intra - abdominally . desmoid tumours are slow growing deep fibromatoses that are histologically benign and have no metastatic potential.11 other cutaneous lesions that have been described in gardner syndrome include fibroma , lipoma , leiomyoma , neurofibroma , basal cell carcinoma and pigmented skin lesions.12 only unique and specific findings are observed in dental and skeletal structures , which can easily be diagnosed by an orthodontist or a general dentist . therefore , the aim of this report is to present new cases of this syndrome , to evaluate it from an orthodontic perspective , and to bring this rare anomaly to the attention of the orthodontic community . a 21-year - old male patient , one of two siblings , presented to our department with dental deficiencies , chewing and aesthetic concerns and asymmetry that had newly emerged in his face . anamnesis taken from the patient established that his mother and sister had been diagnosed with gardner syndrome . , we determined an angle class i molar relationship , and we observed that a large number of permanent tooth eruptions had not been completed in the anterior and posterior regions . no anomaly was observed in any intraoral soft tissue ( figures 1 and 2 ) . at radiological examination , congenital deficiency in the right and left upper central teeth , delayed eruption in the maxillary and mandibular canines and 1 and 2 premolars and supernumerary teeth were observed . there was an increase in density in the structure of the bony trabecular and smooth - nerve radiological formations in the right condyle region and right and left lower jaw angulus region ( figures 3 and 4 ) . the 24-year - old female patient of the two siblings presented to our department with a desire for a more regular structure . the patient stated at anamnesis that she had undergone more than 15 general surgical operations . congenital deficiency of the permanent canine tooth in the left lower jaw , and delayed eruption in the 1 canine and 2 premolars in the upper jaw and in the 1 and 2 premolars in the lower jaw were observed . microdontia was observed in the left upper 2 molar , and a buried and irregular root morphology in the 3 molar in the left lower jaw ( figures 5 and 6 ) . variations in the bone trabecular structure and regular radiopaque lesions in the condylar region were observed . following medical consultations , both sibling patients commenced treatment with the scheduling of orthodontic , surgical and prosthetic therapy ( figures 7 and 8) . a 21-year - old male patient , one of two siblings , presented to our department with dental deficiencies , chewing and aesthetic concerns and asymmetry that had newly emerged in his face . anamnesis taken from the patient established that his mother and sister had been diagnosed with gardner syndrome . , we determined an angle class i molar relationship , and we observed that a large number of permanent tooth eruptions had not been completed in the anterior and posterior regions . no anomaly was observed in any intraoral soft tissue ( figures 1 and 2 ) . at radiological examination , congenital deficiency in the right and left upper central teeth , delayed eruption in the maxillary and mandibular canines and 1 and 2 premolars and supernumerary teeth were observed . there was an increase in density in the structure of the bony trabecular and smooth - nerve radiological formations in the right condyle region and right and left lower jaw angulus region ( figures 3 and 4 ) . the 24-year - old female patient of the two siblings presented to our department with a desire for a more regular structure . the patient stated at anamnesis that she had undergone more than 15 general surgical operations . congenital deficiency of the permanent canine tooth in the left lower jaw , and delayed eruption in the 1 canine and 2 premolars in the upper jaw and in the 1 and 2 premolars in the lower jaw were observed . microdontia was observed in the left upper 2 molar , and a buried and irregular root morphology in the 3 molar in the left lower jaw ( figures 5 and 6 ) . variations in the bone trabecular structure and regular radiopaque lesions in the condylar region were observed . following medical consultations , both sibling patients commenced treatment with the scheduling of orthodontic , surgical and prosthetic therapy ( figures 7 and 8) . gardner syndrome , which has an autosomal dominant character and emerges in relation to the x gene , has an incidence ranging between 1 in 4,000 and 1 in 12,000 , depending on region.13 it is caused by a dominantly inherited mutation in the adenomatous polyposis coli gene localized on chromosome 5.14 several of these manifestations occur in the oral and maxillofacial region and may be determined during routine dental examination . while a solitary osteoma of the jaw is a common incidental finding in dental panoramic radiography , if more than three such lesions are found this is highly suggestive of gardner syndrome.14 similarly , dental abnormalities such as supernumerary , absent or unerupted teeth and odontomas are often determined in routine radiography.14 in addition to clinical palpation , dental panoramic radiography is very a effective means of detecting the multiple osteomas of the jaws that are a characteristic of gardner syndrome.15 the general dental practitioner may be the first health care professional to suspect such a diagnosis . osteomas and odontomas generally emerge in the paranasal sinuses and mandible , particularly in the angulus and corpus regions.1618 pain is rarely observed at these patients and it is asymptomatic . osteomas and odontomas are generally observed in the post - pubertal period.17 lesions cause facial asymmetry as a result of expansion . they manifest themselves as well defined radio - opacities as a result of routine radiological investigations while inside the medullary bone before cortical expansion . radiologically , periosteal and endosteal osteomas reveal themselves as well defined nervous sclerotic radiopaque lesions.1920 after diagnosing these osteomas and adontomas , they must be resected under general anesthesia , because of the unreachable regions like paranasal sinuses , condylar and angular region . also , recurrence of osteomas and odontomas after inadequate surgery could be seen and to eliminate possible occurrence , several surgeries could be performed . orthodontic treatment is not a valuable option for these patients because osteomas and the increased density of the bone would inhibit tooth movement . the density of the bone is so dense to erupt impacted tooth so surgical extraction would be the most suitable alternative . after extraction of all impacted tooth conventional partial or total prosthetic rehabilitation must be performed . histopathological evaluation of resected tissues following surgical intervention , followed by other dental procedures are recommended . although characteristic findings are observed in dental and skeletal structures , which can easily be diagnosed , it is often overlooked by many medical and dental professionals .

gardner syndrome is a rare , autosomal dominant syndrome . it will follow a positive course with diagnosis and treatment by medical and dental specialists . orthodontists or general dental physicians can easily diagnose the syndrome through radiological images taken in addition to dental and skeletal findings . the aim of this study was therefore to report two cases of this syndrome and to evaluate it from an orthodontic perspective in order to attract the attention of orthodontists to this rare anomaly .

during 20092014 , we identified 20 persons who were admitted to 2 tertiary - care hospitals in rennes and paris , france , with culture - positive xdr tb infections . patients were identified through hospital database searches ; patient data were extracted from medical charts . for each patient , we performed direct examination of sputum smears ; cultures on lowenstein - jensen medium ; genotypic resistance profiling ( genotype mtbdr plus ; hain lifescience , nehren , germany ) ; and in vitro drug susceptibility testing ( dst ) on lowenstein - jensen medium , according to the proportions method . all patients were isolated in negative - pressure rooms until their respiratory sample culture results converted from positive to negative ( hereafter referred to as culture conversion ) . medical and surgical therapeutic options were determined during multidisciplinary meetings involving infectious diseases , respiratory diseases , microbiology , and thoracic surgery departments . in agreement with world health organization guidelines ( 3 ) , we selected anti - tb drug therapy on the basis of results from previously used agents or genotypic and phenotypic dst . throughout hospitalization , treatment toxicity was carefully monitored through clinical assessments , routine laboratory tests , therapeutic drug monitoring , audiograms for patients on aminoglycosides , and weekly electrocardiograms . treatment efficacy was monitored through thoracic imaging and monthly examination of respiratory samples . for patients with nondisseminated pulmonary tb , surgery was considered at the initiation of medical treatment if success of the treatment was deemed unlikely because of extensive lesions or after 3 months of optimized medical treatment if sputum conversion was not achieved . in agreement with procedures implemented by the french information protection commission the 20 xdr tb patients ( table 1 ) had recently arrived in france from georgia ( n = 17 ) , armenia ( n = 2 ) , and the russian federation ( n = 1 ) ; median duration between arrival and hospitalization was 2 ( interquartile range [ iqr ] 17 ) days . median delay from admission to initiation of any anti - tb treatment was 18 ( iqr 1125 ) days . loss of > 5% of total bodyweight . body temperature > 38c during at least 3 weeks . during the intensive phase of treatment , each patient all patients required long - term central venous access for administration of amikacin or carbapenems . duration of medical treatment was individualized but continued a minimum of 12 months after culture conversion . median length of stay in the acute - care setting was 67 ( iqr 55124 ) days . * the following grade 3 or 4 treatment - associated adverse events ( common terminology criteria for adverse events , http://evs.nci.nih.gov/ftp1/ctcae/ctcae_4.03_2010-06-14_quickreference_5x7.pdf ) were reported in 18 patients : digestive side effects ( 14 patients ) , hepatitis ( 1 patient ) , peripheral neuropathy ( 7 patients ) , neuropsychiatric side effects ( 3 patients ) , and hearing impairment ( 3 patients ) . no grade 3 or 4 nephrotoxicity or cytopenia or significant qt interval prolongation were reported . adverse events related to anti - tb agents were managed by a wide range of symptom treatments . thoracic surgery was performed in 8 patients ( lobectomy in 5 , pneumonectomy in 3 ) , of whom 2 had severe postsurgical complications . six of these patients were culture - positive before surgery , and their cultures converted a median of 25 days postsurgery ( iqr 2033 days ) . after a median follow - up of 22 ( iqr 1527 ) months , sputum cultures had converted for 19 patients , 4 of whom had completed treatment and a median of 38 ( iqr 2940 ) months of posttreatment follow - up . median time from treatment initiation to culture conversion was 100 ( iqr 75114 ) days . this small series of xdr tb cases managed in a high - income country illustrates the potential safety and efficacy of multidisciplinary and individualized treatment with a multidrug regimen that includes new anti - tb agents ( e.g. , bedaquiline ) ; innovative use of older agents ( e.g. , linezolid ) ; and the combination of imipenem plus amoxicillin / clavulanate . the final outcome could not be ascertained for most study patients because they are still receiving antimycobacterial therapy ; however , the 90% survival rate after a median follow - up of 22 months after treatment initiation is reassuring and compares favorably with survival rates of 66% , 54% , and 38% in the united states ( 4 ) , south africa ( 5 ) , and the united kingdom ( 6 ) , respectively . the high rate of microbiologic conversion in our study ( 95% ) also reflects the potentially achievable treatment efficacy , even in the context of previously treated xdr tb cases . our findings should be interpreted cautiously because of the small number of patients and the relatively short follow - up at the time of this writing . however , the overall figures of culture conversion are more satisfactory than those previously reported in high - income countries , where conversion rates ranged from 46.7% to 76.1% ( 4,610 ) , and in high - prevalence settings , where conversion rates are lower ( 5,11,12 ) . preliminary results from a study conducted in south africa were more favorable : samples from 48 ( 76% ) of 63 patients with 6 months follow - up were culture - negative ( 13 ) . postsurgery sputum conversion was rapidly achieved for patients in our study ; thus , pulmonary resection surgery , although risky , may also have contributed substantially to treatment successes . patients were referred to our centers soon after arriving in france , causing communication difficulties for patients with a limited understanding of french and english . medical histories were long and complex , and most patients were in advanced stages of pulmonary tb . the numerous side effects observed during prolonged anti - tb regimens must be optimally and intensively managed ; otherwise , patients may not complete treatment . because of the limited number of potentially active anti - tb agents , drugs with documented long - term toxicities must also be included in multidrug regimens . the high incidence of breakthrough candidemia cases ( 5/20 patients [ 25% ] ) was not anticipated , although prolonged exposure to broad - spectrum antimicrobial drugs and long - term central venous access are acknowledged risk factors for candidemia . this risk must be taken into account when considering treatment of xdr tb with carbapenems and amoxicillin / clavulanate . the overall good tolerability of linezolid may be a result of the low dosage ( routinely , 600 mg / d initially , decreased to 300 mg / d if toxicity is suspected , even with limited evidence ) . financial , social , and cultural aspects of the management of vulnerable and marginalized patients are also essential and time - consuming . prolonged hospital stays were necessary for patients in our study , resulting in high healthcare costs , as previously reported in south africa ( 14 ) . . however , failure to adequately address these issues would translate into additional xdr tb transmission in the community and increased illness and death , which could result in a much higher societal burden . previous experience in high - income countries has documented that comprehensive care of tb patients is cost - effective , even in the most vulnerable and marginalized populations , especially when multidrug - resistant or xdr tb are involved ( 15 ) . our results reflect the situation in a high - income setting with free access to all potentially active drugs , extensive investigation of responsible strains ( e.g. , using dst and genotypic tests ) , daily monitoring of adverse events , regular multidisciplinary meetings to tailor treatment to any new event and evaluate the need for thoracic surgery in selected cases , dedicated medical and paramedical staff , and psychosocial support . unfortunately , the situation may not be the same in the countries most affected by xdr tb .

we report 20 cases of extensively drug - resistant tuberculosis managed in france . treatment was individualized and included bedaquiline and linezolid for most patients and surgery in 8 patients . at last follow - up ( 22 months ) , 19 patients had achieved conversion from positive to negative on culture testing . these promising results of comprehensive management obtained in a small series deserve confirmation .

it is well known that the shape and size of the inorganic nanoparticles have a great influence on their physical properties . in recent years , the synthesis of nanoparticles with well - controlled morphology and size has received lots of interest for their potential applications in nanoscale plasmon photonics , drug delivery , calorimetric sensing , nanoelectronics , catalysis , and information storage [ 35 ] . two general strategies are usually employed for the bottom - up chemical synthesis of nanomaterials : one is the use of the templates , which could confine the shape and size of nanoparticles ; the other is the use of the capping agents , which could control the direction and dimension of nanoparticles during the growth process [ 7 , 8 ] . cuprous oxide ( cu2o ) , which has excellent optical and magnetic properties , is a relatively nontoxic p - type semiconductor with a direct bandgap of 2.17 ev . tailoring the architecture of cu2o crystals has received extensive attention . over the past few decades , a variety of well - controlled cu2o micro-/nanostructures such as cubes [ 1015 ] , octahedra [ 1619 ] , dodecahedra , nanowires , and hollow spheres have been synthesized by various methods . comparing with other methods , electrochemical deposition is a convenient way of preparing many well - defined structures with high uniformity . it has been reported that cu2o could be deposited onto different substrates such as pt , cu , au , indium - doped tin oxide ( ito ) , and stainless steel using electrochemical method , most of which concentrated on the fabrication of cu2o films or nanowires . three main methods have been reported to prepare cu2o octahedra ( a ) solution - phase route with surfactants ; ( b ) reduction method with glucose , hydrazine hydrate , and ascorbic acid ; ( c ) -irradiation with triton x-100 water - in - oil microemulsions . few reports can be found to synthesize cu2o octahedra by electrochemical deposition onto the al foils with the existence of capping agents , and the formation mechanism of cu2o octahedra is not clear yet . here , we report the electrochemical deposition of single - crystalline cu2o octahedra onto aluminum ( al ) foils using alkaline cupric sulfate solutions stabilized by lactate ions . a djs-292 potentiostat with a standard three - electrode system was used for cu2o octahedra deposition . an ag / agcl electrode in a saturated kcl solution was used as a reference electrode and a platinum coil as a counterelectrode . after rinsing several times with acetone and the electrolyte solution consisted of 0.4 m cupric sulfate and 3 m lactic acid ( la ) . by complexing with the lactate ions , the ph of the solution was adjusted to 9 by 4 m naoh solution , and a dark blue solution was obtained under constant stirring . the electrochemical deposition was performed potentiostatically with a potential of 0.3 v ( versus ag / agcl ) for 30 min and the temperature of the electrolyte was kept at 60c by water bath . in order to analyze the effect of other anions , cuso4 was replaced with cucl2 with the other parameters unchanged . the specimen for transmission electron microscopy observation was prepared by evaporating a drop of the dispersion onto a carbon - film - coated copper grid . morphology examinations were performed using xl30 s - feg scanning electron microscope ( sem ) . selected - area electron diffraction ( saed ) , bright - field ( bf ) imaging , and energy dispersive x - ray spectroscopy ( eds ) analyses were carried out using a jeol jem 2100f transmission electron microscope ( tem ) operating at 200 kv . electron energy - loss spectroscopy ( eels ) was carried out on a cm200 feg transmission electron microscope operating at 200 kv . we recorded more than 150 nanoparticles and carried out a statistical analysis of the nanoparticles which showed that the average edge length of the octahedra is 300 10 nm . it can be seen clearly from the low - magnification sem image ( figure 1(a ) ) that the shape of the particles is a regular octahedron . the octahedra have slightly different orientations due to the anisotropy of the rough surface of al foil . the enlarged sem images of the octahedra viewed from different directions are shown in figures 1(b ) and 1(c ) , which depict clearly that the particles are perfect octahedra with eight { 111 } planes . the edge lengths are 300 and 295 nm , respectively . when increasing the deposition time to 1 h , no evident change of the octahedra size was observed . the octahedron looks like a pyramid ( figure 1(b ) ) viewed from the top and a rhombus ( figure 1(c ) ) from the side . careful examination of the sem images shows that there are lots of pores or network on the al substrate surface after the deposition , which could result from the erosion of the base . in order to clarify the role of lactic acid in the formation of cu2o octahedra , we also carried out the electrochemical deposition without addition of lactic acid in the electrolyte . when no lactic acid was added in the electrolyte , the flocculent precipitates were produced rapidly after the addition of naoh solution into the cuso4 electrolyte and the morphology of the as - deposited products changed drastically , which is shown in figure 1(d ) . two morphologies , one being aggregates composed of irregular particles , and the other being dendrites , can be found in figure 1(d ) . this suggested that the lactic acid has a great influence on the formation of cu2o octahedra . when cucl2 was used as a copper salt in this experiment , the shape of most particles will become irregular . to determine the chemical composition of the octahedra , energy dispersive x - ray spectroscopy ( eds ) was performed . the typical eds spectrum from the particles in figure 1(a ) indicates that the particles are composed of cu and o. the quantification of the spectrum shows that the ratio of cu and o is close to 2 : 1 , which suggests that the particles have a chemical formula of cu2o . the morphology and microstructure of the cu2o octahedra most of the nanooctahedra look like a square ( figure 2(a ) ) and a rhombus ( figure 2(b ) ) in the projected images , which correspond to figures 1(b ) and 1(c ) . for the octahedra with eight { 111 } planes , the line connecting any two corners that are not in the same face is along the 100 direction . in figure 2(a ) , we assume that the direction perpendicular to the paper outwardly is along direction , then the two adjacent edges of the square that are perpendicular to each other are along [ 1 - 10 ] and directions , respectively . in figure 2(b ) , the rhombus is obtained viewed from the side of the octahedron . it can be seen clearly that two diagonal lengths of the rhombus are not equal , of which the longer diagonal is upward . figure 2(c ) shows a typical hrtem image of the region enclosed by a square in figure 2(b ) . the interplanar spacing is measured to be 2.21 , which corresponds to the ( 002 ) crystal plane of cu2o . the saed pattern ( figure 2(d ) ) taken from an individual octahedron in figure 2(b ) suggests that it is single crystalline . careful examinations of figures 2(b)2(d ) show that the growth direction of cu2o octahedra is along 001 , which is indicated by a white arrow . in which the preferred orientation of the cu2o films is along 100 direction when deposited at ph = 9 . the diffraction spots in figure 2(d ) can be indexed as ( 11 - 1 ) , ( 111 ) , and ( 002 ) , respectively , using the lattice parameter of cu2o ( a = 4.2696 ) , which is in good agreement with the eds analysis result . in a typical eels spectrum acquired from a single octahedron , two peaks at 530 and 932 further study shows that the shapes of particles are all octahedra in the presence of lactic acid , and sem images are shown in figure 3 . figure 3(a ) shows that the average size of the octahedra is 63.5 nm when the ratio of lactic acid and cuso4 is 0.75/0.4 . as the ratio decreases to 1.5/0.4 , the size rises to 105 nm ; but when the ratio increases up to 4.5/0.4 and 6/0.4 , the size decreases to 167.5 and 132.5 nm ( figures 3(b ) and 3(c ) ) , respectively . this suggests that the size of the octahedra increased initially and then decreased with the increase of the concentration of the lactic acid . in order to clarify the effect of ph it suggests that the octahedra can form in alkaline solution if the other reaction parameters are kept constant . at ph = 8 , the average size of the octahedra in figure 4(a ) is about 382 nm , which is larger than others . when ph rises to 9 , the size is approximately 300 nm ( figure 4(b ) ) , relatively smaller than that deposited at ph = 8 . however , when the ph values are up to 11 and 12 , the size of the octahedra has an obvious decrease compared with those obtained at lower ph , which were about 92 and 87 nm , respectively . from the typical eds spectrum , it is found that the particles have a chemical formula of cu2o . in the crystal structure of cu2o shown in figure 5(a ) , the oxygen atoms are arranged in a body - centered - cubic manner , with each oxygen atom being surrounded by a tetrahedron of copper ions , each of which has two oxygen neighbors . the { 100 } and { 111 } surfaces in cubic cu2o are different in the surface atom structures and bonding as well as the possibility of chemical reactions . it is believed that during the crystal growth process , the crystal faces with higher growth rate will be eliminated first and the morphology is defined by the crystal faces with the slowest growth speed . the shape of the crystals was determined by the ratio ( r ) of the growth rate along the 100 direction to that along the 111 direction . the preferential crystal growth along the 111 direction leads to the formation of the nanocubes , while the high growth rate of { 100 } planes leads to the formation of the octahedra . lee et al . deposited spherical cu2o clusters onto al substrate in acidic solutions , and cu2o thin films were also synthesized on al foils . leopold et al . discussed the reaction scheme of cu2o nanocrystals deposited on coppers for the self - oscillations and explained the sudden decrease in the potential and increase in the local ph with precipitation model . based on the previous work and experimental results , we proposed a growth mechanism for the cu2o octahedra . the electrode reactions can be described as follows : ( 1)cul22+oh[cul2(oh)]3(2)2cul22+2e+2ohcu2o(s)+4l2+h2o(3)2[2cul2(oh)]3+2ecu2o(s)+4l2+h2o(4)l2+h2ohl+oh the formation process of cu2o octahedra is shown in figure 6 . at the initial stage , under the effect of the electric field and coulomb force , the double layer can form on the electrodes ( figure 6(a ) ) . in alkaline solution , the cu(ii ) has two forms in the presence of lactic acid , one being cul2 and the other being [ cul2(oh ) ] . the cu(ii ) complexes in the diffusion layer were reduced into cu2o ( reactions ( 2 ) and ( 3 ) ) and the l ions were liberated . then , the cu2o adsorbed on the surface of the cathode and nuclei formed in an extremely short time ( figure 6(b ) ) . the lactate ions , as a face selective adsorption additive , could be adsorbed on the { 111 } planes and confines the crystal growth along 111 directions . at the same time , the lactate ions could be protonated and oh ions were released ( reaction ( 4 ) ) , which could balance the local ph close to the cathode to a certain extent . in this process , so4 and oh ions might play important roles as the face selective adsorption additives to control the final shape of the cu2o crystals . therefore , the { 100 } planes were eliminated and finally cu2o octahedra were formed . then the ripening mechanism was dominant in the subsequent steps , which led to the size increase of cu2o octahedra . with the increase of the time , the diffusion layer became thicker and the concentration of lactate ions in the diffusion layer increased . the size of the octahedra was gradually stabilized because no enough cu(ii ) complexes in the diffusion layer could be reduced and no extra cu2o compounds were formed on the surface of the octahedra , which is demonstrated in figure 6(c ) . as the depletion of oh ions , the ph value of the electrolyte tended to be neutral ( ph = 7.5 after the deposition for 30 min ) and the reaction will be terminated . single - crystalline cu2o octahedra have been deposited onto the al foils by a simple electrochemical deposition method . the size of the octahedra firstly increases and then decreases with the increase of mole ratio of lactic acid / cuso4 , while the size of the octahedra decreases with ph . the cu2o octahedra can be obtained through the synergic effect of face selective additive adsorption upon the particle growth and ripening mechanism with the change of the ph .

a simple electrochemical deposition was developed to synthesize the cuprous oxide ( cu2o ) octahedra on aluminum foils . the average edge length of the octahedra is about 300 nm . the chemical composition of the octahedra was determined using energy dispersive x - ray spectroscopy and electron energy - loss spectroscopy . the microstructure of the octahedra was investigated using transmission electron microscopy . the formation mechanism of the octahedra is proposed .

aspirin - exacerbated respiratory disease ( aerd ) is a syndrome characterized by chronic hyperplastic rhinosinusitis , nasal polyposis , asthma , and aspirin sensitivity , as described in 1922 by szczeklik et al . [ 1 , 2 ] . the prevalence of aerd is variable ; stevenson and szczeklik reported in 2006 that aerd occurs in 3% of adult patients with asthma in the united states , with the onset of symptoms during the third decade of life , and that it is more common in women than in men , with approximately 70% versus 30% in europe and 57% versus 43% in the usa . the mechanisms underlying aspirin intolerance are not fully defined , with current research focusing on cyclooxygenase 1 ( cox-1 ) inhibition by aspirin and other nsaids diverting arachidonic acid metabolism from cox pathways to the lipoxygenase ( lo ) pathway . this leads to increased synthesis of the cysteinyl - leukotrienes ( lt ) , ltc4 , ltd4 , and lte4 , resulting in bronchoconstriction , mucus hypersecretion , and possibly the development of polyps and urticaria . the biological plausibility of this hypothesis fact has led to the search for polymorphisms in genes responsible for lt synthesis , to explore associations between these polymorphisms and local tissue levels of the proteins . other factors such as polymorphisms in the genes for proinflammatory cytokines including tnf , il1b , il6 , and il8 are involved in chronic inflammatory and autoimmune diseases . interleukin 1 ( il-1 ) is a cytokine associated with inflammatory responses and found in two forms , il-1 ( produced by the il1a gene ) and il-1 ( il1b ) , with both genes located on chromosome 2 . il-1 is expressed in nasal polyps , nasal epithelium , macrophages , activated t lymphocytes , and monocytes ; its expression is regulated by adhesion molecules , and others inflammatory cytokines . il1b polymorphisms have been associated with inflammatory bowel disease and gastric cancer among other diseases . recently , genetic polymorphisms in proinflammatory cytokines such as il-1 have been recognized as key players in the pathogenesis of asthma . similarly , il-8 has been implicated in the asthmatic inflammatory process , and genetic variation in this cytokine has been associated with both the susceptibility and the severity of this disease . in the present study , we have investigated the frequencies of polymorphisms in the genes encoding these two cytokines in aerd patients . patients with aspirin - exacerbated respiratory disease ( aerd ) ( n = 78 ) and aspirin - tolerant asthma ( ata ) ( n = 135 ) were recruited from the allergy and otolaryngology departments at the instituto nacional de enfermedades respiratorias ( iner ) . healthy control subjects ( hcs ) all participants underwent simple spirometry , inhaled methacholine challenge , and nasal challenge with lysine - aspirin ( l - asa ) according to international guidelines to determine the degree of bronchial hyperresponsiveness and confirm aerd diagnosis . the aerd group had positive l - asa and methacholine challenges , the asthmatic group had positive methacholine challenge , but negative l - asa challenge , and the healthy control subjects were volunteers with negative l - asa and methacholine challenges . a positive l - asa challenge was defined as a decrease of at least 40% in total nasal airflow after l - asa application compared with baseline measures ; methacholine challenge was considered positive with a decrease of at least 20% in forced expiratory volume in one second ( fev1 ) compared with baseline fev1 after the administration of different concentrations of methacholine ( beginning with 0.03 mg / ml , increasing gradually the concentration twice every 2 minutes until the concentration of 32 mg / ml ) ; in case it does not have it , it is considered negative . the study was approved by the science and bioethics committees of iner , and all participants gave their informed consent [ 8 , 9 ] . patients and healthy control subjects had ancestry of at least two generations born in mexico and were thus considered to be mexican mestizo in descent [ 10 , 11 ] . peripheral blood was drawn by venipuncture , and genomic dna was obtained using the commercial bdtract dna isolation kit ( maxim biotech , san francisco , calif , usa ) . the dna was quantified by absorption of ultraviolet light at 260 nm wavelength using an actgene spectrophotometer ( actgene , inc . we selected two polymorphisms in two genes related to chronic inflammation : rs16944 in il1b and rs4073 in il8 . allelic discrimination of snps rs16944 ( il1b ) and rs4073 ( il8 ) was performed by real - time pcr ( rt - pcr ) on a 7300 real time pcr system ( applied biosystems , calif , usa ) using taqman commercial probes ( applied biosystems , usa ) for each of the polymorphisms mentioned above and followed the cycling program : preread 50c , 1 minute ; absolute quantitation : 50c , 2 minutes , 1 cycle ; 95c , 10 minutes , 1 cycle ; 95c , 15 seconds , 60c 1 min , 40 cycles ; postread 50c , 1 minute . the results were assessed taking into account the allelic discrimination and absolute quantitation in all samples ; additionally , we included four contamination controls per plate ( nontemplate controls ) . the fluorescence signal detectors used were vic which was assigned to the b allele and fam assigned to the a allele for both snps . statistical analysis was performed between groups of cases ( aerd and ata ) versus the healthy control subjects by test with 3 2 tables , using spss ( v. 15.0 ) software for windows , to identify the difference between the allele and genotype frequencies of each polymorphism evaluated . in addition , odds ratios and 95% confidence intervals were calculated with epi - info ( v. 6.04 ) software . we performed a genetic association study of the il8 ( rs4073 ) and il1b ( rs16944 ) gene polymorphisms in the three groups . genetic data for the snps included in this study are shown in table 1 ; minor allele frequency ( maf ) of the polymorphisms tested in healthy control subjects had a similar distribution to that reported in international databases ( table 1 ) . gene frequencies for each genotype within the three subject groups are shown in table 3 . the frequency of genotypes aa , at , and tt of the il8 rs4073 snp was not statistically significant and different between the three studied groups . analysis of gg and ga genotypes of the il1b ( rs16944 ) snp for aerd and ata patients versus the healthy control subjects showed nonstatistically significant associations . interestingly , the aa genotype showed increased frequency in the aerd patients when compared to the ata group ( gf = 0.19 versus 0.07 ) ; this association was statistically significant ( p = 0.018 , or 2.98 , and ci 1.177.82 ) ( tables 3 and 4 ) and was not found when aerd or ata groups were compared to healthy control subjects . there is no difference in aa versus ag + gg using contrast of healthy control subjects versus aerd patients ( data not shown ) . the airways of aspirin - sensitive patients are characterized by chronic inflammation with cell infiltration even when they are not exposed to aspirin or other nsaids . in addition to alterations in the metabolism of arachidonic acid , several proinflammatory cytokines have been associated with aerd . the role of il-1 , however , has not been investigated previously . here , we report that aerd patients show an increased frequency of the il1b-511 polymorphism ( rs16944 aa genotype ) compared to aspirin - tolerant asthmatics . interleukin-1 has been reported to be involved in the genesis of both asthma [ 13 , 14 ] and chronic rhinosinusitis with nasal polyposis in a turkish population . most studies have attempted to establish the association of polymorphisms in the il1b promoter gene , mainly at positions-511 g / a ( rs16944 ) and -31 c / t . for example , park et al . , in 2004 , did not find any association between these polymorphisms and either asthma or atopy in a korean population . in 2007 , erbek et al . described a susceptibility for developing nasal polyps associated with the il1b-511 polymorphism ( rs16944 ) , but mfuna endam et al . , in 2010 , failed to reproduce this finding in canadian patients with chronic rhinosinusitis . in 2003 , allen et al . did not find any association with il1 gene polymorphisms in asthmatic families ( n = 244 ) , but they reported an association with the dna microsatellite d2s308 in these asthma families ( p = 0.00001 ) . in parallel , karajalein et al . evaluated 245 patients with asthma and nasal polyposis and did not find any association between the polymorphism il1b-511 c / t and nasal polyps . evidence for the role of il-1 in pulmonary immune responses has been gathered in murine models of allergic asthma using il-1r1-deficient [ il-1r1 ( / ) ] mice ; changes observed in these mice include significant reduction of pulmonary eosinophilic inflammation , diminished goblet cell hyperplasia , and reduction of cell recruitment to the lungs , as compared to control balb / c mice . however , there are no studies linking gene promoter polymorphisms and levels of expression of the cytokine in the lung microenvironment . in the present study , we have demonstrated that the frequency of the il1b-511 polymorphism ( rs16944 aa genotype ) is three - fold higher in aerd ( 19.2% ) than in ata patients ( 7.4% ) , suggesting that patients carrying this polymorphism may exhibit genetic susceptibility to develop aerd . findings on the biological functionality of the rs16944 polymorphism have not been consistent across studies . the aa genotype has been associated with higher gastric mucosal levels of il-1 in bacterial infections , while mononuclear cells from subjects with the gg genotype showed an increased release of il-1 after stimulation with lipopolysaccharide . recent studies suggest that the functional role of rs16944 may depend on il1b promoter region haplotypes including rs16944 [ 2326 ] . although the findings are inconsistent , these previous studies suggest that rs16944 could affect the expression levels of il-1. our report is the first demonstration of the involvement of il1b polymorphism in aerd . the sample size is relatively small , particularly in the aerd group , which may limit the statistical power , so it would be desirable to replicate our findings in an independent population . future studies must investigate whether this cytokine is released in the airways of aerd patients and whether its levels relate to genetic polymorphisms in the il1b gene . interleukin-8 has been implicated in asthma and found in high concentrations in bronchoalveolar lavage fluid of patients with acute asthma exacerbations . in fact , polymorphic il8 alleles ( 251 t and 781c ) have been associated with asthma in a european population [ 7 , 27 ] , but not in asthmatics of korean origin ; the differences could be explained by the different ethnic populations studied . in contrast , korean asthmatics were found to show four nonsynonymous amino acid substitutions in the il-8 receptor a ( il8ra ) and an association of one synonymous variation in il8rb . in the present study , we did not find a significant difference in the rs4073 a / t between the aerd group and ata patients .

aspirin exacerbated respiratory disease ( aerd ) is characterized by chronic hyperplastic rhinosinusitis , nasal polyposis , asthma , and aspirin sensitivity . the mechanisms which produce these manifestations of intolerance are not fully defined , current research focuses on cyclooxygenase 1 ( cox-1 ) inhibition , metabolism of arachidonic acid , and the cox pathway to the lipoxygenase ( lo ) route , inducing increased synthesis of leukotrienes ( lt ) . the biological plausibility of this model has led to the search for polymorphisms in genes responsible for proinflammatory cytokines synthesis , such as il1b and il8 . we performed a genetic association study between il8 - 251 ( rs4073 ) and il1b-511 ( rs16944 ) polymorphisms in aerd , aspirin - tolerant asthma ( ata ) , and healthy control subjects . using allelic discrimination by real - time pcr , we found statistically nonsignificant associations between aerd , ata , and healthy control subjects for the gg and ga genotypes of il1b ( rs16944 ) . interestingly , the aa genotype showed an increased frequency in the aerd patients versus the ata group ( gf = 0.19 versus 0.07 , p = 0.018 , or 2.98 , and 95% ci 1.177.82 ) . this is the first observation that il1b polymorphisms are involved in aerd . thus , future studies must investigate whether interleukin-1 is released in the airways of aerd patients and whether it relates to genetic polymorphisms in the il1b gene .

decentration can lead to undesired complications such as decreased visual acuity , astigmatism , glare , and monocular diplopia , which would overcome the purposes of the surgery ( 1 , 2 ) . to minimize the risk of decentration measurement of the angle kappa between the visual and papillary axes plays an important role in this process . positive and negative angle kappa values correspond to the reflection of corneal light nasally and temporally , respectively ( 3 ) . a positive angle kappa 5 is physiologic , whereas values > 5 can lead to pseudostrabismus ( 4 ) . hyperopic eyes show large angle kappa in comparison to myopic eyes ; therefore , a small decentration in these eyes can lead to severe complications . the angle kappa is commonly measured in cases of strabismus and plays an important role in the preoperative assessment . one method that can be used to measure the angle kappa is the orbscan ii device , which is widely used preoperatively in photoablation surgeries . the purpose of this study was to determine the mean angle kappa and its intercepts among normal young adults , who comprise the target population for keratorefractive surgery . in a non - random simple sampling , a total of 977 cases among the patients , who were referred to the khatam eye center ( a specialized eye hospital in mashhad , northeast of iran ) from march 2011 to february 2012 and claimed to be healthy , were enrolled in this observational cross - sectional study . exclusion criteria were as follows : history of any deviation or strabismus , with or without orthoptic or surgical treatment ; any intraocular , corneal , or keratorefractive surgery ; using contact lens ; any corneal anomaly ; any ophthalmic or systemic drug consumption ; and hyperopic spherical refraction > + 3.00 diopters ( d ) , myopic spherical refraction < -5.00 d , or cylindrical refraction > 2.00 d. these criteria were defined to exclude cases with refractive errors that tend to induce pathologies . this study was registered with the ethics committee of mashhad university of medical sciences , and clearance was obtained . considered ethical codes for this study were 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 14 , 17 , and 20 . complete ophthalmologic and orthoptic examinations were performed , including slit lamp biomicroscopy and dilated pupil fundoscopy . the orbscan ii device ( bausch and lomb , technolas , ny ) one acquisition was done per eye , unless an unacceptable result was obtained that would mandate repetition . for measurements with the orbscan ii device the examiner used the joystick of the device to make adjustments such that the final result would be a sharply focused image of the eye . descriptive analysis was used to determine the mean values and the student 's t - test was used to compare differences . in a non - random simple sampling , a total of 977 cases among the patients , who were referred to the khatam eye center ( a specialized eye hospital in mashhad , northeast of iran ) from march 2011 to february 2012 and claimed to be healthy , were enrolled in this observational cross - sectional study . exclusion criteria were as follows : history of any deviation or strabismus , with or without orthoptic or surgical treatment ; any intraocular , corneal , or keratorefractive surgery ; using contact lens ; any corneal anomaly ; any ophthalmic or systemic drug consumption ; and hyperopic spherical refraction > + 3.00 diopters ( d ) , myopic spherical refraction < -5.00 d , or cylindrical refraction > 2.00 d. these criteria were defined to exclude cases with refractive errors that tend to induce pathologies . this study was registered with the ethics committee of mashhad university of medical sciences , and clearance was obtained . considered ethical codes for this study were 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 10 , 11 , 14 , 17 , and 20 . complete ophthalmologic and orthoptic examinations were performed , including slit lamp biomicroscopy and dilated pupil fundoscopy . the orbscan ii device ( bausch and lomb , technolas , ny ) one acquisition was done per eye , unless an unacceptable result was obtained that would mandate repetition . for measurements with the orbscan ii device the examiner used the joystick of the device to make adjustments such that the final result would be a sharply focused image of the eye . descriptive analysis was used to determine the mean values and the student 's t - test was used to compare differences . a total of 977 healthy young adults , aged 18 to 45 years , participated in this observational cross - sectional study . the study population consisted of 614 females and 363 males ( p < 0.001 ) . figure 1 shows the distribution of angle kappa in degrees in different ages according to sex . the mean angle kappa was 4.97 1.38 , with a mean of 5.00 1.36 in males and 4.96 1.30 in females ( p = 0.63 ) . the means of angle kappa in the right and left eyes were 5.16 1.44 and 4.78 1.31 , the means of horizontal ( x - axis ) angle kappa were -0.44 0.28 and 0.37 0.25 in the right and left eyes , respectively ( p = 0.012 ) . the means of vertical ( y - axis ) angle kappa were -0.11 0.31 and -0.07 0.34 in the right and left eyes , respectively ( p = 0.01 ) . the mean of horizontal angle kappa was -0.02 0.49 , with a mean of -0.02 0.50 in males and -0.02 0.49 in females ( p = 0.93 ) . the mean vertical angle kappa was -0.09 0.32 , with a mean of -0.09 0.33 in males and -0.09 0.32 in females ( p = 0.74 ) ( table 2 ) . we measured the variables in the right and left eyes separately ( tables 3 and 4 ) . the angle kappa plays an important role in refractive surgery , and inaccurate preoperative measurements of this angle can lead to serious surgical complications associated with decentration ( 1 , 5 ) . in patients with strabismus , precise measurement of the angle kappa prevents the under - calculation or over - calculation of the degree of deviation ( 3 ) . in patients with a large angle kappa , the lens of prescription glasses can result in a large prismatic effect , which can disturb the best - corrected visual acuity ( 6 ) . angle kappa is increased with age ( 7 ) . to achieve more accurate results in the preoperative assessment , we measured the angle kappa in a large sample of a normal population . hashemi et al . previously measured the angle kappa distribution in a population of tehran residents with a wide age range ( 6 ) . their findings encouraged us to restrict our sampling to the population that was most likely to undergo refractive surgery ( age range , 18 - 35 years ) . therefore , our results might be more reliable for estimating the angle kappa in this population ( 8) . we used the orbscan ii device because of its very precise measurements and excellent reproducibility with only one acquisition per eye . to reduce the risk of systematic bias , a single operator used the orbscan ii . the orbscan ii finds the center of the pupil and finds where the perpendicular axis to the pupil center intercepts the cornea . in the reports , the plus or cursor sign ( + ) shows the corneal apex and the small " k " shows the intercept of the pupillary axis . the cornea periphery is assumed 360 , initiating at the 3-oclock position and rotate counterclockwise . for example , the locus is at 346.47. therefore , the kappa angle is 4.59 at ( @ ) 346.47. the third and fourth are the intercepts in x - axis and y - axis , respectively . the dimension of the intercept is divided into x - axis ( horizontal ) and the y - axis ( vertical ) . in our example , it is + 0.19 mm in the left of the corneal apex and -0.11 mm below the corneal apex . among the 977 individuals ( 1954 eyes ) who were examined , there were more women than men ( p < 0.001 ) , and the values obtained from women would have more effect on the overall results . the angle kappa for both men and women decreased with age , according to the linear regression test . we observed a significant difference between the mean angle kappa in the right and left eyes . no previous study had obtained this result , which did not seem to be accidental due to the large number of cases . further investigations are needed to resolve this difference . in comparison to the reported value of 4.96 1.38 in this study , hashemi et al . reported a mean angle kappa of 5.46 previously ( 6 ) ; however , we used a different age range with a smaller refractive error than they did . because a higher refractive error can result in larger angle kappa , lower angle kappa results were expected in our study . ( 4 ) used an age range similar to ours ( 20 - 40 years ) and observed an average angle kappa of 5.22. in wachler et al . the angle kappa was reportedly greater in patients with hyperopia ( 8) while hashemi et al . unfortunately , we did not divide patients into groups on the basis of their refraction and hence , we could not comment on the angle kappa distribution among different refractive groups . in another recently published study , performed in our center , the angle kappa changes after photorefractive surgery were evaluated in a population different from this study s and it was found that in 96 eyes , the angle kappa had not changed significantly after the surgery ( 4.97 1.24 preoperatively and 4.99 1.10 at six months postoperation ) . findings of the current study were the same as our previous population ( 9 ) . moreover , we found just another document about the measurement of kappa angle in normal population . basmak et al . in 100 normal individuals , compared synaptophore with the orbscan , and the effect of refraction on the kappa angle . they found that a correlation exists between positive refractive errors and large positive angle kappa values . moreover , data gathered by orbscan showed a little bit higher values in comparison to synaptophore ; however , the orbscan system provides angle kappa values with quantitatively established precise measurements ( 10 ) . park et al . have reviewed the concept of angle kappa , its measurement and distribution in normal populations , and its implications in refractive surgery and concluded that evidences about the kappa angle effects on refractive surgery were growing . decentered treatment might be induced by ignoring it and visual symptoms might aggravate the vision . in treating refractive errors in modern era , compensating kappa angle is important in achieving optimal correction ( 11 ) . although a large sample size in this study could assume a good evaluation of the amount of angle kappa in refractive surgery cases , one of our limitations was ignoring the spherical equivalent of patients for more precise classification of angle kappa , which is known to be affected by this variable .

background : the angle kappa is important in proper centration of corneal ablation in keratorefractive surgery . orbscan ii device is widely used preoperatively in photoablation surgeries and can be used to measure the angle kappa.objectives:this study aimed to determine the mean angle kappa and its intercepts in healthy young iranian adults.patients and methods : in this cross - sectional study , orthotropic patients ( age range , 18 - 35 years ) who were referred to the khatam eye hospital ( mashhad , iran ) were included . exclusion criteria were as follows : history of any eye deviation or strabismus with or without orthoptic or surgical treatment ; any intraocular , corneal , or keratorefractive surgery ; contact lens use ; any corneal anomaly ; any ophthalmic or systemic drug consumption ; and hyperopic spherical refraction > + 3.00 diopters ( d ) , spherical refraction > -5.00 d , or cylindrical refraction > 2.00 d. all of the parameters were measured by the same operator through an orbscan ii device.results:a total of 977 healthy participants who aged 18 to 45 years were included consecutively . the study population consisted of 614 females and 363 males . the average angle kappa was 5.00 1.36 at 240.21 97.17 in males and 4.97 1.30 at 244.22 94.39 in females ( p = 0.63 ) . the average horizontal ( x - axis ) angle kappa was -0.02 0.49 , with a mean of -0.02 0.50 in males and -0.02 0.49 in females ( p = 0.93 ) . the average vertical ( y - axis ) angle kappa was -0.09 0.32 , with a mean of -0.09 0.33 in males and -0.09 0.32 in females ( p = 0.74).conclusions : by using the normal angle kappa determined in this study , pseudodeviations can be identified more precisely in those who might undergo keratorefractive surgery .

primary infection known as chickenpox , mostly occurs in childhood , with mild clinical course in immunocompetent hosts , but it can cause significant morbidity in healthy adults with life threatening forms in immunocompromised persons . vzv establishes latency in sensory ganglia , and can be reactivated years later as herpes zoster . circulating vzv - specific antibody can prevent primary infection but innate and cellular responses are more important in its severity and duration ( 2 ) . clinical studies suggest that t cell immunity plays a key role in the protection against vzv primary infection . few studies found significant depression of cd4 + t lymphocytes , augmentation of cd8 + t - lymphocytes and changes in cd4/cd8 ratio but none of them were compared to clinical course of illness ( 3 , 4 ) . we performed a prospective clinical study which included 69 immunocompetent persons with confirmed chickenpox in a period july 2014 - january 2016 . patients were divided into two groups : group with mild clinical presentation who were treated as outpatients , and group with moderate , severe or life - threatening clinical presentation which were hospitalized . study also included 30 healthy volunteers with age and sex similar to the other groups . we checked general characteristics such as age , sex , complications , clinical course of illness , percentage values of cd4 + , cd8 + t - lymphocytes and cd4/cd8 ratio . values for cd4 + , cd8 + t - lymphocyte percentage and cd4/cd8 ratio was obtained using facs canto , bd biosciences flow cytometer and bd multitest 6-color tbnk immunofluorescent test . values with normal distribution were expressed as meanstandard deviation . to compare mean values for variables without normal distribution chi - square test was used . one - way anova test was used for statistical evaluation of more than three groups . correlation of monitored variables is determined by pearsons test . to determine influence of these variables to a clinical presentation we used logical regression ( backward method ) . p - values less than 0.05 were considered statistically significant . clinical presentation of the illness cd4 + percentage values in the groups cd8 + percentage values for all groups cd4/cd8 ratio values for the groups mean age in outpatient group was 28.47 years with standard deviation ( sd ) 10.3 while in the other group was 24.57 ( sd=14.14 ) , with no statistically significant difference between groups ( p>0.05 ) . females were dominant in outpatients group ( 65%:35% ) , while males were in higher number in other group ( 71%:29% ) . chi - squared test found statistically significant difference between these two groups ( p<0.05 ) . the number of complications vary from zero to four per patient , and all were presented in a hospitalized patients . mean value of cd4 + percentage for outpatient group was 44.06 ( sd 11.48 ) and for a group of hospitalised patients it was 28.20 ( sd=12.70 ) . one - way anova test found statistically significant difference between group of hospitalised patients and outpatients , as well as hospitalised patients and control group ( p<0.0001 ) . values for percentage of cd8 + t - lymphocytes were as follows : outpatients 30.15 ( sd=9.46 ) ; hospitalised patients 38.34 ( sd=15.52 ) ; control group 28.40 ( sd=7.34 ) . one - way anova test found statistically significant difference between group of hospitalised patients and outpatients , as well as hospitalised patients and control group ( p<0.0001 ) . cd4/cd8 ratio was 1.74 ( 0.40 - 8.10 ) in group of outpatients , 1.05 ( 0.10 - 3.60 ) in group of hospitalised patients and 1.73 ( 0.80 - 3.70 ) in a control group . one - way anova test found statistically significant difference between group of hospitalised patients and outpatients , as well as hospitalised patients and control group ( p=0.006 ) . using pearson s correlation factor we have found very strong negative correlation between cd4 + percentage value and clinical presentation ( r=0.61 , p<0.0001 ) ; strong positive correlation between cd8 + percentage value and clinical picture and also weak negative correlation between cd4/cd8 ratio and clinical presentation . in addition we performed regression analysis to determine which of mentioned parameters have the strongest influence to clinical presentation . values of cd4 + percentage have a very strong influence as a prognostic factor to clinical presentation and possible severity of clinical picture ( beta coefficient = 0.56 , p<0.0001 ) . results of our study correlate with other studies regarding age and sex of the patients , where most of the them with complications were males , age 21 - 40 , primary because of preexisting medical conditions ( 5 ) . several studies suggest that cellular immunity has a key role in control of vzv primary infection ( 6 , 7 ) . patients with primary agamagloblinaemia develop mild clinical form , while patients with deficiency of cellular immunity develop severe and life - threatening forms of chickenpox ( 8) . so far , there is no prognostic marker for a severity of clinical picture and outcome of the disease , which can be measured in short time and predict further development of the illness . in our study we tried to investigate if values of cd4 + and cd8 + t - lymphocytes percentage , so as cd4/cd8 ratio , can be considered as relevant prognostic factors for clinical course of chickenpox . we measured values of these parameters from blood samples taken from the patients in acute phase of disease , 24 - 72h after development of the rash , and correlate with presented complications and severity of clinical picture . values of cd4 + t - lymphocytes mostly decrease in acute phase of all viral infection , so as vzv , with recovery during the time . for significant number of diseases it can be strong prognostic factor for possible coinfections and complications in clinical course ( 3 , 9 , 10 ) . in our study decrease of cd4 + percentage was very significant , compared to the group with mild clinical form and control group . also cd8 + percentage value increased in acute phase of illness among hospitalized patients with presented complications . early studies suggest similar dynamic of these subsets of t - lymphocytes ( 11 ) . significant difference between these patients and outpatients , so as control group , was confirmed with anova test . cd4/cd8 ratio is very important in follow - up of some viral diseases and other medical conditions ( 12 , 13 ) . we found significant decrease in values of cd4/cd8 in hospitalized patients , while values in group of outpatients and controls were almost the same . further comparison using regression analysis found values of cd4 + percentage of t - lymphocytes as a strong predictive factor for clinical course of the disease . also values of cd8 + t - lymphocyte percentage were in a strong correlation with clinical pictures . according to the results of our study , we can consider values of cd4 + and cd8 + t - lymphocyte subsets as strong predictive factor for a clinical course of chickenpox in immunocompetent patients . values of cd4 + t - lymphocytes have the strongest influence , while cd4/cd8 ratio stays as a prognostic factor , but not so strong like in other viral diseases , such as hiv .

objective : to investigate possible prognostic values of cd4 + , cd8 + t - lymphocytes , cd4/cd8 ratio to clinical course of chickenpox in immunocompetent hosts.materials and methods : we performed a prospective study which included 69 immunocompetent patients with chickenpox who were addmited to clinic for infectious disease , clinical center university of sarajevo , in a 18 month period . all patients were divided into two groups depending on clinical presentation on admission . patients with mild clinical form were dedicated to outpatient group , and patients with moderate , severe or life - threatening clinical forms were dedicated to hospitalized group . also 30 healthy volunteers are included in study as a control group . we analyzed values of cd4 + , cd8 + percentage , cd4/cd8 ratio with comparison to clinical course of chickenpox . all specimens were taken in acute phase of illness.results:values of cd4 + percentage were significantly declined in a group of hospitalized patients , compared to group of outpatients and control group . values of cd8 + percentage were higher in a group of hospitalized patients , while cd4/cd8 values were lower in comparison to a group of outpatients and control group.conclusion:we found significant correlation between these parameters and clinical course of chickenpox .

osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue . osteoporotic bones have same size and appearance as the normal bone from the outside but have a thin layer of cortical bone and trabecular bone loss inside and are more fragile than normal bone . serum estradiol levels remain fixed at under 30 pg / ml 1 year after menopause . lower estrogen levels increased osteoclastic activity , reduced osteoblastic activity in the bone , and are responsible for rapid bone loss in women . the most common symptom is bone pain in patients with postmenopausal osteoporosis ( po ) . the most common physical complaints are pain due to fractures , reduced mobility , spinal deformity , and shortened height . older age , low - income levels , lack of activity , sedentary lifestyle , duration of menopause , and history of fractures are associated with a decrease in bmd . several methods have been developed to assess health status and quality of life ( qol ) associated with osteoporosis , including a qol questionnaire from the european foundation for osteoporosis-41 ( qualeffo-41 ) . major depression has been repeatedly reported to be associated with low bmd in the spine and hip . excessive activity of the hypothalamic - pituitary - adrenocortical axis has been consistently demonstrated in major depressive disorder , whereas depressive symptoms have been reported in patients with osteoporosis , especially in the postmenopausal period . reported that depression has frequently been associated with osteoporosis . however , the nature of this link , and whether it is direct or indirect , remains to be explored . bisphosphonates are the most commonly used drugs for the prevention and treatment of osteoporosis . once - yearly zoledronic acid ( za ) 5 mg is a type of bisphosphonate . the purpose of this study was to investigate the effectiveness of once - yearly za 5 mg on depression and qol in the women with po . a total of 88 newly diagnosed women in 2 years between 2012 and 2014 with po referred to the endocrinology clinic of samsun ondokuz mays university medicine faculty and treated with once - yearly za 5 mg ( aclasta novartis ) were included in this self - controlled prospective cohort study . za was chosen for po treatment because of proven efficacy , ease of use , low cost of treatment , and not requiring follow - up . bmd levels were measured by dual - energy x - ray absorptiometry ( dxa ) from the lumbar ( l1l4 ) and femoral neck regions . osteoporosis is 2.5 standard deviations below the mean bmd of healthy adults of the same sex and race . a qol questionnaire from the qualeffo and beck depression inventory ( bdi ) was given to patients at baseline and 12 months . the qualeffo-41 questionnaire has five domains , with 41 items in total : pain ( 5 - items ) ; physical function ( 17 - items ) ; social function ( 7 - items ) ; general health perception ( 3 - items ) ; and mental function ( 9 - items ) . exclusion criteria were as follows : active psychiatric diseasesactive hematological , oncological cancerssecondary osteoporosisactive metabolic bone diseasespreviously received treatment for osteoporosisfractures ( osteoporotic , traumatic)stage 45 renal failure ( creatinine clearance 30 ml / min)hypercalcemia ( 11 mg / dl ) or hypocalcemia ( 8 mg / dl)bone and joint deformities affecting static standing alone . active psychiatric diseases active hematological , oncological cancers secondary osteoporosis active metabolic bone diseases previously received treatment for osteoporosis fractures ( osteoporotic , traumatic ) stage 45 renal failure ( creatinine clearance 30 ml / min ) hypercalcemia ( 11 mg / dl ) or hypocalcemia ( 8 mg / dl ) bone and joint deformities affecting static standing alone . written informed consent was obtained from each participant following a detailed explanation of the objectives and protocol of the study , which was conducted in accordance with the ethical principles stated in the declaration of helsinki and approved by the institutional ethics university committee approval number is 71522473.050.02.05/54 . all patients were supported with daily oral vitamin d ( 880 iu ) and oral calcium ( 1000 mg ) . mean differences of continuous data were measured through t - test , and median differences of categorical data were measured by mann whitney u and fisher 's exact tests . differences between parameters before and after treatment were assessed by paired sample t - test . mean differences of continuous data were measured through t - test , and median differences of categorical data were measured by mann differences between parameters before and after treatment were assessed by paired sample t - test . demographic characteristics once - yearly za 5 mg treatment was found to be effective for treating po . baseline mean l14 t - scores and femoral neck region were measured at 3.30 and 2.39 in dxa . l14 t - scores increased 2.60 and for the femoral neck region increased 2.09 after treatment at 12 months ( p = 0.001 ) [ table 2 ] . the effects of once - yearly zoledronic acid 5 ( mg ) pain scores decreased from 17.44 to 13.95 ( p = 0.001 ) ; physical function scores decreased from 47.29 to 40.51 ( p = 0.001 ) ; social function scores decreased from 20.4 to 16.67 ( p = 0.001 ) ; general health perception scores decreased from 20.19 to 16.22 ( p = 0.001 ) ; mental function scores decreased from 32.1 to 30.9 ( p = 0.001 ) ; and total scores decreased from 27.48 to 23.65 ( p = 0.001 ) after once - yearly za treatment [ table 3 ] . changes in domains of quality of life questionnaire from the european foundation for osteoporosis-41 and beck depression inventory the bdi includes 21 items . a maximum of three points are obtained from one item . bdi points decreased from 16.51 to 13.42 ( p = 0.001 ) after once - yearly za treatment [ table 3 ] . both bdi point levels are consistent with mild depressive symptoms , but the decrease in bdi points was statistically significant . once - yearly za treatment is an effective treatment for po . once - yearly za treatment improved qol and reduced depression . our study is the first demonstrating the relationship between once - yearly za treatment and both qol and depression in the literature . it has a prolonged dosing interval and fewer side effects than other bisphosphonates . once - yearly za can be used in treatment and prevention of po and glucocorticoid - induced osteoporosis as well as treatment of male osteoporosis . a meta - analysis of nine clinical trial showed that za is an effective treatment for osteoporosis . significantly , higher bmd and lower fractures were found . in our study , za treatment was found to be effective in terms of bmd levels as in 9 's clinical trial . some of these studies were conducted with patients with osteoporosis , and some were conducted with patients with osteoporotic fractures . in all of these studies , osteoporosis with or without fracture was found to be related with low qol . in the literature , we found only one study demonstrating the relationship between once - yearly za treatment and qol . za treatments were found to be effective in po and increase qol , but the qualeffo-41 questionnaire was not used in that study . ours is the first study showing the relationship between once - yearly za treatment and qol using the qualeffo-41 questionnaire in terms of depression . depression is associated with several chronic conditions such as diabetes mellitus , cardiovascular diseases , menopause , and osteoporosis . these limitations in movement , as well as pain , lead to breaks in daily activity , and patients may become isolated . our patients scored 16.51 points for bdi at the beginning of the once - yearly za treatment . these results are consistent with some mild depressive symptoms as well , but the decrease in bdi points was statistically significant . the most important one is the small number of participants and the short study duration . the other is that we did not compare our participants with participants who not using za treatment for osteoporosis once - yearly za treatment is effective in po while also increasing qol and decreasing depression . once - yearly za treatment is easy to use and has fewer side effects . fg ; found the subject and the patientscv wrote the articleaa ; made the statistical analysismha ; made the tablesrc ; made the last corrections . fg ; found the subject and the patients aa ; made the statistical analysis rc ; made the last corrections .

background : osteoporosis affects quality of life ( qol ) and may lead to depression in women . the purpose of this study was to evaluate the effects of zoledronic acid ( za ) treatment on depression and qol in women with postmenopausal osteoporosis ( po).materials and methods : a total of 88 newly diagnosed women with po were included in this study . all patients were treated with once - yearly za ( 5 mg ) . a qol questionnaire from the european foundation for osteoporosis and beck depression inventory were given to patients at baseline and at 12 months . the results for baseline and post - 12th month were compared , and bone mineral density ( bmd ) levels were compared.results:the consumption of once - yearly za ( 5 mg ) treatment increases bmd at levels of lumbers 14 ( p = 0.026 ) , total hip t score 's p value is same as femoral neck ( p : 0,033 ) . za 5 mg treatment also improved qol ( p = 0.001 ) and reduced depression ( p = 0.001).conclusion : za treatment increases bmd levels and qol while reducing depression . once - yearly za ( 5 mg ) may be considered for postmenopausal women as a first - line treatment .

obviously , there are many predisposing conditions leading to atelectasis . in addition to aspiration of materials or accumulation of endobronchial secretions , we have to consider not only endobronchial lesions , such as mucosal edema , fibrous tissue , granuloma , and maligant tumor , but also extrabronchial pathology compressing an airway . however , it is not so easy to determine the cause of bronchial stenosis or obstruction unless bronchofiberscopic examinations are indebted . since bronchogenic cancer seems to be on the increase , we often regard certain cases of atelectasis discover as complications of bronchogenic malignancy , but later it was disclosed endobronchial tuberculosis after examination with the flexible bronchoscope . moreover , we emphasize that bronchofiberscopic examination is a very important tool for detecting endobronchial tuberculosis and making a differential diagnosis . fifty three patients with endobronchial tuberculosis ( 4.7% ) out of 1,132 subjects who had a flexible bronchofiberscopic examination at the department of internal medicine of hanyang university hospital between the beginning of march 1982 and the end of december 1985 are included in this study . for diagnostic confirmation , positive stainings of acid - fast bacilli were identified on the tissue sections , sputum , and/or specimens aspirated through endoscopic biopsy and brushing or washing - out for cytology and culture . prior to the bronchofiberscopic examination , after topical application of 4% lidocaine around the upper airway , a fujinon dro - i or fujinon dro - il fiberoptic bronchoscope was inserted for endoscopic observation . stainings for acid - fast bacilli were positive in the sputum and/or bronchial washings of 67.9% of the patients . the remaining 32.1% of the patients , diagnoses were confirmed by culture or positive staining for afb , or bronchofiberscopic biopsy specimens ( table 2 ) . as shown in table 3 , chest pain was complained of 20.8% of the patients , and production of mucus , dyspnea , hemoptysis , and fever were complained of in 18.9 , 17 , 17 , and 9.4% of the cases , respectively . findings on the chest x - ray were abnormal in twenty three out of 53 patients . no predilective lesion site was apparent on chest x - ray films ( table 4 ) . the left lower and upper bronchi , however , are the most frequently involved , obstructive sites observed by means of bronchofiberscopy ( table 5 ) . endoscopic pictures of endobronchial tuberculosis showed mucosal swelling , edema , redness , erosion , or occasional ulceration and loss of light reflex from granulation , along with narrowing of the lumen . occasionally a light yellowish - white colored miliary nodule was observed . cicatrical stenosis or obstruction covered by whitish pseudomembrane was a common finding in the patient with atelectasis caused by endobronchial tuberculosis . after the pseudomembrane was desquamated , tenaceous secretions which had been exposed around the opened site were visible . pathological findings were essentially chronic granulomatous inflammation showing caseation necrosis , or nonspecific chronic inflammation . the barking cough was not responsive to antitussive medication but it did respond well to steroids along with antituberculous combination chemotherapy . although the early detection of endobonchial tuberculosis by identification of acid - fast bacilli is highly desirable , it is not easy to accomplish , because features of the initial chest films are usually nonspecific . therefore , it is thought that the bronchofiberscopic approach is mandatory for the diagnosis of endobronchial tuberculosis . the most common initial lesion of endobronchial tuberculosis is infiltration of lymphocytes into the bronchial mucosa , and the next is partial stenosis by considerable mucosal congestion and edema . development of caseous necrosis with formation of tuberculous granuloma can be found at the mucosal surface . fibrotic change of the lamina propria as well as healing of mucosal ulcerations or erosions with or without squamous metaplasia formerly would progress to cicartrical stenosis . the spectrum of endobronchial tuberculosis we encountered in this series of patients was somewhat characteristic . a five to six times higher incidence in females than in males was noted . these results are quite different from those of another report , in which the peak incidence was noticed in old and weak females beyond 50 years of age . however , in our study also , a lage peak was noted one in the 7th decade . it is thought that the initial peak in the third decade is representative of the general situation in korea where tuberculosis is endemic , and that the late peak of old age occurs , not because of reinfection , but as a result of the reactivation of the primary lesion when the patient is in an immunocompromised states . old age , alcoholism , prolonged therapy with steroids , diabetes mellitus , and silicosis are known as risk factors for reactivation of the primary lesion . bronchofiberscopically , whitish pseudomembrane causing stenosis or obstruction of bronchi was characteristic finding in the patients with atelectasis caused by endobronchial tuberculosis . this means , in turn , that bronchofiberscopy is a very useful tool in relieving atelectasis caused by cicartrical obstruction . since the squamous metaplasia and nonspecific chronic inflammatory change could be associated with other diseases , microbiological confirmation from bronchofiberscopic brushing and/or washings is required . the other feature that was nearly universal in our patients was evidence of the usefulness of medication with steroid for relieving the barking cough as also noted in other literature . in view of the fact that tuberculosis is one of the common endemic diseases in korea , young , female patients , whose coughing is barking in nature and resistant to general antitussive agents , should be considered to possibly have endobronchial tuberculosis . furthermore , we would like to emphasize that the bronchofiberscopic approach is a substantially useful means of making a differential diagnosis in atelectasis in old patients of cancer - risk age .

the clinical and bronchofiberscopic features of endobronchial tuberculosis in 53 patients were investigated . these patients comprised 4.7% of some 1,132 subjects who had undergone flexible bronchofiberscopic examinations . the peak incidence occurred in the third and fourth decades , a secondary peak appeared in the seventh decade , a five to six times higher incidence was noted in the female than in the male . staining for acid - fast bacilli was positive in 67.9% of the patients sputums and or specimens of bronchial washings . a barking cough was the most common chief complaint . next in order were chest pain , production of mucus , dyspnea , hemoptysis , and fever . twenty - three out of 53 patients showed abnormalities on their chest films.the flexible bronchoscope revealed tuberculous lesions characterized by mucosal swelling or edema , redness , erosion , ulceration , hypertrophy with luminal narrowing , and cicartical stenosis due to whitish pseudomembrane . the left lower and upper bronchi were involved most frequently.the majority of the patients who were suffering from a barking cough were resistant to antitussive agents but were responsive to steroid combination chemotherapy with antituberculous drugs.in conclusion , the bronchofiberscopic approach is not only helpful in the differentiation of endobronchial tuberculosis from bronchogenic cancer but it can also be used for relieving atelectasis .

mantle cell lymphoma ( mcl ) is a mature neoplasm of the b lymphocytes classified under the category of indolent nonhodgkin lymphomas ( nhl ) . however , unlike other indolent forms of nhl , mcl behaves more aggressively despite treatment 1 . mcl comprises about 67 percent of adult nhls in the united states and europe with an incidence rate of 48 cases per million per year 1 , 2 , 3 . the median age of diagnosis is 68 years with more frequent occurrence in caucasian males than females 4 , 5 , 6 , 7 . the cell of origin for mcl is a naive b cell in 80% of the cases , but the remaining cases are derived from antigenstimulated b cells . the translocation t(11,14 ) ( q13;q32 ) is universally present in mcl and is the primary genetic defect that results in unsuppressed expression of the protooncogene ccnd1 . there are a variety of other genetic defects also involved , including loss of tumor suppressor genes and activation of other oncogenes 8 . around 70% of cases of mcl present for the first time with advancedstage disease . around threequarters of patients most common extranodal sites appear to be that of the bone marrow ( bm ) , spleen , liver , gastrointestinal ( gi ) tract , and the waldeyer 's ring 9 , 10 , 11 . in terms of gi tract involvement , ascites has been described alongside lesions such as gastric ulcers , lymphomatous intestinal polyposis or peritoneal lymphomatosis . aside from ascites , serosal lymphomatosis with pleural and pericardial effusions has been described in later stages in the setting of known mcl with positive lymph node status or bm . development of serosal effusion in the course of malignant lymphomas , either primary or otherwise , is rare and is considered as one of the adverse factors affecting overall survival 12 . however , the presence of peritoneal lymphomatosis with abdominal ascites as the first and primary presentation is rare and only few cases have been reported in the literature 13 . flow cytometry ( fcm ) and immunohistochemical staining of the ascitic fluid have helped clinicians identify a diagnosis in such cases . we found the fcm results of samples from different sites could be concordant or discordant within the same patient . as in our case , mcl cell markers in the peritoneal fluid may be able to serve as surrogate for conventional bm aspirate and biopsy . we are presenting a case of a 46yearold el salvadorian male with a past medical history of rheumatoid arthritis , dyslipidemia , and type 2 diabetes mellitus , who presented to the hospital with the complaints of sore throat , shortness of breath , cough , and chills . he also mentioned increasing abdominal distension over the last 3 months associated with significant unintentional weight loss of approximately one hundred pounds . his family history was significant for a son that was diagnosed with acute lymphoblastic leukemia at the age of 14 , who has since been in remission . on examination , generalized wasting was noted . he was noted to be febrile at 102f , tachycardic , tachypneic , and hypotensive in the emergency room . initial laboratory workup showed marked leukocytosis of 71.6 k / ul with absolute lymphocytosis of 61.2 k / ui . laboratory evaluation also revealed a hemoglobin at 4.9 gm / dl and platelet count of 111 k. a peripheral smear showed more than 50% atypical lymphocytes , multiple bands , and multisegmented neutrophils without evidence of blasts . with the presumptive diagnosis of septic shock from pneumonia , he was admitted to intensive care unit . hemodynamic support was provided in the form of vasopressors , mechanical ventilation , and transfusion of blood products . further workup revealed elevated uric acid of 10 mg / dl and lactate dehydrogenase ( ldh ) of 278 u / l . serum protein electrophoresis , histoplasma antigen , aspergillus antigen , hiv , and hepatitis panel , epstein ct scan of head , neck , chest , abdomen , and pelvis was performed and showed significant pelvic , retroperitoneal , and axillary lymphadenopathy . peritoneal carcinomatosis with marked hepatosplenomegaly , ascites and opacification of maxillary and ethmoid sinuses were also noted . peripheral blood fcm and cytogenetics were subsequently performed showing t(11:14)+ , cyclin d1 + , cd5 + , cd10 , cd23. with this data , the diagnosis of mcl was made ( fig . as mentioned before , blood smear showed atypical lymphocytes which , in the settings of leukocytosis , could not be explained merely by infection but also secondary to a neoplastic process . flow cytometry graphs of the peripheral blood [ left ] and peritoneal fluid [ right ] . following stabilization from septic shock , he underwent a bm biopsy which showed extensive involvement by the mcl ( figs . 2 and 3 ) . he presented with ann arbor stage 4 disease , hemoglobin less than 12 , an elevated ldh , and an ecog performance status of 2 . with this data , he was stratified as a highrisk stage 4 mcl . cytological analysis of which was consistent with mcl by fcm ( figs . 1 and 4 ) . h / e stain of the bone marrow showing predominant lymphocytes infiltration . from left to right showing the ihc stains of bone marrow cells positive for cyclin d1 , cd 20 , and cd 3 markers . thereafter , he was started on chemotherapy with cyclophosphamide , doxorubicin , vincristine , and dexamethasone and received two cycles of therapy . despite discharge after further stabilization , he had multiple admissions from progression of his symptoms and recurrence of ascites that required multiple paracentesis . due to inadequate response to the therapy , he was then switched to palliative chemotherapy with the use of bortezomib for seven cycles . ascites , as described in our patient , with the finding of peritoneal carcinomatosis is considered an unusual presentation for mcl and has been rarely described in literature . this case reflects the importance of cytological analysis of peritoneal fluid in a patient with intractable ascites not contributing from other comorbidities . in the event a bm analysis can not be made , this may serve as an alternative method of diagnosis . throughout history , mcl has carried different names such as intermediate lymphocytic lymphoma , centrocytic lymphoma , mantle zone lymphoma , and lymphocytic lymphoma of intermediate differentiation 2 , 3 . since the 1990s , all these names were categorized under mcl after finding that all described cases carried the t(11 , 14 ) ( q13 ; q32 ) 8 . being a tumor rising from b cells , the surface markers that are detected by immunohistochemistry include panb cell antigens sox11 could be a useful marker in cyclin d1negative mcl 12 , 13 , 14 . though the translocation t(11 , 14 ) ( q13;q32 ) is the primary genetic defect , other genetic defects include loss of tumor suppressor genes like atm , cdkn2a , and tp53 with the concurrent activation of some oncogenes like myc , syk , bcl2 8 , 14 . the presentation of the mcl can vary from chronic / indolent form to a more fulminant course resulting in shortened overall survival 1 . diffuse large bcell lymphoma being the most common of all nhl has been associated with ascites . in a case series of 101 cytologypositive cases of malignant ascites , only 8% were shown to be lymphoma 15 . in another case we find that gi tract involvement with or without ascites have been seen in indolent lymphoma to aggressive mcl 12 , 13 , 17 , 18 , 19 , 20 . infiltration due to tumor mass or vascular leakage due to stimulation by the vascular endothelial growth factor contributes to the pathogenesis of the ascites . ascites , usually described as bloody in nature , can be present concurrently with gi tract involvement , peritoneal lymphomatosis , or multiple lymphomatous polyposis of the intestine . gastric mcl is more likely to occur with other gi diseases such as crohn 's disease and adenocarcinoma . ( table 1 ) 12 , 13 , 17 , 18 , 19 . illustrating five cases of mantle cell lymphoma with ascites on presentation lap , lymphadenopathy . flow cytometric analysis was performed in four of the five cases and the expression of cytological markers in both ascitic fluid and bm or peripheral blood . one of the cases presented as postsurgical seeding following splenectomy resulting in peritoneal involvement 19 . in the cases without bm involvement , cytological markers were consistent with mcl and patients were treated as such 12 , 13 , 17 , 18 . two previous studies showed that different specimens from different sites in the same patient with nhl carry the same set of cytological markers most of the time 21 , 22 , 23 . mentioned in his study of 29 patients with nhl that if there is discordance in results , then it is either secondary to two different primary lymphomas in the same patient or a result of modulation of antigen expression of the tumor , in relation to the host environment 22 . in one study , it was observed that discordant antigen expression was associated with a more aggressive course of disease 23 . so far , the data are very limited as there are few cases that are able to be studied . treatment for this particular disease is quite complex as very few treatment options provided a complete and longlasting response . depending on the performance status , comorbidities , and age of the patient , current guidelines suggest that those with an improved performance status are more likely to be treated with combination treatment regimens such as rhypercvad / rhdmtxarac regimen . those with a poorer performance status are suggested to be treated with rchop or rcvp based regimens 8 . intraperitoneal application of rituximab was shown by martina chrysandt et al . to be effective in local control of the disease process in one of the case though we remain unsure if we could use mcl cytological markers in the peritoneal fluid as a surrogate to conventional bm biopsy and testing , the data are promising in terms of concordance . if bm testing is not able to be performed or testing has shown a lack of involvement of the bm by mcl , peritoneal sampling may be able to confirm a diagnosis .

key clinical messageascites with the finding of peritoneal carcinomatosis is considered an unusual presentation for mantle cell lymphoma ( mcl ) and has been rarely described in literature . this case reflects the importance of cytological analysis of peritoneal fluid in a patient with intractable ascites not contributing from other comorbidities . in the event a bone marrow ( bm ) analysis can not be made , this may serve as an alternative method for diagnosing mcl taking into consideration the good concordance between peritoneal fluid and bm cytological markers .

education is a series of purposeful activities planned by the educators , in the form of interaction between them and the learners ( 1 , 2 ) . education is one of the most important ways of ensuring the success of plans in all dimensions of the society . in addition , learning includes all the skills and knowledge gained by one , over the course of their life ( 3 - 6 ) . eliminating confounding factors in education can increase the effectiveness of education ( 7 - 9 ) . one of the major confounding factors in education is the educational environment ( 10 ) . some studies believe that emergency department overcrowding ( edo ) can affect the training of emergency medicine residents ( emr ) while others do not ( 11 - 19 ) . on one side , the excessive workload can create opportunities for learning and increase the efficiency of learning but on the other hand , less time is available for the interaction between the educator and the student ( 16 ) . therefore , this study aimed to evaluate the effect of edo on the efficiency of emrs education . study design and setting this cross - sectional study aimed to evaluate the effect of edo on the efficiency of emrs education . the study was carried out in 2013 - 2014 in shohadaye haftome tir hospital , tehran , iran . the protocol of study has been approved by the ethics committee of shahid beheshti university of medical sciences . the participants were all second year emrs who were willing to take part in the study . the ability of the attend to teach the principles was evaluated in resuscitation room and the acute care unit . data collection was done using a questionnaire , which was filled out by the second year residents . the residents evaluated her / his attends on the subject of teaching skills , creating a fear - free environment , willingness to teach , accessibility , level of busyness during the shift , number of visits / shift , interpersonal relationship skills , and their overall teaching scores . also both the resident and attend were asked about the crowding of the shifts . each question was given a score ranging from 1 to 10 ( 1 being the least and 10 the most possible score ) . in addition , the emergency crowding score was calculated based on the national emergency department overcrowding scale ( nedocs ) . at the end of each 12-hour shift using nedocs if the score was less than 100 , the department was considered not overcrowded and if it was higher than 100 , the shift was considered overcrowded . the reliability of the questionnaire was approved by 2 emergency medicine specialists and 1 epidemiologist . the validity of the questionnaire was confirmed by calculating kronbach s alpha ( 0.79 ) . statistical analysis the appropriate sample size for this study was 130 , which was calculated by considering the standard deviation of 1 not overcrowded and 1.5 in overcrowded hours ( 20 ) , power of 90% , confidence level of 95% ( =0.05 ) , and error of 0.5 . the relationship between the department overcrowding and the quality of education was evaluated using independent sample t - test . in all the analyses p<0.05 was considered as significance level . 130 questionnaires were filled out during 61 shifts ( 26 night shifts and 35 day shifts , 27 residents evaluated 8 attends ) . the attend s ability to teach was not affected by overcrowding in the resuscitation room . in the overcrowded shifts the number of visits done by the attend were significantly higher ( p=0.008 ) ( table 1 ) . it is notable that similar results were seen regarding the attend s training ability in the acute care unit ( table 2 ) . also in this unit , the number of visits done by the attend were significantly higher in the overcrowded shifts ( p=0.03 ) . the mean score regarding the evaluated factors in the resuscitation room based on the department s crowding the mean score regarding the evaluated factors in the acute care unit based on the department s crowding the results of this study showed that from the emrs point of view , the attends achieve the highest scores in creating a fear - free environment , interpersonal relationship skills , accessibility and teaching skills during edo . it is worth noting that the total teaching score achieved by the attends was 6.8 ( out of 10 ) in the resuscitation room and 6.5 ( out of 10 ) in the acute care unit . it was also demonstrated that edo has no effect on the attends teaching skills and abilities . some researchers believe that emergency department overcrowding can negatively affect emergency residents training and learning ( 14 - 19 ) . in contrast to the results of the present study , skeff et al . express in their study that job stress has a negative impact on education ( 21 ) . propose in their review study that overcrowding might affect the interaction between the educator and the student as this interaction needs a calm environment for asking questions , concentrating on the educator s training and reaching a conclusion regarding the educator s instructions . these researchers express that the department overcrowding is an important factor causing time limitations for training . also excessive workload and the need to take care of and treat the patients leaves little time for the attends to ask the residents questions and wait for their answers ( 14 ) . however , the results from the present study showed that overcrowding did not affect the attends education score . firstly , as can be seen , the studied emergency departments are crowded most of the time and therefore the constant crowding can result in the emergency medicine attends being adapted to these situations and having their skills developed so that they can give the necessary education in little time . secondly , the attends who have participated in this study have had relatively high interpersonal relationship skills ( a score of 8.2 out of 10 ) . therefore , the interaction between the residents and the attends has been more affected by this factor rather than the edo . but in line with the results of this study , mahler et al . determined that no significant difference exists between the residents perceptions regarding the educational value in the overcrowded and non - overcrowded times ( 22 ) . these researchers express that in the overcrowding period , the residents do less visits and treatment processes while the attends are busier . therefore , it is possible that the residents have more time to learn , study and observe the correct treatment processes done by the attend . the emergency department overcrowding gives the residents the opportunity to observe various clinical cases and directly observe the correct ways of managing and treating the patients because at the times of overcrowding , the attends do more visits . therefore , we can say that the edo possibly not only does nt impact the attends presented education negatively , but also can result in an increase in the efficiency of the education . the principles of the educational system , including the points of view , beliefs , schedules , and regulations can all affect the teaching methods . rigid and inflexible regulations and nonprofessional decisions , and the educational system being in line with the students needs or not can all affect education ( 3 , 10 , 23 ) . based on the results of the present study , edo has no effect on the educational skills and abilities of the attends . they achieve the highest scores in creating a fear - free environment , interpersonal relationship skills , accessibility and teaching skills in both overcrowded and non - overcrowded situations . all authors passed four criteria for authorship contribution based on recommendations of the international committee of medical journal editors .

introduction : creating a calm and stress - free environment affects education significantly . the effects of the emergency department overcrowding ( edo ) on the training of emergency medicine residents ( emr ) is a highly debated subject . therefore , this study aimed to evaluate the effect of edo on efficiency of emr s education . methods : in this cross - sectional study , the effects of overcrowding on emr s education in the resuscitation room and acute care unit . data collection was done using a questionnaire , which was filled out by the second year emrs . the crowding level was calculated based on the national emergency department overcrowding scale ( nedocs ) . the relationship between the two studied variables was evaluated using independent sample t - test and spss 21 statistical software . results:130 questionnaires were filled out during 61 shifts . 47 ( 77.05% ) shifts were overcrowded . the attend s ability to teach was not affected by overcrowding in the resuscitation room ( p=0.008 ) . the similar results were seen regarding the attend s training ability in the acute care unit . conclusion : it seems that the emergency department overcrowding has no effect on the quality of education to the emrs .

a 32-year - old man was referred with dull , aching right flank pain for 3 years . the patient was evaluated by abdominal computerized tomography , which revealed incomplete duplication of the right urinary system with lower pole moiety hydronephrosis . an endopyelotomy with the acucise ( applied medical ) ureteral cutting balloon device was planned . with the patient in the dorsal lithotomy position , a 0.038-inch guidewire was inserted into the lower pole of the collecting system , and an acucise cutting wire was pre - aligned in the posterolateral position . we introduced the acucise over the guide wire and advanced it just proximal to the upj stricture . under c - arm fluoroscopy , the acucise cautery balloon wire was used to incise the narrowed ureteropelvic junction in the posterolateral direction . the operative retrograde pyelography confirmed a successful incision of the narrowed ureter through extravasation of contrast medium . an intravenous pyelography at 3 months postoperatively showed marked reduction of the hydronephrosis in the lower pole moiety ( fig . a 54-year - old man was referred to our institution for investigation of persistent pyuria . the abdominal computerized tomography demonstrated an incompletely duplicated collecting system on the right side with marked hydronephrosis and multiple renal stones of the lower pole moiety ( fig . retrograde pyelography confirmed the findings and revealed that the lower pole pelvis was extremely dilated with grade iii hydronephrosis , which suggested concomitant lower pole upjo ( fig . a right lower pole upjo associated with multiple renal stones with an incomplete duplicated collecting system was diagnosed , and an antegrade endourologic procedure was planned . cystoscopy and then retrograde pyelography were performed and showed narrowing at the upj at the right lower moiety , with severe dilation of the adjacent lower pole of the renal pelvis . a ureteral catheter was inserted at the level beneath the upj of the lower pole moiety . next , the patient was placed in a prone position , and retrograde instillation of contrast was performed to opacify the pelvicocaliceal system . percutaneous access was established at the mid calyx , and then tract dilation was performed by balloon dilation with a 30 fr catheter at a pressure of 12 atm . through the 30 fr amplatz sheath , the stones were fragmented by using a pneumatic lithotriptor under fluoroscopic control . all stone extractions were successful , and we found no evidence of residual calculi on imaging . after a 21 fr sheath was advanced up to the renal pelvis , the upjo was identified easily . the narrowed ureter was incised with a cold knife as far as the periureteral fat and visualized widely . a 6 fr double j stent was placed in the lower pelvis for 4 weeks . postoperative intravenous pyelography confirmed that the obstruction had been successfully relieved and that all renal stones had been successfully removed ( fig . a 32-year - old man was referred with dull , aching right flank pain for 3 years . the patient was evaluated by abdominal computerized tomography , which revealed incomplete duplication of the right urinary system with lower pole moiety hydronephrosis . an endopyelotomy with the acucise ( applied medical ) ureteral cutting balloon device was planned . with the patient in the dorsal lithotomy position , a 0.038-inch guidewire was inserted into the lower pole of the collecting system , and an acucise cutting wire was pre - aligned in the posterolateral position . we introduced the acucise over the guide wire and advanced it just proximal to the upj stricture . under c - arm fluoroscopy , the acucise cautery balloon wire was used to incise the narrowed ureteropelvic junction in the posterolateral direction . the operative retrograde pyelography confirmed a successful incision of the narrowed ureter through extravasation of contrast medium . an intravenous pyelography at 3 months postoperatively showed marked reduction of the hydronephrosis in the lower pole moiety ( fig . a 54-year - old man was referred to our institution for investigation of persistent pyuria . the abdominal computerized tomography demonstrated an incompletely duplicated collecting system on the right side with marked hydronephrosis and multiple renal stones of the lower pole moiety ( fig . 3 ) . retrograde pyelography confirmed the findings and revealed that the lower pole pelvis was extremely dilated with grade iii hydronephrosis , which suggested concomitant lower pole upjo ( fig . a right lower pole upjo associated with multiple renal stones with an incomplete duplicated collecting system was diagnosed , and an antegrade endourologic procedure was planned . cystoscopy and then retrograde pyelography were performed and showed narrowing at the upj at the right lower moiety , with severe dilation of the adjacent lower pole of the renal pelvis . a ureteral catheter was inserted at the level beneath the upj of the lower pole moiety . next , the patient was placed in a prone position , and retrograde instillation of contrast was performed to opacify the pelvicocaliceal system . percutaneous access was established at the mid calyx , and then tract dilation was performed by balloon dilation with a 30 fr catheter at a pressure of 12 atm . through the 30 fr amplatz sheath , the stones were fragmented by using a pneumatic lithotriptor under fluoroscopic control . all stone extractions were successful , and we found no evidence of residual calculi on imaging . after a 21 fr sheath was advanced up to the renal pelvis , the upjo was identified easily . the narrowed ureter was incised with a cold knife as far as the periureteral fat and visualized widely . a 6 fr double j stent postoperative intravenous pyelography confirmed that the obstruction had been successfully relieved and that all renal stones had been successfully removed ( fig . the embryological concept proposed to explain the association of ureteral duplication with abnormal bifurcation of the ureteral bud is as follows . when the ureteral bud bifurcates shortly after its origin from the mesonephric duct , incomplete ureteral duplication occurs . if the two buds develop close to the normal points of ureteral origin , from the mesonephric duct , a complete duplication results . however , ureteral duplication associated with upjo is rare , and most cases occur in the lower pole of an incompletely duplicated system . this occurs as either a congenital or an extrinsic compression with aberrant or accessory renal vessels . in addition , high - grade vesicoureteral reflux may play a casual role in the evolution of some cases of upjo . it is postulated that dilatation of the collecting system as the result of reflux may lead to elongation , tortuosity , kinking , and fibrosis of the ureter . this may be complicated by fixation of the upj from periureteral inflammation , leading to persistent upjo . it is likely that the cause of upjo in our patients was congenital . during fetal life , the ureter undergoes a continuous process of obstruction and recanalization , which , if incomplete , may produce narrowing and obstruction . in addition , johnston reported that the fetal ureter may show intraluminal muscular invaginations or folds , which can persist postnatally , and they may produce upjo . surgical treatment of lower pole upjo must be planned so that as much functioning renal parenchyma as possible is spared . dismembered pyeloplasty , end - to - side pyeloureterostomy , and ureterocalicostomy all are potential surgical treatments ; these options should be tailored and modified depending on the intraoperative findings at the time of the procedure . according to shelfo et al , an ipsilateral pyeloureterostomy ( ipu ) is a common surgical procedure used to manage ureteral duplication with lower pole upjo . however , open pyeloplasty has several drawbacks , including substantial postoperative pain due to the flank incision and prolonged convalescence . to minimize morbidity , several endoscopic techniques have been developed as alternatives to open surgery , and the endoscopic approach to upj has been successful for both the anterograde and retrograde procedures , offering the advantages of shorter operative time , less morbidity , reduction of postoperative analgesic requirements , and shorter hospital stay . the minimally invasive techniques that have been developed over the recent past continue to evolve . since chandhoke et al described the acucise endopyelotomy in 1993 , it has been used for dramatic advances in the field of endourology and has allowed for precise , directed endopyelotomy procedures to be performed with high immediate success rates of 87.5% to 100% , the variance of which most likely reflects patient selection . long - term patency , however , is reportedly 61.5% to 85% after 37 to 60 months of follow - up . the time to failure after endopyelotomy averages 10 to 20 months , but it is becoming increasingly clear that patients treated with endopyelotomy require longer follow - up with renal scintigraphy or intravenous pyelography . doo et al reported that the failure rate after endopyelotomy does not nadir until 36 months . the main conditions that decrease the success rates of antegrade or retrograde endopyelotomy are the presence of crossing vessel adjacent upjo , a very large renal pelvis , and a high insertion of the ureter into the renal pelvis . additional contraindications include extensive periureteral fibrosis , a bleeding diathesis , a ureter too small to accommodate an endopyelotomy stent , and a long , ( > 2 cm ) stenosed ureteropelvic segment . but , even in these cases of endourologic failure , salvage pyeloplasty can provide long - term patency , especially if the failure is due to an initially missed crossing vessel or a redundant renal pelvis . braga et al reported a 100% success rate after salvage pyeloplasty over an average follow - up of 47 months . although open pyeloplasty remains the standard treatment , the minimally invasive endoscopic procedures are an attractive option and could be the first line of treatment if proper patient selection is used , for example , for upjo resulting from an aperistaltic segment or minor stricture in the absence of a crossing vessel . with respect to long - term outcomes , these endourologic procedures may be limited , but endourologic failures can be salvaged with pyeloplasty in most cases .

we present two cases of symptomatic lower pole moiety ureteropelvic junction obstruction ( upjo ) in a partially duplicated collecting system that were successfully treated with minimally invasive endourologic procedures . in the first case , we performed retrograde endopyelotomy with the acucise ureteral cutting balloon device , and in the latter case , we performed percutaneous nephrolithotomy and antegrade endopyelotomy because of the presence of multiple renal stones . subsequent intravenous pyelography confirmed marked resolution of the obstruction , and both patients remained asymptomatic during 1 year of follow - up .

stormwater catch basins are common sources of permanent or semipermanent standing water in urban and suburban residential areas and are considered to be important habitats for culex pipiens , a primary mosquito vector of west nile virus ( wnv).15 because tens of thousands of these structures can exist within a mosquito control program s operational area , it is common practice to treat all or most of these basins with at least a single application of extended - release larvicides in the form of tablets or briquets ( altosid xr , fourstar , and natular xrt ) designed to provide larval control from 30 to as long as 180 days ( about 26 weeks ) . these products have grown in popularity as the prospect of a single application that can potentially last an entire season is appealing logistically and financially to many mosquito control and wnv management programs . for more than a decade , the north shore mosquito abatement district ( nsmad ) has applied extended - release larvicides seasonally to approximately 50,000 catch basins in the 13 communities within the district s 207 km ( 80 square miles ) operational area located just north of chicago , il , usa . this is performed as part of the nsmad s efforts to reduce local populations of the local wnv vector species , c. pipiens . however , there is growing evidence that extended - release larvicides are not effective for as long as expected.2,49 here , we report the findings observed from two years of routine catch basin monitoring performed by the nsmad staff . although not a part of a formal study , we hope to utilize monitoring data to ( 1 ) identify the proportion of extended - release larvicide treatments that did not provide the advertised maximum duration of control in catch basins and ( 2 ) determine if there was a spatial pattern in the decrease in treatment efficacy . to guide the catch basin larvicide program , the nsmad divides its operational area into 76 approximately one - square mile ( 2.6 km ) treatment maps ( fig . monitoring effectiveness of the larvicide treatments was conducted as described previously.8 each week during the period from june to september of 2014 and 2015 , at least five catch basins were inspected by a single nsmad technician for the presence of mosquito larvae and pupae from each of 1223 treatment maps . monitoring was performed by removing the circular grate of each structure with a manhole hook and taking two dip samples using a standard 350 ml dipper . the total number of immature stages of mosquitoes collected in each dip was recorded for each dip as well as the number of late immature stages ( fourth instar larvae and pupae ) . in those cases where catch basin sump water was clear enough to see the entire bottom of the structure , when possible , a search of the bottom was made using the dipper to determine if larvicide tablets were present but hidden by sediment and debris in the sump . treatment protocols for the 2014 season consisted of applying natular xrt 180-day extended - release tablets ( xrt , 6.25% spinosad ; clarke mosquito control products , inc . ) and natular t30 30-day tablets ( t30 , 8.33% spinosad ; clarke mosquito control products , inc . ) and have been published previously.8 for the 2015 season , initial larvicide applications began in the first week of june and ended in the second week of august . basins in 54 treatment maps received a single xrt , basins in 21 maps received a single t30 , and basins in one map received a single fourstar 180-day briquet ( 6% bacillus thuringiensis israelensis and 1% bacillus sphaericus ; central life sciences ) . the second round of larvicide treatments began from mid - august 2015 once the first round of larvicide applications had completed and extended to mid - september with basins in 9 xrt - treated maps and 12 t30-treated maps receiving an additional t30 tablet and basins in 5 xrt - treated maps receiving a combined application of bva 2 mosquito oil ( 97% mineral oil ; adapco , inc . ) and vectolex fg granules ( 7.5% b. sphaericus ; valent biosciences biotechnology company ) . data from 2014 and 2015 were combined for the subsequent analyses . a larvicide application was deemed to have failed when one or more late immature stages ( fourth instar larvae and pupae ) were observed in the two dip samples . this indicates that the larvicide s active ingredient failed to kill these mosquitoes despite being exposed for at least a week during their earlier larval stages . the nsmad set 5% as an acceptable failure level ( number of treated basins holding $ 1 fourth instar larva or pupa divided by the total number of treated basins monitored ) for monitored basins in a treatment map . those treatment maps observed to hold a higher percentage would indicate that an alternative to extended - release larvicides should be considered for that area . precipitation data were downloaded from a nearby weather station of the national oceanic and atmospheric administration s national weather service forecast office located at the chicago ohare airport ( http://www.nws.noaa.gov/climate/index.php?wfo=lot ) . these data were used to compare the amount of rainfall in the 2014 and 2015 seasons with the rainfall in the earlier years . during 2015 ( 1,103 ) and 2014 ( 1,064 ) , a total of 2,167 catch basins were monitored after treatment with extended duration larvicide products . of these treated basins , extended - release larvicide applications failed before the expected duration of control had passed in 540 catch basins ( 24.9% ) . from 2014 to 2015 , a total of 316 ( 65.9% ) of the 479 basins with visible sump bottoms were observed to be missing the tablets . of those missing the tablets , 37 basins ( 13.2% ) had at least one or more fourth instar larva or pupa in the two dip samples . of the 163 basins observed to contain a larvicide treatment during an inspection , only three basins ( 1.8% ) were found to have at least one or more fourth instar larva or pupa in two dip samples . since 2014 and 2015 , the treated basins were monitored from 53 of the 76 treatment maps , and of these , only 11 maps ( 20% ) were found with a percentage of failing basins of 5% ( fig . 1 ) . the rest of the maps had failure rates ranging from 8% to 85% . the highest failure rates were observed in the maps located in the southeast part of the nsmad s operational area ( fig . 1 ) . in the second half of the 2015 season , following the determination that natular xrt and t30 tablets were not providing the expected duration of control , alternative control procedures were evaluated . five xrt - treated maps located in the southeast part of the district received an additional combined application of bva 2 mosquito oil and vectolex fg granules . also basins in one treatment map received a single fourstar 180-day briquette instead of xrt or t30 tablets . according to the vectolex fg label , four weeks ( approximately 30 days ) eighteen of the bva 2- and vectolex fg - treated basins were sampled within four weeks of the application of these larvicides , and of these , seven basins ( 38.9% ) held late immature mosquito stages . bva 2 , as other mosquito larvicide oils , provides immediate but short - term control and tends to break down quickly when the water surface is disturbed ( eg , from an influx of rain and runoff ) . bva 2 was applied to kill existing late immature stages immediately , while vectolex would provide a sustained control of newly hatched mosquito larvae . twenty - eight fourstar - treated basins were sampled within seven weeks of the initial applications , and of these , 14 basins ( 50.0% ) held late immature mosquito stages . for basins treated with 180-day larvicides , failures were found at 115 weeks after applications with a mode of five weeks ( 65 of the 472 basins ) . for basins treated with 30-day larvicides , failures were found at one to four weeks after treatment with a mode of three weeks ( 27 of the 68 basins ) . the precipitation for the months of june to september in both 2014 and 2015 was similar to that of the previous four years ( table 2 ) . over the two years of catch basin monitoring , failure of extended - release ( 180 and 30 days ) larvicides was observed in approximately 25% of treated catch basins distributed throughout the nsmad s operational area . preliminary observations on the use of vectolex fg granules and fourstar briquets as alternatives to natular xrt and t30 tablets did not provide an improved duration of control , with 38.9% of vectolex - treated basins failing within four weeks of treatment and 50% of fourstar - treated basins failing within 180 days of treatment . these observations require further investigation as fewer basins were treated with these larvicides and sampled when compared to those treated with natular. there did appear to be geographic heterogeneity in the performance of the extended duration larvicides across the district . in these current analyses , larvicides applied to basins located in the southeast quarter of the district failed before the expected control duration had passed at a higher percentage than other areas . however , it is clear that some treatment maps had relatively low percentages or no failing basins . indeed , long - term control was achieved in 75.1% of all sampled treated basins . in basins where the treatment product was visually confirmed to be present , only 1.8% of the basins were found to have failed when compared to 13.2% of basins with missing treatments . that larvicides appear to work in some basins and not in others suggests that the causes of failure are more associated with basin - specific physical factors , such as sump volume and the amount and type of debris captured in basins , rather than the effectiveness of the active ingredient . it is possible that the larvicide products may have been lost prematurely either through flushing out of basins or via rapid degradation from high inflows of rain and/or runoff.8 similarly , the dispersal of active ingredients may be hindered when tablets and briquets became completely buried in sump debris.8 collectively , these phenomena may play a significant role in the treatment failures we observed . whether such factors are permanently associated with specific basins or whether this is a condition that varies over time as other related factors change ( eg , weather , water use , and catch basin maintenance frequency ) is yet to be determined with additional research . it is important for all catch basin larviciding programs to routinely monitor basins and identify areas prone to failure as well as identify other larvicide alternatives .

since the mid-1990s , the north shore mosquito abatement district ( nsmad ) has applied extended - release formulations of mosquito larvicides to approximately 50,000 catch basins in the suburbs north of chicago , il , usa . this is performed as part of nsmad s efforts to reduce local populations of the west nile virus vector , culex pipiens . analyses from nsmad s monitoring of larvicide - treated basins throughout the district over the 2014 and 2015 seasons suggest that larvicides intended to provide extended durations of control ( 30180 days ) failed to provide control for the maximum duration specified on the product label in approximately 25% of the district s basins . for larvicides designed to last up to 180 days ( or about 26 weeks ) , failures were found at 115 weeks after treatment with most found at five weeks posttreatment . for larvicides formulated to last up to 30 days , failures were found at one to four weeks after applications with most found at three weeks posttreatment . the highest percentages of failing basins ( ie , containing late - stage mosquito larvae or pupae during the specified product effectiveness period ) were found in communities on the eastern side of the district , bordering lake michigan . as the larvicides appeared to function properly in the majority of monitored basins , it appears that the failures likely resulted from basin - specific physical factors ( ie , basin volume , sediment content , and hydrology ) that cause either product removal or a reduction in the concentration of the larvicide s active ingredient below the effective levels in these basins .

the number of yearly deaths from melanoma continues to increase , and the overall melanoma mortality rate is one of the few cancer mortality rates not on the decline . these realities combined with increasing evidence of the lack of efficacy of the abcde criteria have necessitated ongoing efforts to enhance the earlier clinical detection of melanoma [ 38 ] . most approaches to melanoma diagnosis have included some predominant emphasis or combination of emphases on recognition of changing lesions , recognition of outlier ( ugly - duckling ) lesions , and specific melanoma characteristics , with the most utilized criteria being the abcde criteria ( a for asymmetry , b for border irregularity , d for 6 mm diameter , and e for evolving lesions ) . many recently published strategies have rejected the diameter criterion as well as abandoned all or portions of the abcde mnemonic [ 3,5,912 ] . many of these proposed strategies , including the d for dark proposal i offered , have also added emphasis on recognition of darkness as a particular feature of concern in pigmented lesions [ 5,1012 ] . i have recently reviewed the compelling rationale for both an increased emphasis on darkness and rejection of the diameter criterion in the clinical diagnosis of melanoma . the georgia approach to melanoma diagnosis uniquely incorporates many elements of these strategies in a complementary manner to increase the sensitivity of diagnosis of early melanoma ( figure 1 ) . in their review of melanoma diagnosis , marghoob and scope discuss the concepts of a screening examination to identify lesions of possible concern and then the specific lesion assessment that follows . this distinction is important because the screening examination determines the sensitivity of melanoma recognition , and it is the screening examination that really describes how most practitioners examine patients and how patients examine each other . first , the georgia approach places increased emphasis on the screening examination by initial , distinct discussion and clarification of its function . second , the approach includes both of the two screening strategies that have been used in most melanoma educational materials , change and ugly duckling identification . third , the approach adds the easily perceived , easily communicated , highly sensitive , specific ( compared to change and ugly duckling identification ) screening feature of darkness . a major tenet of physical diagnosis , particular for early diagnosis , is that one sees what one looks for . a strategy based on recognition only of any lesion that changes or differs from other lesions inadequately considers this principle . the added benefit of looking specifically for dark lesions as part of a screening examination for melanoma can not be overstated ; many melanomas , particularly small melanomas , can be recognized because of , and only because of , their intensity of pigment . nonetheless , with melanoma , as with screening features for nearly every disease , no one feature has 100% sensitivity . the description of the screening examination for melanoma detection includes the instruction to examine the skin in order to detect any lesion that stands out because of being dark , different , or changing . each of the three screening features has non - redundant as well as complementary importance in the recognition of melanoma . the screening examination should usually include two looks , one for any lesion that stands out at all , which should allow detection of changed or ugly duckling lesions , and a second look to identify lesions of any size that stand out because of appearing , even focally , dark . consequently , the emphasis on darkness as a screening feature should only enhance the sensitivity of diagnosis of melanoma . though the impact of the abcde criteria on melanoma detection has been uncertain , the publication and utilization of these criteria are ubiquitous , and the criteria have many supporters . as marghoob and scope help elucidate , however , the role of the abcde criteria is not as a screening approach , as they have been utilized , but as a spot evaluation , and the criteria can also help to assess the level of concern when comparing similar lesions . thus , the criteria have value , but one that requires this more precise explanation . the meanings of the a , b , c , and e in the georgia approach are unchanged from usual use : a for asymmetry , c for color variation , and e for evolving unlike other lesions . what is critical to the utility of the abcde criteria , however , is the change of the d to signify dark and not 6 mm diameter . with this change , and without altering the familiar mnemonic , the criterion never present in the earliest melanomas is replaced by the single criterion that characterizes many early melanomas . it can now be stated more accurately that most melanomas have one or more of the abcde criteria and that the criteria are relevant to the diagnosis of early melanomas . as a criterion of an individual lesion , similar to its utilization as a screening feature , the characteristic of darkness has non - redundant value and , in addition , enhances the application of other criteria . there is increasing support for the strategy of melanoma recognition based on the concept that a melanoma will differ in appearance from one s usual moles , referred to as the ugly - duckling rule . the possible utility in this concept is reflected in the georgia approach both as a screening feature ( different ) and in the e for evolving description ( has a mole . . unlike others on your body ? ) . in the third component of the georgia approach , the ugly - duckling sign is specifically defined , conveying additional emphasis on and understanding of this strategy and its application . nodular melanomas represent a minority of melanomas but contribute disproportionately to melanoma mortality , and the final portion of the georgia approach is devoted to specific education about the diagnosis of this melanoma subtype . the varied presentations of nodular melanomas , including as amelanotic lesions , are specifically discussed , as is the particular relevance of change and ugly duckling recognition to the diagnosis of these melanomas . the inclusion of the nodular melanoma pictured adds further emphasis on both the diagnosis of nodular melanomas and of the relevance of change recognition to their diagnosis . nonetheless , as nodular melanomas have metastatic potential both in a shorter time frame and when smaller in diameter than other melanomas , the previously discussed addition of dark as a screening feature and the d for dark change may have particular impact on decreasing mortality by enhancing the earlier diagnosis of this melanoma subgroup . in addition to the potential impact on the diagnosis of earlier nodular melanomas by removing any diameter consideration , many early nodular melanomas , similar to other melanoma subtypes , are characterized by their dark pigment . in their review of melanoma diagnosis , marghoob and scope discuss the concepts of a screening examination to identify lesions of possible concern and then the specific lesion assessment that follows . this distinction is important because the screening examination determines the sensitivity of melanoma recognition , and it is the screening examination that really describes how most practitioners examine patients and how patients examine each other . first , the georgia approach places increased emphasis on the screening examination by initial , distinct discussion and clarification of its function . second , the approach includes both of the two screening strategies that have been used in most melanoma educational materials , change and ugly duckling identification . third , the approach adds the easily perceived , easily communicated , highly sensitive , specific ( compared to change and ugly duckling identification ) screening feature of darkness . a major tenet of physical diagnosis , particular for early diagnosis , is that one sees what one looks for . a strategy based on recognition only of any lesion that changes or differs from other lesions inadequately considers this principle . the added benefit of looking specifically for dark lesions as part of a screening examination for melanoma can not be overstated ; many melanomas , particularly small melanomas , can be recognized because of , and only because of , their intensity of pigment . nonetheless , with melanoma , as with screening features for nearly every disease , no one feature has 100% sensitivity . the description of the screening examination for melanoma detection includes the instruction to examine the skin in order to detect any lesion that stands out because of being dark , different , or changing . each of the three screening features has non - redundant as well as complementary importance in the recognition of melanoma . the screening examination should usually include two looks , one for any lesion that stands out at all , which should allow detection of changed or ugly duckling lesions , and a second look to identify lesions of any size that stand out because of appearing , even focally , dark . consequently , the emphasis on darkness as a screening feature should only enhance the sensitivity of diagnosis of melanoma . though the impact of the abcde criteria on melanoma detection has been uncertain , the publication and utilization of these criteria are ubiquitous , and the criteria have many supporters . as marghoob and scope help elucidate , however , the role of the abcde criteria is not as a screening approach , as they have been utilized , but as a spot evaluation , and the criteria can also help to assess the level of concern when comparing similar lesions . thus , the criteria have value , but one that requires this more precise explanation . the meanings of the a , b , c , and e in the georgia approach are unchanged from usual use : a for asymmetry , c for color variation , and e for evolving unlike other lesions . what is critical to the utility of the abcde criteria , however , is the change of the d to signify dark and not 6 mm diameter . with this change , and without altering the familiar mnemonic , the criterion never present in the earliest melanomas is replaced by the single criterion that characterizes many early melanomas . it can now be stated more accurately that most melanomas have one or more of the abcde criteria and that the criteria are relevant to the diagnosis of early melanomas . as a criterion of an individual lesion , similar to its utilization as a screening feature , the characteristic of darkness has non - redundant value and , in addition , enhances the application of other criteria . there is increasing support for the strategy of melanoma recognition based on the concept that a melanoma will differ in appearance from one s usual moles , referred to as the ugly - duckling rule . the possible utility in this concept is reflected in the georgia approach both as a screening feature ( different ) and in the e for evolving description ( has a mole . . unlike others on your body ? ) . in the third component of the georgia approach , the ugly - duckling sign is specifically defined , conveying additional emphasis on and understanding of this strategy and its application . nodular melanomas represent a minority of melanomas but contribute disproportionately to melanoma mortality , and the final portion of the georgia approach is devoted to specific education about the diagnosis of this melanoma subtype . the varied presentations of nodular melanomas , including as amelanotic lesions , are specifically discussed , as is the particular relevance of change and ugly duckling recognition to the diagnosis of these melanomas . the inclusion of the nodular melanoma pictured adds further emphasis on both the diagnosis of nodular melanomas and of the relevance of change recognition to their diagnosis . nonetheless , as nodular melanomas have metastatic potential both in a shorter time frame and when smaller in diameter than other melanomas , the previously discussed addition of dark as a screening feature and the d for dark change may have particular impact on decreasing mortality by enhancing the earlier diagnosis of this melanoma subgroup . in addition to the potential impact on the diagnosis of earlier nodular melanomas by removing any diameter consideration , many early nodular melanomas , similar to other melanoma subtypes , are characterized by their dark pigment . whatever changes occur in terms of melanoma diagnosis because of screening recommendations or technology , no strategy will reach its potential without the earliest possible clinical recognition of melanoma . the components of the georgia approach accomplish the following : first component : clarifies and emphasizes the role of a screening examination ; adds dark to both change and ugly duckling identification as screening features ; communicates the screening features simply and succinctly.second component : continues to utilize but more precisely defines the role of the abcde criteria and changes the meaning of the d to dark.third component : discusses both the ugly duckling sign as a general rule as well as specific issues relevant to the diagnosis of nodular melanomas . first component : clarifies and emphasizes the role of a screening examination ; adds dark to both change and ugly duckling identification as screening features ; communicates the screening features simply and succinctly . second component : continues to utilize but more precisely defines the role of the abcde criteria and changes the meaning of the d to dark . third component : discusses both the ugly duckling sign as a general rule as well as specific issues relevant to the diagnosis of nodular melanomas . each of these three components has non - redundant potential to enhance the diagnosis of melanoma . by unifying and integrating all of the components in a logical manner , however , the georgia approach uniquely prioritizes and maximizes the sensitivity of diagnosis of early melanomas . during this period of transition in the clinical diagnosis of melanoma , i encourage other practitioners , departments , and societies to consider and adapt the georgia approach , as well .

current clinical approaches to melanoma diagnosis have not been associated with a decrease in mortality from this cancer . the components of the new approach presented are , first , a screening examination to look for any lesion that stands out because of being dark , different , or changing ; second , when a single lesion is recognized to be of concern for any reason , that lesion is then evaluated in more detail utilizing the abcde criteria , with the d signifying dark and not 6 mm diameter in this mnemonic ; and , third , additional discussion of the ugly duckling sign and of the recognition of nodular melanomas . since the georgia society of dermatology and dermatologic surgery was the first state or national society to endorse this approach , i refer to it as the georgia approach .

comminuted fracture is defined as the presence of multiple fracture lines resulting in many small pieces within the same area of the mandible ( e.g. , angle , body , ramus , or symphysis)1 . in extensive communited fractures , multiple sites ( exceeding one region and involving the neighbouring region ) of the mandible are splintered , crushed , pulverized , or broken into several pieces1,2 . extensive comminuted mandibular fractures occur when a high - energy impact is applied onto a region of the mandible . the high - energy impact seen in gun shots , traffic accidents , and falls can lead to enough concentrated force on the mandible to cause multiple sites of comminuted fractures3,4 . traditionally , extensive comminuted mandibular fractures have been considered to be indications for closed reduction in order to avoid periosteal stripping and devascularization of the comminuted bone segments5 . in the last 30 years , however , there has been a change in the treatment perspective of such injuries driven by advancements in rigid fixation techniques2 . some reports3,5,6,7 insist that open reduction and internal fixation is a better treatment option and causes lower complication rates than closed reduction in some comminuted mandibular fractures . however , it is still controversial whether closed reduction is the optimal treatment for comminuted fractures as compared to open reduction and internal fixation . the decision for the proper treatment can be complicated when condylar fractures accompany the comminuted mandibular fracture . closed reductions with long - term limitation of mouth opening are beneficial for comminuted fracture , but are harmful for condylar fractures . there are two types of condylar fractures , intracapsular and extracapsular , but for practical purposes , the anatomical level of the fracture is divided into three sites : the condylar head ( intracapsular ) , the condylar neck ( extracapsular ) , and the subcondylar region8,9,10 . teeth injuries such as fractures and luxations are frequently accompanied with condylar head or neck fractures . concomitant fractures of the mandibular body often accompany subcondylar fractures and are more frequently bilateral than unilateral11 . in the treatment of condylar fractures , there are conservative methods such as closed reduction with concomitant physical therapy , and surgical methods using open reduction and internal fixation . like other mandibular fractures , early mouth mobilization is essential to prevent adhesion or ankylosis of the temporomandibular joint ( tmj ) . this article reports a case of extensive comminuted mandibular fracture with bilateral condylar fractures treated by open reduction , internal fixation , and reconstruction , and discusses the indications and benefits of treatment options . a 19-year - old male who was in the care of an institution for the disabled due to an intellectual disability and autistic disorder visited the emergency room at inje university ilsan paik hospital ( goyang , korea ) after a fall . his injury included extensive comminuted mandibular fracture between both angles , bilateral condylar fractures , the avulsion or dislocation of all posterior teeth in the mandible , and shattered bony fragments of the alveolus and mandible body . 1 ) his facial injuries were accompanied by fractures on the right tibia and ankle . to make matters worse , his psychological state made it impossible for him to maintain stabilization of his jaws for closed reduction and his tibial fracture kept him on strict bed rest . under general anesthesia , open reduction and internal fixation of the mandibular comminuted fracture were performed using a locking reconstruction plate , mini - plates and screws . a locking reconstruction plate ( stryker - leibinger , kalamazoo , mi , usa ) was adjusted and fixed to both rami with screws . small or non - marginal bone segments were reduced and fixed to each other and marginal bone with mini - plates and screws . . the closed reduction of both condylar fractures was followed by maxillomandibular fixation with steel wires between the arch - bar on the maxillary teeth and the reconstruction plate on the mandible.(fig . 2 ) two weeks later , the maxillomandibular fixation steel wires were released and the patient started mouth - opening exercises for condyle rehabilitation to prevent tmj complications . the patient was allowed a liquid diet per oral and wheelchair ambulation four weeks after the operation . 4 ) after 10 weeks , the patient was able to have a diet of soft - to - mildly hard solids , and more than 30 mm of mouth opening was measured . although it was impossible to achieve panoramic radiographs and computed tomography due to the patient 's psychological problems , infections or bone necrosis were not observed , and signs of non - union were not found on plain radiographs and clinical examination up to this time.(fig . 5 ) reconstruction of the mandible continuity and rehabilitation of oral functions like dieting and mouth opening recovered without significant complications . more follow - up hospital visits were not possible due to personal reasons , although his condition was reported over the phone by his guardian . comminuted mandibular fractures have been treated by several methods : closed reduction , external pin fixation , internal wire fixation , and open reduction and internal fixation . it has been debated whether closed reduction or open reduction and internal fixation is the proper treatment for comminuted mandibular fractures . for extensive comminuted mandibular fractures , closed reduction has long been considered to be the optimal treatment to preserve blood supply to the bone fragments and to prevent secondary infections . however , since kazanjian6 described the open reduction and internal fixation of mandibular comminuted fractures 60 years ago , it has been reported that open reduction and internal fixation is a better treatment with lower complication rates than closed reduction in comminuted mandibular fractures . furthermore , there have been remarkable advancements in fixation materials and techniques . as a result , open reduction and internal fixation tends to be the contemporary treatment of choice . a recent report by smith and teenier5 suggested that open reduction and internal fixation in cases of comminuted mandibular fractures are indicated ( a ) in severe injuries with significant displacement to allow for the restoration of the pre - traumatic anatomic relationships , ( b ) in the edentulous and partially edentulous patient who does not have stable occlusion and may benefit from the open reduction and internal fixation of comminuted fractures , and ( c ) in cases with multiple fractures of the midface , in which the mandible serves as a guide to reposition the midfacial bones . the authors also proposed that closed reduction or conservative treatment is a better choice for minimally displaced comminuted fractures . remodeling can be understood as a process directed to meet the demands of function and growth , and occurs in such a way to allow for the functional adaptation to condylar rotation without translation . for dislocated or severely displaced condylar heads , the remodeling process configures the head parallel to the frontal plane13 . for condylar fractures , conservative treatment is the treatment of choice for the majority of fractures8 . in general , early mouth opening exercises ( i.e. , the early mobilization of the jaw and functional rehabilitation ) is essential for the treatment of condylar fractures14 . adhesion , fibrosis , and ankylosis of the condyle can occur after long periods of maxillomandibular fixation15 . zachariades et al.8 proposed several guidelines for treating condylar fractures , including : 1 ) " displaced condylar fractures with altered occlusion may be satisfactorily treated in 50% of cases with intermaxillary fixation . in cases with displaced fractures , maxilla - mandibular fixation should always be used , even if the occlusion is unchanged on admission . 2 ) " absolute indications for non - surgical treatment are intracapsular condylar fractures , high condylar fractures close to or involving the articular surface , and fractures in growing children . " 3 ) " conservative treatment may be required when the patient 's past medical history does not allow the administration of general anesthesia . " 4 ) " open reduction is recommended for condylar fractures ( especially on one side of bilateral fractures ) associated with fracture(s ) elsewhere in the mandible and/or involving comminuted maxillary fractures . if open reduction and rigid internal fixation is to be used for other mandibular or maxillary fractures , it may also be used for subcondylar fractures to avoid intermaxillary fixation . " 5 ) " open reduction is recommended when it is impossible to achieve pre - traumatic or adequate occlusion by closed reduction , in cases where conservative therapy has failed , and in anterior open bite results " . titanium plates and screws are mostly used for internal fixation , and the plate systems widely used are 1.3 , 1.5 , and 2.0 mm miniplate systems for ordinary fractures and 2.4 and 2.7 mm reconstruction plates systems for comminuted fractures16 . a mandibular reconstruction bone plate can be used to bridge the comminution gap and stabilize the most proximal and distal segments . if major fractured fragments are immobilized , other minor fragments between the major segments can heal well even if unfixed7 . there are two designs of plate - screw locking systems , with the convention being non - locking and the other being locking . non - locking systems achieve stability by the compression between the screw head compassed - plate and the screw - bone interface , which requires anatomically reduced fragments and precisely fitted plates . the drawbacks of this system are the possibility of primary reduction - loss in cases with incompletely adapted plates and disturbances of the blood supply to the compressed cortex . in the latter system , the screw head is locked at both threads of the plate and bone , creating no compression between the plate and bone . this system can produce more rigid construction with less distortion of the reduced fragments and less hindrances to blood circulation . its merits include : ( 1 ) less precision required in plate adaptation , ( 2 ) less alterations in reduced bone segments and the occlusal relationship on screw tightening , ( 3 ) greater stability across the fracture site , ( 4 ) less screw loosening16,17 . for the reasons above , the locking reconstruction plate system can be a valid internal fixation tool for the treatment of comminuted mandibular fractures . in this case , because the fracture was so severe and widespread , discontinuity of the mandible occurred so it could be treated by either closed reduction or open reduction and internal fixation . however , there were several problems that made closed reduction less feasible for this patient . first , all of the patient 's posterior teeth were avulsed or excessively dislocated , the alveolus was fractured , and stable occlusion was completely absent . second , both condylar fractures caused retraction of the mandible and early mouth opening exercises were required to avoid adhesion of the condyles , but could not be practically achieved under closed reduction . finally , patient cooperation was difficult to achieve because of his psychological state . from these reasons , the oral and maxilla - facial surgery team concluded that this comminuted mandibular fracture was an indication for open reduction and internal fixation . in the report by smith and teenier5 , a partially edentulous state without stable occlusion was a suggested indication for open reduction and internal fixation , and early mouth opening exercises after open reduction and internal fixation are essential for tmj rehabilitation . in this case , open reduction and internal fixation with reconstruction and a short period of maxillomandibular fixation were the treatment of choice . considering the limitations of this one case and the short follow - up period , we suggest that open reduction and internal fixation with a reconstruction plate can be a satisfactory treatment option in extensive comminuted mandibular fracture with bilateral condylar fractures .

this following case report describes the open reduction , internal fixation and the reconstruction of an extensive comminuted mandibular fracture with bilateral condylar fractures in a 19-year - old male patient with an intellectual disability and autistic disorder . he suffered fall trauma , resulting in shattered bony fragments of the alveolus and mandibular body between both mandibular rami , the fracture of both condyles and the avulsion or dislocation of every posterior tooth of the mandible . the patient underwent open reduction and internal fixation between both mandibular rami using a reconstruction plate , open reduction and internal fixation of the shattered fragments using miniplates and screws , and the closed reduction of the bilateral condylar fractures .

although the phenomenology of coexisting obsessive compulsive disorder ( ocd ) and bipolar disorder ( bd ) has been identified for more than 100 years,1 the etiological and nosological aspects of this medical issue remain largely unknown . symptoms of ocd may occur before , during , or after the first mood episode and , in most cases , fluctuate with mood swings.2 in this regard , the majority of bd ocd comorbidities are considered to be a subtype of bd , rather than two separate diseases.3 to date , no standard pharmacotherapy for cooccurring bd antidepressants , especially for selective serotonin reuptake inhibitors ( ssris ) , which are first - line options for ocd treatment , are strictly restricted for bd ocd individuals because of the potential to elicit manic / hypomanic switching.4 in majority of the cases , a combination of multiple mood stabilizers or augmentative antipsychotics to mood stabilizers constitute the routine medication regimens.5 however , due to the lack of well - designed clinical trials , case reports of successful treatment in patients with comorbid bd we herein present a case of a young female patient who suffered from recurrent mood episodes and symptoms of ocd . a combination of quetiapine and valproate stabilized her mood ; however , it did not lead to apparent improvement of her ocd symptoms . therefore , a small dose of aripiprazole was added to the mood stabilizers , which consequently achieved significant remission in her obsessive compulsive symptoms . this case report favors the use of augmentative aripiprazole in patients with comorbid bd ocd who respond poorly to mood stabilizers . mrs a , a 28-year - old woman , was admitted to the department of psychiatry in our hospital because of recurrent depressive episodes and aggravating compulsive behaviors . two years prior to admission , this patient developed her first depressive episode after breaking up with her ex - boyfriend . thereafter , this patient became depressed and had insomnia , loss of appetite , and loss of interest . meanwhile , she began to repetitively tidy up her belongings and check whether the windows and doors were closed . there was no suicidal ideation reported at that moment and she could still adhere to the work as a bank staff . her obsessive behaviors gradually aggravated , with repetition rate remarkably increasing from several times per day to dozens of times per day . about half a year prior to admission , this patient reported the first suicidal attempt after fighting with her parents . she went into emotional outburst , stood at the window , and claimed to end her own life . she would rush to the balcony or windows and would attempt to commit suicide by jumping down from the building , while she was also reported with dangerous driving behaviors . consequently , her daily life and job were seriously disrupted . a primary diagnosis of ocd was made , and paroxetine was prescribed at a daily dose of 40 mg . about a week later , the patient became extremely excited , talkative , and vigorous . although paroxetine was discontinued soon afterward and quetiapine was initiated , her manic state lasted for nearly 3 weeks . therefore , hospitalization was suggested by her doctor . after admission , a comprehensive physical and laboratory examinations were performed to exclude unknown underlying physical diseases . besides , cranial magnetic resonance imaging scan was also normal . according to the diagnostic and statistical manual of mental disorders , fifth edition , this patient was dually diagnosed with bipolar i disorder and ocd . quetiapine was gradually titrated up to 700 mg per day with concomitant valproate at 1,000 mg per day . although her emotion became stable with these mood stabilizers , the patient reported an inadequate response in symptoms of ocd . fascinatingly , an add - on therapy of aripiprazole 10 mg per day promoted accelerating alleviation of her obsessive behaviors . meanwhile , no severe adverse events were observed . her remission in emotional and ocd symptoms this work was approved by the institute ethical committee of the first affiliated hospital , zhejiang university school of medicine , and written informed consent was obtained from the patient and her guardians . mrs a , a 28-year - old woman , was admitted to the department of psychiatry in our hospital because of recurrent depressive episodes and aggravating compulsive behaviors . two years prior to admission , this patient developed her first depressive episode after breaking up with her ex - boyfriend . thereafter , this patient became depressed and had insomnia , loss of appetite , and loss of interest . meanwhile , she began to repetitively tidy up her belongings and check whether the windows and doors were closed . there was no suicidal ideation reported at that moment and she could still adhere to the work as a bank staff . her obsessive behaviors gradually aggravated , with repetition rate remarkably increasing from several times per day to dozens of times per day . about half a year prior to admission , this patient reported the first suicidal attempt after fighting with her parents . she went into emotional outburst , stood at the window , and claimed to end her own life . she would rush to the balcony or windows and would attempt to commit suicide by jumping down from the building , while she was also reported with dangerous driving behaviors . a primary diagnosis of ocd was made , and paroxetine was prescribed at a daily dose of 40 mg . about a week later , the patient became extremely excited , talkative , and vigorous . although paroxetine was discontinued soon afterward and quetiapine was initiated , her manic state lasted for nearly 3 weeks . a comprehensive physical and laboratory examinations were performed to exclude unknown underlying physical diseases . besides , cranial magnetic resonance imaging scan was also normal . according to the diagnostic and statistical manual of mental disorders , fifth edition , this patient was dually diagnosed with bipolar i disorder and ocd . quetiapine was gradually titrated up to 700 mg per day with concomitant valproate at 1,000 mg per day . although her emotion became stable with these mood stabilizers , the patient reported an inadequate response in symptoms of ocd . fascinatingly , an add - on therapy of aripiprazole 10 mg per day promoted accelerating alleviation of her obsessive behaviors . her remission in emotional and ocd symptoms was well maintained in the follow - up visits . this work was approved by the institute ethical committee of the first affiliated hospital , zhejiang university school of medicine , and written informed consent was obtained from the patient and her guardians . the condition of bd ocd comorbidity has always been common in clinical practice . however , spurious ocd comorbidity in bd should be carefully differentiated from the true comorbidity . in most cases of comorbid subjects , the ocd symptoms appear to be closely linked to affective symptoms , manifesting dominantly an episodic and mood - dependent course.6 in other words , the ocd symptoms in these individuals were part of bd rather than a separate disease . to date , the optimal treatment protocols for bd our study indicates that low - dose augmentation with aripiprazole may help to relieve the accompanying symptoms of ocd in bd patients . although a combination of mood stabilizers effectively alleviated the emotional symptoms , additional aripiprazole may be necessary to address the remaining symptoms of ocd . to our knowledge , the dose of aripiprazole ( 10 mg per day ) in our patient was lower than other documented cases ( 1525 mg per day).7,8 moreover , no published literature has ever discussed the impact of augmentative medications on suicidal risk in bd ocd patients . aripiprazole , an atypical antipsychotic , acts as a partial agonist at the d2 and 5-ht1a receptors , as well as an antagonist at 5-ht2a receptor.9 aripiprazole monotherapy , or as an adjuvant to mood stabilizers , is efficacious in managing acute mania and stabilization phases of bd , but not bipolar depression.10 besides , recent evidence favors the use of augmentative aripiprazole for ssris - refractory ocd.11,12 however , long - term use of aripiprazole is associated with increased risk of extrapyramidal syndromes ( epss).10 therefore , defining the minimum effective dose of aripiprazole is essential for preventing epss . in our patient , of note , the add - on therapy to mood stabilizers was initiated after partial remission in emotional symptoms . the aforementioned information implies a promising two - step strategy for bd ocd treatment . that is , first to attenuate the mood problem with mood stabilizers and then , if necessary , deal with the obsessive behaviors with an adjuvant , such as the employment of aripiprazole indicated in our study . this two - step strategy not only helps avoid the unnecessary add - on medications if adequate response was observed with mood stabilizers but also facilitates the determination of minimum effective dose of the adjuvant . the suicidal risk in bd ocd patients has not been fully elucidated , as well as drug - induced suicidal ideations . ocd comorbidity reported more suicidal attempts than those without morbidity.13 several antipsychotics , including risperidone,14 olanzapine,15 quetiapine,16 and aripiprazole,7,8 were suggested due to the benefits in relieving the ocd symptoms in bd patients . however , in these studies , little attention has been paid to the emergent suicidal ideations following the antipsychotic augmentation . a few case reports documented the possible link of using aripiprazole with suicidal ideation.17 however , epidemiological data in large sample revealed that consuming aripiprazole was not associated with more suicide events compared to other atypical antipsychotics.18 moreover , aripiprazole users had reported significantly lower risk of all - cause mortality among various antipsychotics.19 given the recurrent onset of suicidal attempts in our patient , special attention should be paid to the suicidal profiles of antipsychotic augmentation in bd to conclude , the present case study provides supporting evidence that aripiprazole augmentation to mood stabilizers was efficacious in patients with bd besides , paying special attention to suicidal risk surround antipsychotic augmentation was also suggested . in the future ,

comorbid obsessive compulsive disorder ( ocd ) and bipolar disorder ( bd ) have long been an intractable problem in clinical practice . the increased risk of manic / hypomanic switch hinders the use of antidepressants for managing coexisting ocd symptoms in bd patients . we herein present a case of a patient with bd ocd comorbidity , who was successfully treated with mood stabilizers and aripiprazole augmentation . the young female patient reported recurrent depressive episodes and aggravating compulsive behaviors before hospitalization . of note , the patient repetitively attempted suicide and reported dangerous driving because of intolerable mental sufferings . the preexisting depressive episode and ocd symptoms prompted the use of paroxetine , which consequently triggered the manic switching . her diagnosis was revised into bipolar i disorder . minimal response with mood stabilizers prompted the addition of aripiprazole ( a daily dose of 10 mg ) , which helped to achieve significant remission in emotional and obsessive compulsive symptoms . this case highlights the appealing efficacy of a small dose of aripiprazole augmentation for treating bd ocd comorbidity . well - designed clinical trials are warranted to verify the current findings .

uterine rupture rarely occurs during pregnancy , but it is a critical obstetric complication associated with maternal and fetal mortality and morbidity.1 it is known that the rate of uterine rupture increases in patients with a history of uterine surgery , such as cesarean section or myomectomy . it is however , not yet known what kinds of complications this procedure can cause in pregnant women . here we report a case of spontaneous uterine rupture in the 35th week of gestation after a laparoscopic adenomyomectomy . a 42-year - old , gravida 2 , para 0 woman was referred to our hospital at the 11th week of gestation . before she got pregnant , she had had sterility treatment , but it had nt been successful . the findings in the operation were as follows : the lesion of adenomyosis existed at the posterior wall of the uterus and the lesion and rectum adhered to each other firmly . a vertical incision was made in the middle of the posterior wall of the uterus , and the adenomyosis lesion was enucleated as much as possible ( 50 g in total ) . the patient s singleton pregnancy was uneventful and she was admitted at the 30th week of gestation for the purpose of bed rest . this was done because past reports suggest that uterine rupture after laparoscopic adenomyomectomy typically occurs around the 30th week of gestation . the patient s hospital stay was incident - free , and a cesarean section was due to be performed at the 34th week of gestation to achieve optimal trade - off between fetal lung maturation and fetal prematurity . however , the patient s cesarean section was moved to the 35th week of gestation due to her strong request . on the scheduled date the patient had undergone combined spinal epidural anesthesia , and was experiencing frequent uterine contractions when a weak pain suddenly occurred . after 13 minutes of uterine contractions , vaginal bleeding was observed while sterilizing the vagina . cesarean section was performed immediately and a female neonate , weighing 2,283 g , was delivered 31 minutes after uterine contractions had begun . the neonate s apgar scores were 7 and 8 at 1 and 5 minutes , respectively . umbilical arterial gas analysis indicated no acidosis ( ph 7.267 , base excess 3.4 ) . the rectum and omentum adhered to the posterior uterine wall , where there was a scar from the previous adenomyomectomy . one area did not have a muscle layer and was covered with only uterine serosa adjacent to the ruptured area . this was repaired with a three - layer suture and total sutured length was 78 cm . the patient s postoperative process proceeded without complications and the patient was discharged at a postoperative date of 12 days . informed consent was obtained from the patient orally , in order to retain the anonymity of the patient . two important clinical issues were identified : 1 ) after a laparoscopic adenomyomectomy , a pregnant uterus might rupture easily by rather weak and short uterine contractions ; 2 ) uterine contractions followed by uterine bleeding might be useful for the diagnosis of uterine rupture . first , after laparoscopic adenomyomectomy , a pregnant uterus might rupture easily by rather weak and short uterine contractions . a recent review by morimatsu et al showed that the rate of uterine rupture after adenomyomectomy during pregnancy is 6.0%2 in contrast to the entire rate of uterine rupture during pregnancy , which is 0.035%.3 this is much higher than the rate of complications after cesarean section ( 0.27%0.7%)4,5 or myomectomy ( 2.45%).6,7 we determined some reasons why uterine rupture frequently occurs in pregnant women with prior laparoscopic adenomyomectomies . a lesion of adenomyosis tends to remain around the edges of excisions and the area to be sutured , which might lead to weak connections between sutured edges . if a lesion of adenomyosis is enucleated widely to eliminate the lesion , the uterus will be small and irregular in shape , which leads to a diminished capacity to expand.8 with a laparoscopic adenomyomectomy , it is particularly difficult to delineate the border of the lesion because of a lacking sense of touch and deep sensation.9 only five publications have presented cases of uterine rupture during pregnancy in patients with prior histories of adenomyomectomy ( laparoscopic 4 , laparotomic 1 ) ( table 1).2,8,10,11 according to 96 reported cases ( table 2),2,816 the rate of uterine rupture during pregnancy was 6.25% ; this is similar to the review reported by morimatsu et al.2 it would appear that the frequency of uterine rupture after laparoscopic adenomyomectomy is higher than that of laparotomic adenomyomectomy ( tables 1 and 2 ) , but there is no cohort study to compare these so far . uterine rupture or dehiscence during pregnancy tends to occur more frequently after laparoscopic myomectomy than after laparotomic myomectomy . specifically , the frequency of uterine dehiscence is 1.854.94% in laparoscopic6,7 and 0% in laparotomic ( this finding is extremely limited because it depends on only 69 cases from two reports).6,7 we guess that uterine rupture or dehiscence is similarly more common in laparoscopic than in laparotomic adenomyomectomy cases . second , uterine contractions followed by uterine bleeding might be useful for the diagnosis of uterine rupture . uterine rupture does not have any typical symptoms and is often asymptomatic.17,18 classical symptoms and signs are abdominal pain , external bleeding , vital signs indicating shock , disappearance of labor pain , and signs of fetal distress etc . in this case , the patient experienced both abdominal pain and external bleeding . a pregnant uterus after laparoscopic adenomyomectomy might rupture easily by rather weak and short uterine contractions . furthermore , uterine contractions followed by uterine bleeding might be useful for the diagnosis of uterine rupture . when uterine contractions are followed by uterine bleeding in pregnant women that have had a prior adenomyomectomy , this must be considered a potential sign of uterine rupture . if physicians are planning to perform surgery for treating sterility and infertility , they should carefully choose the modality of surgery and get more detailed informed consent from patients with adenomyosis . further reports should be accumulated to develop more reliable and safe operative techniques , and to establish guidelines for pregnancy after adenomyomectomy in women of reproductive age .

uterine rupture rarely occurs during pregnancy , but it is a critical situation if so . it is already known that a history of uterine surgeries , such as cesarean section or myomectomy , is a risk factor for uterine rupture . currently , the laparoscopic adenomyomectomy is a widely performed procedure , but associated risks have not been defined . we observed a case of spontaneous uterine rupture in a patient during the 35th week of gestation , after a laparoscopic adenomyomectomy . a 42-year - old , gravida 2 , para 0 woman became pregnant after a laparoscopic adenomyomectomy and her pregnancy was conventional . at a scheduled date in the 35th week of gestation , after combined spinal epidural anesthesia and frequent uterine contractions , a weak pain suddenly ensued . after 13 minutes of uterine contractions , vaginal bleeding was evident . a cesarean section was performed , and the uterine rupture was found in the scar . after a laparoscopic adenomyomectomy , a pregnant uterus can easily rupture by rather weak and short uterine contractions , and is characterized by vaginal bleeding . when uterine bleeding is observed in pregnant women that have a history of adenomyomectomy , one should consider uterine rupture .

evaluation of students competencies is one of the essential tools for assessing success of education programs in accomplishment of its objectives . on the other hand , evaluation is a major determinant of students learning patterns . in other words some believe that ethical evaluation of medical students should emphasize on ethical knowledge and moral reasoning while some others think that in addition to these objectives , compassion , respect and altruism are essential moral competences which need to be evaluated ( 3 ) . it means that although moral reasoning is an important goal , this competency does not necessarily end to ethical and professional practice of students . the other challenge in moral evaluation is that how it is possible to evaluate students ` attitude and values and ethical practice in a valid and reliable way ( 4 ) . in published literatures there are so many papers introducing and discussing different tools for evaluation of ethical attitude , reasoning and behavior ( 2 , 57 ) . defining issue test ( dit ) , sociomoral reflection measure ( srm ) , and moral judgment interview ( mji ) have been developed for evaluation of moral reasoning , not being enough specific they are used generally for research purpose though ( 8) . in practice , for evaluation of students medical ethics competency , methods such as multiple choice questions , short essay , portfolio , objective structured clinical examination ( osce ) , faculty evaluation and 360 degree evaluation are being used ( 2 , 7 ) . although there is no consensus among ethicists on the best evaluation method , they all agree that different methods should be used ( 7 ) . this method not only evaluates trainee s ethics knowledge but also assesses their moral reasoning and ethical behavior . nowadays increasing number of medical ethics osce stations are including in comprehensive exams in different educational phases in medical schools around the world ( 2 , 911 ) . in iran , there is a consensus about the necessity of evaluation of graduate s ethical competency among medical education leaders and they have mandated adding some medical ethics multiple choice questions ( mcq ) to pre - internship comprehensive exam , residency entrance exam , annual residency and board exam . since multiple choice question method alone is not enough for moral competency evaluation , we decided to assess practicality of evaluation of ethical competency by designing and conducting an osce station for medical ethics . success of this method could convince educational leaders to use other methods for evaluation of graduate s ethical competency . in this paper we present our experience of including one medical ethics station in seven endocrinology osce stations of endocrinology board exam . we used bioethics osce experience of toronto center for bioethics to design one station on truth telling . the scenario is about an inoperable pancreatic cancer patient whose wife asks physician not to tell the diagnosis to the patient . a standardized patient played the role of the patent s wife in this station and talked to examine physicians . we also used two global rating questions using likert scale to score their ethical decision making and communication skill . this station was pilot tested in a medical ethics education workshop in may 2009 which the standardized patient was trained for . in pilot conduct of this station one of workshop attendees participated as the examinee and other six participants rated his performance . all scores were very close to each other , indeed 5 out of six participants gave the same mark to the examinee and the reliability of station was 0.83 . participants also evaluated the face and content validity of the checklist . based on their suggestion the finalized station included in the osce part of the endocrinology board exam in september 2009 . time for each physician s interview with simulated patient in ethics station was 5 minutes . one rater ( first author ) was present in the station to fill checklists and rate examinees . most participants had good to excellent communication skill and only one participant did not communicate with the standardized patient and easily accepted her request ( table 1 ) . in their ethical decision making , % 26 ( 5 ) of participants had poor performance and only 3 of them had good or acceptable ethical encounter . most participants asked for the patient s wife reason for her request ( 15 people ) and almost all of them ( 18 people ) mentioned that patient had right to know about his condition . the most prevalent mentioned justification for patient s right was the need to plan for the rest of life ( 12 people ) . two people told that patient might ask about his condition and one participant gave several different reasons for refusing her request such as she is not telling lie to patient because it is unprofessional , finally patient would find out they were hiding something form him , also if he heards about his condition he would lose his trust on physicians and would be affected by a worse emotional stress . nine participants refused to withhold the truth from patient , however no one acknowledged the patient s right not to know . all of them believed that they had to give information to the patient in any case . there was a significant correlation between participant s score of communication skill and score of their ethical decision making ( r=0.48 , p=0.03 ) . although the mean score of board osce for those with good ethical performance was higher , this correlation was not significant ( table 2 ) . a positive correlation has been observed between participants osce score and their communication skill score but it was not significant . mean ethical performance score of female participants ( 2 , 17 ) was significantly higher than male ones ( 1.43 out of 5 ) ( p=0.01 ) , however there was no significant difference between their communication skill . small though , this experiment showed practicability of conducting and including an osce ethics exam in evaluation of trainees . low score of participant s ethical performance was due to lack of training in their educational course and we could not expect them to show good ethical competency just by reading ethics text books . osce is a good method for integrated evaluation of trainees knowledge and skills in facing with ethical dilemmas . if we just use multiple choice questions for evaluation of ethics competency , students learning will be limited to knowledge while using methods that could evaluate their moral judgment and behavior will encourage them to learn practical ethics competencies . moreover standardized patient could be used as a teaching method . in teaching medical ethics besides reflection and discussion on ethical dilemmas , students need to practice their ethical skills and receive feedbacks on their practice ( 13 ) . we should notice that osce method alone is not enough for precise evaluation of ethical practice . since the pattern of all ethics station could be recognized by students and they could get ready for showing good competency in those stations , being able to have ethical performance is not equal to having ethical practice ( 5 ) . in other words , thus other evaluation methods such as 360 degree evaluation are needed to assess this dimension of educational objectives in medical ethics ( 2 ) . furthermore osce method is very costly and having enough number of ethics station will pose logistical difficulties . in a study conducted by singer et al , 46 ethics station had internal consistency reliability ( cronbach s ) of 0.28 to 0.46 . they estimated that at least 41 ethical stations are needed in an osce test for achieving acceptable internal consistency of 0.8 ( 12 ) . although inter - rater reliability of our station in its pilot phase was good , because of small sample size in the pilot study , we should have evaluated its reliability in the main study . unfortunately due to logistical problems we were not able to have two raters , so we did not evaluate inter - rater reliability of the station . the other important pitfall of our study was that one station has not content validity for assessing ethical performance . in other words , we could not be sure of ethical competency of physicians in encountering with different types of ethical problems in their professional life through watching their conduct in facing with just one ethical problem . this study showed that it is practical to develop an ethics station in comprehensive medical exams in different phase of medical education course and this method could motivate medical students to learn ethical practice . despite all straight points of this evaluation method , it should be noticed that conducting one or two osce station in graduate comprehensive exam is not enough for evaluation of their ethical practice and other complementary evaluation methods such as continuous peer and faculty evaluation of students during their educational course are necessary .

in this study we discuss our experience of including an ethics objective structured clinical examination ( osce ) station in endocrinology board exam.one osce station on truth telling was developed and a standardized patient was trained for role playing in this station . based on a pilot study , the evaluation checklist got modified . then the finalized station added into the osce phase of endocrinology board exam.based on this experience , adding ethics station in board exams is practical and reasonable . since osce method could evaluate students ethical decision making and communication skill it could be used in combination with other kinds of evaluation in assessing ethics competency of graduates . using this method could push the ethics learning approach toward more practical and skill based ones .

mdc1a is caused by mutation of the laminin -2 gene ( lama2 ) , localized to chromosome 6q22 - 23 . patients with mdc1a present with severe neonatal hypoxia often requiring ventilatory assistance , markedly delayed motor development , and generalized muscle atrophy with the weakness of limb and trunk muscles leading to contractures and joint deformities . in contrast with other cmd patients , those with merosin deficiency have high creatine phosphokinase ( cpk ) levels and white matter abnormalities on brain imaging techniques . here we report the clinical manifestations , result of muscle biopsy and genetic studies in five turkish patients with mdc1a . the patient 1 was a 6-year - old boy and first attended our hospital at the age of 4 years due to hypotonia , weakness , poor weight gain , and contracture of knees . from birth , he exhibited marked hypotonia with generalized muscle weakness . by 3 years of age , the patient was able to hold his head up but was unable to sit alone . at the age of 5 years , the patient was able to sit unsupported , but not stand . he had joint contractures of upper and lower extremities , myopathic facies , and pectus carinatum . nerve conduction studies were normal , and electromyography ( emg ) showed a myopathic pattern . magnetic resonance imaging ( mri ) of the brain was performed and showed high signal in the periventricular and subcortical white matter [ figure 1a and b ] . periventricular and subcortical white matter signal the patient 2 was the daughter of patient 1 . she had global hypotonia and was able to sit and was not able to stand . the distal tone of the four extremities was decreased , and deep tendon reflexes were diminished . cerebral mri was performed in another hospital and revealed high signal in the periventricular and subcortical white matter . we analyzed the lama2 gene sequencing and revealed a homozygous mutation c. 639delg in the patient 1 and 2 . the patient 3 was a 7-month - old girl who presented to our hospital with complaints of developmental motor delays . her serum cpk level was 4073 u / l , and her echocardiogram was normal . mri of the brain revealed hyperintense lesions in the periventricular white matter on t2a sequencing . we studied the lama2 gene sequencing and revealed a homozygous mutation p.r1350 ( c. 4048 c > t ) . the patient 4 was a 3 and a half year - old boy who presented with hypotonia , weakness , poor weight gain , and respiratory problem , and could not sit or stand . he had general hypotonia , myopathic facies , pectus excavatum , and he was not able to sit and stand . furthermore , he had a hemangioma on the left temple , chest , and wrist . his serum cpk level was 2120 u / l and mri of the brain showed similar findings with other patients . hemangioma on the left temple , chest , and wrist in the patient 4 the patient 5 was a 6-month - old boy who had hypotonia . his biochemical investigations were normal except for elevated serum cpk levels ( 2950 u / l ) . echocardiography was normal , and mri of the brain showed hyperintense lesions in the periventricular white matter . we performed the lama2 gene sequencing and revealed a homozygous mutation p.r2578 ( c. 7732 c > t ) in two of them . the patient 1 was a 6-year - old boy and first attended our hospital at the age of 4 years due to hypotonia , weakness , poor weight gain , and contracture of knees . from birth , he exhibited marked hypotonia with generalized muscle weakness . by 3 years of age , the patient was able to hold his head up but was unable to sit alone . at the age of 5 years , the patient was able to sit unsupported , but not stand . he had joint contractures of upper and lower extremities , myopathic facies , and pectus carinatum . nerve conduction studies were normal , and electromyography ( emg ) showed a myopathic pattern . magnetic resonance imaging ( mri ) of the brain was performed and showed high signal in the periventricular and subcortical white matter [ figure 1a and b ] . periventricular and subcortical white matter signal the patient 2 was the daughter of patient 1 . she had global hypotonia and was able to sit and was not able to stand . the distal tone of the four extremities was decreased , and deep tendon reflexes were diminished . cerebral mri was performed in another hospital and revealed high signal in the periventricular and subcortical white matter . we analyzed the lama2 gene sequencing and revealed a homozygous mutation c. 639delg in the patient 1 and 2 . the patient 3 was a 7-month - old girl who presented to our hospital with complaints of developmental motor delays . her serum cpk level was 4073 u / l , and her echocardiogram was normal . mri of the brain revealed hyperintense lesions in the periventricular white matter on t2a sequencing . we studied the lama2 gene sequencing and revealed a homozygous mutation p.r1350 ( c. 4048 c > t ) . the patient 4 was a 3 and a half year - old boy who presented with hypotonia , weakness , poor weight gain , and respiratory problem , and could not sit or stand . he had general hypotonia , myopathic facies , pectus excavatum , and he was not able to sit and stand . furthermore , he had a hemangioma on the left temple , chest , and wrist . his serum cpk level was 2120 u / l and mri of the brain showed similar findings with other patients . hemangioma on the left temple , chest , and wrist in the patient 4 the patient 5 was a 6-month - old boy who had hypotonia . his biochemical investigations were normal except for elevated serum cpk levels ( 2950 u / l ) . echocardiography was normal , and mri of the brain showed hyperintense lesions in the periventricular white matter . we performed the lama2 gene sequencing and revealed a homozygous mutation p.r2578 ( c. 7732 c > t ) in two of them . mdc1a is an autosomal recessive neuromuscular disorder caused by mutations in the lama2 gene encoding the laminin - a2 chain a component of the skeletal muscle extracellular matrix protein laminin-211 . laminin-211 , the most abundant laminin in muscle , is also expressed in schwann cells , the synaptic basal lamina of peripheral nerves , heart , epidermis and fetal trophoblastic tissue . typical clinical features of mdc1a or merosin - deficient cmd include severe floppiness at birth , elevated serum cpk , delayed motor milestones , white matter changes as seen on brain mri . in literature , several studies have reported respiratory insufficiency , feeding difficulties , cardiomyopathy , sensory and motor demyelinating neuropathy , seizure , and external ophthalmoplegia . severe proximal weakness was also present from birth or developed within the first 6 months . di blasi et al . reported 9 patients with mdc1a from 1 sudanese and 3 saudi families . another study presented similar results : five of 13 patients with residual merosin and two of 33 patients with absent merosin could walk independently . leite et al . in a study of 25 brazilian patients with mdc1a reported that bilateral white matter involvement was frequent in the parietal , frontal , and temporal regions , brain stem , cerebellum , and internal and external capsules were also affected in the minority of cases . however , they described that there were no correlations with sites of white matter abnormalities and clinical or merosin status . in another study , di blasi et al . reported mri or ct , oliveira et al . performed in 22/26 patients , revealed white matter changes in all cases . in addition , they detected that other cerebral changes included abnormal gyration in three patients . in our study , all the patient showed the typical phenotype of mdc1a , including features such as hypotonia , elevated serum creatine kinase , delayed motor development , and t2 hyperintensity on brain mri . in the patient 3 , 4 , and 5 , we detected two lama2 gene mutations which have been described previously . coral - vazquez et al . reported an 8-month - old mexican female infant , from a consanguineous family , with mdc1a and they detected homozygous mutation p.r2578 in lama2 gene as similarly in our patient 4 and 5 . from the 1 month of life , the patient was hypotonic with poor intake , irritability , reduced spontaneous movements , and poor suction . physical examination showed generalized muscle weakness and contractures of elbows , wrists , knees , and ankles . patients should be suspected as mdc1a if they have early - onset severe hypotonia with joint contractures , motor developmental delay with moderately increased cpk levels , and abnormal cerebral imaging findings . muscle biopsy and molecular genetic testing should be performed for diagnosis and especially for the genetic counseling .

context : congenital muscular dystrophy type 1a ( mdc1a ) is caused by mutations in the laminin -2 gene encoding laminin-a2.aims:the purpose of this study is to determine clinical and genetic results in five turkish patients with mdc1a.setting and designs : five children with mdc1a were retrospectively analyzed.results:three ( 60% ) were boys , and 2 ( 40% ) were girls . parental consanguinity was found in all the families . in all the patients , hypotonia , weakness , delayed motor milestones , markedly elevated creatine phosphokinase ( cpk ) concentration , and brain white matter abnormalities on magnetic resonance imaging were detected . mutation analysis was performed in all the patients , and 3 different mutations were detected . however , a mutation in patient 1 and 2 has not been previously described in the literature.conclusions:when a patient presents with severe congenital hypotonia , muscle weakness , high serum cpk levels , and white matter abnormalities , should be suspected as mdc1a .

intestinal obstruction is a common surgical emergency frequently due to adhesions , tumors , inflammatory disorders , volvus , and external or internal hernias . they can occur mainly in patients who have undergone gastric surgery and in multiple sites of the gastrointestinal tract . there are many treatments for intestinal obstruction due to phytobezoar ( medical , endoscopic , and surgical ) though some patients have not undergone surgery . the use of laparoscopy in acute intestinal obstruction has been avoided by some surgeons because of technical difficulties and increased risk of bowel injury . however , various studies have reported laparoscopic management of intestinal obstructions with the improvement of laparoscopic skills . this report describes a case of small - bowel obstruction due to bezoar ( mango seed ) treated with laparoscopy . a 74-year - old male was admitted after 24 hours of abdominal pain and vomiting . a physical examination showed normal vital parameters , a distended abdomen , and no evidence of peritonitis or abdominal external hernias . an abdominal x - ray revealed dilation of the small bowel and a circular image in the inferior right quadrant of the abdomen . a colonoscopy identified a hard mass in the terminal ileum , which could not be removed endoscopically . a laparoscopy by the open technique was performed with a 10-mm port placed in the umbilicus . after an initial diagnostic laparoscopy , 2 additional 5-mm working ports were placed under direct vision , 6 cm above the umbilicus and 6 cm below it in the middle line of the abdomen . the abdominal cavity was inspected carefully with atraumatic bowel graspers to minimize the risk of bowel injury . a mechanical obstruction due to a hard intraluminal mass was located approximately 5 cm from the ileocecal junction ( figure 1 ) . the small bowel was examined from the ligament of treitz to the cecum to ensure that the obstruction did not involve other areas . an ileotomy was performed with a harmonic scalpel ( ultracision ethicon endo surgery ) along the longitudinal axis ( figure 2 ) , which allowed the removal of a 5.05.04.0-cm phytobezoar that could not be milked towards the colon ( figure 3 ) . a larger incision on the umbilicus was made to facilitate the removal of the bezoar . the ileotomy was closed along the longitudinal axis with interrupted suture using 3 - 0 vicryl ( figure 5 ) . the postoperative course was uneventful , and the patient stayed in the hospital for 4 days . the final diagnosis was intraluminal small - bowel obstruction due to phytobezoar ( mango seed ) . ileotomy was performed with a harmonic scalpel ( ultracision , ethicon endo - surgery ) along the longitudinal axis . removal of 5.0 5.0 4.0 cm phytobezoar ( mango seed ) from ileum . the ileotomy was closed along the longitudinal axis with interrupted suture using 3 - 0 vicryl . phytobezoars are an uncommon cause of intestinal obstruction , and an accurate preoperative diagnosis is difficult to obtain . the main causes reported in the medical literature are oranges , coconuts , cherry tomatoes , and others . they can occur mainly in patients who have undergone gastric surgery and in multiple sites of the gastrointestinal tract . bezoar formation has also been described in patients with coexisting illnesses affecting gastrointestinal motility , such as guillain - barr syndrome , myotonic dystrophy , and hypothyroidism . patients with psychiatric illnesses are at an increased risk for bezoar formation due to the possible ingestion of hair and medications . a number of surgical , endoscopic , and pharmacologic treatments have been proposed with differing results . many articles report gastric phytobezoar removal by the endoscopic technique or by using cellulase , but these are reports with few cases , the stomach is easier to access than the ileus , and a well - trained physician is needed . there are a few reports about the successful treatment of phytobezoar in the ileus by endoscopy or cellulase . laparotomy has been the gold standard treatment for intestinal obstruction when surgical intervention is necessary , although laparotomy itself is an independent risk factor for bowel obstruction . in this case , we tried to remove the obstruction endoscopically , but this was not possible because the seed was adhered to the bowel and could have caused a perforation or injury . mango seeds are very hard and the fibers very resistant ; consequently , cellulose was not a good option . with the improvement in laparoscopic techniques , many authors have considered the laparoscopic approach as an alternative to conventional laparotomy in select cases of intestinal obstruction . there are no defined guidelines for selecting patients with small - bowel obstruction for the laparoscopic approach . authors have described some criteria that may be useful to identify patients with small - bowel obstruction who can undergo laparoscopy , which include mild abdominal distension , a proximal obstruction , partial obstruction , shorter duration of symptoms , and others . multiple previous operations , documented intraabdominal adhesions , and sepsis are relative contraindications for laparoscopy . the literature has demonstrated postoperative complication values varying from 0% to 5.7% in patients who undergo laparoscopic treatment for intestinal obstruction compared with 0% to 18.6% for laparotomic treatment . the average postoperative ileus rate was also shorter in the laparoscopic group ( range , 1.5 to 2.2 days ) than in the laparotomic group ( range , 3 to 4.7 days ) . some reports mention hospital stay varying from 2.5 days to 6.6 days in the laparoscopic group and 5.8 days to 16.8 days in the laparotomic group . some authors suggest that laparoscopic surgical techniques lead to fewer intraabdominal adhesions by reducing tissue trauma . gentle manipulation of the intestines should be done to avoid damage to the distended and friable bowel . the open technique to place the first port the procedures performed with open access are safer because the surgeon involved has a direct view of the abdominal contents ; the contrary occurs when the procedure is performed in a blind this is very important when the patient may have a dilated bowel as in cases of bowel obstruction , because there is an increased chance of intestinal injury caused by the trocar since the bowel is closer to the abdominal wall . vertical incisions in the middle of the abdomen were used , because incisions could easily be increased if conversion to laparotomy was necessary . pneumoperitoneum was established to a maximum pressure of 13 mm hg , because high pressures could interfere with cardiopulmonary function . once safe access is obtained , adequate visualization is necessary to insert the remaining ports . atraumatic graspers should be used to manipulate the friable and dilated small bowel . in this case , the authors opened the small bowel intraabdominally because the pneumoperitoneum pressure of 13 mm hg helped to maintain the bowel contents inside the intestine , and the mango seed was placed into a bag avoiding cavity contamination . the enterotomy was closed longitudinally , contrary to most surgical principles , because in this case , the intestine was very fragile and the transversal closure led to more tension in the suture , and we observed the bowel lumen was sufficiently ample after the longitudinal closure . the intestinal resection was not necessary because the bowel segment was viable without signs of necrosis . several studies suggest that laparoscopy reduces postoperative complications , postoperative ileus , hospital stay , and adhesion formation . the laparoscopic approach is a feasible method in the management of bezoar - induced intestinal obstruction when performed by a well - trained and experienced laparoscopic surgeon in select patients .

phytobezoars are a rare cause of small - bowel obstruction and an accurate preoperative diagnosis is very difficult . after diagnosis , the majority of patients in this study underwent surgery . the conventional management of small - bowel obstruction is done by laparotomy . many studies have demonstrated that laparoscopy can be an alternative to laparotomy for the treatment of small - bowel obstruction in select patients , and it also brings the benefits of minimally invasive surgery . this report demonstrates the case of a patient with intestinal obstruction caused by phytobezoar ( mango seed ) who was treated laparoscopically . during the laparoscopy , a hard mass 5 cm proximal to the ileocaecal junction was palpable with graspers . an ileotomy was then performed . the bezoar was extracted and inserted into a bag . in this case , the intestinal obstruction management by laparoscopy was safe and feasible .

we discuss the management of a patient after its recurrence , involving the upper respiratory tract i.e. nasopharynx and oropharynx , which compromised the airway . the patient was referred for anesthesia on three different occasions with different presentations owing to the recurrence of symptoms . the presence of an oropharyngeal membrane with a small opening made airway management a challenge . rhinoscleroma is a chronic , granulomatous infection , caused by klebsiella rhinosleromatis , affecting the nasopharynx , oro - pharynx , larynx , trachea and bronchi . it is common in the second and third decade of life , with females more frequently affected . treatment consists of prolonged antibiotic treatment , surgery to remove the obstruction and laser therapy to treat airway compromise and tissue deformity . this progressive infection , involving the upper respiratory tract , may pose a challenge in airway management . however , he had no long - term relief and the symptoms progressed . in the last six months , he developed difficulty in breathing and swallowing . oral examination revealed a membrane at the level of uvula covering the oropharynx with a central opening of approximately 8 mm diameter through which he managed swallowing [ figure 1 ] . ct scan and mri scan showed a concentric narrowing at the level of the oropharynx [ figures 2 and 3 ] with sparing of the lower respiratory tract . flexible fiber - optic bronchoscopy ( with a 6 mm scope ) under la revealed uninvolved vocal cords , but patient had discomfort and was unable to hold his breath during the procedure . oro - pharyngeal membrane visible at the level of uvula covering the oropharynx with a central opening of approximately 8 mm diameter mri of the airway sagittal section showing the membrane in the oropharynx and no involvement of the airway below mri coronal view showing narrowing of the oropharynx due to the membrane ( shown by arrow ) premedication with 20 mg omeprazole and glycopyrrolate 0.2 mg intramuscularly was given . after preoxygenation , anesthesia was induced with 120 mcg fentanyl , propofol 1mg / kg and sevoflurane in titrated doses . after ensuring adequate mask ventilation , succinylcholine 1.5mg / kg was given . although an ideal laryngoscopy could not be performed , moving the tongue gently with the laryngoscope helped visualize the membrane . a 15 fr bougie was inserted via the hole in the membrane and tracheal rings were well felt . a non - laser shielded 5 mm i d endotracheal tube ( ett ) was negotiated , over the bougie , through the opening . membrane was resected with diode contact laser and the tissue was sent for histopathology evaluation . the induction was done as in the previous instance but we were unable to negotiate the bougie , and two attempts at blind intubation with 5 mm i d ett and an attempt with a smaller ett were unsuccessful . post operatively , the tracheostomy was kept and patient discharged on fourth postoperative day with tracheostomy tube in situ . rhinoscleroma leads to fibrosis of the airways with consequent deformity , atresia or complete obstruction of the airway . diagnosis is made on the basis of clinical presentation , histopathology , bacteriological culture and serological investigations . the extent of oropharyngeal and tracheobronchial involvement can be accurately assessed with ct or mri scans , although very few studies have described imaging features of rhinoscleroma.[79 ] the nasal cavity is the most often affected ( 95 - 100% ) , but the lesions may also involve larynx ( 15 - 40% ) , nasopharynx ( 18 - 43% ) , oral cavity , paranasal sinuses ( 26% ) , soft tissues of lips , nose , trachea ( 12% ) and bronchi ( 2 - 7% ) . sharing the airway with the surgeon is of utmost concern to an anesthesiologist . in the case reported , a trial at oral intubation guided by a gum elastic bougie was done as the patency of the pharynx distal to the membrane on mri and ct scan was confirmed [ figures 24 ] . we avoided blind nasal intubation since the nares seemed blocked and the ct image showed some synechiae in the nasal passage . the feel of the tracheal rings by the bougie guided us the insertion of the ett . a fiberoptic bronchoscope would have helped in visualizing the membrane , as it done in the ent clinic , but we only had a 6 mm scope , which would have permitted only a larger ett over it . trauma to the membrane or bleeding had to be avoided . a supraglottic airway could not be used . jet ventilation would have made the patient prone to barotrauma as airway pressures can not be controlled with its use . retrograde intubation would have been tedious as passing the guide wire through the small opening would have been very difficult . as the pharyngoplasty took only fifteen minutes , ett was not changed to a bigger size later . ct scan showing narrowing of the oropharynx due the membrane ( shown by arrow ) fatal airway obstruction has been reported after evading tracheostomy in a patient who seemed to be improving following antibiotic treatment . pharyngoplasty is often a day care procedure performed using laser , and is associated with minimal blood loss , edema , and quick recovery . routinely , it does not need the patient to have a tracheostomy , as lubricated airways , post - surgery , maintain the airway patency well . in our patient , at the second instance , the opening in the oropharyngeal membrane was smaller . we were however reluctant to do a tracheostomy knowing that the symptoms would be relieved on resection of the membrane . despite three attempts with smaller sized ett we did not expect recurrence , as the patient had undergone laser and electrical cautery resection , but there was recurrence . the third time , the patient presented with respiratory distress that warranted an immediate tracheostomy . he had not responded to prolonged antibiotics , anti - inflammatory drugs , steroids or even surgery and finally needed a permanent tracheostomy . close observation for prolonged periods of time is essential to recognize reactivation of quiescent lesions . trauma caused by excision and laser can incite more fibrosis and lead to recurrence of the primary problem with a vengeance . the recurrence rate of rhinoscleroma has been cited to be up to 25% of the treated cases in 10 years . in patients with an oropharyngeal membrane with a solitary opening , the size of the opening , pathology and involvement of the oropharynx , nasopharynx and the tracheobronchial tree must be evaluated . it is important to consider the site of airway obstruction and ensure availability of equipment to secure the airway . fiberoptic bronchoscope is an important tool in assessing the airway patency but can precipitate respiratory distress and a bougie may be helpful . tracheostomy should be performed if the opening is small or if the airway is affected at multiple levels .

rhinoscleroma is a rare entity encountered in anesthesia practice . we discuss the management of a patient after its recurrence , involving the upper respiratory tract i.e. nasopharynx and oropharynx , which compromised the airway . the pateint was referred for anesthesia on three different occasions with different presentations owing to the recurrence of symptoms.the presence of an oropharyngeal membrane with a small opening made airway management a challenge . the patient was successfully managed on all three occasions . imaging facilitated assessment and subsequent airway management .

rheumatoid arthritis ( ra ) is the most frequent chronic autoimmune inflammatory rheumatism , with a worldwide prevalence around 1% . ra severity is related to joint destruction characterised by erosion and space narrowing that is responsible for joint functional disability [ 24 ] . early diagnosis and treatment are crucial in order to prevent joint destruction and preserve joint function defining the window of opportunity concept [ 5 , 6 ] . since few years , the concept outside - inside suggested a beginning of ra disease also in the subchondral bone marrow . in fact , a subchondral bone loss at the metacarpal phalangeal head starts since the early phase of ra disease . furthermore , joint inflammation due to synovitis is one of the most powerful predictors of new bone erosion . so , the synovial membrane was the first actor mainly described by production of some mediators induced by inflammatory cytokines such as tnf or others . these mediators induced cartilage matrix degradation and subchondral bone loss [ 10 , 11 ] . these data support a strong interaction between synovial membrane , cartilage , and subchondral bone . inflammatory joint induced the release of specific protein fragments from its various compartments into the serum and the urine , which may be used as tissue specific biomarkers . by this way , biomarkers of each component of the joint could be useful to manage ra patients . tnf inhibitors and other biologics reduce synovitis , biomarkers of inflammation , and bone destruction . these tnf inhibitors are able to block joint destruction , even if ra disease is still active [ 1315 ] . in 2014 , in front of early ra patient , the goal of early ra therapy is to obtain remission according to the new criteria for remission acr / eular . however , though clinical remission was obtained , in some patients a structural progression can occur probably due to persistence of joint inflammation [ 18 , 19 ] . exploration with specific biomarkers of each component of the joint could be helpful to investigate this paradigm . in daily practice in 2014 , only das28 combining clinical parameters with erythrocyte sedimentation rate ( esr ) or c - reactive protein ( crp ) is used . so , they are not strongly correlated with joint involvement . despite its large usefulness in daily practice , das28 fails to strongly predict the joint progression or a real remission . at the time of personalized medicine , which aims to individually improve treatment management , biomarkers of the joint will be useful in ra especially at the early stage . the aim of this paper is to review some biomarkers of synovial , cartilage , and bone turnover in ra , clarify their utility in ra management , and analyze data in remission . matrix metalloproteinase-3 ( mmp-3 or stromelysin 1 ) is a proteinase secreted by synovial fibroblasts and chondrocytes . its activity results in degradation of aggrecan core protein , cartilage link protein , fibronectin , and collagen types iv , vii , ix , and xi . mmp-3 is present in ra synovial fluid and overexpressed in rheumatoid synovium [ 23 , 24 ] . one mmp-3 polymorphism was described to be associated with higher joint damage in ra [ 25 , 26 ] . otherwise , serum mmp-3 level was suggested as a predictor for joint destruction in early ra [ 27 , 28 ] or established ra [ 29 , 30 ] . correlation between serum mmp-3 level and joint damage progression appeared to be independent of rheumatoid factor ( rf ) or acpa status . the next step was to assess mmp-3 variation induced by ra therapy and particularly during biological therapies . anti - tnf therapy decreased mmp-3 expression in ra patients [ 32 , 33 ] . similar results were observed with tocilizumab ( il-6 blocker ) or abatacept ( inhibitor of costimulation ) . its level was similar in ra patients in remission or not induced by anti - tnf therapy . however , normal mmp-3 level in ra patients treated with tocilizumab was predictive to absence of relapse after tocilizumab cessation . to summarize , high mmp-3 level was associated with disease activity and joint progression in ra patients and should be used in association with usual inflammatory markers to follow therapy efficiency . however , this biomarker was never tested in patients in clinical remission to predict structural remission . another synovial biomarker considered in ra is the glycosylated form of pyridinoline ( pyd ) . pyd is mainly a bone resorption biomarker but is also related to remodeling of cartilage and synovium . the glycosylated analogue of pyd , glucosyl - galactosyl - pyd ( glc - gal - pyd ) , can be assessed in urine and appeared to be specific to synovial tissue . urinary glc - gal - pyd level was higher in patients with early ra than controls and its high level is associated with higher risk for the progression of joint damage . in established ra , urinary glc - gal - pyd was associated with changes of the erosion , joint space narrowing ( jsn ) , and the total sharp score . after one year of anti - tnf therapy , the levels of urinary glc - gal - pyd was similar in ra patients with or without progressive joint damage over one year of anti - tnf therapy , but its reduction over one year was higher in patients with progressive joint damage . these results suggested that , in some patients , other mechanisms were possibly involved than tnf related inflammation . the last synovium biomarker recently developed is the nitrated type iii collagen ( iiinys ) , which was explored in both osteoarthritis ( oa ) and ra patients . in patients with joint disorder , its level was the highest in ra patients which suggests that it is related to synovial tissue inflammation . we attempted to describe synovial biomarkers and put out their interest in ra management . despite many studies reviewed , no data are currently available to predict relapse in ra patients in remission then , we focused on three main cartilage biomarkers with a summary of their characteristics in table 2 . two are biomarkers of cartilage breakdown , whereas the third one is a biomarker of cartilage formation . cartilage is mainly composed of collagen type ii ( 70% ) and proteoglycans including aggrecan which is the most abundant one . mmps and aggrecanases are mediators of cartilage degradation . collagen type ii c - telopeptide ( ctx - ii ) is a neoepitope generated from mmps , derived from the carboxy - terminal part of type ii collagen . in early ra , urinary ctx - ii level was higher than in controls , and patients with high ctx - ii level have a higher risk for the progression of joint damage over 1 year , independent of the extent of joint destruction at baseline and of clinical indices of disease activity . in established ra , urinary ctx - ii level was associated with rapid radiologic progression or changes of the jsn sharp score over one year . then , ctx - ii was assessed during anti - tnf therapy in ra patients . after one year of anti - tnf therapy , the levels of urinary ctx - ii were similar in ra patients with or without progressive joint damage over one year of anti - tnf therapy . in patients with progressive joint damage , reduction of urinary ctx - ii was higher than in others . cartilage oligomeric matrix protein ( comp ) is a noncollagenous extracellular matrix protein mainly found in cartilage maintaining the integrity of the collagen network . serum comp was reduced in ra patients in remission induced by anti - tnf therapy compared to other patients . in early ra , early changes in serum comp levels were related to radiological outcome over the first 5 years . serum propeptide of type iia procollagen ( piianp ) arises from the maturation of type iia procollagen . its level was decreased in patients with oa or ra . in ra patients treated with low - dose corticosteroids , no data are at this time available to describe their interest to predict relapse in ra patient in remission . bone homeostasis is highly regulated by balance between new bone formation and removing old bone . bone formation markers included the serum bone formation markers total osteocalcin ( oc ) , the alkaline phosphatase bone isoenzyme ( balp ) , and the c- and n - propeptide of type i collagen ( picp and pinp ) . bone degradation is driven by osteoclasts and results in stimulation by rankl induced by il-1 , il-6 , or tnf . osteoclasts secrete cathepsin k , which degrades the collagen type i and releases c - terminal crosslinked telopeptide of type i collagen ( ctx - i ) , or n - terminal crosslinked telopeptide of type i collagen ( ntx ) neoepitope . the crosslinked carboxyterminal telopeptide of type i collagen ( ictp ) is another fragment of c - telopeptide end , which is not released with cathepsin k action but probably mmps [ 52 , 53 ] . other type i collagen crosslinks are pyridinoline ( pyd ) and deoxypyridinoline ( dpd ) . in established ra , uncoupling with low level of bone formation markers and high bone resorption markers was described in 1999 . oc , a bone formation marker , was reduced in ra without destruction compared to controls . on the contrary , ctx - i , a catabolic bone marker , is higher in ra patients with destruction compared to other ra patients . this uncoupling was recently confirmed by using an innovative way to assess bone damage in ra by high - resolution peripheral quantitative computed tomography ( hr - pqct ) . trap 5b level , a catabolic bone marker , was associated with bone erosions , whereas bone alkaline phosphatase ( bap ) was associated with osteophytes . furthermore , in longitudinal studies , catabolic bone markers ( ctx - i or pyd ) are also good predictors for radiologic progression in ra [ 47 , 58 , 59 ] . like cartilage and synovium turnover markers , ratio between bone formation markers and bone resorption markers increased during one year of treatment , suggesting improvement of the bone remodeling balance , mainly due to a decrease in bone resorption . a differential effect was observed at one year of anti - tnf therapy between ictp and ctx - i . ictp , which is related to mmps activity , remained decreased at one year , whereas ctx - i level , which is related to cathepsin k , returned to its baseline level at one year . this suggests a strong effect of anti - tnf on local subchondral bone related to joint inflammation . since tnf blockers already showed a reduction of the bone biomarker unbalance , tnf blockers also demonstrated a positive effect on bone mineral density in ra patients with or without a clinical response as observed at the joint level . all these data support that anti - tnf therapy is not only able to prevent joint destruction , but it is also able to prevent bone loss in ra patients . similarly , with tocilizumab , bone formation biomarker pinp increased whereas bone resorption markers , ictp and ctx - i , decreased . this suggests a nonspecific effect of a pathway but an effect on suppression of joint inflammation . denosumab reduced both serum pinp and ctx - i levels over one year , whereas urinary ctx - ii decreased only at 3 months . since denosumab targets rankl , but not a proinflammatory cytokine , ra disease was not improved , but it reduced erosion progression . so according to the target , drugs have different effects . blocking inflammation reduces bone loss , but blocking pathway induced in bone loss reduced it without effect on ra activity . among all these biomarkers , only ctx - i has demonstrated its ability to be associated with joint destruction , sensitivity to treatment , and prediction of joint progression we showed that synovium , cartilage , and bone turnover biomarkers are correlated with ra activity . to summarize furthermore , these biomarkers could be useful to identify ra patients with high risk of rapid disease progression . since these biomarkers reflected different compartments involved in ra , they will be useful to define structural remission in ra . some of these reviewed biomarkers compose the multibiomarker disease activity ( mbda ) test developed to quantify ra disease activity . recent data suggested that low mbda was associated with clinical remission criteria [ 67 , 68 ] . treat - to - target strategy emerged since few years to manage early ra patients . only one study combining clinical and biomarkers demonstrated its utility in the treat - to- target strategy . however , we need more studies to generate more data to define the place of these biomarkers in ra remission . at this time

objective . the aim of this review is to clarify the usefulness of bone , cartilage , and synovial biomarker in the management of rheumatoid arthritis ( ra ) therapy in remission . synovial biomarkers . high mmp-3 levels are associated with joint progression in ra patients , but there is no data about their utility in clinical remission . iiinys and glc - gal - pyd seem to be more specific to synovium , but more studies are required . cartilage biomarkers . unbalance between cartilage break - down biomarkers ( urinary ctx ii and comp ) and cartilage formation biomarker ( piianp ) was described . this unbalance is also associated with joint destruction and prognosis of destruction . no data are available on patients in remission . bone biomarkers . ra activity is correlated with an increase of bone resorption markers such as ctx i , pyd , and tracp 5b and a decrease of bone formation markers such as oc and balp . ra therapies seem to improve bone turnover in limiting bone resorption . there is no study about bone marker utility in remission . conclusion . biomarkers seem to correlate with ra activity and progression . they also could be used to manage ra therapies , but we need more data on ra remission to predict relapse .

the celiac trunk ( ct ) is the first ventral branch of abdominal aorta and arises at the level of t12/l1 . the main branches of ct include left gastric , common hepatic , and splenic arteries . ct supplies the primary organs of the supracolic abdominal compartment . after arising from ct , the common hepatic artery runs downward and to the right to reach the first part of the duodenum . at this level the hepatic artery proper ascends in the right free margin of lesser omentum and divides into right and left hepatic arteries . presence of collateral branches , complete absence of the trunk , and bifurcation of the trunk are the reported variations of ct . very few reports pertaining to the unusual course of rha have been reported in the literature . knowledge of arterial variations of ct and its branches is useful in planning and executing the radiological interventions and surgeries in supracolic abdominal compartment . the present case is of tremendous importance because the loop of the rha might get injured during laparoscopic cholecystectomy . during the routine dissection classes for first - year undergraduate medical students , we observed concurrent arterial variations in the supracolic abdominal compartment . these variations were found in a male cadaver of indian origin , aged approximately 60 years . the left gastric artery arose from the abdominal aorta , very close to the origin of ct , at the level of twelfth thoracic vertebra . the common hepatic artery was tortuous and it terminated in front of the portal vein by dividing into right and left hepatic arteries [ figures 1 and 2 ] . the rha gave origin to gda in front of the bile duct and then made a characteristic loop around the bile duct with convexity to the right side , and then entered the liver by passing through the porta hepatis behind the bile duct [ figure 2 ] . the splenic artery passed along the upper border of the pancreas to reach the spleen . dissection of the supracolic compartment of the abdominal cavity showing the origin of celiac trunk ( ct ) in the form of hepatosplenic trunk and origin of left gastric artery ( lga ) directly from abdominal aorta , close to the origin of ct . origin of right hepatic artery ( rha ) and left hepatic artery ( lha ) is also seen . note the origin of gastroduodenal artery ( gda ) from the right hepatic artery ( rha ) in front of bile duct ( bd ) . [ splenic artery ( sa ) , common hepatic artery ( cha ) , portal vein ( pv ) , stomach ( s ) , pancreas ( p ) ] dissection of the supracolic compartment of the abdominal cavity showing the characteristic loop of right hepatic artery ( rha ) around the bile duct with convexity to the right side , before entering into porta hepatis and detached portion of gastroduodenal artery ( gda ) from the right hepatic artery ( rha ) . [ celiac trunk ( ct ) , splenic artery ( sa ) , common hepatic artery ( cha ) , right hepatic artery ( rha ) , left hepatic artery ( lha ) , portal vein ( pv ) , bile duct ( bd ) , pancreas ( p ) , stomach ( s ) ] the variations in the ct are due to unusual embryological development of the ventral splanchnic branches of the aorta . usually , ct branches into the splenic , common hepatic , and left gastric arteries . all the three of its branches might come directly from the abdominal aorta as independent branches . additional branches of the ct other than its usual branches are commonly referred to as collaterals . mburu et al . have reported the prevalence of collateral branches from ct , in 20.3% cases . a study conducted on the branching pattern of ct in kenyan population observed that the ct trifurcated in 61.7% and bifurcated in 17.9% of cases . different patterns of bifurcation of the ct such as gastrophrenic , hepatosplenic , hepatogastric , and lienogastric trunks have been reported . chitra have reported the incidence of hepatosplenic trunk in 13.1% and 2% cases , respectively . in the present case , we observed the hepatosplenic trunk with left gastric artery arising from the abdominal aorta , close to the origin of ct . computerized tomographic angiography is usually used to reveal the vascular variations of the upper abdomen . a sound knowledge of possible existence of vascular variations , as observed in the present case , is essential for radiologists and surgeons to prevent iatrogenic injuries in this region . earlier , a cadaveric study documented the origin of gda from the ct , in 3.61% of cases . gda may also arise from the superior mesenteric artery and right or left hepatic artery . nishida et al . have reported a case of gda steal syndrome during liver transplantation . this syndrome is characterized by low arterial flow towards the graft caused by a shift of flow into gda . therefore , awareness of possible existence of aberrant origin of gda is important for recognition and successful ligation of gda to prevent such consequences . in the procedure of hepatic arterial infusion pumps in hepatic arterial chemotherapy and also for liver and/or colon resection , hence , the knowledge of varied origin of gda from the rha , as in our case , is important for radiologists and surgeons for successful cannulation . the variations in the course of rha , in relation to the bile duct , are very rare . earlier , few reports have showed the presence of the tortuous rha forming the caterpillar hump which is also called as moynihan 's hump . in their study , the loop was formed around the common hepatic duct . in the present case , we report a rare case of tortuous common hepatic artery and the tortuous rha forming caterpillar hump , winding around the bile duct . the characteristic sinuousness of the rha is more susceptible to injury following the surgical procedures such as resection of tumor of the pancreatic head and other invasive interventions such celiacography and chemoembolisation of pancreatic and liver tumors and during cholecystectomy . further , gda arose from this artery close to its loop . while performing hepatic arterial chemotherapy , the aberrant origin of gda from the looped course of rha invites injury unless it is carefully recognized and dissected . though hepatosplenic trunk is not a rare finding , tortuous course of both the cha and rha is not common . further , the origin of gda from the rha close to the looped course has immense importance in the procedure of hepatic arterial chemotherapy .

celiac trunk usually trifurcates and supplies the organs in the supracolic compartment . the vascular variations are common in this region . there are reports on the variant course of right hepatic artery ( rha ) . the tortuous rha forming a caterpillar hump is a rare finding and also its providing origin to gastroduodenal artery ( gda ) is an important observation . during routine dissection of abdomen of approximately 60-year - old male cadaver , concurrent arterial variations were observed . the celiac trunk bifurcated into splenic and common hepatic arteries . the left gastric artery arose from the abdominal aorta . the common hepatic artery was tortuous and divided into right and left hepatic arteries in front of portal vein . the rha gave origin to gda and then made a characteristic loop around the bile duct with the convexity to the right side . knowledge of arterial variations of celiac trunk and its branches is useful in planning and executing the radiological interventions and surgeries in the supracolic abdominal compartment .

chronic chylous ascites , associated with malignant obstructions in the lymphatic channel , does not usually cause acute abdominal pain . that is , chyle extravasation into the peritoneal cavity is rarely associated with the sudden development of peritonitis ( 1 ) . we present a case of acute chylous peritonitis in a patient with advanced gastric carcinoma who presented with signs and symptoms of peritonitis caused by ovarian torsion . the department of surgery was consulted for the finding of milky peritoneal fluid in a 41-yr - old female undergoing a complete abdominal hysterectomy with bilateral salphingo - oophorectomy ( tah - bso ) by a gynecologist at our institution . the patient had been admitted to the yonsei university medical center , seoul , korea , for chemotherapy due to advanced gastric carcinoma . a previous computed tomography ( ct ) scan had shown bilateral metastatic ovarian tumors . during her stay , a physical examination revealed direct tenderness to palpation , rebound tenderness , and guarding ; she was also noted to have a palpable left supraclavicular node . a chest radiography was normal ; an emergent abdominal pelvic ct scan showed increased bilateral ovarian tumors with minimal intraperitoneal fluid collection ( fig . the initial blood laboratory results showed a total leukocyte count of 3,600/l with 58% neutrophils , hb 12.8 g / dl , platelet count 245,000/l , na 143 mm / l , k 3.9 mm / l , cl 103 mm / l , bun 13.6 mg / dl , creatinine 0.9 mg / dl , glucose 116 mg / dl , ast 20 iu / l , alt 14 iu / l , and total bilirubin 0.6 mg / dl . based on the physical examination and ct findings , peritonitis caused by ovarian torsion was strongly suspected , leading a gynecologist to perform an exploratory laparotomy on an emergency basis . in the operative field , however , a minimal to moderate amount of milky peritoneal fluid was observed in the pelvic cavity and along the right paracolic gutter . after the tah - bso , the patient was evaluated at the department of surgery for chylous ascites . on intraperitoneal exploration , the stomach seemed to be tethered to the pancreas , but there was no evidence of peritoneal carcinomatosis . diffuse lymphatic ectasia and milky fluid discharge were noted around the small bowel mesentery ( fig . she was given a fat - free diet , and no evidence of reoccurrence of ascites was noted on clinical observation , such as the measurement of daily body weight and abdominal circumference . chylous ascites is an uncommon finding , with an incidence of 1 in 20,000 hospital admissions ( 2 ) . paracentesis is the most important diagnostic modality and reveals milky peritoneal fluid with a triglyceride concentration 2 to 8 times that of plasma ( 3 ) . malignant lymphoma is the most common cause of chylous ascites and accounts for 50% of cancer - related cases ( 4 ) . malignant invasion causes lymphatic channel fibrosis and disruption of the peritoneal cavity lymphatic system , enhancing extravasation distal to the obstruction . other malignancies such as colon , pancreatic , stomach , ovarian cancers , and intestinal carcinoid , kaposi sarcoma , and lymphangiomyomatosis ( 5 ) can also cause chylous ascites . other etiologies include infectious diseases , such as peritoneal tuberculosis and lymphatic filariasis , lymphatic system congenital anomalies , radiation side effects , abdominal surgery complications , and portal hypertension from liver cirrhosis ( 6 ) . chronic chylous ascites usually does not present with acute abdominal pain , as mentioned previously . in the present case , the abrupt onset was accompanied by peritoneal signs that led to an emergency exploratory laparotomy due to a concern of ovarian torsion caused by large bilateral ovarian krukenburg 's tumors . strictly speaking , the operative finding did not show any evidence of acute inflammatory changes in the patient 's peritoneal cavity ; however , clinical symptoms definitively suggested peritonitis , requiring immediate surgical intervention . therefore , the diagnosis of acute chylous peritonitis may be more appropriate than that of chylous ascites , depending on the clinical setting . although there was no gross lymphadenopathy or peritoneal cancer seeding , microscopic metastasis in the small lymphatic system was suspected as the etiology . later it was revealed that the patient had left supraclavicular engorgement , which subsequently decreased after the laparotomy . disruption of the abdominal cavity peripheral lymphatic system , caused by thoracic duct obstruction from a metastatic left clavicular lymph node , resulted in sudden extravasation and acute chylous peritonitis . in our hypothesis , if it had not been for the chylous ascites , the abrupt onset of chylothorax might have occurred , and would have presented with dyspnea as the initial symptom . the optimal management of chylous ascites includes a protein - rich , low - fat diet , medium - chain triglycerides , sandostatin , and orlistat ( xenical ) ( 7 - 10 ) . total parenteral nutrition can be used to decrease lymphatic flow and to promote lymphatic disruption closure . although no drain catheters were placed , there was no evidence of further peritoneal fluid collection . in this case , the symptoms and signs of peritonitis were present ; however , there was no accompanying fever , leukocytosis , or intraperitoneal free air . although spontaneous acute chylous peritonitis is rare , the disease should be considered in a patient with underlying malignant disease and signs of peritoneal irritation without associated leukocytosis , fever , and intraperitoneal free air . in these cases , laparoscopy prior to laparotomy would have confirmed chylous ascites and resulted in a less invasive surgical procedure .

the extravasation of chyle into the peritoneal space usually does not accompany an abrupt onset of abdominal pain with symptoms and signs of peritonitis . the rarity of this condition fails to reach preoperative diagnosis prior to laparotomy . here , we introduce a case of chylous ascites that presented with acute abdominal pain mimicking peritonitis caused by ovarian torsion in a 41-yr - old female patient with advanced gastric carcinoma . an emergency exploratory laparotomy was performed but revealed no evidence of ovarian torsion . only chylous ascites was discovered in the operative field . she underwent a complete abdominal hysterectomy and salphingo - oophorectomy . only saline irrigation and suction - up were performed for the chylous ascites . the postoperative course was uneventful . her bowel movement was restored within 1 week . she was allowed only a fat - free diet , and no evidence of re - occurrence of ascites was noted on clinical observation . she now remains under consideration for additional chemotherapy .

missile injuries of the anterior skull base usually occur during war or warlike situations ; however , in the united states , > 100 americans die by suicide on an average day , and 50 of these suicides involve the use of firearms.1 the anterior skull base is the most common region of the skull base injured by a cranial missile . most csf leaks can be broadly classified into traumatic ( most frequent ) , nontraumatic ( tumors ) , spontaneous , and iatrogenic.2 the clinical presentation usually is of unilateral clear rhinorrhea that can be continuous or persistent . the patient can complain of a saltwater taste sensation ; fewer patients experience a sweet taste sensation . also , the halo sign ( clear ring surrounding a central bloody spot on gauze ) can be present . high - resolution computer tomography ( ct ) is a vital diagnostic and planning tool in patients with cranial and maxillofacial trauma . ct cisternography , radionuclide cisternograms , magnetic resonance imaging ( mri ) , -2 transferrin , and intrathecal fluorescein are also part of the armament used in the diagnosis of csf leaks . the goals of surgery in patients with gunshot wounds to the head are to evacuate a hematoma , achieve hemostasis , debride the wound , provide dural closure , and repair the skull base . we present two cases of patients with csf leak after gunshot wound to the skull base . a 16-year - old young man with a history of a self - inflicted gunshot wound with point of entry through the mouth with a 3-cm exit wound on top of the head . ( a ) noncontrast axial computed tomography consistent with a gunshot wound with entry point at the left parasagittal midline hard plate ( white arrow ) . ( b ) fracture of the inner table of both frontal sinuses with multiple fragments within the frontal sinuses and along the interhemispheric fissure ( white arrow ) . ( c ) the trajectory coursed cranially through the left nasal cavity , left ethmoid air cells , left frontal lobe , and exited through the left frontal bone . ( d ) posterior intracranial view shows missile trajectory entering through the skull base and exiting through the left frontal bone ( arrow ) . the patient underwent endoscopic reduction and debridement of a frontal sinus encephalocele and csf leak repair . the bone fragments were debrided as well as the brain tissue within the cavity . a large posterior table defect in the left frontal sinus the brain tissue was covered with duragen ( integra lifescience corporation , plainsboro , new jersey , united states ) . the mucosa of the frontal sinus was removed , and abdominal fat was packed to obliterate the cavity . a mucosal graft was not feasible due to the location and extent of the defect . to date the patient is without any complaints of clear rhinorrhea or a salty taste sensation . nasal endoscopy shows a bilateral patent frontal sinus recess with no evidence of obstruction or drainage . ( a ) sagittal magnetic resonance t1 fluid - attenuated inversion recovery scan shows postoperative result of frontal sinus obliteration and frontal sinus encephalocele repair . bilateral frontal cortical and subcortical encephalomalacia from sequela from gunshot wound injury ( arrow , a and b ) . ( b ) residual pneumatization of the left frontal sinus ( arrowhead , a and b ) . no evidence of frontal sinus mucocele formation . a 19-year - old female patient presented with a self - inflicted gunshot wound to the right frontal lobe with right intracerebellar hematoma . upon arrival , neurosurgeons performed a first attempt to repair the frontal sinus floor with an inner table of bone flap . the bullet involved the frontal sinus , the posterior ethmoid , nasal septum , right sphenoid sinus , and medial pterygoid plate with a major bullet fragment lodged into the right , at c2-c3 vertebral level , without lesions of the cervical spine . ( a ) coronal head computed tomography ( ct ) shows the skull base fracture ( arrow ) . ( b ) sagittal view of head ct shows bullet entry in the forehead through the anterior and posterior walls of the right frontal sinus ( arrow ) . one month after discharge , the patient was complaining of right - sided clear rhinorrhea , with no salty taste sensation in her mouth . postfrontal craniectomy ct was done , and the patient was scheduled for endoscopic csf leak repair ( fig . right anterior ethmoidal air cells opacification ( arrowhead ) with fracture of ethmoid sinus roof ( arrow ) . then 0.1 ml of preservative - free 10% fluorescein was mixed with 10 ml of csf and slowly injected intrathecally over 30 minutes . the sites of the csf leak were identified at the ethmoid frontal junction anteriorly and in the posterior ethmoidal cells . previous harvested abdominal fat was positioned at the site of the leaks , which resulted in cessation of the fluorescein - identified leak . both grafts were supported with surgicel ( ethicon , inc . , somerville , new jersey , united states ) followed by duraseal ( confluent surgical , inc . , waltham , massachusetts , united states ) . nexfoam ( hemostasis , saint paul , minnesota , united states ) were placed to further support the graft , and two merocels ( medtronic , mystic , connecticut , united states ) were placed in the right nasal cavity . to date there is no evidence of csf leak . a 16-year - old young man with a history of a self - inflicted gunshot wound with point of entry through the mouth with a 3-cm exit wound on top of the head . ( a ) noncontrast axial computed tomography consistent with a gunshot wound with entry point at the left parasagittal midline hard plate ( white arrow ) . ( b ) fracture of the inner table of both frontal sinuses with multiple fragments within the frontal sinuses and along the interhemispheric fissure ( white arrow ) . ( c ) the trajectory coursed cranially through the left nasal cavity , left ethmoid air cells , left frontal lobe , and exited through the left frontal bone . ( d ) posterior intracranial view shows missile trajectory entering through the skull base and exiting through the left frontal bone ( arrow ) . the patient underwent endoscopic reduction and debridement of a frontal sinus encephalocele and csf leak repair . the bone fragments were debrided as well as the brain tissue within the cavity . a large posterior table defect in the left frontal sinus the brain tissue was covered with duragen ( integra lifescience corporation , plainsboro , new jersey , united states ) . the mucosa of the frontal sinus was removed , and abdominal fat was packed to obliterate the cavity . a mucosal graft was not feasible due to the location and extent of the defect . to date the patient is without any complaints of clear rhinorrhea or a salty taste sensation . nasal endoscopy shows a bilateral patent frontal sinus recess with no evidence of obstruction or drainage . ( a ) sagittal magnetic resonance t1 fluid - attenuated inversion recovery scan shows postoperative result of frontal sinus obliteration and frontal sinus encephalocele repair . bilateral frontal cortical and subcortical encephalomalacia from sequela from gunshot wound injury ( arrow , a and b ) . ( b ) residual pneumatization of the left frontal sinus ( arrowhead , a and b ) . a 19-year - old female patient presented with a self - inflicted gunshot wound to the right frontal lobe with right intracerebellar hematoma . upon arrival , neurosurgeons performed a first attempt to repair the frontal sinus floor with an inner table of bone flap . the bullet involved the frontal sinus , the posterior ethmoid , nasal septum , right sphenoid sinus , and medial pterygoid plate with a major bullet fragment lodged into the right , at c2-c3 vertebral level , without lesions of the cervical spine . ( a ) coronal head computed tomography ( ct ) shows the skull base fracture ( arrow ) . ( b ) sagittal view of head ct shows bullet entry in the forehead through the anterior and posterior walls of the right frontal sinus ( arrow ) . one month after discharge , the patient was complaining of right - sided clear rhinorrhea , with no salty taste sensation in her mouth . postfrontal craniectomy ct was done , and the patient was scheduled for endoscopic csf leak repair ( fig . right anterior ethmoidal air cells opacification ( arrowhead ) with fracture of ethmoid sinus roof ( arrow ) . then 0.1 ml of preservative - free 10% fluorescein was mixed with 10 ml of csf and slowly injected intrathecally over 30 minutes . the sites of the csf leak were identified at the ethmoid frontal junction anteriorly and in the posterior ethmoidal cells . previous harvested abdominal fat was positioned at the site of the leaks , which resulted in cessation of the fluorescein - identified leak . both grafts were supported with surgicel ( ethicon , inc . , somerville , new jersey , united states ) followed by duraseal ( confluent surgical , inc . , waltham , massachusetts , united states ) . nexfoam ( hemostasis , saint paul , minnesota , united states ) were placed to further support the graft , and two merocels ( medtronic , mystic , connecticut , united states ) were placed in the right nasal cavity . to date there is no evidence of csf leak . csf is an ultrafiltrate of plasma produced by the choroid plexus that offers mechanical and immunologic protection for the brain . a csf rhinorrhea is defined as a fistula between the dura and the skull base with csf discharge through the nose.3 about 70 to 80% of csf leaks are secondary to trauma and evident within the first 2 days , first week , or within the first 3 months.2 4 energy deposited along the missile trajectory shatters the bone and lacerates soft tissues , which makes it difficult to diagnose a csf leak upon arrival.5 also , the surrounding edema associated with the trauma can conceal these leaks momentarily , so csf leaks can be revealed after this edema subsides or necrosis of the surrounding tissues occurs . the greatest concern with a csf leak is the potential for meningitis , with a generally accepted rate of 10%.6 approximately 35% of patients with recurrent meningitis have csf leaks secondary to trauma.2 a missile traversing the face creates a communication between air - filled mucus - secreting cavities and the subarachnoid spaces with wound contamination through the missile entry point from oropharyngeal commensal staphylococcus , gram - negative or gram - positive rods.7 a 2006 cochrane review8 concluded that no evidence indicates that prophylactic antibiotics reduce the risk of meningitis in patients with skull base fractures with active csf leak . however , there are no data to apply this statement to patients with gunshot wounds to the head . high - resolution ct is vital for the planning and prognosis of patients with a gunshot wound to the head ; it is also the preferred method to localize the site of a skull base fracture . however , ct cisternography or mri may be required to diagnose csf rhinorrhea . in the presence of a skull base fracture on ct and a clinical csf leak , there is no need for a further confirmatory test . in cases where a confirmatory test is needed , the -2 transferrin assay is the test of choice because of its high sensitivity and specificity.4 9 intrathecal fluorescein has been used to confirm and intraoperatively localize csf leaks.2 4 the recommended dilution is 0.1 ml of 10% intravenous fluorescein in 10 ml of the patient 's own csf that is infused slowly over 30 minutes . a yellow fluid leaking in the nose should be visualized in the vicinity of the defect , and the use of a blue - light filter makes the sensitivity even higher . patients with csf leaks < 7 days have an 11% chance to develop meningitis versus 88% of those lasting > 7 days . surgical treatment is indicated when they last > 1 or 2 weeks.10 patients with increased intracranial pressure , such as those who experience intracranial trauma , make hernias at points of weakness ; these patients have a less successful rate of csf leak closure and more risk of developing meningoencephalocele.4 nonetheless , the success rate of surgical closure is 95% for csf leaks associated with trauma.11 in patients with a gunshot wound to the head , neurosurgical intervention is usually required , so it is reasonable to repair an evident csf leak . however , when intracranial trauma is present , the associated significant brain edema makes an early repair likely to fail because of elevated intracranial pressure . in agreement with other authors,12 13 we believe the use of a lumbar drain does not provide an additional benefit in the treatment of csf leaks associated with gunshot wounds to the head , especially because of the risk of overdrainage and the resultant pneumoencephalos . endoscopic closure of csf leaks was first described by wigand in 1981 , and to date , it continues to be the preferred method of csf leak closure because of its high success rate ( 9097%).2 3 4 9 10 14 in cases of trauma , an open approach for repair of these lesions is still favored . we present two cases where satisfactory endoscopic csf leak repair was performed after gunshot wound to the head . the primary goal of the repair is to separate the intracranial from the extracranial spaces . in the cases presented , an endoscopic repair was favored to minimize brain manipulation of an already severely injured brain . cranial base repair with fat and/or mucosa is utilized in other instances and highly successful . postoperative recommendations are 30 degrees of head elevation , bed rest , stool softeners , antiemetics , blood pressure management , and recommendations to refrain from sneezing , nose blowing , coughing , and valsalva maneuvers . endoscopic closure of anterior skull base csf leaks is now recognized as the treatment of choice for most csf leaks . in those cases resulting from firearm injuries , treatment should be decided by the severity of neurologic deterioration throughout the emergency period and the existence or absence of associated intracranial lesions . the risk of suppurative sequelae in patients with a missile trajectory though the skull base are high , especially when the sinuses have been compromised , so the timing for surgery should be decided with great care and with a multidisciplinary approach . in selected patients in whom the primary concern is the repair of a csf leak and there is no need to address intracranial injuries , an endoscopic endonasal repair can be safe and effective .

objectives to describe two cases of cerebrospinal fluid ( csf ) leak repair after gunshot wound to the head . design retrospective review of two cases . settings a large regional tertiary care facility . participants two patients with gunshot wounds to the skull base . main outcome measures preoperative and postoperative physical and radiologic findings . results patients in this series underwent endoscopic surgery , debridement , and repair of csf leaks after gunshot wounds to the head . to date , the patients are without csf leak . conclusions endoscopic closure of anterior skull base csf leaks in patients with gunshot wounds can be safe and effective . treatment should be decided by the severity of neurologic deterioration throughout the emergency period and the existence or absence of associated intracranial lesions . timing for surgery should be decided with great care and with a multidisciplinary approach .

gonadal dysgenesis refers to a variety of clinical conditions in which abnormal development of the fetal gonad is present . it consists of 46 , xy gonadal dysgenesis , mixed gonadal dysgenesis ( mgd ) , and 45 , x turner syndrome . mgd , a disorder of sex development ( dsd ) , is defined in individuals who typically have a differentiated gonad on one side and a streak gonad or streak testis ( usually intra - abdominal ) on the other side . however , true hermaphroditism ( th ) cases have both unequivocal ovarian tissue and testicular elements independent to their karyotypes . th and mgd should be differentiated , and a counseling physician should be consulted to decide for early gonadectomy in mgd to prevent the high risk of malignancy . sex chromosome mosaicism ( 45 , xo/46 , xy ) is the most common karyotype expressed in mgd and may cause formation of a dysgenetic or malformed gonad . ambiguous genitalia is the most common presentation for individuals with a 45x/46xy karyotype accounting for about 60% of involved individuals . in clinical examination , for this reason , a chromosomal study via karyotyping is necessary to be done for any patient with penoscrotal hypospadias and undescended testis . measurement of the level of anti - mllerian hormone ( amh ) , which is usually insufficient in dysgenetic gonad , can also help us to differentiate any type of intersexual condition . in these conditions , the patients have female reproductive organs such as a hemi - uterus and fallopian tube in testicular dysgenesis . meanwhile , patients with impaired testosterone secretion show the level of amh either within normal limit or slightly elevated . y chromosome behavior is a strong risk factor for germ cell tumors ; however , hormone production via saving testis is very varied and depends on each case individually [ 1113 ] . the correlation of clinical phenotype in mgd with cancer risk has been shown to be as high as 52% . in mild mgd , however in more severe mgd , testicular cancer may be observed at a younger age . we present a rare case with mgd and a new pattern of chromosome in the karyotype , 45 , x/46 , x , + mar(y ) . a ten - year - old boy was referred to the pediatrics clinic of hazrat rasul akram hospital with left - sided cryptorchidism , penoscrotal hypospadias , and growth retardation . his height was 118.7 cm , and his body weight was 22 kg ( 25th percentile ) . he was raised in a nursery center as a result of his father s incompetence and some family problems , which might be the reason why he had not sought any medical advice earlier . his physical examination consisted of a significant short stature , low - set hair line , a gonadal phenotype similar to male genitalia with hypospadias , chordee penis , and a left - sided undescended testis ( udt ) . in karyotype , 20 metaphases were assessed on the basis of gtg technique at 450500 band resolution including five plates ( 25% ) of 45x , and the remaining plates ( 75% ) revealed 46 chromosomes with a small marker chromosome ( 45 , x /46 , x , + mar . thus , a molecular study was planned to determine the origin of the marker chromosome . in the molecular study , dna was extracted from peripheral blood leukocytes to seek the sex - determined region of the y chromosome ( sry ) gene by pcr technique . the specific probes for x and y chromosomes were also applied to approach the origin of the marker in a fish study . these results revealed presence of both x and y chromosomes and sry genes which were compatible with a male phenotype . ultrasound examination revealed no left testis in the scrotum or inguinal canal , and no sign of remnants of mllerian structures , such as the uterus , was appreciated . after counseling with the patient , his family , and pediatric psychologist , the decision was made to pronounce the patient male gendered . subsequently , explorative laparoscopy was offered , and left testis was seen on the left internal ring . in addition , the fallopian tube and a single ovary were seen on the same side , but no uterus was observed . laparoscopy orchiectomy was performed , and remnants of mllerian duct were excised . in a histopathologic review of specimen , streak ovary , fallopian tube , and testis were confirmed . the patient was referred for urology and endocrinology evaluation , and a trial of gh therapy for treatment of short stature was considered . johansen and coworkers reported structural rearrangement of the y chromosome in 63% of mgd patients . therefore , pcr was performed for the sex - determining region of the y chromosome ( sry ) upon proposal of mgd as the primary diagnosis . most mgd cases require corrective surgery because of the two mismatched gonads . in case of the decision to convert to male gender if the child s phallus is small , she would function better as a female ; therefore , the testis should be removed . normal right side testis in our patient produced adequate testosterone to enhance puberty and body shape formation . in addition , the patient was raised as a male , and he preferred to stay as such . although there is no exact prediction of tumor risk in normal appearing males with mosaic ( 45x , 46xy ) karyotype , tumor risk was anticipated low in our patient due to normal testicular differentiation and maturation process present in the clinical manifestation , including a normal external masculinization score ( ems ) and bilaterally descended testes . therefore , according to this observation , we decided to preserve our patient s right testis with close follow - up in order to prevent gonadoblastoma formation . however , early diagnosis and evaluation is very important for preventing psychological sequels as well as ruling out other abnormalities . meanwhile , a complete and sufficiently careful medical evaluation and genetics counseling of neonates referred to nurseries is highly recommended to avoid any delayed and insufficient diagnostic , conservative , therapeutic , and psychological care in children with guardians rather than their biological parents . johansen et al . reported an adequate gonadal function in male gender to produce pubertal phase . , acts as a sign of clinically malfunctioning gonads in patients with a very low ems . phonotypical males with a 45 , x/46 , xy karyotype and its variants assume to have normal testicular function and spontaneous puberty even in patients with ambiguous genitalia . however , some patients might need hormone replacement therapy ( hrt ) after spontaneous pubertal onset . in male patients with mgd , the cause of infertility is udt and dysgenetic testis . the prevalence of growth retardation is high although it seems not to be due to growth hormone ( gh ) deficiency . in our case , providing a multidisciplinary approach to managing these children is crucial , like our medical team , which included a pediatric endocrinologist , genetics counselor , laparoscopic surgeon , and psychologist . a multidisciplinary approach is necessary and crucial for early diagnosis and proper management of these patients in order to prevent mental and social sequels . all authors declare that they have no financial conflict of interest , and the supporting organization has supported the scientific aspect of the research . author namestudy concept and designacquisition of datastatistical analysis and interpretation of datadrafting of the manuscriptcritical revision of the manuscript for important intellectual contentadministrative , technical , and material supportfahimeh soheilipourommolbanin abedbabak behnammohammadreza abdolhosseinipeyman alibeigiabdolreza pazouki(corresponding author) written informed consent was obtained from the patient for publication of this case report and accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal on request , however it is in persian .

highlightsthe clinical presentation of mixed gonadal dysgenesia is known as criptorcidism and undesending testis.mixed gonadal dysgenesia with mosaism 45 , x/46 , x , + mark karyotype are rare case.we present a rare patient case with mixed gonadal dysgenesis as a disorder of sex development ( dsd ) and a new pattern of chromosome in the karyotype , undergoing laparoscopic procedure for sex correction .

alpha - thalassemia ( thal ) is one of the most common hemoglobin genetic abnormalities that caused by reduced or absent production of the alpha globin chains ( 1 ) . clinical manifestation of thal varys from mild microcytic to life - threatening anemia ( 2 ) , thus thalassemia can lead to microcytosis ( 3 ) . the thal is prevalent in southeast asian , mediterranean , and middle eastern populations ( 1 ) , where malaria has been epidemic . southeast asia is one of the regions with the highest frequency of the -thalassemia genes . for example one of the highest incidences of -thalassemia in the world ( 5 - 10% ) has found in the northern thailand ( 4 ) . in iran surprisingly , rahim has reported the overall frequencies of -thalassemia in the southwest region of iran , as 57% among microcytic and hypochromic anemia patients ( 6 ) . hb electrophoresis is an expensive test for routine surveillance of neonates , even in high risk regions for the -thalassemia gene but there are some cheaper tests for its prediction . mean corpuscular volume ( mcv ) below 90 femtoliters ( fl ) and mean corpuscular hemoglobin ( mch ) below 30 picograms ( pg ) were found to be very high predictive parameters for -thalassemia detection ( 7 ) . hence , low mcv and mch in high risk regions of countries can point to the presence of this condition and considered also as key points for its detection . although iron deficiency may also lowers the cause low mcv and mch values ( 6 ) . during in the neonatal period , although microcytosis can occur because of the iron deficiency caused by fetomaternal hemorrhage , but it is extremely uncommon ( 2 ) . nonetheless it can be presumed that almost all microcytosis cases in this period are associated with thalassemia . since -thalassemia does not present in neonatal period , almost all are due to other type , thal ( 2 ) . on the other hand , identification of thal in neonatal periods is very important to prevent unnecessary interventions ( such as iron therapy ) in patients with microcytic anemia ( 8) . for instance , newborn carriers with thal usually have a slight to moderate ( 15% ) increase in hb bart ( 4 ) when measured by hemoglobin electrophoresis or hplc . since the hb barts tends to disappear a few weeks after birth , the diagnosis of thal is not possible for most laboratories , after the neonatal period , and these patients are labeled wrongly as iron deficient anemia , etc . although there are several studies in this field , but -thal is more studied than thal in iran because of its clinical importance and there are not enough data on the frequency of thal in different places of iran . since iranian population is a mixture of different ethnic groups , it is crucial to figure out the frequency and distribution of -thalassemia in various regions of the country . the present study aimed to determine the prevalence of microcytosis in newborns who born in akbarabadi hospital in tehran , iran . this was a cross sectional study on 1001 iranian newborns who born in akbarabadi hospital , tehran , iran . this study was done from march 2010 to march 2011 and approved by the ethical committee of the tehran university of medical sciences and written informed consent was obtained from the parents of eligible infants . exclusion criteria were as follow : gestational age less than 37 , neonatal hemoglobin lower than 14 , severely malnourished mothers ( with body mass index lower than 18 kg / m2 ) , and mothers with any chronic medical disease such as diabetes mellitus . for determining the overall prevalence of neonatal microcytosis , routine red blood cell parameters were investigated by automated cell counters ( sysmex k800 , and sysmex kx-21 ) . neonatal microcytosis was defined as mcv below 94 femtoliters ( fl ) and mch below 29.5 picograms ( pg ) at birth towards the presence of thal ( 9,10 ) . all statistical analysis was performed using spss-17 software , and the value of p<0.05 considered as significant level . most of these neonates were male ( 51.4% ) and the rest ( 48.6% ) female . the sd for weight and gestational age of newborns were 2.844 ( 0.253 ) and 38.485 ( 1.869 ) respectively . the mcv of neonates were 114.2 fl ( 95% ci : 113.5 - 114.9 ) in which twenty three ( 2.3% ) had mcv less than 94 fl that identified as microcytosis and 4 ( 0.4% ) had low mch and mcv . the frequency of newborns with normal and abnormal mcv and mch is presented in table 2 . in neonates with microcytosis , low mch although anemia is absent or unremarkable in thal trait , it is important to diagnose the disorder to understand the cause of microcytosis and to avoid repeated expensive analysis and/or prolonged iron therapy . for these reasons , several countries have initiated universal prenatal screening programs to address thal . in our study , 2.3% of our newborns had microcytosis ( mcv < 94 fl ) and only 0.4% showed both low mcv and mch ( mch < 29.5 ) . we did not perform any hb electrophoresis for these cases but it seems that mcv<93.6 can predict thal with 90.9% sensitivity and 82.2% specificity ( 11 ) . schmaier et al . in their study showed that 9 ( 4.5% ) of 200 infants had mcv 94 and of these , 6 ( 67% ) had hb barts . they concluded that mcv and mch screening of newborn can be an easy way for the alpha thalassemia detection . neonatal mcv 94 and mch 29.5 should be followed by hb electrophoresis ( 9 ) . shahriari et al also found that frequency of mcv < 100 fl among shirazian newborns was 32.15% in which 2.35% with mcv < 100 fl showed hb barts using hb electrophoresis . all of these 2.35% , had mcv lower than 93.6 fl and mch lower than 28.75 . this will prevent of expensive tests in adulthood especially in premarital screening tests ( 12 ) . hadavi et al have reported 4.2 deletion in iranian subjects , with a prevalence of 3.5% ( 13 ) . the frequency of thal was 3.6% among turkish newborns in a study that employed globin gene mapping analysis of dna ( 14 ) . additionally , thal trait was observed in 0.63% of participants in a study conducted in the antalya region of turkey ( 15 ) . despite these results , a neonatal screening survey of thal among the united arab emirates ( uae ) nationals demonstrated that 49% of the studied cases had -globin gene defect ( 16 ) . the differences between result of our study and these studies may caused by variation in cut off point for mcv and different sample size and study location . furthermore we did not study anemic newborns and hb > 14 was one of the main inclusion criteria . although in our study , the prevalence of microcytosis was lower than other studies , but it is considerable since 2.3% prevalence of microcytosis was among newborns with normal hemoglobin . it may strongly suggest that thalassemia within these newborns . we did not evaluate cases with hb electrophoresis because of our limitations , therefor further studies to investigate of thalassemia by hb electrophoresis among newborns with normal hemoglobin and low mcv is strongly suggested .

background : identification of thalassemia ( thal ) a common cause of microcytosis during neonatal periods is an important step prevent unnecessary interventions . thus , low the mean corpuscular volume ( mcv ) and the mean corpuscular hemoglobin ( mch ) may consider as -thalassemia key detection points . the present study aimed to determine the prevalence of microcytosis among neonates who born in tehran , iran . methods : cord blood samples were collected from 1001 newborns after birth in labor room and their red blood cell parameters were investigated . results : mcv was 114.2 fl ( 95% ci : 113.5 - 114.9 ) and twenty three neonates ( 2.3% ) had mcv less than 94 fl that classified as microcytosis and 4 ( 0.40% ) had both low mch and mcv . conclusion : low mcv especially in normal hb newborns may hints for thal detection .

it initially presents with difficulty swallowing and is a chronic progressive condition that usually does not resolve . although the specific cause is unknown , the primary pathology involves the inability of the lower esophagus to relax , resulting in delayed passage of food and liquid into the stomach . clinical symptoms range from initial dysphagia to heartburn , a feeling of fullness in the chest and sometimes weight loss . the objective work - up includes barium radiography , esophagoscopy , and esophageal manometry . in patients with achalasia barium radiography often reveals a classic 1 ) in which the dilation tapers into the lower esophagus , because of the chronic buildup of food contents . long - term sequelae include an increased risk of the development of esophageal cancer in patients diagnosed with achalasia . 1bird s beak appearance of lower esophagus during an upper gastrointestinal x - ray swallow study bird s beak appearance of lower esophagus during an upper gastrointestinal x - ray swallow study the objective of treatment is to resolve symptoms in this usually progressive disease . conservative maneuvers have included the use of muscle relaxing medications or injections and dilation of the lower esophagus with endoscopically guided balloons . these usually result in temporary relief only rather than achieving long - term resolution of the problem . surgical intervention involving splitting of the restrictive external muscle of the lower esophagus and upper stomach with subsequent wrapping of the upper stomach partially around the lower esophagus results in symptom relief in 85% of people 10 years after surgery and in approximately 65% of people 20 years after surgery . achalasia was first described , with its initial treatment , by thomas willis in 1679 . treatment and instrumentation have rapidly evolved since his first description of dilation of the esophagus using a tapered whale bone . in 1887 , russel described initial balloon dilatation using a silk bag over a rubber balloon . this surgical technique involved splitting the outer muscle of the lower esophagus to relieve internal narrowing and associated swallowing difficulties . this procedure was subsequently popularized by approaches through the abdomen or through the chest . in the early 1990s , during the beginning of the era of minimally invasive surgery , thoracoscopic and laparoscopic heller myotomy were described . prompt recovery and good outcomes quickly enabled clinicians to conclude that surgical treatment was the optimum primary treatment of choice for amelioration of symptoms in patients with achalasia . laparoscopic heller myotomy using standard laparoscopic techniques has evolved into an extremely safe and efficient technique of reducing symptoms in the treatment of achalasia . preliminary case series demonstrated that early outcomes were favorable and the perioperative course was much improved compared with an open laparotomy or thoracotomy . perioperative complications were reduced and the complications secondary to the trauma of the incision were largely eliminated . laparoscopic heller myotomy has now been widely reported with large case series with relatively good outcomes in both early and late results [ 68 ] . in addition , favorable outcomes have been achieved in some series in which laparoscopic heller myotomy was offered as the first - line therapy . although patient satisfaction , relief of symptoms , and recovery time were categorized as favorable , these large case series still reported a significant number of intraoperative esophageal perforations ranging between 1 and 15% . in these series , the mucosal perforations were identified to have occurred as a technical failure during the course of the division of the muscle fibers from the underlying esophageal mucosa . the clinical relevance of these complications may be uncertain , and when the perforation is recognized at the time of surgery and repair performed immediately the outcomes are still usually good . these perforations expose the patients to a prolonged hospital stay and the risk of an esophageal leak , however . delayed diagnosis of an esophageal perforation is a potential fatal complication and is one of the most significant and serious risks of heller myotomy . management in this situation requires broad - spectrum antibiotic coverage , proximal bowel decompression and rest , potential operative drainage , debridement and reconstruction of the injured tissues , and sometimes intravenous nutritional support for a prolonged period of time . different surgical techniques have been described to avoid the perforation of the underlying mucosa and have included the injection of epinephrine into the submucosal plane , blunt dissection , sharp dissection , and intraoperative esophagoscopy to evaluate the esophageal mucosa and detect underlying perforations . the da vinci surgical system ( intuitive surgical , inc ; sunnyvale ca , usa ) is currently the only robotic telesurgical device marketed and approved for general surgery in the united states . the device is a computer interface that interacts with the operating surgeon who sits at a control panel connected to a bedside actuator with instrument holders and a camera manipulator ( figs . 2 , 3 ) . motion is enhanced by filtering fine motor tremor and providing motion scaling between the hand - piece and the activator arm , enabling up to 5-to-1 scaling . innovations have now incorporated 5 mm instrumentation enabling reduced abdominal wall trauma and addition of a fourth working arm for enhanced mobility , tissue handling , and retraction . 3the da vinci surgical robot in use with head surgeon operating from the console the da vinci surgical robot in use with assistant surgeons alongside operative table the da vinci surgical robot in use with head surgeon operating from the console the robotic device has the unique ability to enhance surgical technique and , therefore , optimize surgical outcome . these advantages specifically are fine motor control , three - dimensional magnification , and motion scaling . these may be significant in operative procedures such as heller myotomy or in cases when optimum completion of the operation requires these specific surgical techniques . it is this enhancement of surgical performance that may have improved the surgical outcomes mentioned above regarding recent case series comparing robotic telesurgery with historic laparoscopic approaches to heller myotomy . using this model it may be reasonable to identify some surgical procedures and interventions , for example heller myotomy , that can specifically benefit from this type of therapy . at the author s institution robotic telesurgery for achalasia preoperative preparation of patients with achalasia may include a prolonged period of fasting to completely empty the esophagus . clear liquids for 48 h preoperatively are routine , especially in cases of severe esophageal dilatation . preoperative hospital admission may be necessary for patients to enable them to maintain fasting with intravenous hydration . preoperative antibiotics and oral anti - fungal medications should be included to help reduce the amount of contamination within the esophagus . the patient is positioned on a split leg table or in a modified lithotomy ( legs apart and gently angled down ) position after the induction of general anesthesia . the bedside component of the robot is positioned over the patients left shoulder after accessing the abdomen through four ports . the patient is placed with the head of the bed angled upwards and the patient s motion must be completed before docking to the robot ports . two working ports are used with downward traction of the upper part of the stomach by the assistant or the fourth arm of the robot . the esophageal hiatus of the diaphragm is identified and the crura are circumferentially dissected free of peritoneal attachments . the distal esophagus is dissected , and a soft rubber penrose drain is usually placed around the distal esophagus for traction , enabling dissection up into the lower mediastinum . the esophageal myotomy is created using the electrocautery hook of the robotic device ( fig . the articulation of this arm provides precise control and helps keep the end of the hook directly parallel to the esophageal mucosal wall . this dissection is aided by a curved dissector on the opposite arm , to help completely separate the muscle fibers . when the submucosal is plane is developed between the outer esophageal musculature and the inner mucosa , the division of the muscle fibers is carried 810 cm proximal and at least 2 cm distally from the junction of the esophagus and stomach . the gastric dissection is clearly identified by the disordered character of the vasculature of the gastric submucosa . the mucosa is carefully inspected for injury and for complete division of all muscle fibers . the muscular bundles bordering the esophageal diaphragmatic hiatus are reapproximated behind the esophagus using non - absorbable sutures ( fig . 5 ) . a partial gastric fundoplication is then created using a 90 anterior dor or a 270 posterior toupet fundoplication ( fig . patients are allowed liquids post operatively and then are maintained on a soft diet for several days . the rubber penrose drain is used for retraction of the abdominal esophagus during this stepfig . note : the abdominal esophagus is coursing through the diaphragm in the top of the photographfig . 6operative completion of the heller myotomy and posterior 270 toupet fundoplication operative step of longitudinal esophageal myotomy using electrocautery . the rubber penrose drain is used for retraction of the abdominal esophagus during this step operative step of diaphragmatic posterior crural repair using robotic instrumentation . note : the abdominal esophagus is coursing through the diaphragm in the top of the photograph operative completion of the heller myotomy and posterior 270 toupet fundoplication postoperative patients should receive routine follow - up consisting of surveillance endoscopy every 3 years in anticipation of early detection of asymptomatic pathology . patients who complain of recurrent symptoms should undergo formal evaluation and work - up as outlined for initial patients suspected of having achalasia . long - term postoperative results for achalasia patients are good , particularly when patients are selected with preoperative lower esophageal sphincter pressures greater than 35 mmhg . for a group of 174 patients reported overall symptomatic relief of dysphagia in 87% of patients 15 years after heller myotomy and dor fundoplication with 9% of patients requiring medical / surgical treatment of symptomatic reflux and 4% of patients requiring esophagectomy for malignant disease or recurrent disease not amenable to repeat myotomy and fundoplication . in patients who require re - operation for recurrent dysphagia following esophagomyotomy symptoms often present within the first postoperative year and the root cause is usually inadequate or healed myotomy . although success can usually be achieved , results from repeat esophagomyotomy are less impressive than adequate initial operations . it is indicated after failed medical therapy , pneumatic dilation , non - resecting surgical , and redo procedures . although laparoscopic heller myotomy has emerged as the treatment of choice for achalasia , the intraoperative esophageal perforation rate of 115% has remained a significant problem that has prompted investigation of improvements of this operative technique . in 2000 , the da vinci surgical system ( intuitive surgical , inc ; sunnyvale ca , usa ) a robotic telesurgical device , entered the market . the advantages reported include a stable work platform , a magnified three - dimensional image , fine motor control of articulated instruments , and motion scaling , which are uniquely designed to facilitate surgery requiring fine tissue manipulation . they provide a narrower field of view of the operative site and they provide the surgeon with essentially no tactile feedback . with these advantages and hurdles in mind , a variety of surgical procedures have been reported using robotic telesurgical devices . initial data obtained before food and drug administration approval was obtained in clinical trials performing cholecystectomy and gastroesophageal fundoplication . after food and drug administration approval brief clinical reports described cholecystectomy , fundoplication , colon resection , pancreatic resection , heller myotomy , and other general surgery procedures [ 19 , 22 ] . with experience , case series were presented which eventually demonstrated the safety and feasibility of robotic general surgery procedures [ 22 , 23 ] . reports have also been presented that look at traditional laparoscopic procedures compared with robotic telesurgical assistance . reported a comparison case series of gastroesophageal fundoplication performed by standard laparoscopy or with robotic telesurgical assistance . both techniques were safe and associated with low occurrence of complications ; no clear benefit was seen in the robotic group , however . use of the da vinci robotic telesurgical device to perform a heller myotomy was first reported in 2001 and a subsequent small case series was then reported [ 23 , 25 ] . the academic robotic surgery group , comprising surgeons from ohio state university , columbus , oh , usa , johns hopkins university , baltimore , md , usa , and the university of illinois at chicago , chicago , il , usa , has prospectively collected data on 104 robotic telesurgical heller myotomies , the largest reported case series , which were performed without a single esophageal perforation . similar results favoring the robotic telesurgical approach were obtained in three subsequent published series comparing robotic telesugical heller myotomy with laparoscopic heller myotomy [ 2628 ] . this improvement over standard laparoscopic studies which reflected the esophageal perforation rate of 115% may be related to the advantages of the robotic telesurgical technique and surgical enhancement the device offers compared with laparoscopic techniques . one pilot study evaluated the technique of pancreaticojejunostomy after pancreatic head resection using the robotic surgical device . five patients were enrolled and underwent a computer - enhanced pancreaticojejunostomy using a 60 suture in an open abdomen after pancreatic head resection . robotic assistance also has the potential to contribute to the evolving technology of natural orifice transluminal endoscopic surgery ( notes ) in which therapeutic approaches to abdominal surgical diseases are being pursued via an endoscope that is advanced from an intraluminal position within the stomach , vagina , bladder , or rectum into the abdominal cavity to perform a variety of diagnostic and therapeutic maneuvers . this was first attempted with simple peritonoscopy and has recently advanced to organ retrieval , for example appendectomy [ 30 , 31 ] . although no formal treatments for achalasia by a notes approach have been published , a treatment involving transgastric peritonoscopy with retroflexion and endoscopic myotomy with potential intraluminal gastroesophageal plication may prove to be feasible for treatment of achalasia with end results similar to heller myotomy and fundoplication .

the craft of surgery has always relied on the use of instruments . innovations in surgery have paralleled innovations in instrumentation . advances in surgical instrumentation continue today and have enabled huge strides in surgical procedures and outcomes during this generation . computers and related technology are now changing the interface between the surgeon and the patient , and are poised to improve patient outcomes by enhancing the surgeon s skills and training . the application of computer enhanced telemanipulators , or robots , may specifically enhance operations , for example heller myotomy , that require good visualization and precise careful dissection of delicate structures . this review covers the pathophysiology of achalasia and its history of medical and surgical treatment , leading to modern robotic telesurgical approaches . improvements in outcome from medical to standard surgical to robotic telesurgical approaches are discussed . current operative technique for robotic telesurgical treatment of achalasia is described and the authors conclude with a glimpse of where , in the future , current research endeavors will lead us in the treatment of achalasia .

an increasing number of medical specialties such as dermatology , oncology , radiology , surgery , cardiology , and psychiatry use telemedicine routinely.in a country like greece , which consists of several small islands dispersed around a mountainous mainland with many remote parts , telemedicine is not only beneficial but rather necessary for high - quality healthcare provision to its population.the services of telemedicine in their modern form appeared in greece in 1991 . due to the low reliability of the plain old telephone service ( pots ) at the beginning of these efforts , the implementations became wireless , via satellite links .however , the digitization of the pots and the general improvement of the telecommunication infrastructure , especially the deployment of gsm ( global system for mobile communications ) networks , which took place since then , have favoured further developments in the field [ 35 ] . telecardiology and specifically transtelephonic electrocardiographic transmission ( tet ) remains the most widespread form of telemedicine since it can ensure a valid , reliable , and objective assessment of cardiac rhythm and function.however , its use in sports medicine is not so widely mentioned , and relevant studies are very scarce in the international literature . perhaps the only known application in this area is the follow - up of patients with cardiovascular disease during their rehabilitation exercise [ 610 ] . with the increasing number of individuals having physically active lifestyles , transient risk of cardiovascular events during exercise is not rare , especially among athletes with unrecognized cardiovascular diseases.therefore , at least annual preparticipation screening is generally recommended prior to participation in sports.in order to increase the number of athletes properly tested , the screening program should be accurate , practical to apply under field conditions to large numbers of subjects , and have relatively low cost . the purpose of the study was to evaluate whether it was technically feasible and effective for a general practitioner ( gp ) to examine amateur soccer players in their playfields and transmit , when this was judged necessary , a 12-lead ecg and a clinical record to a sports medicine base for further evaluation by a cardiologist . a secondary purpose was to determine whether the data could be reliably transmitted via the cellular communication system , as an alternative in the absence of a fixed telephone line . ten percent of the active soccer clubs of the prefecture of thessaloniki , in northern greece , participated in this study . specifically , from the total of 230 soccer clubs , 23 of urban and rural areas were randomly selected . the study population included 506 young soccer players , who were asked to fill in a questionnaire so that information about the medical record of the athlete and his family could be collected.additionally , anthropometric and clinical data were recorded , that is , height , weight , systolic and diastolic blood pressure , and resting heart rate . all athletes underwent physical examination , including precordial auscultation in both the supine and standing positions . murmurs were further evaluated with the valsalva maneuver.additionally , resting 12-lead ecg was performed in all subjects . in the case of unusual findings , as judged by the gp , from the medical history , physical examination and/or ecg , the latter together with a clinical record were transmitted from the examination site to the laboratory of sports medicine for further evaluation by a cardiologist . the device used for storing and transmitting the ecg was a portable electrocardiograph ( cardiette excel 106scp ) with an internal modem and a capability of connecting to an external one with a transmission speed of up to 19.2 kbps.an important feature of the electrocardiograph was the compression of data before transmission , which allowed high quality 12-lead recordings to be sent in small files . in the absence of a fixed telephone line ( pots ) , a dual - band gsm ( 900/1800 mhz ) modem was used ( siemens tc35 terminal ) working with the circuit switched data ( csd ) bearer service of a national operator with more than 99% geographical coverage and a nontransparent data rate of 9.6 kbps.the data calls from the electrocardiograph were terminated at a workstation running the software package medibox cardiobox of h&c medical devices s.p.a . and connected with a modem to the pots.the communication between the cardiologist sitting in front of this workstation and the medical team in the field for reporting was always carried out with a mobile phone.following the initial assessment , 58 athletes were given further appointments for echocardiography , stress test , and 24-hour holter monitoring of ecg or blood pressure . descriptive statistics were used to describe categorical variables.for statistical analysis , the statistics toolbox of matlab was used ( the mathworks inc . , ma , usa ) . the correlation coefficient was derived to assess the association between the reception level of gsm and the number of failed transmissions . the locations where the preparticipation screening took place were at a distance between 4 and 82.2 km ( 19.35 18.22 km ) from the specialised examination centre at the laboratory of sports medicine , which is situated at the center of the city of thessaloniki . the mean transportation time of the healthcare team ( one gp and one nurse ) from the city centre to the locations of the athletes was 23.26 minutes ( sd 17.73 ) . most of the soccer clubs ( n = 16 or 69.6% ) had their own sports facilities , where the athletes were examined . however , only a small number ( n = 5 or 21.7% ) among them could offer an infirmary . therefore , the screening was performed at other sites ( e.g. , offices , canteens , dressing rooms ) for the remaining soccer clubs . a fixed telephone line was available only at 17 sites ( 73.9% ) , whereas a gsm signal was present everywhere . the physical characteristics of the 506 soccer players who were examined are shown in table 1 . taking into account the importance of the family history in identifying athletes at risk of sudden death during sports , we found that 28.3% of the athletes had a family history of cardiovascular disease . concerning their personal history , 8.1% of the athletes reported symptoms such as chest pain or discomfort during exercise . from the physical examination , mild ( 1/6 ) systolic murmurs were found in 15.2% and hypertension ( brachial blood pressure . a total of 142 ecgs were transmitted either by pots ( n = 108 or 76% ) or gsm ( n = 34 or 24% ) . ecg transmission on the first attempt was achieved in 93% and 91% of the cases , respectively . the ecg transmission was deemed unsuccessful in case of disconnects due to technical difficulties . the mean time for recording and storing the ecg was 180 s ( sd 46 ) . the transmission time was 60 seconds ( sd 23 ) depending on the file size , which ranged between 6 and 11 kb . the above mean transmission time also includes repeated attempts.the mean connection time was 24 sesconds ( sd 4 ) . the high rate of transmission failure was due to the low reliability of pots connection or bad reception level in the case of gsm data calls ( table 2 ) . additionally , there was a weak but significant correlation coefficient between the reception level and the number of failed transmissions ( r = 0.66 , p < .005 ) . at the end of each day , the cardiologist at the laboratory of sports medicine examined the records and the ecgs of the athletes tested during the day . there was no disagreement between the cardiologist and the gp on the ecgs that were not sent . with regard to the transmitted clinical records and ecgs , the cardiologist at the laboratory of sports medicine , who had monitored and examined them , agreed only in 74 cases with the gp in the playfield on the need to have sent the ecgs due to the existence of suspicious findings . however , from the 74 cases , 16 athletes were not referred for further cardiovascular assessment as the cardiologist diagnosed that the findings were without clinical significance . from the remaining 58 cases , 49 athletes were referred for echocardiography , 7 were subjected to a stress test , and 2 to a 24-hour ambulatory holter monitoring . after further evaluation , all of them were , eventually , permitted to participate in physical activities . our results indicate that telecardiology and specifically tet , interpreted by a sports medicine centre - based cardiologist , allows a rapid assessment of athletes at risk of adverse events during exercise , without the presence of a sports cardiologist.thereby , qualitative care at lower cost can be provided to a large population and can improve compliance.it is also shown that utilizing the advancement of telecommunications , gsm transmission of ecg , is reliable and flexible , and can be used as an alternative when there are no facilities . several studies have already proven that tet is useful and reliable , and can provide early diagnostic information in cardiac patients with symptoms such as chest pain , dyspnea , palpitations , and so forth , [ 1116 ] . so far , the cellular telephone communication system has been used to transmit 12-lead ecgs from ambulances to a hospital [ 3 , 5 ] , especially in case of chest pain . however , this is the first study introducing tet in sports medicine and specifically in the preparticipation screening of athletes . in this study , a store - and - forward transmission method was used.alternatively , real - time transmission could have been used , which , however , would have required a larger bandwidth and would cost more.it should be mentioned here that wired broadband services are not widely available in greece.indeed , in 2005 , about 67% of home internet connections were still dial - up connections on the pstn ( public switched telephone network ) .among midband solutions , isdn is more popular with 21% and adsl is gaining in popularity ( 8% ) very slowly , mainly due to the high prices.on the other hand , most mobile operators in greece provide a general packet radio service ( gprs ) with higher data transfer rates within urban areas , but a financial analysis must be done before one moves towards this solution , due to the different way of charging ( per data volume , instead of calling time ) and the initial cost of equipment . it is worth comparing the results of the current study with a similar one in the literature , which was conducted in athens , greece . reported that the mean connection time between the telemedicine unit and the base unit was 28 seconds , a value that is very close to the one reported here . they also mention a success rate of 93% for the first attempt , which compares very well with the 91% of our study . one important difference between the two studies is the achieved data throughputs , which is about the double in kyriacou et al . , but this could be attributed to the service used , since the authors mention the high speed circuit switched data ( hscsd ) , which offers high data transfer rates.two more points are worth mentioning from our work : first , the reception level was correlated with the efficiency of the gsm data link and , second , the small mean total time needed to test each subject , that is , four minutes for recording , storing , and transmitting the ecg . one shortcoming of the study , which needs to be addressed in its future follow - ups , was that it did not consider checking the accuracy of transmission . one way would have been for the cardiologist to have compared , at the end of the day , the received ecgs against their print - outs from the portable electrocardiograph and not just reviewing all the printed ecgs . in conclusion , it managed to distinguish the cases , which required further examination , and significantly reduced the logistics effort needed for the examination of all the subjects at the specialized medical centre . however , before it can be claimed that the procedure used in the present study can be generalized to other forms of preparticipation screening , a more careful cost - benefit analysis and an accuracy checking need to be performed .

transtelephonic electrocardiographic transmission ( tet ) is the most widespread form of telecardiology since it enables clinicians to assess patients at a distance . the purpose of this study was to assess the efficacy and effectiveness of tet either by fixed telephone line ( pots ) or by mobile phone in the preparticipation screening of young athletes . a total of 506 players , aged 20.5 6.2 years , from 23 soccer clubs in the prefecture of thessaloniki , greece , were physically examined in their playfields by a general practitioner ( gp ) and had their ecg recorded . in 142 cases , and on the judgment of the gp , the ecg was transmitted via pots and/or global system for mobile communications ( gsm ) to a specialised medical centre where it was evaluated by a cardiologist . the mean total time for recording , storing , and transmitting the ecg was four minutes per subject . it was found that the success rate for transmission at first attempt was similar for both fixed and mobile networks , that is , 93% and 91% , respectively . the failure rate in the gsm network was correlated to the reception level at the site of transmission . only in about half ( n = 74 ) of the transmitted ecgs did the cardiologist confirm abnormal findings , although in 16 , they were considered to be clinically insignificant . consequently , 58 athletes were referred for further medical examination . our results indicate that tet ( either by fixed telephone line or by mobile phone ) can ensure valid , reliable , and objective measurements , and significantly contribute to the application of medical screening in a great number of athletes . therefore , it is recommended as an alternative diagnostic tool for the preparticipation screening of athletes living in remote areas .

the clinical history and video - eeg features of a young boy , who presented with episodic chest pain , is described to illustrate this atypical presentation . a 14-year - old boy preparing for his final exams was brought by his mother for evaluation of episodic left - sided chest pain of 2 weeks duration . the pain which lasted a few seconds to half a minute was described as sharp , excruciating and localized to the lower chest on the left side and involved an area of only two finger breadths . the frequency varied from 1 to 8 episodes per day with variable severity but consistent location . there were no accompanying clinical features like breathlessness , diaphoresis , palpitation , fear , abnormal behavior or movements . there was no antecedent illness or trauma ; no history of febrile seizures , encephalitis or perinatal insult . he was evaluated by a pulmonologist and cardiologist who performed relevant investigations including a chest ct scan , electrocardiogram , and echocardiogram which returned normal findings . he was referred to a psychiatrist but the family preferred to get an opinion at our neurology center . an interictal eeg was initially performed which showed spike - and - wave discharges in the awake state distributed frontocentrally over the left hemisphere ( fig . 1 ) . this prompted us to obtain a long term video - eeg recording . during the 24 h of study , five events were recorded of which only one was associated with a clear - cut ictal pattern . the clinical semiology was dominated by severe localized chest pain in the right lower chest ( as opposed to the typical left - sided location for chest pain ) . however some paucity of movements were observed on the right side especially the right upper limb . the initial part of the ictal recording was obscured by artifact while a nicely evolving 4.04.5 hz rhythm was noted in the parasagittal region a few seconds after clinical onset . a 910 hz faster rhythm was also observed in the left mid and posterior temporal regions which did not show evolution ( fig . 2 ) . a 1.5 tesla mri of the brain did not reveal any focal pathology . the electroclinical data offered definitive proof for the ictal origin of the phenomenology from the left hemisphere . this drug was chosen as first line , because the family wanted seizure freedom in a short time as his exams were due in two days . he has had no seizures , behavioural or cognitive abnormalities during the last four months of follow - up . epileptic pain as a somatosensory manifestation of seizures is not uncommon but as a solitary presentation of epilepsy is extremely rare and diagnostically challenging . pazarci et al . who searched for this elusive symptom in their data base of 4736 patients identified only 9 patients . their experiences consisted of nuchal pain , headache , abdominal pain and pain in the extremities ( peripheral pain ) . the ictal eeg more often showed hemispheric or diffuse abnormalities than focal well - defined ictal activity . in our patient the lateralization was clearly evident compared to localization although the parasagittal region showed the most unequivocal changes . all the patients in their study who had lateralized peripheral pain had an abnormal mri while our report describes mr - negative algic seizures . structural abnormalities were a universal feature of patients with peripheral pain in a previous series of 8 patients with ictal pain . one of the patients had only biparietal atrophy evident on mri whose spect study corroborated the finding . the electrographic abnormalities were either restricted to the parietal area or hemisphere on the surface eeg . intracranial recordings in three patients showed seizure onset from inferior parietal lobule / parietal operculum or medial parietal lobe . in another analysis of retrospective data of more than five thousand patients , the authors found pain associated with seizures associated with epilepsy in 10 patients of whom 8 had peripheral location of pain . three of their patients had a normal mri while two had a central location of ictal onset which is comparable to our observation . however none of these patients in any of the above mentioned series had pain as the sole manifestation of epilepsy thus making our observation a novel one . the major studies which address epileptic pain due to seizures associated with epilepsy are summarised in table 1 , , , . none of the patients in these reports had isolated chest pain as an ictal manifestation which makes this case unique and challenging . the patient had several events during the long term recording without any eeg abnormalities until he had an event with definite ictal abnormalities . this emphasizes the need for a high index of suspicion to discover the ictal origin of unexplained pain . pain has a localization more or less similar to somatosensory aura . when the seat of origin is the primary sensory area , a secondary sensory area ( ssa-2 ) involvement produces vague or complex sensations which are more diffuse in distribution . posterior insular involvement can also produce sensory phenomena like warmth or dysesthesias which encompasses a widespread cutaneous distribution . supplementary somatosensory - motor area and cingulate cortex are the other anatomical sites whose involvement can result in sensory manifestations . the ictal origin of pain in the present report was established by the presence of electrographic abnormalities and response to antiseizure drugs . this bears resemblance to ictal epileptic headache observed especially in the pediatric age group diagnosis of painful seizures which is based on similar grounds . the location and nature of ictal pain is variable as evidenced in this report of pure left - sided chest pain . a dedicated evaluation by video - eeg telemetry can be invaluable in establishing the diagnosis in such cases .

purposeto investigate the probable ictal origin of unexplained episodic chest pain and if possible to lateralize and localize the epileptic focus.methodsa 14 year old boy presented with episodic short lasting localized chest pain . his cardiac and other systemic work - up were normal . mri brain did not reveal any structural pathology . video telemetry was done for characterization of the paroxysms.resultsinterictal record showed left fronto - central epileptiform discharges . a left hemispheric , predominantly centroparietal ictal rhythm was identified . the possible localizations of this unusual semiology are somatosensory areas i and ii , supplementary sensorimotor area , posterior insula and cingulate cortex . patient responded remarkably to antiseizure drugs.conclusionpain is a rare manifestation of epilepsy observed in less than 1% of patients . when present , it is usually accompanied by other focal features . this rare occurrence of epileptic seizures masquerading as angina is a novel observation .

in gynecology endosalpingiosis is a benign condition in which fallopian tube - like epithelium is found outside of the fallopian tube . endosalpingiosis is associated with the formation of psammoma bodies , which may lead to the misdiagnosis of malignancy such as serous carcinoma.1 the significance of endosalpingiosis is not settled ; medical experts differ on whether it causes pelvic pain , or is an incidental ( asymptomatic ) finding discovered in the course of investigating pelvic pain , menstrual irregularities or infertility . endosalpingiosis is occasionally found in lymph nodes , and may be misinterpreted as an adenocarcinoma metastasis . in one study , they found that 34.5% of endosalpingiosis cases had concurrent endometriosis ; 40% of the endosalpingiosis group were postmenopausal . in contrast , there was no significant link between endosalpingiosis and infertility nor chronic pelvic pain . a 75-year - old woman , gravida 2 , postmenopausal women , presented with vaginal bleeding which occurred a week ago . she had hyperlipidemia and took medical therapy . under the impression of pelvic mass , cancer antigen 125 ( ca-125 ) , ca 19 - 9 , complete blood cell count , serum chemistry , contrast enhanced - abdomen - computer tomography were done . ca 19 - 9 is 9.8 u / ml , ca-125 is 13.5 u / ml and glucose is 118 mg / dl . in contrast enhanced chest computer tomography , image showed multiseptated cystic mass in left adnexa which adhesion with left psoas muscle , adjacent small and large bowel loops and there is possibility of underlying chronic inflammatory process with abscess ( fig . vaginal bleeding is caused by the atrophic vaginitis considering that the patient 's age is 75 years old . endosalpingiosis is a non - neoplastic process and is generally considered to be derived from the secondary mllerian system , which consists of structures covering the peritoneal mesothelium , the adjacent mesenchyme in the small pelvis and the lower part of the female abdominal cavity.3 proliferation of these structures can result in the creation of three different types of lesions : endometriosis , which occurs most frequently , and the less common endosalpingiosis and endocervicosis.4 the symptom of endosalpingiosis is not settled ; medical experts differ on whether it causes pelvic pain,5 or is an incidental ( asymptomatic ) finding discovered in the course of investigating pelvic pain , menstrual irregularities or infertility.6 the causes of the endosalpingiosis are unknown . in this case however , it is almost always an incidental finding , either at the time of operation or , more commonly , on microscopic examination.7 it is most commonly encountered on the pelvic peritoneum covering the uterus , fallopian tubes , ovaries and culde - sac . less frequent sites include the pelvic parietal peritoneum , omentum , bladder and bowel serosa , paraaortic area and skin.8 only a few examples of tumor - like cystic endosalpingiosis localized to the female pelvis have been described , and most of these cases are reported to be derived from the serosal surface of the uterus and the ovary 6 - 10 or from the paraovarianregion.8 for diagnosis of endosalpingiosis , pathology on excision ( e.g. biopsy ) , is needed . it is characterized by cysts with tubal - type epithelium ( e.g. ciliated epithelium ) surrounded by a fibrous stroma . unlike endometriosis , it is not associated with hemorrhage . a tubal - type epithelial surrounded by endometrial - type stroma is a variant of endometriosis , not endosalpingiosis . endosalpingiosis is occasionally found in lymph nodes , and may be misinterpreted as an adenocarcinoma metastasis.9 the pathological differential diagnosis of endosalpingiosis is discussed in detail in previously reported cases.7,10,11,12,13,14 however , the clinical differential diagnosis of an intramural mass , whether it causes any symptoms or not , is more important for clinicians when discussing further surgery with the patient . therefore the symptoms and the imaging findings of this rare entity are very important . as endosalpingiosis , endosalpingiosis appears to affect an older age group , with 40% of endosalpingiosis cases occurring in postmenopausal women.2 premenopausal women with endosalpingiosis were more likely to have a gynecologic malignancy.2 endosalpingiosis appears to affect postmenopausal women at a much higher rate than previously thought , and in consequence the average age of women presenting with endosalpingiosis was higher than expected.2 in this case , 75-year - old woman , gravida 2 , postmenopausal women , presented with vaginal bleeding was reported . however , it must be kept in mind that vaginal bleeding can be caused by endosalpingiosis , especially in the postmenopausal elderly women . possibility of endosalpingiosis must be considered in the differential diagnostic spectrum of vaginal bleeding , thus avoiding the problem of misdiagnosis of endosalpingiosis .

in gynecology , endosalpingiosis is a benign condition in which the fallopian tube - like epithelium is found outside the fallopian tube . the thirty - four point five percent of endosalpingiosis cases have concurrent endometriosis and 40% of the endosalpingiosis group are in postmenopausal states . in contrast with endometriosis , there are no significant links between infertility , chronic pelvic pain and endosalpingiosis . the symptoms of endosalpingiosis are not yet settled . endosalpingiosis is almost always an incidental finding ; it is commonly found through microscopic examinations , and is then confirmed by pathologists for excision and biopsy . therefore , the clinical differential diagnosis of an intramural mass is more important for clinicians when discussing further surgery with the patients . we report case of woman who has endosalpingiosis and is presented with vaginal bleeding . we first suspect the disease during physical examination . under the impression of pelvic mass , laboratory tests and radiological images of contrast enhanced chest computer tomography are taken . images show multisepted cystic masses in left adnexa . to rule out the pelvic mass , we executed exploratory laparotomy . pathologic results show endosalpingiosis near the ovary section . but the endosalpingiosis , is not generally considered a pathology , and thus , no treatment is necessary .

it is critical to treat perianal abscess with a proper selection of antibiotics as well as surgical drainage . along with these treatments various aerobic / anaerobic strains might be responsible for perianal abscess . according to a recent study in taiwan , escherichia coli was the major pathogen responsible for perianal abscess in patients without a history of diabetes mellitus , whereas klebsiella pneumoniae was found to be responsible in patients with diabetes.1 k. pneumoniae , a gram - negative short bacillus , causes invasive infections such as pneumonia and urinary tract infections , and is also known to be the major pathogen responsible for pyogenic hepatic abscess in asia.2,3,4,5 risk factors for invasive infections include diabetes mellitus and a history of abusive alcohol consumption.6,7,8 however , no study has been published focusing on k. pneumoniae - induced proctitis in south korea or indeed other countries . in the present study , we report the case of a patient with diabetes mellitus and a history of alcohol abuse , and review the relevant literature ; the patient presented with severe k. pneumoniae - induced proctitis , as well as perianal abscess , and was thus treated with incision drainage and empiric antibiotics . a 61-year - old man complained of abdominal pain and perianal pain , and was missing meals due to loss of appetite over two weeks before admission . he was hospitalized because his serum creatinine level was 5.28 mg / dl after examination at a nearby hospital . he was on medication for diabetes mellitus , which was diagnosed five years ago , and informed us that he had been drinking two bottles of soju ( korean vodka , approximately 20% alcohol v / v ) four times per week for the last 40 years . he drank particularly heavily every day over the two weeks prior to admission . over the last 35 years , the patient had been smoking 1.5 packs of cigarettes per day . at admission , his blood pressure , pulse , breathing rate , and body temperature were 106/68 mmhg , 100 pulse / min , 20 breaths / min , and 37.1 , respectively . the patient had acute signs , abdominal pain , and mass lesions accompanying oppressive pain upon rectal examination . in subsequent blood tests , white blood cell count , hemoglobin , platelet count , and crp were found to be 9,000/mm , 12.6 g / dl , 43,000/mm , and 23.29 mg / dl , respectively . in the biochemical analyses of serum , total protein , albumin , bun , creatinine , total bilirubin , ast , alt , glucose , and glycated hemoglobin were 7.5 g / dl , 3.3 g / dl , 82.2 mg / dl , 2.6 mg / dl , 2.28 mg / dl , 57 iu / l , 77 iu / l , 287 mg / dl , and 7.7% , respectively . radiological examinations , such as abdominal ct to assess oppressive pain in abdominal and perianal areas , could not be performed owing to the elevated serum creatinine levels . after sufficient supply of fluids , his creatinine level was normalized but he experienced a high fever ( 38 - 39 ) and diarrhea on the 4th day of hospitalization . blood and fecal tests were performed , and ciprofloxacin ( 800 mg ) was administered via intravenous injection . his symptoms were not alleviated , and he underwent sigmoidoscopy on the 7th day of hospitalization . the endoscope was inserted up to the sigmoid colon ( anal verge 30 cm ) . in the sigmoid colon , there was intestinal mucosa edema with gastric ulceration covered by yellowish exudates . most ulcers were round - shaped and relatively deep , and their boundaries were clear and accompanied by rubefaction . in the rectum , more excessive yellowish extrudes were shown with deeper and bigger ulcerations , covering most of intestinal mucosa ( fig . the bases and boundaries of the ulcerations were biopsied , and nonspecific chronic inflammation was found ( fig . owing to the possibility of pseudomembranous colitis , stool culture and toxin tests were performed to check for clostridium difficile infection , and metronidazole ( 1.5 g ) was administered via intravenous injection . even though the results were negative for c. difficile , and metronidazole was administrated , the patient still complained of fever and diarrhea , leading us to administer vancomycin ( 500 mg , orally ) on the 10th day of hospitalization as an empiric prescription for a differential diagnosis of pseudomembranous colitis . the administration of vancomycin did not alleviate his severe fever and diarrhea , and the patient therefore underwent follow up sigmoidoscopy . in the follow - up sigmoidoscopy the entire rectum was covered with white - yellowish extrudes and the intestinal mucosa was damaged and had a spider web appearance ( fig . the intestinal mucosa was seriously damaged , and intestinal lumens were indistinguishable , making it impossible to insert the endoscope any further than the rectum . an abdominal ct scan was performed in order to monitor the range of lesions and their surroundings . in addition , on the 15th day of hospitalization , the patient underwent rectal mri as the mass - like lesions with oppressive pains in the anus had not improved , and an anal fistula opening accompanying ulcerations was suspected ( fig . multiple edemas were found on the wall of the entire sigmoid colon and rectum , while the proximal colon and small intestinal walls seemed relatively normal . in and around the rectum and anus , there were abscesses accompanied by gas , rectal fistulas , and anal fistulas ( fig . 4 and 5 ) . therefore , the patient underwent sigmoidostomy as well as perirectal abscess incision and drainage on the 16th day of hospitalization . upon pus culture , the presence of extended - spectrum beta - lactamase producing k. pneumoniae was confirmed ; therefore , the antibiotics were switched to ertapenem . ertapenem ( 1 g ) was administered intravenously over two weeks , and the patient was discharged on day 17 as his symptoms had improved . according to a multi - institutional study , 21.1% of k. pneumoniae was found in the stool culture of healthy subjects . of them , 4.9% represented serotype k1 k. pneumoniae.4 k. pneumoniae is able to form colonies in the oral cavity , skin , and intestines . k. pneumoniae can also cause invasive infections in the respiratory tract and urinary tract , and the major risk factors for such infections are excessive drinking and diabetes mellitus.9,10,11 in a recent study , it was found that k. pneumoniae was mainly responsible for perianal abscess in diabetes mellitus patients.1 further , in another study , it was demonstrated that gram - negative strains were identified in 59% of cultures from the pharynx of chronic drinkers , of which k. pneumoniae was the most prevalent.12 diabetes mellitus is known to impede white blood cell functions , chemotaxis , and phagocytosis , thereby increasing the risk of invasive infection.13 drinking also increase the risks of invasive infection as it induces the dysfunction of macrophages , thymus - derived lymphocytes , and b lymphocytes , and hinders the formation of reactive oxygen species.14 the present case of a patient with diabetes mellitus and a history of alcohol abuse might be related to poor glycemic control due to daily drinking over the two weeks prior to hospitalization , thus allowing k. pneumoniae to form intestinal colonies and induce an invasive infection . in the pus culture , we were able to isolate extended - spectrum beta - lactamase - producing k. pneumoniae . this might be because general k. pneumoniae was responsible in an early stage of infection , and " superselection " occurred upon exposure to empiric antibiotics . in south korea , invasive infections induced by k. pneumoniae commonly present with hepatic abscess , while some may cause metastatic infections too.3,15 in a study conducted in taiwan , of 187 patients with primary liver abscess due to k. pneumoniae , 12.3% had metastatic infections . among the patients with metastatic lesions ( 23 patients ) , there were 14 cases ( 60.8% ) of endophthalmitis , 10 cases ( 43.4% ) of pulmonary abscess , six cases ( 26.0% ) of brain abscess , five cases ( 21.7% ) of prostate abscess , two cases ( 8.6% ) of osteomyelitis , and one case ( 4.3% ) of psoas abscess.16 in addition , in common with the present case , there are a few reports suggesting that k. pneumoniae can induce metastatic infections accompanying perianal abscess . for instance , jung et al . reported that k. pneumoniae induced endogenous ophthalmitis accompanying abscess on the prostate as well as the tissue surrounding the anus . in another case , lee et al . also reported chronic inflammatory demyelinating polyradiculopathy accompanying perianal abscess induced by k. pneumoniae.17,18 to the best of our knowledge , however , no study has been reported a case of k. pneumoniae - induced colitis / proctitis with perianal abscess in south korea or other countries . in the present case , empiric antibiotics did not alleviate k. pneumoniae - induced sigmoid colonic and rectal infections . instead , the symptoms were aggravated , and fistula and abscess formed , leading us to perform surgical drainage . in a domestic study , the causative organism was identified in 40%19 of infectious colitis cases , while we were unable to isolate the causative organism in stool or blood cultures . furthermore , it was not possible for us to find the causative organism from tissue culture or endoscopic biopsy , and empiric antibiotics were therefore provided . causative or accompanying lesions in the abdominal cavity were not identified because of acute renal failure present at admission , which made medical imaging tests impossible . no improvement in symptoms was found with antibiotic treatment , although renal function was improved . therefore , abdominal contrast - enhanced ct was performed , revealing an abscess producing gas in the rectum and anus . immediate surgical drainage was performed for the perianal abscess , and extended - spectrum beta - lactamase - producing k. pneumoniae was isolated from the abscess culture . the antibiotics were replaced with ertapenem , and proctitis and the perianal abscess subsequently improved . there are 77 serotypes of k. pneumoniae , and of these serotype k1 and k2 possess the most significant virulence and resistance to phagocytosis.20 although we did not investigate the serotype of k. pneumoniae in this patient , it is likely that either serotype k1 or k2 k. pneumoniae induced the infections , giving rise to the rectal and perianal abscesses . even though infectious colitis is commonly treated with fluids and empiric antibiotics , immediate imaging examinations such as ct and mri should be performed in situations where such antibiotics do not improve symptoms in order to diagnose complications such as fistula opening and abscess . in addition , early administration of proper antibiotics via appropriate culture tests using relevant specimens and immediate surgical means ( e.g. , drainage and fistulectomy ) are warranted to prevent the necessity for major surgery . the present report is the first domestic / international case report and literature review of a male patient with a history of diabetes mellitus and a history of chronic drinking treated with incision drainage and sigmoidostomy for perirectal / perianal abscess and fistula opening , as well as severe proctitis induced by k. pneumoniae infection . early imaging tests , as well as appropriate treatments , are critical for the successful treatment of colitis that is not improved by the administration of fluids and empiric antibiotics .

klebsiella pneumoniae ( k. pneumoniae ) can at times cause invasive infections , especially in patients with diabetes mellitus and a history of alcohol abuse . a 61-year - old man with diabetes mellitus and a history of alcohol abuse presented with abdominal and anal pain for two weeks . after admission , he underwent sigmoidoscopy , which revealed multiple ulcerations with yellowish exudate in the rectum and sigmoid colon . the patient was treated with ciprofloxacin and metronidazole . after one week , follow up sigmoidoscopy was performed owing to sustained fever and diarrhea . the lesions were aggravated and seemed webbed in appearance because of damage to the rectal mucosa . abdominal computed tomography and rectal magnetic resonance imaging were performed , and showed a perianal and perirectal abscess . the patient underwent laparoscopic sigmoid colostomy and perirectal abscess incision and drainage . extended - spectrum beta - lactamase - producing k. pneumoniae was identified in pus culture . the antibiotics were switched to ertapenem . he improved after surgery and was discharged . k. pneumoniae can cause rapid invasive infection in patients with diabetes and a history of alcohol abuse . we report the first rare case of proctitis and perianal abscess caused by invasive k. pneumoniae infection .

hba1c is a retrospective analyte of the carbohydrate metabolism reflecting the mean blood glucose levels during the last 6 to 8 weeks . clinical studies revealed a close relation between late diabetic complications and the concentration of glycated proteins in blood . therefore hba1c determination is widely used to assess the metabolic status and to monitor the medical treatment of diabetic patients . the diabetes control and complications trial ( dcct ) and the united kingdom prospective diabetes study ( ukpds ) used hba1c as one of the main indicators for the quality of diabetes management , . hba1c is meanwhile recommended for screening of diabetes , since hba1c concentrations in blood are not affected by acute metabolic alterations in the patients . standardization of hba1c determinations affords the establishing and implementation of a reference measurement procedure with the highest accuracy possible . at the end of the 80s a certified reference material of hba1c was not available and an high performance liquid chromatography ( hplc ) peak of hba1c analysis developed by goldstein and co - workers became the reference for the calibration of hba1c measurement . the hplc procedure was accepted as a common voluntary consensus standard for the hba1c determination in the dcct- and ukpds - studies . moreover , the procedure was applied as standard protocol for analytical devices for hba1c measurements . the national glycohemoglobin standardization program ( ngsp ) became the basis for the calibration of hba1c measurements in the usa . according to this calibration hba1c values are reported in % of blood haemoglobin concentration . further investigations showed that the separation of hba1c from other proteins by hplc was incomplete and the specificity was not appropriate for international standardization . at the end of the 90s , the international federation of clinical chemistry ( ifcc ) had established a working group to develop an international reference measurement procedure for hba1c traceable to a standard of higher metrological order . the principle of the ifcc reference measurement procedure was the proteolytic treatment of the blood sample with endoproteinase glu - c cleaving glycated or non - glycated hexapeptides from the n - terminal -chains of the haemoglobin . the ratio of the glycated and non - glycated n - terminal hexapeptides of the haemoglobin -chain expressed in percent was defined as the ifcc unit . the decision created considerable confusion , since from now on there were two different calibrations with the same unit on the market . the results between the laboratories of the working group were regularly monitored by intercomparison surveys . the quality of measurements , expressed in terms of inaccuracy and imprecision , was improved during the measurement campaigns . from the collected data of the ifcc working group a master equation was developed to convert values from ifcc units into ngsp units and vice versa . since 2007 , laboratories in europe , australia , and japan calibrated their analytical systems for hba1c according to the ifcc reference measurement procedure and started to report their results in mmol / mol to avoid confusions ; us laboratories remained with ngsp calibration and express hba1c values in ngsp % . the effort of the ifcc working group resulted in a remarkable improvement with respect to the ngsp consensus calibration . however , the key problem of the ifcc reference measurement procedure revealed to be the quality of hba1c and hba0 calibrator preparations and their traceability to the si standard . during the inter - comparison studies a more robust lc - ms reference measurement procedure improving the reproducibility of measurement was established , . in a recent study the traceability of hba1c , measurement results to si units has been achieved by isotope - dilution mass spectrometry , using glycated and non - glycated -n - terminal hexapeptides of defined purity and stated uncertainty of measurement as calibrators and deuterated -n - terminal hexapeptides as internal standards . the traceability is accomplished by hydrolysis of the unlabelled hexapeptide standards and the determination of the amino acid concentration by lc - id - ms calibrated with certified amino acid standards ( figure 1 ( fig . 1 ) ) . in a recent article little et al . claim the development of hba1c standardization from chaos to order during the last 15 years with the ngsp and ifcc standardization efforts and discuss problems arising from the implementation of the ifcc reference system . unbroken chain of comparison using a reference measurement procedure of highest metrological order and , if possible , a reference material of highest metrological level which is traceable to si units . with this iso standard the traceability of measurement the new reference measurement procedure is appropriate to set target values in external quality assessment schemes . in figure 2 ( fig . 2 ) the dispersion of routine values around the different target values is demonstrated in a recent external quality assessment scheme ( eqas ) for hba1c . the three possible target values ( consensus value , ifcc reference measurement procedure value , and idms value ) are given in this scheme . the new calibration using the lc - id - ms procedure leads to slightly higher hba1c levels than the recent calibration according to the ifcc reference measurement procedure . in summary , a new standardization of hba1c measurement has been established at the highest level of accuracy , with stated uncertainty of measurement and with traceability to si units following the ifcc reference measurement protocol using lc - id - ms as procedure of highest metrological order .

glycated haemoglobin ( hba1c ) measurements are used in clinical studies and for the management of diabetic patients . various efforts were made to standardize the hba1c measurements with consensus standards and standards based on a reference measurement procedure with external calibration . according to iso 17511 a standard should meet highest accuracy possible , have a defined uncertainty of measurement and the calibration should be traceable to si units . for hba1c this has been realized using a lc - id - ms procedure based on the existing reference measurement procedure .

laboratory testing is a highly complex process , and although laboratory services are relatively safe , they are not as safe as they could or should be . clinical laboratories have long focused their attention on quality control methods and quality assessment programs dealing with the analytical aspects of testing . however , a growing body of evidence accumulated in recent decades demonstrates that quality in clinical laboratories can not be assured by merely focusing on purely analytical aspects.15 more recent surveys of errors in laboratory medicine have concluded that mistakes occur more frequently before ( preanalytical ) and after ( postanalytical ) the test is performed . the risk of errors due to analytical problems has been significantly reduced over time , but there is evidence that carelessness may still have a serious impact on reporting . mistakes made during the entire testing process are referred to as laboratory errors , although these may be due to haste or poor instruction and communication on the part of personnel , actions taken by others involved in the testing process ( eg , physicians , nurses , phlebotomists , and laboratory technicians ) , or a poorly designed process , all of which are beyond the control of the laboratory . constant turnover of staff in the emergency department and use of travelling nurses present a difficult challenge in terms of maintaining good practice . further , there is evidence that laboratory information is often only partially utilized.68 point of care testing ( poct ) is a modern approach that could help to resolve some health care problems because it is centered on the needs and satisfaction of patients , particularly if laboratory departments have to provide a lot of test answers in a short space of time . this methodology is defined as medical testing at or near the site of patient care , to support timely , safe , and effective acute care ( cardiac , metabolic , coagulation , respiratory distress ) . however , this strategy must be of the same standard as that in the central laboratory , and necessitates the involvement of more personnel from specialties outside the laboratory.9 in the changing landscape of the health care system , hospitals are becoming increasingly involved in the treatment of acute disease , and clinical laboratories have to increase their efficiency . therefore , laboratory professionals , who are required to reduce costs , simplify processes , and decrease staff numbers , have considered the possibility of incorporating emergency testing into their routine work as a result of the improved productivity and flexibility of laboratory automation . in many situations , it is faster to perform both routine and emergency testing , with priority given to emergency testing , thereby simplifying laboratory processes and improving turnaround time . however , if the turnaround time does not satisfy physicians in the emergency department , the laboratory may need to take action to reduce the time interval between receiving requests and providing results . this improves clinical decision - making and patient management . the creation of large core laboratories as the centerpiece of pathology consortiums will increase the demand for poct unless transport of specimens and information technology facilities are radically improved.10 this paper describes the most frequent and risky analytical errors , especially in the preanalytical phase , occurring at the children s hospital in trieste , northeast italy , related to the laboratory and emergency departments . the use of poct as a modern pathology service involves information and instruction management about the importance to compare the test results with an external quality control . the purpose of this research was to demonstrate that meetings and audit processes involving sanitary personnel from both the laboratory and emergency departments can improve the performance of poct and decrease the number of preanalytical laboratory errors . this work was conducted between january 2012 and june 2013 , and involved sanitary personnel from three medical units ( neonatology , resuscitation , delivery room ) and technicians in the laboratory department . studying this period of time , the preanalytical errors of tests sent to the laboratory department were examined . in the same period the emergency department was provided with three new poct and the related external quality control of the analysis . three meetings were held with physicians , nurses , and laboratory technicians , to highlight two problems , ie , preanalytical errors and analytical methodologies used for poct . for poct in the emergency department , we used a hematology analyzer ( abacus junior 30 , radiometer , milan , italy ) to determine hemoglobin , hematocrit , mean corpuscular hemoglobin , mean corpuscular hemoglobin concentration , mean corpuscular volume , mean platelet volume , plateletcrit , platelets , red blood cells , red cell distribution , and white blood cells , and two blood gas instruments ( abl 800 flex , radiometer , milan , italy ) to analyze pco2 , ph , po2 , calcium , chloride , glucose , lactate , potassium , and sodium . riqas reports from randox laboratories ltd ( crumlin , uk ) were used for external quality control . the test was used to test for a statistically significant difference between the number of preanalytical errors made at the beginning and end of the study . all members of the nursing staff signed a consent form to confirm their voluntary participation in the study , and accepted the methodology of the course , ie , objectives , teaching and learning methods , and expected outcome . the core laboratory director provided weekly external quality control reports for poct , and a review of preanalytical errors was undertaken . after 6 months , the laboratory director held the first meeting with sanitary personnel of the emergency and laboratory departments , to explain the problems identified and the methodology needed to solve these problems . at the end of the study , the results were forwarded to the medical units and key points were discussed ( tables 14 ) . of 800 samples examined in the laboratory department in january 2012 , we identified 64 preanalytical errors ( 8.0% ) , classified as hemolysis , insufficient sampling , late arrival , not conforming to medical protocol , and without diagnosis ; however , in june 2013 , of 800 samples examined , only 17 preanalytical errors ( 2.1% ) were identified , representing a significant decrease ( p<0.05 , test ) . during the study , there was an improvement in external quality control for poct from 3 or 2 standard deviations or more to one standard deviation for all parameters . in the emergency department setting , time is an important factor in the assessment , diagnosis , and stabilization of patients , and every effort should be made to save time when collecting laboratory specimens . nurses often collect blood from an existing intravenous catheter to avoid a second venepuncture , thereby increasing efficiency and decreasing patient discomfort ; however , increased hemolysis rates have been attributed to the practice of obtaining blood specimens in this way . data collection points demonstrated that drawing blood through an intravenous catheter was associated with hemolysis more frequently than using an intravenous catheter with a connected syringe . the principal problems identified were to do with transport of specimens , deviation from diagnostic protocols , and software programs used in the laboratory . other observations noted by sanitary personnel included the finite staffing resources available in the emergency department and the high workload of staff caring for disabled pediatric and small for date neonatology patients , which can reduce the efficiency of certain procedures . such problems were often due to poor communication , and action should be taken by all sanitary personnel involved in the testing ( physicians , nurses , and phlebotomists in the laboratory and emergency departments ) and transport process . in the collaborative approach to ensuring overall quality , the risk of errors and mistakes in laboratory testing must be minimized to guarantee the total quality of a laboratory service.1116 health personnel in the emergency department can affect tests in the laboratory , but nurses and doctors must be educated , given specific instructions , and complete courses on poct . the improvement in external quality control seen in this study demonstrates that nursing staff in the emergency department can provide more efficient patient care . their frequent execution , almost weekly , making sure data diagnostic process , can facilitate clinical decision , leading to a decrease in specimen recollection rates . it is important to improve specimen acceptability results in quicker laboratory results , to physicians who can have available the patient test report sooner ; this positively affects patient outcomes in the emergency department . the study shows only a decrease in errors , but it does not ensure in general that appropriate therapies were given . poct is not the solution to preanalytical nursing errors , but is important with regard to the needs of patients.17,18 in the past , laboratory testing in italy has been performed by physicians and laboratory technicians in a central laboratory , with some testing performed by satellite laboratories separate from the central laboratory , but still involving laboratory personnel . attitudes concerning laboratory testing have changed significantly in the last few years and the economic problem of personnel cost imposes , in a modern approach , that technology poct can be used by nurses at or near the site of patient care monitoring the patient without hospital admission . maintaining the status quo ( a central laboratory and other satellite laboratories ) is not a good strategy for survival in laboratory medicine today.1922 high - quality biological samples are needed , but are not sufficient alone for the quality of laboratory results . the total quality of a test is determined by control of analytical and preanalytical processes and by cooperation between laboratory technicians and other health care professionals , especially nurses . this is essential for reducing errors and for better analytical performance . training protocols must be established and all potential operators must achieve an adequate level of competence . the content of the training program ( including temperature , time , and modality of transportation to avoid contamination ) and assessment of knowledge / skill levels should be documented in a training manual with a job description , that includes sample requirements , specimen collection , sample preparation , stability of reagents , and calibration of instruments.23,24 international guidelines and recommendations , along with procedures for quality and performance control , must also be approved and used for poct in the emergency department . laboratory medicine , like all health care , takes place in a dynamic , rapidly changing environment . as the standard of care changes , technology develops , and the economics of health care continue to change , the technology of poct will be challenged to find new strategy . it means this approach to affront the clinical needs of the standard of care will be more used in the future . by understanding and considering poct in the next future this concept may become aware of best way to meet the needs of medical care at residence ( ie , management of coagulation therapy).2527 recognition of normal and abnormal results , as well as an understanding of the multidisciplinary action needed in the event of an abnormal result are essential.2830 faster is not always better , and in our experience poct should be restricted to measurement of vital functions requiring an immediate response , eg , blood glucose , hemoglobin , and electrolytes ( sodium , potassium , ionized calcium).31 the authors do not recommend introduction of poct in the emergency department to solve the problem of inappropriate samples and inadequate transport to the laboratory department . however , collaboration and instruction of all sanitary personnel involved is essential to deal with preanalytical errors , performance of poct , and external quality control , to maintain patient safety , and to improve risk management . the lack of studies like this can carry two other considerations , ie , the limits of a very expensive technology and the difficult in applying it , not only in the hospital but also at place of residence.32 further studies and experience are necessary to resolve these questions .

involvement of health personnel in a medical audit can reduce the number of errors in laboratory medicine . the checked control of point of care testing ( poct ) could be an answer to developing a better medical service in the emergency department and decreasing the time taken to report tests . the performance of sanitary personnel from different disciplines was studied over an 18-month period in a children s hospital . clinical errors in the emergency and laboratory departments were monitored by : nursing instruction using specific courses , poct , and external quality control ; improvement of test results and procedural accuracy ; and reduction of hemolyzed and nonprotocol - conforming samples sent to the laboratory department . in january 2012 , point of care testing ( poct ) was instituted in three medical units ( neonatology , resuscitation , delivery room ) at the children s hospital in trieste , northeast italy , for analysis of hematochemical samples . in the same period , during the months of january 2012 and june 2013 , 1,600 samples sent to central laboratory and their related preanalytical errors were examined for accuracy . external quality control for poct was also monitored in the emergency department ; three meetings were held with physicians , nurses , and laboratory technicians to highlight problems , ie , preanalytical errors and analytical methodologies associated with poct . during the study , there was an improvement in external quality control for poct from 3 or 2 standard deviations or more to one standard deviation for all parameters . of 800 samples examined in the laboratory in january 2012 , we identified 64 preanalytical errors ( 8.0% ) ; in june 2013 , there were 17 preanalytical errors ( 2.1% ) , representing a significant decrease ( p<0.05 , 2 test ) . multidisciplinary management and clinical audit can be used as tools to detect errors caused by organizational problems outside the laboratory and improve clinical and economic outcomes .

similarly , in germany , approximately 10.9% of the population is involved in accidents annually , and trauma is the second commonest cause of hospitalization . trauma registries have been established globally in an effort to improve the management and outcome of trauma patients . in 1991 , the scottish trauma and audit group ( stag ) was established to assess and improve the management of trauma patients in scotland . this national trauma audit was conducted for a decade , from 1992 to 2002 in 28 hospitals across scotland , collecting data for 52,676 trauma patients . at the same time , the deutsche gesellschaft fuer unfallchirurgie ( dgu ) , being the german society for trauma surgery , established the german trauma registry ( gtr ) in 1993 with an aim to develop guidelines for the management of multiply injured patients . inclusion of patients was originally voluntary , it has since become compulsory for trauma units to record this data for audit purposes . the scottish system relies primarily upon a paramedic service to provide pre - hospital care . the german management of pre - hospital trauma differs ; a greater priority is given to include physician input prior to an arrival to the emergency department , with administration of advanced trauma life support ( atls ) . this study compares the management of polytrauma between scotland and germany using data from stag and the gtr registries , respectively . we present the differences of injury severity , anatomical pattern of injury , and the pre - hospital management between the scottish and german populations , relating these to patient outcome . inclusion criteria for this audit were : patients 12 years of age or more , an admission to hospital for at least 72 hours , or died as a result of injury . patients aged over 65 years of age with an isolated fracture of the neck of femur or pubic rami were excluded . length of stay and patient mortality at 3 months from presentation were the main outcome parameters . one of the key findings of this audit was that the survival rate for seriously injured patients increased from 65.3% to 78.9% over the duration of the audit from 1992 to 2002 . as a result , this audit was discontinued in 2002 as it was concluded from the improved survival rates that management of trauma patients in scotland was significantly better than the rest of the uk . criteria for patient inclusion within the registry was admission through the emergency department ( ed ) after an acute traumatic injury , requiring intensive care unit ( icu ) admission for the same time period or dying in the ed . the registry is open to every hospital and trauma department in germany , in addition , some neighboring countries , such as the netherlands , austria and switzerland , with more than 100 trauma units participate on a voluntary basis . maintenance of data is completed by doctors whilst the patient is still in hospital and following that specially trained personnel ensure that a minimum set of mandatory data is available to allow for participation in the registry . a retrospective analysis of all trauma patients with an injury severity score ( iss ) of 16 or more that were entered into both registries ( stag and gtr ) , from 1 january 2000 to 31 december 2002 was performed . patients aged over 65 years of age with an isolated fracture of the neck of femur or pubic rami were excluded from the gtr . the iss and the revised trauma score ( rts ) were used to assess the anatomical injury severity score ( ais ) and physiological indices of the injury , respectively . the iss and rts were used to calculate the trauma and injury severity score ( triss ) , which was then used to calculate the standardized mortality ratio ( observed / predicted ) for both populations . data criteria obtained from the stag and gtr datasets data collected from both groups was analyzed using statistical package for the social sciences version 17.0 to derive frequencies , means and percentages for the various parameters and confirmation of normal distribution . the data was normally distribution , and a student 's t - test was used for continuous and chi - squared test was used for discontinuous data . there were 227 patients identified from the stag registry and 6878 patients from the gtr registry , were used in our study . the mean age for both groups was > 40 years with a predominantly male population , the majority of which had sustained blunt trauma . the number of injuries sustained per patient in both groups was similar with each patient incurring a mean of 2.3 -_2.4 injuries . the only significant difference was of iss between the groups , with scottish patients having an average score of 24.9 and german patients having an average score of 29.8 , however , there was no significant difference in the rts ( p = 0.6 ) . epidemiological and injury characteristics for both groups table 3 shows the comparison of pre - hospital management interventions . there was a significant difference between both populations , with a considerably higher rate of pre - hospital interventions in the german group . pre - hospital interventions for both groups table 4 shows the regional incidence of injuries and the mean ais score for each region . german patients sustained significantly more facial , chest , abdominal and extremity injuries than the scottish population . there was , however , no significant difference for the incidence of head and external injuries . the severity of these regional injuries only reached a significant difference for chest and abdominal injuries . incidence of regional injuries and mean ais score per region for both groups both , the mean time from injury to arrival to the ed ( 73 vs. 247 minutes , p = 0.001 ) and the time spent in the ed ( 83 vs. 168 minutes , p = 0.001 ) , were significantly longer for the scottish patients [ figures 1 and 2 ] . mean time from injury to arrival to the ed for both groups ( 73 vs. 247 minutes , p = 0.001 ) mean time spent in the ed for both groups ( 83 vs. 168 minutes , p = 0.001 ) table 5 illustrates the outcome parameters . the standardized mortality ratio was significantly greater for the scottish population [ table 5 ] . there was , however , a large difference in the cohorts analyzed with 227 patients in the scottish group and 6878 patients in the german group . this difference is probably related to the actual population size of the individual countries , with over 5 million in scotland and over 80 million in germany . the population density also differs , as scotland 's average population density is 66 persons per square kilometer , and in germany , there are 230 persons per square kilometer . therefore we critically accepted the different cohort sizes . a recent prospective study in the west of scotland compared the outcomes of patients suffering moderate to severe trauma in urban versus rural environments . they demonstrated no significant differences for length of inpatient stay or mortality for either group , despite a significantly longer time from scene to the ed for rural patients . these results are supported by our study , as the longer transfer times we observed , are probably related to distance from the ed and may not result in a worse outcome ; the standardized mortality ratio was greater for the scottish population , although several authors have concerns in the use of triss methodology to compare differing trauma centers . most registries do not include patients who are dead at the scene or die on route to the ed . these patients are lost to the analysis and are not included in the stag or gtr datasets . therefore , we can not conclude if patients , who die before reaching the ed , may have survived if they had reached definitive care earlier . this may have led to a selection bias in our study groups , with critically ill patients dying before arrival to hospital in scotland , therefore , being excluded , whereas the same critical patient in germany may arrive at hospital earlier and become part of the register . the shorter pre - hospital times in the german group are probably due to greater use of air transportation of polytrauma patients by helicopter emergency medical services ( hems ) in germany . the main advantages of hems are : 1 ) shortened overall time to patient arrival at hospital , 2 ) potentially better pre - clinical therapy due to the presence of a highly qualified medical team , 3 ) efficient , fast , and if needed , long - distance transport to level 1 trauma centers . scotland only has 4 air ambulance aircrafts , whereas germany has far more units available in all regions , allowing for more flexible usage and shorter pre - hospital times . the use of air transport has been shown to have a positive effect on the mortality of polytrauma patients . a prospective study , comparing patients transferred by ground ambulance or hems to hospital of polytrauma patients revealed that primary transfer by hems to a level 1 trauma center reduced mortality , compared with transfer to a regional hospital by ground ambulance . they attributed this to superior pre - hospital therapy by the hems team in combination with specialist care at the level 1 trauma center . legislative differences exist between the countries that may contribute to the difference in pre - hospital times . in germany , there exists legislation called the rettungsdienstgesetze ( emergency medical services act ) that governs rescue protocols and the hilfsfrist ( period to help ) ; the time it takes from receiving the emergency call to the arrival of adequate emergency assistance to the scene . this varies regionally throughout germany , but on average , the deadline for emergency assistance to reach the scene is 10 to 15 minutes . this act demands that emergency medical services providers to fulfill the deadline in 95% of emergencies . thus , unlike in scotland where such legislation does not exist , there is an additional responsibility upon the german rescue services and consequently shorter pre - hospital times . scottish polytrauma patients received less pre - hospital interventions , compared to the german patients who received more aggressive intravenous fluid replacement , a higher rate of intubations , and prescribed more anesthetic drugs . the first responders to the scene in scotland are mainly ambulance paramedics or technicians who perform basic life support ( bls ) techniques . they do receive training in endotracheal intubation , intravenous cannulation and fluid administration , and in the use of anesthetic drugs , but the rate at which these are used is relatively low . this may be due to a desire for prompt transfer to a facility for definitive treatment or inexperience of the practitioner . despite this variation in pre - hospital interventions , there was no significant difference demonstrated of physiological parameters upon arrival to the ed , reflected by similar rts for both populations . it is possible for advanced life support ( als ) providers to tailor their on - scene management to stabilize the severely injured patient and not delay transfer to definitive management , as this may be detrimental to patient outcome . patient with an iss of 16 or more , have a significantly increased risk of mortality , and it is this group of patients that benefit most from rapid evacuation to definitive care . previous studies[2022 ] have discussed if there is a tendency for als personnel to waste precious time performing als procedures . trunkey et al and lewis et al have suggested that some als skills are necessary whilst others are a waste of precious time in the field . despite a significantly higher iss in the german group , the unadjusted mortality rates were similar for both populations . one explanation for the higher iss observed in the german population could be the greater use of computer tomography scans used for their patients ( 73.6% vs. 78.5% , p = 0.03 ) . this may have resulted in more covert chest and abdominal injuries being identified , for which we demonstrated a significantly higher prevalence in the german population . this would have also influenced the triss and hence the observed difference in the standardized mortality rates , despite similar unadjusted mortality rates . on the other hand , regional injury severity also differed significantly for chest and abdominal injuries . here , one would expect , that the higher rate of ct scans had no influence , since e.g. severe pulmonary contusions would also be visible on plain chest x - ray . furthermore , comparison of iss alone between differing populations does not take into account other case - mix variables , such as pre - existing medical conditions that influence mortality , although these have a lesser affect on severely injured trauma patients ( iss > 16 ) . it would seem the observed diversity in pre - hospital times and pre - hospital interventions between the groups do not make a difference to overall survival . management of the trauma patient is a multifaceted process , where management and transport to the ed is just one step . this may reflect the need for longer resuscitation , which in germany has already been commenced pre - hospitalization and hence less time is spent in the ed . this theory , however , is not supported by the initial physiological parameters , with similar rts for both groups . it is neither an aim nor in the scope of this study to draw conclusions or derive indications as to which approach to trauma management is superior . this is due to the multi - factorial reasons , unique to individual countries and regions , some of which have been discussed . this study is a novel comparison of two differing populations and their hospital management of the severely injured patient . both the scotland and german populations have similar demographics . the german population , however , present with more severe injuries which may be reflected in the lower standardised mortality ratio . despite longer pre - hospital transfer times and more interventions in the german group , no significant difference was demonstrated in rts upon arrival , or unadjusted mortality rates .

introduction : the management of trauma patients differs depending upon the healthcare system available.aim:to compare the pre - hospital management and outcome of polytrauma patients between two countries with differing approaches to pre - hospital management.materials and methods : the scottish trauma and audit group ( stag ) and the german trauma registry ( gtr ) databases were used to compare the management and outcome of trauma patients in scotland and germany . severely injured patients ( injury severity score ( iss ) > 16 ) were analyzed for a 3 year period ( 2000 to 2002 ) . patient demographics , pre - hospital interventions , iss , revised trauma score ( rts ) , time from scene of injury to arrival to the emergency department ( ed ) , 120 day mortality and standardized mortality ratios using triss methodology were compared.results:there were 227 patients identified from the stag registry and 6878 patients from the gtr registry . there was a significant difference in iss ( 24.9 vs. 29.8 , p = 0.001 , respectively ) . no significant difference was observed for the rts ( p = 0.2 ) . there was a significantly higher rate of pre - hospital interventions in the german group ( p < 0.001 ) . the mean time from an injury to arrival to the ed ( 73 vs. 247 minutes , p = 0.001 ) was longer for the scottish patients . there was no difference for an unadjusted mortality rate between the groups , but the standardized mortality ratio was significantly greater for the scottish population ( 3.8 vs. 2.2 , p = 0.036).conclusion : despite variation in pre - hospital transfer times and interventions , no significant difference was demonstrated in rts upon arrival , or for the unadjusted mortality rates .

the expression " early childhood caries " ( ecc ) is used to refer to any stage of caries lesion in any surface of primary teeth of children up to 71 months of age7,11 . the national survey carried out in 2002 - 20032 revealed a caries prevalence of 26.8% among 18 - 36-month - old brazilian children , and 23.2% among the inhabitants of the southeastern region of the country . using the criteria proposed by the world health organization ( who)19 , in which a tooth is considered carious only if there is a visible evidence of a cavity , this national survey included data referring only to cavitated caries lesions ( ccl ) and non - cavitated caries lesions were not considered . although the inclusion of the initial stages of caries in epidemiological surveys is questionable because of the possibility of lesion reversal , its identification is socially relevant , as it gives the opportunity of early intervention1,7,18 . this study aimed to determine the prevalence of ccl and ecc , evaluating the contribution of different variables in its occurrence in children up to 36 months of age attending public daycare centers in municipalities with different fluoride concentration in the water supply . the study was conducted with children up to 36 months of age in public daycare centers of two municipalities located in the southeastern region of brazil : clementina , in which fluoride is not added to the water supply and the natural fluoride content is lower than 0.40 mg f / l17 ( low fluoride content - lfc ) , and gabriel monteiro , in which fluoride is added to the water supply in an optimal concentration that ranges from 0.60 to 0.75 mg f / l17 ( adequate fluoride content - afc ) . in the daycare centers , the children take cow 's milk from nursing bottles sweetened with sugar , and are fed sugar - containing snacks like biscuits and sweetened drinks ( juices and tea ) daily . neither the caregivers were aware of the need to brush the children 's teeth , nor the daycare centers offered preventive oral health programs . after approval by the research ethics committee of the so paulo state university , the parents were invited to participate in the survey and , upon acceptance , they were interviewed about the following issues : the economic classification of the family , using the classification proposed by the brazilian association of research companies , the parents ' age and educational level , nursing habits , consumption of water from the public water supply , use of dentifrice , access to dental assistance and background knowledge of oral health care . exclusion criteria were the refusal to answer the questionnaire , absence of parental consent for clinical examination of the children or absence of teeth in the child . clinical examinations were carried out under natural light , by a single examiner , trained and calibrated , who assumed a knee - to - knee position and was helped by an assistant and by a note taker . a plaque - disclosing solution was applied to the buccal and palatal / lingual surfaces . the dental crowns were examined two days later for the presence of caries lesions . for ccl , the same codes and criteria established by the who19 were applied . therefore , a tooth was considered carious only if there was a visible evidence of a cavity . since there was a need to include early caries lesions in this study , the criteria proposed by the american dental association ( ada)7 for ecc were used . therefore , in pits and fissures , a distinct chalky white enamel directly adjacent to or into a pit or fissure or a light to dark brown discolored area was considered ecc , while in smooth surfaces , a distinct chalky white enamel adjacent or close to the gingival margin was considered ecc . the means and standard deviation ( mean sd ) of the examined children 's ages and the means , standard deviation and 95% confidence interval ( mean sd ; 95% ci ) of the dmft and dmfs were calculated . fisher 's exact test ( a=0.05 ) was applied to access the association between variables studied , using biosestat 4.0 software program . from a total of 88 children , 68 ( 77.3% ) were examined . in the lfc municipality , 38 children aged 8 to 36 months ( 23.70 8.30 ) participated in the study , while in the afc municipality , 30 children aged 8 to 36 months ( 23.63 9.28 ) were examined . the dmft and dmfs indices calculated for the study sample are presented in table 1 . afc = with adequate fluoride content ; lfc = with low fluoride content . considering all children fisher 's exact test revealed the existence of statistically significant differences ( p<0.05 ) regarding the economic classification , mother 's educational level and duration of breastfeeding . higher prevalence of ccl was associated with lower economic classification , lower mother 's education level ( 8 years of study ) and higher duration of breastfeeding ( > 12 months of age ) . economic classification proposed by the brazilian association of research companies . average monthly family income : high - u$ 213 to 1,402 - classes b and c ; low - u$ 103 to 212 - classes d and e. ; afc = with adequate fluoride content ; lfc = with low fluoride content . fisher 's exact test revealed statistically significant differences ( p<0.05 ) regarding to age group , duration of the habit of drinking milk before bedtime , and age at which oral hygiene started . higher prevalence of ecc was associated with the older age group , higher duration of the bedtime feeding habit ( > 12 months of age ) , and later start of oral hygiene ( > 12 months of age ) . average monthly family income : high - u$ 213 to 1,402 - classes b and c ; low - u$ 103 to 212 - classes d and e. ; afc = with adequate fluoride content ; lfc = with low fluoride content . although a reduction in the prevalence of caries in preschoolers has been observed12 , ecc is still considered a public health problem because its a predisposing factor to the occurrence of caries disease in the permanent dentition , impairs normal feeding , leading to growth alterations , causes pain and discomfort , and may bring communication and psychosocial problems , affecting the child 's life quality4,6,10 . considering only the 18 - 36-month age group , 22.2% of the children presented ccl ( table 2 ) , which is a higher incidence than that reported by brando , et al.1 ( 2006 ) . however , the children taking part in that study had had an easy access to dental care , which demonstrates the importance of early dental care . when data were collected from children who had not had access to dental care , such as those taking part in the present study , as reported elsewhere 4,13,15 , in the present study , dental caries had an early onset in the examined children . caries prevalence increased with age and ecc prevalence presented a statistical significance ( p<0.05 ) with regards to age group ( table 3 ) . this can be explained by the so called " window of infectivity " , defined as that period between the ages of 16 and 32 months , in which the children is infected with streptococcus mutans , although some studies indicate that infection may occur at a younger age , even before 14 months of age14 . in the present study , the parents were only asked about nursing habits , but it is important to mention that the children consumed sugar - containing snacks daily in the daycare centers . the relationship between caries and milk feeding is controversial in the literature . in the present study , the children who were breastfed beyond 12 months of age presented higher prevalence of ccl ( p<0.05 ) , confirming the findings of dini , et al.6 ( 2000 ) . in children that presented ecc , prolongation of the habit of milk feeding at bedtime beyond the age of 12 months was considered statistically significant ( p<0.05 ) , corroborating the findings of milgrom , et al.13 ( 2000 ) . nighttime milk feeding , mainly bottle - feeding , seems to be associated with the beginning of colonization of the baby 's mouth10 , presence of a large number of cariogenic microorganisms13,14 , increase in sucrose consumption , mainly by baby bottle , and reduction in oral hygiene practices8 . children who started oral hygiene earlier presented a lower prevalence of ecc ( p<0.05 ) , which corroborates the findings of previous studies4,5 . relationship between the quality of oral hygiene and caries prevalence was not observed in the present study . fraiz and walter8 ( 2001 ) and santos and soviero18 ( 2002 ) observed a relationship between the presence of caries lesions and the amount of biofilm visible without the use of disclosing agents in children younger than 36 months old . these results can be explained by the methodological differences and by the fact that , although the population examined in this study presented great amount of bacterial biofilm , it may not contain cariogenic bacteria . among the socioeconomic variables , when only ccl were considered , the economic classification of the children examined and the mother 's educational level were significantly different ( p<0.05 ) . a higher prevalence of ccl was associated with a lower economic classification and a lower mother 's educational level , confirming the findings of dini , et al.6 ( 2000 ) . economically deprived individuals living under less privileged social and environmental conditions , usually have a poorer health behavior and are therefore are more susceptible to diseases , including oral diseases.3 according to the parents , in the afc municipality , only 54.5% of the children consumed water from the public supply . this is probably the reason why water fluoridation , which has a recognized action to reduce dental caries5 , did not showed a statistical significance in the present study . the use of fluoridated dentifrice did not determine a lower caries prevalence , which might be explained by the time that the children stay in the daycare center , without brushing their teeth . furthermore , most parents affirmed that they had never been instructed with regards to their children 's oral health . access to dental care did not present a relationship with caries prevalence , corroborating the findings of cario , et al.4 ( 2003 ) . many of the children examined in the present study had never been to the dentist . after completion of data collection , considering the children 's age ( 36 months old ) , a high prevalence of dental caries ( ccl and ecc ) was observed in the present study . higher prevalence of ccl was associated with lower socioeconomic status , lower mother 's educational level and higher duration of breastfeeding . higher prevalence of ecc was associated with older age group , higher duration of bedtime feeding habit , and later start of oral hygiene . although the water fluoride content did not show statistical significance with respect to the presence of caries lesions , the children presented a lower caries prevalence in the municipality with adequate fluoride content . caries prevention strategies on this population should include instructions parents and daycare center employees about oral hygiene , dietary habits , in addition to access to dental care services .

this study determined the prevalence of cavitated caries lesions ( ccl ) and early childhood caries ( ecc ) , and the contribution of some variables in children up to 36 months of age attending daycare centers in municipalities with different fluoride levels in the water supply : afc ( adequate fluoride content ) and lfc ( low fluoride content ) . after approval of the ethics committee , the parents were interviewed . the children were clinically examined using the same codes and criteria established by the who ( world health organization ) and the ada ( american dental association ) . fisher 's exact test ( p<0.05 ) was applied for statistical analysis of data . the dmft indices calculated in the lfc and afc municipalities were 0.57 and 0.68 , respectively . considering all children examined , 17.6% presented ccl and 33.8% ecc . the economic classification , mother 's education level and duration of breastfeeding were considered statistically significant with regards to ccl prevalence . the age group , duration of the habit of drinking milk before bedtime and age at which oral hygiene started were considered statistically significant with regards to ecc prevalence .

malakoplakia is a rare , chronic , granulomatous inflammatory disease that was first described by michaelis and gutmann in 1902 . the name " malakoplakia " was derived from the greek " malakos " ( soft ) and " plakos " ( plaque ) in 1903 by von hansemann . malakoplakia is most commonly found in the urinary tract , but has been reported in the gastrointestinal tract , lung , brain , lymph node , adrenal , tonsil , conjunctiva , skin , bone , abdominal wall , pancreas , retroperitoneum , and female genital tract . malakoplakia is associated with many coexisitng conditions , such as organ transplantation , tuberculosis , sarcoidosis , allergic conditions , cytotoxic chemotherapy , acquired immunodeficiency syndrome , malignancies , steroid use , alcohol abuse , poorly controlled diabetes , ulcerative colitis , and malnutrition . , we report a case of malakoplakia in an otherwise healthy 19-year - old female with a review of the literature . a 19-year - old female was referred to our hospital following the discovery of multiple polyps in the rectum with sigmoidoscopy . her clinical symptoms were recurrent low abdominal pain and loose stool with blood and foul odor 4 to 5 times a day for 3 months . when the patient was admitted , she was in relatively good condition with no specific past medical history and did not complain of fever , chill , anorexia , weight loss , or cold sweating . on physical examination , there were no definite abnormal findings except for mild epigastric tenderness and slightly increased bowel sounds . blood pressure was 110/76 mmhg , pulse rate 106 beats per minute , body temperature 36.3. laboratory tests revealed hemoglobin at 9.0 g / dl , white blood cell ( wbc ) count at 9,050/l with 26.6% neutrophils , 27.2% lymphocytes , 15.2% monocytes , and 0.8% eosinophils . a peripheral blood smear showed normocytic normochromic anemia , fe of 18 g / dl , total iron binding capacity of 286 g / dl , 0.8% reticulocytes , and stool occult blood over 1,000 ng / ml . inflammatory markers such as c - reactive protein ( crp ) and erythrocyte sedimentation rate ( esr ) were mildly elevated to 3.03 mg / dl and 42 mm / hr , respectively . urine analysis with microscopic exam showed no abnormality . stool acid - fast bacillus and tuberculosis polymerase chain reaction were negative , and gram stain showed wbc 10 to 25 and a number of gram - positive cocci and gram - negative bacilli . in the stool culture , salmonella or shigella was not isolated and blood cultures were negative . serum igg , ige , and hemolytic complement 50 ( ch50 ) complement levels were slightly elevated to 1,800 mg / dl , 236 iu , and 54.2 u / ml , respectively . colonoscopy revealed very diverse circular or flat elevated mucosal lesions up to 10 cm in size from the cecum to the descending colon , small nodules , mass - like lesions , and erosive small polypoid lesions throughout the colon , particularly in the sigmoid colon ( fig . after colonoscopy , we initially suspected atypical lymphoma or malignancy . however , lactate dehydrogenase and tumor markers such as carcinoembryonic antigen , ca 125 , ca 19 - 9 , and -fetoprotein were within normal range and an abdominopelvic computed tomography scan revealed no other abnormal findings , except for localized multiple small reactive lymph node enlargements along the mesentery . histological examination of colon lesion biopsies revealed dense histiocyte infiltration with round inclusions of varying sizes in the cytoplasm . many of these inclusions had round laminated structures with a central dark area and peripheral pale halo . these structures were stained with periodic acid - schiff ( pas ) , alcian blue , prussian blue , and gomori methenamine silver stains to confirm the presence of michaelis - gutmann bodies with pathognomonic features of malakoplakia ( fig . these diagnostic tests confirmed the diagnosis of malakoplakia . during antibiotic treatment , diarrhea and abdominal pain improved so she was discharged with instructions to take 500 mg ciprofloxacin twice a day , 25 mg bethanecol three times a day , and 60 mg ascorbic acid once a day by mouth . after the treatment started , the symptoms of abdominal pain and diarrhea disappeared in a week . after 2 months , crp , esr , and hemoglobin were nearly normal with values of 0.32 mg / dl , 2 mm / hr , and 12.5 g / dl , respectively . the patient remained on this regimen for 6 months . during the treatment period , no drug side effects were observed . previous abnormal colonoscopy findings were remarkably improved after 6 months of follow - up , and returned to normal after the end of 12 months ( fig . the gastrointestinal tract is the second most common site of involvement by malakoplakia , and most of these cases involve the rectum and colon . clinical manifestation of colonic malakoplakia is very diverse , from asymptomatic to diarrhea , abdominal pain , rectal bleeding , intestinal obstruction , vomiting , malaise , fever , and constipation . endoscopically , malakoplakia commonly presents in the early stages as soft yellow to tan mucosal plaques or in the late stages as raised , grey to tan lesions in various sizes with peripheral hyperemia and a central depressed area . malakoplakia can be diagnosed by histology with the presence of the mineralized basophilic structures and michaelis - gutmann bodies . the etiology and pathogenesis of malakoplakia is still not fully understood , but multiple possible mechanisms have been suggested . the involvement of microorganisms is supported by reports of patients with malakoplakia who have chronic infections with various organisms such as escherichia coli , proteus , mycobacterium tuberculosis , and staphylococcus aureus . infections induced by the microorganisms mentioned above are much more common than malakoplakia ; therefore , other factors must contribute . malakoplakia may also be caused by a defect in lysosomal processing of microorganisms undergoing phagocytosis by macrophages or monocytes . therefore , incompletely digested microorganisms accumulate in lysosomes and lead to mineralization of calcium and iron salts on residual microorganism glycolipids . these michaelis - gutmann bodies can be intracellular or extracellular when stained with pas , prussian blue for iron , and von kossa for calcium . the assembly of microtubules is stimulated by cyclic guanosine monophosphate ( cgmp ) and inhibited by cyclic adenosine monophosphate ( camp ) . both low cgmp level and reduced -glucuronidase activity have been reported in patients with malakoplakia . in this patient , we initially suspected atypical lymphoma , familial adenomatous polyposis , or other uncommon cancers because of a wide variety of mucosal lesions throughout the colon . we performed multiple random colonic biopsies to verify the diagnosis and , in all biopsies , michaelis - gutmann bodies characteristic of malakoplakia were observed . no definite infectious signs were checked , as the patient did not have any specific infectious disease such as pneumonia or otitis media in her childhood . we could not measure polymorphonuclear leukocyte function through stimulation by cgmp and inhibition by camp . there may also be a corrlation between immunosuppression or chronic prolonged iellness and malakoplakia because immunodeficient individuals and patients receiving chemotherapy or immmunosuppressive therapy for transplantation constitute a considerable portion of malakoplakia cases . furthermore , malakoplakia seems to be correlated with malignant neoplasms and systemic diseases , such as systemic lupus erythematosis , mycotic infections , liver diseases , sarcoidosis , ulcerative colitis , cachexia , and drug addiction . some authors hypothesized that the coincidence of malakoplakia with colonic and rectal adenocarcinoma might begin with local alteration of gut flora and advised physicians to carefully search for a colorectal neoplasm when malakoplakia appears histologically . however , the patient in this study was not immunocompromised and did not have any suspicious findings of autoimmune disease . generally , malakoplakia should be differentiated from crohn 's disease , military tuberculosis , sarcoidosis , whipple disease , chediak - higashi syndrome , and malignancies such as colon cancer and lymphoma . to rule out a particularly serious malignant disease and evaluate the response to treatment , follow - up colonoscopies with random biopsies were performed four times at 3 , 6 , and 12 months , and at 6 months after the end of treatment for a total follow - up period of 18 months . the first strategy is to increase the intracellular cgmp to camp ratio using cholinergic agonists such as bethanechol and ascorbic acid to improve lysosomal function . the second therapeutic strategy is to treat the presumed microorganism infection within the colon by antibiotics . the antibiotics trimethoprim / sulphamethoxazol , rifampicin , and particularly ciprofloxacin have all been used in the treatment of malakoplakia , because these are able to enter macrophages and contribute to intracellular microorganism death . the duration of treatment is not fixed , but long - term treatment is advised , although its efficacy still remains debated . according to the report , an underlying condition is the most crucial factor affecting malakoplakia mortality , and significant morbidity is related to the chronic underlying condition , which can resist local and systemic therapy . in this case , the patient 's symptoms improved very quickly after antibiotic treatment . since her symptoms and clinical results improved without aggravation after medical treatment , we speculated that she suffered from malakoplakia without coexisting disease and that immune maturation with aging might play a role . the etiology of colonic malakoplakia in this patient was unclear since there were no microorganisms in the stool and blood culture . the patient had no specific past medical history and was not immunodeficient , did not have a malignancy or any chronic illness , and was not in the most frequently affected age group . in korea , three cases of malakoplakia have been reported [ 8 - 10 ] . one of these cases was treated surgically , another treated by endoscopic polypectomy , and the last one treated medically . this is the first case of malakoplakia with very diverse mucosal lesions throughout the entire colon in a healthy young female with no associated disease . our case illustrates that when very diverse and atypical mucosal lesions are detected on colonoscopy , physicians should consider malakoplakia .

malakoplakia is a rare granulomatous disease that occurs commonly in the urinary tract and secondarily in the gastrointestinal tract . most reported cases of malakoplakia are associated with immunosuppressive diseases or chronic prolonged illness . here , we report a rare case of malakoplakia in a young healthy adolescent without any underlying disease . a 19-year - old female was referred to our hospital following the discovery of multiple rectal polyps with sigmoidoscopy . she had no specific past medical history but complained of recurrent abdominal pain and diarrhea for 3 months . a colonoscopy revealed diverse mucosal lesions including plaques , polyps , nodules , and mass - like lesions . histological examination revealed a sheet of histiocytes with pathognomonic michaelis - gutmann bodies . we treated the patient with ciprofloxacin , the cholinergic agonist bethanechol , and a multivitamin for 6 months . a follow - up colonoscopy revealed that her condition was resolved with this course of treatment .

staphylococcus aureus is an important food - borne pathogen involved in a variety of invasive diseases ( 1 ) . it produces many toxins as well as non - toxic enzymes and can facilitate bacterial attack and proliferation in the body of host ( 2 ) . some strains produce staphylococcal enterotoxins ( ses ) that can cause food poisoning if food containing preformed se is ingested . symptoms of staphylococcal food poisoning ( sfp ) have a rapid onset ( 2 to 6 h ) and may include vomiting , stomach pain and diarrhea ( 3 ) . enterotoxins from s. aureus strains can be classified into 18 serological types : a - u ( except s , f and t)(2,4 - 9 ) . the ses are a group of heat stable and pepsin resistant exotoxins encoded by genes in the chromosome , pathogenicity island , phages or plasmids ( 2 ) . for production of sufficient amount of toxin to cause intoxication symptoms , 10 cfu / ml or cfu / g enterotoxigenic strains of bacteria are needed ( 10 ) . ses are low molecular weight proteins ( mw 26.900 29600 kd ) ( 11 ) . sea is a leading cause of food intoxication ( 12 ) and is an extremely potent gastrointestinal toxin , as little as 100 ng is sufficient to cause symptoms of intoxication ( 13 ) . milk and milk products have frequently been implicated in staphylococcal food poisoning and contaminated raw milk is often involved ( 2 , 3 ) . s. aureus mastitis is a serious problem in dairy production and infected animals may contaminate bulk milk . human handlers , milking equipment , the environment and the udder and teat skin of dairy animals are other possible sources of bulk milk contamination ( 3 , 14 ) . surveys to detect classical enterotoxins and to identify enterotoxin genes in s. aureus from milk and milk products have been conducted in many counties including italy , norway , turkey , brazil and iran ( tehran ) ( 16 - 20 ) . however , there are no published reports about presence of sea gene in milk and its products in tabriz - iran . therefore , this study was conducted to investigate the presence of sea gene of s. aureus in organic milk and cheese using pcr method in tabriz - iran . a total of 200 samples ( 100 milk samples , 100 cheese samples ) were collected from milk collection points and food stores in tabriz , iran . the samples were collected in sterile containers , immediately kept in an ice box and transported to the laboratory . the samples were investigated microbiologically for the presence of s. aureus , according to the standard method no . 6806 - 1 of the institute of standards and industrial research of iran ( isiri ) . the milk and cheese samples were diluted in ringer and pepton water , respectively . from each diluted solutions produced , 1 ml was transferred to brain- heart infusion broth and incubated at 37c for 24 h. baird- parker agar supplemented with potassium tellurite and egg yolk emulsion was used for isolation of s. aureus . after 24 - 48 h incubation at 37c , the bpa plates were analyzed for the presence of s. aureus , which appeared as black colonies with transparent zone . biochemical confirmation tests ( gram staining , coagulase , catalase , oxidase , vp and growth on mannitol salt agar ) were carried out for final identification of the suspected s. aureus isolates . for dna isolation , biochemically confirmed single colonies of s. aureus isolates on bpa were cultured on lb broth . dna extraction procedure was done by a commercial kit ( cinna pure kit ) , according to the supplier s instructions on the bacterial cells pellet from an overnight culture in lb broth . the primers used for the detection of nuc and sea genes are listed in table 1 . pcr reactions were performed in reaction buffer ( 10x ) , mgcl2 ( 50 mm ) in a total volume of 25 l , containing 5 l of template dna , 0.75 l of each primers ( 10 pm ) , 0.25 l of dntp ( 10 mm ) , 0.2 l of taq dna polymerase ( 5 unit/l ) and 14.05 l of ddh2o . pcr was performed under the following conditions : initial denaturation at 94c for 5 min , subsequently followed by 30 cycles of 94c for 1 min , 55c for 1 min and 72c for 1 min with a final extention of 5 min at 72c . pcr reaction was conducted like the previous test but with some changes in annealing temperature ( 50c for 1 min ) . the presence of 552 bp amplicon indicates the positive samples for sea gene in these isolates . a total of 200 samples ( 100 milk samples , 100 cheese samples ) were collected from milk collection points and food stores in tabriz , iran . the samples were collected in sterile containers , immediately kept in an ice box and transported to the laboratory . the samples were investigated microbiologically for the presence of s. aureus , according to the standard method no . 6806 - 1 of the institute of standards and industrial research of iran ( isiri ) . the milk and cheese samples were diluted in ringer and pepton water , respectively . from each diluted solutions produced , 1 ml was transferred to brain- heart infusion broth and incubated at 37c for 24 h. baird- parker agar supplemented with potassium tellurite and egg yolk emulsion was used for isolation of s. aureus . after 24 - 48 h incubation at 37c , the bpa plates were analyzed for the presence of s. aureus , which appeared as black colonies with transparent zone . biochemical confirmation tests ( gram staining , coagulase , catalase , oxidase , vp and growth on mannitol salt agar ) were carried out for final identification of the suspected s. aureus isolates . for dna isolation , biochemically confirmed single colonies of s. aureus isolates on bpa were cultured on lb broth . dna extraction procedure was done by a commercial kit ( cinna pure kit ) , according to the supplier s instructions on the bacterial cells pellet from an overnight culture in lb broth . the primers used for the detection of nuc and sea genes are listed in table 1 . pcr reactions were performed in reaction buffer ( 10x ) , mgcl2 ( 50 mm ) in a total volume of 25 l , containing 5 l of template dna , 0.75 l of each primers ( 10 pm ) , 0.25 l of dntp ( 10 mm ) , 0.2 l of taq dna polymerase ( 5 unit/l ) and 14.05 l of ddh2o . pcr was performed under the following conditions : initial denaturation at 94c for 5 min , subsequently followed by 30 cycles of 94c for 1 min , 55c for 1 min and 72c for 1 min with a final extention of 5 min at 72c . pcr reaction was conducted like the previous test but with some changes in annealing temperature ( 50c for 1 min ) . the presence of 552 bp amplicon indicates the positive samples for sea gene in these isolates . in the present study , s. aureus was observed in 54 ( 27 % ) out of 200 samples : 9 from milk and 45 from cheese samples . the number of bacteria in contaminated samples by cfu / ml is shown in table 2 . for further molecular confirmation of s. aureus colonies , pcr reaction for nuc gene was performed . results showed that 7 out of 54 s. aureus isolates harbored sea gene ( table 2 ) . several researchers have reported different results of the number of bacteria in contaminated dairy products by cfu / ml ( 10 , 20 , 21 ) . variations in s. aureus count in dairy products may depend on sanitary precautions during milk processing chain . the existence of s. aureus in food and dairy products was previously confirmed by imani fooladi in iran ( 20 ) . sea is the most common enterotoxin recovered from food poisoning outbreaks in the usa ( 77.8% of all outbreaks)(24 ) . in the current study considering the findings of brakstad et al.(22 ) , and comparing them to our study , it can be stated that the pcr for amplification of the nuc gene has potential for rapid diagnosis and confirmation of s. aureus isolates . the present study aimed to evaluate the prevalence rate of sea gene in organic milk and cheese in tabriz , iran . outside of iran , various results have been reported on the presence of s. aureus and its enterotoxins in milk and its products ( 28 - 31 ) . in the current study , we found that 27% of the organic milk and cheese samples were contaminated by s. aureus . pcr results for sea gene , showed that 12.96% of the isolates possessed sea gene . similar level of incidence was reported by holeckova et al . , ( 32 ) , imani fooladi et al . , ( 20 ) and el - jakee et al . this discrepancy could be attributed to the improvements in the handling and sanitary procedures during milking and its processing . it was concluded that even though the level of microorganisms in dairy products was not sufficient to cause disease , the presence of toxins could be considered a potential risk for public health . several conditions such as delay in processing , inadequate refrigeration , poor personal hygiene and post process contamination are associated with staphylococcal growth and enterotoxin production ( 34 ) . therefore it is essential to ensure high safety standards for preventing staphylococcal food poisoning . in conclusion , the results of this study provides some important preliminary data about the prevalence of enterotoxigenic s. aureus in organic milk and cheese in tabriz , iran . consumption of organic milk and specially cheese is still widespread and could cause a potential risk to public health , so an effective reduction of contamination levels could be achieved by improving sanitation and hygiene procedures . further investigations are needed to evaluate the production of other toxins in milk and cheese .

background and objectivesstaphylococcal food poisoning is a gastrointestinal disease , which is caused by consumption of contaminated food with enterotoxins produced by staphylococcus aureus ( ses ) . milk and its products are known sources of food borne diseases . this study was carried out to evaluate the prevalence of enterotoxigenic s. aureus strains in organic milk and cheese in tabriz - iran.materials and methodsa total of 200 samples ( 100 milk samples and 100 cheese samples ) were collected from farms and milk collection points in tabriz - iran . the samples were cultured and identified by standard bacteriological methods , then pcr was performed to detect sea gene.results and conclusionstaphylococcus aureus was found in 27% of all samples ( milk and cheese ) . results of pcr showed that 12.96% of s. aureus isolates possessed sea gene . it suggested the potential public health threat of s. aureus resulting from contamination of dairy products . so , efforts are required to improve safety standards for preventing staphylococcal food poisoning .

the incidences of neuropsychiatric manifestations , like affective disorder or depression , are increasingly reported in general psychiatric and neurological practices , due to high - stress lifestyle . there are many contributing psychological , neuropsychiatric , and medical factors that should be investigated . the antiphospholipid syndrome ( aps ) , also known as lupus anticoagulant syndrome or anticardiolipin antibody syndrome , is a rare form of autoimmune coagulopathy.1,2 aps is characterized and diagnosed by recurrent vascular thrombosis or pregnancy - related morbidity , in the presence of circulating antiphospholipid ( apl ) antibodies . it is usually observed in young adults with , the most common neurologic manifestation being transient ischemic attack ; other manifestations include stroke , seizure , or acute encephalopathy.1,2 it can be easily overlooked if the patient presents with progressive neuropsychiatric disorders , such as depression or dementia . herein , we report two young women with aps who presented with similar neuropsychiatric disorders but different radiological manifestations . a 35-year - old female experienced progressive mental decline and depression for more than 2 years . initially she was treated at a psychiatric outpatient department ( opd ) , for 1 year . the depressive symptoms improved , but cognitive impairment did not show improvement ; hence , she was referred to the neurological opd . initial laboratory analysis revealed elevated erythrocyte sedimentation rate ( esr ) ( 312 mm / h ) and positive antinuclear antibody ( ana ) test ( 1:80 ) . dementia was suspected , based on the clinical presentation , and she was admitted for further examination . her history revealed four episodes of fetal abortion and diagnosis of aps 3 years previously , by medical record ; she had discontinued treatment for aps for 2 years . laboratory findings indicated anemia ( hemoglobin : 11.3 g / dl ) , thrombocytopenia ( platelet count : 76000/l ) , and abnormal coagulation function ( partial thromboplastin time [ ptt ] : 73.4/29.3 s ; prothrombin time [ pt ] : 11.2/10.8 s ; international normalized ratio [ inr ] : 1.16 ) . her autoimmune profiles were positive for anticardiolipin antibody ( acl ) , lupus anticoagulant antibody ( lac ) , ana , rheumatoid arthritis factor ( ra ) , apl immunoglobulin ( ig)g and igm , anti - ro , and showed decreased complement protein ( c)3 and c4 levels ( table 1 ) . the findings of brain magnetic resonance imaging ( mri ) were multiple old infarcts with encephalomalacia in bilateral cerebral hemispheres and the left cerebellar hemisphere ( figure 1 ) . her cognitive ability screening instrument ( casi ) score was 19 ( cutoff value is 85 , below is abnormal result).3 the casi - estimated mini - mental state examination ( mmse - ce ) score was 9 ( cutoff value is 25 , below is abnormal result ) . assessment with the neuropsychiatric inventory ( npi ) indicated disinhibited behavior . according to the report of neuropsychological testing warfarin was prescribed to control coagulopathy , along with a disease - modifying antirheumatic drug ( hydroxychloroquine ) . however , we lost this patient to follow - up for unknown reason . a 22-year - old unmarried female developed progressively depressive mood over a period of 1 month . gradually , her verbal output decreased , with incoherent speech , and she developed mild left upper limb weakness . intermittent involuntary movements of her four limbs were observed for several days before her referral to the neurological opd . neurological examination revealed abulia and slight decrease in the muscle power of her left upper limb . immediately brain computed topography ( ct ) was performed ; the results revealed a hyperdense , gyriform lesion along the cortices of the right temporoparietal lobe , with perifocal edema ( figure 2a ) . following this , she was transferred to a medical center hospital . at the emergency department , the laboratory blood test revealed anemia ( hemoglobin : 11.3 g / dl ) , thrombocytopenia ( platelet count : 75000/l ) , and normal coagulation function ( ptt : 30.6/28.6 s ; pt : 10.9/10.7 s ; inr : 1.04 ) . the brain ct findings were discussed with a neurosurgeon , and arteriovenous malformation ( avm ) with hemorrhage was suspected ( figure 2 ) . the brain mri finding was subacute to chronic infarction with hemorrhagic transformation in the right temporoparietal lobe ; the differential diagnosis was encephalitis with petechial hemorrhage ( figure 3 ) . further laboratory findings indicated an abnormal autoimmune function ( positive acl , lac , and anti-2 glycoprotein - i antibody , and elevated c3 level ) ( table 1 ) , and abnormal thyroid function . based on the neuropsychological testing , borderline dementia with depression and delusion were diagnosed ( table 2 ) . an eeg examination showed normal background activity with an intermittent theta wave over the right hemisphere . the final diagnosis was established after consulting the rheumatologist ; the aps was complicated by cerebral hemorrhagic infarction accompanied by borderline dementia , depression , suspected seizure , and concomitant hyperthyroidism . the follow - up brain ct 17 days later revealed encephalomalacia in the right temporoparietal lobe , with partial resolution of hemorrhagic transformation . because of the bleeding tendency underlying the recent hemorrhagic infarction , we prescribed acetylsalicylic acid instead of warfarin for temporary stroke prevention . a 35-year - old female experienced progressive mental decline and depression for more than 2 years . initially she was treated at a psychiatric outpatient department ( opd ) , for 1 year . the depressive symptoms improved , but cognitive impairment did not show improvement ; hence , she was referred to the neurological opd . initial laboratory analysis revealed elevated erythrocyte sedimentation rate ( esr ) ( 312 mm / h ) and positive antinuclear antibody ( ana ) test ( 1:80 ) . dementia was suspected , based on the clinical presentation , and she was admitted for further examination . her history revealed four episodes of fetal abortion and diagnosis of aps 3 years previously , by medical record ; she had discontinued treatment for aps for 2 years . laboratory findings indicated anemia ( hemoglobin : 11.3 g / dl ) , thrombocytopenia ( platelet count : 76000/l ) , and abnormal coagulation function ( partial thromboplastin time [ ptt ] : 73.4/29.3 s ; prothrombin time [ pt ] : 11.2/10.8 s ; international normalized ratio [ inr ] : 1.16 ) . her autoimmune profiles were positive for anticardiolipin antibody ( acl ) , lupus anticoagulant antibody ( lac ) , ana , rheumatoid arthritis factor ( ra ) , apl immunoglobulin ( ig)g and igm , anti - ro , and showed decreased complement protein ( c)3 and c4 levels ( table 1 ) . the findings of brain magnetic resonance imaging ( mri ) were multiple old infarcts with encephalomalacia in bilateral cerebral hemispheres and the left cerebellar hemisphere ( figure 1 ) . her cognitive ability screening instrument ( casi ) score was 19 ( cutoff value is 85 , below is abnormal result).3 the casi - estimated mini - mental state examination ( mmse - ce ) score was 9 ( cutoff value is 25 , below is abnormal result ) . assessment with the neuropsychiatric inventory ( npi ) indicated disinhibited behavior . according to the report of neuropsychological testing warfarin was prescribed to control coagulopathy , along with a disease - modifying antirheumatic drug ( hydroxychloroquine ) . a 22-year - old unmarried female developed progressively depressive mood over a period of 1 month . gradually , her verbal output decreased , with incoherent speech , and she developed mild left upper limb weakness . intermittent involuntary movements of her four limbs were observed for several days before her referral to the neurological opd . neurological examination revealed abulia and slight decrease in the muscle power of her left upper limb . immediately brain computed topography ( ct ) was performed ; the results revealed a hyperdense , gyriform lesion along the cortices of the right temporoparietal lobe , with perifocal edema ( figure 2a ) . following this , the laboratory blood test revealed anemia ( hemoglobin : 11.3 g / dl ) , thrombocytopenia ( platelet count : 75000/l ) , and normal coagulation function ( ptt : 30.6/28.6 s ; pt : 10.9/10.7 s ; inr : 1.04 ) . the brain ct findings were discussed with a neurosurgeon , and arteriovenous malformation ( avm ) with hemorrhage was suspected ( figure 2 ) . the brain mri finding was subacute to chronic infarction with hemorrhagic transformation in the right temporoparietal lobe ; the differential diagnosis was encephalitis with petechial hemorrhage ( figure 3 ) . further laboratory findings indicated an abnormal autoimmune function ( positive acl , lac , and anti-2 glycoprotein - i antibody , and elevated c3 level ) ( table 1 ) , and abnormal thyroid function . based on the neuropsychological testing , borderline dementia with depression and delusion were diagnosed ( table 2 ) . an eeg examination showed normal background activity with an intermittent theta wave over the right hemisphere . the final diagnosis was established after consulting the rheumatologist ; the aps was complicated by cerebral hemorrhagic infarction accompanied by borderline dementia , depression , suspected seizure , and concomitant hyperthyroidism . the follow - up brain ct 17 days later revealed encephalomalacia in the right temporoparietal lobe , with partial resolution of hemorrhagic transformation . because of the bleeding tendency underlying the recent hemorrhagic infarction , we prescribed acetylsalicylic acid instead of warfarin for temporary stroke prevention . in the two young patients with initial presentations of progressive depression and mild cognitive impairment , it is likely that an organic brain lesion could have been overlooked during diagnosis . notably , detailed review and investigation should be performed when patients present with obscure stress events , failed medication response , and persistent neuropsychiatric symptoms . the common differential diagnoses of young patients with neuropsychiatric disorders or dementia include structural disease , autoimmune encephalopathy , vasculopathies , psychiatric illness , etc . the reversible and treatable underlying disorders should be given priority.4 central nervous system ( cns ) involvement is a prominent feature of aps ; many acute neurological manifestations have been described in aps patients . however , there are limited reports on the psychiatric manifestations associated with aps , such as depression and mania.5 primary aps is considered a rare autoimmune disease and secondary aps is closely related to systemic lupus erythematosus ( sle ) , hematologic disorders , infection , and some medications . in the case of sle , there is an association between neuropsychiatric symptoms and specific antibodies;6,7 in particular , apl antibodies have been associated with stroke , vascular dementia , and epilepsy.810 in our first case , the patient did not completely satisfy the diagnostic criteria of probable sle , after consultation with the rheumatologist.11 however , sle might be diagnosed at a later stage in the clinical course , and hence , regular follow - up visits were strongly advised . in the second case , unlike the usual images of acute stroke , those of aps might mimic tumor mass , vascular malformation , and inflammatory lesion at the subacute to chronic stage . it is necessary to conduct careful investigations , with the cooperation of experts from various disciplines . another important inference from these two case studies is that aps might present as similar neuropsychiatric disorders ( ie , depression or dementia ) arising from different cerebrovascular lesions involving the contributory circuits and resulting in vascular depression and vascular dementia . early intervention will allow good prognosis . regarding the treatment of aps - related neuropsychiatric disorders , the symptomatic control of vascular complications and management of underlying autoimmune coagulopathy ( disease - modifying antirheumatic drugs and anticoagulation agents ) are suggested . for vascular depression , the antidepressant of selective serotonin reuptake inhibitor ( ssri ) type might be the considered choice because of its lesser influence on the cardiovascular system . on the other hand , the circulation - promoting agents and acetylcholinesterase inhibitors could be useful for vascular dementia , according to the patient s clinical status . additionally , many nonpharmacological interventions are available and are suggested as concomitant therapy for intensive care of neuropsychiatric disorders . because the incidences of progressive neuropsychiatric disorders in the young are increasing , we have underscored the clinical relevance of the differential diagnoses of systemic autoimmune diseases with cns involvement , such as aps . brain imaging is an essential tool to prevent any delay in the detection of structural lesions and facilitate the early intervention with good prognosis .

the antiphospholipid syndrome ( aps ) is a rare form of autoimmune coagulopathy . in this syndrome , the most common neurologic abnormality is transient ischemic attack . this can be easily overlooked if a patient presents with progressive neuropsychiatric disorders , such as depression or dementia . we report two cases of young women , aged 35 and 22 years , presenting with progressive depression and mental decline over a certain period . the neuropsychological diagnoses of the two patients were , respectively , dementia with disinhibition and borderline dementia with depression . brain magnetic resonance imaging showed multiple old infarcts with encephalomalacia in the former case , and only one cortical hemorrhagic infarction , over the right temporoparietal lobe , observed in the latter case . the outcomes of the two cases were also very different . progressive neuropsychiatric disorders are increasingly observed in the young ; therefore , aps and other autoimmune diseases should be considered during the differential diagnosis . brain imaging examinations may prevent a delay in the detection of a structural lesion and facilitate the early intervention with good prognosis . careful investigations by experts from different disciplines are always encouraged in complicated cases .

the diagnosis requires a high index of suspicion and is often delayed ; nearly 15% of iatrogenic tracheal injuries from emergency intubations are identified at post - mortem . the recognition that post intubation tracheal rupture ( pitr ) has a distinct etiology , characteristic pattern of injury and a high perioperative risk particularly in the critically ill , has led to a more conservative management approach , and two cases illustrate this . in the emergency department , a 76-year - old woman , intubated out of hospital , following a prolonged seizure , developed acute airway obstruction , which resolved on endotracheal suctioning of mucosal tissue debris . cardiac arrest with pulseless electrical activity ensued . bilateral tension pneumothoraces , apparently related to jugular central venous catheterization , were relieved by thoracocentesis and tube thoracostomy . a plain chest radiograph ( cxr ) [ figure 1 ] demonstrated subphrenic and subcutaneous air . computed tomography [ figures 2a and b ] confirmed extensive subcutaneous air , residual pneumothoraces , pneumomediastinum and tension pneumoperitoneum . plain chest radiograph demonstrating endotracheal tube in situ , bilateral tube thoracostomies , extensive subcutaneous emphysema , and subphrenic air ( arrow ) computed tomography of the thorax . pockets of air around the paratracheal soft - tissue ( thick arrow ) raise the suspicion of a tracheal defect near the endotracheal tube tension pneumoperitoneum . the arrow signifies the anterior abdominal wall in the intensive care unit ( icu ) , she was stable . bronchoscopy demonstrated a 4 cm long full thickness defect in the posterior membranous trachea , 1 cm proximal to the carina [ figure 3a ] . following consultation , thoracic surgical repair of the tracheal tear or complex stenting were ruled out due to the high operative risk . bridging the defect by double lumen endotracheal tube ( ett ) beyond the distal end of the tear was not possible due to the proximity of the main carina , and risk of the herniation of the ett cuff into the posterior wall defect , therefore , a cuffed ett was placed proximal to the defect , and a low volume lung ventilation strategy was adopted , to allow the defect to recover without over - distension and exacerbating pneumomediastinum . mechanical ventilation was as follows : volume ( 5 - 6 ml / kg ) , frequency ( 25/min ) , pressure limited ( mean airway pressure < 25 cm h2o ) ventilation with permissive hypercapnia . tazobactam - piperacillin was commenced empirically for suspected mediastinitis and pneumonia . as part of a cluster care strategy , blind tracheal suctioning , and patient rotation post - pyloric feeding was established after confirming an intact esophagus and twice - daily bronchoscopy for airway clearance , and correct ett position above the proximal defect . bronchoscopic view of the trachea beyond the distal end of the endotracheal tube at day 1 . just proximal to the carina ( thin arrow ) is the lower edge of a large full thickness defect in the posterior tracheal wall ( thick arrow ) . beyond the visible clot was the mediastinum and anterior aspect of the esophagus the patient was weaned with percutaneous tracheostomy and discharged from icu after 27 days . bronchoscopic view of the trachea at day 32 , 1 week after discharge from intensive care . complete spontaneous healing of the tracheal defect had occurred ( arrow ) a 69-year - old female was admitted with coma following a mixed overdose of benzodiazepines and narcotics . she was intubated , using an ett with stylet . a 7 cm posterior tracheal tear extending to 2 rings above the carina contained large thrombus and mucopus . the ett was withdrawn to above the proximal extent of the defect and meropenem for suspected mediastinitis ( penicillin allergy ) . thoracic surgical consultation was sought due to the size and length of the defect , the potential for failure of bridging , and the chance of mediastinitis . conservative management was advised , unless active endobronchial bleeding or progressive ventilatory failure ensued . a protective ventilation strategy , avoidance of blind tracheal suctioning and cluster care to avoid excessive ett movement on patient repositioning were adopted . in the emergency department , a 76-year - old woman , intubated out of hospital , following a prolonged seizure , developed acute airway obstruction , which resolved on endotracheal suctioning of mucosal tissue debris . cardiac arrest with pulseless electrical activity ensued . bilateral tension pneumothoraces , apparently related to jugular central venous catheterization , were relieved by thoracocentesis and tube thoracostomy . a plain chest radiograph ( cxr ) [ figure 1 ] demonstrated subphrenic and subcutaneous air . computed tomography [ figures 2a and b ] confirmed extensive subcutaneous air , residual pneumothoraces , pneumomediastinum and tension pneumoperitoneum . plain chest radiograph demonstrating endotracheal tube in situ , bilateral tube thoracostomies , extensive subcutaneous emphysema , and subphrenic air ( arrow ) computed tomography of the thorax . pockets of air around the paratracheal soft - tissue ( thick arrow ) raise the suspicion of a tracheal defect near the endotracheal tube tension pneumoperitoneum . the arrow signifies the anterior abdominal wall in the intensive care unit ( icu ) , she was stable . bronchoscopy demonstrated a 4 cm long full thickness defect in the posterior membranous trachea , 1 cm proximal to the carina [ figure 3a ] . following consultation , thoracic surgical repair of the tracheal tear or complex stenting were ruled out due to the high operative risk . bridging the defect by double lumen endotracheal tube ( ett ) beyond the distal end of the tear was not possible due to the proximity of the main carina , and risk of the herniation of the ett cuff into the posterior wall defect , therefore , a cuffed ett was placed proximal to the defect , and a low volume lung ventilation strategy was adopted , to allow the defect to recover without over - distension and exacerbating pneumomediastinum . mechanical ventilation was as follows : volume ( 5 - 6 ml / kg ) , frequency ( 25/min ) , pressure limited ( mean airway pressure < 25 cm h2o ) ventilation with permissive hypercapnia . tazobactam - piperacillin was commenced empirically for suspected mediastinitis and pneumonia . as part of a cluster care strategy , blind tracheal suctioning , and patient rotation post - pyloric feeding was established after confirming an intact esophagus and twice - daily bronchoscopy for airway clearance , and correct ett position above the proximal defect . bronchoscopic view of the trachea beyond the distal end of the endotracheal tube at day 1 . just proximal to the carina ( thin arrow ) is the lower edge of a large full thickness defect in the posterior tracheal wall ( thick arrow ) . beyond the visible clot was the mediastinum and anterior aspect of the esophagus the patient was weaned with percutaneous tracheostomy and discharged from icu after 27 days . bronchoscopic view of the trachea at day 32 , 1 week after discharge from intensive care . a 69-year - old female was admitted with coma following a mixed overdose of benzodiazepines and narcotics . she was intubated , using an ett with stylet . persistent leak around her ett , despite cuff inflation and tube changes initiated bronchoscopy . a 7 cm posterior tracheal tear extending to 2 rings above the carina contained large thrombus and mucopus . the ett was withdrawn to above the proximal extent of the defect and meropenem for suspected mediastinitis ( penicillin allergy ) . thoracic surgical consultation was sought due to the size and length of the defect , the potential for failure of bridging , and the chance of mediastinitis . a protective ventilation strategy , avoidance of blind tracheal suctioning and cluster care to avoid excessive ett movement on patient repositioning were adopted . the ett was secured proximal to the defect 's upper extent , with low volume ventilation , so reducing strain on the tear . there was insufficient intact trachea to allow conventional placement of ett distal to the tear . therefore , an approach directed at reducing factors that might prevent or delay healing was implemented . this approach can easily be applied in non - specialist icus for large full thickness pitr near the carina . increased risk of pitr is associated with female gender , short stature , difficult airway anatomy , steroid use , chronic obstructive pulmonary disease and underlying connective tissue disease . mechanical factors are also implicated ; use of rigid stylets , incorrectly sized etts , cuff over - inflation , head movement or vigorous coughing poor prognosticators are diagnosis outside the operating theatre ( delayed diagnosis ) , necessary operative intervention , and emergency intubation . pitr typically causes longitudinal lacerations of the posterior membranous trachea , rarely extending into the main bronchi . the injury occurs from the ett tip catching a flaccid portion of the trachea or from radial traction due to cuff over - distension . in mechanically ventilated patients , the resulting air leak into surrounding tissues may lead to tension pneumothorax and pneumomediastinum . the most common presenting features of pitr are subcutaneous air , pneumomediastinum , and pneumothorax . in ventilated patients , a persistent air leak may be the only sign , whilst self - ventilating patients may exhibit respiratory distress . in the first case , abdominal distension and subsequent tension pneumoperitoneum occurred after relief of acute airway obstruction owing to a tracheal membranous flap being released . the high positive airway pressure through the pitr likely maintained an air pressure gradient between the mediastinum and peritoneum across the central diaphragmatic crura . plain cxr may show subcutaneous air , pneumomediastinum , pneumoperitoneum or pneuomthoraces other signs are a displaced ett , an eccentric cuff or dilated trachea . diagnosis is confirmed by tracheobronchoscopy , allowing precise delineation of location , extent , and depth of the pitr , and accurate repositioning of ett . the management of pitr is guided by whether the patient is self or mechanically ventilated , and whether an operative approach is required . determinants include location and , length of defect , time to diagnosis and sequela ( e.g. , mediastinitis , bleeding or progressive respiratory failure ) . surgery is suggested when bridging of the tr is not feasible . yet , the decision for surgery or not is most challenging in critically - ill mechanically ventilated patients , with tr . here , conservative management is felt most likely to fail , but conversely , these patients pose the highest perioperative risk for surgical repair . criteria for conservative management and its increasing trend in selected cases include cardiovascular stability , the absence of sequela such as progressive air leaks or sepsis , and no esophageal injury . risk stratification of patients according to their ventilatory status , underlying pathology and nature of the pitr ( < 4 cm long ) , allowed 17 of 18 patients to be treated conservatively . consideration for surgical repair were rapid progression of air leaks , mediastinitis , and ventilatory deterioration . in the largest case series , ( n = 30 ) a conservative approach for pitr was independent of length of defect . recommendations were drainage of symptomatic air collections , early extubation if possible , perioperative risk stratification and bridging of the tracheal defect this is simple bridging by passing a single lumen tube beyond the pitr or by selective endo - bronchial intubation using two endobronchial tubes passed through a large tracheostomy . non - invasive ventilation was used successfully in a subgroup with respiratory compromise due to protrusion of the esophagus into the trachea . two main surgical approaches for repair of tr are right thoracotomy for middle / lower third defects or left cervical approach for upper third tears . their use in benign central airways disease , including pitr , must be balanced against potential complications including misplacement , migration , and airway stenosis . stenting is considered where conservative treatment fails and the risk of surgical repair is deemed too high . supportive measures for pitr aim to avoid sequlae such as mediastinitis and delayed healing of the rupture , whilst early broad - spectrum antibiotics are indicated where mediastinitis is suspected . cluster care nursing procedures performed 1 - 2 times / day and ett external fixators will minimize possible disruption to the tracheal tear . there is no consensus on specific modes of ventilation , but high ventilatory pressures should be avoided . the use of high frequency oscillatory ventilation would seem intuitive in this setting ; although , there are no published reports . to facilitate low pressure ventilation and avoid coughing and straining , some authors have recommended avoiding ng tubes in the presence of full thickness tracheal tears as they make contribute to the formation of tracheoesophageal fistulas . a systematic review of 182 cases of pitr reported a female preponderance ( 85.7 ) . all those diagnosed intraoperatively ( n = 31 ) were managed surgically at the time . those diagnosed later , who required surgical management had a two fold increase in mortality . in summary , a multidisciplinary approach to pitr in critically ill patients , with risk stratification ( including triggers for surgical intervention or airway stenting ) can allow conservative management , even in large , and non - bridgeable tears . a combination of protective ventilation , cluster care , and regular bronchoscopy allow spontaneous repair . illustrates this [ figure 4 ] . a management algorithm for post intubation tracheal rupture , modified from wurtz et al . conservative management represents elements of non - respiratory support , irrespective of self - ventilation , non - invasive ventilation or mechanical ventilation .

tracheal rupture is an infrequent , severe complication of endotracheal intubation , which can be difficult to diagnose . post - intubation tracheal rupture ( pitr ) is distinct from non - iatrogenic causes of tracheobronchial trauma and often requires different treatment . the increasing adoption of pre - hospital emergency services increases the likelihood of such complications from emergency intubations . effective management strategies for pitr outside specialist cardiothoracic units are possible . two cases of severe pitr , successfully managed non - operatively on a general medical - surgical intensive care unit , illustrate a modified approach to current standards . the evidence base for pitr is reviewed and a pragmatic management algorithm presented .

ischemic mitral regurgitation can be defined as moderate to severe mitral leak precipitated by acute myocardial infarction . valve repair is now the procedure of choice , but some cases can pose difficult anatomy . most patients with ischemic mitral regurgitation have predominant annular dilatation at the posterior commissure and require only ring annuloplasty . if papillary muscle elongation or rupture occurs , gore - tex artificial chordal replacement performs well . with ischemic mitral regurgitation accompanying posterior ventricular aneurysms , standard trans - atrial mitral repair provides the best results , with associated aneurysms being repaired concurrently . surgical approaches and technical outcomes of mitral repair in ischemic mitral regurgitation are illustrated in 5 patients using operative images and echocardiograms . each method is illustrated , including ring annuloplasty , pericardial leaflet augmentation , artificial chordal replacement , and ventricular aneurysm repair . using these techniques , virtually all ischemic mitral regurgitation can be repaired , with consequential patient benefits , even in the most complex anatomy . ischemic mitral regurgitation has been shown to have better outcomes when managed with valve repair . using combinations of annular , leaflet , and chordal procedures , even complex ischemic mitral regurgitation can undergo autologous reconstruction with excellent long - term results . several divergent concepts currently exist about the prognosis and management of ischemic mitral regurgitation ( imr ) . they range from little can be done to modify the dismal prognosis - to mitral repair can cure the disorder ; from mitral repair should be uniform - to prosthetic replacement achieves more certain results . one problem is that conclusions have been based on multiple different surgical approaches between centers , and also , statistical techniques often have been suboptimal . thus , it is likely that outcome benefits did vary between institutions , with differences in surgery and other factors , accounting for the divergent conclusions . the goal of this paper is to review repair techniques for imr used over the past 25 years at duke university medical center and to document observed outcome characteristics . imr can be defined as mitral regurgitation precipitated by myocardial infarction , with essentially normal leaflet and chordal support . imr usually is associated with myocardial necrosis , rather than reversible ischemia , and the infarction is usually inferior . fact , mitral valve competence requires the integrated function of all five aspects of the valve - annulus , leaflets , chordae , papillary muscles , and ventricular wall . as defined in george burch s classic 1966 papillary muscle dysfunction paper , most cases involve predominant posterior annular dilatation , but others experience leaflet tethering due to infarct expansion . rarely , papillary muscles can elongate or rupture , producing leaflet prolapse . the common type of imr involves the posterior wall , usually is caused by right and/or circumflex coronary occlusion , produces moderate posterior - lateral left ventricular ( lv ) dysfunction , and usually will not reverse with revascularization alone . as described in the 1980 s , the decision to repair the valve should be based on the appearance of moderate or severe imr on the intra - operative transesophageal echo ( tee ) , sometimes with provocative volume loading from the pump before bypass . surgical techniques . posterior annular dilatation is an important mechanism of imr , and has been almost uniformly corrected in our practice with a true - sized full rigid or semi - rigid ring . it has been shown that fixed reduction in anterior - posterior annular geometry is extremely important in this entity . these patients often have minor leaflet abnormalities , such as fetal commissural cusps or clefts , predisposing them to opening up the valve with ischemic posterior annular dilatation . occasionally , leaflets can be tethered by infarct expansion , contributing to lack of valve closure . as langer showed , a posterior leaflet autologous pericardial patch can be used to compensate for the tethering , and this approach provides a large margin of safetylong - term , especially if further geometric changes occur . for leaflet prolapse due to elongated or ruptured papillary muscles , gore - tex artificial chords can be placed to a viable papillary muscle , adjusting chordal lengths after ring placement , as we have described . the first patient is a 77 year old man , experiencing an acute circumflex infarct that produced acute moderate to severe mitral regurgitation ( mr ) and congestive heart failure . on tee ( figures 1 a , b ) , there is loss of valve coaptation at the posterior commissure ( red arrow ) , due to annular dilatation from a large posterior lateral infarct ( green arrow ) . this produced the characteristic loss of coaptation area and a central mr jet , but both leaflets are at the annular plane and not tethered or prolapsed ( figure 1c ) . after simple insertion of a full rigid ring , the valve is entirely competent ( figure 1d ) . panel a is a short axis view of the left ventricle , showing an expanded posterior - lateral wall infarct ( green arrow ) . panel b shows a gap in mitral coaptation at the posterior commissure during systole ( red arrow ) , producing a central regurgitant jet ( panel c ) , but the leaflets are at the annular plane . this is the most common echocardiographic appearance of ischemic mitral regurgitation . in panel d , the second patient is a 55 year old obese diabetic who experienced a right coronary infarct and imr 6 months earlier that were treated with right coronary artery ( rca ) stenting . despite revascularization , imr and she then developed an in - stent stenosis in the rca and an additional left anterior descending coronary artery ( lad ) lesion , and her ventricle showed residuals of the inferior infarct , with generalized dilatation . there was loss of central mitral coaptation , due to annular dilatation , a hint of tenting and leaflet tethering ( figure 2a ) , and moderate to severe mr with a central jet ( figure 2 b).when the valve was inspected , however , the posterior leaflet seemed fine with good closure and minimal tethering on valve testing by ventricular distension with cold saline ( figure 2c ) . therefore , the valve is repaired by simple placement of a carpentier ring , with good recovery of competence , and no residual leak ( figure 2d ) . so , most ischemic mitral regurgitation ( mr ) can be repaired with full ring annuloplasty alone , which achieves excellent results , with a documented 2% late reoperation rate , 9% late moderate mr recurrence rate , and quite satisfactory echocardiographic results . clinical images in a patient with chronic ischemic mitral regurgitation . panel a shows a hint of leaflet tethering ( green arrow ) , with both leaflets slightly below the annular plane . in panel c , the posterior leaflet seems to coapt well ( red arrow ) with no evidence of tethering during valve testing with cold saline injection . therefore , a simple ring annuloplasty was performed , and in panel d , the valve is completely competent . the third patient is a frail elderly female presenting with an acute circumflex infarct and severe imr , treated initially with percutaneous coronary intervention ( pci ) . unlike the first 2 patients , she had prominent posterior leaflet tethering by echocardiography ( figure 3a ) , and severe lv dysfunction , mainly in the lateral wall due to the infarct . on emergency angiography , she had an occluded circumflex artery , but also lad and rca stenoses . the circumflex was stented , but the imr persisted , the heart failure remained severe , and the ejection fraction continued at a 0.20 level . a magnetic resonance viability study was performed . in imr patients with low ejection fractions , we will operate if 2 of the 3 regions appear viable . in fact , this patient seemed to have good residual myocardium everywhere . upon inspecting the valve , the right aspect of the posterior leaflet was tethered , and the posterior leaflet would nt coapt , even with saline distension . in figure 3b , one can see the posterior leaflet pulled down into the ventricle with tethering from infarct expansion . a gluteraldehyde - fixed autologous pericardial patch was inserted into the posterior leaflet to compensate for the tethering , and the valve became nicely competent . most of what is seen in figure 3c is patch , with the posterior leaflet moving down into the ventricle to become the entire coaptation area , and the valve is entirely competent ( figure 3d ) panel a shows both leaflets tented into the ventricle and not closing properly due to tethering ( green arrow ) . direct inspection in panel b reveals taught posterior leaflet chords at the posterior commissure , inhibiting valve closure ( red arrow ) . after insertion of an autologous pericardial patch into the posterior leaflet and placement of a carpentier ring ( panel c ) , the valve is entirely competent with a large coaptation area ( panel d ) . the margin of safety provided by the patch may reduce later imr recurrence with further infarct expansion , or other problems . a transthoracic echocardiogram , obtained 6 months postoperatively , showed good valve opening , and only trivial residual leak . the fourth patient is a 57 year old man who had a major right coronary infarct , producing severe mr , a posterior lv aneurysm , and severe heart failure . he also had lad disease , and - there was a large posterior wall aneurysm ( figure 4a ) . the aneurysm was resected and closed primarily , approximating viable aneurysm edge to viable edge and removing all non - contractile scar . upon inspecting the valve , he had a chronically ruptured posterior papillary muscle at the posterior commissure , with severe prolapse that was not appreciated on the echo ( figure 4b ) . a 2 - 0 gore - tex artificial chord was placed to a viable papillary muscle and stuffed into the ventricle for later retrieval . after ring placement , after repair , the valve was nicely competent ( figure 4c ) , with no residual leak ( figure 4d ) . panel a is the left ventriculogram from a patient with severe ischemic mitral regurgitation and a large posterior wall aneurysm ( green arrow ) . in panel b is shown an associated chronically ruptured papillary muscle producing prolapse of a posterior commissural cusp ( red arrow ) . in panel c , an artificial chord has been placed to the commissural cusp , along with a carpentier ring , and the valve is completely competent ( panel d ) . combined chords and patches . the last patient is a 61 year old man with a remote coronary bypass for an inferior infarction , and severe persistent imr due to simultaneous leaflet tethering and prolapse - a rare combination . in figure 5a , one can see 2 separate jets of imr , with the posterior leaflet tethered down into the ventricle ( figure 5b ) and a segment of anterior leaflet prolapsing ( figure 5c ) . thus , the patient had simultaneous posterior leaflet tethering from infarct expansion , and anterior leaflet prolapse due to papillary muscle elongation . with a patch to the posterior leaflet and an artificial chord to the anterior leaflet , the valve was completely competent with good leaflet position and no residual leak ( figure 5d ) . this case illustrates that some varieties of imr can be quite complex , but with various combinations of full rings , pericardial patches , and artificial chords , the vast majority can be effectively repaired . intraoperative transesophageal echo frames from an ischemic mitral regurgitation patient with both posterior leaflet tethering and anterior leaflet prolapse . after repair of both lesions with a posterior leaflet pericardial patch and a chord to the anterior leaflet , the valve is fully competent ( panel d ) . outcome characteristics of mitral repair.from several sources , it is now clear that the generally poor prognosis after mitral valve repair for imr ( a 56% 5-year unadjusted survival in our series ) is due primarily to the adverse patient profiles that are characteristic of this population , such as advanced age , numerous co - morbidities , and left ventricular dysfunction . if these baseline risk factors are taken into account with a cox model ( figure 6 ) , valve repair seems to restore these patients to an adjusted survival that is similar to standard coronary bypass . also of note in this analysis , is the average 14% better risk - adjusted survival with valve repair , as compared to prosthetic valve replacement , which is consistent with most recent analyses . survival curves over 15 years of follow - up adjusted with a cox proportional hazards model for differences in all important baseline patient characteristics . the blue curve represents adjusted survival characteristics for 16,209 patients having coronary bypass alone without intraoperative transesophageal ( group 1 ) . the red curve represents adjusted survival for 3,181 patients with mild - to - moderate intraoperative transesophageal treated with coronary bypass alone ( group 2a ) . the green curve is adjusted survival for 416 patients with moderate - to - severe intraoperative transesophageal managed with mitral valve repair ( group 2b ) . and finally , the brown curve represents adjusted survival of 106 patients with moderate - to - severe intraoperative transesophageal receiving mitral valve replacement ( group 2c ) . mitral repair for moderate - to - severe intraoperative transesophageal restored adjusted survival to levels equivalent to standard coronary bypass patients with similar risk profiles . mitral valve replacement achieved an average 14% lower risk - adjusted survival over 15 years , as compared to valve repair . in summary , the pathophysiology of ischemic mr can be complex , with aspects involving the annulus , leaflets , chords , papillary muscles , and ventricular wall . based on our clinical experience , mitral valve repair should be the procedure of choice for moderate or worse imr , as encountered in the coronary disease population . finally , effective mitral repair restores imr patients to a prognosis that is similar to standard coronary bypass , for a given patient s age and co - morbidities , and repair seems superior to valve replacement in all subsets .

introductionischemic mitral regurgitation can be defined as moderate to severe mitral leak precipitated by acute myocardial infarction . valve repair is now the procedure of choice , but some cases can pose difficult anatomy . this review will illustrate current techniques for repairing complex ischemic mitral regurgitation.methodsmost patients with ischemic mitral regurgitation have predominant annular dilatation at the posterior commissure and require only ring annuloplasty . full rigid rings are used preferentially . with leaflet tethering , adjunctive autologous pericardial patches are effective in restoring leaflet coaptation . if papillary muscle elongation or rupture occurs , gore - tex artificial chordal replacement performs well . with ischemic mitral regurgitation accompanying posterior ventricular aneurysms , standard trans - atrial mitral repair provides the best results , with associated aneurysms being repaired concurrently.resultssurgical approaches and technical outcomes of mitral repair in ischemic mitral regurgitation are illustrated in 5 patients using operative images and echocardiograms . each method is illustrated , including ring annuloplasty , pericardial leaflet augmentation , artificial chordal replacement , and ventricular aneurysm repair . using these techniques , virtually all ischemic mitral regurgitation can be repaired , with consequential patient benefits , even in the most complex anatomy.conclusionsischemic mitral regurgitation has been shown to have better outcomes when managed with valve repair . using combinations of annular , leaflet , and chordal procedures , even complex ischemic mitral regurgitation can undergo autologous reconstruction with excellent long - term results .

valproic acid ( vpa ) has a clinical use as an anticonvulsant and mood - stabilizing drug , primarily in the treatment of epilepsy , bipolar disorder , and , less commonly , major depression . hyperammonemia ( ha ) has been generally associated with liver failure or rare genetic mutations in enzymes participating in the urea cycle . however , in some patients treated with vpa , severe ha has been observed in the absence of liver failure and resulting in vomiting , ataxia , behavioral changes , lethargy , somnolence , or , in extreme cases , coma . numerous cases of severe and life - threatening ha related to the vpa treatment mostly in children , adolescents , and also adults have been previously reported in the medical literature ( > 220 published reports in medline since 1980 by search using vpa and ha as keywords in august 2012 ) . the exact mechanism of vpa - induced encephalopathy is unclear but relates to the accumulation of toxic vpa metabolites and elevated ammonia levels [ 2 , 3 ] . the prior limited data from exclusively japanese cohort suggested that patients treated with vpa and who carry the t1405n ( 4217c > a , rs1047891 ) missense single nucleotide polymorphism ( snp ) in the carbamoyl phosphate synthetase 1 gene might be more likely to experience ha . the main goal of this project was to investigate , for the first time in caucasian cohort , if carbamoyl phosphate synthetase 1 ( cps1 ) gene t1405n missense variant can be associated with increased occurrence of ha in subjects treated with vp . this prospective multicenter cohort study was performed between april 2011 and september 2012 using the study protocol which was approved by irb at psu hershey medical center , hershey , pa , usa , and institute of psychiatry and neurology in warsaw , poland . all subsequent caucasian adult patients treated with vpa ( irrespective of age and gender ) and satisfying the inclusion and exclusion criteria were enrolled into the study . inclusion criteria included adults ( > 18 years of age ) and treatment with vpa for the period of > 1 year . exclusion criteria included pregnancy , severe hepatic disease ( as documented by both clinical diagnosis and grossly abnormal liver function tests ) , end - stage kidney disease , that is , requiring dialysis , and advance mental retardation that prevents signing of the informed consent . ha was defined as the plasma ammonia level > 65 mol / l ( representing values larger than 95 percentile of the normal range by standard laboratory testing ) at the time of enrollment . whole blood samples were collected into edta - tubes and frozen at 80c until analysis . genomic dna ( gdna ) was extracted from blood sample employing membrane ultrafiltration method using fuji minigene 80 semiautomatic extractor ( fujifilm life sciences distributed by autogen , holliston , ma , usa ) , according to the manufacturer 's recommendations . the saliva samples were collected into oragene containers ( dna genotek , canada ) and extracted according to the manufacturer 's recommendations . gdna analysis of clinical samples was performed in triplicates using custom snp real - time pcr taqman genotyping assay ( applied biosystems , foster city , ca , usa ) and according to the manufacturer 's protocol . briefly , gdna was incubated with two custom designed flanking primers for amplifying the sequence of interest and two taqman mgb probes for detecting specific alleles containing a reporter dye ( vic and fam ) at the 5 end of each allele - specific probe and nonfluorescent quencher at the 3 end of the probe . the real - time pcr analysis was performed using taqman universal master mix , no amperase ung in 384-well optical plate using an applied biosystems prism 7900ht sequence detection system at pshmc genomic core facilities , hershey , pa , usa . following pcr amplification , endpoint fluorescence measurements from each well will be obtained , and the alleles present in each sample were identified . the primary analysis for the first specific aim utilized univariate logistic regression with a carrier status for minor allele as independent variable and a presence of ha ( yes / no ) phenotype as dependent variable . the logistic regression procedure enabled us to estimate the log of the odds ratio ( or ) , a measure of the increase in odds of experiencing ha for subjects carrying the variant compared to the wild - type subjects . we obtained 95% confidence interval around this estimate and the p value for the or . the p value was compared with the predefined cutoff for statistical significance ( alpha = 0.05 ) . a significant association between carrying t1405n variant and increased risk of vpa - induced ha has been expected , therefore , the association was adjusted for the predefined covariates to determine whether the association between cps1 4217c > a and risk of vpa - induced ha remains significant after inclusion of factors . given the expected population incidence of vpa - induced ha of approximately 10% , expected frequency for minor allele of 0.35 , alpha level = 0.05 , and the power of 0.8 , at least 140 patients were needed to detect or > 4 for experiencing ha in carriers of minor allele . in total , 142 subjects were enrolled in the study , from which 97 were enrolled in hershey , pa , usa , and 45 in warsaw , poland . in 95% of the enrolled patients , the observed plasma level of ammonia ranged between 9 and 181 mol / l ( mean standard deviation 31.6 16.4 mol / l ) in the investigated cohort of patients , and ha ( defined as ammonia plasma level > 65 mol / l ) was observed in total of 11 ( 7.7% ) of patients treated with vpa . the distribution of cps1 genotypes for the polymorphism within overall study population fulfilled hardy - weinberg criteria ( fisher 's exact test , p > 0.05 ) . the observed genotype distribution ( cc denotes homozygosity for the c - encoded thr1405 variant , aa homozygosity for the a - encoded asn1405 variant , and ac heterozygosity for polymorphism at position 1405 ) in investigated patients was cc : ca : aa = 69 : 61 : 13 , n = 142 ) . no significant differences among the two centers were observed in genotype distribution or clinical characteristics in patients enrolled in the study with exception of statistically significant more patients on multiple antiepileptic medications in pennsylvania cohort and higher level of ammonia in the warsaw cohort ( table 1 ) . the univariate analysis of the carriers and noncarriers of the thr1405 variant revealed a significant association with ha phenotype in the overall study group ( p = 0.009 , odds ratio 5.4 with 95% confidence interval of 1.5818.43 ) . multifactorial logistic regression indicated that thr1405 carrier status is independently associated with ha after adjusting for study center , age , gender , total 24 hr vpa dose , vpa plasma concentrations , and the number of concomitant antiepileptic medications administered with vpa ( not shown ) . no significant differences between medians of absolute blood concentrations of ammonia were observed in the three genotypes for the investigated variant ( figure 1 ) or carrier versus noncarriers of the investigated minor allele . identifying early biomarkers for patients at risk for vpa - induced ha remains an elusive research goal . both heterozygous and homozygous carrier states of the t1405n polymorphism and concomitant administration of two or more anticonvulsants with vpa were shown previously to be independent risk factors for developing ha in the relatively small cohort of patients ( n = 79 ) from japan and single case report from our laboratory [ 4 , 5 ] . in the recent larger study , yamamoto et al . identified several other risk factors for ha in pwe , including vpa dose and use of hepatic enzyme inducers , although genetic polymorphism was not analyzed in this study . built on the previous reports , we hypothesized that in a caucasian population of patients without liver failure and treated with vpa , genetically determined variations in cps1 function would be associated with increased incidence of ha . our data confirms this hypothesis , because we did observe that the percentage of patients with ha was significantly higher in the carriers of the minor allele when compared with the carriers of two wild - type alleles for the investigated polymorphism ( i.e. , dominant model of inheritance ) . because the current study was not powered to investigate other factors involved in ha , we can not conclude with absolute certainty that other factors ( e.g. , vpa dose , concomitant use of other anticonvulsants ) could be associated with increased occurrence of ha in the investigated cohort of patients during prolonged vpa treatment . the urea cycle is an essential process for the removal of ammonia from the body , and its initial step is the conversion of ammonia and bicarbonate into carbamoyl phosphate via hepatic mitochondrial cps1 . the effects of vpa on urea metabolism are complex and occur in the liver mitochondria . inherited deficiency of cps1 with severe ha is a rare autosomal recessive disorder with a prevalence of 1 : 200,0001 : 800,000 ( http://omim.org/entry/237300 ) . at present , more than 60 severe deficiency - causing mutations in the cps1 gene have been identified ( 2012 human genome mutation database , http://www.hgmd.org/ ) . less severe deficiency or reduced activity of cps1 is thought to be associated with vpa - induced ha . vpa preferentially inhibits cps1 , which in turn may lead to a dose independent increase in the concentration of its substrate ammonia in the blood [ 7 , 8 ] . vpa may also inhibit carnitine transportation into the mitochondria which is responsible for the shift in the balance of metabolism towards protein degradation with subsequent ha . t1405 polymorphism in the cps1 gene results in a threonine to asparagine amino acid substitution at an important cofactor ( i.e. , n - acetylglutamate ) binding site in exon 36 of cps1 . previous studies demonstrated the association of the cps1 t1405 polymorphism with neonatal pulmonary hypertension and necrotizing enterocolitis [ 1012 ] . several studies reported that asymptomatic ha patients had problems related to seizure control , developmental delay , and intellectual disability [ 13 ] . in addition , it was reported recently that the preexisting ha may be further exacerbated in stress - related situations ( perioperative period for surgical procedures ) which may increase the postoperative risk for these patients [ 13 , 14 ] . it is important therefore to establish risk factors for an elevated ammonia level and to perform the measurement of ammonia irrespective of whether patients are asymptomatic or not , in particular in situations which may lead to further exacerbation of ha . in conclusion , the t1405n ( 4217c > a , rs1047891 ) missense was found to be a significant risk factor for the occurrence of ha in caucasian patients undergoing vpa therapy , even in subjects with normal plasma levels of vpa .

numerous cases of severe and life - threatening hyperammonemia ( ha ) related to the treatment of epileptic seizures with valproic acid ( vpa ) have been previously reported in the medical literature . the aim of this prospective , multicenter study was to verify the putative association between t1405 polymorphism and occurrence of vpa - induced ha in the cohort of 142 adult caucasian patients with epilepsy treated with vpa for at least 1 year and with normal liver functions . the nonsynonymous t1405n polymorphism genotyping was performed by real - time taqman pcr genotyping . in addition to plasma ammonia level , concentrations of liver enzymes and total vpa were measured in plasma with standard laboratory methods . ha ( defined as ammonia plasma level > 65 mol / l ) was observed in total of 11 ( 7.7% ) of patients treated with vpa , and the carrier status for the investigated polymorphism was significantly ( p = 0.009 , odds ratio 5.4 with 95% confidence interval of 1.5818.43 ) associated with the occurrence of ha . the results of this study support a notion that in the caucasian patients with epilepsy undergoing vpa therapy , a t1405n ( 4217c > a , rs1047891 ) nonsynonymous variant was a significant risk factor for the occurrence of ha , even in patients with normal plasma levels of vpa .

hypertension ( ht ) is not an adult disease anymore ; it is a silent disease that is generally asymptomatic in childhood and adolescent period . it plays the important pathophysiological role in the development of the reduction in baroreflex sensitivity and retinal alteration . hypertension studies in children and adolescents are of great importance since control at this stage is likely to prevent adverse sequelae in later life . hypertension is a major cause of morbidity , which unless controlled in early life , may tend to introduce a high risk in adulthood . a previous worldwide report records the prevalence of hypertension in children as ranging from 3% to 16.2% . the diversity of the results in hypertension studies stems from the different criteria used , selection of the age group and study population ( ethnic ) , study area ( urban and rural ) , culture , as well as dietary habits ( socioeconomic ) . this study was to detect the prevalence and risk factors of hypertension in children / adolescents aged 10 to 17 years . the objectives and the importance of the study were first explained to the teachers and parents . the children / adolescents aged 1017 years in each selected school in chennai were examined . two field survey teams , each comprising a medical officer and a social scientist were formed . the physician elicited medical history and carried out clinical examination including measurement of blood pressure ( bp ) . the social scientist recorded the background information such as the food frequency questionnaire ( ffq ) and anthropometric measurements . after getting the child to sit for five minutes , with the back supported and both feet on the floor , systolic and diastolic blood pressures ( sbp ) were measured on the right arm extended over a table at the level of heart with a calibrated standard sphygmomanometer . a set of different sized cuffs was used to circle the arm completely up to two - thirds of the upper arm without overlapping . systolic pressure was recorded when the initial sound was heard ( phase i of the korotkoff sound ) ; diastolic pressure was recorded at the disappearance of the sound ( phase v of the korotkoff sound ) . the arithmetic mean of these three sitting bp measurements was used as the mean sitting office bp ( mssbp ) . a cross check of 57% of the hypertension subjects at different times by different teams was done for both accuracy and consistency . every effort was made to avoid staff - child interaction , such as talking , in order to maximize reproducibility . every effort was made to have the same staff member take the bp measurements of the same child , at the same time of day , using the same equipment . hypertension was defined as mssbp above the 95 percentile for age , gender , and height as per recommendation of the national high blood pressure education program working group on high bp in children / adolescents ( nhbpep fourth report 2004 ) . the height and weight were measured with the child standing without shoes ; body mass index ( bmi ) was calculated for all children / adolescents . information on risk factors for hypertension like family history of hypertension and diabetes mellitus were asked for their socioeconomic status was also assessed . their reduced physical activities ( arbitrarily children who engaged in a physical activity < 30 min for 4 days per week ) posed a high risk . hours of watching television and their monthly consumption of oil were also noted as high risk factors . the fourth report on the diagnosis , evaluation and treatment of high bp in children and adolescents is an authentic source of childhood and adolescent hypertension ( 2004 ) . in this report , definition and classification of hypertension in children / adolescents we followed the same ffq - pure study from the south india described earlier for the study monthly per capital income was assessed by the children with a score of 1629 , and above ; modified kuppusamy scale ( 2007 ) was assigned to the upper socioeconomic status and < 15 lower socioeconomic status . the factors found to be significant by univariate analysis , namely the family history of hypertension , diabetes mellitus , obesity , high socioeconomic status , and female gender were included for multivariate analysis . the data were collected and entered , after which we manually checked and rechecked for accuracy . those variables found to be significantly associated were then studied by multivariate analysis logistic regression . they were screened for hypertension and associated risk factors . there were 2107 girls and 1799 boys [ table 2 ] . prevalence of hypertension among 10 - 17 year old children and adolescents by age and gender the overall prevalence of hypertension was 9.5% ( 371 ) of 3906 children / adolescents studied ; the prevalence of hypertension in boys was 8% ( 144 of 1799 ) with peak prevalence around 1215 years of age . children / adolescents with both systolic and diastolic hypertension were 31 ( 21% ) out of 144 . of the girls , the overall prevalence was 10.7% ( 227 ) of 2107 children , with peak prevalence around 1216 years of age . isolated systolic hypertension was present in 60 girls ( 26.4% ) ; diastolic hypertension alone was seen in 106 children ( 47% ) and 61 ( 26.6% ) out of 227 children had both systolic and diastolic hypertension . univariate analyses of risk factors for hypertension in these children / adolescents were done [ table 3 ] . univariate analysis for association between various risk factors and hypertension among 10 - 17 year old children and adolescents the overall prevalence of obesity was 2.7% among the hypertensives ( 106 out of 3906 ) ; 2.1% ( 75 out of 3535 ) in the normotensive obesity in boys was 2% ( 36 out of 1799 ) and 3.32% ( 70 out of 2107 ) in girls . the overall prevalence of overweight was 5.25% ( 205 out of 3906 ) . in normotensives , the prevalence of overweight was 4.8% ( 170 out of 3535 ) and it was 9.43% ( 35 out of 371 ) in hypertensives . overweight in boys was 2.17% ( 39 out of 1799 ) and 7.87% ( 166 out of 2107 ) in girls . a positive family history of hypertension among hypertensives was 13.2% compared to 8.3% of the normotensives . a positive family history of diabetes mellitus in the hypertensives was 5.3% as against 3.6% of the normotensives . the prevalence of hypertension in children / adolescents of low socioeconomic families was 8.85% as against 10.2% in children / adolescents of high socioeconomic families . children / adolescents with hypertension were more likely to be obese than children / adolescents with normal bp ( odds ratio [ or ] : 1.21 [ 2.726.48 ] 95% confidence interval [ ci ] ) . children / adolescents with hypertension were 1.6 times more associated with a family history of hypertension than children with normal bp ( or : 1.66 [ 1.202.30 ] 95% ci ) children who had hypertension were 1.3 times more likely to be girls than the normotensives ( or : 1.39 [ 1.111.72 ] 95% ci ) . the factors found to be significant by univariate analysis were included in multivariate analysis [ table 4 ] . family history of hypertension ( or : 1.67 [ 1.212.33 ] 95% ci ) obesity ( or : 4.67 [ 3.007.27 ] 95% ci ) , and overweight ( or : 2.17 [ 1.473.22 ] 95% ci ) were found to be independent risk factors associated with hypertension in the study population . multivariate logistic regression showed that cases had 1.67 times higher family history , were 4.67 times more obese and were 2.17 times more overweight compared to control children . multiple logistic regression analysis - factors for hypertension in children and adolescents aged 10 - 17 years the mean systolic and diastolic bp levels of children were studied in relation to age in both males and females . in both sexes , systolic and diastolic bp of boys and girls with age noted agrees with the findings in the task force committee report and other studies . the varying results may be due to varying age groups in the study , the different criteria adopted to define hypertension , and the basic differences between racial groups as relates to geographic , dietary , and cultural factors . in this study , there were more hypertensive girls ( 10.8% ) than boys ( 8.0% ) , results which do not correlate with those of other studies , in which hypertensive boys were 11.9% ; girls were 11.4% ; prevalence of overweight ( 7.87% ) and obesity ( 3.32% ) in girls was higher than overweight ( 2.17% ) and obesity ( 2% ) in boys . in our study , the prevalence of obesity was 2.7% , which is higher than that reported by another another study . positive family history of diabetes mellitus among hypertensives was 5.3% as against 3.6% in normotensives , which is similar to the study by chanda et al . hypertension in obese children / adolescents was 8.35% , which was twice what was observed by other study groups . in this study , there was a positive family history of hypertension in 8.3% , which is less than what was observed by another indian study . significant risk factors for hypertension in adolescents in our study by univariate analysis were obesity , overweight , and a positive family history of hypertension , which agreed with a previous study . there is an increasing trend toward a high prevalence of hypertension in children of school age as a result of obesity and positive family history of hypertension and diabetes mellitus . high socioeconomic status , faulty lifestyle , dietary habits , and physical inactivity are key factors which must be dealt with immediately and aggressively . based on our findings , hypertension is no more a disease that comes at a later stage in life . it is crucial to advise obese children to modify their lifestyle with respect to diet , exercise , and salt intake to maintain a normal bp and avoid the childhood onset of adult hypertension .

background : since the data of primary hypertension ( ht ) in children is scanty in india , this study attempted to evaluate ht by a multidimensional investigation of the various risk factors in children and adolescents.materials and methods : a total of 3906 subjects were recruited , all of whom lived in chennai , an urban area of tamil nadu . the children and adolescents aged from 10 to 17 years were selected by random sampling . the children / adolescents were randomized into one control and further divided into two groups . the national high blood pressure education program fourth report ( 2004 ) and anthropometric body mass index ( bmi ) , food frequency questionnaire ( pure ) were followed in the study.results:out of 3906 children , 2107 were girls and 1799 boys . on screening , we found 9.5% to be hypertensive with the prevalence rate of boys and girls 8% and 10.8% , respectively . overall obesity was 2.7% , ( boys 2% , girls 3.32% ) ; hypertensives and normotensives were 8.4% and 2.1% , respectively . we found that overweight ( odds ratio [ or ] : 2.06 [ 1.403.01 ] 95% confidence interval [ ci ] ) , obese children ( or : 1.21 [ 2.726.48 ] 95% ci ) , and those with a family history of ht ( or : 1.66 [ 1.202.30 ] 95% ci ) had increased risk of hypertension . females were 1.39 times ( or : 1.39 [ 1.111.72 ] 95% ci ) more at risk of getting ht . multivariate analysis showed that obese children / adolescent were four times more likely to have ht than children with normal bmi ( or : 4.67 [ 3.007.26 ] 95% ci].conclusion : family history of ht , obesity , and female gender are associated with a high risk of ht . the prevalence of ht was higher among obese adolescents than among slender subjects . this may be related to their sedentary lifestyle , faulty eating habits , high fat content in the diet and little physical activity .

insulin resistance ( ir ) plays a crucial role in the pathophysiology of metabolic syndrome ( mets ) , which is associated with an increased risk of cardiovascular disease and type 2 diabetes . from the standpoint of primary prevention , it is important to identify the patients at risk of mets , especially at an early stage when ir contributes to the clustering of borderline metabolic risk factors . homeostasis model assessment of ir ( homair ) is a useful model for assessing ir in largescale clinical research , and it has been validated by the gold standard method the hyperinsulinemiceuglycemic clamp technique . healthassociated reference interval of homair , which covers the central 95% of 2153 healthy japanese subjects , by applying the stringent c28a3 document from the clinical and laboratory standards institute . we have established the reference interval for homair as between 0.4 and 2.4 , and proposed that homair 2.5 be considered a reasonable indicator of ir in a japanese population as recommended by the japan diabetes society . healthassociated reference interval and is defined for use by clinicians to diagnose or manage patients . the present study focused on ir as a marker of earlystage mets and aimed to establish a an optimal cutoff point for homair to discriminate mets in nondiabetic japanese subjects was determined by receiver of the 7305 healthcheck examinees ( 4042 men and 3263 women ) who first visited the health evaluation and promotion center at tokai university hachioji hospital between april 2007 and march 2011 , 6868 examinees ( 3727 men and 3141 women ) were included in the present study after exclusion of those with fasting plasma glucose ( fpg ) 126 mg / dl and those on medication for diabetes . the present study was crosssectional in design , and was approved by the ethics committee of tokai university school of medicine ( 11r096 ) and complied with the helsinki declaration . waist circumference ( wc ) was assessed at the end of expiration , measuring the minimum circumference at the level of the umbilicus to the nearest 0.1 cm . blood pressure ( bp ) was measured at the right upper arm with the patient in a sitting position . fasting serum immunoreactive insulin ( iri ) was measured by fluorescenceenzyme immunoassay ( st aiapack iri ; toso , tokyo , japan ) . the intra and interassay coefficients of variation were 1.42.3 and 2.64.6% , respectively , and crossreactivity with proinsulin molecules was 2.0% . homair was calculated as : fpg ( in mg / dl ) iri ( in u / ml)/405 . mets was diagnosed if subjects had increased waist circumference ( 85 cm for men and 90 cm for women ) plus at least two of the following criteria : fpg 110125 mg / dl , hypertension ( systolic bp 130 mmhg , diastolic bp 85 mmhg , or on medication ) and dyslipidemia ( tg 150 mg / dl , highdensity lipoprotein cholesterol < 40 mg / dl , or on medication ) . the roc curve of homair for detecting mets was produced , and the area under the curve ( auc ) with its 95% confidence interval ( ci ) was calculated . to determine the optimal point , the square root of [ ( 1 sensitivity ) + ( 1 specificity ) ] was calculated , which is the point on the roc curve with the shortest distance from the upper left corner . spss statistics version 19.0 software ( spss , chicago , il , usa ) was used for statistical analyses . the average homair was 1.63 for men and 1.36 for women . among the 3727 men and 3141 women , mets was diagnosed in 594 men ( 15.9% ) and 81 women ( 2.6% ) . homair values were significantly higher in mets subjects ( 2.68 1.70 for men and 3.21 2.44 for women ) compared with nonmets subjects ( 1.43 0.90 for men and 1.31 0.83 for women ) . the auc ( 95% ci ) was 0.794 ( 0.7750.813 ) for men and 0.883 ( 0.8520.913 ) for women . the optimal point of homair yielding the minimum value of the square root of [ ( 1 sensitivity ) + ( 1 specificity ) ] was 1.7 for both sexes , which was lower than the upper limit of the reference interval . a homair value of 1.7 was also the point that maximized the product of sensitivity and specificity , with a sensitivity and specificity of 73.4% and 70.5% for men , and 81.5% and 77.0% for women , respectively . the prevalence of homair 1.7 was 36.5% in men and 24.5% in women . hypertension is defined as systolic blood pressure ( bp ) 130 mmhg , diastolic bp 85 mmhg , or on medication . dyslipidemia is defined as triglycerides ( tg ) 150 mg / dl , highdensity lipoprotein cholesterol ( hdlc ) < 40 mg / dl , or on medication . bmi , body mass index ; firi , fasting immunoreactive insulin ; fpg , fasting plasma glucose ; homair , homeostasis model assessment of insulin resistance ; mets , metabolic syndrome . the receiver operating characteristic curves of homeostasis model assessment of insulin resistance ( homair ) for detecting metabolic syndrome in men and women . the optimal points were determined by calculating the square root of [ ( 1 sensitivity ) + ( 1 specificity ) ] . the present study aimed to determine the optimal cutoff point for homair to discriminate mets , and the proposed optimal cutoff value was 1.7 , based on the point producing the greatest discriminatory ability on roc analysis . the concept of ir as a common etiology of mets , proposed around 1990 and given various names including syndrome x and the insulin resistance syndrome , was included in the first diagnostic criteria for mets by the world health organization in 1998 . however , in the later mets definitions , the central feature of the syndrome has shifted entirely away from ir to a collective of metabolic abnormalities that have better predictive value for cardiovascular disease , perhaps because there has been hardly any consensus on the cutoff points for the classification of ir . it is also problematic that the types of range or limit for homair ( i.e. healthassociated or reference interval that is derived from the central 95% of a normal distribution of healthy reference individuals , there is no single standard method to determine a decisionbased range or limit . rather , it depends on the type of decision to be made , such as screening , assessment of risk , diagnosis of disease or disease management . roc analysis was used in the present study , which is one of the most useful approaches to specify the cutoff points that have the greatest clinical value in discrimination . in the present study , the optimal cutoff value for homair to discriminate mets was 1.7 , as determined by roc analysis using 6868 nondiabetic japanese subjects . to the best of our knowledge , this is the first study to determine a cutoff point for homair to discriminate mets in a japanese population . several reports have determined homair cutoff points for the diagnosis of mets as 1.22 , 1.7 , 2.3 and 2.34 by roc analysis in other ethnic populations ( table 2 ) . the possible reasons for the inconsistency might be the differences in ethnicity and clinical backgrounds , including body mass index . therefore , the cutoff value specific for the japanese population is needed , and the present result shows higher sensitivity and specificity than the values of the other studies . aha / nhlbi , american heart association / national heart , lung , and blood institute ; atp iii , adult treatment panel iii ; homair , homeostasis model assessment of insulin resistance ; idf , international diabetes federation ; m , men ; w , women . the prevalence of homair 1.7 was 36.5% in men and 24.5% in women , whereas 15.9% of men and 2.6% of women had mets . the discrepancy between the prevalence of homair 1.7 and that of mets was larger in women than in men . when maximal sensitivity , as well as maximal specificity , is to be prioritized , the issue of a high falsepositive rate is inevitable . from the standpoint of primary prevention , we consider that it is much more important not to overlook mets than to exclude nonmets , and to give advice on lifestyle modifications to as many people as possible . in addition , we consider that it is not appropriate to diagnose mets by homair , because the prevalence of mets was 32.1% for men and just 8.6% for women , even in the subjects with homair 1.7 . in conclusion , homair = 1.7 was determined as the optimal cutoff value for identifying subjects at high risk for mets . with the aim of health guidance for mets , we propose that homair < 1.7 should be considered as a target .

abstractwe have recently established a healthassociated reference interval of homeostasis model assessment of insulin resistance ( homair ) between 0.4 and 2.4 . in the present study , the aim was to establish a decisionbased limit of homair for the discrimination of metabolic syndrome ( mets ) in nondiabetic japanese subjects . the receiver operating characteristic curve of homair for detecting mets was developed using data from 6868 nondiabetic subjects ( 3727 men , 3141 women ) . the optimal cutoff point was determined based on the point that yielded the minimum value of the square root of [ ( 1 sensitivity)2 + ( 1 specificity)2 ] . homair = 1.7 was determined as the optimal cutoff value , with a sensitivity and specificity of 73.4% and 70.5% for men , and 81.5% and 77.0% for women , respectively . in conclusion , the optimal cutoff value for homair to discriminate mets in nondiabetic japanese subjects appears to be 1.7 . ( j diabetes invest , doi : 10.1111/j.20401124.2012.00194.x , 2012 )

a 75-year - old caucasian female , awaiting elective laparoscopic cholecystectomy , complained to her general practitioner of persistent cough , dyspnoea and low - grade fever that had lasted for more than one month . she presented to the emergency department , where a chest radiograph showed areas of consolidation in the lower lobes and in the right apex . another course of antibiotics was prescribed and her symptoms improved . to ensure resolution of the pneumonia , prior to laparoscopic cholecystectomy , twenty days later the patient had a high resolution computed tomography ( hrct ) scan in our institution . ct images showed the resolution of the pneumonia , but revealed an anomalous supernumerary bronchus directly arising from the right side of distal trachea corresponding to tracheal bronchus ( trb ) . tracheal bronchus ( trb ) is a congenital supernumerary bronchus to the right upper lobe that arise directly from the lateral wall of tracheal , generally located 3 cm proximal to the carina ( fig . 1 ) . trb is an incidental finding in man , with a low prevalence ( 15% ) , conversely it is a normal finding in pigs and for this reason it is also called it can be classified into two types : ( 1 ) supernumerary , as an accessory bronchus , and ( 2 ) displaced when the entire upper lobe ( usually right side ) is supplied by this bronchus . the congenital abnormality is usually asymptomatic : the accessory bronchus is discovered , as incidental finding , during radiological investigation or bronchoscopy . trb may also be related to inflammatory conditions due to retained secretions and may cause recurrent pneumonia , chronic bronchitis and atelectasis as in the case discussed . multidetector ct permits a direct diagnosis of trb , non - invasively , and is able to correctly identify the origin of the right upper lobe bronchus with 3d airway reconstructions ( fig . 2 ) . the use of volumetric hrct allows multiplanar reconstructions to accurately evaluate the bronchus path and calibre and to guide management ( video ) . supplementary video 1 related to this article can be found , in the online version , at doi:10.1016/j.ejro.2014.10.001 . video 1ct virtual bronchoscopy video shows an endoscopic reconstruction of the distal trachea , from which an anomalous ct virtual bronchoscopy video shows an endoscopic reconstruction of the distal trachea , from which an anomalous in fact , special care is required during intubation : if trb anomaly is not diagnosed , endotracheal tube could provoke the occlusion of the bronchus , which could lead to the collapse of the lobe , , .

a 75-year - old female underwent a high resolution computed tomography ( hrct ) scan for recurrent bronchitis and cough . hrct images showed an anomalous supernumerary bronchus to the right upper lobe directly arising from the right side of distal trachea , corresponding to tracheal bronchus ( trb ) . trb can cause recurrent right upper lobe pneumonia and special care is requiring during endotracheal intubation .

the proximal femur nail antirotation ( pfna ) is the recent addition to the growing list of intramedullary implants for trochanteric fracture fixation . we report our results of low velocity trochanteric fractures internally fixed by proximal femur nail antirotation . a prospective study was conducted to assess the results of 122 elderly patients with low velocity trochanteric fractures [ 39 stable ( ao ; 31-a1 ) and 83 unstable ( ao ; 31-a2 and a3 ) ] treated with pfna from december 2008 to april 2010 . varus collapse was seen in 14 patients and helical blade cut out in one patient . good results with relatively low complication rates can be achieved by pfna in trochanteric fractures in the elderly . attention to implant positioning , fracture reduction and the biomechanical advantages of intramedullary ( i m ) implants make gamma nail ( gn ) and proximal femur nail ( pfn ) an attractive option especially in unstable fractures.1 initial reports have suggested that i m nails may have an advantage over sideplate devices in unstable fractures but have not demonstrated a clear superiority and have a reported complication rate of around 20%.24 the incidence of neck screw cutout has reduced considerably with improvements in the surgical technique but still remains the most common mode of fixation failure56 with i m implants . the proximal femur nail antirotation ( pfna ) was developed aiming to reduce this complication and initial studies have shown promise.78 with this background , we analyzed our results with the pfna in low velocity trochanteric fractures in the elderly . 122 patients with trochanteric fractures treated with the pfna from 2008 december to 2010 april were reviewed . independently mobile patients over 65 years admitted with a trochanteric fracture following a low velocity fall were included in the study . high velocity fractures ( road traffic accidents , fall from a height of more than 5 feet ) , polytrauma patients , pathological fractures , intracapsular fractures , subtrochanteric fractures , and patients presenting more than 2 weeks after injury were excluded . the institutional review board approved the study and informed consent was obtained from patients prior to surgery . a standard surgical technique for nail and blade insertion recommended by the manufacturer ( pfna ii , synthes , india ) was followed . percutaneous fracture - reduction techniques were used if satisfactory reduction in two planes could not be achieved before the nailing procedure . the nail was locked distally in the dynamic mode for stable fractures ( a1 ) and in the static mode for unstable fractures ( a2 and a3 ) . weight bearing as tolerated was allowed routinely from the day after surgery irrespective of the fracture subtype . final analysis was performed between may and july 2011 . at followup , visual analog scores ( vas ) , the mobility scores described by parker and palmer9 were recorded and hip abductor strength assessment was done according to the medical research council ( mrc ) grading . immediate postoperative radiographs were evaluated for fracture reduction , tip apex distance ( tad ) , and zone position of the helical blade . fracture reduction was classified as satisfactory and not satisfactory according to modified baumgaertner 's criteria.10 helical blade position in the lower half of the neck and central central in the femoral head with a tip - apex distance of < 25 mm was considered satisfactory . followup radiographs were assessed for union , loss of reduction and fixation , helical blade sliding ( measured using the technique described by watanabe et al.11 ) , migration , and cut out . categorical variables were expressed as proportions and were assessed using pearson 's chi - square test . internal subgroup analysis was performed comparing stable with unstable fractures and well fixed ( good reduction and ideal blade position ) fractures with poorly fixed ( poor reduction and/or unsatisfactory blade position ) fractures with respect to fracture reduction , helical blade positioning ( tad ) , functional outcome , and complications , and the level of significance was assessed with p value ( significant when < 0.05 ) . the mean age was 74 years ( 6696 years ) and there were 69 females and 53 males . 39 fractures ( 32% ) were classified as ao type a1 , 68 ( 56% ) a2 and 15 ( 12% ) type a3 fractures . a total of 111 patients were available for final followup after accounting for deaths and patients lost in followup . eight patients died , three in the acute postoperative period due to systemic causes and five during followup . of the 111 patients available for followup , fracture reduction was classified as satisfactory [ figure 1 ] in 94 patients . poor fracture reductions ( p = 0.001 ) and unsatisfactory blade positions ( p = 0.028 ) were significantly high in unstable fractures . poorly reduced fractures also demonstrated a high incidence of unsatisfactory blade positions ( p = 0.001 ) . x - ray ( l ) hip joint anteroposterior view ( a ) and lateral view ( b ) showing a well - reduced type ao ; 31-a2 fracture fixed with the pfna demonstrating excellent blade position and ( c ) satisfactory outcome at final followup the mean vas score at the final followup was 1.60.99 . slight - to - moderate abductor weakness was seen in 36 patients ( mrc grades iii and iv ) . a total of 72 ( 65% ) patients returned to their pre - injury status and 88% were community ambulant . fracture stability did not have significant bearing on clinical and functional outcome measures [ table 2 ] . varus collapse ( change in neck shaft angle of > 5 ) was the most common [ figure 2 ] . 12 of the 14 were seen in unstable fractures ( p = 0.09 ) and 10 of the 14 in poorly fixed fractures ( p = 0.001 ) . other complications include helical blade cut out in one patient , medial migration of the helical blade into the hip joint in three patients [ figure 3 ] , delayed union in a patient addressed with total hip replacement , and symptomatic back out of the helical blade due to excessive sliding in two patients . the incidence of complications was significantly low in patients with stable fractures ( p = 0.049 ) and well - fixed fractures ( p = 0.033 ) compared to unstable and poorly fixed fractures [ table 3 ] . ( a and b ) varus collapse following stabilisation of a 31-a2 fracture with a large posteromedial fragment in a 91 years female x - ray ( rt ) and ( lt ) hip joint with proximal femur showing the postoperative migration of the helical blade into the hip joint pfna incorporates the use of the helical - shaped blade to achieve fixation into the femoral neck unlike the use of screws in the earlier generation i m devices . the blade insertion technique compacts cancellous bone that makes it suitable for osteoporotic fracture situations.12 the blade concept has also been shown in vitro to be biomechanically superior to screws in terms of axial and rotational stability.1314 though the overall complication rate was 19% , the rate was only 9% in well - fixed fractures . a vicious cycle was evident in unstable fractures with poor reduction leading to poor implant placement and consequently higher complication rates . unsatisfactory blade position was directly related to the fracture reduction rather than fracture stability . though the overall tad was high in unstable fractures , the difference was mainly due to unsatisfactory fracture reductions in the unstable fracture group . an ideal blade position could be achieved only in 73% of the patients in the current study , which may be explained by the poor reductions precluding the surgeons from achieving an ideal blade position and the learning curve on the part of the surgical team . however , the deviation is not very different from the reported incidence of around 21%.15 only low velocity falls were included in the study , which is an indirect measure of osteoporosis . a cut out rate of 0.8% indicates an excellent outcome compared with the previously reported rates of 24% with i m devices.16 despite the theoretical advantages of the blade being anti - varus collapse and anti - rotation , varus collapse was the most common complication seen in the study accounting for 2/3 of all complications . 86% of all varus collapse occurred in patients with either an unsatisfactory blade position or poor reduction or both . minimal limp was seen in 42 ( 37% ) patients at the last followup which may indicate damage to the abductors during surgery and a degree of shortening . 88% of the patients were community ambulant with or without assistive devices at the last followup indicating that majority of the patients had benefitted from the procedure . overall complication rate of 19% does not indicate a significant improvement from the previous i m devices but the study showed a very low cut - out rate reflecting the effectiveness of the bone impaction technique and the anti - rotation concept of the pfna . there were no femoral shaft fractures and the overall reoperation rate of 5.7% is comparable with the reported rate of 1.210%.1718 apart from inherently unstable fractures , poor fracture reduction and unsatisfactory blade position in the femoral head are the chief factors in determining the complication rates . attention to these factors and improvement in the learning curve can play a significant role in improving outcome and reducing complications with i m osteosynthesis using the pfna.1920

background : the proximal femur nail antirotation ( pfna ) is the recent addition to the growing list of intramedullary implants for trochanteric fracture fixation . the initial results in biomechanical and clinical studies have shown promise . we report our results of low velocity trochanteric fractures internally fixed by proximal femur nail antirotation.materials and methods : a prospective study was conducted to assess the results of 122 elderly patients with low velocity trochanteric fractures [ 39 stable ( ao ; 31-a1 ) and 83 unstable ( ao ; 31-a2 and a3 ) ] treated with pfna from december 2008 to april 2010 . followup functional and radiological assessments were done . results obtained were compared between stable and unstable fracture patterns using statistical tools.results:the mean followup was 21 months ( 1228 months ) . 11 patients were lost in followup . union was achieved in all but one patient . varus collapse was seen in 14 patients and helical blade cut out in one patient . stable and satisfactorily reduced fractures had a significantly better radiological outcome . functional outcome measures were similar across fracture patterns . 65% of the patients returned to their preinjury status . the overall complication rate was also significantly higher in unstable fractures.conclusion:good results with relatively low complication rates can be achieved by pfna in trochanteric fractures in the elderly . attention to implant positioning , fracture reduction and a good learning curve is mandatory for successful outcomes .

a 45year old male patient with recurrent symptomatic documented supraventricular tachycardia for the last 8 years was referred to our department for an electrophysiological ( ep ) study . the ecg during the symptoms showed a narrow qrs complex tachycardia at 180 beats / min ( bpm ) . an arterial hypertension and a diabetes mellitus type ii had been well treated for the last couple of years . the ep study was performed under a fasting state and under sedation with midazolam . at the time of the procedure the patient was in sinus rhythm ( sr ) ( heart rate ( hr ) : 76 bpm ; pqinterval : 156 msec ; qrsinterval : 82 msec ) . one diagnostic catheter was placed in the higher right atrium ( hra ) , one in the apex of the right ventricle and one in the coronary sinus ( cs ) . the av node conduction time ( ahinterval ) and conduction time through hispurkinje system ( hvinterval ) were normal , with 115 msec and 48 msec , respectively . using progressive atrial extrastimulus testing and under administration of orciprenaline , a typical atriovenricular node reentry ( avnrt ) tachycardia with a cycle length ( cl ) of 330 msec could be induced . first , the inferoposterior site of the septal annulus of the tricuspid valve at cs ostium was targeted . the location was confirmed by fluoroscopy , and on typical electrophysiological signals for slow pathway , 10 rf impulses ( one rf impulse = 60 sec ) were delivered at and around this site but with a transient effect . for stable catheter position and a better result a long sheath was insert and six rf impulses were applied at a more medial site , during which junctional rhythm occurred . the mean temperature that was achieved was 45c and the mean energy that was delivered was 35 watts . in all attempts , the longest possible distance from the av node was kept . following the last energy delivery , the ecg showed a sr with a hr of 76 bpm , pqinterval of 210 msec , and a qrsinterval of 85 msec . incremental atrial pacing hereafter and at the end of the study showed no dropped beats . during the observational time of 20 min , avnrt was not inducible anymore , also not under administration of orciprenaline ( a cumulative dose of 0.5 mg over 15 min ) . at the end of the study , the av node effective refractory period ( averp ) was 370 msec and the retrograde averp was 430 msec . the ecg at the end of the study showed a normal sr ( hr 78 bpm ; pqinterval 185 msec ; qrsinterval 80 msec ) . before discharge the ecg at discharge showed a normal sr ( hr 85 bpm ; pqinterval : 176 msec ; qrsinterval 82 msec ) . two days later the patient presented to our emergency department complaining of palpitations and lightheadedness . the resting ecg showed a thirddegree av block with a high junctional rhythm ( hr : 65 bpm ; qrsinterval 85 msec ) ( figure 1 ) . the patient was admitted to our telemetric monitoring ward and permanent pacemaker implantation was discussed . there was no sign of pericardial effusion or any other changes compared to the echocardiography done during the first admission . as the av block was interpreted as a consequence of the prior rf ablation , we immediately initiated an antiphlogistic therapy with an intravenous bolus ( iv ) of 250 mg prednisolone , which was continued orally for another 5 days with 50 mg / day . additionally , ibuprofen 600 mg twice daily was administered . under this therapy a regression of the thirddegree av block was observed in the telemetric monitoring . shortly after the initial administration of the prednisolone iv bolus the following 2 days , there were only a few dropped beats , predominantly at night . by the end of day 5 of antiphlogistic treatment the ecg at resolution of complete av block , showed a sr with a hr of 69 bpm ( pqinterval 224 msec and qrsinterval 86 msec ) ( figure 3 ) . the holter ecg after therapy administration and before discharge revealed a normal sr during the recording . ecg at complete resolution of third degree av block , showing a sinus rhythm with a firstdegree av block . after a 1 year followup period the patient presented to our outpatient clinic without any symptoms . the ecg at oneyear followup showed a normal sr with a hr of 78 bpm ( figure 4 ) . the holter ecg ( 24 h ) at oneyear followup revealed a normal sr with a minimal hr of 54 bpm and maximal hr of 120 bpm . we report a case of a thirddegree av block sensitive to prednisolone occurring 72 h after a rf ablation for the treatment of an avnrt . avnrt is one of the most common supraventricular tachycardia , affecting most commonly patients of young age . rf ablation is , even though an invasive therapy , currently the firstline treatment for symptomatic avnrt patients with success rates exceeding 90% after the first attempt . av block during or after a rf ablation is a rare but feared complication , occurring in approximately 510% of cases of fast pathway versus 12% of slow pathway ablations 1 . thus , modification of the slow pathway is the preferred type of procedure . in most cases pathophysiological reasons are either direct damage to the av node or increased vagal tone caused by pain during the ablation procedure or by direct stimulation of parasympathetic nerve fibers of the atrium 2 . risk factors associated with the development of av block after successful slow pathway modification are a prolonged printerval prior to the procedure , which seems to have a higher incidence in older patients and in those with structural heart disease 3 . furthermore ablation at the near side of av node and the appearance of a transient av block during the procedure both have a strong positive predictive value of development of a highdegree av block thereafter 4 , 5 . nevertheless , in clinical practice most patients with an avnrt , do not have any structural heart disease or other serious comorbidities . the presence of a highdegree av block as a complication of an rf ablation would inflict the need of a permanent pacemaker implantation that might not be well accepted by the patient regarding his long expected lifetime and the overall benign nature of avnrt . the rapid recovery of the av node conduction in the presented case after administration of an antiphlogistic medication is opposed to the common notion that highdegree av block after rf ablation is a consequence of irreversible damage to the av node with the necessity of permanent pacemaker implantation . a possible explanation for the delayed development of a symptomatic av block in our patient could be that around the region of rf application inflammation and edema caused impaired myocardial and av node conduction . several cases have described late av block formation after rf ablation reaching from several hours to several months after the ablation with the need of permanent pacemaker implantation . largely , this had been explained by late tissue retraction and scar formation around the ablated area . they argued that after successful rf ablation there is a continuous healing process in the rf lesion , marked by inflammation , leading to formation of fibrosis over a period of weeks to months . this fibrosis could lead to extension of the initially ablated area leading to late conduction disturbance 6 . haissaguere et al . described a progression of tissue lesion as a cause of the appearance of prolonged pr intervals or a wenckebach block following several days after rf ablation 7 . our results show a progressive decrease in pqinterval after administration of antiinflammatory drugs over a few days . these findings suggest that the reversibility of the av block in the presented case is due to the early administration of antiphologistic medications . we believe that this could have prevented the development of late thermal injury that would have otherwise caused irreversible damage to the conduction properties of the av node with the necessity of permanent pacemaker implantation . we suggest that at least in the case of delayed development of av block following rf ablation , the initial inflammatory response with edema and tissue swelling with the possibility of a late development of fibrosis and an irreversible damage to the av node could be successfully treated and prevented with antiphlogistic medication . in our opinion , this could be of great potential concerning the young age of the patients often undergoing the procedure and the burden of a permanent pacemaker implantation . asp , mh : collected ablated data . as , db , pa : collected and analyzed ecg .

key clinical messagea patient developed a transient firstdegree av block during a radiofrequency ablation of an atrioventricular nodal reentrant tachycardia . three days later the patient presented with a thirddegree av block . it resolved within 24 h under antiphlogistic therapy . patient was asymptomatic without necessity for pacemaker implantation at 12 months followup .

choriocarcinoma is a highly malignant gestational trophoblastic disease associated with high urine and serum -hcg levels . to date , few studies have reported pulmonary embolism ( pe ) and pulmonary hypertension caused by choriocarcinoma of the pulmonary artery . here , we report a young female patient with choriocarcinoma of the pulmonary artery who was clinically misdiagnosed with pulmonary thromboembolism ( pte ) and died of acute cardiopulmonary failure very soon after embolectomy . a 25 year - old female patient first experienced an episode of sudden dyspnea and frequent coughing after routine physical activity . she was initially diagnosed at a local hospital with acute pneumonia based on a chest x - ray , which showed several small , scattered radio - opaque shadows on both lungs . six months later , the patient was referred to our hospital because of severe orthopnea . upon arrival , arterial blood gas analysis showed that the values of ph , paco2 , and pao2 were 7.502 , 26.3 mmhg , and 50 mmhg , respectively , under 2 l / minute oxygen inhalation . an emergent contrast - enhanced ct scan showed occlusion of the left pulmonary artery and right inferior pulmonary artery ( fig . the scan further revealed multiple patchy , cord - like , nodular fuzzy shadows in bilateral lungs ( fig . meanwhile , a diagnosis of pe was made based on echocardiographs , which revealed severe pulmonary hypertension ( pulmonary systolic pressure , 105 mmhg ) and mild tricuspid regurgitation . although her d - dimer test value was only 0.27 g / ml , a pulmonary angiograph was still performed via the right femoral vein , which showed complete occlusion of the left pulmonary artery and right inferior pulmonary artery . a : ct scan demonstrates occlusion of the left pulmonary artery and right inferior pulmonary artery . b : ct scan shows multiple patchy , cordlike , nodular fuzzy shadows in bilateral lungs . the patient claimed that she was a non - smoker , did not use oral contraception , and had experienced three previous spontaneous abortions ( the most recent occurring one year previously ) . the patient had spent more than 10 hours playing card games every day during the past four years . an angiographic procedure for direct injection of 400,000 iu urokinase failed to dissolve the emboli . since her pe was believed to have derived from deep venous thrombi ( sedentary clinical history ) , a filter was also placed in the inferior vena cava . the condition of the patient continued to deteriorate with progressive tachypnea , cyanosis , non - productive cough , and hemoptysis ; therefore , a pulmonary embolectomy was carried out using a cardiopulmonary bypass procedure . complete obstruction of the openings of the left pulmonary artery and right inferior pulmonary artery by the yellow - pink soft emboli was observed . the emboli were completely removed to re - establish blood flow from the bronchial artery . at the time of re - warming prior to decannulation , the pulmonary artery systolic pressure ranged from 90 - 110 mmhg and surpassed the aortic systolic pressure . the hemodynamic situation was so unstable that a 5 mm hole was made in the atrial septum to mitigate the condition . the patient was then transferred to the cardio - thoracic intensive care unit . in spite of intensive efforts , the patient ultimately succumbed to cardiopulmonary failure and acute renal failure approximately 14 hours after embolectomy . pathologic evaluation of pulmonary emboli showed macroscopic fragments of yellow - pink tissue measuring 4 cm at the greatest dimension ( fig . post - mortem histological evaluation showed that the viable tumor constituted only a thin peripheral rim with a central area of necrosis and focal hemorrhage ( fig . the tumor cells consisted of an intimate amalgamation of multinucleate syncytiotrophoblasts , mononucleate cytotrophoblasts , and intermediate trophoblasts . there was considerable cytological atypia in the trophoblasts with hyperchromatic nuclei and abnormal mitotic figures ( fig . lack of villi and new blood vessel formation comprised the unique morphological features consistent with choriocarcinoma . immunohistochemical staining demonstrated strong reactivity for hcg in syncytiotrophoblasts ( fig . 2c ) and strong cytokeratin positivity was observed in all the tumor cells ( fig . the diagnosis of choriocarcinoma embolism was confirmed . a : macroscopic examination of the yellow - pink soft embolus obtained during pulmonary embolectomy . b : tumor characterized by atypical trophoblasts with polymorphic and hyperchromatic nuclei as well as abnormal mitotic figures . choriocarcinoma of the pulmonary artery has been described as a rare cause of pe and pulmonary artery hypertension ( pah ) . such cases represent a potentially fatal emergency due to cardiopulmonary failure . however , the diagnosis is difficult to establish because of the tendency of these tumors to present characteristics of more common diseases such as pte . almost all choriocarcinomas of the pulmonary artery present with pe , and pah occurs after nonmolar abortions ( mostly spontaneous abortions ) and rarely after normal pregnancies . the low incidence of choriocarcinoma of the pulmonary artery and the long latency after a live birth or nonmolar abortion make early diagnosis of this condition very challenging . bagshawe first reported choriocarcinoma of the pulmonary arteries , identified at necropsy in patients who died of pah in 1959 . he suggested that choriocarcinoma emboli could be the result of a progressive neoplastic obstruction of pulmonary arteries leading to pah and respiratory distress . in addition to the case reported here , we reviewed 10 cases of pulmonary choriocarcinoma presenting with pe and pah reported between 1991 and 2008 ; the findings of these 11 cases are summarized in table 1 . almost all of the patients ( 10/11 ) had a history of abortion with latency periods ranging from two months to six years and no primary uterine tumor identified . among these cases , seven ( 7/10 ) were spontaneous abortion and , only one patient ( 1/11 ) a normal delivery three years previously . the most important risk factor , a history of hydatidiform mole , was absent from the cases included in our review ; almost all cases occur after a spontaneous abortion and rarely after normal full term pregnancy . owing to regular check - ups for potential malignant sequelae after hydatidiform molar pregnancies , few of these patients present with advanced disease , such as pulmonary hypertension . therefore , almost all trophoblastic tumors that occur after a normal pregnancy are choriocarcinomas . e : etoposide ; m : methotrexate ; a : actinomycin d / dactinomycin ; v : vincristine ; cyc : cyclophosphamide ; car : carboplatin ; cis : cisplatin ; aned : alive with no evidence of disease ; dod : dead of disease ; na : not available ; pe : pulmonary embolism ; pte : pulmonary thromboembolism ; mcc : metastatic choriocarcinoma ; el : embolectomy . . almost all results of pelvic ultrasound and gynecologic examination of the uteri and ovaries were negative , even by autopsy . rare cases of pe due to choriocarcinoma in women occurring many years after hysterectomy have been reported . moreover , tanimura and colleagues revealed trophoblasts in the pulmonary arteries in autopsies of nine of ten patients who died after delivery or abortion . therefore , it has been speculated that primary choriocarcinoma of the pulmonary arteries in women may be due to malignant transformation of normal villous trophoblasts which entered the pulmonary artery at the time of abortion or delivery ; however , the others consider that pulmonary choriocarcinoma derives metastatically from a regressed tumor previously present in the uterus . similar to our case , patients commonly present with non - specific symptoms such as chest pain , cough and dyspnea , as well as abnormal findings of chest x - rays ( diffuse radiopaque shadows in the bilateral lungs ) . these manifestations are commonly misdiagnosed as pneumonia due to the absence of molar pregnancy history and gynecologic symptoms . as the quantity and volume of the pulmonary artery embolus increases , symptoms of pulmonary hypertension are present . chest ct imaging may show intraluminal contrast filling defects ( emboli ) in the pulmonary artery down to the segmental and subsegmental levels , as well as multiple peripheral opacities in both lungs . at this stage , thoracic surgeons frequently misdiagnosed the condition as pulmonary thromboembolism and as a result , the duration from onset to treatment ranged from one to 12 months ( average 6 months ) . typically , serum -hcg levels in patients with choriocarcinoma of the pulmonary artery are high , ranging from 1,000 miu / ml to over 1,000,000 miu / ml , and urine pregnancy tests are always positive . in most developed countries , urine and/or serum -hcg evaluation is a routine screening test in female patients regardless of the disorders that bring them to clinics . however , there are still many hospitals around the world ( especially in developing countries ) in which urine and/or serum -hcg is still not on the list of routine tests . similarly , the clinician responsible for the case described here noted the long sedentary history of the patient but disregarded the three spontaneous abortions ; therefore , urine and/or serum -hcg tests were consistently omitted . thus , urine and/or serum -hcg test should always be a frontline test ordered when female patients present with the symptoms of pe and pah to rule out the possibility of choriocarcinoma . seckl and coworkers reported three cases of young women with complete remission following chemotherapy of choriocarcinoma embolism . the diagnosis was based mainly on high -hcg levels in non - pregnant women , indicating that a definitive histological diagnosis is not essential before initiation of chemotherapy , particularly since surgery is associated with considerable morbidity . recently , fdg - pet / ct has been utilized to assist diagnosis for increased metabolism of the embolus . multiagent chemotherapy includes etoposide , methotrexate , actinomycin d , cyclophosphamide , cisplatin , vincristine , and dactinomycin , leading to a cure rate in excess of 89% . thus , chemotherapy coupled with biochemical and radiological monitoring constitutes an attractive management approach for pulmonary choriocarcinoma embolism therapy . in conclusion , pulmonary choriocarcinoma embolism is now a curable disease which is commonly associated with spontaneous abortion , a long latency and empty uteri . in order to avoid unnecessary deaths , it is very important for the clinician to recognize the non - specific clinical characteristics in the early stages and to use urine and/or serum -hcg as the frontline test in the fertile female patients who are clinically suspected of pe ; the earlier the diagnosis and initiation of chemotherapy , the better the prognosis .

abstractcases of pulmonary embolism and pulmonary artery hypertension caused by choriocarcinoma represent a rare clinical emergency . we report a case of a 25-year - old woman who presented with pulmonary embolism and hypertension and died soon after complete pulmonary embolectomy . a related literature review revealed that almost all of these patients had previously experienced a spontaneous abortion ( average , 6 months ) and were not pregnant .

the utilization of plant and leaf extracts in animal production has found widespread scientific and commercial acceptance as a strategy to improve the health status and performance of the animals [ 18 ] . leaf extracts also have appetizing and digestion - stimulating properties and antimicrobial effect [ 912 ] . according to ifon and basir leaf vegetables supply minerals , proteins , and vitamins which could complement the inadequacies of most feedstuffs . reported that leaf protein has the potential for supplying good quality food proteins than would be obtained with cereals , legumes , and oil seeds . telferia occidentalis ( fluted pumpkin ) is a leaf vegetable that is widely cultivated in the tropics and subtropics . chemically t. occidentalis leaf extract contains 21.31% crude protein , 6.41% crude fibre , 5.50 ether extract , 10.92% ash , and 3121me ( kcal / kg ) . the protein from t. occidentalis leaves can be harvested and fed to farm animals as solution in the form of protein concentrates . according to ladeji t. occidentalis leaves contain 30.5% crude protein , 3.0% crude lipid , 87.3% crude fibre , and 8.4% total ash . the authors noted that the leaves had low level of tannic acid ( 4.75 + 0.50 mg/100 g dm ) and oxalate ( 0.45 + 2.10 mg/100 g dm ) , but high level of phytic acid ( 20.5 + 2.10 mg/100 g dm ) . in view of the relative abundance of t. occidentalis leaf in the study area , the present study was designed to evaluate the performance and haematological characteristics of starter broilers fed different levels of t. occidentalis leaf extract . this experiment was conducted at the poultry unit of animal science department , ebonyi state university , abakaliki with the approval of the animal ethics committee of the university . one kilogram ( 1 kg ) of freshly cut t. occidentalis leaves with the stalk was separated from the stem , washed with clean water to remove dirt and sand , drained , and chopped . this was then squeezed and filtered with sieve to obtain a homogenous extract of the fluted pumpkin leaves . the homogenous leaf extract was prepared at the interval of three ( 3 ) days and served to the animals fresh according to treatments . a total of two hundred ( 200 ) 8-day - old marshal strain commercial broiler chicks were randomly allotted to five ( 5 ) treatments in a completely randomized design ( crd ) . each treatment was replicated four ( 4 ) times with ten ( 10 ) birds per replicate and fed with commercial broiler starter diet . telfairia occidentalis leaf extract was added at 0 , 40 , 80 , 120 , and 160 ml / litre of drinking water representing t1 , t2 , t3 , t4 , and t5 , respectively . supplementation of telfairia occidentalis leaf extract and recording of water intake started on the first day of the experiment and was recorded daily . feed intake was also recorded daily while body weight was recorded at the beginning of the study and subsequently weekly . four ( 4 ) birds were selected at random from each of the treatments and bled via wing veins using sterile needles and syringes . 2 ml of blood were collected into properly labelled sterilized bottles containing ethylenediaminetetra - acetic acid ( edta ) as anticoagulant for haematological analysis . the packed cell volume ( pcv ) , red blood cell ( rbc ) , white blood cell ( wbc ) , and the haemoglobin ( hb ) concentrations were measured using the wintrobe 's microhaematocrit , improved neubauer haemocytometer , and cyanomethaemoglobin methods , respectively . mean corpuscular haemoglobin ( mch ) , mean corpuscular volume ( mcv ) , and mean corpuscular haemoglobin concentration ( mchc ) levels were calculated from pcv , hb , and rbc according to bush . data collected were subjected to one - way analysis of variance , while the differences between the treatment means were compared using duncan 's new multiple range test as outlined by obi . statistical significance was assumed at a value of p < 0.05 . all statistical analysis was performed with spss software ( version 10.0 , spss inc ) . the performance of starter broilers fed t. occidentalis leaf extract is as presented in table 1 . there were significant differences ( p < 0.05 ) in final body weight , body weight gain , feed conversion , and protein efficiency ratios of birds among the treatments . birds fed on t3 ( 80 ml fple / litre of water ) recorded significantly ( p < 0.05 ) the highest body weight gain compared to birds in the other treatment groups . there was no significant ( p < 0.05 ) variation in weight gain of birds in t1 ( 0 ml ) , t2 ( 40 ml ) , t4 ( 120 ml ) , and t5 ( 160 ml ) . the higher weight gain of birds fed 80 ml fple suggests that this level may have stimulated higher digestion of the nutrient consumed by the birds and greater efficiency in the utilization of feed resulting in enhanced growth . zhang et al . had earlier reported that plants extracts possess digestion stimulating properties . the result further strengthened the findings of nworgu and machebe et al . who reported that broilers tolerated lower levels of t. occidentalis and gongronema latifolia leaf extracts , respectively . the comparable weight gain of birds fed higher levels of t. occidentalis leaf extracts ( 120 ml and 180 ml ) and the control ( 0 ml ) is an indication that the concentration was within the tolerable limits of the birds and as such did not suppress the growth of the birds . according to ladeji et al . and nworgu et al . , t. occidentalis contains low levels of saponins , tannic acid , phytate , and oxalate which are nutritional factors that depress animal growth . however , in the present study they didnot exert any negative influence on the growth of the animals indicating that the concentration of the toxicants inherent in the concentration of the leaf extract was not toxic to the animals . there was no significant ( p < 0.05 ) variation in the feed intake of birds among the treatment . however , birds fed t. occidentalis leaf extract consumed numerically ( p < 0.05 ) lower feed than the control . the numerical decrease may be attributed to the improvement in the energy and protein consumption of birds resulting from the enhanced nutrient availability to birds fed t. occidentalis leaf extracts . there was no significant ( p < 0.05 ) difference in the water intake of the birds . this implies that t. occidentalis did not impact any significant change in the odour and taste of the water , since the sense of taste and smell are important factors in determining what birds consume like other monogastric animals . there were significant ( p < 0.05 ) differences in the feed conversion and protein efficiency ratios of the birds among the treatments . the feed conversion and protein efficiency ratio of birds fed fple were significantly ( p < 0.05 ) better than the control while birds fed 80 ml fple recorded the best feed conversion and protein efficiency ratios . the best fcr and per recorded by birds served 80 ml fple was as a result of the higher weight gain of the birds . the better fcr observed in birds fed t. occidentalis leaf extract suggests that fple increased the ability of the birds to utilize available nutrients in the feed and the extract . this observation is in agreement with the reports of machebe et al . and nworgu that birds fed leaf extracts had better feed conversion ratio than the control . there was no significant ( p < 0.05 ) difference in the per of birds fed 160 ml / l of t. occidentalis leaf extract ( t5 ) and the control ( t1 ) . / l of t. occidentalis leaf extract is an indication that fple positively influenced the protein utilization by the birds . there was no significant ( p > 0.05 ) interactions of the experimental factors with regard to haematological indices among the treatments ( table 2 ) . however , there was marginal increase in the haemoglobin ( hb ) , packed cell volume ( pcv ) , white blood cell ( wbc ) , and red blood cell ( rbc ) levels of birds fed fple . according to maxwell et al . , blood parameters are important in assessing the quality and suitability of feed ingredients for farm animals . babatunde et al . also reported that blood parameters are the major indices of physiological , pathological , and nutritional status of an organism and changes in the constituent compounds of blood when compared to normal values could be used to interpret the metabolic stage of an animal as well as the quality of feed . the pcv , hb , rbc , and wbc recorded in the present study fall within the normal range for healthy broiler chicken as reported by anon and iacuc . this portrays the nutritional status of the birds and thus suggesting adequate nourishment of the birds . the numerical differences observed in the pcv , hb , rbc , and wbc of birds fed fple inferred that they were better utilized and assimilated into the blood stream for use by the birds . in conclusion , considering the effects of different levels of t. occidentalis leaf extracts on weight gain , feed intake and feed gain ratio of the birds , it appears that 80 ml fple / litre of water gave the best result and should be used for broiler starters .

this experiment was conducted to determine the effect of aqueous extract of telfairia occidentalis ( fluted pumpkin ) leaf on the performance and haematological indices of starter broilers . a total of 200 , 8-day - old broiler chicks were randomly allotted to five ( 5 ) treatments , each with 4 replicate groups containing 10 chicks and fed with standard starter broiler diets . telfaria occidentalis leaves extract ( fple ) was added at 0 , 40 , 80 , 120 , and 160 ml / litre of drinking water . growth performance and haematological indices were evaluated . results showed that there was significant ( p < 0.05 ) difference in weight gain , feed conversion , and protein efficiency ratios of the birds among the treatments . birds fed 80 ml fple / litre of water had significantly the highest weight gain and the best feed conversion and protein efficiency ratios . there was no significant ( p > 0.05 ) variations in the feed and water intakes of the birds . results also show no significant ( p > 0.05 ) difference in haematological indices of birds among the treatments . the results of this study indicate that , for enhanced weight gain and feed conversion efficiency , birds should be fed 80 ml fple / litre of water .

periodic limb movement disorder ( plmd ) is diagnosed when there are periodic limb movements during sleep ( plms ) exceeding norms for age , clinical sleep disturbance , and the absence of another primary sleep disorder or reason for the plms . pathological periodic limb movement index ( plmi ) is defined as > 15 movements / h in adults . periodic limb movement disorder is rarer than restless legs syndrome ( rls ) , which is characterized by the sensory motor symptoms frequently associated with plms , usually occurring at night and leading to disrupted sleep and daytime fatigue as in neuromuscular disorders . several medications are known to induce and/or to worsen plmd ( i.e. , antidepressants , antihistamines , and antipsychotics ) . although alternative rls / plmd treatments include antiepileptic drugs ( aeds ) , in contrast , topiramate ( tpm)-induced rls also associated with plms was described in four patients affected by epilepsy , . we report a case of tpm - induced plmd in a patient affected by cryptogenic temporal lobe epilepsy lacking a history of previous sleep disorders . a 34-year - old male affected by cryptogenic temporal lobe epilepsy previously treated with carbamazepine ( up to 1200 mg per day ) manifested monthly complex partial seizures . topiramate slowly titrated up to 250 mg per day induced seizure freedom and , afterward , carbamazepine was discontinued . concurrently , he complained of insomnia , nonrestorative sleep , and daytime sleepiness ( epworth sleepiness scale ( ess ) score : 16 ) . in addition , his wife reported the appearance of frequent nocturnal leg movements that were never previously observed . serum examination ( blood count , electrolytes , liver and renal function , thyroid hormones , and iron and ferritin levels ) was unremarkable . therefore , our patient underwent a full polysomnography ( psg ) that showed a severe plmd ( plmi : 62.7/h ) associated with high plm arousal index ( plmai : 11.9/h ) ; low sleep efficiency ; high sleep latency , wakefulness after sleep onset , and number of awakenings ; high percentage of light sleep ( n2 ) ; and low percentage of slow - wave sleep ( n3 ) ( see table 1 ) . periodic limb movements during sleep were strictly associated with periodic electroencephalographic arousals and cyclic alternating pattern ( cap ) . in particular , cap oscillations were triggered by plm with higher presence of cap subtypes a2 and a3 ( see fig . 1 ) . these cap subtypes represent an arousal phenomenon that likely leads to clinical correlates of disturbed sleep . therefore , because of the progressive impairment of insomnia and daytime dysfunction , tpm was slowly discontinued and switched to valproate up to 900 mg per day . during tpm discontinuation and after complete withdrawal , the patient underwent full psg ( tpm : 50 mg per day ) . periodic limb movement index and periodic limb movement arousal index showed a significant improvement and , after tpm discontinuation , reached a normal value ( plmi < 15/h ) . in addition , the cap rate exhibited a slight reduction , an increase of cap phase a1 and a parallel reduction of phases a2 and a3 . all psg data are summarized in table 1 . in order to evaluate the association between tpm and plmd , the naranjo probability scale documented a probable association ( naranjo score : 8/13 ) between plmd and tpm intake . this is the first publication , to our knowledge , to describe tpm - induced plmd in a patient affected by cryptogenic temporal lobe epilepsy previously not complaining of sleep disorders . although there is a high night - to - night variability of plmi in plmd / rls that may influence our results , this issue is still controversial , and the nocturnal pattern of plm occurrence was highly reliable across nights , suggesting that a single - night study may be sufficiently sensitive to confirm diagnosis and associated sleep disturbances . therefore , we can state that plmd was probably induced by tpm in our patient . in addition , rls and plmd pathophysiology is highly debated ; a common central dysregulation of dopaminergic system seems to be implicated . although such aeds may be effective treatments for rls and plmd , tpm - induced rls was previously described in a few cases , . topiramate enhances gaba function and inhibits ampa and kainate glutamate pathways , inducing an extracellular modulation of dopamine release in the mesocorticolimbic dopamine system . these experimental lines of evidence are confirmed by its efficacy against alcohol , nicotine , and cocaine addictions , . therefore , we can hypothesize that tpm may modulate the dopaminergic pathway , thereby inducing plmd in subjects with specific individual susceptibility . on the other hand , high levels of eeg arousals and/or cap sequences prior to leg movements confirm the presence of sleep impairment in these patients , . periodic limb movements are short movements that can be entrained by central pattern generators in reciprocal oscillatory coupling . specifically , cap phases a2 and a3 that represent arousal phenomena are more probably associated with disturbed sleep as also demonstrated polygraphically in our patient ( fig . 1 ) . the patients are typically not aware of these limb movements , but quality of sleep may be compromised , and the bed partners might recognize plms . even though the literature failed to document a clear correlation between plms severity and sleep disruption , haba - rubio et al . found a correlation between plms and tiredness , sleep efficiency , and psychological well - being . periodic limb movement disorder , insomnia , and diurnal symptoms promptly recovered after drug discontinuation in our patient suggesting a probable association with tpm . we are aware that , regarding the mutual interactions between sleep and epilepsy , not only sleep deprivation and daytime sleepiness but also abnormal sleep per se represent well - known potential triggers for seizures and are themselves influenced by epilepsy in a sort of reciprocal effect . notwithstanding , comorbidities and pharmacological treatment are other commonly accepted major factors that influence this interplay . therefore , an accurate clinical history and psg study in selected cases could be useful in order to recognize potential drug - induced sleep disorders . on behalf of all authors , the corresponding author states that there is no conflict of interest .

periodic limb movement disorder ( plmd ) is characterized by pathological periodic limb movements during sleep , insomnia and/or diurnal sleepiness , and the absence of another primary sleep disorder . we report a patient with complex partial seizures who developed plmd while taking topiramate ( tpm ) . he had no evidence of metabolic and/or other conditions inducing plmd . he also had fragmented sleep and disruptive plms on polysomnography , and plms subsided with change of antiepileptic drug . topiramate may modulate the dopaminergic pathway by inhibition of glutamate release , thereby inducing plmd as observed in our patient . although a single case does not allow any generalization , plmd should be considered in patients complaining of insomnia and treated with tpm .

renal cell carcinoma ( rcc ) can metastasize to any location in the body , and distant metastases are common , being present in 30% to 40% of patients with metastatic disease . the most common sites affected are the lungs ( 76% ) , regional lymph nodes ( ln ) ( 66% ) , bone ( 42% ) , and liver ( 41% ) . however , only 1.5 to 3.5% of rcc patients show solitary metastasis , and only 1% have metastasis confined to the head and neck . moreover , cases of metastatic rcc with a non - identifiable kidney mass are extremely rare . here , we report a case of metastatic rcc in only a supraclavicular ln with no evidence of a primary kidney lesion . a 69-year - old man presented with a 2-week history of a progressively enlarging supraclavicular mass in april 2009 . written consent was obtained from the patient for publication of the study . upon physical examination , his body temperature was 37.3 , blood pressure 130/90 mmhg , and pulse rate 75/min . a head and neck examination revealed a palpable firm , fixed , non - tender , 8 cm - sized mass in the right supraclavicular area with no other evident lymphadenopathy , and an abdominal examination revealed no palpable mass . his complete blood cell count , chemistry findings , and renal functionwere normal . urine dipstick and microscopy tests revealed no hematuria or abnormal cells . computed tomography ( ct ) of hematoxylin and eosin staining revealed that tumor cells were polygonal with clear cytoplasm and vesicular nuclei with prominent nucleoli ( fig . immunohistochemical staining showed that tumor cells were positive for pancytokeratin ( 1 : 300 , leica , newcastle upon tyne , uk ) , vimentin ( 1 : 200 , dako , glostrup , demark ) , and cd10 ( 1 : 100 , leica ) ( fig . 2b ) , but negative for thyroid transcription factor 1 ( 1 : 300 , leica ) , cytokeratin 7 ( 1 : 600 , neomarkers , fremont , ca ) , cytokeratin 20 ( 1 : 150 , dako ) and hepatocyte specific antigen ( 1 : 50 , leica ) . based on these findings , a diagnosis of metastatic clear cell rcc was made , after which the patient underwent abdominal / pelvic ct ( fig . 3b ) . the results revealed no tumor in either kidney , and no further metastatic lesions ; accordingly , he was diagnosed as having metastatic rcc in a supraclavicular ln only , without an identifiable kidney mass . the patient was initially treated with radiotherapy ( 4,000 cgy administered in 15 fractions over a period of 3 weeks ) , which induced tumor shrinkage , after which he was administered sunitinib ( 50 mg / day consecutively for four weeks followed by two weeks off per cycle ) . after two cycles , a follow - up ct scan revealed that the supraclavicular ln had markedly decreased in size ( fig . the acute toxicity ( grade 3 hand - foot syndrome , asthenia , and grade 2 thrombocytopenia ) led to dose reduction ( 25 mg / day consecutively for four weeks followed by two weeks off ) . after 20 months of sunitinib under the reduced dose , no tumor progression was observed . repeated follow - up abdominal / pelvic ct for 20 months has revealed no evidence of a primary renal tumor . the most common metastatic sites of rcc are the lungs , regional ln , bone , and liver , and it is uncommon for rcc to present a solitary metastasis at an unusual site . the mechanism of metastasis to unusual sites has not been clearly explained , but the mechanism of solitary metastasis of rcc to the head and neck region ( an unusual site ) is explained as follows . batson 's paraspinal plexus is a rich , valve - less venous anastomosis with prevertebral , vertebral , and epidural systems , and this rich venous system offers little resistance to the spread of tumor emboli . accordingly , the vertebral venous plexus offers a means of bypassing the pulmonary venous system and facilitates metastasis in the head and neck region without lung involvement . metastases that do not follow normal hematogenous flow patterns may also be explained by a right - to - left heart shunt , spontaneous regression of lung disease , or microscopic seeding of lung parenchyma . moreover , non - identifiable kidney lesions are extremely rare in metastatic rcc . in such cases , the disease presents as carcinoma of an unknown primary form with a clear cell neoplasm . however , diagnostic pathology has improved remarkably , and the routine use of electron microscopy and immunohistochemistry and the emerging field of molecular genetics are enabling more precise diagnoses . differential diagnoses in malignant neoplasms composed of clear cells include hepatocellular carcinoma , adrenal cortical carcinoma and clear rcc . hepatocellular carcinoma is positive for cytokeratin , epithelial membrane antigen ( epithelial markers ) , and hepatocyte specific antigen , but negative for vimentin , whereas adrenal cortical carcinoma is positive for vimentin , but negative for epithelial markers . rcc is positive for epithelial markers , vimentin , and cd10 , similar to the neoplastic cells in our case . a number of previous case reports have also described cases of metastatic clear cell renal carcinoma without a primary renal mass . in the case of metastatic rcc , no renal tumor was observed initially , but a renal tumor did appear after two years . bhatia et al . also reported a case of cutaneous facial rcc with no known primary tumor . it is not known why the primary lesion remains occult , but it may be involved or too small to be detected . nevertheless , these lesions could be silent renal tumors ; therefore , close monitoring is essential . as in our case , patients with single site involvement ( brain , liver , subcutaneous tissue , bone , intestine , ln , or others ) should be treated using aggressive local therapy such as resection , radiation therapy , or both , because a minority enjoy long - term , disease - free survival . in addition to definite local therapy , these patients should also receive systemic therapy based on one of the newer regimens because they seem to confer better survival . in our case of solitary metastasis in a supraclavicular ln , radiation therapy was applied and systemic therapy was performed with sunitinib , which is a standard treatment for metastatic rcc . as a result , the patient has been well for the last 20 months without disease progression . sunitinib is a multitargeting receptor tyrosine kinase inhibitor of vascular endothelial growth factor and of platelet - derived growth factor receptor . in a recent phase iii trial , progression - free survival was found to be longer and quality of life to be better for patients with metastatic rcc treated with sunitinib than for those treated with interferon- . not infrequently , clinicians and pathologists encounter malignant neoplasms composed of clear cells that have sources and natures that can not be determined by conventional morphological studies . therefore , immunocytochemical staining for cytokeratin , epithelial membrane antigen , vimentin , and fat are of considerable diagnostic help in rcc . this case report suggests that even in the absence of a primary kidney lesion , clinicians must consider the possibility of metastatic rcc when evaluating patients with clear cell carcinoma from an unknown primary site . furthermore , if only one metastatic site is present , a local modality such as surgical resection or radiotherapy should be applied , and if necessary , systemic treatment like sunitinib added .

although metastasis is relatively frequent in cases of renal cell carcinoma ( rcc ) , metastasis in the cervical or supraclavicular lymph node ( ln ) is relatively rare . moreover , cases of metastatic rcc with a non - identifiable kidney mass are extremely rare . here , the authors report a case of metastatic rcc in a supraclavicular ln without a primary kidney lesion . a 69-year - old man presented with a progressively enlarging right supraclavicular mass . incisional biopsy of the affected supraclavicular ln was performed , and histological examination revealed metastatic rcc . however , no tumor was found in either kidney , despite various examinations . the patient was treated with radiotherapy followed by sunitinib . after three months on sunitinib , a follow - up computed tomography scan revealed that the supraclavicular ln had markedly decreased , and after 20 months , the disease had not progressed . this case suggests that , even when there is no primary kidney lesion , clinicians must consider the possibility of metastatic rcc when evaluating patients with clear cell carcinoma with an unknown primary site .

over the last 20 years , a significant paradigm shift has occurred in the treatment of atherosclerotic arterial disease . endovascular interventions , including angioplasty and stenting , have become the first - line approach for the treatment of patients with simple and complex peripheral atherosclerotic lesions , including challenging - to - access iliac lesions . initially , treatment was aimed at angioplasty of focal short segment lesions ; however , as new stents and technical developments have been introduced , endovascular treatment has been expanded to include combined angioplasty and stenting of more complex , chronic lesions , with good long term results . the abbott absolute pro vascular self - expanding stent system ( abbott laboratories , abbott park , il , usa ) was created with the intent to improve upon previous stent designs and to have the ability to be utilized as a first - line endovascular treatment for both simple and complex iliac artery lesions . this review addresses the change in the endovascular treatment of iliac atherosclerotic disease , with a specific focus on the absolute pro s new stent design and clinical effectiveness . iliac artery atherosclerotic disease can greatly impact patients overall quality of life , limiting walking ability and leading to chronic pain and morbidity . conventional treatment has been limited to an open surgical approach , generally associated with long hospital stays and significant perioperative morbidity and mortality.1,2 however , due to superior outcomes , most of these patients now undergo primary endovascular treatment . as previously mentioned , initial interventions focused on primary angioplasty of focal iliac lesions , which was evaluated by becker et al.3 this group compiled the results of treatment with angioplasty alone reported in the literature , which showed an average technical success rate of 92% , a 2-year patency of 81% , and a 5-year patency of 72% . over time , with the development of superiorly designed devices , catheters , and wires , the results of angioplasty alone for iliac stenosis continued to show improved results in the literature . tegtmeyer et al4 followed becker s initial study with their own single - center series of 200 patients , in whom they found an initial technical success rate of 94.7% with angioplasty alone and a 7.5-year cumulative patency rate of 85% . in spite of these favorable results in the literature , high rates of restenosis continued to be prevalent in published studies , especially in lesions with eccentric , calcified , or ulcerated plaques as well as in lesions found in patients with multilevel disease . attention then turned to focus on evaluating primary stent placement verses primary angioplasty with selective stent placement . the dutch iliac stent trial4 was conducted for the purpose of addressing and evaluating which was the most effective treatment strategy . this study assigned 279 patients to undergo either primary stent placement or angioplasty with selective stent placement . the researchers found that selective stent placement led to better long - term preservation of symptomatic relief ; however , they found no difference in hemodynamic treatment outcome , iliac artery patency , or the quality of life between the groups . other studies that followed the dutch trial had results that showed a preference for primary stent placement , due to the reduced risk of vessel rupture and distal embolization as well as the superior long - term patency provided.57 proceeding forward , studies focused on the stent type as the limiting variable for interventional success . among the stents used , the palmaz balloon expandable stent ( johnson & johnson interventional systems , warren , nj , usa ) and the self - expandable wallstent venous endoprosthesis with unistep plus delivery system ( boston scientific corp , natick , ma , usa ) resulted in a 1-year primary patency of 87% and 78% , respectively , with secondary patency rates of 91% and 86% , respectively.8,9,10 primary patency , in these studies , appeared to be limited by intimal hyperplasia and progressive atherosclerotic disease as well as by technical limitations , including imprecise placement and difficulty with intra - arterial deployment of the stent in complex iliac lesions.11 other trials then looked at covered stents versus bare - metal stents , in the treatment of iliac disease . a multicenter , prospective , randomized , controlled trial was conducted by mwipatayi et al12 to evaluate covered balloon - expandable stents vs bare - metal stents , in the treatment of iliac artery atherosclerotic disease . this study involved 125 iliac artery lesions , with results showing no difference in transatlantic inter - society consensus ( tasc ) type b lesions ; however the researchers did find that covered stents had higher long - term patency rates in both tasc type c and d lesions.12 the major disadvantage in this study was that the covered stents that were used required larger delivery systems , exposing the patient to a higher risk of groin complications , including pseudo aneurysm and hematoma formation . in addition to covered stents , another alternative to balloon - expandable stents that was hypothesized to have superior long - term patency was the class of flexible self - expandable stents . self - expanding stents are often used for treatment in femoropopliteal disease , where stent fracture of the stiff balloon - expandable stents usually used in this area is an issue of major concern , leading to in - stent restenosis and reduced patency . higashiura et al13 chose to further investigate the prevalence of stent fractures in self - expanding stents used in iliac artery lesions and found these to be very rare in this location ( 5% in nitinol stents ) . their findings revealed that stent placement in chronically occluded lesions was a risk factor for stent fracture in iliac lesions ; although , compared with the occurrence in femoropopliteal lesions , fracture rarely negatively affected vessel patency . the effectiveness , safety , and patency of self - expanding nitinol stents , in particular , of the jostent selfx stent system ( abbott laboratories ) were also evaluated in an independent project by hamer et al.14 twenty - seven patients , with 34 lesions involving the common and external iliac arteries , were treated in their study . the inclusion criteria was defined as the presence of a clinically relevant stenosis in either the common or external iliac artery , with a lumen narrowing of > 50% , or a mean translesion pressure gradient of > 10 mm . measured results found immediate technical success rates of 94% , with 96% of patients reporting clinical improvement of at least one rutherford category14 after the initial procedure . at 6-month follow up , results showed 85% of patients presented with sustained improvement by at least one clinical category , and the primary patency was measured as 96% . this was comparable with the results of other self - expandable stents reported in the literature ; such as of the wallstent ( 93%97% ) , the cragg endopro system i stent ( 9498% ) ( mintec minimally invasive technologies sarl , la ciotat , france ) and the memotherm stent ( cr bard inc , covington , ga , usa ) ( 95%98%).1519 despite favorable results , a few disadvantages of the jostent selfx were noted by operators , including poor visibility of the stent during fluoroscopy , as well as the inability to correct stent localization after commencing the stent deployment . the reviewed literature shows that stent placement , whether primary or selective , is a valuable tool in the treatment of iliac atherosclerotic disease ; however , long - term results could still be improved by improved stent design and delivery.5,6,810,14,15,18 abbott s stent design for the absolute pro was aimed at overcoming some of the shortcomings in the design of previously available stent and deployment systems . the absolute pro , a self - expanding nitinol stent system , is made of a flexible material to allow the stent to conform to challenging and complex iliac lesions . its design also incorporates technology to enhance stent visibility , and a delivery system designed for minimal friction during stent deployment as well as for precision of stent placement , providing the user the ability to reposition or remove stent during initial deployment . this device is compatible with a small 6f sheath , with available stent diameters ranging from 610 mm and available length sizes between 20100 mm . the absolute pro received fda approval following the results of the mobility trial,20 a company - sponsored , nonrandomized , two - arm , multicenter study that evaluated the safety and effectiveness of the absolute pro and omnilink elite ( omnilink elite vascular balloon - expandable stent system ; abbott laboratories ) stents . in the absolute pro arm , all subjects enrolled had symptomatic peripheral arterial disease with 76% of lesions treated located in the common iliac artery , and 62.8% a total of 151 patients were enrolled in the absolute pro arm of the study . the primary endpoint evaluated was the occurrence of major adverse events at 9 months , defined as death , myocardial infarction , restenosis , need for open revascularization , or limb loss . the secondary endpoints included device , technical , and procedure success ( defined as achievement of successful delivery , deployment and removal of stent with final in - stent residual stenosis of less than 30% ) as well as improvement in ankle - brachial index ( abi ) , walking capacity , rutherford and becker clinical category . the study results showed the major adverse event rate of the absolute pro was 6.1% , well below the study s goal of 19.5% ( determined based on the existing literature and previous published studies ) . serious adverse events for the first 30 days after procedure , found dissection to be the most prevalent event at 2.6% . for events between 31 days and 326 days after procedure , the most prevalent events included restenosis ( 5.3% ) , other peripheral vascular disease , not otherwise specified ( 4% ) , and angina ( 3.3% ) . analysis of the secondary endpoints showed that 95.9% of lesions had a 9-month hemodynamic success ( defined as abi improvement greater then 0.1 compared with baseline or deterioration less then 0.14 compared with postprocedure values ) . restenosis , defined as greater then 50% stenosis , occurred in 13/151 ( 8.4% ) lesions . the study device success was found to be 96.4% , with seven device malfunctions among the 193 devices . the technical success , on a per lesion basis , was 87.3% , with no major adverse effects occurring through postprocedure day 2 . the overall procedure success was then measured to be 85.4%.20 following the mobility trial came a second study investigating the absolute pro stent , the bravissimo trial.21 this was a prospective , nonrandomized , multinational , multicenter , controlled trial centered in belgium and italy . the purpose of the bravissimo study was to validate both the omnilink elite and the self - expanding nitinol absolute pro stent in tasc type a and b lesions as well as to evaluate their expanded use in tasc type c and d iliac lesions . the primary endpoint in this study was primary patency at 12 moths , as determined by duplex ultrasound . there were a total of 325 patients enrolled into the study ; of these , 190 were in the tasc a / b group and 135 in the tasc c / d group . the baseline risk factors were comparable in all groups . in the tasc a / b group , 88% of patients were claudicants , with 12% found to have critical limb ischemia . in the tasc c / d group , 74% were claudicants , and 26% had critical limb ischemia . in the tasc a / b group , the 12-month primary patency was 97.1% for lesions treated with the absolute pro stent . in the tasc c / d group , the preliminary 12-month primary patency results show 95% primary patency for the absolute pro stent . these results support an endovascular - first approach for tasc a / b as well as for tasc c / d aortoiliac lesions . based on the preliminary industry - sponsored data , the absolute pro appears to be another good option for the treatment of both focal and complex iliac atherosclerotic lesions . the design is easy to use , allows for a low profile access system with good visualization on imaging , and has the ability to be repositioned qualities that show the benefit of improvements compared with other available models . also , the reviewed literature which demonstrates excellent long - term results for stents with similar designs as the absolute pro , shows strong support for the use of this new competitive product . irrespective of which stent model or device design is chosen , the endovascular treatment of iliac artery disease has emerged as the new standard of care and will continue to evolve with the advent of innovative devices and newly generated technologies .

management of iliac artery disease has evolved over the years , from a surgical - only approach to a primarily endovascular - only approach as the first line treatment option . this has been continuously improved upon with the advent of new devices and applied technologies . most recently in particular , the literature has shown good , reliable outcomes with the use of self - expandable stents in iliac artery atherosclerotic lesions . nevertheless , no device is without its limitations , and the absolute pro vascular self - expanding stent system was designed with the intent of overcoming some of the shortcomings of other available stents while maintaining acceptable postprocedural outcomes . based on preliminary industry - acquired data , it has achieved these goals and appears to be an emergent competitor for the treatment of both focal and complex iliac artery lesions .

the national tb prevalence survey in eritrea was conducted from february through october 2005 ( 6 ) . in 40 selected villages , a census ( which included information about sex and age ) was taken of 875 persons in each village . all persons > 15 years of age were asked to provide a morning and a spot sputum sample . persons who had 2 positive sputum samples were informed about the test results and referred for treatment . those who had 1 positive sputum sample were referred to a nearby healthcare facility for further smear examination . if results of smear examination were negative , thoracic radiographs were taken and evaluated by 2 experienced radiologists . the case definition for a sputum smear positive case was at least 2 sputum specimens positive for acid - fast bacilli by ziehl - neelsen staining and microscopy or at least 1 sputum specimen positive for acid - fast bacilli and radiographic abnormalities consistent with active pulmonary tb ( classification of the national tuberculosis control program in eritrea ) . using the prevalence estimate obtained from the survey and 2 different models , we calculated the cdr for 2004 . in model 1 , described by styblo , cdr = ( notification rate / prevalence rate ) / ( 0.5 + 0.83 [ notification rate / prevalence rate ] ) ( 7,8 ) . in model 2 , described by dye et al . , cdr = ( notification rate / prevalence rate ) / ( [ notification rate / prevalence rate ] + 0.5 ) ( 9,10 ) . we then compared the calculated cdr with the cdr estimated by the world health organization ( who ) to evaluate whether comparable conclusions about tb case detection would be obtained . a total of 38,047 persons were included in the prevalence survey . of those > 15 years of age , 18,152 ( 94.6% ) provided at least 1 sputum sample ( figure ) . the prevalence of new smear - positive tb was estimated at 90/100,000 ( 95% confidence interval [ ci ] 35145/100,000 ) in persons > 15 years of age . in 2005 , 44.7% of the eritrean population was < 15 years of age ( 11 ) , which resulted in an overall new smear - positive tb prevalence of 50/100,000 ( 95% ci 1980/100,000 ) under the assumption of no cases in persons < 15 years of age . summary of tuberculosis prevalence survey in eritrea , 2005 . in 2004 , 17/100,000 new smear - positive cases were reported ( 2 ) . for eritrea , the cdr provided by who is considerably lower than that calculated from the results of the national tb prevalence survey . both estimates indicate that eritrea has not reached the 70% target for case detection . however , the who estimate suggests that the program needs to improve case detection by a factor of 5 , whereas the survey estimate suggests that case detection needs to be improved by a factor of 1.6 . two explanations may account for the large difference : 1 ) the cdr derived from the tb prevalence survey is too high because of an underestimation of the prevalence of smear - positive tb , or 2 ) the cdr estimate published by who is too low because of an overestimation of the incidence of smear - positive tb . in the national tb prevalence survey , measures were taken to ensure high quality of the results ; e.g. , training of data collectors , repeat census taking , reexamination of all slides found positive on fluorescence microscopy , and reexamination of a 5% random sample of the negative slides . persons who had smear - positive tb may have been missed because they did not provide a specimen ; however , because only 5% of eligible persons did not provide a specimen , this can explain only a slight underestimation . furthermore , recorded reasons for not providing a specimen seem to be unrelated to a higher chance of having tb . the quality of the provided specimens may have been suboptimal because instructing and motivating persons to provide a sputum sample is challenging . for diagnosis of tb , microscopic examination of saliva is less sensitive than examination of sputum ; however , in 50% of saliva samples from patients with a positive sputum sample , bacilli can be demonstrated ( 12,13 ) . for 27,647 samples that appeared to be saliva , smear assuming that only 50% were detected , a maximum of 12 smear - positive tb patients may have been undetected . taking this into account results in a prevalence of 87/100,000 . using this estimate , model 1 provides a cdr of 30% and model 2 a cdr of 28% the possibility that persons who provided a saliva sample were not able to produce a sputum sample because they did not have pathologic pulmonary changes should also be taken into consideration . estimation of the incidence of smear - positive tb in eritrea is complicated by the fact that no data from tuberculin or prevalence surveys were available . the only data available for eritrea were reporting data , which experts assessed as being of low quality ( 14 ) . use of this limited information will result in an uncertain incidence estimate , which may result in an unreliable cdr . for most countries in africa , little information is available for estimating the prevalence of disease and progress towards the millennium development goals ( http://unstats.un.org/unsd/mi/mi_goals.asp , accessed 2006 aug 30 ) . on the basis of case reporting , tb was rightly declared an emergency by african health ministers at the who africa regional committee in maputo in 2005 ( 15 ) . to be able to fight this emergency , more reliable information about the prevalence of tb in africa is needed . furthermore , for global tb control , reliable information about the tb epidemic in africa is needed because 28% of the incident smear - positive cases occurred in the who african region in 2004 ( 2 ) . in conclusion , the example of eritrea shows that a large gap may exist between available estimates of tb prevalence and actual tb prevalence in africa . national tb prevalence surveys in africa would help provide better information on tb prevalence and case detection .

we used results from a national tuberculosis prevalence survey in eritrea to calculate case detection rate ( cdr ) and compared it with the published cdr . the cdr obtained from the survey was 40% , whereas the cdr published by the world health organization was 3 lower ( 14% ) .

the reca gene was first identified in escherichia coli more than 40 years ago , and hundreds ( if not thousands ) of papers have shown this gene to be centrally important to both the recombination and repair of dna . while genetic recombination helps create genetic diversity and therefore increases the fitness of a population , pathways for genetic recombination appear to have arisen as a mechanism for the repair of dna , using an identical or homologous stretch of one dna molecule to repair a second dna molecule that has been damaged . the reca protein is produced quite copiously in bacteria after massive dna damage and actually can be the single most abundant protein in the cell . in addition , pure reca protein in vitro can catalyze a remarkable reaction in which two dna molecules exchange a strand . these reactions have served as models for the action of rad51 , the eukaryotic homolog of reca . the active forms of both reca and rad51 are helical protein polymers formed on dna , and this has made many high - resolution structural studies difficult or impossible . electron microscopic and topological studies had shown that reca has a profound effect on dna structure when it binds : the dna is stretched by ~50% , and the dna is untwisted by almost a factor of two , from ~10 to ~19 base pairs per turn . since the human rad51 protein has been shown to induce similar changes in dna , it is reasonable to believe that this unusual dna structure is important for the mechanism of genetic recombination . a crystal structure of reca protein had been solved many years ago , but based upon electron microscope observations , the filament within the crystal appeared to be in a compressed inactive conformation . furthermore , the crystal did not contain dna , so it provided few clues about how reca induced this unusual dna conformation . modeling studies for stretched dna have been attempted , but these are relatively unconstrained by detailed experimental observations . a very challenging study using nuclear magnetic resonance ( nmr ) was undertaken to look at oligonucleotides complexed with reca , but the interpretation of those results appears to have depended upon the assumption that the structure is actually uniform , with every base in the same conformation . a new crystal structure of a complex between reca and dna has been solved , and one of the most surprising observations is that there is no uniform stretched dna structure . three bases adopt a fairly b - like conformation ( figure 1 ) , with stacking of the bases to exclude solvent within these triplets , and then there is a very large stretch and a left - handed twist to reach the next set of triplets . the left - handed twists interspersed between the triplets in right - handed b - like conformations account for the global untwisting that has been measured , whereas the stretching of ~7.8 between triplets accounts for the global average of ~5.1 rise per base or base pair ( from ~3.4 per base pair in b - dna ) . in addition to giving us the first high - resolution picture of this unusual dna conformation ( and one that is likely to be conserved from bacteria to humans ) , the crystal structure is a technical tour de force . the problem with many helical polymers is that , unless there are exactly two , three , four , or six units per turn , the polymer can not be crystallized so that every subunit is in an identical environment . polymerization can also be competing with crystallization , so that under the conditions of high protein concentrations needed for crystallization many polymeric proteins will polymerize . pavletich and colleagues solved this problem for reca by engineering a reca polyprotein containing four , five , or six copies of reca linked together , with the ends modified to prevent polymerization . the new crystal structure also shows that reca subunits have the ability to rotate in the filament from the position seen in the first crystal filament , consistent with predictions made using both electron microscopy and spectroscopy . the subunits of the active filament are bound to atp , whose hydrolysis releases the dna from the filaments . this rotation brings atp molecules bound to one subunit into a cleft between adjacent subunits where they can be hydrolyzed . three bases are stacked and have a b - like twist but are separated from adjacent triplets by regions of left - handed twist and extreme stretching . this conformation appears to be the basis of a search for homology with a second dna molecule that will locally have a b - like conformation . although the new crystal structure provides a major advance in understanding how reca - like proteins function , many questions still remain . however , these questions now can be examined in a framework that is very different from the one that has existed previously . it has been known that a second dna molecule can be untwisted by the complex of reca bound to a first dna molecule , but the new crystal structures do not provide direct information about how dna is untwisted at this second binding site . models can be built , and the new framework provides many constraints that will aid in designing experimental tests . all of this will advance our understanding of how the fundamental biological process of homologous genetic recombination takes place , and will undoubtedly have an impact on human health as well . diseases like cancer can be caused by defects in the repair of damaged dna , so a molecular understanding of how proteins such as human rad51 act in the repair of dna will be crucial for many advances .

the reca protein has been the most intensively studied protein involved in homologous genetic recombination , but until recently very little has been known about the molecular details of how reca can bring two dna molecules into juxtaposition and switch strands between them . a recent reca - dna crystal structure provides some striking new insights .

rheumatoid arthritis ( ra ) and other connective tissue disorders are frequently associated with certain types of corneal or / and scleral pathology such as peripheral ulcerative keratitis , dry eye syndrome , and scleritis . it is also known that these conditions may lead to perforation of the eye by compromising the integrity of its outermost layers . keratoconus ( kc ) is generally regarded as an isolated condition with no apparent ophthalmic or systemic associations at the time of diagnosis . however , elevated levels of corneal proinflammatory cytokines such as interleukin ( il)-1 have been linked to corneal thinning , implying the involvement of the immune system in the pathogenesis of kc . only a small number of autoimmune diseases ( e.g. , ra , asthma , inflammatory bowel disease ) have been related to kc , while others have not ( e.g. , systemic lupus , crohn s disease , myasthenia gravis , and multiple sclerosis ) . cell - mediated mechanisms are suggested to play a pivotal role in the pathogenesis of ectatic corneal disorders and kc itself . further , confocal microscopy has revealed that in patients with ra , the central corneal and stromal thicknesses are significantly lower compared with controls , and these patients have significantly higher numbers of hyperreflective stromal cells . the activation of these keratocytes is mediated by proinflammatory cytokines , such as il-1 and il-6 . we report a case of paracentral corneal perforation in a patient with keratoconus and a previously undiagnosed connective tissue disorder . a 53-year - old man presented in the emergency room complaining of severe ocular pain with sudden onset and a significant decrease in visual acuity in his left eye . regarding his ocular history , the patient noted that his ophthalmologist had been modifying his spectacle prescription annually over the last 13 years because of the increasing myopic shift . the patient reported no systemic drug intake except for analgesics for constant lumbar back pain . the patient s best corrected visual acuity was measured cf at 10 cm for the left and 20/60 for his right eye . his spectacle prescription at the time of the examination was : 1.00/5.5 100 os and 4.5/4.5 70 od . slit lamp biomicroscopy revealed a paracentral corneal perforation , 1 2 mm , accompanied by iris prolapse , corneal thinning , and a markedly shallow anterior chamber in the left eye . the right eye displayed clinical features of moderate keratoconus , which was confirmed by corneal topography ( magellan mapper , nidek ; figs . 1 and 2).fig . steep corneal curvature on biomicroscopy raised suspicions of a coexistent keratoconus topography image demonstrating significant keratoconus on the right eye the patient was immediately prepared for surgical intervention in order to preserve the integrity of the affected eye . amniotic membrane ( am ) was primarily available and transplanted in an attempt to seal the perforation and promote corneal healing ( fig . cryopreserved am was attached over the perforation in multiple layers and covered with an epithelial - side - up , limbal - sutured sheet . the surgical technique involved scraping of residual corneal epithelium and 360 limbal peritomy of the conjunctiva prior to am transplantation . the outermost of the multiple layers was sutured with 8/0 vicryl on the cornea whereas the overlaid transplant was sutured at the limbus with a running 10/0 nylon . a bandage contact lens was applied at the end of the operation in order to promote reepithelialization of am and to prevent mechanical rubbing of the transplant on blinking.fig . 3photo of left eye on second post - op day after amniotic membrane transplantation in multiple layers in an attempt to maintain the eye s anatomical integrity photo of left eye on second post - op day after amniotic membrane transplantation in multiple layers in an attempt to maintain the eye s anatomical integrity further blood tests revealed a significantly elevated rheumatoid factor at 2,170 iu / ml ( reference value < 20 iu / ml ) . specific blood tests in addition to detailed clinical examination carried out by an orthopedic surgeon and immunologist confirmed the diagnosis of ra , and the patient was referred to rheumatologists for further assessment . the operated on eye displayed a well - formed anterior chamber , without any leakage , over the 3 post - op weeks . visual acuity was slightly improved to cf at 50 cm . however , reepithelialization failed to cover am completely whilst subsequent tissue thinning resulted in re - leakage at week 4 postoperatively . one month after corneal grafting and while on systemic immunosuppressants , the patient developed endophthalmitis with unfavorable outcome . kc is a noninflammatory corneal disorder in which stromal thinning and ectasia result in an atypical corneal shape . although the etiology is not completely understood , there is evidence suggesting that kc probably represents a multifactorial process . kc with acute hydrops can be complicated with spontaneous corneal perforation ; however , this has been reported mainly in cases with advanced kc . nevertheless , spontaneous perforation in mild to moderate kc cases has also been reported recently . ophthalmic involvement in autoimmune disorders such as ra , systemic lupus erythematosus , and sjgren syndrome has been extensively described . however , many patients experience ocular sequelae during the course of undiagnosed immunological disorders . reduced tear secretion , chronic inflammation of the ocular surface , as well as ultrastructural abnormalities are believed to play a major part in decompensating the ocular surface . this condition may lead to spontaneous perforation in sporadic cases . in our case , am transplantation was used as a first - line solution since previous studies showed that urgent penetrating keratoplasties in perforated eyes displayed higher rates of graft failure compared to those performed several weeks to months following the perforation [ 10 , 11 ] . multilayer am transplantation has been reported to promote epithelial healing and reduce inflammation , neovascularization , and scarring in a diversity of external eye disorders . am - related local anti - inflammatory effects contribute to faster and more efficient reepithelialization . furthermore , am serves as a biological scaffolding in cases where normal tissue is lost and promotes reinforcement or even sealing of small perforations . am has been used in patients with ra - related epithelial defects as a temporizing solution with the aim for delayed reconstruction . however , as solomon and colleagues reported , am transplantation showed poorer outcomes in patients with systemically undertreated ra compared to other autoimmune conditions like ocular pemphigoid or even sjogren s . other authors have proposed cyanoacrylate and fibrin glue adhesives as an efficacious solution in cases where corneal perforations occur [ 13 , 14 ] . in our case , am transplantation was preferred over other treatment modalities mainly due to severe inflammation of the ocular surface and the small size of the perforation . besides , the diagnosis of ra had not yet been established . furthermore , penetrating keratoplasty does not represent a first - choice operation in our country due to the relatively restricted number of centers authorized to perform corneal transplantations and to limited availability of corneal grafts . in our patient , although the am transplant initially provided a sufficient corneal sealing , it failed as a long - term solution due to poor reepithelialization and the progressive tissue degradation . recurrent aqueous humor leak necessitated an emergent penetrating keratoplasty , which took place in another center . there are quite a few studies that extensively describe the relationship between ra and ocular surface disorders that may permanently affect vision [ 15 , 16 ] . kc is another thoroughly studied condition that , apart from major refractive alterations , may occasionally cause corneal perforation when undiagnosed or / and untreated . to the best of our knowledge , this is the first report of a case with corneal perforation arising from coexistent kc and ra . it seems possible that the impact of these conditions is more severe when they interact . we should therefore raise awareness and either rule out or efficiently treat underlying connective tissue disorders in patients with kc . this article is distributed under the terms of the creative commons attribution license which permits any use , distribution and reproduction in any medium , provided the original author(s ) and source are credited .

purposethe purpose of this study is to report a case of corneal perforation in a patient with undiagnosed keratoconus and underlying rheumatoid arthritis.methodsthis is a retrospective case study based on the patient s medical records and followed by a brief review of the literature.resultsa 53-year - old patient was referred to our department for acute pain and sudden decrease of visual acuity in his left eye . corneal perforation was detected and attributed to a previously undiagnosed and untreated keratoconus . additional laboratory work - up and clinical examination revealed a coexisting rheumatoid arthritis . amniotic membrane was originally transplanted in order to maintain the structural integrity and promote healing of the perforated eye . subsequently , the patient underwent a penetrating keratoplasty , though with unfavorable results due to postoperative endophthalmitis.conclusionsrheumatoid arthritis may be associated with higher risk of corneal perforation in patients with ectatic degenerative diseases such as keratoconus .

whole disc organ culture is needed for preclinical testing of biological repair of the degenerate intervertebral disc . such organ culture is hampered by two major limitations : first , obtaining adequate nutrition through the calcified cartilage end plates and adjacent vertebral bone ; second , by loss of tissue integrity if the end plates are removed from the discs . in this work we use a bioreactor and a recently described technique for whole disc isolation that overcomes these problems six bovine caudal discs were isolated by parallel bone cuts close to the cartilage end plates , and the bone and the adjacent calcified part of the cartilaginous end plate was removed ( cep discs ) . it consists of a culture chamber in which the disc can be dynamically loaded in a uniform manner . the discs are loaded in the culture chamber by upper and lower platens , which conform to the shape of the remaining cartilaginous end plate and permit fluid flow across its surface . load displacement behavior was monitored throughout the culturing period for five discs because of exclusion of one contaminated disc . cell viability was evaluated on termination of the experiment in a 1 mm slice through the center of the disc , visualized using a live / dead fluorescence assay ( live / dead , invitrogen ) and confocal microscopy . we have to date cultured bovine discs for 4 weeks under cyclic physiological loading , with maintained cell viability . the morphological changes for the discs are the following : on average the discs decreased 7.7% in height , increased 5.9% in diameter , and increased 2.5% in weight compared with the time of isolation . the proportion of live - to - dead cells was analyzed in the center of np and af . a viability of 88.4% 3.9 was observed in the np and 80.8% 8.9 in the af after a total of 4 weeks in culture . using a novel disc preparation and isolation method along with an axially loading bioreactor , we were able to culture bovine caudal discs for a total of 28 days . the bioreactor culture system is ideally situated for studying intervertebral discs in an in situ environment . the culture system also provides an experimental platform where numerous parameters can be evaluated , eg , o2 tension , glucose levels , and the effect of growth factors . as such , it is equally useful for studying the role of load in inducing disc degeneration or the role of biological stimuli in restoring disc function . the three bioreactor units that form the bioreactor system ; a e , loading unit ; f k , culture chamber unit .

selected abstracts delivered at the 9th annual aospine north america fellows forumconsistent with ebsj 's commitment to fostering quality research , we are pleased to feature some of the most highly rated abstracts from the 9th annual aospine north america fellows forum in banff , canada . enhancing the quality of evidence in spine care means acknowledging and supporting the efforts of young researchers within our aospine north america network . we look forward to seeing more from these promising researchers in the future .

the brachial plexus supplies the upper extremity and is formed by the fusion of the anterior primary rami of the cervical ( c5 - 8 ) and the first thoracic ( t1 ) spinal nerves . the five roots fuse to form three trunks which further branch into anterior and posterior divisions behind the clavicle . these divisions reunite to form the medial , lateral , and posterior cords arranged around the axillary artery . the medial pectoral nerve ( mpn ) arises from the medial cord ( c8 , t1 ) , usually pierces and supplies the pectoralis minor ( pmi ) . a few branches of mpn also supply pectoralis major ( pmj ) . the lateral pectoral nerve ( lpn ) carries fibers from c5 - 7 to supply the pmj . lpn communicates with the mpn to form a loop - the ansa pectoralis ( ap ) , in front of the thoracoacromial artery ( taa ) and hence lpn also supplies the pmi . thus , pectoral muscles are normally supplied by lpn , mpn , and sometimes terminal branches from ap ( superior , middle , and inferior pectoral nerves ) may also innervate these muscles . though some researchers have reported the ap to be absent , others have reported a 100% incidence in their studies . if ap is present , it connects mpn with the lpn in front of the first or second part of axillary artery ; however , it is mostly distal to the lateral thoracic artery ( lta ) . loukas et al . in 28% specimens found the ap directly connecting the lpn and mpn . the mpn may be connected to the anterior divisions of the upper trunk ( 5% ) , middle trunk ( 25% ) or to the deep branch of the lpn ( 42% ) . such anatomical variability in the formation of the ap are not known to affect the limb functions , but knowledge of such variations are essential in the evaluation of unexplained sensory and motor loss after trauma and surgical explorations . during routine dissection of an embalmed 70-year - old male cadaver , a variant pattern of the brachial plexus was encountered in the left side . the skin and subcutaneous tissue were dissected off , and the exposed pectoral muscles were reflected toward their insertion . branches of the axillary artery were inspected and later trimmed for better visualization of the cords . the lpn arose by a single root from the lateral cord , just distal to the origin of the taa , and measured 2.8 cm in length . the mpn originated from the medial cord just distal to the lta and was 3.3 cm in length . lpn and mpn united to form a loop - the ap , anterior to the second part of the axillary artery . this conjoint nerve trunk pierced the deep surface of pmi to supply it ; thereafter it branched and supplied the pmj [ figure 1 ] . concurrently , in the brachial plexus , a nerve communication ( nc ) existed between the lateral cord and the medial root of median nerve ( mrm ) . this further communicated ( c ) with the conjoint trunk from the ap [ figure 2 ] . thereafter the fibers of mrm and the lateral root of median nerve ( lrm ) united at the junction of upper and middle one - third of the arm to form the median nerve ( mn ) . nerve communication ( nc ) - between the medial root of median nerve ( mrm and lateral cord ( lc ) ; communication ( c ) - between ansa pectoralis ( ap ) and nerve communication ( mc : medial cord : mpn : medial pectoral nerve , lpn : lateral pectoral nerves , lrm : lateral root of median nerve , aa : axillary artery , cb : coracobrachialis , mcn : musculocutaneous nerve , un : ulnar nerve ) diagrammatic representation of the dissection highlighting the nerve communication ( nc ) receiving a twig from the conjoint trunk ( c ) of ansa pectoralis ( mc : medial cord , mpn : medial pectoral nerve , lpn : lateral pectoral nerve , lrm : lateral root of median nerve , aa : axillary artery , cb : coracobrachialis , mcn : musculocutaneous nerve , un : ulnar nerve ) the right side brachial plexus was found to be normal . we describe a rare variant , wherein the entire lpn and mpn initially united to form the ap , which solely supplied the pectoral muscles through a common trunk . we observed lpn to emerge from the lateral cord by a single root lateral to the second part of the axillary artery . lpn may arise by a single root from the lateral cord or by two to three roots from the anterior divisions of upper and middle trunks . mpn branched off the medial cord , arising just distal to the lta by a single root . the mpn may arise from the medial cord ( 25% - loukas et al . ; 49.3% - porzionato et al . ) or from the anterior division of the lower trunk ( 43.8% - porzionato et al . ; certain authors have observed ap to have 100% incidence in their studies while others have found it to be absent . in the present report , the mpn and lpn communicated in front of the second part of axillary artery to form the ap . a single nerve trunk originated from the ap to supply the pectoral muscles and also communicated with the mn . afshar and golalipour observed a similar single nerve trunk from the ap , but it supplied the muscular axillary arch of latissimus dorsi . gupta et al . also reported a loop communication between mpn and lpn with a pseudoganglion like thickening . variations of the brachial plexus may arise due to alterations in the migration of muscles derived from somites into the early upper limb mesenchymal primordium leading to modifications of the primitive segmental arrangement of nerves . the anomalous innervation of the pectorals becomes particularly important while performing an axillary breast augmentation , wherein an implant is placed between the pectorals or during lymph node dissection procedures , though injury to few of the nerve branches of either pectorals usually leads to little consequence . the pectoralis muscle island flaps are used for head , neck , and axillary reconstructive surgeries and currently neuromuscular blockade of pectoral muscles is being employed for pain relief by decreasing the muscle tone in orthopedic procedures such as shoulder dislocation . such surgical procedures may be tricky in cases like ours , as an inadvertent sacrifice of the nerve by an unaware surgeon would lead to atrophy of both muscles because of a common nerve supply . in the brachial plexus , mn formation has been frequently reported to be variable with communications with other nerves being common . in our present study , this communication also received fibers from ap , which were probably destined to form the mn and hitch - hiked through one of the pectoral nerves to reach it . injury to such rare communications of the brachial plexus could result in an unexplained atrophy of the pectorals and/or unexplained loss of power in few muscles supplied by mn .

the knowledge of innervation of pectoral muscles is important to surgeons performing breast surgeries , axillary lymph node dissection , harvesting pectoralis major / minor for flaps , and during neurotization procedures where the pectoral nerves are particularly at risk . the present case describes the innervation of the pectoral muscles solely by a nerve trunk arising from the ansa pectoralis ( ap ) - the loop of medial and lateral pectoral nerves . interestingly , there was also a communication between the ap and roots forming the median nerve . it is imperative for the operating surgeons to be aware of these rare variations in order to prevent denervation and subsequent atrophy of the pectoral musculature .