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[ "most commonly affects people of african descent . in nigeria , sickle cell anaemia affects about 1 - 3% of the nigerian population . couples at risk for the transmission of genetic diseases can now choose ivf and pgd to avoid the problem of selective abortion that is associated with pre - natal diagnosis during pregnancy . rapid dna analysis methods have become available , and these techniques are now widely used for prenatal diagnosis.910111213 pre - implantation genetic diagnosis ( pgd ) is a procedure that has emerged against the backdrop of in vitro fertilisation ( ivf ) technology . in nigeria , this process of ivf was first introduced by ashiru et al.14 following their pioneering work , we were able to advance this technique for patients with infertility,1516 and now for patients with advanced maternal age and sickle cell disorders with the use of pgd . the average life expectancy for people with sickle cell anaemia is less than 50 years . the most common form of pgd involves the extraction of one or two cells from the pre - implantation embryo , often around the 8-cell stage .", "results provided after 48 hours showed that 5 ( 33% ) of the biopsied cells were of genotypes unaffected by sickle cell anemia ; of these , three were heterozygous carriers of hb s ( as ) and two were homozygous for hba ( aa ) . couple already have a 2-year - old child who is affected with sickle cell anaemia . the patient was a 29-year - old woman and spouse with heterozygous genotype ( as ) . a single blastomere was biopsied for embryos at 6 - 8 cell stage with less than 50% fragmentation [ figures 1 and 2 ] . blastomere showing nucleus fifteen biopsied cells were sent for genetic screening and analysed using pgd / pcr technique [ figure 3 ] . oocytes with 2pn were assessed on day 2 after injection for embryonic development . on day 3 , the protocol was also approved by the research and ethics committee of the centre . following 3 weeks of oral contraceptive use , the patient was down - regulated using a gnrhanalog ( leuprolide ) .", "three unaffected embryos ( two heterozygous normal and one homozygous ) were transferred on day 5 at blastocyst stage . endometrial lining was prepared for fet using increasing doses of estradiolvalerate from 2 mg daily up to 8 mg with weekly monitoring of the endometrium . two vitrified normal embryos ( one hbas and one hbaa ) were thawed both at hatched blastocyst stage and transferred [ figure 4 ] .", "the advent of ivf as a treatment for infertility has created the opportunity to study the chromosomal constitution of surplus human pre - implantation embryos . our results demonstrate that pgd for the detection of sickle cell anaemia is a powerful diagnostic tool for carrier couples who desire a healthy child but wish to avoid the difficult decision of whether to abort an affected foetus . , this is the first unaffected pregnancy and delivery after successful pgd for sickle cell anaemia . , the only alternative for couples with a high genetic risk was to undergo prenatal diagnosis followed by termination of an affected pregnancy ." ]
a couple , both carriers of the sickle cell anaemia trait ( genotype hbas ) with an offspring already affected with the genetic disease underwent a pre - implantation genetic diagnosis / polymerase chain reaction screening of biopsied blastomeres . dna analysis of single blastomeres was carried out to find out indicated a viable intra - uterine pregnancy with embryos which carried the sickle cell mutation , which resulted in a livebirth ( hbas ) . pgd / pcr in combination with ivf appears to be the most suitable treatment plan for patients who are at a higher risk of reproducing offspring affected with inheritable genetic diseases .
[ "we previously reported pulse rate - associated loci from the korea association resource ( kare ) genomewide association study ( gwas ) , comprising 8,842 samples in the korean population . in this study , we extended the previous study and reexamined the relevance of pulse rate - associated single - nucleotide polymorphisms ( snps ) from an additional gwas of 3,703 korean samples . however , few genes are known to be associated with pulse rate , and the underlying mechanism for pulse rate remains unraveled . high pulse rate is negatively correlated with lifespan in mammals , including humans . despite the importance of pulse rate as a risk factor for various diseases , since various health - related phenotypes are closely correlated with pulse rate [ 1 - 3 ] , measuring pulse rate is commonly used for diagnosing and accessing medical conditions . metabolic syndrome is associated with poor exercise capacity and poor heart rate recovery in patients who have coronary disease . moreover , pulse rate is known to be positively correlated with triglycerides and negatively correlated with high - density lipoprotein cholesterol .", "the methods for genotyping and quality control for the kare gwas have been described elsewhere . for the hexa gwas , in the discovery stage , the association results for pulse rate were obtained from the kare study . pulse rate of kare was measured 3 times while the participant was lying down , and the average value was used for the analysis ( before the first measurement , participants rested for 5 min , and 3 measurements were taken at least 30 s apart ) . in hexa - shared cohorts , the first measurement of the participants , who rested for 5 min , santa clara , ca , usa ) . from 4,302 genotyped samples , we excluded samples with a low call rate ( 95% , n = 443 ) , high heterozygosity ( n = 25 ) , outliers ( n = 26 ) , and gender inconsistencies ( n = 8) , and those obtained from individuals who had developed any kind of cancer ( n = 61 ) were excluded from subsequent analyses , along with related or identical individuals whose computed average pairwise identity - by - state value was higher than that estimated from cryptic first - degree relatives of samples ( n = 33 ) . snp markers with a high missing genotype rate ( > 5% ) , minor allele frequency ( maf ) ( < 0.01 ) , and significant deviation from hardy - weinberg equilibrium ( p < 1 10 ) were excluded , leaving a total of 627,659 markers to be examined in 3,703 individuals . the snp association for pulse rate was tested by linear regression analysis with an additive model , adjusting for age , sex , and recruitment area . genomic dna was extracted from 4,302 participants from an urban cohort and genotyped with affymetrix genome - wide human snp array 6.0 ( affymetrix , inc . ,", "in the discovery stage , the association results for pulse rate were obtained from the kare study . the standardized examinations that were applied in this survey included 4,302 participants aged 40 to 70 years . subjects for the replication stage were recruited from the health examinee cohorts , called hexa - shared cohorts .", "pulse rate of kare was measured 3 times while the participant was lying down , and the average value was used for the analysis ( before the first measurement , participants rested for 5 min , and 3 measurements were taken at least 30 s apart ) . in hexa - shared cohorts , the first measurement of the participants , who rested for 5 min , was used .", ", we excluded samples with a low call rate ( 95% , n = 443 ) , high heterozygosity ( n = 25 ) , outliers ( n = 26 ) , and gender inconsistencies ( n = 8) , and those obtained from individuals who had developed any kind of cancer ( n = 61 ) were excluded from subsequent analyses , along with related or identical individuals whose computed average pairwise identity - by - state value was higher than that estimated from cryptic first - degree relatives of samples ( n = 33 ) . snp markers with a high missing genotype rate ( > 5% ) , minor allele frequency ( maf ) ( < 0.01 ) , and significant deviation from hardy - weinberg equilibrium ( p < 1 10 ) were excluded , leaving a total of 627,659 markers to be examined in 3,703 individuals . the methods for genotyping and quality control for the kare gwas have been described elsewhere . for the hexa gwas , genomic dna was extracted from 4,302 participants from an urban cohort and genotyped with affymetrix genome - wide human snp array 6.0 ( affymetrix , inc . ,", "the snp association for pulse rate was tested by linear regression analysis with an additive model , adjusting for age , sex , and recruitment area . the kare gwas and replication gwas were combined by an inverse - variance meta - analysis method , assuming fixed effects , with cochran 's q test used to assess between - study heterogeneity . meta - analysis calculations were performed using metal ( http://www.sph.umich.edu/csg/abecasis/metal ) in the r program ( version 2.7.1 ) .", "the discovery gwas for pulse rate included 352,225 snps profiled with affymetrix genome - wide human snp array 5.0 in 8,842 individuals from the ansung and ansan cohorts as described previously . the association analysis identified several genomic locations as potentially associated with pulse rate . unlike the previous gwas , we did not apply a threshold with a p < 0.01 in both ansung and ansan cohort in addition to a combined p < 1 10 for the snp selection for the replication study so that we could include more promising snps for their association with pulse rate . were finally chosen to validate in the independent population - i.e. , the hexa cohort , comprising 3,703 individuals . in the replication study , thus , fine mapping surrounding this locus by targeted resequencing is highly recommended to discover the causal variants for pulse rate .", "in this study , we performed a genomewide scan for pulse rate and identified 3 loci accounting for the variation in pulse rate . our study was relatively underpowered to discover additional novel loci and demonstrated that large - scale genomewide meta - analysis comprising hundreds of thousands samples is required for understanding the missing heritability of pulse rate . two of 3 loci were previously reported and replicated once again in an independent hexa - shared cohort . however , no dramatic decrease in statistical significance was observed , and no interaction was found between rs2892767 and rs12110693 ( table 3 ) . we performed multiple linear regression analyses , conditioning the snps to each other to find a significantly stronger proxy for pulse rate ." ]
pulse rate is known to be related to diverse phenotypes , such as cardiovascular diseases , lifespan , arrhythmia , hypertension , lipids , diabetes , and menopause . we have reported two genomewide significant genetic loci responsible for the variation in pulse rate as a part of the korea association resource ( kare ) project , the genomewide association study ( gwas ) that was conducted with 352,228 single nucleoride polymorphisms typed in 8,842 subjects in the korean population . gja1 was implied as a functionally causal gene for pulse rate from the kare study , but lacked evidence of replication . to re - evaluate the association of a locus near gja1 with pulse rate , we looked up this signal in another gwas conducted in a health examinee - shared cohort of 3,703 samples . not only we were able to confirm two pulse rate loci ( 1q32.2a near cd46 and 6q22.13c near locl644502 ) identified in the kare gwas , we also replicated a locus ( 6q22.31c ) near gja1 by the lookup in the health examinee gwas . considering that the gja1-encoded protein is a major component of cardiac gap junctions , a functional study might be necessary to validate its genuine molecular biological role in the synchronized contraction of the heart .
[ "this complication usually occurs during abdominal aortic surgery and is an unusual complication following live donor nephrectomy . therefore , it is of utmost importance to minimize the risks of this procedure and thus maximize donor safety . live kidney donors are healthy individuals who willingly undergo major surgery to improve the well - being of another individual .", "a 39-year - old mediterranean female with a bmi of 26 , underwent an elective , living - related , transperitoneal left - sided totally robot - assisted donor nephrectomy using the da vinci surgical system . donor nephrectomy was performed by a transplant surgeon and assisted by a second transplant surgeon , as described elsewhere [ 2 , 3 ] . briefly , the procedure was performed with the da vinci surgical system s using three arms with a fenestrated bipolar forceps ( endowrist bipolar cautery instrument ; intuitive surgical , sunnydale , usa ) in arm 1 , a monopolar cautery hook ( endowrist monopolar cautery instrument ; intuitive surgical , sunnydale , usa ) to dissect structures in arm 2 and the camera ( 3d vision system 12 mm 30 endoscope ; intuitive surgical , sunnydale , usa ) in arm 3 . the medium - chain triglyceride - based diet was continued for a total of 4 weeks after which a second abdominal ultrasonography was done , which showed no fluid in the abdomen . on postoperative day 19 , the patient noted bright red fluid leakage from the pfannenstiel incision without any further symptoms and contacted the nurse practioner .", "in this case report , we describe the first reported complication of chylous ascites after total robot - assisted donor nephrectomy . this complication is more common in major oncological surgical procedures , where lymph nodes are often resected .", "", "" ]
we present the first case report of chylous ascites following total robot - assisted donor nephrectomy . a 39-year - old female underwent a transperitoneal left - sided total robot - assisted donor nephrectomy . the procedure was uneventful and the patient was discharged without any symptoms . at postoperative day 29 , the patient presented with abdominal pain , nausea and a distended , painful abdomen with shifting dullness . she was diagnosed with chylous ascites by ultrasonography and puncture analysis , and treated with therapeutic drainage and dietary restriction . after 4 weeks , she was free of symptoms . the occurrence of this complication is rare after donor nephrectomy . fortunately , the complication can be successfully treated within a few weeks with minimal discomfort for the patient as demonstrated in this case . it is of utmost importance to minimize the risks and limit discomfort for live kidney donors who willingly undergo major surgery to improve the well - being of another individual .
[ ", we aimed to investigate the influence of obesity on the association between epicardial fat thickness ( eft ) and circadian bp changes in patients with recently diagnosed essential hypertension ( eh ) , with a gender subgroup analysis . furthermore , a higher prevalence of hypertension among overweight adults is found in women than in men , which may indicate different susceptibilities based on gender . given these facts although body mass index ( bmi ) is associated with the severity of ambulatory hypertension and an increase in daytime bp , bmi does not reflect body fat distribution . epidemiological studies have found that epicardial fat is two to three times more common among females than males and that excessive body weight increases the risk of diabetes mellitus ( dm ) and cardiovascular diseases approximately one - and - a - half to two times higher in women than it does in men . obesity is a worldwide phenomenon , with an incidence increasing in parallel with obesity - associated diseases such as insulin resistance , type 2 diabetes mellitus , and hypertension . moreover , a nondipping pattern of bp has been reported to occur in several conditions that are frequently associated with obesity .", "this cross - sectional observational single - center cohort study included patients who underwent 24 h abpm and echocardiography between january 2008 and october 2013 . additionally , for both sbp and dbp , the magnitude of the nocturnal decline in bp ( nocturnal decline ) was calculated as follows : daytime average bp minus nighttime average ; the percentage change in bp from day to night ( % day night bp ) was calculated as ( daytime bp nighttime bp ) 100/daytime bp . with this latter data , a normal dipper pattern was diagnosed when the reduction in the average sbp and dbp during the nighttime was 10% of the average daytime values . the nocturnal bp status was also assessed and expressed as either nocturnal normotension or hypertension , with nocturnal hypertension defined as a nighttime bp of 120/70 mmhg . a total of 441 consecutive patients , who underwent office bp measurements , 24-hour abpm , and laboratory measurements for cardiovascular risk factors and echocardiography , were analyzed . because the presence of type 2 dm is known to be associated with increased eft regardless of obesity [ 6 , 7 ] , we also excluded overt type 2 dm from the analysis to avoid its possible confounding impact on the association between eft and circadian bp variability in our hypertensive patients with or without obesity . following the recommendations of the european society of hypertension , a normotensive state was defined as a mean daytime ambulatory systolic and diastolic bp < 135/85 mmhg by abpm , associated with", "circadian bp profile and bp variability assessed by 24-hour mean bps variation were increased in hypertensive patients , especially in hypertensive obese patients , without gender difference ( all p 's < 0.05 ) . moreover , the proportion of patients with a nondipping pattern was the highest among the hypertensive obese patients . a total of 441 patients with eh ( male / female , 236/205 ; mean age , 50.7 13.8 ) and 83 normotensive normal weight patients ( controls , male / female , 42/41 ; mean age , 51.0 13.3 ) were analyzed , and their clinical features and ambulatory blood pressure parameters according to gender are given in table 1 ( male ) and table 2 ( female ) . although there were no significant differences in hr variability among the groups , hypertensive obese patients had higher daytime and 24-hour mean hr and male hypertensive obese patients also had higher nighttime hr than control patients ( all p 's < 0.05 ) . although total cholesterol levels were higher in hypertensive obese patients of both genders than in the controls , male hypertensive obese patients had higher triglycerides and female hypertensive obese patients had lower hdl cholesterol than controls ( all p 's < 0.05 ) . although there was no significant difference in systolic function , hypertensive patients showed significantly increased wall thickness and enlarged left atrial diameter , which were more prominent among hypertensive obese patients , without gender difference ( tables 3 and 4 ) .", "although circadian bp profile and bp variability were increased in hypertensive obese patients without gender differences , female patients had significantly higher eft and greater daytime bp variability than male subjects . bp variability was associated with sbp and eft only in female patients ; therefore , eft may be a more valuable parameter in the evaluation of bp severity and obesity in women than in men . eft may be a more valuable parameter in the evaluation of bp severity and obesity in women than in men . , we investigated the relationship between the parameters derived from 24-hour abpm ( 24-hour sbp and dbp , and bp variability ) in nondiabetic hypertensive patients with or without obesity . the relationship among eft , obesity , and circadian bp variability was affected by gender in different manners ." ]
this study aimed to investigate the effects of gender on the association between epicardial fat thickness ( eft ) and circadian blood pressure ( bp ) changes in patients with recently diagnosed essential hypertension ( eh ) . a total of 441 patients with eh ( male / female : 236/205 , mean age : 50.7 13.8 ) and 83 control patients underwent 24-hour ambulatory bp monitoring and echocardiography . obese eh patients had higher circadian bp profile with bp variability , wall thickness , and left ventricular mass than nonobese eh patients and controls ( all p 's < 0.05 ) without gender differences . eft was higher in female than in male patients ( 7.0 2.5 versus 5.9 2.2 mm , p < 0.001 ) and higher in the obese female eh group ( 7.5 2.6 mm ) than in the control ( 6.4 2.8 mm ) or nonobese eh group ( 6.7 2.8 mm ) among women , whereas eft did not vary among males ( 5.9 1.9 versus 6.0 2.7 versus 5.9 2.4 mm , p = 0.937 ) . multivariate logistic regression analysis demonstrated that the 24-hour mean bp variability was associated with sbp ( p = 0.018 ) and eft ( p = 0.016 ) in female patients , but not in male patients . the relationships among circadian bp variability , obesity , and eft were affected by gender in different manners . eft may be a more valuable parameter in the evaluation of bp severity and obesity in women than in men .
[ "during the past 2 decades , laparoscopic surgery has gained worldwide popularity resulting from its well - known characteristics of less postoperative pain , fewer complications , earlier discharge , and better cosmesis . keyless abdominal rope - lifting surgery ( kars ) is a novel , gasless ( isobaric ) , single - incision laparoscopic surgical technique used in various gynecologic operations and cholecystectomies . besides being a single - incision laparoscopic technique smaller skin incisions in laparoscopic surgery were related to fewer unwanted side effects , including less postoperative pain . however , in recent studies comparing conventional and single - incision laparoscopic surgical procedures , the postoperative pain scores were not different . , kars does not require carbon dioxide ( co2 ) use to inflate the abdominal wall and the intra - abdominal pressure is not elevated during the operation . in addition , postoperative shoulder pain seems to be more frequently observed after laparoscopic surgical procedures in which the intra - abdominal pressure is elevated to between 12 and 18 mm hg by use of co2 . in this study we aimed to compare the postoperative pain levels for kars and conventional multiport laparoscopy performed for adnexal cysts .", "thus the groups of this cross - sectional prospective clinical study were formed according to the women 's choice as the kars or conventional co2 laparoscopy groups . initial visual analog scale ( vas ) scores of 5.7 1.42 and 6.3 1.42 in patients undergoing kars and conventional laparoscopy , respectively , indicated that we needed at least 30 operations in each group to perform a study with a statistical power of 80% at an level of .05 . women who were diagnosed with an adnexal cyst and in whom a laparoscopic operation was indicated were invited to choose one of the operative techniques . beginning in november 2011 , intraoperative and postoperative pain management for all operations performed in our unit was standardized ; thus the uniform management approach allowed us to collect and analyze the data from different surgical techniques . although kars has been performed in our institute since the first half of 2010 , the study included benign ovarian cysts operated on between november 2011 and june 2013 . the abdominal access time in kars patients included the time needed for the construction of the pathway into the abdominal cavity and the placement of the lifting ropes . in conventional laparoscopy patients , kars has common features of conventional laparoscopy and laparotomy . during the creation of the abdominal access pathway , we used the operative laparoscopy study group 's classification system for staging intra - abdominal adhesions : 0 , none ; 1 , filmy and avascular ; 2 , dense and vascular ; and 3 , binding and cohesive .", "kars has common features of conventional laparoscopy and laparotomy . during the creation of the abdominal access pathway , lifting of a particular area ( eg , protrusion of the peritoneal folds or adipose tissue into the operative field , particularly in overweight patients ) can be managed by a suture just penetrating the skin and tied to the same retractor . there is no need to use trocars ( keyless ) to prevent gas leakage , and any surgical instrument ( a laparoscopic hand instrument or a conventional surgical hand instrument ) that can pass through the incision can be used .", "kars has common features of conventional laparoscopy and laparotomy . during the creation of the abdominal access pathway , depending on the need for multiple instrument use or the depth and thickness of the subcutaneous tissue , the length of the incision may be adjusted smaller or larger . after the skin incision , the subcutaneous tissue is dissected bluntly with the tip of a fine instrument until the underlying fascia is reached . the umbilical fold is lifted with 2 clamps bilaterally and a third clamp at the center of the umbilicus . the opening is bluntly widened with the moderate stretching force of 2 fine retractors . at this stage , the surgeon can examine the intra - abdominal viscera by using his or her index or little finger to identify possible adhesions .", "lifting of a particular area ( eg , protrusion of the peritoneal folds or adipose tissue into the operative field , particularly in overweight patients ) can be managed by a suture just penetrating the skin and tied to the same retractor . there is no need to use trocars ( keyless ) to prevent gas leakage , and any surgical instrument ( a laparoscopic hand instrument or a conventional surgical hand instrument ) that can pass through the incision can be used . if the operation is limited to the pelvis , the retractor used does not limit the surgeon 's motions . however , if an additional operation is anticipated at the upper side of the abdominal cavity , the placement of the retractor should be changed . if the intra - abdominal operative space is not adequate to perform the operation , additional lifting sutures can be placed at the sites at which further elevations are required .", "the fascial layer is closed with continuous unlocked sutures while the lifting sutures assist the elevation of the fascial layer . the umbilical incision and the scars of the veress cannula are nearly indemonstrable 1 month after surgery . one month after the operation , the umbilical incision and the scars of the veress cannula are nearly indemonstrable ( figure 4 ) . 3 - 0 or 4 - 0 intracutaneous absorbable sutures and hidden into the umbilical fold .", "co2 laparoscopy is performed with the use of a 10-mm port ( infraumbilical port for the telescope ) and two 5-mm ports ( lateral ports for the hand instruments ) placed after the creation of co2 pneumoperitoneum using the veress needle . at the end of the surgical procedures , all fascial - layer incisions of the 10-mm ports are sutured before the placement of skin sutures ; however , only the skin incisions of 5-mm ports are closed with no . 3 - 0 or 4 - 0 intracutaneous absorbable sutures .", "the test was used to assess the probability of existence of shoulder pain in the 2 groups . a logistic regression model was created to study the confounding factors that influenced the perception of shoulder pain . the distribution of variables was studied by use of kurtosis , skewness , and shapiro - wilk tests . normally distributed variables of the 2 groups were compared by use of the student t test , and non normally distributed variables were compared by use of the mann - whitney u test . the hosmer - lemeshow test showed that the model fit ( = 13 762 , p = .88 , n = 77 ) .", "the total operative time correlated positively with the abdominal access time , weight and body mass index of the women , adhesion score , cyst diameter , cyst rupture rate , length of hospital stay , and shoulder pain frequency ( p < .05 ) . the total operative time correlated positively with the abdominal access and rope - lifting process time , weight and body mass index of the women , adhesion score , cyst diameter , cyst rupture rate , length of hospital stay , and shoulder pain frequency ( p < .05 ) . in the conventional laparoscopy group , during a 20-month period , 77 women with benign ovarian cysts were operated on by kars ( n = 32 ) or conventional co2 laparoscopy ( n = 45 ) . most of the intraoperative and postoperative findings were similar in the 2 groups ( p > .05 ) ; however , the abdominal cavity access and total operative times in the kars group were significantly longer than those in the conventional laparoscopy group ( p < .05 ) . logistic regression for postoperative shoulder pain predicted that shoulder pain was affected only by the operation type and duration ( table 4 ) .", ", our study is the first comparing the postoperative pain scores and additional analgesic requirements of a gasless single - incision laparoscopic technique with conventional multiport co2 laparoscopy . in comparison with conventional co2 laparoscopy , kars performed to treat benign ovarian cysts causes less postoperative abdominal and shoulder pain . in addition , the gasless single - incision technique should be compared with single - incision laparoscopic surgical procedures using co2 to create pneumoperitoneum . postoperative pain scores during single - incision and conventional multiport co2 laparoscopic surgical procedures were compared previously ; however , the abdominal viscera was inflated by using co2 in all these studies . in our study all the operations for ovarian cysts were performed by the same surgical team under the same operating theater conditions .", "in comparison with conventional co2 laparoscopy , kars performed to treat benign ovarian cysts causes less postoperative abdominal and shoulder pain .", "to our knowledge , our study is the first comparing the postoperative pain scores and additional analgesic requirements of a gasless single - incision laparoscopic technique with conventional multiport co2 laparoscopy . postoperative pain scores during single - incision and conventional multiport co2 laparoscopic surgical procedures were compared previously ; however , the abdominal viscera was inflated by using co2 in all these studies . in our study all the operations for ovarian cysts were performed by the same surgical team under the same operating theater conditions .", "although the study included a control group , the participants determined which operative technique they would undergo ; thus the study lacks the power of randomization . pain sensation is subjective and may even differ for the same individual under different conditions . it develops motivations to avoid damaging conditions , to be cautious about the damaged tissue , and to prevent future conditions related to pain . from this point of view , we did not gather information about the past pain experiences of the patients . the vas pain scores measured pain severity at the beginning and second , fourth , and 24th hours of the postoperative period ; however , the pain scores between the fourth and 24th hours were missing . postoperative shoulder pain was evaluated by its presence or absence ; however , its severity was not evaluated . although the frequencies of previous operations were similar in both groups , we can not truly argue that the pain sensation , perception , and definition of the participants were similar .", "in addition , the gasless single - incision technique should be compared with single - incision laparoscopic surgical procedures using co2 to create pneumoperitoneum . we used a standardized pain management protocol in both groups ; thus our results suggest that the single - incision gasless laparoscopic technique yielded better pain scores than conventional co2 laparoscopy . gynecologic operations including myomectomy , hysterectomy , ovarian cyst resection , colposuspension , and radical hysterectomy were performed by various surgeons . although single - incision laparoscopic surgery was found to be feasible , safe , and reproducible in gynecology patients with benign and cancerous diseases , only a few articles suggested better postoperative pain scores , and some of them were case reports or pilot studies . in 2011 fagotti et al published their randomized controlled trial comparing postoperative pain after conventional laparoscopy and laparoendoscopic single - site surgery ( less ) for benign adnexal disease . gargiulo and nezhat concluded that the improved postoperative pain with single - incision laparoscopic surgical procedures was not proven in comparison with the conventional multiport co2 laparoscopies .", "kars seems to cause less postoperative pain during the management of benign ovarian cysts in comparison with conventional multiport co2 laparoscopy ." ]
background and objectives : keyless abdominal rope - lifting surgery is a novel , gasless , single - incision laparoscopic surgical technique . in this study we aimed to compare the postoperative pain from keyless abdominal rope - lifting surgery with carbon dioxide laparoscopy performed for benign ovarian cysts.methods:during a 20-month period , 77 women underwent surgery for a benign ovarian cyst . keyless abdominal rope - lifting surgery and conventional carbon dioxide laparoscopy techniques were used for the operations in 32 women and 45 women , respectively . the 2 operative techniques were compared with regard to demographic characteristics ; preoperative , intraoperative , and postoperative data including early postoperative pain scores ; and frequency of shoulder pain and analgesic requirements.results:data regarding demographic characteristics , preoperative findings , cyst diameters and rupture rates , intra - abdominal adhesions , intraoperative blood loss , and postoperative hospital stay did not differ between groups ( p > .05 ) . however , the mean operative and abdominal access times were significantly longer in the keyless abdominal rope - lifting surgery group ( p < .05 ) . visual analog scale pain scores at initially and at the second , fourth , and 24th hours of the postoperative period were significantly lower in the keyless abdominal rope - lifting surgery group ( p < .05 ) . similarly , keyless abdominal rope - lifting surgery caused significantly less shoulder pain and additional analgesic use ( p < .05).conclusion : keyless abdominal rope - lifting surgery seems to cause less pain in the management of benign ovarian cysts in comparison with conventional carbon dioxide laparoscopy .
[ "precise identification of risk factors is of great importance for recognition of high - risk cases in which ercp should be avoided if possible or protective modalities should be considered to minimize patients risk of morbidity and mortality . the present study examined prospectively the potential patient- and procedure - related risk factors , including esr , for pep in iranian population . pep is the most common severe complication.1,6,7 numerous studies have looked at risk factors for pep,14,616 with varied results , possibly because of different study designs , different candidate predictor variables , and differences between settings . we know that inflammatory biomarkers are useful at 2448 hours post procedure in predicting pep , and a few studies have evaluated pre - procedure inflammatory markers , especially c - reactive protein ( crp ) elevation , as predictors of pep.1723 none of the previous studies has focused on pre - ercp erythrocyte sedimentation rate ( esr ) as a potential risk factor for pep . despite the importance of identifying risk factors for pep , pancreatitis , the commonest adverse event following endoscopic retrograde cholangiopancreatography ( ercp ) , has been found to occur at widely varying rates , in 1% to 15.1% of pateints.14 post - ercp pancreatitis ( pep ) has been found at lower rates in recent studies because noninvasive methods , such as magnetic resonance cholangiopancreatography ( mrcp ) and endoscopic ultrasonography ( eus ) , have superseded diagnostic ercp.5 despite improvement of our knowledge , equipment , and methods for ercp , complications are still a significant hazard with this procedure .", "during a four - year period ( 20082012 ) , 780 patients who underwent ercp in a tertiary care hospital were analyzed in this prospective study . patients in acceptable condition were discharged one to two days after ercp ; otherwise , they received longer inpatient care based on the severity of their complications and illness . successful cannulation was defined as free and deep instrumentation of the biliary tree , and a cannulation attempt was defined as sustained contact with the cannulating device and the papilla for at least five seconds.17 difficult biliary cannulation was defined as the failure of biliary access despite 10 minutes of attempted biliary cannulation or more than five attempted unintentional pancreatic cannulations.18 any complications taking place during or following the procedure were also entered into the records . all the patients had a follow - up visit two weeks after discharge from hospital . the patients were referred to this center from different parts of iran , which enhances the ability to generalize the findings for the iranian population . patient- and procedure - related data , including demographics , characteristics , clinical information and technical details , and findings from ercp procedures were recorded prospectively on a detailed data sheet . indications for ercp were determined by participating endoscopists before the procedure , on the basis of generally accepted diagnostic indications for ercp.5 laboratory evaluations , including those of alkaline phosphatase ( alp ) , alanine transaminase ( alt ) , aspartate aminotransferase ( ast ) , bilirubin , and serum amylase , were performed on the first day of hospitalization , and the results were used as pre - ercp laboratory parameters .", "between 2008 and 2012 , 780 patients ( male : female ratio 393:387 , mean age 57.5 years ) underwent diagnostic and therapeutic ercp with the primary diagnosis of hepatobiliary disorders . , there was no difference in the incidence of pep between guide wire - assisted ercp or conventional contrast - assisted cannulation . female gender , history of recurrent pancreatitis , pre - ercp hyperamylasemia , and difficult or failed cannulation could not predict pep . regarding the cannulation techniques serum amylase was found to be elevated to more than 200 units / l in 102 patients ( 13.7% ) three hours after ercp and more than 800 units / l in 60 patients ( 7.7% ) . in all , 446 ( 70% ) participants underwent wire - guided cannulation and others ( 30% ) underwent sphincterotome biliary cannulation using contrast injection as the conventional method . successful biliary cannulation was technically achieved in 82.5% of all patients at ercp , although in 13.0% of them , cannulation failed .", "we have identified two risk factors for the development of pep : age < 65 years and esr > 30 . we found that raised esr > 30 mm / hour is a significant factor that independently predicts increased risk of pep . another risk factor for the development of pep in our study was increased esr level before ercp ( esr > 30 ) . although it seems that our study is the first study to evaluate pre - ercp esr level as a risk factor for developing pep , many other studies have evaluated the role of pharmacologic agents in reducing the incidence or severity of pep.2,10,2227 several agents , most of which have an anti - inflammatory effect , have been tested in clinical trials . in terms of attenuating the inflammatory response ,", "performing ercp may be safer in the elderly and in patients with low levels of serum esr because they may be less at risk of pep . using pre - ercp anti - inflammatory pharmacologic agents like nsaids might be beneficial , by lowering esr level and reducing related risk of pep ." ]
backgroundpancreatitis remains the most common complication of endoscopic retrograde cholangiopancreatography ( ercp ) , resulting in substantial morbidity and occasional mortality . there are notable controversies and conflicting reports about risk factors of post - ercp pancreatitis ( pep).aimto evaluate the potential risk factors for pep at a referral tertiary center , as a sample of the iranian population.materials and methodsbaseline characteristics and clinical as well as paraclinical information of 780 patients undergoing diagnostic and therapeutic ercp at taleghani hospital in tehran between 2008 and 2012 were reviewed . data were collected prior to the ercp , at the time of the procedure , and 2472 hours after discharge . pep was diagnosed according to consensus criteria.resultsof the 780 patients who underwent diagnostic ercp , pancreatitis developed in 26 patients ( 3.3% ) . in the multivariable risk model , significant risk factors with adjusted odds ratios ( ors ) were age < 65 years ( or = 10.647 , p = 0.023 ) and erythrocyte sedimentation rate ( esr ) > 30 ( or = 6.414 , p < 0.001 ) . female gender , history of recurrent pancreatitis , pre - ercp hyperamylasemia , and difficult or failed cannulation could not predict pep . there was no significant difference in the rate of pep in wire - guided cannulation versus biliary cannulation using a sphincterotome and contrast injection as the conventional method.conclusionsperforming ercp may be safer in the elderly . patients with high esr may be at greater risk of pep , which warrants close observation of these patients for signs of pancreatitis after ercp .
[ "the aim of the study was to evaluate and compare the efficacy of 4% articaine hydrochloride and 2% lignocaine hydrochloride for the orthodontic extraction . it also contains maximum 0.6 mg na - sulfite in 1.0 ml and sodium chloride . once injected , absorption starts from the site of injection into the vascular compartment.1 the unbound local anesthetic is distributed throughout all the body tissue . due to the presence of thiophene ring local anesthesia is being used since long . in 1943 , lofgren synthesized the first modern anaesthesia.1 it is lidocaine , which was an amide derivative of diethyl amino acetic acid . it has a thiophene ring in its molecule instead of usual benzene ring.2,3 this is most commonly used in germany . it is because of the high density and the firm adherence of palatal mucosa to the underlying bone . commercially articaine for dental use is available in 4% solution with epinephrine 1:200000 or 1:100000 .", "no palatal anesthesia was injected , but the desired anesthetic effect was achieved with the above . on the other hand , control sites ( group 2 ) were injected with 0.8 - 1 ml of 2% lignocaine hcl containing 1:100000 adrenaline , incrementally in the buccal vestibule . the study was carried out on 50 patients at outpatient department of oral and maxillofacial surgery who needed bilateral maxillary premolar extractions for orthodontic purpose . experimental sites ( group 1 ) were injected with 0.5 - 1 ml of 4% articaine hcl containing 1:100000 adrenaline , incrementally in the buccal vestibule . when the objective symptoms were checked , it was found that palatal anesthesia was absent hence additional 0.5 ml was injected to obtain a desired result . after assessing the signs and symptoms of obtaining complete anesthesia patients included in this study were in the age group of 15 - 25 years , both genders and systemically healthy . all the patients were explained about visual analog scale ( vas ) before injecting local anesthesia . bleeding disorders , hypertensive , diabetic , pregnant , allergic to local anesthetics , reluctant and medically compromised patients were excluded from the study .", "pain rating showed that there was no significant difference in pain score in articaine palatal and buccal group ( p > 0.8892 ) , whereas a significant difference was noted in lignocaine palatal and buccal group ( tables 3 and 4 ) . all the parameters , i.e. , drug volume , time of onset , duration of anesthesia and pain rating were recorded for entire patients . the mean onset time of lignocaine anesthesia was 1.337 0.2369 , whereas in articaine group the mean time was 1.012 0.2058 min . this indicates that onset time of articaine was significantly less than lidocaine ( p < 0.0005 ) ( table 2 ) . the mean administered volume of articaine and lignocaine were 0.779 0.1305 and 1.337 0.2369 respectively . duration of pain in group 1 was 69.08 18.247 and 55.66 6.414 in group 2 patients .", "it is a well - known fact that palatal anesthesia is a very painful experience even though surface anesthesia is used . recent studies have shown that articaine carries lot of advantages over other anesthetic agents.4 in this study , we observed that the palatal infiltration was required in approximately 98% of cases when lignocaine was used , whereas in articaine group palatal anesthesia was never required . hence , if articaine is used , patients can be relieved from the painful palatal anesthesia without compromising with safety and efficacy . , it goes biotransformation in both liver and plasma and hence gets cleared much quickly .", "certain added advantages like shorter time of onset , longer duration of action and greater diffusion property makes it an ideal anesthetic agent to be used in dentistry ." ]
background : articaine in an anesthetic agent , which is used less frequently in dentistry . it differs from other agents due to the presence of a thiophene ring in its molecular structure . few groups of researchers claim that it is superior to lignocaine . hence , the purpose of this study was to compare the efficacy of 4% articaine hydrochloride and 2% lignocaine hydrochloride in the orthodontic extraction.materials and methods : the study was carried out in 50 patients who needed the orthodontic extraction in the age group from 15 to 25 years . experimental sites were injected with 0.5 - 1 ml of 4% articaine hcl containing 1:100000 adrenaline , incrementally in the buccal vestibule without palatal anaesthesia . control sites were injected with 0.8 - 1 ml of 2% lignocaine hcl containing 1:100000 adrenaline , incrementally in the buccal vestibule . all the parameters , that is volume , duration , time of anesthesia and pain rating were noted and statistically compared.result:when statistically compared mean volume of articaine ( 0.779 0.1305 ) was less than lignocaine ( 1.337 0.2369 ) . mean time of onset of articaine was 1.012 0.2058 min , whereas that of was 1.337 0.2369 . pain rating showed not much difference , but in the lignocaine group palatal anesthesia was required in all the patients . finally , the mean duration of anesthesia in articaine group was 69.08 18.247 , whereas in the lignocaine group was 55.66 6.414.conclusion:articaine has proved its usefulness in all regards . literatures have proved its usefulness . like other anesthetic , it is safe and more effective . it surpasses the need of additional palatal anesthesia . rapid inactivation in liver and plasma reduces the risk of the drug overdose . all the above factors make it an ideal anesthetic agent to be used in dentistry .
[ "rassf1 isoform a ( rassf1a ) is the most characterized member of the rassf family . importantly , all isoforms contain a ras association ( ra ) domain either in their c - terminal ( rassf1 - 6 ) or n - terminal ( rassf7 - 10 ) regions . to date , no known catalytic activity has been described for this family , and the general consensus supposes that rassf proteins function as scaffolds to localize signaling in the cell . the ras association domain family ( rassf ) consists of 10 members : rassf1 - 10 .", "these findings suggest that perhaps hippo signaling serves a more global role in regulating organ integrity , structure , and response to injury , and that perturbation of this pathway can lead to aberrant growth and dysfunction . it has been implicated in the negative regulation of cell cycle progression , cell proliferation , and cell survival . the hippo signaling pathway is a highly conserved kinase cascade that was originally discovered in drosophila and has been shown to be a critical regulator of cell proliferation , survival , and organ growth . the biological relevance of rassf1a - mediated activation of hippo signaling has also been investigated .", "deletion mutants of rassf1a revealed an important function of the n - terminus of rassf1a that disrupts the binding of active ras and raf-1 , thus preventing erk activation and cardiac myocyte growth . to better understand the function of rassf1a in cardiac myocytes in vivo , we crossed genetically altered mice harboring a floxed rassf1a allele with mice harboring the cre recombinase transgene driven by the -mhc promoter . conditional deletion of salvador ( sav1 ) in the embryonic heart , driven by nkx2.5-cre expression , caused increased myocyte proliferation and cardiac enlargement and was mediated by hyperactivation of yap and subsequent wnt/-catenin - regulated gene expression . in a similar vein , direct targeting of yap expression in the developing mouse heart further demonstrated its role in governing both myocyte proliferation and heart growth . interestingly , we found that increased rassf1a expression in the heart caused increases in mst1 activation , cardiac myocyte apoptosis , and fibrosis , and led to worsened function following pressure overload . . taken together , these results provide further evidence that activation of hippo signaling , via increased mst1 or lats2 expression , inhibits cardiac myocyte growth and promotes apoptosis in the adult heart using genetically altered mouse models we showed that increased expression of mst1 , and subsequent activation of the hippo pathway , caused increased apoptosis , dilated cardiomyopathy , and premature death . these data strongly implicated tnf- as a critical paracrine factor influencing the cardiac myocyte growth response to stress in vivo .", "rassf1a signaling is diverse and our knowledge regarding rassf1a function is rapidly expanding . given that a bridge from cancer to cardiovascular biology is in place , it is likely that as additional rassf1a mechanisms of action are discovered , its impact on cardiac biology will continue to grow . fueled by the initial reports described herein , investigation into the role of rassf1a in cardiovascular biology has begun to accelerate . yet many questions remain outstanding . among them it is likely that additional complexities remain to be uncovered and will ultimately influence possible interventions to manipulate rassf1a and treat heart disease . what are the molecular constituents of the rassf1a complex ? does rassf1a have additional mst1-independent functions in the heart , as has been demonstrated in tumor cell lines ? exposure to diverse signals and cues in the extracellular milieu may also contribute to varied outcomes downstream rassf1a . as we continue to elucidate the role of rassf1a and hippo signaling in the heart , what are the upstream inputs that regulate rassf1a function ? what is the mechanism responsible for rassf1a cell - type - specific , we speculate that the difference in proliferative capacity between cardiac myocytes and fibroblasts may explain the distinct effects of rassf1a signaling in the heart . there may also be differences in the expression or localization of signaling components , thereby modulating their ability to effectively signal in certain cell types ." ]
the rassf proteins are a family of polypeptides , each containing a conserved ras association domain , suggesting that these scaffold proteins may be effectors of activated ras or ras - related small gtpases . rassf proteins are characterized by their ability to inhibit cell growth and proliferation while promoting cell death . rassf1 isoform a is an established tumor suppressor and is frequently silenced in a variety of tumors and human cancer cell lines . however , our understanding of its function in terminally differentiated cell types , such as cardiac myocytes , is relatively nascent . herein , we review the role of rassf1a in cardiac physiology and disease and highlight signaling pathways that mediate its function .
[ "we report the case of an adult woman with psoriatic arthritis who developed acute severe hepatitis following long - term treatment with mtx . it is one of the most commonly used medicines in the treatment of rheumatoid arthritis or psoriatic arthritis .", "mtx was stopped in the year 2005 due to remission of the disease . in 2009 , monitoring of liver enzymes performed every 6 months showed an elevation < 2 times the normal levels on average of asat and alat since 2010 . assessing the risk - benefit ratio and given the severe decompensation of the disease , mtx was continued . in may 2013 , patient presented with jaundice following the development of asthenia and weight loss . it was reintroduced at a dose of 15 mg / week due to decompensation of the disease . after 4 months , all laboratory parameters had normalized , and serum was negative for antimitochondrial and antinuclear antibodies . antimitochondrial antibodies ( titer > 1/40 ) and antinuclear antibodies ( titer of 1/640 ) were detected in serum . routine laboratory investigations for infection with hepatitis a , b , and c viruses and serology for cytomegalovirus and epstein - barr virus were negative .", "hepatic fibrosis is a usual adverse reaction reported with long - term use of mtx therapy in psoriatic patients . patients taking mtx are more likely to discontinue therapy because of adverse drug effects rather than because of lack of efficacy . adverse effects of mtx are , usually , mild and self - limiting , but may include serious adverse drug reactions such as hematopoietic suppression , pulmonary , and hepatotoxicity . appearance of autoantibodies and transitory autoimmune disease associated with infliximab in a patient with psoriatic arthritis has also been documented and the preexistent serological signs of autoimmunity are believed to be a risk factor for the development of similar autoimmune reactions .", "this report confirms the need to monitor liver enzymes carefully in patients with psoriatic arthritis using long - term treatment with mtx . further research is needed to identify the exact mechanism and establish , if possible , primary means of prevention of this serious adverse effect . clinicians must collaborate with the pharmacovigilance center to detect and notify serious adverse effects of mtx ." ]
methotrexate ( mtx ) is one of the most commonly used medicines in the treatment of psoriatic arthritis . the drug can produce steatosis and cirrhosis . autoimmune hepatitis is a rare and serious adverse effect . we describe the case of a 53-year - old woman who developed autoimmune hepatitis after a long - term use of mtx for psoriatic arthritis . hepatitis was completely resolved 4 months after stopping this drug . the pathophysiologic mechanisms of a drug - induced autoimmunity are unclear and complex . this report confirms the need to monitor liver enzymes carefully in patients using long - term treatment with mtx for psoriasis or rheumatoid arthritis .
[ "mirizzi syndrome is a rare complication of cholecystolithiasis characterized by jaundice due to compression of the common hepatic duct . the diagnosis may not be immediately apparent , and management is controversial with open surgery still recommended by some authors .", "laparoscopic retrograde ( fundus first ) cholecystectomy was carried out utilizing a laparoscopic liver retractor . a case is detailed herein of a 67-year - old man who presented with abdominal pain , fever , and jaundice . the diagnosis of mirizzi syndrome was made at ercp , and a stent was placed through the papilla . a dilated bile duct was found on ultrasound , but the gallbladder could not be seen .", "in this particular case , it was not possible at ercp to get a guidewire and stent past the obstruction . a stent was left through the papilla , below the obstruction and this allowed primary duct closure during surgery .", "laparoscopic ultrasound is useful to locate the impacted stone and to partially replicate the touch of the surgeon 's hand , which is not available in laparoscopic surgery . ercp is useful to confirm the diagnosis and allows stenting to alleviate the jaundice and facilitate the subsequent operation . acute mirizzi syndrome should be suspected when a patient presents with acute cholecystitis and jaundice with dilated intrahepatic ducts on ultrasound .", "mirizzi syndrome ( ms ) is biliary obstruction from compression of the common hepatic duct ( chd ) by a gallstone impacted in the cystic duct . the syndrome was initially described in 1948 by pablo luis mirizzi , professor of surgery in cordoba , argentina , and he erroneously postulated that the extrinsic pressure and inflammation induced spasm of the chd . csendes further subdivided type ii depending on the size of the fistula and the degree of destruction of the wall of the chd . mcsherry classified the syndrome into 2 groups : type i where extrinsic compression of the bile duct occurs and type ii where erosion occurs of the wall of the chd by the stone with formation of a cholecysto - choledochal fistula . although a rare condition , many controversial aspects still surround the definition and management of ms . to illustrate the true ms and the value of a combination of endoscopic retrograde cholangiopancreatography ( ercp ) and laparoscopic surgery , a case the classical ultrasound findings are of a contracted gallbladder , dilated intrahepatic ducts , and a normal common bile duct ( cbd ) . precise diagnosis may be difficult initially because the condition may be confused with choledocholithiasis and cholangitis .", "the guidewire kept going into the gallbladder , and it became apparent that there was an ms with the obstructing stone in the cystic duct causing compression of the chd ( figure 2 ) . note the narrow common bile duct and the dilatation of the common hepatic and intrahepatic ducts . a computed tomogram ( ct ) scan was done and showed a contracted gallbladder with a calcified stone causing biliary obstruction ( figure 3 ) . at laparoscopic cholecystectomy , an acutely inflamed the gallbladder ( gb ) has been dissected from the liver retrograde , and the liver retractor is in place . the stone is impacted in the cystic duct , which is anterior and parallel to the common hepatic duct .", "operative cholangiography is advocated to improve the safety of cholecystectomy , but an accurate transcystic cholangiogram will not be possible in ms . a standard technique in open surgery for the difficult laparoscopic cholecystectomy was the fundus - first approach . this can be replicated in laparoscopic surgery by the use of a liver retractor and means that exposure does not rely on traction on the fundus of the gallbladder . in ms , ms is a rare cause of jaundice due to extrinsic compression of the chd and is present in approximately 0.35% of cholecystectomies . if ercp is to be used as definitive treatment , sophisticated techniques may be needed for these cases , including the use of a mother and baby scope and electrohydraulic or laser lithotripsy . in the case more often , ercp is used to make the diagnosis and insert a stent to alleviate the jaundice and allow planning of an elective operation . it is generally accepted that an increased risk of bile duct injury exists during surgery for ms , and laparoscopic surgery may increase this risk . ercp may provide definitive treatment for ms ; however , the impacted stone can create real difficulties .", "in addition , the fitness of the patient for surgery and the complexity of the pathology are important for planning the therapeutic approach . in my opinion , ms should ideally be treated by a combination of ercp and stenting with laparosocopic in ms , even if an operation is planned , preoperative ercp and stenting should be considered because this approach should simplify and improve the safety of the operation . stenting overcomes the resistance of the choledochal sphincter , and even if accurate closure of the opening in a friable and inflamed duct is not possible , it should avoid the development of a significant biliary fistula . careful planning combined with modern equipment should allow most cases to be managed without t - tubes , destruction of the choledochal sphincter , or open surgery ." ]
background : mirizzi syndrome is a rare complication of cholecystolithiasis characterized by jaundice due to compression of the common hepatic duct . the diagnosis may not be immediately apparent , and management is controversial with open surgery still recommended by some authors.method:a case is detailed herein of a 67-year - old man who presented with abdominal pain , fever , and jaundice . a dilated bile duct was found on ultrasound , but the gallbladder could not be seen . the diagnosis of mirizzi syndrome was made at ercp , and a stent was placed through the papilla . laparoscopic retrograde ( fundus first ) cholecystectomy was carried out utilizing a laparoscopic liver retractor.results:in this particular case , it was not possible at ercp to get a guidewire and stent past the obstruction . a stent was left through the papilla , below the obstruction and this allowed primary duct closure during surgery.conclusion:acute mirizzi syndrome should be suspected when a patient presents with acute cholecystitis and jaundice with dilated intrahepatic ducts on ultrasound . ercp is useful to confirm the diagnosis and allows stenting to alleviate the jaundice and facilitate the subsequent operation . laparoscopic ultrasound is useful to locate the impacted stone and to partially replicate the touch of the surgeon 's hand , which is not available in laparoscopic surgery .
[ "dirofilaria immitis ( the canine heartworm ) is a filarial nematode naturally hosted by dogs , cats , foxes , muskrat , raccoons , and bears . pathologically , spherical subpleural infarct with a central thrombosed artery containing the parasite in stage of degeneration is most commonly seen [ 4 - 6 ] . in the republic of korea ( = korea ) , the first case of human pulmonary dirofilariasis was reported in 2000 . in this report patients with pulmonary dirofilariasis are usually asymptomatic ; however , occurrence of cough , chest pain , hemoptysis , and wheezing has been described in some patients .", "at first we considered a percutaneous needle biopsy for diagnosis , but biopsy was considered not technically feasible due to the location of the nodule . after surgical resection , the patient was discharged without any complications and is being followed up in healthy conditions . although it looked as a benign inflammatory nodule such as cryptococcal infection , malignancy could not be excluded ( fig . a 48-year - old male was referred to seoul national university hospital after a routine check - up at a local hospital due to abnormal findings seen in chest ct .", "another case of dirofilariasis in the liver reported in korea was actually a misdiagnosis of hepatic capillariasis . usually d. immitis invades the lungs in human cases , but reports of human dirofilariasis involving other organs like the subconjunctiva , liver , and subcutaneous sites are also available . the chest ct images and pathologic findings of our case were similar to the first korean dirofilariasis case . human pulmonary dirofilariasis was first reported in 1887 , when de magalhes documented the discovery of a single male and a single female filarial worm in the left ventricle of a boy from rio de janeiro , brazil . in 1961 , dashiell reported the first case involving the lung ." ]
dirofilariasis is a rare disease in humans . we report here a case of a 48-year - old male who was diagnosed with pulmonary dirofilariasis in korea . on chest radiographs , a coin lesion of 1 cm in diameter was shown . although it looked like a benign inflammatory nodule , malignancy could not be excluded . so , the nodule was resected by video - assisted thoracic surgery . pathologically , chronic granulomatous inflammation composed of coagulation necrosis with rim of fibrous tissues and granulations was seen . in the center of the necrotic nodules , a degenerating parasitic organism was found . the parasite had prominent internal cuticular ridges and thick cuticle , a well - developed muscle layer , an intestinal tube , and uterine tubules . the parasite was diagnosed as an immature female worm of dirofilaria immitis . this is the second reported case of human pulmonary dirofilariasis in korea .
[ "a 5-year clinical study demonstrated the clinical success of 2sis.24 the purpose of this study was to compare the stress distribution of various types of 2sis that were installed and restored in severely atrophied maxillary molar sites . the 2si approach is a minimally invasive procedure that solely utilizes residual bones to overcome unfavorable bone quantity and quality in the maxillary posterior area . this is due to the small implant - to - bone contact area and the inferior bone quality.123 moreover , the severe bone loss caused by sinus pneumatization or chronic periodontitis , which leads to a reduction in the height of the remaining residual ridge , can further increase the implant failure rate.4 in addition , the occlusal load in the posterior area is 3 - 5 times higher than that in the anterior area.5 to address these problems , various bone graft techniques to augment the insufficient bone volume and thereby ensure the success of maxillary posterior implants have been proposed.6 such surgical methods have been accepted as clinically meaningful procedures . given the above facts and the disadvantages , success rate of bone grafting in a severely atrophied maxilla is not very promising .", "the von mises stress was measured in the interface of implant - bone , implant / abutment complex , and at the bone of the peri - implant area in all models . to assess the stress distribution abutment for each implant diameter was connected , and the occlusal surface area of the definitive prosthesis was constructed to have the same shape . an implant was designed to be installed on the missing maxillary first molar area on the maxilla with a pneumatized sinus , 0.5 mm cortical bone on top and bottom , and 3 mm cancellous bone ( fig . the mechanical properties of the bone , gold , and titanium were set as previously described ( table 1).2526 the implant bone interface was constructed with 100% contact for complete stress transfer to the surrounding bone . the 2si groups were categorized into 1 ) np oblique ( two narrow implants were obliquely installed ) , 2 ) np vertical ( two narrow implants were installed in palatal residual bone due to the resorption of buccal bone ) , and 3 ) np horizontal ( two narrow implants were installed in distal residual bone due to the mesial bone resorption ) . a gold crown on the abutment ( rigid , osstem , seoul , korea ) was connected with the implant .", "stress distribution of the peri - implant bones was relatively small and even in the 2si groups . analyses of stress distribution in the implant - bone interface of an implant in the buccal side ( np-1 ) showed an evenly distributed stress pattern in the np - horizontal and np - oblique groups , whereas the np - vertical group exhibited a relatively high stress pattern in the top and center areas of the interface ( fig . the 2sis showed the most even stress distribution and rp implant showed the largest stress pattern on the peri - implant bones ( fig . as for the stress on the peri - implant bone , a more even stress distribution was observed in the center position implant than in the cantilever position implant . when axial loading was applied , higher von mises stress was observed on the implant - bone interface in the rp implant than in the wp implant or 2si implants . stress patterns at the implant / abutment complex of single implants were similar to that of the 2si groups ( fig .", "as an alternative to bone graft on a severely atrophied maxillary posterior area , single wide implant or splinting of multiple implants can be performed.2123 the results from the this study showed that , multiple implants , even with a short length and narrow diameter , offer a favorable implant - bone interface , peri - implant bone , and implant - abutment complex . the use of 2sis , which place np implants in the most dense bone area in the buccal and palatal sides and utilize residual bones per se without surgical difficulties , is a procedure allowing enhanced osseointegration and favorable stress distribution . in addition , stress on the implant - abutment complex was analyzed to estimate the risk of fracture in a narrow implant . stress on the implant / abutment complex was lower than that in the implant - bone interface or peri - implant bones . this is because it was difficult to estimate the effect of stress distribution solely based on the stress pattern at the localized implant - bone interface in case of a severely atrophied bone .", "when axial loading or oblique loading was applied , the highest level of stress was observed on the implant - bone interface and peri - implant bones in a single rp implant and the lowest stress distribution was exhibited in 2si conditions . the highest level of stress was concentrated on the implant / abutment - contacting surface of the single wide implant and the lowest level of stress was on the implant / abutment complex of 2sis . the stress distributions based on various bone levels and implant installation conditions in a severely atrophied maxillary posterior area were analyzed ." ]
purposethe aim of this study was to investigate the stress distribution of 2-short implants ( 2sis ) installed in a severely atrophic maxillary molar site.materials and methodsthree different diameters of internal connection implants were modeled : narrow platform ( np ) , regular platform ( rp ) , and wide platform ( wp ) . the maxillary first molars were restored with one implant or two short implants . three 2si models ( np - oblique , np - vertical , and np - horizontal ) and four single implant models ( rp and wp in a centered or cantilevered position ) were used . axial and oblique loadings were applied on the occlusal surface of the crown . the von mises stress values were measured at the bone - implant , peri - implant bone , and implant / abutment complex.resultsthe highest stress distribution at the bone - implant interface and the peri - implant bone was noticed in the rp group , and the lowest stress distribution was observed in the 2si groups . cantilevered position showed unfavorable stress distribution with axial loading . 2si types did not affect the stress distribution in oblique loading . the number and installation positions of the implant , rather than the bone level , influenced the stress distribution of 2sis . the implant / abutment complex of wp presented the highest stress concentration while that of 2sis showed the lowest stress concentration.conclusion2sis may be useful for achieving stable stress distribution on the surrounding bone and implant - abutment complex in the atrophic posterior maxilla .
[ "the aim of this retrospective study was to investigate the skeletal manifestations of hydatid disease in serbia , it 's demographic distribution , site involvement , complications , and bone tissue comorbidities . hydatid disease ( echionococcosis ; hydatidosis ) is a parasitic disease , endemic in many sheep raising countries ( australia , south america , mediterranean countries , russia , middle east , and central asia ) . epidemiological studies have been conducted in some countries , while in serbia , montenegro , bih , and albania no information is available about the precise incidence in humans . adult cestodes of echinococcus granulosus inhabit the small intestine of a definitive host ( dogs , foxes , and wolves ) and produce infective eggs . through the feces , either cestode segments or free eggs theoretically , they can occur at any site except the teeth , nails , and hairs .", "data obtained from medical records included the age at the moment of diagnosis , sex , localization of hydatid cyst , copresence of hydatid cyst in localizations other than the bone tissue , presence of skeletal complications , bone comorbidities , and diagnosis based on radiographies . in order to standardize the data , the radiological assessment was made on standard radiography , having in mind the length of the study period and diagnostic procedures available for that time . changes in the bone structure were classified as tumefaction ( sharply or unshapely demarcated area of altered bone structure ) , cysts ( sharply demarcated lytic bone lesion with geographical borders ) , or fractures ( in cases where fracture line occured ) . in some patients , altered bone structure was able to be classified as cyst or tumefaction preceding the pathological fracture , while in other cases , no alteration of the bone structure was radiologically visible aside of the fracture line . materials in the study comprised all the cases with histologically verified bone hydatidosis during the period between 1971 and 2010 in the territory of serbia . the study was conducted by reviewing the medical database of institute for pathology ( faculty of medicine in belgrade ) which is a reference institution in serbia for bone pathology .", "bone tissue comorbidities refer to bone tuberculosis in a patient with spinal hydatid disease ( 2.4% ) and to presence of fistula detected in 2 patients ( 4.9% ) , 1 with spinal and 1 with pelvic hydatidosis . the age of the patients at the time of diagnosis was from 7 to 77 years . the spine was the most commonly involved site with the predominance of the thoracic segment . the mean age of all patients was 40.918.8 years . in order to explore the age distribution of ce ,", ", bone tissue destruction develops through 3 mechanisms ; as the consequence of the cystic lesion expansion and its compression on surrounding tissues , ischemic processes through compression and obstruction of nutrient vessels , and cellular processes like osteoclast proliferation around the compressed bone tissue . in the absence of pericyst formation , our results reported primary involvement of the spine ( 75% ) , with the predominance of lumbar over thoracic segment . in patients with bone ce radiological diagnosis of osseous hydatid disease is also difficult because of non - specific findings . therefore , preoperative diagnosis of skeletal hydatid disease is difficult , and conclusive diagnosis is often made intraoperatively and by histological verification [ 26 - 28 ] . paraplegia is the most serious complication of vertebral hydatidosis appearing in up to 75% of patients with spinal ec . these asymptomatic patients are not surprising in consideration that hydatid disease is anywhere in the body and often discovered as an incidental finding ." ]
although serbia is recognized as an endemic country for echinococcosis , no information about precise incidence in humans has been available . the aim of this study was to investigate the skeletal manifestations of hydatid disease in serbia . this retrospective study was conducted by reviewing the medical database of institute for pathology ( faculty of medicine in belgrade ) , a reference institution for bone pathology in serbia . we reported a total of 41 patients with bone cystic echinococcosis ( ce ) during the study period . the mean age of 41 patients was 40.918.8 years . in 39% of patients , the fracture line was the only visible radiological sign , followed by cyst and tumefaction . the spine was the most commonly involved skeletal site ( 55.8% ) , followed by the femur ( 18.6% ) , pelvis ( 13.9% ) , humerus ( 7.0% ) , rib ( 2.3% ) , and tibia ( 2.3% ) . pain was the symptom in 41.5% of patients , while some patients demonstrated complications such as paraplegia ( 22.0% ) , pathologic fracture ( 48.8% ) , and scoliosis ( 9.8% ) . the pathological fracture most frequently affected the spine ( 75.0% ) followed by the femur ( 20.0% ) and tibia ( 5.0% ) . however , 19.5% of patients did n't develop any complication or symptom . in this study , we showed that bone ce is not uncommon in serbian population . as reported in the literature , therapy of bone ce is controversial and its results are poor . in order to improve the therapy outcome , early diagnosis , before symptoms and complications occur , can be contributive .
[ "this may lead to adverse health effects in workers ; therefore , the government has implemented regulations to protect worker health , such as the occupational safety and health ( osh ) act . based on the employment contract , every employer has a certain amount of control / power and the expectation that workers will follow work - related requests . however , worker behavior is constrained by various workplace pressures such as working conditions , including what is considered to be accepted working behavior and overall morale of the working group . workers ' health may be protected by his / her own preventive behavior , despite numerous health hazards in the workplace . recently , psychosocial factors such as work - related stressors have been included as hazard factors in the workplace , and health promotion activities have become an important component of worker health management before symptoms and signs of occupational diseases manifest . in this article , we reviewed the various kinds of surveillance systems for occupational diseases in korea and resultant data , and suggest reformation of the workers ' health management system . adverse health effects induced by unexpected incidents may present as occupational injuries , but occupational diseases can appear due to long term continuous exposure to harmful chemicals , dust , noise , etc . to prevent occupational diseases , it is important to manage worker health via health monitoring for early detection of abnormal conditions . it is very important for worker health management to monitor the level of worker exposure to hazards in the workplace ; for example , health check - ups including absorption of hazard materials , so called ' biological monitoring ' .", "the prevalence rate of stress is the highest one among male workers , but musculoskeletal disorders are the highest among female workers ( 2 ) ( table 3 ) . another method of investigation of the magnitude and profile of occupational diseases is the national survey method ; however , this method is less developed . since 1998 , there were three kinds of nationwide surveys : first , is the national workers ' health interview survey ; second , is the national survey on workplace safety and health management ; and third , is the working conditions survey ( wcs ) . since 2000 , the number of occupational diseases has increased continuously from 4,051 in 2000 to 11,472 in 2007 . however , after 2007 occupational disease cases decreased . in particular , occupational diseases accounted for 8,721 cases in 2009 , representing a decrease of 1,013 persons ( 10.4% ) compared to the previous year 's 9,734 persons in 2008 ( 1 ) ( fig . data on occupational diseases compensated as industrial accidents are collected and analyzed by the korea occupational safety and health agency ( kosha ) . the osh act yearly trends in size of occupational diseases as industrial accidents in korea may be reflected by changes in institutions of industrial accident compensation . every survey has included some questions about worker 's experiences of occupational disease . according to the wcs , the magnitude of occupational diseases experienced as symptoms and signs is detailed hereafter : among the various symptoms and signs , the highest prevalence rate is that of musculoskeletal disorders ( 18.1% ) ; the second most frequent is that of stress ( 17.9% ) ; back pain is the third ( 16.8% ) ; and overall fatigue is the fourth ( 16.7% ) .", "yearly trends in size of occupational diseases as industrial accidents in korea may be reflected by changes in institutions of industrial accident compensation . in particular , brain and heart disease and musculoskeletal disorders since 2000 , the number of occupational diseases has increased continuously from 4,051 in 2000 to 11,472 in 2007 . however , after 2007 occupational disease cases decreased . in particular , the number of fatal occupational diseases increased until 2003 , but has since shifted to a decreasing trend . data on occupational diseases compensated as industrial accidents are collected and analyzed by the korea occupational safety and health agency ( kosha ) . the osh act recently , these work - related diseases were the most of compensated cases except for coal worker 's pneumoconiosis ( table 1 , 2 ) . industrial accident is defined in the industrial accident compensation insurance act , and occupational diseases are included as industrial accidents .", "another method of investigation of the magnitude and profile of occupational diseases is the national survey method ; however , this method is less developed . since 1998 , there were three kinds of nationwide surveys : first , is the national workers ' health interview survey ; second , is the national survey on workplace safety and health management ; and third , is the working conditions survey ( wcs ) . according to the wcs , the magnitude of occupational diseases experienced as symptoms and signs is detailed hereafter : among the various symptoms and signs , the highest prevalence rate is that of musculoskeletal disorders ( 18.1% ) ; the second most frequent is that of stress ( 17.9% ) ; back pain is the third ( 16.8% ) ; and overall fatigue is the fourth ( 16.7% ) . the working conditions survey is using the same questionnaire as the fifth survey of the european founplace wcs in order to compare korea and the eu . the third one was conducted in 2006 and focused on psychosocial factors of workers ' health in the workplace . the first one was done only one time in 1998 for workers in manufacturing sectors . the second one was done a total of 5 times between 2000 and 2008 , and the sixth survey was done in 2009 . the prevalence rate of stress is the highest one among male workers , but musculoskeletal disorders are the highest among female workers ( 2 ) ( table 3 ) .", "the health examination is focused on early detection of occupational diseases , and its results are used as information for workplace management in order to protect worker health . the special health examinations are comprised of health screening tests for early detection of selective occupational diseases in workers exposed to specific hazard factors such as noise , dust , organic solvent , etc . the general health examination is a mass screening test for finding health problems including occupational diseases of workers without exposure to hazard factors . cases diagnosed as ' suspicious cases of occupational disease ' are recommended to be transferred to non - hazardous workplaces . some of them may be compensated based on diagnosis of occupational diseases through the workers ' compensation insurance system health examinations for worker health protection are classified into two different types : special health examination and general health examination . the health examination is defined as a screening test for occupational diseases , so there is no confirmatory diagnosis in the health examination process . ' health examinations are very effective in finding asymptomatic chronic diseases , such as pneumoconiosis , hearing loss and some poisonings .", "every employer should do working environment measurement in order to identify hazard factors in the workplace and the level of worker exposure to these factors . if the level of worker exposure is higher than the occupational exposure level in korea , the employer should immediately act to reduce it . the working environment measurement institution , regulated by the osh act , is in charge of assessing and , ultimately , reducing the level of worker exposure to hazard factors in the workplace . the special health examination is based on working environment measurement , such as selection of the examinee .", "finally , occupational health surveillance is an important means of discovering new associations between occupational agents and accompanying diseases . discovery of rare diseases , patterns of common diseases , or suspicious exposure - disease associations through surveillance activities in the workplace can provide vital leads for a more conclusive scientific evaluation of the problem and possible verification of new occupational diseases ( 5 ) . the main purpose of occupational health surveillance is to identify the incidence and prevalence of known occupational diseases and injuries ( 5 ) . other dominant fatal occupational diseases , such as brain and heart diseases , will also decrease because general health programs have focused on prevention of hypertension , one of the most important causal factors of brain and heart diseases in workers . in the general population , the morbidity rate of brain and heart diseases has shown a recent downward trend . occupational health surveillance entails the systematic monitoring of health events and exposures in working populations in order to prevent and control occupational hazards and their associated diseases and injuries ( 5 ) . the trend in fatality rate can be reflected by the trend in fatal pneumoconiosis and brain and heart disease , as these two categories of occupational diseases predominate total occupational diseases . the magnitude of occupational diseases and associated fatality rate in korea have gradually increased since 2007 .", "most of the current surveillance system in korea depends upon the osh act . from the viewpoint of surveillance , the occupational management system in korea is well designed except for the national survey system . in the future , national surveys for detection of occupational hazards and ill - health outcomes of workers should be developed . recently , data mining has been used in order to estimate the national burden of occupational disease with other international statistics . in korea , this technique can be also introduced for development of the management system of occupational diseases . the existing surveillance system of occupational disease can be improved by providing more refined information through statistical analysis of surveillance data . the present system of surveillance for management of occupational diseases mainly depends upon the workers ' compensation and health examination systems . based on considerable information , occupational disease management can be accomplished in order to protect and promote worker health . many kinds of information are required to suggest the etiology of poor worker health , such as hazard , exposure level and related information in workplace ." ]
the management system of occupational diseases in korea can be assessed from the perspective of a surveillance system . workers ' compensation insurance reports are used to produce official statistics on occupational diseases in korea . national working conditions surveys are used to monitor the magnitude of work - related symptoms and signs in the labor force . a health examination program was introduced to detect occupational diseases through both selective and mass screening programs . the working environment measurement institution assesses workers ' exposure to hazards in the workplace . government regulates that the employer should do health examinations and working conditions measurement through contracted private agencies and following the occupational safety and health act . it is hoped that these institutions may be able to effectively detect and monitor occupational diseases and hazards in the workplace . in view of this , the occupational management system in korea is well designed , except for the national survey system . in the future , national surveys for detection of hazards and ill - health outcomes in workers should be developed . the existing surveillance system for occupational disease can be improved by providing more refined information through statistical analysis of surveillance data .
[ "a cross - sectional retrospective study was carried out according to world health organization guidelines over 6 months and included 197 general practitioners ( gps ) and 19,700 prescriptions.this study revealed that the overall index of rational drug prescribing ( irdp ) indicator for gps was below the optimal prescribing practice level.we found disparities in the irdp between gps at different health facilities . gps at national insurance fund facilities scored lower than those at state ministry of health facilities or other health facilities such as those owned by private interests , universities , and non - governmental organizations .", "the objective of this study was to use the who / inrud prescribing indicator to assess the quality of prescribing among gps at different types of phccs . we used prescribing indicators as a benchmark among gps at primary healthcare centers ( phccs ) and as a baseline for regular assessment of prescribing quality . in sudan , we used the assessment regimen created by who / inrud to evaluate prescribing performance according to the adopted standards to monitor the improvement of rationality in prescribing practice . before rational prescribing the world health organization ( who ) and the international network of rational use of drugs ( inrud ) have developed widely used core prescribing indicators to assess the prescribing quality of primary healthcare facilities and to enable comparisons between health facilities and prescribers . to our knowledge , no prescriber - based study has been conducted in sudan ; one study of the national health insurance fund ( nhif ) has been conducted in health facilities . can be promoted , the prescribing practices of those who provide 80 % of the services must be ascertained.table 1previous prescribing quality studies in sudanyeararealevelmean no . these previous studies were conducted to investigate prescription patterns ; however , our study investigated the prescribing practices of general practitioners ( gps ) and used the largest sample and a unique study unit . thus , the appropriate use of medicines is an essential factor in the provision of quality health services , patient safety , and the rational use of health resources .", "the study was conducted in gezira state , which represents 27 % of nhif ; we targeted all gps ( 220 ) providing services for nhif subscribers at the primary healthcare level . the reference period of retrospective data collection was 6 months , representing the last quarter of 2014 and the first quarter of 2015 . the unit of analysis used was gp ( 100 prescriptions for each gp).table 2adjusted prescribing standards from who and inrud indicatorsprescribing indicatorsoptimal leveloptimal irdpmean medicines per prescription ( whether or not drugs dispensed)<2 1medicines prescribed by generic name ( % ) 100 1prescriptions with an antibiotic ( % ) 30 1prescriptions with an injectable dosage form ( % ) 10 1medicines prescribed from nhif gp s medicines list ( % ) 1001complementary indicator , average cost of prescription ( sdg)20.31 ( proxy) \n inrud international network for the rational use of drugs , irdp index of rational drug prescribing , nhif national health insurance fund , sdg sudanese pound , who world health organization adjusted prescribing standards from who and inrud indicators \n inrud international network for the rational use of drugs , irdp index of rational drug prescribing , nhif national health insurance fund , sdg sudanese pound , who world health organization to determine prescribing rationality and quality at the gp level , we used the index of rational drug prescribing ( irdp ) developed by yuxin and mingguang . we collected 100 prescriptions for each gp according to who / inrud guidelines for comparisons between prescribers . of the 220 gps , 197 ( 90 % ) had valid prescriptions over the 6 months , and the total valid number of observations was 19,700 prescriptions . trained technical professionals collected the data . prescription collection was based on systematic random sampling , with an interval determined by dividing the gp s total prescriptions by 100 . data were reviewed and entered twice in a microsoft excel spreadsheet before being exported to stata-12 for analysis .", "the unit of analysis used was gp ( 100 prescriptions for each gp).table 2adjusted prescribing standards from who and inrud indicatorsprescribing indicatorsoptimal leveloptimal irdpmean medicines per prescription ( whether or not drugs dispensed)<2 1medicines prescribed by generic name ( % ) 100 1prescriptions with an antibiotic ( % ) 30 1prescriptions with an injectable dosage form ( % ) 10 1medicines prescribed from nhif gp s medicines list ( % ) 1001complementary indicator , average cost of prescription ( sdg)20.31 ( proxy) \n inrud international network for the rational use of drugs , irdp index of rational drug prescribing , nhif national health insurance fund , sdg sudanese pound , who world health organization adjusted prescribing standards from who and inrud indicators \n inrud international network for the rational use of drugs , irdp index of rational drug prescribing , nhif national health insurance fund , sdg sudanese pound , who world health organization to determine prescribing rationality and quality at the gp level , we used the index of rational drug prescribing ( irdp ) developed by yuxin and mingguang . we used the who / inrud standard method for calculating prescribing indicators ( table 2 ) . data were reviewed and entered twice in a microsoft excel spreadsheet before being exported to stata-12 for analysis . data at the gp level were clustered to represent the three types of health facilities . the index of each prescribing indicator was calculated by dividing the optimal value by the achieved value for each gp . moreover , for each type of health facility , the irdp was applied for comparison . the prescriptions data were transferred to who investigation format , checked again for accuracy , entered into an excel sheet , and individually checked once more for precision and completeness .", "a total of 81.19 % of the prescribed medicines were from the eml , and generics accounted for 46.34 % of prescriptions , which is some distance from the optimal required level of 100 % . the average number of medicines per prescription ( 2.55 : maximum 15 , minimum 1 ) indicated a poly - pharmacy pattern , with prescriptions involving antibiotics ( 54.71 % ) and injectable formulations ( 12.84 % ) . the prescribing quality indices revealed that prescribing practice was nowhere near the optimal index of 5 , with nhif facilities having a lower index ( 3.08 ) than smoh facilities ( 3.46 ) and health facilities owned by others ( 3.75 ) ( table 3 ) . the average cost per prescription was 40.57 sudanese pounds ( sdgs ) ( table 3 ) . the optimal index is 5 ; however , the overall irdp score for gps was 3.39 ( range 2.14.8 ) . values for nhif facilities were farther from the prescribing indicator standards than were smoh and other health facilities , except for the percentage of prescriptions containing antibiotics ( nhif 45.91 vs. smoh 57.24 vs. others 56.84 % ) ( table 3).table 3prescribing indicators and health facility typestype of health facility owner or operatorsmohnhifotheroverallnumber of gps1264328197average number of drugs per prescription2.442.972.42.55medicines prescribed by generic name ( % ) 48.9638.4749.2846.34prescriptions containing antibiotics ( % ) 57.2445.9156.8454.71prescriptions containing injectable formulations ( % ) 12.5515.589.9712.84drugs prescribed from gp s medicines list ( % ) 82.9772.6589.2781.19average cost of prescription ( sdgs)36.0759.5431.6940.57irdp3.463.083.753.39 \n gp general practitioner , irdp index of rational drug prescribing , nhif national health insurance fund , sdg sudanese pound , smoh state ministry of health prescribing indicators and health facility types \n gp general practitioner , irdp index of rational drug prescribing , nhif national health insurance fund , sdg sudanese pound , smoh state ministry of health the correlation between gps and irdp was statistically significant at p < 0.001 .", "the objectives of this study were to use the who / inrud prescribing indicator to assess the quality of prescribing among gps at different types of phccs . we conducted a cross - sectional retrospective study over 6 months that involved 197 gps with valid prescriptions , representing 90 % of the total study population ( 220 ) . the percentage of prescriptions containing antibiotics was 54.71 % , a considerably high result according to the who guideline benchmark of 30 % antibiotic use .", "further studies should be conducted to determine the factors causing the considerable discrepancies ( 2.14.88 irdp ) between gps at health facilities owned by the nhif , the smoh , and others ( private interests , universities , and ngos ) . the present study used the largest sample to date and a unique study unit to investigate prescribing rationality among gps at different types of health facilities providing health services for insured patients in gezira state , sudan . appropriate medicine use is essential to the provision of quality health services , patient safety , and the rational use of health resources . the study revealed that the overall irdp score for gps was less than optimal and characterized by significant disparities between gps at different health facilities , with nhif facilities receiving a lower index .", "the opinions expressed by the authors do not necessarily reflect the opinions of the chulalongkorn university , thailand , or the national health insurance fund , sudan .", "" ]
backgroundthe appropriate use of medicines is essential for the provision of quality health services , patient safety , and the rational use of health resources . in sudan , general practitioners ( gps ) provide 80 % of insured patients health services . pharmaceutical service costs have been increasing since 2010.objectiveswe aimed to use the world health organization ( who ) and international network for the rational use of drugs prescribing indicators to assess prescription quality among gps in different types of primary healthcare centers ( phccs ) within the national health insurance fund ( nhif ) in gezira state , sudan.methodwe followed established who guidelines to conduct a cross - sectional retrospective study . the study was carried out over 6 months and involved 197 gps with valid prescriptions , representing 90 % of the total study population of 220 gps . we collected a systematic random sample of 100 prescriptions for each gp and used stata 12 to analyze the 19,700 prescriptions.resultsthe mean standard deviation number of medications was 2.55 1.32 per patient ; 46.32 % of drugs prescribed were generics ; 54.71 % of prescriptions were for antibiotics and 12.84 % were for injectable formulations ; and 81.19 % of prescribed medicines were from the nhif medicines list . the overall index of rational drug prescribing ( irdp ) indicator was 3.39 , and the average cost per prescription was 40.57 sudanese pounds ( sdg ) . disregarding prescriptions for antibiotics , the prescribing quality of gps in nhif facilities was farther from optimal prescribing practice than those in state ministry of health - owned facilities and facilities owned by private groups , universities , and non - governmental organizations.conclusionthe present study provides strong evidence of irrational prescribing practice among gps , with significant disparities , particularly in terms of antibiotic overuse , generic drug underuse , and adherence to the nhif medicines list .
[ "blunt traumatic infrarenal aortic injuries are rare , with a few case reports in the literature . this article presents the case of a young woman found to have an intimal flap in the infrarenal abdominal aorta after a car accident , and the injury progressed to a pseudoaneurysm over 3 months .", "a 47-year - old woman with a history of hypertension and smoking was involved in a high - speed motor vehicle accident and presented to the emergency department with back pain . what appeared to be either an intimal flap or a small amount of contrast extravasation outside of the infrarenal aorta could be seen . therefore , an open replacement of her infrarenal aorta was performed using a dacron 22 mm graft . in the operating room , operative repair was recommended , but the patient s aorta measured only 18 mm at the aortic bifurcation and was too small for even the smallest endovascular stent graft available at our institution .", "this case report highlights the need for delayed imaging for even minor intimal flaps or small aortic injuries after trauma , since progression does occur . blunt abdominal aortic trauma occurs in only 0.040.1% of all nonpenetrating traumas [ 3 , 4 ] . and only one study has compared conventional open repair with endovascular repair for blunt injuries of the abdominal aorta and found similar results in both groups . endovascular repair is generally favored since the injuries tend to be focal and discrete , making them quite amenable to a short graft .", "" ]
blunt traumatic infrarenal aortic injuries are unusual , and the formation of a delayed pseudoaneurysm of the aorta is even more rare . in this report , a young woman developed a small intimal flap of the infrarenal aorta after a motor vehicle accident which progressed into a 3 cm pseudoaneurysm after 3 months . operative repair was successful and the patient recovered . this case illustrates the importance of repeat imaging of small blunt aortic injuries since progression can occur .
[ "strains carrying proa - tev - rpt1 were grown in 6 l of sd medium to od600 0.8 to 1.2 . bp1 was then released from the resin by incubating with actev protease ( invitrogen ) at 2.5 unit / l culture in proteasome buffer containing 2 mm atp and protease inhibitors for 1 hr at 30c . resins were collected at 900 g for 2 min at 4c and washed with proteasome buffer containing 50 mm nacl three times , followed by a final wash with proteasome buffer alone . cells were harvested , washed once with ice - cold water and drop - frozen in liquid nitrogen . frozen yeast samples were then ground using an mm301 grinding mill ( restch ) under liquid nitrogen following manufacturer s instructions , or using a mortar and a pestle as previously described24 . eluates were concentrated using ultrafree-0.5 centrifugal filter device with 30 kda nmwl ( millipore ) .", "strains carrying proa - tev - rpt1 were grown in 6 l of sd medium to od600 0.8 to 1.2 . bp1 was then released from the resin by incubating with actev protease ( invitrogen ) at 2.5 unit / l culture in proteasome buffer containing 2 mm atp and protease inhibitors for 1 hr at 30c . resins were collected at 900 g for 2 min at 4c and washed with proteasome buffer containing 50 mm nacl three times , followed by a final wash with proteasome buffer alone . cells were harvested , washed once with ice - cold water and drop - frozen in liquid nitrogen . frozen yeast samples were then ground using an mm301 grinding mill ( restch ) under liquid nitrogen following manufacturer s instructions , or using a mortar and a pestle as previously described24 . eluates were concentrated using ultrafree-0.5 centrifugal filter device with 30 kda nmwl ( millipore ) .", "", "" ]
substrates of the proteasome are recognized and unfolded by the regulatory particle ( rp ) , then translocated into the core particle ( cp ) to be degraded1 . a hetero - hexameric atpase ring , containing subunits rpt1-rpt6 , is situated within the base subassembly of the rp1 . the atpase ring sits atop the cp , with the rpt c - termini inserted into pockets in the cp26 . we have identified a novel function of the rpt proteins in proteasome biogenesis through deleting the c - terminal residue from each rpt . our results indicate that assembly of the hexameric atpase ring is templated on the cp . we have also identified an apparent intermediate in base assembly , bp1 , which contains rpn1 , three rpts , and hsm3 , a chaperone for base assembly . the rpt proteins with the strongest assembly phenotypes , rpt4 and rpt6 , were absent from bp1 . we propose that rpt4 and rpt6 form a nucleating complex to initiate base assembly , and that this complex is subsequently joined by bp1 to complete the rpt ring . our studies show that assembly of the proteasome base is a rapid yet highly orchestrated process .
[ "worldwide , head injury is the single largest cause of death and disability following an injury . most patients with severe traumatic brain injuries ( tbi ) in developing countries are discharged to home - based care due to lack of rehabilitative facilities and health insurance . however , resources have not been diverted adequately by governments toward prevention , management and rehabilitation of head injuries in lamic such as india . those patients who are discharged in an unconscious state are particularly difficult to manage at home and are prone to decubitus ulcers , respiratory infections , inadequate nutrition , and physiotherapy . head injury is the leading cause of disability in people under 40 , severely disabling 150200 people per million annually . in 2005 the burden of head injury is greatest in low- and middle - income countries ( lamic ) , where 85% of the world 's population live . patients , who remain unresponsive to the environment even though their eyes may be open , are considered to be in a vegetative state ( vs ) . a persistent", "in this retrospective study carried at one trauma center in india , a prospectively maintained neurotrauma registry was queried from may 2010 to february 2013 for patients who had severe traumatic brain injury glasgow coma score ( gcs 8) at admission and had a motor response of m5 or lower on the gcs at discharge . unconsciousness was described as patients with a motor score of m5 or lower on the gcs irrespective of the verbal ( v ) or eye ( e ) response . the questions asked were : ( 1 ) is the patient alive ? ( 2 ) if alive , is the patient responding to commands ( conscious ) ? ( 3 ) if the patient is conscious , is he able to perform activities of daily living like feeding himself , going to toilet independently and going to preinjury occupation ? if the family members replied that patient had gone back to preinjury occupation it was considered as glasgow outcome scale ( gos ) 1 , if patient was able to perform activities of daily living , but not able to go back to work it was considered as gos 2 , if patient was conscious but not able to do activities of daily living , it was considered as gos 3 . if a patient remained unconscious , it was gos 4 and if the patient had died it was gos 5 . demographic and clinical data was analyzed , and outcome assessed at 6 months after injury using a telephonic questionnaire . gos 13 was considered as the unfavorable outcome and gos 45 was considered as a good outcome .", "average hospital stay was 24.31 days ( range : 864 days ) and was 16.71 days for m5 , 20.63 days for m4 , 26.33 days for m3 , 30.59 days for m2 and 16.3 days for m1 patients [ table 1 ] . mortality and outcome at 6 months with respect to motor scores at the time of discharge the discharge motor score was m5 in 32 ( 19.3% ) , m4 in 44 ( 26.5% ) , m3 in 59 ( 35.5% ) , m2 in 44 ( 26.5% ) and m1 in 9 ( 5.4% ) . of these 166 ( 10.9% ) were unconscious ( motor response m5 on the gcs or lower ) at discharge from the hospital . 54 ( 52.9% ) patients had died and 32 ( 31.4% ) remained unconscious ( vegetative ) at 6 months . 100% of m1 , 90.6% of m2 , 94.3% of m3 , 72.2% of m4 , and 60% of m5 patients had an unfavorable outcome at 6 months . only 16 patients ( 15.7% ) had a good outcome ( gos 12 ) at 6 months post injury .", "gcs has remained a robust scale for assessment and prognostication in tbi and the motor score ( m response ) continues to have the highest predictive value within the gcs . the outcomes of these patients have also not been studied properly . in our study , patients with m2 motor response had the longest hospital duration with unfavorable outcome occurring in 90% of these patients at 6 months . 54 ( 52.9% ) patients ( who were unconscious at discharge ) had died and 32 ( 31.4% ) remained unconscious ( vegetative ) at 6 months with only 16 patients ( 15.7% ) having good outcome ( gos 12 ) at 6 months . our study had a reasonable follow - up of 61.4% of the patients at 6 months and showed the poor outcomes in this subgroup of patients . this study also shows that the majority of the patients ( nearly 85% ) who are discharged in an unconscious state will either die or become vegetative . furthermore , a significant number ( 10.9% in our study ) are discharged in the unconscious state . as all studies are based on admission gcs , it is also often not possible to assess how many patients remained unconscious at the time of discharge and became vegetative at 6 months . interestingly , however , there are no studies on the outcome of patients who are discharged from the acute care facility in this unconscious state .", "this is the only study of its kind on patients who remain unconscious at discharge following severe tbi and reveals that around 50% will die , and another 30% become vegetative within 6 months of discharge ." ]
introduction : it is well - known that severe traumatic brain injuries ( tbi ) have a poor outcome . however , what is not well - known is the outcome for those who survive but remain unconscious at the time of discharge from the hospital.aims and objectives : to assess the outcome of severe tbi patients who have a motor response of m5 or lower on the glasgow coma score ( gcs ) at discharge from a single centre in india.materials and methods : in this retrospective study carried at one trauma centre in india , a prospectively maintained neurotrauma registry was queried from may 2010 to february 2013 for patients who had severe traumatic brain injury ( gcs 8) at admission and had a motor response of m5 or lower on the gcs at discharge . demographic and clinical data were analyzed , and outcome glasgow outcome scale ( gos ) assessed at 6 months using a telephonic questionnaire.observations and results : there were a total of 1525 patients with severe tbi in the study period . of these 166 ( 10.9% ) were unconscious ( motor response m5 or lower on the gcs ) at discharge from the hospital . 139 were males and 27 females with a mean age of 33.9 years . after a mean hospital stay of 24.31 days , the discharge motor score was m5 in 32 ( 19.3% ) , m4 in 44 ( 26.5% ) , m3 in 59 ( 35.5% ) , m2 in 44 ( 26.5% ) , and m1 in 9 ( 5.4% ) . telephonic follow - up was available in 102 ( 61.4% ) of the patients . 54 ( 52.9% ) patients had died and 32 ( 31.4% ) remained unconscious ( vegetative ) at 6 months . only 16 patients ( 15.7% ) had a good outcome ( gos 12 ) at 6 months following an injury.conclusions:this is the only study of its kind on patients who remain unconscious at discharge following severe tbi and reveals that around 50% will die and another 30% remains vegetative at 6 months of discharge . only a small percentage ( 15% in our study ) will become conscious and partially integrated in the society .
[ "the current paper reviews the characteristics and health benefit of highly marbled beef from wagyu and hanwoo cattle . in fact , meat has played a crucial role in human evolution of a healthy and well balanced diet ( pereira and vicente , 2013 ) . their marbling has been increased over many decades to meet domestic consumer preferences . in both countries , furthermore , meat plays a pivotal role in nutritious diets . high quality marbled beef not only has excellent eating quality , but also contains a lot of beneficial fatty acids ( troy et al . , 2016 ) . in this regard , in the past , fat was not given a good image in its role towards human health , although fat is an important energy resource for human . highly marbled beef is greatly prized for traditional meat cooking methods such as sukiyaki for japanese and gogigui for korean . because of these demands , the use of heifers and steers instead of bulls , intensive feeding system , and genetic ability of wagyu and hanwoo cattle have resulted in greater fat deposition in these breeds compared to european breeds . as intramuscular fat ( imf ) improves beef quality at least in juiciness and flavor ( hornsterin and wasserman , 1987 ; wheeler et al . , 1994 ) although beef has these three functions , the main food in both japan and korea is boiled rice while beef is a side dish .", "in this review , wagyu and hanwoo are used to describe the japanese black breed and the brown coat color hanwoo , respectively . in 2013 , a total of 2.64 million heads of cattle were fed for beef production in japan . the average live and carcass weights of hanwoo cattle at slaughter ( 26 - 30 mon of age ) were 719 kg and 430 kg , respectively ( kape , 2015 ) . approximately 1.71 million heads were japanese black cattle ( maff , 2013 ) , and approximately 873,400 were holstein cattle . the total number of slaughter cattle was 1,007,000 , including 883,593 hanwoo cattle , 66,485 holstein cows , and 56,923 holstein heifers and bulls ( kape , 2015 ) . the number of cattle farming households was 99,858 , including 89,403 hanwoo farmers ( kape , 2015 ) . during the last decade , all four types of wagyu cattle have played important roles locally and in the history of mixed farming .", "hanwoo beef with qg 1 or 1 is considered as a premium class of beef in korea . the korean carcass grading system presently has three levels of yield grade ( yg ) for meat amount ( a , b , and c ) and five levels of meat quality grade ( qg ) ( 1 , 1 , 1 , 2 , and 3 ) ( kape , 2016 ) . for beef quality grading in japan , wagyu carcasses are evaluated by accredited graders from the japan meat grading association ( jmga ) in accordance with beef carcass grading standards . the bms of korean carcass grading system has been changed by the addition of marbling number . in 1992 , when the carcass grading system was established for the first time in korea , the bms had only 5 numbers ( 1 to 5 ) with 3 qg ( 1 , 2 , and 3 ) . however , in 1997 , new qg 1 was added with new bms no . 6 and no . of hanwoo cattle slaughtered in 2015 , 10.0% were qg 1 , 26.4% were qg 1 , and 31.4% were qg 1 ( kape , 2016 ) . furthermore , in 2004 , another new qg 1 was added with new bms no . 8 and no .", "therefore , the sensory of tenderness could be qualitatively affected by histological difference in marbling due to difference in tissue disorganization extent . this marbling quality contributes to the tenderness of beef because imf deposits are found mainly between muscle fiber bundles , resulting in the disorganization of perimysium connective tissue ( nishimura , 2015 ; sasaki et al . , 2012 ) . ( 2009 ) have reported that the imf contents in the longissimus muscle of wagyu , german angus , belgain blue , and holstein friesian are 23.3% , 4.4% . the plentiful marbling of wagyu and hanwoo beef has attracted attention . in both japan and korea , recently , korea also began to discriminate between fine and coarse marbling in hanwoo beef . the value of cattle carcasses is determined by a qg which considers marbling as a decisive determinant . since the liberalization of beef importation although imf content is the most dominating determinant of beef quality , the imf content is not the only parameter that decides the quality grade of beef carcass .", "there are several types of fatty acids : 1 ) monounsaturated fatty acids ( mufa ) , 2 ) polyunsaturated fatty acids ( pufa ) , and 3 ) saturated fatty acid ( sfa ) . sfa : saturated fatty acids , mufa : monosaturated fatty acids , pufa : polysaturated fatty acids . the difference in fatty acid composition might be attributed to the influence of different diets , forage , and grain feeding , although fatty acid profile in ruminants is not a direct reflection of the dietary fatty acid composition due to hydrogenation by rumen microorganism ( enser et al . , 1998 ) . it is generally accepted that the concentration of oleic acid in beef adipose tissue is dependent on scd expression and activity . sfa : saturated fatty acids , usfa : unsaturated fatty acids , mufa : monosaturated fatty acids , pufa : polysaturated fatty acids . 1999b ) have reported interesting correlations between scd enzyme activity and fatty acid composition in bovine adipose tissue .", "interest in beef fat and fatty acids has been increasing , especially in highly marbled beef such as wagyu and hanwoo because fatty acids composition in the diet have impact on human health . consumption of fat and cholesterol has been reported to be linked to cardiovascular disease , obesity , and cancer ( micha et al . , 2010 ; many research studies have shown that the imf of wagyu and hanwoo beef contains a lot of mufa that could prevent arteriosclerosis . thus , although some consumers in japan and korea consider highly marbled wagyu and hanwoo beef as being unhealthy , there is no scientific evidence to indicate that beef that is high in oleic acid will increase risk factors for diseases ( smith , 2016 ) . consequently , the role of animal fats in the diet should be re - evaluated because scientists around the globe increasingly doubt the validity of the so called diet - heart hypothesis in this regard , inclusion of high fat foods with superior sensory properties in a balanced diet such as highly marbled wagyu and hanwoo beef is likely to gain wider acceptance as a well - being food in the near future . these health recommendations are obviously in conflict with the health of highly marbled wagyu and hanwoo beef .", "in japan and korea , highly marbled wagyu and hanwoo cattle are greatly prized for traditional meat cooking methods . great attention has been paid to more accumulation of imf to produce high quality grade beef . literature suggests that imf content varies on the basis of feeding time , finishing diet , and breed type . many researches have shown that wagyu and hanwoo cattle have high potential of accumulating imf and producing highly marbled beef . they are heart - healthy dietary fat because they can lower ldl - cholesterol while increasing hdl - cholesterol . clinical trials have also indicated that highly marbled beef does not increase ldl - cholesterol and that beef high in oleic acid can consistently increase hdl - cholesterol . finally , literatures have concluded that high - oleic acid beef such as wagyu and hanwoo beef may reduce risk factors for cardiovascular diseases ." ]
this review addresses the characteristics and health benefit of highly marbled wagyu and hanwoo beef . marbling of wagyu and hanwoo beef has been increased in japan and korea to meet domestic consumer preferences . wagyu and hanwoo cattle have high potential of accumulating intramuscular fat ( imf ) and producing highly marbled beef . the imf content varies depending on the feeding of time , finishing diet , and breed type . imf increases when feeding time is increased . the rate of imf increase in grain - fed cattle is faster than that in pasture - fed cattle . fatty acid composition are also different depending on breeds . highly marbled wagyu and hanwoo beef have higher proportions of monounsaturated fatty acid ( mufa ) due to higher concentrations of oleic acid . mufas have little effect on total cholesterol . they are heart - healthy dietary fat because they can lower low - density lipoprotein ( ldl)-cholesterol while increasing high - density lipoprotein ( hdl)-cholesterol . clinical trials have indicated that highly marbled beef does not increase ldl - cholesterol . this review also emphasizes that high oleic acid beef such as wagyu and hanwoo beef might be able to reduce risk factors for cardiovascular disease .
[ "the fe(ii ) complex with tptz has a twice higher molar absorptivity coefficient ( 2.2 10 l mol cm ) than the fe(ii ) complex with 1,10-phenanthroline ( 1.1 10 l mol cm ) . we report a simple and cost - effective spectrophotometric method for the reliable analysis of nac and mpg in pharmaceutical formulations . the method is also based on the coupled redox - complexation reaction between nac or mpg and fe(iii ) but uses 2,4,6-tripyridyl - s - triazine ( tptz ) as the chromogenic reagent . mpg is primarily used in the treatment of cystinuria , but studies have shown that mpg can be used as a chelating , cardioprotecting , and radioprotecting agent , as well as an antidote to heavy metal poisoning . a number of electrochemical [ 59 ] , fluorometric [ 1012 ] , chemiluminescence [ 1315 ] , and liquid chromatographic [ 1618 ] methods have been developed for the determination of nac and mpg in biological samples and pharmaceuticals . a coupled redox - complexation reaction has been reported for the spectrophotometric analysis of nac and mpg using 1,10-phenanthroline as the chromogenic reagent . in the present work , collins et al . have introduced tptz as chromogenic reagent for determination of fe(ii ) . intravenous and oral administration of nac have been extensively used in the management of paracetamol ( acetaminophen ) poisoning .", "two different pharmaceutical formulations of nac were analysed by the present spectrophotometric method , that is , fluimukan 200 mg granules , and fluimukan akut 600 mg dispersible tablets ( lek , ljubljana , slovenia ) . nac and mpg concentrations in pharmaceutical preparations were determined by using daily prepared calibration curves . the absorbance of the produced fe(ii)-tptz complex was measured at = 593 nm against a blank solution , prepared in the same manner with 1.0 ml water instead of 1.0 ml sample solution . the eleven solution of every analyte were prepared for the concentration range from 1.0 m to 100.0 m . m ) was used to cover the ph range 3.24.0 . for solutions of ph 1.0 and 2.0 , these solutions were further diluted quantitatively with water to obtain suitable concentrations for the analysis by the proposed spectrophotometric method .", "the proposed method is based on the coupled redox - complexation reaction . in the first ( redox ) step of the reaction ( see ( 1 ) ) , rsh compound ( nac or mpg ) reduces fe(iii ) to fe(ii ) whereas rsh molecules themselves oxidize to thiyl radicals rs which combine to form the disulfide rssr . in the second step of the reaction ( see ( 2 ) ) , in situ formed fe(ii ) is immediately complexed by 2 molecules of tptz to form the deep - blue coloured , highly stable fe(tptz)2 \n complex which absorbs light at \n max at 593 nm . the effect of some possible interfering cations and anions on the analysis of a fixed concentration of 40.0 m for nac and mpg was investigated for the maximum molar ratio of foreign ions . these results indicate that the proposed method is accurate for the determination of nac and mpg in their commercially available pharmaceutical preparations without any significant interference by common pharmaceutical excipients which do not absorb light in the visible region . the results of the present study confirm these previous results for the drugs nac and mpg serving as the reducing agents . in the literature , we were not able to find the standard reduction potential for nac and mpg . this means that the proposed method with the tptz is selective for the determination of nac and mpg . the influence of excipients that can commonly accompany nac and mpg in pharmaceutical formulations was also studied .", "undoubtedly , hplc is one of the most widely used techniques in routine analysis of pharmaceuticals , but it involves expensive instrumental set which many laboratories in developing and underdeveloped countries can not afford . the proposed equilibrium spectrophotometric method based on the coupled redox - complexation reaction of the thiol drug nac or mpg with fe(iii ) and tptz can be applied in every analytical laboratory as a reliable method for the determination of nac or mpg in pharmaceutical preparations . due to the use of tptz regular excipients and additives present in the pharmaceutical preparations of nac and mpg do not interfere in this method . the coloured fe(tptz)2 \n complex is stable in an extended period of time up to 24 hours ." ]
a simple spectrophotometric method for the determination of n - acetyl - l - cysteine ( nac ) and n-(2-mercaptopropionyl)glycine ( mpg ) in pharmaceutical preparations was developed , validated , and used . the proposed equilibrium method is based on a coupled two - step redox and complexation reaction . in the first step , fe(iii ) is reduced to fe(ii ) by nac or mpg . subsequently , fe(ii ) is complexed with 2,4,6-tripyridyl - s - triazine ( tptz ) . several analytical parameters of the method were optimized for nac and mpg analysis in the concentration range from 1.0 m to 100.0 m . regression analysis of the calibration data showed a good correlation coefficient ( 0.9999 ) . the detection limit of the method was 0.14 m for nac and 0.13 m for mpg . the method was successfully applied to quantify nac and mpg in pharmaceutical preparations . no interferences were observed from common pharmaceutical excipients .
[ "management of arteriovenous malformations ( avms ) remains challenging because of their unpredictable behavior and high recurrence rate if treated by curettage alone without inadequate ligation of the feeder vessels . we present our experience in treating palatal vascular malformation using direct ethanol sclerotherapy as a cheep therapeutic modality for treatment of deeply seated vascular lesion . these malformations grow proportionately with age , and may involve multiple anatomical spaces and encase critical neuromuscular structures , associated with nerve damage , massive bleeding , and deformity . vascular malformation is known as one of the major therapeutic problem even to the most experienced clinicians . sclerotherapy is an effective , conservative and low cost technique for the treatment of benign vascular lesions , included vascular malformation .", "treatment success was determined clinically by reduction in lesion size , ability of the patient to chew and to clean his teeth without bleeding , patient experience to pain and by patient satisfaction . twenty one - year old saudi male patient presented to the department of oral and maxillofacial surgery clinic at king abulaziz university complaining of swelling on the right side of the face ( figure 1a ) . the patient was advised to have ethanol directly injected into the lesion as surgical excision was hazardous and difficult to achieve . the procedure and possible complications were explained to the patient and family and they agreed to that option . under general anesthesia using fibro optic intubations , as the lesion was approaching the soft palate and there was a fear that routine nasal intubations could be hazardous to the airway , contrast medium was injected toward the engorged vascular lesion using a no . patient disagree with that option and disappear for 18 months and returned back with severe gingival inflammation around the whole right maxillary quadrant which appeared covered by heavy calculus as he could not brush his teeth because of bleeding that he described as extensive ( figure 1c ) .", "for example : surgical excision can lead to significant loss of motor function , cosmetic problems , nerve damage , or massive bleeding and the complicated anatomy of the face and neck , may result in significant loss of motor function , cosmetic problems , nerve damage , or massive bleeding if surgery is adopted . the use of sclerotherapy in the management of vascular anomalies has increased and replaced the traditional role of surgical therapy , especially for the venous lesions that are surgically difficult or at inaccessible areas . ethanol is used most of often due to its low cost , antiseptic quality , wide availability and easy of use ; however , it requires general anesthesia because the procedure is very painful . absolute ethanol was adopted as a new scleroagent for this complex form of venous defects to improve overall treatment results with acceptable morbidity and recurrence rates . it has the advantage of low cost , no external scaring , and few complications compared to surgical treatment .", "vascular malformations were treated with direct percutaneous injection of absolute ethanol , which resulted in remission , and alleviation of their symptoms , with no major complications . this technique provides a simple , low cost and reliable alternative treatment for venous malformation in the face and neck . absolute ethanol sclerotherapy can deliver excellent results as an independent therapy to the infiltrating type of extra - truncular form of vm . complications can occur but are rare . the morbidity involved should be clearly understood and accepted by the patient and family , and the risk of acute and chronic complications , either major or minor ," ]
arteriovenous malformation is treated by variety of techniques over the years . sclerotherapy is considered an effective and conservative technique for the treatment of benign vascular lesions and replaced the traditional role of surgical therapy , especially for the venous lesions that are surgically difficult or at inaccessible areas . absolute ethanol was adopted as a new sclerosant agent for this complex form of venous defects to improve overall treatment results with acceptable morbidity and recurrence rates . sclerotherapy has the advantage of no external scaring , low cost , and few complications in comparison to the surgical treatment .
[ "the aim of this study was to characterize the risk factors for development of rickets in elbw infants fed with high mineral containing preterm formula . however , it is often practically difficult to achieve ideal nutrition support in sick elbw infants , the current incidence of rickets in elbw infants is unknown , and the relationship of the severity of overall illness and degree of prematurity in this population is unclear . since mineral enriched formula for the preterms began 30 yr ago , it is the standard practice to provide minerals in an attempt to reach in utero mineral accretion rates . in theory , under ideal conditions , the adventage of high mineral intake formulas should be associated with a marked reduction of rickets . in the 1980s , the prevalence of rickets in extremely low birth weight ( elbw ) infants was around 50% and was 17% for fractures ( 1 , 2 ) . there is little information , however , beyond 1985 , concerning the incidence of rickets in extreme prematurity and factors that relate to its occurrence . after introduction of a high mineral containing diet in the late 1980s , the prevalence decreased to 30% or lower ( 3 , 4 ) .", "as a retrospective case - control study , medical records of 55 elbw infants admitted into the severance children 's hospital nicu from 2004 to 2008 that survived until 1 month of age were reviewed . moderate / severe bpd was defined in infants requiring either 28 days of supplemental oxygen therapy with oxygen , nasal continuous positive airway pressure ( cpap ) or positive pressure ventilation at 36 weeks postmenstrual age or discharge , whichever came first , whose gestational age was younger than 32 weeks , or at 56 days postnatal age or discharge , whichever came first , in infants whose gestational age was older than 32 weeks . all infants had their serum alkaline phosphatase ( alp ) , calcium ( ca ) and phosphate ( p ) levels reported weekly and bone screen radiography at 1 month of age . for nutritional care , fortified human milk ( ca 131 mg/100 kcal , p 71 mg/100 kcal ) or a mineral fortified preterm formula ( ca 112 - 141 mg / kcal , p 52 - 63 mg / kcal ) was used . during parenteral nutrition , ca , p and multivitamins with trace minerals were added to parenteral nutrition , appropriately . severe pnac was defined as elevation of db greater than 4.0 mg / dl for more than 1 month and aspartate aminotransferase ( ast ) and alanine aminotransterase ( alt ) greater than 60", "the present retrospective review of database in this study was approved by the institutional review board of the yonsei university health system , severance hospital ( approval no . , 4 - 2012 - 0157 ) .", "twenty - four elbw infants ( 26.3 1.9 weeks , 792 99 g ) were diagnosed as rickets of prematurity , and 31 infants without rickets ( 27.2 2.3 weeks , 871 93 g ) were the control group . rickets of prematurity was diagnosed in 43.9% of elbw infants and fracture in 13% . for the rickets group , 7 infants ( 29% ) showed g1 , 14 infants ( 58% ) g2 and 3 infants ( 13% ) g3 . common neonatal illnesses such as hmd , air leak , nec , rop , ivh and periventricular leucomalacia ( pvl ) were not different between the groups . in multiple regression analysis after adjustment of gestation and birth weight , rickets in elbw infants significantly correlated with severe pnac ( or 18.5 ; 95% ci , 1.1 - 285 ; p = 0.042 ) and moderate / severe bpd ( or 3.2 ; 95% ci , 1.2 - 26.5 ; p = 0.04 ) ( table 3 ) . the mean level of peak alp was significantly higher in the rickets group than the control group ( 952.2 413.8 vs 524.7 158.2 the duration of hospitalization and parenteral nutrition were significantly longer in the rickets group versus the control group ( table 1 ) . in univariate analysis , elbw infants with rickets had a significantly higher occurrence of pda ( p = 0.025 ) , pnac ( p = 0.041 ) , severe pnac ( p = 0.013 ) , bpd ( p = 0.019 ) , and moderate / severe bpd ( p = 0.012 ) ( table 2 ) . the cumulative amounts ( either enteral or parenteral ) of ca and p administration during hospitalization were not different between the groups . for the rickets group in comparison with the control group , mean days on oxygen and ventilator use were significantly longer ( p < 0.05 ) .", "we suggest that in elbw infants with severe pnac or moderate / severe bpd , aggressive prevention or treatment for rickets and fractures can be instituted earlier in the course of management . it is also the first to characterize and compare risk factors and neonatal morbidities for rickets of prematurity in elbw infants . this is the first study to focus on the incidence of rickets in elbw infants after 2 decades of fortified formula use in korea ." ]
risk factors for rickets of prematurity have not been re - examined since introduction of high mineral formula , particularly in elbw infants . we analyzed the incidence and the risk factors of rickets in extremely low birth weight ( elbw ) infants . as a retrospective case - control study from 2004 to 2008 , risk factors were analyzed in 24 patients with rickets versus 31 patients without . the frequency of rickets in elbw infants was 24/55 ( 44% ) . infants with rickets were diagnosed at 48.2 16.1 days of age , and improved by 85.3 25.3 days . by radiologic evaluation , 29% were grade 1 rickets , 58% grade 2 and 13% grade 3 . in univariate analysis , infants with rickets had significantly higher incidence of patent ductus arteriosus , parenteral nutrition associated cholestasis ( pnac ) , severe pnac and moderate / severe bronchopulmonary dysplasia ( bpd ) . in multiple regression analysis , after adjustment for gestation and birth weight , rickets significantly correlated with severe pnac and with moderate / severe bpd . serum peak alkaline phosphatase levels were significantly elevated in rickets ( p < 0.001 ) . in elbw infants , the incidence of rickets of prematurity remains high and the incidence of severe pnac and moderate / severe bpd was significantly increased 18 and 3 times , respectively .
[ "kyphosis is a progressive curvature of the thoracic spine , which results in rounding or bowing of the back . a curved spine accompanied by restricted neck motion and poor lung reserve present challenges for an ophthalmic surgeon , who is used to patients neck and head resting flat on the operating table and the eye in the horizontal position . intraoperative difficulties include poor view , inability to maneuver surgical instruments properly and constant threat of elevated vitreous pressure . several innovative solutions have been published , including the maximal reverse trendelenburg position and pillows under the head and neck , use of a donut and wedge - shaped head positioner , allowing patients to remain in the upright sitting position while their head is positioned horizontally in a modified waiting room chair , performing surgery while standing [ 5 , 6 ] , using a 4-section orthopedic operating table , or laying the patients on their sides . however", "a 49-year - old obese male with controlled secondary glaucoma needed cataract surgery in the right eye . 2 ) . while trying to focus the microscope , it became evident that by grasping the eye at the inferior limbus with a fine forceps and pulling it upwards , it could be moved to a more desirable horizontal position . the patient could only recline to about 40 from the vertical axis despite maximal reverse trendelenburg position and a number of pillows under his back , neck , head and legs ( fig . the past ocular history was positive for recurrent uveitis and glaucoma shunt surgery in the right eye . the anesthesiologist was reluctant to use general anesthesia because of the patient 's disability and poor health . in the operating room ,", "patients with kyphosis may present several unique challenges to an eye surgeon , the foremost being the inability to lay the head and neck in the ideal horizontal position . a wedge - shaped pillow with a built - in donut for the positioning of the head has been used by some surgeons . the surgeon can still sit on the preferred temporal side of the patient and perform intraocular surgery of choice . with this maneuver we have found that a single retraction suture at the inferior limbus can rotate the eye to any desired position .", "the authors have no financial or proprietary interest in the materials described in the article ." ]
we describe a 49-year - old man with advanced kyphosis and dense cataract , who could only recline to about 40 from the vertical axis despite a maximal reverse trendelenburg position and pillows under the head , neck , shoulders and knees . with a single corneal retraction suture at 6 o'clock , the eye could be rotated horizontally , which enabled the surgeon to perform a complex cataract surgery despite prior glaucoma shunt , posterior synechiae , a small pupil and the need to stain the capsule . as the eye can be brought into any desired position with a retraction suture , patients with kyphosis or other conditions that prevent them from assuming a supine position can still have safe intraocular procedures . this maneuver reduces the need to tilt patients to an uncomfortable position that may cause pain , increased breathing difficulty and elevated posterior vitreous pressure .
[ "we have also shown that bis- and tris ( indolyl)alkanes can be synthesized in presence of bronsted acid in water . in continuation of our research in hydrated media , herein , we wish to disclose the dual catalytic activity of the system i2-sds - h2o which behaves as a lewis acid for the cleavage of 2,3-diaza-1,3-butadiene , 1-aza-1,3-butadienes , and oximes to produce carbonyls and amines , and the resulting reaction mixture reacts with indoles to produce bis ( indolyl)alkanes in situ at room temperature under neutral conditions . , we reported that surfactant- ( sds- ) mediated cleavage of c = n bonds could be achieved with acetic anhydride and surfactant - i2-water can be used for the deprotection of imines to carbonyls . , bisindoles are recently emerging as extremely important class of compounds because of their novel antibacterial and anticancer activities [ 1921 ] .", "the system was also applied to the reaction of 1-aza-1,3-butadienes 7 with indole ( 2 ) which produced bis ( indolyl)alkanes 8 in very good yield eliminating aryl amine in the reaction mixture ( table 4 ) . it was found that the best result was obtained by the application of 15 mol% of i2 containing sodium dodecyl sulphate ( sds ) and water at room temperature ( entry 1 , table 1 ) . in absence of the catalyst no formation of 3a all the products were characterized by their ir , h nmr , c nmr , and mass spectral data and also by comparison with the literature report ( scheme 2 ) [ 24 , 25 ] . in order to further explore the efficiency of the i2-sds - h2o system the reaction of the oximes 6 and indoles 2 was studied . when oximes ( 1 mmol ) and indole ( 2 mmol ) were allowed to react under the same reaction condition described earlier , bis - indolylalkanes formed ( table 3 ) . the product was filtered off and the filtrate was treated with benzaldehyde in ethanol . the resulted product was benzaldoxime , which proved the liberation of hydroxylamine during the reaction . i2-sds - h2o system was applied to the reaction of indole ( 2 ) and 2,3-diaza-1,3-butadiene derivatives ( table 2 , entries a", "in conclusion , we have shown the dual catalytic activity of i2-sds - h2o system which deprotects the azadienes , oximes , and azabutadienes and produces bis ( alkyl)indoles in situ when indole is present in the reaction medium . the two - step reaction can be carried out without using acid , transition metals , and organic solvents . besides , the reaction condition is mild and can be done in water under neutral condition which contributes to the criteria of green chemistry .", "chemical shifts are expressed in units relative to tetramethylsilane ( tms ) signal as internal reference . identical reaction condition was followed when 1-aza-1,3-butadienes and oximes were used as reactants . in this case , 2 mmol of indoles were used to react with 1 mmol of imines . the spectral data of the compounds are available in the supplementary material available online at doi : 105402/2012/635835 . 2,3-diaza-1,3-butadiene ( 1 mmol ) and indole ( 4 mmol ) were added and stirred in the presence of sodium dodecyl sulphate ( sds ) ( 0.02 g ) for the stipulated time . , 15 mol% of i2 was first dissolved in water ( 10 ml ) ." ]
a novel catalytic system consisting of i2-sds - h2o has been developed which cleaves 2,3-diaza-1,3-butadiene , 1-aza-1,3-butadienes , oximes and in presence of indoles in the medium uses the corresponding aldehyde products to produce bis(indolyl)alkanes in situ . this one pot simple and mild dual catalytic system works in water at room temperature under neutral conditions .
[ "parental drug misuse and its effects on children and families are policy priorities in the uk and elsewhere ( flavin & paltrow , 2010 ; hm government , 2010 ) . polydrug use is the norm among drug users in the uk , and benzodiazepine use is common ( bird & robertson , 2011 ; department of health ( england ) , 2007 ; hay , gannon , casey , & mckeganey , 2009 ; jones , mogali , & comer , 2012 ) . increased risks and harm , and a range of adverse effects are associated with long - term benzodiazepine use ( lader , 2011 , 2014 ; obrien , 2005 ) . however , existing research on drug use and parenting has tended to focus on opioids , opioid substitution therapy ( ost ) , or crack cocaine ( radcliffe , 2009 , 2011 ; rhodes et al . , 2010 ) , and in the case of pregnancy , also alcohol , nicotine , marijuana and amphetamines ( behnke & smith , 2013 ) . in this paper , we found no published literature which compared benzodiazepine and opioid dependence , from the perspective of parents , or expectant parents . therefore the aim of our study was to address this gap in the evidence and to undertake a comparative thematic analysis of the ways in which parents accounted for their use of opioids , ost and benzodiazepines during and after pregnancy . we examine accounts provided by polydrug - dependent parents about their use of , and dependence on , benzodiazepines as compared to ost .", "( carol , 9 months postnatal ) in contrast , while women occasionally noted adverse effects of benzodiazepine use , this was generally focused on pregnancy and risks to the unborn baby . this was a longitudinal , qualitative study involving 19 opioid - dependent service users over the course of approximately one year in order to examine changes over time in participants experiences with healthcare services , drug use and parenting . the potential harms associated with benzodiazepine use , including the potential for cognitive impairment and acute withdrawal symptoms , appeared little understood or acknowledged in most participant accounts . those women dependent on multiple substances ( the majority ) described a careful balance of trying to stabilise or reduce one or more prescriptions , whilst avoiding relapse to illicit drug use . a clear contrast between parents accounts of opioid and benzodiazepine use and dependence was that the latter were often framed as a legitimate method of managing anxiety , negative emotions and past trauma . thus , participants constructed benzodiazepine use and dependence as a legitimate means to help them regulate problem emotional states which might otherwise interfere with their ability to live a normal life and effectively parent their children . benzodiazepine use and dependence for women these narratives supported participants arguments that their benzodiazepine use , whether illicit or prescribed , was controlled and unproblematic .", "this was a longitudinal , qualitative study involving 19 opioid - dependent service users over the course of approximately one year in order to examine changes over time in participants experiences with healthcare services , drug use and parenting . there are local guidelines both for the management of substance misuse in pregnancy ( whittaker , 2003 ) , and parental substance use ( elbeg , 2013 ) . the truth , but rather as a resource through which to explore how parenting and drug use are understood , negotiated and mutually constructed ( bury , 2001 ; rhodes , bernays , & houmoller , 2010 ) . the study was carried out in scotland in an area with a mixed socio - economic profile , containing areas of significant deprivation . ost services for drug - dependent patients are delivered via primary care and specialist community - based substance misuse services . notably , a large number of patients in the area are prescribed benzodiazepines in addition to ost .", "participants , recruited via healthcare practitioners , were interviewed at around 2832 weeks gestation ; 23 months postnatal ; and 69 months postnatal . eleven reported heroin use in the 12 months prior to the first interview and thirteen reported benzodiazepine use during the study period . in five cases , diazepam was prescribed long - term alongside ost . all were receiving ost at the first interview , primarily methadone , with a minority prescribed buprenorphine or dihydrocodeine . inclusion criteria were opioid - dependence , being an expectant or recent parent , and > 18 years . semi - structured interviews , lasting between 45120 minutes , addressed participants social background , drug use , experiences with parenting , and involvement with services . five participants were first - time parents , fourteen other participants had between one and three children , aged 219 . this reflects the pattern of poly - drug use and prescribing practices in this geographical setting ( bird & robertson , 2011 ) . in total ,", "the present paper is based on analysis of two content codes : benzodiazepine use and methadone practice . this was supplemented by close reading of transcripts and thematic coding by authors ac and aw ( ritchie , spencer , & oconnor , 2003 ) . accounts were compared and contrasted and analytic themes were generated and agreed by the research team .", "participants gave informed consent and were provided with a 20 voucher for each interview completed .", "a common theme across parents accounts of all drug use was that their substance use helped to support their attempts to engage in normal daily life , providing a better context in which to undertake parenting . ( iona , antenatal ) women stressed a keen awareness that use of a range of substances might have negative effects on their babies . positive meanings were sometimes ascribed to ost which was portrayed as enabling parents to manage their opioid - dependence in a legal , safer and relatively more socially acceptable manner ( chandler et al . , 2013 ) . those women dependent on multiple substances ( the majority ) described a careful balance of trying to stabilise or reduce one or more prescriptions , whilst avoiding relapse to illicit drug use . this was particularly the case for parents who had only recently ceased use of illicit opioids:[t]he only way to have a normal life [ ] and keep a normal life to normality , to being able to live again is a methadone prescription .", "a common theme across parents accounts of all drug use was that their substance use helped to support their attempts to engage in normal daily life , providing a better context in which to undertake parenting . ( iona , antenatal ) women stressed a keen awareness that use of a range of substances might have negative effects on their babies . positive meanings were sometimes ascribed to ost which was portrayed as enabling parents to manage their opioid - dependence in a legal , safer and relatively more socially acceptable manner ( chandler et al . , 2013 ) . those women dependent on multiple substances ( the majority ) described a careful balance of trying to stabilise or reduce one or more prescriptions , whilst avoiding relapse to illicit drug use . this was particularly the case for parents who had only recently ceased use of illicit opioids:[t]he only way to have a normal life [ ] and keep a normal life to normality , to being able to live again is a methadone prescription .", "a clear contrast between parents accounts of opioid and benzodiazepine use and dependence was that the latter were often framed as a legitimate method of managing anxiety , negative emotions and past trauma . ( carol , 9 months postnatal ) in contrast , while women occasionally noted adverse effects of benzodiazepine use , this was generally focused on pregnancy and risks to the unborn baby . the potential harms associated with benzodiazepine use , including the potential for cognitive impairment and acute withdrawal symptoms , appeared little understood or acknowledged in most participant accounts . these narratives supported participants arguments that their benzodiazepine use , whether illicit or prescribed , was", "benzodiazepine use and dependence for women was frequently normalised : women described using prescribed and illicit benzodiazepines to manage anxiety , perform household chores or regulate sleep patterns . the potential harms associated with benzodiazepine use , including the potential for cognitive impairment and acute withdrawal symptoms , appeared little understood or acknowledged in most participant accounts . ( carol , 9 months postnatal ) in contrast , while women occasionally noted adverse effects of benzodiazepine use , this was generally focused on pregnancy and risks to the unborn baby . but , fae their angle , i m no , they must think i m a total madman , which i m no. ( stuart , 8 months postnatal ) stuart alludes to the existence of gendered stereotypes about benzodiazepine dependence suggesting that use among women and mothers is accepted , but that among men and fathers is seen as dangerous or evidence of severe personality dysfunction . while the other men in the study did not make this gendered link explicit , the four male participants who reported illicit use of benzodiazepines provided similar accounts in other ways .", "this longitudinal qualitative study explored accounts of poly - drug use within the context of pregnancy and parenting , highlighting differential understandings and practices surrounding benzodiazepine and opioid use . our findings support these recommendations , especially the need for enhanced education and training of both clinicians and patients , and extra provision of non - pharmacological interventions to promote the psychological and social functioning of parents on ost . our findings suggest a need for further preventative measures and targeted education to address benzodiazepine use and dependence within the context of pregnancy and parenting , especially in populations of parents engaged in ost programmes where stability on opioids may detract from issues associated with benzodiazepine use and dependence . reviews of benzodiazepine prescribing ( sirdifield et al . , 2013 ) , crucially , our analysis indicates important differences in the way opioid and benzodiazepine use are understood and narrated within the context of parenthood . unlike benzodiazepine use", "further qualitative exploration in different geographical areas and populations is needed , as it is likely that local or cultural contexts may shape the types of narratives expressed in respect of the range of substances consumed . this was an in - depth , qualitative exploration of the accounts of nineteen drug - dependent parents on ost in a specific geographical area . our findings may have limited applicability to opioid dependent parents who are not engaged in ost programmes . however , the contrasting accounts depicted here underline the importance of qualitative research in illuminating understandings about the meanings that drugs of addiction have for those who use them ( neale , allen , & coombes , 2005 ) . as such , our findings and conclusions should be read as indicative and suggestive rather than definitive .", "although long - term benzodiazepine use and dependence among opioid - dependent populations has been a topic of concern for some decades ( who , 1996 ) and is associated with increased risks and harm ( lader , 2011 , 2014 ) , research regarding the impact on pregnancy , parenting and family life has been limited ( acmd , 2003 ) . education and policy initiatives should pay greater attention to the kind of narratives and strategies that are employed in addressing benzodiazepine use and dependence within opioid dependent populations , especially in respect of the parenting and child welfare agenda . our findings suggest that parents frame benzodiazepine use and dependence as largely unproblematic , less stigmatising and more legitimate than ost . we suggest these divergent accounts can be understood as drawing on differing cultural meanings attached to ost and benzodiazepine use , which are reflected in policy and practice . as such , prevention ," ]
aimsto explore the ways in which opioid - dependent parents accounted for their use of opioids and benzodiazepines during and after pregnancy.methodslongitudinal qualitative interviews [ n = 45 ] with 19 opioid - dependent adults recruited in scotland , uk , were held during the antenatal and post - natal period . interviews focused on parenting and parenting support within the context of problem drug use and were analysed using a narrative informed , thematic analysis . findingsthe majority of participants described using benzodiazepines in addition to opioids . almost all indicated a desire to stop or reduce opioid use , whereas cessation or reduction of benzodiazepines was rarely prioritised . in stark contrast to opioid dependence , benzodiazepine dependence was portrayed as unproblematic , therapeutic and acceptable in the context of family life . whereas opioid dependence was framed as stigmatising , benzodiazepine use and dependence was normalised . an exception was benzodiazepine use by men which was occasionally associated with aggression and domestic abuse.conclusionsdrug-dependent parents attach different meanings to opioid and benzodiazepine use and dependence in the context of parenthood . divergent meanings , and stigma , may impact on stated commitment to stability or recovery from dependent drug - use . attention should be paid to the way in which policy and practice regarding ost and benzodiazepines reflects this divergence .
[ "the aim of this study was to explore the vascular and cardiac changes of opg and trail in experimental models of dyslipidemia and diabetes . epidemiological studies have shown that there is an association between circulating opg , trail , and cvd . , we hypothesized that dyslipidemia and diabetes , which are two well known risk factors for cvd , could modify the vascular and cardiac expression of opg and trail , leading to an increased opg / trail ratio at a tissue level . opg and trail are both members of the tnf superfamily , and they are widely expressed in different tissues , including the heart and the vessels , in health and disease states [ 4 , 5 ] . although initially opg actions seemed to be limited to bone metabolism and those of trail to host defense against tumors , recent studies have suggested that both molecules might actually be involved in cvd development and progression . in industrialized countries , cardiovascular disease ( cvd ) remains the predominant cause of morbidity and mortality .", "a total of 12 male c57bl/6j ( cnt ) mice and 24 male apolipoprotein e null ( apoe ) mice on a c57bl/6j background , aged 6 weeks , were studied for 14 weeks . at 6 weeks of age , circulating levels of opg and trail were measured in the sera by elisa ( r&d systems duoset # dy459 and # dy1121 ) . in half of the animals in each group , the gene expression of opg and trail was analyzed by real - time quantitative rt - pcr using the taqman system ( life technologies ) for opg and the sybr green system ( life technologies ) for trail . apoe mice were further randomized to saline ( apoe ) or streptozotocin ( apoe + dm ) , which were delivered intraperitoneally in five consecutive daily doses . in particular , sbp was assessed by a computerized noninvasive tail cuff system in conscious mice . the other half that was snap - frozen in liquid nitrogen was used either for gene expression analyses or for immunohistochemical stainings . gene expression of opg and trail was determined by real - time quantitative rt - pcr ( reverse transcription - polymerase chain reaction ) in aortic and cardiac tissue . in order to isolate mrna from the aorta and the heart , tissue was homogenized and processed as previously reported .", "apoe mice had higher levels of total cholesterol and triglycerides as compared to the cnt mice . in line with the study protocol , the mice in the apoe + dm group were hyperglycemic . moreover , diabetes was associated with a significant reduction of body weight and a significant increase of total cholesterol as compared to nondiabetic apoe mice . it has already been argued that opg , which circulates at much higher levels than its ligands ( rankl and trail ) , may be a more stable overall measure of opg / trail activity than trail . as for cardiac changes , dyslipidemia was associated with a significant increase in cardiomyocyte size ( figures 1(c ) and 1(d ) ) , indicating cardiomyocyte hypertrophy , with no further increase after the induction of diabetes . in the aorta , the induction of diabetes was associated with a significant increase in opg gene expression and in the opg / trail ratio , while dyslipidemia had no effect on opg / trail ratio as compared to controls ( figure 2(a ) ) . by contrast , in the heart , dyslipidemia was the major determinant of opg / trail tissue changes , not only by increasing opg but also by reducing trail gene expression . so dyslipidemia increased significantly cardiac opg / trail ratio , with no further differences after the induction of diabetes ( figure 2(b ) ) . as for cardiac trail , trail protein expression decreased in the apoe and apoe + dm groups ( data not shown ) . the levels of circulating", ", we evaluated the effects of dyslipidemia , alone and in combination with diabetes , on aortic and cardiac opg and trail expression and found that while diabetes is the major determinant of opg / trail tissue changes in the vessels , dyslipidemia is it in the heart . patients with coronary artery disease have an increased opg / trail ratio , which further increases in the group of patients who develop heart failure . dyslipidemia and diabetes by contrast , we showed that trail administration to mice with diabetic cardiomyopathy had cardioprotective effects , as it reduced cardiac fibrosis and apoptosis , which are generally contributing to cardiac remodeling . in conclusion , here we found that both dyslipidemia and diabetes affect opg / trail ratio in the cardiovascular system . this could contribute to the changes in circulating opg / trail which are observed in patients with diabetes and cvd ." ]
background . dyslipidemia and diabetes are two of the most well established risk factors for the development of cardiovascular disease ( cvd ) . both of them usually activate a complex range of pathogenic pathways leading to organ damage . here we hypothesized that dyslipidemia and diabetes could affect osteoprotegerin ( opg ) and tnf - related apoptosis - inducing ligand ( trail ) expression in the vessels and the heart . materials and methods . gene and protein expression of opg , trail , and opg / trail ratio were quantified in the aorta and the hearts of control mice , dyslipidemic mice , and diabetic mice . results . diabetes significantly increased opg and the opg / trail ratio expression in the aorta , while dyslipidemia was the major determinant of the changes observed in the heart , where it significantly increased opg and reduced trail expression , thus increasing cardiac opg / trail ratio . conclusions . this work shows that both dyslipidemia and diabetes affect opg / trail ratio in the cardiovascular system . this could contribute to the changes in circulating opg / trail which are observed in patients with diabetes and cvd . most importantly , these changes could mediate / contribute to atherosclerosis development and cardiac remodeling .
[ "compounds 14 , 7 , 8 , and 11 were \n synthesized following our previously reported synthetic routes . these data indicate that the three - dimensional molecular \n shape of ( )-palmyrolide a was crucial for the interaction \n with vgscs . in order to support these observations and to better \n , we examined \n the ability of these compounds to antagonize veratridine - stimulated \n na influx in murine primary cerebrocortical neurons . nonlinear regression analysis of concentration response \n data for active analogues of ( )-palmyrolide a. a three - parameter \n logistic fit of the palmyrolide a analogue inhibition of the response \n to veratridine is shown for each active compound . we \n previously demonstrated that veratridine is a partial agonist at neurotoxin \n site 2 on the vgsc subunit . we have confirmed and extended these original \n findings by demonstrating that synthetic ( )-palmyrolide a \n ( 1 , figures 2a and 3a ) and its enantiomer ( 3 , figures 2c and 3c ) produced concentration - dependent \n antagonism of veratridine - induced increase in neuronal [ na]i .", "these \n findings suggest that both synthetic ( )-palmyrolide \n a and its enantiomer function with equal potency as vgsc antagonists \n to block veratridine - induced sodium influx . with regard to identification \n of the pharmacophore of this natural product using detailed nmr \n and computational approaches with the natural product and three diastereomeric \n analogues , it was found that the c-5c-7 anti / c-7c14 syn arrangement of stereocenters \n produces a unique combination of three - dimensional shape and electrostatic \n potential that is responsible for the potent biological activity of \n the natural product . in an effort to understand , it appears that the \n intact macrolide is required since acyclic versions were inactive \n as inhibitors of vgscs . moreover , analogues lacking the enamide double \n bond were of high potency in this assay , and thus this functionality \n appears unnecessary for blocking vgscs . finally , the similar biological \n activity found for the natural stereoisomer and its enantiomer , continued \n investigations in this area will focus on uncovering the specific \n molecular target and associated binding site , which may also assist \n in future analogue development of novel sodium channel blocking analgesics \n derived from palmyrolide a.", "[ na]i measurement and full in situ calibration of sodium - binding benzofuran isophthalate fluorescence \n ratio were performed as described previously . topspin ( bruker biospin ) was used to analyze coupling constants \n in the h nmr and hetloc spectra . were identified , then compared with the distances between \n these atoms in the ensemble of selected structures . molecular \n dynamics simulations were nonperiodic , vacuum simulations with a distance - dependent \n dielectric term . using sander in the amber 14 package each starting \n structure was energy minimized , then subjected to 20 ps of simulated \n annealing with the nmr - derived restraints in which the temperature \n was raised from 10 k to 600 k then cooled to near 0 k. the simulated \n annealing was run 20 times for each structure with a different random \n number seed each time . the plate was then transferred \n back to the incubator for 15 min to allow the cells to equilibrate \n after washing and placed in a flexstation ii ( molecular devices ) chamber \n to detect na - bound sbfi emission at 505 nm ( cells were \n excited at 340 and 380 nm ) ." ]
a small library of synthetic ( )-palmyrolide a diastereomers , analogues , and acyclic precursors have been examined with respect to their interaction with voltage - gated sodium channels ( vgscs ) . toward this goal , the ability of ( )-palmyrolide a and analogues to antagonize veratridine - stimulated na+ influx in primary cultures of mouse cerebrocortical neurons was assessed . we found that synthetic ( )-palmyrolide a and its enantiomer functioned as vgsc antagonists to block veratridine - induced sodium influx . a detailed nmr and computational analysis of four diastereomers revealed that none had the same combination of shape and electrostatic potential as exhibited by natural ( )-palmyrolide a. these data indicate that the relative configuration about the tert - butyl and methyl substituents appears to be a prerequisite for biological function . additional testing revealed that the enamide double bond was not necessary for blocking veratridine - induced sodium influx , whereas the acyclic analogues and other macrolide diastereomers tested were inactive as inhibitors of vgscs , suggesting that the intact macrolide was required .
[ "the online version of this article ( doi:10.1007/s00414 - 009 - 0352 - 9 ) contains supplementary material , which is available to authorized users .", "if a comparable relationship exists between humans and their skin microbiota , as has been observed for h. pylori , new methods for human geographic origin determination could be developed based on dna analysis of fingertip microflora , with interesting new applications to molecular analyses of physical fingerprints left at crime scenes . microbes can negatively interfere with the postmortem assessment of alcohol abuse and in this way pose problems for forensic investigators . however , microbial forensics is often chiefly associated with the detection of highly pathogenic microbes to which humans are deliberately exposed in cases of biological terrorism [ 2 , 3 ] . however , human fingertip microflora left behind on touched objects at crime scenes may potentially contain forensically relevant information that may be useful for human host inferences accessible via microbial dna fingerprinting of physical fingerprints . numerous human genetic markers have been suggested for inferring human genetic ancestry mostly to the continental level [ 47 ] , and a recent study indicated that inferring the subregion of origin of an unknown european may be feasible from autosomal genetic data .", "a coagulase test with slidex staph plus ( biomrieux , marcy - letoile , france ) was performed to detect staphylococcus aureus isolates . staphylococcus epidermidis sensu stricto was identified among the isolates by a species - specific polymerase chain reaction assay as described elsewhere . genotyping bacterial isolates in order to generate dna fingerprints for the most relevant bacterial isolates , all staphylococcal isolates were subjected to pulsed - field gel electrophoresis ( pfge ) . were classified with the i d 32 staph api system ( biomrieux , marcy - letoile , france ) . was placed next to the first . whereas the first fingerprint was expected to provide a mixture of transient and resident microbiota agar plates from bangladeshi volunteers were shipped by courier to rotterdam after overnight incubation at 37c for further analyses . given the diversity in genotypes encountered in the time - wise resampling experiments using dutch volunteers ( see below ) , this procedure was not repeated for the volunteers from bangladesh . gram staining and the determination of catalase activity were applied for the identification of staphylococci using commercially available test kits ( biomrieux , marcy - letoile , france ) .", "table 2staphylococcus species and pfge types from bangladeshi fingerprints before washing with soap representing elements of the transient ( tm ) microflora and after washing representing resident fingertip microflora ( rm ) staphylococcus species and pfge types from bangladeshi fingerprints before washing with soap representing elements of the transient ( tm ) microflora and after washing representing resident fingertip microflora ( rm ) to conclude , we see only limited geographic differentiation between microbial dna fingerprints from dutch europeans and bangladeshi south asians , indicating that geographic inferences of human hosts from fingertip microbial dna analysis is not feasible . furthermore , our results from dna profiling of transient and resident fingertip microflora show that human fingertip microflora is too dynamic and thus does not fulfill the criteria required for forensic marker developments to infer any human host information from physical fingerprints . however , any human host inference from fingertip microflora using physical fingerprints would require that the transient microflora is representative of the resident endogenous microflora of the same individual and is not simply reflecting microbial species / strains picked up from the environment . to test this prerequisite , we investigated and compared by means of dna fingerprinting techniques the transient superficial skin microbiota and the resident endogenous microflora of human fingertips within several individuals . developing forensic dna markers for human host inferences from physical fingerprints relies on the examination of the transient exogenous microflora left behind together with the physical fingerprint .", "" ]
human fingertip microflora is transferred to touched objects and may provide forensically relevant information on individual hosts , such as on geographic origins , if endogenous microbial skin species / strains would be retrievable from physical fingerprints and would carry geographically restricted dna diversity . we tested the suitability of physical fingerprints for revealing human host information , with geographic inference as example , via microbial dna fingerprinting . we showed that the transient exogenous fingertip microflora is frequently different from the resident endogenous bacteria of the same individuals . in only 54% of the experiments , the dna analysis of the transient fingertip microflora allowed the detection of defined , but often not the major , elements of the resident microflora . although we found microbial persistency in certain individuals , time - wise variation of transient and resident microflora within individuals was also observed when resampling fingerprints after 3 weeks . while microbial species differed considerably in their frequency spectrum between fingerprint samples from volunteers in europe and southern asia , there was no clear geographic distinction between staphylococcus strains in a cluster analysis , although bacterial genotypes did not overlap between both continental regions . our results , though limited in quantity , clearly demonstrate that the dynamic fingerprint microflora challenges human host inferences for forensic purposes including geographic ones . overall , our results suggest that human fingerprint microflora is too dynamic to allow for forensic marker developments for retrieving human information.electronic supplementary materialthe online version of this article ( doi:10.1007/s00414 - 009 - 0352 - 9 ) contains supplementary material , which is available to authorized users .
[ "carlucci and colleagues have recently studied patient - ventilator interactions in 69 acutely ill patients receiving non - invasive ventilation ( niv ) for a variety of reasons . this study is important as it underscores that patient - ventilator trigger dys - synchrony is common and can be a major barrier to niv effectiveness . assisted / supported mechanical ventilation is designed to interact with patient muscle activity and ' share ' the work of breathing . if properly done , assisted / this study also underscores the fact that the causes of trigger dys - synchrony are complex and affect all types of patients requiring assisted / supported mechanical ventilation [ 3 - 5 ] . like invasive mechanical ventilation , niv trigger dys - synchrony can stem from insensitive / poorly responsive breath triggering mechanisms . however , other factors also involved likely include ventilatory muscle loading patterns and their effects on the ventilatory controller , ventilatory muscle function , lung volumes at end - expiration ( that is , intrinsic positive end - expiratory pressure ( peep ) ) , gas exchange effectiveness , and cortical inputs to the patient 's ventilatory control center such as pain [ 3 - 5 ] . in addition , the triggering process with niv can be further hampered by the mask system with its inherent leaks and claustrophobia exaggerating dyspnea and neural drive . , the ventilatory 's flow and pressure delivery must synchronize with patient effort during all three phases of breath delivery : breath initiation , flow delivery , and breath termination ( cycling ) . flow synchrony is defined as the ability of the ventilator to provide flow in accordance with patient demand as manifest by the ventilatory muscle contraction pattern .", "", "" ]
patient - ventilator trigger dys - synchronies are common with the use of assisted forms of mechanical ventilatory support , including non - invasive mechanical ventilatory support ( niv ) . future system designs need to address this in order to improve the effectiveness of niv .
[ "we report a case of predominantly external jugular vein ( ejv ) involvement in an adolescent male with negative blood culture results . postanginal septicaemia in the early 20 century ; originally associated with a mortality reaching 90% it involves a classic triad of oropahryngeal sepsis , internal jugular vein ( ijv ) thrombophlebitis and metastatic abscess formation ( 1 ) . clinical findings can therefore vary considerably from neck pain and swelling associated with thrombophlebitis to pleuritic chest pain , haemoptysis , dyspnoea or arthralgia as a result of septic thromboemboli .", "a twelve year old boy presented to the children s assessment unit with a 24 hour history of unilateral face and neck swelling on a background of seven days progressive sore throat and dysphagia . a provisional diagnosis of tonsillitis had been made five days earlier by the local gp and a course of erythromycin and penicillinv commenced . he remained afebrile throughout , developed no subsequent complications and was discharged home to complete seven weeks of oral antibiotics . the patient remained in hospital on iv antibiotics for a total of 14 days , the noted swellings slowly decreased in size , blood results normalized and the trismus resolved . lastly an echocardiogram was sought confirming a normal heart with no septal defects , vegetations or thrombus .", "despite ijv thrombophlebitis forming a main diagnostic criterion for ls , we report a case in which the primary vascular involvement is that of the ejv , with a corresponding normal ijv . a recent history of a sore throat in conjunction with sepsis and or a suggestive and often declining clinical picture should always prompt early antibiotic therapy whilst a diagnosis of ls is sought ; hopefully preventing the development of late embolic complications . the role of anticoagulation however remains controversial with no conclusive literature evidence ; the decision should therefore be made on clinical grounds ; assessing severity of symptoms , poor treatment response and degree of thrombus extension ." ]
oropharyngeal infections are routinely encountered within general practice and accident and emergency departments . most settle with simple analgesia and antibiotics ; occasionally such patients may develop lemierre s syndrome ( ls ) a rare and potentially fatal sequela that can be easily overlooked . we aim to highlight the main symptoms , pathology , investigations and management .
[ "helicobacter pylori is a gram - negative , spiral and microaerophilic microorganism that was first isolated from the stomach of patients afflicted with peptic ulcer ( 1 , 2 ) . it is suspected that gastroesophageal reflux is involved in the pathogenesis of chronic otitis media . evidence showed that stomach pepsin is present in the middle ear cavity of patients afflicted with chronic otitis media , as compared to the control group , supports this suspicion ( 14 , 15 ) . however , the correlation between chronic suppurative otitis media and its various aspects , such as tympanosclerosis in which deposition of acellular hyaline and calcified deposits accumulate in the lamina propria of the middle ear has not been sufficiently studied ( 20 , 21 ) .", "so , we decided to use the pcr technique to determine the role of h. pylori in tympanosclerosis .", ", samples were taken of the middle ear mucosa of the patients . in patients with sclerotic plaques , the middle ear mucosa of the patients was examined during the surgical operations and based on this clinical evaluation , they were placed in one of the four types of normal , edema and hypertrophy , hyalinized and sclerotic and polyploid with or without cholesteatoma and this classification was recorded in the questionnaire . during the operations this case - control and cross - sectional study was conducted on patients who were diagnosed with chronic infection of the middle ear and were candidates to undergo surgery in the imam khomeini or apadana hospitals of ahvaz in 2013 . patients who had operations for chronic infections of the middle ear and those who had ventilation tube inserted into their ears in the past were excluded from the study . the samples were kept under sterilized conditions at 20 degrees centigrade , and were eventually sent to the laboratory of jundishapur university of medical sciences , ahvaz , iran . in the laboratory , dna was extracted using the roche high - pure template pcr kit ( roche , germany ) according to the manufacture protocol .", "therefore , there was no correlation between the presence of h. pylori and the size of the perforation or dryness of the middle ear . therefore , there was no significant correlation between the presence of h. pylori and the age and gender of the patients . this was a significant difference ( p = 0.002 ) , which means there was a correlation between the presence of h. pylori and tympanosclerosis of the middle ear ( table 1 ) . the biopsy samples of the middle ear mucosa of 31 ( 55.4% ) patients were h. pylori - positive . of the 29 male patients , 15 cases were ( 51.7% ) h. pylori - positive , while of the 27 female patients 16 cases ( 59.3% ) were h. pylori - positive . the most common pathological type of middle ear mucosa was hyalinized and sclerotic type in 19 cases ( 33.9% ) .", "( 26 ) , both show that there is a correlation between the presence of h. pylori and tympanosclerosis , and suggest the presence of h. pylori as the etiology for this disease ; however , neither study can consider h. pylori as the definite pathogenesis for tympanosclerosis . to prove this correlation this study offers a better understanding of the etiological and pathogenic aspects of h. pylori in tympanosclerosis that can be used in designing new treatment methods for this disease . it is thought that gastroesophageal reflux may be involved in the pathogenesis of otitis media and evidence indicating the presence of stomach pepsin in the middle ear cavity of patients with otitis media , as compared to the control group , confirms it ( 14 , 29 ) . our findings suggest that h. pylori probably plays a role in the development of tympanosclerosis . , a study should be designed to evaluate the correlation between tympanosclerosis and h. pylori by considering those pathological changes found in the examination of the middle ear mucosa that attribute the presence of inflammatory symptoms to the activity of h. pylori in the middle ear ." ]
background : tympanosclerosis is a condition caused by calcification of tissues in the middle ear mucosa that sometimes results hearing loss . helicobacter pylori is one of the pathological and etiologic factors in the development of tympanosclerosis.objectives:the purpose of this study was to show the role of h. pylori in the different aspects of chronic suppurative otitis media using the polymerase chain reaction ( pcr ) technique.patients and methods : this case - control and cross - sectional study was performed on all patients with chronic otitis media , candidates for surgical operations , in 2013 . they were allocated into the case group with tympanosclerosis and the control group without tympanosclerosis . during the surgical operation , biopsy was done from middle ear and the samples were studied to see if they contained h. pylori using the pcr method.results:from a total of 19 patients with tympanosclerosis , 16 cases ( 84.2% ) were h. pylori positive , while in the control group 15 ( 45.4% ) cases out of the 37 cases were h. pylori positive , which showed a significant difference ( p = 0.002 ) . age and gender of the patients , ear dryness and perforation size were not correlated with the presence or absence of h. pylori.conclusions:there is a significant correlation between tympanosclerosis and h. pylori ( p = 0.002 ) . this correlation can single out h. pylori as a pathological factor in the development of tympanosclerosis ; however , further studies are needed to prove this correlation .
[ "the goal of this paper is to provide a modern review of the literature thoroughly analyzing the efficacy of gkrs in the treatment of patients with tn , as well as evaluating the treatment planning and methods associated with this evolving modality . trigeminal neuralgia ( tn ) is a disorder of cranial nerve ( cn ) v that results in severe episodes of shock - like or lancinating pain in one or more of its three divisions ( v1v3 ) . stereotactic radiosurgery ( srs ) has proven to be an effective management approach for patients with medically and surgically refractory tn as a primary and repeat treatment modality . since the time of leksell , advancements in radiosurgery and imaging technologies has led to the increasing popularity of srs as a treatment option for patients with tn .", "to identify contemporary studies assessing the clinical outcomes of patients treated with gkrs for tn , a pubmed search from 2006 to april 2011 was performed . clinical 006futcomes did not differ between patients treated with gkrs and patients treated with the percutaneous techniques . the authors reported that patients treated with pfe exhibited superior levels of complete pain relief at 3 years of followup when compared to patients treated with gkrs , balloon compression , and glycerol rhizotomy ( p < 0.01 ) and underwent additional surgery for recurrent facial pain less often when compared to patients treated with the other modalities ( p = 0.02 ) . , no randomized trials have been conducted analyzing the outcomes of patients with tn who are treated with mvd compared to gkrs . in a large review on tn management , in addition , the authors concluded that single - dose srs is an effective treatment for long - term facial pain relief but puts patients at risk for facial numbness or facial paresthesias . we identified six studies comparing patients treated with gkrs with patients treated with one of the various surgical modalities [ 2 , 4044 ] ( table 4 ) .", "srs can be performed by a variety of tools , which include gkrs , cyberknife technology , and linear accelerator ( linac)-based treatment . our analysis yielded one study whose primary endpoint was to devise a method using cyberknife treatment planning that would mimic the dosimetric characteristics of the gk treatment plan in five patients undergoing radiosurgery for tn . patients in bni class iiib experience some trigeminal pain that can be satisfactorily managed with medication . patients in bni class iv experience some trigeminal pain that is not satisfactorily managed with medication . patients in bni class patients in bni class iiia do not experience trigeminal pain but require the use of medication . an area of controversy in the treatment of patients with tn is defining the optimal maximum radiosurgery dose that can be delivered to specific patient subsets .", "although numerous articles have reported mvd to be superior to gkrs in achieving facial pain relief , the findings of these comparison studies are weakened by the vast differences in patient age and comorbidities between the two studied groups and can not be considered conclusive . for patients with medically refractory forms of tn , gkrs has proven to be an effective initial and repeat treatment option . cumulative research suggests that patients treated a single time with gkrs exhibit similar levels of facial pain control when compared to patients treated multiple times with gkrs . however , patients treated on multiple occasions with gkrs are more likely to experience facial numbness and other facial sensory changes when compared to patients treated once with gkrs . further evidence in the form of a phase iii - randomized trial is needed to confirm the clinical outcomes of patients treated with either modality . questions remain regarding optimal gkrs dosing and targeting strategies , which warrants further investigation into this controversial matter ." ]
since its introduction by leksell , gamma knife radiosurgery ( gkrs ) has become increasingly popular as a management approach for patients diagnosed with trigeminal neuralgia ( tn ) . for this reason , we performed a modern review of the literature analyzing the efficacy of gkrs in the treatment of patients who suffer from tn . for patients with medically refractory forms of the condition , gkrs has proven to be an effective initial and repeat treatment option . cumulative research suggests that patients treated a single time with gkrs exhibit similar levels of facial pain control when compared to patients treated multiple times with gkrs . however , patients treated on multiple occasions with gkrs are more likely to experience facial numbness and other facial sensory changes when compared to patients treated once with gkrs . although numerous articles have reported mvd to be superior to gkrs in achieving facial pain relief , the findings of these comparison studies are weakened by the vast differences in patient age and comorbidities between the two studied groups and can not be considered conclusive . questions remain regarding optimal gkrs dosing and targeting strategies , which warrants further investigation into this controversial matter .
[ "a 55-year - old caucasian female was undergoing elective coronary artery bypass surgery following a recent myocardial infarction . approximately 20 minutes after endoscopic vein harvesting started , we noticed the patient 's end - tidal co2 ( etco2 ) had increased from 36 to 44 mmhg followed by increasing pulmonary artery pressure from 42/20 to 60/39 mmhg within 1 minute . coronary artery bypass grafting was completed without further events , and the patient recovered without any adverse neurological sequelae . , we concluded that the source of the gas embolism was most likely from co2 insufflation . however , the mid - esophageal right ventricular inflow - outflow view revealed a massive snowflake appearance suggestive of gas bubbles from the right atrium to the right ventricle ( fig .", "our case not only confirms the vital role of tee in the quick and accurate diagnosis of a co2 embolism during endoscopic vein harvesting but also allowed us to focus on the mid - esophageal bicaval view , a view not commonly used to identify a co2 embolism . in summary , the use of endoscopic vein harvesting for the saphenous vein has become increasingly more common and awareness and prevention of the potential for a co2 embolism is important . as seen in our case , tee played a vital role in detection , and we believe that the mid - esophageal bicaval view should be used as the standard view during endoscopic vein harvesting . although we allowed endoscopic vein harvesting to continue after confirmation of the co2 embolism with direct inspection of the saphenous - femoral vein junction and meticulous closure of the tears were confirmed , further investigation into the safety of this practice is warranted . , we choose to allow continued co2 insufflation to complete saphenous vein harvesting based on the patients stabile hemodynamics and on the observation that a reduction in gas entry to the right heart occurred shortly after detecting the co2 embolism ." ]
a carbon dioxide ( co2 ) embolism during endoscopic vein harvesting is a rare but potentially fatal complication . early and accurate diagnosis is crucial for limiting the extent of the embolism and stabilizing the resulting cardiovascular compromise . we report a case of co2 embolization during endoscopic vein harvesting . transesophageal echocardiography was instrumental in the diagnosis and management of this patient by further improving the decision making process , which resulted in the best outcome . mid - esophageal bicaval view is the best view to determine whether a co2 embolism is coming from the upper or lower extremities .
[ "rather than simply signaling the general presence of termites or providing a diagnosis of the species of termite inhabiting the wood , we postulated that these pellets could be chemically characterized so as to determine the status of a colony as active ( alive ) or inactive ( dead ) . here , we report quantification of the hydrocarbons in pellets of i. minor aged for up to 1 year after they were produced . we document the changes in proportions of selected hydrocarbons as an indication of the length of time since the pellets were excreted . the size , number , and dispersion of drywood termite colonies in a structure can vary greatly , depending on the age of the infestation and the success of preventative or remedial treatments . the economic cost of control and repair of damage is second only to that for subterranean termites ( su and scheffrahn , 1990 ) .", "the iage for each aging period then was regressed against the aging period ( r development core team , 2004 ) . ( 1997 ) using c. brevis and i. snyderi ( light ) from southern florida . in that study , 40 i. snyderi ( pseudergates or workers ) produced 573 pellets over 4 weeks , slightly less than 150 pellets / wk or about 3.5 pellets / individual / wk . in a study with small groups of c. brevis and i. immigrans , grace and yamamoto ( 2009 ) found that these species produced 4.9 to 7.0 pellets / individual / wk . for our study , we assumed that i. minor would produce pellets at roughly the same rate and , therefore , we needed about 3,000 to 5,000 individuals in a tcu for this study . statistical analysis gc - ms peak ( some peaks contained more than one compound or a mixture of positional isomers ) areas were converted to percentages of total hydrocarbon fraction , enabling mean ( sd ) relative amounts of each hydrocarbon peak for workers and alates , and overall mean ( sd ) of each hydrocarbon peak for the fecal pellets , to be calculated.the percentage of each hydrocarbon peak for pellets of each aging period was transformed to the log of the percentage ( dependent variable y ) and regressed against the days of aging ( independent variable x ) . hydrocarbons are presented in the tables for each caste and worker fecal pellets in the order of elution from our gc - ms system . concurrently , three samples of 20 workers , three samples of 20 alates , and one sample of 20 soldiers were also collected for hydrocarbon analysis . extraction procedure and characterization of hydrocarbons hydrocarbons from workers , alates , soldiers , and fecal pellets of i. minor were extracted , characterized , and quantified as previously reported ( haverty et al . , 2005 ) .", "the motivation for our study was to devise a method for the evaluation of the success or failure of drywood termite treatments , including fumigation and local application methods . with the recent classification of sulfuryl fluoride ( the only fumigant active ingredient registered in california ) as a greenhouse gas ( mhle et al . , 2009 ) and relative abundance of hydrocarbon classes from pseudergates , alates , soldiers , and fecal pellets of incisitermes minor ( hagen ) percent of total hydrocarbon composition all peaks with co - eluting olefins and saturated compounds are summarized as olefins hydrocarbons from termite fecal pellets in general , the hydrocarbons from whole - body extracts of i. minor were represented in extracts of fecal pellets . as with whole - body extracts of i. minor , dimethylalkanes were the predominant class of hydrocarbon , followed by olefins and normal alkanes ( table 2 ) . 1total ion chromatogram of cuticular hydrocarbons from a workers of incisitermes minor ( hagen ) and b from fecal pellets from the same collection . ( 1996 ) demonstrated significant seasonal variation in quantities of some hydrocarbons of coptotermes formosanus shiraki from hawaii ; these differences were small and associated with the production of alates . the cuticular hydrocarbons for i. minor pseudergates and fecal pellets were characterized previously ( haverty et al . , 2000 , 2005 ) ." ]
hydrocarbon mixtures extracted from fecal pellets of drywood termites are species - specific and can be characterized to identify the termites responsible for damage , even when termites are no longer present or are unable to be recovered easily . in structures infested by drywood termites , it is common to find fecal pellets , but difficult to sample termites from the wood . when fecal pellets appear after remedial treatment of a structure , it is difficult to determine whether this indicates that termites in the structure are still alive and active or not . we examined the hydrocarbon composition of workers , alates , and soldiers of incisitermes minor ( hagen ) ( family kalotermitidae ) and of fecal pellets of workers . hydrocarbons were qualitatively similar among castes and pellets . fecal pellets that were aged for periods of 0 , 30 , 90 , and 365 days after collection were qualitatively similar across all time periods , however , the relative quantities of certain individual hydrocarbons changed over time , with 19 of the 73 hydrocarbon peaks relatively increasing or decreasing . when the sums of the positive and negative slopes of these 19 hydrocarbons were indexed , they produced a highly significant linear correlation ( r2 = 0.89 ) . consequently , the quantitative differences of these hydrocarbons peaks can be used to determine the age of worker fecal pellets , and thus help determine whether the colony that produced them is alive or dead .
[ "here , we describe \n field - sea , a considerable improvement over sea , which gives accurate \n free energies of transfer of ions and charged solutes , at no additional \n computational cost and with no degradation of the predictions for \n nonpolar and uncharged polar solutes . in overview , we studied full \n md simulations of ionic and neutral solutes in tip3p water , described \n below , and found that the results could be captured by using a solvation \n free - energy field surface ( in field - sea ) , instead of using precomputed \n waters ( as in sea ) . there \n is a need for computer methods that can calculate the aqueous solvation \n free energies of solute molecules accurately and efficiently . moreover , \n we found that a weakly charged solute atom that is adjacent to a strongly \n charged solute atom retains some of the restrictions of its solvating \n water molecules that its neighboring charge has ; see figure 1 . field - sea captures this effect using an adaptive \n boundary method . a solvent water molecule around a solute molecule .", "below , we describe the field - sea approach to computing solvation \n free energies . the original sea model is described elsewhere , and our related explicit - solvent and linearized poisson boltzmann \n equation modeling ( lpbe ) are described \n in the supporting information ( si ) . in both the original sea and the new \n field - sea described here , first , in a precomputation step , various \n model spheres are solvated in an explicit - solvent model , such as tip3p . \n we consider the gsolv of monatomic ions as an initial test . for molecular \n solutes ,", ", we investigate the solvation \n free energies of a full series of capped amino acids with field - sea . \n as the size of solute increases , computing the total solvation the solvation boundaries \n in field - sea are made from a set of surface dots . imagine a diatomic solute with partially \n charged atom a covalently connected to partially \n charged atom b. our tip3p simulations show that when \n atom a attracts water molecules , it also shrinks \n the solvation shell of waters around atom b. in this \n way , the solvation surface around the diatomic molecule a b can be more complex than the simple union \n of independent spherical solvation shells around atoms a and b. to address such situations , we developed \n an adaptive method that gives a more explicit - like solvation boundary . to test our adaptive boundary method , we made up 22 fictitious \n diatomic solutes ( see si table s4 ) , computed \n their solvation free energies , and compared to their solvation in \n tip3p . show , lpbe \n ( cyan diamond ) and field - sea ( cyan circle ) both yield solvation free \n energies that agree well with tip3p calculations . these results indicate that the accuracy of field - sea does not degrade \n as the solute size further increases .", "sea captured the physics of solvation by \n presimulating toy spheres in explicit water , collecting a database \n of structural and energetic properties of those waters and then assembling \n at run time the solvation physics as sums over appropriate toy spheres \n to properly represent a given solute . in field - sea , this procedure \n differs in using a solvation free - energy field , rather than explicit \n waters . we have \n described field - sea , a method for computing solvation free energies \n of solutes in water . furthermore , field - sea uses an adaptive boundary , allowing \n solvating waters to approach a solute atom to different degrees depending \n on neighboring atoms . relative to sea , field - sea captures the solvation \n free energies of ions and charged solutes accurately , is faster to \n compute , and has no degradation of performance on nonpolar and polar \n solutes . both sea and field - sea offer advantages over implicit - solvent \n modeling in that they entail no adjustable solute atom radii parameters . \n it improves upon an earlier method called sea \n ( semi - explicit assembly ) ." ]
previous work describes a computational solvation model called semi - explicit assembly ( sea ) . the sea water model computes the free energies of solvation of nonpolar and polar solutes in water with good efficiency and accuracy . however , sea gives systematic errors in the solvation free energies of ions and charged solutes . here , we describe field - sea , an improved treatment that gives accurate solvation free energies of charged solutes , including monatomic and polyatomic ions and model dipeptides , as well as nonpolar and polar molecules . field - sea is computationally inexpensive for a given solute because explicit - solvent model simulations are relegated to a precomputation step and because it represents solvating waters in terms of a solute s free - energy field . in essence , field - sea approximates the physics of explicit - model simulations within a computationally efficient framework . a key finding is that an atom s solvation shell inherits characteristics of a neighboring atom , especially strongly charged neighbors . field - sea may be useful where there is a need for solvation free - energy computations that are faster than explicit - solvent simulations and more accurate than traditional implicit - solvent simulations for a wide range of solutes .
[ "healthy and cystic liver tissues were compared and mentioned gst enzyme importance for diagnostic biomarker in hydatid cyst disease . however , the hydatid cyst diagnosis technique is under developing due to specificity and sensitivity problems . in the present study , gst enzyme activity of hydatid cyst protoscolices ( parasite ) , diagnosis of hydatid disease is done by a combination of clinical signs , imaging techniques , cyst fluid examination , serological tests and molecular techniques ( 9 ) . hydatidosisis term used to refer to infection with the parasite larva in humans and echinococcosis restricted to infection with the adult stage in carnivorous animals ( 1 ) . recently , the genetics , structure and function of the human cytosolic gst enzyme with emphasis on their roles in the cellular metabolism has been defined ( 2 ) . gst activity was detected in most mammalian tissues , especially in the liver which plays a key role in detoxification .", "ten samples of parasites were obtained from 10 liver infected with hydatid cysts of sheep slaughtered at a localabattoir ( karaj , iran ) . independent t - test was performed to compare the mean values of protein concentration and enzyme activity between healthy and cystic liver tissues or parasite and liver tissues . molecular weights of sample proteins were compared with respect to the protein marker ( 12 ) . to detect the molecular weight , rf(ratio factor ) of ladder bands then they were homogenized with 3 volumes of homogenizing buffer , pbs ph 6.5 , in a glass homogenizer , so the suspension were centrifuged ( 10000 g for 30 minat 4c ) and supernatant stored at -20c ( 12 ) . the protein concentration in the extract solutions of protoscolices and sheep liver tissues sheep livers ( 10 health liver samples and 10 infected samples ) were obtained at a local abattoir and washed 3 times with pbs buffer ph 7.2 . sds - page and coomassie blue staining were used to separate and stain the protein components of samples respectively .", "ten samples of parasites were obtained from 10 liver infected with hydatid cysts of sheep slaughtered at a localabattoir ( karaj , iran ) . parasites samples were washed 3 times with pbs buffer , ph 7.2 , freeze - thawed 3 - 6 times in liquid nitrogen and and water bath 37c respectively and sonicated in a 150w ultrasonic disintegrator,10 sec on and 5 sec off on ice until no intact psc were visible microscopically ( approximately 15 min ) . then resulted suspension was centrifuged ( 10000 g for 30 min at 4c ) and supernatant was stored at -20c ( 11 ) .", "sheep livers ( 10 health liver samples and 10 infected samples ) were obtained at a local abattoir and washed 3 times with pbs buffer ph 7.2 . then they were homogenized with 3 volumes of homogenizing buffer , pbs ph 6.5 , in a glass homogenizer , so the suspension were centrifuged ( 10000 g for 30 minat 4c ) and supernatant stored at -20c ( 12 ) .", "the protein concentration in the extract solutions of protoscolices and sheep liver tissues were estimated by the method of bradford using bovine serum albumin as the standard ( 12 ) .", "gsts activity was assayed spectro photometrically at 25c with reduced glutathione ( gsh ) and 1-chloro-2 , 4-dinitrobenzene ( cdnb ) as substrates . cdnb 100 mm from 4c and gsh 100 mm from -20c freezer were removed and allowed to thaw at room temperature , when thawed , incubated at 30c in water bath . for each assay was prepared one ml of assay cocktail ( 980lpbs ph 6.5 , 10l of 100 mm cdnb and 10 l of 100 mm gsh ) , then removed 100 l of cocktail and its remaining placed 900 l of it into 1.5 ml cuvette . to zero spectrophotometer , was used 1 ml of distilled water and to the blank cuveet added 100l pbs to 900 l of cocktail and measured absorbance at 340 nm , every1 minute , for 3 min . to the test cuvette was added 100 l of sample to 900 l cocktail , mixed and measured absorbance at 340 nm as above ( 13 ) . protosolices and liver extract samples were removed from -20c freezer and allowed to thaw on ice .", "molecular weights of sample proteins were compared with respect to the protein marker ( 12 ) . to detect the molecular weight , rf(ratio factor ) of ladder bands sds - page and coomassie blue staining were used to separate and stain the protein components of samples respectively . was calculated , standard curve was prepared in excel software and finally proteins mw were determined .", "independent t - test was performed to compare the mean values of protein concentration and enzyme activity between healthy and cystic liver tissues or parasite and liver tissues .", "the mean values of protein amounts and gsts activity for parasite , healthy and cystic liver samples molecular weight of proteins ( kda ) from the extracts of parasite and liver tissues in sds - page . the mean values of protein concentrations and enzyme activities for parasite , healthy and infected liver samples are presented in table 1 . similar cross protein bands is observing in parasite and liver sample but has been not recorded by databse . 64072 ) identified proteins of parasite according to molecular weight by using protein database(http://web.expasy.org ) identified proteins of sheep liver tissue according to molecular weight by using protein database(http://web.expasy.org ) lanes 1 - 3 are healthy liver samples . lanes 4 - 6 are cystic liver samples .", "the mean values of protein concentrations and enzyme activities for parasite , healthy and infected liver samples are presented in table 1 . significant higher gst specific activities in cystic liver samples was observed as compared with healthy liver ( p < 0.05 ) . protein concentration of healthy liver was higher than infected liver ( p < 0.05 ) . statistical t - test showed gst enzyme activity of parasite was lower than healthy liver tissues ( p < 0.05 ) .", "the mean values of protein amounts and gsts activity for parasite , healthy and cystic liver samples molecular weight of proteins ( kda ) from the extracts of parasite and liver tissues in sds - page . 64072 ) identified proteins of parasite according to molecular weight by using protein database(http://web.expasy.org ) identified proteins of sheep liver tissue according to molecular weight by using protein database(http://web.expasy.org ) similar cross protein bands is observing in parasite and liver sample but has been not recorded by databse . extract samples of protoscolices , healthy and cystic liver tissues were analyzed by sds - page electrophoresis and the results are shown in fig . 1 . sds - page gel shows gst protein bands with 24kda in parasite and 25kda in healthy liver samples . lanes 7 - 9 are parasite samples ( protein marker , peqgold i , lot - no .", "the reduction of protein synthesis as a result of hydatid cyst causes to decrease protein concentration . therefore gst activity difference between healthy and infected host liver tissue could be concerned for hydatid cyst diagnosis . however , other infections cause to hepatocyte damage , thus gst elevation must be evaluated with other clinical and paraclinical parameters of hydatid cyst disease . increase of liver protein and gst in infected mice indicates the occurrence of oxidative stress in hepatocytes due to infection ( 18 ) . research protein bands with 24kda and 25kda were found in parasite and liver tissues respectively . hepatic cells contain high levels of gst enzyme which has been found to be an indicator of hepatocyte injury in transplantation , toxicity and infections ( 17 ) .", "gst activity in cystic liver tissue could be concerned as a biomarker for hydatid cyst diagnosis with other parameters of hydatidosis ." ]
abstractbackgroundthe aim of this study was to detect the glutathione s - transferase(gst ) enzyme activity of healthy / cystic liver as a diagnostic biomarker for hydatidosis . in order to compare with liver tissue , the level of the gsts enzyme activity of parasite was also determined.methodsparasites were collected from sheep liver tissue with hydatid cysts at a local abattoir and washed with pbs buffer . collected parasites and liver tissues were sonicated or homogenized respectively . extract solution samples were centrifuged and stored at - 20c . gst enzyme activities were measured in the extract of parasite and liver tissue samples ( healthy and infected livers ) . protein amounts and protein bands were detected using bradford and sodium dodecyl sulfate polyacrylamide gel electrophoresis ( sds - page ) methods respectively . to determine significant difference between two groups , two - sample t - test was performed.resultsgst specific activities of healthy / infected livers and parasites were estimated 304 , 1297 and 146 u / ml / mg respectively . significant higher gst specific activities in cystic liver than healthy liver was observed ( p < 0.05 ) . t - test analysis showed gst activity of parasite was lower than healthy liver tissue . sds - page showed gst protein bands with 24 kda in parasite samples and25 kda in liver tissues.conclusiongst activity incystic liver tissue could be concerned as a biomarker for hydatid cyst diagnosis with other hydatid disease parameters .
[ "we studied fibrinolytic activity , as measured by tpa and pai-1 activity , and a marker of endothelial dysfunction , as measured by tpa antigen , in a population sample with normal glucose tolerance at baseline and analysed data according to conversion to diabetes or not over nine years of follow - up . the possibility of elevated pai-1 being a very early risk marker of the insulin resistance syndrome and diabetes was raised . furthermore , haemostatic variables related to endothelial function , such as von willebrant factor and factor viii , also predicted diabetes , especially in women . data are lacking regarding other aspects of the fibrinolytic system and the development of diabetes , such as the activities of pai-1 and tissue plasminogen activator ( tpa ) or the mass concentration of the endothelial - derived tpa ( \" tpa antigen \" ) , factors related to cvd [ 15 - 19 ] thus , there are two questions related to fibrinolytic variables and the development of diabetes . if so , do these changes predict future diabetes , independent of the influence of the insulin resistance syndrome , thereby pointing to other pathways to the diabetic state such as endothelial dysfunction ? firstly , do subjects with normal glucose tolerance , who later convert to diabetes , have disturbances in the fibrinolytic system and endothelial function that could explain their increased risk of cvd even before diabetes ensues ? the risk of stroke and myocardial infarction is considerably increased in subjects with diabetes . already at the time of diagnosis of type 2 diabetes , many patients have manifest cardiovascular disease ( cvd ) .", "participants , who denied having diabetes in the baseline survey and answered affirmative to the question \" do you have diabetes mellitus ? \" at follow up , were defined as incident cases of known diabetes mellitus according tho the who criteria from 1999 . in november 2002 , a questionnaire exploring details related to the diagnosis of diabetes , and to the type and duration of current hypoglycaemic treatment was sent to them . a total of 2,000 randomly selected subjects aged 25 to 64 years were invited . in all , 1,583 persons participated ( 79.2 % ) . this study was performed within the framework of the northern sweden monica study . in 1990 serum insulin was determined by radio immunoassay with a double - antibody solid - phase technique ( phadaseph insulin ria , pharmacia diagnostics ab , uppsala , sweden ) in 1999 , all participants , alive and still living in the area , were recalled for a follow - up examination . the same questionnaire and anthropometrical measurements as in the baseline survey were used . case records were scrutinised to confirm diabetes diagnosis and time for start of insulin therapy . a 75-gram oral glucose tolerance test ( ogtt ) was performed after an overnight fast in a randomly selected subset of subjects without known diabetes . subjects that started their insulin treatment within two years of diagnosis were classified as type 1 . altogether 1,148 ( 72.5 % ) subjects turned up for re - examination . subjects who previously had performed an ogtt with normal or impaired glucose tolerance , and answered no to the question \"", "means or medians are given for those who remained non - diabetic and those who converted to diabetes . because the distributions for serum triglycerides , insulin and the fibrinolytic variables are highly skewed , we used logarithmically transformed values ( i.e. geometric means ) . the risk of incident diabetes was compared across quartiles of the fibrinolytic variables , calculated from the total sample . logistic regression was used for calculation of odds ratios and 95% confidence intervals ( ci ) for the development of diabetes comparing the quartile with highest risk with the other three pooled quartiles . stepwise adjustment for age and sex , waist , serum insulin , triglycerides and diastolic blood pressure was used .", "the lowest quartile of tpa activity was associated with a 3-fold increase in the risk of diabetes , which was attenuated after adjustment for waist circumference . the risk of developing diabetes increased with increasing quartiles of tpa antigen and pai-1 activity and decreased in a similar way for tpa activity ( figure 1 ) . in the highest quartile of tpa antigen ( above 8.7 five hundred and fifty - one subjects who initially had normal glucose tolerance returned for re - examination . a new ogtt was done in 477 of those with normal glucose tolerance and without clinically diagnosed diabetes . after further adjustment for diastolic blood pressure , fasting insulin and triglycerides , no prediction from low tpa activity on diabetes development was seen . the risk of developing diabetes or igt during follow up ( n = 66 ) increased stepwise across quartiles of tpa antigen , from 7.8% to 19.8% ( p = 0,003 , test for linear trend ) . when adjusted for age and sex , the odds ratio for the highest vs. the three lower quartiles of tpa antigen was 1.9 ( ci 1.011.6 , p = 0.04 ) but diminished further when also waist circumference was adjusted for , or = 1.3 ( ci 0.636.5 , p = 0.5 ) . quartiles 13 of tpa antigen and pai-1 activity were contrasted with the fourth quartile and , for tpa activity , the first quartiles with quartile 24 ( table 2 ) . logistic regression analysis for fibrinolytic variables at baseline with incident type 2 diabetes as the dependent variable . diastolic blood pressure did not differ but both fasting triglycerides , insulin , fasting and post load plasma glucose were higher in subjects with subsequent diabetes .", "subjects with normal glucose tolerance , who subsequently develop type 2 diabetes over the ensuing nine years , are already at baseline characterised by impaired fibrinolysis and endothelial dysfunction . low tpa activity and high pai-1 activity is mainly explained by the presence of abdominal obesity but also by other metabolic disturbances characteristic of the insulin resistance syndrome , such as high serum levels of triglycerides and insulin . thus , the development of type 2 diabetes is preceded by many years of perturbations in fibrinolytic and endothelial function , which increases the risk of atherothrombotic disease long before overt diabetes is present . pa1 - 1 is partly synthesised in fat cells and its activity is strongly related to abdominal obesity as mirrored by high waist circumference or whr . we therefore find it plausible that the relation between high tpa and diabetes is a marker of some early disturbance in the vascular wall that operates independent of obesity and inflammation . high levels of tpa antigen independently predict cardiovascular events both in a healthy population and in patients with prevalent coronary disease .", "changes in endothelial function are independent from the insulin resistance syndrome and point towards a distinctly different pathway both for cardiovascular disease and for the development of diabetes . to answer a classical question from 1990 yes , the clock for coronary heart disease seems to start ticking before the onset of clinical diabetes ! the early prediabetic state , with normal glucose tolerance , is characterised by both impaired fibrinolysis and endothelial dysfunction years before glucose levels increase .", "bmi = body mass index ci = confidence interval crp = c - reactive protein cvd = cardiovascular disease igt = impaired glucose tolerance monica = monitoring of trends and determinants of cardiovascular disease ngt = normal glucose tolerance ogtt = oral glucose tolerance test pai-1 = plasminogen activator inhibitor-1 tpa = tissue plasminogen activator", "", "bs and bl participated in the design of northern sweden monica study and participated in its design and coordination . me drafted the research on fibrinolysis within the monica project , performed the statistical analysis and drafted the manuscript .", "supported by grants from norrbotten and vsterbotten counties , by the joint committee of northern sweden health care region , the swedish public health institute and the swedish medical research council ." ]
backgroundimpaired fibrinolysis is found in impaired glucose tolerance and type 2 diabetes , associated with components of the metabolic syndrome . there are no data concerning fibrinolysis in subjects with normal glucose tolerance that convert to diabetes.methodswe studied the activities of tissue plasminogen activator ( tpa ) and plasminogen activator inhibitor-1 ( pai-1 ) and the levels of tpa antigen ( a marker of endothelial dysfunction ) in 551 subjects with normal glucose tolerance in 1990 in relation to incident diabetes during nine years of follow-up.resultssubjects with diabetes at follow - up ( n = 15 ) had significantly lower baseline tpa activity and higher pai-1 activity and tpa antigen than non - converters . the risk of diabetes increased linearly across quartiles of pai - activity ( p = 0.007 ) and tpa antigen ( p < 0.001 ) and decreased across quartiles of tpa activity ( p = 0.026 ) . the risk of diabetes with low tpa activity or high pai-1 activity persisted after adjustment for age and sex but diminished to a non - significant level after further adjustments . the odds ratio of diabetes for high tpa antigen was 10.4 ( 95% confidence interval 2.740 ) adjusted for age and sex . after further adjustment for diastolic blood pressure , waist circumference , insulin , triglycerides , fasting and post load glucose the odds ratio was 6.5 ( 1.333 , p = 0.024).conclusionsimpaired fibrinolysis and endothelial dysfunction are evident in subjects with normal glucose tolerance who later develop diabetes . high tpa antigen is predictive of future diabetes independent from the metabolic syndrome .
[ "recent meta - analyses have used mixed treatment comparisons in which both direct and indirect comparisons were used.11,12 duloxetine , a second - generation norepinephrine reuptake inhibitor that has demonstrated efficacy , safety , and tolerability in patients with mdd,1316 has been the subject of several recent mixed treatment comparisons . a recent analysis by cipriani et al12 compared the effects of 12 new - generation antidepressants in adults with mdd , and gartlehner et al11 conducted an analysis of 234 studies that included placebo as a comparator . however , these results are not applicable to clinical practice in japan , because they included data from patients taking duloxetine up to 120 mg / day , which is twice the maximum dosage ( 60 mg / day ) approved in japan . the primary purpose of the current study was to provide clinicians with efficacy results that would allow a comparison of duloxetine 60 mg / day with four approved ssris in japan . another drawback was the inclusion of patients who took antidepressants not approved or not even available for use in japan . therefore , it is uncertain whether these results can be applied to daily clinical practice in countries ( eg , japan ) where the approved dosage for duloxetine is 4060 mg / day and ssris are limited to four compounds , ie , paroxetine , sertraline , escitalopram , and fluvoxamine . to the best of our knowledge , there are no meta - analyses that compare the efficacy of duloxetine 60 mg / day with these ssris . selective serotonin reuptake inhibitors ( ssris ) , serotonin and norepinephrine reuptake inhibitors , and noradrenergic and specific serotonergic antidepressants are categorized as first - line treatments in many countries , including japan.1,2 thus , health care providers have the opportunity to choose an antidepressant from a variety of first - line treatment options . to select the most appropriate treatment for each patient , it is important for clinicians to be aware of the differences in efficacy between comparable antidepressants at the doses approved in their countries . one long - standing approach to comparing efficacy has been meta - analysis of several randomized controlled trials that compare widely used treatments.310 however , results have been inconsistent , perhaps partly due to the use of different methodologies .", "we reviewed this database and selected randomized controlled trials that included duloxetine and ssri for the acute treatment of mdd . the primary objective of the study was to determine whether duloxetine 60 mg / day was noninferior to paroxetine 20 mg / day in the acute treatment of patients with mdd , as assessed by the baseline - to - endpoint change in hamd17 total score over an 8-week period.13 the hmcr study was a multicenter , randomized , 8-month , placebo - controlled , double - blind study that evaluated the comparative efficacy of duloxetine and escitalopram for patients with mdd.14,15 the primary objective was to compare the onset of antidepressant efficacy for patients taking duloxetine 60 mg / day or escitalopram 10 mg / day . the eli lilly clinical trial database contains all clinical trials of duloxetine for patients with mdd that were conducted by eli lilly or its partners outside of japan . the hmat study ( groups a and b ) was a multicenter , parallel , double - blind , randomized , placebo - controlled and active comparator - controlled study with a blinded placebo lead - in and placebo lead - out . the hmcv study was a multicenter , randomized , double - blind , double - dummy , parallel , active treatment - controlled phase iii trial comparing the efficacy and safety of duloxetine 60 mg / day and paroxetine 20 mg / day for inpatients and outpatients with mdd .", "we reviewed this database and selected randomized controlled trials that included duloxetine and ssri for the acute treatment of mdd . the eli lilly clinical trial database contains all clinical trials of duloxetine for patients with mdd that were conducted by eli lilly or its partners outside of japan . the primary objective of the study was to determine whether duloxetine 60 mg / day was noninferior to paroxetine 20 mg / day in the acute treatment of patients with mdd , as assessed by the baseline - to - endpoint change in hamd17 total score over an 8-week period.13 the hmcr study was a multicenter , randomized , 8-month , placebo - controlled , double - blind study that evaluated the comparative efficacy of duloxetine and escitalopram for patients with mdd.14,15 the primary objective was to compare the onset of antidepressant efficacy for patients taking duloxetine 60 mg / day or escitalopram 10 mg / day . this objective was evaluated by testing the hypothesis that the percentage of patients taking duloxetine who met onset criteria at week 2 was not inferior to ( or at least as good as ) the percentage of patients taking escitalopram .", "our analyses included two groups : all randomized patients who had a hamd17 total score 15 and a subgroup of more severe patients who had a hamd17 total score 19 . the primary endpoint was mean change from baseline in hamd17 total score at week 8 . secondary endpoints were mean change in hamd17 subscale score , response rate , remission rate , and mean change in hamilton anxiety rating scale ( hama ) total score from baseline to week 8 . safety and tolerability measures included patient - reported treatment - emergent adverse events and overall rates of study discontinuation due to adverse events . continuous variables were calculated using analysis of covariance based on last observation carried forward values as follows : one analysis of covariance model was calculated for each study ( counting the groups a and b of the hmat study as two studies ) , with a fixed effect for investigator , treatment , and baseline score as covariates .", "nausea ( 25.7% ) , dry mouth ( 17.3% ) , dizziness ( 12.6% ) , constipation ( 11.0% ) , and decreased appetite ( 11.9% ) had a higher incidence than in placebo - treated patients , but the rates of these adverse events were similar between duloxetine - treated and ssri - treated patients except for nausea and dry mouth . for the more severe subgroup with hamd17 total scores 19 at baseline , again statistically significant differences were found in mean change in hamd17 total scores at week 8 , but greater efficacy for duloxetine was seen with the bech , maier , and retardation subscale scores compared with ssris : hamd17 bech ( 0.62 [ 1.16 , 0.08 ] ) , hamd17 maier ( 0.65 [ 1.18 , 0.12 ] ) , and hamd17 retardation ( 0.45 [ 0.83 , 0.07 ] ) . in the total population , hamd17 total score effect sizes for duloxetine and ssri versus placebo were comparable ( 0.260 and 0.256 , respectively ) . , no statistically significant differences were found in the mean change in hamd17 total score at week 8 between duloxetine - treated and ssri - treated patients ( 10.08 and 9.69 , respectively ) . however , the differences between duloxetine versus placebo and ssri versus placebo were statistically significant ( p<0.01 ) . statistically significant differences were shown for the duloxetine - treated versus placebo - treated patients ( or 1.61 ; 95% ci 1.112.33 ) and the ssri - treated versus placebo - treated patients ( or 1.83 ; 95% ci 1.272.64 ) .", "at baseline , patients were mostly middle - aged ( mean age 40.842.0 years ) , female ( range 63.8%67.4% ) , with mean hamd17 total scores ranging from 17.6 to 19.0 and mean hama total scores ranging from 14.4 to 15.8 . completion rates were approximately 70% ( 68.6% for duloxetine - treated patients , 72.3% for ssri - treated patients , and 66.8% for placebo - treated patients ) . the majority of patients were caucasian ; patients from east asia accounted for approximately 30% of duloxetine - treated and ssri - treated patients ( table 2 ) . adverse events were common reasons for discontinuation ( duloxetine - treated patients , 8.9% ; ssri - treated patients , 7.1% ; placebo - treated patients , 6.0% ; see table 3 ) . discontinuation due to lack of efficacy was more likely in placebo - treated patients than in duloxetine - treated or ssri - treated patients ( 13.3% versus 3.2% and 3.2% , respectively ) .", ", no statistically significant differences were found in the mean change in hamd17 total score at week 8 between duloxetine - treated and ssri - treated patients ( 10.08 and 9.69 , respectively ) . however , the differences between duloxetine versus placebo and ssri versus placebo were statistically significant ( p<0.01 ) . a comparison of the mean changes in hamd17 total , subscale scores and hama total score from baseline at week 8 ( last observation carried forward ) is shown in table 4 ; corresponding effect sizes are shown in figure 1 . in the total population duloxetine and ssri were comparable on most other efficacy measures ; however , duloxetine - treated patients showed a greater mean change from baseline in hamd17 retardation subscale score compared with ssri - treated patients ( least squares mean difference [ 95% ci ] ) ( 0.33 [ 0.60 , 0.07 ] ) . for the more severe subgroup with hamd17 total scores 19 at baseline , again statistically significant differences were found in mean change in hamd17 total scores at week 8 , but greater efficacy for duloxetine was seen with the bech , maier , and retardation subscale scores compared with ssris : hamd17 bech ( 0.62 [ 1.16 , 0.08 ] ) , hamd17 maier ( 0.65 [ 1.18 , 0.12 ] ) , and hamd17 retardation ( 0.45 [ 0.83 , 0.07 ] ) . in the total population , hamd17 total score effect sizes for duloxetine and ssri versus placebo were comparable ( 0.260 and 0.256 , respectively ) .", "the response rates at week 8 were 42.0% for the duloxetine - treated patients , 44.5% ( n=307 ) for the ssri - treated patients , and 24.4% ( n=77 ) for the placebo - treated patients . no statistically significant difference was found between the duloxetine - treated and ssri - treated patients ( or 1.05 ; 95% ci 0.801.37 ) . statistically significant differences were shown for the duloxetine - treated versus placebo - treated patients ( or 1.61 ; 95% ci 1.112.33 ) and the ssri - treated versus placebo - treated patients ( or 1.83 ; 95% ci 1.272.64 ) .", "the remission rates at week 8 were 35.2% for the duloxetine - treated patients , 36.1% ( n=249 ) for the ssri - treated patients , and 21.2% ( n=67 ) for the placebo - treated patients . no statistically significant differences were found at week 8 for the duloxetine - treated versus ssri - treated patients ( or 1.11 ; 95% ci 0.641.92 ) , the duloxetine - treated versus placebo - treated patients ( or 1.53 ; 95% ci 0.743.18 ) , or the ssri - treated versus placebo - treated patients ( or 1.60 ; 95% ci 0.773.33 ) .", "the most common treatment - emergent adverse events are summarized in table 5 . among duloxetine - treated patients , nausea ( 25.7% ) , dry mouth ( 17.3% ) , dizziness ( 12.6% ) , constipation ( 11.0% ) , and decreased appetite ( 11.9% ) had a higher incidence than in placebo - treated patients , but the rates of these adverse events were similar between duloxetine - treated and ssri - treated patients except for nausea and dry mouth .", "our results show that duloxetine and ssri treatment within their respective approved dosage in japan demonstrated comparable efficacy with regard to overall depressive symptoms . however , certain hamd17 subscale scores responded differently to duloxetine compared with ssris , and this may clarify the difference in clinical attributes among these antidepressants . first , when assessing overall efficacy using the mean changes in hamd17 total scores from baseline , both duloxetine and ssri demonstrated greater efficacy than placebo , but did not indicate any significant difference between each other for either the total population ( hamd17 total score 15 ) or the more severe population ( hamd17 total score 19 ) . on the one hand , this is consistent with a prior report by thase et al,4 where all randomized patients across any severity were analyzed and no significant difference in efficacy between duloxetine and ssri was found . second , when assessing energy and interest using retardation subscale scores , duloxetine showed greater efficacy regardless of baseline depression severity ( hamd17 total score 15 or 19 ) .", "further research that includes all available ssris using flexible dosing within their full therapeutic ranges will make it possible to generalize conclusions to the ssri group as a whole . the integrated database only included studies that were conducted by eli lilly or its partners outside japan ; therefore , sponsorship bias can not be fully mitigated . using this database resulted in inclusion of fewer studies than publication - based meta - analyses ; however , this methodology enabled us to analyze individual patient data that are not available in many publications . in addition , the exclusion of patients randomized to duloxetine > 60 mg / day limits the ability to generalize conclusions in some countries with approved dosages above a maximum of 60 mg / day , but this was not within the scope of our analysis . another limitation of this meta - analysis is that it only consisted of two ssris ( paroxetine and escitalopram ) although four ssris are available in japan . similarly , using this global database resulted in inclusion of caucasians as the majority ( 58.3% ) of the patient population . lastly , in these analyses , no correction for multiplicity was performed , so superiority based on p - values can not be assessed .", "comparison between duloxetine and ssri demonstrated comparable efficacy within the japan - approved dose range in patients with mdd . results of the hamd17 subscale analysis indicated that duloxetine might be superior to ssris in improving loss of energy and interest ." ]
backgroundapproved doses of antidepressants in japan are usually lower than those in the usa and european union , but to date meta - analyses comparing antidepressants have all used the higher doses approved in the usa and european union and often have used indirect comparisons . the purpose of this study was to conduct an integrated database analysis of patient level data to compare the effects of duloxetine with those of selective serotonin reuptake inhibitors ( ssris ) at the doses approved in japan.methodspooled data were analyzed from four randomized , double - blind , placebo - controlled studies that compared duloxetine at the dose range approved in japan ( 4060 mg / day ) with other ssris ( paroxetine 20 mg / day or escitalopram 10 mg / day ) and placebo in patients with major depressive disorder . in total , 1,694 patients were included in the analysis ( duloxetine , n=688 ; selective serotonin reuptake inhibitors , n=690 ; placebo , n=316 ) . the primary outcome measure was the mean change from baseline at week 8 in 17-item hamilton rating scale for depression ( hamd17 ) total and subscale scores.resultsduloxetine and both selective serotonin reuptake inhibitors were superior to placebo in hamd17 total score at week 8 in both the all - randomized group and the more severe subgroup ( hamd17 total scores 19 ) . duloxetine was superior to ssris in improving the hamd17 retardation subscale score ( least squares mean difference [ 95% confidence interval ] ) : all - randomized group , 0.33 [ 0.60 , 0.07 ] , p=0.015 ; severe subgroup , 0.45 [ 0.83 , 0.07 ] , p=0.020).conclusionwithin the dose range approved in japan for patients with major depressive disorder , duloxetine and selective serotonin reuptake inhibitors demonstrated comparable overall efficacy , with a possible advantage for duloxetine in improving loss of energy and interest . to the best of our knowledge , this analysis is unique not only in evaluating dosages specific to japan , but also in using individual patient data and the same endpoint across studies to allow for strictly direct head - to - head data comparisons as opposed to pooling direct and indirect comparisons .
[ "this paper sets out to discuss the possibility of supplementing the above - described methods with methodological approaches and concepts from another discipline based in cultural studies , namely medical anthropology ( or medical ethnology ) , and to apply these in the context of a specifically designed form of experience to which students are exposed . outside of germany we all have a very different understanding of how we define a need for help . the seminar medical care on the fringes of society : participant observation and change in perspectives has been designed with these approaches and experiences in mind . , medical anthropology is an established discipline in university departments , degree courses and associations .", "the new teaching concept was developed on the basis of the following findings and considerations : in the standard degree courses required by the regulations for licensing doctors medical students will get to experience doctor - patient interaction almost exclusively in a hospital setting or in doctors surgeries , in other words , in institutional environments which in terms of their organisation and management of internal procedures are driven by the rationality of medical thinking ( in addition to political and economic requirements ) . as a result , the esa provides services aimed at improving the health of women and men in housing difficulties , bearing in mind the unusual living conditions of these people . that a profound knowledge of the particular needs of homeless people as well as of institutional and legal possibilities in dealing with homeless people plays a central role in designing and implementing meaningful teaching concepts the aim was to systematically draw students attention to the following aspects and dimensions : the significance of each particular life situation , experience of suffering and particular ways of patients interaction in order to design ( medical ) support services that will pick up on their specific needs ; in this context the concept and method of field research and participant observation from ( medical ) anthropology is taught;the unsettling impact an unfamiliar setting can have in the context of doctor / patient interaction , and as a consequence gaining awareness of the importance of one s own subjectivity ( i.e. , of the medical staff ) in one s dealing with persons requiring help ; in this context the modified concept of counter - transference from ethno - psychoanalysis ( following devereux ) is addressed;getting to know and immersing themselves in the living environments , health problems and specific needs of people living on the fringe of society following the model of cultural immersion approaches , : aside from more general phenomena such as poverty and physical neglect , we are dealing here with precarious conditions in terms of hygiene and nutrition , multimorbidity , often coinciding with psychiatric comorbidity , along with the effect of stigmatisation and shame over the ( non-)use of available ( medical ) support services .", "the seminar is structured into a preparatory theoretical - methodological module , a practical module , namely the field work ( in the winter semester with the klte - bus , in the summer semester visiting social work in the context of the esa ) , and a follow - up module . the structure of the responsible social institutions , particularly those based in frankfurt ( fv , esa ; among others ) is presented and practical information on the planned field trip given . in addition , students are familiarised with the experience of patients rejecting their offer of support , which can often be disconcerting ; this includes introducing them to the different perceptions people have of illness , and to the concept of counter - transference . the seminar groups consist of around 10 students ; this figure is based upon the limited number of individuals when accompanying the klte - bus and in the context of the esa ( one student per appointment ) . students are informed about the legal , social and medical situation of people on the fringe of society ; previous experience and expectations from students are likewise discussed .", "somewhat in contrast likewise an unanimous perception the relevance for hands - on practical application ( relevant for my training as a doctor ) was recognised but felt to be less positive ( grades b and c ) . in answering the open questions , the on - site experience with social workers and ( in a different response ) the both in the evaluation and occasionally also in the essays the wish was expressed to actually extend the practical part of the seminar . arrangements for receiving written feedback from seminar participants at predefined intervals ( one , two and five years ) have been made , and interviews about the long - term effects of learning and reflection processes are planned with focus groups . the questions was the seminar interesting ? and the seminar encouraged reflection received the top grade ( a ) . the essays too contained statements that reflected the intensity of the seminar and the potential inherent in the anthropological approach complemented by field work and participant observation . three questions were of a general nature ( please assess how much you have learned ; relevance for training as a medical doctor ; overall school grade ) , six related to specific aspects of the seminar , such as design and structure of the teaching concept , preparation of the lecturer , availability and comprehensibility of relevant information / literature or learning environment . the overall feedback on the structure of the course , on the preparation of the lecturer ( b.m . ) and on the learning environment was between positive and very positive ( grade b or a in analogy to the school grading system ) .", "the preliminary experiences we gained with the teaching concept providing medical care on the fringe of society : participant observation and change in perspective illustrate that the spectrum of methodological approaches in q 2 ( ao ) can indeed be complemented by concepts from medical anthropology , in combination with exposing students to people in extreme social situations . further , opportunities will have to be created that will enable cooperation with such institutions that are willing to set up the organisational framework and make available their expertise to enable the direct contact of students with people on the fringe of society in their everyday living environments . the method of field research ( or inspired by this in the context of medical training that of cultural immersion ) has proven to be very helpful for understanding the perceptions and needs of socially or ethically marginalised groups , and in principle all other groups in health care , , , , [ . in relation to this in the context of the new teaching concept the attention on social determinants of health and how they impact on the pathogenesis and course of health conditions , it will be necessary to know and familiarise oneself with the central ( medical ) anthropological concepts and methods . yield synergies with other teaching concepts , for example in medical sociology , community medicine / public health or general medicine , , which focus on similar matters . collaborations with community medicine practitioners working for example at technical colleges / fachhochschulen or other institutions outside universities could likewise bear relevance . the teaching project therefore ties in with international models that likewise seek to integrate these teaching objectives in their medical training . will learn how to put themselves in the position of different protagonists in a range of medical settings , and practice the skill of reflecting critically upon putative conceptual / theoretical and normative - ethical assumptions in medicine .", "the new curricular option described here could only be realized through the co - operation and engagement of many members of staff at the frankfurter verein fr soziale heimsttten e.v . as well as the elisabeth - straen - ambulanz frankfurt / m . ( esa ) . we want to express special thanks to heiko ewald and christine heinrichs , together with the staff of the kltebus-project , the ostpark - project , the beratungszentrum fr aufsuchende sozialarbeit , as well as dr .", "" ]
this paper examines the new teaching concept providing medical care on the fringe of society : participant observation and change in perspectives in the context of the interdisciplinary field of querschnittsbereich 2/q 2 ( the transdisciplinary section under ao , the german regulations for licensed physicians ) that explores the history , theory and ethics of medicine . the disciplinary approach usually adopted in q 2 is supplemented with concepts from medical anthropology ; in addition students will be exposed to people in extreme social situations . the aim is to make students aware of and invite them to reflect upon : the importance of participant observation in the specific on - site setting of medical thinking and acting ; the importance of the subjectivity of all those involved in doctor / patient interaction ; and the fact that key medical terms ( such as the need as seen by the physician vs. the need as seen by the patient ) are essentially context - dependent in their interpretation . at a more general level students will learn how to put themselves in the position of different protagonists in a range of medical settings , and practice the skill of reflecting critically upon putative conceptual / theoretical and normative - ethical assumptions in medicine .
[ "the present study was performed to determine the actual status of infection with foodborne trematodes by recovery of adult flukes from riparian people of saravane and champasak province , lao pdr . the primary goal was to control opisthorchiasis in endemic areas and to reduce the incidence of cholangiocarcinoma in the mekong river basin . after completion of the international collaboration project between the korea association of health promotion and ministry of public health ( moph ) , lao pdr on the control of intestinal helminthiases in lao pdr from 2000 - 2004 , a new 5-year project plan was started in 2007 to control foodborne trematode infections by the korea foundation for international healthcare and moph , lao pdr . in this new project , lao peoples democratic republic ( lao pdr ) is located in the middle of the indochina peninsula , and the mekong river runs through the whole length of the country from north to south . until the 1990s , the liver fluke opisthorchis viverrini and soil - transmitted nematodes , including ascaris , trichuris , and hookworms , were the major helminths prevalent among the laotian people [ 5 - 8 ] . in 1991 , foodborne liver and intestinal flukes are important groups of parasites from the public health point of view [ 1 - 4 ] .", "most villagers were agricultural workers , and some had caught freshwater fish from small streams and ponds and consumed them raw or improperly cooked . a total of 1,460 fecal samples ( 1 sample per person ) were collected from the villagers ( 717 men and 743 women , 12 - 82 years - of - age ) from december 2009 to june 2010 . 1 ) . small riverside villages , each having 200 - 300 residents , located near the mainstream or tributaries of the mekong river were selected for this study , which included 12 villages ( in 6 districts ) in both saravane and champasak province . saravane province ( capital city , saravane ) is located about 500 km south from vientiane , and champasak province ( capital city , pakse ) is located nearby and just south of saravane province ( fig . fecal examinations and anthelmintic treatments were officially approved by the ministry of public health , laos , under the terms of the korea - laos agreement on foodborne trematodiases control in laos ( 2007 - 2011 ) . samples were transported to the malaria stations in saravane and champasak province within 2 - 3 days of collection and were stored at 4 until examined . thirty people who were positive for ste were selected for adult worm recovery at the malaria station . after obtaining informed consent , trematode eggs 23 - 32 m in size were collectively recorded as small trematode eggs ( ste ) . they were treated with a single oral dose of 40 mg / kg praziquantel ( distocide@ ; shinpoong pharm . ,", "the highest worm load of h. taichui collected from a single person was 129,159 in champasak province , followed by 97,791 and 71,647 in saravane province . the overall helminth egg positive rate was 78.8% and 66.4% in saravane and champasak province , respectively ( table 1 ) . the adult worm collection was completed in 30 people ( 15 men and 15 women ; 20 - 65 years ; 19 in saravane and 11 in champasak ) ( table 2 ) .", "the overall helminth egg positive rate was 78.8% and 66.4% in saravane and champasak province , respectively ( table 1 ) . the most highly prevalent was ste , which included eggs of o. viverrini , heterophyids , and lecithodendriids , with a prevalence of 69.9% ( 46.5 - 87.2% by district ) and 46.3% ( 7.5 - 73.9% by district ) in saravane and champasak province , respectively ( table 1 ) . the district showing the highest ste prevalence was toumlane ( 87.2% ) in saravane province and pathumphon ( 73.9% ) in champasak province . there were some mixed infection cases involving different kinds of nematodes , trematodes , and cestodes . paksong , an urban area of champasak province , displayed the lowest ste prevalence ( 7.5% ) among the 12 districts surveyed . the egg positive rates were not significantly ( p>0.01 ) different between men and women ( data not shown ) . other parasite eggs detected in saravane and champasak province included hookworms ( 20.1% and 22.1% , respectively ) , ascaris lumbricoides ( 5.7% and 4.0% , respectively ) , trichuris trichiura ( 0.8% and 5.6% , respectively ) , taenia spp .", "the highest worm load of h. taichui collected from a single person was 129,159 in champasak province , followed by 97,791 and 71,647 in saravane province . the total number of h. taichui specimens recovered in saravane and champasak province were 409,738 ( n=19 ; average 21,562 per person ) and 132,865 ( n=11 ; average 12,078 per person ) , respectively , which was markedly higher than the other helminth parasite species ( table 2 ) . the adult worm collection was completed in 30 people ( 15 men and 15 women ; 20 - 65 years ; 19 in saravane and 11 in champasak ) ( table 2 ) . two haplorchis spp . comprised 99.96% ( 99.95% and 99.98% in saravane and champasak province , respectively ) of the total helminth specimens recovered , whereas o. viverrini comprised only 0.04% ( 0.04% and 0.01% in saravane and champasak province , respectively ) . a total of 543,852 helminth specimens were recovered ( average of 18,128 per person ; range 6 - 129,238 worms per person ) . small numbers of specimens were collected for taenia saginata , c. formosanus , p. molenkampi , and e. japonicus from a small number of people ( table 2 ) .", "the present report of intestinal flukes , including h. taichui and h. pumilio , from people in champasak province is novel . therefore , it is suggested that the procedure we used is a reliable method for recovery of both liver and intestinal flukes from humans . the present study indicated that the sole use of fecal examinations to detect helminth eggs does not fully allow the determination of the actual prevalence and intensity of liver and intestinal flukes in lao pdr . the hyperendemicity of h. taichui infection among riparian people in saravane province was closely correlated with the report of metacercarial prevalence in fish in saravane province ." ]
in this study , we found that haplorchis taichui , a heterophyid intestinal fluke , is highly prevalent , with heavy worm loads , among riparian people in saravane and champasak province , lao pdr . fecal specimens were collected from 1,460 people ( 717 men and 743 women ) in 12 riparian ( mekong river ) districts and were examined by the kato - katz fecal smear technique . the overall helminth egg positive rate was 78.8% and 66.4% in saravane and champasak province , respectively . the positive rate for small trematode eggs ( ste ) , which included h. taichui and other heterophyids , opisthorchis viverrini , and lecithodendriids , was 69.9% and 46.3% in saravane and champasak province , respectively . to obtain adult flukes , 30 ste - positive people were treated with 40 mg / kg praziquantel and then purged . whole diarrheic stools were collected 4 - 5 times for each person and searched for fluke specimens using a stereomicroscope . mixed infections with various species of trematodes ( h. taichui , haplorchis pumilio , o. viverrini , prosthodendrium molenkampi , centrocestus formosanus , and echinochasmus japonicus ) and a species of cestode ( taenia saginata ) were found . however , the worm load was exceptionally high for h. taichui compared with other trematode species , with an average of 21,565 and 12,079 specimens per infected person in saravane and champasak province , respectively , followed by h. pumilio ( 41.9 and 22.5 , respectively ) and o. viverrini ( 9.4 and 1.5 , respectively ) . these results show that diverse species of intestinal and liver flukes are prevalent among riparian people in saravane and champasak province , lao pdr , with h. taichui being the exceptionally dominant species .
[ "for patients and families , the issue of data quality is personal . when treatment decisions or research conclusions are based on incomplete or inaccurate information a misdiagnosis , an incomplete medication list , the wrong demographic data", "thanks in part to the power of health information technology , individuals have new opportunities to be part of the solution when it comes to assessing and improving data quality . building on a framework for data quality ,", "as the source of patient - centered data , consumers have important roles to play in reviewing and confirming their own health information and should be engaged partners in efforts to understand and improve the quality of electronic health data .", "for patients and families , the issue of data quality is personal . when treatment decisions or research conclusions are based on incomplete or inaccurate information a misdiagnosis , an incomplete medication list , the wrong demographic data thanks in part to the power of health information technology , individuals have new opportunities to be part of the solution when it comes to assessing and improving data quality . i have overlaid opportunities for patient engagement at each step of the process , underscoring the critical role of individuals as the original data stewards ( see figure 1 ) . consumers are not only the foundation of the data quality framework kahn et al . , but have important roles to play in reviewing and confirming their own health information along the chain of data stewardship . recognizing patients and families as sources of valuable information and powerful forces for change in identifying and preventing errors will also help to foster a culture of safety and build a sense of partnership between providers and patients in the mutual pursuit of better health and care . building on kahn et al.s figure following the chain of data stewardship ,", "the number of people with online access to their electronic health information is growing by leaps and bounds . before the health information technology for economic and clinical health ( hitech ) act , patients had a right to receive a copy of their health records within 3090 days under the hipaa privacy rule . now , thanks to meaningful use , patients have the ability to view online , download , and transmit their own records within 36 hours after a hospital discharge , or within four business days after a doctor receives the health data.1 health information is increasingly available at the click of a button with blue button . blue button is an easy , secure method for individuals to download their medical records in digital form from a secure website offered by doctors , insurers , pharmacies or other health - related services.2 implementation of these policy changes is underway , and there are undoubtedly individuals who still struggle to access their own health information ( electronically or otherwise ) , and work is necessary to improve the experience and utility of online access for patients . nonetheless , online access to clinical information is an opportunity to partner with patients and families to assess and enhance the quality of health care data .", "i recently heard a speaker at the office of the national coordinator ( onc ) s consumer summit affectionately refer to the benefits of this new capability as an army of free fact checkers . these and other patient generated health data complement clinical information generated by care teams to provide a comprehensive view of an individual s health , thus enhancing data quality , as well as enabling more meaningful conclusions to be drawn from secondary uses of this data . with greater online access to their health information and new tools to electronically communicate and share information with providers , patients and families can help improve the accuracy and reliability of data stored in medical records . survey data show that online access has a positive impact on patients knowledge of their health , ability to communicate with doctors , and ability to correct information ( for 63 percent of patients ) . more frequent online access has an even greater impact on ability to correct information ( 71 percent for frequent users , compared with 48 percent for less frequent users).4 a 2014 nationwide survey found that patients with online access to their health information overwhelmingly use this capability : 86 percent log on at least once a year , and more than half ( 55 percent ) log on three or more times per year . in fact , the absence of health information produced , shared , and reviewed by patients themselves contributes to poor data quality . as patients and families get easier access to their medical records and health data , possibly for the first time , it is inevitable that they will have feedback corrections , additions , and observations to share .", "consumers have much to gain from , and contribute to , activities to assess and improve data quality.8 efforts to adopt and implement a comprehensive data quality framework should preserve and reinforce the role of individuals as the original data stewards , generating and sharing critical information to inform better research , safer clinical care , and ultimately improved health outcomes . as the original generators and stewards of their own health data , individual patients and consumers are the foundation in the data stewardship chain outlined in kahn et al.s data quality framework . individuals can review and verify data further down the stewardship chain via a portal offered by a health information exchange ( hie ) . underlying changes to clinical culture are also necessary : moving toward viewing patients as active partners in their care , rather than as passive recipients.6 great strides are being made in patient - centered outcomes research , as exemplified by the patient centered outcomes research institute ( pcori ) , which funds research and supports patients and other stakeholders to meaningfully partner with researchers throughout the research continuum . looking forward , we must also broaden our focus beyond current data types and quality issues to consider relevant health data outside traditional clinical settings , such as social determinants of health ( building on the institute of medicine s recommendations),7 and their place and impact in the data quality framework ." ]
introduction : for patients and families , the issue of data quality is personal . when treatment decisions or research conclusions are based on incomplete or inaccurate information a misdiagnosis , an incomplete medication list , the wrong demographic data care safety , quality , and outcomes suffer and patients and families suffer.opportunity for change : thanks in part to the power of health information technology , individuals have new opportunities to be part of the solution when it comes to assessing and improving data quality . building on a framework for data quality , there are numerous opportunities for patients to be part of feedback loops to understand and improve data quality are presented.foundation for the future : as the source of patient - centered data , consumers have important roles to play in reviewing and confirming their own health information and should be engaged partners in efforts to understand and improve the quality of electronic health data .
[ "adverse drug reactions ( adrs ) , including interactions , in older people are a common cause of admission to hospital1 and are also a common cause of disease in hospitalized patients . frail elderly patients appear to be particularly at risk of adrs . in some cases , this is because insufficient account is taken of the effect of age and frailty on the pharmacokinetic and pharmacodynamic of the drug , especially in relation to hepatic2 and renal elimination.3 although many adrs are recognized during the drug development process and before licensing , this is not always the case , especially when they are uncommon or rare.3 moreover , patients with severe cognitive impairment may not be able to refer symptoms related to an adr , making the recognition of this clinical condition a medical problem.4 rhabdomyolysis is a clinical and laboratory syndrome that is caused by various etiologies , involving the skeletal muscle.5 rhabdomyolysis is characterized by the leaking of myoglobin and other intracellular proteins and electrolytes into the circulation , and may be associated with a wide variety of diseases , injuries , medications , and toxins.5 it is important to recognize drug - induced rhabdomyolysis because clinical effects are usually reversible.4 rhabdomyolysis related to macrolide - statin interaction has previously been described.68 clarithromycin , like other macrolides , is an inhibitor of cyp450 3a4 , the major enzyme responsible for the metabolism of several drugs , in particular some statins like simvastatin and atorvastain.69 to date , rhabdomyolysis related to clarithromycin has been reported in only one previous case report.10 we report the case of a 90-year - old caucasian male , admitted to the university hospital of pisa for dyspnea , who experienced rhabdomyolysis related to clarithromycin treatment .", "indeed , serum and urinary antigen and antibody exams excluded the presence of legionella pneumophila , streptococcus pneumoniae , and mycoplasma pneumoniae while virus infection assessments were not performed . on the second day of hospitalization , for continuing sinus tachycardia , in the absence of any evident causes ( fever , hypotension , arterial - venous fistula , thyrotoxicosis , suspected drug treatments , etc ) beta - blocker treatment ( bisoprolol 1.25 mg , daily ) was added and a cardiac markers curve was restarted ( figure 1 ) . the patient was discharged home on the sixth hospital day ( figure 1 ) with the diagnosis of iatrogenic rhabdomyolysis and acquired pneumonia of unknown etiology . a diagnosis of rhabdomyolysis was made and clarithromycin was stopped , while the concomitant therapy with ceftriaxone , bisoprolol , and aerosol with salbutamol and oxitropium was continued .", "clarithromycin , like other macrolides , is an inhibitor of cyp450 3a4 , the major enzyme responsible for the metabolism of several drugs , in particular some statins as simvastatin and atorvastatin.3,69 rhabdomyolysis related to macrolide and statins interaction has previously been described ; however , rhabdomyolysis related to clarithromycin has been reported in only one previous case report.8,10 in our case , there was an evident temporal sequence between clarithromycin exposure - withdrawal and the onset - recovery from rhabdomyolysis biochemical signs , while other potential causes of muscle damage were reasonably excluded . overall , these findings allowed us to make the diagnosis of rhabdomyolysis with sufficient warranty . although clarithromycin associated rhabdomyolysis is mainly due to pharmacokinetic interactions , a direct muscle toxicity might be postuled.5,10 the diagnosis of rhabdomyolysis , unless there is a high index of suspicion , can be missed since muscular pain , swelling , and tenderness may not be prominent or even absent ." ]
rhabdomyolysis is a clinical and laboratory syndrome that is caused by various etiologies , involving the skeletal muscle . clarithromycin , like other macrolides , is an inhibitor of cyp450 3a4 , the major enzyme responsible for the metabolism of several drugs , in particular some statins . rhabdomyolysis related to macrolide statin interaction has previously been described . to date , rhabdomyolysis induced by clarithromycin has been described in only one previous report . we describe the case of a 90-year - old caucasian male , admitted to the university hospital of pisa for dyspnea , who developed rhabdomyolysis associated with clarithromycin administration .
[ "supravalvar mitral ring is a circumferential ridge or membrane arising from the left atrial wall overlying the mitral valve and frequently attached to the mitral valve.1 variable in thickness and extent , the ring ranges from a thin membrane to a thick discrete fibrous ridge.2 the membranous variety may be difficult to detect because the membrane often adheres to the anterior mitral valve leaflet while remaining just proximal to the posterior mitral leaflet . we herein present a case of a supraventricular ring in a 17-year - old male , who presented with syncope . adhesion to the valve may impair the opening of the leaflets , and this impairment may be the main mechanism of mitral valve inflow obstruction in some patients .", "about 15 years ago , he had undergone a cardiac operation for ventricular septal defect ( vsd ) closure and mitral valve repair . in chest x - ray there was a free floating high redundant obstructive membrane in the left atrium that was attached to the mid portion of the anterior mitral valve leaflet and also in the medial and base of the posterior mitral valve leaflet and large papillary muscles in the left ventricle ( figure 1 ) . after heparinization , extracorporeal circulation was established between the venae cava and the ascending aorta . following a median sternotomy ,", "supravalvar mitral ring rarely occurs as an isolated defect ; other congenital heart defects coexist in 90% of patients . shone s complex is a combination of four congenital heart defects : supravalvar mitral ring , parachute mitral valve , subvalvar aortic stenosis , and aortic coarctation . the mitral valve itself is often abnormal and stenotic at the valvar or subvalvar level ; fusion of leaflets , a small valve orifice , and abnormal papillary muscles are common abnormalities .", "preoperative identification of a supravalvular mitral ring is the target for obtaining good surgical results . for the identification of this congenital heart disease ," ]
supravalvar mitral ring is a rare congenital heart defect of surgical importance . the condition is characterized by an abnormal ridge of the connective tissue on the atrial side of the mitral valve . it often substantially obstructs the mitral valve inflow . we herein introduce a case of a supravalvar mitral ring in a 17-year - old male , who was admitted to our hospital with cardiac syncope . he had undergone a cardiac operation for ventricular septal defect ( vsd ) closure and mitral valve repair 15 years before . transthoracic echocardiography , transesophageal echocardiography , and finally cardiac catheterization revealed a neglected supravalvular mitral ring . the ring was resected in a second operation , and the patient was discharged from the hospital symptom free .
[ "a literature review was carried out in international electronic databases including pubmed , web of sciences , cumulative index to nursing and allied health literature ( cinahl ) , scopus , ebsco , embase and science direct without any time limitation , using the search terms qualitative research , authors of the present article endeavor to shine a light on the ethical issues affecting researchers and propose strategies to face the ethical challenges of qualitative studies , so as to provide applicable and trustworthy outcomes these keywords were also searched on national electronic databases including scientific information database ( sid ) , iran medex and medical articles library ( medlib ) using the same strategy . given that the researcher is considered to be the research instrument , and the plan of inquiry needs to be developed and altered as the study progresses , a qualitative researcher can not depend upon traditional approaches to address certain concerns such as bias and credibility . qualitative research is sometimes defined as interpretive research , and as interpretations can be incorrect or biased , the findings may be controversial ( 3 ) . however , qualitative research is not only useful as the first stage of quantitative research , but can also play a key role in validating it or in providing a different viewpoint on the same social phenomena ( 4 ) . . this could be the basis for the formulation of specific ethical guidelines in this regard . in the recent millennium , the constant trend of change in the demands of the community as well as transforming the trend of knowledge production has highlighted the necessity for researchers to adopt a more comprehensive approach .", "however , it was favored by various disciplines and experts of different branches of science and humanity such as health care , psychology , nursing , management , political science , education , and communication studies ( 2 , 7 ) . up to the 1970s , qualitative research was solely employed by anthropologists and sociologists . during the 1970s and 1980s , qualitative research has been conducted in the field of nursing in order to identify , describe and explain related concepts , experiences and phenomena and to develop the nursing knowledge . qualitative studies provide nurses with sensitivity to the lived experiences of individuals from different nursing care aspects ( 4 , 8) . , qualitative research has been performed to achieve the concepts of patient care and other main perceptions in the nursing profession .", "it is argued that humans have increasingly become the instrument of choice for naturalistic research due to certain characteristics : they are highly responsive to environmental stimuli , have the ability to interact with the situation , pull together different pieces of information at multiple levels simultaneously , and perceive situations holistically ; moreover , they are able to process findings the instant they become available , can present immediate feedback , and feel unusual responses . thus , nurse researchers must be aware of the impact of the questioning on the participants , and in order to decrease such harmful effects on human subjects , the reflexive approach is recommended ( 10 ) . in qualitative studies researchers in the case of nurses who perform qualitative research , ethical issues are raised when the nurse - patient relationship in the research area leads to some degree of therapeutic communication for the participants ( 9 ) . the researcher is involved in all stages of the study from defining a concept to design , interview , transcription , analysis , verification and reporting the concepts and themes . nevertheless , researchers need to improve the abilities that make them appropriate human instruments and consequently , their interpersonal skills are of major importance in natural settings and study processes ( table 1 ) ( 13 , 14 ) . therefore , whenever instruments are involved in qualitative research , a human being will be an integral part of the process ( 12 ) . are often required to clarify their role in the research process ( 11 ) . in the qr procedure", "the relationship and intimacy that is established between the researchers and participants in qualitative studies can raise a range of different ethical concerns , and qualitative researchers face dilemmas such as respect for privacy , establishment of honest and open interactions , and avoiding misrepresentations ( 19 ) . ethically challenging situations may emerge if researchers have to deal with contradicting issues and choose between different methodological strategies in conflict arises . therefore , qualitative health researchers need to clarify that the research they carry out will benefit science and can contribute to the improvement of health policy ( 5 ) . the qualitative method is utilized to explain , clarify and elaborate the meanings of different aspects of the human life experience . clarifications need to include the following issues : the nature of the study , the participants potential role , the identity of the researcher and the financing body , the objective of the research , and how the results will be published and used ( 27 ) .", "therefore , qualitative health researchers need to clarify that the research they carry out will benefit science and can contribute to the improvement of health policy ( 5 ) . the relationship and intimacy that is established between the researchers and participants in qualitative studies can raise a range of different ethical concerns , and qualitative researchers face dilemmas such as respect for privacy , establishment of honest and open interactions , and avoiding misrepresentations ( 19 ) . many people consider it necessary to participate in research that their peers , community and/or society may benefit from . ethically challenging situations may emerge if researchers have to deal with contradicting issues and choose between different methodological strategies in conflict arises . clarifications need to include the following issues : the nature of the study , the participants potential role , the identity of the researcher and the financing body , the objective of the research , and how the results will be published and used ( 27 ) .", "overall , the role of the researcher as ( a ) stranger , ( b ) visitor , ( c ) initiator , ( d ) insider - expert or other should be well defined and explained ( 3 ) . as brenner quoted kvale state that , preparing an ethical protocol can cover issues in a qualitative research project from planning through reporting ( 30 ) the principle of no harm to participants ought to be considered by researchers , who should be aware of the potential harms that might be inflicted upon study subjects . obviously , sometimes a conflict between the right to know ( defended on the basis of benefits to the society ) and the right of privacy ( advocated based on the rights of the individual ) may happen ( 27 , 28 ) . therefore , researchers should seriously consider the potential impact they may have on the participants and vice versa , and details of such interactions should be clearly mentioned in research proposals ( 23 ) . it is getting increasingly common for research ethics committees to seek documented proof of consent in a written , signed , and ideally , witnessed form . furthermore , in investigations of sensitive topics where written consent puts the informants at risk , audio recorded oral consent would be more appropriate ( 30 ) . the qualitative method is utilized to explain , clarify and elaborate the meanings of different aspects of the human life experience .", "interviewers should be properly scheduled to provide the researcher with sufficient recovery time and reduce the risk of emotional exhaustion , while allowing ample time for analysis of the objective and emotional aspects of the research . the probability of exposure to vicarious trauma as a result of the interviews needs to be evaluated . the researchers , therefore , play the role of a mediator between the experiences of the respondents and the community of concerned people ( 28 , 31 ) . ethnography has singular characteristics . when a researcher aims to study the culture of certain people , living amongst them is inevitable . in qualitative research , data are collected with a focus on multifaceted interviews and narratives to produce a description of the experiences . researchers can benefit from supervision sessions directed at learning , mentoring and skill development , all of which can foster their ability to carry out research without risking their health . adequate professional supervision ( which may be outside of the university ) can be of service to researchers in dealing with the potential stress associated with the study ( 35 37 ) . in order to gain explicit data , ethnographers need to know the role of instrument details .", "considering the aforementioned challenges , it is recommended to conduct further research in order to provide meticulous and explicit ethical protocols , guidelines and codes with respect to qualitative studies . it is argued that qualitative research that deals with sensitive topics in depth can pose emotional and other risks to both participants and researchers . it is noteworthy that such research should be directed towards making a difference in people s lives , improving care delivery in different settings and at all levels , and providing a framework for health sciences without any ethical disturbances . as a result of the extensive body of research in the field of medical sciences , therefore , it is necessary for researchers to continuously update their investigation skills in terms of methodology and find novel techniques to better carry out studies in the field of health and sociology . as explained before , therefore , development of practical strategies and communicating them to researchers can be of great benefit and assist them in conducting more perceptive qualitative studies . clear protocols for dealing with distress should be in place so that both parties involved in research can use them if necessary ." ]
considering the nature of qualitative studies , the interaction between researchers and participants can be ethically challenging for the former , as they are personally involved in different stages of the study . therefore , formulation of specific ethical guidelines in this respect seems to be essential . the present paper aimed to discuss the necessity to develop explicit guidelines for conducting qualitative studies with regard to the researchers role . for this purpose , a literature review was carried out in domestic and international databases by related keywords.health care providers who carry out qualitative research have an immense responsibility . as there is no statistical analysis in qualitative studies , the researcher has to both evaluate what he or she observes and to interpret it . providing researchers with the necessary skills and applying stringent supervision can lead to better extraction of reliable information from qualitative studies . this article presents a debate in order to illustrate how researchers could cover the ethical challenges of qualitative studies and provide applicable and trustworthy outcomes.researchers face ethical challenges in all stages of the study , from designing to reporting . these include anonymity , confidentiality , informed consent , researchers potential impact on the participants and vice versa . it seems of paramount importance that health care providers , educators and clinicians be well informed of all the different aspects of their roles when acting as qualitative researchers . hence , these adroit roles need to be well defined , and the use of practical guidelines and protocols in all stages of qualitative studies should be encouraged .
[ "there is limited data on the antibiotic resistance of bacteria in fish and other cultured organisms sampled directly from fish farms as well as the aquaculture environment . this sector is challenged with the diverse type of diseases and bacterial infections ; and antibiotics are an excellent tool to circumvent the problem [ 14 , 15 ] . the presence of bacteria with multiple antibiotic resistance found in food products has become a threat to public health as there is potential that the carried or acquired genes are transferred to other bacteria of clinical significance [ 1618 ] . some antibiotics which are commonly used in food - producing animals are also used in human medicine , reducing the antibiotic 's efficiency when treating infections and increasing the morbidity and mortality associated with diseases . since the discovery of penicillin in 1928 by a scottish scientist alexander fleming followed by the release of many other earlier drugs onto the market to treat infection , the development of drug resistance in various sectors including aquaculture has been reported [ 13 ] . antimicrobial agents have been widely used in fish farming for either therapeutic , prophylactic , or other purposes . the misuse and abuse of the antimicrobial drugs are among the important factors that have contributed to the rise of resistant microbes around the world . the evolution of bacteria towards antibiotic resistance has been accelerated distinctly by selective pressure due to inappropriate and overuse of the antibiotics [ 3 , 9 ] . in the efforts to cope with this problem the use of antibiotics needs to be monitored from time to time to evaluate the emergence and spread of bacterial resistance towards antimicrobial agents [ 5 , 21 ] .", "cultured species refers to fish or shrimp . in kuching , bintulu , and miri , ninety - four bacterial isolates from 17 different genera were assessed for their susceptibility to different antibiotics utilizing the disk diffusion method according to method described by clinical and laboratory standards institutes ( clsi ) on mueller - hinton agar ( mha ) . sampling was carried out at aquaculture farms located at selected districts in sarawak , malaysian borneo , including kuching , bintulu , limbang , miri , and sampadi ( lundu ) . the cultured organisms collected were the fish while in limbang and sampadi ( lundu ) , the cultured organisms collected were shrimps . the isolation , designation , and identification of the isolates were carried out as reported by kathleen and coworkers earlier . three types of samples were collected which were the sediment , water , and cultured species .", "the antibiotic profile of the bacterial isolates from the aquaculture fish and shrimps and their environment is shown in table 1 . . isolated from water in limbang aquaculture farm was resistant towards 12 out of 19 antibiotics tested , which was the highest amount of antibiotic resistance observed in this study . isolates with mar < 0.2 were determined as isolates recovered from low risk sources of contamination while isolates with mar > 0.2 were from high risk sources . in this study , in this study , commonly used antibiotics in both veterinary and human medicine were selected for the antibiotic susceptibility testing .", "assessment of the antibiotic resistance among aquaculture bacteria against antimicrobial agents is important for update on the bacterial antibiotic resistance patterns . isolation of antibiotic resistant bacteria from aquaculture products and aquaculture environment indicates the health risk associated with the aquaculture . awareness on antibiotic resistance threat should be instilled in the community regardless of age as precaution and prevention step against dissemination of antibiotic resistant bacteria . many surveillance programs had also been introduced to monitor the emergence and spread of antibiotic resistant bacteria . there had been reports on detection of antibiotic resistance genes in bacteria isolated from aquaculture products that can be transferred to human microbiota . thus , any source of antibiotic resistant bacteria must be carefully monitored . in antibiotic resistance analysis it is part of a surveillance system aiming at monitoring emerging antibiotic resistant bacteria and their widespread . banning of antibiotics has aided in reducing the number of antibiotic resistant bacteria in an environment . alternatives to treatment using antibiotics like probiotics , vaccines , and antimicrobials from plants should be also considered . although antibiotic usage in the studied farms has been stopped decades ago , antibiotic contamination is still possible as there may still be residues of antibiotics left in the environment .", "although antibiotic resistance in aquaculture in the malaysian borneo is still in its infancy , the need for continuous monitoring of the antibiotic resistance patterns should not be overlooked and the community should be educated on the awareness of antibiotic resistance and its implication on human health and environment . the mar indexing has revealed that 63.1% of the isolates came from low antibiotic usage area ." ]
the administration of antimicrobials in aquaculture provides a selective pressure creating a reservoir of multiple resistant bacteria in the cultured fish and shrimps as well as the aquaculture environment . the objective of this study was to determine the extent of antibiotic resistance in aquaculture products and aquaculture 's surrounding environment in sarawak , malaysian borneo . ninety - four identified bacterial isolates constituted of 17 genera were isolated from sediment , water , and cultured organisms ( fish and shrimp ) in selected aquaculture farms . these isolates were tested for their antibiotic resistance against 22 antibiotics from several groups using the disk diffusion method . the results show that the highest resistance was observed towards streptomycin ( 85% , n = 20 ) , while the lowest resistance was towards gentamicin ( 1.1% , n = 90 ) . the multiple antibiotic resistant ( mar ) index of the isolates tested ranged between 0 and 0.63 . it was suggested that isolates with mar index > 0.2 were recovered from sources with high risk of antibiotic resistant contamination . this study revealed low level of antibiotic resistance in the aquaculture bacterial isolates except for streptomycin and ampicillin ( > 50% resistance , n = 94 ) which have been used in the aquaculture industry for several decades . antibiotic resistant patterns should be continuously monitored to predict the emergence and widespread of mar . effective action is needed to keep the new resistance from further developing and spreading .
[ "with an incidence rate of 0.92% , maternal puerperal lower extremity nerve injuries are rare . lateral femoral cutaneous neuropathy ( meralgia paraesthetica ) is the most common , followed by femoral neuropathy . the presented case involved a 32-year - old woman with bilateral heel numbness due to bilateral neuropathy of the medial calcaneal nerve due to external compression during vaginal delivery . nerve injuries are more likely to occur in nulliparae , in cases of prolonged stages of labour and assisted vaginal deliveries .", "a diagnosis of bilateral neuropathy of the medial calcaneal nerve , most likely due to longstanding pressure on both heels with epidural analgesia as a predisposing factor , was made . a 32-year - old woman presented to our neurology outpatient clinic with tingling and numbness in both heels . , a near - nerve needle conduction study of the medial calcaneal nerve was not performed .", "bilateral neuropathy of the medial calcaneal nerve due to external compression during delivery using epidural analgesia is very rare . prolonged labour with spinal analgesia and a continuation of analgesia during episiotomy probably masked signs of external compression on both heels . however , no details about delivery or analgesia in that patient were mentioned . in epidural analgesia during delivery , a motor block is unwanted , and thus voluntary muscle movements are possible , which makes longstanding external compression of nerves uncommon . in our patient ,", "bilateral medial calcaneal nerve neuropathy as a result of external compression is a rare complication of epidural obstetric analgesia .", "" ]
we describe the case of a 32-year - old woman who developed bilateral heel numbness after obstetric epidural analgesia . we diagnosed her with bilateral neuropathy of the medial calcaneal nerve , most likely due to longstanding pressure on both heels . risk factors for the development of this neuropathy were prolonged labour with spinal analgesia and a continuation of analgesia during episiotomy . padded footrests decrease pressure and can possibly prevent this neuropathy .
[ "the aim of this study was to evaluate , using a conventional pcr assay , the prevalence of mhf and cmhm infections in stray cats from colonies in milan and to identify possible risk factors for these infections . their zoonotic potential has recently been substantiated by the molecular identification of a feline haemoplasma isolate ( mhf ) in an hiv - positive immunocompromised human patient . three feline haemoplasma species are described : mycoplasma haemofelis ( mhf ) , candidatus mycoplasma haemominutum ( cmhm ) , and candidatus mycoplasma turicensis ( cmt ) . these feline haemoplasmas are the causative agents of infectious anemia in cats and in several mammalian species .", "conventional pcr was performed on blood samples to amplify dna associated with haemoplasmas ( mhf and cmhm ) . association between the three groups of haemoplasma status ( haemoplasma positive , mhf positive only , and cmhm positive only ) and categorical variables ( age , gender , colony of origin , bcs , season of sampling , health status , presence or absence of selected clinical and cbc abnormalities , felv / fiv status , and t. gondii test results ) were analysed by univariate analysis using the chi - squared test ( cell frequencies of > 5 ) or fisher 's exact test ( cell frequencies of 5 ) . during a 2-year collection period ( january 2008 to january 2010 ) , blood samples were taken from 260 stray cats from urban colonies in milan ( northern italy ) , under a trap - neuter - release ( tnr ) program approved by the local authority of the city council . the results of these serological tests have been already published and were reanalyzed with the present results . the cats were not systematically examined for the presence of ticks or fleas and so rates of ectoparasitism were not recorded . unhealthy cats were defined as cats with one or more of the following clinical abnormalities : lymph node enlargement , pale mucous membranes , stomatitis , or signs of ocular and respiratory infections . the seasonal analysis based on the date of sample collection", "haemoplasmic dna was detected in 33.1% ( 86/260 , 95% ci 26.540.9% ) of blood samples . of the positive samples , 28 cats ( 10.8% , 95% ci 7.215.6% ) were infected with mhf and 58 cats ( 22.3% , 95% ci 16.928.8% ) were infected with cmhm . no significant associations were found with cbc abnormalities and haemoplasma pcr - positive results ( figure 1 ) or in the number of anaemic and nonanaemic cats using a t - test . characteristics of the population and association between risk factors and haemoplasma pcr status ( negative or positive ) are reported in table 1 and between mhf alone and cmhm alone positive results in table 2 .", "we present the first study investigating the prevalence of haemoplasmas in urban stray colony cats from the city of milan in northern italy . regardless of these limitations , we believe that this study provides new and useful information on feline haemoplasma infections in stray cats in italy . the prevalence of haemoplasma infection in our sample showed a similar pattern to that reported worldwide in client - owned [ 57 , 915 , 1719 ] and stray cats [ 1923 ] .", "from this study it can be concluded that feline haemotropic mycoplasma mhf and cmhm are common in the stray cat population of milan . indeed , pet cats with outdoor access in this region should be regularly monitored and treated for ectoparasites to minimize health risks . importantly , feline blood donors in this area should undergo pcr screening for these infections before donations and preferably donors should be drawn from exclusively indoor cats that receive regular flea control ." ]
this study investigated the prevalence of feline haemoplasma infections in a number of stray cat colonies in milan , northern italy . blood samples from 260 stray cats were evaluated , with conventional pcr , for the presence of dna associated with mycoplasma haemofelis ( mhf ) and candidatus mycoplasma haemominutum ( cmhm ) . odd ratios ( or ) were calculated to identify risk factors for haemoplasma infections . pcr was positive in 86 out of 260 subjects ( 33.1% ) , with a prevalence of 10.8% ( 28/260 cats ) for mhf and 22.3% ( 58/260 cats ) for cmhm . no coinfections were registered . there were significant associations between infections and season of sampling , that is , a negative association between winter sampling and a haemoplasma positive status ( or = 0.29 , p = 0.001 ) , or cmhm positive status ( or = 0.29 , p = 0.01 ) . haemoplasma infections are common in stray cats in milan . thus , domestic cats with outdoor access should be routinely monitored and treated for ectoparasites to minimize risks of disease acquisition . moreover , as these infections are transmitted via blood , feline blood donors from this area should be screened by pcr and preferably be drawn from a population of indoor cats regularly treated for fleas .
[ "in a case - control study , 140 patients including two equal groups of traumatic due to traffic injuries and non - traumatic patients were evaluated . using the persian version of the conners adult adhd rating scale ( caars ) self - report ( screening version ) the diagnosis of adhd was for children , a rating scale for diagnosing adhd in children designed by delavar & et al can be used ( 13).structured clinical interview for dsm - iv ( scid ) scid is a widely - used clinical tool for the classification of psychiatric disorders based on dsm- iv criteria . the overall internal consistency of the conner 's adult adhd rating scale was estimated as cronbaches of 0.83 . in case the conners adult adhd rating scale ( caars ) conner 's adult adhd rating scale is used to screen and treatment follow up of patients and its validity and reliability are in accordance with dsm - iv . among its good characteristics the reliability and feasibility of the persian version of this diagnostic instrument were already determined as fair to good for most diagnostic categories ( kappa > 0.6 ) . the study was performed in two university hospitals in tabriz , iran during a 13- month period - august 2008 to september 2009 .", "the conners adult adhd rating scale ( caars ) conner 's adult adhd rating scale is used to screen and treatment follow up of patients and its validity and reliability are in accordance with dsm - iv . among its good characteristics the diagnosis of adhd was for children , a rating scale for diagnosing adhd in children designed by delavar & et al can be used ( 13).structured clinical interview for dsm - iv ( scid ) scid is a widely - used clinical tool for the classification of psychiatric disorders based on dsm- iv criteria . this questionnaire had been translated to persian by icss ( institute for cognitive science studies ) in tehran . in this study , the overall internal consistency of the conner 's adult adhd rating scale was estimated as cronbaches of 0.83 . in case is having multiple indices including attention deficit index ( subscale a ) , hyperactivity - impulsivity index ( subscale b ) , adhd symptoms total index ( subscale c ) , and adhd index ( subscale d ) . the reliability and feasibility of the persian version of this diagnostic instrument were already determined as fair to good for most diagnostic categories ( kappa > 0.6 ) .", "in addition , the chi - square and fisher exact tests were used for categorical variables . in all cases , the p values less than 0.05 were considered statistically significant . comparisons were made using independent samples t - test and mann - whitney u - test for numerical variables according to data distribution .", "no significant statistical difference was found between case and control groups on age , gender , educational level and occupation . with respect to type of vehicle , 25 cases had a car accident ( 35.7% ) and 45 had a motorcycle accident ( 64.3% ) . accordingly , the percent of subjects with accident history was significantly higher in case group ( p= 0.24 ) . furthermore , the mean driving hours in case group was significantly more compared to controls . subscales ' scores higher than 70 were considered positive.adhd index was positive in 3 ( 4.3% ) subjects in both case and control groups . adhd total symptoms were positive in 7 ( 10% ) and 10 ( 14.3% ) cases in both case and control groups respectively p= 0.438 , or= 1.5 ( 0.5- 4.2 ) , ci : 95% . in a subscale , inattentive symptoms were observed in 5 ( 7.1% ) and 6 ( 8.6% ) participants in case and control groups respectively p= 0.753 , or=1.2 ( 0.4- 4.2 ) , ci : 95% . in b subscale ( hyperactive - impulsive symptoms were observed in 7 ( 10% ) and 6 ( 8.6% ) participants in case and control groups respectively pv= 0.771 , or= 0.8 ( 0.3- 2.7 ) , ci : 95% . no significant difference was observed between the two groups with respect to other factors .", "in this study , the frequency of adult adhd was compared between traumatic adult patients ( due to traffic injuries ) and a control group . accordingly , adhd index was positive 4.3% in both case and control groups , adhd symptoms total were positive 10% , 14.3% in case and control groups respectively . the current study is the first report from tabriz- iran on the association of adhd to traffic injuries . besides the epidemiological studies , there are numerous clinical trials showing the strong association between adhd and car accidents . accordingly , it seems that most car accidents involving driver injury are not related to adhd . difference in driving duration is another major factor and the mean daily driving hours were significantly higher in patients with car accidents .", "this study showed that the odds of adult adhd was not significantly higher in drivers with traffic injuries compared with the matched controls . therefore , larger scale studies stratified for different types of traffic accidents are recommended to further investigate such an association", "most of the traffic injuries cause death but these case were not included in our study ." ]
objectivenowadays , it is well known that the attention - deficit / hyperactivity disorder ( adhd ) is not confined to children and adolescents . recent data showed that a considerable portion of the general adult population may be affected by adhd . on the other hand , the impact of adhd on driving performance , a major area of adult life , has gained enthusiasm . more recent studies revealed an association between adult adhd and undesirable driving problems . this study was performed to determine the association between presence of adult adhd and traffic injuries.methodsin this case - control study , in a 13 month period , 140 subjects ( 70 drivers / riders injured in traffic accidents , and 70 age- and sex - matched non traumatic controls ) were selected to participate in the study and were placed in two groups . subjects with psychiatric comorbidities were excluded . the conners adult adhd rating scale ( caars ) self - report ( screening version ) was used for screening adult adhd in both groups . finally , the occurrence of this condition was compared between the case and control groups.resultssixty- nine males and one female were recruited in each group with a mean age of 29.319.32 ( 18 - 61 ) years in the case and 29.039.07 ( range : 18 - 60 ) years in the control groups ( p > 0.05 ) . previous history of traffic accident was significantly higher in the case group ( 15.7% vs. 4.3% , p=0.024 ) . the mean driving time in a day was also significantly higher in the case group . in the case group , the scores of caars ( the adhd index , adhd symptoms total , inattentive subscale and hyperactive / impulsive subscale ) were positive ( higher than 70 ) in 4.3 , 10 , 7.1 and 10 percent of patients respectively . among the controls , the corresponding proportions were 4.3 , 14.3 , 8.6 and 8.6 percent respectively . the two groups were comparable for the mentioned rates.conclusionthe results of this study revealed no significant association between adhd and traffic injuries in tabriz- iran .
[ "region , the methylation of which is related to tissue specific gene expression . therefore , in the present investigation we have explored the possibility that methylation of the promoter contributes to the control of crh expression in trophoblast cells . crh is a 41-amino - acid peptide hormone synthesized in the paraventricular nucleus of the hypothalamus . we used the bewo choriocarcinoma cell line in the experiments , which is a well - characterized trophoblast model exhibiting dynamic dna methylation as well as ability to syncytialise and increase crh expression when stimulated with camp [ 1921 ] . because of this relationship , it is believed that the regulation of placental crh production is linked to the mechanism that determines the length of pregnancy and triggers labour and delivery . its function in the central nervous system is to stimulate the hypothalamic - pituitary - adrenal ( hpa ) axis as part of the stress response .", "expression levels of the crh mrna were determined relative to alien rna according to the ct method . the alien rna transcript served as a reference rna of equal abundance in all samples and pcr runs . no - template control and no - reverse transcriptase controls for all samples were included to detect residual genomic dna . contaminating dna was removed by dnase treatment using the turbo dna - free kit ( ambion / life technologies ) following the routine protocol . primer sequences for amplifying alien cdna are proprietary and were used according to the manufacturer 's instructions ( stratagen / integrated sciences ) . the crh cdna primers were designed and optimised by sehringer et al . and are listed in table 1 . the bisulfite - converted and pcr - amplified dna was ligated into the pgem - t easy vector using reagents provided by the manufacturer ( promega ) . the 10 l reaction mixtures contained ligation buffer , 3 weiss units of t4 dna ligase , 50 ng of pgem - t easy vector , and pcr product at 3 : 1 insert : vector molar ratio .", ", we have determined the effects of 8-br - camp and 5-aza - dc on the methylation of the 9 cpg sites present in the crh proximal promoter . the significant effects of 5-aza - dc on crh mrna expression suggested that dna methylation was involved in the control of crh gene activity . to explore this further the methyltransferase inhibitor eliminated the methylation differences among individual cpgs in the presence of 8-br - camp as well ( figure 4 ) . treatment with the dna methyltransferase inhibitor 5-aza - dc decreased methylation at all cpg sites compared to vehicle , except for cpg 4 , where methylation was relatively low . furthermore , 5-aza - dc abolished the differences between the methylation levels of the individual cpgs .", "the aim of this study was to explore the involvement of promoter methylation in crh gene regulation in human trophoblast cells . our results show that the crh promoter follows this general trend , which is different from primary trophoblasts , where crh promoter methylation does not change in culture and remains unaltered by 5-aza - dc and 8-br - camp under the conditions where bewo cells show methylation changes . for this reason , bewo cells this suggests the possibility that 5-aza - dc may potentially influence crh expression indirectly through intervening gene products generating synergy between 8-br - camp and 5-aza - dc . moreover , 5-aza - dc decreases dna methylation globally increasing or repressing the activity of numerous genes [ 4143 ] . placental crh expression is predictive of gestational length and is influenced by pregnancy disorders [ 4 , 30 ] .", "we have utilized the dynamic changes of dna methylation in the bewo cell line to explore the relationship between this epigenetic chromatin modification and crh gene expression in a trophoblastic cell type . clonal bisulfite sequencing revealed the cpg site - specific and allele independent partial methylation of the crh proximal promoter and classified it as an intermediately methylated region of the genome . furthermore , our results are consistent with the possibility that dna methylation controls crh expression indirectly , but any intervening factor that may regulate crh expression by a dna methylation - dependent mechanism remains to be determined . the data suggest that promoter methylation determines the contribution of the cre , its various associated transcription factors , and a trophoblast specific alternative camp - response element to crh gene regulation ." ]
corticotropin releasing hormone ( crh ) production by the human placenta increases exponentially as pregnancy advances , and the rate of increase predicts gestational length . crh gene expression is regulated by camp in trophoblasts through a cyclic amp - response element ( cre ) , which changes its transcription factor binding properties upon methylation . here we determined whether methylation of the crh proximal promoter controls basal and camp - stimulated crh expression in bewo cells , a well - characterized trophoblastic cell line . we treated the cells with 8-br - camp and the dna methyltransferase inhibitor 5-aza-2 deoxycytidine ( 5-aza - dc ) and determined the effects on crh mrna level and promoter methylation . clonal bisulfite sequencing showed partial and allele independent methylation of cpgs in the crh promoter . crh mrna expression and the methylation of a subset of cpgs ( including cpg2 in the cre ) increased spontaneously during culture . 8-br - camp stimulated crh expression without affecting the increase in methylation . 5-aza - dc decreased methylation and augmented 8-br - camp - stimulated crh expression , but it blocked the spontaneous increase of crh mrna level . we conclude that the crh promoter is a dynamically and intermediately methylated genomic region in bewo cells . promoter methylation did not inhibit crh gene expression under the conditions employed ; rather it determined the contribution of alternative camp - independent pathways and camp - independent mechanisms to crh expression control .
[ "these ab initio calculations consist of the following steps : the choosing the model structures , geometry optimization , natural bond orbital analysis ( nbo ) , atoms in molecules analysis ( aim ) , and spectroscopic nmr parameter calculations , which are currently among the most popular methods used for conformational analysis . the aim of the work described in the present paper was to clarify the role of intramolecular hydrogen bonds in clindamycin using quantum chemical calculations . we then characterize the conformations and molecular properties , focusing on the intramolecular hydrogen bonds . the three compounds lincomycin ( a natural antibiotic produced by streptomyces lincolnensis and discovered in 1961 ) , clindamycin , and pirlimycin ( two semi - synthetic derivatives of lincomycin ) comprise a group of clinically important antibiotics known as lincosamides . the structure of lincomycin ( fig . no systematic and accurate study of the conformational behavior of clindamycin in the gas phase and in solution has been reported . although the accuracy of ab initio calculations is still below the state - of - art accuracy of experimental spectroscopic data , these calculations provide information about the shape of the potential energy surface ( pes ) without the need for any initial assumptions . characterizing the conformational changes and their possible effects on the encounter with and binding to the ribosome are important aspects of understanding the mechanism of action of lincosamides . to the best of our knowledge ,", "nmr spectroscopy is one of the techniques used to investigate molecular structures and interactions . in the last part of our work , we calculated the nmr chemical shifts and spin spin coupling constants for the gas - phase optimized geometries at the b3lyp/6 - 31 g level . the two ribosome - complexed structures show similar clindamycin conformers , and in one the pyrrolidynyl propyl group is rotated by 180. in this work , we used two significantly different conformers of clindamycin , which were taken from ribosome clindamycin complexes of deinococcus radiodurans ( pdb code 1jzx ) and haloarcula marismortui ( pdb code 1yjn ) . four structures of clindamycin are available in the protein data bank ( as of may 2011 ) . three of these structures are in complex with the bacterial ribosome [ 1315 ] , while one is in complex with linb . the coordinates of residues within 10 of each clindamycin atom were considered , and partial charges were assigned based on the g43b1 gromos96 force field . in this way , we studied the effect of the charged ribosome environment on the conformations of the lincosamides . the second model that was used to describe the environment of the antibiotic , and mimics the surroundings of the antibiotic in the ribosomal rna , was the model with point ions placed around the antibiotic [ 22 , 23 ] .", "to summarize , nbo analysis indicates that the occupancy of the antibonding c15h39 orbital in the a conformer or the o6h37 orbital of the eight - member moiety in the b conformer should be an overall indicator of conformational stability . this analysis indicates that the main influence on the stability of the b conformer is the ihb between the two moieties of the molecule . our results show that the most important is the energy profit from the formation of the ihb . the presence of hydrogen - bond donors ( o h , n therefore , the charge transfer between the pyrrolidine - derivative ring and the six - atom sugar ( methylthiolincosamide ) , which are linked via an amide bond , is the dominant factor in the greater stability of the b conformer . the second - order perturbation energy ( e ) due to the interaction energy between the donor and acceptor orbitals in the central part of the molecule together with the charge transfer ( ct ) between two moieties of the molecule are presented in table 3 . the selected orbital interactions ( with a stabilizing effect of over 8 kcal / mol ) additionally , for the a conformer , we found quite a strong interaction between the lone pair orbital on o4 and the antibonding c12c11 orbital ( 0.068 au ) .", "the differences in the geometries of the two clindamycin conformers are related almost exclusively to the ihbs in the central part of the molecule . for the most stable conformer , b , an eight - atom ring is formed , whereas a six - atom ring is found in the a conformer . our results show that the most important is the energy profit from the formation of the ihb . the presence of hydrogen - bond donors ( o h , n bottom : values for the a and b conformers of clindamycin , lincomycin , and pirlimycin ( optimized using a redundant coordinate algorithm in vacuum ) in the pcm model of solvent and in the point ions . bottom : values for the a and b conformers of clindamycin , lincomycin , and pirlimycin ( optimized using a redundant coordinate algorithm in vacuum ) in the pcm model of solvent and in the point ions .", ", nbo analysis indicates that the occupancy of the antibonding c15h39 orbital in the a conformer or the o6h37 orbital of the eight - member moiety in the b conformer should be an overall indicator of conformational stability . additionally , for the a conformer , we found quite a strong interaction between the lone pair orbital on o4 and the antibonding c12c11 orbital ( 0.068 au ) . therefore , the charge transfer between the pyrrolidine - derivative ring and the six - atom sugar ( methylthiolincosamide ) , which are linked via an amide bond , is the dominant factor in the greater stability of the b conformer .", "this analysis indicates that the main influence on the stability of the b conformer is the ihb between the two moieties of the molecule . according to criteria elaborated by the aim theory , we found two types of intramolecular h - bonds in clindamycin : typical hydrogen bonds of type ch oc in the a conformer and oh o = c in the b conformer , and unconventional h - bonds of type oh x ( x = o , cl ) in both conformers ( fig . topological analysis of the electron density distribution provides evidence for bonding interactions through the discovery of a ( 3 , 1 ) critical point ( bcp ) , which is a key topological descriptor of internuclear interactions , while the laplacian of the electron density values at the critical point bcp is another sensitive measure of the properties of a classical bond .", "chemical shifts are sensitive to subtle changes in the electronic structure , which depends in a rather complex manner on the molecular structure , we will now discuss the dependence of the calculated nmr chemical shifts on the conformation and the ihb . as usual , the central part of the molecule is the most interesting part to consider for this purpose . the experimental c nmr chemical shifts of clindamycin fall within the interval 1690 pm . the chemical shifts of the carbon atoms are predicted to be located in their usual ranges : (c = o ) near to 185 ppm , (c h ) close to 70 ppm . the oxygen acts as the roton acceptor for the oh group , and its chemical shift is lower for the b conformer than for the a conformer of clindamycin . the chemical shift of the hydroxyl oxygen o6 is the highest for the a conformer ( considering its absolute value ) , and the same is true of the oxygen o7 in the ring.table 5b3lyp / aug - pcs-1 calculated chemical shifts for both clindamycin exp - opt conformers optimized at the b3lyp/6 - 31 g level in vacuum . intramolecular hydrogen bond more than the a conformer ( 185.1 ppm ) is stabilized by the c19o9", "we focused on the sensitivities of electronic structure parameters such as nbo atomic charges , bond critical points , nmr chemical shifts , and spin spin coupling constants to the conformation of clindamycin . internal rotations in clindamycin were investigated in vacuum and within the framework of the ief - pcm model . using nbo analysis , and with the aid of the aim theory , we have quantum chemically characterized the two conformers of each of the known lincosamides clindamycin , lincomycin , and pirlimycin at the b3lyp/6 - 31 g level . the presence of this internal hydrogen bond between the pyrrolidine - derivative ring and the six - atom sugar ( methylthiolincosamide ) is the main influence on conformer stability in vacuum and in water . the two most stable conformers of clindamycin exhibit c = oh o intramolecular hydrogen bonds . according to nbo and aim analyses ," ]
lincosamides are a class of antibiotics used both in clinical and veterinary practice for a wide range of pathogens . this group of drugs inhibits the activity of the bacterial ribosome by binding to the 23s rna of the large ribosomal subunit and blocking protein synthesis . currently , three x - ray structures of the ribosome in complex with clindamycin are available in the protein data bank , which reveal that there are two distinct conformations of the pyrrolidinyl propyl group of the bound clindamycin . in this work , we used quantum mechanical methods to investigate the probable conformations of clindamycin in order to explain the two binding modes in the ribosomal 23s rna . we studied three lincosamide antibiotics : clindamycin , lincomycin , and pirlimycin at the b3lyp level with the 6 - 31 g * * basis set . the focus of our work was to connect the conformational landscape and electron densities of the two clindamycin conformers found experimentally with their physicochemical properties . for both functional conformers , we applied natural bond orbital ( nbo ) analysis and the atoms in molecules ( aim ) theory , and calculated the nmr parameters . based on the results obtained , we were able to show that the structure with the intramolecular hydrogen bond c = o h o is the most stable conformer of clindamycin . the charge transfer between the pyrrolidine - derivative ring and the six - atom sugar ( methylthiolincosamide ) , which are linked via an amide bond , was found to be the dominant factor influencing the high stability of this conformer.figuremolecular graph of more stable conformer of clindamycin .
[ "initial evaluations suggest that pcmcs can provide timelier assessment , lead to a high degree of satisfaction among referring physicians , patients , and caregivers , and streamline access to specialists . in order to retain the fidelity of such programs and consistency with initial training and practice guidelines , and this paper describes the results of a consensus approach to identify qis and quality improvement mechanisms in an ontario - wide network of interprofessional pcmcs , and identify potential barriers and facilitators to the implementation of a quality assurance framework . however , dementia care predominantly resides with geriatric specialists , who are in short supply in canada and elsewhere , delaying access to care . to enhance the care of persons with dementia , effective early diagnosis and management models are required to mitigate its impact on patients , caregivers , and health - care systems . enhancing primary care capacity the rising prevalence of alzheimer s disease and related dementias ( henceforth referred to as dementia ) is emerging as a leading global health system challenge . quality indicators ( qis ) , based on best practices , define achievable benchmarks and a quality assurance framework facilitates practice improvement through targeted , educational quality improvement mechanisms . to our knowledge practice drift and ensure ongoing high quality of care , quality assurance frameworks are needed .", "links to the web - based survey were electronically distributed to all pcmc clinicians ( n = 283 ) and ontario specialists through the ontario medical association sections of geriatric medicine ( n = 123 ) and neurologists ( n = 134 ) , and the canadian association of geriatric psychiatrists ( n = 305 ) . after each round , qis and improvement measures in the lower two tertiles of agreement ( i.e. , with mean ratings less than 7 ) were excluded , and those remaining were reviewed by the authors guided by respondent comments . respondents were asked to rate the qis and quality improvement mechanisms using a continuous integer 9-point scale , with 1 representing the least important and 9 the most important . we identified 38 candidate qis and quality improvement mechanisms for dementia care by reviewing existing clinical guidelines and quality indicator and improvement compendiums developed with standardized methods ( table 1 ) . qis and quality improvement mechanisms deemed redundant or containing duplicate themes were combined or amended with attention to preserving their intent and conciseness . a delphi technique was deployed to obtain agreement from pcmc clinicians and dementia specialists on preferred qis and quality improvement mechanisms . two authors ( gh , vb ) independently analyzed all written comments using descriptive content analysis and incorporated the feedback into the presentation of qis and quality improvement mechanisms in the second delphi round .", "respondents were asked to rate the qis and quality improvement mechanisms using a continuous integer 9-point scale , with 1 representing the least important and 9 the most important . we identified 38 candidate qis and quality improvement mechanisms for dementia care by reviewing existing clinical guidelines and quality indicator and improvement compendiums developed with standardized methods ( table 1 ) . a delphi technique was deployed to obtain agreement from pcmc clinicians and dementia specialists on preferred qis and quality improvement mechanisms . the delphi technique is an iterative consensus process , wherein surveys are used to solicit opinions from groups , and responses summarized and redistributed in a subsequent round for consideration .", "links to the web - based survey were electronically distributed to all pcmc clinicians ( n = 283 ) and ontario specialists through the ontario medical association sections of geriatric medicine ( n = 123 ) and neurologists ( n = 134 ) , and the canadian association of geriatric psychiatrists ( n = 305 ) . after each round , qis and improvement measures in the lower two tertiles of agreement ( i.e. , with mean ratings less than 7 ) were excluded , and those remaining were reviewed by the authors guided by respondent comments . qis and quality improvement mechanisms deemed redundant or containing duplicate themes were combined or amended with attention to preserving their intent and conciseness . data from the preceding round , including number of respondents , rating means , and standard deviations , were included in the subsequent round .", "two authors ( gh , vb ) independently analyzed all written comments using descriptive content analysis and incorporated the feedback into the presentation of qis and quality improvement mechanisms in the second delphi round . student s t - test was used to identify significant differences between pcmc clinicians and specialists . spss version 23.0 ( ibm corp . ) was used , with two - sided p values of < .05 as the threshold for statistical significance .", "our challenge is to maintain evidence based salience , which ultimately facilitates improved quality of life for persons with dementia and their family [ pcmc clinician , delphi round 2 ] . descriptive content analysis identified three themes related to potential barriers and facilitators to the establishment of a quality assurance framework in pcmcs : 1 ) its perceived importance , 2 ) collaboration and role clarity , and 3 ) the implementation process . almost all respondents mentioned the need to maintain high - quality care through ongoing , targeted training on pertinent clinical knowledge and consistency of approach among pcmc teams . two survey rounds were conducted between april and june 2014 . in the first round , 842 surveys were distributed with a response rate of 21.3% . other preferred quality improvement mechanisms included standardized electronic charting forms , self - directed learning activities , and interactive programs . they also identified specialists as agents to promote care quality , particularly in the context of a shared care approach . quality improvement mechanisms characterized by specialist integration , including case discussions , shared care , observerships , and mentorships , ranked highly ( table 5 ) . a second theme pertained to the operationalization and implementation of the quality assurance framework within the context of pcmcs , and identified a lack of clearly delineated responsibilities among referring clinicians , pcmcs , and specialists .", "our challenge is to maintain evidence based salience , which ultimately facilitates improved quality of life for persons with dementia and their family [ pcmc clinician , delphi round 2 ] . descriptive content analysis identified three themes related to potential barriers and facilitators to the establishment of a quality assurance framework in pcmcs : 1 ) its perceived importance , 2 ) collaboration and role clarity , and 3 ) the implementation process . a second theme pertained to the operationalization and implementation of the quality assurance framework within the context of pcmcs , and identified a lack of clearly delineated responsibilities among referring clinicians , pcmcs , and specialists . almost all respondents mentioned the need to maintain high - quality care through ongoing , targeted training on pertinent clinical knowledge and consistency of approach among pcmc teams . they also identified specialists as agents to promote care quality , particularly in the context of a shared care approach .", "almost all respondents mentioned the need to maintain high - quality care through ongoing , targeted training on pertinent clinical knowledge and consistency of approach among pcmc teams . others seemed unfamiliar with the purpose of quality assurance and construed the idea of tracking qis as supplemental work . all are relevant quality indicators for a pcmc [ specialist , round 2 ] . however , a few respondents were unsure why a quality assurance framework was needed at all . most recognized a formal quality assurance framework and individual qis as essential . great indicators and very necessary [ pcmc clinician , round 1 ] . is the intent of the questions to assess what we are doing now or [ what ] we think should be the standard ? [ pcmc clinician , round 1 ] . our challenge is to maintain evidence based salience , which ultimately facilitates improved quality of life for persons with dementia and their family [ pcmc clinician , delphi round 2 ] . this is the canadian consensus guideline that every doc should know [ specialist , round 1 ; emphasis added by authors ] .", "a second theme pertained to the operationalization and implementation of the quality assurance framework within the context of pcmcs , and identified a lack of clearly delineated responsibilities among referring clinicians , pcmcs , and specialists . patients with dementia with great plans should not need constant surveillance and follow up but ... this is not my experience ... they appear to often benefit from a watchdog team to ensure their decisions are being carried out . [ specialist , round 1 ] . information is sent back to referral physician with recommendations for caregiver and patient mostly related to change in medication or treatment , lifestyle modification and support resources [ pcmc clinician , round 2 ] . similar concerns were raised regarding the management of comorbidities . [ my ] assumption is that management of comorbidities is the primary care physician s domain . respondents perceived this as problematic because absence of clarity impedes the capture of clinical documentation relevant to qi measurement . this lack of clarity was considered most problematic with regard to patient follow - up .", "respondents provided several comments on potential barriers to the implementation process of a quality assurance framework in pcmcs . this [ case review ] could be done at the same time , as the specialist mentoring the clinic is in a clinic day with the team [ pcmc clinician , round 1 ] . they also identified specialists as agents to promote care quality , particularly in the context of a shared care approach . i think one of the most important quality indicators is a comparison of the pcmc performance versus the specialist , done on both patients referred to the specialist by the pcmc , and unselected patients seen in the clinic that would not have been referred to the specialist [ specialist , round 1 ] . a second issue identified in relation to the implementation of the quality assurance framework is the need to establish benchmarks to properly interpret qi scores . barriers to the implementation of this framework included role confusion among stakeholders and limited resources .", "this study used a consultative process among primary and specialty providers to identify a core group of qis and preferred quality improvement mechanisms for dementia care . quality assurance can be an effective method to ensure fidelity to best practices and maintain a high standard of care quality . finally , candidate qis and quality improvement mechanisms were not identified through a systematic literature review , but the use of published guidelines and compendiums likely identified the most important elements of quality dementia care , which would thus have remained highly ranked . selected quality improvement mechanisms emphasize a desire for multimodal education and closer collaboration with specialists . assessing care quality and publically reporting the findings are increasingly commonplace . selected qis address care processes , assessment and reassessment , medication review and management , investigations , non - pharmacological management , pharmacological management , and managing concomitant conditions .", "first , only two delphi rounds were conducted because the response rate fell markedly after the first . however , the response rate remained above what is considered appropriate for delphi surveys , and ratings of individual qis , except those related to physical examination , remained stable between rounds . fourth , allied health providers were under - represented and , given their importance in dementia care , additional work is required to further understand and develop their role in an integrated system of dementia care . as the qis were selected by both primary and specialist providers , they are likely applicable to other dementia care settings . third , participation of neurologists in the first round was low and their response was not solicited in the second round . finally , candidate qis and quality improvement mechanisms were not identified through a systematic literature review , but the use of published guidelines and compendiums likely identified the most important elements of quality dementia care , which would thus have remained highly ranked . the relatively lower participation of neurologists in this work , compared to geriatricians and geriatric psychiatrists , is notable and requires further investigation . a second limitation is that the survey was solely distributed within the previously described network of pcmcs , though this model is widely implemented across ontario . fifth , patient and caregivers were not surveyed regarding what they consider to be important qis .", ", the care of persons with cognitive impairment would be enhanced by the development of a practical and realistically feasible quality assurance framework , under whose umbrella both pcmc and specialist services are integrated , and which ensures high fidelity to intended design and best practices , and thus maintains a high level of care quality . an approach whereby clear roles are negotiated among dementia stakeholders can provide sufficient flexibility to meet regional needs ( especially in rural areas where access to specialists is more limited ) , foster more effective collaboration and accountability , and thus facilitate the delivery and measurement of care quality for dementia . within that context , proper field - testing , validation , and evaluation of selected qis and quality improvement mechanisms while this study has identified qis and quality improvement mechanisms to assess care quality for dementia , findings underscore the importance of system integration for the provision of quality dementia care , with specifically defined and mutually understood roles among stakeholders and , where necessary , the reallocation of existing resources to support this approach to care . primary and specialist providers share the responsibility of providing and supporting integrated dementia quality care . as such this work has significant implications on the organization of care for aging patients with complex conditions ." ]
backgroundprimary care - based memory clinics ( pcmcs ) have been established in several jurisdictions to improve the care for persons with alzheimer s disease and related dementias . we sought to identify key quality indicators ( qis ) , quality improvement mechanisms , and potential barriers and facilitators to the establishment of a quality assurance framework for pcmcs.methodswe employed a delphi approach to obtain consensus from pcmc clinicians and specialist physicians on qis and quality improvement mechanisms . thirty - eight candidate qis and 19 potential quality improvement mechanisms were presented to participants in two rounds of electronic delphi surveys . written comments were collected and descriptively analyzed.resultsthe response rate for the first and second rounds were 21.3% ( n = 179 ) and 12.8% ( n = 88 ) , respectively . the majority of respondents were physicians . fourteen qis remained after the consensus process . ten quality improvement mechanisms were selected with those characterized by specialist integration , such as case discussions and mentorships , being ranked highly . written comments revealed three major themes related to potential barriers and facilitators to quality assurance : 1 ) perceived importance , 2 ) collaboration and role clarity , and 3 ) implementation process.conclusionwe successfully utilized a consultative process among primary and specialty providers to identify core qis and quality improvement mechanisms for pcmcs . identified quality improvement mechanisms highlight desire for multi - modal education . system integration and closer integration between pcmcs and specialists were emphasized as essential for the provision of high - quality dementia care in community settings .
[ "symptomatic supravesical obstructive uropathy in a patient with dual functioning kidneys is classically characterized by bilateral hydroureters / hydronephrosis and an empty urinary bladder . our recent experience with a uraemic 56-year - old caucasian showing only unilateral moderate right - sided hydronephrosis is presented . . the evidence for obstruction may be partially or totally absent on ultrasound or computerized tomography , in one or both kidneys [ 68 ] . this obstruction may be secondary to metastatic abdomino - pelvic and retroperitoneal malignancies , ureteric calculi and retroperitoneal fibrosis [ 25 ]", "the pathology report revealed high - grade urothelial carcinoma , grade 3 of 3 , with invasion of the muscularis propria . a 56-year - old caucasian male patient with a past medical history that included hypertension and coronary artery disease and a recent serum creatinine of 88.4 mol / l , was diagnosed 10 days earlier with urinary tract infection ( uti ) . a percutaneous left nephrostogram revealed a previously unrecognized mild hydronephrosis / hydroureter with obstruction at the ureterovesical junction . two days before presentation to us , he developed worsening anorexia , nausea with vomiting and oliguria . a non - contrast computerized tomography examination , on day 2 , again showed unilateral right - sided hydronephrosis , bilateral nephric stranding and urinary bladder wall thickening suspicious for transitional cell cancer ( figure 1 ) .", "a patient with dual functioning kidneys presenting with uraemic symptoms and suspected to have obstructive uropathy must be presumed to necessarily have bilateral renal obstruction [ 610 ] . the classic picture of bilateral hydronephrosis with hydroureters and an empty urinary bladder , in symptomatic uraemia following supravesical obstruction , in patients with dual functioning kidneys , is well acknowledged . however , the presentation of new - onset symptomatic uraemia concurrent with only unilateral hydronephrosis / hydroureter on conventional imaging ( ultrasound , computerized tomography ) should raise the plausibility of non - apparent obstruction of the contra lateral kidney . we would like to remind practicing providers that symptomatic uraemia presenting in the setting of suspected obstructive uropathy must be assumed to imply bilateral renal obstruction , regardless of the results / interpretations of any form of conventional renal imaging . therefore , necessarily , every attempt to decompress both kidneys must be the rule . this is without prejudice to the findings on conventional renal imaging with ultrasound or computerized tomography [ 3,610 ] ." ]
bilateral hydronephrosis is classic for supravesical obstructive uropathy causing uraemia with dual functioning kidneys . recently , a patient presented with uraemia and metastatic urinary bladder carcinoma but only unilateral right - sided hydronephrosis . a right ureteral stent was placed retrograde and no further intervention was planned since the left kidney appeared normal , and since the left ureteric orifice was not visualized . we insisted on a left percutaneous nephrostomy which was successful with prompt urine return . a left nephrostogram revealed unrecognized hydroureter / hydronephrosis . following haemodialysis , kidney function normalized at 3 weeks . for symptomatic uraemia from obstruction , an antegrade and/or a retrograde decompression must be attempted bilaterally to improve renal salvage .
[ "there are now quite a few programs for mimotope based epitope mapping , none of them , however , has a procedure to scan , report and exclude target - unrelated peptides [ 1523 ] . in this study , we describe a web server named sarotup , which is an acronym for scanner and reporter of target - unrelated peptides . sarotup was coded with perl as a cgi program and can be freely accessed and used to scan peptides acquired from phage display technology . in 1985 , smith pioneered phage display technology , an in vitro methodology and system for presenting , selecting and evolving proteins and peptides displayed on the surface of phage virion . since then , phage display has developed rapidly and become an increasingly popular tool for both basic research such as the exploration of protein - protein interaction networks and sites [ 24 ] , and applied research such as the development of new diagnostics , therapeutics , and vaccines [ 510 ] . obviously , target - unrelated peptides are not appropriate candidates for the development of new diagnostics , therapeutics , and vaccines . for mimotope - based epitope mapping , usually , the protein used to screen the phage display library is termed as target and the genuine partner binding to the target is called template .", "we compiled a set of 23 tup motifs from the above two references [ 12 , 13 ] , including 12 motifs specific for the capturing agents , 5 motifs specific for the constant region of antibody , 3 motifs specific for the screening solid phase , 2 motifs specific for the contaminants in the target sample , and 1 motif for a mutation in phage library ( table 1 ) . the old and the new panel of peptides were then used to predict epitope using mapitope or pepsurf [ 15 , 21 , 22 ] . finally , the results were compared to show if sarotup could improve the performance of mimotope - based epitope mapping . the second data set is composed of 100 peptides in raw sequence format . recently , menendez and scott reviewed a collection of target - unrelated peptides recovered in the screening of phage - displayed random peptide libraries with antibodies . , target - unrelated selection is due to a coincident point mutation in the phage library [ 12 , 13 ] . the first group has 77 sequences compiled from the first data set without any known tup motifs ; the second group has 23 sequences sourced from [ 12 , 13 ] with various tup motifs . the mixture of the two groups of sequences made the second data set , which was then used as the sample input and can be used to evaluate the efficiency of sarotup .", "as a free online service , the web interface of sarotup has successfully been implemented as a tabbed web page . these results indicate : ( 1 ) epitope prediction based on mimotope will be interfered if target - unrelated peptides are taken as mimotopes ; ( 2 ) sarotup can improve the performance of mimotope based epitope mapping through cleaning the input data . although the target of all tests described previously were monoclonal antibodies , sarotup can be customized and used in scanning the results from phage display technology using other targets such as enzymes and receptors . target - unrelated peptides are not appropriate candidates for mimotope based diagnostics , therapeutics , and vaccines , since they are mimics to components or contaminants of the screening system rather than target . therefore , it is reasonable to find and exclude possible target - unrelated peptides from the candidate list of new diagnostics , therapeutics , and vaccines . furthermore , sarotup will not only benefit the mimotope - based epitope mapping , but also the development of new diagnostics , therapeutics , and vaccines .", "it is also useful in the development of diagnostics , therapeutics , and vaccines . to our knowledge sarotup , a web application for scanning , reporting and excluding target - unrelated peptides has been coded with perl ." ]
as epitope mimics , mimotopes have been widely utilized in the study of epitope prediction and the development of new diagnostics , therapeutics , and vaccines . screening the random peptide libraries constructed with phage display or any other surface display technologies provides an efficient and convenient approach to acquire mimotopes . however , target - unrelated peptides creep into mimotopes from time to time through binding to contaminants or other components of the screening system . in this study , we present sarotup , a free web tool for scanning , reporting and excluding possible target - unrelated peptides from real mimotopes . preliminary tests show that sarotup is efficient and capable of improving the accuracy of mimotope - based epitope mapping . it is also helpful for the development of mimotope - based diagnostics , therapeutics , and vaccines .
[ "we report an adult who presented with non - specific dizziness and lesions of the scc on magnetic resonance imaging ( mri ) who was diagnosed with hemorrhagic fever with renal failure syndrome ( hfrs ) with serologically proven hantaan virus infection . reversible focal lesions in the splenium of the corpus callosum ( scc ) have been found in patients with various conditions including seizures , antiepileptic drug toxicity or withdrawal , viral encephalitis , hypoglycemia , wernicke 's encephalopathy , marchiafava - bignami disease , sympathomimetic - induced kaleidoscopic visual illusion syndrome , hemolytic uremic syndrome , altitude brain injury , and acute axonal injury . analysis of the current literature revealed that the most frequent cause of reversible focal lesions of the scc is influenza virus - associated encephalitis / encephalopathy ( iaee ) .", "he was diagnosed with hfrs based on the detection of hantaan virus antibody in his serum . the mri findings had resolved completely in follow - up studies conducted on day 14 ( fig . 1 ) . the next day , he developed thrombocytopenia ( 4010/l ) and was transferred to our emergency room for further evaluation . a previously healthy 53-yr - old man presented with a 6 - 7-day history of fever up to 40 and dizziness . he was started on cefotaxime and clindamycin for a suspected infection and transfused with fresh frozen plasma , but his fever ( > 38.0 ) was sustained .", "we report a reversible scc lesion associated with hfrs . to our knowledge , this is the first case of virus - associated encephalitis / encephalopathy in which the pathogen was a hantaan virus . hemorrhagic fever with renal failure syndrome occurs mainly in europe and asia and is characterized by a fever and renal failure associated with hemorrhagic manifestations . the clinical features consist of a triad of fever , hemorrhage , and renal insufficiency ( 5 ) . although it is not certain whether the neurologic symptoms in this patient might have been caused by fever , or scc lesions , or both , we suggest that hfrs patients with neurologic symptoms like dizziness and mental slowing should be considered to have structural brain lesions and to require brain imaging studies . damage to the vascular endothelium , capillary dilatation , and leakage are clinically significant features of the disease ." ]
this is the first case of virus - associated encephalitis / encephalopathy in which the pathogen was hantaan virus . a 53-yr - old man presented fever , renal failure and a hemorrhagic tendency and he was diagnosed with hemorrhagic fever with renal failure syndrome ( hfrs ) . in the course of his illness , mild neurologic symptoms such as dizziness and confusion developed and magnetic resonance images revealed a reversible lesion in the splenium of the corpus callosum . this case suggests that hfrs patients with neurologic symptoms like dizziness and mental slowing should be considered to have structural brain lesions and to require brain imaging studies .
[ "we present a case of critical as with significant symptom manifested as chest pain that was managed successfully without surgical avr or tavr . as is the most common cause of left ventricular outflow obstruction in children and adults . it is most common type of valvular heart disease in europe and north america , occurring in 27% of the population over 65 years of age . medical therapy alone is not effective for the long - term management of aortic valve disease , thus valve replacement remains the standard of care in patients with an acceptable risk profile . we will also briefly review incidence , etiology , grading of as and current guidelines for avr .", "thus , this new onset chest pain in patient with critical as was due to concomitant coronary artery lesion and was amenable to stenting and thus spared this elderly patient from the aortic valve replacement which would have been a high risk surgery for him . a 91-year - old gentleman with history of hypertension , dyslipidemia and as presented to our office on 7/2015 with complaints of new onset sub sternal burning pain of 6 weeks duration . the patient was directly referred for a cardiac catheterization to evaluate his coronary anatomy prior to avr .", "age and comorbidity of the patient posed a high risk for coronary artery bypass graft ( cabg ) with avr . avr and tavr remain the only treatment proven to reduce the rates of mortality and morbidity in this condition . under current guidelines , the onset of symptoms of exertional angina , syncope and dyspnea in a patient who has severe as is a class i indication for surgery . congenitally unicuspid , bicuspid , tricuspid , or even quadricuspid valves may be the cause of as . in adults who develop symptoms from congenital as as is the most common valvular heart condition in the developed world , affecting 3% of people between ages 75 and 85 and 4% of people over age 85 .", "this can lead to less invasive treatment tailored to the need of the patient especially in those with advanced age , significant comorbidities and an extremely high risk for cabg with avr and can also result in decreased cost of care . awareness amongst physicians about the fact that all critical aortic stenosis with chest pain may not require aortic valve replacement is important . pharmacological nuclear stress testing may be another modality that can be used to differentiate etiology of the symptoms ." ]
aortic valve replacement ( avr ) remains the cornerstone of treatment for symptomatic critical aortic stenosis ( as ) . it is a class i indication that symptomatic patients with critical as undergo either surgical or transcatheter aortic valve replacement ( tavr ) . we present a patient with critical as and new angina that was managed successfully with percutaneous coronary intervention ( pci ) of the right coronary artery . physicians should consider that not all patients with critical as and angina necessarily require avr . concomitant pathology leading to the symptoms should be carefully ruled out . this leads to a less invasive , cost effective care plan especially in patients with advanced age and comorbidities for which any type of surgical valvular intervention may pose high risk .
[ "this paper will discuss progress in utilising novel cellular reprogramming techniques to treat rbc diseases . the various blood cell lineages in mammals arise from a multipotent haematopoietic stem cell via particular differentiation pathways . there are a number of severe diseases caused by the disruption of adult globin genes , including thalassaemias and certain types of anaemia . according to the world health organisation , alternative forms of therapy are currently being sought , and stem cell therapies should be considered . there are currently a number of treatments available for patients suffering from thalassaemia and sickle cell anaemia .", "stem cells , both embryonic and adult , have the ability to differentiate into various cell types , making them a potentially attractive treatment option . embryonic stem cells ( escs ) and adult stem cells ( ascs ) each have their own strengths and disadvantages in these strategies . cellular reprogramming potentially overcomes these issues and may offer new treatment methods for a range of diseases , including those of rbcs . takahashi and yamanaka were the first to show that it is possible to take differentiated somatic cells and transform them into cells with pluripotent potential . all of these experiments indicate that it is possible to direct a differentiated cell to another cell fate through the application of extragenic factors . any cells remaining which are still in a pluripotent state could multiply and , without the appropriate growth controls , would have the potential to result in tumours in transplant patients . to potentially avoid the issue of tumour formation and uncontrolled proliferation of ipscs , an alternative methodology known as transdifferentiation is also being considered as a potential treatment strategy .", "advances in cellular reprogramming have raised the attractive possibility that this technology could be utilised to generate a limitless source of immune - matched , pathogen - free erythrocytes for transfusion . they found that hipscs are capable of generating haematopoietic cells with phenotypic and morphological characteristics similar to those derived from hescs ; however , these hipsc - derived cells exhibited a dramatically reduced capacity ( by greater than 1000-fold ) to generate erythroid cells . a subsequent study by lapillone et al . these studies demonstrate that it is possible to differentiate hipscs into mature erythrocytes in vitro for transfusions . in order to utilise these methods to treat rbc diseases successfully the results from this study show that it is possible to produce significant numbers of erythroid cells from fibroblast - derived hipscs , and that thus cellular reprogramming could contribute to the treatment of haemoglobinopathies . furthermore , since these rbcs are generated from transgene - free hipscs , they circumvent problems associated with genomic integration and undesired reactivation of reprogramming factors . another recent study has shown that it is possible to use transdifferentiation to produce haematopoietic cell lineages , including mature erythrocytes . in this work , szabo et al . , however , showed that it was indeed possible to produce significant numbers of mature erythroid cells from hipscs in vitro .", "a promising study has already shown that it is possible to use reprogrammed cells to treat sickle cell anaemia in mice . hanna et al . took cells from the tail tips of a humanized sickle cell anaemic mouse model , in which the mouse -globin genes have been replaced with human -globin , and the mouse -globin genes have been replaced with human and ( sickle ) globin genes , and through adaptation of the protocol developed by takahashi and yamanaka , who reprogrammed these cells into ipscs . this study thus provides an important proof of principle that cellular reprogramming can be employed to correct erythroid disorders , albeit in this case , in conjunction with gene therapy . once this was accomplished , they were able to correct the mutant -globin gene by replacing it with a copy of the wildtype human -globin gene through homologous recombination . following this , blood counts were also performed 12 weeks after transplant , which showed that treated mice had increased rbcs , hb , and packed cell volume as well as reduced reticulocytes , a common indicator of sickle cell disease and severity . firstly , functional correction was evaluated by electrophoresis for the human -globin proteins and , and they found a significant increase in - and a decrease in -globin .", "furthermore , these strategies have been successfully combined with gene therapy to treat a sickle cell anaemia mouse model , suggesting that cellular reprogramming will provide a realistic future alternative to conventional treatment of haemoglobinopathies . , recent advances have shown that cellular reprogramming can now generate large quantities of red blood cells in culture , potentially for use in transfusions . current therapy for these disorders involves packed red blood cell transfusions , which are limited by supply , risk of infection , expense , and patient rejection . normal erythropoiesis is dependent upon the correct expression of globin genes . where globin genes are incorrectly expressed , or are mutated , anaemia or thalassemia results . drug - based therapies involve the nonspecific reactivation of foetal globins and have long - term side effects . in seeking alternative strategies" ]
haemoglobinopathies such as thalassaemia and sickle cell disease present a major health burden . currently , the main forms of treatment for these diseases are packed red blood cell transfusions and the administration of drugs which act to nonspecifically reactivate the production of foetal haemoglobin . these treatments are ongoing throughout the life of the patient and are associated with a number of risks , such as limitations in available blood for transfusion , infections , iron overload , immune rejection , and side effects associated with the drug treatments . the field of cellular reprogramming has advanced significantly in the last few years and has recently culminated in the successful production of erythrocytes in culture . this paper will discuss cellular reprogramming and its potential relevance to the treatment of haemoglobinopathies .
[ "vasopressin 0.6 iu was quickly administered intravenously , and the transesophageal echocardiography ( tee ) revealed a massive gas floating at the orifice of the rca ( fig . the co2 blower was more aggressively used to aid grafting at a flow rate of 3 - 5 l / min . although the patient remained in normal sinus rhythm , complete heart block occurred within minutes , and ventricular pacing was commenced . over the next several minutes , ventricular fibrillation developed ; despite aggressive treatment , including defibrillation , epinephrine , and direct manual cardiac massage , adequate circulation could not be restored , and cardiac massage was continued . upon preparing for emergent conversion to cardiopulmonary bypass ( cpb ) , epinephrine the remaining grafts were performed successfully without conversion to cpb , and no sign of bleeding was observed at the puncture site in the aorta . the patient was in the trendelenburg position , and norepinephrine was infused at a dose of 0.15 g / kg / min . after stabilizer application , there was a temporary deterioration in the patient 's hemodynamic status , which was stabilized without the aid of incremental doses of norepinephrine dosage . the patient had an unremarkable postoperative course without neurologic deficits and was discharged 10 days after the surgery .", "despite using a proximal coronary snare , this method of hemostasis can be incomplete in the presence of severe atheroma or calcification , causing bleeding through the arteriotomy site . however , in the case of a massive embolism with the possible introduction of room air due to venturi effect , hemodynamic collapse can occur and may require aggressive treatment , such as cardiopulmonary resuscitation ( cpr ) with aspiration of the air by direct puncture of the aortic root . however , direct injection to the aortic root following a sternotomy appears to be feasible and may be life - saving , as severe right ventricular dysfunction may limit systemic drug delivery injected through the venous side despite the performance of direct cardiac massage . in the current case , intra - aortic injection of epinephrine may have resulted in a more effective increase in the systemic vascular resistance , thereby increasing the coronary perfusion pressure and thus facilitating emboli clearance . in conclusion , in the rare case of a gas embolism occurring during opcab occurs , the potential for catastrophic results necessitates immediate and appropriate managements including supportive measures , needle aspiration of gas , and cpr with direct cardiac massage . in refractory cases , while considering emergent conversion to cpb , direct injection of drugs to the aortic root can be attempted before initiating cpb . this may be a simple , relatively safe , and life - saving approach for the management of a gas embolism during opcab because a sternotomy has already been conducted ." ]
although compressed gas ( co2 ) blowers have been used safely to aid accurate grafting during off - pump coronary bypass surgery , hemodynamic collapse due to gas embolism into the right coronary artery may occur . supportive measures to facilitate gas clearance by increasing the coronary perfusion pressure have been reported to be successful in restoring hemodynamic stability . however , right ventricular dysfunction and atrioventricular nodal ischemia may hinder effective systemic delivery of the vasoactive medications , even when performing resuscitative measures such as direct cardiac massage . we herein report a case of cardiac arrest that was caused by a right coronary gas embolism and that could not be restored by cardiac resuscitation . when supportive measures fail , direct aortic injection of epinephrine to increase the coronary perfusion pressure can be attempted before initiating cardiopulmonary bypass , and this approach may be life - saving in situations that limit systemic drug delivery from the venous side despite the performance of direct cardiac massage .
[ "multiple sclerosis ( ms ) is a chronic progressive inflammatory and neurodegenerative disease of human central nervous system ( cns ) which usually affects young adults , with a reported median age of onset of approximately 30 years.1 in approximately 85% of patients with ms , the disease is initially recognized by a relapsing - remitting course which may eventually lead to a progressive deterioration of neurological status along with significant loss of neurological function.2 neuropathologically , ms presents with various patterns , however , inflammatory demyelination and oligodendrocyte loss and neuronal and axonal degeneration3 constitute salient features of microscopic examination of ms lesions . currently , the cause and cure for ms remain elusive and in many cases ms ends with significant neurological disabilities . while massive activation of the inflammatory arm of the immune system against putative cns antigen(s ) such as myelin basis protein plays a major role in the pathogenesis of the demyelinating process of ms , the neurodegenerative process prevails in the long run and causes significant cognitive and functional deterioration in affected patients . electrophysiologic examination of demyelinated lesions indicates conduction block as the predominant feature of these lesions .", "in addition , fampridine increases the duration of the pre - synaptic action potential and amplitude which in turn leads to increased transmitter release.13 apart from being a voltage - activated potassium channel blocker , 4-aminopyridine potentiates synaptic and neuromuscular transmission by affecting the beta subunit of voltage - activated calcium channels.14 this novel mode of action of 4-aminopyridine which occurs independent from its blocking effect on the potassium channels , provides another rationale for its positive effect on the neuromuscular function in patients with spinal cord injury , myasthenia gravis and ms . fampridine ( or 4-aminopyridine [ 4-ap ] ) is a broad - spectrum blocker of voltage - sensitive potassium channels , which has been demonstrated to improve conduction and propagation of the action potential along the demyelinated axons .", "hawthorne , ny , usa ) is one of the three isomeric amines of pyridine with chemical formula h2nc5h4n , which acts a selective potassium - channel blocker . compared to an aqueous oral solution , the extended release tablet shows a relative bioavailability of 96% , with a delayed absorption pattern which provides a less rapid rise to a lower maximum plasma concentration . in healthy volunteers who took a single 10 mg dose of dalfampridine dalfampridine , which is a sustained - release oral form of fampridine , is rapidly and completely absorbed from the gastrointestinal tract , however , its absolute bioavailability has not been determined . impairment of ambulation is a major neurological deficit in ms patients and significantly interferes with their quality of life .", "dalfampridine ( ampyra ) is available as 10 mg extended release tablets with relative bioavailability of 96% , peak of plasma concentration of 34 hours and half life of 5.26.5 hours .", "the authors concluded that this clinical trial generated class 1 evidence that treatment of patients with definite ms with extended - release dalfampridinetablets caused meaningful enhancement of walking ability in and the effect of the medication continued persisted between doses . in addition , dalfampridine has been assessed and studied in other cohorts of ms patients in the context of various clinical trials to determine its efficacy in improving ms patients ambulation . in this manuscript only some of the more significant clinical trials have been cited and discussed . , dalfampridine was approved by the fda for symptomatic treatment of ms patients with specific indication for improving walking . in the past the objectives of this clinical trial included assessment of the safety of higher doses of fampridine - sr as well as the efficacy and dose - response to this drug by ms patients .", "based on the animal studies , dalfampridine demonstrates properties of a powerful convulsant stemming from its broad - spectrum suppressing activity on the potassium channels in the peripheral and central nervous systems.11 based on a number of clinical trials of 4-ap side effects consist of dizziness , insomnia , paresthesia , nausea of mild to moderate intensity , tremor , pain , anxiety and seizures.2934 dalfampridine is neither a substrate for nor an inhibitor of the p - glycoprotein transporter , therefore its pharmacokinetics is not affected by the medications which suppress this transporter . dalfampridine is contraindicated in patients with history of epilepsy or history of severe renal insufficiency.35 the reason that dalfampridine use is not recommended in epileptic patients is that epilepsy is characterized by abnormal neuronal depolarization with excessive inhibition on potassium channels , hence a further reduction of potassium channel activity by dalfampridine is not advised . it does not interact with the medications which are substrates for the p - glycoprotein transporter .", "pharmacological agents which block potassium channels have been investigated in the context of clinical trials with positive impact on impulse conduction in experimentally - induced demyelination as well as in patients with ms . pathogenesis of ms involves loss of oligodendrocyte / myelin complex which turn results in re - organization of axolemmal ion channels which leads to conduction abnormalities including conduction delay or block . dalfampridine ( which is marketed as ampyra ) , is an extended release form of fampridine ( 4-aminopyridine ) , which has been recently approved by the us fda for symptomatic treatment of ms patients . while this new oral blocker of voltage - gated potassium channels does not have any impact on the underlying pathology of ms , it has been demonstrated to improve fatigue and walking ability in these patients ." ]
multiple sclerosis ( ms ) is a progressive immune - mediated neurodegenerative disease of human central nervous system ( cns ) , which causes irreversible disability in young adults . the cause and cure for ms remain unknown . pathophysiology of ms includes two arms : inflammatory demyelination and neurodegeneration . the inflammatory demyelination of ms which is mainly promoted by a massive activation of the immune system against putative cns antigen(s ) leads to loss of oligodendrocyte / myelin complex which slows down or halts impulse conduction in denuded axons . practically , loss of myelin significantly reduces signal conduction along the demyelinated axons through alterations in the distribution of axonal ion channels . dalfampridine ( 4-aminopyridine or 4-ap ) is an oral potassium channel blocker , which was recently approved by fda for symptomatic treatment of ms . dalfampridine , which acts at the central and peripheral nervous systems , enhances conduction in demyelinated axons and improves walking ability of ms patients . a number of clinical trials have evaluated the safety and efficacy of fampridine in ms patients with the degree of gait improvement as the main outcome . the objective of this manuscript is to provide an overview of the pharmacology , pharmacokinetics , clinical trials , side effects and interactions of dalfampridine used in treatment of ms patients .
[ "several imaging modalities including pa , occlusal and panoramic radiography , cone beam computed tomography ( cbct ) and ct are used before and after implant treatment as well as in the maintenance sessions . after successful implant placement , the popularity of digital radiography in dentistry is mainly due to the adjustability of digital images by using image inversion , embossed tools , brightness , contrast and magnification enhancement filters [ 49 ] . by applying image inversion to digital images , this study aimed to compare the diagnostic value of unprocessed ( psp ) and inverted digital images for detection of peri - implant defects using scanora software . periapical radiography is usually a suitable imaging modality for long - term follow - ups . radiographically , a thin radiolucent margin around the implant indicates implant mobility and is an important sign of failed osseointegration [ 13 ] . several previous studies have compared the diagnostic accuracy of unprocessed digital images ( psp and charge - coupled device or ccd ) , film - based radiographs and inverted images for detection of peri - implant bone defects and simulated periodontal lesions using image tool and adobe photoshop software programs [ 1214 ] .", "the sensitivity and specificity for detection of small and large peri - implant defects were calculated and compared . four oral and maxillofacial radiologists with at least two years of work experience evaluated all 60 images for presence or absence of peri - implant defects using a efive - point scale : \n definite defectprobable defectnot sureprobably no defectdefinitely no defect \n examiners viewed the images on an 18.5 samsung monitor ( samsung syncmaster e1945nx , 1360 768 ) under adequate lighting . a total of 30 implant placement sites including 10 control sites , 10 sites with 0.425 mm peri - implant space and 10 sites with 0.725 mm peri - implant space were created . independent t - test was used to compare the diagnostic value of unprocessed and inverted digital imaging modalities . study the basis of calculating the absolute sensitivity / specificity was the number of the definitely correct diagnoses and the complete sensitivity / specificity was determined based on the total number of definite and probable correct answers . soft tissue residues were removed and the rib was trimmed to prepare bone segments suitable for the placement of 30 implants . in between imaging stages , the rib segments were stored at 1c temperature to minimize moisture loss .", "soft tissue residues were removed and the rib was trimmed to prepare bone segments suitable for the placement of 30 implants . in between imaging stages , the rib segments were stored at 1c temperature to minimize moisture loss .", "a total of 30 implant placement sites including 10 control sites , 10 sites with 0.425 mm peri - implant space and 10 sites with 0.725 mm peri - implant space were created . to stabilize fixtures in bone , drilling was performed at a diameter of 3.1 mm and height of 6 mm for the apical part of fixtures and the remaining coronal 8 mm was prepared with larger drills to form a gap . all fixtures measuring 3.414.5 mm ( the sicace screw implants 3.4mm/14.5 mm incl . ) were placed into the osteotomy sites at the level of the superior border of the rib ( bone level ) and cover screws were inserted ( figure 1 ) . to simulate soft tissue , an acrylic block ( polymethyl methacrylate ) with 1 cm thickness periapical radiographs were obtained from the bone segments at the same day the fixtures were placed . the sicace screw implants ( sicace , basel switzerland ) ( 3.4mm/14.5 mm ; cylindrical parallel walled ) were placed in the marked areas . osteotomy sites were marked on the superior border of the rib with 15 mm distance from one another . the coronal 8 mm of another 10 sites was enlarged using a 4.85 mm diameter drill ( astra tech drill , stockholm , sweden ) ( 4.85 , 819 mm ) to create 0.725 mm peri - implant space .", "the x ray tube ( 2 ) the simulated soft tissue ( 3 ) bone segment with implant fixtures placed . all radiographs were obtained using digora optime imaging system ( soredex corporation , helsinki , finland ) , psp size 2 sensor ( 40.0mm30.0 mm ) and minray dental x ray system ( soredex , tuusula , finland ) with exposure settings of 60 kv and 7ma for 0.16s . digital intraoral sensor holder ( kerr dental europe , bioggio , switzerland )", "four oral and maxillofacial radiologists with at least two years of work experience evaluated all 60 images for presence or absence of peri - implant defects using a efive - point scale : \n definite defectprobable defectnot sureprobably no defectdefinitely no defect \n examiners viewed the images on an 18.5 samsung monitor ( samsung syncmaster e1945nx , 1360 768 ) under adequate lighting . the examiners were only allowed to adjust the brightness and contrast of digital images ( figure 3 ) . after exposure of sensors , images were stored in dicom files on a computer using a scanora lite software ( palodex , tuusula , finland ) with standard resolution . by applying image inversion , 60 digital images including 30 unprocessed and 30 inverted images were obtained .", "in this study the basis of calculating the absolute sensitivity / specificity was the number of the definitely correct diagnoses and the complete sensitivity / specificity was determined based on the total number of definite and probable correct answers . the sensitivity and specificity for detection of small and large peri - implant defects were calculated and compared . independent t - test was used to compare the diagnostic value of unprocessed and inverted digital imaging modalities .", "a total of 60 digital pa radiographs including 30 unprocessed and 30 inverted radiographs were obtained of 30 implants with the same diameter and length : 10 implants with no defects , 10 with small ( 0.425 mm ) diameter peri - implant defects in the coronal 8 mm and 10 with large ( 0.725 mm ) diameter peri - implant defects in the coronal 8 mm . based on the results , unprocessed images had a higher diagnostic value than inverted images . according to the t - test , in the equality of the means , no significant difference was detected in the sensitivity of unprocessed and inverted images for detection of peri - implant defects ( absolute positive predictive value ) and for detection of a probable lesion ( complete positive predictive value)(p>0.05 ) . however , in the equality of the means , the complete specificity of unprocessed and inverted images was not significantly different ( p>0.05 ) ( table 2 ) . the mean absolute specificity of unprocessed and inverted images was significantly different based on the t - test ( p<0.05 ) and unprocessed images had a higher diagnostic value .", "periapical radiography is conventionally used as the standard follow up radiography after implant placement to assess the peri - implant tissue status . this study showed that unprocessed images had a higher diagnostic value than inverted images for detection of small and large peri - implant defects . similar results were obtained indicating the higher diagnostic accuracy of unprocessed digital images and film - based radiographs than inverted images .", "based on the results , we found that unprocessed digital images had higher diagnostic accuracy than inverted images for detection of small and large peri - implant defects ." ]
objectives : this study aimed to compare the diagnostic accuracy of inverted and unprocessed digitized periapical radiographs for detection of peri - implant defects.materials and methods : a total of 30 osteotomy sites were prepared in three groups of control , study group 1 with 0.425 mm defects and study group 2 with 0.725 mm defects using the sic and astra tech drill systems with 4.25 mm and 4.85 mm diameters . small and large defects were randomly created in the coronal 8 mm of 20 implant sites ; implants ( 3.4 mm diameter , 14.5 mm length ) were then placed . thirty periapical ( pa ) radiographs were obtained using digora imaging system ( soredex corporation , helsinki , finland ) , size 2 photostimulable storage phosphor ( psp ) plate sensors ( 40.0mm30.0 mm ) and scanora software . unprocessed images were inverted using scanora software by applying image inversion and a total of 60 images were obtained and randomly evaluated by four oral and maxillofacial radiologists . data were analyzed using the t-test.results:significant differences were observed in absolute and complete sensitivity and specificity of the two imaging modalities for detection of small and large defects ( p<0.05 ) . unprocessed digital images had a higher mean in terms of absolute sensitivity for detection of small defects , complete sensitivity for detection of large peri - implant defects and definite rule out of defects compared with inverted images.conclusion:unprocessed digital images have a higher diagnostic value for detection of small and large peri - implant defects and also for definite rule out of defects compared with inverted images .
[ "aorto - esophageal fistula ( aef ) , an abnormal anatomical communication between the aorta and esophagus is a rare cause of ugib . we present a case of aef which was initially treated as variceal bleeding and later promptly diagnosed with computed tomography ( ct ) . upper gastrointestinal bleeding ( ugib ) is a major cause of mortality and morbidity accounting for about 56.5/100,000 hospitalization with a mortality rate of 8.2% . all these factors make the timely diagnosis of aef challenging , and at times missed altogether leading to catastrophic consequences . as ulcer related or variceal bleeding constitutes for most of the ugib bleeding , even in elderly who are at risk of aef and the inability of the esophagogastroduodenoscopy ( egd ) to detect most cases , aef is often not diagnosed timely .", "he underwent emergency percutaneous thoracic endovascular aortic repair with aortic stent placement [ figure 2 ] . it revealed type b aortic dissection with rupture and the active extravasation of blood into the esophagus , confirming the diagnosis of aef [ figure 1 ] . however , later in the day , he developed massive hematemesis and hematochezia leading to persistent hemorrhagic shock . a 70-year - old male patient with hypertension with regular ethanol use , presented to a local hospital with complaints of hematemesis and melena from the past 1-day .", "aorto - esophageal fistula is an abnormal anatomical communication between the aorta and esophagus . in 1818 other causes described in the literature are cancer , acid reflux disease , trauma , caustic ingestion , and esophageal biopsies . aef , once considered to be uniformly fatal , is now a treatable condition with timely intervention . once the infection is controlled , the complex aortic and esophageal reconstruction is done in multiples stages . the exact incidence of this condition is not known , as the vast majority of these patients die before a definitive diagnosis can be made . in the past , infections such as tuberculosis and syphilis , leading to aortitis were the common cause of this condition . in this antibiotics era , thoracic aortic aneurysm constitutes for more than half of these cases .", "aorto - esophageal fistula is a rare , but life - threatening condition presenting as ugib . a high level of suspicion is needed , as routine tests performed for ugib typically only detect one - third of cases . avoiding over - resuscitation can be helpful in preventing subsequent hemorrhages ." ]
aorto - esophageal fistula is a rare cause of upper gastrointestinal bleeding . thoracic aneurysm , the most common cause of this condition , will slowly increase over time and can erode the wall of the aorta creating a fistula and leading to torrential bleeding . high clinical suspicion is required for timely diagnosis as common investigations routinely done for gastrointestinal ( gi ) bleeding , including esophagogastroduodenoscopy , fails to detect most cases . the classical triad of midthoracic pain , herald bleeding and fatal hematemesis described in this condition is seen in only one - third of cases . physician should be wary of this condition , especially in elderly patients with uncontrolled gi bleeding and who are also at risk of thoracic aneurysm . computed tomography angiogram detects most cases and emergent endovascular repair with stents controls the initial bleeding . later , both the aorta and the esophagus are repaired and reconstructed in staged procedures .
[ "we have shown that the pn junction formed by combining p - type and n - type gels together in much closer contact rectifies the current . the discovery of the silicon pn junction is a landmark in the development of modern microelectronics . these semiconductor polymeric gels can be doped with both negative ( n - type ) and positive ( p - type ) counter ions as charge carriers . differently current rectifying in semiconductor diodes via diffusion of ionic charges across a pn junction sets up a built in potential ; there is unidirectional current is observed across a membrane where a built in potential arises from diffusion of anions and cations in organic junctions . we considered that the principle of the electrical conductivity in polymeric gels can be changed by doping static ( inactive ) ions having counter ions as charge carriers and these gels can be used to form pn junctions that work similar to inorganic semiconductors . organic - based semiconductors , for example polymeric gels , may have superior properties due to their flexibility against to regulate some physical properties of the materials even after the production , e.g. , by changing the volume of the gel .", "properties and codes of synthesizing semiconducting gels to be able to evaluate the net effect of the doping on the electrical properties , samples p1 , p5 , n1 , and n5 were synthesized without doping agents for comparison with the other samples . p - type hydrogels were synthesized via free radical cross - linking co - polymerization of acrylamide ( aam ) and n , n-methylene bisacrylamide ( bis ) as crosslink agent in the presence of pyranine ( 8-hydroxypyrene-1,3,6-trisulfonic acid , trisodium salt ) in varying amount , 10 , 10 , 10 mol / l [ 10 - 12 ] . the ratios of nipa to bis and nipa to aibn were kept fixed for all samples ; nipa / bis = 50 and nipa / aibn = 71 in dimethylsulphoxide ( dmso ) . these gels were prepared for electrical measurements in similar way with p - type gels . the ratios of aam to bis and aam to aps were kept fixed for all samples ; aam / bis = 31 and aam / aps = 43 in bidistilled water . n - type gels were synthesized , similar to p - type , as free radical cross - linking co - polymerization of n - isopropylacrylamide ( nipa ) and n , n-methylene bisacrylamide ( bis ) as crosslink agent in the presence of methacrylamidopropyltrimethylammonium chloride ( maptac ) in varying amount , 3 10 , 3 10 , 3 10 mol / l [ 13 - 15 ] .", "p - type hydrogels were synthesized via free radical cross - linking co - polymerization of acrylamide ( aam ) and n , n-methylene bisacrylamide ( bis ) as crosslink agent in the presence of pyranine ( 8-hydroxypyrene-1,3,6-trisulfonic acid , trisodium salt ) in varying amount , 10 , 10 , 10 mol / l [ 10 - 12 ] . the ratios of aam to bis and aam to aps were kept fixed for all samples ; aam / bis = 31 and aam / aps = 43 in bidistilled water . thus , pollutions and unreacted chemicals washed out from the gel , and only pyranines , which were bound to the polymer strands chemically [ 10 - 12 ] , were stayed in the gel . after gelation processes were completed , gels were washed with pure water during 15 days with changing their water every day . the samples were deoxygenated by bubbling nitrogen during 10 min , and the gelation was performed in the 1 1 cm square - shaped holders ( 4 cm of volume ) at 60c in a heat bath .", "n - type gels were synthesized , similar to p - type , as free radical cross - linking co - polymerization of n - isopropylacrylamide ( nipa ) and n , n-methylene bisacrylamide ( bis ) as crosslink agent in the presence of methacrylamidopropyltrimethylammonium chloride ( maptac ) in varying amount , 3 10 , 3 10 , 3 10 mol / l [ 13 - 15 ] . the ratios of nipa to bis and nipa to aibn were kept fixed for all samples ; nipa / bis = 50 and nipa / aibn = 71 in dimethylsulphoxide ( dmso ) . these gels were prepared for electrical measurements in similar way with p - type gels . properties and codes of synthesizing semiconducting gels to be able to evaluate the net effect of the doping on the electrical properties , samples p1 , p5 , n1 , and n5 were synthesized without doping agents for comparison with the other samples . aam , nipa , and doping concentrations of the samples were summarized in table 1 .", "the gels , prepared in the slice shapes of area a and thickness d , were swollen to a certain swelling ratio , and then placed between platinum electrodes , and sealed from the air against drying . the current densities per unit mass , j / m , of the gel were measured against the time , the applied voltage and the swelling ratio of the gels .", "the pyranine binds to the polymer chains , over its oh group , chemically during the polymerization as it is discussed in detail in references [ 10 - 12 ] , and they form stable charged sites doped with positive counter ions . thus , the polyacrylamide gel is doped with pyranine having ions as side groups and na as counter ions , so - called p - type semiconducting gel . the penetration of neutral water molecules through the system of large channels located in the vicinity of small blobs is facilitated . the internal electric field due to the charged sites could disturb the tendency between the polymer units ( affinity of the aam momoners to the cross - linker molecules ) because the charge excess has a tendency to form denser polymer regions especially in mesoscale regions . the current occurs mainly due to doped ions ( the counter ions of the doping agent ) . figure 5a clearly shows that the current of the interface between the cationic and anionic gels , which is passing through only one direction , originates directly from the doping effect of the gels . the maptac binds to the polymer chains chemically during the polymerization , thus they form stable charged sites doped with negative counter ions as represented in scheme 1together with the p - type gel .", "in this study , we have shown that p- and n - type doped hydrogels can be synthesized and be used to built pn junction . the synthesis of these gels and making junctions are more simple , inexpensive , and scalable than traditional pn junctions . this strict volume dependence and the randomness of the internal distributions of the heterogeneous regions set a barrier for comparison of the samples from the point of the current amplitudes due to the difficulties to bring the gels to exactly the same swelling ratios and to repeat the synthesis with exactly the same internal morphology . the current voltage characteristic of the polymeric pn junction can be changed by changing doping concentration , swelling ratio etc that will be discussed in our feature works .", "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 ." ]
in this study , we synthesized the new kinds of semiconducting polymeric gels having negative ( n - type ) and positive ( p - type ) counter ions as charge carriers . the polyacrylamide gel was doped with pyranine ( 8-hydroxypyrene-1,3,6-trisulfonic acid , trisodium salt ) , havingions as side groups and na+ as counter ions , so - called p - type semiconducting gel . the doping process was performed during the polymerization where the pyranine binds to the polymer strands over oh group chemically via radical addition . in a similar way , n - isopropylacrylamide ( nipa ) gel was doped with methacrylamidopropyltrimethyl ammonium chloride ( maptac ) , having cl as counter ions , so - called n - type semiconducting gel . here maptac was embedded by copolymerization within the polymer network ( nipa ) . these semiconducting gels can show different electrical properties by changing the concentration of the doping agents , swelling ratio etc . we have shown that the pn junction , formed by combining p - type and n - type gels together in close contact , rectifies the current similar to the conventional si and ge diodes .
[ "we decided to continue observing fdg uptake in the mediastinal and peribronchial lymph nodes rather than prescribing chemotherapy , because metastasis of leiomyosarcoma to the lymph nodes is rare . a chest ct scan done 1 year after surgery demonstrated no changes in the pulmonary nodules and no recurrence of the mass . two months later , en - bloc resection of the retroperitoneal masses with left nephrectomy was performed , and the pathologic diagnosis was metastatic leiomyosarcoma . we performed an excision of the mass in the right lower lobe and excised fine nodules from the parietal and diaphragmatic pleura for biopsy . 3 ) , and we diagnosed them as metastatic leiomyosarcoma . additionally , increased fluorodeoxyglucose ( fdg ) uptake was observed in the peribronchial lymph nodes , the mediastinum , and the supraclavicular lymph nodes . she had undergone a hysterectomy in 2005 , and the pathologic diagnosis was leiomyoma of the uterus . in 2006 ,", "benign metastasizing leiomyoma ( bml ) results from metastasis of a uterine leiomyoma ; thus , bml patients have a history of uterine leiomyoma if there is a very large , newly developed mass that is increasing in size rapidly , or if a malignant mass is found on pet - ct , diagnostic mass resection should be considered . however , preventive resection or diagnostic excisional biopsy is not recommended for all pbml patients , since the occurrence of a malignant change is extremely rare surgical excision is the treatment of choice , but this is only possible in cases of resectable pbml . overall , early diagnosis and complete mass resection are vital in cases of the malignant transformation of pbml . pbml can also undergo malignant transformation ; excluding our case , just 1 case of the malignant transformation of pbml has been reported . the pathogenesis of pbml is unknown , but the most common theory is hematogenous spreading of leiomyoma during uterine surgery ." ]
pulmonary benign metastasizing leiomyoma ( pbml ) is defined as metastasis of a leiomyoma to lung tissue . it was first reported in 1937 . p bml is known as a benign disease , but can undergo malignant transformation . only 1 case of the malignant transformation of pbml to leiomyosarcoma has been reported previously . in this report , we present a case of malignant transformation of pbml .
[ "the purpose of this study was to compare these two questionnaires in the general japanese population , as no previous research has done so , as well as to assess the ability of both instruments to discriminate between subjects with and without persistent ao . another copd screening tool , the international primary care airway group ( ipag ) questionnaire,11 is in use worldwide . copd is a common , usually progressive disease characterized by chronic inflammation of the airways and persistent airflow limitation . it consists of eight items and takes more time to administer than the copd - ps questionnaire . these tools reliably detect airflow limitation in the general population and may facilitate the early , accurate diagnosis of copd in general practice settings.9,10 some copd diagnostic questionnaires have already been reported.1114 the copd population screener ( copd - ps ) , which was developed by a clinician working group in the united states , is a five - item , self - administered questionnaire that was validated for screening individuals in the general population who are at high risk of copd .", "this study was based on data from the hisayama study , which is an ongoing population - based epidemiologic study designed to investigate the morbidity , mortality , and risk factors of cardiovascular and smoking - related diseases in the town of hisayama , japan . according to national census data , the distributions of age and occupations in hisayama have been almost identical to those across japan since the 1960s.17 this cross - sectional study compared the screening efficacy of the copd - ps and ipag questionnaires in copd patients . in 2012 , the final analysis included data for 2,336 subjects with fully completed copd - ps and ipag questionnaires and valid spirometry measurements . receiver operating characteristic ( roc ) curves and areas under the roc curves ( aucs ) were generated to reflect graphically and quantitatively the ability of the copd - ps and the ipag questionnaires to discriminate between subjects with and without persistent ao using the delong method.21 another method proposed by pencina et al22 was also utilized for this purpose ; this approach assesses the ability of a model to reclassify case and control subjects , respectively , on the basis of the individual - estimated probability of an event . we computed the nri and idi and examined the accuracy of the two screening questionnaires in diagnosing ao . the copd - ps is a brief , reliable , self - scored questionnaire to identify individuals likely to have copd .", "this study was based on data from the hisayama study , which is an ongoing population - based epidemiologic study designed to investigate the morbidity , mortality , and risk factors of cardiovascular and smoking - related diseases in the town of hisayama , japan . the town is located in a suburban area adjacent to fukuoka city , a large urban center on kyushu island in the southern part of japan . according to national census data , the distributions of age and occupations in hisayama have been almost identical to those across japan since the 1960s.17 the population of the town is ~8,000 and has been stable for over 50 years .", "this cross - sectional study compared the screening efficacy of the copd - ps and ipag questionnaires in copd patients . in 2012 , registered subjects 40 years of age and older were solicited to participate in a town - wide health checkup that included spirometry . the subjects who provided informed consent to participate in the health checkup independently completed the japanese versions of the copd - ps and ipag questionnaires , and then , in addition to their usual clinical tests , underwent spirometry using a chestgraph hi-105 spirometer ( chest mi , tokyo , japan ) . the final analysis included data for 2,336 subjects with fully completed copd - ps and ipag questionnaires and valid spirometry measurements . of the 2,643 subjects who were enrolled between june 2012 and october 2012 , 307 were excluded for the following reasons : 105 had physician - diagnosed asthma , 22 had a previous lung resection , 159 had poor studied data , and 21 had records with missing data . the highest forced expiratory volume in 1 second ( fev1 ) and fvc values were used for analysis . the results were assessed by two pulmonary physicians , who visually inspected the flow volume curve and excluded subjects without at least two satisfactory tests . the subjects who had pre - bronchodilator ( bd ) fev1/fvc < 0.70 were eligible for post - bd testing , in which spirometry was performed 15 minutes after inhalation of salbutamol ( glaxosmithkline , tokyo , japan ) via a metered - dose inhaler with a spacer , according to the procedure recommended.18 persistent ao was defined as having a post - bd fev1/fvc < 0.70 .", "it consists of five items , three assessing copd - related symptoms on a 5-point scale , one on cigarette use ( 3-point scale ) , and one on the subject s age ( four categories ) . these five items are scored 0 , 1 , or 2 with a summed total score ranging from 0 to 10 . in the japanese version of the copd - ps questionnaire , the copd - ps is a brief , reliable , self - scored questionnaire to identify individuals likely to have copd .", "the ipag questionnaire is also a self - scored questionnaire and has been validated in smokers as a screening tool for copd diagnosis.11 the ipag questionnaire is composed of eight items : one on the subject s age ( four categories ) , one on body mass index ( 3-point scale ) , one on cigarette use ( 4-point scale ) , and five on symptoms / history ( 2- or 3-point scales ) . however , there is no cutoff score for persistent ao in the general japanese population , including never - smokers , and we therefore investigated this issue in this study . a suggested cutoff score of 17 is used for smokers in general health checkup settings and general practices in japan . each question is scored individually , with a summed total score ranging from 0 to 38 .", "another way to evaluate the utility of screening tests is with the likelihood ratio;20 likelihood ratios range from 0 to infinity ; larger numbers provide more convincing evidence of a disease , smaller numbers indicate that the disease is less likely , and ratios close to one lack diagnostic value . receiver operating characteristic ( roc ) curves and areas under the roc curves ( aucs ) were generated to reflect graphically and quantitatively the ability of the copd - ps and the ipag questionnaires to discriminate between subjects with and without persistent ao using the delong method.21 another method proposed by pencina et al22 was also utilized for this purpose ; this approach assesses the ability of a model to reclassify case and control subjects , respectively , on the basis of the individual - estimated probability of an event . in contrast , the idi does not require a prior definition of strata risk and considers the change in the estimation prediction probabilities as a continuous variable . spearman correlations were used to examine the strength of associations between informant and performance measures . for the subjects who used a bd , the nri considers only the changes in the estimated prediction probabilities that imply a change from one category to another . we computed the nri and idi and examined the accuracy of the two screening questionnaires in diagnosing ao . the ability of the model to reclassify is summarized by the net reclassification improvement ( nri ) and integrated discrimination improvement ( idi ) .", "the continuous nri and idi for predicting the presence of ao using the model with the copd - ps questionnaire against the ipag questionnaire were 0.107 ( 95% ci , 0.2730.058 ; p=0.203 ) and 0.014 ( 95% ci , 0.0330.006 ; p=0.182 ) , respectively , and these were not statistically significant ( table 5 ) . classification improved using the model with the copd - ps questionnaire , and for 549 ( 25.1% ) subjects , it became worse , with the net gain in reclassification proportion of 0.056 . for subjects with ao the crude odds ratio ( or ) of the copd - ps questionnaire for ao was 5.52 , and the sensitivity of copd - ps questionnaire was 66.7% and the specificity was 73.4% . in this population - based study that included never - smokers , a cutoff point of 20 on the ipag questionnaire would be adequate for screening for ao ( table 3 ) . the copd - ps and the ipag questionnaires had only a marginal difference in their ability to discriminate between the subjects with and without ao . roc curves were generated to measure the properties of the copd - ps and the ipag questionnaires in discriminating subjects without ao from those with ao .", "the baseline characteristics of the 2,336 subjects stratified by airflow limitation category following post - bd spirometry are presented in table 1 . for the ao and non - ao subjects , respectively , the mean scores were 3.9 and 2.4 , while the median scores were 4 and 2 . the ipag and the copd - ps questionnaires were correlated with fev1/fvc ( r=0.356 and r=0.301 , respectively , p<0.001 ) , and the two questionnaires correlated with each other ( r=0.622 , p<0.001 ; table 2 ) . the ao subjects were older , were more likely to be men , had lower body mass index , had a higher number of pack - years smoked , and were more likely to be former or current smokers ( table 1 ) . the mean and almost all the ao subjects ( 94.0% ) were classified as having mild or moderate copd ; only 6.0% of the ao subjects had severe or very severe copd . the majority of subjects ( 88.9% ) showed an initial fev1/fvc 0.70 . following post - bd spirometry ,", "classification improved using the model with the copd - ps questionnaire , and for 549 ( 25.1% ) subjects , it became worse , with the net gain in reclassification proportion of 0.056 . for subjects with ao , classification was improved in 21 subjects ( 14.0% ) and less accurate in 28 subjects ( 18.7% ) , with the net gain in reclassification proportion of 0.047 . the crude odds ratio ( or ) of the copd - ps questionnaire for ao was 5.52 , and the sensitivity of copd - ps questionnaire was 66.7% and the specificity was 73.4% . in this population - based study that included never - smokers , a cutoff point of 20 on the previously identified cutoff point of 4 was used for the copd - ps questionnaire . the copd - ps and the ipag questionnaires had only a marginal difference in their ability to discriminate between the subjects with and without ao . roc curves were generated to measure the properties of the copd - ps and the ipag questionnaires in discriminating subjects without ao from those with ao .", "in the present population - based study , the japanese version of the copd - ps questionnaire was compared with the ipag questionnaire in a general japanese population at the age of 40 years or older . the ipag questionnaire had superior likelihood ratios of both positive and negative tests compared with those of the copd - ps questionnaire . these findings suggest that the copd - ps and the ipag questionnaires are useful screening tools for detecting persistent ao . in addition , the subjects with a 4 point on the copd - ps questionnaire and those with a 20 point on the ipag questionnaire are at increased risk for ao .", "there were only marginal differences between the two questionnaires in terms of ability to discriminate between subjects with and without ao . it takes ~5 minutes to fill out copd - ps questionnaire , however , the completion of the ipag questionnaire takes ~510 minutes . in this regard , moreover , the copd - ps questionnaire consists of fewer items than the ipag questionnaire and requires less time to complete . the japanese version of the copd - ps questionnaire should be an adequate measure for large - scale screening for possible ao ." ]
backgroundthe incidence of chronic obstructive pulmonary disease ( copd ) is increasing worldwide . in japan and other countries , epidemiological studies have found that many patients with copd are underdiagnosed and untreated , and thus , early detection and treatment of copd has been emphasized . screening questionnaires may have utility in the initial detection of copd.objectivethis study aimed to validate and compare the copd population screener ( copd - ps ) and the international primary care airway group ( ipag ) questionnaires in a general japanese population.patients and methodseligible subjects 40 years of age and older living in the town of hisayama were solicited to participate in a health checkup in 2012 . all subjects 4079 years of age without physician - diagnosed asthma or lung resection were recruited , and 2,336 subjects who fully completed both questionnaires and who had valid spirometry measurements were analyzed . persistent airflow obstruction ( ao ) was defined by a postbronchodilator forced expiratory volume in 1 second / forced vital capacity < 0.70 . receiver operating characteristic curves , net reclassification improvement , and integrated discrimination improvement were used to examine the ability of the copd - ps and ipag questionnaires to discriminate between subjects with and without ao.resultsthe overall area under the receiver operating characteristic curve for the copd - ps questionnaire was 0.747 ( 95% confidence interval [ ci ] , 0.7070.788 ) and for the ipag was 0.775 ( 95% ci , 0.7350.816 ) , with no significant difference ( p=0.09 ) . the net reclassification improvement and integrated discrimination improvement were 0.107 ( 95% ci , 0.2730.058 ; p=0.203 ) and 0.014 ( 95% ci , 0.0330.006 ; p=0.182 ) , respectively.conclusionthe five - item copd - ps questionnaire was comparable to the eight - item ipag for discriminating between subjects with and without ao . the copd - ps is a simple and useful screening questionnaire for persistent ao .
[ "the aim of this study was to assess the incidence and risk of acquiring cmv infection in pregnant women in an urban area in northern italy in the period 20052007 . the human cytomegalovirus ( cmv ) or human herpesvirus 5 is one of the major causes of congenital infections . as far as prevention is concerned , in addition to health education campaigns , the serological screening of pregnant women has been proposed . however , there is no consensus in the scientific community concerning the implementation of screening , and it is not recommended by any public health system because of its cost / benefit ratio , although many doctors in israel , belgium , and france do test their pregnant patients . its clinical manifestations range from asymptomatic forms ( 90% of cases ) to severe fetal damage and , in rare cases , death due to abortion . furthermore furthermore , although the current public health legislation in italy ( law decree 245 of 10 september 1998 ) does not include free cmv antibody screening during pregnancy , it is prescribed by many general practitioners .", "during the three years 20052007 , the microbiology unit of hospital of legnano , received samples for the detection of cmv antibodies from 2817 pregnant women ( mean age 32 years , range 1546 ; 2522 ( 89.5% ) were italian and 295 ( 10.5% ) of foreign origin ) . all of the samples were analyzed for the presence of anti - cmv igg and igm antibodies by means of an enzyme - linked immunosorbent assay ( elisa ) ( eti - cytok - g - plus , eti - cytok - m reverse plus , diasorin , saluggia , italy ) . low igg avidity levels strongly suggest an infection contracted less than three months before , whereas a high avidity tends to exclude this .the elisa igm - positive samples were also tested for the presence of rheumatoid factor ( arthri - slidex , biomrieux , lyon , france ) . in the case of positivity for igm ,", "there were also calculated the density incidence as cases / pregnant woman - trimester and the correlated risk for all women ( seronegative and seropositive ) : they were , respectively , 0.8% ( 95% ci : 0.471.13 ) and 0.4% ( 95% ci : 0.170.63 ) . the cumulative incidence of cmv infection ( new cases observed during pregnancy ) calculated on the basis of the 13 cases with low or moderate igg avidity was 1.4% ( 95% ci : 0.971.83 ) , and the risk of infection during pregnancy , calculated on the basis of all of the women ( seronegative and seropositive ) , was 0.5 100 pregnancies ( 95% ci : 0.240.76 ) . the differences in incidence and risk by age was not statistically significant . to take into account the loss to follow - up within the groups and different admission to the study of women during different trimester , table 4 shows the results of the confirmatory igm elfa and igg avidity tests by trimester of pregnancy .", "the overall prevalence of anti - cmv igg antibodies in our pregnant women was 68.3% ( 95% ci : 66.670.0 ) , without any significant differences between age classes . the incidence and risk of cmv infection in pregnancy found in our area , therefore , support the use of serological screening , certainly in the first trimester when the risk of infection is higher and , in the case of seronegative women , possibly also one screening in the second trimester and one in the third . on the basis of the results of the igg avidity test , the cumulative incidence of cmv infection was 1.4% ( 95% ci : 0.971.83% ) , the density incidence was 0.8% ( 95% ci : 0.471.13 ) , and the risk of infection was 0.5% ( 95% ci : 0.240.76% ) without any significant differences by age . seroconversion or clinical data indicating acute infection were available for three of the five cases with moderate avidity in this study , thus moderate avidity was considered as a potential marker of acute infection ." ]
the fetal consequences of cmv infection make it one of the most serious infections contracted during pregnancy , but the scientific community is divided over the proposed implementation of preventive screening for anti - cmv antibodies . the aim of this study was to assess the incidence and risk of infection during pregnancy in 2817 women who underwent anti - cmv igg and igm antibody screening during the period 20052007 . the prevalence of anti - cmv igg antibodies was 68.3% ( 95% ci : 66.670.0 ) ; the seroconversion rate in the 892 seronegative women was 0.32% ; the results of igg avidity testing revealed an cumulative incidence of 1.4% ( 95% ci : 0.971.83 ) , density incidence of 0.8% ( as cases / pregnant woman - trimester ) ( 95% ci : 0.471.13 ) , and a risk of infection of 0.5% ( 95% ci : 0.240.76 ) . the screening identified 13 cases of primary infection ( 84.6% of which occurred in the first trimester of pregnancy ) . the possibility to identify these cases and consequently to plan appropriate interventions , supports the use of screening during pregnancy , especially in the first trimester when the risk of infection is greater .
[ "when considering a patient 's prognosis with nmibc , it is necessary to consider not only clinical and pathological factors but also take into account the potential effect of the intravesical treatment received and molecular alterations present in the tumors . bladder cancer is the second most commonly diagnosed genitourinary malignancy in the usa , with an estimated 74,000 newly diagnosed cases and 16,000 deaths in 2015 . patients with high - grade ta tumors had a progression - free survival of 61% and a disease - specific survival of 74% , whereas patients with t1 disease had a progression - free survival of 44% and a disease - specific survival of 62% , providing support to the view that grouping all patients with nmibc as one disease is misleading as one patient 's prognosis can be quite different from that of another patient . approximately 50 - 70% of nmibc will recur and roughly 1020% will progress to muscle ( i.e. , muscularis propria ) invasive disease . in patients with low - grade ta disease , commonly accepted risk factors for bladder cancer include cigarette smoking , occupational exposure to aniline dyes , benzidene compounds , analgesic abuse ( phenacetin ) and chronic irritation , such as indwelling catheters . of all newly diagnosed cases of bladder cancer , about 70% present as non - muscle invasive bladder cancer ( nmibc ) ,", "small cell carcinoma of the bladder is considered a systemic disease and chemotherapy followed by tailored local therapy is recommended for patients with non - muscle invasive small cell carcinoma of the bladder . however , spaliviero et al . reported not significantly worse outcomes in conservatively managed t1 micropapillary bladder cancer patients compared with patients treated with early radical cystectomy . given the conflicting findings on the impact of variant histology in smaller studies , the association of variant histology with prognosis deserves further evaluation in larger studies . bcg is currently the most effective intravesical therapy for nmibc , especially in intermediate- and high - risk tumors . a meta - analysis of 24 randomized trials ( n = 4863 ) showed that bcg significantly reduces the risk of progression to muscle - invasive disease after tur in patients with nmibc who receive maintenance bcg . the european organization for research and treatment of cancer ( eortc ) developed risk tables to predict recurrence and progression in patients with nmibc using clinical and pathologic information from 2596 patients enrolled in seven clinical trials that utilized prophylactic treatments after tur . prediction of disease recurrence and progression in patients with non - muscle invasive bladder cancer in another study , millan - rodriguez et al . variant histology such as micropapillary , sarcomatoid and plasmacytoid has been shown to be associated with poor prognosis , and early cystectomy is generally advocated in such cases .", "the panel recommended that identifying definitive criteria for test positivity , a clearly defined patient population , standardization of techniques used to evaluate markers and clearly specified endpoints and statistical methods will help to bring accurate independent prognostic indicators into the clinical management of patients with bladder cancer . the international consensus panel on cytology and bladder tumor markers evaluated the prognostic utility of molecular markers for bladder cancer . for molecular biomarkers to be of clinical use , they should be able to increase the predictive accuracy beyond the standard clinical and pathological parameter models . several investigators have attempted to use molecular biomarkers as prognostic factors to predict outcomes in patients with nmibc . has been reported to have a higher probability of disease progression . in a meta - analysis , p53 was a predictor for recurrence , progression and mortality in patients with bladder cancer .", "future research should focus to enhance the predictive accuracy of the risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi - institutional cohorts . molecular biomarkers such as ki-67 , fgfr3 and p53 appear to be promising in predicting recurrence and progression , but need further validation prior to using them in clinical practice . additional prognostic factors such as depth of lamina propria invasion should be added to new prognostic models to enhance their usefulness . , both the eortc and the cueto risk tables exhibit a poor discrimination for prognostic outcomes and overestimate the risk of disease recurrence and progression in high - risk patients in external validation . patients with low - grade ta disease have very low risk of progression while patients with t1 disease with concurrent cis have a much higher risk of progression , approaching 50% . the eortc and cueto risk tables are the two best - established predictive models for recurrence and progression risk calculation in patients with nmibc . however", "", "", "" ]
introduction : non - muscle invasive bladder cancer ( nmibc ) comprises about 70% of all newly diagnosed bladder cancer , and includes tumors with stage ta , t1 and carcinoma in situ ( cis . ) since , nmibc patients with progression to muscle - invasive disease tend to have worse prognosis than with patients with primary muscle - invasive disease , there is a need to significantly improve risk stratification and earlier definitive treatment for high - risk nmibc.materials and methods : a detailed medline search was performed to identify all publications on the topic of prognostic factors and risk predictions for superficial bladder cancer / nmibc . the manuscripts were reviewed to identify variables that could predict recurrence and progression.results:the most important prognostic factor for progression is grade of tumor . t category , tumor size , number of tumors , concurrent cis , intravesical therapy , response to bacillus calmette guerin at 3- or 6-month follow - up , prior recurrence rate , age , gender , lymphovascular invasion and depth of lamina propria invasion are other important clinical and pathological parameters to predict recurrence and progression in patients with nmibc . the european organization for research and treatment of cancer ( eortc ) and the spanish club urolgicoespaol de tratamiento oncolgico ( cueto ) risk tables are the two best - established predictive models for recurrence and progression risk calculation , although they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation . molecular biomarkers such as ki-67 , fgfr3 and p53 appear to be promising in predicting recurrence and progression but need further validation prior to using them in clinical practice.conclusion:eortc and cueto risk tables are the two best - established models to predict recurrence and progression in patients with nmibc though they tend to overestimate risk and have poor discrimination for prognostic outcomes in external validation . future research should focus on enhancing the predictive accuracy of risk assessment tools by incorporating additional prognostic factors such as depth of lamina propria invasion and molecular biomarkers after rigorous validation in multi - institutional cohorts .
[ "three publicly available data sets of interest in this paper are pediatric acute myeloid leukemia ( aml ) , b - cell chronic lymphocytic leukemia ( b - cll ) , and primary cutaneous melanoma . given that differences in the biology of lung cancer and other diseases exist between men and women [ 14 , 15 ] , investigations to identify genomic biomarkers for clinical assignment of therapies on an individual patient basis are crucial . in this paper , the ratio of between - group to within - group sums of squares ( bw ratio , ) gene selection algorithm is used to obtain a feasible set of influential genes via variable importance ranking procedure in the training phases of 20 trials of 10-fold cv within leave - one - out cross - validation ( loocv ) procedure as illustrated below . , the predictive accuracy of the classifier must be evaluated on a separate set of data . to derive an unbiased accuracy estimate , a nested cross - validation procedure , 20 trials of 10-fold cv within loocv , the most important consideration is the validation / evaluation of a biomarker classifier to assess whether it can accurately and unbiasedly predict new samples based on a set of selected features . two methods are commonly used to develop and assess performance of a classifier : the split - sample procedure and cross - validation procedure . in the split - sample procedure , the sample dataset the prediction accuracy is the average accuracy of the numerous training - test partitions . for model building , wherefore genes are selected only using learning data sets of size ( n 1 ) each , and in the evaluation / validation step a never - touched and left - out single observation in loocv is used to assess the predictive performance of selected genes . in this way , each test case is never used for gene selection . to avoid a bias due to partitions of data ,", "we hypothesize that genomic biomarkers developed from the sex - specific application of classification algorithms will further improve class prediction accuracy . the summary of our algorithm to find sex - specific predictive / prognostic genomic biomarkers for efficacy or toxicity in individualized treatment of patients for serious diseases is as follows . in each loocv trial , firstly , the data is partitioned into a test data set with one observation and the remaining data as the learning data set . sex differences in disease rates or in rates of adverse reactions to treatment are common , which we intend to exploit to obtain sex - specific biomarkers from gene - expression data . , each selected gene has a combined variable importance score that is less than or equal to n. to verify sex - specific biomarkers , we consider the following four different cases : we classify the outcome of ( 1 ) male patients with a set of male - specific genes smj,(2 ) female patients with a set of male - specific genes smj,(3 ) male patients with a set of female - specific genes sfj , and ( 4 ) female patients with a set of female - specific genes sfj . the sets smj and sfj contain prognostic / predictive genes for male and female patients , respectively these most influential genes used in the classification process are identified in order to extract a feasible set of sex - specific genes . for both male and female learning data sets ,", "in this section , we apply the proposed algorithm to the following genomic data sets to find the most meaningful sex - specific predictive / prognostic genomic biomarkers for improving individualized treatment of patients and for evaluating the biomarkers from the proposed algorithm . current chemotherapy enables a high percentage of pediatric patients with aml to enter complete remission ( cr ) , but a large number of them experience relapse ( r ) with resistant disease . because of the wide heterogeneity of aml , predicting a patient 's risk for treatment failure or relapse at the time of diagnosis is critical for the optimal treatment . this gene - expression data set consists of 54 aml pediatric patients ( < 15 years old ) with an oligonucleotide microarray containing 12,566 probe sets and it is also available at ftp://ftp.ncbi.nih.gov/pub/geo/data/soft/gds/gds1059.soft.gz . therefore , we conclude that there exists evidence of male - specific genes in a classification of primary cutaneous melanoma . b - cll is the most common leukemia in the western world , and due to its clinical heterogeneity ( wide range of life expectancy ) and correlations to genomic aberrations , it is important to predict a patient 's vh mutation status at the time of diagnosis for optimal treatment . genomic aberrations and mutational status of the immunoglobulin variable heavy chain ( vh ) gene have been shown to be among the most important predictors for outcome in patients with b - cll .", "we proposed a procedure to find sex - specific prognostic and predictive genomic biomarkers in order to assign individualized treatments in a personalized paradigm using variable importance ranking via combination of 20 trials of 10-fold cv and loocv . we have presented a procedure for finding sex - specific prognostic and predictive genomic biomarkers in order to assign individualized treatments in a personalized paradigm . , no reliable genomic biomarkers have been developed to provide the physician with prechemotherapy information to accurately predict the efficacy of a specific therapy . the procedure is shown to have good sensitivity and specificity in the sense that the sex - specific genes obtained can improve prediction accuracy in classification of individual patient 's prognosis . the proposed procedure to discover predictive and prognostic sex - specific genomic biomarkers for individualized treatment of diseases can play a critical role in developing safer and more effective therapies that replace one - size - fits - all drugs with treatments that focus on specific patient needs . there was no substantial evidence to find female - specific prognostic genomic biomarkers in this data set ." ]
numerous studies have demonstrated sex differences in drug reactions to the same drug treatment , steering away from the traditional view of one - size - fits - all medicine . a premise of this study is that the sex of a patient influences difference in disease characteristics and risk factors . in this study , we intend to exploit and to obtain better sex - specific biomarkers from gene - expression data . we propose a procedure to isolate a set of important genes as sex - specific genomic biomarkers , which may enable more effective patient treatment . a set of sex - specific genes is obtained by a variable importance ranking using a combination of cross - validation methods . the proposed procedure is applied to three gene - expression datasets .
[ "we have applied a duplex - nested pcr for the amplification of both the causative mutation and the y chromosome specific sry gene , and fish for aneuploidy screening of chromosome x , y and 18 . , we describe the successful pregnancy and birth after pgd for otc deficiency with simultaneous analyses of fish and duplex - nested pcr in korea . mutations have been found in all exons and introns with a relative paucity of mutations in the sequence encoding the leader peptide ( exon 1 and a part of exon 2 ) and in exon 7 ( 17 , 18 ) . to our knowledge , only two cases have been reported where specific pgd for otc deficiency were carried out using multiplex or duplex - nested pcr assay and healthy babies devoid of the otc mutation were born ( 19 , 20 ) . in this study otc deficiency ( mim-#311250 ) is an x - linked and co - dominant metabolic disorder with partial penetrance in females ( 15 ) . procedures using polymerase chain reaction ( pcr ) has been applied for single gene defects including x - linked diseases ( 8 - 11 ) .", "a couple was referred to our center after therapeutic termination of the second pregnancy following prenatal diagnosis for otc deficiency . in the first pregnancy , this r320x nonsense mutation was associated with acute neonatal hyperammonemia in their first pregnancy and reduced enzyme activity by 10 - 15% ( 21 ) . the heterozygous otc gene with r320x nonsense mutation ( cgatga ) and wild type was detected in the exon 9 of the female partner by rflp ( fig . 1 ) and direct sequencing ( data not shown ) . was identified to be an affected boy by pcr and direct sequencing on a chorionic villus sample , and the pregnancy was therapeutically terminated . in order to avoid a pregnancy with an affected baby , the couple was counseled for pgd in cheil general hospital . in order to determine the efficiency of single cell pcr and allele drop - out ( ado ) rate , primers used for the detection of the causative mutation and y chromosome specific sry gene were tested using single lymphocytes ( table 1 ) .", "this was carried out by the simultaneous analysis of the duplex - nested pcr for a r320x mutation in the otc gene underlying the otc deficiency and y chromosome - specific loci , and fish for aneuploidy screening of chromosome x , y and 18 . , we report the successful pgd and delivery of a healthy boy in a couple at risk of transmitting the otc deficiency . this strategy could provide higher accuracy for the selection of genetically and chromosomally normal embryos in pgd for single gene defects . thus , our protocol with pcr and fish in this study provides higher accuracy for the selection of genetically and chromosomally normal embryos in the pgd for x - linked co - dominant defects ." ]
ornithine transcarbamylase ( otc ) deficiency is an x - linked co - dominant disorder . a couple , with a previous history of a neonatal death and a therapeutical termination due to otc deficiency , was referred to our center for preimplantation genetic diagnosis ( pgd ) . the female partner has a nonsense mutation in the exon 9 of the otc gene ( r320x ) . we carried out nested polymerase chain reaction ( pcr ) for r320x mutation and fluorescence in situ hybridization ( fish ) for aneuploidy screening . among a total of 11 embryos , two blastomeres per embryo from 9 embryos were biopsied and analyzed by duplex - nested pcr and fish , and one blastomere per embryo from 2 embryos by only duplex - nested pcr . as a result of pcr and restriction fragment length polymorphism analysis , four embryos were diagnosed as unaffected embryos having the normal otc gene . among these embryos , only one embryo was confirmed as euploidy for chromosome x , y and 18 by fish analysis . a single normal embryo was transferred to the mother , yielding an unaffected pregnancy and birth of a healthy boy . based on our results , pcr for mutation loci and fish for aneuploidy screening with two blastomeres from an embryo could provide higher accuracy for the selection of genetically and chromosomally normal embryos in the pgd for single gene defects .
[ "therefore , we investigated \n the effects of an unstable inclined board on the active and passive ankle rom in patients \n with ankle stiffness . studies have reported that balance - training \n programs that alter the somatosensory input , such as the use of an unstable surface to \n induce equalized weight distribution , can be helpful in hemiplegic patients5 . kim et al . used an ankle board with a slope \n in their center to achieve efficient ankle stretching and increased dorsiflexion6 . limited passive ankle dorsiflexion rom during knee extension can \n alter foot positioning and result in compensatory foot movements , leading to an abnormal \n gait , which can result in ankle sprains and lower extremity overuse injuries4 . musculoskeletal stiffness and limited range of motion ( rom ) can restrict functional joint \n movement , particularly during ankle supination following neurological diseases1 .", "group \n 1 performed the ankle dorsiflexion stretching exercise using a wooden inclined board , and \n group 2 performed ankle dorsiflexion stretching exercises using an air - cushioned inclined \n board that provided an unstable surface . the active and passive ankle \n dorsiflexion angles were measured bilaterally using the goniometer before and after the \n study . the study included 10 female patients ( mean age , 22.8 5.3 years ; height , 158.9 3.0 cm ; \n weight , 61.2 4.7 kg ) with ankle stiffness caused by diseases or medical conditions . the patients performed ankle dorsiflexion stretching exercises for 5 min , with a \n 10-min rest between each set , five times a day for 1 week . active and passive ankle dorsiflexion were measured using a standard 31.75 4.45 cm clear \n plastic goniometer , with one increment , a 360 scale , and a bubble level at each end . the \n patients were selected based on ankle stiffness scores obtained using a symptom checker \n tool .", "the amount of active and passive dorsiflexion did not differ between the two groups before \n the exercises , with active dorsiflexion angles of 18.2 6.4 and 19.3 4.2 and passive \n dorsiflexion angles of 23.4 5.5 and 22.6 5.7 in groups 1 and 2 , respectively ( both p \n > 0.05 ) . the stretching exercises significantly ( p < 0.05 ) increased the active and \n passive ankle dorsiflexion angles in both groups compared to those at baseline . the active \n dorsiflexion angle was significantly increased ( p < 0.05 ) in group 2 compared to that in \n group 1 after the exercises . the passive dorsiflexion angles did not differ significantly between the \n groups after the exercises ( p>0.05 ) and were 23.4 5.5 and 32.2 5.3 in group 1 and \n 22.6 5.7 and 35.1 6.0 in group 2 before and after exercising , respectively . the active dorsiflexion angles before and after the exercises \n were 18.2 6.4 and 22.1 5.0 in group 1 and 19.3 4.2 and 28.1 6.9 in group 2 , \n respectively .", "these results suggest that passive ankle exercises using a wooden inclined \n board only stretch muscle and tissue , while exercises using an unstable inclined board \n stretch muscle and tissue , and stimulate activation of the ankle dorsiflexor . however , stretching exercises significantly \n increased the active and passive ankle dorsiflexion angles in both groups compared to those \n at baseline . active ankle \n dorsiflexion was more effectively improved with ankle stretching exercises using an unstable \n inclined board than with exercises using a wooden inclined board . the results showed that ankle stretching exercises using the unstable \n inclined board significantly increased the active dorsiflexion angle compared to that with \n exercises using a wooden inclined board . the \n air - cushioned inclined board provided an unstable surface for performing ankle dorsiflexion \n stretching exercises . , the passive dorsiflexion angles did not differ significantly between the two \n groups after ankle stretching exercises . we believe that the use of the air - cushioned \n inclined board provides somatosensory input and subsequently stimulates active ankle \n dorsiflexion by promoting automatic postural control ." ]
[ purpose ] the present study assessed the effects of using an unstable inclined board on the active and passive ankle range of motion in patients with ankle stiffness . [ subjects ] the study included 10 young female patients with ankle stiffness . [ methods ] the patients were divided into the following two groups : a group that performed ankle dorsiflexion stretching exercises using a wooden inclined board and a group that performed stretching exercises using an air - cushioned inclined board ( unstable inclined board ) . active and passive ankle dorsiflexion angles were measured bilaterally using a goniometer . [ results ] both inclined boards significantly increased active and passive ankle dorsiflexion . after performing ankle stretching exercises , active dorsiflexion significantly increased the unstable inclined board compared to that using the wooden inclined board . however , the passive dorsiflexion angles did not differ significantly between the two groups after ankle stretching exercises . [ conclusion ] the use of an unstable inclined board might stimulate activation of the ankle dorsiflexors in addition to stretching muscle or tissue . active ankle dorsiflexion was more effectively improved with stretching exercises using an unstable inclined board than with exercises using a wooden inclined board .
[ ", we describe a case a young female with ss who presented with features of gitelman syndrome and hypokalemic paralysis . renal tubular involvement in sjgren 's syndrome ( ss ) usually manifests with fanconi syndrome , distal ( type 1 ) renal tubular acidosis ( rta ) , nephrogenic diabetes insipidus , and hypokalemia .", "a 29-year - old female presented with weakness of both upper and lower limb weakness since 15 days . this patient satisfied the american european consensus criteria for diagnosis of primary sjgren 's syndrome ( ss ) . she had a history of dry eyes and dry mouth for the past 6 months . on examination ,", "given the paucity of reports , we believe that ss presenting as acquired gitelman syndrome may be relatively rare . acquired gitelman syndrome should be considered in differential diagnosis of renal involvement in patients with ss . acquired gitelman syndrome is relatively rare . to the best of our knowledge , only five cases of acquired gitelman syndrome have been reported in english literature so far . among these five cases , only two cases have been reported so far . though gitelman syndrome is an inherited disorder ," ]
we report a case of a young female patient who presented with weakness of upper and lower limbs . on evaluation , she had hypokalemia , hypomagnesemia , metabolic alkalosis and hypocalciuria . anti - ro ( ssa ) antibody was positive . she had an acquired gitelman syndrome due to primary sjgren 's syndrome ( ss ) . ss presenting with features of gitelman syndrome is very rare .
[ "inadequate organization has been identified as an important cause of inappropriate courses of treatment for patients in the health care system [ 1 , 2 ] . a response to this challenge has been to focus on integrated health care and co - ordination between the actors involved in the process [ 37 ] . the aim of this study is to explore one particular aspect of follow - up home visits : the motivation and rationale of local care providers to invest time and effort in follow - up home visits . these results are overall convincing and , as a result , on - going work is being done by health authorities to test and further develop follow - up home visits as an initiative , including a programme in copenhagen carried out from 20082011 . at the same time , studies have shown that there are indications that patients prefer primary care follow - up to specialist care .", "motivation and commitment to the process are therefore needed among the actors involved in order to keep things moving and overcome the uncertainties inherent in the process . what motivates organizations to work together ? working together is a challenging task ; it is typically regarded as uncertain whether it will bring benefits equivalent to the resources invested . this perspective has shown us that we need to have a comprehensive view of the factors which make health sector organisations work together . the literature points to two aspects in particular : the object needs to be seen as highly relevant and benefits should be obvious for all involved [ 22 , 25 ] . hence , in order to understand co - operation you also need to look at the question of trust and the quality of inter - organizational networks , as done in inter - organizational network theory . cross - sectoral programs and inter - organizational activities are not based purely on partners ' own needs and resources [ 23 , 24 ] . empirical data were gathered to develop hypotheses and theoretical concepts . at the same time , however , a rough theoretical framework was used as an underlying foundation in the study to ensure that a relevant focus and approach were applied .", "the interviews were structured around the following questions : \n to which extent do the actors in the programme regard the content of and target group for follow - up home visits as relevant?how do the actors in the programme view communication and workflow in relation to a successful implementation of follow - up home visits ? are the benefits obvious ? \n to which extent do the actors in the programme regard the content of and target group for follow - up home visits as relevant ? how do the actors in the programme view communication and workflow in relation to a successful implementation of follow - up home visits ? this paper is based on an evaluation report made by one of the authors for health and social care , city of copenhagen . results were presented and discussed in a steering group with representatives from the main professional groups involved in the programme ( gps , district nurses and hospital staff ) . two focus groups and seven individual interviews were conducted in march may 2010 , giving a total of 23 respondents . the interview transcripts were analyzed under the two headings which form the basic empirical questions in the study : relevance of collaboration and benefits of collaboration . one focus group interview was conducted with seven employees at bispebjerg hospital who were involved in the follow - up home visit programme . quotes from the interviews were grouped under each heading in order to find the quotes which were most illustrative of the views of gps , district nurses and hospital staff . to ensure reliability ,", "the main elements of the guide are : a medication review , a general health assessment ( including a number of relevant tests ) , and an assessment of the need for follow - up arrangements ( home care , rehabilitation etc . ) . gps and district nurses have been instructed to follow this guide in order to ensure that the same standards and procedures are used in the programme but ultimately it is an individual judgment on the part of the gp and district nurse to decide whether all elements in the guide are relevant in each specific case . a guide suggesting the ideal content of a follow - up home visit has been designed as part of the programme . the district nurses also found that the follow - up home visit was a good way of assessing the health situation of the patient : the guide creates a good structure for the home visit . a gp said : we should be able to see what type of medication the patient has . but the patient may have been given some additional medicine by the hospital that we are not aware of , and in this case a home visit is a good way of finding out whether there is a problem with the different types of medicine the patient takes . a nurse at the hospital said : follow - up home visits are especially important in the case of patients where it has not been possible to offer the most appropriate treatment .", "gps and district nurses have been instructed to follow this guide in order to ensure that the same standards and procedures are used in the programme but ultimately it is an individual judgment on the part of the gp and district nurse to decide whether all elements in the guide are relevant in each specific case . the main elements of the guide are : a medication review , a general health assessment ( including a number of relevant tests ) , and an assessment of the need for follow - up arrangements ( home care , rehabilitation etc . ) . a guide suggesting the ideal content of a follow - up home visit has been designed as part of the programme . the district nurses also found that the follow - up home visit was a good way of assessing the health situation of the patient : the guide creates a good structure for the home visit .", "the gps want , however , more information about the efficacy of follow - up home visits . gps in the study find it highly motivating to receive such information if results show an effect on readmission and general health : if research clearly shows that follow - up home visits have a positive effect it would really give us a moral incentive to participate in these visits . a nurse at the hospital said : follow - up home visits are especially important in the case of patients where it has not been possible to offer the most appropriate treatment . communication about the implementation and results of follow - up home visits could , however , be better according to hospital staff . a fax from the hospital to the home nursing services is not enough ( doctor , hospital ) . in the city of copenhagen the staff involved in the programme is very positive towards follow - up home visits . the health and social care administration of the city of copenhagen has sent pamphlets to gps informing them about follow - up home visits , and other forms of information have also been used .", "resources clearly matter ( fees for gps etc . ) but the paper also points to other key factors which need to be taken into consideration when trying to motivate partners to engage actively in a cross - sectoral programme like a follow - up home visit programme . in the following these key factors will be discussed under three sub - headings : the focus of collaboration , a partnership of equals , and the will to co - operate . the analysis illustrates that it is a big challenge to co - ordinate activities across organizational boundaries and motivate actors to participate in cross - sectoral health programs . the learning potentials in integrated care for older people are big , and health care professionals are generally motivated to take part if the learning potential of the experience is clearly communicated . there is a common understanding that the complex needs of frail elderly patients are not adequately dealt with by traditional health care services and require an extra - ordinary and cross - sectoral approach .", "collaboration requires partners to subscribe to common standards , and the fixed structure of follow - up home visits is a powerful way of defining these standards . the medication review is a very illustrative example of how gps and district nurses can work closely together and achieve a shared understanding of the patient 's intake of medicine . thus , the results indicate that the object at the centre of these efforts the focus of collaboration needs to be clearly defined and agreed upon if the actors involved are to be motivated to invest in an extra - ordinary and cross - sectoral activity like follow - up home visits . the analysis indicated that it is beneficial to have agreed upon a common structure for follow - up home visits . the study indicates that the gp gains a very realistic picture of the patient 's medicine intake during the home visit , a picture the gp could not as easily have gained in a different setting . as a result , communication between the gp and the district nurse about a patient 's medicine the results also showed that follow - up home visits aimed at the right target group , and this motivated care providers to take part in the intervention . the guide specifying the ideal content of these visits ensures that common standards and procedures focusing on the patient 's overall situation are followed by all professionals involved . as a result", "the results of the study indicate that district nurses are highly motivated and view these visits as part of a dominant trend in health care , a trend putting more emphasis on primary sector treatment which has evolved as a response to a growing pressure on health services to provide cheaper care than traditional hospital care [ 6 , 8 ] . they are trained to have the prime responsibility for their patients in primary care and find the current state of affairs demotivating . this form of communication between the hospital and gps could give both hospital staff and gps a greater sense of responsibility for follow - up home visits and , as a result , increase the motivation to make these visits . it is important for all providers to have an essential role in follow - up home visits and feel a sense of responsibility in order to feel motivated . they are responsible for contacting the gp , organizing the visit , and co - ordinating the activities following the visit .", "the interviews showed that it is important that all partners can see the benefits of working together and understand how they can contribute to achieve shared goals . gps in particular need to be convinced that an intervention like follow - up home visits can add something extra to their normal practice . hospital staff is given no feedback after follow - up home visits , and need a clearer notion of how this type of intervention fits into the treatment given at the hospital . the results from the study showed that hospital staff also has problems in seeing how they get extra value out of working in partnership . the learning potentials in integrated care for older people are big , and health care professionals are generally motivated to take part if the learning potential of the experience is clearly communicated . basically , the partners in the danish follow - up home visit programme share the understanding that health services need to be more efficient and more coherent . in particular there is a common understanding that the complex needs of frail elderly patients are not adequately dealt with by traditional health care services and require an extra - ordinary and cross - sectoral approach .", "one lesson for current policy is that motivational factors need to be addressed in future collaborative programs in order to fully exploit the potential health benefits . the findings support a basic claim in inter - organizational theory that other factors than resources matter if we want to understand what drives efforts at collaboration . this analysis shows that the focus of collaboration needs to be clearly defined and agreed upon , there needs to be a high degree of equality between the professionals involved , and there has to be a will to co - operate based on a shared understanding of values and learning potentials . the follow - up home visit programme in copenhagen suffered from a lack of motivation among key actors ( especially gps ) to participate and , as a result , readmissions to hospital can be expected to be higher than anticipated prior to the programme .", "susanna bihari axelsson , senior lecturer , associate professor nordic school of public health , box 12133 , nya varvet building 25 , se-402 42 gteborg sweden janne seemann , assistant professor , phd , department of sociology and social work , aalborg university , denmark j.d.h . van wijngaarden , dr , assistant professor , institute of health policy and management , erasmus university rotterdam , p.o ." ]
objectivesthe aim of follow - up visits by the general practitioner and district nurse ( within a week after discharge from hospital ) is to reduce hospital readmissions and improve the overall wellbeing of the patient . there is strong evidence that these programmes are effective , but are difficult to implement because of a number of organizational obstacles , including co - ordination between the organizations involved in the process . in this paper we look at the factors that affect motivation to participate in a cross - sectoral programme in copenhagen , denmark , implementing follow - up home visits to elderly persons.theory and methodsthe analysis is based on inter - organizational network theory in an attempt to explain the role of motivation in network formation between organizational systems . the empirical findings are based on focus groups and in - depth interviews with hospital staff , general practitioners , and district nurses.resultscare providers are motivated to collaborate by a number of factors . the focus of collaboration needs to be clearly defined and agreed upon , there needs to be a high degree of equality between the professionals involved , and there has to be a will to co - operate based on a shared understanding of values and learning potentials.conclusionsthe study concludes that we need to focus on specific care fields and actors to reduce complexity in the area and more fully understand what motivates care providers to participate in cross - sectoral activities , such as a follow - up home visit programme . one lesson for current policy is that motivational factors need to be addressed in future collaborative programmes in order to fully exploit the potential health benefits .
[ "alzheimer s disease ( ad ) is a progressive neurodegenerative disorder starting with mild memory loss and manifesting in severe cognitive decline . our discussion presented here attempts to integrate two major factors that are associated with neurodegeneration , protein homeostasis and aging . today , we know that the progressive deposition of misfolded and aggregation - prone proteins in defined regions of the nervous system is not unique to ad , but a well - described characteristic of several neurodegenerative disorders , including parkinson s disease ( pd ) , huntington s disease ( hd ) and amyotrophic lateral sclerosis ( als ) . recently , it has been proposed that the accumulation of disease - relevant proteins in aggregates might actually even be considered as a protective mechanism to dispose these proteins and remove them from the cellular metabolism [ 13 , 14 ] . generally , within the crowded cellular environment although alois alzheimer already described protein deposits in the brain of demented patients , the question why distinct proteins that are potentially causative for the disease accumulate in discrete brain regions in the course of aging remains unanswered . the fad - linked mutations cause an elevated production of amyloidogenic a , which is the basis for the amyloid hypothesis of ad , stating that a peptides are the key - players in neuronal dysfunction and subsequent neurodegeneration in ad .", "thus , hsf1 and chaperone activity can promote longevity , demonstrating a clear association of chaperones , proteostasis and aging . the analysis of the chaperone capacity of neuronal and muscular tissue of caenorhabditis elegans ( c. elegans ) demonstrates that these tissues indeed display different folding activities and that neurons are particularly sensitive to protein denaturation during heat stress . however , the adaptation of the chaperone network during aging is critical as it is well acknowledged that protein aggregation and disruption of proteostasis are characteristic for aged cells . central players of the protein homeostasis system are molecular chaperones that sense misfolded proteins and , when refolding fails , direct them to the protein - degradation pathways . molecular chaperones are specified as proteins that interact with and participate in folding or refolding of non - native proteins . hsp70 proteins are central players in proteostasis control and increasing hsp70 levels prevent protein aggregation in various disease models that are based on the expression of aggregation - prone proteins [ 32 , 33 ] .", "1the ubiquitin proteasome system ( ups ) and various autophagy routes as the main pathways for protein degradation ( regular turnover ) and of misfolded and aggregated proteins ( and mitochondria ) the ubiquitin proteasome system ( ups ) and various autophagy routes as the main pathways for protein degradation ( regular turnover ) and of misfolded and aggregated proteins ( and mitochondria ) this aggresome - targeting pathway involving bag3 and hsp70 is distinct from other before - described mechanisms as it does not depend on substrate ubiquitination . taken together the molecular chaperone machinery , the ups and the autophagy system are involved in pqc and maintaining proteostasis within aging and disease to prevent protein misfolding and aggregation . some of the factors mentioned so far are involved in linking chaperone functions with cellular protein - degradation pathways , the ups and autophagy , for the removal of misfolded proteins . besides protein aggregation , an accumulation of polyubiquitinated proteins is reported for numerous neurological disorders , which suggests that ups dysfunction plays a prominent role in the pathogenesis of neurodegenerative diseases and moreover in aging . since proteasomal in particular , the mitochondrial respiratory chain is strongly linked to the production of ros and as one consequence may cause protein dysfunction , apoptosis , necrosis , aging and disease [ 49 , 50 ] . most likely , irreversible oxidation may activate chaperones and the ups to induce protein repair of misfolded proteins and lead to ubiquitination and protein degradation . during aging ,", "the malfunctioning proteostasis control results in the accumulation of misfolded and aggregated proteins , which is a general hallmark of aging and neurodegeneration , as observed in pd , hd , als and ad . aging in particular is characterized by decreasing proteostasis capacity and increasing protein damage which are in combination a major challenge for the cell due to the inability to maintain metastable proteins in folded states . to counteract a cascade of protein destabilization caused by metastable proteins which escaped the pqc ad is characterized by the accumulation of intracellular a ( oligomers ) , extracellular high molecular weight deposits of a peptides ( fibrilliar forms ) , and the intracellular aggregation of hyper - phosphorylated tau . indeed , taken together , all these findings suggest an important role for autophagy in the pathogenesis of ad . since aging is the major risk factor of ad [ 7880 ] , the age - dependent loss of proteostasis might be an important contributor to the pathology of ad . besides extracellular a accumulation , the second major hallmark of ad is the intracellular aggregation of tau . the first abnormalities of the lysosomal - endosomal system occur prior to other hallmarks of the disease such as amyloid deposits in the neocortex and persist until massive impairments of the autophagic system emerge in the later stages of the disease .", "collectively , these data suggest that up - regulation of molecular chaperones may suppress formation of ntfs by partitioning tau into a productive folding pathway and thereby preventing tau aggregation . these observations suggest that hsp - induced microglial activation may have a neuroprotective role by facilitating a clearance . besides extracellular a accumulation , the second major hallmark of ad is the intracellular aggregation of tau . tau seems to directly bind to hsp70 and this interaction is mediated by the hsp70 co - chaperone bag1 pointing to a tight interplay between molecular chaperones and the ups in counteracting tau aggregation [ 97 , 98 ] . the two main chaperone scaffolds are hsp70 and hsp90 which are accompanied by a variety of co - chaperones specifying substrate binding and release and are transcriptionally regulated through heat shock elements ( hse ) via the transcription factor hsf1 .", "the ubiquitin proteasome system is the main degradation pathway in the cell and it has been shown that a40 and a42 can block proteasome function in vitro . a42 can inhibit proteasome function to an extent that is comparable to a well - known proteasome inhibitor [ 99102 ] . taken together , these data clearly indicate that proteasome activity is necessary for tau turnover and that aggregated tau inhibits proteasomal function . a42 has also been shown to accumulate predominantly in multivesicular bodies , indicating that these structures are the possible interaction site of a and the proteasome in vivo . further supporting the influence of the ups on a metabolism the protein tau is degraded by the 26s and 20s proteasome in vitro and the use of proteasome inhibitors in cells and animal models leads to an accumulation of tau [ 108111 ] .", ", all these findings suggest an important role for autophagy in the pathogenesis of ad . the first abnormalities of the lysosomal - endosomal system occur prior to other hallmarks of the disease such as amyloid deposits in the neocortex and persist until massive impairments of the autophagic system emerge in the later stages of the disease . taken together furthermore , post - mitotic neurons have to cope with elevated levels of stress and damaged organelles as well as misfolded or aggregated proteins during their lifetime , cellular aging and disease progression , which highlight the importance of an effective degradation system in this particular cell type . besides changes of the autophagic system on a histological level , also molecular regulators of autophagic degradation are altered during ad progression . genes that represent negative regulators of autophagy are repressed , whereas positive modulators are more likely to be up - regulated in the brain of ad patients . however ,", "although there are obviously still many questions to be answered to understand the role of proteostasis in ad ( and also in other age - associated neurodegenerative disorders ) , it is a big step forward in ad research to consider a possible role of pathogenetic pathways that are not directly linked to the usual suspects a and tau . a better understanding of how the proteostasis network is regulated might help to identify targets which lead to prevention of the deleterious loss of neuronal cells and tissue in ad . whether supporting proteome integrity can be a real target for pharmacological intervention for the prevention and treatment of ad is currently still open . autophagy pathways are key mechanisms and of vital importance for cellular function and , especially , for cell survival under adverse conditions . deregulation and changes of chaperones and proteasome activity might have serious implications for aging as well as for age - associated diseases ." ]
alzheimer s disease ( ad ) is one key medical challenge of the aging society and despite a great amount of effort and a huge collection of acquired data on molecular mechanisms that are associated with the onset and progression of this devastating disorder , no causal therapy is in sight . the two main hypotheses of ad , the amyloid cascade hypothesis and the tau hypothesis , are still in the focus of ad research . with aging as the accepted main risk factor of the most important non familial and late onset sporadic forms of ad , it is now mandatory to discuss more intensively aspects of cellular aging and aging biochemistry and its impact on neurodegeneration . since aging is accompanied by changes in cellular protein homeostasis and an increasing demand for protein degradation , aspects of protein folding , misfolding , refolding and , importantly , protein degradation need to be linked to ad pathogenesis . this is the purpose of this short review .
[ "we intended to study this effect and analyze if teriparatide can be an effective adjunct therapy to achieve solid posterolateral fusion mass and reduce the incidence of subsequent screw loosening after multilevel instrumented lumbar fusion surgeries in elderly patients . its action as a direct anabolic agent in bone tissue , consistently increases bone mineral density and thus improves skeletal architecture . since its availability in market multitudinous research to gain insight into use of teriparatide ( 134 recombinant human parathyroid hormone ) for enhancing bone formation in osteoporosis is readily available in the literature . the union rate and hardware - related complications remain a major concern in these patients , especially following multilevel spinal fusion surgeries . developing an adjunct therapy that essentially supplements the mainstay surgical management is of great importance to these patients . another evolving field of interest is the role of teriparatide for enhancing bone graft union and osseo - integration of implants . it is said to accelerate bone graft union and reduce the incidence of pedicle screw loosening after lumbar spinal fusion surgeries .", "an open - labeled , nonplacebo controlled , retrospective , single center study is formulated by shortlisting 62 elderly patients ( male 9 ; female = 53 ) between the age group of 65 to 78 years ( mean age standard deviation [ sd ] = 70.1 3.7 ) , who underwent instrumented lumbar fusion for various degenerative pathologies over a period of time . , patients were given an option of postoperative teriparatide use and opting to it was solely based on their own decision . in total , 30 patients who accepted for long - term daily use of teriparatide were in the experimental group and remaining 32 patients were in the control group . all of them had received multilevel lumbar fixation ( 3 levels or 4 vertebral segments ) with pedicle screw constructs and postero - lateral intertransverse fusion with a combination of local bone graft and allograft . selection was irrespective of individual bone mineral density ( bmd ) status , as bmd scoring was not done as a part of routine preoperative evaluation in patients undergoing multilevel spinal fusions . outcome analysis was done using radiological data which included antero - posterior ( ap ) , conventional lateral view , and dynamic stress lateral view radiographs taken at 12 months follow - up ( figs . 1 and 2 ) . ( c ) mri images showing severe degeneration of disc levels and canal stenosis from l1l5 .", "the incidence of screw loosening was 13.4% in the teriparatide group and 24.4% in the control group . group 1 or the experimental group ( n = 30 ; mean age sd = 69.8 3.8 years ) was those in whom teriparatide was administered and group 2 ( n = 32 ; mean age sd = 70.4 3.6 years ) was the control group . nonunion was noted in 10 patients ( 33.3% ) of teriparatide group and 16 patients ( 50% ) in the control group . the 16.7% advantage procured with teriparatide use was not statistically significant ( p = 0.20 ) ( table 2 ) . duration of teriparatide administration averaged 7.4 2.4 months in the experimental group . follow - up data were available for a mean duration of 25.4 months for those in the experimental group and 27 months for those in the control group . even though follow - up was done for a longer duration , analyzing outcome further after 1 year may not be related to teriparatide use . sixty - two elderly patients ( age = 6578 years ; mean = 70.11 years ; male = 9 , female = 53 ) are divided into 2 groups based on teriparatide administration following surgery . the presence of concomitant medical comorbidities in group 1 ( dm = 14 ; ba = 4 ) and group 2 ( dm = 11 ; ba = 4 ) was matched .", "our study is foremost to discuss the effect of teriparatide on multilevel posterolateral fusions in elderly patients . according to our preliminary results , the percentage of patients achieving solid fusion following teriparatide use was found to be more than that of the control group . besides that , use of teriparatide effectively reduced the incidence of subsequent screw loosening which proved to be statistically significant . animal studies yielded promising results for teriparatide usage to enhance postero - lateral fusion mass in rat models . in human studies relating to teriparatide it is said to play a reasonable role in treatment of osteoporosis . apart from being used in osteoporotic individuals , insights into its action on many other conditions are unraveling . elderly patients with chronic unresolving symptoms due to degenerative spine disease are prone to have poor surgical outcomes .", "our study evaluates the radiological outcome following postoperative teriparatide administration in patients undergoing multilevel instrumented lumbar fusion surgery . even though percentage of solid fusion was more among patients who used teriparatide , the difference was not statistically significant . however , teriparatide was more significantly influential in reducing the incidence of subsequent pedicle screw loosening .", "being a retrospective study , there are few methodological shortcomings that may have influenced our outcome . use of ct as an evaluation tool to assess bone graft union could have been more empirical . the lack of preoperative bmd data , variation in surgical indications , and differential treatment durations of teriparatide administration may have biased the sample . considering the selected sample size , the study may be underpowered to draw potential conclusions ." ]
abstractelderly patients with chronic nonresolving symptoms due to degenerative spine pathologies are prone to have poor surgical outcomes and hardware - related complications , especially following multilevel instrumented lumbar fusion surgeries . with intention of analyzing if teriparatide can be an effective adjunct therapy to surgical management , radiological outcomes are studied . sixty - two elderly patients were divided into 2 similar groups . group 1 ( n = 30 ; mean age = 69.83 years ; fusion levels = 137 ; screws = 269 ) had taken teriparatide ( 20 mcg sc injection , once daily ) for a duration of 7.4 2.4 months following surgery and group 2 ( n = 32 ; mean age = 70.38 years ; fusion levels = 144 ; screws = 283 ) did not take teriparatide . radiological evaluation was done to determine the state of postero lateral fusion mass and to investigate the incidence of pedicle screw loosening at 1-year follow - up . unilateral or bilateral bridging bone formation across the transverse process of adjacent vertebras showing continuous trabeculation suggestive of solid fusion was obtained in 66.7% patients in the teriparatide group and 50% patients in the control group ( p = 0.20 ) . 13.4% of the total no . of screws showed signs of loosening in the teriparatide group , compared to 24.4% in the control group ( p = 0.001 ) . percentage of patients achieving solid fusion following teriparatide use was found to be more than that of the control group . this difference may have clinical importance but was not statistically significant . however , teriparatide use was more significantly influential in reducing the incidence of subsequent pedicle screw loosening .
[ "this study aims to establish the prevalence of hypertension , diabetes , obesity , and metabolic syndrome in the participants of a major health screening programme in nepal . metabolic syndrome ( ms ) is a constellation of overweight / obesity , hypertension , and disturbances of lipid and carbohydrate metabolism . each component of ms is a known risk factor for the development of type 2 diabetes , atherosclerosis , and coronary artery disease ( cad ) . central obesity , one of the components of ms , predicts the occurrence of diabetes and overall cardiovascular risk . according to the world health organization 's recent update , diabetes , hypertension , and obesity are one of the top five continuing risk factors for cardiovascular deaths in the world . the international diabetes federation ( idf ) takes central obesity as a prerequisite for the diagnosis of ms with the association of any two of the other factors , that is , high blood pressure , abnormal blood glucose , high levels of triglycerides , and low levels of high - density lipoprotein . the world health organisation describes ms as the presence of type 2 diabetes or impaired glucose tolerance with any two of the following characteristics : obesity , high levels of triglycerides , low levels of high - density lipoprotein , and hypertension .", "the subjects were the participants of the programme for detection and management of chronic kidney disease , hypertension , diabetes and cardiovascular disease , a community - based screening programme in eastern nepal . in this community - based programme nepal is one of the poorest countries of the world at the 136th position of human development index . a series of community awareness programmes were conducted in a specific locality with the help of local leaders , medical students , and community volunteers . various screening centres such as permanent centers ( in health clinics , community centers , etc . ) and temporary screening centers ( in schools , clubs , houses of worship , and private homes ) were used to screen the population . the research team also collected general information on the participants ' demographic data , diet , smoking , alcohol consumption , and physical activity . the data recorded included family and medical history for kidney disease , high blood pressure , diabetes , cardiovascular disease and any current medication or treatment .", "gender , age , education level , and physical activity show a positive association with the prevalence of metabolic syndrome . the prevalence of ms ( ncep scores ) had a significant positive relationship with education levels and physical activity . generally , among the total participants and the specific participants with ms , the presence of abnormal lipids was higher than the other factors defining ms . however , the presence of abdominal obesity was higher among ms participants using idf criteria ( figure 2 ) . \n the females had a higher prevalence of ms than males . according to the ncep criteria , the age groups 4160 and 6180 had a higher prevalence of ms than the lower age group .", "the results did not show substantiate relationship between smoking histories , diet , family history of cardiovascular , and metabolic syndrome . it is important to observe the prevalence of diabetes , hypertension , and obesity individually and also the combination of risk factors as metabolic syndrome to predict the risk of cardiovascular disease . the low prevalence of general body obesity compared to western countries , metabolic syndrome is growing into a significant public health problem in asia . inadequate maternal nutrition in pregnancy , low birth weight , and childhood obesity may be important factors for the development of metabolic syndrome and diabetes . specifically in children and young individuals , a high intake of n-6 pufa is correlated with hyperinsulinaemia . in adults , these found that education levels significantly influence the knowledge of hypertension and the awareness of cardiovascular risk . this suggests that there is a need to improve the awareness of health and use education to prevent or reduce the risk of ms and cardiovascular risks in these groups . these findings suggest the need for specific attention to control the disease prevalence in nepal .", "the ms prevalence may be due to lack of awareness and unhealthy lifestyles , so health education and more preventive measures should decrease the prevalence of ms and cardiac risks in nepal . abdominal obesity , with the revised reference values , is an important risk due to its physiological relationship to the other ms risk factors ." ]
background . this study was carried out to establish the prevalence of cardiovascular risks such as hypertension , obesity , and diabetes in eastern nepal . this study also establishes the prevalence of metabolic syndrome ( ms ) and its relationships to these cardiovascular risk factors and lifestyle . methods . 14,425 subjects aged 20100 ( mean 41.4 15.1 ) were screened with a physical examination and blood tests . both the international diabetic federation ( idf ) and national cholesterol education programme 's ( ncep ) definitions for ms were used and compared . results . 34% of the participants had hypertension , and 6.3% were diabetic . 28% were overweight , and 32% were obese . 22.5% of the participants had metabolic syndrome based on idf criteria and 20.7% according to the ncep definition . prevalence was higher in the less educated , people working at home , and females . there was no significant correlation between the participants ' lifestyle factors and the prevalence of ms . conclusion . the high incidence of dyslipidemia and abdominal obesity could be the major contributors to ms in nepal . education also appears to be related to the prevalence of ms . this study confirms the need to initiate appropriate treatment options for a condition which is highly prevalent in eastern nepal .
[ "hence , simulator \n horseback riding exercise equipment using virtual reality has been developed for use at home \n and in small spaces . horseback riding exercise is one such therapy . in research conducted by arajo et al . as balance ability and falls are closely related in the elderly , exercise therapies need to \n focus on the maintenance of such ability7 . \n although various therapeutic approaches have made with horseback \n riding exercise in the previous studies there is a lack of research on the effects of \n horseback riding exercise equipment on the balance and gait abilities of elderly patients \n with osteoarthritis . the treatments include muscle strength \n training , electrical stimulation , manual therapy , aquatic therapy , balance therapy , and \n pharmacotherapy6 . osteoarthritis is \n a degenerative disease that causes severe pain in elderly patients with low pain thresholds . \n 8 where elderly individuals performed \n horseback riding exercise for eight weeks , the researchers reported that the exercise \n significantly improved the participants balance and muscle strength .", "experimental procedures were performed in accordance with the protocols established by the \n institution of animal care and use committee ( iacuc ) at the daegu university . include criteria was aged 65 years or over ( table \n 1table 1.general characteristics of the subjectsvariablessubjects ( n=15)gender ( m / f)6/9age ( years)76.5 7.7height ( cm)160.6 9.7weight ( kg)54.7 9.8mean sd ) , and with a history of none falls in previous year , lower pain for perform \n experiment , and visual or auditory damage , nervous system or of the vestibular organ \n problems , who ca nt understand the contents of the experiment were excluded . after providing \n information study all subjects received a participation agreement . in this study , the subjects , while providing conventional physical therapy , 8 weeks three \n times a week the movement of the horse riding equipment , was carried out for 30 minutes . \n before performing horse riding simulation exercise , subjects were educated about exercise \n program through a research assistant s demonstration . in this study , used the slimrider \n ( shinhwa , mx-0004se , korea ) , which is a horse riding simulator . while performing a horse \n riding equipment exercise , subjects were effort to maintain the correct posture . exercise \n intensity was increased gradually according to the state of the subjects while performing \n the exercise , the research assistant were always observed to prevent falling . in order to evaluate the balance of the elderly , it was using the frt ( functional reach \n test ) and sbbsf ( short form berg balance scale ) . the spss for windows ( version 18.0 ) was used for data analysis of the study . in order to \n compare the differences between before and after , it was analyzed using the paired t - test .", "in this study , sfbbs scores and range of frt increased significantly after horse riding \n simulator exercise ( table 2table 2.comparison of measurement values at pre - test and post - testvariablesprepostsfbbs ( score)18.6 5.822.3 4.4**frt ( cm)19.7 9.526.3 7.5*mean sd .", ", the static , dynamic , and functional balance abilities of osteoarthritis patients who \n undertook horseback riding exercises on exercise equipment were measured using a frt and \n sfbbs . osteoarthritis causes severe pain in elderly patients who have a low threshold for pain and \n high disability scores , thereby resulting in a low quality of life , increased risk of falls , \n and poor balance ability1 , 2 , 6 . in the present \n study the findings are in \n accordance with those of study that stroke patients performed horseback riding exercise for \n 35 min five times a week for eight weeks and arajo8 in which elderly patients performed horseback riding exercise for \n eight weeks . the results suggest that horseback riding exercise \n equipment can improve dynamic and functional balance abilities . they are also in accordance with the results of han jun - young16 in a study of stroke patients who \n performed horseback riding exercise for 12 weeks that an eight - week - long horseback riding \n exercise significantly improved the bbs scores of osteoarthritis patients . in general \n elderly , the average bbs score is 20.60 4.0817 . in the present study ," ]
[ purpose ] the aim of this study was to examine the effects of horse - riding simulator exercise on balance in elderly with knee osteoarthritis . [ subjects and methods ] fifty elderly patients with knee osteoarthritis were recruited , a horse - riding simulator group performed exercise three times a week for eight weeks . and each exercise was performed for 30 minutes . [ results ] the horse - riding simulator group showed significant differences after the intervention in short form berg balance scale , functional reaching test . [ conclusion ] the results of this study indicate that horse - riding simulator exercise is effective on knee osteoarthritis . therefore , horse - riding simulator exercise can be used balance training for knee osteoarthritis .
[ "we focus on shh medulloblastoma and discuss how cell senescence shapes the natural history and molecular evolution of this childhood cancer . are characterized by activation of the hedgehog ( hh ) signaling pathway and are often driven by mutations in hh pathway components . here , medulloblastomas can be classified in 4 different molecular subtypes : wnt , shh , group 3 and group 4 . each of these molecular subtypes has specific underlying molecular features , gene expression , demographic characteristics and prognosis . sonic hedgehog ( shh ) medulloblastomas", ", we found that , contrary to li - fraumeni syndrome ( where tp53 germ - line mutations lead to hh signaling mutations ) , hh signaling hyperactivity leads to cell senescence in preneoplastic lesions and creates selection pressure for the inactivation of p53 or p16 , which allows the progression from preneoplasia to advanced medulloblastoma ( fig . we found that apoptosis levels are the same between preneoplastic lesions and advanced medulloblastoma , eliminating apoptosis as an essential tumor suppressor in this model of shh medulloblastoma . however , the problem for understanding brain tumor development lies in the inability to detect and obtain precancerous lesions ; therefore , genome sequencing of advanced brain tumors only offers a snapshot of the mutations present in advanced tumors but does not show the order in which mutations are acquired during tumor progression . to address this question , we used ptch1 heterozygous mice , a well - established model of shh medulloblastoma ( fig . 2 ) . moreover , tp53 mutations have recently been identified as a key event in the pathogenesis of medulloblastoma recurrence . although the specific roles of p53 in medulloblastoma are still largely unknown , the presence of recurrent tp53 mutations suggests that p53 signaling plays an important role in driving medulloblastoma tumorigenesis .", "together , these findings provide strong evidence that hh signaling leads to a functional inactivation of p53 signaling that allows gcp proliferation and , in some instances , medulloblastoma formation . however , the presence of somatic p53 mutations in ptch1 medulloblastoma demonstrates that the ability of shh signaling to functionally suppress p53 signaling is not always sufficient to inactivate p53 activity in a tumorigenic context . for many years the fact that p53 mutations , which are acquired spontaneously during medulloblastoma formation , lead to senescence evasion provides an explanation for the presence of somatic tp53 mutations in human shh medulloblastoma . this may explain why p53 activity is downregulated during neurogenesis to allow cell proliferation and brain formation .", "recently , we also found that the ligand shh induces dna damage in gcps , an effect that requires the presence of the hh receptor boc and cyclind1 . therefore , we propose that high levels of hedgehog signaling shape the molecular evolution of medulloblastoma by leading to ois and creating selection pressure to inactivate p53 in order to evade ois . these results support the hypothesis that gcps are sensitive to replicative stress and that hedgehog signaling likely causes replication stress . , the fact that we found cell senescence and ptch1 loh in medulloblastoma preneoplastic lesions suggests that high levels of hedgehog signaling in preneoplasia likely cause high levels of oncogenic stress and this leads to cell senescence .", "eglexternal granule - cell layergcpsgranule cell precursorshhhedgehogiglinternal granule - cell layeroisoncogene - induced senescenceshhsonic hedgehog external granule - cell layer granule cell precursors internal granule - cell layer oncogene - induced senescence", "", "sms is recipient of the mcgill james o. and maria meadows fellowship and ircm challenge - gupards et gazelles gourmands scholarship . work done in the charron lab was supported by grants from the canadian institutes of health research ( cihr ) , the fonds de recherche du qubec - sant ( frqs ) , and the canada foundation for innovation ( cfi ) ." ]
abstractthe mechanisms leading to brain tumor formation are poorly understood . using ptch1+/ mice as a medulloblastoma model , sequential mutations were found to shape tumor evolution . initially , medulloblastoma preneoplastic lesions display loss of heterozygosity of the ptch1 wild - type allele , an event associated with cell senescence in preneoplasia . subsequently , p53 mutations lead to senescence evasion and progression from preneoplasia to medulloblastoma . these findings are consistent with a model where high levels of hedgehog signaling caused by the loss of the tumor suppressor ptch1 lead to oncogene - induced senescence and drive p53 mutations . thus , cell senescence is an important characteristic of a subset of shh medulloblastoma and might explain the acquisition of somatic tp53 mutations in human medulloblastoma . this mode of medulloblastoma formation contrasts with the one characterizing li - fraumeni patients with medulloblastoma , where tp53 germ - line mutations cause chromothriptic genomic instability and lead to mutations in hedgehog signaling genes , which drive medulloblastoma growth . here we discuss in detail these 2 alternative mechanisms leading to medulloblastoma tumorigenesis .
[ "the clinical working diagnosis was pregnancy - related vt of right ventricular outflow tract origin . a 33-year - old woman , ( gravida 3 , para 2 ) , at 34 weeks of gestation , presented with episodes of lightheadedness , and dyspnea . she was asymptomatic until 18 weeks of gestation , when she started having episodes of palpitations associated with presyncope . cardiac monitoring showed multiple episodes of monomorphic , non - sustained ventricular tachycardia ( vt ) with left bundle branch morphology , consistent with vt originating from the right ventricular outflow tract ( fig .", "given the absence of structural heart disease and risk factors for coronary disease or arrhythmia , the clinical diagnosis was catecholamine - sensitive pregnancy - related vt of right ventricular outflow tract origin . a 24 year woman ( gravida 4 , para 2 ) presented to her local emergency department at 24 weeks gestation because of shortness of breath , cough , and chest tightness developing over the previous day . the patient was diagnosed with an asthma exacerbation and treated with nebulized salbutamol 2.5 mg , which relieved her symptoms . shortly thereafter , she developed runs of asymptomatic nonsustained vt with a left bundle branch block pattern ( fig .", "ventricular tachycardias ( vt ) may be seen in pregnancy and can manifest as a new onset arrhythmia or be exacerbated by pregnancy and can cause concern for the well - being of both the mother and the fetus . given the sensitivity of majority of vts in pregnancy to catecholamines , a cardioselective beta - blocker , in particular metoprolol , in the absence of contraindications is considered first line therapy.12 alternatively lidocaine can also be used to treat stable vt.14 idiopathic vt originating from the rvot and with a lbbb morphology responds well to beta - blockers , while idiopathic lvot vt with rbbb morphology generally responds well to verapamil . in stable patients with sustained vt acute therapy can be initiated with either intravenous procainamide , which is safe , well - tolerated and is not associated with teratogenicity . in addition to cardiac diseases , several systemic non - cardiac disorders , including severe electrolyte derangements , thyroid function abnormalities , pulmonary embolism , anemia , and drug overdose may present with ventricular arrhythmias .", "based on the ecgs ( qrs morphology of a left bundle branch block pattern with an inferior axis , and clinical findings ) both patients were diagnosed with idiopathic vt originating from the rvot . the lower dose for the second patient was chosen because of suspected asthma exacerbation ; however the dose was slowly increased to 50 mg po every 12 hours . in our cases , further investigations did not reveal a secondary cause of the patients arrhythmias . both patients tolerated treatment well and had no further documented episodes of vt on long - term cardiac monitoring .", "pregnant patients may present with ventricular tachycardia during any trimester careful and timely clinical , electrocardiographic , as well as echocardiographic assessment help identify those individuals with structural cardiac abnormalities such as congenital heart disease or peripartum cardiomyopathy , as well as those with long qt syndrome who will need specific management beyond therapy for the arrhythmia . in those stable patients with structurally normal hearts , identification of the location of origin of tachycardia will help in choice of appropriate medical therapy ." ]
ventricular tachycardia although not common , can occasionally complicate pregnancy . its presence may indicate an underlying cardiac structural abnormality , or undiagnosed congenital arrhythmic disease . however , some pregnant patients with ventricular tachycardia have structurally normal hearts . two cases of ventricular tachycardia in pregnant patients with structurally normal hearts are presented and an approach to diagnosis and management of such patients are discussed .
[ "the aim of this study was to investigate system - wide changes in protein expression during growth on dibenzofuran , a nontoxic surrogate for dibenzo - p - dioxin , as compared to nonselective growth media . thus , any changes measured in response to cells grown on dibenzofuran should represent cell - wide effects related specifically to the growth substrate and not to unanticipated extraneous effects . acetate was selected as the nonselective alternate substrate , as growth on this compound was observed to influence expression of select proteins , including the dioxin dioxygenase . the present study builds on previous work and utilized difference gel eletrophoresis ( dige ) coupled with mass spectrometry ( ms ) to exploit recently gathered rw1 genome data . when used together , these tools yield information on the response of cells of s. wittichii rw1 to dioxin exposure and the bacterium 's degradative activity toward this recalcitrant compound . therefore , global analyses of protein expression profiles may be a more informative tool for understanding the physiological mechanisms of biodegradation .", "samples were randomized to reduce the effect of dye bias and in - gel variations . the reducing agent dtt ( dithiothreitol ; 1.3 mg per tube ) and ipg ( immobilized ph gradient ) buffer ( 0.5% ) were added , and the samples incubated and mixed in the dark at room temperature for approximately 1 h. samples were then applied to 24 cm ph 47 ipg strips ( ge healthcare ) and focused for 60 kvh using the following protocol : 12 h rehydration at 30 v ; 1 h step and hold at 500 v ; 7 hour gradient to 1,000 v ; step and hold at 1,000 v for 1 hour ; gradient to 8,000 v for 3 h ; step and hold at 8,000 v until 60 kvh . database and literature searches were used to further characterize and classify the proteins identified by maldi - tof ms . where ambiguous names were encountered , blastp searches were used to identify homologous proteins from orthologous species . peak masses were searched using the mascot online search engine ( http://www.matrixscience.com/ ) with the following settings : database , ncbi entire database ( 5.6 million entries ) ; no missed cleavages ; monoisotopic peaks ; no fixed modifications ; variable modification of methionine oxidation ; error tolerance of 150 ppm . twenty - five g of crude cell lysates of rw1 biological replicates grown on dibenzofuran ( n = 3 ) and acetate ( n = 3 ) were labeled using cy dyes ( ge healthcare ) as described elsewhere . external calibration was conducted using a standard peptide mixture ( bradykinin , insulin b chain , p14r , and acth ) , and internal calibration was carried out using trypsin autolysis peaks .", "a mascot search of the entire ncbi database using mass spectral data generated by peptide mass fingerprinting identified 23 of the 44 proteins ( 52% ) . the unchanged proteins represented basic cell functions , although biosynthesis , catabolism , and transport proteins dominated the identities . all protein identifications corresponded to the genome of s. wittichii strain rw1 . among the 16 proteins upregulated during growth on dibenzofuran , 7 were successfully identified ( table 1 ) . among the 6 proteins downregulated during growth on dibenzofuran , these proteins , along with 22 proteins selected due to their high abundance in both growth conditions , were further analyzed and identified using mass spectrometry ( figure 3 ) . crude cell lysates from s. wittichii rw1 grown on dibenzofuran showed that , of all proteins observed , 22 proteins were modulated in response to changes in culture conditions .", "dige and 2d electrophoresis are an accepted strategy for mining microbial proteomes for biomarkers related to a number of processes [ 2830 ] . this study highlights a number of proteins that were changed in response to dibenzofuran exposure , opens the door to a greater understanding of how s. wittichii rw1 performs and regulates the degradation of dioxins , and suggests ways to enhance the biodegradation of dioxins . furthermore , the field of bioremediation can benefit from methods suitable for monitoring microbial biomarkers in field samples to inform on progress in site bioremediation . proteomic technology has emerged in microbiology more rapidly than in other fields for several reasons ." ]
sphingomonas wittichii rw1 is a bacterium of interest due to its ability to degrade polychlorinated dioxins , which represent priority pollutants in the usa and worldwide . although its genome has been fully sequenced , many questions exist regarding changes in protein expression of s. wittichii rw1 in response to dioxin metabolism . we used difference gel electrophoresis ( dige ) and matrix - assisted laser desorption / ionization mass spectrometry ( maldi - ms ) to identify proteomic changes induced by growth on dibenzofuran , a surrogate for dioxin , as compared to acetate . approximately 10% of the entire putative proteome of rw1 could be observed . several components of the dioxin and dibenzofuran degradation pathway were shown to be upregulated , thereby highlighting the utility of using proteomic analyses for studying bioremediation agents . this is the first global protein analysis of a microorganism capable of utilizing the carbon backbone of both polychlorinated dioxins and dibenzofurans as the sole source for carbon and energy .
[ "we compare , for the first time , a novel ba formulation ( containing bosexil , inci : lecithin , bse ) with a placebo formulation in the treatment of psoriasis or eczema . a third arm of the trial received a formulation of vaccinium myrtillus seed oil , which was previously demonstrated as an efficient local treatment for psoriatic lesions.20 another structural variety is given by the presence of a carbonyl group and an acetyl group in 11-keto bas ( kba ) and 3-o - acetyl - bas ( akba ) , respectively.10 animal studies and pilot clinical trials support the efficacy of bses for the treatment of a variety of inflammatory diseases such as inflammatory bowel disease , rheumatoid arthritis , osteoarthritis , and asthma.1114 in 2002 , the european medicines agency classified bse as an orphan drug for the treatment of peritumoral brain edema.15 the main anti - inflammatory properties of bas are attributed to suppression of leukotriene formation via inhibition of 5-lipoxygenase ( 5-lo ) by kba and akba.15 the mechanistic model has to be fully elucidated , but there is some evidence of an indirect action of bas leading to an irreversible inhibition of 5-lo by a ca2 + -mediated pathway.16 bas also inhibit the human leukocyte elastase , released in inflammation- and hypersensitivity - based human disorders , thus further supporting ba s antiphlogistic properties.17 in activated human monocytes , akba conveys inhibition of nuclear factor ( nf)-kb and subsequent downregulation of tnf- expression , via its direct inhibition of i kappa b kinase ( ikk).18 noteworthy is that when the ikk inhibition by bas has been investigated in the cd18 hypomorphic ( cd18[hypo ] ) mouse model of psoriasis , the suppressive effects on nf - kb signaling have been confirmed , thus suggesting that targeting nf - kb with bas may be an effective strategy for the treatment of psoriasis.19 since both psoriasis and erythematous dermatitis present a prevalent inflammatory component and bas have a documented inhibitory activity in some pathways with a major role in inflammation , especially in nf - kb pathway , we developed a formulation containing bas with potential efficacy in patients with psoriasis and erythematous dermatitis . in this double - blind study , other therapies including phototherapy , antimicrobials , antihistamines , and systemic immunosuppressives are also therapeutic options.1 psoriasis is an autoimmune , chronic , noncontagious , recurrent , inflammatory skin disorder . in western populations ,", "we validated this statistical procedure in a previous study on the efficacy of v. myrtillus seed oil.20 as an internal control , we compared the effects of bosexil and v. myrtillus with the same placebo . the psoriasis area severity index ( pasi ) and the eczema area and severity index ( easi ) patients were randomly assigned , in a 1:1:1 ratio and according to a computer - generated numerical table , to one of the following groups : bosexil , v. myrtillus seed oil , or placebo . thus , the change of condition generated the following categories of patients : in remission : when individuals with scores > 0 at t0 have score = 0 at t30 ; improved : when individuals have lower scores at t30 than at t0 ; unchanged : when individuals have the same scores at t0 and t30 ; worsened : when individuals have higher scores at t30 than at t0 . efficacy was statistically assessed through a procedure based on the individual s permanence or migration state ( primary end point ) depending on the entity of the score assigned to a symptom at t30 in comparison with the corresponding baseline score ( t0 ) . clinical assessments were carried out at baseline ( t0 ) and at the end of the trial ( t30 ) , and included the evaluation of scales and erythema in the case of psoriasis and the evaluation of itch and erythema in the case of eczema . this is a randomized , placebo - controlled , double - blind study performed at the department of dermatology at the university of varese ( italy ) in collaboration with velleja research and the local health agency 1 ( asl1 ) in the piacenza ( italy ) area .", "the comparison between groups was performed using pearson s chi - square test ; responses were evaluated with a markov - like procedure .", "each group consisted of ten patients affected from psoriasis and ten patients with erythematous dermatitis ( except the bosexil group , in which patients with dermatitis numbered nine ) . at t0 , signs of scales and erythema improved both with bosexil and with the v. myrtillus seed oil treatment in comparison with placebo . all groups were similar in terms of severity of the disease . however , three patients in the placebo group , one in the v. myrtillus group , and two in the bosexil group suspended the treatment before t30 and were included with a score of 3 in the statistical analysis . no significant difference in terms of age or sex figure 2 shows pictures of some psoriasis patients one treated with bosexil , one treated with v. myrtillus seed oil , and the other assigned to placebo . p=0.0281 ) without any case of worsening . treatment with v. myrtillus seed oil formulation improved erythema in 10% of cases , but 30% of patients were in remission at the end of therapy , therefore indicating that v. myrtillus seed oil treatment had positive effects on psoriatic erythema in 40% ( p=0.253 ) of cases . in terms of scales , v. myrtillus seed oil improved the symptomatology in 80% of patients , and 20% was unchanged ( p=0.0003 ) . in patients with erythematous eczema ( table 6 ) , the bosexil - containing formulation improved both itch ( 60% of cases , p=0.0115 ) and erythema ( 60% of cases , p=0.0115 ) , without any case of worsening . v. myrtillus seed oil treatment improved itch and erythema in 66.7% ( p=0.0020 ) and 77.8% ( p=0.0068 ) of patients , respectively . the results from the change of condition ( primary end point ) analysis between placebo ( group a ) and two formulations ( bosexil and v. myrtillus seed oil ) are summarized in tables 5 and 6 . in patients with psoriasis ( table 5 ) ,", "treatment with v. myrtillus seed oil formulation improved erythema in 10% of cases , but 30% of patients were in remission at the end of therapy , therefore indicating that v. myrtillus seed oil treatment had positive effects on psoriatic erythema in 40% ( p=0.253 ) of cases . in terms of scales , v. myrtillus seed oil improved the symptomatology in 80% of patients , and 20% was unchanged ( p=0.0003 ) . in patients with erythematous eczema ( table 6 ) , signs of scales and erythema improved both with bosexil and with the v. myrtillus seed oil treatment in comparison with placebo . the results from the change of condition ( primary end point ) analysis between placebo ( group a ) and two formulations ( bosexil and v. myrtillus seed oil ) are summarized in tables 5 and 6 . in patients with psoriasis ( table 5 ) , the bosexil - containing formulation improved both itch ( 60% of cases , p=0.0115 ) and erythema ( 60% of cases , p=0.0115 ) , without any case of worsening . v. myrtillus seed oil treatment improved itch and erythema in 66.7% ( p=0.0020 ) and in particular , patients who received placebo had unchanged scales and erythema , and in 10% of cases worsened . treatment with bosexil formulation improved scales ( 70% of cases , p=0.0001 ) and erythema ( 60% of cases ,", "in patients with psoriasis ( table 5 ) , signs of scales and erythema improved both with bosexil and with the v. myrtillus seed oil treatment in comparison with placebo . in particular , patients who received placebo had unchanged scales and erythema , and in 10% of cases worsened . p=0.0281 ) without any case of worsening . treatment with v. myrtillus seed oil formulation improved erythema in 10% of cases , but 30% of patients were in remission at the end of therapy , therefore indicating that v. myrtillus seed oil treatment had positive effects on psoriatic erythema in 40% ( p=0.253 ) of cases . in terms of scales , v. myrtillus seed oil improved the symptomatology in 80% of patients , and 20% was unchanged ( p=0.0003 ) . treatment with bosexil formulation improved scales ( 70% of cases , p=0.0001 ) and erythema ( 60% of cases ,", "in patients with erythematous eczema ( table 6 ) , the bosexil - containing formulation improved both itch ( 60% of cases , p=0.0115 ) and erythema ( 60% of cases , p=0.0115 ) , without any case of worsening . v. myrtillus seed oil treatment improved itch and erythema in 66.7% ( p=0.0020 ) and 77.8% ( p=0.0068 ) of patients , respectively .", "the pasi and easi scores observed in the three groups are reported in tables 7 and 8 , respectively . figure 2 shows pictures of some psoriasis patients one treated with bosexil , one treated with v. myrtillus seed oil , and the other assigned to placebo .", "this study aimed to compare , for the first time to our knowledge , the efficacy of topical preparation of bosexil and v. myrtillus seed oil vs a placebo in individuals with a diagnosis of psoriasis or erythematous dermatitis . bas in bosexil formulation were more active in the treatment of psoriatic scales than erythema , and were similarly efficient to treat itch and erythema in patients affected by eczema . consistently with previous results,20 this study confirmed the efficacy of v. myrtillus seed oil preparation in the treatment of major symptoms in both psoriasis and eczema , such as erythema and scales and erythema and itch , respectively .", "in conclusion , bas contained in bosexil and formulated according to the phytosome delivery system21 may be eligible components for the formulation of preparation with anti - inflammatory properties for the treatment of psoriatic and eczematous symptoms . we speculate that this formulation could also be applied to other inflammatory skin disorders , including contact , atopic , seborrheic , nummular , chronic palmoplantar , and generalized exfoliative or chronic lichen simplex dermatitis ." ]
backgroundboswellic acids ( bas ) show anti - inflammatory properties in a variety of inflammatory diseases , including rheumatoid arthritis , osteoarthritis , and asthma . a topical administration route is currently used to deliver active compounds in psoriatic and eczematous patients . in this double - blind study we compare a novel ba formulation ( containing bosexil , inci [ international nomenclature of cosmetic ingredients ] : lecithin , boswellia serrata resin extract ) with a placebo formulation . a third arm of the trial received a formulation of vaccinium myrtillus seed oil , previously demonstrated as an effective local treatment for psoriatic lesions.methodspatients with psoriasis or erythematous eczema were randomly assigned , in a 1:1:1 ratio , to bosexil , v. myrtillus seed oil , or placebo . in order to evaluate the effects of treatment , the changes of scales and erythema from diagnosis to the end of treatment were scored in psoriatic patients , while changes in itch and erythema were analyzed for erythematous eczema patients . psoriasis area severity index and eczema area and severity index scores were also calculated.resultsin patients with psoriasis , scales and erythema improved both with bosexil and the v. myrtillus seed oil treatment in comparison with placebo . in particular , the treatment with bosexil formulation improved scales ( 70% of cases ) and erythema ( 50% of cases ) without any case of worsening . in patients with eczema , the administration of placebo did not result in any improvement in 90% of cases , and in the remaining 10% worsened both itch and erythema . bosexil formulation improved both itch ( 60% of cases ) and erythema ( 60% of cases ) without any case of worsening . v. myrtillus seed oil improved itch and erythema in 66.7% and 77.8% of patients , respectively.conclusiona topical formulation of bosexil may be promising for the treatment of psoriasis and erythematous eczema . long - term studies are recommended to evaluate the adherence to this topical treatment and its clinical benefits in real life .
[ "the fragment was confirmed by sequencing and ligated to the ecori and bamhi \n sites of the peyfp - c1 vector to give the in - frame fusion gene . the binding to each protein was visualized using a select western blotting detection system \n ( ge healthcare bio - sci . local dna damage induction using laser and cell imaging : local dna damage \n induction using laser and cell imaging was conducted as described previously [ 9 , 11,12,13 ] . immunoblotting : the extraction of total lysates and western blot analysis \n were conducted based on the previous methods [ 11 , \n 13 ] . a cattle xlf gene \n ( nm_001075393.1 ) with an artificial ecori site at the 5 end and bamhi site at the 3 end \n was synthesized . the cells were cultured for 2 days and then monitored under an fv300 confocal \n laser scanning microscope ( olympus , tokyo , japan ) as previously described [ 9 , 11 , 12 ] .", "expression and localization of cattle xlf in cattle cells : we examined the \n expression and subcellular localization of xlf in cattle cells . to clarify the \n localization of xlf in living cattle cells during the interphase , we examined the expression \n and localization of eyfp - cattle xlf in mdbk cells . the c - terminal region ( ctr ) of cattle xlf is essential for the nuclear localization \n and recruitment of xlf to dsbs in cattle cells : to determine the region essential \n for nuclear localization of cattle xlf , we investigated the localization of cattle xlf and \n its mutant . ( b , c ) subcellular localization of xlf in cattle ( mdbk ) cells \n during the cell cycle . ( b , c ) subcellular localization of xlf in cattle ( mdbk ) cells \n during the cell cycle . these results demonstrate that the core nhej factors , xlf \n and ku70 , are expressed in cattle cells . we \n observed that a n - terminal deletion mutant eyfp - cattle xlf ( 162299 ) as well as the wild \n type eyfp - cattle xlf , accumulated at the dsbs sites in the living mdbk cells ( fig . 3c and \n data not shown ) . on the other hand , the mutant protein eyfp - cattle xlf ( 162287 ) failed to \n accumulate at the dsbs sites , which was detected by the dsb marker h2ax ( fig . 4c and 4d ) , indicating that deletion of the \n c - terminal end 12 amino acids abolished the recruitment of cattle xlf to dsbs . these results indicate that 12 c - terminal amino \n acids ( amino acids 288299 ) of cattle xlf are vital for the nuclear localization of xlf in \n cattle cells ( fig . the images shown \n are a representative example for interphase cells or mitotic phase cells ( c ) . to elucidate the localization of xlf in cattle cells", "these findings suggest that the mechanisms regulating of the \n localization and recruitment to dsbs play a key role in the function of cattle xlf . we found that xlf as well as other core nhej protein ku70 \n is expressed in cattle cells , and the localization of cattle xlf changes dynamically during \n the cell cycle . , we examined the expression and subcellular localization of cattle xlf and its \n mutants in cattle cell line mdbk . moreover , our data showed that the ctr of cattle xlf \n is vital for the nuclear localization of xlf and for the accumulation of xlf at dsbs \n in vivo . , \n we conclude that the xlf ctr is important for the accumulation of xlf at dsbs in both human \n and cattle cells , although the role of the c - terminal region of xlf remains controversial in \n human cells ." ]
clinically , many chemotherapeutics and ionizing radiation ( ir ) have been applied for the treatment of various types of human and animal malignancies . these treatments kill tumor cells by causing dna double - strand breaks ( dsbs ) . core factors of classical nonhomologous dna - end joining ( c - nhej ) play a vital role in dsb repair . thus , it is indispensable to clarify the mechanisms of c - nhej in order to develop next - generation chemotherapeutics for cancer . the xrcc4-like factor ( xlf ; also called cernunnos or nhej1 ) is the lastly identified core nhej factor . the localization of core nhej factors might play a critical role in regulating nhej activity . the localization and function of xlf have not been elucidated in animal species other than mice and humans . domestic cattle ( bos taurus ) are the most common and vital domestic animals in many countries . here , we show that the localization of cattle xlf changes dynamically during the cell cycle . furthermore , eyfp - cattle xlf accumulates quickly at microirradiated sites and colocalizes with the dsb marker h2ax . moreover , nuclear localization and accumulation of cattle xlf at dsb sites are dependent on 12 amino acids ( 288299 ) of the c - terminal region of xlf ( xlf ctr ) . furthermore , basic amino acids on the xlf ctr are highly conserved among domestic animals including cattle , goat and horses , suggesting that the ctr is essential for the function of xlf in domestic animals . these findings might be useful to develop the molecular - targeting therapeutic drug taking xlf as a target molecule for human and domestic animals .
[ "our results showed that the uptake of folic - acid modified nanoparticles by 5rp7 cancer cells was also much higher than that of 3t3 cells . this modification can be used for successful targeting of cancer cells expressing the folate receptor . folic acid modification of magnetic nanoparticles could be used to facilitate uptake to specific cancer cells for cancer therapy and diagnosis .", "nanostructures can play a major role in medicine , especially in cancer diagnosis and therapy.3 magnetic nanoparticles have been investigated for various biomedical applications , nanoparticles , and prospected in diagnostic research for magnetic resonance eg , fe3o4 imaging and application of nanotechnologies in medicine.4 magnetic nanoparticles could enhance therapeutic effects and reduce side effects of drugs when used in combination with conventional cancer treatment.5 the combination of fe3o4 magnetic nanoparticles with different chemotherapeutics may provide new strategies in the treatment of specific cancer cells.6 moreover , fe3o4 nanoparticles are the only magnetic nanomaterials approved for clinical use by the us food and drug administration , and the preparation method is relatively simple.7 we aimed to determine whether the anticancer effects of methacrylamido - folic acid ( ma - fol ) would have improved anticancer activity if incorporated into magnetic nanoparticles . one strategy to realize efficient and specific cellular uptake of nanoparticles is to modify the nanoparticle surface with a ligand that is efficiently taken up by target cells via receptor - mediated endocytosis.18 the objective of this research was to assess the potential effects of fe3o4 magnetic nanoparticles modified with ma - fol on 5rp7 cancer cells and nih/3t3 cells . we demonstrated that magnetic fe3o4 nanoparticles coupled with folic acid can inhibit tumor proliferation and induce apoptosis of cancer cells in a dose- and time - dependent manner .", "it binds to negatively charged phospholipid surfaces with a higher specificity for phosphatidylserine , a membrane phospholipid , than for most other phospholipids.21 in apoptotic cells , phosphatidylserine is translocated from the inner leaflet of the plasma membrane to the outer leaflet , thereby exposing phosphatidylserine to the exter nal environment.22 a facsaria ( bd cor poration , bedford , ma ) flow cytometer was used for analysis of the cells . a recent report nanoparticles by cells suggested that the uptake of fe3o4 could be quantitatively measured using flow cytometric light scatter.6 annexin v binding was performed using an annexinv - fitc kit ( bd corporation ) as described by the manufacturer . uptake of nanoparticles modified with folic acid by nih/3t3 and 5rp7 cancer cells , as well as nanoparticle size and morphology , were determined using a tem ( fei tecnai biotwin ) . annexin v - fluorescein isothiocyanate ( fitc ) is a sensitive probe for identifying apoptotic cells . cell viability was determined through staining with trypan blue , and cells were counted using a hemocytometer . to study the cellular uptake of the nanoparticles by flow cytometry and tem , ma - fol - modified magnetic nanoparticles were added to the cell culture media at concentrations of 2.5 g / ml , 4.5 g / ml , and 9 g / ml . 5rp7 ( h - ras - transformed rat embryonic fibroblasts ) and nih/3t3 ( a control cell line of normal mouse embryonic fibroblasts ) were used in these experiments .", "these silylated superparamagnetic iron oxide nanoparticles were mixed with a 5 mg / ml molality of 1 ml ma - fol in 1 ml dimethyl sulfoxide ( sigma - aldrich chemical co ) . superparamagnetic iron oxides ( size 2050 nm ) , were obtained from sigma - aldrich chemical co ( st . louis , mo ) . ph was set to 910 by addition of 1 m naoh solution to obtain anionic folate in solution . the surfaces of 0.1 g iron nanoparticles were modified in 2.5 ml toluene , adding 0.5 ml trimethoxysilyl propyl methacrylate . a solution of methacryloyl benzotriazole19,20 in dioxane ( 15 ml ) was added to the folate solution .", "cell viability was determined through staining with trypan blue , and cells were counted using a hemocytometer . to study the cellular uptake of the nanoparticles by flow cytometry and tem , ma - fol - modified magnetic nanoparticles were added to the cell culture media at concentrations of 2.5 g / ml , 4.5 g / ml , and 9 g / ml . 5rp7 ( h - ras - transformed rat embryonic fibroblasts ) and nih/3t3 ( a control cell line of normal mouse embryonic fibroblasts ) were used in these experiments . the cells were placed in 5 ml of medium without magnetic nanoparticles at the same cell density . the cells were cultured and then reseeded with the nano - particle - dispersed culture media . the cells were washed twice by centrifugation and resuspended in the complete media for reseeding and g rowing in new culture flasks .", ". a recent report nanoparticles by cells suggested that the uptake of fe3o4 could be quantitatively measured using flow cytometric light scatter.6 annexin v binding was performed using an annexinv - fitc kit ( bd corporation ) as described by the manufacturer . it binds to negatively charged phospholipid surfaces with a higher specificity for phosphatidylserine , a membrane phospholipid , than for most other phospholipids.21 in apoptotic cells , phosphatidylserine is translocated from the inner leaflet of the plasma membrane to the outer leaflet , thereby exposing phosphatidylserine to the exter nal environment.22 a facsaria ( bd cor poration , bedford , ma ) flow cytometer was used for analysis of the cells annexin v - fluorescein isothiocyanate ( fitc ) is a sensitive probe for identifying apoptotic cells . annexin v - fitc 5 l and propidium iodide 5 l were added , and the cells were then incubated for 15 minutes at room temperature in the dark , after which 400 l of 1 binding buffer was added to each tube and analyzed in the facsaria .", "uptake of nanoparticles modified with folic acid by nih/3t3 and 5rp7 cancer cells , as well as nanoparticle size and morphology , were determined using a tem ( fei tecnai biotwin ) . cells were deposited on formvar - coated 200300 mesh copper grids and dried , fixed with 2.5% glutaraldehyde in 0.1 m phosphate buffer ( ph 7.4 ) , and left in phosphate - buffered saline overnight at 4c . after being embedded in agar and after fixation in 2% osmium tetroxide , they were thin - sectioned using a diamond knife to a maximum thickness of 100 nm . the cells were dehydrated in graded ethanol , ie , 70 , 90 , 96 , and 100% .", "the interaction between folic acid and folate receptors expressed on the surface of cancer cells might have contributed to the improvement of nanoparticle uptake , based on receptor - mediated endocytosis.37 the schemes for the modification of nanoparticles display tem images ( figure 3 ) of ma - fol - modified with fe3o4 nanoparticles for this purpose , firstly , magnetic nanoparticles were imaged . ma - fol - modified magnetic nanoparticles represent a potential novel delivery system for compounds with anticancer activity because the folate receptor is frequently overexpressed in cancer cells . a logical method to promote internalization of nanoparticles is to modify their surface with a ligand such as folic acid which can be efficiently taken up by cells through receptor - mediated endocytosis.23 folic acid binds to the folate receptors at cell surfaces with very high affinity and is internalized by receptor - mediated endocytosis.24,26 more importantly , folic acid is stable , poorly immunogenic , and has the ability to target cancer cells preferentially because the folate receptor is frequently overexpressed on the surface of cancer cells . ma - fol was used to target preferentially cancer cells with folate receptors expressed on their surfaces , and to facilitate the nanoparticles to transit across the cell membrane . the results of this study confirm that cancer cells have more folate receptors , and that a 4.5 g / ml concentration of folic acid - modified magnetic nanoparticles causes apoptosis in 5rp7 cells . this suggests that the modification of magnetic nanoparticles with ma - fol could be used to resist nonspecific uptake and thus avoid their recognition by macrophage cells , and simultaneously facilitate nanoparticle uptake to specific cancer cells for cancer therapy . in flow cytometry results , the population of annexin v - positive live cells in the cancer cell line increased in a time - dependent manner , and most ( 12.9% ) of the cells became annexin v - positive at 48 hours at a concentration of 4.5 g / ml .", "furthermore , it needs to be investigated whether nanoparticles could cause long - term changes in systemic activity . this modification containing folic acid can be used for successful targeting of tumor cells expressing the folate receptor . this study has important implications in cancer cell imaging , tumor ablation , and drug delivery because of its targeting efficacy . future studies will focus on determining the stability and targeting efficacy of this modification in vivo . however , the effect and usage of such combinations need to be investigated further in in vivo experiments ." ]
background : magnetic nanoparticles show great promise for use as tools in a wide variety of biomedical applications . the purpose of this study was to investigate the potential effects of methacrylamido - folic acid ( ma - fol)-modified magnetic nanoparticles on 5rp7 ( h - ras - transformed rat embryonic fibroblasts ) and nih/3t3 ( normal mouse embryonic fibroblasts).methods : the cytotoxicity and viability of 5rp7 and nih/3t3 cells were detected . the percentage of cells undergoing apoptosis was analyzed by flow cytometry using annexin v - fluorescein isothiocyanate staining . nanoparticle internalization into 5rp7 and nih/3t3 cells was visualized by transmission electron microscopy.conclusion:in this study , folic acid coupled to the surface of iron oxide for selective binding to cancer cells and immobilized the surfaces of magnetic nanoparticles . this complex improves cell internalization and targeting of cancer cells . we detected increased apoptosis using flow cytometry and transmission electron microscopy.results:folic acid modification of magnetic nanoparticles could be used to facilitate uptake to specific cancer cells for cancer therapy and diagnosis . our results showed that the uptake of folic - acid modified nanoparticles by 5rp7 cancer cells was also much higher than that of 3t3 cells . this modification can be used for successful targeting of cancer cells expressing the folate receptor .
[ "on the basis of the collected data , participants were dichotomized into those with or without lbp , while indicating the sports discipline in which they were injured or that they were injured after cumulative fatigue due to the large number of hours spent in practicing sports and physical activities . in 1 week , all students practice for a total of 16.5 h , spending 1.5 h in each of the following sports : soccer , handball , basketball , volleyball , judo , weightlifting , swimming , athletics , and gymnastics . this is a retrospective cross - sectional survey involving students at the higher institute of sport and physical education in the city of sfax . data on age , weight , height , and smoking habits are collected routinely when students join the institute , and then the sport in which the student is injured in the low back is registered in the institute health service files . furthermore , every registered injury causing lbp was recorded with its severity , but the most important detail for us was the sport in which the student was injured . the question used systematically by the doctor of the institute health service to identify and estimate lbp cases was about the present injury and if and when they had lbp in the past . only students injured in the first or second year were taken into account , because the following years involve only athletics and gymnastics .", "data on age , weight , height , and smoking habits are collected routinely when students join the institute , and then the sport in which the student is injured in the low back is registered in the institute health service files . this is a retrospective cross - sectional survey involving students at the higher institute of sport and physical education in the city of sfax . on the basis of the collected data , participants were dichotomized into those with or without lbp , while indicating the sports discipline in which they were injured or that they were injured after cumulative fatigue due to the large number of hours spent in practicing sports and physical activities . in 1 week , all students practice for a total of 16.5 h , spending 1.5 h in each of the following sports : soccer , handball , basketball , volleyball , judo , weightlifting , swimming , athletics , and gymnastics . only students injured in the first or second year were taken into account , because the following years involve only athletics and gymnastics . furthermore , every registered injury causing lbp was recorded with its severity , but the most important detail for us was the sport in which the student was injured . the question used systematically by the doctor of the institute health service to identify and estimate lbp cases was about the present injury and if and when they had lbp in the past .", "chicago , il , usa ) . the chi - square test was used to test associations between lbp and other categorical variables ( sex , obesity , and smoking habit ) , and to compare the prevalence of lbp between males and female . statistical significance statistical analyses were done using the spss statistical package , version 11.5 ( spss , inc . ,", ". percent prevalence of lower back pain related to fatigue and type of sports in males and females . the increased prevalence of lbp is less in basketball and athletics and even lower in soccer , weightlifting , and swimming ( fig . however , if we analyze the prevalence of lbp in terms of sex in each sport , we find that the prevalence of lbp was significantly higher among males than females in handball ( p<0.05 ) and significantly lower in athletics ( p<0.05 ) table 2 shows that the prevalence of lbp was significantly higher ( p<0.001 ) among females ( 17.6% ) than among males ( 12.5% ) . prevalence of lower back pain ( lbp ) by gender , obesity and smoking lbp : low back pain ; standard body mass index ( bmi ) categories : underweight ( bmi of<18.5 ) , normal weight ( bmi of 18.5<25 ) , overweight ( bmi of 25<30 ) , and obese ( bmi of 30 ) ; smoking : cigarettes per day ; no smoking : not currently smoking . in the analysis of risk factors for lbp in sports training , we found that in both sexes combined , lbp was positively associated with fatigue ( caused by the long time spent in training ) , gymnastics , judo , handball , and volleyball .", "we believe that students should perform exercises to strengthen the muscles of the arms and back , and increase coordination of the upper extremities and the lumbar region with regular activities that have been proven to be effective for the prevention of lbp . our results show that a greater amount of physical activity increased the risk of lbp mainly in gymnastics , judo , handball , and volleyball . imaging is used to show the severity of the injury rather than the severity of the pain associated with it . the relatively low prevalence of lbp in our study in soccer and weightlifting may be due to the system of this sports and physical education institute which is focused mainly on knowing how to teach these sports ( gestural technique and pedagogy ) and not on researching performance . these findings are generally in accordance with the literature . in a study focused on identifying the types of physical activity associated with increased occurrence of lbp in schoolchildren , skoffer and foldspang ( 6 ) noted that lbp was increased by the number of hours jogging , playing handball , and doing gymnastics . swimming activates the muscles of the trunk , for example , the erector muscles of the spine , so swimming might be a means to prevent lbp . however , our results on soccer are at odds with those of bejia et al . ( 42 ) , who reported that soccer was positively associated with chronic lbp in tunisian schoolchildren and adolescents . similarly , our findings on weightlifting contrast with those of calhoon and fry ( 43 ) , who reported that lbp was one of the most frequent injuries in this sport .", "lbp was strongly associated with the amount of time reserved to practice the different sports planned in this sports and physical education institute . the sports identified as posing the greatest risk for lbp were gymnastics , judo , handball , and volleyball , followed by basketball and athletics .", "imed ajili ) and the administration of the sports and physical education institute of sfax ( tunisia ) for their assistance .", "" ]
introductionfor obvious reasons , athletes are at greater risk of sustaining a lumber ( lower ) spine injury due to physical activity . to our knowledge , no previous studies have examined the prevalence of low back pain ( lbp ) in a tunisian sports and physical education institute.aimto assess the prevalence of lbp in different sports among students studying in a sports and physical education institute in tunisia , to determine the causes of the injuries , and to propose solutions.methodsa total of 3,379 boys and 2,579 girls were studied . a retrospective cross - sectional survey was conducted on a group of students aged 18.524.5 years at the higher institute of sport and physical education of sfax to estimate the prevalence of lbp and its relation to the type of sports . data on age , weight , height , smoking , and the sport in which the student was injured in the low back were collected from the institute health service records from 2005 until 2013.resultslbp was reported by 879 of the 5,958 study participants ( 14.8% ) . the prevalence of lbp was significantly higher ( p<0.001 ) in females ( 17.6% ) than in males ( 12.5% ) . lbp prevalence did not differ by body mass index or smoking habit ( p>0.05 ) . the sports associated with the higher rates of lbp were gymnastics , judo , handball , and volleyball , followed by basketball and athletics.conclusionlbp is frequent among undergraduate students of a sports and physical education institute in tunisia . it is strongly associated with fatigue after the long periods of training in different sports . gymnastics , judo , handball , and volleyball were identified as high - risk sports for causing lbp .
[ "therefore , this study explored the meaning of health as perceived by iranian kurdish diabetic patients in order to develop an appropriate multidisciplinary outlook toward this ethnicity of patients . prior studies have shown lack of awareness about the concept of health among iranian kurdish diabetic patients . although the concept of health is gaining more importance and it has constantly been improved and changed by the passage of time ( 15 , 16 ) , few studies are reported to have focused on health and illness , particularly with regard to diabetic patients belonging to different ethnic groups ( 17 ) . therefore , the understanding of diabetic patients perceptions can help the development of precautionary programmes for diabetics ( 14 ) . diabetes is incurable , and has the third highest mortality rate on the planet ( 8) . the probability of the incidence and prevalence of this disease has increased recently ( 9 ) . in 2004 , it was estimated that by 2030 , this number will have grown to 366 million ( 10 ) and in 2010 , the number of people afflicted by diabetes was estimated to increase up to 439 million by 2030 ( 8) . furthermore , one of the most important aspects with regard to health perception , manifests when patients suffer from a chronic disease , through which their perception of health is affected ( 5 , 6 ) . consequently , investigating the perception of health - related meaning among this ethnic group can increase the knowledge about the nature of health and its effects .", "considering the aim of this research , a qualitative approach with a conventional content analysis approach was used . a purposive sampling method was used to select the candidates for the study from among the diabetic patients who were admitted to the centre . the conventional content analysis was used for data analysis ; this method is generally adopted with a study design which aims to describe a particular phenomenon . researchers analysed all the data in order to gain a new insight and expand their knowledge about it . by analyzing the literature that they had collected on the participants , and reading the transcriptions of all the participants interviews word by word , the researchers tried to use a set of measures for increasing the rigor of the data and thereby increase the scientific precision of the results , including : the allocation of a proper place and sufficient time for data collection , due communication with participants , using the supplementary views of colleagues , reviewing the participants hand writing and examining the data by all engaged researchers . one of the advantages of this approach is that the results of the participants responses in the study can be obtained without imposing preconceived categories or theoretical perspectives ( 20 , 24 ) . content analysis is a unique qualitative method , which encompasses a host of analytic approaches that offer flexibility to a researcher , and are of theoretical and substantive interest with regards to the case being studied ( 20 , 21 ) .", "content analysis is a unique qualitative method , which encompasses a host of analytic approaches that offer flexibility to a researcher , and are of theoretical and substantive interest with regards to the case being studied ( 20 , 21 ) . considering the aim of this research , a qualitative approach with a conventional content analysis approach was used .", "the inclusion criteria for the participants were : having kurdish ethnicity irrespective of gender , having diabetes type 2 , while at the same time having a lapse of at least five years since the diagnosis of diabetes , the absence of psychiatric disorders , and finally , having the ability to communicate . a purposive sampling method was used to select the candidates for the study from among the diabetic patients who were admitted to the centre . the research was conducted over a ten - month period during 2014 , in the diabetes care centre of tohid hospital at the kurdistan university of medical sciences in sanandaj , in the center of the kurdistan province in western - iran . the sample was restricted to 20 because no new data emerged after the twentieth interview . therefore , the researcher was completely saturated with data to achieve a new understanding and insight about the phenomenon . the sample size was determined only when the interviewing stage reached saturation ( 22 ) .", "the researchers attempted to translate the participants descriptions in a manner in which they closely corresponded to their meaning in kurdish , while making them grammatically correct for english readers . the interviews began with a general question about health and its perception , and proceeded to seek a deep understanding of participants perception . two of the author s colleagues checked the accuracy of the transcriptions by matching the corresponding transcripts with the tape - recorded version of the interviews . further , the patients were asked to describe all the factors that could affect their health . the kurdish transcripts were analysed and only the verbatim quotations intended for publication were translated into english . twenty interviews were conducted in kurdish language ; each interview was tape - recorded with the participants permission . examples of questions asked during the interview were as follows : when do you feel healthy ? an interview guideline was defined to direct the interviews toward the aims of the study .", "through these inquiries , the researchers tried to use a set of measures for increasing the rigor of the data and thereby increase the scientific precision of the results , including : the allocation of a proper place and sufficient time for data collection , due communication with participants , using the supplementary views of colleagues , reviewing the participants hand writing and examining the data by all engaged researchers .", "they were also assured of the data confidentiality ; this meant that their names and other significant details , that might reveal their identity , would not be published in the study report . they were assured that their care would not be affected if they chose not to participate in the study . the participants were assured that they could leave the study at any time even after they had signed the consent form . all the participants names were changed into codes during the transcription of the interviews , data was locked in separate locations and the coded information was used for data analysis and discussions . all participants were volunteers and written consent was obtained from each of them in which the voluntary nature of the participation was mentioned . this study was approved by the research committee of the kurdistan university of medical sciences , no.572.14 .", "researchers analysed all the data in order to gain a new insight and expand their knowledge about it . by analyzing the literature that they had collected on the participants , and reading the transcriptions of all the participants interviews word by word , in this study , the conventional content analysis was used for data analysis ; this method is generally adopted with a study design which aims to describe a particular phenomenon . this method is also described as inductive category development ( 23 ) , where researchers do not use predetermined data groups . one of the advantages of this approach is that the results of the participants responses in the study can be obtained without imposing preconceived categories or theoretical perspectives ( 20 , 24 ) . the researchers defined the categories on the basis of the type of data and avoided using predetermined categories . this type of design is usually appropriate when the existing theory or research literature on a phenomenon is limited ( 20 ) .", "the syndrome of the healthy body and the happy heart is an accepted concept among the laymen and is considered as an ideal and a prayer for every person . meanwhile , the average number of years which had lapsed since diagnosis of diabetes was seven years with a range of 517 years . based on the thoughts and feelings of the participants , the following three main themes emerged : the syndrome of the healthy body and the happy heart life without compulsory limitations the syndrome of the healthy body and the happy heart is an important theme that emerged in our study . twenty diabetic patients participated in this study ; the participants included seven men with an age range from 53 to 80 years ( average age : 68 years ) and thirteen women with an age range from 32 to 55 ( average age : 40 years ) . this theme is a kurdish idiom concerning health . according to this theme ( bivy bi ) , health marks the presence of particular characteristics , which is an established symbol in the history of kurdish literature .", "the syndrome of the healthy body and the happy heart is an accepted concept among the laymen and is considered as an ideal and a prayer for every person . this theme is a kurdish idiom concerning health . according to this theme ( bivy bi ) , health marks the presence of particular characteristics , which is an established symbol in the history of kurdish literature . the syndrome of the healthy body and the happy heart is an important theme that emerged in our study . it refers to the ancient kurdish description about health as being associated with not only physical well - being but also vivacity , satisfaction , and calmness of the mind . the participants always used local terminology to describe their ideas of health , and their descriptions and perception of health indicated that health is tantamount to worshipping god , for them . similarly , the participants wished good health to each other with the idea that health implies a healthy body and a contented heart .", "all the participants mentioned that life without any compulsory limitations is one of the important dimensions of health and that they wished they could eat all kinds of food and participate in any occasion and be like others . one of the women ( 43 years old ) said , when i eat rice , i need more water , and then i know that i am not healthy but fatigued , and i feel like travelling to the mountains and running away for a longer time , and then i suffer from sleeplessness and my body feels weak ( p 13 ) . sometimes , i want to eat some comestibles that our family bought between us , but i can not do that , and this is so hard for me when you can participate in a ceremony or accompany someone , do anything that you want , or eat anything that you like , you feel a sense of freedom from others and you can go anywhere without worrying about your medicines , this freedom is very fantastic for some participants , the limitations had led to the feeling that they were different from others", "in general , spirituality is subjective ; the individual and personal concept that each person defines is based on his or her understanding and on the evidence that spirituality improves mental and physical health . most of the participants primarily belonged to the category that perceived health as exalted spirituality , and believed in satisfying self and others and trusting and honoring god . a woman ( 52 years old ) said , some of the people whose heart is near to god have good health , because honoring god helps to heal them , and when the spirit is healthy , the body is healthy . and , a healthy spirit in a healthy body , which believes in prayer and spirituality , finds calmness and peace participants emphasis on achieving exalted spirituality in their lives was tantamount to health for them . ( p 18 ) , and , healthy patients who have the virtue to trust in god and are honest , do nt lose their spirituality , religion or prophet (p 11 ) another participant said , when i pray to god , i think about how fortunate i am to be born in this world , and then i am happy (p 6 ) .", "the themes that emerged in our study showed these instances briefly . in this study , participants talked about the effects of diabetes on physical and psychological health , which indicated that our results were similar to those of other studies ( 28 , 29 ) . as the results for this group of diabetic patients indicated , health is composed of the syndrome of the healthy body and the happy heart , life without compulsory limitations , and exalted spirituality . for all patients , health perception and points of view are the important factors that affect health behaviour and determine any related behaviour ( 25 , 26 ) . an individual may be ill and yet may feel healthy ; therefore , many people can compare their health status during suffering from illness with that in the past ( 22 , 27 ) . the results of our study primarily indicated that the factors that affect health perception include complaining about the illness , side effects and outcomes of the disease , and the extent of the complaints that make the patient feel sick . hence , considering the important effect of calmness of mind on diabetic patients health perception and points of view , we , as health care professionals , ought to be obliged to associate a disturbed mind with bad health . patients with chronic diseases encountered some social and emotional problems due to changes in their lifestyle ( 36 ) .", "nurses need to pay more attention to diabetic patients limitations and facilitate a programme to improve their health in conjunction with other health care teams . the professional health - care provider team ought to consider health perception among patients , and then they apply this knowledge for setting up suitable health improvement programs . although nursing and other health care professionals have the responsibility to help those patients achieve peace of mind , the patients families should also play an active role in the health care programme and treatment process . studying health perception among patients with chronic diseases is an important factor that facilitates the development of appropriate programmes , to improve health levels among such patients . in this regard ," ]
introductionhealth is an exclusive and subjective phenomenon , and one of the most important situations with regard to perception of health , arises when patients suffer from a chronic disease.this study was conducted within the qualitative research framework and aimed to explore the meanings of health as perceived by a group of iranian diabetic patients.methodsa descriptive qualitative analysis design was used . data were collected through semi - structured interviews with 20 participants among diabetic patients , who were admitted to the diabetes care centre of tohid hospital of the kurdistan university of medical sciences , sanandaj , iran during a ten - month period in 2014 . interviews were transcribed and analysed through conventional content analysis.resultsbased on the findings of the study , three major health - related themes emerged : 1 ) the syndrome of the healthy body and the happy heart ( physical well - being vivacity , satisfaction , and calmness of the mind ) , 2 ) life without compulsory limitations ( lack of dietary limitations , no activity limitations , lack of social limitations ) , and 3 ) exalted spirituality ( satisfying self and others , trusting god , remembering god).conclusionhealth care providers should consider the meaning of health in special groups , chiefly in patients with chronic diseases . it facilitates the development of appropriate programmes to improve desirable health levels among diabetic patients .
[ ", we try to clarify this topic from the perspective of avicenna and traditional persian medicine ( tpm ) . however , proper amount of daily water intake in a healthy individual is controversial . there is a prevalent thought that we all have to drink eight glasses of water daily", "furthermore , medline , embase , scopus , iranmedex , and science iranian database ( sid ) focusing on the keywords traditional medicine , water intake , fluid , and complementary and alternative medicine were reviewed to find relevant information . the most important traditional persian medical encyclopedia , al - qanun fil - tibb ( canon of medicine ) , was reviewed .", "avicenna believed that the demand for daily water is not the same in different individuals . he believed that water in extra amount quenches the hararat - e - ghariezi , which is the basal internal heat to convey normal homeostasis and metabolism in the body . the determinant variables mentioned in his book , the canon of medicine , comprises mizaj ( temperament ) , health status , age , sex , season , place , habits , occupation , etc .", "several factors determine the actual need of any person to drink water . consequently , recommending a specific amount of daily water intake for all is illogical . moreover , important recommendations of tpm sages on an appropriate amount of water intake should be considered to prevent associated disorders ." ]
background : fluid intake is an essential factor in having a normal homeostasis . however , proper amount of daily water intake in a healthy individual is controversial . there is a prevalent thought that we all have to drink eight glasses of water daily , however , it lacks enough supportive evidence at least for healthy individuals . here , we try to clarify this topic from the perspective of avicenna and traditional persian medicine ( tpm).methods : the most important traditional persian medical encyclopedia , al - qanun fil - tibb ( canon of medicine ) , was reviewed . furthermore , medline , embase , scopus , iranmedex , and science iranian database ( sid ) focusing on the keywords traditional medicine , water intake , fluid , and complementary and alternative medicine were reviewed to find relevant information.results:avicenna believed that the demand for daily water is not the same in different individuals . the determinant variables mentioned in his book , the canon of medicine , comprises mizaj ( temperament ) , health status , age , sex , season , place , habits , occupation , etc . he believed that water in extra amount quenches the hararat - e - ghariezi , which is the basal internal heat to convey normal homeostasis and metabolism in the body.conclusion:several factors determine the actual need of any person to drink water . consequently , recommending a specific amount of daily water intake for all is illogical . moreover , important recommendations of tpm sages on an appropriate amount of water intake should be considered to prevent associated disorders .
[ "it was visually noted that subcutaneous fat in the abdominal region was still present , despite severe losses in the peripheral limbs , protruding ribs , and lack of prominent chest and shoulder musculature . a 34year - old male presented for general examination on day 49 of a 50-day self - imposed fast , seeking approval to continue his fasting behavior . during this period , history following the onset of fasting behavior was unremarkable , but included severe abdominal cramps between days 7 and 21 of fasting , development and frequent occurrence of vasovagal syncope on transition from sitting to standing , and the near - cessation of fecal movement . 2 ) . during a six - minute walk test , this individual covered 342 m , which was below expected performance for a healthy male adult.2 a mild scoliosis was observed while walking ; however , it is unclear if this is related to fasting . personal history involved an oscillating mass between 85 and 134 kg over a 10-year period . at the start of fasting ,", "days 35 involved one solid meal per day , with 23 solid meals during days 57 , and the resumption of three solid food meals per day for 7 days following breaking of fast . in the following 23 days resumption of feeding initially involved liquids such as vege table soups , with the resumption of solid foods three days following breaking of fast . , diet was reported to be of caffeine and alcohol free , low carbohydrate ( a piece of bread every 13 days ) , and high servings of fruit and vegetables . self - estimation of diet by volume was 20% animal protein ( chicken and fish ) and 80% fruit or vegetables ; validated , quantifiable measures of intake and caloric content are not available . one month following initial presentation , the patient returned for follow - up examination during which body composition , resting metabolic rate , urine , and venous blood were recorded . blood biochemistry returned to within normal range , with the exception of direct bilirubin ( table 1 ) .", "this report does not indicate support for such behavioral choices , and the projections of metabolic energy provision by starting adiposity assume no other perturbations to homeostasis , such as impaired immune response , liver and renal function , or cardiovascular events . it is tempting to suggest that guidelines to physicians for advice to the fasting individual reflect body mass , and specifically mass of adiposity at start of fasting behavior . one prior report of long - term fasting in obese individuals for 3040 days demonstrated body mass losses between 10.6% and 20.5% , but does not report on function of individuals.4 it seems self - apparent and supported by this limited evidence , such that the starting mass is a key variable in survival of extreme fasting , and not the amount of loss . it is noteworthy , therefore , in this case study that moderate physical function appears maintained at day 49 , as assessed by general observation and results of the six - minute walk test . simple frank starling mechanics combined with a failure of autonomic regulation may thus explain elevated blood pressure ." ]
a 34-year - old obese male ( 96.8 kg ; bmi , 30.2 kg m1 ) volitionally undertook a 50-day fast with the stated goal of losing body mass . during this time , only tea , coffee , water , and a daily multivitamin were consumed . severe and linear loss of body mass is recorded during these 50 days ( final 75.4 kg ; bmi , 23.5 kg m1 ) . a surprising resilience to effects of fasting on activity levels and physical function is noted . plasma samples are suggestive of early impairment of liver function , and perturbations to cardiovascular dynamics are also noted . one month following resumption of feeding behavior , body weight was maintained ( 75.0 kg ; bmi , 23.4 kg m1 ) . evidence - based decision - making with the fasting or hunger striking patient is limited by a lack of evidence . this case report suggests that total body mass , not mass lost , may be a key observation in clinical decision - making during fasting and starvation .
[ "one of the important developments in the surgical approach is peeling of the internal limiting membrane ( ilm ) . tangential tractions on the vitreomacular interface are usually responsible for the development of idiopathic macular holes . the most difficult aspect of surgery is due to the tight attachment of the ilm to the retina and its extreme thinness and transparent nature . to increase the visibility of the ilm indocyanine green ( icg ) and trypan blue have been used by many researchers in peeling of the erm and ilm . there are different opinions on the amount and concentration of dye required , and exposure duration in the vitreous space . in many studies , because of intraretinal accumulation of icg and its toxic effects on retinal pigment epithelium , visual field defects after surgery and possible optical nerve atrophy have been considered.8,10,11 recently , brilliant blue ( bb ) has been used in preclinical studies as it has minimal toxic effect and provides effective membrane staining.9,12 in this study , the anatomical and visual outcomes of pars plana vitrectomy ( ppv ) and ilm peeling with bb in the treatment of idiopathic macular holes has been examined .", "fifty eyes of 48 patients who had 23 g ppv and ilm peeling as a treatment for macular holes between july 2007 and december 2009 were retrospectively evaluated in the authors clinic . cases in different macular hole stages were compared in terms of anatomical and functional results . anatomical and functional outcomes of macular hole patients who underwent 23 g ppv and ilm peeling with bb were evaluated . all patients underwent measurement of best - corrected visual acuity and intraocular pressure , anterior segment and fundus examinations before surgery . inclusion criteria were : diagnosis using noncontact - lens biomicroscopy and optical coherence tomography ( oct ) of stages 2 , 3 , and 4 idiopathic macular hole according to the gass classification . best - corrected visual acuity , intraocular pressure , and complications were recorded for each visit .", "all operations were performed under local anesthesia . following the introduction of a 23 g infusion cannula at the inferotemporal site , after liquid air exchange , air gas exchange was performed ( 16% c3f8 or 18% c2f6 ) . after 60 seconds , peeling of the ilm was performed using a 23 g diamond - dusted membrane scraper ( synergetics inc , fort collins , co ) and 23 g eckardt end - gripping forceps ( dorc , zuidland , the netherlands ) for an area of at least 3 disc diameters . brilliant blue 0.3 ml ( fluoron gmbh , ludwigsfeld , germany ) was injected to the posterior pole via a 23 g dualbore cannula . imaging systems used were the volk miniquad xl ( volk optical ltd , mentor , oh ) during vitrectomy and volk central retina ( volk optical ltd ) during ilm peeling . after core vitrectomy , triamcinolone acetonide ( kenacort - a ; bristol myers squibb , new york , ny ) was used to remove the posterior hyaloid .", "iatrogenic retinal tears developed in four patients during surgery and were successfully treated intraoperatively . in one patient , a nasal retinal tear developed near the optic nerve while removing the posterior hyaloid . one of the phakic cases had preoperative lens opacity and vitrectomy and phacoemulsification was performed together with intracapsular lens implantation . postoperative mean best - corrected visual acuity ( and comparison with preoperative values ) was obtained as : 0.48 0.26 at 3 months ( p < 0.05 ) , 0.52 0.27 at 6 months ( p < 0.05 ) , 0.42 0.30 at 9 months ( p < 0.05 ) , and 0.41 0.31 at 12 months ( p < 0.05 ) . when assessed together , the final visits ( at 12 months ) demonstrated that visual acuity had increased in 41 eyes ( 82% ) , whereas , in 6 eyes ( 12% ) , visual acuity remained unchanged . because of recurrent macular holes , three cases showed a decrease in visual acuity . the mean preoperative visual acuity of stage 2 macular hole patients was higher than that of stage 3 or 4 patients . patients , preoperative visual acuity compared with postoperative 3-month scores showed an increase , but this was not statistically significant ( p = 0.056 ) . during the postoperative period , visual acuity reduced between months 3 and 6 due to cataract development . in patients who underwent phacoemulsification after 6 months , increase in visual acuity between 6 and 12 months after surgery was statistically significant due to cataract surgery ( p < 0.05 ) . in stage 3", "the authors of this study have observed intraretinal accumulation in postoperative fundus fluorescein angiography of patients for whom icg was used . the authors of this present study think that biological adaptation to bb is better than to icg . the use of bb is easier than icg and tb because of its granular structure and easy dissolution in intraocular irrigation . early cataract surgery following macular hole surgery may increase the risk of re - opening of the hole,28 there are also studies that report no such risk.29,30 therefore , in patients developing cataract , phacoemulsification surgery was performed at least 6 months after macular hole surgery to prevent a recurrence . as the thin and semitransparent structure of the ilm complicates visualization during surgery , in patients with ilm peeling , there may be small asymptomatic paracentral scotomas , irregularity in nerve fiber layers , and retinal microhemorrhages due to iatrogenic retinal trauma.3136 chromovitrectomy has been developed as a method to improve ilm visibility , shorten the duration of surgery , and reduce iatrogenic retinal trauma.36 many dyes , such as indocyanine green ( icg ) , infracyanine green ( ifcg ) , trypan blue ( tb ) , bb , and triamcinolone acetonide ( ta ) , are used to dye the ilm . since the first report of kelly and wendel2 on the treatment of macular holes by pars plana vitrectomy and gas tamponade , anatomical and functional success rates have increased with developments in vitreoretinal surgery . cataract development is the most prevalent complication of macular hole surgery in phakic eyes . in this study group , cataract development", "ilm peeling in macular hole surgery provides beneficial effects on anatomical outcome , independent of disease stage . in terms of visual outcome" ]
purpose : the evaluation of anatomic and visual outcomes in macular hole cases treated with internal limiting membrane ( ilm ) peeling , brilliant blue ( bb ) , and 23-gauge pars plana vitrectomy ( ppv).materials and methods : fifty eyes of 48 patients who presented between july 2007 and december 2009 with the diagnosis of stage 2 , 3 , or 4 macular holes according to gass classification who had undergone ppv and ilm peeling were included in this study . pre- and postoperative macular examinations were assessed with spectral - domain optical coherence tomography . 23 g sutureless ppv and ilm peeling with bb was performed on all patients.results:the mean age of patients was 63.34 9.6 years . stage 2 macular hole was determined in 17 eyes ( 34% ) , stage 3 in 24 eyes ( 48% ) , and stage 4 in 9 eyes ( 18% ) . the mean follow - up time was 13.6 1.09 months . anatomic closure was detected in 46/50 eyes ( 92% ) , whereas , in four cases , macular hole persisted and a second operation was not required due to subretinal fluid drainage . at follow - up after 2 months , persistant macular hole was detected in one case and it was closed with reoperation . at 12 months , an increase in visual acuity in 41 eyes was observed , while it remained at the same level in six eyes . in three eyes visual acuity decreased . there was a postoperative statistically significant increase in visual acuity in stage 2 and 3 cases ( p < 0.05 ) , however , no increase in visual acuity in stage 4 cases was observed.conclusion:ppv and ilm peeling in stage 2 , 3 , and 4 macular hole cases provide successful anatomic outcomes , however , in delayed cases , due to photoreceptor loss , it has no effect on functional recovery . bb , used for clarity of ilm , may be beneficial due to its low retinal toxicity .
[ "a total of 339 white patients with type 2 diabetes who had survived an mi were studied . the study included 340 whites from italy with type 2 diabetes ( according to american diabetes association 2003 criteria ) and coronary artery disease ( cad ) , as indicated by previous myocardial infarction ( mi ) or > 50% stenosis of at least one major vessel at coronary angiography , or both . most of these patients ( n = 160 ) were further studied for incident major cardiovascular events in the prospective ghs ( see above ) . they are part of two ongoing investigations on the genetics of cad in type 2 diabetes ( 30,36,37 ) . of these , a time - to - event analysis was conducted by means of cox proportional hazards regression models using the breslow approach in the case of ties and reported as hazard ratios ( hrs ) along with their 95% ci . the time to event", "a total of 339 white patients with type 2 diabetes who had survived an mi were studied . the study included 340 whites from italy with type 2 diabetes ( according to american diabetes association 2003 criteria ) and coronary artery disease ( cad ) , as indicated by previous myocardial infarction ( mi ) or > 50% stenosis of at least one major vessel at coronary angiography , or both . they are part of two ongoing investigations on the genetics of cad in type 2 diabetes ( 30,36,37 ) . of these , of these , 43 ( 16.2% ) had diabetes , a proportion similar to that reported by a nationwide epidemiologic study of kidney disease in italy ( 35 ) .", "of these , 43 ( 16.2% ) had diabetes , a proportion similar to that reported by a nationwide epidemiologic study of kidney disease in italy ( 35 ) . the study included 340 whites from italy with type 2 diabetes ( according to american diabetes association 2003 criteria ) and coronary artery disease ( cad ) , as indicated by previous myocardial infarction ( mi ) or > 50% stenosis of at least one major vessel at coronary angiography , or both . this study comprises 283 whites with end - stage renal disease ( esrd ) , with 231 requiring hemodialysis and 52 receiving long - term ambulatory peritoneal dialysis ( 34 ) . information on the occurrence of nonfatal events was sought yearly from study participants and confirmed by a review of hospital records if cardiovascular events were reported . if patients did not report to a scheduled visit , information on the occurrence of cardiovascular events these individuals were cases of the cross - sectional case - control gargano heart study ( ghs ) ( 30 ) and were consecutively recruited at the scientific institute casa sollievo della sofferenza from 2001 to 2008 and monitored until the end of 2009 .", "a total of 339 white patients with type 2 diabetes who had survived an mi were studied . casa sollievo della sofferenza in san giovanni rotondo ( gargano , center east coast of italy ) , as cases of the cross - sectional case - control ghs ( 29 ) . most of these patients ( n = 160 ) were further studied for incident major cardiovascular events in the prospective ghs ( see above ) . another 170 were recruited in boston from the beth israel deaconess medical center ( bidmc ) and the joslin clinic ( which serves as the bidmc diabetes clinic ) as part of an ongoing investigation on the genetics of cad in type 2 diabetes that has been described previously ( 37 ) . they are part of two ongoing investigations on the genetics of cad in type 2 diabetes ( 30,36,37 ) . of these ,", "all subjects underwent a clinical examination and a standardized interview ( at the time of recruitment and at each subsequent time point , if applicable ) , which was identical in all three prospective samples . a fasting blood sample ( collected between 8:00 a.m. and 9:00 a.m. ) was obtained from the prospective study participants and the cross - sectional study participants recruited in italy . presence of hypertension was defined as a systolic blood pressure 130 mmhg or diastolic blood pressure 85 mmhg , or both , or the presence of antihypertensive treatment . a random blood sample was obtained from the cross - sectional study participants recruited in boston . current and former smokers were considered as one group and compared with those who never smoked . bmi was calculated by dividing the weight ( in kilograms ) by the square of height ( in meters ) .", "genotyping of the enpp1 k121q polymorphism ( rs1044498 ) was performed by taqman allele discrimination ( assay c_16190162_10 ; applied biosystems , foster city , ca ) on the ht7900 platform ( applied biosystems ) .", "deviations from hardy - weinberg equilibrium were investigated by exact test . because of the low number of qq individuals , only the dominant genetic model was tested by comparing individuals carrying the k121/q121 or the q121/q121 genotype ( q121 ) ( i.e. , kq heterozygotes + qq homozygotes ) to k121 homozygotes ( kk ) . in prospective studies , a time - to - event analysis was conducted by means of cox proportional hazards regression models using the breslow approach in the case of ties and reported as hazard ratios ( hrs ) along with their 95% ci . the time to event the discriminatory power of prediction models was assessed by estimating the survival c - index ( 39 ) and by measuring the integrated discrimination improvement ( idi ) ( 40 ) . a value of p < 0.05 was considered significant . the assumption of proportionality of the hazards was tested by using scaled schoenfeld residuals . in cross - sectional studies , the association between enpp1 q121 variant and age at mi was analyzed by multiple linear regression analysis , and results are given as regression coefficients . genotype - by - obesity interaction was tested by adding a cross - product term to the regression model . patients characteristics are reported as mean and sd for continuous variables and as frequencies and percentages for categoric variables .", "given the previous evidence for an enpp1-by - obesity interaction in the modulation of traits related to insulin resistance ( 2527,29,30,3941 ) , we investigated this hypothesis in our study . in the ghs , which entirely consisted of patients with type 2 diabetes , we indeed observed a significant interaction between the q121 variant and obesity . thus , we further investigated the q121-by - obesity interaction in a pooled analysis of the three studies after stratification by diabetes status . in the diabetic stratum ( n = 395 ) , the q121 variant was associated with an increased risk of incident events among the 177 obese ( fig . we studied three cohorts of subjects who were at very high risk of major cardiovascular events : the ghs individuals with type 2 diabetes and previously diagnosed cad ; the tor vergata atherosclerosis study ( tvas)individuals from the general population who had experienced an mi ; and the cardiovascular risk extended evaluation in dialysis ( creed)individuals with esrd who required dialysis . survival curves for major cardiovascular events in obese ( a ) and nonobese ( b ) patients with type 2 diabetes .", "we studied three cohorts of subjects who were at very high risk of major cardiovascular events : the ghs individuals with type 2 diabetes and previously diagnosed cad ; the tor vergata atherosclerosis study ( tvas)individuals from the general population who had experienced an mi ; and the cardiovascular risk extended evaluation in dialysis ( creed)individuals with esrd who required dialysis . no significant differences in baseline characteristics across genotype groups were observed in any of the three studies . clinical features of very high - risk individuals in the three prospective studies data are expressed as absolute numbers , percentage , or mean ( sd ) .", "the average mean ( sd ) follow - up was 37.1 ( 19.4 ) months ( range 191 ) in the ghs , 30.6 ( 11.3 ) months ( range 137 ) in the tvas , and 36.3 ( 22.0 ) months ( range , 169 ) in the creed . during follow - up , 43 major cardiovascular events occurred in the ghs , 39 in the tvas , and 94 in the creed , resulting in respective incidence rates of 4.2 , 10.8 , and 11.7 per 100 person - years ( table 2 ) . in all studies , incidence rates per 100 person - years were numerically higher in q121 carriers than in kk homozygotes : 5.4 vs. 3.6 in the ghs , 19.2 vs. 8.1 in the tvas , and 14.1 vs. 10.8 in the creed ( table 2 ) . the increased risk of events associated with the q121 variant remained significant ( hr 1.55 [ 95% ci 1.142.12 ] , p = 0.005 ) after adjusting for bmi and diabetes , both of which had been reported to be associated with the q121 variant ( 3840 ) , as well as after further adjustment for age , sex , hypertension , and smoking status ( hr 1.45 [ 95% ci 1.052.00 ] , p = 0.022 ) . kaplan - meier survival curves are shown for major cardiovascular events in ghs ( a ) , tvas ( b ) , and creed ( c ) . the addition of the k121q genotype did not improve the risk discrimination provided by the predictive model that included age , sex , bmi , smoking status , hypertension and diabetes , as indicated by the survival c - index , which went from 0.704 to 0.713 ( p = 0.94 ) , or by the idi , with 0.42% improvement ( p = 0.16 ) .", "given the previous evidence for an enpp1-by - obesity interaction in the modulation of traits related to insulin resistance ( 2527,29,30,3941 ) , we investigated this hypothesis in our study . in the ghs , which entirely consisted of patients with type 2 diabetes , we indeed observed a significant interaction between the q121 variant and obesity . an association between the variant and risk of events was present among the 159 subjects who had a bmi 30 kg / m ( hr 3.56 [ 95% ci 1.2110.5 ] , p = 0.02 ) , but not among the 171 individuals who had a bmi < 30 kg / m ( 0.91 [ 95% ci 0.402.06 ] , p = 0.82 ; p = 0.039 for interaction ) . thus , we further investigated the q121-by - obesity interaction in a pooled analysis of the three studies after stratification by diabetes status . in the diabetic stratum ( n = 395 ) , the q121 variant was associated with an increased risk of incident events among the 177 obese ( fig . survival curves for major cardiovascular events in obese ( a ) and nonobese ( b ) patients with type 2 diabetes . , we hypothesized that the genotype - by - obesity interaction might be specific to diabetes .", "to seek replication of the gene - by - obesity interaction observed in patients with diabetes , we analyzed the association between the q121 variant and age at mi in two cross - sectional samples of individuals with type 2 diabetes who had had a previous mi . in contrast , no significant difference in age at mi was observed among nonobese subjects : 59.2 ( 10.5 ) in 41 q121 carriers versus 57.2 ( 10.4 ) in 110 kk homozygotes ( p = 0.16 ; p = 0.025 value for q121-by - obesity interaction ) . virtually identical results were obtained when duration of diabetes was also added to the multivariate model , with q121 carriers having had an mi at a significantly younger age than kk individuals among obese ( p = 0.039 ) but not among nonobese ( p = 0.20 ) individuals ( p = 0.032 for interaction ) . 64 q121 carriers had had the mi almost 3 years earlier than the 124 kk homozygotes , at 54.5 ( 9.6 ) vs. 57.2 ( 8.9 ) years of age ( p = 0.035 ) . to make the analysis comparable to that of prospective studies , sex , smoking status , hypertension , and bmi , but not age ( due to its collinearity with age at mi and diabetes because all study participants were diabetic ) were included as covariates . among obese subjects , in addition , when bmi was considered as a continuous trait , it was inversely related to the age at mi among q121 carriers ( = 0.44 [ 95% ci 0.75 to 0.12 ] , p = 0.008 ; fig . clinical features of patients with type 2 diabetes who survived an mi in the two cross - sectional studies data are expressed as number , percentage , or mean ( sd ) .", "our results indicate that the enpp1 k121q polymorphism predicts acceleration of major cardiovascular events in very high - risk patients . an additional important result of our study is that the effect of the q121 variant was modulated by obesity in diabetic patients among whom the risk of incident events was five times higher in q121 than in kk genotype carriers . thus , pending further validation in larger studies , one can hypothesize clinical implementation of the q121 variant as a marker of early cardiovascular events among obese diabetic patients . pending confirmation in further larger studies , the q121 variant has the potential to become a clinical tool for identifying those very high - risk patients who are especially prone to major cardiovascular events and need , therefore , to be targeted with specific and even more aggressive preventive strategies . the increased risk conferred by the q121 variant is independent of that of age , sex , bmi , diabetes , and cigarette smoking ." ]
objectiveinsulin resistance ( ir ) and cardiovascular disease may share a common genetic background . we investigated the role of ir - associated enpp1 k121q polymorphism ( rs1044498 ) on cardiovascular disease in high - risk individuals.research design and methodsa prospective study ( average follow - up , 37 months ) was conducted for major cardiovascular events ( myocardial infarction [ mi ] , stroke , cardiovascular death ) from the gargano heart study ( ghs ; n = 330 with type 2 diabetes and coronary artery disease ) , the tor vergata atherosclerosis study ( tvas ; n = 141 who had mi ) , and the cardiovascular risk extended evaluation in dialysis ( creed ) database ( n = 266 with end - stage renal disease ) . age at mi was investigated in cross - sectional studies of 339 type 2 diabetic patients ( n = 169 from italy , n = 170 from the u.s.).resultsincidence of cardiovascular events per 100 person -- years was 4.2 in ghs , 10.8 in tvas , and 11.7 in creed . hazard ratios ( hrs ) for kq+qq versus individuals carrying the k121/k121 genotype ( kk ) individuals were 1.47 ( 95% ci 0.802.70 ) in ghs , 2.31 ( 95% ci 1.224.34 ) in tvas , and 1.36 ( 95% ci 0.882.10 ) in creed , and 1.56 ( 95% ci 1.152.12 ) in the three cohorts combined . in the 395 diabetic patients , the q121 variant predicted cardiovascular events among obese but not among nonobese individuals ( hr 5.94 vs. 0.62 , p = 0.003 for interaction ) . a similar synergism was observed in cross - sectional studies , with age at mi being 3 years younger in q121 carriers than in kk homozygotes among obese but not among nonobese patients ( p = 0.035 for interaction).conclusionsthe enpp1 k121q polymorphism is an independent predictor of major cardiovascular events in high - risk individuals . in type 2 diabetes , this effect is exacerbated by obesity . future larger studies are needed to confirm our finding .
[ "also , recent data support the combined roles of protein - coding genes and non - coding rnas , such as micrornas , in the pathogenesis of frequent diseases ( such as cancer , immune and cardiac disorders ) . the authors developed a modular device composed of a sensor ( an aptamer ) and a gene - regulatory component ( a hammerhead ribozyme ) and tested its ability to affect the expression of cytokines important for the function of t - lymphocytes in mouse and human systems . second , the authors applied the synthetic rna regulatory device to a significant medical issue , the use of adoptive cell transfer ( act ) . finally , the presented gene regulatory system showed significant advantages over available gene regulatory techniques ( synthetic inducible promoters ) ; in particular , it provides a wide range of flexibility for clinical settings .", "", "", "", "since july 2007 he has been an associate professor in experimental therapeutics at the md anderson cancer center and studies the roles of micrornas and other non - coding rnas in cancer initiation and progression , as well as the mechanisms of cancer predisposition , and explores new rna therapeutic options for cancer patients . gac received his md and phd at carol davila university of medicine in bucharest , romania . after working on cytogenetics as an undergraduate student with dragos stefanescu in bucharest , he completed training in cancer genomics in massimo negrini 's laboratory at the university of ferrara , italy . in 2000 , he began working in gac 's laboratory studying the roles of non - coding rnas , including micrornas in the initiation and development of gastrointestinal cancers , as well as the identification of new non - coding rna biomarkers . he became a postdoctoral fellow at the kimmel cancer center in philadelphia , in carlo croce 's laboratory . the focus of his scientific research is understanding the roles of non - coding rnas in gastrointestinal cancers . in march 2009 skl graduated from yonsei university medical school , seoul , south korea with an md and phd and is an assistant professor in the department of gastroenterology , severance hospital , seoul .", "work in gac 's laboratory is supported in part by nih , by dod , by developmental research awards in breast cancer , ovarian cancer and leukemia spores , and by a 2009 seena magowitz pancreatic cancer action network aacr pilot grant . gac is supported as a fellow at the university of texas md anderson research trust , as a fellow of the university of texas system regents research scholar and by the cll global research foundation ." ]
synthetic rna - based regulatory systems are used to program higher - level biological functions that could be exploited , among many applications , for in vivo diagnostic and therapeutic applications . chen and colleagues have recently reported a significant technological advance by producing an rna modular device based on a hammerhead ribozyme and successfully tested its ability to control the proliferation of mammalian t lymphocytes . like all exciting research , this work raises a lot of significant questions . how quickly will such knowledge be translated into clinical practice ? how efficient will this system be in human clinical trials involving adaptive t - cell therapy ? we discuss the possible advantages of using such new technologies for specific therapeutic applications .
[ ", we present two cases of idms with different wt1 gene mutations that had previously been reported in association with dds . the nephropathies in dds are characterized by the histological finding of diffuse mesangial sclerosis ( dms ) , a finding also described in some cases of congenital nephrotic syndrome ( isolated diffuse mesangial sclerosis , idms ) . however , analysis of a large number of patients might provide clues to the role of each mutation , and might help in understanding the normal physiology of nephrogenesis and the prediction for tumorigenesis . in this report wt1 has been shown to play a role in kidney induction ( 2 ) and during later steps of nephrogenesis ( 3 ) , and there are suggestions that wt1 may play an important role in the maintenance of normal podocyte function ( 4 ) . besides wilms ' tumor , a number of human diseases have been shown to be associated with mutations of the wt1 gene ( 5 ) .", "analysis of the wt1 exon 8 sequence revealed the presence of a heterozygous g to a base substitution , converting arg to his ( fig . analysis of the sequence of wt1 exon 9 revealed the presence of a heterozygous g to t base substitution , converting asp to tyr , and a heterozygous 395 ser ( tcc ) > ser ( tca ) polymorphism ( fig . a wt1 mutation was identified by direct sequencing of a wt1 pcr product obtained from genomic dna from white blood cells . the patient is now 13 months old , and is well and on peritoneal dialysis , expecting renal transplantation .", "analysis of the wt1 exon 8 sequence revealed the presence of a heterozygous g to a base substitution , converting arg to his ( fig . a wt1 mutation was identified by direct sequencing of a wt1 pcr product obtained from genomic dna from white blood cells . the patient is now 13 months old , and is well and on peritoneal dialysis , expecting renal transplantation . a renal biopsy was performed at the age of 111 days , and 30 glomeruli were examined .", "analysis of the sequence of wt1 exon 9 revealed the presence of a heterozygous g to t base substitution , converting asp to tyr , and a heterozygous 395 ser ( tcc ) > ser ( tca ) polymorphism ( fig . she was maintained on total parenteral nutrition due to uncontrolled chylothorax that resulted from internal jugular vein catheterization , and the patient died at the age of six months due to multiple serious infections and failure to thrive . peritoneal dialysis was commenced with a temporary shift to hemodiafiltration because of dialysate leakage at the exit site . sustained hypertension ( 120/80 mmhg ) responded to an angiotensin - converting enzyme inhibitor . a renal biopsy was performed at the age of 29 days and light microscopy showed small glomeruli with various degrees of mesangial sclerosis ( fig .", "the mutation present in the second patient was previously reported in a dds patient with early onset esrf resulting from dms , ambiguous genitalia , and a 46 xy karyotype . frasier syndrome ( fs ) is another distinctive disease associated with wt1 mutation , characterized by male pseudohermaphroditism and nephropathy with late onset esrf , and a frequent association with gonadoblastoma ( 20 ) . our report is limited to two patients , but both mutations were already associated with dds , and the early onset esrf in patients with the 396 asp ( gac ) > tyr ( tac ) mutation is distinctively similar . our two cases are female with karyotype 46 xx , which might be the reason for the absence of gonadal abnormalities , and we suspect that if a patient is born with karyotype 46 xy , there may be a possibility of dds development . although male patients have been described ( 14 , 22 ) , idms most often occurs in females ; however , the percentage of patients with wt1 mutation - positive idms , the sex ratio and the associated risk of wilms ' tumor are still unknown ." ]
here we report two cases of isolated diffuse mesangial sclerosis ( idms ) with early onset end - stage renal failure . these female patients did not show abnormalities of the gonads or external genitalia . direct sequencing of wt1 pcr products from genomic dna identified wt1 mutations in exons 8 ( 366 arg > his ) and 9 ( 396 asp > tyr ) . these mutations have been reported previously in association with denys - drash syndrome ( dds ) with early onset renal failure . therefore we suggest that , at least in part , idms is a variant of dds and that investigations for the wt1 mutations should be performed in idms patients . in cases with identified wt1 mutations , the same attention to tumor development should be required as in dds patients , and karyotyping and serial abdominal ultrasonograms to evaluate the gonads and kidney are warranted .
[ "the aim of present study was to derive a phototoxicity ratio between the results of the nanotio2 experiments conducted in the absence of sunlight and conducted in the presence of solar or simulated solar radiation ( ssr ) . to achieve this aim , we searched the literature for studies that included nanotio2 experiments both with and without irradiance under the same experimental setup and otherwise identical conditions . therefore , the phototoxicity ratio can be used to correct endpoints of the toxicity tests with nanotio2 that were performed in absence of natural sunlight or ssr . recently , it has been argued that photoactivation of nanotio2 under natural levels of sunlight is sufficient to affect the output of lc50 and ec50 values in standard toxicology tests 11 , 12 . the majority of studies investigating nanotio2 toxicity did not take photoactivation into account and performed tests either in dark conditions or under indoor commercial artificial lighting that did not simulate natural solar irradiation . it is expected that regulators will use the phototoxicity ratio when deriving thresholds for nanotio2 because the majority of the published literature reported toxicity endpoints for nanotio2 in the absence of natural sunlight or ssr . titanium dioxide ( tio2 ) is a component of many sunscreens , soaps , shampoos , toothpastes , cosmetics , paper products , plastics , ink , paint , and building materials 1 in both its bulk form and its nanoform .", "a comprehensive literature review was conducted to collect available toxicity endpoints for nanotio2 . the literature search ( september 2014 ) was performed within 4 databases web of science , scopus , google scholar , and the university of british columbia library database using the following keywords in various combinations : titanium dioxide , tio2 , nanoparticles , phototoxicity , photoactivation , ec50 , lc50 , ic50 , and lowestobservedeffect concentration ( loec ) . review of nanotitanium dioxide ( tio2 ) phototoxicity to various species anatase ( a ) or rutile ( r ) . thus , uva and uvb approximations were performed on the studies reporting full spectrum with factors of 0.057 and 0.003 for uva and uvb , respectively . spearman rank correlation was performed between the phototoxicity ratio value and time duration of the reported toxicity test , time duration of irradiance , irradiance intensity , insolation , and the organism taxa to determine whether any of these variables drove the output value . in the case of organism taxa , for the purpose of analysis , abstracts of numerous hits were read , and downloaded papers were checked for useful information . only papers that reported results under the same environmental conditions for 2 different nanotio2 exposure groups ( with and without ssr ) in the form of ec50 , lc50 , ic50 , loec , or a ratio were selected . such conversions allowed us to determine whether uva and uvb levels used in the studies were of environmental relevance by comparing the data with published averaged uva and uvb levels over europe .", "the literature search resulted in 25 usable references , from which 62 pairs of data were generated for calculation of a phototoxicity ratio ( table 1 ) . in total , experiments were performed on 20 different species , ranging from bacteria to amphibians . comparison of uncorrected data ( top ) , corrected data with median phototoxicity ratio ( middle ) , and corrected data with 75% phototoxicity ratio quartile ( bottom ) obtained in the absence of sunlight or simulated solar radiation ( ssr ) with true data obtained in the presence of sunlight or ssr . when the data were analyzed for susceptibility of bacteria , algae , invertebrates , fish , and amphibians to phototoxicity , the invertebrates were significantly different compared with other groups . the majority of the studies have used the same nanotio2 products ( p25 degussa ) , resulting in a fairly similar size span of primary particle diameter . once the data were corrected by dividing data obtained in the absence of sunlight or ssr with a median phototoxicity ratio or a 75% quartile phototoxicity ratio value , there was no longer statistical difference compared with the data obtained in the presence of sunlight or ssr ( figure 2 ) . on the other hand , the spearman rank correlation test was not statistically significant for phylogeny and phototoxicity ratio ( decreased or increased phototoxicity of nanotio2 from species on the lower organism stadium , such as bacteria , toward more complex organisms , such as amphibians ) . nanotio2 was significantly more toxic to invertebrates after exposure to light compared with other groups , resulting in a greater phototoxicity ratio ( kruskalwallis followed by post hoc multiple comparison ) . the discrepancy between the mean and median was caused primarily by the data associated with the cladocera taxon .", "a significant difference was observed between the phototoxicity ratios of 2 analyzed groups : aquatic species belonging to order cladocera , and all other aquatic species . a median phototoxicity ratio value and a 75% quartile were chosen as the most practical approach for correcting nanotio2 toxicity endpoints obtained in the absence of sunlight or ssr . using a median phototoxicity ratio value in correction is a more conservative approach , whereas using the 75% quartile lowers the chance of underestimating toxicity and may be favored by risk assessors when analyzing previously published data . , the present study found that nanotio2 is phototoxic to aquatic species , because the phototoxicity ratio values were substantially greater than 1 for the majority of analyzed studies . the fact that the cladocera taxon was more sensitive to nanotio2 phototoxicity can not be explained by the intensity of irradiation or received insolation during testing , because such correlation was not statistically significant ( spearman rank correlation test ) . in cladocerarelated experiments , existing literature on the subject is likely credible for the purpose of risk assessment because the insolation levels used in experimental setups did not exceed uv levels under natural conditions at the water surface . the order cladocera is very sensitive and prone to nanotio2 phototoxicity , at least in laboratorybased toxicity tests .", "all of the data used for calculation and statistical analysis are presented in table 1 of the present study , with corresponding references ." ]
abstracttitanium dioxide nanoparticles are photoactive and produce reactive oxygen species under natural sunlight . reactive oxygen species can be detrimental to many organisms , causing oxidative damage , cell injury , and death . most studies investigating tio2 nanoparticle toxicity did not consider photoactivation and performed tests either in dark conditions or under artificial lighting that did not simulate natural irradiation . the present study summarizes the literature and derives a phototoxicity ratio between the results of nanotitanium dioxide ( nanotio2 ) experiments conducted in the absence of sunlight and those conducted under solar or simulated solar radiation ( ssr ) for aquatic species . therefore , the phototoxicity ratio can be used to correct endpoints of the toxicity tests with nanotio2 that were performed in absence of sunlight . such corrections also may be important for regulators and risk assessors when reviewing previously published data . a significant difference was observed between the phototoxicity ratios of 2 distinct groups : aquatic species belonging to order cladocera , and all other aquatic species . order cladocera appeared very sensitive and prone to nanotio2 phototoxicity . on average nanotio2 was 20 times more toxic to noncladocera and 1867 times more toxic to cladocera ( median values 3.3 and 24.7 , respectively ) after illumination . both median value and 75% quartile of the phototoxicity ratio are chosen as the most practical values for the correction of endpoints of nanotio2 toxicity tests that were performed in dark conditions , or in the absence of sunlight . environ toxicol chem 2015;34:10701077 . 2015 the author . published by setac .
[ "we report 2 patients infected with panton - valentine leukocidin ( pvl)positive mrsa t034 . each patient had a medical history typical of that reported for community - acquired mrsa of other lineages , which in most cases are pvl positive ( 8) . the first patient , a previously healthy 36-year - old male physiotherapist , sought medical care in march 2006 for a small abscess in his axilla . culture of the abscess grew mrsa . presence of meca gene was confirmed by pcr ( 9 ) . during the next 2 months , subsequent screening of family members for mrsa on several occasions found only the father to be repeatedly positive .", "these strains carry pvl , a toxin partly responsible for the increased virulence of several of the mrsa clones in the community ( 8) . despite several recent publications concerning st398 mrsa , most previous reports have described asymptomatic carriage in persons exposed to occupational hazards ( e.g. , veterinary personal and pig farmers ) ( 1,2,7 ) . however , severe clinical infections have been described ( 46 ) . in our patients these strains caused repeated infections that needed medical attention , even hospitalization . few have reported pvl in this lineage , which is believed to be of animal origin ( 2,4,6,13 ) . these case reports suggest that strains of this lineage may impose a threat in the community , even to patients with no obvious animal contact . since neither patient had even a remote connection to animals and we found no common source of infection , these strains may already be more common in our region than we had thought ." ]
panton - valentine leukocidin ( pvl)positive methicillin - resistant staphylococcus aureus ( mrsa ) , sequence type 398 is believed to be of animal origin . we report 2 cases of infection due to pvl positive mrsa , spa type t034 , in patients in sweden who had had no animal contact .
[ "the selective melatonin receptor agonism effect of ramelteon is useful for insomnia.1 ) here we wanted to present a refractory chronic migraine case , who had significant improvements in migraine after using ramelteon .", "the precipitating factors were the stress , increase in physical activities and sudden cold weather . the moderate or severe pain intensity was aggravated by or causing avoidance of increased physical activity . the migraine also exacerbated her insomnia problems , with fragmented sleep and inadequate sleep duration as 12 hours ( insomnia severity index [ isi ] score , 23 ) . the residual symptom between the migraine episodes were the head tense feeling , but not achieveing headache severity . she did nt have any comorbid mental disorder except insomnia . due to the fear of abuse potential related to hypnotics the computed tomography revealed no significant findings of other causes for headache , such as tumor or hemorrhage . in addition , her migraine severity started to decline ( midas scores , 11 ) .", "in this case , we found significant improvements in migraine severity and insomnia after the use of ramelteon . since the patient did nt have insomnia before the first onset of migraine . the use of ramelteon , a kind of mt1 and mt2 agonist , could also relieve the pain even lack of free radical scavenger effects.3 ) the state - of - art treatment of refractory chronic migraine also includes the ramelteon due to selective m1 receptor agonism.6 ) from the successful experience in this case , we can consider the use of ramelteon for refractory chronic migraine with insomnia . therefore we could speculate that the ramelteon had significant effects in migraine in such mild prolongation of sleep duration ." ]
the selective melatonin receptor agonism effect of ramelteon is useful for insomnia . here we wanted to present a refractory chronic migraine case , who had significant improvements in migraine after using ramelteon . the possible mechanism for the ramelteon in the migraine relief might be related to melatonin effects .
[ "therefore , our study was aimed to determine is levels and three different types of antioxidant enzyme activities gsh - px , gr , and sod , in t2d with ati and li . , oxidative stress can be an important component for astrocytic cell death following metabolic stress . until now , experimental studies provided evidence of an association between ischemic stroke and increased oxidative stress [ 8 , 9 ] , but data in humans are still heterogeneous and limited . previous results implied that the majority of antioxidant enzyme activity was significantly reduced in acute ischemic stroke , possibly as a consequence of increased oxidative stress while the recent finding suggested increased levels of glutathione dependent enzymes as an adaptive mechanisms during acute cerebral ischemia . finally , due to novel facts it was previously suggested that atherothrombotic infarction ( ati ) and lacunar infarction ( li ) , as two different subtypes of ischemic stroke , might also differ in the set of the relevant risk factors , with ati being more associated to the atherogenic risk factors in contrast to li . in addition , changes in enzymatic antioxidative defense mechanisms in patients with stroke are still controversial .", "in this study we included a total of 93 patients with t2d , ascribed to the following groups : t2d patients with ati ( group a , n = 30 ) , and t2d with li ( group b , n = 30 ) , and t2d without ischemic stroke ( group c , n = 33 ) . simultaneously , we involved a total of 93 nondiabetics , matched with the t2d patients regarding gender and age , and also comprising the following groups : nondiabetics with ati ( group d , n = 30 ) , nondiabetics with li ( group e , n = 30 ) , and nondiabetics without stroke ( group f , n = 33 ) . t2d was diagnosed in accordance with the criteria of the world health organization . all the patients , with or without ati and li , showed the similar level of their physical activity . the evaluation of insulin sensitivity was done by frequently sampled intravenous glucose tolerance test ( fsigt ) with minimal model analysis . the metabolic tests were implemented at least after 6 months from the occurrence of the ischemic stroke . 0.3 g / kg body weight of glucose was injected and the blood samples for plasma glucose ( pg ) and plasma insulin ( pi ) determination were taken immediately before and 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 12 , 14 , 16 , 20 , 23 , 24 , 25 , 27 , 30 , 40 , 50 , 60 , 70 , 80 , 90 , 100 , 120 , 160 , and 180 minutes after intravenous glucose stimulation .", "the age , gender , duration of diabetes , and duration from the onset of ischemic stroke were similar in t2d patients and nondiabetics with different subtypes of ischemic stroke , together with hba1c levels , implying satisfactory metabolic control before metabolic investigation was done . however , ldl - c level was significantly higher in t2d patients with ati compared to the t2d patients with li and t2d patients without stroke and also in nondiabetics with ati compared to nondiabetics with li and healthy controls . simultaneously , this model identified decreased insulin sensitivity si and the level of gr and gsh - px in nondiabetics with ati , but predominantly decreased insulin sensitivity si in nondiabetics with li ( table 2 ) . this analysis identified that decreased insulin sensitivity si and the decreases of gr were related to both ati and li in t2d patients . there is no difference in prevalence of hypertension in patients with t2d and ati or li and t2d without ischemic stroke , while it was significantly higher in nondiabetics with ati or li than in healthy controls .", "in this study , we directly measured the is level , together with three different types of antioxidant enzyme activities , gsh - px , sod , and gr , in t2d patients and nondiabetic individuals with two different subtypes of ischemic stroke in type 2 diabetics . our results have shown decreased is level in t2d patients with two different subtypes of ischemic stroke , ati and li , compared to t2d without stroke , while we could not demonstrate the difference between the subtypes , and the same pattern of is changes was found in the nondiabetics . to our knowledge the results imply that higher levels of insulin resistance combined with lower levels of gr , detected in t2d patients compared to nondiabetics , were underlying the onset of li together ati in t2d in contrast to the findings in nondiabetics . in this context , taken together , our data imply that insulin resistance exerts its pathogenic influence on the level of gluthatione dependent antioxidant enzymes , especially in t2d . the multiple regression analysis applied to our data has demonstrated that decreased is together with the decreases in gr are related to both ati and li in t2d patients . in nondiabetics , the decreases in si levels and the diminished gr our results are consistent with the findings that li represents the most frequent ischemic stroke subtype in t2d .", "the results also imply that atherogenic influence of decreased is in the different subtypes of stroke in t2d might be exerted through a significantly reduced glutathione dependent antioxidant enzyme activity , while the mechanisms relating the effects of insulin resistance and decreased antioxidant enzyme activity remain to be clarified . in conclusion , our results suggest that the presence of different subtypes of ischemic stroke is associated with insulin resistance and diminished antioxidant enzyme activity in both subtypes of ischemic stroke in t2d ." ]
we analyzed ( a ) insulin sensitivity ( is ) and ( b ) glutathione peroxidase ( gsh - px ) , glutathione reductase ( gr ) , and superoxide dismutase ( sod ) antioxidant enzyme activity in type 2 diabetic ( t2d ) patients with atherothrombotic infarction ( ati ) ( group a ) , lacunar infarction ( li ) ( b ) , or without stroke ( c ) and in nondiabetics with ati ( d ) , li ( e ) , or without stroke ( f ) . ati and li were confirmed by brain imaging is levels were determined by minimal model ( si index ) , and the enzyme activity by spectrophotometry . in t2d patients , si was lower in a and b versus c ( 1.14 0.58 , 1.00 0.26 versus 3.14 0.62 min1/mu / l 104 , p < 0.001 ) and in nondiabetics in d and e versus f ( 3.38 0.77 , 3.03 0.72 versus 6.03 1.69 min1/mu / l 104 , p < 0.001 ) . also , gsh - px and gr activities were lower in a and b versus c ( gsh - px : 21.96 3.56 , 22.51 1.23 versus 25.12 1.67 ; gr : 44.37 3.58 , 43.50 2.39 versus 48.58 3.67 u / ghb ; p < 0.001 ) and in d and e versus f ( gsh - px : 24.75 3.02 , 25.57 1.92 versus 28.56 3.91 ; gr : 48.27 6.81 , 49.17 6.24 versus 53.67 3.96 u / ghb ; p < 0.001 ) . decreases in si and gr were significantly related to both ati and li in t2d . our results showed that decreased is and impaired antioxidant enzymes activity influence ischemic stroke subtypes in t2d . the influence of insulin resistance might be exerted on the level of glutathione - dependent antioxidant enzymes .
[ "in particular , we were interested in the differentiation between different types of soil such as grasslands ( pasture , meadow ) , allotment gardens , and forests , as well as fluvial sediments , the relationship of soil parameters ( carbon - to - nitrogen ratio ) on the occurrence of bacterial spores , and the distribution of spores in relation to sampling depth . the aim of this study was to adopt the fluorescence - based method to determine the spore content in soils sampled from various locations . a complex is formed in the presence of terbium which shows a very strong and distinctive fluorescence spectrum .", "the number of spores in the soil samples was determined using standard addition method with spores of b. subtilis . the identical dpa extraction protocol was applied for soil samples . however , microscopy was not possible due to the presence of mineral particles interfering the observation . elemental composition ( carbon , hydrogen , nitrogen ) of soil was performed with a chn-932 elemental analyzer ( leco corp . , st . sampling sites were located in the surroundings of zurich ( switzerland ) : grassland soil , meadow ( municipalities of mnnedorf ; uerikon ; stfa ; and dbendorf ) , allotment garden ( university of zurich , irchel campus ) , pasture ( university of zurich , irchel campus ; municipality of wdenswil ) , forest soil ( municipality of stfa ) , and aquatic sediments ( river glatt in dbendorf ) . lyophilized aliquots of approximately 1 g were transferred to an eppendorf micro test tube ( 2 ml ) and ground ( by adding a 6 mm glass bead ) in tissuelyser ( retsch , haan , germany ) for 5 1 min . samples were microwaved ( berghof microwave digester mws-1 , with built - in in situ infrared temperature control ) in teflon tfm screw cap digestion vessels . after additional 30 days of incubation until vegetative cells were not present anymore after inspection by microscopy spores were harvested by centrifugation , immediately frozen in liquid nitrogen followed by lyophilization .", "the two methods evaluated ( microwaving , autoclaving ) for the mobilization of dpa from bacterial spores gave similar results . our results show that grassland soils ( meadow , allotment garden , and pasture ) contains much more bacterial spores than forest soils and fluvial sediments . highest spore numbers up to 4 10 spores per gram dry soil were found in agriculturally used land ( meadow , pasture ) , less in forest soil . the method based on terbium fluorescence for the detection of total numbers of bacterial endospores in soils is fast and easy .", "in summary , microwave treatment of soil samples followed by the measurement of fluorescence after addition of terbium proved to be a fast and easy method to assess the content of bacterial spores . our study might provide a basis for the detection of hot spots of endospores in soil ." ]
spore formation is a survival mechanism of microorganisms when facing unfavorable environmental conditions resulting in dormant states . we investigated the occurrence of bacterial endospores in soils from various locations including grasslands ( pasture , meadow ) , allotment gardens , and forests , as well as fluvial sediments . bacterial spores are characterized by their high content of dipicolinic acid ( dpa ) . in the presence of terbium , dpa forms a complex showing a distinctive photoluminescence spectrum . dpa was released from soil by microwaving or autoclaving . the addition of aluminium chloride reduced signal quenching by interfering compounds such as phosphate . the highest spore content ( up to 109 spores per gram of dry soil ) was found in grassland soils . spore content is related to soil type , to soil depth , and to soil carbon - to - nitrogen ratio . our study might provide a basis for the detection of hot spots of bacterial spores in soil .
[ ", we investigated the time - ordered changes of pro - apoptotic and anti - apoptotic factors to determine the role of the upr signaling pathway in cognitive decline of 5fad mice alzheimer 's disease ( ad ) is a common neurodegenerative disease in the central nervous system . many studies have shown that ers is involved in the development and progression of neurodegenerative diseases such as ad , parkinson 's disease , huntington 's disease , and amyotrophic lateral sclerosis although the underlying mechanisms still remain blurred . . the outcome may clarify the role of ers in the pathological progression of ad . genetic mutations in ad lead to a overexpression in the brain and subsequent neurotoxicity , which leads to pathogenesis .", "the 5fad app / ps1 transgenic b6/sjl mice with five familial inherited ad mutant genes ( app k670n / m671l [ sweden]+i716v [ florida]+v717i [ london]+ps1 m146l+l286v ) under the control of the neuron - specific thy-1 promoter and wild - type ( wt ) b6/sjl mice with the identical genetic background were provided by prof . the 5fad transgenic and wt mice at 2 , 7 , or 12 months of age were used for subsequent experiments with 1014 animals per group ( n = 12 in each 2-month - old group , n = 10 in each 7-month - old group , n = 10 in the 12-month - old wt group , and n = 14 in the 12-month - old 5fad group ) . the prefrontal cortex region was selected as regions of interest , and the identical area within the measuring frame in a 10 objective lens was labeled . subsequently , the proteins were transferred to polyvinylidene fluoride ( pvdf ) membranes and blocked with 3% nonfat milk or 5% bsa in tbst buffer at room temperature for 2 h. the membranes were incubated at 4c overnight with the following primary antibodies : grp 78 ( 1:200 ) , chop ( 1:500 ) , sapk / jnk ( 1:1000 , cell signaling , boston , usa ) , p - sapk / jnk ( thr183/tyr185 ) ( 1:1000 , cell signaling ) , caspase-12 ( 1:500 , cell signaling ) , cleaved caspase-3 ( 1:500 , cell signaling ) , syvn1 ( 1:2000 , abcam ) , -actin ( 1:2000 , abcam ) , and -iii tubulin ( 1:100,000 ) . the clear brown cellular boundaries were considered positive although positive cells outside the frame were rejected . the escape latency(s ) and number of crossings over a hidden platform in 60 s were recorded .", "the 5fad transgenic and wt mice at 2 , 7 , or 12 months of age were used for subsequent experiments with 1014 animals per group ( n = 12 in each 2-month - old group , n = 10 in each 7-month - old group , n = 10 in the 12-month - old wt group , and n = 14 in the 12-month - old 5fad group ) . the 5fad app / ps1 transgenic b6/sjl mice with five familial inherited ad mutant genes ( app k670n / m671l [ sweden]+i716v [ florida]+v717i [ london]+ps1 m146l+l286v ) under the control of the neuron - specific thy-1 promoter and wild - type ( wt ) b6/sjl mice with the identical genetic background were provided by prof . they were raised , 45 animals / cage , under 12-h light/12-h dark conditions at 22c25c with a humidity of 5060% . all protocols and procedures used in this study experimental animals were housed in a pathogen - free colony ( ivc system , tecniplast , italy ) and allowed free access to food and water . were approved by the institutional animal care and use committee at fujian medical university in compliance with the us national institutes of health marry jo ladu ( department of anatomy and cell biology , university of illinois at chicago , usa ) .", "the escape latency(s ) and number of crossings over a hidden platform in 60 s were recorded . morris water maze tests were performed as described previously . the swimming behavior of mice was evaluated four times a day for 5 days . the swimming trace was monitored by camera and analyzed with smart 2.0 software ( panlab , barcelona , spain ) .", "the prefrontal cortex region was selected as regions of interest , and the identical area within the measuring frame in a 10 objective lens was labeled . the clear brown cellular boundaries were considered positive although positive cells outside the frame were rejected . cells that were lightly stained or had irregular shapes were excluded from quantification . 6 mice were randomly selected from each group and 3 consecutive sections of each mouse were measured . brain tissues were cut along the central sagittal suture , and the left hemisphere was fixed in 4% mice were anesthetized using 10% chloral hydrate by intraperitoneal injection ( 3 ml / kg ) . then , left ventricular perfusion was performed and brain tissues were isolated quickly on ice . immunohistochemistry was performed as follows : brain slices were washed with tris - buffered saline ( tbs ) and treated with 10% hydrogen peroxide at room temperature for 10 min to diminish endogenous catalase activity . the slices were imaged using a microscopy ( leica dm 4000b , germany ) , and image acquisition was performed with image - pro express 5.1 image analysis software ( media cybernetics , rockville , md , usa ) . for quantitative analysis ,", "brain slices were washed with tbs buffer and blocked with a specific buffer ( containing 5% donkey serum [ ds ] , 0.25% bsa , 0.3% triton x-100 , tbs ) at room temperature for 1 h. the primary antibodies ( diluted in 2% ds , 0.25% bsa , 0.3% triton x-100 , tbs ) used were : 6e10 , grp 78 ( 1:50 , santa cruz , ca , usa ) , chop ( 1:50 , santa cruz ) , glial fibrillary acidic protein ( gfap ) ( 1:4000 , millipore , boston , usa ) , and -iii - tubulin ( 1:4000 , abcam ) . the 6e10 was co - incubated with grp 78 , chop , gfap , and tubulin primary antibodies . alexa fluor 488- or 594-conjugated donkey anti - mouse or anti - rabbit igg ( 1:1500 , invitrogen , carlsbad , ca , usa ) were then added and incubated at room temperature in the dark for 1.5 h. the 4,6-diamidino-2-phenylindole ( dapi ) ( diluted by 1:8000 in h2o ) was then added and incubated for 5 min . prolong gold antifade reagent ( invitrogen ) was used for slice mounting , and slices were imaged using confocal microscopy ( leica tcs sp5 , leica microsystems wetzlar gmbh , germany ) .", "subsequently , the proteins were transferred to polyvinylidene fluoride ( pvdf ) membranes and blocked with 3% nonfat milk or 5% bsa in tbst buffer at room temperature for 2 h. the membranes were incubated at 4c overnight with the following primary antibodies : grp 78 ( 1:200 ) , chop ( 1:500 ) , sapk / jnk ( 1:1000 , cell signaling , boston , usa ) , p - sapk / jnk ( thr183/tyr185 ) ( 1:1000 , cell signaling ) , caspase-12 ( 1:500 , cell signaling ) , cleaved caspase-3 ( 1:500 , cell signaling ) , syvn1 ( 1:2000 , abcam ) , -actin ( 1:2000 , abcam ) , and -iii tubulin ( 1:100,000 ) . horseradish peroxidase - labeled goat anti - rabbit or anti - mouse iggs ( 1:2000 ) were subsequently added and incubated at 37c for 1.5 h. imagej software ( national institutes of health , bethesda , ma , usa ) was used for quantitative analysis . supernatants were collected and proteins were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis ( sds - page ) . the mixture was incubated on ice for 30 min , and lysis was performed using the ultrasound method . isolated mouse cortical tissues were added into tissue lysates ( 1% triton x-100 , 50 mmol / l sodium fluoride , 2 mmol / l sodium orthovanadate , 10 mmol / l -sodium glycerophosphate , 10 mmol / l sodium pyrophosphate , 1% protease inhibitor cocktail [ p8340 , sigma - aldrich , st .", "escape latency in the behavior analysis was performed using a repeated - measure multiway analysis of variance ( anova ) while other data were evaluated using two - way anova . if the main effects and the interaction were significant , the genotypes were compared by student 's t - test , or multiple conditions among the same genotype were evaluated with one - way anova . quantitative data were expressed as the mean standard error ( se ) and analyzed with the graphpad prism 6.01 software package ( graphpad , san diego , ca , usa ) .", "5fad : transgenic mice with five familiar alzheimer 's disease ; wt : wild - type mice ; grp 78 : glucose - regulated protein 78 ; syvn1 : ubiquitin ligase synovial apoptosis inhibitor 1 ; a : amyloid ; 6e10 : the antibody targeting a ; gfap : glial fibrillary acidic protein ; dapi : 6-diamidino-2-phenylindole . the present data displayed that p - jnk / jnk increased mildly in 5fad mice at 2- and 12-month - old when in comparison with the levels detected in wt mice although the increase was not statistically different . , these data suggest that ers - specific chop and cleaved caspase-12 are sustainably upregulated in 5fad mice . these observations indicate that cell apoptosis in 5fad mice is not dependent on the jnk pathway [ figure 3c ] . taken together", "to investigate cognitive changes , we tested mice 's behavioral performance in the morris water maze . we found that compared with age - matched wt mice , 7- and 12-month - old 5fad mice displayed a prolonged escape latency ( f = 14.710 , p < 0.01 for 7-month - old ; f = 5.939 , p < 0.05 for 12-month - old ) , indicating an obvious decline in learning ability and memory retention . in the probe trial , scale bar = 100 m ; 5fad : transgenic mice with five familiar alzheimer 's disease ; wt : wild - type mice ; a : amyloid ; v : the fifth layer of the frontal cortex . the number of neuron - positive staining in 12-month - old 5fad decreased in the fifth layer of the cortex when compared with that of the age - matched wt mice , indicating neuronal loss in 5fad mice ( n = 6 , t = 2.987 , p < 0.05 ) [ figure 1d and 1e ] . the declined cognition in 7-month - old 5fad mice and the loss of neurons in the frontal cortex of the 12-month - old ones . a accumulation was increased in the brain tissues of 7-month - old mice and amyloid plaque deposition appeared around neurons secreting a. in 12-month - old mice , a large amount of plaque deposition was observed in the brain tissues [ figure 1b ] .", "grp 78 is a chaperone specifically localized in the er , whose expression increases in response to ers and serves as an er - specific marker . in wild mice , syvn1 , a component of the erad pathway , is involved in the degradation of abnormal proteins to reduce ers - induced apoptosis . at the age of 7 months and 12 months , these data indicate that grp 78 is expressed mainly in neurons , not in astrocytes . 5fad : transgenic mice with five familiar alzheimer 's disease ; wt : wild - type mice ; grp 78 : glucose - regulated protein 78 ; syvn1 : ubiquitin ligase synovial apoptosis inhibitor 1 ; a : amyloid ; 6e10 : the antibody targeting a ; gfap : glial fibrillary acidic protein ; dapi : 6-diamidino-2-phenylindole .", ", these data suggest that ers - specific chop and cleaved caspase-12 are sustainably upregulated in 5fad mice . these observations indicate that cell apoptosis in 5fad mice is not dependent on the jnk pathway [ figure 3c ] . taken together although chop is rarely expressed in normal neurons , its expression can be increased by ers to promote er - specific apoptosis . in the current study , the present data displayed that p - jnk / jnk increased mildly in 5fad mice at 2- and 12-month - old when in comparison with the levels detected in wt mice although the increase was not statistically different .", "in 5fad mice , we observed that neuronal loss and cleaved caspase-3 increase at the age of 12 months , cognitive deficit at the age of 7 months and 12 months . therefore , the ers - associated proteins examined here represent neuronal ers and reveal the impact of the upr on neuronal functions under a-induced stress conditions . in this study , we selected mice at 2 , 7 , and 12 months of age to investigate the changes of ers - associated proteins in 5fad mice and wt mice . these findings suggest that 2-month - old 5fad mice exhibit enhanced ers - associated upr pathway , consistent with intracellular a aggregation in neurons . schematic drawing shows that activated upr pathways of ers induced by intraneuronal -amyloid in 5fad mice . interestingly , no significant differences in pjnk / jnk levels were found between 5fad mice and wt mice at different periods , which indicates that the pjnk / jnk pathway is not involved in a-induced ers . under sustained stress conditions caused by the a-associated toxic effects , imbalanced regulation of grp 78 or syvn1 and chop or cleaved caspase-12 may be involved in the resistance to the restoration of er homeostasis in a-secreting neurons . if the development of ers can be delayed or reduced appropriately or the protective functions of the upr can be enhanced exogenously , the capacity of the er to tolerate abnormal proteins can be increased to delay cell damage and disease progression .", "xiao - dong pan ) and the national and fujian province 's key clinical specialty discipline construction programs . this work was supported by grants from the national natural science foundation of china ( no .", "" ]
background : amyloid ( a ) deposits and the endoplasmic reticulum stress ( ers ) are both well established in the development and progression of alzheimer 's disease ( ad ) . however , the mechanism and role of a-induced ers in ad - associated pathological progression remain to be elucidated.methods:the five familial ad ( 5fad ) mice and wild - type ( wt ) mice aged 2 , 7 , and 12 months were used in the present study . morris water maze test was used to evaluate their cognitive performance . immunofluorescence and western blot analyses were used to examine the dynamic changes of pro - apoptotic ( ccaat / enhancer - binding protein homologous protein [ chop ] and cleaved caspase-12 ) and anti - apoptotic factors ( chaperone glucose - regulated protein [ grp ] 78 and endoplasmic reticulum - associated protein degradation - associated ubiquitin ligase synovial apoptosis inhibitor 1 [ syvn1 ] ) in the ers - associated unfolded protein response ( upr ) pathway.results:compared with age - matched wt mice , 5fad mice showed higher cleaved caspase-3 , lower neuron - positive staining at the age of 12 months , but earlier cognitive deficit at the age of 7 months ( all p < 0.05 ) . interestingly , for 2-month - old 5fad mice , the related proteins involved in the ers - associated upr pathway , including chop , cleaved caspase-12 , grp 78 , and syvn1 , were significantly increased when compared with those in age - matched wt mice ( all p < 0.05 ) . moreover , ers occurred mainly in neurons , not in astrocytes.conclusions:these findings suggest that compared with those of age - matched wt mice , ers - associated pro - apoptotic and anti - apoptotic proteins are upregulated in 2-month - old 5fad mice , consistent with intracellular a aggregation in neurons .
[ "thus , in this study , we aimed at identifying ip in symptomatic multivessel cad patients and compared the results among patients with and without type 2 dm . ischemic heart disease is the most frequent [ 5 , 6 ] and is associated with the highest morbidity and mortality in patients with type 2 dm . despite the advances in the treatment of coronary artery disease ( cad ) , morbidity and mortality are still high , especially in patients with type 2 dm . moreover , despite the evolution in the treatment of hyperglycemia , patients with both cad and diabetes have worse clinical outcomes , irrespective of the treatment applied . a substantial effort has been put forth to investigate any promising cardioprotective strategy to effectively reduce myocardial infarct size . thus , recent studies have focused on the understanding of such myocardial responses , aiming at discovering the mechanisms of myocardial protection to achieve less aggression and a better prognosis .", "this was a prospective study that included patients with symptomatic cad followed by the medicine , angioplasty , or surgery study ( mass ) research group . briefly , it was determined by the analysis of studies with similar methodologies that included only diabetic patients and studies that included only nondiabetic patients . by the differences in t-1.0 mm in diabetic and nondiabetic patients , and accounting for an expected loss of 30 % of patients who do not demonstrate the ip phenomenon ( estimated based on the experience of our research group ) other parameters recorded during sets were the total exercise time , the occurrence and density of supraventricular and ventricular arrhythmias , and st - segment deviation morphology , during exercise and recovery phases . the following parameters were systematically measured : resting heart rate and arterial blood pressure , heart rate and arterial blood pressure at peak exercise , t-1.0 mm in seconds , rate pressure product ( rpp ) at the onset of t-1.0 mm , and exercise duration in seconds . exclusion criteria were single - vessel cad , left main cad , impaired systolic ventricular function ( defined as an ejection fraction < 0.50 ) , recent and negative treadmill exercise test , high - risk positive treadmill exercise test , limiting angina symptoms , an acute coronary syndrome in the prior 3 months , electrocardiographic signs that could make difficult the interpretation of ischemic changes ( left bundle - branch block , st - segment deviation ) , arrhythmias like atrial fibrillation or flutter , severe valvular disease , cardiomyopathies , or patient refusal to participate in this study . , 70 patients with diabetes and 70 without diabetes should be included to test the null hypothesis that the population means were similar ( power 0.9 and alpha error 0.05 ) .", "this was a prospective study that included patients with symptomatic cad followed by the medicine , angioplasty , or surgery study ( mass ) research group . multivessel cad was confirmed by the finding on cineangiocoronariography of atherosclerotic stenosis of at least 70 % obstruction in 2 or more coronary artery territories . briefly , patients were enrolled who had angina symptoms , multivessel cad , preserved left systolic ventricular function , and a recent , positive ischemic treadmill stress test . treadmill exercise tests were considered positive for myocardial ischemia if a horizontal or downsloping st - segment deviation was 1.0 mm , associated or not with thoracic discomfort . the systolic ventricular function was measured by transthoracic echocardiography and was considered preserved if ejection fraction was 0.50 . exclusion criteria were single - vessel cad , left main cad , impaired systolic ventricular function ( defined as an ejection fraction < 0.50 ) , recent and negative treadmill exercise test , high - risk positive treadmill exercise test , limiting angina symptoms , an acute coronary syndrome in the prior 3 months , electrocardiographic signs that could make difficult the interpretation of ischemic changes ( left bundle - branch block , st - segment deviation ) , arrhythmias like atrial fibrillation or flutter , severe valvular disease , cardiomyopathies , or patient refusal to participate in this study . the diagnosis of type 2 dm was based on american diabetes association guidelines diagnostic criteria .", "after cardiologic evaluation , all patients were instructed to stop medications with cardiovascular properties 5 days before sets . patients were also recommended to not perform physical activities during the period without the use of medications and were under appropriate nutritional control . diabetic patients were also instructed to stop antidiabetes medications 5 days before the tests . a telephone contact was available 24 h a day in case of questions or worsening symptoms . before treadmill test initiation ,", "the improvement in ischemic parameters ( t-1.0 mm and rpp ) in the second exercise test compared to the first one indicated the presence of ip . other parameters recorded during sets were the total exercise time , the occurrence and density of supraventricular and ventricular arrhythmias , and st - segment deviation morphology , during exercise and recovery phases . the following parameters were systematically measured : resting heart rate and arterial blood pressure , heart rate and arterial blood pressure at peak exercise , t-1.0 mm in seconds , rate pressure product ( rpp ) at the onset of t-1.0 mm , and exercise duration in seconds . a 12-lead electrocardiogram was also obtained at each 1.0-min interval during exercise , at peak exercise , each minute up to 5 min during the recovery phase , at the onset of 1.0 mm st - segment depression , during arrhythmias , and when it was clinically relevant . both arrhythmias and st - segment morphology were graded according to their density and severity . according to the levels of fasting glycemia and glycosylated hemoglobin from baseline , patients were separated into quartiles . for fasting glycemia , the quartiles were defined as quartile 1 : < 90 mg / dl , quartile 2 : 90100 mg / dl , quartile 3 : 101125 mg / dl , and quartile 4 : 126 mg / dl . for glycosylated hemoglobin , tests were conducted during the same period each day , 1 h after lunchtime , on the same treadmill , ( mat 2100 treadmill and a fukuda denshi ml8000 stress test system ( fukuda denshi ; bunkyo - ku , tokyo , japan ) . a 12-lead electrocardiogram , heart rate , and arterial blood pressure were obtained with the patient in the standing position at baseline . criteria for interrupting the exercise test were st - segment depression 3.0 mm , st segment elevation 2.0 mm , maximum age - related heart rate , severe arterial hypotension or hypertension , severe chest pain , physical exhaustion , and sustained arrhythmias . all patients underwent 2 sets , symptom limited , with a 30-min interval between them . the modified bruce protocol was applied .", "the sample size calculation has been previously published elsewhere . briefly , it was determined by the analysis of studies with similar methodologies that included only diabetic patients and studies that included only nondiabetic patients . by the differences in t-1.0 mm in diabetic and nondiabetic patients , and accounting for an expected loss of 30 % of patients who do not demonstrate the ip phenomenon ( estimated based on the experience of our research group ) , 70 patients with diabetes and 70 without diabetes should be included to test the null hypothesis that the population means were similar ( power 0.9 and alpha error 0.05 ) .", "data are expressed as mean standard deviation or as absolute frequencies and percentages . all tests were 2-sided , and a value of p < 0.05 was considered significant . continuous variables were compared using an unpaired student s t test or mann whitney test , when appropriate .", "ip = ischemic preconditioning ; q = quartile ( s ) . cad = coronary artery disease ; ckd = chronic kidney disease ; cva = cerebrovascular accident ; ecg = electrocardiogram ; ef = ejection fraction ; et = exercise test ; dm = diabetes mellitus ; ip = ischemic preconditioning ; set = sequential exercise test ( s ) study flow chart . of dm stands for diabetic patients , non - dm nondiabetic patients , ip + ischemic preconditioning present , ip - ischemic preconditioning absent , et exercise test hemodynamic parameters , heart rate and blood pressure in the 4 groups of patients , diabetic and nondiabetic , according to the demonstration of ip data are expressed as means standard deviation . dm stands for diabetes mellitus , ip + ischemic preconditioning present , ip - ischemic preconditioning absent , et exercise test . *", "dm stands for diabetic patients , non - dm nondiabetic patients , ip + ischemic preconditioning present , ip - ischemic preconditioning absent , et exercise test dm stands for diabetic patients , non - dm nondiabetic patients , ip + ischemic preconditioning present , ip - ischemic preconditioning absent , et exercise test hemodynamic parameters , heart rate and blood pressure in the 4 groups of patients , diabetic and nondiabetic , according to the demonstration of ip data are expressed as means standard deviation . . dm stands for diabetes mellitus , ip + ischemic preconditioning present , ip - ischemic preconditioning absent , et , exercise test . * . dm stands for diabetes mellitus , ip + ischemic preconditioning present , ip - ischemic preconditioning absent , et exercise test . * dm stands for diabetes mellitus , ip + ischemic preconditioning present , ip - ischemic preconditioning absent , et , exercise test . * dm stands for diabetes mellitus , ip + ischemic preconditioning present , ip - ischemic preconditioning absent , et exercise test . * the p values are from the comparison of et2-et1 among diabetic and nondiabetic patients rpp in exercise test 1 ( et1 ) and exercise test 2 ( et2 ) and the difference between the 2 tests ( et2-et1 ) in diabetic and nondiabetic patients who demonstrated ip ( ip+ ) or who did not demonstrate ip ( ip- ) data are expressed as means standard deviation the p values are from the comparison of et2-et1 among diabetic and nondiabetic patients regarding rpp , the group of diabetic patients who demonstrated ip had an improvement of 3,011 2,430 bpm x mmhg , whereas nondiabetic patients had an improvement of 2,081 2,139 bpm x mmhg ( table 4 , p = 0.01).table 4rpp in exercise test 1 ( et1 ) and exercise test 2 ( et2 ) and the difference between the 2 tests ( et2-et1 ) in diabetic and nondiabetic patients who demonstrated ip ( ip+ ) or who did not demonstrate ip ( ip-)et1et2et2-et1 \n p value*dm / ip+22,841 4,50025,853 4,7423,011 2,4300.01non - dm / ip + 23,094 5,31225,175 5,4852,081 2,139 dm / ip -22,705 4,00022,124 3,686580 2,2500.43non - dm / ip -23,910 5,38022,869 5,3511,050 2,027data are expressed as means standard deviation .", "the improvement in the total exercise time comparing the 2 sets was similar between the groups of diabetic and nondiabetic patients ( 20 39 s versus 17 36 s , respectively , p = 0.60 ) . the improvement in the frequency and severity of arrhythmias had similar results among diabetic and nondiabetic patients who experienced ip ( 50 % versus 63 % of patients demonstrated improvement in arrhythmias , respectively ; p = 0.41 ) . the improvement in the st - segment deviation morphology was also similar among diabetic and nondiabetic patients ( 38.5 % versus 48.3 % , respectively , p = 0.41 ) .", "when the total group of patients ( n = 174 ) was stratified according to the demonstration of ip , the frequency of diabetic patients as well as the levels of fasting glycemia and glycosylated hemoglobin were similar between the 2 groups , as shown in table 6.table 6frequency of diabetes mellitus , and levels of fasting glycemia and a1c in the study population according to the expression of ipip + ( n = 122)ip - ( n = 52 ) \n p valuedm n ( % ) 62 ( 50.8)24 ( 46.1)0.57fasting glycemia121.3 42.6118.9 34.10.72a1c6.63 1.66.32 1.20.25data are expressed as means standard deviation and as absolute and relative frequencies \n dm stands for diabetes mellitus , a1c glycosylated hemoglobin , ip + ischemic preconditioning present , ip - ischemic preconditioning absent frequency of diabetes mellitus , and levels of fasting glycemia and a1c in the study population according to the expression of ip data are expressed as means standard deviation and as absolute and relative frequencies \n dm stands for diabetes mellitus , a1c glycosylated hemoglobin , ip + ischemic preconditioning present , ip - ischemic preconditioning absent in addition , when we stratified patients by quartiles of glycemia and glycosylated hemoglobin , there was no statistical difference in terms of ip demonstration among the different quartiles ( fig 3graphs showing the percentage of patients who demonstrated ischemic preconditioning ( ip+ in blue ) and who did not demonstrate ischemic preconditioning ( ip - in red ) stratified into quartiles of a1c ( graph a ) and fasting glycemia ( graph b ) . ip = ischemic preconditioning ip = ischemic preconditioning ; q = quartile ( s ) .", "considering that diabetes is an independent risk factor for the occurrence of major cardiovascular events and mortality [ 5 , 6 ] , it is reasonable to consider that diabetes might damage the protective mechanism of ip in cad patients , leading to worse outcomes . , our study showed that patients with type 2 dm demonstrated ip in similar frequency and intensity compared with nondiabetic patients and , interestingly , our data indicated an improvement in ischemic parameters associated with diabetes . however , in this study , the presence of type 2 dm did not have any deleterious effects on the myocardial protective mechanism termed ischemic preconditioning . in this context the analyses of the data showed a better ischemic response evaluated by rpp in diabetic patients . one mechanism that may interfere with such a prognosis may be the presence of a protective myocardial phenomenon , termed ischemic preconditioning . because diabetes is an independent risk factor for the occurrence of major cardiovascular events , it is reasonable that it may compromise this cardioprotective mechanism , leading to worse outcomes .", "this prospective study on ip in humans had a sample size powered enough to compare ip demonstration in 2 populations with matched clinical characteristics and evaluated the possible interference of diabetes on a myocardial protective mechanism . the group of patients with diabetes was under strict control of hyperglycemia , and this is observed by the controlled levels of fasting glucose and glycosylated hemoglobin in the group of diabetic patients . assuming that hyperglycemia may interfere negatively with ip , it is possible that the result of this study would be different in a population under less strict hyperglycemic control .", "one mechanism that may interfere with such a prognosis may be the presence of a protective myocardial phenomenon , termed ischemic preconditioning . because diabetes is an independent risk factor for the occurrence of major cardiovascular events , it is reasonable that it may compromise this cardioprotective mechanism , leading to worse outcomes . , the response of the myocardium to an ischemic insult may probably play an important role in prognosis . contrary to the initial expectation , the analysis of our data revealed that diabetic patients showed this protective phenomenon similarly to nondiabetic patients .", "in this study , diabetes mellitus did not substantially affect myocardial ip in symptomatic cad patients ." ]
backgroundthe influence of diabetes mellitus on myocardial ischemic preconditioning is not clearly defined . experimental studies are conflicting and human studies are scarce and inconclusive.objectivesidentify whether diabetes mellitus intervenes on ischemic preconditioning in symptomatic coronary artery disease patients.methodssymptomatic multivessel coronary artery disease patients with preserved systolic ventricular function and a positive exercise test underwent two sequential exercise tests to demonstrate ischemic preconditioning . ischemic parameters were compared among patients with and without type 2 diabetes mellitus . ischemic preconditioning was considered present when the time to 1.0 mm st deviation and rate pressure - product were greater in the second of 2 exercise tests . sequential exercise tests were analyzed by 2 independent cardiologists.resultsof the 2,140 consecutive coronary artery disease patients screened , 361 met inclusion criteria , and 174 patients ( 64.2 7.6 years ) completed the study protocol . of these , 86 had the diagnosis of type 2 diabetes . among diabetic patients , 62 ( 72 % ) manifested an improvement in ischemic parameters consistent with ischemic preconditioning , whereas among nondiabetic patients , 60 ( 68 % ) manifested ischemic preconditioning ( p = 0.62 ) . the analysis of patients who demonstrated ischemic preconditioning showed similar improvement in the time to 1.0 mm st deviation between diabetic and nondiabetic groups ( 79.4 47.6 vs 65.5 36.4 s , respectively , p = 0.12 ) . regarding rate pressure - product , the improvement was greater in diabetic compared to nondiabetic patients ( 3011 2430 vs 2081 2139 bpm x mmhg , respectively , p = 0.01).conclusionsin this study , diabetes mellitus was not associated with impairment in ischemic preconditioning in symptomatic coronary artery disease patients . furthermore , diabetic patients experienced an improvement in this significant mechanism of myocardial protection .
[ "most malignant heart tumors are sarcomas : myxosarcoma , liposarcoma , angiosarcoma , fibrosarcoma , leiomyosarcoma , osteosarcoma , synovial sarcoma , rhabdomyosarcoma , undifferentiated sarcoma , reticulum cell sarcoma , neurofibrosarcoma , and malignant fibrous histiocytoma . arrhythmias can develop from intraatrial invasion , which can also lead to massive pericardial effusion and tamponade . if the tumor mass is located in the left atrium or ventricle , embolic infarction might occur .", "successfully transplanted a patient after tah implantation , with an occult intracardial malignancy , after a cancer - free period of 14 months . before the operation a 55-year - old man presented signs of progressive cardiac decompensation during the last 4 months due to tumorous obstruction of the mitral valve . in 2014 the patient underwent resection of a suspected myxoma ( 824124 mm ) in the left atrium . the patient first presented with recurring tumor mass on the posterior mitral leaflet ( pml ) max . furthermore , autotransplantation was rejected for the same reasons . the severe mitral valve stenosis precluded use of a left ventricular assist device ( lvad ) or biventricular assist device ( bivad ) . the new approach introduced by bruckner et al . implantation of a self - expanding stent valve would also require an intact mitral valve annulus .", "cardiopulmonary bypass was established via the ascending aorta and venae cavae cannulation . following aortic cross - clamping , the apex , ascending aorta , and pulmonary trunk the left atrium showed infiltration of the intraatrial septum by the sarcoma after resection of the mitral valve ( figure 2 ) . extensive left atrial resection , a bovine pericardial patch was implanted to expand the pulmonary vein orifice with a 4 - 0 prolene suture . to allow postoperative tissue edema , we decided to leave the thorax open . after sufficient volume substitution , the patient was transferred to the icu under moderate catecholamine support and no ventilation . the atrial cuffs were prepared and broad felt strips for suture support were placed . due to", "under continuous anticoagulation for tah , there was a major risk for secondary bleeding due to the size of the media infarction . chromogenic in situ hybridization could not confirm an amplification of mdm2-gene , and translocation of syt - gene locus was ruled out . hence , the classification was undifferentiated high - grade spindle cell sarcoma , grade 2 using the french fdration nationale des centres de lutte contre le cancer ( fnclcc ) grading . histological workup showed a malignant mesenchymal neoplasm with spindle cell formations and heterologous chondroid and osseous components , with dystrophic calcifications .", "chondrosarcomas are cartilaginous tissue sarcomas . our patient was first diagnosed with primary cardiac chondrosarcoma . patients with mechanical assist devices are prone to suffer from thrombotic events [ 1316 ] , device malfunctioning , wound infections , and bleeding complications . there were no signs of assist malfunction during icu stay . with atrial infiltration and major excision of healthy tissue , implantation of tah after initial resection , relapse of the cardiac mass in the left atrium was diagnosed as early as 14 months later .", "this intervention was the second attempt to help the patient with a long - term solution after first recurrence of an atrial tumor . a multidisciplinary team and truthfully informed next of kin are hugely important when taking decisions in such a high - risk case . the surgical options and possibilities were discussed at length with the patient and his family before the tah implantation ." ]
backgroundtotal artificial heart ( tah ) implantation in patients with aggressive tumor infiltration of the heart can be challenging.case reportwe report on a patient with a rare primary undifferentiated high - grade spindle cell sarcoma of the mitral valve and in the left atrium , first diagnosed in 2014 . the referring center did a first resection in 2014 . in the course of 17 months , computer tomography ( ct ) scan again showed massive invasion of the mitral valve and left atrium . partial resection and mitral valve replacement was not an option . we did a subtotal heart excision with total artificial heart implantation . in this report we discuss complications , risk factors , and perioperative management of this patient.conclusionspatients with aggressive tumors of the heart can be considered for tah implantation .
[ "as we watch the effects of the legalization of cannabis in colorado , washington , alaska , oregon , and the district of columbia , other jurisdictions are debating the future of this illicit drug . cannabis is a prominent political , health , and law enforcement issue in north america that is currently receiving a great deal of attention . how can we prevent commercialization promoting increased rates of use within a legalization model ? where does marijuana for medical purposes fit into the picture , if at all ? this concern is even more pressing when it comes to the cognitive , physical , and mental health harms to adolescents who use cannabis .", ". this muchneeded work will provide clarity to misperceptions about cannabis , and make sense of some conflicting evidence about the effects of cannabis use and the impact of early or regular use during a time when the brain is still developing . by integrating neuroscience with the behavioral and social context of cannabis use by youth the current understanding of the impact of cannabis policy on market forces , such as healthcare costs , lost productivity costs , and tax revenues , for example , is very limited , as is overall understanding of how perception , use , and outcomes interrelate around this drug . in an effort to help clear the smoke , the canadian centre on substance abuse is currently undertaking a comprehensive review and synthesis of the literature on the effects of cannabis use during adolescence that will highlight key areas for action in policy , practice , and research the findings from this reviewed research highlight the complexity of the issues surrounding youth consumption of cannabis . youth are confused with the mixed messages they are receiving from discussions ranging from legalization to the use of cannabis for medical purposes , which points to the need for a coordinated , comprehensive , factual , and consistent approach to increasing awareness of this drug and its impact . , this report will provide a muchneeded resource for those working with youth and those involved in making decisions about policies , programs , or practices related to cannabis . more research is also needed to shed light on the influence of cannabis policy on public health , public safety , and other outcomes .", "aj porathwaller has provided expert testimony at the standing committee on health 's ( hesa ) recent report on marijuana 's health risks and harms , october 2014 ." ]
cannabis is the most commonly used illicit substance among youth . recent policy developments and ongoing debate related to this drug underscore the urgent need to clear the smoke and better understand what the scientific evidence says about the health and behavioral effects of cannabis use , particularly on youth whose brains are undergoing rapid and extensive development .
[ "hypertension and its sequelae , heart failure ( hf ) , are a progressive disease . hypertension ( htn ) is the most common comorbidity in the world with significant public health implications [ 1 , 2 ] . the overall u.s . heart failure in comparison to the most prevalent gender malignancies ( bowel cancer in men and breast cancer in women ) , was associated with worse long - term survival . african - american adults have the highest rates ( 44% ) of hypertension in the world and are more resistant to treatment . the disastrous duo , htn and hf , should be recognized , and a tailored focus on management in special populations , high - risk ethnic minority groups especially blacks who are disproportionately burdened should be developed . among racial groups ,", "stage a represents a critically important group because many of the risk factors including hypertension can be effectively controlled and by doing so may prevent development of cardiovascular diseases including hf . the other approach , adopted by the american college of cardiology / american heart association ( acc / aha ) guidelines , emphasizes disease progression . classified as stages a , b , c , and d , each of these stages has definable characteristics and recommended interventions . to emphasize the progressive nature of hf and the need to prevent its development or progression to end - stage disease ( stage d ) [ 18 , 23 ] , current hf guidelines define patients in stage a as those at increased risk for hf without evidence of structural heart disease or symptoms of hf . patients are in stage b when they present with evidence of structural heart disease but without current or prior symptoms of hf . this scheme is fluid and its class fluctuates in the same patient depending on their subjective assessment and clinical status . the most common is the new york heart association ( nyha ) classification , mainly based on functional capacity and subjective level of symptoms severity .", "there is a need for further randomized clinical trials with cpap therapy among high - risk ethnic minorities especially blacks to assess whether treatment of osa has similar long - term effects and to evaluate the effect on htn and hf morbidity and mortality . several studies have shown the efficacy of treatment of hypertension in preventing hf [ 2427 ] . we will focus on the most common , preventable and treatable secondary form of hypertension , obstructive sleep apnea ( osa ) . although , allhat trials and other trials showed diuretics is the first - line of antihypertensive therapy and is still the most commonly prescribed antihypertensive medications , this is challenged by recent studies as published in february jacc and presented in the european society of htn meetings . several large , randomized clinical trials have shown that specific classes of medication have mortality benefit in patients with heart failure [ 2834 ] . in the most recent guidelines for the diagnosis and management of hf in adults , the american college of cardiology foundation ( accf)/american heart association ( aha ) recognized the need for specific recommendations for special population .", "taking into consideration , lifestyle and pharmaceutical interventions , our changing health care community needs to emphasize the essential nature of the patient - provider relationship and establish trust and collaboration . in the past , this has been accomplished through physician , patients , family member , and other caretaker awareness , increased education of both provider and patients , and establishment of community outreach programs . we recommend an additional emphasis on the implementation of specialty care in patients with heart failure in collaboration with the primary care provider . these measures have contributed to an increase in compliance and a reduction in the risk of hospitalizations [ 23 , 87 ] .", "the dramatic improvement in the management of hf and hypertension over the last 50 years has allowed us to start to target specific populations and provide more evidence - based treatment that will lead to an improvement in mortality . the management team needs to take into consideration new evidence and develop tailored strategies for effective treatment , especially for hypertension , one of the main causes of hf and many other cardiovascular complications in african africans . there are disparities in the prevalence , treatment , and control of hypertension and the incidence and morbidity and mortality of heart failure between blacks , a diverse and heterogeneous population , and whites ." ]
hypertension ( htn ) is the most common co - morbidity in the world , and its sequelae , heart failure ( hf ) is one of most common causes of mortality and morbidity in the world . current understanding of pathophysiology and management of htn in hf is mainly based on studies , which have mainly included whites . among racial groups , african - american adults have the highest rates ( 44% ) of hypertension in the world and are more resistant to treatment . there is an emerging consensus on the significance of racial disparities in the pathophysiology and treatment options of hypertension and heart failure . however , african americans had been underrepresented in all the trials until the initiation of the a - heft trial . since the recognition of obstructive sleep apnea ( osa ) as an important medical condition , large clinical trials have shown benefits of osa treatment among patients with htn and hf . this paper focuses on the pathophysiology , causes of secondary hypertension , and treatment of hypertension among african - american patients with heart failure . there is increasing need for randomized clinical trials testing innovative treatment options for african - american patients .
[ "radiological investigations and therapeutics have become an integral part of the management of critically ill patients in the intensive care unit ( icu ) . we , therefore , carried out this study to determine the total radiation exposure to icu resident doctors involved in the course of their duties . the conclusion of these studies is that the level of radiation exposure is extremely low and does not pose a hazard to icu personnel . none of these studies have considered the additional radiation exposure to icu personnel involved in the management of critically ill patients in the radiology department . in our icu in a tertiary care cancer referral center , resident doctors working on 12 h shifts in the icu are also responsible for the transport and management of icu patients when they undergo diagnostic and therapeutic procedures in the radiology department . a number of studies have looked at radiation exposure in critically ill patients undergoing repeated radiological procedures .", "the primary outcome of this study was to quantify the cumulative radiation exposure to the resident doctors working in the icu over a period of 6 months in the course of their duties . the secondary outcomes were to measure the cumulative scattered radiation exposure in various areas of the icu calculated as the average of readings of icu tld badges over 6 months and the estimated cumulative radiation exposure to the resident doctors per year . we conducted a prospective , observational study in the icu and postanesthesia care unit ( pacu ) of a 500-bedded tertiary care cancer referral center in mumbai , india from september 2012 to february 2013 . residents provide care for patients in the icu and pacu and also accompany patients from these locations for radiological procedures in the ct scan or interventional radiology suites . is the pacu with 23 beds , subdivided into 14 postoperative recovery room beds and 9 intensive care beds [ figure 2 ] . in addition , three tlds were kept in nursing stations in icu , and one tld was placed in the pacu .", "the control tld placed in the department of anesthesia served as a measure of baseline atmospheric ionizing radiation , and all other values are reported above this baseline . since this was recorded in a 3 month period , the projected reading for similar exposure throughout the year , even assuming a 24 h duty period , would be 0.4 msv , which is well below the safety limit of 20 msv / year . the mean values in the first and last 3 months were 0.052 and 0.069 msv respectively , though the highest individual value approached 0.1 msv . the results of dosimetric analysis of residents tlds during the two phases are shown in table 2 . readings from tlds placed in the nursing station and doctors ' duty room during both phases were immeasurable .", "radiation exposure to doctors managing critically ill patients in the icu is minimal and acceptable . it is reassuring that the results of our study confirm that the extent of radiation exposure to critical care physician during the course of his duty is well within acceptable limits . this development has also infiltrated the field of critical care medicine , and radio - diagnosis and interventional radiological procedures now play a key role in the management of critically ill patients . while this advancement offers the advantages of rapid bedside diagnosis , and cost - effective and minimally invasive treatment options to critically ill patients , it carries the danger of exposure of patient and physician to radiation . in addition , where icu doctors are responsible for transport of patients to the radiology suite , the extent of radiation exposure is increased . a study performed in a trauma icu ( ticu ) has concluded that radiation exposure is not a significant occupational hazard for the ticu personnel .", "literature on radiation exposure among icu doctors is scarce . in addition to bedside radiological procedures , the risk of exposure may be increased if the same doctors accompany icu patients for out - of - icu radiological investigations . however , we found that if standard safety precautions were followed , cumulative radiation exposure to icu resident doctor was well within permissible limits and was not the cause of concern and hence routine personal dosimetric monitoring is not needed for residents in icu . however , in view of changing practice , there is a need to repeat such audits periodically to monitor radiation exposure ." ]
background and aims : with the expanding use of diagnostic and therapeutic radiological modalities in critically ill patients , doctors working in intensive care units ( icus ) are increasingly exposed to ionizing radiation . this risk of radiation exposure occurs not only during bedside radiologic procedures , but also when icu physicians accompany patients to radiology suites . the aim of this study was to quantify levels of radiation exposure among medical professionals working in the icu.materials and methods : the study was carried out prospectively over 6 months in the icu of a tertiary - referral cancer hospital . two teams consisting of 4 icu resident doctors each were instructed to wear thermoluminescent dosimeters ( tlds ) during their duty shifts . standard radiation protection precautions were used throughout the study period . tlds were also placed in selected areas of the icu to measure the amount of scattered radiation . tlds were analyzed at the end of every 3 months.results:the readings recorded on tlds placed in the icu were almost immeasurable . the mean value of residents ' radiation exposure was 0.059 msv , though the highest individual reading approached 0.1 msv . the projected maximum yearly radiation exposure was 0.4 msv.conclusions:if standard radiation safety precautions are followed , the cumulative radiation exposure to icu resident doctors is well within permissible limits and is not a cause of concern . however , with the increasing use of radiological procedures in the management of critically ill patients , there is a need to repeat such audits periodically to monitor radiation exposure .
[ "this is largely to blame on lack of access to viral load quantification , because this is considered a mandatory component of the diagnostic work - up in all international liver society guidelines . without a viral load measurement , despite the huge burden of hepatitis b worldwide , with an estimated 350 million people chronically infected , very few patients in low- and middle - income countries are currently receiving antiviral treatment . lack of access to viral load testing and antiviral treatment of hbv and hcv in resource - limited settings is a silent epidemic with major consequences . the world health organization ( who ) estimates that about 1 million people die from chronic hbv and hcv infection each year , which places viral hepatitis on the top 10 leading causes of mortality globally . an estimated 130150 million people are chronically infected with hepatitis c virus ( hcv ) globally , and the prevalence is higher in certain areas such as north africa and central and east asia . however , prior to starting treatment of hepatitis c , hcv rna measurements are required to establish the diagnosis of chronic hcv infection , which is a major obstacle in many places in the world . the situation for hepatitis c is somewhat different because the main obstacle to treatment has been expensive and toxic treatment regimens . with the release of new direct acting antivirals for hepatitis c it is virtually impossible to establish whether a hepatitis b surface antigen ( hbsag ) positive individual has chronic hepatitis b , characterized by a level of hepatitis b virus ( hbv ) dna > 200020 000 iu / ml and continued necro - inflammation in the liver .", "the solution to this challenge would be to develop reliable , cheap , and easy - to - use assays that can be performed at the site of patient care ( point - of - care assays ) . hence , although high - quality rdts can be used with confidence in screening for hbv and hcv , health authorities should warn against the use of unreliable ( and often very cheap ) rdts with poor sensitivity and specificity . numerous rapid diagnostic tests ( rdts ) for hepatitis b and c are commercially available , most of which provide a test result within 530 minutes ; however , the diagnostic accuracy varies from excellent to very poor . a recent meta - analysis by shivkumar and colleagues found that the sensitivity of hbsag rdts used to screen for hepatitis b infection varied from 42 to 100% and the specificity from 0 to 100% first , serological tests are used to screen for hepatitis markers and exclude co - infections . furthermore , stringent requirements for storage and shipment of plasma to the referral laboratory are barriers in settings with limited infrastructure . thereafter , a new battery of tests is needed to distinguish past or inactive infection from chronic hepatitis . . the same authors also reviewed anti - hcv rdts used for hepatitis c screening and found sensitivities ranging from 0 to 100% and specificities from 81.6 to 100% .", "this novel assay will build on their existing genedrive ( epistem , manchester , uk ) device , which is a rapid , easy to use , sensitive , handheld pcr platform already ce - ivd marked for other genotype tests , such as mycobacterium tuberculosis identification and antibiotic resistance testing . the uk biotechnology company epistem received a prestigious grant award in 2013 to develop an hcv point - of - care device for viral load testing and genotyping . the first products were recently launched , including the alere q analyzer ( alere inc . , commercial actors have not shown the same interest in low - tech diagnostics for hbv and hcv ; however , many of the technological advances for hiv can be modified to detect other viruses . currently , there is one product , truenat ( molbio diagnostics , goa , india ) , for hbv dna quantification which is advertized as a point - of - care assay . the us - based company wave 80 biosciences is developing a point - of - care kit for hbv dna quantification as well as a qualitative assay for hcv rna detection , building on their existing hiv viral load assay eoscape - hiv ( wave 80 biosciences , san francisco , ca , usa ) . even though serological point - of - care assays for hepatitis b and c are widely available , the same is not the case for virological analyses . however ,", "far too often advanced technology has been shipped to low - income countries with good intentions , but ended up in a storeroom because of insufficient training , lack of maintenance , and shortage of reagents . it is important , therefore , that point - of - care assays should be designed specifically to operate under basic conditions with minimal maintenance requirements and not just be high - tech solutions forced to fit low - tech settings . partly , this has to be blamed on the manufacturers , who rarely offer training or service agreements to low- and middle - income countries . sustainability is another major concern with all technological devices , and it should be a prerequisite that the manufacturers provide adequate training and service agreements locally . furthermore , sensitivity of the assay should be high enough to ensure treatment for those who need it , and even more importantly , specificity must be close to 100% to avoid unnecessary and expensive treatment in uninfected individuals . both the initial cost for the machine , but also the consumables thereafter must be priced reasonably . with regard to hbv , repeated tests over time are usually required , and the accumulated cost of viral load testing can be high . for hepatitis c , on the other hand , one viral load measurement prior to treatment and another 24 weeks after treatment would be sufficient if patients are being treated with the new direct acting antivirals . the international nongovernmental organization mdecins sans frontires published their desired specifications for a point - of - care hiv viral load assay a few years ago , and the same specification would also apply to an ideal hbv or hcv assay : no need for specialized laboratory facilities closed system to avoid contamination long shelf life in tropical climate no need for cold chain transportation or refrigerated storage affordability is an important issue if treatment for viral hepatitis is to be scaled - up globally .", "dbs can be a valuable tool for the pretreatment evaluation of patients with hepatitis c , but might be more troublesome in hepatitis b due to a reduced sensitivity in the lower range of viral loads . as described by greenman and colleagues in the current issue of jvh , dried blood spots ( dbs ) can be a feasible and reliable alternative to point - of - care assays for viral hepatitis . thus , more studies are needed to evaluate the precision of dbs for hbv dna quantification , especially in the lower range around the decision threshold of 200020 000 iu / ml . in conclusion , and in viral hepatitis , the decision to start treatment is rarely a matter of urgency .", ". however , assay performance under standardized conditions in europe or north america does not necessarily reflect real - life application in sub - saharan africa , and it is crucial to carry out independent field testing of these instruments before large scale use can be recommended . finally , sustainable funding mechanisms for diagnostics and treatment of viral hepatitis must be established . recently , the pharmaceutical company gilead announced that they work with generic drug manufactures in india to produce high - quality , low - cost sofosbuvir for developing countries , raising expectations that this game - changing drug might become available in low- and middle - income countries . management of viral hepatitis is going through a revolution with the launch of new direct acting antivirals for hepatitis c treatment . point - of - care viral load assays for hepatitis b and c have the potential to bridge this gap and prove valuable tools for expansion of treatment globally then our colleagues in resource - limited settings might be able to treat viral hepatitis in the not so distant future . scaling up of hiv treatment globally would have been impossible without major donor programs such as pepfar , unitaid and the global fund to fight aids , tuberculosis , and malaria . drug availability , however , is not the only issue . in the absence of viral load measurements ," ]
viral hepatitis claims one million lives each year . scaling up treatment for hepatitis b and c in resource - limited settings is not possible without access to reliable diagnostic tools . this article gives an overview of current technologies and the pipeline for easy - to - use assays for serological and virological analyses , which can be performed at the site of patient care ( point - of - care assays ) . furthermore , the utility of dried blood spots for hepatitis b and c viral load testing is discussed . in addition to simple and reliable diagnostics , there is a need for a sustainable funding scheme and generic production of antiviral drugs to reduce the burden of viral hepatitis worldwide .