Datasets:

anumafzal94

/

10k-pubmed-4096

like 0

a 47-year - old asian woman had bilateral uneventful cataract surgery for central cortical opacity . phacoemulsification via clear corneal incision and implantation of hydrophilic acrylic intraocular lens ( iol ) with polymethylmethacrylate modified c - loop haptics were done in the left eye first and the right eye later with interval of 2 days . the left eye was operated first among three operative cases of cataract and the right eye was operated third among four operative cases of cataract . preoperatively , the cornea was clear with normal specular microscopic finding , and inflammation was not detected in the anterior chamber of both eyes . the patient had not have any systemic or ocular disease other than diabetes that was controlled well under medication , and diabetic retinopathy was not presented in both eyes . on postoperative day 1 of each eyes , right eye had grade 1 + white blood cells in the anterior segment with uncorrected visual acuity ( ucva ) of 20/25 , while left eye had trace of white blood cells with ucva of 20/25 . levofloxacin and prednisolone acetate 1% eye drops were prescribed 4 times a day in both eyes . on postoperative day 7 of right eye , anterior inflammation improved and prednisolone acetate 1% was switched to fluorometholone 0.02% in both eyes . on postoperative day 11 of the right eye , the patient visited appealing mild right ocular pain , and the ucva was dropped to 20/30 presenting diffuse corneal edema . grade 2 + white blood cells and puff balls were shown in the anterior chamber and inflammatory plaques on the surface of iol were also found [ fig . 1 ] . however , the cell was not found in the vitreous and it was so clear enough to examine the retina [ fig . 2 ] . since anterior segment inflammation had been controlled with prednisolone acetate 1% immediately after cataract surgery and the vitreous did not present inflammatory cells , the patient was recommended to use prednisolone acetate 1% every 2 h and continue to use levofloxacin in the right eye . on postoperative day 14 of right eye , cellular reaction decreased to grade 1 + and plaques of iol surface disappeared partially . the patient was recommended to use prednisolone acetate 1% every 2 - 4 h until next visit . on postoperative 1 month of right eye , the white blood cells and inflammatory plaques were not observed , and visual acuity improved to 20/20 . on specular microscopic examination , the right eye had lower endothelial cell density than the left eye ( 2343 cells / mm vs. 2758 cells / mm ) , higher mean cell area ( 426 116 m vs. 362 57 m ) , and higher coefficient variation ( 27 vs. 15 ) , [ fig . the left eye had a normal uncomplicated course during whole treatment period of right eye . ( a ) slit lamp biomicroscopic image of the right eye on postoperative day 11 showing white blood cells in anterior chamber and white inflammatory plaques on the surface of intraocular implant . ( b ) on 20 days after intense use of prednisolone acetate 1% , white blood cells disappeared and inflammatory plaques was not observed on the surface of the intraocular implant ( a ) fundus photograph of right eye on postoperative day 11 . the retinal vessels and the optic disc margin are well visualized through clear vitreous even though anterior segment inflammation coexist . ( b ) on 20 days after intense use of prednisolone acetate 1% , anterior segment inflammation improved and clearer view of the retina was presented specular microscopic image of both eyes on postoperative 1 month . ( a ) the shape and size of endothelial cells are irregular in damaged eye with toxic anterior segment syndrome . ( b ) in contrast to damaged eye , regular hexagonality was observed in control eye toxic anterior segment syndrome is recognized as a specific noninfectious condition but may cause injury in a wide region of the anterior segment . the most common finding is diffuse limbus to limbus corneal edema secondary to damage from a toxic insult to the endothelial cell layer . inflammatory white plaques on the surface of iol , inflammatory debris puff ball , hypopyon , and fibrous reactions can be presented by widespread breakdown of the blood - aqueous barrier . in general , the inflammation improves with topical and/or oral steroids . the most common symptom is blurred vision and the patient may experience pain , but most cases are asymptomatic . in contrast to tass , 74 - 79% of patients with infectious endophthalmitis report pain and visual symptoms that develop a mean of 4 - 7 days postoperatively . and inflammed anterior segment including a variable hypopyon and vitreitis are observed in infectious endophthalmitis . in this case , since anterior segment inflammation had been controlled with prednisolone acetate 1% immediately after cataract surgery and clear vitreous was presented in the course of disease , infectious endophthalmitis was hardly suspected . in addition , i needed to differentiate propionibacterium acnes endophthalmitis , which has chronic disease course responding to steroid initially . acnes endophthalmitis after cataract surgery is characterized by an indolent low - grade uveitis with latent onset , an initial response to topical steroids , and the frequent absence of more typical endophthalmitis signs and symptoms . a characteristic clinical feature of the syndrome is the presence of a white intracapsular plaque that has been shown histologically to be composed of sequestered organisms inside the peripheral capsular bag . other important clinical findings include conjunctival injection , keratic precipitates , and vitreitis . in this case , the lens material and cortex were removed completely during the surgery and there was no retained white material in the capsular bag . in addition , any vitreous inflammation was not noted in the course of disease . from those points , while most reported tass cases are acute , there have been several instances of delayed - onset tass following cataract surgery . have reported 10 cases of delayed - onset inflammation after hydrophilic acrylic iol ( memory lens ) , which has been theorized that a residual polishing compound on the memory lens was responsible for the postoperative inflammation . another potential source of delayed - onset tass is the ingress of ophthalmic ointment used postoperatively in the anterior segment of the eye . werner et al . described that an oily material coating the anterior surface of the iol or forming small globules within the anterior chamber was found in a group of delayed - onset tass . in view of the onset time , this case seemed to be masked for early postoperative period under prednisolone acetate 1% and emerge after switching to fluorometholone 0.02% mimicking delayed onset tass . on specular microscopic findings , the eyes with tass were characterized by lower endothelial cell density than the control eyes , higher mean cell area ( coefficient of variation ) and lower mean percentage of hexagonal cells . in this case , the eye with tass had lower endothelial cell density than control eye ( 2343 cells / mm vs. 2758 cells / mm ) , higher mean cell area ( 426 116 m vs. 362 57 m ) , and higher coefficient variation ( 27 vs. 15 ) . this is considered as toxic response of endothelium , which is in a line of toxic endothelial cell destruction syndrome . these include reactions to abnormalities in the ph or ionic composition of irrigating solutions and reactions to residual denatured viscoelastic agents or residual detergent injected during surgery with reusable cannulas or tubing . immune reactions to residual lens cortex , preservatives , or endotoxins could be causative factors of tass . in recent times , bodnar et al . have demonstrated that the most commonly identified risk factors for tass arise from problems with the instrument - cleaning process . of these , inadequate flushing of the hand pieces , the use of enzymatic detergents , and the use of ultrasound baths are the most prevalent . none of my surgical devices , instruments , viscoelastic materials , or other materials used in surgery had not been changed for several years in my surgery environment . even , there had been no difference of surgical devices and materials including antiseptic solutions in operating room between the eye with tass and control eye in this case . however , i used same iol produced by one company , and the possibility of the difference of manufacture between two iols is low . it is difficult to point out the causes accurately , so i am cautiously assuming that inadequate flushing the ports of the phaco , i and a handpieces , or cannulated instruments from previous cases caused tass in this case . i demonstrated mild nature of tass , which was masked during early postoperative period under prednisolone acetate 1% and mimicked delayed onset tass after switching to weaker steroid . this case showed rapid clearing of inflammation in the anterior chamber and the cornea without any sequelae after intense use of prednisolone acetate 1% . in addition , this case reminds me of the importance of watching and monitoring whole surgical processes from preparation to sterilization , and suggests that immediate postoperative inflammation of anterior segment after cataract surgery can not be neglected even its nature is mild , and should be followed sufficiently .

toxic anterior segment syndrome ( tass ) is an acute sterile postoperative anterior segment inflammation that may occur after anterior segment surgery . i report herein a case that developed mild tass in one eye after bilateral uneventful cataract surgery , which was masked during early postoperative period under steroid eye drop and mimicking delayed onset tass after switching to weaker steroid eye drop .

proteus syndrome is a hamartomatous disorder consisting of disproportionate , asymmetric overgrowth of body parts , malformations of the capillary , venous and lymphatic types , and dysregulated adipose tissue . disproportionate overgrowth and giant hemangiomas have also been reported to involve the viscera such as spleen . we hereby present a case of traumatic injury to a pathologic spleen in a patient of proteus syndrome . the decision - making with regard to surgery or non - operative management in such unusual cases of splenic injury is complicated due to the possibility of pathology in spleen with high chances of bleeding . a 20-year - old female , a known case of proteus syndrome , presented four days after fall from a bike . she was referred to our level i trauma center after being managed non - operatively for three days at a different hospital in view of increasing abdominal distention and pain . the exact details of the treatment given were not available . on admission in the emergency department ( ed ) , abdominal examination revealed significant distention with tenderness over the left hypochondrium without rebound tenderness or guarding . the general physical examination was remarkable for the manifestations of proteus syndrome that included arteriovenous malformations and hemihypertrophy of her left leg with multiple lipomas over the abdomen [ figure 1 ] . her hemoglobin was 2.9 g / dl with packed cell volume ( pcv ) of 12% , platelet count of 1,08,000 cells / cubic mm , and pt - inr of 1.29 . ultrasonogram ( usg ) of the abdomen showed a moderately enlarged spleen with cystic reticulated appearance . contrast - enhanced tomography ( cect ) of the abdomen showed a non - enhancing enlarged spleen of size 17 cm 15 cm 10 cm [ figure 2 ] , massive hemoperitoneum with normal liver and kidney with no leakage of the contrast . in view of low hemoglobin and possibility of intra - operative findings included an enlarged spleen with 3 cm laceration along the lower pole and 2 liter of hemoperitoneum . her injury severity score ( iss ) was 9 ( 3 for splenic injury ) . pathological examination showed an enlarged spleen of size 17 cm 15 cm 10 cm with spongy cut surface , weighing 230 gm . histological examination showed multiple vascular spaces lined by single flattened layer of endothelium filled with fibrin and red blood cells , suggesting a hemangiolymphangioma [ figure 3 ] . she required 5 units of blood transfusion in the peri - operative period , and her hemoglobin increased to 8.7 gm% with a hematocrit of 30% , platelet count of 1,30,000 cells / cubic mm , and pt - inr of 1.20 . she was discharged on the 5 post - operative day and is doing well at 6 months of follow - up . disproportionate growth of toes with vascular malformations cect scan of the abdomen showing enlarged spleen h and e 400 showing multiple cystic spaces lined by flattened endothelial cells , filled with eosinophilic material and blood , separated by fibrous stroma , extensively replacing the splenic architecture proteus syndrome , first described by cohen and hayden in 1979 , is a congenital dysplasia syndrome of patchy , irregular overgrowth of multiple body tissues and cell lineages arising from a mosaic mutation . it was named by wiedemann et al . in 1983 after the greek god proteus who could change his form at will . around 200 cases have only been reported worldwide till now . once thought to have neurofibromatosis , joseph merrick ( also known as the elephant man and studied by treves in the 1800s ) is now , in retrospect , thought by clinical experts to actually have had proteus syndrome . common findings are hemihypertrophy , subcutaneous and visceral hamartomatous tumors , pigmented nevi and exostoses . partial gigantism with limb or digital overgrowth is pathognomonic , with an unusual body habitus and , often , cerebriform thickening of the soles of the feet may be present . the patient in our discussion had hemihypertrophy and vascular malformations over the left lower extremity with digital overgrowth and multiple lipomas over the abdomen . kts is characterized by vascular malformations , unusual varicosities , and asymmetric enlargement of the limbs , whereas in proteus syndrome , vertebral , visceral malformations , and other malformations can occur independent of vascular malformations . classical hemangiomas are often present at birth and regress spontaneously while in proteus syndrome , they appear after birth and grow gradually . these vascular malformations are larger , softer , and more disseminated with histopathology showing variable portions of vascular , lymphatic , and organ tissue . giant hemangiomas in spleen , causing kasabach - merritt syndrome and chronic dic have been reported in proteus syndrome . spontaneous rupture is a risk with such large hemangiomas and occurs in about 25% of such cases . magnetic resonance ( mr ) imaging is more sensitive and specific than other modalities in the diagnosis of splenic hemangioma . in our case , spleen was grossly enlarged with usg and ct scan showing multiple cystic spaces raising the possibility of vascular malformations . non - operative management is currently being advocated in the management of splenic injury if the following criteria are satisfied- hemodynamic stability ( systolic blood pressure > 90 mmhg is generally accepted ) , blunt abdominal injury , absence of associated intestinal injuries , normal level of consciousness , and 24 hour availability of trauma surgeons . a case of non - operative management of splenic injury in a patient with proteus syndrome complicated with kasabach - merritt syndrome has been reported where a 23-year - old male suffered a grade iii injury after a fall from a horse and was successfully managed with embolization of splenic artery . in our case , delayed splenic rupture could be one of the possible reasons for late deterioration . in view of enlarged spleen with cystic spaces raising suspicions of giant hemangiomas , progressively increasing abdominal distention with pain , two other cases of proteus syndrome involving pubic fractures and recurrent clavicular fractures following trauma have been reported . we suggest that non - operative management ( nom ) should be abandoned , and operative management should be undertaken in splenic trauma if there is some pre - existing splenic pathology ( like in our case splenomegaly with possibility of splenic hemangioma ) along with evidence of hemorrhage or infarction of spleen or significant abdominal pain . nom may still be tried in pathological spleen with trauma if the injury is minimal ( aast grade i injury ) with no significant hemorrhage , abdominal pain , and at no time , the patient had been under hemorrhagic shock / hypotension .

a 20-year - old female with proteus syndrome sustained splenic injury after fall from a bike . she was initially managed non - operatively at a different hospital for three days and was then referred to our level i trauma center in view of increasing abdominal pain and distention . on admission in the emergency department ( ed ) , her pulse rate was 120 per minute and blood pressure was 108/68 mm hg . clinical examination showed a distended abdomen with left hypochondrial pain . ultrasonogram ( usg ) and computed tomography ( ct ) of the abdomen showed splenomegaly and grade iii splenic injury with significant hemoperitoneum . her hemoglobin was 2.9 g / dl with packed cell volume ( pcv ) of 12% . in view of low hemoglobin and possibility of pathologic spleen , splenectomy was done . microscopic examination of the spleen showed hemangiolymphangioma . the patient was discharged on the 5th post - operative day and is doing well at 6 months of follow - up .

angioplasty and stent implantation are often used in the treatment of peripheral arterial occlusive disease ( paod ) . nitinol alloys , the most commonly used as a self - expanding stent material , provide increased flexibility and radial force that allow the stent to adapt to the vessel shape . however , specific stresses and physiological environments can lead to stent fracture . the authors experienced 2 cases of stent fracture among 40 cases of superficial femoral artery ( sfa ) stenting for 14 months . here , we report on 2 cases of stent fractures and include a pertinent literature review . a 75-year - old man presented with recurrence of short distance claudication in the left leg . the patient had hypertension and a previous history of femoropopliteal bypass due to paod on his right sfa . fourteen months ago , the patient underwent primary stenting of the left sfa to treat total occlusion with two overlapping self - expanding stents ( smart , cordis , miami , fl , usa ) . the stent deployed in the distal sfa was 7 mm in diameter and 15 cm in length , and the stent deployed in the proximal sfa was 7 mm in diameter and 12 cm in length with an overlap of 2 to 3 cm . roentgenogram of stents showed complete transverse linear fracture with partial displacement in hunter 's canal distal to the stent overlap area ( fig . femoropopliteal artery bypass with reversed great saphenous vein was done resulting in the resolution of the claudication ( fig . 3 ) . a 72-year - old man with hypertension and ischemic coronary artery disease presented with recurrence of 500 m claudication in both legs . four months ago , the patient underwent primary stenting for chronic total occlusion of sfa due to symptoms of the 500 m claudication . the distal stent was 7 mm in diameter and 15 cm in length , and the proximal stent was 7 mm in diameter and 12 cm in length with 2 cm of overlap in mid sfa . roentgenogram revealed 3 strut fractures without displacement in the mid - sfa portion ( fig . 4 ) , and subsequent angiography revealed multiple in - stent restenosis as well as stent fracture sites ( fig . the narrowed portion of the stented site was dilated with a 6 mm balloon and a 7 60 mm stent was inserted at the site of stent fractures ( fig . a 75-year - old man presented with recurrence of short distance claudication in the left leg . the patient had hypertension and a previous history of femoropopliteal bypass due to paod on his right sfa . fourteen months ago , the patient underwent primary stenting of the left sfa to treat total occlusion with two overlapping self - expanding stents ( smart , cordis , miami , fl , usa ) . the stent deployed in the distal sfa was 7 mm in diameter and 15 cm in length , and the stent deployed in the proximal sfa was 7 mm in diameter and 12 cm in length with an overlap of 2 to 3 cm . roentgenogram of stents showed complete transverse linear fracture with partial displacement in hunter 's canal distal to the stent overlap area ( fig . femoropopliteal artery bypass with reversed great saphenous vein was done resulting in the resolution of the claudication ( fig . a 72-year - old man with hypertension and ischemic coronary artery disease presented with recurrence of 500 m claudication in both legs . four months ago , the patient underwent primary stenting for chronic total occlusion of sfa due to symptoms of the 500 m claudication . the distal stent was 7 mm in diameter and 15 cm in length , and the proximal stent was 7 mm in diameter and 12 cm in length with 2 cm of overlap in mid sfa . roentgenogram revealed 3 strut fractures without displacement in the mid - sfa portion ( fig . 4 ) , and subsequent angiography revealed multiple in - stent restenosis as well as stent fracture sites ( fig . 5 ) . the narrowed portion of the stented site was dilated with a 6 mm balloon and a 7 60 mm stent was inserted at the site of stent fractures ( fig . revascularization with nitinol stent implantation has better long - term results than angioplasty alone ; however , the cumulative incidence of femoropopliteal stent fracture varies from 2 to 65% in several studies looking specifically for stent fractures . type i fracture involves only a single strut ; type ii involves multiple struts that can occur at different sites ; type iii involves multiple strut fractures resulting in a complete transverse fracture without displacement ; type iv results in a complete transverse linear fracture with stent displacement ; and type v is spiral fracture . mild stent fractures rarely lead to complications , however , multiple , migrated severe stent fractures are associated with restenosis or re - occlusion at the stented site . stent fractures occur as a result of a combination of several factors ; physical and anatomical environment , procedural choice , and structural characteristics of the stent itself . sfa is the most common site of infrainguinal paod , but revascularization using an endovascular stent in the sfa is subject to some vulnerable points in this physical and anatomical environment . the mechanical force exerted by the surrounding thigh muscle may cause stent compression or fracture . reported that stent fracture incidence increases with stent length , with the fracture rate being significantly lower in segments less than 8 cm . the overlapped segment may act as fulcrum for stent fracture by focusing the stress on a specific stent site . structural characteristics of the stent also contribute to stent fracture when implanted in a specific setting . nitinol stents , the most commonly used self - expanding stents , have great biocompatibility , elasticity and shape - memory properties ; however their super - elasticity limits the stiffness of the stented vessel creating a hinge point predisposing to stent fracture . however , at times , re - canalization of the occluded stent is impossible . in this case , organization and fibrotic thrombotic in - stent material is the main cause , and many attempts for treatment have been reported by several authors . reported subintimal double - barrel restenting of an occluded primary stented sfa , they passed a guide wire through the subintima of the occluded stent , and created a neo - lumen side - by - side with the occluded primary stent leading to native lumen . two self - expandable stents were positioned in a double - barrel fashion to prevent elastic recoil . otherwise , palena et al . reported a direct stent puncture technique , which consisted in puncturing directly at the occluded point and introduction of a guide wire with a j - shaped tip . another proximal site was punctured and the guide wire was snared through the occluded point recanalizing the occluded lumen with a satisfactory angiographic result . early detection of stent fracture and close follow - up might allow endovascular revascularization of stent obstruction . although there is no universal consensus , jaff et al . suggests a standardized stent surveillance program in which high resolution digital x - ray images are obtained , and follow - up images at 12 , 36 , 60 months after stent deployment are compared to the baseline image obtained following stenting . at each time point , it is recommended to obtain at least 2 views of the stent with different anatomic positions of the limb such as extended and flexed knee . in conclusion , femoral artery stenting is a common treatment for paod . however , stent fracture is one of the factors limiting long - term patency . we experienced two cases of stent fractures and recognized that a stent surveillance program is important for early detection and treatment before stent occlusion .

stent fracture is one of the major factors compromising implanted stent patency due to its consequences including in - stent restenosis , thrombosis , perforation , and migration . stent fracture can occur from stress ( extrinsic or intrinsic ) and biomechanical forces at different implantation sites . we report on 2 cases of stent fractures and pertinent literature . one patient , a 75-year - old male , presented with recurrence of claudication 14 months after superficial femoral artery stenting ; a femoral artery occlusion with stent fracture was found , and he underwent femoropopliteal bypass . the other patient , a 72-year - old male presented with recurrence of claudication ; a stent fracture was found without femoral artery occlusion , and he was treated with additional femoral artery stenting to secure the fracture site .

brucellosis is a highly contagious zoonosis caused by bacteria of the genus brucella and is listed in class b animal epidemics by the world organization for animal health ( oie ) . the genus has six classic species : b. abortus , b. melitensis , b. suis , b. canis , b. ovis and b. neotomae . recently , the marine species b. ceti , b. pinnipedialis , b. microti and b. inopinata were included in the genus ( foster et al . the incidence of human brucellosis is estimated by the oie at 500,000 new cases per year worldwide . however , official statistics is widely acknowledged to be underestimated and , in a considerable number of cases , the origin of the infection is not identified . the majority of human cases worldwide is attributed to b. melitensis ( pappas et al . , 2005 ) . in general , b. melitensis and b. suis are more virulent in humans than b. abortus or b. canis ( who , 2006 ) . other species can cause infection in humans , but only rarely ( diaz aparicio , 2013 ) . the disease is more prevalent in western parts of asia , india , middle eastern , southern european and latin american countries . the transmission of brucella infection and its prevalence in a region depend on several factors , such as dietary habits , methods of processing milk and milk products , social customs , husbandry practices , climatic conditions , socioeconomic status and environmental hygiene ( mantur and amarnath , 2008 ) . as the infectious dose is very low , infections are an occupational risk for farmers , veterinarians , abattoir workers ( schneider et al . , 2013 ) , laboratory personnel and others who work with animals and consume their products ( pepin et al . , 1997 ) . human brucellosis is transmitted by inhalation , animal contact and the consumption of dairy products and undercooked meat products . the consumption of traditional dishes , such as raw liver , can cause human infection ( malik , 1997 ) . however , it has been estimated that even 10 - 100 microorganisms are sufficient to cause the disease in humans ( pappas et al . , 2006 ) . thus , contaminated meat and meat products could represent a source of infection , especially if they come from animals slaughtered during the acute phase of the disease ( fao / who , 1986 ) and if they are consumed raw or undercooked . the handling and preparation of infected meat and offal may give rise to the contamination of other foodstuffs and kitchen utensils ( who / cds / epr/2006.7 ; who , 2006 ) . tests carried out in the us on the carcasses of bovine and swine that were slaughtered because infected revealed that 1.2% of the bovine carcasses and 3.5% of the swine carcasses were contaminated by brucella spp . ( sadler , 1960 ) . in a similar study conducted in india on 100 carcasses of goats , two of the 700 neck muscle samples analysed tested positive for brucella melitensis ( randhawa and karla , 1970 ) . other studies have shown that the offal of slaughtered ruminants constitutes a risk for transmission of the infection ( fatma and mahdey , 2010 ; sekulovski , 2008 ) . in orderto evaluate the prevalence of contamination of meats and to assess the risk of infection for consumers and professionally exposed workers , an investigation on 307 carcasses of bovines , sheep and goats that were slaughtered because they had resulted positive on serological testing for brucella spp . was performed . the study was carried out within the framework of the national programmes for the eradication and monitoring of animal diseases and the prevention of zoonoses in italy , approved by decisions 2011/807/ue and 2012/761/ue of the european commission ( 2011,2012 ) . the study lasted 12 months and was carried out in 10 abattoirs in southern italy , where brucellosis infection is still widespread on cattle , sheep and goat farms . after slaughter , swab samples were taken from 307 carcasses : 40 cattle , 60 sheep and 207 goats . these animals came from 24 different farms and were slaughtered because they had proved positive on serological tests for brucella spp . in previous studies ( randhawa and karla , 1970 ; fatma and mahdey , 2010 ) brucella spp . contamination of the carcasses of slaughtered animals had been evaluated by means of microbiological tests carried out on samples of muscle or organ tissue . in the present study , swab samples were taken in accordance with the procedure indicated by the decision of the european commission ( 2001 ) : duplicate samples were taken by means of swabs both dry and moistened in a sterile aqueous solution which were wiped over the external and internal surfaces of the carcasses immediately after slaughter and before storage in refrigerators . a total of 608 swab samples were taken ; no transport medium was deemed necessary , as the samples were promptly consigned to the laboratory , where they underwent polymerase chain reaction ( pcr ) analysis for brucella spp . in accordance with the following procedure . for dna extraction , a commercially available kit ( qiaamp dna mini kit ; qiagen , valencia , ca amplification was carried out by means of a nested pcr technique , based on a published protocol ( romero et al . , 1995 ; the second step utilised a pair of oligonucleotides that are internal to those used in the first step and produce a smaller fragment ; they prove functional only if the result of the first pcr is specific . ( 5-tcgagcgcccgcaagggt - gagcgg-3 ) and r2 ( 5-aaccatagtgtctc - cactaacc-3 ) allowing an amplification product of 905 bp . in the second step of pcr , the primer pairs r0 ( 5-tagctagttg - gtggggtaaaggc-3 ) and r1 ( 5-caggcttgcgcccattgtcc-3 ) were used allowing an amplification product of 144 bp . to prepare the reaction mixture for the first pcr , 12.5 l of a commercially available pcr master mix ( pcr master mix ; promega corp . , madison , wi , usa ) was used at a 1x concentration for each sample . the reaction mixture contains 50 units / ml of taq polymerase , 400 mm of datp , dgtp , dctp , dttp and 3 mm of mgcl2 . to the reaction mixture , 0.5 l of each primer f4 and r2 at a concentration of 0.2 m and 6.5 l of h2o were added , with a final reaction volume of 25 l . as a positive control in pcr , the negative control was made up only of master mix and water . to prepare the reaction mixture for the second pcr , the thermal profile of the first pcr involved an initial denaturation at 95c for 4 followed by 35 cycles of denaturation ( at 94c for 1 ) , annealing ( at 54c for 1 ) and extension ( at 72c for 1 ) and a final extension at 72c for 7. the thermal profile of the second pcr was the same as the first one except for the cycle number that consisted of 30 cycles in the second pcr . in accordance with italian law and with the aim of eradicating brucellosis in cattle , sheep and goats , the carcasses of infected animals may be freely marketed if the outcome of post - slaughter examination is favourable , while all the internal organs and the udders must be destroyed . parts of these organs were therefore removed and subjected to culture tests for the bacteriological identification and typing of brucella spp . by means of the technique described in the manual of the office international des epizooties , ch . this involves : streaking on brucella agar medium added with a selective supplement and horse serum ; incubation at 37c in an atmosphere enriched with 5 - 10% co2 ; and observation for up to 10 days . subsequent species typing of the isolated strains was carried out at the national reference centre for brucellosis in teramo ( italy ) by means of the pcr - restriction fragment length polymorphism technique , in accordance with the procedure prescribed in vol . the biomolecular tests revealed the presence of brucella spp . in 25/307 carcasses ( 8% ) : 1 bovine carcass ( 2.5% ) of a 9-year - old cow ; 9 carcasses of sheep ( 15% ) aged between 18 months and 5 years , all from the same farm ; and 15 carcasses of goats ( 7.2% ) aged between 12 months and 6 years and coming from 5 different farms ( figure 1 ) . the 25 carcasses found to be contaminated with brucella spp . belonged to 25 animals slaughtered in 6 different slaughterhouses . the bacteriological tests carried out on the organs of all 307 animals examined allowed isolating brucella spp . in 136/307 cases , i.e. 44% the typing analysis allows detecting type 3 brucella abortus in the cattle organs , and type 3 brucella melitensis in the sheep and goats organs . the organs , specifically the lymph nodes , from all the carcasses that had tested positive on pcr on swabs , also proved positive on bacteriological testing for type 3 brucella abortus ( the bovine carcass ) and for type 3 brucella melitensis ( the sheep and goat carcasses ) . the results obtained show that the carcasses ( i.e. , the meat ) of animals slaughtered due to brucella spp . this situation is the same as that seen in the case of other pathogens , like salmonella spp . , for which specific laboratory tests are prescribed and measures have to be taken . in the present study , the percentage of meats that proved to be contaminated was far higher than in the studies quoted above ( sandler , 1960 ; randhawa and karla , 1970 ) . contamination by brucella spp . was detected in a higher percentage of sheep carcasses than cattle or goat carcasses , while the bacteriological tests conducted on the organs detected the highest percentage of contamination among goats . the only brucella serotypes isolated from the organs were type 3 brucella abortus in cattle and type 3 brucella melitensis in sheep and goats . these are the only serotypes that have been isolated in recent years in the geographical area considered ( casalinuovo et al . , 2011 ; de massis et al . , 2014 ) thus , the environments and facilities of slaughterhouses may also be severely contaminated , thereby constituting a risk of contagion for staff involved in butchery and meat handling , and a risk of contamination of the carcasses of other animals that are not infected by brucellosis . indeed , the positivity of the carcasses involved 6/10 slaughterhouses . our samples were taken at the end of the butchery process , when the carcasses were ready for storage in refrigerators or delivery to retail outlets . this means that each contaminated carcass could in turn contaminate equipment and utensils and other meats or foodstuffs . consequently , even in domestic kitchens , contamination could further involve other equipment , utensils and food products . indeed , as brucella spp . survives well at the temperatures reached by refrigerators or freezers , other refrigerated or frozen foods may become contaminated . pcr testing of swab samples taken from the carcasses of animals that had tested positive for brucella proved to be useful . this practice could be applied systematically , since this noninvasive sampling technique does not damage commercial meat cuts , is economically advantageous , and requires far less time ( 24 - 48 h ) than detection by means of culture media . carcasses that resulted positive for pcr might be sequestered and potentially submitted to different confirmation tests . annex i , section iv , chapter ix , f , of regulation ( ce ) n. 854/2004 ( european commission , 2004 ) deals with what should be done with meat from infected animals , and lays down preventive measures to be taken with regard to the specific risks of brucellosis . indeed , the regulation requires that animals proving positive or uncertain for brucellosis have to be slaughtered separately , and that precautions have to be taken to avoid the risk of contaminating other carcasses , the butchery process and the abattoir staff . the udders , genital organs and blood of such animals are classified as unfit for human consumption , while their meat can be freely marketed . only if postmortem examination reveals lesions attributable to acute infection by brucella spp . otherwise , the meat of these animals , just like the meat of healthy animals , is allowed to enter the food chain . these measures are justified by the need to avoid the destruction of large amounts of meat , which is a valuable food source . nevertheless , the results of the present study show that the carcasses , and consequently the meat , of animals positive for brucellosis may be contaminated by brucella spp . this means that consumers may be exposed to the risk of infection , so they should be sufficiently informed with regard to the origin of the meat at the time of purchase .

a study was conducted in order to evaluate the contamination by brucella spp . of meat from animals slaughtered because they had resulted positive for brucellosis at some time during their life . after slaughter and before delivery to market outlets , swab samples were taken from 307 carcasses of infected animals : 40 cattle , 60 sheep and 207 goats . the swabs were subsequently analysed by means of polymerase chain reaction ( pcr ) tests . in addition , bacteriological tests were carried out on the lymph nodes and internal organs of the same animals . brucella spp . was detected by means of pcr in 25/307 carcasses ( 8% ) : 1 bovine ( 2.5% ) , 9 sheep ( 15% ) and 15 goats ( 7.2% ) and was isolated by means of a cultural method in 136/307 carcasses ( 44% ) . moreover , additional analysis , performed on lymph nodes from the same carcasses that had proved positive by pcr , allowed highlighting type 3 brucella abortus in the bovine carcass and type 3 brucella melitensis in the sheep and goat carcasses . the study shows that cattle , sheep and goats meat of animals slaughtered because they had tested positive for brucellosis may be contaminated by brucella spp . as this could constitute a real risk of transmission to both butchery personnel and consumers , the meat of animals infected by brucella spp . should be analysed before being marketed . in this respect , pcr technique performed on swabs proved to be more useful , practical and faster than the traditional bacteriological method .

noninvasive mechanical ventilation ( nimv ) refers to the application of artificial ventilation without an invasive access to the airway ( i.e. , without using an endotracheal or tracheostomy tube ) . the increased popularity of nimv among clinicians and researchers alike is justified by the fact that it spares the patient the complications associated with invasive mechanical ventilation ( imv ) like nosocomial pneumonia ( 21% ) , sinusitis ( 5 - 25% ) , and other airway problems . this , coupled with the availability of better and more accessible interfaces , has greatly increased the usage of nimv over the last decade . its success or failure is essentially determined by appropriate patient selection , correct choice of interface , its correct application , and proper patient monitoring . nimv has assumed a prominent role in the management of acute respiratory failure , and its success in various conditions is supported by literature . the benefits of nimv have been studied most extensively in hypercapnoeic respiratory failure associated with ae - copd by means of multiple , well - designed , randomized controlled trials . other less extensively studied conditions of hypercapnoeic respiratory failure with weaker recommendations in favor of nimv usage include neuromuscular diseases , chest - wall deformities , acute asthma , acute respiratory failure in obstructive sleep apnea / obesity - hypoventilation syndrome , and interstitial lung disease ( ild ) . nimv has also been found to be beneficial in carefully selected patients of hypoxemic respiratory failure , particularly cardiogenic pulmonary edema , and less so in community acquired pneumonia ( cap ) , acute respiratory distress syndrome ( ards ) , and chest trauma with flail chest , among others . the variability in the success of using nimv in different clinical conditions prompted us to conduct this study with the objective of evaluating the feasibility , efficacy , and outcome of using nimv in tertiary care centres . this observational , retrospective study was conducted over an 18-month period ( between november 1 , 2009 and april 30 , 2011 ) in two tertiary level referral medical institutions in north india . a total of 184 consecutive subjects who were treated with nimv ( irrespective of indication ) during the study period were included . criteria of inclusion were patients of respiratory failure with ( a ) respiratory rate > 25/min ; ( b ) signs of increased work of breathing ; ( c ) arterial blood gas ( abg ) analysis showing ph < 7.35 or partial pressure of carbon dioxide ( paco2 ) > 45 mmhg , partial pressure of oxygen ( pao2 ) < 60 mmhg . the exclusion criteria were the same as the contraindications to nimv application , namely cardiac / respiratory arrest , severe encephalopathy ( glasgow coma scale score < 10 ) , severe upper gastrointestinal bleeding , hemodynamic instability , unstable arrhythmias , facial surgery / trauma / deformity , upper airway obstruction , inability to cooperate / protect airway / clear secretions , and high risk for aspiration . all patients were grouped according to the underlying clinical condition that prompted the application of nimv . nimv was started by pulmonologists in the emergency department and , if required , patients were shifted to intensive respiratory care unit ( ircu ) . bilevel positive airway pressure ( bipap ) system ( resmed , vpap iii sta ) with a full - face mask was used to apply nimv using st mode . the outcome of nimv usage in each group was measured in terms of the number of patients cured by nimv and those who failed on nimv . patients who failed on nimv were further evaluated regarding requirement of intubation and those who subsequently survived or expired . the other variables collected in the study included abg parameters ( ph , paco2 , and pao2 ) and the mean duration of nimv application . paired t test and analysis of variance ( anova ) the outcome of nimv usage in each group was measured in terms of the number of patients cured by nimv and those who failed on nimv . patients who failed on nimv were further evaluated regarding requirement of intubation and those who subsequently survived or expired . the other variables collected in the study included abg parameters ( ph , paco2 , and pao2 ) and the mean duration of nimv application . paired t test and analysis of variance ( anova ) out of a total of 184 patients who were included in the study , most of the patients belonged to the age group 41 - 59 years ( 78 patients , 42.39% ) [ table 1 ] . the number of male patients ( 95 patients , 51.6% ) slightly exceeded the number of female patients ( 89 patients , 48.4% ) . the most common indication for application of nimv in our centers was acute exacerbation of copd ( 148 patients , 80.43% ) . other less common indications for nimv were cap ( consolidation ) , ards , pulmonary edema , bronchiectasis , ild , asthma , and kyphoscoliosis . demographic characteristics of study subjects in copd patients , the change in ph , paco2 , and pao2 from baseline to after 24 h and at the time of discharge was significant ( p < 0.0001 by paired t test and anova ) . however , in non - copd patients , the change in ph and paco2 from baseline to after 24 h and at the time of discharge was not significant , but the change in pao2 values from the baseline to at the time of discharge was significant ( p < 0.00001 by paired t test and anova ) [ table 2 ] . abg trends in copd and non - copd patients at admission , after 24 h of nimv application , and at discharge the mean duration of nimv usage in ae - copd patients was 8.35 5.98 days [ table 3 ] . patients with underlying ild required the maximum duration of nimv support ( 17 8.48 days ) ; 134 of the 148 patients with underlying copd ( 90.54% ) were improved with nimv . all patients with underlying cap ( 8 numbers ) , pulmonary edema ( 6 numbers ) , bronchiectasis ( 6 numbers ) , or kyphoscoliosis ( 2 numbers ) were benefitted with nimv , while none of the patients with ards ( 6 numbers ) showed any improvement . among ild and asthma patients , 50% ( 2 out of 4 ) patients showed improvement with nimv and 13.04% ( 24 out of 184 ) patients on nimv required intubation and mechanical ventilation . most of the complications were in the form of worsening respiratory distress despite nimv application , which necessitated endotracheal intubation and invasive ventilation . the latter brought along associated complications like ventilator - associated pneumonia , sepsis , and cardiac arrest . the most promising use of nimv appears to be in patients of ae - copd with hypercapnoeic respiratory failure who are on standard medical treatment . the results of our study strongly support and encourage the use of nimv as the first - line ventilatory treatment in this group of patients . these patients showed significant improvement in abg parameters at the time of discharge as compared to the baseline values . in this regard , numerous randomized controlled trials have been conducted in the past that highlight the benefits of nimv usage in this group of patients in terms of reduced rate of endotracheal intubation and mortality , shortened length of icu and hospital stay , and reduction of complications like nosocomial pneumonia . meta - analyses of these trials have also confirmed benefits of nimv in ae - copd . studies have also found that early initiation of nimv is associated with better outcome compared to delayed initiation . even in sick patients who required immediate intubation , nimv was shown to avoid intubation in almost 50% of the patients in a prospective randomized controlled trial by conti et al . nimv was not found to be beneficial in copd patients with mild exacerbation . in this study , copd patients were the ones who most commonly presented with type 2 respiratory failure ( respiratory acidosis ) . nimv application facilitated co2 wash - out in these patients and helped regain normocapnea ( from 66.48 16.24 at baseline to 56.37 12.37 at discharge , p < 0.0001 ) [ table 2 ] and a normal ph ( from 7.334 0.08 at baseline to 7.421 0.062 at discharge , p < 0.0001 ) [ table 2 ] . non - acidotic copd patients were also benefited by nimv as it helped decrease the respiratory rate by resting the respiratory muscles and thereby reducing the work of breathing , improving patient comfort , and possibly preventing the onset of frank respiratory failure and acidosis . regarding patients of cap , our results differ from those of previous studies in that all our 8 patients of cap this could possibly be attributed to the fewer number of cap patients in our study . previous published studies on the use of nimv in hypoxemic respiratory failure in cap have shown conflicting results . some of these have shown no major benefit of nimv in this group of patients . on the other hand , a randomized controlled trial done on patients with severe cap and hypoxemic respiratory failure in a subgroup of copd patients has demonstrated major benefit of nimv . however , these studies largely lead to the conclusion that nimv may be useful in carefully selected cap patients , particularly those with concomitant copd . whatever may be the reason , a trial of nimv may not prove harmful , if not useful , in this group of patients . in our study , none of the patients having ards could be benefitted by nimv and mortality rate following intubation was nearly 67% . usefulness of nimv in ards is questionable , as suggested by the limited studies available . in a study by rocker et al . two other studies that included ards patients in comparing nimv with a conventional approach found that the rate of endotracheal intubation in ards patients randomized to nimv was 40% and the mortality rate in these patients was 35% . it may be concluded that nimv should be very carefully applied to ards patients who are preferably hemodynamically stable , in an intensive care setting . a beneficial outcome was seen in all 6 patients of pulmonary edema in whom nimv was applied in the present study . among the causes of hypoxemic respiratory failure , nimv has been found to be very effective in patients of cardiogenic pulmonary edema in previous studies . a study by nava et al . , revealed that , in these patients , nimv , in comparison to medical therapy plus oxygen , resulted in an improvement of pao2/fio2 ratio , respiratory rate , and dyspnea , but had no beneficial effect on intubation rate , hospital mortality , and duration of hospital stay . thus , in addition to standard medical therapy , nimv appears to be a feasible supplementary treatment in acutely decompensated patients of cardiogenic pulmonary edema . among asthmatics , as far as the use of nimv in bronchial asthma is concerned , the evidence is inconclusive . a retrospective analysis shows rapid improvement of blood gases and less hypercapnea in asthmatics treated with nimv . a randomized controlled trial showed beneficial effect of nimv in selected patients of asthma in terms of improved lung function , faster alleviation of symptoms , and reduced need of hospitalization . thus , nimv may be tried in those asthmatics that respond inadequately to medical therapy and have no contraindication for nimv usage , preferably in the icu . no randomized controlled trials have examined the effect of nimv in patients of chest wall deformity like kyphoscoliosis and neuromuscular diseases . only some retrospective case series suggest that nimv alleviates gas exchange abnormalities and avoids intubation in this group of patients who present with respiratory failure . thus , nimv may be beneficial in these patients when they present with acute - on - chronic respiratory failure . to conclude , this study demonstrates the feasibility and efficacy of nimv applied in regular clinical practice . the results strongly support and encourage the use of nimv as a first - line ventilatory treatment in ae - copd patients with respiratory failure . nimv should also be considered in other causes of respiratory failure as a promising step toward prevention of mechanical ventilation .

background : noninvasive mechanical ventilation ( nimv ) is the delivery of positive pressure ventilation through an interface to upper airways without using the invasive airway . use of nimv is becoming common with the increasing recognition of its benefits.objectives:this study was done to evaluate the feasibility and outcome of nimv in tertiary care centres.materials and methods : an observational , retrospective study conducted over a period of 18 months in two tertiary level hospitals of north india on 184 consecutive patients who were treated by nimv , regardless of the indication . nimv was given in accordance with the arterial blood gas ( abg ) parameters defining respiratory failure ( type 1/type 2).results : the most common indication of nimv in our hospitals was acute exacerbation of chronic obstructive pulmonary disease ( ae - copd 80.43% ) , and 90.54% ae - copd patients were improved by nimv . application of nimv resulted in significant improvement of ph and blood gases in copd patients , while non - copd patients showed significant improvement in partial pressure of oxygen ( pao2 ) alone . the mean duration of nimv was 8.35 5.98 days , and patients of interstitial lung disease ( ild ) were on nimv for the maximum duration ( 17 8.48 days ) . none of the patients of acute respiratory distress syndrome were cured by nimv ; 13.04% patients on nimv required intubation and mechanical ventilation.conclusion:this study demonstrates and encourages the use of nimv as the first - line ventilatory treatment in ae - copd patients with respiratory failure . it also supports nimv usage in other causes of respiratory failure as a promising step toward prevention of mechanical ventilation .

despite its many advantages reported over two decades ago , chemotherapy - induced nausea and vomiting ( cinv ) are the most undesirable and common side effects of chemotherapy among patients undergoing cancer treatment . the incidence of nausea and vomiting , the most common side effects , is 70 - 80% . they are not only improper and undesirable , but also cause pulmonary and metabolic effects , nutritional deficit , dehydration , acute renal failure , esophageal injuries , electrolyte imbalance , weakness , and also increase infection sensitivity and stop children 's normal activity . cinv is an important cause of disturbing the normal pattern of cancer treatment and can influence children 's willingness to continue scheduled chemotherapy . antiemetics administration is essential and considered the proper method to reduce nausea and vomiting , but they are not useful for all patients and often cause undesirable side effects including agitation , dizziness , anorexia , hypotension , arrhythmia , and rash , which can increase the problems in the patients . in recent years , complementary therapies are increasingly integrated into cancer programs and the numbers of people that use complementary and alternative medicine have increased . different studies have shown that massage reduces anxiety , depression , eating disorders , stress , and asthma in children . wolf et al . found massage and acupuncture significantly decreased postoperative pain in patients with cancer . another study showed that 5-min foot massage is effective in reducing the severity of nausea . it was shown that two - session foot massages reduced nausea and heart rate and improved objective pain experiences in each session . although massage is used for children with cancer , few studies have assessed its effectiveness on cinv in children . it only needs time . by considering the fact that pediatric nurses are important members of medical health groups and have essential role in pediatric cancer care , their skills and performances could improve the quality of the care . therefore , this study was conducted to find the effect of massage therapy on cinv in pediatric cancer . this study is a randomized controlled trial in which the effects of massage therapy on nausea and vomiting indices within and during 48 h after chemotherapy were assessed . this is a two - group randomized controlled trial in which randomization was done by randomized number table . the sample size , based on a pilot study , was 70 ( 35 each in control and intervention groups ) . the inclusion criteria included : diagnosed cancer by an oncologist , at least 3 days hospitalization for chemotherapy protocol , being 4 - 18 years old , and no history of any other health history issues or any disease other than cancer . exclusion criteria included : diagnosed psychosomatic disorders , loss of consciousness , gastrointestinal and nervous system cancer , wilm 's tumor and any other mass or surgery in the abdominal area , patients using sedatives or opium drugs , having sore and injury in the massage area , metastasis , participants under radiation , children with port - a catheter , and having single parent . we used swedish massage with effleurage , petrissage , friction , and tapping movements with mild to moderate pressure . in three sessions , children were massaged for 20 min , 24 and 0.5 h before chemotherapy and 24 h after chemotherapy by the therapist , who was skilled in massage therapy . the massage was provided in a private room at the hematology / oncology ward and blankets were available . parents remained in the room during the child 's massage , during chemotherapy , and in the ward . the participants continued with the therapy they had been using when they joined the study and parents remained behind the child in the ward and during the chemotherapy program . therapist stayed with the children in the control group 24 and 0.5 h before chemotherapy and 24 h after chemotherapy to eliminate emotional effect . barf ( baxter animated rating face ) scale was used for 4 - 9-year - old children and visual analogue scale ( vas ) for 9 - 18-year - old children to assess nausea severity . vas is a proved device that has efficiency and precision in the assessment of nausea intensity and used in different studies . then we decided to use the barf scale for 4 - 9-year - old children . barf is a self - report pictorial animated rating face scale used for measuring nausea in children under 9 years of age . it has six faces depicting the levels of nausea and has good reliability ( r = 0.819 ) . in our study also , it showed good reliability ( r = 0.852 ) . a four - item rating scale was used to assess vomiting severity . in this scale , severity of vomiting was numbered from 0 to 3 ( 0 , no vomit no severity ; 1 , mild ; 2 , moderate ; 3 , severe ) based on the vomiting episodes during the first 24 h and for the following 2 days after chemotherapy . nausea and vomiting indices were documented by a research assistant during chemotherapy and by parents after chemotherapy for 48 h. data were analyzed by spss version 11.5 . seventy - four children entered in our study ( massage = 37 and control = 37 ) , but the analyses were done on 70 children because of four eliminations from the study ( two in the control group due to patients not filling the forms completely and two in the massage group because of fever and neutropenia that cancelled their chemotherapy program ) . kolmogorov smirnov test showed that the indices of nausea and vomiting were not normally distributed . therefore , non - parametric statistical tests were used for the analysis . mean age of the participants was 8.6 3.3 years . classification of age groups by mann whitney ( m - w ) u - test was not significant . there were 60% ( n = 21 ) boys in the intervention group and 51.4% ( n = 18 ) in the control group . no significant differences were found between the intervention and control groups , with regard to sex on statistical test . acute lymphocytic leukemia was the most common type of cancer in each group ( intervention = 71.4% and control = 71.4% ) , and chi - square fisher 's exact test showed no significant difference between the two groups regarding the type of cancer . chemotherapeutic agents in regard to their emetic potential are classified into three emetic risk groups : high , moderate , and low . fisher 's exact test showed no significant differences between the intervention and control groups regarding the chemotherapy emetic potential . length , weight , economic status , location , and child birth showed no significant difference between the two groups . statistical test was used to analyze the incidence ( yes or no ) of nausea and vomiting . m - w u - test was used to analyze the frequency and severity of nausea and vomiting and also the duration of nausea . the findings showed no significant differences in the levels of nausea and vomiting during chemotherapy between the two groups . incidence of nausea during 48 h post - chemotherapy and its overall incidence between the two groups showed significant statistical differences ( p = 0.027 ) . other findings such as frequency , duration , and the intensity of nausea , and the intensity and frequency of vomiting are summarized in tables 1 - 3 separately . indices of nausea during and after chemotherapy severity of vomiting during and after chemotherapy frequency of vomiting during and after chemotherapy kolmogorov smirnov test showed that the indices of nausea and vomiting were not normally distributed . therefore , classification of age groups by mann whitney ( m - w ) u - test was not significant . there were 60% ( n = 21 ) boys in the intervention group and 51.4% ( n = 18 ) in the control group . no significant differences were found between the intervention and control groups , with regard to sex on statistical test . acute lymphocytic leukemia was the most common type of cancer in each group ( intervention = 71.4% and control = 71.4% ) , and chi - square fisher 's exact test showed no significant difference between the two groups regarding the type of cancer . chemotherapeutic agents in regard to their emetic potential are classified into three emetic risk groups : high , moderate , and low . fisher 's exact test showed no significant differences between the intervention and control groups regarding the chemotherapy emetic potential . length , weight , economic status , location , and child birth showed no significant difference between the two groups . statistical test was used to analyze the incidence ( yes or no ) of nausea and vomiting . m - w u - test was used to analyze the frequency and severity of nausea and vomiting and also the duration of nausea . the findings showed no significant differences in the levels of nausea and vomiting during chemotherapy between the two groups . incidence of nausea during 48 h post - chemotherapy and its overall incidence between the two groups showed significant statistical differences ( p = 0.027 ) . other findings such as frequency , duration , and the intensity of nausea , and the intensity and frequency of vomiting are summarized in tables 1 - 3 separately . indices of nausea during and after chemotherapy severity of vomiting during and after chemotherapy frequency of vomiting during and after chemotherapy according to the findings of this study , nearly all indices of nausea and vomiting significantly decreased after chemotherapy by massage and showed it is as a useful method for control of cinv in children , besides the routine cancer treatment . but although massage decreased nausea and vomiting during chemotherapy , the decrease was not significant . studies show that acute cinv occurs 1 - 2 h after chemotherapy by the first 24 h and delayed cinv occurs 24 - 72 h after chemotherapy . in our study , during chemotherapy , patients had no nausea or vomiting , except those who had anticipatory type , because the effect of chemotherapeutic drugs did not start and the effect of massage was not significant during chemotherapy . the most important point of this study was assessing all the indices of nausea and vomiting , including intensity , frequency , and incidence of nausea and vomiting , and also nausea duration , while other studies such as that of najafi et al . have only examined the nausea index and not the other indices of nausea and vomiting . the results of najafi et al . , dune et al . , and grealish et al . these investigations also showed that massage therapy is an effective method to reduce the cinv . also described that massage is useful for symptom management including nausea in children with cancer . wolf et al . found combined massage acupressure to decrease the symptoms of children with cancer , such as nausea , but that was not significant . it may be a result of the small sample size ( massage = 16 and usual care = 7 ) in their study , and if the study had been done in a larger sample size , the effect of massage might have been significant . since in our study massage therapy was performed in three sessions of 20 min each and two sessions of the massage were done before beginning the chemotherapy protocol , it shows the positive effect of this intervention on nausea and vomiting , and then confirms our findings . in addition , by the three - massage session , we were not only able to control acute nausea and vomiting , which starts 1 - 2 h after chemotherapy , but also delayed nausea and vomiting , which occurs 24 - 72 h after chemotherapy . since good control of acute cinv can improve delayed and anticipatory cinv , we conclude that good control of cinv in the beginning of the chemotherapy program leads to good control of cinv in the other treatment stages and improves the patient 's well - being . different studies have shown that stress and pain are two important factors that increase cinv and that massage causes relaxation , reduces stress and pain in patients , therefore massage therapy can also help to improve cinv by reducing stress and pain and enhancing psychological and physiological well - being . in addition , massage has a psychological impact on patients and the involvement of psychological phenomenon affects the limbic system , the center of people 's feelings , which is connected to vomiting center by neurological fibers ; so , it can be effective in improving nausea and vomiting by connecting massage signals to the limbic system and vomiting center . but additional researches need to examine the real mechanism of massage therapy on nausea and vomiting . the results of the present study could be a guideline for nurses , which enable them to , relying on their competencies and knowledge , as well as communicating them to the parents , have a useful contribution in reducing the patients sufferings . but as this investigation was performed in children as three sessions of 20 min each , and a child 's cooperation and endurance is lower than adult 's , it is suggested that further studies should examine the short - term effects of massage on nausea and vomiting indices .

background : nausea and vomiting are the most common and unpleasant side effects of chemotherapy , and they may prevent successful treatment completion . antiemetics not only can not control nausea and vomiting completely but also have numerous side effects . so it is necessary to find other methods for a better control . this study aimed to assess the effect of massage therapy on chemotherapy - induced nausea and vomiting in pediatric cancer.materials and methods : in this randomized controlled clinical trial study , 70 patients ( 4 - 18 years of age ) under chemotherapy were divided into two ( massage therapy and control ) groups randomly . in the massage group at 0.5 h and 24 h before and 24 h after chemotherapy , the patients were massaged ( swedish massage ) for 20 min , respectively . all indices of nausea and vomiting ( incidence , severity , time , and length ) were assessed by visual analogue scale ( vas ) and barf scales and other questionnaires and documented.results:the results of mann whitney and chi - squire tests indicated that in the massage group , the incidence of nausea was 25.7% , the severity , length , and times of nausea were 20% , 54 min , and 0.35 times , respectively , and the severity and times of vomiting were 0.24 scores and 0.31 times lower than those of the control group ( p < 0.05 ) , respectively . but vomiting incidence in the two groups showed no significant difference ( p = 0.192).conclusions : massage therapy reduced chemotherapy - induced nausea and vomiting . so , nurses can use it and educate it to the patients families . nurses , besides using it clinically , can provide instructions to families for involving them in the treatment process and they feel they are more efficate in care of their suffering children .

the accessory parotid gland , or the accessory parotid , is a nodule of normal salivary tissue that is separate from the main parotid gland and it is located on the masseter muscle , and it is connected to stensen 's duct at that level ( 1 ) . although accessory parotid gland is a common variation ( 2 ) , a fistula from an accessory parotid gland to the facial skin is extremely rare ( 3 , 4 ) . it was reported that congenital fistula from an accessory parotid gland could be diagnosed with performing ct sialography or ct fistulography ( 5 ) . we report a case of congenital fistula arising from an accessory parotid gland and it was treated by chemocauterization of the fistula with trichloroacetic acid ( tca ) , and this was accompanied with a botulinum toxin injection to the accessory gland parenchyma . a 1-yr - old girl presented with a salivary discharge at the facial skin of her right cheek . ct sialography was done and a sialo - cutaneous fistula from an accessory parotid gland was diagnosed ( fig . 1 ) . she also had a skin tag on the tragus of the right ear . at that time the clinical examination demonstrated a 1 mm - sized opening located at the facial skin 1 cm lateral to the angle of mouth . it revealed that the flow from the accessory gland was about 10% of the total flow of a parotid gland . according to our previous experience ( 5 ) , fistulectomy was scheduled , but aesthetic considerations for the young girl made the surgical plan change to more conservative management . under general anesthesia , although the accessory gland was too small to be clearly identified , 16 iu of botulinum toxin was injected to the accessory gland under ultrasound guidance . after thin adhesive film was attached on the buccal skin around the fistula opening to prevent spillage of corrosive agent from unwanted skin injury , about 2 ml of 40% tca solution was injected into the tract with a small metal suction tip ( fig . after several days , a tensely inflated sialocele formed and the opening was found to be completely closed up . aspiration was done with long subcutaneous tunneling from behind so as not to make an iatrogenic sialo - cutaneous fistula . during one year follow - up , there was no more salivary leakage or sialocele . because congenital fistula from an accessory parotid gland is a very rare condition , there is no proven treatment of choice for this type of lesion . there is a case report that a fistula was managed by open translocation to the oral cavity using delore 's method ( 3 ) . in our previous experience ( 5 ) , a 5-yr - old girl with a congenital cutaneous fistula from an accessory parotid gland was successfully treated with excision of the accessory parotid gland and duct . although the skin incision was performed along the skin tension line , a scar on the face inevitably remained . to prevent facial scarring , tca is a potent cauterizing agent that has been used for chemical peeling and the treatment of papilloma . what we use in practice is neutralized by the serum and it is systemically non - toxic . we have performed cases of tca cauterization for the treatment of pyriform sinus fistula , and we reported on its feasibility ( 6 ) . tca permeates into the fistula and makes it possible to close the entire fistula tract . in this case , the fistula opening was obliterated with tca cauterization in the early postoperative days . this might have happened because granulation tissues and necrotic tissue debris from injured epithelium of the tract blocked the relatively long fistulous tract . botulinum toxin injection to minimize salivary secretion ( 7 ) was thought to be ineffective in this case because of the difficulty in demarcating the small accessory parotid gland . although sialocele occurred repeatedly , it was controlled completely with repeated aspiration for about one month . it might be very important to make a long subcutaneous tunnel while aspirating the accumulated saliva not to make a new uncontrollable sialo - cutaneous fistula . the level 35 - 50% tca is the spectrum of medium - depth peeling , and 45% or 50% tca corresponds to a wounding level of mid to deep reticular dermis ( 8) . so it would be hardly possible for 40% tca to penetrate the epithelialized fistulous tract and to injure the nerves and vessels . in conclusion , tca cauterization is an easy and effective option for the treatment of congenital fistula from the accessory parotid gland , especially from the aesthetic point of view .

congenital sialo - cutaneous fistula arising from the accessory parotid gland is extremely rare . although the fistula tract can be successfully excised after making a skin incision along the skin tension line around the fistula opening , a facial scar inevitably remains . we here report a case of sialo - cutaneous fistula that was treated with chemocauterization with trichloroacetic acid ( tca ) . tca cauterization is an easy and effective option for the treatment of congenital fistula from an accessory parotid gland , especially from the aesthetic point of view .

basal cell adenoma ( bca ) is a rare entity belonging to the group of basaloid tumors and was named so by kleinssaser and klein ( 1967 ) . it was initially included in the group of nonpleomorphic adenomas of the salivary gland , more specifically subsequently , the 1991 who classification of salivary gland tumors included it in the category of benign epithelial neoplasms as a discrete entity . less frequently , it may involve minor salivary glands , with upper lip being the most common site , followed by buccal mucosa . it is a slowly progressive benign neoplasm which on computed tomography scan indicates a well - circumscribed lesion . clinically , it usually appears as painless , firm and mobile slow - growing mass , more common in the 7 decade with a female predilection ( 2:1 ) , except for the membranous type which bears an equal male : female distribution . it gives a uniform histologic appearance dominated by basaloid cells arranged in solid , trabecular , tubular or membranous patterns . solid bca is formed by small cells organized in a compact manner . in the trabecular and tubular subtypes , groups of cells exist in narrow bands and ductal structures or a combination of both . a membranous subtype is constituted by external cells in a stockade pattern and by an intense hyalinized basal membrane . a 70-year - old male patient reported with the complaint of the unhealed wound in the mouth for 6 months after he pulled out a loose upper right molar himself . he also reported a gradually increasing swelling and numbness over the right maxillary sinus region , blocked nostril and decreased hearing from the same side of the lesion . extraorally , the patient had diffuse swelling over the right maxillary sinus region extending over the ala of the nose [ figure 1 ] . intraorally , there was an unhealed socket of 17 with necrosed bone inside , surrounded by everted margins [ figure 2 ] . extra orally diffuse swelling over the right maxillary sinus extending onto the ala of nose intraoral examination revealed unhealed socket of 17 surrounded by everted margins and necrosed bone within contrast - enhanced computed tomography revealed an ill - defined heterogeneously enhancing neoplastic mass of size 6.1 cm 3.8 cm 3.3 cm involving the right maxillary sinus and extending to ethmoid sinus , masticator space and infratemporal region causing destruction of the walls of the maxillary sinus . contrast - enhanced computed tomography exhibiting nonhomogeneous enhancing lesion destroying walls of maxillary and ethmoid sinus , upper right alveolus and extending into masticator space and infratemporal region incisional biopsy showed an encapsulated mass consisting of isomorphic basaloid cells forming trabecular and tubular structures in a scanty stroma . these structures were seen infiltrating into the overlying epithelium [ figure 4 ] and showed two cell populations : peripheral tall columnar and central round to ovoid cells . the central cells displayed discohesiveness giving stellate reticulum - like appearance in a considerable portion of the lesion . some of the central areas showed the presence of mucous cells and mucin filled spaces [ figure 5 ] . at places , the tumor cells formed canalicular structures enclosing hemorrhagic spaces [ figure 6 ] . a provisional diagnosis of ameloblastoma and differential diagnosis of basal cell adenocarcinoma ( bcac ) , bca and canalicular adenoma were made . periodic acid - schiff stain revealed patchy positivity at the periphery of islands and in the cytoplasm of the central cells indicating a salivary gland origin [ figure 8 ] . on immunostaining , strong positivity for calponin in the peripheral basaloid cells was suggestive of myoepithelial cells [ figure 9 ] . cytokeratin ( ck 19 ) positivity in the central cells and cells in cords was suggestive of luminal cells [ figure 10 ] . final diagnosis of locally aggressive bca was given based on the histopathologic and immunohistochemical findings . because of the extensive lesion , the patient was referred to the higher center for treatment . however , patient refused treatment because of general illness . basaloid islands and cord - like structures infiltrating the overlying epithelium , areas of mucous cells and mucin filled spaces are also seen ( h&e stain , 40 ) peripheral palisaded arrangement of columnar cells and central loose cells showing stellate reticulum - like appearance with interspersed mucous cells ( h&e stain , 400 ) tumour cells forming canalicular and tubular structures enclosing haemorrhagic spaces ( h&e stain , 100 ) calretinin negativity ruled out ameloblastoma ( ihc stain , 400 ) periodic acid schiff ( pas ) stain positivity at periphery of islands and cytoplasm of central cells ( pas stain , 400 ) calponin immunostaining shows strongly positive peripheral cells of the lesion suggestive of myoepithelial cells ( ihc stain , 400 ) ck 19 showed patchy positivity in the center of islands at places and the tubular structures ( ihc stain , 400 ) ki-67 index < 5% ( ihc stain , 400 ) bca is a rare benign neoplasm characterized by the basaloid appearance of the tumor cells and absence of the myxochondroid stromal component as present in pleomorphic adenoma ( who 2005 ) . it was reported as a distinct entity for the 1 time by kleinsasser and klein in 1967 . batsakis is credited for reporting the first case in the american literature in 1972 and suggesting the intercalated duct reserve cell as the histogenetic source of bca . later studies endorsed the origin of bca to myoepithelial and/or intercalated duct lineage . in the armed forces institute of pathology , series up to 75% of bcas are reported in parotid gland , 5% in submandibular gland and 6% in intraoral location with upper lip being the most common site , followed by the buccal mucosa . an incidence of approximately 1% in the oral minor salivary gland has been reported by takahashi et al . it occurs most commonly in the 6 or 7 decade of life in the present case , age of the patient was in accordance with the literature , whereas the site of neoplasm was rare and unique with only single case reported previously in english literature ( 2012 ) . the ill - defined and extensive nature of the lesion along with a patient 's complaint of decreased hearing from the same side ear , blocked nostril and numbness over the involved region exhibited an aggressive nature of the lesion in contrast to the usual presentation of the bcas . most of the imaging studies done on bca concluded it of having well - defined and smooth marginal morphologies . a few cases have shown nonhomogenous enhancements with either cystic areas , linear bands or stellate - shaped areas of nonenhancement . in the present case , ill - defined , nonhomogeneous enhancing mass causing local destruction a feature not previously reported in bca so far raised the suspicion of malignancy . the first cell type is a basaloid cell frequently found peripherally , in the cell nests and cords arranged in a palisaded manner . they are cuboidal or columnar cells and are usually single - layered , but multiple layers may be seen peripherally . the second cell type is larger with modest cytoplasm , indistinct cell borders and a pale - staining oval nucleus located at the center of the tumor nests . the electron microscopic and immunohistochemical evaluation of the bca have shown luminal ( ductal ) and nonluminal cells ( myoepithelial and basal cell ) of variable differentiation . the luminal cells may show basosquamous or rarely true squamous cell differentiation , even forming keratin pearls . nonluminal cells may be devoid of specific differentiations or show ultrastructure features indicative of myoepithelial cell development . similarly , immunoreactivity to s100 and vimentin was seen in most bcas but was typically localized to peripheral tumor cells . in a study of 14 cases of bca , zarbo established that staining with antibodies to -sma and calponin was of equivalent measure in all the bcas . in an another study by de arujo et al . on 114 cases of minor salivary gland tumors , it was observed that luminal cells from bca , pleomorphic adenoma , adenoid cystic carcinoma and epithelial myoepithelial carcinoma expressed ck 7 , 8 , 14 and 19 . p63 a nuclear marker for basal / stem cells of stratified epithelium and myoepithelial cells is strongly positive in bca . this marker , however , is of limited use in the differential diagnosis because most other diagnostic considerations , aside from canalicular adenoma , are positive as well . basal / myoepithelial cell component is a key and essential diagnostic criterion . in the present case , immunopositivity for calponin and ck 19 confirmed participation of both myoepithelial and luminal cells aiding the final diagnosis of bca . globally , it has been accepted that the bca may adopt an ameloblastoma - like pattern because of the palisaded nature of the peripheral layer of basaloid cells . the distinction could be especially problematic for lesions that occur in the odontogenic regions , which fortunately are uncommon . in the present case , however , ameloblastoma can be ruled out by the fact that , reverse polarization of nuclei typical of peripheral ameloblast - like cells is not observed in bca . who ( 2005 ) has defined bcac as cytologically and histomorphologically similar to bca but is an infiltrative epithelial neoplasm with potential for metastasis . owing to the extensive local destruction , bcac was also considered in the differential diagnosis , but the low ki-67 index did not support the suspicion of a malignant neoplasm , i.e. , bcac or basaloid squamous cell carcinoma ( bscc ) . bcac can be distinguished from bca by its infiltrative and metastatic potential , but its extensive infiltrative growth has been rarely encountered and is essentially a low - grade malignancy . regional recurrences or distant metastases have been described in bcac since it was first reported , but later authors have noted that certain of these cases have unusual histologic features that are seen in some other similar tumors such as adenoid cystic carcinoma . to identify additional morphological and immunohistochemical characteristics that can assist in differentiating bcacs from bcas , jung et al further , bcas with capsular invasion shared several pathologic features with bcacs . based on these findings , they suggested that it can be difficult to distinguish early stage bcacs from bcas that exhibit minimal capsular invasion because of lack of immunohistochemical or molecular evidence supporting the notion that bcas with capsular invasion may be early bcacs . none of their patients diagnosed as bcac manifested recurrences or metastases after surgery with or without radiotherapy . therefore , they posited that the bca can be viewed as an infiltrative neoplasm and questioned the category of its malignant counterpart bcac . basaloid islands were seen either infiltrating from or into the epithelium giving the impression of bscc . however , the deeper tissue showing the presence of many canaliculi with double layered cells , enclosing hemorrhagic spaces with very scanty stroma a feature of canalicular adenoma ruled out bscc . tubular trabecular variants of bca at low power can be confused with canalicular adenoma , but closer examination can reveal participation of both luminal and basal cells and more collagenized stroma compared to canalicular adenoma . lack of myoepithelial cells in canalicular adenoma further helps in the diagnosis . in the past , later , in 1983 , gardner and daley showed the distinction between bca and canalicular adenoma . none of the smooth muscle cell antibodies bind cells of canalicular adenoma allowing specific immunohistochemical differentiation . on the other hand , recurrence and malignant transformation in canalicular adenoma are rare . in ameloblastoma , the rate of recurrence reported in various reviews is diverse and range from 20% to 90% . the recurrence rate after conservative therapy ( 34.7% ) comes out to be about twice that associated with radical therapy ( 17.3% ) . this rare entity can thus be summarized as a great mimicker and may mislead a clinician causing diagnostic threat leading to severe morbidity and fatality . thus , recognizing and aiding proper therapy is a must . moreover , larger studies and literature review for bca and bcac is must to distinguish these two varieties or confirm the behavioral status of these lesions . although bca is a rare lesion in the minor salivary glands , it should be considered in the differential diagnosis of a palatal lesion . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed . the authors certify that they have obtained all appropriate patient consent forms . in the form the patient(s ) has / have given his / her / their consent for his / her / their images and other clinical information to be reported in the journal . the patients understand that their names and initials will not be published and due efforts will be made to conceal their identity , but anonymity can not be guaranteed .

basal cell adenoma ( bca ) is a rare basaloid tumor , with only 20% of cases occurring in minor salivary glands . histologically , bca is characterized by the presence of basaloid cells and may frequently be mistaken with canalicular adenoma , basal cell adenocarcinoma , adenoid cystic carcinoma and basaloid squamous cell carcinoma . immunohistochemistry may aid in arriving at a final diagnosis as in the present case . reported here is a case of locally aggressive bca . histologically , the lesion mimicked ameloblastoma and other entities which posed a diagnostic challenge . there are no reports of bca presenting as an aggressive lesion available in english literature so far ; moreover , merely a single case of bca of maxillary sinus has been previously reported to the best of our cognition . this case report highlights the rarity of this tumor with regards to its site of origin , clinical behavior and histopathological mimics .

ciliopathies are recently categorized group of genetic disorders that occur due to dysfunction of primary cilia and can affect multiple organ systems . the predominant features of this syndrome are retinal dystrophy , obesity , polydactyly , learning disability , hypogonadism , and renal abnormalities . though structural renal abnormalities are common in these patients , chronic kidney disease as a feature of this syndrome has been reported rarely . an 18-year - old female was referred to our hospital for evaluation of swelling of legs of 2 months duration . there was history of bone pain , polydipsia , and polyuria for the past 3 years . patient had difficulty in night vision since 8 years of age and difficulty in distant vision since 9 years of age . her height and weight were 136 cm ( < 10 centile ) and 58 kg respectively with a body mass index of 31.4 kg / m . physical examination was notable for the absence of secondary sexual characters in the form of absence of axillary , pubic hair , and poor breast bud development . she had post axial polydactyly in both her legs , central polydactyly in her right hand and clinodactyly of left little finger [ figures 1 and 2 ] . her visual acuity was decreased to counting fingers at 1 m in both the eyes . picture showing central polydactyly in right hand and clinodctyly in left hand picture showing post axial polydactyly in both feet fundus picture showing retinitis pigmentosa investigations revealed hemoglobin - 7.6 gm / dl , urea - 64 mg / dl , creatinine - 10.6 mg / dl , calcium - 7.0 mg / dl , inorganic phosphorus - 5.6 mg / dl , and serum albumin - 3.7 gm / l . urine analysis revealed trace proteinuria with no active sediments . she had features of secondary hyperparathyroidism with serum alkaline phosphatase of 1157 u / l and intact pth of 418.3 pg / ml . her fasting and post prandial blood glucose were 57 and 87 mg / dl respectively . renal biopsy revealed interstitial fibrosis and tubular atrophy in 75% of the area examined suggestive of chronic interstitial nephritis [ figure 4 ] . kidney biopsy ( pas stain ) showing features suggestive of chronic interstitial nephritis the combination of pigmentary retinopathy , polydactyly , mild mental retardation , obesity , and renal failure fits well with the diagnosis of bbs . the primary features of this syndrome are early - onset retinal dystrophy , obesity , limb defects , mental retardation , hypogonadism , and renal abnormalities . the onset is often earlier and progression more rapid than in isolated typical retinitis pigmentosa . postaxial polydactyly is the most common limb defect , though brachydactyly , partial syndactyly , fifth finger clinodactyly , and a prominent gap between the first and second toes were also noted . the renal abnormalities as a part of this syndrome have been recognized only recently . in a seminal study by beales et al . , 26 ( 46% ) out of 57 patients had renal structural abnormalities which included renal parenchymal cysts , communicating calyceal cysts , calyceal clubbing and blunting , fetal lobulation and scarring , dysplastic kidneys , unilateral agenesis , vesicoureteric reflux , bladder obstruction , horseshoe kidney , and ectopic kidney . though only 5% had chronic renal failure , renal failure is the most common cause of mortality in these patients . all the three modalities of renal replacement therapy namely hemodialysis , peritoneal dialysis , and transplantation can be optimally used in these individuals . the other secondary features are hearing loss , speech disturbances , pigmented naevi , hypertension , diabetes mellitus , congenital heart disease , cardiomyopathy , hepatic fibrosis , nephrogenic diabetes insipidus , hypothyroidism , hirschsprung 's disease and abnormal dentition . mutations in 16 genes ( bbs1 to bbs12 , mks1 , nphp6/cep290 , sdccag8 , and sept7 ) have been identified to cause the bbs phenotype . bbs has been recently included in the broad category of ciliopathies , a class of genetic diseases that occur due to primary ciliary dysfunction . the primary cilium projects from the cell surface of most mammalian cells . increasing evidence suggests that primary cilia are key coordinators of signaling pathways during development and in tissue homeostasis . to the best of our knowledge , only 13 cases of bbs have been reported from india . out of the 13 reported cases , only two patients had end stage renal disease ( esrd ) . our patient is probably the third with bbs to present with esrdse . to conclude , bbs is a rare cause of esrd . elucidation of the genetics and pathogenesis of this disease may yield novel therapeutic options in the future .

bardet biedl syndrome is a rare autosomal recessive disorder , recently categorized as ciliopathy characterized by dysfunction of primary cilia which results in myriad manifestations in various organ systems . though renal abnormalities can occur in this syndrome , renal failure is a rare presentation . the author reports a case of 18-year - old female who presented with polydactyly , obesity , retinitis pigmentosa , learning disability and renal failure .

we used the cross - sectional method ( descriptive / correlational design ) in the present study . jam ( 104 males , 74 females ) . using a cluster - sampling technique , the subjects were selected from the undergraduate students of different disciplines at torbat - jam university . the age of the participants ranged from 18 to 31 ( mean= 22.2 years , sd=2.21 ) . all participants completed paper and pencil versions of the brbq and neo questionnaire . the basic religious beliefs questionnaire ( 1 , 23 ) and neo questionnaire ( 28 , 29 ) were used for data collection . the basic religious beliefs questionnaire ( brbq ) . this questionnaire was made by rajaei and colleagues in 2009 , and includes 50 items in three subscales of religious beliefs , human , existence and god . each item asks subjects to rate their opinions about their religious beliefs on a scale of 1 ( strongly agree ) to 5 ( strongly disagree ) . in one study on 440 university students , cronbach 's coefficient alpha for the total score was 0.96 , and the reported acceptable reliability for brbq ( 23 ) . the neo questionnaire was first made by mccrare and costa in 1985 and included 181 items to investigate the big five of personality . a shorter version of this questionnaire ( the five factor inventory ) was later designed . this inventory consisted of 60 items based on the factor analysis of scores of neo personality inventory performed in 1986 . answering these items is possible through the 5-degree likert scale ( 28 , 29 ) . this questionnaire has been normalized in iran by groosi ( 30 ) and validity of this questionnaire came out to be 0.83 , 0.75 , 0 . 80 , 0.79 , for pactors c , a , o , e and n , respectively using test - retest method on 208 students with a three - month interval . sample consisted of 178 students of the islamic azad university in torbat jam ( 104 males , 74 females ) . using a cluster - sampling technique , the subjects were selected from the undergraduate students of different disciplines at torbat - jam university . the age of the participants ranged from 18 to 31 ( mean= 22.2 years , sd=2.21 ) . all participants completed paper and pencil versions of the brbq and neo questionnaire . the basic religious beliefs questionnaire ( 1 , 23 ) and neo questionnaire ( 28 , 29 ) were used for data collection . the basic religious beliefs questionnaire ( brbq ) . this questionnaire was made by rajaei and colleagues in 2009 , and includes 50 items in three subscales of religious beliefs , human , existence and god . each item asks subjects to rate their opinions about their religious beliefs on a scale of 1 ( strongly agree ) to 5 ( strongly disagree ) . in one study on 440 university students , cronbach 's coefficient alpha for the total score was 0.96 , and the reported acceptable reliability for brbq ( 23 ) . the neo questionnaire was first made by mccrare and costa in 1985 and included 181 items to investigate the big five of personality . a shorter version of this questionnaire ( the five factor inventory ) was later designed . this inventory consisted of 60 items based on the factor analysis of scores of neo personality inventory performed in 1986 . answering these items is possible through the 5-degree likert scale ( 28 , 29 ) . this questionnaire has been normalized in iran by groosi ( 30 ) and validity of this questionnaire came out to be 0.83 , 0.75 , 0 . 80 , 0.79 , for pactors c , a , o , e and n , respectively using test - retest method on 208 students with a three - month interval . table 1 demonstrates correlations between the three categories of basic religious beliefs ( human , existence and god ) and five personality traits . correlations between basic religious beliefs and five personality traits . data in table 1 demonstrated that basic religious beliefs have a significant negative correlation with neuroticism ( r= -0.29 ) , and a significant positive relationship with extraversion(r= 0.28 ) , openness(r= 0.14 ) , agreeableness(r= 0.29 ) , and conscientiousness ( r= 0.48 ) . as the data demonstrated , openness has the lowest and conscientiousness has the highest correlation with basic religious beliefs . table 2 illustrates the regression analyses of predictor variables ( basic religious beliefs ) for predicting criterion variables ( big five traits ) . summary of regression analyses for predicting five personality traits data in table 2 demonstrate that basic religious beliefs ( human , existence , god ) can explain different variance of five personality traits , neuroticism(r2=0.08 ) , extraversion(r2=0.07 ) , openness(r2=0.02 ) , agreeableness(r2=0.07 ) and conscientiousness ( r2=0.23 ) . the results of regression analysis showed that basic religious beliefs can anticipate neuroticism , extraversion , agreeableness and conscientiousness traits , but it can not anticipate openness significantly . based on data analysis , the basic religious beliefs have the most positive correlation with conscientiousness factor of personality . people with the conscientiousness trait are conscientious , careful , reliable , hard working and well organized . therefore , one can conclude that religious people have more of these positive traits and are more responsible and have greater achievements in their life than others . the findings of this study are consistent with mccullough , tsang and brion ( 31 ) who found that conscientiousness in adolescence is uniquely related to higher religiousness in early adulthood . and our findings also support the results of the study of mccullough and willoughby ( 32 ) which showed that religion can promote self control and can facilitate self monitoring ; and that these concepts tend to be associated with conscientiousness . data analysis also implies that basic religious beliefs have positive correlations with agreeableness ( good - natured , soft hearted , selfless , sympathetic , forgiving characteristics ) extraversion ( sociable , fun - loving , affectionate , talkative , and joiner characteristics ) . these characteristics can be positive , and help people to arrange effective relationships with others , and this , can lead to better mental health . the results of this study are also consistent with saroglou ( 33 ) and lodi - smith and roberts ( 34 ) . by using meta - analysis , both studies showed that the big five correlates with religious involvement , and concluded that among the big five dimension of personality , agreeableness and conscientiousness have the most reliable correlations with religiousness . on the other hand , in contrast with the results of this study , mccullough , tsang and brion ( 31 ) found no significant correlation between these basic religious beliefs and extraversion . openness reflects , in part , a willingness to consider new ideas , as well as to question one 's values and beliefs , and therefore some might expect a negative relation between openness and religiousness . however , in this study there was a low but positive correlation between basic religious beliefs and openness , but the correlation coefficient was not high . however , mccullough , tsang and biron ( 31 ) reported a positive significant correlation between religiousness and openness . finally , the relationship between basic religious beliefs and neuroticism was found to be negative . it means that religious people should be more calm , at ease , relaxed , secure and comfortable , while the neurotic people are worried , nervous , high - strung , insecure and self conscious . by reviewing 49 studies using meta - analysis , ano and vasconcelles ( 3 ) , concluded that positive forms of religious coping were positively associated with positive psychological outcomes such as life satisfaction and happiness , and negatively associated with negative outcomes , such as anxiety and depression . these findings all show that religiosity is associated with positive emotional states and well - being . due to cross - sectional and correlational nature of the data in this study , some usual limitations in methodology are to be noted . for example , correlational design restricts etiological claims . in addition , it is important to note that association of basic religious beliefs and personality trait was not high . for instance , regression analyses showed that only 0.08% of the variance neuroticism , 0.07% extraversion , 0.02% openness and 0.07% agreeableness were explained by basic religious beliefs . therefore , using other research methods , investigation of the relations of these variables in future studies is recommended . furthermore , we should consider that participants of this study were only selected from university students . thus , we should consider this as a limitation when generalizing the findings to other populations . in sum , based on the findings of this study we can conclude that religiousness and in the other words , trust in god , and the consequences of such a belief , provides some one with relaxation , decreased the life - span stress and more adjustments with the daily hassels and ultimately with positive personality traits , such as , conscientiousness , agreeableness , and openness . basic religious beliefs have a positive relationship with good characteristics that help people resolve the challenges of their lives and identity crisis . these findings are consistance with the religious cognitive emotional theory , which indicates that basic religious beliefs can help people find the meaning of life and resolve their identity crisis ( 1 ) .

objectivespiritual beliefs can help people find meaning of life , and can also influence their feelings , behaviors and mental health . the present research studied the relationship between basic religious beliefs ( human , existence and god ) and five personality factors : neuroticism , extraversion , openness , agreeableness , conscientiousness.methodone hundred seventy eight students of islamic azad university in torbat - jam were randomly selected and completed the basic religious beliefs and neo questionnaires.resultsdata showed that basic religious beliefs have a significant negative correlation with neuroticism ( r=-0.29),and a significant positive relationship with extraversion(r=0.28),openness(r=0.14),agreeableness ( r=0.29),and conscientiousness ( r=0.48 ) . also , the results of the regression analysis showed that basic religious beliefs can anticipate neuroticism , extraversion , agreeableness and conscientiousness , but they can not anticipate the openness factor significantly.conclusionthe findings of this study demonstrate that basic religious beliefs have a positive relationship with good characteristics that help people resolve the challenges of their lives and identity crisis . thus , the results of this study support the idea of religious cognitive emotional theory that religiosity is correlated with positive personality traits .

depression is a mental disorder that is characterized by persistent feelings of sadness and loss of interest . it affects how you feel , think , and behave and it can lead to disturbances of daily habits ( e.g. , work ) . the complexity of depression is demonstrated by the existence of a variety of factors involved in this disorder , such as biological ( e.g. , genetic ) differences and brain chemistry ( i.e. , neurotransmitters , hormones , decreased serotonin levels in the blood , and last , but not least , a person s genes ) . there are many factors that seem to increase the risk of triggering depression as well , including low self - esteem , traumatic / stressful events , drugs , alcohol , and other mental health disorders . untreated depression can lead to eating problems , such as obesity , which in turn can lead to consequences such as heart disease and type 2 diabetes , social isolation , suicide attempts , and alcohol abuse . also , with this condition , there are elements of an inflammatory response , as noted by an increased level of pro - inflammatory cytokines such as interleukin-1 , tumor necrosis factor- , and interleukin-6 . there are , as can now be expected , different types of depression : major depressive disorder ( also known as unipolar depression ) , bipolar disorder , psychotic depression , postpartum depression , and seasonal affective disorder . the major pathophysiological basis for depression appears to be a depletion of the neurotransmitters serotonin , norepinephrine , or dopamine in the central nervous system . in this regard , serotonin emerges as the main neurotransmitter in depression , where it is significantly reduced . levels of dopamine metabolites are consistently reduced in depression , suggesting decreased dopamine turnover . finally , genetic factors play a major role in depression , with 3040% of these patients exhibiting genetic symptoms . the studies revealed a 4050% prevalence of depression in monozygotic twins and 25% in dizygotic twins . there is a correlation between greater family burden and the earlier onset of a disease . there are tens of genes involved in predisposition to depression , interacting with one another and with the environment . clearly , the factors noted earlier support a multiple gene expression pattern in this disorder , given all of its variations and associations . multicellular animals , in general , require a nervous system to mediate reproduction and food acquisition , which are major survival strategies for hunters . the fundamental characteristics of the human central nervous system can be found in single cells , such that they have sensory and motor mechanisms that are appropriate ( integrated ) . clearly , even at the single - cell level , a nervous system blueprint , as just noted , provides for novel coping strategies for surviving . indeed , multicellular organisms evolved in such a manner that their cells could differentiate a common functional morphology into specialized cells ( e.g. , nervous tissues ) . here too , allowing the system to further evolve , was its chemical communication system and impulse generator , which operates by way of conformational matching , retaining chemical signaling , once evolved , and thus further developing the blueprint . importantly , given the magnitude of the cellular chemical messenger presence , it is unlikely that evolution will generate another chemical messenger system . cellular chemical communication was so effective that the next stage of evolutionary change in the nervous system involved generating intra - nervous system networking / pathways , which further advanced the coping strategy of endowed animals by providing a mechanism that was ever more sophisticated , rapid , and efficient in its performance . this sophistication allowed animals to remain in complex and difficult environments , exhibiting different behavioral attributes for specific coping strategies . this level of sophistication is so intricate that it can mask the basic original life objectives : reproduction ( e.g. , dna ) and food acquisition for survival of the species . clearly , given its commonality , the origin of the signal must be in dna . it is important to note , we surmise , that novel networking is an ongoing phenomenon . additionally , at the cutting - edge of this novel networking is the newly created ( comparatively speaking ) function of cognition in humans . this enables a whole series of other behaviors to emerge that can now be incorporated into a single phenomenon the mind all within the realm of an organism s control . just unto itself , this was truly an amazing outcome ; however , with its newly evolved internal constructs , there may be major problems ( e.g. , depression ) given its newly created state in the long process of evolution [ 1216 ] . one may also argue that if cognition is such a powerful evolutionary , revolutionizing tool , why have there not been other species exhibiting this phenomenon ? the answer may lie in the first emergence of this phenomenon , in that it actively prohibited cognition from emerging in other species by eliminating them as a perceived threat . the elimination of cognitive competitors can be ascertained from our preference for having basically docile domestic and commercialized animals . outliers from this behavioral characteristic are not tolerated and in actuality may be difficult to deal with . in achieving dominance in our evolution , we speculate that the need for the emergence of a single high - level cognitive species is similar to that for having a single mind in brain evolution , which can organize the functions of a single organism without impairing survival . this is opposed to having multiple minds , which is regarded as pathological since a dysfunctional person exhibiting this phenomenon could not function in our environment . we further surmise that a singularity of mind must be one constructed on the foundation of superiority . this deception can be a driving force in evolution because it is powerfully motivating [ 1719 ] . hence , the phenomenon of humans killing humans , despite creating sophisticated technologies , is hard to diminish because it is part of the cognitive evolutionary story . in the end , dna , the selfish gene , wins , regardless of who has it and their desires to advance . this critical phenomenon of superiority obviously has been retained in evolution and resides at the dna level , insuring its success . depression can be both normal and abnormal and the balance of its expression determines the behavioral outcome / diagnosis . it is a complex pathophysiology based on a heterogeneous syndrome whose etiology is also complex . in keeping with the focus of this mini - review , recent state - of - the - art technologies have revealed this condition may arise from poorly adapted neural circuitries . in part , these circuits are also implicated in coping with stress , sharing commonalities as noted by the co - morbidities . given the many triggers of depression , behavioral process associations , and definitions , it becomes apparent that the pathophysiological problem is one of malfunction of both chemical neuro - signaling and pathway dynamics . we speculate that this abnormality , as well as other disorders ( e.g. , schizophrenia ) , might be occurring because of the newness of cognition in humans . the pathways that have been developed in this regard are complex , having errors in their expression due to their newness , which suggests they are still evolving .

depression can be both normal and abnormal , and the balance of its expression determines the behavioral outcome / diagnosis . it is a complex pathophysiology based on a heterogeneous syndrome whose etiology is diverse as well . within the context of a central nervous system , the nervous system blueprint can be found in single cells ( sensory , motor , and integrative processes ) . these consolidated functions provide for novel coping strategies for survival . the maintenance and evolvement of this system into a central nervous system is based on conserving these functions , including chemical messengers and functionality in having specific cells mediate these primordial functions . additionally , this neural coping strategy provides advantages for dna . thus , with different neural cells at work , pathways / networks would evolve , producing more complex behaviors and become a very critical phenomenon for future advances . this evolvement has taken over 1 billion years to develop . in so doing , as with any new programming ( e.g. , cognition ) , errors will occur . given the widespread qualities of depression , it is surmised that this abnormality , and other psychiatric disorders , may emerge due to inherent neural weaknesses related to cognition being a recent evolutionary development .

huntington 's disease ( hd ) is an autosomal dominant disorder caused by an expanded polyglutamine tract that results in progressive degeneration of neurons , primarily in the putamen , caudate nucleus and cerebral cortex . hd occurs when the gene that encodes huntingtin ( htt ) , located on the short arm of chromosome 4 , shows an expanded cag repeat region following exon 1 ( the huntington 's collaborative research group , 1993 ) . typically , greater than 38 cag repeats correlates with onset of hd in mid - adulthood whereas a mutation greater than 60 cag repeats results in an early - onset form of the disease known as juvenile huntington 's disease ( jhd ) . disease symptomology is clinically diagnosed by chorea , but early cognitive and emotional aberrations such as slowing of psychomotor speed , impairment of attention and memory , as well as executive and visuospatial functions that eventually degrade into dementia along with depression are becoming clearer in hd ( ross et al . , 2014 ) . jhd patients generally show less chorea than adult onset hd with rigidity and dystonia reported as the dominant clinical manifestations . neuropathologically , hd is characterized by striatal atrophy , cortical thinning and degeneration in the prefrontal cortex with jhd also showing aberrations in the cerebellum ( aylward , 2007 ) . life expectancy is 1520 years following clinical diagnosis in adult hd and 10 years in jhd ( gonzalez - alegre and afifi , 2006 ) . pharmacotherapy for hd patients has been difficult despite increased recognition of the disorder , better access to genetic counseling and more availability to specialized care programs . currently only palliative therapies that treat chorea ( tetrabenzaine ) and depression ( ssris ) are approved for hd patients . furthermore , treatment for jhd has been incredibly challenging due to the complex symptomology and needs of pediatric patients . there are no studies to guide the current trial - and - error approach to treating jhd , with anti - parkinsonian agents , anti - psychotics and anti - epileptics being the mostly commonly prescribed drugs ( robertson et al . , 2012 ) . it has been reported that hd patients have lower levels of brain derived neurotrophic factor ( bdnf ) due to inhibition at the transcriptional level by the mutant huntingtin protein ( zuccato et al . , 2011 ) . this reduction in bdnf in the striatum correlates with symptom onset and heightened severity of the disease in transgenic hd mice . canonically , bdnf is known to mediate both the survival and function of striatal neurons . bdnf knockout mice recapitulate the striatal atrophy phenotype of hd patients and indicate that reduced neurotrophic support in the striatum is a major factor contributing to neurodegeneration in hd ( ciammola et al . , 2007 ) . whereas , restoration of bdnf levels are shown to have pro - survival effects and ameliorate hd symptoms in transgenic hd rodent models . therefore , bdnf is considered a prime candidate to treat the underlying neuronal dysfunction observed in hd ( reviewed in fink et al . , 2015 ) . however , direct injections of bdnf have been ineffective due to the short half - life of the recombinant protein . other exogenous delivery methods have been examined such as the use of adeno - associated viral ( aav ) to express bdnf in striatal neurons . this has been shown to induce neurogenesis and promote longer life span in a hd mouse model . interestingly , this effect was potentiated by noggin ( benraiss et al . , 2012 ) , which is a factor secreted by mscs ( diefenderfer et al . , 2003 the use of aav in the clinic has proven difficult due to host immunogenicity to the virus and limited biodistribution ( kordower , 2016 ) . in comparison , bdnf is initially synthesized by cortical neurons and then is transneuronally propagated into the striatum . when bound to trkb , mature bdnf induces receptor dimerization and autophosphorylates tyrosine residues that initiates secondary cascades that regulate neurogenesis , synaptic plasticity ( huang and reichardt , 2003 ) . this is achieved by three major signaling pathways : the phosphatidyl inositol 3-kinase ( pi3k)-serine - threonine kinase ( akt ) , mitogen - activated protein kinase ( mapk ) extracellular related kinase ( erk ) pathway , and the phospholipase cy cam kinase pathway . the use of stem cell therapies has become increasingly attractive as a putative therapy for neurodegenerative disorders . the ability to work synergistically with the endogenous microenvironment to upregulate intrinsic cell proliferation or neuroprotection via trophic factor secretion potentially enhances the overall regenerative potential in the transplanted tissue . mesenchymal stem cells ( mscs ) in particular have generated great interest in regenerative medicine and immunotherapy due to their unique biological properties . mscs are multipotent stem cells derived from a broad subset of adult tissue that are readily accessible . mscs are capable of secreting neurotrophic factors in response to local inflammatory elements , enhancing neurogenesis and synaptogenesis , and inhibiting apoptotic signaling . due to their immune - modulating potential , mscs do not require immunosuppression following allogenic transplantation and have demonstrated a strong safety profile in clinical trials ( figure 1 ) . a representative image of transplanted human bone marrow mesenchymal stem cell that have been engineered with a green fluorescent protein reporter gene following transplantation into the brain of a transgenic huntington 's disease mouse model . a multitude of published articles have demonstrated improvement of either behavioral or neuropathological deficits in rodent models of hd following treatment with mscs . these studies have used mscs from multiple sources including autologous transplantation of unpurified whole bone marrow from rats , purified rat mscs , mouse bone marrow - derived mscs , mouse umbilical cord - derived mscs , human adipose derived mscs , and human bone marrow mscs . decreases in striatal atrophy , reduced medium spiny neuron loss , stimulation of endogenous neurogenesis and reduction of htt aggregation has been observed following transplantation of mscs ( reviewed in fink et al . , 2015 ) . furthermore , mscs have demonstrated improvements in motor and cognitive function , reduced anxiety - like behaviors and extension of lifespan in rodents . trophic support is commonly postulated as the mechanism for the therapeutic potential of mscs such as the secretion of neurotrophic factors that enhance endogenous neurogenic potential . furthermore , the potential for mscs as a delivery vehicle for gene therapy has been examined due to the relative ease of reprogramming these cells ( meyerrose et al . , 2010 ) . in particular , mouse - derived mscs that were reprogrammed to overexpress bdnf in yac128 hd transgenic mice resulted in motor improvement and increased neuron viability following transplantation ( dey et al . , in addition to being readily programmable , mscs migrate to areas of tissue damage unlike direct injection of aav and demonstrate transient engraftment into host tissue as well as persistent sustained therapeutic effect even after cell clearance . in turn , this addresses safety concerns of direct use of viral vectors and associated prolonged immune response while still maintaining efficacy . together , the use of mscs to deliver bdnf as a treatment for hd has been suggested as a clinical therapy that our group is investigating in a series of investigational new drug ( ind)-enabling preclinical studies . however , a controversial link between bdnf and epilepsy has been described in the literature , suggesting that sustained chronic overexpression may lead to deleterious effects . the evidence for the link between bdnf and epilepsy is due to the findings of increased levels of the trophic factor following limbic seizures , but conditional knockout or overexpression of bdnf does not severely alter kindling arguing against bdnf having a critical role in initiating seizure - like activity ( scharfman , 2005 ) . our group at the institute for regenerative cures at the university of california , davis has tested the safety and efficacy of genetically - engineered human bone marrow mscs intransgenic hd mouse models and published the results of our ind - enabling studies in molecular therapy ( pollock et al . , 2016 ) . human mscs were isolated and cultured from commercially purchased whole bone marrow and transduced with a lentivirus designed to produce bdnf following good laboratory practice - like conditions . these cells were prepared in a similar manner to cells proposed for a phase i clinical trial . the yac128 and r6/2 transgenic hd mouse models were used for behavioural and histological studies following transplantation to measure efficacy of msc / bdnf as a putative therapy . each mouse received intrastriatal transplantations of 5 10 cells per hemisphere of untransduced msc or msc / bdnf with normosol - treated transgenic and wildtype littermate controls . the ability of msc / bdnf to reduce neuropathological deficits was measured by striatal volume 6 weeks post transplantation . interestingly , msc alone reduced this striatal atrophy to approximately 8.4% and msc / bdnf transplantations reduced it to approximately 6% . r6/2 treated with msc / bdnf recapitulated the neurogenesis observed with non - modified mscs , but also demonstrated an increase in mean survivability of 14.9% with msc alone increasing lifespan 9.4% when compared to normosol treated transgenic mice . finally , yac128 mice treated with msc / bdnf showed significantly less anxiety compared to normosol - treated yac128 over a 6-week open field study . taken all together , human msc and msc / bdnf are both therapeutically relevant strategies in ameliorating hd symptomology observed in these two stains of transgenic mice . these results , along with the abundance of peer - reviewed articles ( fink et al . , 2015 ) provide compelling evidence for the use of genetically - engineered msc as a candidate therapy for changing the trajectory of disease progression in patients diagnosed with early - stage hd ( figure 2 ) . investigational new drug ( ind ) trial design . a representative schematic of advancing a basic research project to a food and drug administration - approved clinical trial . the necessary steps and funding agencies for the use of mesenchymal stem cell / brain derived neurotrophic factor for huntington 's disease ( hd ) irc : institute for regenerative cures ; mds : medical doctors ; poc : proof of concept ; ucd : university of california , davis . a host of rodent studies demonstrate the therapeutic potential of mscs for hd , but there are current limitations to how well these models recapitulate the disease in humans . r6/2 mice are widely used to model behavioural deficits and extend the lifespan of these animals ; however therapies aimed at preventing neuronal loss would be unsuccessful due to the lack of neuropathology in this model . conversely , studies aimed at the metabolic dysfunction or at the extending the lifespan of mice in the yac128 or bachd mouse models would be unsuccessful as these mice exhibit weight gain that is uncharacteristic of the human condition and have a normal lifespan compared to wild - type littermates . currently , large genetic animal models for hd are being pursued to open new avenues in hd research ( jacobsen et al . , 2010 ) . more importantly , large animals may better represent major neuroanatomical structures relevant in the human hd brain that are missing in rodent models . this will allow for large animal safety studies to accurately access delivery of stem cells and to perform long - term toxicology studies . it is likely that any clinical study where mscs are transplanted into human patients will hinge on the demonstration that they are both safe and feasible in such a trial . immune - suppressed mice xenografted with human mscs show a month long engraftment potential whereas allogeneic msc engraftments in macaque monkeys have been more variable due to presentation of immunogenicity ( isakova et al . , 2014 ) . macaques transplanted with allogeneic / opposite sex mscs demonstrated weak immune response , with increased transplantation size resulting in reduced engraftment duration suggestive that matched or partially matched cells from allogeneic sources may result in longer msc engraftment . while msc clinical trial design should still undergo further refinement , countless clinical trials have not shown a need for human leukocyte antigen ( hla ) matching or immune suppression for stable msc engraftment in humans ( fibbe et al . , 2013 ) . however , the transient nature of mscs may be beneficial as a potential safeguard against prolonged immune response . mscs have been well tolerated in phase i / ii clinical trials without adverse events in a variety of diseases with no tissue matching . currently , atherys , sanbio and brain - storm therapeutics have all concluded phase ii clinical trials with mscs with no reported adverse effects in either acute or chronic neurodegenerative insults such as ischemic stroke or amyotrophic lateral sclerosis ( als ) . importantly , brain - storm cell therapeutics concluded a phase i / iia clinical trial in patients with amyotrophic lateral sclerosis using autologous mscs induced to express neurotrophic factor ( nurown ) with mild and transient adverse effects reported . strikingly , treated als patients demonstrated slowed disease progression following the conclusion of the phase iia trial with improvements in breathing and reduced motor decline compared to pre - treatment ( petrou et al . , 2016 ) . currently , studies are underway to evaluate msc / bdnf in a dose dependent manner and additional long - term safety studies in preparing of an ind application to the fda . the proposed future clinical trial ( hd - cell ) is designed to demonstrate safety of intrastriatal injection transplantation of genetically - modified mscs to treat hd in patients screened in an ongoing observation study ( pre - cell : clinicaltrials.gov identifier nct01937923 ) at the university of california , davis . given the growing support for mscs in clinical trials of various neurodegenerative diseases , preclinical and in vivo biosafety data using human msc / bdnf , and the current lack of treatments available for hd , it is believed that genetically engineered msc are a strong lead candidate for the treatment of huntington 's disease .

progress to date from our group and others indicate that using genetically - engineered mesenchymal stem cells ( msc ) to secrete brain - derived neurotrophic factor ( bdnf ) supports our plan to submit an investigational new drug application to the food and drug administration for the future planned phase 1 safety and tolerability trial of msc / bdnf in patients with huntington 's disease ( hd ) . there are also potential applications of this approach beyond hd . our biological delivery system for bdnf sets the precedent for adult stem cell therapy in the brain and could potentially be modified for other neurodegenerative disorders such as amyotrophic lateral sclerosis ( als ) , spinocerebellar ataxia ( sca ) , alzheimer 's disease , and some forms of parkinson 's disease . the msc / bdnf product could also be considered for studies of regeneration in traumatic brain injury , spinal cord and peripheral nerve injury . this work also provides a platform for our future gene editing studies , since we will again use mscs to deliver the needed molecules into the central nervous system .

sepsis was defined as gbs bacteremia in the presence of consistent clinical signs and symptoms . capsular typing was performed by a multiplex pcr as described ( 9 ) , and the hypervirulent st-17 clone was detected by real - time pcr , as reported ( 6 ) . susceptibility testing , antibiograms , and mics were performed according to clinical and laboratory standards institute recommendations ( www.clsi.org ) . antimicrobial drug resistance genes were detected by using the multiplex pcr as described ( 10 ) . we studied 109 gbs strains responsible for neonatal invasive infections ; 36% ( n = 39 ) and 64% ( n = 70 ) were responsible for eod and lod , respectively ( table ) . eighty percent of eod cases occurred during the first 24 hours after birth , with a male : female ratio of 0.9 ; 72% were associated with sepsis , and 28% with meningitis . maternal cultures obtained in the last 6 weeks before delivery were available for 64% of the cases . a capsular serotype was assigned to all isolates with a distribution as follows : types iii ( 61.5% ) and ia ( 28.2% ) were predominant compared to types ib ( 5.1% ) , ii ( 2.5% ) , and v ( 2.5% ) ( table ) . eod meningitis gbs strains were of type iii in 81.8% of isolates , and all these strains were st-17 positive . * gbs , group b streptococcus ; cps , capsular serotype ; eod , early - onset disease ; lod , late - onset disease . sepsis was associated with 2 cases of parotitis , 1 case of osteomyelitis , 1 of spondylodiscitis , and 1 of orchitis . lod had a male : female ratio of 1.15 , and 82.6% of cases occurred during the first 8 weeks of life , with a peak ( 63% ) at 48 weeks ( data not shown ) . sepsis occurred in 27.1% of lod cases and meningitis in 65.7% . in 5 cases of lod , less frequent manifestations were observed : sepsis was associated with parotitis ( 2 cases ) , osteomyelitis ( 1 ) , spondylodiscitis ( 1 ) , and orchitis ( 1 ) . three cases ( 4.5% ) of recurrent invasive infections were reported . for 2 of these 3 cases , the first episode was early meningitis with a relapse of meningitis 23 weeks later , despite correct antimicrobial drug treatment . the third case was a late - onset sepsis that relapsed as a sepsis after the infant had received 3 weeks of amoxicillin . none of these infants was fed breast milk , which ruled out the possibility of contamination by this route . the death rate for lod was 14.5% ; 90% of deaths were associated with meningitis . capsular type distribution of gbs lod isolates was as follows : type iii was largely predominant ( 83% ) compared with types ia ( 7.4% ) , ib ( 4.5% ) , and v ( 1.5% ) ( table ) . among strains responsible for meningitis , 87% were of type iii and almost all ( 92.5% ) belonged to the hypervirulent st-17 clone . all 109 gbs strains tested were susceptible to penicillin ( mic90 0.016 mg / l ) , amoxicillin ( mic90 0.016 mg / l ) , cefotaxim ( mic90 0.016 g / ml ) , imipenem ( mic90 0.032 g / ml ) , rifampin ( mic90 0.032 g / ml ) , vancomycin ( mic90 0.75 g / ml ) , and displayed low - level resistance to gentamicin ( mic90 8 g / ml ) . also , 95.5% were resistant to tetracycline because of the presence of tet(m ) associated with tet(o ) or tet(l ) in 3 and 1 strains , respectively . resistance to erythromycin was detected in 13.8% of the isolates and was not correlated with the capsular type or the onset of disease . erythromycin resistance was caused by the presence of mef(a ) ( 46.6% ) , erm(a ) ( 26.6% ) , or erm(b ) ( 20% ) . in france , screening of pregnant women for gbs colonization and iap for women detected positive was implemented in 2001 but , despite these recommendations , eod continues to occur ( 11 ) . in this report , 36% of cases were eod . for 71% of eod cases , maternal vaginal screening before delivery had not been conducted or was negative for gbs , thus likely explaining the persistence of eod , as already suggested by others ( 12,13 ) . in our study , lod represents the majority of cases ( 64% ) , which is consistent with findings in countries where a screening approach , together with iap , was adopted ( 2,11,13 ) . clinical symptoms were significantly associated with the time of infection onset : eod was mostly associated with sepsis ( 72% ) , whereas lod was more frequently responsible for meningitis ( 65.7% ) ( p<0.01 ) . deaths , all associated with meningitis , were higher in lod ( 14.5% ) than in eod cases ( 2.5% ) . the predominance of capsular type iii among infants with meningitis is well - known ( 3,58,14,15 ) . in our study , type iii accounted for 83% of lod and was significantly associated with meningitis ( 85.9% ; p<0.01 ) in both eod and lod . moreover , the hypervirulent clone st-17 was significantly predominant among lod cases ( 75% ; p<0.03 ) and accounted for 93% of gbs type iii strains responsible for meningitis . this overrepresentation of st-17 among invasive neonatal strains is now well recognized worldwide and highlights the fact that this clone is well adapted to neonate pathogenesis and may possesses specific virulence traits that enhance its invasiveness in this population ( 58,14,15 ) . early detection of this clone among colonizing strains in pregnant women or in neonates at delivery may therefore constitute the basis for developing new prevention strategies . an attractive alternative to iap is vaccinating young women to subsequently protect neonates against gbs infections . conjugate vaccines composed of capsular polysaccharides and tetanus toxoid have already been evaluated ( 1 ) . recent studies have suggested that protein antigens induce protective immunity in animal models , and surface proteins common to many strains would have a potential role in vaccine development ( 1 ) . for this reason immunogenic antigens specific to the st-17 clone should be considered in designs of future vaccine .

clinical features and molecular characterization of 109 group b streptococci causing neonatal invasive infections were determined over an 18-month period in france . sixty - four percent of the strains were from late - onset infections , and 75% were capsular type iii . the hypervirulent clone st-17 was recovered in 80% of meningitis cases .

cancer is a major public health problem and one of the most common causes of death worldwide , including iran . generally , gastrointestinal tract cancers , majority of which occurs in stomach , esophagus , colon , or rectum are most common organ system involved with more than 38% of all cancers and account for nearly half of all cancer causes of deaths in iranian cancer patients . undoubtedly , being diagnosed of having a life threatening disease such as cancer is devastating and has an enormous effect on patients quality of life ( qol ) . world health organization ( who ) defined qol as the individuals perception of their position in life in the cultural context and in the value system in which they live , and in relation to their goals , expectations , standards , and concerns . the measurement of qol has become a vital and often required part of health outcomes appraisal . for patients with chronic disease such as cancer , which can affect the qol of these patients and their families , measuring qol provides a remarkable way to determine the impact of health care when cure is not possible . the assessment of qol can help to facilitate communication with cancer patients and identification of their individual preferences , for example , to select a specific treatment or care plan . on the other hand , qol is not only an important issue for individual cancer patients . therefore , the measurement of qol is an important outcome measure in all cancer patients , but it becomes even more important in patients with metastatic cancers , where , with very few exceptions , cure is no longer the goal . in this situation , survival time prolongation , palliation of symptoms , and qol optimization become the goals of care . previous studies have reported that in several different types of cancer including metastatic cancers , there was a relationship between the patients qol scores and their clinical outcome . qol scores may be an independent predictor of survival in these patients . despite the importance of assessing the qol in cancer patients , especially in patients with metastatic cancer , and also the relatively high incidence rates of gastrointestinal tract cancers in iran ; little is known about qol in patients with metastatic gastrointestinal cancer . the aim of this study was to evaluate the qol with its various dimensions and also its associated factors such as demographics and clinical characteristics among iranian patients with metastatic gastrointestinal tract cancer using a cancer - specific questionnaire , in sari , northern iran . in this cross - sectional study , after obtaining approval from the mazandaran university of medical sciences ethical committee and informed consents from the patients , a total of 250 patients of both sexes , with metastatic gastrointestinal tract cancer referring to the one oncology center related to the mazandaran university of medical sciences , sari , iran , for medical follow - up , were recruited . patients were eligible for the study if they had the ability to understand and the willingness to participate in the study and also had a histologically or cytologically confirmed diagnosis of metastatic gastrointestinal tract cancer and were informed of the diagnosis . exclusion criteria were the presence of a known psychiatric or cognitive disorder or not willing to participate in the study . patients who met the inclusion criteria were assessed regarding their qol with a specific questionnaire by one researcher . the persian versions of the european organization for research and treatment of cancer quality of life questionnaire - core 30 ( eortc qlq - c30 ) and a background information form were used to assess patients qol , sociodemographic data ( gender , age , educational status , marital status , and employment status ) and clinical characteristics . the eortc qlq - c30 is a cancer - specific , self - administered 30-question instrument for evaluating the qol in cancer patients . the questionnaire items are grouped into five functional scales ( physical functioning , role functioning , emotional functioning , cognitive functioning , and social functioning ) ; three symptom scales ( fatigue , nausea and vomiting , and pain ) ; six symptom single - item scales ( dyspnea , insomnia , appetite loss , constipation , diarrhea , and financial difficulties ) , and one global health status ( ghs)/qol scale . of the 30 items , 28 are scored on four - point likert scales and the remaining two items ( 29 and 30 , for global health status ) are scored on modified seven - point linear analog scales . scores were derived from mutually exclusive sets of items , with scale scores ranging from 0 to 100 after linear transformation . higher scores for the functioning and ghs / qol scales indicated a higher level of functioning and a better qol , respectively , whereas higher scores in symptom scales represented a higher level of symptom . the eortc qlq - c30 questionnaire has been previously used in cancer patients with good validity and reliability in iran . the questionnaire was completed by interview for illiterate or low - literacy patients . data were analyzed using the statistical package for the social sciences ( spss ) version 16 ( spss inc . , the chi - square , student 's t - test , and analysis of variance ( anova ) were used to analyze the data . out of 250 patients with metastatic gastrointestinal cancer , 146 ( 58.4% ) were female and 104 ( 41.6% ) were male . the mean age of patients was 58.83 8.02 years ranging from 44 - 70 and patients aged over 60 years accounted for 70% ( n = 175 ) . in the whole sample , 220 were married , 96 ( 38.4% ) were illiterate , and 80 ( 32% ) were unemployed . among 250 patients , 193 ( 77.3% ) had diabetes mellitus . in the whole sample , the median time since start of treatment was 6 months in 152 ( 60.8% ) of patients and only in 17 ( 6.8% ) of patients the treatment took more than 25 months . the patients also resorted to religious therapies for treatment that the highest religious therapy used was through making a vow ; where 130 ones ( 52% ) were involved in 117 ( 46.8% ) of patients abused psychoactive drugs and 44.4% ( n = 111 ) of patients had a history of surgical treatment . in 32% findings about qol have shown that the mean scores for the functional scale , ghs , and symptoms scales in this study were 56.53 , 59.63 , and 39.08 , respectively . ( the score 100 indicates the best health condition and the score 0 implies the worst health condition ) . there was a significant association between patients gender and their social functioning ( p = 0.017 ) and also their emotional functioning ( p = 0.015 ) . in functional scale of the qol , the highest complaint from the patients was related to physical functioning with mean score 49.54 for men and the least cognitive functioning complaint was related to women with mean score 84.13 [ table 1 ] . patients functioning scores on the eortc qlq - c30 based on gender ( the higher values indicate a higher level of functioning and quality of life , min . : 0 , max . : 100 ) in the symptom scales , the highest complaint was of the financial difficulties with the mean score 89.95 for men and the least complaint was related to diarrhea with mean score 14.15 for women [ table 2 ] . patientsy symptom scores on the eortc qlq - c30 based on gender ( the higher values indicate a greater degree of symptoms , min . : 0 , max . : 100 ) also a statistically significant relationship was found between the age and the organs of gastrointestinal tract which has been cancerous [ table 3 ] . relationship between the age and the organs of gastrointestinal tract which has been cancerous analyzing various domains of the patients qol in terms of the age categories have been shown a statistically significant relationship between symptoms scale ( p = 0.001 ) and global health status ( p = 0.048 ) with age [ table 4 ] . there was no relationship between the qol and sociodemographic variables such as age , gender , marital status , and employment status . this study aims to analyze the qol and its related factors in patients suffering from metastatic gastrointestinal cancer . in this research , the patients mean score has been 50.16 in physical function scale , 56.30 in social function , and 57.63 in general health status . in a study conducted by blazeby et al . , on the short - term outcomes of the patients undergoing esophageal cancer surgery and its relationship with qol , the patients mean score was 79 in physical function , 69 in role playing function , 70 in emotional function , 80 in cognitive function , 72 in social function , and 62 in general health status . also , in the study by kobayashi et al . , the mean scores were as 77 for social function , 68 for role playing function , 67 for emotional function , 67 for cognitive function , 72 for social function , and 58 for general health status . as observed , except for the cognitive function where the iranian patients got higher score than similar studies , in the other domains , the score achieved by iranian patients has been far lower than patients in other countries . in this study , the lowest score is related to the physical function while in the studies by blazeby et al . and kobayashi et al . the highest score concerning qol was for cognitive function index that is consistent with the result of a study by blazeby et al . as seen from comparing qol scores in iran and the other countries , qol in european countries is better than that in iran . this issue can be attributed to the more supporting of these patients by ministry of health in those countries and also therapeutic supports given by cancer support services . however , in iran due to financial problems and expensive treatment expenditures , the patients quality of life has been affected negatively . in this study , there was a significant statistical relationship between age and the disease , so that , the risk of developing gastrointestinal cancer increases with age ( 59 years old and more ) which is consistent with the results of a studies by blazeby et al . and mahan et al . moreover , there is a significant statistical relationship between age and disease symptoms index and also between age and general health status that is in line with results of the other . but smith et al . and redhwan et al . suggested that aging has resulted in quality life improvement . perhaps the difference in the results is due to cultural differences and the number of research sample . in this study , there was no statistical relationship between type of metastatic gastrointestinal cancer and the patients qol domains . the study by schulz et al . indicated that the type of cancer has effect on the patients quality of life . for example , the individuals who are afflicted by rectum and colon cancer had lower life quality compared to those with breast cancer . besides , viklun et al . asserted that the patients undergoing stomach cancer surgery have more optimal quality of life relative to the ones who had esophageal cancer surgery . maybe the reason behind the differences is the study instruments and its related dimensions , different culture , and samples number . in this study , all patients had gastrointestinal metastatic cancer and the same issue partially justifies the gap between the two studies . also in this study , the rate of esophageal cancer in men was more than that in women . in various studies , the prevalence of esophageal cancer is higher in males than females , so that the results of these studies confirm the results of this study . regarding the relationship between marital status and ool , the result of this study shows that there is no relationship between marital status and ool . perhaps , it can be claimed that the effect of marriage on the individuals ool is due to the cultural and social differences . the results of the studies by taria et al . , engel et al . , and avis et al . revealed that job has relationship with qol . however , the study findings by ozaras et al . revealed no statistically significant relationship between job and qol . this gap could be attributed to difference in research time period , insurance system support in the country , and different study areas . the result of the study indicated that there is no significant statistical relationship between the level of education and qol in the patients . the result of study that has been conducted by kwan et al . is consistent with the result of this study in this regard . however , the results of other studies found a significant relationship between the level of the education and qol . these differences might be related to the different sample numbers , measurement instrument , and type or stage of the disease . the study results have demonstrated that the individuals with metastatic gastrointestinal cancer were suffering from substantial disturbances in their qol , especially in social function scale and emotional function which get worse with age . thus , providing psychological counseling and psychotherapy services to deliver culturally appropriate mental health care and social support for these patients and their families which can lead to the improvement of qol in these patients is strongly recommended . the difference between the results of this study and similar studies in other countries is probably due to the lack of appropriate and sufficient supporting treatments , insufficient psychotherapy , counseling , and psychological services and no appropriate education program to the patients and their families . some of the limitations of this study include that the patients who participate in this study did not have a good morale , although their participation in the study was good . also , this study was conducted in a single center in mazandaran , northern iran . therefore , we are not able to generalize this result to the whole population of patients with metastatic gastrointestinal tract cancer . hence , the results of this study need to be interpreted with caution . other studies in patients with various cancers to verify the generalizability of our findings are warranted .

context : quality of life ( qol ) is an important issue in all cancer patients ; especially in patients with metastatic cancer . but there is very little information available about qol in patients with metastatic gastrointestinal cancer.aims:the aim of this study was to evaluate the quality of life and its associated factors among iranian patients with metastatic gastrointestinal tract cancer.materials and methods : in this cross - sectional study , a total of 250 patients with metastatic gastrointestinal tract cancer were recruited from the one oncology center related to the mazandaran university of medical sciences , sari , between march 2012 and august 2013 . their qol was evaluated using the eortc qlq - c30 questionnaire ( persian version).results : in this study , the overall qol score of patients with gastrointestinal tract cancer was 57.63 , which was relatively optimal . there was a statistically significant relationship between symptoms scale and general health status domains of quality of life with age ( p < 0.05 ) . also , there was a significant association between patients gender and their social functioning ( p = 0.017 ) and also their emotional functioning ( p = 0.015).conclusions : the findings suggest that in patients with metastatic gastrointestinal cancers , the most affected functions in their qol were social and emotional functioning which get worse with age . thus , providing psychological counseling and psychotherapy services to deliver culturally appropriate mental health care and social support for these patients and their families which can lead to the improvement of qol in these patients is strongly recommended .

a 26-year - old male , an unmarried rickshaw puller working temporarily in a jute mill in nodakhali , southern west bengal , presented to the psychiatry outpatient department with persistent fear for 23 days that his penis was shrinking into his abdomen which was making him progressively weak . he became intensely anxious and was unable to sleep well at night and repeatedly brooded over the thought . he denied any addiction or habitual intake of any psychotropic drugs , while his informant and medical records failed to show any premorbid psychiatric illness . he promptly reacted by immersing himself in a nearby pond for 1416 hours overnight which resulted in symptomatic chest infection in his lungs . two days following the event , six laborers presented with similar symptoms and they promptly followed similar preventive measure as well . none of the cases could qualify for any other codable axis i diagnosis . the occurrence led us to arrange for a small medical camp in the vicinity to spread awareness and group psychotherapy , and the outbreak subsided after 56 days . a 53-year - old divorced senior worker , who was show caused by the authority recently for irregularities in his professional commitment , working as a mechanic in the same jute mill suddenly noticed his penis growing smaller and shrinking into his abdomen . this resulted in a panic , and he frantically reached for help in the emergency department of the hospital . he had learnt that a similar occurrence had occurred 1 week back nearby his quarter , which caused the victims to immerse themselves in ice - cold water . he admitted taking country liquor at least on two to three occasions per week , amounting to 12 pints each time on an average , though he was abstinent for the last 15 days . his condition caused his nephew , who had been on a vacation in bihar , to come back to the state . in 23 days , the nephew started having similar complaints that resulted in intense panic and had to be admitted to surgery observation ward following abrasive injury over the glans which reportedly occurred as he tried to pull out his penis from the abdomen , which he thought was retracting . he recovered within 3 days but the news was followed by an outbreak of similar illness among 11 workers in the same jute mill and they resorted to immersing themselves in a pond nearby . they believed that the disease was occurring due to increased heat accumulated within the body that needed to be cooled down . another medical camp was arranged , and assurance followed by group psychotherapy resulted in reduction of symptoms within 67 days . immediately prior to the outbreak , there was a prolonged cease work in the jute mill discussed and the workers were not getting their salaries for the last 1 year which led to financial instability . the demographics and other relevant particulars of the two case clusters discussed herewith are briefly summarized in [ table 1 ] . a 26-year - old male , an unmarried rickshaw puller working temporarily in a jute mill in nodakhali , southern west bengal , presented to the psychiatry outpatient department with persistent fear for 23 days that his penis was shrinking into his abdomen which was making him progressively weak . he became intensely anxious and was unable to sleep well at night and repeatedly brooded over the thought . he denied any addiction or habitual intake of any psychotropic drugs , while his informant and medical records failed to show any premorbid psychiatric illness . he promptly reacted by immersing himself in a nearby pond for 1416 hours overnight which resulted in symptomatic chest infection in his lungs . two days following the event , six laborers presented with similar symptoms and they promptly followed similar preventive measure as well . none of the cases could qualify for any other codable axis i diagnosis . the occurrence led us to arrange for a small medical camp in the vicinity to spread awareness and group psychotherapy , and the outbreak subsided after 56 days . a 53-year - old divorced senior worker , who was show caused by the authority recently for irregularities in his professional commitment , working as a mechanic in the same jute mill suddenly noticed his penis growing smaller and shrinking into his abdomen . this resulted in a panic , and he frantically reached for help in the emergency department of the hospital . he had learnt that a similar occurrence had occurred 1 week back nearby his quarter , which caused the victims to immerse themselves in ice - cold water . he admitted taking country liquor at least on two to three occasions per week , amounting to 12 pints each time on an average , though he was abstinent for the last 15 days . his condition caused his nephew , who had been on a vacation in bihar , to come back to the state . in 23 days , the nephew started having similar complaints that resulted in intense panic and had to be admitted to surgery observation ward following abrasive injury over the glans which reportedly occurred as he tried to pull out his penis from the abdomen , which he thought was retracting . he recovered within 3 days but the news was followed by an outbreak of similar illness among 11 workers in the same jute mill and they resorted to immersing themselves in a pond nearby . they believed that the disease was occurring due to increased heat accumulated within the body that needed to be cooled down . another medical camp was arranged , and assurance followed by group psychotherapy resulted in reduction of symptoms within 67 days . immediately prior to the outbreak , there was a prolonged cease work in the jute mill discussed and the workers were not getting their salaries for the last 1 year which led to financial instability . the demographics and other relevant particulars of the two case clusters discussed herewith are briefly summarized in [ table 1 ] . koro has been characterized with three cardinal symptoms , i.e. ( 1 ) a belief or delusion of retraction of penis into the abdomen ; ( 2 ) intense panic with physical signs of anxiety ; and ( 3 ) the use of mechanical means to prevent penile retraction . koro has been discussed in connection with a few koro - like syndromes or genital retraction syndrome , otherwise unclassified . in this article , all the cases suffered from the syndrome failed to qualify for any other axis 1 psychiatric diagnosis and the mode of presentation of the mass hysteria was characteristic of koro . most of the cases believed that the disease was caused either due to overindulgence to masturbatory practices or nocturnal emission . both may be considered as a violation to the prevailing folk rule system governing sexual practices in the community . possibility of sexual inadequacy in a few cases may also be considered to be a potential precipitating cause . moreover , economic instability and uncertainty over the future may have arisen in a few cases due to longstanding cease work in the jute mill prior to the event , which may be considered as an important psychodynamic triggering factor . comorbid substance abuse was found in a few cases which has been linked with the occurrence of koro . however , course of koro is usually acute , brief , and self - limiting , though a few chronic koro - like syndromes have been described . most of the cases encountered in this article had such a characteristic short course without any significant residual illness . in this article , all the cases were males with a relatively low socioeconomic background . most of the cases were unmarried ( 84.21% ) and were employed but irregularly paid at the office ( 87.47% ) . only a few cases admitted of having a premorbid psychotic illness ( 12.53% ) or substance abuse ( 12.53% ) , and a few admitted of homosexuality ( 15.79% ) and commercial sex worker exposure ( 12.53% ) . commonest health - seeking behavior observed in these cases was immersing in water ( 57.89% ) , while surgical emergency was encountered in one of the cases ( 5.26% ) . koro remains prevalent in non - chinese and non - indonesian nations , contrary to the common belief . it is still more prevalent in areas where literacy levels have not reached satisfactory levels . prevailing socioeconomic upheavals and economic uncertainty continue to play an important role in causation of the disease . the case clusters described in the article show how group psychotherapy and awareness campaigns can effectively eradicate the syndrome .

koro is a culture - bound syndrome that is characterized by the belief of retraction of genitals into the abdomen . it was initially reported in asian countries , as having a usual acute and brief course . two case clusters have been described in this article . both occurred in the same jute mill in southern west bengal among the workers . the case clusters depict unique socioeconomic factors and interesting health - seeking behavior toward koro . all the cases had a self - limiting course and reasonably good outcome . the case cluster yet again confirms that koro is not as rare as it is thought of and social and economic factors continue to play an important role in the etiology of the disease .

giant intracranial aneurysms have a lower propensity to bleed than small and medium - sized lesions and they may present with symptoms secondary to mass effect . while the diagnosis of a giant aneurysm can be readily made on radiology if there is any circulating component within the aneurysmal sac , establishing a pre - operative diagnosis becomes difficult if the aneurysm is completely thrombosed . the absence of a circulating component and the visualization of a large thrombus would lead to consideration of various other differentials depending on the location of the lesion . a 45-year - old male presented with complaints of progressivelyworsening vision in his left eye and headache since 6 months . he also complained of gait ataxia and occasional social incontinence of urine . on examination , visual acuity in mri brain revealed a large left basifrontallesion extending superiorly and distorting the corpus callosum [ figure 1 ] . the lesion was hyperintense on t1-weighted images ( wi ) [ figure 1a ] and hypointenseon t2wi[figure 1b ] . the lesion did not enhance on gd - contrast sequences and no blood flow was demonstrated within the lesion on contrast mr angiography ( mra ) . ct angiography ( cta ) demonstrated displacement of left anterior and middle cerebral arteries ; there was no enhancement within the lesion [ figure 1d ] . ( a ) t1-weighted coronal image showing a t1 hyperintense lesion . ( b ) t2wi demonstrating the hyppointense capsule as well as contents . ( d ) ct angiogram demonstrating the distortion of the left mca and acas based on the location and presence of a large thrombus , adifferential of giant cavernous hemangioma was considered . however , the mri appearance of a well - delineated sac with a thrombus within it was not entirely concordant with this diagnosis . however , digital subtraction angiogram ( dsa ) did not reveal any filling of contrast within the sac of the lesion . the dsa also revealed that the left middle cerebral artery was displaced inferiorly by the lesion [ figure 2a ] . the left a1 was not well visualized ; both a2s were filling on right carotid injection and a round shift of the a2s was noted [ figure 2b ] . since dsa did not demonstrate any contrast within the lesion , a possibility of intracerebral intravascular papillary endothelial hyperplasia ( masson 's tumor ) was also considered , although this is a rare lesion within the brain . the a2s are shifted to the right due to the mass effect of the lesion . no contrast is seen within the lesion a left pterional craniotomy was made and the lesion approached via the trans - sylvianroute . there was a good plane of cleavage and capsular resection was performed in a piecemeal manner . , a portion of the capsule was found to be significantlyadherent to the left a1-a2 junction . there were areas of calcification in this area that further rendered dissection from the a1-a2 complex difficult [ figure 3a ] . multiple perforators were found arising from the a1a2 junction and traversing posteriorly ; these were adherent to the capsule . postoperative contrast - enhanced ct and mri revealed no residual capsule[figure 3b ] and subsequent dsa revealed preserved flow in all vessels and no fresh abnormality [ figure 3c ] . histopathology of the resected specimen was diagnostic of aneurysmal wall with thrombus [ figure 3d ] . follow - up dsa is planned to ensure that no regrowth of the aneurysm has occurred . ( a ) intraoperative image showing the optic chiasm ( star ) ; the lesion ( horizontal arrow ) is closely adherent to the left a1 ( vertical arrow ) . ( c ) postop angiogram demonstrating the right internal carotid artery supplying both a2 arteries across a patent acoma . ( d ) photomicrograph of the aneurysm wall composed of fibrocollagenous wall , congested blood vessels , lymphocytic infiltrate and hemosiderin laden macrophages ( h and e 400 ) spontaneousand complete thrombosis of giant intracranial aneurysm is reported to occur in 3 - 20% of cases . the majority of giant aneurysms that have been reported to have undergone spontaneous thrombosis arose from the cavernous segment of the internal carotid artery . there are singlecase reports of giant posterior cerebral artery , superior cerebellar artery and pericallosal artery aneurysmsthat underwent spontaneous thrombosis . there exist no previous reports of giant anterior communicating artery aneurysms undergoing spontaneous thrombosis . in the present instance , aneurysm was not considered as the top preop differential since the lesion did not enhance on contract administration . intra - operatively , the only clues to the nature of the lesion werethe presence of a multi - lamellatedthrombuswithin the cavity and the attachment to the anterior communicating artery . totally thrombosed giant aneurysms can be confused with other tumors like cavernous hemangiomas , masson 's tumor , oligodendrogliomas and occasionally meningiomas . there are several hypotheses to explain the phenomenon of spontaneous thrombosis in giant intracranial aneurysms . the fundus of a giant aneurysm may itself compress the parent artery , resulting in stenosis and a low - flow state . this may lead to intra - aneurysmal clot formation ultimately resulting in thrombosis of the aneurysm . a large aspect ratio ( indicative of a small neck ) could also result in a low - flow state . extension of the thrombus to the neckwould result in a further reduction of blood flow within the sac resulting in total thrombosis . it is possible that in the present case similar mechanisms could have been responsible for complete isolation of the aneurysmal sac from the circulation . the formation of a neo - intimal layer in the narrow neckcould explain the absence of bleedingdespite close dissection of the sac from the a1a2 junction . pre - operative dsa is an absolute imperative to establish the diagnosis of large thrombosed intracranial mass lesions . this lesion was not recognized as an aneurysm at surgery owing to the complete absence of bleeding and the calcification at the neck ; thus , the neck was not clipped . however , it is generally recommended that a clip be placed across the neck since there have been several reports of regrowth of giant aneurysms that have not been clipped and completely excluded from circulation . spontaneous thrombosis of giant intracranial aneurysms is a rare phenomenon . but aneurysms need to be considered in the differential diagnosis of mass lesions located in close proximityto cerebral vasculature . the aim of surgery would be to decompress the surrounding neural structures . a clip application across the neck may not be necessary if there is no filling of the sac while dissecting close to the neck .

giant anterior communicating artery aneurysms are rare . apatient presented with visual dysfunction , gait ataxia and urinary incontinence . mri showed a giant suprasellar mass . at surgery , the lesion was identified as being an aneurysm arising from the anterior communicating artery . the difficulty in preoperative diagnosis and relevant literature are reviewed .

a traumatic right diaphragmatic rupture as the result of blunt trauma is a rare condition . the overall incidence of diaphragmatic rupture after blunt trauma is 0.8 - 3.6% ( 1 ) . most injuries are due to vehicular - related incidents ( 79.5% ) and falling from a height ( 15.9% ) ( 2 ) . right - sided tears are significantly less likely than left - sided tears , 27.3% and 68.2% respectively ( 3 ) . the correct diagnosis of diaphragmatic injury is initially missed in 12%-66% ( 1 ) delayed diagnosis and treatment of diaphragm rupture is associated with increased rates of morbidity and mortality . in our case on our outpatient clinic , a 37-year - old man was presented with 31 years before a fall from a wall of 3 meters on his right side . next to this major event the man was involved in a moped -car accident with only his face wounded , 18 years ago . during his life the patient presented to us with primary complaints of progressive , stabbing pain in the upper right abdomen and right lower thorax with simultaneous periods of dyspnoea . the symptoms worsened over a year , eventually leading to shortness of breath during rest . beside this presentation the patient had right upper abdominal pain while eating spicy food . on admission , his vital signs were stable and colour was fair . pulmonary examination revealed diminished breath sounds at the basal right hemithorax and the diaphragm was determined to be higher on the right by percussion . the diagnosis was confirmed by thoracic - abdominal x - rays and computerised tomography ( ct ) imaging , which revealed intra - thoracic displacement of the liver and also the gallbladder ( figure 1 ) . an elective thoracotomy in the sixth intercostal space was performed with repairing the diaphragmatic hernia ( figure 2 ) . the liver with gallbladder was replaced in the abdominal cavity , after adhesiolysis of the lung from pleura and diaphragm , whereupon the diaphragm was closed tensionless by running technique with non - absorbable sutures . two drains were left behind , one near the diaphragm and one in the right upper thorax . right sided diaphragmatic rupture with consequently hepatothorax is a rare condition . blunt traumatic diaphragm rupture a delay could result in increased rates of morbidity and mortality ( 5 ) . in case of hepatothorax , hypovolemic shock can occur , because of possible kinking of the inferior vena cava with obstruction of the blood . in this case there was a lateral impact on the chest , which distorted the chest wall and sheared the diaphragm . there remains doubt about the cause of delayed diagnosis and treatment of this diaphragm injury , since it could occur as the result of either delayed rupture or delayed detection . even if the herniation did not take place initially it would result in herniation eventually , because of the significant discrepancy between the intra - thoracic pressures and higher intra - abdominal pressure . most of the diaphragmatic ruptures occur on the left side , because the right diaphragm is congenitally stronger than the left . moreover the liver partially protects the right side as the impact can be spread over a large area . pain in the upper abdomen and lower thorax , dyspnoea , cyanosis and hypotension are typical symptoms of diaphragmatic injury , but if the rupture is small the patient can remain symptom free for a long time . the true incidence of traumatic diaphragm rupture is unknown because in 12 - 66% ( 1 ) of major trauma victims , the diagnosis is missed . there is no consensus yet , on the gold standard of imaging technologies to diagnose diaphragm rupture . based on the literature , diagnosis of diaphragmatic injury requires a high index of suspicion regardless whether you make an x - ray or ct . the choice of surgical approach includes thoracotomy , laparotomy , or both if it is necessary . the decision to repair the diaphragm either way is dictated by the stability of the patient and the presence of other associated organ injuries .

a traumatic right diaphragmatic rupture is an uncommon condition , as it occurs in 0.8 - 3.6% after blunt trauma . it is challenging to find the diagnosis immediately and is illustrated by the incidence of 12 - 66% initially missed diagnosis ( 1).most blunt traumatic diaphragm ruptures are an indication for early aggressive surgical intervention by way of thoracotomy , laparotomy , or both if it is necessary . delayed diagnosis and treatment of diaphragm rupture is associated with increased rates of morbidity and mortality . therefore , diagnosis of diaphragmatic injury requires a high index of suspicion . we report a case of a 37-year - old man with right diaphragmatic rupture after blunt injury 31 years prior to admission .

male patients aged > 40 years with type 2 diabetes of duration < 5 years and a1c < 9.0% were studied . those with severe extracranial internal carotid artery ( ica ) stenosis , known as coronary arterial disease , and those receiving insulin were excluded . all gave written informed consent and underwent exercise tolerance testing ( ett ) to exclude subclinical coronary arterial disease . peripheral ( radial ) pulse - wave analysis ( pwa ) and ( carotid - radial ) pulse - wave velocity ( pwv ) were measured . blood was drawn for measurement of routine parameters and vascular endothelial growth factor , soluble intercellular adhesion molecules , e - selectin , and c - reactive protein levels . thereafter , a 45-ml infusion of 0.8 mol kg min clinical - grade l - nmma ( clinalfa / bachem - ag , weil - am - rhein , germany ) dissolved in normal saline was given intravenously over 15 min . ica , middle cerebral artery , pwa , and pwv parameters were repeated upon cessation of infusion and 10 , 20 , and 30 min thereafter . participants were then randomized to either 300 mg allopurinol or a matching placebo , each taken orally once daily for 2 weeks . following this , all assessments were repeated . a 2-week washout period then ensued , after which repeat assessment , a 2-week dose of the other agent ( placebo or allopurinol ) , and the final assessment occurred . the primary end point was change in ica flow induced by the l - nmma infusion and expressed as area under the flow - per - time curve ( auc ) measured from the start of infusion to 20 min after its completion ( 3,4 ) . a negative auc signifies the expected reduction in ica flow following l - nmma infusion . based on our previous pilot data ( 3 ) , a sample of 20 patients would enable detection of a clinically significant improvement in l - nmma responsiveness following allopurinol ( to 75% of that seen in nondiabetic individuals ) with 90% power ( = 5% ) . secondary end points were change in augmentation index ( measured during pwa ) , pwv , and blood markers . standard crossover study analysis techniques were employed , and differences between the study periods were compared using paired nonparametric tests ( wilcoxon 's signed - rank test ) . a mixed - effects model was generated to adjust for any effect of treatment ordering . ten completed the protocol ; one had a positive ett , two failed to attend after the ett and the first visit , and one was unable to receive l - nmma during his last study visit . the study was terminated early as a result of the national lack of availability of l - nmma . of those recruited , mean sd age was 53.1 10.8 years , 85.7% ( n = 12 ) had coexisting hypertension , 78.6% ( n = 11 ) were receiving oral hypoglycemic agents , 78.6% were receiving ace inhibitor or angiotensin receptor blocker therapy , 64.3% were receiving antiplatelet therapy , and 92.3% were on lipid - lowering therapy . ica flow fell by a median of 4.8% ( 95% ci 17.3 to 9.4 ; p = 0.25 ) . we saw no change in blood pressure parameters where aucs were considered or in the augmentation index or pwv following l - nmma ( table 1 ) . allopurinol treatment significantly augmented the reduction in ica flow following l - nmma infusion ( table 1 ) . ica flow fell by a median of 11.9% ( 95% ci 2.5 to 23.3 ; p = 0.04 ) following l - nmma after treatment with allopurinol . the mixed - effects model revealed results consistent with the main analysis ( p = 0.046 for allopurinol vs. placebo ) and found no significant order effect ( p = 0.51 ) . allopurinol led to an improvement in response to l - nmma in 8 of the 10 individuals . the preinfusion augmentation index , pwv ( table 1 ) , and l - nmma ( data not shown ) did not differ significantly between the treatment periods ( table 1 ) . no significant differences were seen in any of the blood markers ( table 1 ) . treatment with allopurinol enhanced this effect , implying that allopurinol improves basal levels of no activity , causing them to approach those previously seen in healthy volunteers ( 3 ) . these results contrast with a previous study where forearm blood flow responses were improved following allopurinol ( 5 ) , but we employed different techniques and did not design our study to detect differences in these parameters . interestingly , at the baseline visit , we failed to replicate the increase in the augmentation index or pwv following l - nmma seen previously in healthy volunteers ( 6 ) , and it may be that this response is also impaired in those with diabetes . the potential beneficial effects of allopurinol on the vasculature are twofold : it reduces xanthine oxidase mediated o2 production ( 7 ) and reduces serum uric acid ( 8) . previous studies have shown a beneficial effect of xanthine oxidase inhibition on measures of forearm or coronary endothelial function ( 9 ) , but this is the first human study to show improvement in cerebrovascular function . we followed a rigorous protocol , and improvements in peripheral vascular responses to l - nmma have been shown following treatment with other cardiovasculature - protective agents ( 10,11 ) . however , we studied fewer patients than intended because of the lack of ongoing availability of l - nmma , which reduces our statistical power , but the consistency of effect we saw is reassuring . our dosing period was short , and we can not exclude the possibility that the changes we saw may subsequently be reversed by other sources of o2 . also , we have only examined the effect on endothelial no synthase activity , and other forms of no and o2 production may be important . in summary , our data show that xanthine oxidase inhibition with allopurinol improves cerebral no activity , which may benefit cerebrovascular health .

objective type 2 diabetes increases risk of stroke , perhaps because of impaired cerebrovascular basal nitric oxide ( no ) activity . we investigated whether this activity is improved by a 2-week course of the xanthine oxidase inhibitor allopurinol.research design and methods we performed a randomized , double - blind , placebo - controlled crossover study . we measured the response to infusion of ng - monomethyl - l - arginine ( l - nmma ) in males with type 2 diabetes before and after allopurinol or placebo . the primary end point was the change in internal carotid artery flow following l - nmma infusion , expressed as the area under the flow - per - time curve.resultswe enrolled 14 participants . allopurinol improved responses to l - nmma when compared with responses associated with placebo ( p = 0.032 ; median reduction in internal carotid artery flow following l - nmma of 3,144 ml [ 95% ci 3757,143]).conclusions xanthine oxidase inhibition with allopurinol appears to improve cerebral no bioavailability , as evidenced by a greater response to infusion of l - nmma .

a 75-year - old woman ( height 150 cm , weight 63.5 kg ) was admitted to the hospital for phased total knee replacement on the both sides under the diagnosis of bilateral degenerative arthritis . blood test , ekg , chest x - ray , and pulmonary function test performed prior to surgery were within normal ranges , and echocardiography showed ejection fraction of 60% , and manifested diastolic dysfunction of the left atrium . the patient 's blood type was o rh - positive and the preoperative cross matching and antibody screening test turned out to be negative . under general anesthesia , right total knee replacement arthroplasty was first performed and after surgery she received 2 units of packed red blood cells ( rbcs ) . two weeks after surgery , preoperational test for left total knee replacement indicated that hemoglobin level was 10.2 g / dl and hematocrit was 29.2% , and the antibody screening test was negative . on surgery day , she received 0.2 mg of glycopyrrolate intramuscularly one hour before induction of anesthesia . in the operating room , ekg , noninvasive blood pressure monitoring and a pulse oximetry monitor were placed . anesthesia was induced with propofol 120 mg and rocuronium 50 mg , and maintained using o22 l / min and n2o 2 l / min , and sevoflurane 2 vol% after tracheal intubation . for continuous monitoring of blood pressure and arterial blood gas analysis , 20 g catheter was placed to the left radial artery and central venous catheter was inserted to the internal jugular vein for central venous pressure ( cvp ) . one hour and 20 minutes after the onset of surgery when the total amount of blood loss was estimated more than 800 ml , transfusion of packed rbcs was started . a cross - matching test turned out to be negative again , suitable for transfusion . during transfusion , the patient showed stable vital signs . five minutes after 1 unit of packed rbcs was transfused , red - colored urine , which was suspected as hemoglobinuria , was observed . for immediate treatment , fluid then we asked the department of laboratory medicine to conduct abo - rh blood typing test of the patient 's and the donor 's blood , cross - matching , antibody screening test , direct anti - globulin test ( dat ) and indirect anti - globulin test ( iat ) , and urinalysis . hereafter , no big blood loss developed and the surgery was completed without further transfusion . except for the incidence of red - colored urine sustained during surgery , patient 's vital signs were stably maintained . at the completion of surgery when her spontaneous respiration and consciousness were confirmed , red - colored urine sustained even in the recovery room , but the color was waning and the patient 's vital signs were normal , so she was referred to a ward . post - operative test results showed that the transfused blood and patient 's blood were compatible and that antibody screening test result was negative . urinalysis findings indicated 3 + blood , 0 rbc / hpf , and 2 + protein . examination of patient 's blood tested by an independent laboratory to determine more exact cause revealed that anti - di antibody was identified in an unexpected antibody screening test . since the next day of surgery hemoglobin level measured right after surgery was 8.7 g / dl , showing a decrease , but thereafter no significant change further took place and bun and creatinine level also sustained in the normal range , not followed by any other transfusion reaction . potential adverse effects from blood transfusion involve contamination , acute immunologic hemolytic reaction , delayed extravascular hemolysis , febrile allergic transfusion reaction , erythrocytolysis , etc . among these reactions , acute immunologic hemolytic reaction is mainly developed by incompatible blood transfusion of abo blood group or by unexpected antibody present in the blood . for the patient in this case , cross - matching tests conducted before transfusion and immediately after red - colored urine developed were both negative . the main purposes of cross matching are : 1 ) to prevent acute hemolytic transfusion reaction due to abo blood group incompatibility by detecting patient 's anti - a and anti - b antibodies against rbcs to be transfused ; 2 ) to prevent acute hemolytic transfusion reaction developed by the response of recipient 's unexpected antibody to the counterpart antigen of donor 's blood . what is definitely necessary for the 2nd purpose is the indirect anti - globulin method including an antiglobulin phase . when detecting igm that reacts even at room temperature such as anti - a or anti - b antibody in 1 ) , it is possible to identify agglutination reaction by centrifugal sedimentation following after reaction of rbcs and serum at room temperature , which is called " immediate spin phase " or " saline phase " . the main purpose of the immediate spin phase is to prevent abo blood group incompatibility . when the absence of unexpected antibody in recipient 's specimen is confirmed ( by negative antibody screening result ) or when an emergency situation makes it impossible to perform a test for incompatibility by unexpected antibody ( in cross - matching test of anti - globulin method , it takes at least 15 to 30 minutes for the reaction time of serum ) , it is a routine for rbcs to be taken out only after immediate spin phase . in the present case , unexpected antibody screening test performed at our hospital was negative while the patient had no abnormal medical history . as bleeding during surgery is regarded as emergency transfusion , cross - matching test was performed only with immediate spin phase and the result turned out to be negative ( compatible ) when transfusion was performed . for the causes of acute hemolytic reaction developed during surgery in the present case , while the results of the tests performed by an independent blood center were unknown , the following three scenarios were to be considered : 1 ) drug - induced hemolysis : this assumption is supported by the fact that iat was positive while antibody screening test was negative . even though there is no abnormality in previous transfusions , such drugs as acetaminophen , antihistamine , cephalosporin , etc . can induce hemolytic reactions or positive results of dat by forming immune complex in combining with the red cell membrane of blood product . 2 ) hemolysis induced by unexpected antibody of low potency : in presence of low - potency antibody , it is possible that although antibody screening test is negative , hemolytic reaction can develop when antibody is activated by transfusion . even if a test performed is still negative after exhibition of hemolytic reaction , such possibility can not be completely excluded . it is because there are some cases in which the manifestation of unexpected antibodies such as ' kidd ' can be identified late or clinical manifestation can be presented at even low potency when the antibody screening test is negative . 3 ) hemolysis induced by anti - di antibody : among the antigens of diego blood group , di and di are the most significant ones . in the frequency of diego phenotypes , di(a - b+ ) is found 90% of korean population , followed by di(a+b+ ) , 9.75% , and di(a+b- ) , 0.25% . di is classified as a high - frequency antigen regardless of ethnicity while the prevalence of di differs among races . the di antigen is rare in caucasians , but occurs with high incidence in asians and american indians . for koreans anti - di antibody has relative high positive reaction rate in koreans [ 3 - 6 ] . it has been reported that anti - di antibody was detected in a patient who was given transfusion repeatedly in korea , besides incidences of delayed hemolytic transfusion reaction due to anti - di antibody . because antibody screening panels for an unexpected antibody screening test currently used in korea are mostly imported abroad , there is a high probability that the di antigen is not contained . even though anti - di antibody is present in patient 's serum , it is not detected in unexpected antibody screening test , which keeps transfusion reaction from being prevented . on the basis of the lab results from the independent blood center that the patient was negative for di antigen and positive for anti - di antibody , we made a diagnosis of acute hemolytic reaction due to anti - di antibody . considering that she had a history of a surgery previously performed at another hospital when she may have received transfusions and that she was given a transfusion two weeks ago , it is highly likely that anti - di antibody was produced by transfusion . since she had no specific adverse effects of transfusion performed two weeks ago , we assume that she would be first exposed to di antigen at the time of transfusion or that there was no side effect because there would be no anti - di antigen in the donor 's blood even if she had already have anti - di antibody . if our hospital had performed an unexpected antibody screening test with antibody screening panels containing di antigen , it would have been possible to detect anti - di antibody and to prevent transfusion reaction by preparing blood free of di antigen at transfusion . on the contrary to the reports that anti - di antibody is an immune antibody , generally causing delayed hemolytic transfusion reaction , the present case experienced acute hemolytic transfusion reaction . fortunately , the patient was recovered without much adverse effect because the amounts of blood loss and transfusion were not large . if acute hemolytic transfusion reactions due to anti - di antibody develop when emergency transfusion or massive transfusion is required , however , it will take a long time to diagnose and prepare for blood . therefore , considering that koreans have a high incidence rate of positive reactions for di antigen and anti - di antibody , it is necessary that unexpected antibody screening test before transfusion should include a test to identify anti - di antibody .

many medical institutions in korea have recently been performing an antibody screening test as one of the essential elements of a pre - transfusion test . the dia antigen is well known as one of the antigens with low incidence among caucasians ; however , it has been discovered with a relatively higher incidence among mongoloid populations . the frequency of the dia antigen among the korean population is estimated to be 6.4 - 14.5% . but in korea , a screening panel of cells from abroad without dia positive cells has been commonly used when a patient has an unexpected antibody screening test . here we report a case of acute hemolytic transfusion reaction due to anti - dia antibody . to prevent other transfusion reaction by anti - dia antibody , addition of dia positive cells as unexpected antibody screening test is recommended .

stroke impairs an individual s motor , sensory , cognitive , and emotional control . an individual s capability to select sensory information for postural stability and process it suitably in spatial and temporal templates may be remarkably impaired by a stroke , leading to delayed balance reactions in various situations1 . these problems make postural control difficult and consequently contribute to disturbed performance of functional activities and walking2 . furthermore , inappropriate somatosensory information arising from the affected side likely contributes to postural instability3 . recent concepts require the understanding of trunk and neck controls that are required to maintain static and dynamic balance , although the proprioceptive feedback mechanism within the lower limbs has been traditionally considered an important component of optimal balance4 . in impaired proprioceptive processes of the lower limbs , compensation by the vestibulospinal reflexes and proprioceptive input from the cervical region may be inevitable for maintaining appropriate body balance5 . with the high density of proprioceptors such as muscle spindles and the golgi tendon organ , the cervical region plays an essential role in an individual s ability to recognize their spatial orientation and body position and maintain equilibrium in changing environments during daily activities6 . that is , its contributions to maintenance of static and dynamic balance may be responsible for the regular connection between afferent inputs from joint and muscle proprioceptors and those from visual and vestibular systems . although some studies have investigated the effects of sensory feedback for improving balance and postural control , their findings have failed to provide sufficient evidence7 , 8 . therefore , in this field , studies should focus on exploring novel methods to reinforce the balance control mechanism in patients with chronic poststroke hemiparesis , which increases functional performance , rather than investigating the efficacy of current therapeutic strategies . to our knowledge , proprioceptive training using neck movements has received little attention in the management of patients with chronic poststroke hemiparesis , despite its easy application and comfort of use for clinicians . hence , this study aimed to investigate a proprioceptive training procedure using cervical movement and report the results . the inclusion criteria were as follows : first onset of stroke and onset duration of > 6 months , no cognitive impairment ( > 24 points on the mini - mental state examination - korean version)9 , ability to stand and walk 10 meters independently without supervision ; and no orthopedic or other neurological disorders that impede balance function . prior to initiation of the study , detailed information about the experimental procedure and safety were provided to the subjects , each of whom signed a written consent form . general subject characteristics are summarized in table 1table 1.general characteristics of the subjectssubject 1subject 2subject 3genderfemalefemalemaleage ( years)626466duration since stroke ( months)595484hemiplegic sideleftleftrightstroke typehemorrhagehemorrhagehemorrhagemmest - k282928mmse - k : mini - mental state examination - korean version . mmse - k : mini - mental state examination - korean version outcome measures included the stability and weight distribution indices under the eyes - open and eyes - closed conditions measured by a tetrax system ( sunlight medical ltd . , ramat gan , israel ) using four force plates to detect the ground reaction force for both feet during standing , timed up and go ( tug ) , and proprioception tests . the tetrax system measures the pressure transferred to the force plates during standing and analyzes the data after amplification and filtering . the stability index represents the extent of postural sway and an individual s ability to compensate for it , and greater instability is indicated by greater values10 . further , the weight distribution index suggests the extent of weight distribution to both sides when standing on the force plates , and a higher score indicates a more severe pathological condition10 . the test - retest reliability of measurements obtained with the tetrax system is reportedly high ( r = 0.88)11 . the tug is an assessment tool that is used to evaluate a subject s mobility and dynamic balance . in the tug , subjects are instructed to rise from a chair , walk 3 m , turn around , return to the chair , and sit down12 . the intra- and inter - test reliabilities were r = 0.99 and r = 0.98 , respectively13 . the proprioception test was performed using a method that blindly assesses the repositioning error of the cervicocephalic region14 . for this test , subjects sat on a chair with a backrest facing a screen placed 1 m in front of them . a laser pointer was positioned at the middle top of the head to indicate the movement of the neck on the screen with a red dot . the first step was to identify the neutral head position by maintaining the red dot within a round 1-cm area for 3 s , and then the subjects rotated their heads 30 to the right . the outcome was determined by measuring the error interval between the neutral position and the repositioning point . subjects received a daily conventional therapy program , which comprised strengthening and stretching exercises for the upper and lower limbs and therapist - guided functional training , followed by proprioception training . proprioception training included a self - detection effort to trace a neutral position from various directions of cervical movement15 . the initial step , in which the subjects sat on a chair with a backrest , was the same as that for the proprioception test procedure . during the training , the trajectory of the red dot projected from the laser pointer offered real - time feedback about cervical movement . prior to the training , a round area with a 30-cm diameter was marked on the screen at head height . all training procedures were performed with the eyes covered with an eye patch . to recognize the neutral position of the neck , the subjects maintained a neck position and then directed the red point to the round target on the screen for 3 s. after this procedure , the neck was positioned at the end range of flexion , extension , and rotation for 3 s each , the order of which was randomly generated using microsoft excel . the patients were then instructed to return to the neutral position . when they managed to successfully aim the laser pointer at the target area for 3 s , verbal feedback was provided . the training was performed for 30 min daily , 5 times a week for 4 weeks ( for a total of 20 sessions ) . this study was a case series with the aim of reporting the treatment findings of a very small population with chronic stroke . thus , to illustrate the intervention effects directly , outcome data were provided as actual pre- and post - test scores without the use of statistical analysis . table 2table 2.comparison of pre- and post - training outcomes for all subjectssubject 1subject 2subject 3pre - testpost - testpre - testpost - testpre - testpost - teststability indexeyes - open23.5122.5324.5223.5528.5627.55eyes - closed48.6745.6748.9844.2551.2350.27weight distribution indexeyes - open7.827.558.327.929.369.23eyes - closed10.489.6811.5710.2512.6911.47tug ( sec)15.0514.5517.1216.5015.6915.30proprioception test ( cm)8.937.548.968.679.968.82tug : timed up and go test represents the changes in the stability index , weight distribution index , tug test score , and proprioception test score . the stability indices for subjects 1 , 2 , and 3 decreased by 4.17% , 3.96% , and 3.54% under the eyes - open conditions , respectively , and by 6.16% , 9.66% , and 1.87% under the eyes - closed conditions , respectively . the weight distribution index was reduced by 3.45% , 4.81% , and 1.39% under the eyes - open conditions , respectively , and by 7.63% , 11.41% , and 9.61% under the eyes - closed conditions , respectively . the tug test scores of all subjects showed improvements of 3.32% , 3.62% , and 2.49% respectively , and the proprioception test scores increased by 15.57% , 3.24% , and 11.45% , respectively . it is generally accepted that systematic processing and integration of visual , vestibular , and proprioceptive information from each part of the body has a great influence on maintaining optimal postural stability and movement control in space during daily activities . hence , impaired sensory perceptions after stroke may be among the greatest challenges for maintaining postural control and stable balance patterns2 . the pathological changes of the nervous system , the lack of movement and asymmetrical posture , contribute to decreased proprioceptive function after stroke . our results focused on the feasibility of neck proprioceptive training for improving the balance function of patients after stroke and demonstrated favorable effects on static and dynamic balance function . asymmetrical posture in stroke may be closely associated with a biased weight distribution to the unaffected side , leading to postural instability with detrimental effects on balance during various activities . the neck is an essential component in the regulation of one s head and body orientation in space and is necessary for maintaining balance16 . the abundance of peripheral proprioceptive organs in the cervical region , especially in the upper cervical muscles , is greatly advantageous in controlling and organizing somatosensory information related to balance and movement7 . proprioceptive information from these organs plays an important role in an individual s ability to adapt to a changing environment by controlling postural perturbations . this knowledge supports our hypothesis that neck proprioceptive training improves the balance function of patients after stroke . as described here , the stability and weight distribution indices showed greater improvements under the eyes - closed conditions than under the eyes - open conditions . vision provides strong sensory feedback to support an individual s physical control and performance and is frequently used to compensate for impaired proprioceptive function during movement17 . however , under conditions of visual deprivation , proprioceptive input from the cervical region may be a major factor in the recognition of spatial orientation , position , and equilibrium7 . in such aspects , the favorable outcome of the proprioceptive test observed here may be strongly related to the improved static and dynamic balance scores . the improved tug test scores observed here imply that neck proprioceptive training can be adapted for improving mobility and walking after stroke . although the implication is that the use of neck proprioceptive training may be clinically feasible for increasing balance function , there are several limitations to generalizing our results . first , because this study included only three patients after stroke and there was no control group , it may be difficult to interpret our findings beyond this group . second , our purpose was to assess the balance function of these patients after training ; therefore , the results can not be understood as physical performance findings . finally , the findings did not demonstrate our subjects abilities in a changing outdoor environment .

[ purpose ] this study investigated the effects of neck proprioceptive training on the balance of patients with chronic poststroke hemiparesis . [ subjects ] three patients with chronic stroke were recruited for this study . [ methods ] the subjects underwent neck proprioceptive training using the red light of a laser pointer ( 30 min daily , five times per week for 4 weeks ) . outcome measures included the stability and weight distribution indices measured with a tetrax system and timed up and go ( tug ) and proprioception tests . [ results ] for all subjects , the stability and weight distribution indices increased by 1.879.66% in the eyes - open and eyes - closed conditions , and the tug and proprioception test scores improved by 2.4915.27% . [ conclusion ] neck proprioceptive training may be a good option for improving the balance function of patients with chronic poststroke hemiparesis .

different methods have been described for improving the stability of fixation,56 including impaling the shaft into the head , placing a tension suture through the rotator cuff , or using an intramedullary cortical graft . we used cortico - cancellous strut graft medially in conjunction with a fixed - angle implant on the lateral side . x - rays of shoulder joint with proximal humerus ( a ) anteroposterior view ( b ) lateral view showing cavitation effect of long standing pseudarthrosis of fracture of surgical neck of humerus we treated seven cases of pseudarthrosis of the surgical neck of the humerus between 2004 and 2010 . there were four women and three men , ranging in age from 22 to 65 years . the initial treatment was a sling in three patients , u - slab in two patients and internal fixation in two . the diagnosis of pseudarthrosis was obvious in all cases because of mobility and crepitus at the fracture site . all the cases were treated with a tricortical medial buttress bone graft and fixed - angle fixation device on the lateral side . a locking proximal humerus plate ( lphp synthes ) was used in six cases , and a bent reconstruction plate ( synthes ) was applied in one case . the one in which reconstruction plate was applied was operated before the advent of locking plates . the limb was immobilized in 30 of abduction over a cushion for 6 weeks , followed by a sling for another 6 weeks . patient was walking with arm immobilized over a 6-inch cushion , wrapped with sticking tape to the chest [ table 1 ] . the clinical details of the cases patients were permitted to use their limb for day - to - day activities after 3 months . the fracture was declared united clinically as there was no abnormal mobility and also no pain . radiologically , the union was confirmed by the presence of new bone formation across fracture and incorporation of bone graft . the head per se was not visible ; as it was intracapsular ; only its fracture surface was visible . the reduction was checked on an image intensifier , and the construct was temporarily stabilized with one or two k - wires . a fixed - angle fixation device ( locking compression plate or lcp ) the space was now created on the medial side of the fracture by careful sharp dissection . a 34 cm tricortical graft taken from ipsilateral iliac crest was placed in this space , supporting the head . the strut graft was held to the shaft with two cortical screws , through the plate or outside it [ figure 2 ] . the shoulder was immobilized in 30 abduction over a pillow in the axilla , for 6 weeks , after which intermittent shoulder mobilization was started . x - ray shoulder joint with arm ( anteroposterior view ) showing strut graft held with two long screws the head per se was not visible ; as it was intracapsular ; only its fracture surface was visible . the reduction was checked on an image intensifier , and the construct was temporarily stabilized with one or two k - wires . a fixed - angle fixation device ( locking compression plate or lcp ) the space was now created on the medial side of the fracture by careful sharp dissection . a 34 cm tricortical graft taken from ipsilateral iliac crest was placed in this space , supporting the head . the strut graft was held to the shaft with two cortical screws , through the plate or outside it [ figure 2 ] . the shoulder was immobilized in 30 abduction over a pillow in the axilla , for 6 weeks , after which intermittent shoulder mobilization was started . x - ray shoulder joint with arm ( anteroposterior view ) showing strut graft held with two long screws all cases had useful function of the shoulder [ figure 3 ] . although we did not use any instrument for quantifying shoulder function , the patients were satisfied with a stable shoulder with useful activity . we did not encounter any intraoperative and immediate postoperative complications . in one case , avascular necrosis ( avn ) patients were assessed as successful cases if union occurred and they could do activities of daily living . ( a ) preoperative x - rays of shoulder joint ( anteroposterior view ) with arm showing nonunion of the surgical neck , ( b ) postoperative anteroposterior x - ray shows fracture union , ( c and d ) clinical photographs showing shoulder functions ( a ) x - ray shoulder joint ( case no . 5 ) anteroposterior view shows fracture union with avascular necrosis of head of the humerus , ( b ) clinical photograph of same patient showing good function despite avn of the head of the humerus nonunion of surgical neck of humerus is not a common problem.12 from treatment viewpoint , these can be divided into two types : one , where the bone stock is essentially preserved , and the other where pseudarthrosis has developed . the former is relatively easy to treat by conventional methods of internal fixation , but the ones with pseudarthrosis are difficult treatment issues due to the deranged patho - anatomy . persistent mobility at the pseudarthrosis , by pestle and mortar effect , causes cavitation of the head , and over a period , the head fragment becomes like a shell of bone . the replacement in such cases is described , but reported results are not good.34 attempts continue to achieve healing in these rather complex cases.79 the stable internal fixation is crucial if one has to achieve union in such nonunions . achieving stable internal fixation is difficult in nonunion of surgical neck of humerus considering that the proximal fragment is small and osteoporotic and there is excessive mobility at the fracture site ( pseudarthrosis ) . sheck reported improved stability of the basic internal fixation by impaling the distal fragment into the head and by tension - band wiring of the rotator cuff to the shaft.5 the author also used extramedullary strut on the lateral side to add to stability . disadvantage of this technique is that most of the cases so managed needed spica immobilization and second surgery for removal of implants . walch et al.6 used intramedullary cortical strut autograft obtained from fibula , tibia or iliac crest to regain the length and improve stability . though good results have been shown with the use of this technique , there are disadvantages . secondly , the procedure requires preparation of the cortical graft to make it fit to go into the medullary cavity . furthermore , preparation of the medullary cavity to accept the graft needs extensive dissection , a rather non - biological approach in a nonunion situation . failure due to graft fracture and persistent nonunion has not been reported by the author . our current technique is simpler and is based on the understanding of mechanical forces involved in this fracture . brunner et al.10 have reported varus collapse in fresh cases treated with lcp due to loss of medial support at the fracture . we observed intraoperative difficulty in exposure of fracture site ( due to extensive scarring ) and subpereiosteal elevation of tissues from medial side . the temporary stabilization of hypermobile pseudarthrosis , proper placement of plate and ensuring the secure hold of bone graft to the main bone with one or two screws was most important . gardner et al.11 have reported 30% loss of reduction in these fractures , where medial buttress was missing . these reports support our hypothesis that medial buttressing is important in achieving a stable construct in these fractures , particularly in those with pseudarthrosis . our results in this rather small series support our belief that buttress cortico - cancellous graft on the medial side along with a fixed - angle device on the lateral side makes it a stabile construct and helps in the union of this rather unstable and difficult nonunion . technically , it is an easier procedure as there is little graft harvest morbidity and no preparation of the graft or host side is required . it is recommended , particularly , for cases of pseudarthrosis where the head is osteoporotic and unstable , and there is a significant cavitation of the head . the small sample size and lack of functional objective evaluation of cases we have used this technique in seven cases of pseudarthrosis of surgical neck of the humerus to achieve fracture union .

background : pseudarthrosis of surgical neck of humerus is uncommon condition . different methods of improving the stability of fixation have been described , including impaling the shaft into the head , placing a tension suture through the rotator cuff , or using an intramedullary cortical graft . we report our results of cortico - cancellous strut graft medially to counter the varus force , in conjunction with a fixed - angle implant on the lateral side.materials and methods : we used this technique in seven cases of pseudarthrosis of surgical neck of the humerus . there were four women and three men , ranging in age from 22 to 65 years . all were treated with a tricortical medial buttress bone graft and fixed - angle fixation device on the lateral side . a locking proximal humerus plate ( synthes ) was used in six cases , and a bent reconstruction plate ( synthes ) was applied in one case . the one in which reconstruction plate was applied was operated before the advent of locking plates . the limb was immobilized in 30 of abduction over a cushion for 6 weeks , followed by a sling for another 6 weeks.results:the followup varied from 18 to 96 months . all our cases healed within mean 5.1 months ( range 46 months ) . there was one case of avascular necrosis . all cases had useful function of shoulder.conclusion:the medial buttressing by strut graft with external fixation by laterally placed fixed angle plate is successful to achieve fracture union in pseudarthrosis of surgical neck of humerus .

beta - thalassemia major results from acute reduction or lack of synthesis of beta globin chains and can be produced by gene mutations . this causes much of the production of alpha - globin chains which are not able to produce hemoglobin tetramer . about 15,000 people are known as thalassemic in iran , and about 3,000,000 people are carrying thalassemia gene . in beta thalassemia major , tissue damage occurs due to oxidative stress , and it happens because of the accumulation of iron in the body . spontaneous oxidation of unpaired alpha - globin chains leads to production of super oxide ions and hydrogen peroxide[47 ] . reduction in the total peroxyl radical trapping capacity ( trap ) , which indicates decreased antioxidant defense mechanism , is seen in this disease . toxic oxygen metabolites are scavenged by antioxidant enzymes such as super oxide dismutase ( sod ) and glutathione peroxidase ( gpx ) . sod reacts directly with h2o2 and then enzymes ( catalase and gpx ) come to practice . thus , these three enzymes , in addition to specific roles , work together against oxidant factors[5 , 8 , 9 ] . vitamin e is the most important fat soluble antioxidant and considered as the primary step for antioxidant defense system . numerous studies have demonstrated reduced serum level of this vitamin in beta - thalassemic patients[1012 ] . one study conducted on beta - thalassemia intermedia patients indicated that vitamin e supplementation improved balance of the antioxidant system and inhibited the process of lipid peroxidation in patients . in addition to vitamin e , zinc deficiencies in beta- thalassemia major patients have been reported in some studies[11 , 1320 ] . zinc plays several profoundly and biologically important roles such as causing structural effects in more than 300 metalloenzymes like super oxide dismutase . specific dietary recommendations for thalassemic patients minimize consumption of iron in the diet , and unfortunately result in the reduction of zinc intake . furthermore , chelator factors administered to prevent the accumulation of iron , cause an excretion effect on zinc in these patients[7 , 24 , 25 ] . micronutrient deficiencies , especially of vitamin e and zinc in beta - thalassemia major patients have been reported frequently . however , there is no published data about supplementation of these nutrients in thalassemia major patients . so , we conducted a trial to investigate the joint and separate effects of vitamin e and zinc supplementation on antioxidant status such as gpx , sod and total antioxidant capacity [ tac ] in beta thalassemia major patients . this double blind randomized clinical trial was carried out on 120 beta - thalassemic major patients older than 18 years admitted to taleghani and amiralmomenin hospitals in the golestan province ( northern iran ) in 2009 . inclusion criteria were the history of continuous treatment with blood transfusion and desferal as a chelator agent . exclusion criteria were diabetes mellitus , smoking , hepatitis b and c and consumption of any supplements at least three months before the study . the patients were randomly assigned into four groups including 30 subjects in each group using a random allocation method ( random allocation method was a random permuted block or block balanced randomization using 8 characters blocks containing a , b , c and d ) . the first and second groups were asked to take a supplement of 220 mg zinc sulfate containing 50 mg zinc daily for three months and 400 mg vitamin e supplement daily for three months . blood samples were obtained from subjects after a 12-hour fasting , just before they received transfusion at beginning and end of the study , and stored at -70 c until assay . serum vitamin e level was measured by hplc ( knuer germany ) . in order to determine serum zinc concentration , serum zinc was analyzed by flame atomic absorption spectrophotometry ( chem 's tech analytical uk , 2000-a.a.s ) . in order to assess the enzyme activity of sod and gpx , the whole blood was rinsed three times with 0.9% saline normal . activities of gpx and sod of rbc were assessed by rancel and ransol ( randox , uk ) kits . statistical analysis was carried out on statistical package for social sciences ( spss for windows , release 11.0 , 2002 , spss , chicago , il , usa ) . paired t - test was used for comparison of the mean for changes of different variables before and after intervention phases . significant level was set 0.05 and all the statistical tests were carried out as two sided . one hundred and twenty subjects including 57 males and 63 females participated in this study . the mean ( sd ) age for all groups was 21.1 ( 9.7 ) years . serum zinc concentration in group 1 and 3 , was significantly increased ( p<0.007 and p<0.005 , respectively ) . serum concentration of vitamin e , in group 2 and 3 was significantly increased ( p<0.001 ) . mean gpx activity in groups 1 , 2 , and 3 showed significant decrease ( p<0.015 , p<0.032 and p<0.029 , respectively ) . mean bmi in groups 1 , 2 , and 3 revealed significantly positive changes ( p<0.001 ) . mean sod activity and serum tac did not show significant changes in any of the studied groups . no significant difference was seen in fourth ( control ) group , which did not use any supplements ( table 1 ) . mean ( sd ) of variables before and after interventions g1 : group 1 , or zinc supplemented group . red blood cells in thalassemics have morphologic abnormalities , which result in increased susceptibility of thalassemic red cells to the exogenous peroxidant threat . two mechanisms for inadequate peroxidant defense in thalassemics are insufficient vitamin e levels in red blood cells and plasma , and decreased activity of several enzymes including sod and gpx , which are the first line of defense against oxidant stress . according to the results ( table 1 ) , mean serum levels of vitamin e in all groups at beginning of the study were lower than the normal range . vitamin e deficiency in thalassaemias is attributed to its increased consumption pursuant to the oxidative stress[5 , 7 ] ; chronic hepatic iron overloads , while causing a substantial reduction of serum lipids , can also lead to concurrent reduction of serum vitamin e. some studies have reported a serum zinc deficiency in beta thalassemia patients , which was related to hyperzincuria resulted from the release of zn from hemolyzed red cells[18 , 19 , 20 ] . in our studied subjects , 16% had a serum zinc deficiency ( data are not shown ) ; however , mean serum zinc was not low . similarly , mehdizadeh et al also did not report a zinc deficiency in beta thalassemic patients . absence of predominant zinc deficiency in our patients may have resulted from regular transfusion therapy . our findings indicate that supplementation with zn , vitamin e or both of these causes a significant increase in serum level of zinc in the first group , increased serum vitamin e in the second group , and increased serum zinc and vitamin e levels in the third group with no significant difference in the control group . therefore , these interventions , especially vitamin e supplementation had favorable effects on serum vitamin e levels in patients , considering that base level of vitamin e in serum of all studied groups was lower than the normal limit . oxidative stress is the result of an imbalance between free radical production and reduced degradation . an increased oxidant stress and a decreased antioxidant status promote peroxidative damage to cell and organelle membranes . it is well documented that disturbances of oxidant - antioxidant balance occur in hemoglobinopathies , especially in thalassemia and sickle cell diseases . removal of toxic oxygen metabolites is the putative function of antioxidant enzymes such as sod and gpx . it has already been demonstrated that oxidative stress induces antioxidative enzymes , including sod and gpx . as indicated in table 1 , prior to interventions , sod and gpx activities in all groups were much higher than in those of healthy subjects[31 , 32 ] . significant increase in catalytic activities of sod and gpx also were found in beta - thalassemic erythrocytes of beta - thalassemic carriers in the study of filiz et al . the increased activity of sod in beta thalassemia may be involved in scavenging the superoxide radical ( o2- ) , thereby producing more hydrogen peroxide in the erythrocytes . the increased activity of gpx in beta - thalassemia may be involved in detoxifying hydroxyl radical ( oh ) . this finding suggests that high iron produces an oxidative stress in cells , which respond by increasing their antioxidant defenses . the increase of intracellular antioxidant enzymes might be hypothesized to be a direct effect of increased intracellular iron on gene expression . based on our results ( table 1 ) , sod and gpx activities in subjects were also higher than normal limits at the end of the study . however , gpx activity showed a significant reduction in all treated groups . therefore , all three types of interventions had protective effects on this enzyme , and were effective in elevating the antioxidant status . pfeifer et al reported that after vitamin e administration , thalassemic patients presented a significant reduction in levels of erythrocyte rbc - reactive oxygen species ( ros ) and serum thiobarbituric acid reactive substances ( tbars ) , and concluded that it could be useful for reducing oxidative damage in other target organs of beta - thalassemia intermediate patients . mei - ling cheng et al demonstrated that supplementation with vitamin e prevents oxidative damage to low - density - lipoprotein ( ldl ) and erythrocytes in beta thalassemia patients . in addition to vitamin e , it was established that zinc can reduce the iron - mediated oxidation of lipids ( including red blood cells ) , proteins , and dna . the precise antioxidant role of zinc is unclear , but two mechanisms were proposed ; first the competitive effect of zinc with iron and copper on the surface of cell membrane for special protein binding which is specific for preventing the production of the toxic oh radical . the second one is binding to the sh groups in some proteins and preventing them from oxidation . sidhu et al found that in zinc and protein deficient rat the activities of gpx , catalase , and peroxidation of lipids were increased . our results confirmed antioxidant effect of zinc ( table 1 ) , as seen in zinc supplemented group gpx activity also reduced significantly . according to the results the study of rahul naithani , et al in beta - thalassemia major patients showed that sod increases significantly , and it may be a compensatory mechanism to keep formation of superoxide anions checked to combat the oxidative stress . kessab - chekir , et al observed that iron , ferritin , sod , gpx and tbars were increased in 56 beta - thalassemic patients ; however , vitamin e and trap reduced considerably . meral , et al reported that because of increased lipid peroxidation in beta thalassemic patients a compensatory increase will be seen in sod and gpx activity . our findings confirmed the results of above mentioned study , and showed higher sod activities in patients . similar to our findings , carpino et al indicated despite the increased activity of sod in transfusion dependent thalassemics , tac did not change . dissayabutra et al reported despite vitamin e and vitamin c supplementation in beta - thalassemia major patients , tac did not change during the study period . it was suggested that various methods , including tac , developed to measure the total antioxidant capacity of serum , have been indicated as useful tools to predict the risk of free radical - induced tissue damage . changes in contributors such as uric acid and bilirubin , the levels of which increase in thalassaemia because of hemolysis , may mask marked changes in other essential antioxidants . it seems that these conditions also contributed to unchanged sod activity and tac in our subjects . low bmi in beta - thalassemic patients is common . according to findings ( table 1 ) bmi of all treated subjects increased significantly , which was indicative of well - being of patients and positive effect of supplementation . similar results were seen in das et al study . it should be noticed that , we did not evaluate other components of the cellular antioxidant defense system such as catalase , glutathione , uric acid , bilirubin , vitamin c , etc . if more enzymatic and non enzymatic antioxidants were measured , we could have a complete evaluation of the antioxidant status in these patients . our findings indicated that beta - thalassemic patients were under enhanced oxidative stress condition , and vitamin e deficiency . administration of selective antioxidants revealed helpful effects , especially on serum vitamin e and gpx activity as components of antioxidant system , and on general well - being of the subjects . further studies are suggested with different dose and duration of antioxidant supplements to determine their benefits in beta thalassemic patients .

objectivein beta thalassemic patients , tissue damage occurs due to oxidative stress and it happens because of the accumulation of iron in the body . this study was conducted to determine the effect of zinc and vitamin e supplementation on antioxidant status in beta - thalassemic major patients.methodsthis double blind randomized clinical trial was carried out on 120 beta thalassemic patients older than 18 years . patients were randomly categorized in four groups . zinc ( 50mg / day ) and vitamin e ( 400mg / day ) supplements were administered for former and latter group , respectively . in the third group both supplements were administered in similar doses . the fourth ( control ) group received no supplement . the effect of supplementations on serum zinc and vitamin e , superoxide dismutase ( sod ) , glutathione peroxidase ( gpx ) , total antioxidant capacity ( tac ) and body mass index ( bmi ) were measured at the beginning and the end of the study.findingsserum zinc levels in group 1 and 3 were significantly increased ( p<0.007 and p<0.005 , respectively ) . serum vitamin e levels in group 2 and 3 were also increased significantly ( p<0.001 ) . mean gpx activity in group1 , 2 and 3 decreased significantly ( p<0.015 , p<0.032 and p<0.029 , respectively ) . mean sod activity and tac did not show significant change after supplementation . bmi had significant increase in all treated groups ( p<0.001).conclusionour results suggest that beta thalassemic patients have enhanced oxidative stress and administration of selective antioxidants may preclude oxidative damage .

the relationship between fluoride and human health has been studied for years and scientists have recognized the variable fluoride concentrated in teeth and bones of humans ( 1 ) . most health researches focus on chronic fluoride exposure from drinking water , because that is the easiest way to quantify for a community served by a public water supply . however , food provides another potentially important pathway , as do toothpaste and other products used for dental health ( 2 ) . fluoride gets concentrated in hard tissues of human body and plays an important role in mineralization of bones and teeth . there are many studies regarding fluoride in drinking water and tooth dmft index in children ( 3 ) . fluoride can be absorbed by human body via drinking water , food , toothpaste , mouthwash products and via air . breast milk is considered an important nutrient for infants , especially in the first six months of life , where milk is considered as the main diet . after 6 months of age , the dietary importance of milk gradually changes due to supplementation of other foods . hence , it is important to identify the potential milk source of fluoride concentration intake in an infant s diet and to evaluate the need for fluoride supplementation ( 7 ) . there are only few studies on the level of fluoride in drinking water , black tea and tea liquor and powdered milk in iran ( 812 ) . the level of fluoride in human milk has been the topic of investigation for many years . we conducted this study to determine levels of fluoride in breast milk of lactating mothers in golestan province ( bandar gaz and nokande cities ) and to correlate it with fluoride content in drinking water for domestic use . twenty mothers were randomly chosen from 450 lactating mothers , and then breast milk samples were taken three times during every two months and analyzed . totally 60 samples of breast milk were collected from lactating mothers in bandar gaz and nokande cities during 2012 . all of the reagents used in the analyses of fluoride were reagent grade and supplied by merck inc . the fluoride stock solutions ( 0.5 mmol / ml ) were prepared monthly and stored at 4 c . working standard solutions of different concentrations were prepared daily by diluting the intermediate standard solution with de - ionized water . a metrohm ( model 744 ) bench top ph / ion meter ( fluoride ion - selective electrode as working electrode and silver / silver chloride as reference electrode ) was used for potentiometric determination of fluoride in milk samples . the ph of the sample solutions was monitored simultaneously with a conventional glass ph electrode . the fluoride concentration in dry milk samples was determined by comparing the potential of the sample solutions with calibration curve constructed from a series of standard fluoride solutions . the fluoride ise determined fluoride concentration by measuring the potential difference across an interface that responds only to fluoride . the accuracy of the fluoride ion selective electrode was also evaluated by the recovery test . recoveries of fluoride from milk sample spiked with three different amounts of sodium fluoride were tested . this method showed a very good accuracy due to the high recovery ( 13 ) . twenty water samples were collected from 7 wells drinking water in 2012 from bandar gaz and nokande cites in golestan province iran . the standard spadns method was used with a dr/2000s spectrophotometer ( hach company , usa ( 14 ) . the normality of variables was evaluated using kolmogorov - smirnov and shapiro - wilk tests . spearman s rho correlation analysis was used to assess any possible relationship between fluoride levels of breast milk and levels of fluoride in drinking water . twenty mothers were randomly chosen from 450 lactating mothers , and then breast milk samples were taken three times during every two months and analyzed . totally 60 samples of breast milk were collected from lactating mothers in bandar gaz and nokande cities during 2012 . all of the reagents used in the analyses of fluoride were reagent grade and supplied by merck inc . the fluoride stock solutions ( 0.5 mmol / ml ) were prepared monthly and stored at 4 c . working standard solutions of different concentrations were prepared daily by diluting the intermediate standard solution with de - ionized water . a metrohm ( model 744 ) bench top ph / ion meter ( fluoride ion - selective electrode as working electrode and silver / silver chloride as reference electrode ) was used for potentiometric determination of fluoride in milk samples . the ph of the sample solutions was monitored simultaneously with a conventional glass ph electrode . the fluoride concentration in dry milk samples was determined by comparing the potential of the sample solutions with calibration curve constructed from a series of standard fluoride solutions . the fluoride ise determined fluoride concentration by measuring the potential difference across an interface that responds only to fluoride . the accuracy of the fluoride ion selective electrode was also evaluated by the recovery test . recoveries of fluoride from milk sample spiked with three different amounts of sodium fluoride were tested . this method showed a very good accuracy due to the high recovery ( 13 ) . twenty water samples were collected from 7 wells drinking water in 2012 from bandar gaz and nokande cites in golestan province iran . the standard spadns method was used with a dr/2000s spectrophotometer ( hach company , usa ( 14 ) . the normality of variables was evaluated using kolmogorov - smirnov and shapiro - wilk tests . spearman s rho correlation analysis was used to assess any possible relationship between fluoride levels of breast milk and levels of fluoride in drinking water . the concentrations of fluoride in breast milk , and in drinking water are presented in table 1 , 2 . fluoride levels of water in bandar gaz and nokandeh were in range of 0.30.5 mg / l and 0.60.8 mg / l , respectively . the means and standard deviation for f concentration in breast milk and drinking water were 0.0021880.00026224 ppm and 0.58500.22542 ppm , respectively . the minimum and maximum levels of f were 0.0014 ppm and 0.0025 ppm , respectively . human breast milk contained lower fluoride concentration , considering that mean fluoride in drinking water is about 0.530.09 mg analysis of data showed that the variables were not normally distributed so the spearman correlation coefficient between two variables calculated ( s = 0.65 ) and it was significant ( p=0.002 ) . concentration of fluoride in breast milk and water in nokandeh , golestan province , iran concentration of fluoride in breast milk and water in bandar gaz , golestan province , iran fluoride concentration of breast milk and drinking water samples ( ppm ) our study revealed the means and standard deviation for f concentration in breast milk and drinking water was in range of 0.0021880.00026224 ppm and 0.58500.22542ppm , respectively . levels of minimum and maximum of f were 0.0014 ppm and 0.0025 ppm , which comply with who guidelines . according to who , levels of fluoride in breast milk should be in range 5 - 10 g / l ( 15 ) . fluoride concentration in studding water samples ranged from 0.3 to 0.8 ppm ( table 1 , 2 ) . forty five percent of the samples had a fluoride level lower than the permissible limit , 55% of the samples had a level within the optimum limit of 0.5 to 1.5 ppm ( 16 ) . result showed that fluoride content in breast milk had correlation with drinking water ( s = 0.65 ) and ( p=0.002 ) . table 3 , which is in accordance to similar studies conducted in iran and worldwide . revealed that levels of fluoride in breast milk had correlation to levels of fluoride drinking water consumed by the mothers ( 17 ) . in egypt , , 0.01110.0044 ppm , and 0.4820.117 ppm , respectively . a significant direct correlation between fluoride content in breast milk and drinking tap water no correlation was found between breast milk fluoride content and fluoride levels in either drinking water or water for domestic use ( r = 0.09 , p = 0.32 , r = 0.04 , p = 0.65 respectively that disagrees with our finding ( 18 ) . it is recommended in areas with high concentrations of fluoride in water , in order to reduce the amount of daily intake by mothers , fluoride be removed from drinking water by proper process ( 19 ) . all the samples had detectable levels of fluoride implying that mother 's nutrition in the area studied is widely affected the f concentration of breast milk . the present study was carried out to understand if the low and high f concentration in bandar gaz and nokande water could cause low and high fluoride intake of human breast milk , respectively . the f content in human breast milk depends on various factors , such as drinking tea and other source of fluoride ingestion provides far more fluoride than is contained in drinking water alone . our study shows that fluoride concentration in water can directly act on its concentration in breast milk . we speculate that modifying the f concentration in water can affect accessibility of fluoride for infants . ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc . ) have been completely observed by the authors .

background : fluoride is an essential element for human health . however , excess fluoride in drinking water may cause dental and/or skeletal fluorosis . drinking water is the main route of fluoride intake . the aim of the present study was to measure fluoride levels in human breast milk collected from two regions of golestan province , northern iran with different amount of fluoride concentration of drinking water in bandar gaz and nokande cities and to correlate it with fluoride concentrations in drinking water used by mothers living in these two areas.methods:twenty samples of water were collected from seven drinking water wells during 2012 from bandar gaz and nokande in iran during 2012 . fluoride concentration of water samples was measured using spadns method . sixty breast milk samples were collected from lactating mothers of bandar gaz and nokande cities . content in breast milk was determined using standard f ion - selective electrode . spearman s rho correlation analysis was used to assess any possible relationship between fluoride levels in breast milk and in drinking water.results:the means and standard deviation for f concentration in breast milk and drinking water were 0.0021880.00026224 ppm and 0.58500.22542 ppm , respectively . analysis of data showed that the variables were not normally distributed so the spearman correlation coefficient between two variables calculated ( s = 0.65 ) and it was significant ( p=0.002).conclusion : fluoride concentration in water can directly act on its concentration in breast milk . we speculate that modifying f concentration in water can affect accessibility of fluoride for infants .

mucormycosis is a rare angioinvasive fungal infection , leading to vascular thrombosis , tissue infarction , necrosis and ulceration . the disease occurs almost exclusively in immunocompromised individuals though cases in immune - competent host have also been described . cytomegalovirus ( cmv ) is frequent in posttransplant period especially in those , who have received depleting antibodies . in addition to its directly attributable effects in the involved organs , active cmv disease has immunomodulatory effects , which predispose to other serious infections as well as acute rejections . gastrointestinal ( gi ) mucormycosis is rare and occurs primarily in the extremely malnourished patients especially infants or children and is thought to arise from ingestion of the fungi . presence of cmv infection in gi tract may trigger invasive fungal infections in renal transplant recipient by its immunomodulatory effects . early diagnosis requires a high index of suspicion and an emergent evaluation to allow early initiation of antifungal / antiviral and surgical therapy . a 45-year - old male with end - stage renal disease ( esrd ) underwent a live donor abo - incompatible renal transplant ( recipient - b positive , donor - a positive ) with wife as donor . both recipient and donor were seropositive for cmv . for preconditioning , he received rituximab ( 200 mg ) followed by two sessions of double filtration plasmapheresis and iv immunoglobulin ( 10 g ) to decrease the anti a titers from 1:64 to < 1:8 ( target titers for our center ) . tacrolimus ( 0.05 mg / kg / day ) and mycophenolate ( 1000 mg / day ) was started 1-week prior to transplant . in postoperative period , there was initial diuresis ; however , 6 h after surgery , urine output dropped . color doppler flow imaging showed no evidence of arterial or venous thrombosis with raised resistive indices . in view of persistently low urine output despite adequate fluid resuscitation , re - exploration was done . on postoperative day 1 , patient developed drop in hemoglobin ( 10.7 g / dl to 7.7 g / dl ) and platelets ( from 1.2 lacs / cmm to 50,000/cmm ) with evidence of schistocytes on peripheral smear and biochemical evidence of hemolysis . tacrolimus trough level was 22.3 ng / ml . in the absence of positive c4d staining and other histological evidence suggestive of antibody - mediated rejection , the tma was thought to be tacrolimus induced . on 1-week posttransplant , he developed generalized tonic - clonic seizures with respiratory distress requiring intubation and mechanical ventilation . his condition gradually improved with an increase in urine output and decreasing serum creatinine levels . patient was gradually weaned off the ventilator and dialysis was also stopped ( serum creatinine 3.1 mg / dl ) . c0 level was 68.90 ng / ml . in view of recurrent vomiting , upper gi endoscopy was done , which revealed deep , round punched out hemorrhagic ulcerations involving the esophagus and corpus of the stomach along with necrotic - ulcerative lesions involving the lesser curvature of the stomach . gastric biopsy from the involved regions revealed broad , nonseptate hyphae with right angled branching on sections stained with h and e and grocotts stain , suggestive of mucormycosis [ figure 1 ] . also , there was evidence of intranuclear inclusion bodies in gastric mucosa suggestive of cmv gastritis , which was confirmed by immunohistochemistry [ figure 1 ] . blood cmv viral load was 2200 copies / ml . ( a ) higher magnification reveals broad nonseptate mucor hyphae ( original magnification , h and e , 40 ) . ( b ) grocotts stain reveals gastric mucosal epithelial fragment at the lower end and necrotic suppurative exudate at the upper end ( original magnification , grocotts , 4 ) . ( c ) higher magnification of the necrotic area reveals broad nonseptate hyphae of mucormycosis ( original magnification , grocotts , 40 ) . ( d ) cytomegalovirus ( cmv ) immunostain shows nuclear positivity in the affected cytomegalic cells ( original magnification , cmv ihc , 20 ) patient was started on intravenous liposomal amphotericin b ( 3 mg / kg / day ) and ganciclovir ( 2.5 mg / kg / day ) . computed tomography scan of the abdomen showed pneumoperitoneum and dehiscence of posterior wall of the stomach with leak of contents . patient was taken for urgent exploratory laparotomy , which revealed 3 cm 3 cm rent in the posterior wall of the stomach . ( rtx - rituximab , dfpp - double filtration plasmapheresis , il2ra - interleukin 2 receptor antagonist , mp - methyl prednisone , hd - hemodialysis ) traditionally , renal transplant across blood groups was considered as contraindication in the past ; however , with the availability of present day immunosuppression , this no longer holds true . the commonly used triple - drug immunosuppression along with induction therapy has improved graft survival but leaves the patient susceptible to a variety of opportunistic infections , of which fungal and viral infections are the leading cause of morbidity and mortality . the reported incidence of opportunistic fungal infections is 610% of all recipients of solid organ transplants in india . mucormycosis is a rare life - threatening infection caused by fungi ; classified as zygomycetes . invasive gi mucormycosis is extremely rare and occurs almost always in malnourished or immunocompromised patients . the first case of gi mucormycosis in a renal transplant recipient was described by winkler et al . , in a patient who had received antirejection therapy with steroids and anti thymocyte globulin in postoperative period , making her a susceptible candidate for infections . there have been very few case reports of gastric mucormycosis in renal transplant recipients in last decade . our patient developed invasive gastric mucormycosis within 4 weeks of transplant with severe dyspeptic symptoms and was diagnosed on the basis of upper gi endoscopy and biopsy . patient also had evidence of coexistent cmv infection on gastric biopsy , which probably predisposed to the fungal infection in this patient . being abo incompatible transplant , he received rituximab and plasmapheresis as preconditioning therapy and received interleukin 2 receptor antagonist as induction therapy . he also received prolonged high doses of steroids , as he was off tacrolimus and mycophenolate in view of tacrolimus - induced tma and sepsis . the occurrence of cmv infection early in the course can be attributed to over immunosuppression , which may predispose to other opportunistic infections by its indirect effects like invasive fungal infection in this case . this can be due to multiple intubations including ryle 's tube , which may have acted as portal of entry . the course of the disease was rapidly fatal due to angio - invasive nature of mucormycosis in spite of surgical exploration and debridement along with antifungal and antiviral treatments at appropriate time . ju et al . , reported a case of renal transplant recipient , who received antirejection therapy with steroids and okt3 on postoperative day 18 and presented with sudden onset massive hematochezia . however , the disease was fatal in our patient in spite of gastrectomy and treatment with liposomal amphotericin b and ganciclovir . andrews et al . , reported two cases of renal transplant recipient with cmv infection , who had received anti thymocyte globulin for induction therapy and high doses of steroids for rejection . successful outcome of disease depends upon early tissue diagnosis , efficient antifungal therapy and surgical debridement of necrotic tissue if indicated . the treatment of established cmv disease requires valganciclovir or intravenous ganciclovir until cmv replication is no longer detected . the morbidity and mortality of mucormycosis and cmv infection in renal transplant recipient remains high . there are very few cases of mixed cmv and mucormycosis in renal transplant recipients in the literature . improvement in patient outcome requires preventive strategies and early management of infection on emergent basis .

opportunistic infections are common in immunocompromised patients , such as solid organ transplant recipients . both fungal and viral infections in posttransplant period increase morbidity and mortality . cytomegalovirus ( cmv ) remains one of the most important pathogens . cmv disease may manifest as a nonspecific febrile syndrome or tissue - invasive infections . zygomycosis is a rare infection , usually presents in rhino - cerebral , pulmonary and disseminated forms ; gastrointestinal ( gi ) tract being a rare site of involvement . newer techniques for early diagnosis and efficient therapies are essential for a better outcome of the disease ; however , mortality rate remains high despite aggressive therapy . we report a renal transplant recipient , who developed gastric mucormycosis along with tissue invasive cmv disease , within 4 weeks of renal transplant and was diagnosed on the basis of upper gi endoscopy and gastric biopsy . the patient succumbed to the infection in spite of gastrectomy , antifungal and antiviral therapy .

our study population comprised 296 healthy 6- to14-y - old african american and caucasian children residing in pittsburgh , pa . subjects were participants in dr . rajakumar s national institutes of health - funded ( r03 and k23 grants ) vitamin d clinical research protocols designed to assess the seasonal and racial differences in vitamin d status of african american and caucasian children ( short longitudinal observational study , n = 140 ) and refine the serum 25(oh)d thresholds for defining vitamin d insufficiency in children [ randomized controlled trial ( rct ) of 1000 iu of vitamin d3 vs. placebo for 6 mo , n = 156 ] . children with hepatic or renal disease , disorders of vitamin d or calcium metabolism , malabsorptive disorders , or cancer , and those on treatment with anticonvulsants or systemic glucocorticoids were excluded from participation in the observational study and the clinical trial . children enrolled in the clinical trial were not taking oral contraceptives , depot medoroxyprogesterone , vitamin d containing multivitamins , or vitamin d supplements . the university of pittsburgh institutional review board approved the vitamin d research protocols , and signed parental informed consent and participants assent were obtained prior to enrollment . the institutional review board at georgia state university approved the dietary analysis done for the study reported here . subjects height and weight were measured at baseline and at the 6 mo follow - up visit ; bmi was calculated . subjects were classified as obese if age and gender based bmi was 95th percentile . dietary intake was recorded by participants at both time points using the sffq and the lffq . michael holick ( boston university medical center ) for assessment of vitamin d intake and sunlight exposure in adults . the sffq has 21 questions and is designed for completion by the participant or the parent . seventeen of the questions focus on vitamin d and calcium rich foods , since dr . rajakumar s initial study was designed to assess the intake of these nutrients ( supplemental data ) . the lffq is a semi - quantitative ffq designed by the harvard medical school ( copyright 1995 brigham and women s hospital ) that addresses intake of 7 food groups with 152 questions requesting information on dietary intake over the past year . completed sffqs were analyzed using the food processor sql ( version 10.4.0 , esha research ) . nutrient intake data comprised 17 nutrients , including total energy , dietary calcium , and dietary vitamin d. the mann - whitney u test was used to determine if there was a significant difference between anthropometric and nutrition variables by race at each time point since the distribution of these variables was skewed in our population . internal validity was determined by comparing vitamin d intake reported on the lffq with that reported on the sffq at each time point using the spearman rank correlation statistic . correlations were interpreted using the following guidelines : r = 0.00.3 weak , r = 0.30.6 modest , and r = 0.61.0 good . using a 2 x 2 contingency table , external validity of the sffq was evaluated using sensitivity , specificity , ppv , and npv equations . the table cell values were determined by whether or not subjects met the aap recommendation for vitamin d of 400 iu / day ( 30 ) and the iom and endocrine society clinical practice guideline recommendation of 600 iu / day , as reported by the lffq ( x ) and sffq ( y ) . statistical analyses were conducted using spss ( version 18 , 2010 , ibm corp ) . our study population comprised 296 healthy 6- to14-y - old african american and caucasian children residing in pittsburgh , pa . subjects were participants in dr . rajakumar s national institutes of health - funded ( r03 and k23 grants ) vitamin d clinical research protocols designed to assess the seasonal and racial differences in vitamin d status of african american and caucasian children ( short longitudinal observational study , n = 140 ) and refine the serum 25(oh)d thresholds for defining vitamin d insufficiency in children [ randomized controlled trial ( rct ) of 1000 iu of vitamin d3 vs. placebo for 6 mo , n = 156 ] . children with hepatic or renal disease , disorders of vitamin d or calcium metabolism , malabsorptive disorders , or cancer , and those on treatment with anticonvulsants or systemic glucocorticoids were excluded from participation in the observational study and the clinical trial . children enrolled in the clinical trial were not taking oral contraceptives , depot medoroxyprogesterone , vitamin d containing multivitamins , or vitamin d supplements . the university of pittsburgh institutional review board approved the vitamin d research protocols , and signed parental informed consent and participants assent were obtained prior to enrollment . the institutional review board at georgia state university approved the dietary analysis done for the study reported here . subjects height and weight were measured at baseline and at the 6 mo follow - up visit ; bmi was calculated . subjects were classified as obese if age and gender based bmi was 95th percentile . dietary intake was recorded by participants at both time points using the sffq and the lffq . michael holick ( boston university medical center ) for assessment of vitamin d intake and sunlight exposure in adults . the sffq has 21 questions and is designed for completion by the participant or the parent . seventeen of the questions focus on vitamin d and calcium rich foods , since dr . rajakumar s initial study was designed to assess the intake of these nutrients ( supplemental data ) . the lffq is a semi - quantitative ffq designed by the harvard medical school ( copyright 1995 brigham and women s hospital ) that addresses intake of 7 food groups with 152 questions requesting information on dietary intake over the past year . completed sffqs were analyzed using the food processor sql ( version 10.4.0 , esha research ) . nutrient intake data comprised 17 nutrients , including total energy , dietary calcium , and dietary vitamin d. the mann - whitney u test was used to determine if there was a significant difference between anthropometric and nutrition variables by race at each time point since the distribution of these variables was skewed in our population . internal validity was determined by comparing vitamin d intake reported on the lffq with that reported on the sffq at each time point using the spearman rank correlation statistic . correlations were interpreted using the following guidelines : r = 0.00.3 weak , r = 0.30.6 modest , and r = 0.61.0 good . using a 2 x 2 contingency table , external validity of the sffq was evaluated using sensitivity , specificity , ppv , and npv equations . the table cell values were determined by whether or not subjects met the aap recommendation for vitamin d of 400 iu / day ( 30 ) and the iom and endocrine society clinical practice guideline recommendation of 600 iu / day , as reported by the lffq ( x ) and sffq ( y ) . statistical analyses were conducted using spss ( version 18 , 2010 , ibm corp ) .

previous studies have found a high prevalence of vitamin d deficiency in children , yet few validated dietary vitamin d assessment tools are available for use in children . our objective was to determine whether a short food frequency questionnaire ( sffq ) can effectively assess vitamin d intake in children . vitamin d intake ascertained by a sffq was compared with assessments by a previously validated long food frequency questionnaire ( lffq ) in a population of 296 healthy 6- to 14-y - old children ( 54% male , 60% african american ) from pittsburgh , pa . the questionnaires were completed at two points 6 mo apart . median reported daily vitamin d intake from the sffq ( baseline : 380 iu , follow - up : 363 iu ) was higher than the lffq ( 255 iu and 254 iu , respectively ) . reported median dairy intake , including milk , cheese , and yogurt , was 3.7 cups / day , which meets the usda recommendation for children . vitamin d intake reported by the 2 questionnaires was modestly correlated at baseline and follow - up ( r = 0.35 and r = 0.37 , respectively ; p < 0.001 ) . these associations were stronger in caucasians ( r = 0.48 and r = 0.49 , p < 0.001 ) than in african americans ( r = 0.27 and r = 0.31 ; p = 0.001 ) . the sensitivity of the sffq for predicting daily vitamin d intake , defined as intake of 400 iu on both the sffq and lffq , was 65% . specificity , defined as intake of < 400 iu on both questionnaires , was 42% . vitamin d requirements may not be met despite adequate consumption of dairy products . the sffq was found to be a modestly valid and sensitive tool for dietary assessment of vitamin d intake in children .

cerebellar tissue was taken from a dead 12-year - old stallion from a privately owned ranch in the municipality of juarez in nuevo leon state , mexico , approximately 240 km south of the texas border . the horse was first observed with neurologic symptoms on june 20 , 2003 , and it was euthanized 7 days later . the horse had never been outside the state of nuevo leon and had not been vaccinated against wnv . the tissue sample was immediately placed on dry ice and transported to the biosafety - level-3 facilities at colorado state university for processing . although we were unable to isolate virus from the sample by passing brain homogenate in vero cells , we successfully amplified viral rna . total rna was extracted from approximately 100 g of cerebellar tissue with trizol reagent ( invitrogen , carlsbad , ca ) , according to the manufacturer 's instructions . the prm - e genes were amplified as two fragments by reverse transcription - polymerase chain reaction ( rt - pcr ) by using primers designed from the nucleotide sequence of the prototype wn - ny99 strain ( genbank accession no . pcr amplifications were performed by using ex taq dna polymerase ( takara biomedicals , shiga , japan ) , which has 3 5 exonuclease activity . amplification products were separated by agarose gel electrophoresis , visualized with crystal violet , and extracted by using the rapid gel extraction system ( invitrogen , carlsbad , ca ) . the resulting dna fragments were reamplified by pcr because of the low rna copy number in the original material and purified by using the qiaquick pcr purification kit ( qiagen , valencia , ca ) . purified dnas were sequenced on both strands with an abi 377 dna sequencer ( davis sequencing , davis , ca ) and eight pairs of wnv - specific primers . the nucleotide sequence of the prm - e genes of the wnv from nuevo leon state , mexico ( designated mexnl-03 ) was submitted to genbank ( genbank accession no . this region comprises 2004 nucleotides and corresponds to nucleotides 466 to 2469 of the genomic rna of the wn - ny99 strain ( 8) . alignment of the mexnl-03 sequence with other known sequences in the genbank database showed that it was most closely related to the homologous regions of three wnv isolates collected in harris county , texas , in june 2002 ( strains 119 , 123 , and v1151 ; genbank accession numbers ay185908 , ay185909 , ay185911 respectively ) . the mexnl-03 sequence differed from the harris county isolates in three nucleotide positions ( 0.15% divergence ; table ) . in all cases , one change was in the prm gene at position 549 , and two changes were in the e gene at positions 1179 and 1356 . all substitutions were in the third codon position , and none resulted in an amino acid change . nucleotide numbers correspond to those of the prototype new york strain ( wn - ny99 ) . isolated from a chilean flamingo ( phoenicopterus chilensis ) ( collection date : 06/01/99 ) . isolated from a bluejay ( cyanocitta cristata ) and passaged once in vero cells ( collection date : 06/14/02 ) . ay185908 . the nucleotide sequence of mexnl-03 differed from that of the wn - ny99 strain ( genbank accession no . two mutations were in the prm gene ( positions 549 and 660 ) , and four mutations were in the e gene ( positions 1179 , 1356 , 1442 , and 2466 ) . the u to c substitution at 1442 resulted in an amino acid change ( val ala ) ; all other substitutions were silent . the u to c substitution at 549 and a to g substitution at 1179 have not been reported in any wnv isolates from the united states . however , an isolate collected in illinois in 2002 ( genbank accession no . several more divergent strains of wnv , such as a kunjin virus isolated in australia in 1960 ( genbank accession no . the prm - e genes of mexnl-03 differed from tm171 - 03 ( genbank accession no . five mutations were in the prm gene , and eight mutations were in the e gene . a phylogenetic tree was constructed by bayesian analysis using the complete prm - e gene sequences of 49 wnv strains , including this wnv from nuevo leon state , mexico ( figure 1 ) . phylogenetic trees were also generated using neighbor - joining ( nj ) , maximum parsimony ( mp ) , and maximum likelihood ( ml ) analyses ( data not shown ) . in the bayesian tree , the wnv isolates from north america formed a monophyletic group consisting of two sister clades ( denoted as clade 1 and 2 ) . mexnl-03 shared a close phylogenetic relationship with isolates from inland texas , consistent with our nucleotide sequence alignments . these viruses , along with isolates from colorado , illinois , alabama , and tabasco state , belonged to a nested clade ( denoted as 1a ) within clade 1 . the statistical support for clade 1a by parsimony and distance bootstrap analyses were 64% and 66% , respectively . the other wnv isolates that clustered in clade 1 were from the eastern united states . clade 2 contained wnv isolates from the southeast coastal area of texas and the northeastern united states . the wnv isolates from coastal texas formed a nested clade ( denoted as 2a ) , confirming previous results ( 13,14 ) . phylogenetic analysis of west nile virus ( wnv ) from nuevo leon state , mexico . sampling of trees from the posterior probability distribution used the metropolis - coupled markov chain monte carlo algorithm to allow running of multiple markov chains . a run with four chains was performed for 90,000 generations , under a general time - reversible model ( all six types of substitutions occur at different rates ) with parameter value estimation for base frequencies , substitution matrix values , and rate heterogeneity . rate heterogeneity was estimated by using a distribution for the variable sites and assuming a certain portion of sites to be invariable . the phylogenetic analysis is based on the 2004-nt fragment encoding the complete prm - e genes of 49 wnvs . the tree is rooted by using the prototype wnv strain from uganda in 1937 ( genbank accession no . the parsimony - informative sites , corresponding to nucleotide positions 660 , 1442 , and 2466 , were important in defining the topologic features of the tree ( figure 2 ) . all 21 wnv strains in clade 1a contained a unique c to u substitution at 2466 . all , except for the five most basal isolates , contained a unique c to t substitution at 660 and all , except for tm171 - 03 , contained a unique t to c substitution at 1442 . tm171 - 03 was basal to the other wnv strains in clade 1a , and this topologic arrangement was due to the single nucleotide difference at 1442 . however , we consider it unlikely that tm171 - 03 was the predecessor of the other viruses in clade 1a . in addition , the parsimony and distance bootstrap analyses did not significantly support this topologic arrangement ( bootstrap values = 50% and 51% , respectively ) . moreover , wnv isolates from the northeastern united states occupied the basal position of clade 1 . similarly , the basal position of clade 2 was occupied by wnv isolates from the northeastern united states . thus , our findings suggest that the wnv isolates circulating in the united states and mexico diverged from a common ancestor from the northeastern united states . parsimony - informative sites in the premembrane and envelope genes of selected west nile viruses used in the phylogenetic analyses . the trees generated by nj , mp , and ml analyses showed the same overall topologic features to the bayesian tree , except that all of the coastal texas isolates were basal to the israeli isolate ( data not shown ) . furthermore , the wnv isolates from maryland and new jersey , as well as most of the isolates from new york , occupy the basal positions of clade 1 of the nj / mp / ml trees . as a result , we have not shown the bootstrap values for clades 1 and 2 of the bayesian tree because their composition does not match exactly to the corresponding clades of the nj / mp / ml trees . however , the bayesian analysis provides a more robust and efficient phylogenetic tool compared to more conventional phylogenetic techniques ( 15 ) . the data presented here indicate that wnv was introduced into nuevo leon state , mexico , from inland texas . a likely mode of introduction was by infected birds traveling for short distances ( 16 ) . earlier studies have provided serologic evidence of wnv infection in horses or birds in the nearby mexican states of coahuila , tamaulipas , and chihuahua ( 4,5,17 ) . taken together , our sequence data and the findings from the serosurveys indicate that wnv activity is now widespread in northern mexico , as well as in other regions in mexico ( 5,6,18 ) . the geographic distribution of wnv in the americas will likely continue to expand ; thus , enhanced wnv surveillance in mexico is warranted .

west nile virus rna was detected in brain tissue from a horse that died in june 2003 in nuevo leon state , mexico . nucleotide sequencing and phylogenetic analysis of the premembrane and envelope genes showed that the virus was most closely related to west nile virus isolates collected in texas in 2002 .

cantrell et al . reported five cases in 1958 , describing a pentad of findings that included : ( 1 ) supraumbilical wall defect , ( 2 ) defect of the lower sternum , ( 3 ) deficiency of the anterior diaphragm , ( 4 ) defect of the diaphragmatic pericardium , and ( 5 ) various intracardiac defects . occurrence of the full pentalogy is rare and the survival rate of the patients with complete pentalogy is low , with outcome being dependent on the severity of the cardiac malformation , extra cardiac defects , and other associated anomalies . the child was the second for the parents ; the first had died at one year of age from ill health . the baby was born in a peripheral health center and was 18 hours old when she was transferred to our hospital . pregnancy and delivery were supervised and there was no history of maternal illness during the pregnancy . examination revealed a non - cyanosed anicteric baby , who was not in any obvious respiratory distress . the chest examination showed an obvious anterior chest wall defect covered by skin , which was pink and membranous over the epigastrium . breath sounds were well heard all over the chest , only the first and second heart sounds were heard over the precordium . child with epigastric omphalocoele echocardiography could not be performed in our center because the echocardiography machine could not be adapted for pediatric use , and the parents could not afford the investigation in a private diagnostic center . the child was on admission for seven weeks , and 70% alcohol ( ethanol ) dressing of the membranous covering over the epigastrium was done daily to encourage epithelialization . the father who was a carpenter could not afford any further investigations , or the cost of admission , and requested for child 's discharge against medical advice . a 36-hour - old female child was brought to our hospital following referral from a health center . the child cried spontaneously at birth , and the weight on presentation was 2.5 kg . the mother was a 30-year - old para 3 ( two were alive ) woman . physical examination showed an acyanosed , anicteric child who had a right subconjuctival hemorrhage and was not in any obvious respiratory distress . only heart sounds i and ii were heard . a thin membranous covering of the epigastrium about 3 cm in diameter was noted , with a raised fibrous raphe , of about 5 mm extending from the membranous covering of the epigastrium to a normal appearing umbilical stump [ figure 2 ] . noticeable midline fibrous raphe a chest radiograph revealed a centrally placed globular heart , with good lung expansion and markings , bilaterally [ figure 3 ] . echocardiography could not be done in our center , and the parents could not afford the investigation in a private diagnostic center . parents who were peasants requested for the child 's discharge , against medical advice , on financial grounds . the child was discharged on the sixth day of admission and has been lost to follow up . chest x - ray showing centrally placed globular heart this patient was referred to our unit from a peripheral health center at six weeks of age . the child was referred on account of a chest wall defect , which was noticed at birth . the mother was a remarried widow who had three other children who were alive and well . chest wall examination revealed a complete sternal defect with visible cardiac impulse beneath the anterior chest wall skin covering . the heart rate was 144 per minute , and only heart sounds i and ii were heard , no murmur . a chest x - ray revealed a centrally placed heart , with normal lung fields . the child was offered admission , with a view to have an early surgical intervention , but the parents refused this on financial grounds . the child was the second for the parents ; the first had died at one year of age from ill health . the baby was born in a peripheral health center and was 18 hours old when she was transferred to our hospital . pregnancy and delivery were supervised and there was no history of maternal illness during the pregnancy . examination revealed a non - cyanosed anicteric baby , who was not in any obvious respiratory distress . the chest examination showed an obvious anterior chest wall defect covered by skin , which was pink and membranous over the epigastrium . breath sounds were well heard all over the chest , only the first and second heart sounds were heard over the precordium . child with epigastric omphalocoele echocardiography could not be performed in our center because the echocardiography machine could not be adapted for pediatric use , and the parents could not afford the investigation in a private diagnostic center . the child was on admission for seven weeks , and 70% alcohol ( ethanol ) dressing of the membranous covering over the epigastrium was done daily to encourage epithelialization . the father who was a carpenter could not afford any further investigations , or the cost of admission , and requested for child 's discharge against medical advice . a 36-hour - old female child was brought to our hospital following referral from a health center . the child cried spontaneously at birth , and the weight on presentation was 2.5 kg . the mother was a 30-year - old para 3 ( two were alive ) woman . physical examination showed an acyanosed , anicteric child who had a right subconjuctival hemorrhage and was not in any obvious respiratory distress . only heart sounds i and ii were heard . a thin membranous covering of the epigastrium about 3 cm in diameter was noted , with a raised fibrous raphe , of about 5 mm extending from the membranous covering of the epigastrium to a normal appearing umbilical stump [ figure 2 ] . noticeable midline fibrous raphe a chest radiograph revealed a centrally placed globular heart , with good lung expansion and markings , bilaterally [ figure 3 ] . echocardiography could not be done in our center , and the parents could not afford the investigation in a private diagnostic center . parents who were peasants requested for the child 's discharge , against medical advice , on financial grounds . the child was discharged on the sixth day of admission and has been lost to follow up . this patient was referred to our unit from a peripheral health center at six weeks of age . the child was referred on account of a chest wall defect , which was noticed at birth . the mother was a remarried widow who had three other children who were alive and well . chest wall examination revealed a complete sternal defect with visible cardiac impulse beneath the anterior chest wall skin covering . the heart rate was 144 per minute , and only heart sounds i and ii were heard , no murmur . a chest x - ray revealed a centrally placed heart , with normal lung fields . the child was offered admission , with a view to have an early surgical intervention , but the parents refused this on financial grounds . cantrell 's pentalogy ( cp ) is a rare congenital anomaly in which defects of the anterior abdominal wall , sternum , and diaphragm are associated with cardiac anomalies.[14 ] full pentalogy occurs rarely . presence of the pentad is considered by some to be the full spectrum , with absence of some of the components seen as incomplete forms of the pentalogy . cp is 2.7 times more common in boys , and african americans may be more predisposed . the error in the embryology appears to occur in a segment of the lateral mesoderm . the cardiac abnormalities are due to a faulty development of the epimyocardium and the sternal and abdominal wall defects represent a faulty ventromedial migration of the paired mesodermal primordial structures . the diaphragmatic and the pericardial defects are secondary to a developmental failure of the transverse septum . these abnormalities seem to occur around day 14 to 18 of embryonic life . through the resulting sternal and abdominal wall defects many factors may play a role in the pathogenesis of cp and ventral midline defects . judging from the phenotypic variability of these defects , factors such as genetic aberrations and external mechanical forces may be implicated . some workers believe that the pathogenesis of this syndrome can be linked to mechanical teratogenesis ( band disruptions ) following rupture of the chorion or yolk sac . the mechanical teratogenesis concept seeks to explain the numerous malformations that could be seen in these infants , exclusive of the torso . toyama , after a review of 61 cases of cp , suggested the following classifications : class 1 , definite diagnosis , with all five defects present ; class 2 , probable diagnosis , with four defects , including intracardiac and ventral abdominal wall abnormalities present ; and class three , incomplete expression , with various combinations of defects , including a sternal abnormality present . our three cases may be regarded as incomplete expression of the syndrome , as we were not able to demonstrate an intracardaic defect or a deficiency of the anterior diaphragm in any of them , due to constraints in performing echocardiography . patients should be reviewed by a pediatric anesthetist before surgery , due to the peculiarities of anesthesia that may arise from the component anomalies . we intended a repair of the sternal cleft in these patients , to provide a bony protection for the mediastinal structures . the technical and financial constraints we encountered , however , precluded this line of management . the constraints we experienced in the management of these patients are rather sadly recurrent in pediatric surgical practice in this region , where a majority of the population survive on less than 1 us dollar daily , and only about 2 3% of government expenditure is allocated to health . due to a non - encompassing health insurance , therefore , healthcare is in direct competition with the basic needs of food , shelter , and clothing . this will explain the willingness of our patients relatives to seek for discharge against medical advice on financial grounds . policy makers do not regard surgery as a component of basic healthcare and often dismiss pediatric surgery as being capital intensive and catering to an insignificant minority . this inclination has accounted for the paucity of equipments needed for the optimal care of our patients . surgical repair of the sternal cleft should be done early to protect the mediastinal structures and eliminate a cosmetic deformity .

pentalogy of cantrell is a rare upper midline syndrome that may present in association with anomalies outside the torso . the pentad the supraumbilical body wall defect , sternal defect , deficiency of the anterior diaphragm , defect of the diaphragmatic pericardium , and the intracardiac anomalies was first described by cantrell et al . , in 1958 . the defect is said to be more common in males , and survival is dependent on the cardiac malformations and on the degree of completeness of the syndrome . we report three cases of cantrell 's pentalogy managed in our unit . two of the patients were females and one a male . all were seen at peripheral health centers before being referred to us . age at presentation for the girls was 18 hours and 36 hours , respectively , the boy presented at the age of six weeks . all of their parents were unschooled manual workers . all patients presented with a defect in the supraumbilical body wall , bifid sternum , and a visible cardiac impulse . we were unable to do echocardiography to rule out intracardiac anomalies in the three patients . the thin membranous covering of the epigastrium in the female patients was managed conservatively . both female patients were discharged against medical advice as requested by their parents , due to financial constraints . the male patient was lost to follow up after two clinic visits . a multidisciplinary approach to the management of this syndrome is recommended .

gingival recession ( gr ) has been defined as the condition in which the gingival margin is located apical to the cementoenamel junction and the root is exposed to the oral environment , resulting in problems such as root caries , dental hypersensitivity , and esthetic problem , probably one of the most esthetic concerns associated with the periodontal tissue . however , till date the exact mechanism for gingival recession is not well understood , as various etiological factors have been reported . the main etiological factor for gr is due to the accumulation of dental plaque resulting in gingival inflammation . along with these , the other risk factors include developmental defect such as bone dehiscence , chronic trauma that may arise from habits such as chronic impaction of foreign bodies against the gingiva , frictional injury due to scratching of gingival , and also abnormal tooth cleaning . others include tooth malposition of teeth , gingival ablation , abnormal frenum attachment , ageing , smoking , and iatrogenic dentistry . unlike other periodontal conditions such as pockets and furcation involvement that are unnoticed or unrecognized , gr however is clinically visible and the changes are well noticed and reported by the patient to the dentist that is of great concern . a large number of epidemiological studies have been done on the prevalence and occurrence of gingival recession in western population than in indian population . the prevalence varied from 50 - 90% among these populations . however , periodontal disease is more prevalent in developing countries than in developed countries and since recession is a sign of periodontal disease it is of great concern . the aim of this study is to estimate the prevalence , severity , and extent of gingival recession in patients who attended for outpatient department of vishnu dental college , bhimavaram , andhra pradesh , india , and also to assess the potential risk factors for the same . samples of 2837 patients were examined of which 627 ( 22% ) were included into the study . study population age ranged from 16 - 80 years ( mean : 32.5 sd ) there were 424 ( 67.6% ) males ; 203 ( 33.4% ) females . gingival recession was defined as distance from the cementoenamel junction ( cej ) to the free gingival margin ( fgm ) was measured with the help of university of north carolina-15 ( unc-15 ) probe . all permanent fully erupted teeth excluding third molars were examined and measurements were made at six sites per tooth : mesio buccal , mid buccal , disto buccal , mesio lingual , mid lingual , disto lingual , and the highest measurement was recorded . gingival recession was scored as zero if the fgm was located at the cej , and was assigned a negative if fgm was coronal to cej . age and gender classification of study population the study was reviewed and approved by the institutional review board of vishnu dental college , bhimavaram , india . written informed consent was taken from every participant prior to the study and at the end of the study all the patients were treated according to the particulars mentioned in the case sheet . both the examiners were trained , intraexaminer and interexaminer reliability was assessed with kappa statistics . prevalence was defined as the percentage of individuals having at least one tooth with the condition and extent as the percentage of teeth per person having at least one site with the condition . mean gingival recession was calculated and was used as a measure of the condition severity in the population . severity was also assessed as the threshold for gingival recession . a total exposure to cigarette was calculated for current smokers only and was made separate for younger ( 16 - 35 years ) and older ( > 35 years ) cohorts . the presence of supragingival dental calculus was categorized in to three categories according to the percentage of sites with calculus . data analysis was done with statistics package for the social sciences ( spss ) software version-10 . a weight variable was used to adjust the probability of selection and deviations in the sample distribution from the target population distribution by age and gender . pairwise comparisons of crude estimations were carried out by using wald 's test and 95% confidence intervals were calculated . a new variable was calculated and used as the department variable in the analysis , based on the extent of gingival recession 1 or 3 mm for individual below 35 and above 35 years . hence , the subjects were scored as having localized or generalized recession in between 1% and 15% , or 16% of the teeth were affected , respectively . individuals without 1 or 3 mm recession below 35 years or above 35 years were used as the reference group in the model . in both the analyses the multinomial logistic regression method was used to assess the contribution of the independent variables to the probability of occurrence of localized or generalized gingival recession , separately , compared to nonoccurrence of gingival recession . the probability of occurrence of recession was expressed as a relative risk ratio ( rrr ) that is equivalent to the odds ratio statistics in the ordinary logistic regression . samples of 2837 patients were examined of which 627 ( 22% ) were included into the study . study population age ranged from 16 - 80 years ( mean : 32.5 sd ) there were 424 ( 67.6% ) males ; 203 ( 33.4% ) females . gingival recession was defined as distance from the cementoenamel junction ( cej ) to the free gingival margin ( fgm ) was measured with the help of university of north carolina-15 ( unc-15 ) probe . all permanent fully erupted teeth excluding third molars were examined and measurements were made at six sites per tooth : mesio buccal , mid buccal , disto buccal , mesio lingual , mid lingual , disto lingual , and the highest measurement was recorded . gingival recession was scored as zero if the fgm was located at the cej , and was assigned a negative if fgm was coronal to cej . the study was reviewed and approved by the institutional review board of vishnu dental college , bhimavaram , india . written informed consent was taken from every participant prior to the study and at the end of the study all the patients were treated according to the particulars mentioned in the case sheet . both the examiners were trained , intraexaminer and interexaminer reliability was assessed with kappa statistics . prevalence was defined as the percentage of individuals having at least one tooth with the condition and extent as the percentage of teeth per person having at least one site with the condition . mean gingival recession was calculated and was used as a measure of the condition severity in the population . severity was also assessed as the threshold for gingival recession . a total exposure to cigarette was calculated for current smokers only and was made separate for younger ( 16 - 35 years ) and older ( > 35 years ) cohorts . the presence of supragingival dental calculus was categorized in to three categories according to the percentage of sites with calculus . data analysis was done with statistics package for the social sciences ( spss ) software version-10 . a weight variable was used to adjust the probability of selection and deviations in the sample distribution from the target population distribution by age and gender . pairwise comparisons of crude estimations were carried out by using wald 's test and 95% confidence intervals were calculated . a new variable was calculated and used as the department variable in the analysis , based on the extent of gingival recession 1 or 3 mm for individual below 35 and above 35 years . hence , the subjects were scored as having localized or generalized recession in between 1% and 15% , or 16% of the teeth were affected , respectively . individuals without 1 or 3 mm recession below 35 years or above 35 years were used as the reference group in the model . in both the analyses the multinomial logistic regression method was used to assess the contribution of the independent variables to the probability of occurrence of localized or generalized gingival recession , separately , compared to nonoccurrence of gingival recession . the probability of occurrence of recession was expressed as a relative risk ratio ( rrr ) that is equivalent to the odds ratio statistics in the ordinary logistic regression . in all 79.4% , 45.6% , 16.2% of the individuals and 37.5% , 13% , 4.8% of teeth per individual showed gr 1 , 3 , and 5 mm , respectively . the prevalence , severity , and extent of recession were correlated with the age [ table 2 ] . recession was present but recession threshold 3 and 5 mm affected only small percentage of teeth in subjects younger than 45 years . on the other hand moderate recession was ubiquitous in the older age group . among subjects aged 45 years or old , 79% of subjects and 32% of teeth per subject had recession more than 3 mm . percentage of subjects and teeth per subject with gingival recession by age in subjects less than 35 years , mandibular central and mandibular lateral incisors showed the highest prevalence of gingival recession of 1 mm with ( 35% ) and ( 26% ) of these teeth effected , respectively . other teeth showing high prevalence of gingival recession were the maxillary first molar ( 19% ) , maxillary first premolar , and mandibular second premolar . table 3 shows subjects younger than 35 years , there was no statically significant difference in prevalence or extent of recession between males and females . however , in individuals above 35 years , males consistently showed higher prevalence and extent of recession than their counter parts . the percentage of teeth with recession 2 mm ( 0.008 ) and 5 mm ( 0.001 ) was relatively more for males than females . the relative risk of males having recession 1 mm was 1.8 times more when compared to females . percentage of subjects more than 35 year old and percentage of teeth per subject with gingival recession by sex assessment of risk for having gingival recession more than 1 mm in subjects of age above 35 years the prevalence of recession in smokers was relatively high when compared to normal individuals . individuals who were moderate to heavy smokers below 35 years having recession 1 mm had significant higher prevalence of recession compared to nonsmokers . the relative risk for localized recession was 2.1 for moderate to heavy smokers and for generalized recession it was 4.2 for the same [ table 5 ] . the relative risk for recession 1 mm in subjects above 35 years in moderate to heavy smokers is 2.1 for localized recession and 3.2 for generalized recession . young subjects who were heavy smokers and individual 35 years who were moderate to heavy smokers had a significantly higher prevalence of recession ( p < 0.01 ) and had higher percentage of teeth affected ( p < 0.01 ) in smoking group compared to nonsmokers . furthermore , in both age groups individuals with higher percentage of teeth with supragingival calculus had a significantly higher prevalence ( p < 0.01 ) and percentage of teeth ( p < 0.01 ) showing recession . assessment of risk for having gingival recession more than 1 mm in subjects of age below 35 years furthermore , in both age group individuals with a high percentage of teeth with supragingival calculus had a significantly higher prevalence and percentage of teeth with recession . the relative risk for localized recession 1 mm was 3.8 for individuals less than 35 years [ table 4 ] . this is the first epidemiological study done in hospital population in india to evaluate the prevalence of gingival recession . results indicate that gingival recession is a common condition with a prevalence of 68% for males compared to females who had 32% gingival recession . in general , these findings are consistent with the previous cross - sectional studies were 65% of norwegian and sri lankans had gingival recession by the age of 22 years . by 30 years of age more than 75% of norwegian and 90% of sri lankans had one or more sites with gingival recession and at these ages only 16% and 22% of buccal surfaces showed recession between 1 - 2 mm . in us studies , the prevalence of gingival recession of 1 mm or greater was 58% for persons between 30 and 90 years of age . mandibular central and lateral had highest prevalence of gingival recession when compared to other teeth that was consistent with other studies that could be attributed to local factors such as plaque and calculus . however , this was in contrast to the findings of the uk - based study were they reported high prevalence of gingival recession in upper canines , first premolar , lower canines , first premolar and incisors in a group aged between 25 - 70 who suffered with dentinal hypersensitivity . reported high prevalence of gingival recession involving premolars . in this study , males had more percentage of gingival recession compared to their counterpart that was consistent with the previous studies . however , maintenance of good oral health is arguably the best method to prevent and control progression of periodontal disease . various risk factors are associated with gingival recessions that include age , high frenum , trauma from tooth brushing , calculus , and smoking . it is evident that prevalence of calculus is much higher in most developing countries than in the developed countries . in this study > 80% individual above 35 years had > 40% of teeth covered with calculus and was strongly associated with gingival recession that was consistent with previous studies showing a correlation between calculus and recession . cigarette smoking was strongly associated with occurrence of localized and generalized gingival recession in both the age groups , that is , 35 and 35 years that was statistically significant . there is a strong association between cigarette smoking and attachment loss ; however , there is inconsistency between smoking and gingival recession that could be due to the reporting of the data or the study design were few used cross - sectional and case control studies were as others used 6 months follow up studies to report the data . in this study , there was high prevalence of periodontal disease and calculus was a common finding suggesting an association between these two . the cross - sectional study design of this study does not permit an unequivocal inference about the causal relationship between the studied risk indicators and gingival recession . however , it can be concluded that high prevalence of gingival recession could be associated to improper oral hygiene and cigarette smoking , which emphasizes the need for management of recession . initial treatment would be preventive measures such as quitting smoking and measures to improve oral hygiene , followed by surgical correction as it would be easy to motivate them since they are all hospital population .

objective : gingival recession ( gr ) is a common manifestation in most populations , and is considered as an early sign of periodontal disease . gr is an intriguing condition where various factors play an important role in its etiology . only few studies have been undertaken to assess the prevalence and risk factors for gr in patients visiting dental hospitals . the aim of this study is not only to estimate prevalence , severity , and extent of gr in hospital population , of vishnu dental college , bhimavaram , andhra pradesh , india , but also to assess the potential risk factors for the same.materials and methods : in this study , 2837 patients were examined of which 627 were included into the study . the age range was 16 - 80 years . subjects were interviewed using a structural questionnaire , and full mouth clinical examination was done to assess recession.results:of all subjects examined 45.6% , 16.2% of individuals and 13% , 4.8% of teeth per individual showed gr > 3 mm . prevalence and severity of recession was correlated with age . recession was present but recession threshold 3 and 5 mm affected only small percentage of teeth in subjects younger than 45 years . mandibular incisors showed the highest prevalence of gr 1 mm with 61% of teeth being affected . smoking and presence of supragingival calculus were most significantly associated localized and generalized recession.conclusion:prevalence of periodontal disease is high among this population based on the presence of gingival recession in most the individuals . high prevalence of gr is significantly associated with supragingival calculus and smoking habits . this suggests a need to improve their periodontal condition through education , motivation , and improving their periodontal health .

the presentation of this technological hazard may range from a mild socio - personal distress to a gross disorganization in behavior and self - care . we reported a case of two brothers , diagnosed with internet gaming addiction , who showed grossly disorganized behavior and severely compromised self - care . the condition was managed by pharmacological and non - pharmacological therapies , with sustained improvement after 6 months follow up . internet gaming addiction may cause severe personal , social , and occupational problems . despite the range of severity and various presentations of this disorder rapid and extensive proliferation of the internet has resulted in better opportunities for research , communication , and information . useful to some extent , this modern day technological wonder has largely caused decline in physical and mental well - being owing to its potential for causing addiction in the form of pornography , excessive gaming , chatting for long hours , gambling , and online shopping . goldberg in 1995 introduced the term internet addiction for pathological compulsive internet use ( 1 ) . excessive internet gaming has been described as a specific subtype of internet addiction ( 2 ) . according to some reports , up to 90% of american youngsters still , it has not been classified under main disorders as adequate research - based evidence is lacking . the presentation of internet gaming disorder may range from a mild socio - personal distress to a gross disorganization in behavior and self - care . we report two brothers diagnosed with internet gaming addiction , with grossly disorganized behavior and severely compromised self - care . messrs a and b were two unmarried brothers , belonging to a nuclear family of upper socioeconomic class of urban background of delhi . mr a is 19 years old , studying in 12 standard while mr b is 22 years old , studying in 2 year of engineering in haryana , india . both brothers were brought by their parents with the complaints of insidious onset , gradually progressive excessive online gaming , irritability , decline in studies performance , and impaired self - care for the past 2 years . the problem began when both brothers used to stay together at home and started playing online game with their virtual internet friends from different countries . due to difference in gmt ( greenwich mean time ) across all countries , they had no specific timing for games and hence the gaming interfered with their sleep and daily routine . the duration of online gaming progressed from 2 - 4 hours per day to 14 - 18 hours per day over the initial few months . the behavior and self - care of these brothers became so compromised and disorganized that while playing the games , they urinated and defecated in their clothes , did not change clothes for days , did not bathe , skipped their meals , did not pick up phones or open doors even to their parents . they were not concerned even when strangers entered the house in their presence and robbed the house . their home was robbed twice of cash and costly articles in their presence , during the last 2 months while they were preoccupied in playing online games . they shouted at parents , abuse and hit them and even locked in their rooms when stopped from playing game . the patients were admitted in view of above problems , the severity of gaming addiction . their general physical examination , systemic examination , and laboratory investigation were within normal limits . on interviewing , irritability , and craving for games the aim of the treatment was to reduce irritability , improve sleep , daily routine , and self - care along with enhancing motivation and reducing craving for online games to prevent future relapses . diagnostic psychometric assessment revealed impulse control problems , depressive cognitions , and delinquency in both brothers . fluoxetine 20 mg / day was started ( increased to 40 mg / day ) along with clonazepam 0.5 mg as required for sleep . it included limit setting , motivational interviewing , motivation enhancement therapy , activity scheduling , family and individual therapy , distraction techniques , and positive reinforcement using principles of behavior therapy . during the one month stay in the hospital , both patients improved considerably with reduced irritability and craving for online games , better self - care and hygiene , improved sleep , and interest in studies . the improvement maintained during the 6 months follow up , even after stopping fluoxetine with simple methods of behavior therapy using parents as co - therapists . , it has great technological value in research , communication , information , leisure activities , business transactions , and learning . however , there is always a dark side to new technologies . in case of internet , it turns to an addiction which is a recent concept and still under research . internet gaming addiction is the latest phenomenon in the world of internet ( 5 ) . for many adolescents , a market research company has estimated the china s worth online gaming market as $ 12 billion in 2013 . a recent review article reported prevalence estimates ranging from 0.2% in germany to 50% in korean teenagers ( 6 ) . although internet gaming disorder has not been classified under main disorders of dsm-5 , researchers have realized that internet gaming is increasingly being used by people of all ages , especially younger population , who may face severe consequences associated with compulsive use of games ( 6 ) . according to dsm-5 ( 4 ) , internet gaming disorder refers to the persistent and recurrent use of the internet to engage in games , often with other players , leading to clinically significant impairment or distress as indicated by 5 ( or more ) criteria in a 12-month period . these criteria comprise lack of control over the use of internet games , preoccupation with internet gaming , psychological withdrawal , developing tolerance for games and need for increase use of games , loss of other significant interests , use of internet games despite negative consequences , and significant decline in social and occupational domains ( 4 , 6 ) . all these signs and symptoms were observed or reported in the described case report of patients . internet gaming addiction is a disorder that is most dramatically expressed with games known as massively multiplayer online games ( mmos ) ( 7 ) and specially massively multiplayer online role - playing games ( mmorpgs ) like world of warcraft ( 8) . mmorpgs are games played by thousands of players at the same time ( massively multiplayer ) . because these games are played online , there are no spatial or temporal boundaries and they allow players to adopt various virtual roles . hence , these games are specially engineered to maximize the amount of time a player stays in the game . the same was observed in the patients where they used to play such games with virtual friends across different countries and at odd hours . the psychological consequences vary and include difficulty in real - life relationships , disturbances in sleep , work , education , socializing , attention , academics , and memory . it may include aggression and hostility , stress , and high loneliness ( 6 , 9 - 11 ) . most of these disturbances were evident in both patients . considering the shared features with addiction disorders , which are evident from the above case , internet gaming addiction could be placed alongside the main disorders in the future classificatory systems . dsm-5 needs to consider the severity classifiers for the disorder , which might present variedly depending upon the content and type of games , cultural context of gaming , and associated personality type . internet addiction is a new and emerging group of disorders in indian subcontinent ( 12 ) . it has proliferated and spread across the subcontinent , in spite of deeply knit family systems and parental supervision . systematic studies need to be undertaken in indian subcontinent to evaluate the prevalence and type of gaming addiction . crucial steps in curtaining this evolving epidemic must be taken in the form of legal limitations on sale / purchase , setting the age limit , and restricting access to online games .

introduction : the internet is considered a beneficial tool in research , communication , and information . still , its excessive and prolonged use has the potential of causing addiction . the presentation of this technological hazard may range from a mild socio - personal distress to a gross disorganization in behavior and self - care . no reported study on internet gaming addiction is available from india.case presentation : we reported a case of two brothers , diagnosed with internet gaming addiction , who showed grossly disorganized behavior and severely compromised self - care . the condition was managed by pharmacological and non - pharmacological therapies , with sustained improvement after 6 months follow up.conclusions:internet gaming addiction may cause severe personal , social , and occupational problems . despite the range of severity and various presentations of this disorder , dsm-5 lacks the severity classifier . early identification and management may result in complete recovery .

primary tumors of the pleura can be benign or malignant and they may manifest as either diffuse or localized neoplasms . benign tumors are less common than the malignant ones , they are localized and arise from the submesothelial mesenchymal cells with a fibroblastic differentiation . in most cases , the solitary fibrous tumor of the pleura ( sftp ) can be asymptomatic ; sometimes , it causes symptoms ( as dyspnea , cough , chest pain ) following the compression of airways and pulmonary parenchyma . the best therapy for sftp is complete surgical resection with a long - term follow - up . we present two cases of sftp in two different patients , a new mother with a polyarticular paraneoplastic syndrome and an old man with obstructive pulmonary disease who had underestimated the occasional finding on the chest x - ray of a pulmonary small peripheral mass 4 years before . a 36-year old woman was admitted to the emergency department of our hospital with widespread polyarticular pain and fever ( t < the patient had given birth to a baby 1 week before the onset of the symptoms . with the worsening of fever ( t > 39c ) , a chest computed tomography ( ct ) scan was performed revealing [ figure 1a b ] a large inhomogeneous mass in the upper lobe of the left lung ( 18 11 9 cm ) . the ct scan also showed compression and atelectasis of the lung parenchyma with ipsilateral pleural effusion ; there were no significant lymphadenopathies of the main stations of the thorax . therefore , the patient was allocated to the division of pulmonology . at admission , she did not report dyspnea , cough , or chest pain but persistent polyarticular pain and fever ; the blood tests [ including waaler - rose and anti - neutrophil cytoplasmic antibody ( anca ) ] were normal except for a mild leukocytosis ( 13,360 cells / mm ) and an increase of c - reactive protein ( crp ) ( 16,65 mg / dl ) ( normal value : < 0,5 mg / dl ) . we decided to perform a ct - guided biopsy of the mass ; histological examination revealed the presence of sftp cells cd34+/b - cell lymphoma 2 ( bcl-2)+ with proliferative activity ( expressed with the index of proliferation ki-67 ) less than 5 . following this result , diagnosis of sftp was processed and joint pain and fever were considered as epiphenomena of the tumor ( paraneoplastic syndrome ) . therefore , the pulmonary lesion was surgically removed with subsequent reexpansion of the lung . case 1 - chest ct scans at the left pulmonary apex level ( a ) and at the aortic arch level ( b ) ; case 2 - chest ct scans performed for biopsy show an intraparenchymal neoplasm near the anterior chest wall ( c ) and at the aortic arch level ( d ) a 75-year old man was admitted to our hospital because of a chest x - ray that showed an opacity ( 5,8 4,9 cm ) in the left lung with mild dyspnea and productive cough that began 3 months earlier . the patient had a clinical and functional diagnosis of chronic obstructive pulmonary disease ( copd ) , with a moderate smoking habit ( 30 packs / year ) , chronic systemic hypertension , abnormal electrocardiogram findings ( brugada syndrome ) , diabetes mellitus ( dm ) ( type ii ) . a ct scan , performed 4 years before , had shown a smaller mass ( 3,5 2,5 cm ) on the left lung , next to the chest wall in comparison with that documented during hospitalization . at that time , no diagnosis was reached since the patient refused to undergo diagnostic biopsy . routine tests were normal including blood gas analysis ( ph 7,43 , paco2 45 mmhg , pao2 81 mmhg , and sao2 96% ) . due to increased mass dimension in comparison with previous ct scan , the patient was asked again to undergo a ct - guided biopsy of that lesion and he agreed [ figure 1c d ] . histological examination associated with the presence of cells cd34+/bcl-2 + was compatible with a sftp . the thoracic surgeon performed mass resection with a complete recovery of the patient . a 36-year old woman was admitted to the emergency department of our hospital with widespread polyarticular pain and fever ( t < the patient had given birth to a baby 1 week before the onset of the symptoms . with the worsening of fever ( t > 39c ) , a chest computed tomography ( ct ) scan was performed revealing [ figure 1a b ] a large inhomogeneous mass in the upper lobe of the left lung ( 18 11 9 cm ) . the ct scan also showed compression and atelectasis of the lung parenchyma with ipsilateral pleural effusion ; there were no significant lymphadenopathies of the main stations of the thorax . therefore , the patient was allocated to the division of pulmonology . at admission , she did not report dyspnea , cough , or chest pain but persistent polyarticular pain and fever ; the blood tests [ including waaler - rose and anti - neutrophil cytoplasmic antibody ( anca ) ] were normal except for a mild leukocytosis ( 13,360 cells / mm ) and an increase of c - reactive protein ( crp ) ( 16,65 mg / dl ) ( normal value : < 0,5 mg / dl ) . we decided to perform a ct - guided biopsy of the mass ; histological examination revealed the presence of sftp cells cd34+/b - cell lymphoma 2 ( bcl-2)+ with proliferative activity ( expressed with the index of proliferation ki-67 ) less than 5 . following this result , diagnosis of sftp was processed and joint pain and fever were considered as epiphenomena of the tumor ( paraneoplastic syndrome ) . therefore , the pulmonary lesion was surgically removed with subsequent reexpansion of the lung . case 1 - chest ct scans at the left pulmonary apex level ( a ) and at the aortic arch level ( b ) ; case 2 - chest ct scans performed for biopsy show an intraparenchymal neoplasm near the anterior chest wall ( c ) and at the aortic arch level ( d ) a 75-year old man was admitted to our hospital because of a chest x - ray that showed an opacity ( 5,8 4,9 cm ) in the left lung with mild dyspnea and productive cough that began 3 months earlier . the patient had a clinical and functional diagnosis of chronic obstructive pulmonary disease ( copd ) , with a moderate smoking habit ( 30 packs / year ) , chronic systemic hypertension , abnormal electrocardiogram findings ( brugada syndrome ) , diabetes mellitus ( dm ) ( type ii ) . a ct scan , performed 4 years before , had shown a smaller mass ( 3,5 2,5 cm ) on the left lung , next to the chest wall in comparison with that documented during hospitalization . at that time , no diagnosis was reached since the patient refused to undergo diagnostic biopsy . routine tests were normal including blood gas analysis ( ph 7,43 , paco2 45 mmhg , pao2 81 mmhg , and sao2 96% ) . due to increased mass dimension in comparison with previous ct scan , the patient was asked again to undergo a ct - guided biopsy of that lesion and he agreed [ figure 1c d ] . histological examination associated with the presence of cells cd34+/bcl-2 + was compatible with a sftp . the thoracic surgeon performed mass resection with a complete recovery of the patient . we have reported two cases of sftp diagnosed by transthoracic biopsy : the first of a young , new mother with fever and widespread joint pain without significant respiratory symptoms and the other of a 75-year old man with cough and dyspnea attributed to his copd and who was aware of having a pulmonary neoplasm from 4 years , the nature of which he had never ascertained . sftp is rare benign tumor and is more frequent in the sixth / seventh decade of life in both the sexes with a modest predominance among females . generally , solitary fibrous tumors of the pleura are isolated , well - defined masses while conglomerate or multifocal ones are rare presentations . approximately , half of the masses are pedunculated , with vascular supply maintained by the pedicle . sometimes , large tumors can produce symptomatic atelectasis or in rare cases hemoptysis by compression of a bronchus . furthermore , large tumors , more frequently than the small ones , produce paraneoplastic syndromes such as digital clubbing and hypertrophic pulmonary osteoarthropathy ( pierre marie - bamberg syndrome ) . in patients with hypertrophic pulmonary osteoarthropathy , bilateral arthritis - like symptoms are common findings ( e.g. joint pain , pain along the long bones , stiffness or swelling of the joints , and edema of the ankles ) . the resection of the tumor usually solves the paraneoplastic symptoms ( they generally disappear within about 25 months or longer after surgery ) but they may appear again with recurrence of the tumor . our first patient showed only joint pain and fever that were unresponsive to antibiotics and no respiratory symptoms despite compression of pulmonary parenchyma caused by the large mass ; on the contrary , the second patient showed respiratory symptoms that were linked to his copd . it is worth mentioning that the slow growth of this tumor of the pleura showed a slight increase in size ( 3,5 2,5 cm vs 5,8 4,9 cm ) in about 4 years . after an initial approach with chest x - rays , the ct scan is the best procedure in order to study more clearly the size and location of the tumor and to plan surgery in the best way . the ct scan visualizes a small sftp as well - defined soft tissue mass near the pleural layer , usually lobular in shape , homogeneous in density and noninvasive ; larger lesions , on the other hand , are generally heterogeneous and may reveal themselves as diffuse pleural opacities on ct scans . sftp can not be diagnosed only by radiological tools and transthoracic tissue biopsy is essential to reach a diagnosis . it is useful to evaluate the positivity of cd34 expression , a cell marker found in mesenchymal cells ( lost in malignant tumors ) , presence of bcl-2 ( b - cell leukemia / lymphoma-2 oncogene ) , vimentin and cd99 ( positive in sftp ) , cytokeratin ( positive in mesothelioma and negative in sftp ) . moreover , the proliferation marker ki-67 can be used to stratify lesions according to their clinical outcome . recently , a cutoff level of a proliferation rate of 12% ( ki-67 ) was suggested to distinguish benign and malignant lesions . the best and the only demonstrated effective treatment of sftp is surgical resection removing pulmonary parenchyma compression and allowing the reexpansion of the lung .

we report two cases of solitary fibrous tumor of the pleura ( sftp ) . the first appeared in a young , new mother as a large mass in the upper lobe of the left lung that caused compression of lung parenchyma without significant respiratory symptoms but with polyarticular paraneoplastic syndrome ; the other was documented by an occasional chest x - ray in a man affected by chronic obstructive pulmonary disease ( copd ) as a small peripheral mass 4 years before and no longer controlled . both patients underwent surgical resection with quick and full recovery . sftp is a benign , slow growing neoplasm that is mostly localized . it appears in adult or elderly patients often with few symptoms . the computed tomography ( ct ) of the chest with contrast medium is important in order to see the shape of the mass and relationships with adjacent structures but only histology can provide the diagnosis . surgery is the best treatment .

klippel - trenaunay syndrome ( kts ) is characterized by triad of port - wine stain , varicose veins , and bony and soft tissue hypertrophy . a 45-year - old male presented with an ulcer over the left ankle . on examination , dilated tortuous veins were present all over the left lower limb including gluteal region . there was associated muscular atrophy of left leg and deformity of left great toe since birth . cavernous hemangiomas were present on his face , chest , back , gluteal region , groin and legs and were observed mostly on the left side [ figures 13 ] . he had no family history of similar disorder and had been asymptomatic till he developed ulcer over left ankle 4 months ago . after initial physical evaluation , investigations were advised . a routine hematology revealed normal results . doppler study revealed incompetence of venous valves at all level in the left lower limb . there was no evidence of arterio - venous fistula or deep venous thrombosis . however , the arteries showed atherosclerotic changes , with sub - cutaneous edema all over the left lower limb . abdominal and pelvic ultrasound revealed subcutaneous soft tissue swellings in the inguinal and gluteal region and abnormally enlarged urinary bladder . computerized tomographic scan of the chest and abdomen revealed paravertebral soft - tissue attenuated masses from d1 to d10 [ figure 4 ] . port wine stain involving face , chest , both upper limbs atrophy of muscles of left leg with deformity of great toe varicosity of veins over buttock and lateral aspect of thigh computer tomography lower chest showing paravertebral soft tissue mass about a century ago , two french physicians maurice klippel and paul trenaunay described two patients with hemangiomatous lesions of the skin associated with asymmetric soft tissue and bone hypertrophy , and coined the term naevus variqueux osteohypertrophique . years later , frederick parks weber noted the occurrence of these findings in association with arteriovenous fistulas . the related klippel - trenaunay - weber syndrome describes those individuals who have an arteriovenous malformation as a component of their syndrome . the classic clinical triad includes capillary malformations ( port wine stain ) , a usually longer and larger extremity because of soft tissue and bone hypertrophy , and atypical mostly lateral superficial varicosity . patients with at least two of the three cardinal features have been classified as having an incomplete form of kts . lesions are usually present since birth and in approximately 75% of patients they appear before 10 years of age . the origin of this syndrome continues to be investigated , and many theories were discussed . later studies conducted by happle suggest that the inheritance of a single abnormal gene could explain the development of this syndrome , as well as the occurrence of sporadic and familial cases . although kts is a sporadic condition , studies report familial cases of kts that have not been inherited in a mendelian pattern , suggesting a multifactorial inheritance . kts was initially described in 1900 as a triad of cutaneous capillary hemangiomas , bony and soft - tissue hypertrophy , and varicosity of veins . most patients often show these three components of the clinical syndrome , and hemangioma is often the first to appear . port - wine stain or flat hemangioma is a vascular malformation present at birth and that does not show tendency toward involution . it increases in proportion to the child 's growth and may involve any part of the body , although face and cervical region are the most commonly affected areas . hemangiomas may be limited or extend to deeper areas of skin , including bones , muscles , and organs , worsening the prognosis of the disease . varicose veins observed in patients with the syndrome may be noticed in early infancy , but they generally become prominent at a later stage and progress until adolescence . these are large lateral veins that start on the foot or leg proximally and extend upto the gluteal region . these areas may remain stable or enlarge gradually , causing pain , lymphedema , thrombophlebitis , and ulcers . hypertrophy is the third symptom to appear in the syndrome and it can be secondary to increase in length of bones and/or increase in circumference due to soft - tissue involvement . it can be observed at birth and progresses during the first year of life . in adolescence , vascular malformations involving the gastrointestinal and genitourinary tracts have been reported and can be a significant source of morbidity and even mortality . patients with vascular malformations of the bladder frequently have associated rectosigmoid or other pelvic organ involvement . rectal and bladder hemorrhage are serious complications of pelvic vascular malformations and have been reported in 1% of cases . involvement of the gastrointestinal tract may be more common in kts than previously believed ( occurring in perhaps as many as 20% of patients ) and may go unrecognized in patients without overt symptoms . therapeutic objectives seek to improve the patient 's condition and treat the consequences of severe lesions . treatment of port - wine stains is usually done with pulsed dye laser therapy that yields better results when applied to lesions in the face and trunk , as compared to extremities . the use of orthopedic braces is a good option to prevent the development of vertebral deformities in case of hypertrophy of the lower limbs . with time , corrective bone surgery may be necessary to treat significant limb length discrepancy , if present . the hypertrophy involves the length as well as the circumference of the involved extremity and is caused by local hyperemia and venous stasis secondary to the vascular anomaly . however , in the present case we observed that capillary malformations were extensively present involving both halves of the body , with obvious hypotrophy of left lower limb . however , in this it may be attributed to regional fatty atrophy and atherosclerosis of vessels . soft - tissue mass was present subcutaneously and in paravertebral area and urinary bladder was abnormally large and highly placed , probably due to neurofibromatosis .

the klippel - trenaunay syndrome ( kts ) is a congenital disorder characterized by capillary malformation , varicosities and bony and soft tissue hypertrophy . this disease has several morbidities like bleeding , deep venous thrombosis , embolic complications and in some cases enlargement of limb that may require amputation . vascular malformations are segmented and never cross midline . however , we came across a case , a 45-year - old male , who presented with varicosity of veins and deformity of left lower limb besides cavernous hemangiomas ( port - wine stains ) scattered all over his face , chest , back , gluteal region , groin and legs since birth . multiple paravertebral soft tissue masses and bladder hypertrophy were also noted due to involving neurofibromatosis . simultaneous occurrence of kts and neurofibromatosis is rarely seen in clinical practice .

india accounts for one - fifth of the global burden of tuberculosis ( tb ) and ranks second in the top 10 countries , next to china with a higher burden of diabetes too . case detection rates for all forms of tb are 59% , but in those patients detected treatment success rates are high at 88% . given the large absolute numbers of patients with tb , the numbers of patients with multidrug resistant tb ( mdr - tb ; resistance to both isoniazid and rifampicin ) are high , with 2% of new cases and 15% of retreatment cases estimated to have mdr - tb . diabetes is a chronic metabolic disorder known for its progressive nature and associated with wide range of complications . apart from this , impairment in immune system is very common among diabetic subjects , which makes them more prone to acquire infections and persistence of the same . world health organization ( who ) has recognised diabetes mellitus ( dm ) as a global epidemic , mostly affecting low , and middle income counties , where 80% of all deaths from dm occur . several epidemiological studies demonstrated that subjects with diabetes are three times at higher risk of getting active tb disease compared to those without diabetes . india is a country with 1.2 billion population ( 17.5% of the world 's population ) . country is undergoing rapid social and economic expansion which is associated with increasing physical inactivity , an unhealthy diet and obesity . consequences of which , there has been an escalating epidemic of dm . in the last 20 years , dm prevalence rates have risen in both urban and rural populations and also amongst the poor . available data suggest that in 2011 there were an estimated 61.3 million adults with dm , giving a national adult prevalence of 8.3% in persons aged 20 years and above . a further 77 million people were estimated to have had impaired glucose tolerance . in terms of absolute numbers and given the size of the population , this makes india one of the highest dm and tb burden countries . the idea that tb and dm share synergetic relationship has been creating growing concern around the world . recently , who and the international union against tuberculosis and lung disease ( union ) have acknowledged the need for international guidelines on the joint management and control of tb and dm and have published a provisional collaborative framework for the care and control of both diseases . this paper describes single centre experience in the bidirectional screening procedures , implementation , monitoring , results and challenges of screening tb patients for dm and dm patients for tb within routine health care settings in the country . this was a prospective observational pilot study carried out in our hospital within the routine health services . patients included all persons aged 15 years and above who were consecutively diagnosed and registered with tb between february to september 30th , 2012 . every patient with confirmed tb started anti - tb treatment immediately . treatment regimens and anti - tb drug formulations were in accordance with those recommended by who and revised national tuberculosis control programme ( rntcp ) of india . the random blood glucose ( rbg ) of diagnosed and registered cases of tb were done on the first visit . if rbg was less than 110 mg / dl , the subject were considered to be non - dm and no further evaluation was done . if rbg was more than 110 mg / dl , the patients were called next day fasting for fasting blood sugar . if fasting blood glucose ( fbg ) 126 mg / dl , patient were considered as cases of dm and enrolled in the study as new dm . on the day first visit , if patient were already known cases of dm , then no further investigations were carried out and included in study as known dm cases . the screening for dm followed national guidelines which stipulate that a fbg is used with cutoff thresholds in line with those recommended by the who . in brief , fbg 126 mg / dl indicates dm ; fbg from 110 mg / dl to less than 126 mg / dl indicate impaired fasting glucose ; fbg < 110 mg / dl is normal . the screening for dm in tb patients followed the guidelines stipulated by the national programme for prevention and control of cancer , diabetes , cardiovascular diseases and stoke in india . similarly screening was carried out every time the patient visited the dm clinic and was based on asking about cough for longer than 2 weeks , fever , weight loss , hemoptysis , and or any suspicion of active tb to account for extrapulmonary tb . patients with a positive symptom screen were referred to tb services for investigation in accordance with the operational guidelines stipulated by the rntcp . in both , screening protocols patients with other risk factors for tb like hiv infection , connective tissue disorders , chronic renal failure , chronic liver disease , malignancies , on long term steroid , or cytotoxic drug therapy , chronic alcoholics and pregnant women were excluded after careful evaluation of present and past histories along with the reports . this was a prospective observational pilot study carried out in our hospital within the routine health services . patients included all persons aged 15 years and above who were consecutively diagnosed and registered with tb between february to september 30th , 2012 . every patient with confirmed tb started anti - tb treatment immediately . treatment regimens and anti - tb drug formulations were in accordance with those recommended by who and revised national tuberculosis control programme ( rntcp ) of india . the random blood glucose ( rbg ) of diagnosed and registered cases of tb were done on the first visit . if rbg was less than 110 mg / dl , the subject were considered to be non - dm and no further evaluation was done . if rbg was more than 110 mg / dl , the patients were called next day fasting for fasting blood sugar . if fasting blood glucose ( fbg ) 126 mg / dl , patient were considered as cases of dm and enrolled in the study as new dm . on the day first visit , if patient were already known cases of dm , then no further investigations were carried out and included in study as known dm cases . the screening for dm followed national guidelines which stipulate that a fbg is used with cutoff thresholds in line with those recommended by the who . in brief , fbg 126 mg / dl indicates dm ; fbg from 110 mg / dl to less than 126 mg / dl indicate impaired fasting glucose ; fbg < 110 mg / dl is normal . the screening for dm in tb patients followed the guidelines stipulated by the national programme for prevention and control of cancer , diabetes , cardiovascular diseases and stoke in india . similarly screening was carried out every time the patient visited the dm clinic and was based on asking about cough for longer than 2 weeks , fever , weight loss , hemoptysis , and or any suspicion of active tb to account for extrapulmonary tb . patients with a positive symptom screen were referred to tb services for investigation in accordance with the operational guidelines stipulated by the rntcp . in both , screening protocols patients with other risk factors for tb like hiv infection , connective tissue disorders , chronic renal failure , chronic liver disease , malignancies , on long term steroid , or cytotoxic drug therapy , chronic alcoholics and pregnant women were excluded after careful evaluation of present and past histories along with the reports . aggregate data of the study , the tuberculosis unit and diabetes centre are shown in tables 1 and 2 . total of 307 patients diagnosed with tb during the study period . among the tb patients 9.77% were smokers , 19.54% were known cases of diabetes , and 15.96% were newly diagnosed cases of diabetes . total of 4,118 diabetes patients were screened for tb in which 111 patients ( 52 new smear positive , 29 new smear negative , 30 new extrapulmonary ) . the key findings of the study are nearly half of the tb patients had either diabetes or prediabetic status . following are the challenges in bidirectional screening of tuberculosis and diabetes . if the blood tests are required to be done after the diagnosis of tb , the patients will have to make additional visits to the health facility and many time patients do not come after repeated phone calls . after patients are referred for diabetes care , getting feedback from the diabetes clinic was a challenge as many patients do ignore . standardized tb treatment under rntcp is available at all levels of health care facilities whereas standardised dm treatment is not guaranteed if patients have to be referred to a health facility near to their place of residence . additional manpower is required if records and reports have to be maintained at primary and secondary health care facilities . the major risk factors associated with tb burden are hiv / aids , malnutrition , air pollution , smoking , alcohol consumption , and diabetes as well . despite a good national tb programme in india recently published clinical research studies in south india in about 1,500 tb patients found a high prevalence of dm , that was about 25% in the state of tamil nadu and about 44% in the state of kerala . the observations of our study are similar to many other studies in india , brazil , and the us - mexico border . the study by jimenez - corona et al . has several observations worth noting . they followed a large sample size totaling 1,262 patients with pulmonary tb ( ptb ) , and found a high prevalence of dm of 29.63% . they were also able to demonstrate that dual disease ( dm+ptb ) was more likely to be associated with increased morbidity : pulmonary cavities , delayed sputum conversion > 60 days , higher probability of treatment failure , and higher recurrence and relapse rates . in the present study number of tb patients diagnosed after screening dm patients is very small ( 2.7% ) . in a systematic review of literature jeon et al . , demonstrated that screening of diabetics yielded active tb prevalence rates ranging from 1.7% in sweden to 36% in korea . screening would have higher yield in a country like india where tb prevalence is estimated at 283/100,000 with high dm prevalence estimated to be 8.3% of all adults . in this high - prevalence setting , screening 100,000 people with dm would yield around 2,000 to 3,000 cases of tb . although routine screening for diabetes takes place in some hospitals , if it is done in all health care facilities , it will lead to better and earlier detection of dm , earlier and better treatment of dm and improved clinical outcomes of anti - tb treatment . the strengths of this study are that we implemented screening within the routine system with no special budget allocated to support these activities . we think that because of their higher risk for tb and the fact that patients with dm are anyway more likely to attend health facilities , the marginal costs for tb screening using a symptom - base approach are likely to be small and to prove cost effective . the association of two diseases from two different categories , i.e. , infectious diseases and noncommunicable diseases indicate the need for the bidirectional screening . similarly , in the patients diagnosed with any form of active tb , the presence of history of diabetes must be confirmed , if they are not previously diagnosed with diabetes then subject them to diabetes screening . diabetic patients are at higher risk of developing new as well as reactivation of old tb disease . diabetes management during tb treatment is individailzed , through monitoring the blood glucose and adjusting the diabetic medications keeping the details of diabetes related complications and comorbidities in mind . screening for active tb in dm clinics should lead to earlier detection of tb and earlier and better treatment of tb . screening of tb patients for dm also leads to earlier detection of dm and better treatment and favourable outcome for tb as well as dm . hence we conclude , " bidirectional screening of tuberculosis patients for diabetes and diabetes patients for tuberculosis is feasible and imperative in routine health care settings . "

to assess the feasibility and results of screening diabetes mellitus ( dm ) patients for tuberculosis ( tb ) and tb patients for dm within the routine health care setting . prospective observational study carried out within the diabetes centre and pulmonary medicine department from february 2012 to september 2012 . the screening for active tb in dm and dm in tb patients is followed as per the guidelines of the revised national tuberculosis control programme and national programmes in india . total of 307 patients diagnosed with tb during the study period . among the tb patients 9.77% were smokers , 19.54% were known cases diabetes , and 15.96% were newly diagnosed cases of diabetes . total of 4,118 diabetes patients were screened for tb in which 111 patients found to have tb . the strengths of this study are that we implemented screening within the routine health system . it is feasible to screen dm patients for tb resulting in high rates of tb detection .

cardiovascular disease ( cvd ) is the leading cause of death for both men and women in the united states . according to the american heart association ( aha ) , by the year 2030 , the prevalence of cardiovascular disease is expected to increase by 9.9% , and the prevalence of heart failure and stroke are expected to increase by approximately 25% . it is estimated that this will raise the total direct cost for healthcare to $ 818 billion and the total indirect cost due to lost productivity to $ 275 billion.1 on the other side of the atlantic , one in five europeans die because of coronary heart disease before the age of 75.2 however , the burden of cardiovascular disease is not limited to developed countries anymore . in 2005 , of the 58 million deaths that occurred worldwide , almost 30% were due to cvd.3 this is three times more deaths than are caused by all infectious diseases including hiv / aids , tuberculosis , and malaria combined.4,5 nearly 80% of these cvd - related deaths occur in lower middle income countries , and one half of these deaths occur in women . it is projected that cvd will be responsible for 25 million deaths worldwide in 2020 . although several risk factors for cvd are non - modifiable ( age , male gender , race , and family history ) , many others are amenable to intervention . these include elevated blood pressure , abnormal blood sugar , high cholesterol , smoking , obesity , a high fat and high calorie diet and excess stress . the aha recommends that blood pressure be kept under 140/90 , fasting blood sugar be less than 110 mg / dl , low - density lipoprotein cholesterol stay below 100 mg / dl , smoking be stopped , a body mass index of less than 25 kg / m be maintained , and a heart healthy diet be eaten . moderate alcohol intake ( less than two drinks per day ) , and aspirin taken in low doses among high risk groups are also recommended for their cardiovascular benefits . the cardiovascular effects of leisure time physical activity are compelling.7,8 the aha recommends that all americans invest in at least 30 minutes a day of physical activity on most days of the week , given its substantial health benefits ; however , most healthy adults remain sedentary and fail to get an adequate amount of physical activity.9 inactivity or a sedentary lifestyle is associated with increased cardiovascular events and premature death.10 sedentary behavior , measured by television viewing time , has been associated with adverse cardiovascular health , increased obesity , diabetes mellitus , cancer , and early death.11 a review of several studies has confirmed that prolonged total sedentary time ( measured objectively via accelerometer ) has a deleterious relationship with cardiovascular risk factors , disease , and mortality outcomes.12 on the other hand , health benefits of adequate physical activities like walking , swimming , cycling , or stair climbing are well documented . regular exercise has been shown to reduce type 2 diabetes,13,14 some cancers,15,16 falls,17 osteoporotic fractures,18 and depression.19 improvements in physical function2022 and weight management2326 have also been shown . there is also an increase in cognitive function,27,28 enhancement of the quality of life,29 and decrease in mortality.30,31 several occupational studies have shown adequate physical activity also provides extensive cardiovascular benefits.3237 chair bound double - decker bus drivers in london have more coronary heart disease than mobile conductors working on the same buses.38 postal workers delivering mail by foot similarly have lower incidence of coronary disease than their office based colleagues.39 railroad workers and longshoremen have reduced incidence of coronary heart disease compared to those in less active occupations.40,41 well conducted long term studies have also documented the cardiovascular beneficial effects of regular exercise . leisure time exercise reduced cardiovascular mortality during a 16 year follow up of men with high risk of coronary heart disease in the mrfit study.42 in the honolulu heart study , elderly men walking more than 1.5 miles per day similarly reduced their risk of coronary disease.43 walking was associated with cardio - protection in the nurses health study,44 and moderate activity in post - menopausal women was similarly associated with a reduced risk of coronary disease in the iowa study.4 people engaging in regular exercise have also demonstrated other cvd benefits such as decreased rate of strokes and improvement in erectile dysfunction . there is also a 3-year increase in lifespan in these groups.46 regular physical activity helps reduce several cardiovascular risk factors including obesity,47,48 dyslipidemia,49,50 hypertension,51,52 metabolic syndrome,53 and diabetes mellitus.54,55 among patients with established coronary disease , regular physical activity has also been found to help improve angina - free activity,56 prevent heart attacks,57 and result in decreased death rates.58 in patients with heart failure , exercise improves heart function and quality of life.59,60 it also improves walking distance in patients with peripheral artery disease.61 supervised exercise programs such as cardiac rehabilitation in patients who have undergone percutaneous coronary interventions , heart valve surgery , have stable chronic heart failure , are transplantation candidates or recipients , or have peripheral arterial disease result in significant short and long term cvd benefits.6264 in 1995 , the centers for disease control and the american college of sports medicine recommended that all americans try to engage in at least 30 minutes of moderate intensity physical activity on most or preferably all days of the week.65 therapeutic activity should incorporate a range of motion exercises , resistance training , as well as an aerobic workout . leisure related aerobic activities such as walking , hiking , and gardening are generally more enjoyable , making them more conducive for long term adherence.66 mild to moderate resistance training may be achieved by weight lifting , weight bearing calisthenics , or other resistance exercises involving the major muscle groups . they recommend that 810 exercises be performed on two non - consecutive days of the week , with 812 repetitions of each exercise terminated by volitional fatigue . these provide an effective method for improving muscular strength and endurance , attenuating the rate - pressure product and improving coronary risk factors.67,68 range of motion and stretching exercises such as yoga reduce sympathetic activity and improve several other cardiovascular risk parameters . since data indicates that cardiovascular disease begins early in life , physical interventions such as regular exercise should be started early for maximal effect.6972 it is critical that lifelong health promoting behaviors , such as physical exercise , be introduced to youngsters . the us department of health and human services for young people recommends that school students achieve a target of 60 minutes of daily exercise.73 this may be achieved via a mandated curriculum involving moderate to vigorous activity during 50% of the physical education class time . transition from high school to college is associated with a steep decline in physical activity . in addition to renovating outdated facilities , universities can help by developing mandatory health curricula teaching fitness based courses . provision of convenient and adequate exercise time as well as free or inexpensive college credits for documented workout periods can further enhance compliance . free health club memberships and paid supervised exercise time could help promote a continuing exercise regimen . government sponsored subsidies to employers incorporating such exercise programs can help decrease the anticipated future cardiovascular disease burden in this population . general physicians can play an important role in counseling patients and promoting exercise.74,75 although barriers such as lack of time , inadequate or no reimbursement of physicians , and patient non - compliance exist,76 medical reviews support the effectiveness of physician counseling , both in the short term77,78 and long term.79 the good news is that the percentage of adults advised to exercise by physicians in the united states has increased from 22.6% in 2000 to 32.4% in 2010.80 physician empowerment , with training sessions and adequate reimbursement for their services , and patient tailored interventions with written materials , reminders , and follow up visits will further increase this percentage.81 we expect that this should also greatly enhance patient compliance and ensure long term adherence . risk factors for cvd are consistent throughout the world , and this includes lack of physical activity . although the benefits of leisure time physical activity for reducing cvd are irrefutable , only one in three americans meets the minimal recommendations for activity as outlined by the centers for disease control , the american college of sports medicine , and the aha . physical activity is an easy , inexpensive , and effective way to avoid cvd , and the benefits accrue , irrespective of the age at which a person initiates an exercise program . reduced cvd burden as a result of regular exercise will not only improve the quality of life , but will increase the lifespan for millions of humans worldwide . there will also be an economic benefit to all the countries in the world with a saving of billions of health related dollars .

regular physical activity during leisure time has been shown to be associated with better health outcomes . the american heart association , the centers for disease control and prevention and the american college of sports medicine all recommend regular physical activity of moderate intensity for the prevention and complementary treatment of several diseases . the therapeutic role of exercise in maintaining good health and treating diseases is not new . the benefits of physical activity date back to susruta , a 600 bc physician in india , who prescribed exercise to patients . hippocrates ( 460377 bc ) wrote in order to remain healthy , the entire day should be devoted exclusively to ways and means of increasing one s strength and staying healthy , and the best way to do so is through physical exercise . plato ( 427347 bc ) referred to medicine as a sister art to physical exercise while the noted ancient greek physician galen ( 129217 ad ) penned several essays on aerobic fitness and strengthening muscles . this article briefly reviews the beneficial effects of physical activity on cardiovascular diseases .

host genetic factors are major determinants of susceptibility to infectious disease in humans ( 1 ) . htlv - i is a persistent virus , infecting 10 - 20 million people worldwide . most infected people remain healthy , but 1 - 2% develops a progressive paralytic myelopathy ( htlv - i - associated myelopathy ; ham / tsp ) and a further 2 - 3% develops an aggressive t cell leukemia / lymphoma . ham / tsp is a chronic debilitating inflammatory disease of the central nervous system , characterized by axonal damage and demyelination , most pronounced in the midthoracic spinal cord . furthermore some of the self - immune diseases such as uveitis and polymiositis are found to be resulted from this virus ( 2 - 5 ) . the endemic regions affected with this virus include the south - west of japan , caribbean islands , and some regions of the usa ( 6 ) . the other parts with less prevalence of the virus are taiwan and some regions of africa and israel . mashhad in the north of iran has been recognized as a new endemic region of the virus ( 10 , 11 ) . the symptoms include weakness or dryness in one or both feet , backache and no control on urine . one - third of the patients become paralyzed after 10 years and one half of them are not able to walk ( 12 ) . on the contrary to alt in which the number of the male patients is a little more , ham affects the female disproportionately . high proviral load and being female are two factors of high risk of ham / tsp and the relative risk of ham / tsp increases when the provrial load becomes clearly more than one copy in any pbmcs ( 13 , 14 ) . both the class i mhc proteins ( hla - a , -b , and -c ) , which present viral peptides for recognition by virus - specific ctl , and class ii mhc proteins ( hla - dr and -dq ) , which present peptides to cd4 t cells , are likely to be important in the immune response to htlv - i infection ( 15 , 16 and 17 ) . the results of several previous studies have suggested associations between various hla class i or class ii alleles and susceptibility to t cell leukemia / lymphoma or ham / tsp ( 18 - 22 ) . however , small sample size , mixed ethnicity , lack of adequate controls , or lack of staging in these studies precluded a definite conclusion . if the relationship between htlv-1 infection and class ii is considered as the factor of susceptibility to disease , it may help in understanding pathogenesis of ham / tsp . the supplied peptides of axon antigens bonded to the products of mhc class ii activate cd4+on the surface of t lymphocytes and the activated cd4+can cross the blood - cerebral obstacle and identify the cell affected with virus . the activated cd4 + causes apoptosis through producing cytokins and damage to the cell affected with virus and the peripheral cells may play a role in cns ( 23 , 24 ) . both mhc class i and class ii molecules are important in determining the recognition of htlv - i peptides and for the generation of an effective immune response . the predominant cytotoxic t lymphocyte response ( ctl ) against tax protein , which is necessary for viral expression , can be restricted by a wide variety of mhc class i molecules in htlv - i infected subjects . it has been suggested that no single mhc class i allele is associated with ham / tsp ( 15 , 25 ) . in japanese htlv - i - infected subjects has been demonstrated that expression of hla - a*02 and hla cw*08 alleles reduced the proviral load of htlv-1 and consequently the risk of ham / tsp , while hla - b*5401 allele increased the proviral load and the risk of ham / tsp in htlv - i carriers . furthermore , hla - drb1 * 0101 increased the risk of ham / tsp in carriers in the absence of hla - a*02 ( 18 , 21 ) . the aim of this study was to investigate the frequency of hla - dqb1 alleles in htlv - i - infected individuals and healthy controls resident in mashhad . the studied subjects were 66 , including 16 ham / ts patients , 20 asymptomatic carriers and 30 healthy controls . sixteen of 20 ham / tsp patients were female ( 60% ) and 72% of htlv - i carriers were female . the mean age of patients was 44.1414.62 and the mean age of htlv - i carriers was 51 10.22 . all patients fulfilled established criteria for ham / tsp when they examined by neurologist and htlv - i carriers had symptoms of htlv - i - associated diseases . all of the ham / tsp patients , htlv - i carriers and healthy controls had the same ethnic background . the study protocol was approved by the ethics committee of mashhad university of medical sciences . 10 cc blood was taken from all the subjects for dna extraction and serum preparation . serum samples were screened for htlv - i antibody by enzyme linked immunosorbent assay ( elisa ) according to the manufactures ' instruction ( diapro , italy ) and reactive samples were confirmed by western blotting ( genelab diagnostic , singapore ) . dna was extracted by non - enzyme salting out method using biogen kit ( mashhad - iran ) according to manufacturer 's instruction . polymerase chain reaction with sequence - specific primers ( pcr - ssp ) method was carried out to determine hla - dqb1 alleles according to the previously published method ( 26 ) . briefly , seven alleles of hladqb1 were detected using specific primers in eight pcr reactions . this procedure currently detected dqb1 alleles including 0501 - 0504 , 0601 - 0609 , 0201 , 0301 - 0305 , and 0401 - 0402 which corresponding to the serological specificities dq4 , dq5 and dq6 alleles , whereas the dq2 , dq7 , dq8 and dq9 specificities were amplified by two primer mixes . we used at least 2 primers ( primm - italy ) for each reaction ( table 1 , 2 ) . the studied subjects were 66 , including 16 ham / ts patients , 20 asymptomatic carriers and 30 healthy controls . sixteen of 20 ham / tsp patients were female ( 60% ) and 72% of htlv - i carriers were female . the mean age of patients was 44.1414.62 and the mean age of htlv - i carriers was 51 10.22 . all patients fulfilled established criteria for ham / tsp when they examined by neurologist and htlv - i carriers had symptoms of htlv - i - associated diseases . all of the ham / tsp patients , htlv - i carriers and healthy controls had the same ethnic background . the study protocol was approved by the ethics committee of mashhad university of medical sciences . 10 cc blood was taken from all the subjects for dna extraction and serum preparation . serum samples were screened for htlv - i antibody by enzyme linked immunosorbent assay ( elisa ) according to the manufactures ' instruction ( diapro , italy ) and reactive samples were confirmed by western blotting ( genelab diagnostic , singapore ) . dna was extracted by non - enzyme salting out method using biogen kit ( mashhad - iran ) according to manufacturer 's instruction . polymerase chain reaction with sequence - specific primers ( pcr - ssp ) method was carried out to determine hla - dqb1 alleles according to the previously published method ( 26 ) . briefly , seven alleles of hladqb1 were detected using specific primers in eight pcr reactions . this procedure currently detected dqb1 alleles including 0501 - 0504 , 0601 - 0609 , 0201 , 0301 - 0305 , and 0401 - 0402 which corresponding to the serological specificities dq4 , dq5 and dq6 alleles , whereas the dq2 , dq7 , dq8 and dq9 specificities were amplified by two primer mixes . we used at least 2 primers ( primm - italy ) for each reaction ( table 1 , 2 ) . the frequency of hla - dqb1 alleles was calculated in ham / tsp patients , asymptomatic carriers and healthy control groups . the frequency of hla - dqb1 * 07 was significantly higher in patients with ham / tsp ( 75% ) compared with healthy controls ( 30% ) ( p = 0.004 , or=8.52 ) ( table 1 ) . the hla - dqb1 * 02 and dqb1 * 05 was positive in 7 ham / tsp patients , while in healthy control group 24 subjects were positive . the frequency of both hla - dqb1 * 07 and hla - dqb1 * 06 alleles in ham / tsp patients was more than the ones if they infected with more than the ones free of it if they are infected with htlv-1 ( p- value=0.0009 and rr=10.95 ) ( table 3 ) . in the present study we examined the frequency of hla - dqb1 allele in ham / tsp patients , asymptomatic carriers and healthy controls . our results indicated that the individuals with dqb1 * 07 allele are susceptible to be affected with this disease 7 times more than the ones lacking this allele , suggesting hla genes play a significant role in the susceptibility to ham / tsp disease . within african population , two antigens determined dr15 and dq1 , occurred at significantly increased frequency among htlv - i carriers compared with seronegative control subjects ( 42% versus 22% for dr15 [ odds ratio { or } = 2.7 ; 95% confidence interval { ci } = 1.0- 7.2 ] and 78% versus 53% for dq1 [ or = 3.1 ; 95% ci = 1.2 - 8.5 ] ) . asymptomatic carriers were shown to have an hla class ii allele distribution similar to that of patients with atl , and the frequencies of the alleles drb1 * 1501 , drb1 * 1101 , and dqb1 * 0602 were significantly greater in patients with atl and asymptomatic carriers than in patients with ham / tsp . in addition , haplotypes drb1 * 1101-dqb1 * 0301 and drb1 * 1501-dqb1 * 0602 were significantly increased among patients with atl compared with patients with ham / tsp ( 28 ) . we also showed that the individuals with hla - dqb1 - 2 and hla - dqb-5 are 1.5 times more susceptible to develop ham / tsp compared with the subjects who lacked these alleles , therefore , these two alleles may be considered as the protective factors . rafatpanah et al ( 19 , 20 ) demonstrated that the frequency of hla - drb1 * 01 was significantly increased in ham / tsp patients compared with carriers ( p 0.028 ; or=9.4 ) . the frequency of hla - cw*08 was also significantly increased in ham / tsp patients compared with controls ( p=0.03 ; or=13.5 ) . it has been showed that there is an association between hla class i , hla - a30 allele and htlv - i infection ( 15 , 20 ) . kitze et al showed that the ham / tsp patients with particular hla haplotypes ( a24cw7b7dr1dq5 , a2cw7b7dr1dq5 , a24cw - b52dr15dq6 , a11cw1b54dr4dq4 , and a24cw1b54dr4dq4 ) express more frequently intrathecal synthesis of antibodies against htlv-1 synthetic peptides , especially against htlv-1 env gp21 synthetic peptides ( 21 ) . an association of hla - drb1 * 0101 with disease susceptibility also was identified , which doubled the odds of ham / tsp in the absence of the protective effect of hla - a*02 ( 22 ) . in the present study , the frequency of hla - dqb1 * 07 in ham / tsp patients was high . it seems that there is a correlation between hla - dqb1 * 07 and disease susceptibility . the genotype of hla - dqb1 * 06 and 07 was more frequent in patients with ham / tsp compared with control group ( 26 ) . this results is different from the results obtained kitze et al ( 25 ) who reported that there is a higher risk to develop ham / tsp among the individuals with hla - dq-0105 haplotype . this discrepancy may be associated with the difference in the genetic background of studied population ( 27 ) . although we find an association between hla - dqb1 alleles and ham / tsp , however the study should be repeated with more sample size . furthermore , the study of other hla class i and class ii alleles should be taken into account to understand a more comprehensive role of hla alleles in disease susceptibility .

objective(s ) : htlvi-1 is the first human retrovirus with limited endemic regions in the world . the epidemiological studies have shown that the genetic background and immune response to the virus have a significant role in htlv - i - associated diseases . among the genes are involved in htlv - i infection , the role of human leukocytes antigen ( hla ) have been studied in different population . in the present study we examined the association between hla - dqb1 alleles and htlv - i infection in ham / tsp patients , htlv - i carriers and healthy controls in north east of iran , mashhad.materials and methods : the blood samples of 16 patients with ham / tsp , 20 htlv-1 carriers , and 30 healthy individuals were taken and dna was extracted by salting out method . hla - dqb1 typing was performed using pcr - ssp method and the frequency of hla - dqb1 alleles were compared by fischer exact test.results : there was a significant difference between ham / tsp patients and healthy controls in the frequency of hla - dqb1 * 07 ( p=0.004 , rr=7 ) . furthermore , we found that possession of hla- dqb1 * 02 or hla - dqb1 * 05 increased the risk of disease 1.5 times.conclusion : the data presented here suggest that both hla - dqb1 * 07 and hla - dqb1 * 06 are associated with disease development .

the ever - increasing size of homologous sequence datasets and complexity of substitution models stimulate the development of better methods for building phylogenetic trees . likelihood - based approaches ( including bayesian ) provided arguably the most successful advances in this area in the last decade . different strategies have then been used to tackle this problem , mostly based on stochastic approaches . markov chain monte carlo methods are probably the most valuable tools in this context as they provide computationally tractable solutions to bayesian estimation of phylogenies ( 1,2 ) . stochastic approaches have also been used to address optimization issues in the maximum likelihood framework . hence , simulated annealing ( 3 ) and genetic algorithms ( 4,5 ) were proposed to estimate maximum likelihood phylogenies from large datasets . however , the hill climbing principle is usually considered faster than stochastic optimization and sufficient for numerous combinatorial optimization problems ( 6 ) . recently , guindon and gascuel ( 7 ) described a fast and simple heuristic based on this principle , for building maximum likelihood phylogenies . several simulation studies ( 7,8 ) demonstrated that the tree topologies estimated with this approach are as accurate as those inferred using the best tree building methods currently available . these studies also showed that this new method is considerably faster than the other likelihood - based approaches . using this heuristic , the analysis of large datasets is now achieved in reasonable computing time on any standard personal computer ; e.g. only 12 min were required to analyse a dataset consisting of 500 rbcl sequences with 1428 bp from plant plastids . this paper introduces phyml online , a web interface to the phyml ( phylogenetic inferences using maximum likelihood ) software that implements the heuristic described by guindon and gascuel ( 7 ) . phyml online provides a number of useful options ( e.g. nonparametric bootstrap ) , and proposes quite recent models of sequence evolution [ e.g. wag ( 9 ) and dcmut ( 10 ) ] . the core of the heuristic is based on a well - known tree - swapping operation , namely nearest neighbour interchange , which defines three possible topological configurations around each internal branch ( 11 ) . for each of these configurations , the length of the internal branch that maximizes the likelihood is estimated using numerical optimization . the difference of likelihood obtained under the best alternative topological configuration and the current one defines a score . a score with positive value indicates that the best alternative topological configuration yields an improvement of likelihood . a score with negative value indicates that the current topological configuration can not be improved at this stage and only the length of the internal branch is adjusted . these calculations are performed independently for every branch and they define a set of ( topological or numerical ) modifications , each of which corresponds to an improvement of the current tree regarding the likelihood function . the standard approach would only apply one of these modifications , typically that corresponding to the internal branch with best score . here this proportion is adjusted so as to increase the likelihood at each step , ensuring convergence of the algorithm . this way , the current tree is improved at each step , both in terms of topology and branch length , and only a few steps ( usually a few dozen or less ) are necessary to reach an optimum of the likelihood function . this explains the speed of this algorithm whose time complexity is o(pns ) , where p represents the number of refinement steps that have been performed and n is the number of sequences of length s. phyml online is a web interface to the phyml algorithm ( figure 1 ) . by default , the input data consists of a single text file containing one or more alignments of dna or protein sequences in phylip ( 12 ) interleaved or sequential format . examples of sequence datasets in phylip format are given in the user 's guide section of the web site . setting the parameters of a phylogenetic analysis through the interface is straightforward . the first step is the selection of the substitution model of interest . alignments of homologous dna and amino acid sequences can be examined under a wide range of models ( jc69 , k80 , f81 , f84 , hky85 , tn93 and gtr for nucleotides , and dayhoff , jtt , mtrev , wag and dcmut for amino acids ) . variability of substitution rates across sites and invariable sites can also be taken into account . the parameters that model the intensity of the variation of rates across sites and the proportion of invariables sites can be fixed by the user or estimated by maximum likelihood . note that the parameters of the substitution model can be estimated under a fixed tree topology or not . the fixed topology option is useful when describing the evolutionary process is more important than estimating the history of sequences . an option is available to assess the reliability of internal branches using nonparametric bootstrap ( 13 ) which is possible to achieve for even large datasets , thanks to the speed of phyml optimization algorithm . the bootstrap values are displayed on the maximum likelihood phylogeny estimated from the original dataset . trees estimated from each bootstrap replicate , as well as the corresponding substitution parameters , can also be saved in separate files for further analysis ( e.g. computation of confidence intervals for the substitution parameters or estimation of a consensus bootstrap tree , as performed by phylip 's consense ) . multiple trees can also be used as input and further optimized by the algorithm described above . this might prevent the tree searching heuristic to be trapped in local maxima . when combined with the fixed tree option , the multiple input trees approach also facilitates the comparison of the fit of different phylogenies estimated from a single dataset . user 's guide section gives details on the format of multiple sequence and tree files . sequences [ and starting tree(s ) if provided ] are uploaded on our server , a 16-processor ibm computer running linux 2.6.8 - 1.521custom smp , and a maximum likelihood analysis is performed using the phyml algorithm . the first file presents a summary of the options selected by the user , maximum likelihood estimates of the parameters of the substitution model that were adjusted , and the log likelihood of the model given the data . this applet runs the program atv ( 14 ) that provides numerous options to display and manipulate large phylogenetic trees . the phyml online server is located at laboratoire d'informatique , de robotique et de microlectronique de montpellier : . the phyml software has been implemented in c ansi and is available under gnu general public licence . binaries , example datasets , sources and documentation are distributed free of charge for academic purpose only .

phyml online is a web interface to phyml , a software that implements a fast and accurate heuristic for estimating maximum likelihood phylogenies from dna and protein sequences . this tool provides the user with a number of options , e.g. nonparametric bootstrap and estimation of various evolutionary parameters , in order to perform comprehensive phylogenetic analyses on large datasets in reasonable computing time . the server and its documentation are available at .

the study was done at a medium - sized teaching community hospital . using the electronic record system , we were able to generate a list of all patients who have undergone abdominal computerized tomography ( ct ) scans at our institution during the month of january 2010 . the reports of ct scans were reviewed looking for adrenal masses and other abnormalities of the adrenal glands ( tumor , bulky , cyst , adenoma , incidentaloma , nodule , and swelling ) . once patients with an adrenal mass(es ) or other abnormalities were identified , outpatient charts for initial biochemical testing and follow - up imaging were reviewed by either directly accessing the electronic medical records or by calling primary care physician 's offices . patient charts were reviewed for demographics , medical history , indication for abdominal imaging , biochemical investigations , and subspecialty endocrinology consultations used for initial evaluation of the adrenal mass(es ) . furthermore , to assess if appropriate follow - up was performed , we also reviewed the patient charts for the 2 years following the initial discovery of the adrenal mass(es ) to look for any features indicative of adrenal hormonal overproduction . we specifically searched for documentation of resistant hypertension , features of cushing syndrome , paroxysmal hypertension , hypokalemia , and hirsutism . twenty adrenal masses were incidentally discovered on 723 abdominal cts performed , with a prevalence of 2.76% . the mean age for patients with one or more incidental adrenal masses was 70.4514.74 years ( meansd ) . appropriate biochemical and follow - up imaging was only ordered in 2 of 20 patients who were referred to an endocrinologist . one of these two patients referred to an endocrinologist had labile hypertension ; however , the work - up was negative for pheochromocytoma . seven of 20 patients with incidental adrenal mass(es ) did not get any hormonal investigation or follow - up imaging studies . three patients in whom no hormonal work - up was done had features suggesting adrenal hormonal excess . six patients underwent a repeat ct scan for non - adrenal reasons , and no change in the mass size was noted . the charts of two patients could not be found in our system because these patients did not have primary care physicians affiliated with our hospital . the incidence of incidental adrenal lesion(s ) in our study was 2.76% , which is similar to the incidence reported in other studies ( 1 , 68 ) . incidental adrenal masses were more commonly seen in older patients with an average age of 70.4 years in our study . in the study by eldeiry et al . other studies have also reported higher prevalence of incidental adrenal masses in older age groups ( 7 , 8) . only a small fraction of patients received appropriate biochemical work - up and radiological assessment and follow - up . even though most incidental adrenal masses are benign and non - functional ( 6 ) , appropriate work - up suggested by the published guidelines is required in order to diagnose malignant and functional masses . in our study , 2 of 20 patients had probable metastatic lesions ; both of these patients died within 1 year of the discovery of their adrenal masses . three of 20 patients had clinical features that could represent a functional adrenal mass ; two of which had resistant hypertension and one of which had morbid obesity , diabetes mellitus , and hypertension . one of the important parameters to report on adrenal masses is the attenuation value on unenhanced ct images , also known as the hounsfield units ( hu ) . benign masses generally have low hu ( < 10 hu ) , whereas most malignant mass have high attenuation values ( > 20 hu ) . in our study , the hu was reported in only 6 of 20 patients ( 30% ) . three of the six patients with available hu values had values > 20 units ( table 1 ) . six of 20 patients in the study had a history of malignancy , and hu was reported in only one of these six patients ( table 1 ) . in the study by eldeiry et al . ( 6 ) , only 41% of patients with adrenal incidentaloma(s ) had reported hu attenuation values on the ct scan reports . an endocrinology referral was made in 2 of 20 patients ( 10% ) , and an appropriate work - up was accomplished in these two patients . this strongly suggests the need for endocrinology referrals , as specialists typically follow updated guidelines for management . our study supports previously published data on the overall lack of adherence to published guidelines for incidental adrenal nodules . proper work - up will likely improve morbidity and mortality in patients with adrenal incidentalomas . practice improvement may be accomplished by provider education and flagging the findings of adrenal incidentalomas , which can be easily performed in the modern era of electronic medical records . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

introductionadrenal incidentalomas are defined as masses picked up on imaging studies that were done for apparently different reasons . with frequent use of imaging modalities , incidental adrenal masses are commonly encountered in clinical practice . guidelines are currently available for the diagnosis and management of adrenal incidentalomas , but the appropriateness of initial work - up and subsequent follow - up of incidental adrenal masses in the community hospital setting is unknown.objectivewe studied the appropriateness of initial work - up and follow - up of incidental adrenal masses discovered on abdominal computerized tomography ( ct).methodsin our retrospective study , we reviewed sequential ct scans of the abdomen performed in the month of january 2010 at a community hospital . once patients with one or more adrenal masses were identified , outpatient charts for initial biochemical testing and follow - up imaging were obtained either through directly accessing the electronic medical records or through contacting primary care physician 's offices . patient charts were reviewed to assess the data for the next 2 years following the discovery of an adrenal abnormality.resultstwenty adrenal masses were incidentally discovered on 723 abdominal cts performed within the month of january 2010 resulting in an overall incidence of 2.76% . of the patients with incidentally discovered adrenal masses , appropriate biochemical and follow - up imaging were only performed in patients referred to an endocrinologist ( 2 of 20 patients ) . thirty percent of patients with incidental masses received a repeat ct scan for non - adrenal reasons , and no change in the mass size was noted.conclusiondespite published guidelines , the initial work - up and follow - up of patients with an incidentally discovered adrenal mass is unsatisfactory . there is a desperate need for education of providers regarding appropriate work - up of incidental adrenal masses .

most articles on microarray technology , particularly reviews , begin with some over - reaching statement on their potential to illuminate the biological world . while resisting this temptation , we must acknowledge the increasing power of high - throughput expression profiling using high - density arrays . a quick medline search of all papers referenced with the term ' microarray ' shows an exponential increase since the first paper describing the approach by pat brown 's group six years ago ( figure 1 ) . a calculated projection based on the number of papers this year to date predicts a total of around 500 microarray publications for 2001 . the technology is quickly becoming a mainstay in the ' array ' of tools available to the molecular biologist , and we expect it to be broadly applicable to our favorite genetically tractable organism , the laboratory mouse . the total for 2001 is projected from the total number of publications to date this year . the production of mouse microarrays has lagged somewhat behind the production of arrays from humans and from those model organisms for which full genome sequence is available , such as yeast or caenorhabditis elegans . oligonucleotide - based arrays from sources such as affymetrix ( santa clara , ca , usa ) have been in production for a number of years , but their high cost has been a barrier to widespread general use in academia . the cdna array effort has been hampered largely by the scarcity of large , well - annotated cdna clone sets from mouse tissues . minoru ko at the national institute on aging ( nia ; national institutes of health , bethesda , md , usa ) has developed a 15,247 clone set derived from mice largely at early developmental time points , with libraries covering stages from the early blastocyst to embryonic day ( e ) 7.5 ( for which there are embryo and ectoplacental cone samples ) . this set will have added to it later this year a further 11,000 clones derived from sequencing of similar libraries , and libraries from trophoblast stem cells , hematopoietic stem cells , embryonic stem cell line r1 , newborn heart , brain , and kidney , and mesenchymal stem cells ( m.s . the set has been sequence - verified and is cloned into a vector system with binding sites for both sp6 and t7 polymerases flanking the insert , so that riboprobes for in situ hybridization studies can be generated directly . the average insert size is estimated to be roughly 1.5 kilobases ( and we have found this generally to be the case ) . the clone set has been widely distributed to a number of centers for microarray printing , including our own local facility at the ontario cancer institute ; these centers are currently in various stages of production . the riken institute in japan has also recently described a 21,076 cdna clone set thought to represent at least 12,890 unique genes , which was generated from sequencing just under one million total expressed sequence tags ( ests ) . this group of clones has the major advantage that more than 60% are full - length cdnas , because of the methods used in library construction . also , these clones are derived from a broad spectrum of adult and developmental stages of various tissues , which provides a nice complement to the much earlier stages used to derive cdna libraries for the nia 15,247 clone set . a quick analysis indicates that there are at least 26,700 non - redundant clones between the two sets . although arrays have been generated from these clones by riken ( see below ) , they have not yet been made widely available to the scientific community . as a result , we will probably see more work initially in the literature that uses microarrays printed from the nia set in combination with custom - derived clones . arguably the most comprehensive mouse arrays available are the murine genome u74 set from affymetrix . this group of three arrays provides coverage of roughly 36,000 mouse genes , of which about 30,000 are known only as ests . as mentioned previously , however , there has not been widespread use of these arrays because of the prohibitively high cost of the arrays and the associated scanning hardware . but given the advantages of oligonucleotide - based arrays for interrogating multiple regions of a transcript or alternatively spliced forms , in addition to their flexibility for array design , we expect the adoption of this platform for array technology to increase in the future . operon technologies ( alameda , ca , usa ) has recently introduced a mouse 7,000 oligonucleotide set that is available for purchase for array printing;the size of this and similar sets is likely to increase substantially in the near future . in general , given the advances in size and availability of sets of mouse cdna clones and oligonucleotides , we foresee an increase in the number of centers making the initial investment to start microarray facilities and capitalize on this technology . printing cdnas has the advantage of replicating directly the microarrays printed elsewhere , although it does have the disadvantage of laborious amplification of cdna inserts for printing and difficulties in managing a large number of clones . oligonucleotide arrays eliminate some of these problems and offer a number of flexibility advantages in array printing , but they come with higher initial start - up costs . although we are moving in the direction of a ' whole - genome microarray ' as we approach the completion of the mouse genome - sequencing project , it is likely that many groups will focus on smaller , custom , gene groupings to reduce both costs and the engineering difficulties associated with printing arrays of higher density . although to date only a small number of mouse microarray studies have been published in the literature , we expect a tidal wave of papers over the next two to three years as this technology becomes widely available . minoru ko 's group has described experiments using nylon arrays printed from their nia 15,247 clone set . in profiling comparisons of e12.5 placenta and whole embryos , they identified 720 genes that appeared ( statistically , from triplicate measurements ) to be upregulated in the placenta . of these , 181 were represented by novel ests not previously known to be placentally enriched , increasing the total number of genes known to be highly expressed in the placenta by about five - fold . the placenta - specific expression pattern was confirmed for one of these novel genes ( h3018bo6 ) by in situ hybridization ; homology searches suggest that it could be a novel member of the placental growth - related hormone family . the riken group has created cdna microarrays printed on glass slides from a set of 18,000 clones enriched for full - length cdnas . in a recent paper , gene expression was profiled in a total of 49 different adult and embryonic tissues . data were normalized using rna from e17.5 whole embryos , which has a number of practical advantages as an external reference over using individual tissues , given the ease of rna preparation from whole embryos and the diversity of expressed genes . data were then clustered to look at the underlying order in gene expression amongst various tissues . as expected , the observed expression profiles correlated well with the tissues from which cdnas were originally cloned . further analysis of expression patterns in the developing nervous system showed unique clusters associated with apoptotic cell death in neural remodeling and with different phases of the cell cycle . in an analysis of expression patterns of metabolic pathways , a separation of enzymes into 78 different synthetic and degradative metabolic pathways interestingly , genes were clustered into groups of those ubiquitously expressed and those with tissue - specific patterns . in a more detailed analysis of enzymes in the glycolytic pathway , tissue - specific differences were identified in gene products for glycolytic enzymes derived from muscle versus those present in liver and kidney . using the affymetrix system , zirlinger et al . have recently analyzed differential gene expression in selected regions of the brain using arrays containing approximately 34,000 genes . they screened by in situ hybridization a series of 33 genes identified to be amygdala - enriched from array experiments and found that a number of them had expression patterns restricted to the subnuclei of the amygdala . using the earlier mu11k array , containing 11,000 gene elements , voehringer et al . demonstrated a series of alterations in gene expression in apoptosis - sensitive compared with apoptosis - resistant b - cell lymphoma cell lines before and after irradiation . from these observations , they suggested a model for sensitivity to apoptosis involving induction of transcripts for genes participating in mitochondrial uncoupling and loss of membrane potential . one of the major stumbling blocks for new users is the processing and management of data once microarray hybridization has been done . the number of both freely available and commercial packages that are user - friendly for performing these functions is rapidly increasing . at our institute , we use a combination of the commercial quantarray ( packard biochip technologies , billerica , ma , usa ) and genepix ( axon instruments , union city , ca , usa ) packages to find spots and assign grayscale hybridization intensities . we then use a package developed locally to handle background subtractions and normalizations and to create databases of cumulative experiments for clustering . these are certainly not the only tools available , nor are they necessarily the best , and we anticipate more user - friendly packages for these functions to arrive shortly , given the flurry of activity in the area . what is not yet clear is how best to sort through the data from validated experiments once one has identified groups of genes that are of interest to the individual investigator . one of the big benefits of the freely distributed array data accumulating on the web is the ability to do a greater amount of complex experimental work at the computer , as opposed to the wet - lab bench . there are far too many observations in any large - scale microarray study to comment on all of them in the text of a journal article , and the emerging practice of requiring authors to post data on a website allows other investigators to examine portions of the data relevant to their individual interests . for example , as part of an ongoing project examining lung organogenesis , we have downloaded the riken gene expression database and performed some further analysis on the gut - endoderm - derived tissues in the dataset . this was done over a period of days using both commercial and freely available software on a standard desktop computer . as shown in figure 2a , a topography plot of a statistically selected subset of 113 genes in these tissues reveals a number of unique expression patterns . we identified peaks in the plot from embryonic lung stages corresponding to a number of ests , including one with homology to the ras - related protein rab2 . the blade diagram in figure 2b shows the enhanced expression in the embryonic lung of a series of genes compared with adult lung tissue . this group includes a total of 782 ests of unknown function . using conventional eisen clustering ( figure 2c ) , we found groupings associated with known lung - enriched proteins such as surfactant protein a , in addition to a number of genes that appeared to be enriched at the e16 time point compared with the other lung time points and with whole embryos . ( a ) topography plot of gut - endoderm - derived tissues from the riken mouse dataset . the full dataset for these 14 tissues was filtered by total variance to produce a subset of 113 genes . this subset was clustered two - dimensionally using cluster , and the resulting gene and sample order used to create the pictured topography plot in matlab r12 ( mathworks , natick , ma , usa ) . asubset of 1,319 genes with the highest total variance was selected across the e16 lung , neonatal day 0 lung , and adult lung experiments . genes with peaks at the edges of the diagram are enriched in the respective developmental stages compared to the adult sample . the subset of genes described in ( b ) was clustered one - dimensionally with the whole embryo experiments using the order of samples shown . ( i ) a cluster containing surfactant protein a , a known lung - enriched gene ; ( ii ) a cluster of ests enriched in the e16 lung . we expect the volume of microarray work performed in the mouse to quickly outweigh that of other model organisms for a number of reasons . from a developmental perspective , the mouse is the only genetically tractable model organism that closely resembles humans in the formation of organ systems with similar structure and function to ours . collecting fresh tissue for rna analysis at all developmental and adult stages is a relatively simple task . also , the number of genetic mutants closely resembling human disease processes is dramatically increasing with the expansion of forward - genetic ( mutagenesis ) screens in the mouse , providing many opportunities to perform genome - wide scans of transcripts varying in a particular model of interest . wide application of microarray techniques to embryos , tissues , or cells harboring engineered mutations will create an exponential number of permutations and combinations ripe for investigation . although the future is bright , there is room for improvement in a number of areas . a working draft copy of the mouse genome sequence will certainly aid in making sense of expression data from novel ests . this could potentially narrow down genes of interest to those that have a putative motif or predicted function of interest . as judged by discussion at a recent symposium on statistical aspects of microarray data analysis , there is not yet anything resembling consensus amongst statisticians as to the most appropriate methods to deal with array data . one of the overall challenges to statisticians and computer scientists in general will be the development of analysis software that is readily usable by the uninitiated biologist with data from their first experiment in hand . although many companies currently claim that their products do this and everything else , this has not been the case in our experience . this will no doubt change in the near future , however , given the rapid advancements from academic and commercial activity in the area . the authors thank hidemasa bono and the riken hayashizaki mouse genomics group for sharing data from their microarray database .

microarrays of mouse genes are now available from several sources , and they have so far given new insights into gene expression in embryonic development , regions of the brain and during apoptosis . microarray data posted on the internet can be reanalyzed to study a range of questions .

rheumatoid arthritis ( ra ) affecting the cervical spine is well described in the literature but little attention has been paid to the less common rheumatoid involvement of the thoracic and lumbar regions ( 1 - 4 ) . generally , the thoracic and lumbar portions of the spine are usually spared in ra . however , a review of the literature showed that rheumatoid synovitis with erosive changes can develop in these diarthrodial joints . the vertebral bodies and intervertebral discs may be involved through either enthesitis or an extension of the inflammatory process from the apophyseal joints ( 2 , 3 , 5 - 7 ) . there are few reports describing collapse of the vertebrae affected by ra without synovitis and enthesitis ( 1 , 4 , 5 , 8) . this paper reports a case of multiple pathologic fractures caused by ra in a 47-yr - old woman who was treated with percutaneous vertebroplasty ( pv ) for intractable pain . a 47-yr - old woman was transferred to the department of neurosurgery from the department of rheumatology as a result of unbearable low back pain that had suddenly become aggravated one week earlier . she had been suffering from seropositive ra since the age of 40 yr , and had been treated with bucillamine 200 mg / day , nabumetone 1,000 mg / day in another hospital . one month earlier , she felt severe back pain without trauma and was admitted to our institute . joint swelling was also noted on the small joints of the hands and right elbow but there was no tenderness . the blood examination revealed a white blood cell count , hemoglobin concentration , erythrocyte sedimentation rate and c - reactive protein level of 7,400/ml , 13.1 g / dl , 10 mm / hr , and 2.24 mg / dl , respectively . the rheumatoid factor was high at 56 iu / ml and the anti - nuclear antibody ( ana ) was positive ( 1:160 ) . the anti - cyclic citrullinated peptide antibody ( anti ccp ) was 26 iu / ml . a plain radiographic examination of thoracolumbar spine ( fig . 1a ) revealed multiple thoracolumbar fractures on t11 , l2 , and l3 , and sclerosis of the vertebral end - plate without evidence of osteophyte formation . 1b , c ) revealed vertebral involvement on t11 , l2 , l3 , and l5 , which was hyperintense on the gadolinium - enhanced t1 weighted images . a bone scintigram demonstrated increased uptake in the t12 , l2 , l3 , and l5 spine , multiple metacarpophalangeal and proximalinterphalangeal joints of both hands . dural radiography absorptiometry ( dxa ) revealed moderate osteopenia in the femoral neck ( t score -1.6 sd ) and vertebral body ( t score -2.0 ) . her initial medications included bucillamine , non - steroid anti - inflammatory drugs and combinations of analgesics both intravenously and epidurally for multiple compression fractures . however , she had felt increasing pain while standing and lying down for a month . upon arrival to our department 2a ) showed the minor progression of compression with surrounding sclerosis at t11 , l2 , 3 , 4 , and l5 , and a widening of the intervertebral disc space . 2b , c ) showed significant collapse of the t12 vertebral body with the retropulsion of bony fragments , which was evidence of acute fracture . the patient underwent percutaneous vertebroplasty following a needle biopsy on the t12 vertebra ( fig . 4 ) revealed areas of fibrosis with surrounding acute and chronic inflammatory cell infiltration including neutrophils , plasma cells and lymphocytes . and the bacteriological culture of the specimen for bacteria , fungi and mycobacterium tuberculosis was also negative . finally , a pathological fracture due to the marrow involvement of rheumatoid arthritis was diagnosed based on the absence of any infectious signs , her history of ra and the diagnostic characteristics on the various imaging modalities . after bed rest for one week , she commenced a rehabilitation regimen with a hard corset to regain her walking ability . although the cervical spine is more commonly involved in ra , and atlantoaxial subluxation is well known , there are some reports of thoracolumbar spine involvement in a few patients with ra ( 1 - 3 , 6 - 9 ) . with regard to the disease incidence , heywood and meyers reported a frequency of 0.94% ( seven cases in 746 patients satisfying the criteria of definite rheumatoid arthritis ) ( 2 ) . recently , nakase et al . and sakai et al . suggested that asymptomatic involvement is relatively common ( 7 , 8) . usually , a radiological examination shows disc narrowing without osteophyosis , spondylolisthesis , osteoporosis and ill - defined margins of the apophyseal joints ( 2 , 3 ) . , an ill - defined , blurred and eroded margin of the vertebral end - plates is most important ( 4 ) . previous reports on the involvement of the thoracolumbar spine in ra dealt mainly with the radiological features and pathogenesis ( 1 - 4 , 8) . three pathways for the involvement of the subcervical vertebra include synovitis in the apophyseal joints , inflammation of the disco - vertebral junction and rarely , granulomatous nodule formation in the marrow space of the vertebral bodies ( 2 , 7 ) . synovitis probably begins in the apophyseal joints , slowing erosion of the cartilage and subchondral bone in precisely the same manner as that observed in the peripheral joints . the next lesion , rheumatoid spondylodiscitis , probably begins as an enthesopathy at the discovertebral junction . however , shichikawa et al . suggested two different types of rheumatoid spondylodiscitis based on their histological findings in 2 cases ( 4 ) . one patient showed a loss of intervertebral discs and destruction of the vertebral end plates . they suggested that the inflammatory degeneration of collagen at the junction between the disc and the vertebral end - pate leads to a loss of disc substance and invasive erosion of the end - plate . the other patient showed granulomatous nodular lesions that can develop occasionally in the marrow of the vertebral bodies and then spread , causing osteolysis and weakening , which is followed by collapse of the vertebral body . these lesions demonstrate extensive areas of fibrinoid necrosis surrounded by proliferated connective tissue with some histiocytes , plasma cells and chronic inflammatory cells . in contrast , vertebral bodies with fractures secondary to osteoporosis are characterized consistently by focal areas of endochondral new bone formation adjacent to the avascular necrotic bone and unreactive marrow ( 10 ) . diamond et al . also identified four stages of fracture healing in a histological analysis of fracture healing in an osteoporotic vertebral fracture ( 11 ) . these included : 1 ) fracture hematoma with necrotic bone and fibrovascular stroma ; 2 ) chondrogenesis and bone matrix synthesis ; 3 ) endochondral ossification and woven bone formation ; and 4 ) bone remodelling and modelling . in our case , the histological findings of specimen in conjunction with the clinical and serological data suggested that the spinal lesions were due to rheumatoid arthritis . moreover , it is likely that the inflammatory tissue arose from the marrow space and not from the intervertebral disc , as evidenced by the histological and radiological findings . the surgical treatment of the thoracolumbar lesions affected by ra are quite rare , and they need to be tailored to each patient according to the location of the lesion within the vertebra and the patient 's symptoms ( 2 , 6 , 8 , 9 ) . a laminectomy may allow adequate decompression in selected cases , particularly those with an epidural rheumatoid nodule or spinal stenosis ( 2 , 6 ) . an anterior corpectomy is effective , and adequate decompression can be achieved in patients with marked kyphosis and a collapsed vertebral body . in our case , percutaneous vertebroplasty , which is usually performed using polymethylmethacrylate , is a relatively new treatment for symptomatic vertebral ra . this suggests that patients who present with a pathological compression fracture and intractable back pain are good candidates for pv . however , pv is a palliative treatment , and it is unlikely to reverse the neurological deficits in patients with significant thecal compression as a result of the ra lesion . moreover , the long - term efficacy of vertebroplasty for thoracolumbar involvement of ra is unknown . therefore , a careful and long - term follow - up for the recurrence of symptoms after the procedure is essential . in conclusion , thoracolumbar involvement in rheumatoid arthritis should be more common than previously suggested in the literature . therefore , a careful radiological examination of the spine is essential in patients affected by ra who present with acute low back pain . in the case of a painful pathological fracture due to ra , pv is helpful in eliminating the pain , at least in the short - term .

although little attention has been paid to the less common rheumatoid involvement of the thoracic and lumbar regions , some studies have shown that rheumatoid synovitis with erosive changes can develop in these diarthrodial joints . we report a patient with seropositive rheumatoid arthritis ( ra ) involving the thoracic and lumbar vertebra with a collapse of the t12 vertebra , who was treated with percutaneous vertebroplasty . in this case of a painful pathological fracture due to ra , percutaneous vertebroplasty was found to be helpful in eliminating the pain . the paper presents the histological evidence , the pathogenesis and treatment of the thoracolumbar lesions affected by ra with a review of the relevant literature .

recently , all - ceramic fixed partial dentures ( fpds ) were introduced ; these are currently in use in clinical dental treatment . due to their superior aesthetics , all - ceramic restorations provide a more desirable approach compared with metal - ceramic combinations for the restoration of natural dentition.1 the application of veneering porcelain over a high - strength core ceramic has resulted in the creation of an aesthetically more acceptable laminate composite system , which has been employed in the construction of all - ceramic crowns.2 however , ceramics are brittle and susceptible to failure beyond a critical stress , which is dependent on the internal and surface flaw distributions,3,4 and their fracture problems have not been solved completely.5 manufacturers have adopted novel engineering processing routes to produce all - ceramic dental core materials with strengths in excess of those achieved using metallic frameworks for metal - ceramic restorations.6 the finite element method ( fem ) has been shown to be a useful tool when investigating complex systems.7,8 knowledge of stress distribution is important in the understanding of fatigue yielding.9 overall stress distribution within the tooth / restoration complex is determined by geometry and hard tissue / restorative material arrangement.10 it has also been reported that the majority of failures of all - ceramic fpds originate at the gingival side of the connectors , at the interface of the framework and veneer porcelain.11 thus , the framework design of all - ceramic restorations may have an important effect on stress distribution . furthermore , the distribution of stress influences the success of the treatment.1214 in recent years , alternative materials and designs have been developed to suit different clinical situations,15 and fpds must have a design type that satisfies certain structural requirements . an fpd must provide enough strength to resist the forces of occlusion that cause flexure of the framework , producing stress in the restoration , and the abutment . it is known that the arch - type design is the most efficient method of forming a structure with materials that have good compressive strength and low tensile strength.16 however , to develop theories of prosthesis design , the amount of stress likely to be generated in the oral cavity must be quantified.15 thus , this study aimed at evaluating the effects of framework designs on stress distribution at the supporting bone and supporting implants . the null hypothesis of the current study was that the different framework designs associated with all ceramic restorations would not affect stress distribution . the study was conducted using 3d fem and the solidworks 2007 9.0.3 structural analysis program ( solidworks corporation , usa ) . a 3d fem model was constructed to represent a three - unit implant supporting fpds ; this was used to perform the computer simulation ( figure 1a ) . the model contained a three - unit all - ceramic fpd with two implants ( iti solid screw implants , 3.8-mm diameter , 10-mm bone sink depth ; straumann ag , waldenburg , switzerland ) at each end as abutment . these were supported by alveolar bone structures simulated as spongy bone surrounded by 2 mm of cortical bone . initially , the cross - sections of bone structures included in the mathematical model were hand drawn . they were sketched separately at the front and right planes for each unit in the computer environment . the implant system modeling was conducted using a laser - based 3d scanner ( dental wings , montreal , quebec , canada ) to reproduce the exact dimensions . the coordinates of the contouring points were then joined to form each structure s volume ; together , these defined the final geometry of the fem model ( figure 1b c ) . the simulated geometries used for analysis were three different framework designs ( convex ( 1 ) , concave ( 2 ) , and conventional ( 3 ) pontic framework designs ) ( figure 2a c ) . all - ceramic fpds ( ips e - max press ; ivoclar vivadent ag ) were simulated as the restorative material . the bottom exterior nodes of the alveolar bone in the fem models were fixed in all directions as the boundary condition ( figure 3b ) . a 300-n static vertical occlusal load17 was applied on the node at the center of occlusal surface of the pontic to calculate the stress distributions ( figure 3b ) . as a second condition , frameworks were directly loaded to clearly demonstrate the effect of framework design ( figure 3c ) . the elastic properties of the materials ( young s modulus ( e ) and poisson s ratio ( ) ) were determined from the literature and are given in table 1.15,18 the fem modeling was accomplished using the solidworks software program , and analyses were run with the cosmosworks software program , which is integrated with solidworks . results are presented by considering the von mises criteria.1924 calculated numerical data were transformed into color graphics to better visualize the mechanical phenomena in the models . both a 3d whole - model view and mesiodistal cross - sectional views were presented for each condition . a narrower range was used for the stress indicator scale to better visualize the differences in stress distribution ( 0 to 5 mpa ) . the analysis of the von mises stress values revealed that maximum stress concentrations were located at the loading areas for all models . in addition , high stress values were located at the gingival embrasures of connectors and the cervical regions on the pontic side of abutment implants in all models . the cervical and inter - implantal alveolar bone structure was the other stress concentration area . there were no clear differences in stress distributions among the three design types ( figure 4a c ) . the stress trajectory started from the force application point and continued through the framework to the abutment implants , where it was distributed at the bone structure . the highest stress values observed at the force application areas were 27.3 , 29.1 , and 26.0 mpa for convex , concave , and conventional designs , respectively . the highest value was observed at the veneering porcelain at the force application area of concave design ( 29.1 mpa ) . the stress values observed at the cervical regions of the implants were 1.17 , 1.41 , and 1.35 mpa for convex , concave , and biconcave designs , respectively . the stress values at the alveolar bone structure between implants were 0.310.76 mpa ( figure 5a c ) . the structures maximum von mises stress values with different models are summarized at table 2 . the highest stress values observed at the force application areas of the framework porcelain were 5.12 , 5.34 , and 5.24 mpa for convex , concave , and biconcave designs , respectively . although the maximum stress concentration values were close , clear stress distribution diversities for example , stress values of 4.65.34 mpa clearly occupied more space in the concave design framework than the other design types . in addition , high stress concentration values at the implant neck occupied more space in the concave design . the maximum von mises stress values observed at the cortical bone structure were 0.81 , 1.01 , and 0.68 mpa for convex , concave , and biconcave designs , respectively . while stress was directed toward inter - implantal alveolar bone in the concave framework design , at the opposite was the case for the convex and conventional framework designs ( figure 7a c ) . however , the maximum stress value of 0.81 mpa was clearly more widespread for the convex design type than for the conventional framework design . the maximum von mises stress values of structures with different models and a direct loading of the framework are summarized in table 3 . there were no clear differences in stress distributions among the three design types ( figure 4a c ) . the stress trajectory started from the force application point and continued through the framework to the abutment implants , where it was distributed at the bone structure . the highest stress values observed at the force application areas were 27.3 , 29.1 , and 26.0 mpa for convex , concave , and conventional designs , respectively . the highest value was observed at the veneering porcelain at the force application area of concave design ( 29.1 mpa ) . the stress values observed at the cervical regions of the implants were 1.17 , 1.41 , and 1.35 mpa for convex , concave , and biconcave designs , respectively . the stress values at the alveolar bone structure between implants were 0.310.76 mpa ( figure 5a c ) . the structures maximum von mises stress values with different models are summarized at table 2 . the highest stress values observed at the force application areas of the framework porcelain were 5.12 , 5.34 , and 5.24 mpa for convex , concave , and biconcave designs , respectively . although the maximum stress concentration values were close , clear stress distribution diversities for example , stress values of 4.65.34 mpa clearly occupied more space in the concave design framework than the other design types . in addition , high stress concentration values at the implant neck occupied more space in the concave design . the maximum von mises stress values observed at the cortical bone structure were 0.81 , 1.01 , and 0.68 mpa for convex , concave , and biconcave designs , respectively . while stress was directed toward inter - implantal alveolar bone in the concave framework design , at the opposite was the case for the convex and conventional framework designs ( figure 7a c ) . however , the maximum stress value of 0.81 mpa was clearly more widespread for the convex design type than for the conventional framework design . the maximum von mises stress values of structures with different models and a direct loading of the framework are summarized in table 3 . the stress distribution patterns varied with different framework designs . based on these results , the null hypothesis that the framework design would not affect the stress distribution for implant - supported fpds was rejected . in the present study , using the fem technique , the effect of framework design on amount and distribution of stress was evaluated . however , a theoretical and well - known method for calculating stress distribution within complex structures is fem , which allows the investigator to evaluate the influence of model parameter variation once the basic model has been correctly defined.8 the model used in this study involved several assumptions regarding simulated structures . the structures in the model were all assumed to be homogeneous , isotropic , and linearly elastic . the properties of the materials modeled in this study , however , and particularly the living tissues , are different . in addition , it is important to point out that the stress distribution patterns may have been different depending on the materials and properties assigned to each layer of the model , as well as the model used in the experiments.15 furthermore , only a vertical loading condition was used to compare different designs . horizontal or oblique force applications will be used in future studies . von mises stresses depend on the entire stress field and are a widely used indicator of the possibility of damage occurring.20 the value of the occlusal force was selected to be 300 n. however , it is not necessary for this force to match its real value exactly because standardization between conditions has been ensured in the current study and the conditions have been compared qualitatively with one another.15 chen and xu7 emphasized that the value of fem modeling has to do with relative values calculated for distribution patterns . a comparison of stress distributions with different design types revealed lower stress values in frameworks with the convex design . the stress levels for the conventional design type were close to those of the convex design , but the maximum stress value occurred at more places in the framework structure with the conventional type of design . thus , it may be concluded that , biomechanically , the more favorable framework design was the convex one . it was also seen that the veneering porcelain part of the restorations compensated for the mechanical effects of different framework designs . however , more clinical and experimental studies are needed to support the findings of the current study . occlusal loads are transmitted from the point of force application to the point of retainers and , ultimately , travel through the abutments to the bone structure . moreover , the purpose of a restoration is to maintain strength while resisting the forces of occlusion . thus , fixed partial dentures must include materials and a design type that provides enough strength to resist the forces of occlusion . porcelain has an amorphous structure and this produces physical properties typical of a glass.4 when porcelain is stressed in tension , small flaws tend to open up and propagate , resulting in a low tensile strength.4 however , porcelain is much stronger in terms of compression , because compressive stresses tend to close up flaws.4 it is known that when a beam is loaded , the applied loads have a tendency to cause failure of the beam in two main ways : by shearing or by bending the beam.16 arches are commonly used in several structural forms and represent the most efficient method of forming a structure with materials that have good compressive strength and low tensile strength.16 dental porcelains are among such materials because of the abovementioned properties . in order to achieve the most efficient structural solution , the design engineer ( in this case , the dentist ) , can alter the structural configuration to produce an equilibrium condition made up of compression forces.16 thus , the convex framework design can be the most suitable way for inserting ceramic fpds to restore a missing tooth or teeth . in agreement with this information , the results of the current study revealed that von mises stress values decreased with the use of a convex design type . when dealing with implant - supported fpds , modifying the framework design may help to decrease stress concentrations , but the veneering porcelain element may reduce the effect of a framework with recent restorative materials . further studies that better simulate the oral environment and including fatigue loading are recommended . although the clinical implications that can be derived from this study are important , long term clinical evidence is required . within the limitations of this study , the following conclusions were drawn : the use of a concave design for fpd pontic frameworks increases the von mises stress levels on implant abutments and supporting bone structure.the veneering porcelain part reduces the effect of the framework and compensates for design weaknesses . the use of a concave design for fpd pontic frameworks increases the von mises stress levels on implant abutments and supporting bone structure . the veneering porcelain part reduces the effect of the framework and compensates for design weaknesses .

objectives : the biomechanical behavior of the superstructure plays an important role in the functional longevity of dental implants . however , information about the influence of framework design on stresses transmitted to the implants and supporting tissues is limited . the purpose of this study was to evaluate the effects of framework designs on stress distribution at the supporting bone and supporting implants.methods:in this study , the three - dimensional ( 3d ) finite element stress analysis method was used . three types of 3d mathematical models simulating three different framework designs for implant - supported 3-unit posterior fixed partial dentures were prepared with supporting structures . convex ( 1 ) , concave ( 2 ) , and conventional ( 3 ) pontic framework designs were simulated . a 300-n static vertical occlusal load was applied on the node at the center of occlusal surface of the pontic to calculate the stress distributions . as a second condition , frameworks were directly loaded to evaluate the effect of the framework design clearly . the solidworks / cosmosworks structural analysis programs were used for finite element modeling / analysis.results : the analysis of the von mises stress values revealed that maximum stress concentrations were located at the loading areas for all models . the pontic side marginal edges of restorations and the necks of implants were other stress concentration regions . there was no clear difference among models when the restorations were loaded at occlusal surfaces . when the veneering porcelain was removed , and load was applied directly to the framework , there was a clear increase in stress concentration with a concave design on supporting implants and bone structure.conclusions:the present study showed that the use of a concave design in the pontic frameworks of fixed partial dentures increases the von mises stress levels on implant abutments and supporting bone structure . however , the veneering porcelain element reduces the effect of the framework and compensates for design weaknesses .

breast cancer is the second leading cause of death among women in the united states.1 the increasing use of mammography and increased awareness of breast cancer among women has resulted in early detection of localized breast cancer . this has led to marked improvement in the cure rate for the disease , which is rapidly increasing in incidence . the benefits of screening mammography have been documented in a number of studies , including the breast cancer detection demonstration project and health insurance plan of new york.2,3 the sensitivity of mammography for detection of breast cancer is variable , and 9%63% of all abnormalities reported on mammograms are ultimately diagnosed as malignant.46 needle localization followed by open surgical biopsy was introduced in 1965 as a way of obtaining a histological diagnosis of such lesions . this technique involves placement of a radiopaque wire percutaneously into or near the lesion either under ultrasound or mammography guidance preoperatively by a radiologist . the exact position of the wire relative to the lesion either placed under ultrasound or mammographic guidance is verified by a mammogram . the wire and mammogram guides the surgeon to the exact site of the lesion and avoids unnecessary removal of a large volume of tissue in the event of a benign lesion . on the other hand , it is important to obtain a wide tumor - free resection margin if the lesion turns out to be malignant on histopathology . preoperative needle localization offers an opportunity to make a rapid and accurate excision with minimal trauma and the least tissue damage.79 the cosmetic results assume great importance , considering that about 69% of these lesions are benign.10 the only drawback of this method is that it may lead to inadequate removal of an unexpected cancer , therefore requiring a second operation to achieve a clear margin . preoperative diagnostic procedures that give a surgeon an idea regarding the possibility of a malignant lesion are radiological imaging ( mammography , ultrasound , magnetic resonance imaging ) , image - guided fine needle aspiration cytology , image - guided core needle biopsy , and needle localization followed by open surgical biopsy . needle localization followed by open surgical biopsy is considered to be the most accurate procedure today . we conducted this study to evaluate the usefulness of hook wire localization biopsy under imaging guidance for nonpalpable breast lesions , to assess the correlation between preoperative imaging assessment and final diagnosis , and to determine its usefulness in making a final diagnosis and any associated complications . this was a descriptive retrospective study conducted in the department of radiology , aga khan university hospital . all patients undergoing needle localization biopsy of a breast lesion under mammographic or ultrasound guidance between january 2009 and december 2010 were included . all patients mammograms and ultrasound examinations were categorized using breast imaging - reporting and data system ( bi - rads ) assessment categories . needle localizations were performed either under ultrasound guidance if the lesion was seen on ultrasonography or by stereotactic mammographic guidance for suspicious mammographic abnormalities ( figure 1 ) . all ultrasound - guided needle localizations were performed using a 5 cm 20 g kopan s hook wire needle . after the needle localization was done , two mammographic views were taken in order to provide a road map to the breast surgeon for specimen removal , and the position of the needle was also shown by a line diagram in the patient s confidential file . mammographic stereotactic localizations were done using a 9 cm 20-gauge kopan s hook wire needle , and the procedure was performed using a mammomat 3000 nova siemens mammography machine . after the procedure , all patients were bandaged and immediately sent to the operating theater for the definitive procedure . the excised specimen was then subjected to ultrasound in case of ultrasound - guided needle placement or a magnified mammographic view ( figure 2 ) if the localization was done using stereotactic mammographic guidance to confirm adequate removal of the localized specimen . the percentages of benign and malignant lesions were determined by pathological examination of the surgically removed specimen . a total of 151 mammograms were included , of which 75 were done for screening and 76 for diagnostic purposes . on mammography , the parenchymal patterns were fatty , fibroglandular , heterogeneously dense , and dense in 10 , 62 , 65 , and 14 patients , respectively . the locations of the breast lesions in 52 , 20 , 21 , 25 , and 23 were in the upper outer quadrant , lower outer quadrant , upper inner quadrant , lower inner quadrant , and retroareolar area , respectively . a total of 151 biopsies were carried out , with 80 performed under mammographic guidance and 71 performed under ultrasound guidance . of 80 needle localizations , 54 were done for microcalcifications and 26 were performed for a suspicious mammographic soft tissue density or architectural distortion with or without microcalcifications . localizations done under ultrasound guidance were performed for sono - graphically detected suspicious solid lesions . the overall malignancy rate was 25.16% . of 93 cases reported as malignant , 60 turned out to be malignant and of the 58 cases reported as benign , three were reported to be malignant on histopathology ( table 1 ) . the malignancy rate was 5% for benign lesions and 64% for malignant lesions , respectively . the imaging and pathological findings were concordant in 63.95% of malignant lesions and 95% of benign lesions . needle localization biopsy was able to make the diagnosis in 100% of cases . there were no major complications related to wire localization , eg , hematoma formation or migration of the localization wire . two patients had minor complications following surgical excision in the form of hematoma at the site of excision , and both were treated conservatively . there was complete resolution of the hematoma at the 15-day follow - up visit , giving a complication rate of 1.32% . treatment of breast cancer has progressed from radical mastectomy to a more minimally invasive approach of breast - conserving surgery . while marked improvement has been achieved in the management of breast cancer over recent years the best method available to date for preoperative localization of a nonpalpable breast lesion detected on imaging is the hook wire localization technique described by frank et al.11 this method was used in our study , and lesions detected on ultrasound or mammogram were subjected to ultrasound and stereotactic mammographically - guided needle localizations , respectively . in our study , needle localizations were also performed for lesions that were reported as benign , but with a strong family history of breast cancer or breast cancer diagnosed or treated in the contralateral breast . the malignancy rate for a benign lesion was only 5% , whereas the malignancy rate for lesions reported as malignant on imaging was much higher at 62% . however , the overall malignancy rate in our study was 25.16% , which is comparable with a study by morrow et al12 who reported a malignancy rate of 24% . in their study , a total of 1852 abnormalities in 1550 consecutive patients were prospectively categorized for the level of cancer risk and underwent stereotactic core needle biopsy or diagnostic needle localization and surgical excision . the malignancy rate was between the 19% and 32.2% reported by denning et al13 and schwartz et al,14 respectively . denning et al13 studied 100 patients whereas schwartz et al14 studied 469 patients , so the number of patients included in the study might have affected the overall malignancy rate , because our study had 151 patients , which is in between the number of patients studied by denning et al13 and schwartz et al.14 the concordance rate between the imaging findings and histopathology was 95% for benign lesions and 63.95% for malignant lesions , which is similar to that in the study by jortay et al,15 who reported a concordance of 98% and 64% for benign and malignant lesions , respectively . jortay et al15 studied the contribution of wire localization breast biopsy to the pathological diagnosis of mammographic lesions . their study included 152 patients with nonpalpable breast lesions ; however , all patients were subjected to mammography and all then underwent needle localization and excision biopsy of a localized lesion followed by histopathology . needle localization followed by open surgical biopsy is safe , with a negligible minor complication rate of 1.3% . the complications did not occur during the needle localization procedure , with two patients developing hematomas after open surgical biopsy . furthermore , the biopsy results strongly influence the algorithm for evaluation of suspicious lesions.16 there are a few limitations to our study . it was also a retrospective study , and all patients who underwent needle localizations during the study period were included . perhaps if the study had been conducted prospectively , more stringent patient selection could have been adopted , thus affecting the final outcome . needle localization was done in all patients coming for screening as well as for diagnostic study , eg , in a patient with known malignancy in one breast and having a suspicious lesion on the opposite side . localization biopsy was planned to rule out a second malignant lesion on the contralateral side and this might have affected the malignancy rate in lesions appearing benign on imaging . the study shows that hook wire localization biopsy under imaging guidance for nonpalpable breast lesions is a useful procedure in making the final diagnosis . it is a safe and effective procedure for definitive diagnosis of suspicious lesions on imaging , thus being more helpful if the imaging findings are suspicious .

backgroundthe purpose of this study was to evaluate the usefulness of hook wire localization biopsy under imaging guidance for nonpalpable breast lesions detected radiologically.methodsthis was a descriptive study conducted at the department of radiology , aga khan university hospital , karachi . all patients undergoing needle localization biopsy of a nonpalpable breast lesion under mammographic or ultrasound guidance between january 2009 to december 2010 were included in the study . patients with incomplete medical records were excluded . all patients mammograms or ultrasound were categorized using bi - rads assessment categories . the percentages of benign and malignant lesions were determined by pathological examination of surgically removed specimens . a correlation was sought between preoperative imaging assessment and the final diagnosis . the complications associated with the procedure were also recorded.resultsa total of 151 biopsies were carried out , of which 80 were performed under mammographic guidance and 71 were performed under ultrasound guidance . the mean age of the patients was 51.89 years . the overall malignancy rate was 25.16% . of 93 cases reported radiologically as malignant , 60 turned out to be malignant , and of the 58 cases reported as benign on imaging , three proved to be malignant on histopathology . the sensitivity of imaging findings was 95% and the specificity was 62% . the malignancy rate was 5% for benign lesions and 64% for malignant lesions , respectively . there were no complications related to wire localization , and only two patients had minor complications following surgical excision , giving a complication rate of 1.32%.conclusionhook wire localization biopsy is a safe and effective procedure for definitive diagnosis of suspicious lesions on imaging , and is more helpful if the imaging findings are suspicious .

conidiomata pycnidial , epiphyllous , scattered on lesions of leaves , immersed , punctiform with papillate ostiole . conidia cylindrical or oblong - ellipsoidal , straight or sometimes slightly curved , both ends rounded , sometimes narrowed to one end , not or only slightly constricted at the septa , hyaline , 10~22.5 3~6.3 m ( fig . however , principal hosts of this fungus are chrysanthemum cinerariifolium and c. morifolium ( punithalingam , 1980 ) . . once introduced and established in an area , this fungus is both difficult and costly to eradicate , and control of the disease remains as additional production expense . this fungus was recorded in africa , australasia & oceania , europe , north america and asia ( punithalingam , 1980 ) , however this fungus is not reported in korea according to the korean society of plant pathology ( 2004 ) . conidiomata pycnidial , scattered , immersed , 110~170 m in diam . conidia cylindrical or oblong - ellipsoidal , both ends rounded , straight or sometimes slightly curved , not constricted or rarely slightly constricted at the septa , hyaline , 10~17.5 3.8~5 m ( fig . mel'nik ( 2000 ) recorded asia ( george ) as a distribution area of the fungus . ascospores ellipsoid to oblong with gelatinous sheath , 3~5 transverse septa , 1~3 longitudinal septa , hyaline to brown , 26~38 9~13 m ( fig . 2 ) . according to graham and luttrell ( 1961 ) , leptosphaerulina trifolii , l. briosiana and l. arachidicola were pathogenic , but l. australis , l. argentinensis and l. americana were saprobic . however , irwin and davis ( 1985 ) reported that l. argentinensis was pathogenic to stylosanthes guianensis . in the present work , pathogenicity of the fungus is also needed to study . on the other hand , booth and pirozynski ( 1967 ) , and irwin and davis ( 1985 ) regarded l. australis as a taxonomic synonym of l. trifolii . l. trifolii is plurivorus but especially on economic plants from the following families : cruciferae , euphorbiaceae , gramineae , leguminosae and solanaceae . it causes leaf spot or pepper spot on account of leaves and petioles of diverse plants , particularly forage legumes ( booth and pirozynski , 1967 ) . all three fungi intercepted are not reported in korea according to the korean society of plant pathology ( 2004 ) , and may have risks to domestic plants . it is necessary to inspect and identify thoroughly the presence of these fungi during plant quarantine procedures .

three fungi newly intercepted from importing plants were identified in 2004 . they were ascochyta chrysanthemi on lactuca sativa from china , a. spinaciicola on spinacia oleracea from denmark , and leptosphaerulina australis on brassica oleracea var . capitata from china . the characters of these fungi were described and illustrated .

hellp syndrome represents a severe form of preeclampsia , presenting with hemolysis , elevated liver enzymes , and low platelet count . visual symptoms can be present in up to 25% of patients with preeclampsia , usually in the form of decreased visual acuity . retinal detachment is a rare , but the well - document cause of visual loss in patients with preeclampsia and eclampsia . it is observed in < 1% of patients with preeclampsia , specially in the patients with severe hypertension . in women with preeclampsia and eclampsia , coexistence of hellp syndrome point - of - care ocular ultrasonography allows for bedside detection of ocular pathologies such as retinal detachment , globe rupture , lens dislocation , and vitreous hemorrhage . here , we report a case or retinal detachment in a patient with hellp syndrome , which was detected at the bedside by an intensivist , using ocular ultrasonography . a 26-year - old female , para 2 and gravida 3 , presented with the history of 2 days of swelling of whole body , headache , and blurring of vision associated with decreased urine output . her liver enzymes and lactate dehydrogenase were raised , platelet count was 55,000 per ml , and urine examination revealed 4 plus albuminuria and hematuria . emergency lower segment cesarean section was performed , and the patient was transferred to the intensive care unit . an intensivist , trained in bedside focused ultrasonography , performed ocular ultrasound ( using high frequency linear probe ; frequency range of 613 mhz ; micromaxx ; sonosite , usa ) , which revealed a linear hyperechoic membrane floating off the posterior globe , with the medial end attached to the margin of optic nerve head , which was suggestive of retinal detachment [ figure 1 ] . she was started on injection glyceryl trinitrate , along with amlodipine 10 mg 12 hourly , prazosin 2.5 mg 12 hourly , metoprolol 50 mg 12 hourly , clonidine 100 mcg 12 hourly , and methyldopa 500 mg 6 hourly . with these drug combinations , blood pressure was controlled ( 130/80 mm hg ) and glyceryl trinitrate was tapered and stopped after 24 h. the patient underwent four sessions of hemodialysis for acute kidney injury . renal function and liver function gradually improved . a linear hyperechoic membrane floating off the posterior globe ( marked by white arrow ) , with the medial end attached to the margin of optic nerve head , suggestive of retinal detachment the patient was explained about the favorable prognosis . with the supportive care , ocular ultrasound repeated after 7 days showed regression of retinal detachment [ figure 2 ] . after another 1 week , she had complete recovery of vision . resolving retinal detachment ( marked by white arrow ) . retinal vascular changes , usually in the form of spasm and narrowing of retinal vessels , occur in up to 40%100% of patients with preeclampsia / eclampsia syndrome . arteriolar vasospasm affecting the retinal pigment epithelium leads to breakdown of blood - retinal barrier . subsequent leakage of protein and fluids from the capillaries , into the subretinal space , causes retinal detachment . the combination of microangiopathic hemolysis , hypoalbuminemia , and severe hypertension further contributes to the pathophysiology of retinal detachment . bedside ultrasound by a trained physician has been shown to be reliable and accurate for the diagnosis of retinal detachment . . the incidence of retinal detachment in these conditions can be much higher than actually detected . in our patient , early initiation of aggressive supportive care was coupled with favorable prognostication of visual outcome to the patient . the progressive improvement of vision correlated with both the ophthalmoscopic evidence of resolution of retinal detachment and sonographic appearance of resolution . to conclude , bedside ocular sonography can be a valuable and easily available tool for early detection of retinal detachment in patients with preeclampsia / eclampsia / hellp syndrome , presenting with visual symptoms .

retinal detachment is a rare , but well - known cause of visual impairment in patients with hemolysis , elevated liver enzymes , and low platelet count ( hellp ) syndrome . with supportive care , patients usually improve , with complete recovery of vision . bedside ultrasonography of the orbit can be helpful for early detection of retinal detachment in these patients . here , we present a case of hellp syndrome presenting with severe visual symptoms . retinal detachment was detected with point - of - care ocular sonography , which was confirmed with ophthalmoscopic examination . the patient was reassured of the favorable prognosis . early initiation of aggressive supportive care was followed by progressive improvement of vision , which correlated with sonographic evidence of resolution of detachment . her vision recovered completely in 2 weeks .

since its first formal introduction in the 1976 march of dimes publication , toward improving the outcome of pregnancy , the concept of regionalized perinatal care has functioned as the core model by which hospitals and physicians strive to promptly provide the most risk - appropriate care to every infant and mother . this system stratified perinatal care into three levels of complexity : level i - uncomplicated maternity and newborn care , level ii - uncomplicated and majority of complicated care , and level iii - uncomplicated and all serious complications ( 1 , 2 ) . prior to its initial proposal and throughout the last four decades , the application of regionalized perinatal care has contributed to a decrease in morbidity and mortality for high - risk infants born prematurely or with severe medical or surgical conditions ( 35 ) . in the case of very low birth weight ( vlbw ) infants ( birth weight < 1500 g ) , delivery at non - level iii centers is not desirable and can often lead to neonatal transport to a higher level of care . given the increased morbidity and mortality for vlbw infants born at non - level iii centers , maternal transport is favored over neonatal transport as it leads to more favorable outcomes ( 3 , 69 ) . the importance of reducing neonatal transport is emphasized by the healthy people 2020 goal of reducing vlbw births at non - level iii centers to below 16.3% by 2020.(10 ) in this study , we assessed the frequency of vlbw births at non - level iii hospitals in california in order to better understand the size and characteristics of this at - risk population , and evaluated the duration of their antepartum admission to assist in identifying opportunities for improvement in maternal transport prior to delivery of at risk neonates . we performed a retrospective cohort study using de - identified , linked birth certificate and discharge diagnosis data from the california office of statewide health planning and development for the years 20082010 . this dataset includes maternal and neonatal variables from the birth certificate and hospital discharge data . levels of neonatal care classification have been defined by the american academy of pediatrics.(11 , 12 ) briefly , level ii units are designed to primarily care for infants > 32 weeks gestational age and weighing greater than 1500 grams ; level iii units are capable of providing comprehensive care for infants born < 32 weeks gestational age and < 1500 grams , including mechanical ventilation ; level iv units ( introduced as a classification in 2012 ) have all of the capabilities of a level iii unit , but also have a full range of pediatric medical and surgical specialists . we used the equivalent of the most recent levels of care classification to apply to the study period . the study population included mother / infant pairs of either singleton or the first - born infant of multiple gestations , between 22 0/7 and 42 6/7 weeks , with bw 4001500 g , and maternal admission on or before infant date of birth . although there may have been errors in coding , we considered that birth weights would be more accurate than gestational age coding and therefore did not exclude records based on improbable gestational age . maternal and neonatal variables were characterized by level of care . as a hospital could change level of care from year to year , we considered hospital - year as the unit of analysis . to evaluate the frequency of vlbw births by center level of care , we calculated the absolute number of vlbw births by hospital and the percent of vlbw births over all births by hospital , for all hospitals in california during the study period . descriptive statistics were calculated including mean , standard deviation , mode , median , range , and interquartile range . we also calculated descriptive statistics for the antepartum length of stay in days in order to assess the opportunity for potential transport prior to delivery when indicated . as the length of stay was not measured by hours , we considered that a length of stay greater than 1 day would constitute a time period of at least 24 hours in which maternal transfer could have been arranged . data analysis was conducted using sas 9.4 ( sas institute , cary , nc ) . of 1,508,143 births in the study period , 13,919 ( 9.2% ) were vlbw births , with 14.9% of the vlbw births occurring in non - level iii centers there was a higher proportion of white and hispanic vlbw births at level i centers . level iii centers had higher proportions of mothers with pregnancy - associated morbidities such as hypertension and diabetes compared to both level i and level ii centers . vlbw deliveries at level i centers were more likely to be covered by medi - cal ( state - funded insurance ) compared to other levels of care , while level iii centers had the highest proportion of privately insured patients compared to other levels . when considering individual hospitals , the median % of vlbw births at level i hospitals was 0.3% ( range 0% 4.7% ) annually , while the median % at level ii hospitals was 0.5% ( range 0% 1.6% ) annually ( table 2 ) . this translated to a median of 2 vlbw births and 9 vlbw births annually at level i and level ii hospitals , respectively ( table 2 ) . greater than 50% of vlbw deliveries in level i and level ii hospitals occurred within one day , while 1.6% of level i and 2.7% of level ii births occurred after 14 days of antepartum stay ( table 3 ) . the median antepartum length of stay was longest for level iii centers at 2 days , with the median length of stay less than 1 day for both level i and level ii centers . however , length of stay did exceed greater than 1 day for some vlbw births occurring at level i and ii centers . the interval between maternal admission and delivery , antepartum length of stay > 1 day ( at least 24 hours ) occurred in 14.0% and 26.9% of vlbw births in level in this population - based study , we found that the state of california was meeting the healthy people 2020 goal ( 16.3% ) as early as 2008 to 2010 , with 14.9% of percent of vlbw births at non - level iii centers . there was variation across level i and level ii centers in the proportion and numbers of vlbw births , which indicates that there may be potential for further improvement . level i hospitals had 8.4% of vlbw births , which is decreased the 10.5% seen in a california study covering 19891993.(13 ) birth and early care at level iii centers is associated with better clinical outcomes for vlbw neonates.(1418 ) a retrospective australian study conducted in 1988 noted that mortality in infants transferred between level iii hospitals was significantly greater than in those who remained at the birth hospital , suggesting that transport alone , and not simply birth at a lower level nicu prior to transport , bears significant risk for the infant ( 19 ) . while some maternal transports may not be possible due to the clinical circumstance leading to imminent delivery , our study indicates that there may still be many opportunities for maternal transport in order to avoid neonatal transport . first , variation across centers suggests that some policies at either the institutional or regional level may promote optimal transport practice . second , the timing of maternal admission to the first hospital and delivery was often prolonged , suggesting that delivery was not imminent ( table 3 ) . our dataset did not contain granular data about the status of the fetus or mother including fetal heart rate tracing , vaginal bleeding or uncontrolled maternal hypertension to determine the safety and appropriateness of transport in individual cases . whether non - medical factors play a role in vlbw births in non - level iii centers remains to be determined . financial incentives that dis - incentivize maternal transport may be a factor in some births occurring at level i and ii centers . if maternal transport means loss of charges for the delivery and the initial critical care of a preterm neonate , some hospitals may not actively seek to transport mothers in some circumstances . some level ii centers may also wait until the baby is born in order to see whether less critically ill neonates could be cared for at that hospital , and only choose to transport the neonate as needed . reaching the healthy people goal prior to 2020 indicates that progress has already been made in optimizing the location of birth for preterm newborns . furthermore , the higher risk mother - fetus pairs , such as those having co - morbidities , including hypertensive disorders , were more likely to deliver at level iii centers . we used the neonatal levels of care as the basis for appropriate birthplace of vlbw infants . since the time period of the study , neonatal levels of care have been updated to a i to iv system.(11 , 12 ) with this update however , the appropriate location of birth for vlbw infants remains level iii or iv center , due to studies demonstrating better outcomes with this practice.(14 , 15 ) furthermore , a system of maternal levels of care has been established by acog in order to address appropriate hospital of birth determined by severity of morbidities of mothers.(20 ) it is possible that these guidelines could help to further improve appropriate birth location of vlbw births as many of the high risk conditions that may lead to more fetal transports , such as preeclampsia and obesity , are also associated with preterm birth . a limitation of our study is that intention to resuscitate the very preterm newborn was not indicated . in some cases of extreme preterm birth , there may have been a decision to allow delivery at a non - level iii center to transition to palliative care . in the context of healthcare systems , we do not know the optimal rate at which transfers occur , as trying to have zero vlbw deliveries at non - level iii centers could mean that there may be increased burden on the healthcare system by transferring some mothers who threaten preterm delivery but ultimately do not . the generally low frequency ( 0.33% and 0.55% ) of vlbw births in level i and level ii centers ( table 2 ) is reassuring in the context of the goal of few vlbw births at non - level iii centers . however , it also serves to emphasize that those hospitals would not have appropriate training and equipment to handle such births . given the percentage of women with an interval greater than 1 day between admission and delivery , opportunities likely remain for reducing the vlbw birth rate at inappropriate centers even further . optimizing safe transport of high - risk pregnant women to appropriate centers on a state - wide level is likely to require efforts at both the individual hospitals that face challenges in this area , as well as systems and policies at the regional level in order to promote early identification of maternal transport candidates prior to delivery .

objectiveto assess frequency of very low birth weight ( vlbw ) births at non - level iii hospitals.study designretrospective cohort study using linked california birth certificate and discharge data 20082010 for deliveries of singleton or first - born infant of multiple gestations with birth weight 4001500 g . delivery rates by neonatal level of care were obtained . risk of delivery at non - level iii centers was estimated in univariable and multivariable models.resultsof 1,508,143 births , 13,919 ( 9.2% ) were vlbw ; birth rate at non - level iii centers was 14.9% ( 8.4% in level i , and 6.5% in level ii ) . median rate of vlbw births was 0.3% ( range 0%4.7% ) annually at level i and 0.5% ( range 0%1.6% ) at level ii hospitals . antepartum stay > 24 hours occurred in 14.0% and 26.9% of vlbw births in level i and level ii hospitals , respectively.conclusionfurther improvement is possible in reducing vlbw infant delivery at suboptimal sites , given the window of opportunity for many patients .

prostate - specific antigen ( psa ) is one of the most important tools for the early detection of prostate cancer . an elevated serum psa level is an indication to pursue additional diagnostic evaluation , including ultrasound - guided prostate biopsies , to rule out prostate cancer . however , the major drawback of serum psa testing is that psa is prostate - specific but not prostate - cancer - specific . various physiological and benign pathologic processes , including prostatitis , urinary retention , and ejaculation , can affect the serum psa level [ 3 - 8 ] . also , there are limited data on the effect of hospitalization on the serum psa level . serum psa levels measured at least 24 hours after admission in hospitalized patients have been shown to be decreased compared with those measured in the outpatient department before admission , which suggests that the lack of activity associated with bed rest during hospitalization might decrease serum psa values . however , there have been no reports comparing serum psa levels measured just after admission with those measured in the outpatient department before admission . if serum psa levels measured just after admission are decreased compared with those measured in the outpatient department , only the serum psa levels measured in the outpatient department should be considered for the serial monitoring of psa levels in patients with equivocal serum psa values . therefore , in this study , inpatient serum psa ( ipspsa ) values measured just after admission were compared with the preadmission outpatient serum psa ( opspsa ) values to investigate whether hospitalization influences serum psa values . transrectal ultrasound - guided needle biopsies of the prostate were performed for detecting prostate cancer in 2,017 patients between february 2001 and april 2011 at our institution . the indications for prostate biopsy were serum psa elevation or abnormal findings on a digital rectal examination or transrectal ultrasonography . young patients with serum psa elevation usually underwent prostatitis workup and were given oral antibiotic treatment if needed . the decision to biopsy was based on an elevated repeat psa level after a period of time and the patient 's preference despite being informed of the low risk of prostate cancer . among the total 2,017 patients , the patients who underwent prostate biopsies on an outpatient department basis , in whom preadmission opspsa was not measured at ajou university hospital , who had a pathologic diagnosis of prostate cancer , who had recent clinical evidence of acute urinary retention , or who had an interval of more than 1 month between opspsa and ipspsa were excluded . patients who had been taking 5-reductase inhibitors or phytotherapeutic agents within 6 months of biopsy were also excluded from the analysis . all other medications including -blockers were allowed to be taken until the day of biopsy , except for antiplatelet drugs and anticoagulants , which were instructed to be stopped or switched to short - acting drugs a few days before . finally , we retrospectively reviewed the data of 416 patients who were hospitalized for prostate biopsies ; whose opspsa and ipspsa values were measured in our hospital within 1 month of admission and just after admission , respectively ; and whose prostate biopsy results revealed no evidence of cancer . blood sampling for psa was always instructed to be taken before any procedures that could influence the serum psa level , such as digital rectal examination , prostatic massages , transrectal ultrasonography , and cystoscopy . five milliliters of blood was collected from an antecubital vein and was immediately sent to our hospital 's central laboratory . psa was measured in serum samples by using a microparticle enzyme immunoassay in an asym immunoassay analyzer ( abbott diagnostics , abbott park , il , usa ) until 2006 and afterwards by using an electrochemiluminescence immunoassay ( roche diagnostics gmbh , mannheim , germany ) in a modular e170 analyzer ( hitachi , ibaraki , japan ) . the patients were usually hospitalized at 17:00 to 18:00 in the afternoon for prostate biopsies . samples were obtained for blood tests , including psa , immediately after admission , and prostate biopsies were performed the next day after admission , irrespective of the serum psa level during hospitalization . the opspsa and ipspsa measurements were compared according to age , the presence or absence of chronic prostatitis in biopsy pathology , serum psa levels , and prostate size . statistical analysis was performed by using paired sample t - tests with spss ver . 16.0 ( spss inc . , the mean age of the 416 patients included in this study was 61.6 years ( range , 29 to 85 years ) . among all 416 patients , the mean interval between opspsa and ipspsa measurements was 22.2 days ( range , 3 to 30 days ) . the mean prostate size measured by transrectal ultrasonography was 53.63 ml ( range , 12.8 to 197.9 ml ) . among all 416 patients , the mean ipspsa levels ( 6.69 ng / ml ) were significantly lower than the opspsa levels ( 8.01 ng / ml , p<0.001 ) ( table 1 ) . when the patients were stratified according to age , mean ipspsa levels were significantly lower than opspsa levels in patients aged 40 to 59 years ( p<0.001 ) and 60 years ( p<0.001 ) . the mean ipspsa levels were lower than opspsa levels in patients aged 20 to 39 years , but not significantly so ( p=0.141 ) . when the patients were stratified according to the presence or absence of chronic prostatitis in biopsy pathology , mean ipspsa levels were significantly lower than opspsa levels , irrespective of the presence or absence of chronic prostatitis ( p<0.001 and p=0.001 , respectively ) . when the patients were stratified according to the serum psa level , mean ipspsa levels were significantly lower than opspsa levels in patients with psa of 4 to 9.9 ng / ml ( p<0.001 ) and 10 ng / ml ( p<0.001 ) . the mean ipspsa levels were lower than the opspsa levels in patients with psa < 4 ng / ml , but not significantly so ( p=0.116 ) . when the patients were stratified according to prostate size , mean ipspsa levels were significantly lower than opspsa levels , irrespective of prostate size ( table 1 ) . various physiologic and benign pathologic processes can lead to elevations of the serum psa level . these factors include nonmalignant diseases of the prostate , such as benign prostatic hyperplasia , acute and subacute prostatitis , prostatic ischemia , and infarction of the prostate . urinary retention and ejaculation can also lead to increased psa levels in the absence of prostatic diseases . in addition , physical manipulation of the prostate , such as prostatic massages , cystoscopy , or in rare cases , digital rectal examination , can also increase serum psa levels [ 3 - 8 ] . there have also been many studies of biological variations in serum psa levels [ 11 - 13 ] . a more recent survey of 27 published studies suggested that a single measurement of the serum psa level may not be sufficiently precise for screening and diagnosis of prostate cancer , because the mean biological variation of psa is 20% in the range of 0.1 to 20 ng / ml for men over 50 years . with regard to the daily variability in the serum psa level , mermall et al . reported a circadian variation of serum psa with a nadir value in the early morning and a peak value at midafternoon . by contrast , tekin et al . demonstrated a diurnal rhythm in psa with a peak value at 08:00 and a gradual decline throughout the day until midnight . however , many other studies have reported that the variations in serum psa values during a 24-hour period are random without any diurnal or circadian pattern [ 17 - 20 ] . therefore , it is unlikely that there is an optimal time point during a 24-hour period at which to measure psa , and blood samples for serum psa values can be drawn from patients at any time of day . there have also been a few reports about discrepancies between outpatient and inpatient serum psa values in the same man . stamey et al . reported that serum psa levels measured 24 hours after admission decreased by a mean of 18% with a maximum of 50% when compared with preadmission levels . this may be due to the lack of activity associated with bed rest during hospitalization , and physical exertion owing to ambulatory status could cause an increase in serum psa values . confirmed the findings of stamey et al . by showing a significant difference between outpatient values and inpatient values measured after a minimum of 24 hours of bed rest . however , they found that the stressful exercise of cardiac stress testing during hospitalization had no effect on serum psa values . . also found that the serum psa levels measured 72 hours after hospitalization significantly decreased by a median of 12% compared with the values obtained immediately before admission . although the reasons for this decrease in the serum psa level are uncertain , it is probable that the lack of activity compared with the preadmission ambulatory status could contribute to the decrease in serum psa levels , because blood samples were obtained 24 to 72 hours after admission in the above 3 studies . the effect of exercise on the serum psa level is controversial . whereas exercises such as bicycle riding increased the serum psa levels in some reports , exercises such as bicycle riding or high - altitude trekking did not affect the serum psa levels in others . in the most recent study by loprinzi and kohli , participants were 16% more likely to have an elevated serum psa level for every 1-hour increase in sedentary behavior , and were 18% less likely to have an elevated serum psa level for every 1-hour increase in light physical activity . therefore , those authors suggested that individuals who engage in more sedentary behavior and lower levels of light physical activity have higher serum psa values . in the current study , we obtained the blood samples for ipspsa testing just after admission and found that the ipspsa values were decreased compared with the preadmission levels . therefore , the effects of resting and sedentary behavior did not seem to influence the results . the reasons for the decrease in serum psa levels after hospitalization are still not certain . the decrease in ipspsa levels compared with opspsa levels , although not significant , in patients aged 20.39 years and with psa < 4 ng / ml might have been due to the small sample size of these subgroups compared with the other subgroups . psa variability may be related to analytical variation according to the methods of psa measurement , sample handling , and laboratory processing . therefore , we excluded patients in whom opspsa was not measured in our hospital to eliminate the effects of analytical variation . serum psa was measured by using two different immunoassay systems according to the period of psa testing in our hospital . however , because our focus of analysis was the comparison of opspsa and ipspsa in the same man with an interval between the two psa measurements of within 1 month , and opspsa and ipspsa in the same man were measured by using the same immunoassay system , there should be no analytical variation according to the laboratory processing . we also excluded patients with an interval of more than 1 month between opspsa and ipspsa measurements to minimize the possible effect of biological variation in serum psa levels . we also excluded patients who had a pathologic diagnosis of prostate cancer , because the serum psa level might be influenced during the time interval between the opspsa and ipspsa . in our previous report about short - term ( median interval , 29 days ; range , 7 to 90 days ) psa velocity before prostate biopsy in 670 patients with serum psa levels of 2.5 to 20 ng / ml , median short - term psa velocity ( ng / ml / mo ) , which was defined as ( [ ipspsa - opspsa]/interval [ days])30 , was significantly different between patients with benign histology and those with prostate cancer ( -0.70 and -0.20 , respectively ; p=0.021 ) . the factor of recent ejaculation , which can affect the serum psa level , was not analyzed in this study . another limitation of our study is that the time of blood sampling was different for opspsa and ipspsa . the blood sampling for the former was mostly done in the morning or early afternoon , whereas that for the latter was done in the late afternoon . as discussed earlier , the influence of the timing of psa measurement within a day is controversial . moreover , the steps following the blood sampling , i.e. , from the handling of samples until the analysis , were identical for both , excluding any possible influence from preanalytical differences . nevertheless , we believe that the ipspsa levels were decreased compared with opspsa levels ; thus , the hospitalization itself decreased the serum psa levels . therefore , serum psa values should be measured on an outpatient basis for the serial monitoring of psa . a larger prospective hospitalization decreases serum psa values compared with those measured on an outpatient basis in patients with benign prostatic diseases . therefore , serum psa values should be measured on an outpatient basis for the serial monitoring of psa levels .

purposeto investigate whether hospitalization influences serum prostate - specific antigen ( psa ) values.materials and methodstransrectal ultrasound - guided prostate biopsies were performed for detecting prostate cancer in 2,017 patients between february 2001 and april 2011 at ajou university hospital . of those patients , 416 patients who were hospitalized for prostate biopsies , whose serum psa values were measured at the outpatient department within 1 month of admission and also just after admission , and who had negative prostate biopsy results were included in the present study . we retrospectively reviewed the data of the 416 patients and compared the serum psa values measured in the outpatient department with those measured during hospitalization.resultsamong all 416 patients , the interval between the two psa measurements was 22.2 days ( range , 3 to 30 days ) and the prostate size measured by transrectal ultrasonography was 53.63 ml ( range , 12.8 to 197.9 ml ) . among all patients , mean serum psa levels measured during hospitalization were significantly lower than those measured in the outpatient department ( 6.69 ng / ml vs. 8.01 ng / ml , p<0.001 ) . when stratified according to age , the presence or absence of chronic prostatitis in the biopsy pathology , serum psa levels , and prostate size , the serum psa levels measured during hospitalization were significantly lower than those measured in the outpatient department in all subgroups , except in cases aged 20 to 39 years and those with psa < 4 ng / ml , in whom no significant differences were shown.conclusionshospitalization decreases serum psa values compared with those measured on an outpatient basis in patients with benign prostatic diseases . therefore , serum psa values should be checked on an outpatient basis for serial monitoring .

since the first bacterial genome was completed in 1995 ( 1 ) , more than 170 bacterial genomes have been sequenced ( 2 ) . another 500 are currently being sequenced and many will likely be released in the coming year . with current sequencing technology , it is now possible to sequence and assemble an entire bacterial genome in less than a week . this flood of extremely valuable genomic data is threatening to overwhelm our capacity to assimilate and process it . never before has so much information been available about so many different bacterial species . a growing challenge facing microbiologists and bioinformaticians alike is to find ways to better manage , display and compare these data . several database resources have appeared over the past few years to help in this regard . genbank and embl now maintain up - to - date microbial genome sequence archives , while mip 's pedant ( 3 ) and tigr 's cmr ( 4 ) provide more detailed annotations and statistics on many microbial genomes . however , the tendency for most consolidated microbial databases is to present sequence - related data in a text - only or in a relatively limited graphic format . this text - only approach ignores the rich information that can be gained by displaying interactive graphical maps of individual genes or open reading frames ( orfs ) in their genomic context or by comparing different genomic maps to one another . given the enormous success of ensembl 's ( 5 ) dual textual and graphical approach to presenting metazoan genomes , we decided to investigate the possibility of using a similar concept to present bacterial genomic data . here , we describe a highly visual , fully interactive , self - updating , web - enabled database called bacmap . bacmap is a unique resource that allows users to rapidly compare , explore and search through hundreds of bacterial genomes . bacmap is essentially an electronic atlas of bacterial genomes with hundreds of colorful , clickable maps , all linked to thousands of megabytes of detailed annotation . by pre - calculating the image maps and annotations , bacmap allows users to rapidly search , zoom in , rotate and zoom out of its circular genomic maps . furthermore , no special browser plugins or applets are required , making bacmap fully compatible with a wide range of web browsers , hardware configurations and operating systems . the bacmap homepage contains a list of all publicly released eubacterial and archaebacterial genomes ( 177 at the time of this writing ) . species card , which provides detailed information about the organism in tabular format , including its taxonomy , gram staining properties and number of chromosomes . a brief description of the species , discussing its physiology , general characteristics , ecological niche and relevance to human or animal disease is also given . below each genome entry is a list of the genome 's constituent chromosomes , sorted by length . the text search and blast buttons are linked to the text search and blast search interfaces for the chromosome . stats button displays several graphs concerning the chromosome 's genomic and proteomic characteristics . finally , the map button generates a full - screen circular image of the entire bacterial chromosome . on the lower edge of the image is a brief synopsis of the chromosome , including the genbank accession number of the source sequence . the full view map consists of two concentric rings of forward and reverse strand genes ( protein and rna ) , with tick marks indicating chromosomal position . some maps may contain additional feature rings ( e.g. cog functional classifications ) depending on which annotations are currently available for the chromosome . clicking on any of the tick marks in the sequence ruler expands the map by a pre - defined step , and centers the view on the base closest to the tick mark that was clicked . the map view can also be manipulated using the control panel located at the bottom of the map . expand + button zooms in on the current view , while expand returns to a view showing more of the map with reduced detail . the view can also be shifted along the chromosome backbone in the clockwise and counterclockwise directions , using the hyperlinked gene labels are visible from the first zoom level onwards . pointing to a gene label displays the start and stop positions of the gene , as well as its known or predicted function . clicking on the gene label replaces the map view with the corresponding gene card. the rapid response to these operations is achieved by pre - rendering all the images for each chromosome and the corresponding html image maps . the image rendering is done by a recently developed in - house program called cgview , which was designed to generate annotated images of circular chromosomes or plasmids . on average , more than 4000 png images and html image maps were generated for each chromosome in bacmap . the chromosome maps can be explored manually , or with the assistance of two search tools integrated with the bacmap database . one tool is a boolean text search , which can be used to search for specific gene names , protein names , alternate names or partial names . any matches returned from a text search are shown on a dynamically generated search results map . a textual list of the matching genes is also returned , with hyperlinks provided so that the relevant pre - rendered chromosomal map views and gene cards can be quickly retrieved . the second searching method uses blast ( 6 ) to identify genes that are similar to a user - supplied sequence . the blast method can be used as an alternate route to find genes / proteins if the text search is unsuccessful , or as a means to identify orthologs and paralogs of a sequence of interest . as with the text search , the blast results are shown graphically and textually , with hyperlinks provided for accessing the chromosome maps and gene cards . figure 1 provides a montage of bacmap images to demonstrate the image quality , utility and general operation of the bacmap database . these annotations , presented as gene cards , are accessible by clicking on the gene labels displayed on individual chromosome maps , or by using the text and blast searches . the cards are built using a variety of public databases , such as uniprot ( 7 ) and pdb ( 8) , as well as numerous in - house prediction programs . indeed , many of the annotation methods employed for bacmap were originally developed and validated in the preparation of the cybercell database a comprehensive molecular database on escherichia coli ( 9 ) . each time a new bacterial chromosome is added to the bacmap database , an initial set of gene cards is constructed . these preliminary cards , which can be generated rapidly , serve as a source of basic gene and protein information until the more extensively annotated cards have emerged from the analysis pipeline . the final cards typically contain about 50 + fields of annotation , including information on a variety of sequence statistics , potential orthologs and paralogs , predicted function , predicted secondary structure and predicted subcellular location . the annotations are continually updated as more information becomes available and as better prediction programs are developed . a partial listing of bacmap 's current annotation fields along with their sources and/or methods is given in table 1 . in addition to an extensive collection of genome maps and annotations , bacmap also supports flat file downloads of all textual data associated with each genome . this includes complete genomic dna sequence data , fasta files of all identified genes , fasta files of all identified proteins and a flat file of all the bacmap annotations for each gene / protein . these files are accessed by clicking on the download button associated with each chromosome listed on the bacmap homepage . in addition , bacmap provides a number of charts and graphs for each chromosome , which illustrate nucleotide and amino acid usage , distribution of protein lengths , distribution of functions and distribution of predicted subcellular locations . these charts , which are regularly updated in conjunction with the bacmap gene cards , can be accessed using the stats buttons . while bacmap does not yet support relational queries for comparative genomics , it does support cross - genome comparisons . by separately querying and displaying chromosome segments from two or more species , users may visually compare bacterial orthologs , operon structure , gene synteny or gene context , chromosomal gene distributions or functional localizations . this software obtains new bacterial genome genbank records from the ncbi and then passes them to the programs that generate the bacmap database content . the only database entries that require some limited manual editing are the species cards. to summarize , bacmap is an interactive electronic atlas of bacterial genomes . it builds from and extends upon the very successful visualization concepts originally introduced in ensembl , providing a map - centric or visually centered approach to exploring bacterial genomic data . the rich annotations in bacmap , coupled with its detailed , color - coded image maps , should permit users to look at bacterial genomes with increasing detail . funding for this project was provided by the alberta science research authority , western economic diversification , canada , and genome prairie ( a division of genome canada ) .

bacmap is an interactive visual database containing fully labeled , zoomable and searchable chromosome maps from more than 170 bacterial ( archaebacterial and eubacterial ) species . it uses a recently developed visualization tool ( cgview ) to generate high - resolution circular genome maps from sequence feature information . each map includes an interface that allows the image to be expanded and rotated . in the default view , identified genes are drawn to scale and colored according to coding directions . when a region of interest is expanded , gene labels are displayed . each label is hyperlinked to a custom gene card which provides several fields of information concerning the corresponding dna and protein sequences . each genome map is searchable via a local blast search and a gene name / synonym search . bacmap is freely available at http://wishart.biology.ualberta.ca / bacmap/.

during 20032009 , patients at institut universitaire du cancer , toulouse , were randomly tested for hev infection ; patients who had elevated liver enzymes were routinely assessed for the virus . patients were generally counseled to avoid undercooked foods or products that increased risk for hev transmission according to guidelines from the french ministry of health . hev rna was detected and quantified by pcr testing , and hev igm and hev igg were assessed with commercially available kits : the eiagen hev igg and igm kits ( adaltis , casalecchio di reno , italy ) before 2012 , and the wantai hev igg and igm enzyme - linked immunosorbent assay ( beijing wantai biologic pharmacy enterprise co. , ltd , beijing , china ) since 2012 . diagnosis of hepatitis e required liver enzyme abnormalities and detectable hev rna in serum or fecal samples . chronic hev infection was defined by hev viremia lasting > 3 months ( 1 ) . ribavirin monotherapy was proposed for infected immunocompromised patients beginning in may 2010 , after publication of preliminary data reporting its efficacy in such patients ( 12 ) . assessment for administering ribavirin treatment was made on a case - by - case basis according to clinical and therapeutic context . although there was no formal protocol , the general consensus was to consider ribavirin with the intent to complete treatment for the underlying disease rather than biologic criteria such as alanine aminotransferase levels or hev viral loads . , we identified 26 patients whose laboratory test results showed hev replication . clinical characteristics and treatments of patients with hematologic malignancies before or within the 6 months after the diagnosis of hepatitis e na , not applicable ; nhl , non - hodgkin lymphoma ; sct , stem cell transplant ; ast , aspartate aminotransferase ; alt , alanine aminotransferase ; gt , gamma - glutamyl transferase . aggressive non - hodgkin lymphoma : burkitt - like b cell lymphoma ( n = 1 ) , anaplastic t - cell lymphoma ( n = 1 ) , diffuse large b cell lymphoma ( n = 2 ) . others : myeloproliferative neoplasm ( n = 1 ) ; granulocytic sarcoma ( n = 1 ) ; myeloid variant of hypereosinophilia with fip1l1-pdgfr rearrangement . p value refers to comparison between patients who received ribavirin and patients who did not . data from 6 patients of this cohort were previously reported in a preliminary study ( 6 ) . the diagnosis of hev infection occurred a median of 10 ( range 0227 ) months after identification of the hematologic disorder . no persons in the study had traveled outside france during the year before hepatitis was diagnosed . primary signs and symptoms were fever , diffuse or abdominal pain , vomiting , or asthenia ; 16 patients were asymptomatic . hev rna was detectable in the serum of all patients and in the fecal samples of 88% of patients ( hev strain genotype 3f in 73% , 3c in 23% , and 4b in 4% ) . of 23 tested patients , 9 ( 36% ) had hev igg and 13 ( 61% ) had hev igm . this finding emphasizes the need to rely on hev rna detection rather than serologic results for hev diagnosis in immunocompromised patients . hev was diagnosed concomitantly to the onset ( n = 2 ) or at relapse ( n = 2 ) of the hematologic malignancy , which raises the hypothesis of an association between hev infection and carcinogenesis ( 13 ) . liver test results for 26 patients at diagnosis of hepatitis e and at months 1 , 3 , and 6 , toulouse , france , 20032014 . a ) aspartate aminotransferase st ; b ) alanine aminotransferase ; c ) gamma - glutamyl transferase . twelve patients were treated with ribavirin after a median delay of 1 month ( range 0.512 months ) after the onset of hepatitis . among the 14 patients with acute hepatitis e who did not receive ribavirin , 9 showed spontaneous clearance of hev within the 2 months after diagnosis . the remaining 5 patients had prolonged hev replication lasting > 3 months , including 1 patient who had superimposed nonalcoholic steatohepatitis and had developed overt cirrhosis and refractory ascites . immunosuppression withdrawal in 1 patient , who received allogeneic - sct and in whom chronic hepatitis e developed , resulted in a severe transient incident of elevated liver enzymes , followed by spontaneous clearance of the virus . oral ribavirin was administered to 12 patients at a median dose of 800 mg / d ( range 6001,000 mg / d ) ; 1 patient had chronic hepatitis . in all patients , hev rna became undetectable after 30 ( range 1060 ) days , and liver blood tests were normalized after 2.5 ( range 112 ) months . the heterogeneity of timing and duration of treatment likely reflected the progressive introduction of ribavirin into current practice and the specific context of several patients . in general , 2 consecutive negative pcrs during 1 month were required to discontinue ribavirin . three patients had abnormal liver test results and hev recurred within the month after ribavirin treatment was withdrawn , including 2 who received ribavirin for 1 month only . thus , the combination of a 3-month intake of ribavirin , 2 negative hev blood rnas at month 2 and 3 , and negative rna levels in stools at month 3 seems to be an appropriate approach . overall , aspartate aminotransferase and alanine aminotransferase serum levels were significantly higher at 6 months in patients who did not receive ribavirin compared with patients who did ( p = 0.03 and p = 0.01 , respectively ; technical appendix table ) . ribavirin was well tolerated among 10 of the 12 recipients and did not require specific red blood cells or erythropoietin support . one patient , 84 years of age , became anemic while receiving 1,000 mg of ribavarin per day , but treatment was continued . treatment was discontinued for another patient , 41 years of age , when pruritus developed after 2 weeks of therapy . after sot , chronic hepatitis develops in 60% of untreated hev - infected patients ( 3 ) . here , we show that patients with hematologic malignancies are also at risk for chronic hev infection . sot patients showed a high response rate to ribavirin treatment ( 11 ) . because most hematologic malignancies required intensive immune treatments that should not be postponed , hev infection could notably alter the therapeutic schedule of some patients ( 5,6 ) . cytotoxic treatments or sct were postponed while awaiting hev clearance for 5 patients , of whom 4 reached complete hematologic response . among the 12 ribavirin - treated patients , thus , although spontaneous but unpredictable hev clearance could occur in some patients , therapeutic intervention is often mandatory to fully complete the therapeutic schedule of the underlying disease and to prevent chronic hepatitis . confirming previous reports ( 11,12 ) , a 3-month course of ribavirin induced complete and sustained hev eradication in most if not all patients . moreover , ribavirin may also decrease the risk for nosocomial hev transmission among patients ( 14 ) . the retrospective nature prevented accurate assessment of the incidence of hev infection among patients who have hematologic malignancies . some obvious bias , including occurrence of hev viremia without concomitant liver tests abnormalities or inability to ask patients about their exposure risk to hev , also need further considerations . by inducing a rapid clearance of hev hepatitis e can induce chronic hepatitis and cirrhosis in patients with hematologic cancers ; patients with liver enzyme abnormalities should be screened for hev infection and a 3-month course of ribavirin proposed to avoid postponement in the treatment of patients who have the underlying disease as well as chronic hepatitis or cirrhosis . characteristics and outcomes of patients with hematologic malignancies treated with ribavirin for prevention of chronic hepatitis .

findings among a cohort of 26 patients who had hematologic malignancies and hepatitis e virus ( hev ) infection support that hev can induce chronic hepatitis . however , a 3-month course of ribavirin can induce a rapid viral clearance , reducing the risk for chronic hepatitis and enabling continuation of cytotoxic treatments for underlying malignancies .

high concentrations of factor viii and von willebrand factor ( vwf ) contribute to a hypercoagulable state in hyperthyroidism . lower vwf concentrations in hypothyroidism may protect against venous thrombosis .. studies have suggested hypercoagulable state in hypothyroidism . 45-year - old female presented in emergency with complaints of headache since 1 month , vomiting since 1 day , and weakness with numbness and tingling in right half of body since 12 h. her weakness progressed to quadriparesis overnight . on examination she was drowsy and disoriented . on neurological examination , reflexes were present and muscle tone was normal but power was 1/5 on right side and 3/5 in left half of body . thyroid function tests were suggestive of subclinical hypothroidism t3 - 0.94 ng / ml , t4 - 8.36 g / dl , tsh - 13.92 miu / ml . thrombophilia profile including prothrombin time index / international normalized ratio , serum homocysteine ( 5.6 mol / l ) , ana , lupus anticoagulant , igm and igg cardiolipin antibodies , and apla antibodies were negative . mri brain showed loss of flow void of superior sagittal and left transverse sinuses with altered signal appearing hyperintense on t1w and fluid - attenuated inversion recovery ( flair ) images suggesting thrombosis . she was put on heparin and warfarin . her headache improved after 4 days of treatment and patient was discharged after 7 days with no residual neurological deficit . hypothyroidism favors a procoagulant by decreasing fibrinolysis ( high levels of alfa2-antiplasmin and plasminogen activator inhibitor-1 ) , inducing hyperhomocysteinemia , and high c - reactive protein ( crp ) . decreased fibrinolytic capacity , high crp levels , and coagulation factors abnormalities can occur even in subclinical hypothyroidism . elevated plasma thrombin - activatable fibrinolysis inhibitor levels were observed in patients with mild and overt hypothyroidism , and levothyroxine treatment was effective in reducing these levels . chronic low - grade inflammation and impaired nitric oxide availability in the endothelium have been demonstrated in hypothyroidsm . this case emphasizes the need for thyroid evaluation in all patients with cvt and other venous thromboembolic event even in the absence of clinical signs of hypothyroidism .

cerebral venous thrombosis ( cvt ) is a multifactorial condition which is described as idiopathic in 12.5% of patients . hyperthyroidism has been associated with cvt in many case reports , and increased levels of factor viii and von willebrand factor ( vwf ) have been proposed as the possible link in this association , but only few rare case reports have described an association of hypothyroidism with cvt . we report here a case of autoimmune thyroiditis presenting with cvt .

however , as circles can be generated through recombination between repetitive sequences residing at different genomic loci , recombination between the highly abundant human transposable elements is not an unlikely scenario . one prominent candidate for generating circular dnas would for example be the alu family that is present in more than 1 million copies in human genomes . although several subfamilies of alu elements have evolved during primate evolution , consensus sequences from the different families are highly similar but for a few diagnostic sites . alu elements are further known to participate in unequal homologous recombination , which has been associated with a range of human disease states . although the sizes of coding sequences are highly uniform across eukaryotic genomes , the presence of introns means that the total size of human genes can exceed several hundreds of kilobasepairs . although the possibility of entire human genes ending up in relatively small circular dnas would at first appear to be limited , large circular dnas as well as relatively short human genes would render this scenario far more conceivable . first , a circular dna encompassing 39 kb has been reported in yeast , containing 2 histone genes as well as a centrome and origins of replication . more than 80% of the human genes in the ensembl annotation would fit in circles of this size . second , numerous human genes are deprived of introns and therefore occupying a limited genomic space . intronless human genes presumably generated through retrotransposition using the line l1 machinery are enriched for signal transducing- and regulatory genes , and for tissue - specific expression in brain or testis . clearly , such relatively short genes could be contained in circular dnas from a more modest size range . in nitrogen - deprived yeast cultures amplifications and deletions of the gap1 gene have been associated with the presence of circular dnas harboring the gap1 gene and an origin of replication . as nitrogen limitation results in elevated gap1 expression , this prompted speculations that dna circularization could provide a means for the cell to increase gap1 activity through the presence of multiple gene copies residing in dna circles . although the number of cell divisions varies immensely between human tissues , and the specific nature of mammalian replications origins is still not well - understood , circular dna carrying human genes could increase in numbers , providing additional gene copies to the cell . yet , transcriptional regulation in mammalian cells often works at a regional scale , where genetic promoter regions physically interact with enhancer structures located at a considerable distance . transcription is further regulated by epigenetic modifications , which can travel across larger genomic regions the spread of which intriguingly can be stopped by the presence of transcriptionally active transposable elements . transcription initiated at one genomic site may also drive or repress transcription at neighboring sites . this is referred to as transcriptional interference , a phenomenon that may even shape genome architecture . a gene residing in a circular dna should hence evade such regional regulatory effects , and one may therefore speculate if the major impact of circular dnas is not primarily in gene copy number variations , but in taking genes out of their regulatory context . it is also conceivable that gene copies residing in circular dnas bind regulatory proteins , thereby potentially changing the dynamics and kinetics at other chromosomal loci . similarly , transcripts from genes in circular dnas may act as sinks by binding regulatory rnas as well as proteins . such an effect may obviously manifest itself without the entire gene sequence being present in circular dnas , and circular dnas harboring incomplete gene sequences may serve as previously described regulatory pseudogenes . in summary , we have previously shown that circular dnas are generated from genomic copies of yeast transposable elements . it is currently unknown to which extent this is happening in mammalian genomes rich in transposable element sequences . circular dnas have a huge potential in altering gene copy numbers , and as speculated here in harboring genes that will be taken out of their regulatory context . whether the generation of circular dnas has an adaptive aspect , and may add novel functionality to the cell is of course an entirely different question . as circular dnas from ribosomal genes are found in aging yeast cells , circularization may simply reflect a genomic deterioration associated with cellular decay . the true extent to which human transposable elements are a source for the generation of circular dnas will be determined in coming experiments . but crucially , such experiments need to be tailored toward circular structures both in experimental design and in downstream analysis .

abstractcircular dnas are extra - chromosomal fragments that become circularized by genomic recombination events . we have recently shown that yeast ltr elements generate circular dnas through recombination events between their flanking long terminal repeats ( ltrs ) . similarly , circular dnas can be generated by recombination between ltrs residing at different genomic loci , in which case the circular dna will contain the intervening sequence . in yeast , this can result in gene copy number variations when circles contain genes and origins of replication . here , i speculate on the potential and implications of circular dnas generated through recombination between human transposable elements .

natural killer ( nk ) cells are a subset of lymphocytes that play a central role in the innate immune response to tumors and viral infections . these cells kill by a mechanism involving the release of small cytolytic granules containing granzyme b and perforin that induce cell death in the target cell . although nk cell numbers can be enumerated by immunophenotyping on the flow cytometer , an important limitation in the study of nk cells is the lack of availability of high throughput assays for the detection of the functional activity of nk cells . during degranulation , cytolytic granules in nk cells are released and the lysosome - associated membrane protein-1 ( lamp-1 , cd107a ) which is present on cytolytic granules surface is transported to the cell surface and becomes accessible for antibody binding . this allows identification of activated nk cells , making it an attractive biomarker for assessing the integrity of the granule exocytosis mechanism . the assays reported till date for determination of the degranulation marker use peripheral blood mononuclear cells ( pbmc ) or pure nk cells and k562 cell line as stimulants . pbmc separation or nk cells isolation requires large volume of blood sample which is difficult to obtain especially from pediatric patients below the age of 1 year and patients with cytopenia . cell separation procedures are time consuming and may also lead to loss of physiological conditions , such as soluble factors like cytokines , growth factors , or chemokines . using k562 cell line as stimulant requires specialized cell culture facility for maintaining cell line . thus this assay is not feasible in routine clinical set - up . in 2010 , wheeler et al . reported a degranulation assay using of phytohaemagglutinin ( pha ) instead of k562 cells , which made it feasible in clinical set - up . however , in this assay pbmc were used and thus involves cell separation procedure . for these reasons , we have developed a rapid flow cytometry - based assay for measuring nk cell degranulation using whole blood and phorbol-12-myristate-13-acetate ( pma ) and calcium ionophore ( ca - ionophore ) as stimulants . the results were compared with the conventional assay ( assay using k562 cells as stimulant ) and reproducibility of the assay was evaluated by determining intra - assay and interassay variation . hemophagocytic lymphohistiocytosis ( hlh ) is a disorder of hyperinflammation resulting from impaired clearance of pathogens due to defective nk cell or cytotoxic t cells ( ctl ) . hlh is divided into familial hemophagocytic lymphohistiocytosis ( fhl ) resulting from inherited defect in the granule mediated cytotoxicity of cytotoxic cells ( nk cells and ctl ) and acquired hlh which is caused due to overwhelming trigger of viral infections , malignancies , or rheumatic diseases . fhl can be further subclassified into fhl2 caused due to perforin deficiency ( fhl-2 ; mim 603553 ) and genetic defects affecting proteins involved in transport , membrane fusion , or exocytosis of perforin containing lytic granules such as munc 13 - 4 ( fhl-3 ; mim 608898 ) , syntaxin 11 ( fhl-4 ; mim 603552 ) , and syntaxin binding protein 2 ( munc 18 - 2 ) ( fhl-5 ; mim 613101 ) . griscelli syndrome type 2 ( gs2 ) and chediak - higashi syndrome ( chs ) , caused by mutations in rab27a and lyst , respectively , are also associated with development of hlh . diagnosis of fhl is important as these patients need hematopoietic stem cell transplantation ( hsct ) for long term survival . in literature , the nk cell degranulation assay has been shown to be useful in diagnosis of familial hemophagocytic lymphohistiocytosis ( fhl ) associated with defect in the granule release mechanism ( fhl35 , chs , gs2 ) [ 4 , 6 ] . however in fhl2 patients , perforin protein is defective whereas the granule release mechanism is not affected and hence this assay is expected to be normal in these patients . hence , to validate the usefulness of this assay in a clinical laboratory , it was performed in different groups of hlh patients and the outcome was correlated with the diagnosis . fresh heparinized peripheral blood samples were collected from 30 healthy donors 20 to 55 years of age , including both males and females . further diagnosis of fhl2 ( perforin deficiency ) was carried out by flow cytometry and that of fhl3 ( munc 13 - 4 deficiency ) and fhl4 ( syntaxin 11 deficiency ) by western blotting for respective proteins and also molecular characterization of the respective genes . chediak higashi syndrome ( chs ) and griscelli syndrome 2 diagnosis was based on clinical manifestations and microscopic examination of hair mount and peripheral blood smear . for validation of the proposed assay total , 19 fhl [ 1 fhl2 , 7 fhl3 , 1 fhl4 , 2 chediak higashi syndrome ( chs ) , and 1 griscelli syndrome type 2 ] and 8 acquired hlh patients were evaluated . to determine the specificity of the assay , 18 patients with infections ( namely , 4 viral , 11 bacterial , and 3 fungal ) and receiving treatment for the same this group consisted of patients of age ranging from 7 days to 60 years , both male and female . each subject gave informed consent for participation in the study after the nature and possible consequences of the studies had been fully explained . k562 cells ( a human erythroleukemia cell line ) were cultured in rpmi 1640 media ( gibco , life technologies ) supplemented with 10% ( v / v ) fetal bovine serum ( fbs , sigma ) , l - glutamine at 37c under 5% ( v / v ) co2 . 1.5 l of 1 mg / ml pma ( sigma chem . louis , mo ) was added to 2.5 ml of incomplete rpmi 1640 media to obtain concentration of 0.6 g / ml . serial dilution with incomplete media was carried out to obtain final concentration of 0.15 g / ml . 4.5 l of 1 mg / ml ca ionophore ( ionomycin , sigma chem . louis , mo ) was added to 1.5 ml of incomplete rpmi 1640 media to obtain final concentration of 3 g / ml . absolute white blood cells ( wbc ) count and absolute lymphocyte count ( alc ) was determined using sysmex xs-800i cell counter . for each sample 3 tubes were processed , namely , unstimulated , k562 stimulated , and pma + ca - ionophore stimulated . 100 l of whole blood sample ( alc 2 10 cells / ml ) and 5 l fitc conjugated anti - cd107a ( bd biosciences ) were added to each tube . 200 l of 2 10/ml k562 cells was added to the k562 stimulated tubes . 100 l of pma ( 0.15 g / ml ) and 100 l ca ionophore ( 3 g / ml ) were added to the pma + ca - ionophore stimulated tubes and the final volume was adjusted to 500 l with incomplete rpmi 1640 media . all the tubes were incubated for 2 h at 37c under 5% ( v / v ) co2 . thereafter , samples were washed with pbs and stained with anti - cd56-pe ( ncam16.2 ) and anti - cd3apc ( bd bioscience , san jose , ca ) , followed by erythrocyte lysis of blood samples using facs lysing solution . the flow cytometric analysis was performed on facsaria using diva software ( becton dickinson , san jose , ca , usa ) . the cut - off was set on unstimulated tubes and the increased cd107a expression in the same sample after stimulation was noted . the increase in cd107a expression using k562 as stimulant and pma - ca ionophore as stimulants was compared using statistical tests . statistical analysis . two - tailed t - test was used to compare assays and also normal controls and fhl patients . the results were reported to be statistically significant if the p value was < 0.05 . in our study , the nk cell degranulation assay results obtained using whole blood ( 26 4% ) and pbmc ( 25 4% ) were comparable . till date only one article of comprehensive analysis of nk cell function in whole blood samples has been published . in this report , cd107a surface expression was evaluated by stimulating nk cells with k562 cells using whole blood sample and no significant difference in the results was observed . however , this assay requires k562 cells and thus specialized laboratory with well established cell culture facilities and experienced personnel is essential for maintaining the cell line . it has also been reported that variation in this assay may be observed because of the difference in the source and passage of k562 stimulator cells . this all adds to the cost in clinical set - up and also performing the assay on urgent pediatric samples is not always feasible . thus , considering these difficulties , here we report nk cell degranulation assay using whole blood sample instead of pure cells and pma + ca - ionophore as nk cell stimulants instead of conventional stimulant k562 cell line . k562 cell line is mhc i devoid and hence it acts as target cells for nk cells . whereas pma is a substitute for diacylglycerol ( dag ) , one of the adaptor proteins required for the activation of protein kinase c [ 8 , 9 ] and ca - ionophore increases intracellular calcium levels . therefore , the combination of pma + ca - ionophore facilitates the activation of protein kinase c and an influx of intracellular calcium which are the necessary signaling events for degranulation [ 8 , 11 ] . on comparing assays using these stimulants , it was observed that the difference in upregulation of cd107a expression on nk cells by stimulation with pma + ca - ionophore ( 34.05 8.44 ) was significantly higher than that with k562 cells ( 13.7 4.18 ) ( p < 0.0001 ) ( figure 1 ) . since cd107a is higher by using pma + ca - ionophore , it allows the clear distinction of patients with normal and abnormal granule release mechanism especially in case of borderline degranulation as reported in few patients with late - onset fhl4 and fhl5 . ( 2004 ) had demonstrated upregulation of cd107a expression on nk cells stimulated with pma / ionomycin ( average frequency 21.5% ) . in this study , pbmc were used , the concentration of pma and ionomycin used were 2.5 g / ml and 0.5 g / ml , respectively , and the incubation time was 6 h in presence of monensin ( to avoid internalization of cd107a ) . however in the assay proposed in our study , whole blood was used and in spite of incubating the samples for only 2 h without monensin ; the average frequency observed was 35.6 6.95% ( n = 30 ; range 21.348.8% ) , which is much higher than reported . the interassay and intra - assay coefficient variation for this assay were 3.66% and 5.17% , respectively , thus demonstrating reproducibility of the assay . hemophagocytic lymphohistiocytosis ( hlh ) is a disorder of immune dysregulation and is classified into familial hlh ( fhl characterized by defect in granule exocytosis ) and acquired hlh . specifically , patients with fhl3 , fhl4 , fhl5 , chediak higashi syndrome , and griscelli syndrome are known to have defective granule exocytosis and hence have low expression of cd107a expression on stimulated nk cells . fhl2 patients have defect in perforin expression with normal granule release mechanism whereas acquired hlh patients have no defect in perforin expression and granule release mechanism . hence , to validate this assay , 19 hlh patients , including 1 fhl2 ( prf1 gene defect ) , 7 fhl3 ( unc13d gene defect ) , 1 fhl4 ( stx11 gene defect ) , 2 chs , 1 gs2 , and 8 acquired hlh patients were analyzed . amongst these , as expected fhl3 , fhl4 , gs2 , and chs patients had low expression of cd107a on stimulated nk cells ( 0.24.7% ) compared to fhl2 patients ( 41.8% ) , acquired hlh patients ( 21.648% ) , and healthy controls ( 21.348.8% ) ( p < 0.0001 ) ( figure 2 ) . this assay was not tested in fhl5 patients . to determine the specificity of this assay , it was carried out in 11 patients with bacterial infection , 4 with viral infections , and 3 with fungal infections ; 8 of these patients were receiving treatment for the same . all these patients had expression of cd107a on nk cells in normal range ( 2046% ; normal range 21.348.8% ) , indicating the results of this assay are not influenced by the infection or therapy . to conclude , cd107a is a reliable marker of nk cell cytotoxicity and helps in comprehensive evaluation of nk cell function . since , in the described assay , whole blood is used and no cell line is used , it requires reduced blood volume , is cost - effective , is less time consuming , and avoids necessity for specialized laboratory for cell culture , which makes it applicable in routine clinical set - up . along with the existing perforin assay for identifying fhl2 patients , this assay aids in distinguishing fhl patients with defective granule release mechanism ( namely , fhl3 , fhl4 , gs , and chs ) from acquired hlh patients which is essential in their management .

natural killer ( nk ) cells play important role in innate immunity against tumors and viral infections . studies show that lysosome - associated membrane protein-1 ( lamp-1 , cd107a ) is a marker for degranulation of nk and cytotoxic t cells and its expression is a sensitive marker for the cytotoxic activity determination . the conventional methods of determination of cd107a on nk cells involve use of peripheral blood mononuclear cells ( pbmc ) or pure nk cells and k562 cells as stimulants . thus , it requires large volume of blood sample which is usually difficult to obtain in pediatric patients and patients with cytopenia and also requires specialized laboratory for maintaining cell line . we have designed a flow cytometric assay to determine cd107a on nk cells using whole blood , eliminating the need for isolation of pbmc or isolate nk cells . this assay uses phorbol-12-myristate-13-acetate ( pma ) and calcium ionophore ( ca2 + -ionophore ) instead of k562 cells for stimulation and thus does not require specialized cell culture laboratory . cd107a expression on nk cells using modified nk cell degranulation assay compared to the conventional assay was significantly elevated ( p < 0.0001 ) . it was also validated by testing patients diagnosed with familial hemophagocytic lymphohistiocytosis ( fhl ) with defect in exocytosis . this assay is rapid , cost effective , and reproducible and requires significantly less volume of blood which is important for clinical evaluation of nk cells .

one of the inadvertent complications that occur during implant placement in anterior mandible is a neurosensory alteration in the chin and lower lip due to improper identification and protection of the mental foramen and anterior mental loop . on radiograph the mental foramen presents as a single circular or elliptical radiolucent area bilaterally in the premolar region . several studies comparing different radiographic methods to assess the location of the mental foramen have suggested that digital panoramic radiographs show least error in the imaging of the mental foramen . green et al . demonstrated clear racial differences in the position of the mental foramen . in the present study , the change in position of mental foramen in different age groups and gender related variations were evaluated using digital panoramic radiography . the study group comprised a total of 250 patients who required panoramic radiography for various dental treatments . the age groups were 6 - 12 years , 13 - 18 years , 19 - 30 years , 31 - 50 years , and above 50 years . each age group was divided into two subgroups based on gender having 25 subjects in each subgroup . digital panoramic radiographs were taken using the digital panoramic radiography machine , planmeca promax ( helsinki , finland ) with a total filtration of 2.5 mm aluminium ( al ) equivalent . each radiograph was standardized while taking the radiograph by tilting the patient 's head 5 downward with reference to frankfurt 's horizontal plane as suggested by dharma et al . position of mental foramen ( x ) was fixed in relation to three reference points [ figure 1 ] : parameters measured in the study : alveolar crest ( a ) , base of mandible ( b ) , median reference line ( c ) , and position of mental foramen ( x ) alveolar bone crest ( a)base of mandible ( b)a midline reference point ( c ) ( a line is drawn from the anterior nasal spine to the most inferior portion of mentis ) . alveolar bone crest ( a ) a midline reference point ( c ) ( a line is drawn from the anterior nasal spine to the most inferior portion of mentis ) . measurements in millimeters were taken on both sides of the mandible according to the following parameters : distance from the reference line to mental foramendistance from the alveolar crest to mental foramendistance from the base of mandible to mental foramen . distance from the reference line to mental foramen distance from the alveolar crest to mental foramen distance from the base of mandible to mental foramen . there was no statistical difference between the positions of the mental foramen on either side of a patient and so the mean was taken as a single measurement per sample . the data collected were subjected to statistical analysis using paired student 's t - test . the mean distance of position of mental foramen from reference line , alveolar bone crest , and the base of mandible of each age group are shown in figure 2 . comparisons between male and female patients for each age group are given in tables 15 . graph showing the mean distance of mental foramen position in each age group comparison between males and females in the age group 6 - 12 years comparison between males and females in the age group 13 - 18 years comparison between males and females in the age group 19 - 30 years comparison between males and females in the age group 31 - 50 years comparison between males and females in the age group above 50 years in the 6 - 12 years age group : statistical correlation showed a highly significant increase in the distance of mental foramen from base of mandible in female patients ( p < 0.01 ) , and a marginally statistically significant increase in the mean distance of mental foramen from reference line in the female patients ( p < 0.05 ) when compared with the male patients . in the 13 - 18 years , 19 - 30 years , and 31 - 50 years age group : statistical correlation showed a significant increase in the distance of mental foramen from base of the mandible , reference line , and alveolar crest in the male patients ( p < 0.01 ) when compared with the female patients . in the above 50 years age group : statistical correlation showed a significant increase in the distance of mental foramen from reference line and alveolar crest in the male patients ( p < 0.01 ) when compared with the female patients . both male and females patients showed no statistically significant difference in the distance of the mental foramen from the base of mandible ( p 0.5 ) . anatomically the mental foramen lies midway between the free alveolar border and the border of the mandible closer to the latter . it varies in position according to the age and sex as substantiated in several previous studies . the aim of our study was to determine the radiographic position of mental foramen in relation to anatomical structures in different age groups in males and females . the age groups were determined according to different stages of growth and development as prepubertal , pubertal , adolescent , middle aged , and elderly people . panoramic radiographs have advantages like bilateral visualization of anatomical structures , broader visualization of hard tissue areas , and the ability to visualize adjacent areas , thus allowing for a more standardized localization of mental foramen . mental foramen position may not be revealed in a periapical radiographic film , if the position of mental foramen falls below the edge of the film , previous studies comparing digital panoramic images and conventional panoramic images showed that the measurement errors was less in the former . the variation in position of the mental foramen between females and males in group 1 may be attributed to the hormonal changes induced in growth spurts . in 1927 , hellman identified gender differences in the timing , extent , velocity , and intensity of facial growth and recognized that these changes result in an increase in size and a change in the proportions of the face . this spurt in the peak of incremental growth has been found to occur approximately 2 years earlier in females than males , at mean ages of 12 years and 14 years , respectively . the study by ochoa and nanda et al . showed that the female subjects tended to have the greatest skeletal changes between 10 years and 14 years of age . the male patients had the greatest changes between 12 years and 16 years of age and even up to 18 years of age . in groups 2 - 5 , male patients showed a statistically significant increase in the mean distance of mental foramen position from the midline and alveolar crest . this change in the mean distance of mental foramen position could be due to the growth spurt favoring males after the age of 12 and lag of growth spurt in females . the female patients demonstrated a relative slow down of growth after 14 years of age in mandibular length , whereas in the male patients jaws continued to grow significantly until 16 years of age . the first and fifth groups showed a reduced mean distance of mental foramen position when compared to second , third , and fourth groups . in the fifth age group , the mean distance of mental foramen position from the alveolar bone crest showed the least value when compared to other groups . this may be due to bone remodeling as age advances . in a study conducted by gershenson in 1986 , he found that in children before tooth eruption , the mental foramen is somewhat closer to the alveolar margin ; during the eruption period , the mental foramen descends to half way between the margins and in adults with the teeth preserved , the mental foramen is somewhat closer to the inferior border . with loss of teeth and bone resorption , the mental foramen moves upward closer to the alveolar border . the mental foramen position is not constant and changes as age advances . apart from this , there is a gender - related variation in the position of mental foramen in each age group we have studied . these variations in the position of the mental foramen have been reported to exhibit a clear trend in the pattern of their occurrence in relation to both age and gender . an accurate assessment of position of mental foramen is very useful for the prevention of postsurgical neurovascular complications and also holds the potential of contributing as an aid for forensic identification .

objective : comparative evaluation of the location of mental foramen in different age groups . determine the variation in position of mental foramen with gender using digital panoramic radiography.materials and methods : digital panoramic radiographs of 250 patients were reviewed . the study population was divided into five age groups with 50 patients each . radiographic position of mental foramen was evaluated in each radiograph based on three parameters . measurements were taken in each radiograph using planmeca dimaxis pro version 4.4.0 ( helsinki , finland ) . the collected data were subjected to statistical analysis using paired student 's t-test.results:the mean distance of position of mental foramen showed a significant variation within the five age groups . in the first group , female patients showed an increase in mean distance of mental foramen position in relation to three parameters . from the second to fifth groups , male patient showed an increase in the mean distance of mental foramen position . the first and fifth group showed a reduced mean distance of mental foramen position when compared to other age groups.conclusion:this study concluded that the position of mental foramen varies with age . there was a gender - related variation in position of mental foramen within the population too .

on november 9 , 2005 , a 17-year - old man who arrived at the airport in newark , new jersey , united states , had symptoms consistent with measles . the man was part of a group of 148 refugees from the eastleigh community in nairobi , kenya , who arrived in the united states from november 3 through 15 . genotype b3 ( subgroup b3.1 ) was identified from virus samples from this patient ; the sequence was identical to sequences from measles viruses collected in nairobi and machakos , kenya , in october 2005 ( figure ) . all but 1 of the 6 viruses collected from nairobi ( figure , mvi / nairobi.ken.xx.05 ) were from patients from the eastleigh area of nairobi , where an outbreak of measles had been reported in the somali and ethiopian communities ( 6 ) . a ) dendrogram showing the relationships among the measles reference strains representing the 23 known measles genotypes ( b3 has 2 reference strains ) . clade b ( circled ) is expanded in panel b. b ) midpoint - rooted maximum parsimony tree of nucleoprotein genes ( 450 nt ) of measles viruses from patients in the united states , mexico , the netherlands , canada , and kenya during 2005 and 2006 . the unrooted tree includes sequences from nigeria in 2005 , germany in 2006 , cte d'ivoire in 2004 , and benin in 2005 ( sequences in bold , this study ) as well as selected b3 sequences available from genbank for comparison . the identical sequences from the " kenya outbreak group " are represented by genbank accession number dq888751 , mvi / new jersey.usa/45.05 . the genbank numbers for the sequence from benin ( ben ) and the 3 sequences from cte d'ivoire ( civ ) are ef031461 , ef031458 , ef031459 , and ef031460 . * collected from the dagoretti area of nairobi ; the other nairobi sequences were from cases in the eastleigh area . also in november 2005 , this patient had visited new york city , returned to the netherlands on november 15 , noted a rash on november 23 , and was hospitalized with pneumonia and fever on november 24 . the initial investigation focused on potential settings where exposure may have occurred in new york city . the source of infection was traced to an unrecognized exposure to the patient in new jersey only after analysis of the netherlands viral sequence demonstrated complete identity with the new jersey genotype b3 virus . the possibility of an epidemiologic link between the 2 cases led to the discovery that the dutch visitor had arrived at the newark airport on november 9 and waited in the arrival area for 1 h , along with the group of refugees from nairobi . subsequently , genotype b3 was identified from patients who had had measles during december 2005 in texas , canada , and mexico . in texas , during the first 2 weeks of december , 3 cases of measles were reported in members of a family from houston . the patients had flown directly from houston to the resort area of cabo san lucas , mexico , where they stayed from november 22 through 27 . in mexico , health authorities reported 5 cases of measles beginning on december 12 among baggage handlers and other airport workers at the mexico city airport . although the earlier cases in new jersey and in the netherlands could be traced directly to the outbreak in kenya , the sources of the cases in texas , canada , and mexico were unknown . however , the sequences from texas , canada , and mexico were identical to the sequences directly linked to the outbreak in kenya ( figure ) . measles viruses in the same chain of transmission have identical sequences ( 7,8 ) , which indicates that the source of the virus for the cases in texas , mexico , and canada was likely to have been the outbreak in kenya . virus transmission may have occurred through contact with international travelers in airports or during transit because epidemiologic investigations did not detect other measles cases in cabo san lucas or texas . the exception to possible air travel related exposure was the single case that occurred in canada . this patient had traveled by car , although investigations found no measles cases in the areas visited : bangor , maine ( december 2 ) ; boston , massachusetts ( december 36 ) ; and portsmouth , new hampshire ( december 6 ) . they entered massachusetts on november 10 , 2005 , and by 21 days after arrival , measles had not developed . however , a measles outbreak was detected in southern germany in january 2006 ( 9 ) , and the viral sequence matched that of the kenya outbreak virus ( figure ; mvs / stuttgart.deu/4.06 ) , which indicates that the source of this outbreak was also likely to have been kenya . therefore , b3 viruses with identical sequences could have been introduced into texas , mexico , or canada by travelers infected with b3 virus in europe . although genotype b3 has been the most frequently detected measles genotype in western and central africa ( 4,1012 ) , ours is the first report of the detection of genotype b3 in kenya . moreover , the sequence from a virus isolated in nigeria in june 2005 ( figure ; mvs / yola.nie/25.05 ) was identical to the sequences in the kenya outbreak group . although a link has not been established between nigeria and kenya , a survey of measles genotypes in kenya in 2002 detected only genotype d4 viruses ( 13 ) . sequences of viruses isolated during 2004 and 2005 from cte d'ivoire and benin ( this study ) were included in our analysis ( figure ) because these b3 sequences represent closely related viruses from western africa . the analysis and dissemination of viral sequences from measles cases led to the identification of an unrecognized epidemiologic link at an airport and linked sporadic cases in 4 countries that do not have endemic measles to an ongoing outbreak in kenya . . timely communication of sequence data among epidemiologists and microbiologists is critical for identifying possible links among sporadic cases of measles . the potential for rapid transmission of measles during brief encounters with international travelers underscores the importance of global surveillance of measles virus .

surveillance of measles virus detected an epidemiologic link between a refugee from kenya and a dutch tourist in new jersey , usa . identical genotype b3 sequences from patients with contemporaneous cases in the united states , canada , and mexico in november and december 2005 indicate that kenya was likely to have been the common source of virus .

pulmonary sclerosing hemangioma ( psh ) is a rare benign tumor which was first described by liebow and hubbell . psh is generally considered as benign tumor , but some reports suggested the malignant potential of this tumor . the optimal surgical strategy for treating psh has not been established . the purpose of this study is to compare the outcome of limited resection with that of lobectomy to determine the optimal surgical strategy of this tumor . between january 1995 and december 2007 , 32 patients underwent surgical resection of psh at out institution . their medical records were retrospectively reviewed to compare the clinical characteristics and postoperative outcomes of the two groups with different surgical procedures : lobectomy and limited resection , which was defined as lung resection with an extent smaller than that of lobectomy . there were no clear criteria for the selection of the surgical procedure , but limited resection tended to be preferred for peripheral small - sized tumor , and in the recent series after the introduction of video- assisted thoracoscopic surgery ( vats ) . thirty - one patients were female , and the mean age at operation was 47.8 years , ranging from 23 to 73 years . twelve patients had non - specific subjective symptoms before being diagnosed as having psh , such as cough , chest discomfort , and mild dyspnea . all patients were initially diagnosed with solitary pulmonary nodule ( spn ) on simple chest x - ray , which prompted us to conduct computed tomography ( ct ) scan . psh was suspected in 10 patients , as one of the differential diagnoses in nine cases , and as a single compatible diagnosis in one case . enhanced spiral ct scan in our hospital improved diagnostic accuracy by indicating psh in seven out of eight patients . determination of preoperative pathologic diagnosis was attempted in 12 patients with fine needle aspiration ( fna ) . three patients were misdiagnosed preoperatively as adenocarcinoma of the lung , and three were diagnosed with other benign lung tumors such as hemangioma or hamartoma . in two patients , psh was one of the two differential diagnoses ( i.e. psh and adenocarcinoma ) . the correct preoperative diagnosis of psh was made only in 4 cases . additionally , intra - operative frozen biopsy failed to diagnose psh in one case , who was reported to have bronchioloalveolar carcinoma ( bac ) . lobectomy group included 19 patients , and limited resection group included 13 patients , which consisted of 1 segmentectomy , 5 wedge resections and 7 other minor resections of tumor such as precision excision . ct scan was done between postoperative 3 and 6 months in most of the patients . after initial postoperative ct examination ct scan was performed annually for more than 3 years . student t tests and chi square or fisher exact tests were used to compare the continuous and categorical variables , respectively . a p - value of less than 0.05 was considered significant . the clinical characteristics and pathologic data of the study population are described in table 2 . among 32 patients , one patient with two nodules in the right middle lobe ( rml ) received precision excision of the nodules , and the other patients with two nodules in the right lower lobe received right lower lobectomy . one tumor was located in the major fissure , and the other one was located in the mediastinum as a visceral pleural - based pedunculated mass . the mean diameter of the tumors was 2.6 cm , varying from 1 cm to 8 cm , and the tumor size was larger than 4 cm in diameter only in four patients . lymph node biopsy or dissection was done in 21 , and one patient was found to have lymph node metastasis at the left upper pulmonary vein lymph node . in that case , the patient underwent completion lobectomy because of the possible malignant characteristics of psh with lymph node metastasis . however , there was no clinical evidence of local recurrence or distant metastasis during the 10-year follow - up in this patient . for tumors embedded in pulmonary parenchyma , the tumors located in the interlobar fissure and visceral pleura were solid and well - encapsulated mass without invading adjacent tissue . there was no postoperative complication , and no early or late tumor - related mortality . the mean follow - up period was 39.3 months ( from 2 to 129 months ) , and all patients were free of local recurrence or distant metastasis during the follow - up period . there was no significant difference in basic patient 's characteristics and surgical results between the two groups . the mean hospital stay was significantly shorter in limited resection group ( 4.01 days ) than in lobectomy group ( 6.5 days ) ( p=0.0031 ) . pulmonary sclerosing hemangioma , first described by liebow and hubbell in 1956 , is a rare primary pulmonary tumor . although the biologic behavior of psh is not clear and its histogenesis is still under debates , it has recently been claimed that psh originates from primitive respiratory epithelial cells . psh presents mostly as a single solid mass in the lung , with right - side predominance , but it occasionally exhibits as multiple nodules with an incidence of 4~5% . it can also be found elsewhere ( i.e. mediastinum or pleura ) in the thorax . ever since tanaka and colleagues reported the first case of psh with lymph node metastasis , there have been sporadic reports on its metastatic nature [ 6 - 10 ] . the prognosis of psh does not appear to be affected by these malignant potentials , for there has been no documented mortality caused by psh . among the 32 patients in our study , one patient with a mass located at the interlobar major fissure was found to have regional lymph node metastasis . postoperative permanent pathology revealed findings compatible with psh , and the patient received reoperation for completion lobectomy . the lymph node metastasis was found at the pulmonary vein lymph node in the lobectomy specimen . after 10-year follow - up , there was evidence of tumor recurrence in the adjacent lung parenchyma or lymph nodes . even though many authors in the literatures pertaining to the surgical strategy for psh preferred limited resection ( i.e. wedge resection or enucleation ) to anatomical resection ( i.e. lobectomy ) , there has still been no consensus on the optimal extent of resection for psh . one of the important reasons for this is the inaccuracy of preoperative diagnosis for psh . the cytological findings of psh have been rarely described , and bear a strong resemblance to certain types of pulmonary malignancies . differential diagnoses of psh based on cytology include pulmonary adenocarcinoma , bac , and pulmonary carcinoid . radiologically , psh usually presents as a solitary , well - circumscribed mass without cavitation . the tumor typically shows heterogeneous areas of attenuation , marked enhancement , and air trapping , which is forms " air meniscus sign " on plain chest films . however , these findings can also be seen in tuberculoma , aspergilloma , hamartoma , and lung carcinoma . a chinese group , which favored limited resection in their report of 24 patients with psh , also pointed out the difficulties in the precise preoperative diagnosis of psh . in this study , the radiologic prediction diagnosis of psh was only made in 10 out of 32 cases . preoperative cytological examination with fine needle aspiration was also misleading because eight out of twelve successful diagnostic procedures resulted in misdiagnoses of pulmonary adenocarcinoma ( 5 cases ) or other lung tumors ( 3 cases ) . in one case , even the frozen section in the operating room failed to identify psh , which was misdiagnosed as bac . as our experience accumulates , pathologists in our institution reported 16 cases of psh with 5 unusual presentations , and from then on , the accuracy of preoperative diagnosis of psh has considerably improved . since 2007 , psh was correctly diagnosed in almost all cases ( 7 cases out of 8 by chest ct scan and all 3 cases by fine needle cytology ) . regardless of the extent of surgery , all the patients in our current report are all alive and well at present without the evidence of local recurrence or metastasis . limited resection can decrease hospital stay and costs with a surgical outcome comparable to lobectomy . recent progress in preoperative radiologic and pathologic diagnosis may reduce the probability of unnecessary lobectomy .

backgroundpulmonary sclerosing hemangioma is a rare thoracic tumor , and pathophysiology or clinical course of this tumor is not yet fully described . furthermore , there is no consensus on the standard operative procedure for this tumor.material and methodsmedical records of thirty - two patients , who underwent surgical resection of pulmonary sclerosing hemangioma from 1996 to 2007 , were retrospectively reviewed.resultsnineteen patients underwent lobectomy and thirteen patients underwent limited resection . video - assisted thoracoscopic surgery was performed in 9 patients in the latter group . lymph node dissection was done in 21 patients , and one patient was found to have lymph node metastasis of the tumor . there was no postoperative complication , no early death and no tumor - related late mortality . the mean follow - up duration was 39.3 months ( 2 months~129 months ) , and all patients were free of local recurrence and distant metastasis during this period . there was no significant difference in patient 's characteristics between the two groups , except that the mean hospital stay was shorter in limited resection group than in lobectomy group ( p=0.0031).conclusionpulmonary sclerosing hemangioma usually requires surgical resection for both diagnosis and treatment . limited resection can decrease hospital stay with a surgical outcome comparable to lobectomy , and may be preferred to lobectomy if sufficient resection margin can be achieved .

aminoglycosides continue to represent highly effective antimicrobial agents since their introduction about more than 50 years ago . despite the introduction of highly potent , wide - spectrum antibiotics , aminoglycosides are still considered to be very important against many life - threatening infections especially against gram - negative bacterial infections . they are very commonly used antibiotics worldwide because of certain properties as rapid concentration - dependent bactericidal effects , clinical effectiveness , a low rate of true resistance , synergism with other beta lactam antibiotics , and low cost of therapy [ 3 , 4 ] . however , their efficacy continues to be counterbalanced by significant toxicity especially nephrotoxicity which bring about kidney damage by a direct dose - dependent mechanism [ 5 , 6 ] . nephrotoxicity induced by gentamicin is a complex phenomenon characterized by increase in plasma creatinine and urea levels and severe proximal renal tubular necrosis , followed by deterioration and renal failure [ 7 , 8 ] . as gentamicin administration can induce severe nephrotoxicity , it has become a popular substance used to study drug - induced acute renal failure . the toxicity of aminoglycosides , including gentamicin , is believed to be related to the generation of reactive oxygen species ( ros ) in the kidney [ 8 , 9 ] . the cellular antioxidant status determines the susceptibility to oxidative damage and usually alters in response to oxidative stress . various studies have claimed antioxidant property of drugs for their nephroprotective effects in gentamicin - induced renal damage [ 1114 ] . ursolic acid , an ursane type triterpenoid compound which exists widely in natural plants in the form of free acid or aglycones for triterpenoid saponins has emerged as a molecule of therapeutic importance due to its diverse pharmacological properties and lower systemic toxicities . ursolic acid has been implicated in inhibition of lipoxygenase and cyclooxygenase in hl60 leukemic cells , inhibition of mutagenesis in bacteria , antitumor - promotion , inhibition of histamine release , inhibition of lipid peroxidation , and protection against adriamycin toxicity , antioxidant activity , hepatoprotective activity , antimicrobial activity , inhibition of mouse skin tumorigenesis , anti - inflammatory action , hypolipidemic and antiatherosclerotic effects , antiulcer activity , and cytotoxicity to leukemia cells . herbs like momordica dioica roxb containing ursolic acid as one of its constituents have shown significant nephroprotective activity . however , literature research revealed that the nephroprotective activity of ursolic acid in its pure form has not been established and its probable role has only been postulated with no positive evidence . hence with this background we decided to explore the nephroprotective role of ursolic acid in a murine model which entails the use of a commonly available , economical , and most mechanistically studied model , that is , gentamicin - induced nephrotoxicity in normal wistar albino rats . wistar albino rats of either sex , weighing 150200 g , were used for the study . animals were housed in standard environmental conditions ( 22 3c , 55 5% humidity and a 12 h light / dark cycle ) and fed with standard rodent diet and water ad libitum . the study was approved by the institutional animal ethics committee , kasturba medical college , mangalore , manipal university . gentamicin sulfate ( piramel health care ltd . ) dissolved in normal saline was used to induce renal damage . the test drug , ursolic acid ( sigma aldrich chemicals pvt . ltd . , uk ) was dissolved in 14% dmso , and administered orally in a dose of 2 mg / kg , 5 mg / kg , and 10 mg / kg . after acclimatization , the animals were divided randomly into five groups ( 6 rats / each group ) and placed in metabolic cages separately for collecting 24-hour urine samples . after collecting the first urine samples , the animals were grouped according to table 1 . the test drug ursolic acid was started 3 days prior to the commencement of the study . twenty - four hours after the last injection , urine samples were collected and the animals were euthanized under ether anesthesia . blood samples were collected by cardiac puncture for measuring urea and creatinine as an indicator of kidney damage , using urease ( a nickel metalloenzyme that catalyzes the degradation of urea to ammonia and carbon dioxide ) , and jaff ( the combined use of creatinine , amidohydrolase , and alkaline sodium picrate ) methods , respectively . the kidneys fixed in 10% neutral buffered formalin were processed and embedded in paraffin wax and sections were taken using a microtome . sections ( 5 microns ) were then stained with haematoxylin and eosin and examined under light microscope . they were evaluated and assigned scores as follows : score 0 = normal , score 1 = areas of focal granulovacuolar epithelial cell degeneration and granular debris in tubular lumens with or without evidence of tubular epithelial cell desquamation of small foci ( < 1% of total tubule population ) , score 2 = tubular epithelial necrosis and desquamation easily seen but involving less than half of cortical tubules , score 3 = more than half of proximal tubules showing desquamation of necrosis but involved tubules easily found , and score 4 = complete or almost complete tubular necrosis . score 1 = areas of focal granulovacuolar epithelial cell degeneration and granular debris in tubular lumens with or without evidence of tubular epithelial cell desquamation of small foci ( < 1% of total tubule population ) , score 2 = tubular epithelial necrosis and desquamation easily seen but involving less than half of cortical tubules , score 3 = more than half of proximal tubules showing desquamation of necrosis but involved tubules easily found , and score 4 = complete or almost complete tubular necrosis . data were expressed as mean standard error of mean ( sem ) . the differences among treated groups were analyzed by one - way anova followed by tukey 's test . in the present study , gentamicin ( 80 mg / kg ) when injected for 8 consecutive days caused marked nephrotoxicity as is evident from table 2 , showing significant ( p < 0.001 ) increase in serum urea ( 162.33 9.92 mg / dl ) , serum uric acid ( 3.13 0.123 mg / dl ) , serum creatinine ( 6.85 0.348 mg / dl ) , and blood urea nitrogen ( 75.86 4.636 ursolic acid showed a significant nephroprotective effect as evidenced by a decrease in the renal parameters , that is , serum urea , uric acid , creatinine , and blood urea nitrogen levels when compared to the gentamicin - treated group . moreover , the results as depicted in table 2 also suggest an interesting dose - dependent renoprotective effect with the highest dose ( i.e. , 10 mg / kg ) almost reducing the levels of serum urea , creatinine , and uric acid to normal control levels . the histological changes in the kidney of all the groups were graded and the results are expressed in table 3 . it is further evident from the microscopical study of kidney sections that the kidneys from the saline treated appeared histologically normal ( score 0 ) ( figure 1 ) whereas the gentamicin - treated group showed tubular epithelial loss with intense granular degeneration involving > 50% renal cortex as depicted in figure 2 . in addition to the tubular epithelial loss , some of the tubular epithelium contains tubular casts ( score 4 ) . the histomorphology of rats treated with ursolic acid showed moderate tubular epithelial degeneration with desquamation in patchy areas of the renal cortex ( score 2 ) . treatment with the two lower doses of ursolic acid appeared to mitigate the severity of the gentamicin treatment - induced renal necrosis ( score of 2 - 3 , resp . ) ; whereas the high dose treatment almost completely protected the histological features of kidney from gentamicin - induced alterations as depicted in figures 3 , 4 and 5 . in the present study , we investigated the effect of ursolic acid on gentamicin - induced acute renal failure in a murine model . results of this study confirmed that gentamicin at a dose of 80 mg / kg produces significant nephrotoxicity as evidenced by increase in blood urea nitrogen , serum creatinine , urea and uric acid , and renal tubular necrosis which corroborated with previous reports [ 8 , 1114 , 17 ] . pretreatment with ursolic acid provided marked functional and histological protection against acute renal damage in rats treated with gentamicin . increase in blood urea nitrogen and serum urea , uric acid , and creatinine , induced by gentamicin was prevented by ursolic acid . this study revealed that orally - administered ursolic acid has a significant and dose - dependent protective effect in gentamicin - induced nephrotoxicity in rats . the significance of ursolic acid in the treatment of nephrotoxicity is further increased because of its diuretic potential as well as its lower toxicity . a relationship between oxidative stress and nephrotoxicity has been well - demonstrated in many experimental animal models . in gentamicin - treated rats , a significant increase in lipid peroxidation products malondialdehyde ( mda ) suggesting that the involvement of oxidative stress has been reported . a role of lipid peroxidation in gentamicin - induced acute renal failure has also been described in previous studies . moreover , pretreatment of rats with hydroxyl radical scavengers has been shown to protect against gentamicin - induced acute renal failure . paracetamol - induced nephrotoxicity is proposed to be due to the overproduction of nitric oxide ( no ) and a marked reduction of hepatic and renal intracellular glutathione ( gsh ) levels . the cytoprotection imparted by oleanolic acid , a triterpenoid closely related to ursolic acid in paracetamol - induced nephrotoxicity in rats was proposed to inhibit the overproduction of no and to maintain the level of intracellular gsh through its potent antioxidant activities . gentamicin is known to decrease the activities of catalase , glutathione peroxidase , and the level of reduced glutathione . ursolic acid which is an important component of ocimum sanctum has been shown to inhibit lipid peroxidation and protect against free - radical - induced adriamycin toxicity . treatment of mice with ursolic acid inhibits mitochondrial lipid peroxidation in tumor - bearing rats and returns the increased superoxide dismutase to normal levels . also , its antioxidant activity has been partially held responsible for its preventive and therapeutic effects on acute hepatic injury in rats . therefore , it is not unreasonable to assume that the nephroprotection shown by ursolic acid in gentamicin - induced nephrotoxicity is mediated through its potent antioxidant effects that help to preserve intracellular gsh levels . the antioxidant activity of ursolic acid might have contributed to its nephroprotective effect by inhibiting gentamicin - induced lipid peroxidation . however , other mechanisms of protection like inactivation of the aminoglycoside by electrostatic complex formation or preventing its binding to the brush border membrane or by forming complexes at acidic ph and preventing phospholipid overloading in lysosomes can not be negated also . additional studies are warranted in order to test these assumptions , such as the measurement of gentamicin urinary excretion , the examination of gentamicin , and ursolic acid interactions with brush border membranes , and the effect of treatment on intracellular ca . further studies exploring and linking the antioxidant activities to the nephroprotective effect and evaluation of glomerular filteration rate in ursolic - acid - treated rats might shed more light on the mechanism of renoprotective action of ursolic acid . hence such investigations should be conducted in order to better characterize the attenuation of gentamicin - induced nephrotoxicity by ursolic acid . to conclude , this study provides scientific evidence of the nephroprotective effects of orally administered ursolic acid in a murine model employing gentamicin as a toxicant that directly induces renal damage . it further proposes that observed protective effects of ursolic acid in gentamicin nephrotoxicity could be attributed to its well - known antioxidant potential .

the present study evaluates the nephroprotective effects of ursolic acid in a murine model of gentamicin induced renal damage . wistar albino rats of either sex , weighing 150200 g were divided into 5 groups ; normal saline , gentamicin 80 mg / kg , intraperitoneally for 8 days , ursolic acid at 2 , 5 , and 10 mg / kg , per oral for 8 days , ursolic acid administered 3 days prior and concurrently with gentamicin for 5 days . blood urea , serum creatinine , uric acid and blood urea nitrogen analyses and microscopic examination of kidney were performed . gentamicin treatment caused nephrotoxicity as evidenced by marked elevation in serum urea , serum uric acid , serum creatinine and blood urea nitrogen ( 162.33 9.92 mg / dl , 3.13 0.12 mg / dl , 6.85 0.35 mg / dl and 75.86 4.64 mg / dl ; resp . ) when compared to the saline treated groups . co - administration of ursolic acid with gentamicin decreased the rise in these parameters in a dose dependent manner . histopathological analysis revealed epithelial loss with intense granular degeneration in gentamicin treated rats , whereas ursolic acid mitigated the severity of gentamicin - induced renal damage . to conclude , our data suggest that ursolic acid exhibits renoprotective effect in gentamicin induced renal damage and further studies on its mechanis of action are warranted .

superior mesenteric and celiac artery aneurysm accounts for only 45.5% of all reported visceral artery aneurysms with an estimated incidence of 0.12% in the literature [ 1 , 2 ] . furthermore , the majority of the reported cases are degenerative in nature . their mycotic ( infective cause ) occurrence is rare , and according to patel and johnston 's classification , majority are the result of a primary local source and/or secondary septic embolization . however , no report in the literature has explained their cryptogenic development superior mesenteric artery aneurysm ( smaa ) as a result of enterococcus faecalis ( ef ) . herein , we present a recent , successfully treated case of cryptogenic mycotic aneurysm ( ma ) of sma by ef with short review of the literature . a 77-year - old man with past medical history of atrial fibrillation , hypertension and diabetes mellitus ( type 2 ) presented to the emergency department with 6-week history of supra pubic / left iliac fossa pain and 14-kg weight loss . on examination g / l ) and normal inflammatory markers ( white blood cell count 7.6 10/l , c - reactive protein 22 mg / l ) . due to the nonspecific nature of the abdominal pain and weight loss a computed tomography ( ct ) with contrast was performed . this was associated with mesenteric edema and stranding and multiple local lymphadenopathies ( fig . 1 ) . figure 1:the ct image demonstrating a smaa measuring 4.4 3 cm in size . the ct image demonstrating a smaa measuring 4.4 3 cm in size . exploratory laparotomy was performed , and after meticulous dissection , the proximal and distal ends of the smaa were both isolated and clamped . the entire aneurysm and the surrounding inflammatory tissue , including lymph nodes , were fully excised ( figs 2 and 3 ) . due to good collateral flow ( intestine ) , no bypass or interposition grafting was deemed necessary . given the lack of any identifiable primary or secondary sources and normal echocardiogram , blood cultures were obtained and sent ( along with the specimen ) for histology and microbiology examinations . subsequent blood culture revealed ef ( day 1 ) that was also later identified on the specimen . the patient was immediately started on antibiotics ( vancomycin ) according to the sensitivity of the culture for a period of 6 weeks and discharged on the 6th postoperative day . follow - up ct at 3 months demonstrated complete resection of the aneurysm with no inflammatory changes . the repeated blood culture and serology for inflammatory markers were normal , and the patient reported no complication on follow - up ( fig . figure 4:the postoperative ct image ( 3d reconstruction ) demonstrating complete resection of the aneurysm . the cross section of the excised smaa . the postoperative ct image ( 3d reconstruction ) ef is a gram - positive commensal bacterium that inhabits the gastrointestinal tract of humans . they are listed as the third leading cause of nosocomial infections and mainly affect immunosuppressed individuals . they can cause meningitis , urinary tract and wound infections , but their cardiovascular involvement is rare and is limited to endocarditis ( primary ) . their sequelae can result in septic embolization ( secondary ) , leading to ma of intracranial and coronary arteries ( 0.75.4% ) [ 5 , 6 ] . however , according to the literature , this sequence has led to two reported cases of secondary ma of sma and no reported cases of cryptogenic development . the cryptogenic development of ma is the result of viable circulatory organism that lodges in the arterial endothelium with no identifiable primary or secondary source . the current literature suggests that abnormal intima can serve as a nidus for development of infection resulting in a cumulative endothelial injury , necrosis and formation of aneurysms . intimal abnormality can occur in atherosclerosis , cystic medial necrosis , degenerative arterial disease , connective tissue disorders and noninfective inflammation of arteries . the commonest location for such endothelial changes to act as a platform for development of ma by all organisms is femoral ( 38% ) , followed by abdominal aorta ( 31% ) , sma ( 8% ) , brachial ( 7% ) and iliac arteries ( 6% ) . their management is complex , but bactericidal antibiotics over bacteriostatic are highly preferred and should be started as soon as the diagnosis is suspected . this regimen should not await micro - serological assay , and the optimal duration ( following surgical intervention ) of antibiotics is 6 weeks . due to high rates of mortality and morbidity as a result of rupture , surgical management in the form of excision and/or bypass is highly recommended . if bypass is mandated , autologous graft over prosthetic conduits is advocated to avoid secondary infections and further incidence of re - intervention . in our reported case , due to good collateral flow no bypass or interposition grafting was necessary , but if advocated great saphenous vein , short saphenous vein and/or arm vein remain the best conduit of choice . another recently suggested approach is endovascular exclusion of smaas , but their long - term outcomes are awaited . the investigative modality of choice is currently ct with contrast , and rarely any other investigative modality is required to complement this . due to the vague and nonspecific presentation of such cases , a high index of suspicion and a low threshold for ct imaging are necessary . in conclusion , mas of sma do not present with conclusive signs and symptoms for a clinical diagnosis . a ct scan , in such circumstance , can demonstrate important findings that might otherwise result in significant mortality or morbidity . upon diagnosis , if bypass is granted , autologous graft is highly preferable and all patients should receive antibiotics for a period of 6 weeks irrespective of the surgical modality . written informed consent was obtained from the patient for publication of this case report and accompanying images .

visceral artery aneurysms as a result of arterial degenerative disease are rare ( 0.12% ) , and superior mesenteric artery ( sma ) accounts for 3.2% of all reported series . however , mycotic sma aneurysms ( smaas ) are even rarer , and to the best of our knowledge , this is the first report of cryptogenic mycotic aneurysm of sma by enterococcus faecalis ( ef ) . we report a case of 77-year - old man with 6-week history of supra pubic / left iliac fossa pain , weight loss and fever . the computed tomography demonstrated an incidental finding of 4.4 3-cm smaa with no primary foci . the subsequent serology and specimen confirmed ef . aneurysmectomy without bypass grafting along with antimicrobial therapy resulted in full recovery of the patient .

several histologic subtypes of bladder cancer such as microcystic , micropapillary , and nested variant are seen . the presence of micropapillary component ( mpc ) in urothelial carcinoma was found to be associated with high - grade and advanced stage of tumour , though low - grade and non - invasive cases have been reported . micropapillary variant was first described in 1994 , though fewer than 300 cases have been reported . micropapillary variant of bladder cancer ( mpbc ) occurs in only 0.6 - 6% of bladder cancer cases and shows a strong male predominance . the histology of mpbc resembles that of micropapillary subtypes of breast , lung , stomach and colon , as well as serous ovarian carcinoma . the micropapillary component of these tumours may be encountered on the surface of non - invasive component , the invasive component of the tumour , or in metastatic sites . immunohistochemical profile may help in the evaluation of final diagnosis in controversial cases . in primary tumour , the surface component often presents with delicate filiform projections with secondary or tertiary hierarchical branching . standard recommendations for the treatment of locally advanced disease involve immediate cystectomy with or without perioperative chemotherapy . however , the management of micropapillary variant of bladder cancer that is non - muscle invasive is more controversial . a 58-year - old man presented with macroscopic haematuria , dysuria , and obstructive lower urinary tract symptoms in october 2013 . urine cytology showed the presence of epithelial cells 10 - 15/hpf , polymorphonuclear leucocytes more than 12/hpf , and a background of rbcs in the smear . transurethral resection of bladder tumour ( turbt ) was performed and the tissue was sent for histopathologic examination . histopathologic examination revealed a high - grade urothelial carcinoma extending into the lamina propria , but not into the underlying detrusor muscle ( figure 1a ) and a diagnosis of pt1hguc ( high - grade urothelial carcinoma invading the lamina propria with no invasion into muscle ) was rendered . the patient received intravesical bcg , completed the induction therapy of 6 weeks , and received 3 cycles of maintenance therapy at 3 , 6 , and 12 months of the initial dose . he missed the next dose and reported 6 months later with the complaint of haematuria in february 2015 . a ) hematoxylin and eosin stained section of first biopsy in 2013 shows high - grade urothelial carcinoma invading the lamina propria . b ) higher power ( 20 ) view at this time shows nuclear pleomorphism ( arrow ) . c ) biopsy at the time of recurrence in 2015 showed high - grade micropapillary carcinoma with arrow depicting the micropapillae . he underwent usg abdomen and was diagnosed with urothelial bladder mass ( 2917 mm ) seen along the left lateral wall with mild adjacent perivesical fat stranding with small bilateral obturator nodes and prostomegaly . preoperative ct - scan of the abdomen ( liver , gall bladder , kidney , and prostate ) was normal . morphology showed glandular formations lined by a single layer of tumour cells along with micropapillary formations lined by 2 - 3 cell layer thick epithelium ( figure 1b and c ) . the tumour cells were also seen in sheets invading into the detrusor muscle ( figure 1d ) . the tumour cells were positive for ck7 and ck20 ( figure 2a and b ) and negative for cdx2 , psa and amacr . hence , a final diagnosis of urothelial carcinoma , micropapillary variant with adeno and squamoid differentiation of high - grade , muscle - invasive stage ( pt2hguc ) was given . the patient was treated with radical cystectomy and was found to have no nodal metastasis ( n0 ) . patient s consent has been obtained for reporting the case and all identifiers have been removed . immunohistochemistry analysis of tumour received on recurrence showed ck7 positive in membrane and cytoplasm of tumour cells ( a ) , and ck20 positive in tumour cells of micropapillary variant of urothelium carcinoma ( b ) . micropapillary urothelial carcinoma is recognized as a rare and aggressive variant of urothelial carcinoma , which often presents at a high - stage . the poor prognosis in these cases was recognized to be due to the high incidence of lymphovascular invasion and the high clinical stage at presentation . the morphology is reminiscent of micropapillary tumours primary at other sites . while usually invasive , non - invasive tumours have also been reported . who grade 1 - 2 , non - invasive the presence of microcystic areas raised a few doubts about adenocarcinoma and the possible primary , hence immunohistochemical analysis was performed to confirm the origin . the most common adenocarcinomas metastatic to the bladder are from the prostate , therefore , markers psa ( prostate specific antigen ) and amacr ( alpha - methylacyl - coa racemase ) which are positive for prostate origin , were performed . analysis showed ck7 and ck20 expression in the tumour cells while psa , amacr , and cdx2 were negative . the present case shows progression from a non - invasive lesion to a muscle - invasive lesion in 2 years of follow - up in spite of receiving intravesical therapy with bcg . while the pathogenesis of this tumour is unclear , some authors suggest that it could be a form of glandular differentiation of the tumour . this view is supported by reversed polarity seen in these cases where the tumour cells facing the stroma show secretory properties with the expression of muc1 . the 5-year and 10-year survival rates of 74% and 54% , respectively , with the conventional treatment show that the clinical course is poor . the patient was initially treated with intravesical bcg ( induction and maintenance courses ) after turbt , as it was only diagnosed as high - grade carcinoma and the micropapillary areas were not discernible in the biopsy slide . the patient was non - responsive to bcg and progressed into muscle - invasive disease and the invasion was treated with radical cystectomy . a poor prognosis has been reported for urothelial carcinoma with micropapillary and plasmacytoid morphology , but the case had extensive adhesions and peritoneal metastases at the time of surgery . however , our case presented only with frequent recurrences and muscle invasion , but no extravesical invasion , adhesions or distant metastases . the loss of e - cadherin expression has been noted in high - grade lesions of other cancers . however , it is diffusely expressed in both micropapillary and high - grade urothelial carcinomas and does not contribute in differentiating the two entities . her2/neu gene amplification has , however , been found frequently in micropapillary carcinomas of urinary bladder suggesting that her2 targeted therapy may be useful in suchpatients . the present case highlights the heterogeneous nature of the pt1hguc cases as initially it was found to be the classical high - grade urothelial cancer . however , over time it developed into a more aggressive variant , which did not respond to immunotherapy . initial treatment with radical cystectomy would have been the better option in this case even without the evidence of muscular invasion or perivesical stranding . the expression of her2/neu by both immunohistochemistry and fish ( fluorescence in situ hybridisation ) in such cases may identify cases , which may benefit from her2-targeted therapy .

micropapillary variant of urothelial carcinoma ( uc ) of the bladder is an aggressive tumour , comprising 0.6 - 6% of all uc . it generally presents with high - grade and stage , and has been reported as having a worse prognosis when compared to traditional uc . we report the case of a 58-year - old man who presented with macroscopic haematuria . the patient was diagnosed with high - grade urothelial carcinoma and returned with recurrence after 16 months . histopathology after transurethral biopsy revealed a non - muscle invasive high - grade bladder tumour at first presentation , whereas tumour recurrence was reported after 1.5years . the histopathology at recurrence revealed a high - grade , muscle invasive , micropapillary variant of urothelial carcinoma with focal adenomatous morphology . immunohistochemical expression of ck7+/ck20 + in tumour cells and negativity for psa , amacr , and cdx2 in paraffin section helped in identifying the tumour as primary in the urinary bladder . radical cystectomy was performed and the patient has no distant metastases on follow - up . the specific morphology even within the high - grade urothelial cancer cases is important to discern for proper treatment .

during badminton games , it is necessary for players to use high - level stroke skills in various situations1 . players need to be able to select and execute a large number of stroke , in different situations , after selecting highly strategic shots to disrupt their opponent s readiness , rather than simply returning the shuttlecock2 . for example , when an opponent takes up the ready position in front of the net , it is appropriate to return the shuttlecock by placing a clear shot behind the opponent , and an opponent takes up the ready position in the back section of the court , a drop shot falling near the net is appropriate . during a rally , a player needs to select the most appropriate shot to disrupt an opponent s readiness , and as soon the opponent s readiness disrupted , deliver the most offensive shot to earn a point3 , 4 . reports about strokes have been made in some previous studies of badminton games , which focused on the development of skills for delivering effective services and overhead strokes5 , 6 , or the characteristics of upper - limb muscle activities of skilled badminton players when hitting a smash7 . furthermore , in badminton rallies , quick movements are essential for returning the shuttlecocks at various speeds in all directions . to win a rally , increased leg strength enabling rapidly movement to the spots where the shuttlecock falls8 , and endurance to continue moving without decreasing the speed of movement9 , 10 , are crucial . in addition , in order to effectively return a shuttlecock ( to disrupt an opponent s readiness ) , it is necessary to deliver a stroke in a stable stance . in these situations , players need to instantaneously predict the spot where the shuttlecock will fall , and immediately begin to move to it . however , no studies have examined the mechanisms by which badminton players instantaneously react to shuttlecocks , and move . in which demands , instantaneous lower - limb muscle movements are particularly needed . if badminton players have the ability to instantaneously activate their own lower - limb muscles , the excitability of their spinal motor neurons controlling the fibers of such muscles may be characteristic . the soleus h - reflex has frequently been the focus of previous studies11,12,13 , as it is considered to represent the excitability of spinal motor neurons . accordingly , in line with this , the present study aimed to clarify the characteristics of badminton players motor neuron excitability by examining the soleus h - reflex in the ready position immediately before making a return . sixteen individuals with experience of playing badminton ( mean age : 20.92.1 ; years of experience : 8.33.0 ) and 16 without such experience ( 20.11.2 ) were studied . all subjects were provided with explanations regarding the study objectives and its safety before obtaining their consent to voluntarily participate in this . this study , which was conducted with the approval of the research ethics committee of the health science university ( approval number : 13 ) . neuropack ( nihon kohden ) was used for the measurement of the m- and h - waves . before measurement silver plated electrodes for recording were placed on the skin of the medial part of the soleus on both sides , while bipolar stimulating electrodes were attached to the popliteal fossa of the dominant and non - dominant legs . subsequently , electrical stimulation was intracutaneously applied to the tibial nerves to measure the m- and h - waves in the medial part of the soleus ; and their thresholds and maximum values were recorded by gradually increasing stimulation . for h - wave measurement , the stimulation level was set to obtain h - wave amplitudes of approximately 30% of the maximum m - wave value ( mmax ) , as well as the m - wave of 4 to 8% mmax , at a frequency of 0.2 hz14 . when recording the h - reflex , it was confirmed that the m - wave remained unchanged . when changes were observed , the recorded values were discarded due to considering the possibility of changes in the stimulation level . the h - reflex was measured in the ready position before receiving a shuttlecock with or without a racket held in the dominant or non - dominant hand , in addition to a static upright stance . the subjects were instructed to maintain these 5 stances , and the h - wave was recorded 10 times , and the mean was calculated ( fig . 1fig . 1.h - wave after tibial nerve stimulation of stance in a representative badminton subject ) . h - wave after tibial nerve stimulation of stance in a representative badminton subject among the amplitudes obtained for each stance , the difference between the minimum and maximum h - wave values was calculated . subsequently , the difference between the minimum and maximum m - wave values ( mmax ) as a response to maximum stimulation in the supine position was calculated to normalize the h - wave value as a percentage of the mmax . for statistics , significant differences were examined by performing one - way analysis of variance , followed by multiple comparisons , adopting the tukey - kramer method with a significance level of 5% . the h - wave rate of each stance was calculated , using the values when just standing as 100% ( table 1table 1.h - wave in the badminton and control groups in each stancebadmintoncontrol significantholdingdominant ( % ) 86.510.5108.615.6*non - dominant ( % ) 91.014.7113.527.8without a racketdominant ( % ) 94.915.2103.316.4non - dominant ( % ) 90.813.397.815.8 * : p<0.05 ) . in the badminton group , the h - wave significantly decreased when holding a racket in the dominant hand compared to when standing . in contrast , in the control group , no significant differences were observed between when standing and the other stances . furthermore , the h - wave was suppressed in all stances compared to when standing in the badminton group , while it was promoted in the control group . muscle stimulation excites type ia afferent fibers , and consequently activates spinal alpha motor neurons , leading to the contraction of stimulated muscles ( stretch reflex ) . the h - wave obtained with electrical stimulation has been used as an index for evaluating the spinal control of muscle contraction during the stretch reflex , as it represents the excitability of spinal motor neurons . in previous studies , the soleus h - wave obtained by eliciting stimuli was shown to be greater when standing compared to walking15 , and this may be explained by the mechanism in which the stretch reflex stabilizes the ankle joint when standing ( increased h - wave ) , while it interferes with the swing phase when walking ( decreased h - wave ) . in short , a greater amplitude of the h - wave also varies between different exercise tasks , such as walking and running , and stances , such as prone and standing positions16 , 17 . furthermore , the soleus h - wave has been reported to be greater in swimmers than in non - swimmers18 . on the other hand , the h - reflex level is lower in professional ballet dancers than in athletes in general19 . based on these findings , long - term physical training may specifically influence the excitability of spinal motor neurons . in the present study , on comparison of the soleus h - wave of those with and without experience of playing badminton were compared , and its values was significantly lower in the former when experienced players held in the dominant hand , while those with no experience of playng badminton showed a markedly different tendency . some previous studies reported that the h - wave amplitude is greater in athletes mainly engaged in endurance training than in those mainly engaged in power training20,21,22 . such training - dependent ( endurance / power ) variation in the h - wave may be associated with differences in the lower - limb loading level . for example , the h - wave decreases in the prone position compared to when standing under the influence of gravity17 , and increases in a microgravity environment or underwater11 , 23 . in this respect , continuous badminton training suppresses the soleus h - wave , presumably due to being power - focused . in badminton games , it is necessary for players to deal with shots at various speeds , such as drop shots near the net and high - speed smashes , and appropriately the return shuttlecocks . therefore , badminton players need to increase the instantaneous force of their legs to execute rapid movements . the results of the present study suggest that the excitability of badminton players spinal motor neurons may be suppressed by training to increase the instantaneous force ( power training ) . furthermore , the reduced excitability of spinal motor neurons when playing badminton may be associated with an increased ability to move to feet rapidly . considering that badminton is regarded as a lifelong sport for a wide range of age groups , regardless of the sex , and that it increases the stepping ability ( by suppressing the excitability of spinal motor neurons ) , this sport is also likely to be an effective fall - preventing on approach .

[ purpose ] this study aimed to clarify the characteristics of motor neuron excitability by examining the soleus h - reflex in the ready position adopted immediately before making a return during badminton games . [ subjects ] sixteen individuals with ( badminton group ) and 16 without ( control group ) experience of playing badminton were studied . [ methods ] each subject was instructed to take up various stances for returning a shuttlecock to measure the h- and m - waves in the soleus . [ results ] the h - wave was significantly decreased when gripping a racket was held in the dominant hand than compared to just standing in the badminton group . in contrast , in the control group , no significant differences were observed between when standing and the other stances . [ conclusion ] based on these results , the excitability of spinal motor neurons may have been reduced ( h - wave suppression ) by badminton training to increase the instantaneous force ( power training ) .

a man presented with clinical and radiographic evidence consistent with an acute appendicitis . after an ileocolic resection he was found to have intestinal spirochetosis of the caecum . a 50-year old- male presented to our institution in november with a three - day history of right lower quadrant abdominal pain associated with nausea . upon assessment in the emergency department , he did not appear ill and was afebrile . his white blood cell count was 12.0 x 10 cells / l . computed tomography abdomen and pelvis revealed a markedly dilated appendix measuring 1.3 cm with fat stranding and enlarged lymph nodes . the clinical impression at the time was consistent with an acute appendicitis with a potential caecal neoplasm . computed tomography images obtained preoperatively . the patient was given intravenous antibiotics and taken to the operating room within 5 hours of his initial presentation . a transverse right lower quadrant incision of the abdomen revealed an enlarged , firm appendix adherent to the lateral peritoneum was identified . the area of caecum surrounding the appendiceal base was firm and adjacent mesentery was oedematous . a neoplasm could not be adequately ruled out in the setting of an emergency operation with difficult anatomical visualization . an ileocolic resection was therefore performed with creation of a standard functional end - to - end ileocolic anastomosis using gastrointestinal staplers . the patient was also placed on a 10-day course of antibiotics ( ciprofloxacin and metronidazole ) postoperatively as the intra - operative impression was highly suspicious for a contained perforated viscus . at follow - up 10 days post - discharge the patient complained of occasional loose bowel movements but was otherwise feeling well . ( h&e staining , light microscopy , magnification x 200 ) ( b ) : caecum . note false brush border ( arrow ) composed of intestinal spirochetosis adhering to caecal mucosal epithelium . ( h&e staining , light microscopy , magnification x 400 ) the patient returned for follow up one month after surgery and was clinically well . at a subsequent visit 3 months later , he had a colonoscopy showing few diveritcula and a significant spasm . to our knowledge , he continues to remain asymptomatic . intestinal spirochetosis ( is ) was first discovered in 1719 by van leeuwenhoek who analyzed his own stool and identified small mobile spiral organisms.(1 ) is is a rare disease wherein gram negative bacteria belonging to the spirochetes species infect the gastrointestinal tract . spirochete organisms are classified into 3 groups : spirochaetaceae , leptospiraceae and brachyspiraceae ( 2 ) . two distinct groups have been identified to predominantly colonize human colorectum : brachyspira aalborgi and brachyspira pilosicoli . morphologically , is is characterized by the presence of microorganisms attached to colorectal epithelial cells in a perpendicular fashion . histologically they form a diffuse blue fringe along the border of the epithelial layer ( with hematoxylin - eosin staining ) . although invasion beyond the mucosal border is rare , mast cell and ige plasma cell reactions have been reported . it is suspected that loss of integrity of the mucosal surface may play a role in the mechanism of invasion.(1 ) the epidemiology of is was first described in the 20 century . a report published in 1923 in chicago revealed a 28% prevalence in stools of healthy individuals ( 3 ) . since then , other reports have demonstrated a direct relationship between the incidence of spirochetosis and rapidly growing industrial towns , homosexual men and patients infected with the human immunodeficiency virus ( hiv ) ( 2 ) . prevalence ranges from 1 - 5% in healthy individuals and within developed countries ( 4 ) to 64.3% in healthy individuals in a village in india ( 5 ) . difficulty with measuring prevalence resides in the sensitivities of methods of detection , which over the years has encompassed histology , microscopy , pcr , and in - situ - hybridization from fecal and/or tissue specimens . a retrospective study examined the colonoscopic descriptions of 15 patients with biopsies consistent with is . appearance , an erythematous mucosa was noted in one patient , a lesion was noted in one patient and the remaining 6 patients had normal mucosa ( 6 ) . is has been described to involve the mucosa of the colon , rectum and appendix . the severity of clinical manifestation has been correlated with the degree of histological invasion as evidenced by intestinal epithelial injury . however , it must be noted that presence of fecal spirochetes does not coincide with symptomatology . associated symptoms described include blood tinged feces , abdominal pain , constipation and most commonly diarrhea ( 1 ) . a little over ten cases of systemic spirochetemia ( mainly secondary to b. pilosicoli ) have been described in critically ill patients ( 7 ) . few reports in the literature ( amounting to less than 30 patients ) have described patients with intestinal spirochetosis who presented with a clinical and histological picture of acute appendicitis ( 8,9 ) . in 1984 , henrik - nielson and colleagues studied 681 appendiceal specimens and found is to be associated with 12.3% of clinically suspicious appendicitis that proved to be histologically normal whereas only 0.7% of is cases had a co - existing confirmed appendicitis on histology ( 8) . intestinal spirochetosis in the appendix , therefore , has a spectrum of presentation ranging from asymptomatic to fulminant histologically proven appendicitis . no consensus guidelines for the treatment of intestinal spirochetosis exists as only successful case reports of trial antibiotic regimens have been described . generally , a trial of antibiotic therapy is warranted , especially when the patient is symptomatic and/or histology shows signs of invasion . treatment with metronidazole administered at 500 mg q.i.d . for 10 days has been reported to eradicate symptoms and may lead to negative fecal cultures and improvement in histological features ( 4 ) . at our institution it is estimated that the prevalence of is in the hiv and in the homosexual population is as high as 54% ( 1 ) . most of these patients present with a chronic diarrhea and have a delayed diagnosis secondary to prolonged culture growth and low suspicion of this aetiology . in about two thirds of cases , patients with hiv diagnosed with is suffer from severe underlying disease and/or immunosuppression leading to death ( 10 ) . awareness of this disease entity should be heightened among surgeons especially those who treat patients with hiv .

acute appendicitis is a frequent pathology encountered by general surgeons . on the differential of aetiologies that can lead to this diagnosis lies the spectrum of infectious disease . we present a case report of a patient who presented to our institution as a classic acute appendicitis . upon histological analysis it became evident that he had spirochetosis of the cecum and appendix . this paper reviews the literature on this rare infectious aetiology . a synopsis of the microbiology , epidemiology , clinical manifestations and treatments for intestinal spirochetosis is described . at large , the aim of this paper is to heighten awareness of this disease amongst clinicians and specifically surgeons .

a variety of test methods are discussed for the diagnosis of proximal tooth surfaces . adjuncts such as bitewing radiography and fiber - optic transillumination provide an improvement to unaided vision . unaided visual diagnosis had detected fewer than 50% of caries lesions on occlusal surfaces and even fewer on proximal surfaces . it is not possible to detect only with unaided visual examination in interproximal caries lesions ; radiographs help for proximal caries diagnosis and detection of their lesion depth [ 2 , 3 ] . the combination of visual inspection and bitewing radiographic images is accepted as a standard procedure in proximal caries diagnosis . however , the deeper the radiolucency penetrates enamel and dentine , the higher the probability of cavitation . due to difficulties in proximal caries detection , recently , the new methods of magnifying visual aids such as intraoral camera , magnification loops , and operating microscope are used for caries diagnosis , restorative treatment decisions , root resection , and retrograde canal preparation [ 7 , 8 ] . previous studies [ 9 , 10 ] had investigated the efficiency of operating microscope for occlusal caries diagnosis , but there is insufficient publication [ 5 , 11 ] about usage of this device for proximal caries detection in dental literature . the purpose of this study was to evaluate the efficiency of operating microscope compared with unaided visual examination , conventional and digital intraoral radiography for proximal caries detection by means of receiver operating characteristic ( roc ) curve analysis . the study was based on 48 extracted human posterior permanent teeth , 24 molars and 24 premolars stored in a 5% buffered formalin solution . no specimens exhibited any restoration on the proximal surfaces . organic and inorganic debris were removed by an excavator and then the teeth were cleaned by pumice and water slurry . the models were fixed in a phantom head which was adjusted to a dental unit during the sessions of unaided visual examination and operating microscope assessment . the proximal surfaces coronal to the cementoenamel - junction of the teeth were assessed by two specialists of oral diagnosis and radiology and one specialist of restorative dentistry of at least 10 years of experience independently . to avoid observer fatigue , the models were examined under a dental unit light , by using a dental mirror ( size 5 ) and the air water syringe of the dental unit without any magnification for unaided visual examination . the clinicians evaluated the extent of the carious lesions in the proximal surfaces of the teeth according to a 5-point rating scale ( table 1 ) . then the teeth were examined using an operating microscope 16x magnification ( moller - wedel , dento 300 , wedel , germany ) according to the same scale . the observers assessed the teeth adjusting the height of the operating stool at a 12 o'clock position . the position of operating microscope was not changed to eliminate the position errors during the examinations . after unaided visual and operating microscope examinations were completed , the teeth were mounted in dental stone models 3 in a row ( either 2 premolars and 1 molar or 1 premolar and 2 molars ) with proximal surfaces in contact . conventional bitewing radiographs of the teeth were obtained using a specially designed holder to provide standardized bitewing projection geometry in the buccolingual direction , tangential to the proximal surfaces . the object to film distance was approximately 0.5 cm and the source - to - image receptor distance was 32 cm . size 2 insight ( eastman kodak company , paris , france ) films with an exposure time of 0.16 seconds and ccx intraoral unit ( trophy , instrumentarium , tuusula , finland ) with focal spot of size 0.8 mm , operating at 70 kvp and 8 ma , with 2.5 mm of aluminum - equivalent filtration were used . one centimeter of soft tissue equivalent material was used to simulate scatter radiation and beam attenuation from facial tissues . all film radiographs were developed in automatic film processor ( velopex , extra - x , medivance instruments ltd . , london , uk , and nw107a ) with freshly prepared solutions in the same day . the ccd - based system to be evaluated was the radiovisiography ( rvg , 2000 model , trophy radiologie , paris , france ) . digital images were obtained with 32 cm sensor to focal spot distance with an exposure time of 0.08 seconds under the same standardized conditions and were stored using the rvg image management software . the film radiographs were assessed using a masked light box and a 2x magnification x - viewer ( luminosa , csn industrie , cinisello balsamo , italy ) by three clinicians independently in a quiet room with subdued ambient lighting . images from the digital system were displayed on a 17-inch monitor in the same ambient lighting . the observers indicated their decision separately for each interproximal side of the teeth by masking other side with the use of a black cartoon . they assessed the extent of the carious lesions according to a 5-point rating scale ( table 1 ) . the proximal surfaces were first colored with a solution of propylene glycol with added basic fucsin ( 0.5% ) for 10 seconds and rinsed in tap water . then , the teeth were hemisectioned perpendicularly to the proximal surfaces from their santral fossas by a diamond disc under water - cooling . two sections were obtained , each section was examined under stereomicroscope ( olympus sz 60 , tokyo , japan ) with a 10x magnification . two observers not participating in the study both experienced in histological examination and being blinded to the radiographic appearance of the surfaces evaluated the sections by consensus according to a 5-point confidence scale ( table 1 ) . one way variance of analysis ( anova ) and pairwise comparisons ( scheffe test ) were performed for comparison of observers . the diagnostic accuracies of the four diagnostic systems were assessed from the area under the roc curve ( az ) . the rating scales were dichotomized as presence or absence of caries during the analysis . score 0 in both radiographic and histological scales was detected as absence of caries and the others were detected as presence of caries . histological examination of the teeth confirmed that 61 ( 63.54% ) of the proximal surfaces were caries free , whereas 35 ( 36.46% ) of proximal surfaces determined caries lesions of different depths . the numbers of proximal surfaces for each score according to the histological examination are shown in table 2 . statistically significant difference was found between three observers at 99% confidence interval ( p < .01 ) according to anova . no statistically significant difference was found between 1st and 2nd observers ( p < .05 ) and there was statistically significant difference between both 1st and 3rd observers and 2nd and 3rd observers ( p < the first roc curve ( figure 1 ) is illustrated by considering assessments of 1st observer due to no statistically significant difference between 1st and 2nd observers and the second roc curve ( figure 2 ) is illustrated for 3rd observer . areas under the roc curve ( az ) and standard errors are shown in table 4 and analysis of az values are shown in table 5 . for both 1st and 3rd observers , no statistically significant difference was found between operating microscope - unaided visual examination and film radiography ( insight)-rvg in 95% confidence interval according to pairwise comparison ( p < .05 ) . there was a statistically significant difference between operating microscope - film radiography , operating microscope - rvg , unaided visual examination - film radiography , unaided visual examination- rvg in 95% confidence interval according to pairwise comparison ( p < .05 ) for both 1st and 3rd observers . the efficiency of operating microscope was compared with unaided visual examination , film and digital intraoral radiography for proximal caries detection according to roc analysis in this study . recently , many researchers have advocated the use of roc analysis to assess diagnostic methods for the detection of dental caries . validity of roc analysis can be assessed by increasing the number of tooth surfaces , increasing the rating scale , and uniform distribution of caries depths . in this study , the sample was relatively large , 5-point rating scale was used , and the distribution of caries depths was not uniform . area under the roc curve ( az value ) gives useful information to measure accuracy of a diagnostic system . the az values of unaided visual examination and operating microscope were equal and lower than the radiographic methods . interobserver reliability is an important factor for this aim . on the other hand , training and experience of observers may affect intra- and interobserver agreements . syriopoulos et al . emphasized that diagnosis of the radiologists was significantly closer to actual lesion depth than that of general practitioners . two of the observers were the specialists of oral diagnosis and radiology , the other observer was a specialist of restorative dentistry of at least 10 years of experience in this study . no statistically significant difference was found between the two specialists of oral diagnosis and radiology for all diagnostic systems ( p < .05 ) , but there was a statistically significant difference between the specialist of restorative dentistry and the specialists of oral diagnosis and radiology ( p < .05 ) . the az values were found to be 0.800 , 0.793 , and 0.650 for film radiography , rvg , and both unaided visual examination and operating microscope , respectively , according to assessments of 1st observer . the az values were found to be 0.773 , 0.760 , 0.533 for film radiography , rvg , and both unaided visual examination and operating microscope , respectively , according to assessments of 3rd observer in this study . the az values of 1st observer were higher than 3rd observer for all diagnostic methods . this condition may be due to the fact that the specialists of oral diagnosis and radiology were more experienced than other specialists about diagnostic and radiographic methods . due to difficulty of proximal caries diagnosis with only visual examination , the combination of visual inspection and bitewing radiographic images is accepted as a standard procedure in proximal caries detection [ 5 , 19 ] . machiulskiene et al . reported that the clinical examination alone detected about 60% of the total number of proximal cavitated dentin lesions , and bitewing examination detected about 90% of these lesions . but they emphasized that the clinical examination is a more effective method in noncavitated enamel lesions . in this study , the radiographic methods were better than clinical examinations for proximal caries diagnosis in conformity with previous studies [ 19 , 21 ] . . the operator should be careful and not change the position as far as possible . it was reported that the ideal operator zones are in the 7 to 12 o'clock positions for right - handed operators , and 5 to 12 o'clock for left ones . the researchers studied at 12 o'clock position and not changed the position of operating microscope during the examinations in this study . currently , magnifying visual aids such as magnification eyeglasses , stereo microscope , and also digital imaging with magnification are used in proximal caries detection in some studies and they reported that these methods are effective . however , haak et al . reported that prism loupe or surgical microscope does not improve the ability to diagnose proximal caries . in this study , the efficiency of operating microscope was evaluated by comparing with unaided visual examination , film and digital intraoral radiography for proximal caries detection according to roc analysis . no statistically significant difference was found between operating microscope and unaided visual examination ( p < .05 ) , and there was a statistically significant difference between operating microscope and both two radiographic systems ( p < .05 ) . in conclusion , the efficiency of operating microscope was found statistically equal with unaided visual examination and lower than film and digital intraoral radiography according to roc analysis . because the operating microscope is expensive and requires equipment and operator experience , according to the results of this in vitro study it can be said that use of this device would not improve to make an accurate diagnosis of proximal caries lesions . however , the accuracies of diagnostic methods with magnifying visual aids should be investigated and clinical usefulness of these methods in dental practice should be discussed in vitro and in vivo with several studies in which the numbers of samples are larger and rating scales are increased by comparing conventional methods for proximal caries detection .

objective . the purpose of this study was to evaluate the efficiency of operating microscope compared with unaided visual examination , conventional and digital intraoral radiography for proximal caries detection . materialsand methods . the study was based on 48 extracted human posterior permanent teeth . the teeth were examined with unaided visual examination , operating microscope , conventional bitewing and digital intraoral radiographs . then , true caries depth was determined by histological examination . the extent of the carious lesions was assessed by three examiners independently . one way variance of analysis ( anova ) and scheffe test were performed for comparison of observers , and the diagnostic accuracies of all systems were assessed from the area under the roc curve ( az ) . results . statistically significant difference was found between observers ( p < .01 ) . there was a statistically significant difference between operating microscope - film radiography , operating microscope - rvg , unaided visual examination - film radiography , and unaided visual examination - rvg according to pairwise comparison ( p < .05 ) . conclusion . the efficiency of operating microscope was found statistically equal with unaided visual examination and lower than radiographic systems for proximal caries detection .

traditionally , most educational program design and evaluation have not been considered part of the research enterprise . clinicians or researchers would spend time teaching , but this was considered wholly separate from their other academic pursuits . the work of glassick5 in the late 1990s provided a taxonomy and framework for a more deliberative teaching process with key components of careful design , meaningful evaluation , peer review , and reflective critique intended to spawn opportunities for presentation and publication . with the evolution of the scholarship of teaching , educators began to reflect on the research - like attributes of their work as well as the implications of its design and delivery for their subjects . in 2004 , an article appeared detailing the plight of a grant - funded curricular program in geriatrics.6 the article described how medical students at a university in which faculty initiated curricular change with grant funding ultimately were forced to cancel the program when students protested the fact that they were not consented prior to the innovation and that the project had not undergone irb review . while lacking the historical weight of the belmont report , this cautionary tale raised a number of important points , including ( 1 ) learners may be considered not just passive participants but actually subjects of education research and that educators need to consider their rights and identities when participating in these projects , ( 2 ) a lack of training and awareness among health professions educators about the protection of human subjects and the irb process and a prevailing sense that irb review is an optional process and something to be avoided if possible , and ( 3 ) the growth of external funding raising the possibility that local activities might be influenced by demands and requirements of outside agencies . these points speak to the core of the mission of the irb in that health professions educators need to consider the ethical implications of the design and execution of their work . hpe is recognized as a key ingredient in high - quality nursing and medical care.7 a demand exists for evidence to inform how we educate health care professionals , and educational programs have become a key tool for implementing improvement . admittedly , the science underlying education research is often complex and requires use of a variety of study designs both experimental and quasi - experimental and multiple approaches for evaluation , including both qualitative and quantitative.8 the evolving sophistication and complexity of hpe research point to a need for a centralized source for review of conduct and quality of these projects . moreover , education researchers are gathering , collating , and analyzing large amounts of data . these data need to be collected and stored in a way that ensures its integrity and protects the identity of learners . collaboration across institutions adds an additional layer of complexity to this process.9 it is often the intent of medical and nursing education researchers to disseminate their work through presentation and publication . this intent to generalize has important implications for the use of information and protection of the identity of participants . furthermore , hpe is moving toward measuring impact of teaching interventions on outcomes including patient care . the examination of a learner s performance in real clinical care requires a consideration of how to handle not only the learner data , but also that of the patient as well . finally , consideration must be given to the learner as a vulnerable subject , prone to coercion , exposure , and undue psychological stressors . health professions educators may be best served to reframe these challenges as compelling reasons to engage the irb as a partner in the process of ensuring sound design and the responsible and ethical conduct of educational research . reframing starts with a careful examination of the principles underlying the formation and mission of the irb in the code of federal regulations and a point - by - point examination of their relevance to the education researcher . the responsibility of an irb is to ensure that the regulatory criteria for approval of a study are met and in so doing help protect the rights and welfare of human subjects involved in research , including ensuring that risks of participating in a study are reasonable in relation to the potential benefits . current federal regulations require that all nonexempt human subjects research be approved by an irb before an investigator may conduct a study . making decisions regarding the irb review process for research studies begin with first determining if human subjects are involved and if the investigation is truly designed to contribute to generalizable knowledge.10 the federal policy for the protection of human subjects research is known as the common rule and guides oversight and provides guidance for those engaged in research involving living individuals.11 human subjects research means obtaining data through intervention or interaction with an individual or by using identifiable private information to answer a research question.10 in the case of hpe , learners may be considered there are 3 types of irb reviews for new protocols : exempt , expedited , and full - committee review . the responsibility of an irb is to ensure that the regulatory criteria for approval of a study are met and in so doing help protect the rights and welfare of human subjects involved in research , including ensuring that risks of participating in a study are reasonable in relation to the potential benefits . current federal regulations require that all nonexempt human subjects research be approved by an irb before an investigator may conduct a study . making decisions regarding the irb review process for research studies begin with first determining if human subjects are involved and if the investigation is truly designed to contribute to generalizable knowledge.10 the federal policy for the protection of human subjects research is known as the common rule and guides oversight and provides guidance for those engaged in research involving living individuals.11 human subjects research means obtaining data through intervention or interaction with an individual or by using identifiable private information to answer a research question.10 in the case of hpe , learners may be considered there are 3 types of irb reviews for new protocols : exempt , expedited , and full - committee review . there are specific categories of research involving human subjects that are eligible for exemption ; some types of education research meet the definition for these categories . to assist education project leaders in determining what types of projects meet the exempt education research criteria , the office for human research protections in section 45 cfr 46.101(b1 - 6)10 includes educational research categories that could potentially be considered exempt : research conducted in established or commonly accepted educational settings , involving normal educational practices , such as ( i ) research on regular and special education instructional strategies or ( ii ) research on the effectiveness of or the comparison among instructional techniques , curricula , or classroom management methods ( cfr 46.101.b1 ) . in table 2 , research involving the use of educational tests ( cognitive , diagnostic , aptitude , achievement ) , survey procedures , interview , or observation of public behavior , unless ( i ) information obtained is recorded in such a manner that human subjects can be identified , directly or through identifiers linked to the subjects ; and ( ii ) any disclosure of the human subjects responses outside the research could reasonably place the subjects at risk of criminal or civil liability or be damaging to the subjects financial standing , employability , or reputation ( cfr 46.101.b2 ) . this exemption does not apply when surveys , interviews , or observation of public behaviors include individuals younger than 18 years when the investigator is participating in the activities being observed . examples of education research and types of irb reviews research involving the collection of existing data , documents , or records , if publicly available , or if information is recorded by the investigator in such a manner that subjects are not identifiable ( directly or through identifiers ) may also be exempt ( cfr 46.101.b4).10 careful evaluation of the above categories determines whether an education research project meets the exemption criteria or requires an expedited or full - committee irb review . when a research study does not meet the criteria for exemption , the risks to subjects participating in the project should be further evaluated . in table 2 , federal regulations define minimal risk as the probability and magnitude of harm or discomfort anticipated in the research is not greater in and of themselves than that ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests ( 45 cfr 46.102[i]).10 most education research studies are minimal risk studies when protection of the rights and welfare of subjects involved are carefully considered . education research subjects must not be unduly influenced to participate.13 protection of the identity of involved subjects must be considered . if any information is collected that can directly identify a subject or when an identifier can be linked to this individual , then it is not eligible for exemption unless it meets one of the 6 exemption categories listed in the federal regulations ( 45 cfr 46.101).14 measures to protect the privacy and confidentiality of subjects should be taken and clearly described in the study . when students are directly involved themselves , even exempt education research studies must inform the subjects about the project , and they must be provided details as to how confidentiality of the information will be protected . subjects must also be told that participation is voluntary and that they can refuse to answer questions that they do not wish to answer . written consent may be required if the project includes collection of recorded data via voice , video , digital , or image . individual or group interviews or focus groups may require written consent as well . first consider whether the research is more than minimal risk of harm to subjects and if it involves no procedures for which written consent is normally required outside the research environment ( 45 cfr 46.117.c2 ) . there are many situations where consent documentation can be waived , and the irb can request the investigators to provide subjects with a written statement regarding the research . examination of nursing students perceptions about a specific disease such as human immunodeficiency virus ( hiv ) or cancer and their attitudes toward caring for a patient through interviews or focus groups requires research measures to ensure that student participation is voluntary and anonymity is protected . this type of research would not be exempt and requires informed consent . in comparison , evaluation of the effectiveness of a curriculum designed to allow students to explore their attitudes toward caring for patients with hiv or cancer may be seen as standard educational practice and would meet the criteria for exempt research if anonymity is maintained and no identifiers are collected . even if written consent is not required , learners responding to surveys or other measures should be informed of the voluntary nature of their participation and the intent of the educator to analyze and disseminate the data . hpe researchers and their supporting institutions aspire to innovate in a way that will improve both the ability of the graduating learner and the care they provide . to achieve these goals in a responsible and ethical way , steps must be taken to bridge the gap between their work and the review process . these improvements may take several forms including ( 1 ) education and orientation programs , ( 2 ) expansion of the types of expertise and assistance available at the irb , and ( 3 ) development of hpe - friendly review templates and processes . institutions should begin by introducing programs to inform both educators and irb members about issues specific to education - related projects . educators need to gain greater understanding of the process and definitions set forth in the cfr to more accurately prepare submissions for review . specifically , such programs might focus on criteria for exemption versus review , risk for learners , and indications for consent . health professions educators would also benefit from more in - depth orientation to data management and protection and , specifically , institutional resources designed to help with these issues . the irb itself also should participate in a review of its capabilities for reviewing educational projects . this may involve orientation for its board members on the specific issues and characteristics of education research . in addition , many have proposed that irbs should seek to include reviewers with specific expertise in social and behavioral sciences ( often lacking on medical campuses).15 at institutions with active education research communities , addition of a dedicated chair or board may be necessary . in addition to orientation and education , the development of submission templates and targeted reviews specific for education projects may help the utility and efficiency of the process.16 at duke university , a group of educators from our schools of medicine and nursing developed a template in collaboration with leadership of the irb to address needed improvements in the process . our work followed the example set by the development and implementation of a template for submissions for quality improvement ( qi ) projects.17 our team first met with representative chairs of the irb to discuss the structure and content of the template as well as a plan for piloting the submission and review process . a draft version of the template was circulated among educators and irb members for feedback and revision . the template , derived from the traditional research submission form , offered a modified organization and language to provide a better fit for education - related projects as well as clarity for reviewers ( table 3 ) . a pilot group of submissions was routed to 2 irb chairs involved in the development of the template . the form was posted on the irb web site , and our development team offered a series of workshops for faculty on its use . it is important for health professions educators to consider the ethical implications of conducting education research . increased understanding of the categories for exempt research and how to determine when an education research study does not meet the criteria for exemption are essential for those involved in hpe . specifically , educators need to recognize learners as subjects and anticipate and acknowledge risks inherent in their participation in education research . in addition , educators need to seek greater knowledge and resources for data collection and management to ensure protection of subject identity and study integrity . improvements in the review process for educational research studies will require a collaboration between educators and the irb as outlined in this article . development of education programs for researchers and reviewers , integration of educational expertise on the irb , and standardization and dissemination of submission templates will all enhance the process and improve the quality of the work .

the growth in health professions education ( hpe ) and a desire on the part of nurse and medical educators to disseminate their work have raised important questions about the ethical conduct of education research . at the center of the debate is the institutional review board ( irb ) and its proper role in the oversight of hpe research . this article examines the irb process and types of reviews for education research and presents an education project summary template to use for irb reviews .

the worldwide number of long - term cancer survivors is growing fast with ongoing improvements in cancer therapies [ 1 , 2 ] . however , long - term cancer survivors may suffer from late side effects of cancer therapy . one of these late side effects is radiation - induced heart disease ( rihd ) , which may occur after radiotherapy of thoracic and chest wall tumors whenever all or part of the heart is situated in the radiation field . rihd has been described to occur , for instance , among survivors of hodgkin 's disease [ 3 , 4 ] and breast cancer [ 5 , 6 ] . radiotherapy planning has undergone many improvements over the last decades , with modalities such as intensity - modulated radiation therapy ( imrt ) , image - guided radiation therapy , and proton therapy , leading to reduced exposures of the heart . for instance , patients with hodgkin 's disease , lung cancer , and esophageal and proximal gastric cancer may still receive either a high dose of radiation to a small part of the heart or a lower dose to the whole heart [ 711 ] . in addition , although there is increasing use of concomitant therapies , the extent to which these therapies affect radiotherapy side effects such as rihd is largely unknown . manifestations of rihd include accelerated atherosclerosis , pericardial and myocardial fibrosis , conduction abnormalities , and injury to cardiac valves [ 4 , 12 ] . the disease is progressive and both incidence and severity increase with a higher radiation dose volume , younger age at the time of radiotherapy , a greater time elapsed since treatment , and concomitant use of cardiotoxic chemotherapeutic agents such as anthracyclines . although rihd is widely acknowledged as an impediment to quality of life for certain long - term cancer survivors , from a clinical perspective the only current way to reduce rihd is through efforts to improve radiotherapy treatment planning , as other methods to prevent or reverse rihd are not yet available . hence , pre - clinical studies seek to unravel basic mechanisms of rihd , with the ultimate goal to identify potential targets for intervention . pre - clinical animal models have long been used to study rihd [ 1318 ] . while transgenic mouse models are being used in investigations of radiation - accelerated atherosclerosis [ 19 , 20 ] , wild type rodents are usually not atherosclerosis prone . hence , studies that use rodents to investigate radiation - induced coronary artery disease are limited in number [ 21 , 22 ] . on the other hand , many laboratory animals , including rodent , have been used successfully as models of radiation - induced cardiomyopathy [ 16 , 2327 ] . common doses used in these pre - clinical models of localized heart irradiation are either a single dose between 5 gy and 25 gy , or fractionated schedules of , for instance , 5 daily fractions of 9 gy . some of the histopathological changes in pre - clinical models , such as myocardial degeneration and fibrosis , are also commonly described in human cases of rihd , mainly after exposure to doses of ~30 gy and above [ 3 , 4 , 2830 ] . although clinical and pre - clinical data on the cardiovascular effects of lower radiation doses are growing [ 11 , 31 ] , the focus of this review will be on myocardial injury and cardiac function changes after exposure to higher doses of radiation . previous paper indicate the important role of vascular injury and endothelial dysfunction ( loss of thromboresistance and increased expression of adhesion molecules and cytokines ) in the pathogenesis of normal tissue radiation injury [ 42 , 43 ] . endothelial dysfunction may contribute to profibrotic and proinflammatory environments , which are common aspects of normal tissue radiation injury [ 42 , 44 ] . although the role of endothelial dysfunction in rihd has not been studied in detail , experimental rihd is known to be associated with reduced myocardial capillary density [ 32 , 33 ] , focal loss of endothelial alkaline phosphatase [ 14 , 34 ] , and increased expression of von willebrand factor . hence , microvascular injury and the resulting local ischemic injury are considered to be some of the underlying mechanisms of rihd . radiation - induced vascular injury and endothelial dysfunction are mediated in part by transforming growth factor- ( tgf- ) [ 45 , 46 ] , a pluripotent growth factor that is part of many normal tissue radiation responses [ 4749 ] . previous studies have shown cardiac upregulation of tgf- in rat models of rihd after localized heart irradiation with 20 gy or 5 fractions of 9 gy [ 3638 ] . a tgf--inducing compound was used to investigate the role of tgf- in rihd in the rat . cardiac radiation fibrosis was more severe in animals that had been administered the tgf--inducing compound during the 6-month followup time after irradiation ( unpublished data ) . mast cells , cells that belong to the hematopoietic myeloid lineage , reside in many organs and tissues including the heart . although best known for their role in hypersensitivity reactions , mast cells are also intimately involved in wound healing and tissue remodeling [ 5052 ] . mast cells store and release a wide range of cellular mediators , both via degranulation and via constitutive pathways that do not involve degranulation . increased mast cell numbers are commonly found in coronary atherosclerosis , myocardial fibrosis [ 54 , 55 ] , and also in animal models of rihd [ 40 , 56 ] , where mast cell numbers correlate with myocardial radiation injury . the development and maturation of mast cells depend on the c - kit receptor , which is specific for stem cell factor . several mast cell deficient animal models , based on a mutation in the c - kit receptor or stem cell factor , are available [ 5759 ] . our laboratories have made use of a rat model that is homozygous for a 12-base deletion in the c - kit receptor gene [ 60 , 61 ] . both mast cell - deficient rats and their mast cell - competent wild type litter mates were exposed to localized heart irradiation with a single dose of 18 gy . although mast cell - deficiency was associated with reduced radiation - induced myocardial inflammation and degeneration , other manifestations of cardiac radiation injury such as myocardial fibrosis and ex vivo measures of myocardial stiffness were exacerbated in the absence of mast cells . these studies suggest that mast cells , in contrast to what had been the prevailing assumption but similar to what has been found in some other cardiac disease models [ 62 , 63 ] , play a predominantly protective role in rihd . mast cell - derived proteinases , for instance , have been shown to contribute to both the formation and degradation of endothelin-1 ( et-1 ) [ 6468 ] . et-1 is a 21-amino acid peptide that was first discovered as a potent vasoconstrictor but also has proinflammatory and pro - fibrotic properties [ 69 , 70 ] . the role of et-1 in cardiovascular pathology has been studied extensively [ 71 , 72 ] . both et-1 receptors , eta and etb are expressed by a wide variety of cell types in the heart [ 70 , 73 ] . short - term upregulation of et-1 and its receptors may serve as a mechanism to maintain cardiac function in certain cardiovascular diseases [ 74 , 75 ] . long - term up - regulation of the endothelin system , on the other hand , may have detrimental effects due to the vasopressor , prohypertrophic , and pro - fibrotic properties of et-1 [ 73 , 76 ] . mast cells express the receptor eta , which upon activation by et-1 induces mast cell degranulation , a pathway by which et-1 may enhance the activity of matrix metalloproteinases ( mmps ) in the heart [ 78 , 79 ] . dual inhibition of eta and etb prevented mast cell degranulation and the associated increase in cardiac mmp levels , interstitial collagen degradation , and ventricular dilatation in a rat model of chronic volume overload . on the other hand , in a preliminary study of a rat model of rihd , dual inhibition of eta and etb did not alter radiation - induced functional or structural cardiac changes . moreover , vascular injury seemed aggravated by selective eta inhibition in a rat model of localized intestine irradiation . dosing of receptor antagonists and opposing cardiovascular effects of the eta and etb , receptors [ 83 , 84 ] warrant further studies to clarify the role of et-1 and its two receptors in rihd . they are found in close proximity to nerve terminals or axons in many organs , including the heart [ 86 , 87 ] , and interact with nerves on the molecular level in many ways [ 85 , 88 , 89 ] . mast cells express - and -adrenergic receptors [ 90 , 91 ] . in normal rat myocardium some sensory neuropeptides such as calcitonin gene- related peptide ( cgrp ) , substance p , and neuropeptide y are able to induce or enhance mast cell degranulation [ 93100 ] while others have been shown to inhibit mast cell degranulation [ 101 , 102 ] . mast cells , in turn , affect neuronal growth and function by producing nerve growth factor and by activating proteinase - activated receptor-2 on the surface of neurons [ 104 , 105 ] . cardiac sensory nerves play a protective role in the heart via the release of nitric oxide and cgrp [ 106 , 107 ] . for instance , cgrp plays a protective role in myocardial injury such as from ischemia reperfusion and the cardiotoxic chemotherapeutic agent doxorubicin [ 108 , 109 ] . cgrp is a potent vasodilator but also has beneficial effects in the heart by local downregulation of tumor necrosis factor - alpha ( tnf- ) and upregulation of insulin - like growth factor-1 ( igf-1 ) [ 110 , 111 ] . interestingly , both downregulation of tnf- and upregulation of igf-1 are associated with reduced normal tissue radiation injury [ 112 , 113 ] . in line with this evidence the role of the renin angiotensin system ( ras ) in normal tissue radiation injury has been well defined [ 115 , 116 ] . inhibitors of angiotensin - converting enzyme ( ace ) and antagonists of angiotensin type 1 receptors reduce injury in animal models of localized kidney , lung , and brain irradiation [ 117119 ] . although the role of ras in rihd is less well defined , ras mediators may be upregulated in the heart after irradiation . however , while the ace inhibitor captopril reduced radiation injury in kidney , lung , and skin of rats [ 119121 ] , captopril did not prevent cardiac function loss after localized heart irradiation with 20 gy in a rat model . captopril , on the other hand , did reduce myocardial fibrosis and prevented left ventricular capillary density loss after local heart irradiation . it is not known whether these effects were due to properties of captopril other than its inhibition of ace . inhibition of ace is considered to be cardioprotective in part by suppressing the breakdown of bradykinin by ace . bradykinin , a small peptide hormone that is sometimes considered to aggravate cardiac disease with a significant inflammatory component such as myocardial infarction , is also known to mediate cardioprotection via induction of nitric oxide and prostacyclin [ 124126 ] . bradykinin is formed in the kallikrein - kinin system by proteolytic cleavage of both high- and low - molecular weight kininogen by kallikrein enzymes , but also by the mast cell - derived enzyme tryptase [ 127 , 128 ] . interestingly , the mast cell proteinases chymases are one of the main converters of angiotensin i into angiotensin ii . mast cells seem to hereby provide a particularly large contribution to local extravascular generation of ang ii . the roles of ras and bradykinin in cardiac radiation injury and the potential influence of mast cells herein need further investigation . radiotherapy planning has undergone many improvements over the last decades , leading to improved targeting and reduced normal tissue radiation exposure . nonetheless , some patients with hodgkin 's disease , lung cancer , and esophageal and proximal gastric cancer may still receive either a high dose of radiation to a small part of the heart or a lower dose to the whole heart , which may lead to late manifestations of rihd . some of the basic mechanisms of rihd have begun to emerge from recent pre - clinical studies and include the involvement of vascular injury , mast cells , and the ras . future studies will elucidate the significance of these mechanisms for clinical rihd and their usefulness as targets for intervention in rihd .

radiation - induced heart disease ( rihd ) is a potentially severe side effect of radiotherapy of thoracic and chest wall tumors if all or part of the heart was included in the radiation field . rihd presents clinically several years after irradiation and manifestations include accelerated atherosclerosis , pericardial and myocardial fibrosis , conduction abnormalities , and injury to cardiac valves . there is no method to prevent or reverse these injuries when the heart is exposed to ionizing radiation . this paper presents an overview of recent studies that address the role of microvascular injury , endothelial dysfunction , mast cells , and the renin angiotensin system in animal models of cardiac radiation injury . these insights into the basic mechanisms of rihd may lead to the identification of targets for intervention in this late radiotherapy side effect .

femoral shaft fractures are one of the commonest fractures of lower extremities in children and the commonest complication requiring hospital admission . few degrees of angular deformity and few centimetres of shortening are acceptable in children according to their age group , because children have tremendous re - modelling potential . a variety of methods are used for the treatment of paediatric diaphyseal femur fractures , including immediate spica casting , traction followed by spica casting , external fixators , osteosynthesis with plate and internal fixation with intramedullary rod or flexible intramedullary nail . choice of treatments depends upon the age of children , anatomical site , fracture pattern and preference of the surgeon . traditionally , children below 6 years of age are treated with immediate hip spica and adolescent children are treated with operative methods.13 external fixators are associated with increased chances of pin tract infection and re - fracture . intramedullary rods increase the chances of avascular necrosis of femoral head and damage to the physis . flexible intramedullary nailing has become an increasingly popular method of paediatric femoral fracture fixation.45 systemic reviews and various cohort studies have shown excellent clinical results with flexible intramedullary nails ( rush pins ) for children , and few studies has extended its indication to preschool - going children . however , no randomized controlled trial has been reported comparing flexible intramedullary rush nailing with other mode of management of paediatric diaphyseal femur fracture . we present a randomized controlled trial comparing flexile intramedullary rush pins with immediate spica casting for paediatric diaphyseal femur fracture . a total of 50 children belonging to the age group 3 to 13 years presenting to teaching hospital of national medical college ( november 2010 to december 2012 ) with diaphyseal femur fracture were randomly allocated into group a ( immediate hip spica casting ) and group b ( flexible intramedullary rush pins ) using random number generation technique . in group a , the fracture was reduced on the same day or the next day of presentation to the hospital with fluoroscopy control under general anaesthesia and one and half spica casting was applied [ figure 1 ] . criteria of acceptable reduction were based upon kasser et al . , [ table 1].13 children were admitted to the hospital until parents learned how to take care of spica . follow - up was performed at the 2 week for evaluation of reduction and spica - related complications . radiological evaluation of bridging callus was performed at the 6 week for evaluation of radiological union . if bridging callus was seen at three cortices , the child was asked to bear weight with or without support , according to pain tolerance . if callus was not evident , long leg cast was applied for 4 more weeks . children with femoral shaft fractures : before hip spica x - ray , ( a ) in spica cast , ( b ) after the cast , ( c ) broken spica on 6-week follow - up , ( d ) x - ray on 6-week follow - up ( e ) and final x - ray at 4-month follow - up ( f ) acceptable angulation and shortening in children with a femoral fracture * in group b , under general anaesthesia , two small skin incisions were made on either side of distal metaphysis and two holes are made obliquely facing towards medullary cavity with the help of 4-mm awl , an inch proximal to the growth plate . two pre - contoured c - shaped rush pins were passed retrogradely with fluoroscopy control until both the tips reached just distal to the fracture site . fracture was reduced with manual traction and rush pins are pushed into medullary cavity of proximal fragment under fluoroscopy control [ figure 2 ] . tips of the pins were targeted up to the level of the neck and base of the greater trochanter . care was taken to ensure that the bent distal part of rush pin lied on the cortical surface of the supracondylar of femur without soft tissue impingement . size of the rush pins were measured as 40% of narrowest diameter of femur on ap and lateral view . in initial few cases , we applied posterior long leg plaster of paris back slab , which we later discontinued and used only knee immobilizer post - operatively until the sutures were removed after 2 weeks . as soon as pain was tolerable , the hip and knee were mobilized and non - weight bearing ambulation was allowed . weight bearing was permitted once bridging callus was evident on x - ray on three cortices . follow - up was done at 6 , 12 week , 6 months , 1 year and 2 years for radiological and clinical evaluation [ figure 3 ] . the treatment cost was calculated as the total amount paid to the hospital that covered admission , investigation , operation and hospital stay charges because many indirect costs are associated with total management , which could not be generalized . fixation of flexible intramedullary rush pins procedure in a child with femoral shaft fracture ( a ) and radiographs taken before operation , ( b ) immediately after operation ( c ) and at 14-month follow - up ( d ) radiological and clinical evaluation of the outcome of rush pin fixation success of randomization was tested between two groups . magnitude of difference between the two groups was measured between means in the both group by spss 11.5 software , and the significance of difference was measured by determining p value using chi - square test for qualitative variables and independent t test or man - whitney u test for quantitative variable , depending upon whether p value obtained from kolmogorov - smirnov z test for homogeneity of variance was below or above 0.05 . magnitude of difference between the two groups was measured between means in the both group by spss 11.5 software , and the significance of difference was measured by determining p value using chi - square test for qualitative variables and independent t test or man - whitney u test for quantitative variable , depending upon whether p value obtained from kolmogorov - smirnov z test for homogeneity of variance was below or above 0.05 . table 2 compares the success of randomization between the two groups in terms of age , sex , weight , side , fracture pattern , stability , mode of injury and the anatomical site . success of randomization between groups a and b age in both the groups ranged from 3 to 13 years with a mean age of 6.4 3.46 years . male to female ratio was 2.5:1 and 4:1 in group a and b , respectively . fracture pattern was classified according to ao classification , which showed type 32a1 as the most common pattern of injury . spiral or long oblique fractures or fracture with comminuation more than two - third of the diameter of the bone were considered unstable . fall related injury either from hill slope , tree , cliff or wall was commonest mode of injury , which comprised of 88% of injury in both group a and b. anatomically , femoral diaphysis was the most common site of femur fracture in this study . the mean follow - up period was 16.1 months ( range : 6 - 26 months ) in group a and 17 months ( range : 6 - 28 months ) in group b. one patient in group a could not be followed up at all after discharging from the hospital and hence excluded from the analysis . a total of 16 children in group b who could be trained for ambulation with walking aids started walking much earlier than 14 children in group a with significant mean difference ( 13.38 2.3 days in group b vs. 52.33 4.5 days in group a , p = 0.000 ) . similarly , children in group b started walking without aid with a mean duration of 6.6 1.29 weeks as compared to 10.67 4.32 weeks in group a ( p = 0.002 ) . also , 17 children in group b and 13 in group a were school - going children pre - operatively . the mean duration of return to school was 8.82 01.7 weeks in group b and 15.6 2.98 weeks in group a ( p = 0.000 ) . in group a , clinico - radiological union was achieved within 12 weeks duration in 10 cases , within 16 weeks in 12 cases and within 17 weeks in 2 cases with a mean union time of 13.25 2.43 weeks , whereas allthe fractures united within 12 weeks in group b with a mean duration of 10.76 0.72 weeks ( p = 0.000 ) . children returned to full activities at a mean time of 8.76 2.27 weeks in group b and 12.08 4.51 weeks in group a ( p = 0.027 ) [ table 3 ] . outcome variables comparing two groups a and b children in group b were discharged from the hospital with an average duration of 6.56 2.75 days as compared to 3.32 1.4 days in group a ( p = 0.000 ) . the hospital cost was more for children with fracture managed with rush pins in group b ( us$ 50.68 11.70 ) than in group a ( us$31.04 12.16 ; p = 0.000 ) [ table 3 ] . increased hospital cost in group b can be attributed to longer hospital stay that ranges from 3 to 14 days , as many patients in our teaching hospital come from far and remote distance from where it is not only expensive but also difficult for coming to hospital for the removal of sutures . final outcome at the end of follow - up was evaluated according to flynn 's grading.1 table 4 shows that individually and overall group b had superior outcome as compared to group a ; 19/25 ( 76% ) children had excellent , 5/25 ( 20% ) had satisfactory and 1/25 ( 4% ) had poor result in group b as compared to 4/24 ( 17% ) with excellent , 11/24 ( 49% ) with satisfactory and 9/24 ( 44% ) with poor outcomes in group a ( p = 0.000 ) . flynn 's grading ( 2001 , jpo ) in group a , 3 patients had plaster sores at the perineal area , which recovered with dressing and antibiotics ; 1 child had broken and loosened hip spica on the 2 week [ figure 1d ] and needed re - application of spica ; 4 children had increased angular deformity or overlapping , but within acceptable range on the 2 weeks of follow - up . in group b , one child presented with pin tract infection on the 7 day of surgery , which recovered after trimming of the protruded part ; another child presented with bursitis after 1 year , which recovered after removal of rush pins . one patient had lost anterio - posterior alignment on the 6 week of follow - up . in 1 child , penetration of posterior cortex of base of the neck was identified in subsequent follow - up . rush pin was removed on 6 month and did not show any changes of avascular necrosis till 1 and half years of follow - up . another patient had penetration of greater trochanter but no limb length discrepancy . staheli et al.,6 defined the ideal treatment of femoral shaft fractures in children as one that controls alignment and length , does not compress or elevate the extremity excessively , is comfortable for the child and convenient for the family and causes the least negative psychological impact possible . immediate spica casting or skeletal traction and application of a cast is common method for the treatment of diaphyseal femoral fractures in children and young adolescents and surgical intervention is indicated in open fractures , multi - trauma , concomitant head injuries , burns and neuromuscular wounding . however , psychosocial and economic effects of spica cast immobilization on children and their families have been reported by hughes et al.,7 and many studies advocate early fixation of femur fracture because complications inherent in conservative treatment , such as malunion and shortening , cast intolerance , financial factors and increased hospitalization can be decreased by surgery . among other operative methods , flexible intramedulary nail has been used increasingly due to its simplicity and characteristics of load - sharing internal splint that maintains the length and alignment of the limb until bridging callus is formed and spares the risk of damaging the physis or the blood supply to the capital femoral epiphysis with a proper surgical technique . torsional stability depends upon divergence of the rods in the proximal metaphysis and resistance to sagittal and cornal bending results from spreading of the prebent rods through the diaphysis , size of the rod and material properties of the rod . there are no clinical study comparing efficacy of titanium elastic nail with stainless steel nail like enders nail and rush pins . the young modulus of stainless steel is nearly double the size of titanium ( approximately 200 gpa versus approximately 110 gpa ) , making it a much stiffer material with less elastic properties . lee et al.,8 demonstrated that ender nail fixation of simulated femur fractures maintained fracture length and rotational control with weight bearing of up to 40% of body weight , even in the presence of comminution , whereas mahar et al.,9 reported that the titanium implants provided greater stability in resisting torsional loading and axial compression in both transverse and comminuted fractures in biomechanical comparative study with stainless steel nails . besides elastic property , retrogradely passed adequate size crossed rush pins offer all the advantages of closed reduction technique and internal fixation with flexible intramedullary nails . excellent clinical results using stainless steel flexible nails have been reported for both stable and unstable femur fracture in children . rathjen et al.,10 assumed that the stiffer properties of a stainless steel implant should confer greater fracture stability , especially in the setting of an unstable fracture pattern . cramer et al.,11 reported 10 prospectively evaluated 57 femoral shaft fractures in children treated with ender rods , 21 of which were either spiral fractures or comminuted . although the results were not stratified according to fracture stability , the authors noted no clinically significant leg length discrepancy or malunion . four patients did demonstrate radiographic angular deformities of < 15deviation at final follow - up . simanovsky et al.,12 defined that the flexible intramedullary nails can be an attractive and safe treatment options in children aged 3 - 5 years for femoral shaft fracture and should be brought up and discussed with parents . this study had a prospective design and used a convenience sample , which were its limitations . nonetheless , this study points towards the important that femoral shaft fractures in children can be better treated with surgery . this is a proper scenario within which a randomized controlled trial can be developed to obtain reliable answers without bias . intramedullary crossed rush pins are effective method of management of paediatric diaphyseal femur fracture as compared to primary hip spica in terms of early ambulation and return to normal activities and school earlier . the former gives a predictable clinical pathway and reduces the periods of traction and occupancy of hospital beds .

background : femoral fractures are common in children aged between 2 and 12 yearsand 75% of the lesions affect the femoral shaft . traction followed by a plaster cast is universally accepted as a conservative treatment . we compared primary hip spica or traction followed by hip spica with closed reduction and fixation with retrogradely passed crossed rush pins for diaphyseal femur fracture in 25 children of the age group 3 - 12 years , randomly distributed in each group.materials and methods : fifty children ( age : 3 - 13 years , mean ; 9 years ) with femoral fractures were evaluated ; 25 of them underwent the conservative treatment using immediate hip spica ( group a ) and 25 underwent treatment with crossed retrograde rush pins ( group b).results : mean duration of fracture union was within 15 weeks in group a and 12 weeks in group b. mean duration of weight bearing was 14weeks in group a and 7 weeks in group a. mean hospital stay were 4 days in group a and 8days in group b. the man follow - up period was 16 months in group a and 17 months in group b. complications like angulation , shortening and infection were compared . bursitis and penetration of pins at the site of rush pin insertion is a complication associated with this method of treatment.conclusion:closed reduction and internal fixation with crossed rush pins was a superior treatment method in terms of early weight bearing and restoration of normal anatomy .

a 45-year - old female visited the hospital with a palpable mass on the medial aspect of her thigh . the mass was observed by the patient 3 months previously and the size was perceived to be rapidly increasing . computed tomography of the site showed an 11 cm - sized well - circumscribed mass with heterogeneous intensity , calcification and septation ( fig . 1 ) . a diagnostic incisional biopsy was performed , and the tissue that was biopsied showed cartilage with atypical cytological features and focal necrosis . analysis determined that myxoid stroma surrounded the cartilage , with the presence of some scattered lipoblasts within the myxoid stroma . based on these findings , the biopsy was diagnosed as a malignant cartilage - forming tumor , and wide excision was performed on the entire mass . 2 ) , and each lobulated area was found to have different appearances that ranged from a solid gray fibrotic firm lobule , to a brown fibrotic soft lobule with a focal hemorrhage and cystic change , to a solid gray lobule with a focal glistening translucent myxoid appearance and a bluish firm resilient area with a focal calcification . microscopic analysis revealed that the solid gray fibrotic area showed diffuse proliferation of bland fusiform cells with ovoid elongated nuclei and a moderate to abundant cytoplasm , and fine , delicate capillary vessel networks were noted within the fibrotic area ( fig . the brown fibrotic and hemorrhagic area contained coagulative necrosis of bland fusiform cells with hemorrhage , and a previous biopsy was proposed as the cause for the change in tissue . the myxoid area was characterized by a prominent basophilic myxoid matrix with scattered bland fusiform cells and lipoblasts ( fig . the lipoblasts had eccentrically located , small , elongated nuclei that were pushed to the periphery of the cell by clear , abundant intracytoplasmic vacuoles . the bluish resilient areas , which accounted for about 10% of the tumor volume , were characterized by cartilage with enchondral ossification , which showed mature bone without osteoid ( fig . based on the immunohistochemistry , some of the fusiform cells and the lipoblasts were determined to be s-100 protein positive ( 1:300 , thermo fisher scientific , waltham , ma , usa ) ( fig . 4a ) , but were negative for smooth muscle actin ( 1:500 , dako , glostrup , denmark ) , desmin ( 1:1,000 , dako ) , and myogenin ( 1:100 , dako ) . less than 5% of the cells were determined to be p53 positive ( 1:1,000 , dako ) ( fig . 4b ) , and the ki-67 ( 1:100 , dako ) labeling index was also less than 5% . based on these findings , a diagnosis of myxoid liposarcoma was considered . molecular evaluation was performed on both the typical myxoid liposarcomatous and the cartilaginous areas , to confirm the proposed diagnosis . the final diagnosis was determined to be myxoid liposarcoma with cartilaginous differentiation , and the patient was scheduled for radiation therapy because the tumor was very close to the resection margin . currently , after 6 months of follow - up , the patient has not presented with any evidence of metastasis or reoccurrence . typical myxoid liposarcomatous and cartilaginous areas were marked on a paraffin block after the hematoxylin and eosin slides were reviewed . five 10 m sections of each area were cut from the resection specimen blocks and placed into eppendorf tubes . the total rna was extracted from the formalin - fixed , paraffin embedded samples using an rneasy mini kit ( qiagen , valencia , ca , usa ) following the manufacturer 's instructions . after preparation , 1 g of each of the total rna samples were reverse transcribed using a revertaid first strand cdna synthesis kit ( thermo fisher scientific ) , and a nested polymerase chain reaction ( pcr ) was performed using outer and inner primer sets that were based on a previous report.10 the outer primer set was tls - chop outer forward ( 5'-agcaaagctataatccccctcag-3 ' ) and tls - chop outer reverse ( 5'-gaaggagaaaggcaatgactca-3 ' ) , and inner primer set consisted of tls - chop inner forward ( 5'-gacagcagaaccagtacaacagcag-3 ' ) and tls - chop inner reverse ( 5'-gctttcaggtgtggtgatgtatgaag-3 ' ) . the expected size of the nested pcr products for the three common types of fusion transcripts were 379 bp , 103 bp , and 412 bp for type i ( exons 7 - 2 ) , type ii ( exons 5 - 2 ) , and type iii ( exons 8 - 2 ) , respectively . the results of the nested pcr for this study exhibited type ii fusion transcripts in both the typical myxoid liposarcomatous and cartilaginous areas ( fig . 5 ) . typical myxoid liposarcomatous and cartilaginous areas were marked on a paraffin block after the hematoxylin and eosin slides were reviewed . five 10 m sections of each area were cut from the resection specimen blocks and placed into eppendorf tubes . the total rna was extracted from the formalin - fixed , paraffin embedded samples using an rneasy mini kit ( qiagen , valencia , ca , usa ) following the manufacturer 's instructions . after preparation , 1 g of each of the total rna samples were reverse transcribed using a revertaid first strand cdna synthesis kit ( thermo fisher scientific ) , and a nested polymerase chain reaction ( pcr ) was performed using outer and inner primer sets that were based on a previous report.10 the outer primer set was tls - chop outer forward ( 5'-agcaaagctataatccccctcag-3 ' ) and tls - chop outer reverse ( 5'-gaaggagaaaggcaatgactca-3 ' ) , and inner primer set consisted of tls - chop inner forward ( 5'-gacagcagaaccagtacaacagcag-3 ' ) and tls - chop inner reverse ( 5'-gctttcaggtgtggtgatgtatgaag-3 ' ) . the expected size of the nested pcr products for the three common types of fusion transcripts were 379 bp , 103 bp , and 412 bp for type i ( exons 7 - 2 ) , type ii ( exons 5 - 2 ) , and type iii ( exons 8 - 2 ) , respectively . the results of the nested pcr for this study exhibited type ii fusion transcripts in both the typical myxoid liposarcomatous and cartilaginous areas ( fig . 5 ) . myxoid liposarcomas tend to occur in the lower extremities of young adults , and have a peak incidence in the 4th and 5th decades.3,12 myxoid liposarcomas can be grossly identified as well - circumscribed , multinodular , intramuscular tumors with a gelatinous cut surface and occasional hemorrhage.2,12 histologically , most of the tumors show bland fusiform cells and lipoblasts with varying degrees of cytoplasmic fat formation in the myxoid background with a prominent capillary vascular network.1,2 the fat vacuoles differ in regards to the size and number and tumor cells with a single vacuole have been described as signet ring - type lipogenic cells.1 this study observed cells with characteristics that were similar to typical myxoid liposarcoma with the exception of focal cartilaginous differentiation . the distinct differences between cartilaginous , leiomyomatous and osseous differentiation in myxoid liposarcoma has been described in a previous study.2 previous studies have reported that five cases of similar myxoid liposarcomas have occurred , however there are a total of seven cases if the earlier reports by enzinger and winslow4 and evans1 are counted,5,7,9 although the cartilaginous differentiation in the subtype was briefly described as metaplasia in the early reports by enzinger and winslow4 and evans.1 the distribution of both cartilaginous and myxoid liposarcomatous areas has been reported in some cases to be distinct and different , but other cases have indicated that there was gradual transition between the two.1,4,5,7,9 siebert et al.7 was the only author that described detailed histology of the cartilaginous area , and he also indicated that one of his three cases presented with cytological atypia , while the other two cases did not . this report did not discuss these specific details about the cartilaginous area , however , the image of the area indicated that there was cytological atypia of the chondrocytes.9 as siebert et al.7 discussed , the appearance of the cartilaginous area can cause confusion with other benign or malignant soft tissue tumors . in this case , the situation could potentially be more problematic based on the biopsied material because a differential diagnosis of the myxoid chondrosarcoma from this tumor could be difficult to categorize accurately.2 but myxoid chondrosarcomas rarely show areas of mature cartilage.2 and even if the mature cartilage is noted , cytogenetical analysis of the spindle cell area and the cartilaginous area can be used to support an accurate diagnosis of the tumor.9 follow - up studies of the t(12;16 ) in myxoid liposarcoma have indicated that the translocation is a distinct characteristic feature of the tumor.10,13 - 16 the translocation occurrence percentage was consistently high throughout various studies and many reports showed that over 90% of the myxoid liposarcomas exhibited the cytogenetic abnormality.10,13 - 16 the specific translocation results in the fusion of chop ( also known as gadd153 and ddit3 ) on chromosome 12 and tls ( also referred to as fus ) on chromosome 16.14 - 16 to date , twelve different kinds of tls - chop fusion transcripts have been detected.17 the portions of the genes that fuse can range from almost the entire chop gene to varying lengths of the tls gene , which differs according to the type of fusion transcripts.17 the differences are caused by varied break points within each gene , but generally,18 three types of transcripts are commonly observed and the remaining transcripts are rare.10 previous studies have not identified any specific correlation between the types of fusion transcript and a prognosis.11 however , this study demonstrated a correlation between the type ii fusion transcript and p53 overexpression , and although the tls - chop fusion is found in a high percentage of the myxoid liposarcomas , there are reports of other cytogenetic aberrations . for example , a small number of myxoid liposarcoma cases with an ews - chop fusion have been reported.11 in addition , one study detected an aberration of the p53 gene in about 30% of the myxoid liposarcomas.19 previous studies have determined several prognostic factors of myxoid liposarcoma , which include the percentage of round cell components , tumor necrosis , and p53 overexpression.1,3,11,20 the prognostic importance of round cell components was first identified by enzinger and winslow4 and has been confirmed in follow - up studies.1,3,20 in addition , the overexpression of p53 , determined by a 5% cut off value , was reported to be significantly associated with poor rates of survival.11 this study is the second report of a myxoid liposarcoma with cartilaginous differentiation that was determined to have a type ii tls - chop fusion transcript in both the typical myxoid liposarcoma area and the cartilaginous differentiation area . currently only a small number of cases discuss the histological aspects of the cartilaginous area , and because the chondrocytes do not present with apparent malignant or benign features , the cartilaginous area has not yet been designated into malignant or benign components . however , the study identified areas of ossification that were adjacent to cartilaginous areas . because of the abrupt transition between the two areas and the absence of osteoid formation by the tumor cells , enchondral ossification was considered as the pathophysiological bone formation mechanism instead of osteosarcomatous differentiation . authors of previous case reports have speculated that the heterologous component could be derived from common progenitor cells.9 however , additional follow - up studies are needed to investigate whether the cartilaginous component is created by proliferating mesenchymal cells or by metaplasia .

myxoid liposarcoma is a subtype of liposarcoma . this specific subtype can be identified based on its characteristic histological and cytogenetical features . the tumor has a fusion transcript of the chop and tls genes , which is caused by t(12;16)(q13;p11 ) . most of the fusion transcripts that have been identified fall into three categories , specifically type i ( exons 7 - 2 ) , type ii ( exons 5 - 2 ) , and type iii ( exons 8 - 2 ) . a total of seven myxoid liposarcomas associated with the rare phenomenon of cartilaginous differentiation have been documented in the literature . currently , only one of these cases has been cytogenetically analyzed , and the analysis indicated that it was a type ii tls - chop fusion transcript in both the typical myxoid liposarcoma and cartilaginous areas . this study presents a second report of myxoid liposarcoma with cartilaginous differentiation , and includes a cytogenetical analysis of both the myxoid and cartilaginous areas .

rate equations characterizing the commuting dynamics among subpopulations can be defined by using the variables nkk(t ) and nkk(t ) as ( 5)tnkk(t)=knkk(t)+1kknkk(t)p(k|k ) , ( 6)tnkk(t)=kknkk(t)1nkk(t ) , where kk is the rate at which an individual of subpopulation k commutes to neighboring subpopulation k. then , considering the statistical equivalence of subpopulations with the same degree and the mean field assumption we have k = k k kkp(k|k ) where p(k|k ) is the conditional probability of having a subpopulation k in the neighborhood of a subpopulation k. equilibrium is given by the condition tnkk = tnkk2032 = 0 and yields the relation ( 7)nkk=nkkkk. using the expression nk = nkk(t ) + k k nkk(t)p(k|k ) for total number of individuals of subpopulation k one can obtain the stationary populations in equations ( 1 ) and ( 2 ) . each subpopulation of degree k invaded by the contagion process at the n 1th generation may seed its k 1 neighbors at most ( all of its neighbors minus the one from which it got the infection ) . the probability of finding a subpopulation of degree k in the neighborhood is p(k|k ) . for each neighboring subpopulation , the probability that it has not already been invaded by the contagion process in an earlier generation is m=0n1(1dkm / vk ) . if kk infectious seeds are sent to the neighbor , the outbreak occurs with probability 1r0kk . we can then relate the number of diseased subpopulations at the nth generation with that at the n 1th generation as the spontaneous realization of all these above conditions , ( 8)dkn=kdkn1(k1)[1r0kk]p(k|k)m=0n1(1dkmvk ) . in the early stage of the contagion process we will also consider the case that we are just above the local epidemic threshold , r0 1 1 , so that the outbreak probability can be approximated by 1r0kk(r01)kk . if we also ignore degree correlations between neighboring subpopulations , p(k|k ) = kp(k)/k , we obtain equation ( 3 ) . in order to obtain the explicit expression for the subpopulation reproductive number in equation ( 4 ) we need to derive an expression for kk = ( nkk + nkk ) . if we consider the case in which ( 9)kk=nknk+nknn , where nknn = kknkp(k|k ) is the average total population in the neighborhood of subpopulation k. the above expression assumes that the per - capita mobility rate is rescaled by the number of individuals in the subpopulation , thus leading to k that decreases as nk increases . this behavior account for the effect introduced by large subpopulation sizes ; the overall per capita commuting rate outside of the subpopulation generally decreases in large populations as individuals tend to commute internally . in this case this expression allows the calculation of nkk and using the approximate relation for the fraction of infected cases generated by the end of the sir epidemic introduced into a fully susceptible population 2(r01)/r02 , we obtain the expression for kk : ( 11)kk=2n(r01)r02k2(1+k/k2+)(k+k ) . if we substitute the above relation into equation ( 3 ) we get ( 12)dkn=2n(r01)2r02k2k(1+k/k2+)kp(k)kdkn1(k1)(k+k ) . in order to write a closed form of the above iterative process we introduce the definitions 0nk(k1)dknand1nkk(k1)dkn whose next generation equations are defined as ( 13)n = gn1withn=(0n1n ) , where g is a 2 2 matrix , ( 14)g=2n(r01)2r02k2k(1+k/k2+)(k3k2k2kk4k3k3k2 ) . the global behavior of the contagion process across the network of subpopulations is determined by the largest eigenvalue r * of g as expressed in equation ( 4 ) where f is a function of the moments of degree distribution , ( 15)f(k,k2,k3,k4)1kk2[k3k2+(k4k3)1/2(k2k)1/2 ] . rate equations characterizing the commuting dynamics among subpopulations can be defined by using the variables nkk(t ) and nkk(t ) as ( 5)tnkk(t)=knkk(t)+1kknkk(t)p(k|k ) , ( 6)tnkk(t)=kknkk(t)1nkk(t ) , where kk is the rate at which an individual of subpopulation k commutes to neighboring subpopulation k. then , considering the statistical equivalence of subpopulations with the same degree and the mean field assumption we have k = k k kkp(k|k ) where p(k|k ) is the conditional probability of having a subpopulation k in the neighborhood of a subpopulation k. equilibrium is given by the condition tnkk = tnkk2032 = 0 and yields the relation ( 7)nkk=nkkkk. using the expression nk = nkk(t ) + k k nkk(t)p(k|k ) for total number of individuals of subpopulation k one can obtain the stationary populations in equations ( 1 ) and ( 2 ) . each subpopulation of degree k invaded by the contagion process at the n 1th generation may seed its k 1 neighbors at most ( all of its neighbors minus the one from which it got the infection ) . the probability of finding a subpopulation of degree k in the neighborhood is p(k|k ) . for each neighboring subpopulation , the probability that it has not already been invaded by the contagion process in an earlier generation is m=0n1(1dkm / vk ) . if kk infectious seeds are sent to the neighbor , the outbreak occurs with probability 1r0kk . we can then relate the number of diseased subpopulations at the nth generation with that at the n 1th generation as the spontaneous realization of all these above conditions , ( 8)dkn=kdkn1(k1)[1r0kk]p(k|k)m=0n1(1dkmvk ) . in the early stage of the contagion process we will also consider the case that we are just above the local epidemic threshold , r0 1 1 , so that the outbreak probability can be approximated by 1r0kk(r01)kk . if we also ignore degree correlations between neighboring subpopulations , p(k|k ) = kp(k)/k , we obtain equation ( 3 ) . in order to obtain the explicit expression for the subpopulation reproductive number in equation ( 4 ) we need to derive an expression for kk = ( nkk + nkk ) . this expression depends on the form of commuting rates among subpopulations . if we consider the case in which ( 9)kk=nknk+nknn , where nknn = kknkp(k|k ) is the average total population in the neighborhood of subpopulation k. the above expression assumes that the per - capita mobility rate is rescaled by the number of individuals in the subpopulation , thus leading to k that decreases as nk increases . this behavior account for the effect introduced by large subpopulation sizes ; the overall per capita commuting rate outside of the subpopulation generally decreases in large populations as individuals tend to commute internally . in this case this expression allows the calculation of nkk and using the approximate relation for the fraction of infected cases generated by the end of the sir epidemic introduced into a fully susceptible population 2(r01)/r02 , we obtain the expression for kk : ( 11)kk=2n(r01)r02k2(1+k/k2+)(k+k ) . if we substitute the above relation into equation ( 3 ) we get ( 12)dkn=2n(r01)2r02k2k(1+k/k2+)kp(k)kdkn1(k1)(k+k ) . in order to write a closed form of the above iterative process we introduce the definitions 0nk(k1)dknand1nkk(k1)dkn whose next generation equations are defined as ( 13)n = gn1withn=(0n1n ) , where g is a 2 2 matrix , ( 14)g=2n(r01)2r02k2k(1+k/k2+)(k3k2k2kk4k3k3k2 ) . the global behavior of the contagion process across the network of subpopulations is determined by the largest eigenvalue r * of g as expressed in equation ( 4 ) where f is a function of the moments of degree distribution , ( 15)f(k,k2,k3,k4)1kk2[k3k2+(k4k3)1/2(k2k)1/2 ] .

human mobility and activity patterns mediate contagion on many levels , including : spatial spread of infectious diseases , diffusion of rumors , and emergence of consensus . these patterns however are often dominated by specific locations and recurrent flows and poorly modeled by the random diffusive dynamics generally used to study them . here we develop a theoretical framework to analyze contagion within a network of locations where individuals recall their geographic origins . we find a phase transition between a regime in which the contagion affects a large fraction of the system and one in which only a small fraction is affected . this transition can not be uncovered by continuous models due to the stochastic features of the contagion process and defines an invasion threshold that depends on mobility parameters , providing guidance for controlling contagion spread by constraining mobility processes . we recover the threshold behavior by analyzing diffusion processes mediated by real human commuting data .

epstein barr virus ( ebv ) is associated with several types of malignancies , such as lymphoma , nasopharyngeal carcinoma and gastric carcinoma . ebv - associated gastric carcinoma ( ebvagc ) is a unique type of gastric cancer consisting of neoplastic cells with monoclonal ebv , first described in 1990 . no cases of ebvagc have been reported in solid organ recipients , and only one case has been described in a bone marrow transplant patient . we report a case of ebvagc arising in a renal transplant recipient 33 years after transplantation . a 65-year - old man was admitted to a peripheral hospital in november 2008 complaining of fatigue and dyspnoea on exertion . his medical history reported renal transplantation at the age of 32 for renal failure following paint fixative exposure . three days after transplantation , the patient experienced an episode of acute cellular rejection , which was treated with corticosteroid pulses , graft irradiation and antilymphocytic serum . afterwards , the graft always showed an excellent function ( creatinine clearance > 60 ml / min , proteinuria absent , no further rejection episodes in the follow - up ) . on admission , as the faecal occult blood test was positive , a gastroscopic examination was performed which revealed diffuse redness of the gastric mucosa . multiple endoscopic biopsies were taken and a diagnosis of poorly differentiated adenocarcinoma from the gastric body was established . computerized tomography scan showed diffuse thickening of the posterior wall of the gastric body and fundus , without metastases in other organs . unfortunately , no information was available about any ebv / cmv mismatch as the patient had been transplanted outside italy many years before . the post - operative course was uneventful and the patient was discharged 20 days after surgery . the immunosuppressive regimen was minimal at the time of diagnosis ( azathioprine 50 mg / day and prednisone 8 mg / day ) and was therefore left unchanged . in the follow - up the patient had regular food intake and his s - creatinine remained normal ( 60 mol / l ) . one year after surgery , upper gi haemorrhage occurred , and in december 2009 the patient died of recurrent disease . at gross inspection , the stomach showed diffuse thickening and rigidity of the wall , enlarged rugal folds and a 4 3 cm intraluminal polypoid mass ( figure 1a ) . histology revealed a poorly differentiated diffuse adenocarcinoma involving the whole wall , associated with extensive fibrosis and surface erosion . inflammatory infiltrates consisted of mixed lymphomonocytes including cd3 + t lymphocytes , cd20 + b lymphocytes , cd68 + monocytes and cd79a + plasma cells . in situ hybridization ( ish ) for epstein barr early rna eber ( epstein barr encoded rnas ) showed that ebv genomes were present within the nuclei of almost all neoplastic epithelial cells but not in the inflammatory mononuclear cells ( figure 1b , c ) . ebv presence was confirmed by polymerase chain reaction ( pcr ) using specific primers for ebna1 ( epstein barr nuclear antigen 1 ) and the direct cycle sequencing of ebv pcr product ( 100% identity with ebv genome strain b95 - 8 , a type 1 strain ) . quantitative real - time pcr carried out using the artus ebv tm pcr kit showed a very high number of copies in neoplastic tissue ( 2 600 000 copies/l dna ) ( figure 2a , b ) . macroscopic view of the stomach showing diffuse thickening and rigidity of the wall , enlarged rugal folds and a 4 3 cm intraluminal polypoid mass ( a ) . histological view showing small irregular nests of malignant cells often with acinar pattern ( arrow ) . ebv genomes are well detected within the nuclei of almost all neoplastic epithelial cells . in situ hybridization for epstein direct cycle sequencing of ebna1 showed that the ebv genome was 100% of the b95 - 8 strain , a type 1 strain ( v01555.2 ) ( a ) . quantitative real - time pcr showed a very high number of ebv genome copies ( 2 600 000 copies/l dna ) ( b ) . at gross inspection , the stomach showed diffuse thickening and rigidity of the wall , enlarged rugal folds and a 4 3 cm intraluminal polypoid mass ( figure 1a ) . histology revealed a poorly differentiated diffuse adenocarcinoma involving the whole wall , associated with extensive fibrosis and surface erosion . inflammatory infiltrates consisted of mixed lymphomonocytes including cd3 + t lymphocytes , cd20 + b lymphocytes , cd68 + monocytes and cd79a + plasma cells . in situ hybridization ( ish ) for epstein barr early rna eber ( epstein barr encoded rnas ) showed that ebv genomes were present within the nuclei of almost all neoplastic epithelial cells but not in the inflammatory mononuclear cells ( figure 1b , c ) . ebv presence was confirmed by polymerase chain reaction ( pcr ) using specific primers for ebna1 ( epstein barr nuclear antigen 1 ) and the direct cycle sequencing of ebv pcr product ( 100% identity with ebv genome strain b95 - 8 , a type 1 strain ) . quantitative real - time pcr carried out using the artus ebv tm pcr kit showed a very high number of copies in neoplastic tissue ( 2 600 000 copies/l dna ) ( figure 2a , b ) . macroscopic view of the stomach showing diffuse thickening and rigidity of the wall , enlarged rugal folds and a 4 3 cm intraluminal polypoid mass ( a ) . histological view showing small irregular nests of malignant cells often with acinar pattern ( arrow ) . ebv genomes are well detected within the nuclei of almost all neoplastic epithelial cells . in situ hybridization for epstein direct cycle sequencing of ebna1 showed that the ebv genome was 100% of the b95 - 8 strain , a type 1 strain ( v01555.2 ) ( a ) . quantitative real - time pcr showed a very high number of ebv genome copies ( 2 600 000 copies/l dna ) ( b ) . de novo cancer is a major complication of renal transplant that causes significant short- and long - term mortality . it is responsible for 20% of deaths in renal transplant patients every year and even for 30% of deaths in those patients who have a follow - up time of more than 20 years . despite the high propensity to develop tumours , gastric cancer is rare in grafted patients : only 33 gastric cancers have been described among the 7000 malignancies reported to the israel penn international transplant tumour registry and 7 cases of 172 kidney transplants were reported in the north italian transplant registry . azathioprine is one of the immunosuppressive agents most often linked with post - transplant malignancies as it directly promotes cancer through several mechanisms ( e.g. leading to the mutagenic accumulation of 6-thioguanine in patient dna or selecting clones with dna mismatch repair deficiencies ) . a recent long - term randomized follow - up study suggests that azathioprine- and cyclosporine - based regimens are associated with similar overall long - term cancer risks . thus the total burden of immunosuppression , more than the single agent , appears to be responsible for the increased oncogenic risk . immunosuppressive therapy is also known to be related to a higher susceptibility to viral infections , which could have oncogenic properties . ebvagc , whose prevalence is 1.320% in gastric carcinomas occurring in the general population , is defined as the presence of ebv in gastric tumour cells and is always identified by performing eber ish . to the best of our knowledge , therefore , this is the first case of de novo ebvagc arising in a 65-year - old renal transplant recipient . a previous case has been reported , but it was a case of early onset after non - myeloablative haematopoietic stem cell transplantation for myeloma with subsequent strong immunosuppression due to a severe graft - versus - host disease . here , we have demonstrated ebv in neoplastic tissue by positive ish for eber , gene sequencing for ebna1 and real - time pcr , revealing a very high number of ebv genomes in spite of a low dnaemia . ebv pcr in the peripheral blood is a useful screening tool in transplant recipients ; however , sometimes ebv blood level does not represent a mirror of ebv tissue presence , as was in our case . thus , ebvagc could be underestimated since gastric cancers are not routinely investigated using molecular viral analyses on tissue . ebv has frequently been associated with the hypermethylation in promoters of various tumour - related genes which can lead to uncontrolled cell proliferation and viral propagation . whether genetic alterations precede ebv infection due to long - time duration of immunosuppressive therapy or if these are consequences of ebv infection itself remains to be established through further studies . in particular , it could be interesting to develop a careful molecular tissue investigation of gastric carcinomas which develop in transplanted patients in order to obtain a precise incidence in this patient population . it could be useful for nephrologists or other specialists involved in the monitoring and care of renal transplanted patients to suggest a specific diagnostic screening in high - risk patients . in particular , patients with organ - specific symptoms ( nausea , anaemia , weakness , gastrointestinal bleeding , etc . ) should be promptly subjected to gastrointestinal endoscopy together with molecular ebv / cmv screening of tissue and annual blood screening .

epstein barr virus - associated gastric carcinoma ( ebvagc ) is a unique type of gastric cancer , defined as the presence of ebv in gastric tumour cells , usually identified by in situ hybridization . a poorly differentiated gastric adenocarcinoma was detected in a kidney recipient 33 years after transplantation . neoplastic epithelial cells were ebv positive by in situ hybridization . gene sequencing confirmed the amplicon specificity , and real - time polymerase chain reaction quantified 2 600 000 genomes/l dna in neoplastic tissue . no cases of ebvagc have been reported in solid organ transplants , thus this is the first case of de novo ebvagc arising in a 65-year - old renal transplant recipient .

despite current advances in cancer screening , diagnosis , and therapeutics , pancreatic cancer remains a highly malignant disease with a dismal 5-year survival rate of < 5% . in 2012 , approximately 44,000 people in the united states will be diagnosed with pancreatic cancer with more than 37,000 expected to die from this disease , making pancreatic cancer the fourth leading cause of cancer - related deaths in the country . pancreatic cancer is often diagnosed at an advanced stage owing to nonspecific symptoms and a lack of reliable biomarkers . because of the high number of locally advanced and metastatic cases at the time of diagnosis , only 1520% of patients can undergo potentially curative surgical resection . in addition , response to chemotherapy and radiotherapy is often very poor , making management of the disease extremely challenging for clinicians . resistance to the drug is widespread and may be due to a number of factors including poor drug delivery and inherent chemoresistance of pancreatic tumor cells . combination chemotherapy with leucovorin , fluorouracil , irinotecan , and oxaliplatin is an emerging treatment that offers a better survival outcome compared to gemcitabine , albeit with increased toxicity . in a study of 342 patients , folfirinox treatment resulted in a median 11.1-month overall survival compared to 6.8 months for gemcitabine treatment . it is clear that novel chemotherapeutic approaches are necessary to improve the clinical outcomes of patients with this devastating disease . for these strategies to be viable for clinical use , this article summarizes recent literature ( 1995 to 2012 ) and clinical trials highlighting the current progress on new therapeutic agents and drug delivery methods , and the potential targets for the treatment of pancreatic cancer . a number of therapeutic agents and drugs may serve as alternative molecular approaches to conventional chemotherapies ( table 1 ) . among these agents are small - molecule inhibitors , oncolytic viruses , monoclonal antibodies , suicide genes , and small interfering rna ( sirna ) that target abnormal gene expression , cell - surface receptors , and cell - signaling pathways . studies of these alternative agents may generate improved therapeutic strategies and facilitate progress towards improving the clinical outcome of pancreatic cancer patients . through gene therapy , cancer cell growth can be inhibited by replacing or silencing key genes in pancreatic cancer cell growth pathways involving p53 , retinoblastoma protein ( rb ) , p21 , p16 , kras , and bcl-2 . modulation of kras expression has been shown to inhibit growth of pancreatic cancer cells in vitro and growth of intraperitoneal tumors in xenograft nude mice in vivo . research has also demonstrated that re - expression of the tumor suppressor gene p53 in a subcutaneous nude mouse model inhibits pancreatic tumor growth . sirna and short hairpin rna ( shrna ) can be utilized to post - transcriptionally silence gene expression in a sequence - specific manner . these molecules are being investigated in cancer biology and other fields as powerful tools for regulating expression of genes essential for cellular processes such as survival , proliferation , and drug resistance . shrna silencing of zinc transporter zip4 has been shown to inhibit tumor growth and extend the survival of nude mice with pancreatic cancer xenografts . in addition to re - expressing tumor suppressor genes , gene therapy strategies can also deliver suicide genes to tumor cells , which encode for drug - activating enzymes . pancreatic cancer cells transfected with cytosine deaminase , which converts 5-fluorocytosine ( 5-fc ) to its active form fluorouracil ( 5-fu ) , showed decreased tumor growth when subsequently treated with 5-fu . however , despite strong potential , the success of gene therapy agents , especially in clinical studies , has been limited , perhaps because of the complex nature of pancreatic tumors . simultaneous targeting of multiple gene mutations may be necessary to overcome the effects of extensive crosstalk . the epidermal growth factor receptor ( egfr ) inhibitor erlotinib is fda approved in combination with gemcitabine to treat metastatic pancreatic cancer based on clinical trial results that showed significantly increased overall survival and progression - free survival compared to gemcitabine monotherapy in this patient population [ 10 , 13 ] . egfr , involved in cancer growth and metastasis , promotes epithelial - to - mesenchymal transition for decreased cell adhesion and increased cell migration . overexpression of egfr has been shown to be common in pancreatic cancer and may indicate the potential aggressiveness of the cancer . also , several studies have utilized carbon nanotubes for imaging as a significantly better contrast agent . other investigational therapeutic agents include monoclonal antibodies against targets such as egfr , vascular endothelial growth factor receptor ( vegfr ) , mucin 1 ( muc1 ) , and mesothelin . antibody therapies have the potential to inhibit tumor growth and angiogenesis and provide a method of treating otherwise resistant cancers . oncolytic viral therapies , often using adenovirus and herpes simplex virus , are engineered to replicate selectively in tumor cells , targeting the cells for lysis , cell - to - cell fusion , or immune response . commonly used delivery vehicles for cancer therapies include liposomes and nanoparticles . however , there are few clinical trials using these newer delivery methods in pancreatic cancer . most current pancreatic cancer chemotherapies work systemically and thus are subject to a number of physiologic and chemical limitations that decrease efficacy . unfavorable pharmacokinetics and poor targeting of cancer cells among other issues significantly affect the ability of these drugs to provide greater clinical benefit , and toxicity and side - effects limit acceptable dosages . the newer delivery vehicles not only target specific organs but also offer increased drug solubility , protection against degradation and elimination , decreased toxicity , and reduced resistance . liposomes are vesicles composed of single or multiple phospholipid bilayers that can be loaded with a variety of content including genetic materials and chemotherapeutic drugs . liposomes can improve drug solubility and stability , are biodegradable , and exhibit low toxicity . they have already proven to be viable clinically , with several fda - approved liposome formulations in existence for cancer treatment . liposomes have been used for in vitro gene transfection to protect antisense oligonucleotides , sirna , and shrna from degradation and improve transfection efficiency and targeting . for example , liposomal delivery of both pancreatic and duodenal homeobox 1 ( pdx-1 ) and zip4-targeted shrna was shown to inhibit tumor growth in immunodeficient mice [ 16 , unpublished data ] . the addition of surface ligands can help target liposomes to cells of interest , thereby helping to reduce the toxicity of therapeutic agents and enrich concentrations in target tissues . liposomes can also be pegylated to increase stability and prolong the circulation time of a drug . in a study by cosco and colleagues , pegylated liposomes loaded with gemcitabine increased survival and reduced tumor growth and toxicity in severely compromised immunodeficient ( scid ) xenograft mouse models of pancreatic cancer compared to controls treated with standard gemcitabine . improved liposomal delivery efficiency may further allow lower concentrations of drugs to be used for the same effect , prolong circulation times , improve drug internalization , and decrease unwanted toxic side - effects . the benefits of nanoparticles are a large surface - to - mass ratio and the ability to bind to a number of substances , provide sustained release of drugs , and improve drug circulation and concentration . stearoyl gemcitabine nanoparticles have been found to enhance the effect of gemcitabine on pancreatic cancer cells in vitro , and suppress tumor growth more effectively than normal gemcitabine in a mouse model . nanoparticles can also be targeted to specific locations through the addition of monoclonal antibodies or use of magnetic guidance . recently , carbon nanotubes have emerged as an exciting potential modality for drug delivery and imaging . they are able to absorb a large amount of drug , which can be slowly released , and their stable structure can be modified for improved targeting of therapies . carbon nanotube - delivered cisplatin modified to target egfr - expressing cells was found to selectively kill head and neck squamous carcinoma cells ( hnsccs ) . to improve the targeting of new therapeutic agents to pancreatic tumor cells , the unique expression profile of pancreatic cancer cells can be exploited to differentiate normal , healthy cells from cancer cells . liposomes , nanoparticles , and carbon nanotubes can be modified with monoclonal antibodies or ligands to allow the therapeutic agents to be directed towards specific cells , thus increasing the accumulation of drugs in the target organ and decreasing toxicity to normal cells . potential targets that can be used include egfr , urokinase plasminogen activator receptor ( upar ) , transferrin receptor , her-2 , ca125 , mesothelin , and muc1 . these potential delivery targets have been shown to be overexpressed in pancreatic cancer cells . however , because of the heterogeneity of pancreatic cancer and the variable expression profiles among pancreatic cancer cells , further research is warranted to identify more effective targets for drug delivery . increasing evidence suggests that the tumor microenvironment may play a critical role in pancreatic cancer cell resistance and explain the disparity between preclinical and clinical study results . dense desmoplastic stroma and poor perfusion of the tumor prevent drugs from properly penetrating pancreatic tumors . inhibition of hedgehog signaling has been found to decrease stromal tissue and increase perfusion of the tumor , thus improving survival in a mouse model . for novel therapeutics to be successful , it is likely that there will be a need for a greater understanding of the microenvironment and how it can be overcome for better drug delivery . recent advancements in the development of therapeutic agents and delivery modalities for improved targeting , efficacy , and clinical outcomes in pancreatic cancer are extremely promising . however , because the data are mostly preclinical and the clinical trials are few , more research is necessary to further refine these methods , confirm their safety , and improve delivery specificity . even if targeted delivery is accomplished and the drug enters the cell , it is possible that there will be a response failure . therefore , a greater understanding of pancreatic cell biology is also crucial since the presence of multiple mutations may make single - target treatments insufficient . emerging targeted therapeutic approaches may be exciting , viable opportunities that will tangibly improve the management of this devastating disease .

pancreatic cancer is an incredibly challenging disease due to its high rates of resistance to traditional chemotherapy and radiotherapy . there has been little improvement in the prognosis of pancreatic cancer cases in the past decades , highlighting the crucial need for more effective therapeutic approaches . erlotinib , an egfr inhibitor , and gemcitabine , a nucleoside analog , are currently used in combination for chemotherapy treatment , but new developments in drug delivery systems using liposomes and nanoparticles may be promising new modalities for management of the disease . in addition to standard chemotherapeutic drugs , these delivery systems can be utilized to deliver therapeutic agents such as sirna , oncolytic viruses , small molecule inhibitors , antibodies , and suicide genes . further work is required to elucidate how ligands and antibodies could be used to enhance the targeted delivery of drugs , thus increasing specificity , improving stability , and reducing the effect of the drugs on healthy tissue . despite significant preclinical data , there are currently very few clinical trials involving pancreatic cancer targeted drug delivery . this article summarizes current developments in targeted pancreatic cancer drug delivery , focusing on delivery systems , targets , and therapeutic agents .

third - generation robotics have been shown to enhance the field of cardiac surgery . the da vinci robotic surgical system ( intuitive surgical , mountain view , ca ) some of these procedures include mitral valve repair , pelvic lymph node dissection , adrenalectomy , and nissen fundoplication . surgeons at the east carolina university brody school of medicine in greenville , north carolina , use the system extensively for cardiac and general surgery applications . despite rapid advances in cardiac surgery , robotic surgical systems robotically assisted gynecologic procedures in humans described in the current literature have been limited to bilateral tubal reanastomosis and more recently hysterectomy . using robotics in surgery the da vinci robotic system overcomes many of the limitations of standard laparoscopic surgery : 2-dimensional images , hand tremors , and dexterity limitations . the da vinci generates a 3-dimensional image by using two 5-mm wide - angle cameras within a single 12-mm laparoscope . the 7 degrees of motion freedom give the surgeon a wrist - like feel inside the abdomen . the surgeon operates from a remote console in constant control of the robot using a combination of foot pedals and hand controls . the foot pedals allow control of camera movement , focus , and provide a clutching mechanism for repositioning and centering the hand controls . the hand controls operate the instruments , which are capable of manipulation , dissection , coagulation , and suturing , as well as camera movement . the robotic system does have the capability of harmonics and monopolar cautery , but lacks bipolar cautery . the system 's computer also provides scaling of movement , tremor elimination , and graduated instrument grip . the limitations of the da vinci system include setup time , cost , and tactile / haptic feedback . it has not yet been determined whether robotic systems will significantly help in complex gynecologic surgery . a low - risk , simple procedure was chosen for our foray into robotic surgery cases . to gain the maximum benefit from robotic surgery for a relatively simple procedure this technique was chosen because it requires several different laparoscopic maneuvers ( cautery , sharp dissection , suture ligation ) , is very familiar to surgeons , and provides excellent sterilization results . implementation of robotic surgery requires special training for surgeons and operating room personnel prior to performing procedures . patients in outpatient gynecology clinics at the east carolina university brody school of medicine requesting tubal ligation from october 2001 through november 2001 were selected to undergo the procedure using the da vinci robotic system . the patients consented to the procedure after they were counseled about contraceptive alternatives and specifically about the use of the robotic system for their surgery . two surgeons performed each procedure , one stationed at the console and the other as the patient - side surgeon . after standard scrub and draping , a hulka tenaculum was placed in the uterus for uterine manipulation . two 8-mm trocars were placed in the lower quadrants , lateral to the inferior epigastric arteries , for instrument access . the robot was then positioned just medial to the patient 's right lower extremity and attached to the instrument and camera trocars . this positioning allowed the patient - side surgeon access to the uterine manipulator and access to the robotic arms for instrument replacement . the da vinci robotic system was then used for all aspects of the sterilization procedure . the fallopian tube was grasped in the isthmic portion with the fimbriated end clearly visible . a window was created in the mesosalpinx at an avascular site using the robotic monopolar cautery . a 3-cm tubal segment was ligated proximally and distally using ligatures tied with robotic instruments . the robotic system was removed from the operating site , and the procedure was concluded in standard fashion . the fascia at the 12-mm port site was closed . finally , the skin incisions were closed . the tubal segments were sent to pathology . the operative time was defined as the total time the patient spent in the operating room , which included pre - operative preparation , anesthesia induction , surgical equipment setup , procedure time , anesthesia reversal , and postoperative transportation to the postanesthesia care unit . the average age of the 4 patients selected for robotic surgery was 305.6 years ; average height was 1.620.091 meters ; average weight was 7117.7 kilograms ; and average body mass index was 263.6 . one patient had a past surgical history of a diagnostic laparoscopy with lysis of adhesions . operative time varied from 1 hour 25 minutes to 2 hours 31 minutes with an average operative time of 1 hour 56 minutes 27 minutes . for comparison , the average total operative block time for a standard laparoscopic tubal ligation ( clip or band application ) in our institution is 1 hour 30 minutes , including preoperative preparation , anesthesia induction , surgical equipment setup , procedure time , anesthesia reversal , and postoperative transportation to the postanesthesia care unit . each surgeon was able to decrease actual operative time by 20% on the second procedure . by performing a simple procedure with robotic adaptation , we were able to improve our robot setup time , improve trocar and robot positioning , and gain more familiarity with the surgical instrumentation with each successive operation . our best operative time for surgery with robotic assistance was similar to the standard block time allotted for laparoscopic tubal ligation . we were also able to determine where robotic techniques would have to be supplemented with currently available laparoscopic instruments for gynecology . bipolar cautery would be helpful as would better graspers designed for uterine , tubal , and ovarian manipulation . this is especially important for complex procedures because robotic instrumentation has been developed specifically for general and cardiac surgery applications . based on our experience , performing simple laparoscopic procedures , such as bilateral tubal ligations , is a safe and effective means to gain familiarity with the system before advancing to more complex gynecologic procedures . although it was time - consuming , each surgeon was able to greatly decrease operative times . the future of minimally invasive surgery involves the development of techniques and instruments that will enable the surgeon to perform progressively more intricate and complex surgical tasks in a rapid and safe manner . many complex gynecologic procedures require more advanced surgical technique and extensive dissection with larger , abdominal incisions . while the initial training in robotic surgery was time - consuming , we believe the robotic system makes complex laparoscopic skills easier to perform and will therefore increase a surgeon 's minimally invasive armamentarium .

objectives : to determine the feasibility of using a simple procedure , a bilateral tubal ligation , as a transition procedure when adopting robotic laparoscopy for gynecologic surgery.method:to obtain robotic credentialing and gain experience with the robotic system , the surgeons first went through robotic training , then 4 women desiring permanent sterilization had robotically assisted laparoscopic bilateral tubal ligations performed , using the parkland method.results:total operating room time varied from 1 hour 25 minutes to 2 hours 31 minutes . improvement in operating time for each surgeon was noted with each successive case . best times in robotic cases were similar to those of standard laparoscopy.conclusion:robotically assisted laparoscopic tubal ligation using the parkland method is a satisfactory procedure to provide transition for gynecologic surgeons and operating room personnel to gynecologic robotic surgery .

to report the ultrasound biomicroscopy ( ubm ) and surgical findings in a subject with a syndrome of ectopia lentis , spontaneous filtering blebs , and craniofacial dysmorphism ( traboulsi syndrome ) . case report , using a 40-mhz ubm wide - field anterior segment scan and anterior segment optical coherence tomography ( oct ) . a 16-year - old orphan girl presented with visual loss to the level of 6/60 ( 20/200 ) bilaterally . ubm and anterior segment oct revealed chronic apposition of the iris to the cornea with angle closure , delineation of the bleb tract and rarefaction of the zonules . the girl had abnormal facial features ( a beaked nose and long face ) with normal chromosomal studies , negative fluorescent in situ hybridization study for velocardiofacial syndrome and an absence of signs suggesting marfan syndrome . under general anesthesia , attempts at deepening the anterior chamber with sodium hyaluronate 3% led to a spontaneous dislocation of the lens into the anterior chamber , facilitating its aspiration . best corrected visual acuity did not improve from the preoperative level beyond 6/60 ( 20/200 ) because of central retrocorneal fibrosis . early surgical removal of the lens is necessary in this syndrome to avoid irreversible corneal and trabecular meshwork damage in chronic apposition of the iris to the cornea . ubm can help in the delineation of the bleb tract and document resolution of angle closure after surgery . inadvertent bleb may form as a result of a fistula which allows aqueous to flow from the anterior chamber into the subconjunctival space . most conjunctival blebs follow episodes of scleritis , accidental penetrating injury or ocular surgical procedures ( cataract surgery , scleral fixated intraocular lens implantation , scleral tunnel lensectomy , and cyclophotocoagulation ) . spontaneous filtering blebs are rare and have been observed with few systemic disorders ( scleroderma ) , ocular abnormalities ( terrien 's marginal degeneration and axenfeld syndrome ) , or with systemic conditions , such as familial craniofacial dysmorphism with spontaneous bleb formation [ 6 , 7 ] known in lebanon as traboulsi syndrome . we present the anterior segment imaging and treatment in a case that provides new insights into the pathophysiology of traboulsi syndrome . 1 ) has been complaining of bilateral visual loss for several years . both uncorrected and corrected ( with 7.0 dpt ) she had a central superficial corneal opacification as well as central retrocorneal nodular thickening bilaterally . the posterior pole could be visualized in the left eye with difficulty using a 90-dpt lens and revealing a cup - to - disc ratio of 0.1 . using ultrasonography , the axial length measured 19.41 mm in the right eye and 20.12 mm in the left eye . the cornea was visualized using anterior optical coherence tomography ( oct ) ( visante oct ; carl zeiss meditec inc . , near apposition of the cornea to the iris was clearly demonstrated with angle closure ( fig . few zonules were delineated . besides the apposition of the iris to the cornea with angle closure , both rarefaction of the zonules and bleb tracts were more clearly imaged by ultrasound biomicroscopy ( ubm ) using a 40-mhz ubm probe ( eye cubed ellex ; ellex innovative imaging inc . , , usa ) . under general anesthesia , attempts at deepening the anterior chamber with sodium hyaluronate 3% led to spontaneous dislocation of the lens into the anterior chamber ( fig . 2 ) . deepening of the angle was somewhat more evident on ubm than anterior segment oct after lens removal ( fig . 3 ) , but the bleb height decreased clinically and by ubm ( comparing to the fellow eye ) after surgery ( fig . 5 ) . best corrected visual acuity did not improve from the preoperative level beyond 6/60 ( 20/200 ) partly from the central retrocorneal scar ( fig . the patient declined a second eye surgery to remove the subluxated lens after 4 years of follow - up . 1 ) . she had some features suggestive of velocardiofacial syndrome like a prominent broad nose . genetic consultation ruled out both homocystinuria ( normal serum amino acid quantitation ) and digeorge syndrome ( no deletion in the region 22q11.2 by fluorescent in situ hybridization ) , and confirmed a normal karyotype . traboulsi and colleagues described 6 members of a family with a syndrome of mild facial dysmorphism , subluxation of the crystalline lenses , variable degrees of angle closure with iridocorneal adhesions , patchy iris atrophy , and scleral thinning . three non - operated eyes of two patients had spontaneous filtering blebs that presented as avascular cystic elevations of the superior conjunctiva . systemic work - up of all patients was negative for evidence of diseases known to be associated with dislocated lenses . furthermore , traboulsi and colleagues , subsequently reported 4 members of a lebanese druze family with the syndrome of lens dislocation , spontaneous filtering blebs , scleral thinning , anterior segment abnormalities and a distinctive facial appearance not compatible with marfan syndrome ( negative echocardiogram ) , but with autosomal recessive inheritance . the absence of scleral thinning in the current case may relate to the short eye status hence a thickened sclera . the formation of spontaneous filtering blebs in reported cases of traboulsi syndrome [ 6 , 7 ] may relate to the scleral thinning . scleral thinning occurs in progressive myopia as in the family described by dagi and walton . a posterior channel of communication was apparent on ubm between the bleb and ciliary body similar to the findings in a traumatic bleb as described by khouri et al . . the current syndrome is different from the syndrome described by dagi and walton who described the clinical features of an atypical presentation of ectopia lentis consisting of primary anterior axial lens subluxation in childhood , associated progressive myopia , and complicating angle - closure glaucoma but without bleb formation . this clinical triad consists of rapidly increasing myopia , normal axial length , and progressive axial subluxation . prophylactic lensectomy provides a safe and sight - saving treatment that arrests and , at times , reverses the progression of angle - closure glaucoma . ectopia lentis with anterior axial subluxation and progressive myopia can be a sight - threatening condition when significant forward mobilization of the lens results in synechial angle - closure glaucoma . recognition of this clinical entity can expedite diagnosis and prevent irreversible loss of vision secondary to glaucoma . because the primary mechanism of angle closure is angle crowding , peripheral iridotomy does little to control the rise in intraocular pressure . according to dagi and walton , lensectomy appears to represent the most definitive treatment in this syndrome ; and lensectomy was ultimately required to halt progressive angle closure resulting from relentless axial subluxation . similarly , peripheral iridotomy may be of little value in our case and our therapy is to restore the angle anatomy by lens removal . we hypothesize that uveal effusion in a nanophthalmic or small eye led to angle apposition with anterior segment ischemia resulting in zonular damage and secondary lens subluxation . alternative explanations include : ( 1 ) primary cleft with secondary forward iris movement and corneal iris apposition and ( 2 ) a primary collagen synthesis problem with subsequent scleral melt , bleb formation , and secondary forward iris movement . weakening , stretching , or breakage of the zonules frees the lens to migrate and sublux . ectopia lentis occurs in marfan syndrome as well as in a large number of other inheritable disorders ( homocystinuria , weill - marchesani syndrome , ectopia pupillae , microspherophakia , mandibulofacial dysostosis , etc . ) . it can occur as an isolated abnormality , secondary to ocular trauma or syphilis myopia in the presence of ectopia lentis in marfan syndrome may be due to axial elongation of the eye . in addition , two lenticular mechanisms may also contribute to the myopia , and we suspect they are its cause in the present case : an anterior shift of the lens - iris diaphragm moving the focal point of the eye very anteriorly , as well as an antero - posterior thickening of the lens ( spherophakia - like ) . also , peters anomaly is a possibility in the differential diagnosis of central opacity of the cornea with retrocorneal fibrous tissue and with iridocorneal synechiae . peters anomaly is characterized by central corneal opacity ( leukoma ) , thinning of the posterior aspect of the cornea , iridocorneal adhesions , and keratolenticular adhesion or cataract . the presence of lens abnormalities in peters anomaly is more frequently associated with systemic anomalies such as a cleft lip and palate , short stature , broad hands and feet , and variable mental delay . we presented additional insight into the traboulsi syndrome of facial dysmorphism with spontaneous conjunctival blebs using anterior segment oct and ubm technologies . early lensectomy seems indicated to prevent irreversible corneal scarring and angle damage from chronic apposition of the iris to the cornea .

purposeto report the ultrasound biomicroscopy ( ubm ) and surgical findings in a subject with a syndrome of ectopia lentis , spontaneous filtering blebs , and craniofacial dysmorphism ( traboulsi syndrome).methodscase report , using a 40-mhz ubm wide - field anterior segment scan and anterior segment optical coherence tomography ( oct).resultsa 16-year - old orphan girl presented with visual loss to the level of 6/60 ( 20/200 ) bilaterally . she had a central corneal opacification with retrocorneal fibrosis . the anterior chamber was flat with a very poorly dilating pupil . the lens was central in location . perilimbal conjunctival blebs were bilateral with an intraocular pressure of 8 mm hg . ubm and anterior segment oct revealed chronic apposition of the iris to the cornea with angle closure , delineation of the bleb tract and rarefaction of the zonules . the girl had abnormal facial features ( a beaked nose and long face ) with normal chromosomal studies , negative fluorescent in situ hybridization study for velocardiofacial syndrome and an absence of signs suggesting marfan syndrome . under general anesthesia , attempts at deepening the anterior chamber with sodium hyaluronate 3% led to a spontaneous dislocation of the lens into the anterior chamber , facilitating its aspiration . deepening of the angle was found after lens removal . retrocorneal fibrosis persisted after surgery , but the bleb height decreased . best corrected visual acuity did not improve from the preoperative level beyond 6/60 ( 20/200 ) because of central retrocorneal fibrosis.conclusionsearly surgical removal of the lens is necessary in this syndrome to avoid irreversible corneal and trabecular meshwork damage in chronic apposition of the iris to the cornea . ubm can help in the delineation of the bleb tract and document resolution of angle closure after surgery .

in the fall of 2008 in china , an unprecedented epidemic of urinary stones that affected infants and children after the consumption of melamine - tainted milk powder was reported . totally , 294,000 infants and children had been diagnosed to have urinary stones by the end of november 2008 . more than 50,000 infants and children had been hospitalized and six deaths were confirmed ( 1 ) . although more than half of melamine - related urinary stones cases recovered after a short hospital stay , many infants and children still had residual stones at the time of discharge ( 2 ) . thus , effects of melamine continue to raise concerns for public health in china and probably in other countries all over the world . since the outbreak of melamine - related urinary stones in infants and children , a series of studies have been published concerning the diagnosis , clinical symptoms and treatments of urinary stones , and many epidemiologic investigations are also carried out to explore and identify the features and risk factors , such as gender , age , birth type , urinary malformation , melamine concentration , positive family history and urinary ph . gansu province locating in the northwest of china has low socioeconomic conditions and large population . during this outbreak of urinary stones caused by melamine , a case - control study was performed among 190 infants to explore new influencing factors . 35 objects ( aged 12.8 5.0 months , 25 boys and 10 girls ) were diagnosed with urinary stones and constituted the case group ; 155 ( aged 12.4 4.2 months , 99 boys and 56 girls ) did not have urinary stones and constituted the control group . in general characteristics , there were no significant differences in age , sex , birth weight , family income , etc . between the case and control group ( p > 0.05 ) . the factor -- number of family members , however , exhibited a significant difference ( p = 0.006 ) , and the average numbers of family members in the case and control group were 4.4 and 5.6 , respectively . in feeding conditions , feeding melamine - tainted milk powder and cumulant of exposure showed significant differences . in the case group , 82.9% study subjects were fed with milk powder contaminated by melamine , but only 56.8% infants and children in the control group suffered from the melamine - tainted milk powder ( p = 0.004 ) . furthermore , as compared to the control group , the case group had more cumulant of exposure to melamine ( p = 0.006 ) ( table 1 ) . the medication history of infants and children had significant difference ( p = 0.031 ) . infants and children in the case group received more medications than these in the control ( 60.0% vs. 40.7% ) . however , past medical history of urinary stones of infants and children , family history of urinary stones and medication history of mother during pregnancy did not exhibit significant differences ( p > 0.05 ) ( table 2 ) . the multivariate logistic regression was carried out to identify and assess significant independent risk factors associated with stones in urinary system . the dependent variable was the urinary stones ; the independent variables included number of family members , medication history , feeding melamine - tainted milk powder and cumulant of exposure . the results indicated that or of number of family members was 0.606 ( 95% ci , 0.4110.893 ; p = 0.011 ) ; or of feeding melamine - tainted milk powder was 3.380 ( 95% ci , 1.98111.646 ; p = 0.040 ) ( table 3 ) . gansu province was heavily affected by melamine - tainted milk powder . who recommends that a tolerable daily intake ( tdi ) for melamine is 0.2 mg / kg of body weight ( 1 ) ; however , the average melamine concentration in 52 sanlu infant formula samples collected from gansu province is 1674 mg / kg ( 3 ) . our findings demonstrated that exposure to melamine - contaminated milk powder would lead to the formation of urinary stones , and the number of family members would be a new and significant influencing factor , and more numbers of family members would protect infants and children from urinary stones . this association could be related to the exercise of infants and children . in a big family , infants and children have more chances and time to play with relatives , such as parents , brothers , sisters , etc . as compared to a small family . through more exercise , on the one hand , the risk of stone formation in urinary system would be reduced ; on the other hand , the formed stones could start moving down the urinary system quite a bit faster . it is reported that the augmented aerobic exercise in space may decrease the risk of stone formation in astronauts ( 4 ) . our current study has provided special insights into influencing factors associated with urinary stones , and the findings from this retrospective study would advance the understanding of the epidemiology of urinary stones related to melamine . in general characteristics , there were no significant differences in age , sex , birth weight , family income , etc . between the case and control group ( p > 0.05 ) . the factor -- number of family members , however , exhibited a significant difference ( p = 0.006 ) , and the average numbers of family members in the case and control group were 4.4 and 5.6 , respectively . in feeding conditions , feeding melamine - tainted milk powder and cumulant of exposure showed significant differences . in the case group , 82.9% study subjects were fed with milk powder contaminated by melamine , but only 56.8% infants and children in the control group suffered from the melamine - tainted milk powder ( p = 0.004 ) . furthermore , as compared to the control group , the case group had more cumulant of exposure to melamine ( p = 0.006 ) ( table 1 ) . the medication history of infants and children had significant difference ( p = 0.031 ) . infants and children in the case group received more medications than these in the control ( 60.0% vs. 40.7% ) . however , past medical history of urinary stones of infants and children , family history of urinary stones and medication history of mother during pregnancy did not exhibit significant differences ( p > 0.05 ) ( table 2 ) . the multivariate logistic regression was carried out to identify and assess significant independent risk factors associated with stones in urinary system . the dependent variable was the urinary stones ; the independent variables included number of family members , medication history , feeding melamine - tainted milk powder and cumulant of exposure . the results indicated that or of number of family members was 0.606 ( 95% ci , 0.4110.893 ; p = 0.011 ) ; or of feeding melamine - tainted milk powder was 3.380 ( 95% ci , 1.98111.646 ; p = 0.040 ) ( table 3 ) . who recommends that a tolerable daily intake ( tdi ) for melamine is 0.2 mg / kg of body weight ( 1 ) ; however , the average melamine concentration in 52 sanlu infant formula samples collected from gansu province is 1674 mg / kg ( 3 ) . our findings demonstrated that exposure to melamine - contaminated milk powder would lead to the formation of urinary stones , and the number of family members would be a new and significant influencing factor , and more numbers of family members would protect infants and children from urinary stones . this association could be related to the exercise of infants and children . in a big family , infants and children have more chances and time to play with relatives , such as parents , brothers , sisters , etc . as compared to a small family . through more exercise , on the one hand , the risk of stone formation in urinary system would be reduced ; on the other hand , the formed stones could start moving down the urinary system quite a bit faster . it is reported that the augmented aerobic exercise in space may decrease the risk of stone formation in astronauts ( 4 ) . our current study has provided special insights into influencing factors associated with urinary stones , and the findings from this retrospective study would advance the understanding of the epidemiology of urinary stones related to melamine . ethical issues ( including plagiarism , informed consent , misconduct , data fabrication and/or falsification , double publication and/or submission , redundancy , etc ) have been completely observed by the authors .

melamine is a new risk of urinary stones . gansu province is a heavily affected area and has large population and underdeveloped economy . we hypothesized that number of family members and family income may play significant roles in the formation of urinary stones . a case - control study was performed among 190 infants . results showed that the case group had less numbers of family members than the control ( 4.4 vs. 5.6 , respectively ) . the multivariate logistic regression analysis indicated that number of family members was an independent influencing factor associated with urinary stones ( or , 0.606 ; 95% ci , 0.4110.893 ; p = 0.011 ) . family income , however , did not exhibit a significant difference . observed results suggested that number of family members was a new and significant influencing factor to affect the risk of melamine - associated urinary stones .

diabetes mellitus , a metabolic disorder , results from an inadequate mass of insulin - producing pancreatic beta cells [ 1 - 3 ] . various formulations of short- and long - lasting insulin have been used to control blood glucose levels . however , the tight regulation of insulin in response to physiological change is not possible . the development of a therapeutic method to regulate precisely the blood glucose levels will enable better management of diabetes . islet transplantation into diabetic patients is a promising method for restoring the functional beta cell mass . however , the limited supply of islets can not meet the patient demand , and post - transplant immunosuppression can produce serious side - effects . to overcome these limitations , various methods providing an alternative source of insulin - producing cells are being investigated . some of these methods include engineering non - beta cells to produce insulin , differentiation of insulin- producing cells from embryonic and adult stem / progenitor cells , and transdifferentiation of extra - pancreatic and pancreatic cells . in addition , in vivo regeneration of islet cells is being investigated . in this review , we will provide recent advances , as well as research progress on beta cell replacement and regeneration therapy for treatment of diabetes using various strategies ( fig . islet or pancreas transplantation is a method to normalize metabolic control in a way that can not be achieved with exogenous insulin . it was shown that whole pancreas transplantation ameliorated the complications associated with chronic hyperglycemia and eliminated the need for daily insulin injections . however , pancreas allografting caused immediate surgical risks and long - term complications . the first trial of islet transplantation was performed in rodent models and later in type 1 diabetic patients . further advances in the islet isolation procedure and more effective immunosuppression strategies with a steroid - free regime called the " edmonton protocol " have been made . the success rate in achieving insulin - independence in islet - transplanted patients has been greatly improved . however , the lifelong immunosuppressive regimes to prevent transplant rejection and recurrence of autoimmune responses to beta cells are expensive and decrease the quality of life . a variety of strategies to protect the transplanted islets from immune attack one of these involves preventing the activation of antigen - presenting cells . regulating the immune system by shifting the pathogenic effector cells to protective regulatory cells and blocking co - stimulatory pathways protective effects on transplanted islet cells can be gained by the transduction of genes for the expression of cytokines , antiapoptosis molecules , or growth factors . another strategy to protect islets from immune attack involves the microencapsulation of islets within synthetic polymers . there is easy passage of small molecules , such as glucose , amino acids , and insulin . oxygen deprivation presents another limit for the long - term survival of islets within a microcapsule . a major hurdle for islet transplantation is a lack of an islet source to meet the needs of all type 1 diabetic patients . embryonic , fetal , neonatal , or adult porcine islets are possible sources for transplantation , since easily available pigs have many physiological similarities to humans . however , there is a problem secondary to the hyperacute rejection of xenotransplants that carry the gal--gal antigen . another possible source of beta cells for transplantation is primary beta cells that are immortalized by transduction with oncogenes for expansion . these also have a conditional expression system that can reverse oncogene expression . however , this strategy carries the possibility of impaired insulin secretion and tumorigenicity . in particular , increasing the tolerance of islet transplants and reducing transplant rejection are necessary . there is also a need to find an unlimited source of insulin - producing cells that are required for the wider clinical application of islet transplantation . the engineered cell will become an alternative insulin - producing cell that will have an advantage over intact islets . non - beta cells may not be recognized by beta cell - specific autoimmune responses . a variety of cell types , including fibroblasts , hepatocytes , neuroendocrine cells , and muscle cells , have been engineered to produce insulin with varying degrees of success . since hepatocytes have a glucose - sensing system similar to that in pancreatic beta cells like glucose transporter 2 ( glut2 ) and glucokinase , they draw much attention as target cells for insulin production . a preclinical model of diabetes was corrected by autologous transplantation of primary hepatocytes that were non - virally transduced with a glucose - responsive promoter - regulated insulin gene construct . intestinal k cells , possible surrogate beta cells , contain the necessary enzymes for processing proinsulin to insulin and have exocytotic mechanisms . a murine enteroendocrine cell line expressing insulin under the control of a glucose - dependent insulinotropic polypeptide not only reversed diabetes when transplanted , but also produced insulin in response to glucose . transplantation of bone marrow mesenchymal stromal cells expressing insulin under the glucose - responsive early growth response gene ( egr-1 ) promoter resulted in the remission of diabetes in mice . the regulation of insulin production by glucose - responsive promoters in non - beta cells exhibits slow kinetics , which may cause hypoglycemia . this situation is due to the requirement for insulin transcription and translation , as compared with the rapid release of insulin from beta cells by exocytosis . pancreatic beta cells have unique characteristics specific to the production of insulin , such as specific peptidases , glucose - sensing systems , and secretory granules that can release insulin promptly by exocytosis in response to extracellular glucose levels . thus , it is very difficult to mimic this tight regulation of insulin production in response to physiological levels of glucose in non - beta cells . multiple studies have shown that it is possible to direct in vitro differentiation of stem and progenitor cells toward insulin - producing cells . embryonic stem ( es ) cells have the potential to generate unlimited quantities of insulin - producing cells . theoretically , es cells could be expanded indefinitely in the undifferentiated state and then differentiated into functional beta cells . two major strategies are used for the differentiation of es cells into insulin - producing cells : the embryoid body formation and the definitive endoderm formation . a recent report showed that the stepwise differentiation of es cells , which mimics endogeneous pancreatic development , could generate functional beta cells . however , the yield is still very low and the differentiated beta cells are much less functional as compared with primary islets . more efficient protocols need to be developed for the differentiation of es cells into mature functional beta cells . adult stem cells are the most important source for cell therapy for various disease models , as they are free from the ethical problems of es cells and could provide an unlimited resource . many studies reported that insulin - producing cells can be generated from adult stem / progenitor cells that are present in bone marrow , adipose tissue , liver , intestine , spleen , salivary glands , neuronal tissues , and umbilical cord blood . adult stem / progenitor cells from liver tissue are a good source for making insulin - producing cells , as the liver and pancreas share common bipotential precursor cells within the embryonic endoderm . isolated neurogenein 3 ( ngn3)-positive cells from the injured adult mouse pancreas or clonally identified cells from adult pancreatic islets and ductal populations have the ability to differentiate into cells with beta cell function . umbilical cord blood ( ucb)-derived mesenchymal stem cells ( mscs ) may be an ideal source of stem cells that can be obtained without pain or risk of viral contamination to the donor . ucb - derived mscs have a multi - lineage differentiation capacity under specific manipulation of the culture conditions . several studies have shown that ucb stem cells can be differentiated into insulin - producing cells . adipose tissue - derived stem cells ( adscs ) are located within the stromal vascular fraction of adipose tissue . adscs can be isolated in high numbers from human adipose tissue at low risk to the patient . an interesting study reported the successful differentiation of functional insulin - producing cells from the stem cells of human eyelid adipose tissue using a two - step culture condition . similar to other stem cells , pdx-1-transduced adscs derived from human or murine tissue could differentiate into insulin - expressing cells under specific culture conditions . thus , adscs have the potential as a useful source for cell replacement therapy in diabetes . despite the success of the differentiation protocols , as described in this review , none of the protocols are yet able to produce fully functional mature beta cells . further research is required to understand how endogenous beta cells differentiate and to develop methods for generation of sufficient functional beta cells for clinically applicable therapies for diabetes . approaches for in vivo regeneration are to stimulate replication of beta cells and induce neogenesis . this replication can be stimulated by pregnancy and diabetogenic stimuli , such as glucose and free fatty acids , suggesting that beta cell growth can be artificially induced . growth factors , such as activin a and hepatocyte growth factor , have been used to induce beta cell replication . other factors , like a combination of epidermal growth factor ( egf ) and gastrin , keratinocyte growth factor , betacellulin ( btc ) , and glucagon - like peptide-1 ( glp-1 ) or its long - lasting homolog , exendin-4 , have also been used to induce beta cell replication . in addition , members of the regenerating protein family , such as reg protein and islet neogenesis gene associated protein ( ingap ) , can stimulate proliferation of beta cells and have been investigated as potential therapies for diabetes . both glp-1 and egf have been combined with gastrin as a therapy to restore the beta cell mass . these treatments restored normoglycemia in autoimmune non - obese diabetic ( nod ) mice , both by restoring the beta cell mass and by downregulating the immune response . in a similar study , combination therapy with egf and gastrin induced neogenesis of human beta cells from pancreatic duct cells in vitro , as well as from human pancreatic cells implanted into immunodeficient nod . clinical trials are underway for beta cell regeneration in type 1 diabetes using synthetic exendin-4 ( ac2993 ) . further clinical trials using immune suppressors and egf and gastrin analogs ( e1-inf ) for type 1 and type 2 diabetes have been reported . in phase 2 clinical trials , ingap peptide revealed no consistent treatment effects on fasting glucose , insulin , or c - peptide in type 1 and type 2 diabetic patients , although the effects on hbalc and stimulated c - peptide were promising . the expression of beta cell transcription factors either with or without a signaling molecule , such as a growth factor , has shown to be a successful method of generating new insulin - producing cells . delivery of the pancreatic and duodenal homeobox-1 ( pdx-1 ) gene into the mouse pancreas or intraperitoneal injection of pdx-1 protein induced beta cell neogenesis and ductal proliferation . delivery of the pdx-1 gene along with the btc gene into the pancreas of streptozotocin - induced diabetic rats via ultrasound - targeted microbubble destruction normalized blood insulin and c - peptide levels . intraperitoneal injection of recombinant pdx-1 into streptozotocin - induced diabetic mice increased islet cell numbers and proliferation in pancreata . an exciting report demonstrated that expressing a specific combination of three transcription factors , pdx-1 , ngn3 , and musculoaponeurotic fibrosarcoma oncogene homolog a ( mafa ) , resulted in amelioration of hyperglycemia . the transcription factors were administered by an adenoviral mediated delivery reprogrammed pancreatic exocrine acinar cells into beta cells . these beta cells were indistinguishable from endogenous islet beta cells in size , shape , and ultrastructure . transcription factors , such as pdx-1 and neurod , have been used not only to stimulate new insulin - producing cells in the pancreas , but also to confer beta cell - like characteristics to non - islet tissue , such as in the liver and the intestine . systemic injection of recombinant pdx-1 resulted in expression of insulin and other genes related to pancreatic function not only in the pancreas , but also in the liver . delivery of the pdx-1 gene or neurod and btc genes to the liver resulted in the expression of insulin and other islet - specific genes in liver . these genes ameliorated hyperglycemia in diabetic mice . systemic delivery of pdx-1 carrying the vp16 transcriptional activation domain ( pdx-1/vp16 ) or ngn-3 and btc gene resulted in insulin production in liver . in vivo regeneration in the intestine has also been investigated . forced expression of pdx-1 , mafa , or glp-1 in intestinal epithelia by adenovirus - mediated gene transfer induced the expression of insulin and lowered blood glucose levels in streptozotocin - induced diabetic animals . the injection of stem / progenitor cells was shown to induce insulin - producing cells . it is unclear whether the injected stem / progenitor cells differentiate into insulin - producing cells or exert other effects that preserve or increase the beta cell mass . the injection of allogeneic splenocytes , in combination with complete freund 's adjuvant ( to prevent anti - islet autoimmunity ) , corrected diabetes in diabetic nod mice . however , it remains to be determined whether the injected splenocytes are the true source of insulin - producing cells . a successful clinical trial involving autologous hematopoietic stem cell transplantation and immune suppressor in diabetic patients although beta cell function was shown to be increased , the mechanism of action was unclear . in vivo islet cell regeneration therapy is very challenging . most methods are still in the early stages and are not yet ready for clinical application . islet transplantation is a promising strategy for the reconstitution of a functional beta cell mass . this method provides stable glycemic control without hypoglycemic episodes , as well as independence from exogeneous insulin . however , a shortage of islet donors is a major limiting factor for cell replacement therapy in type 1 diabetes . the differentiation of pluripotent stem / progenitor cells into insulin - producing cells creates a possible source for the generation of therapeutic insulin - producing cells . beta cell growth and differentiation factors , the expression of beta cell transcription factors , and the injection of stem / progenitor cells has been used to regenerate beta cells in vivo . most results have been obtained from studies with animal models , but very little has been tried clinically . the underlying mechanisms for the normal renewal process in adults will accelerate the clinical application of islet cell replacement and regeneration therapy for diabetic patients .

reduction of beta cell function and a beta cell mass is observed in both type 1 and type 2 diabetes . therefore , restoration of this deficiency might be a therapeutic option for treatment of diabetes . islet transplantation has benefits , such as reduced incidence of hypoglycemia and achievement of insulin independence . however , the major drawback is an insufficient supply of islet donors . transplantation of cells differentiated in vitro or in vivo regeneration of insulin - producing cells are possible approaches for beta cell / islet regenerative therapy . embryonic and adult stem cells , pancreatic ductal progenitor cells , acinar cells , and other endocrine cells have been shown to differentiate into pancreatic beta cells . formation of fully functional beta cells and the safety of these cells are critical issues for successful clinical application .

although , electrocardiographic change is not uncommon in patients with cerebrovascular disease including subarachnoid hemorrhage , subdural hematoma , and ischemic stroke,1 - 3 ) typical st - sgement elevation is rare . the precise mechanism is not clear , but it is widely accepted that excess releasing of cathecholamine may influence myocardial contractility and necrosis.2)4)5 ) here , we intend to emphasize that careful attention of neurologic abnormality can enable better prognosis . she was previously healthy and had no symptoms . on arrival , she was drowsy and her blood pressure , pulse rate , respiratory rate and body temperature were 73/50 mm hg , 80 beats per minute , 20 per minute and 36.0 , respectively . electrocardiogram on arrival presented st segment elevation in lead ii , iii , avf , v 5 , 6 and depression in v 1 , 2 ( fig . laboratory examination showed her creatine kinase - mb was 1.21 ng / ml and troponin - t < 0.010 ng / ml . assuming acute myocardial infarction , we conducted emergency coronary angiography but there was no significant stenosis ( fig . 2 ) . echocardiogram exhibited hypokinesia on septum and apex and left ventricular ejection fraction was 43% . during coronary angiography , we then checked brain computed tomography immediately , and found a large amount of subarachnoid hemorrhage and small intracranial hemorrhage in the medial temporal lobe base ( fig . 3 ) . upon cerebral angiographic computed tomography , a small saccular aneurysm in the right posterior communicating artery area after taking right pterional craniotomy and aneurysmal neck clipping , the patient improved and was discharged in 30 days without any neurological sequela . it has been reported that abnormalities of electrocardiogrphy , echocardiography and serum cardiac specific markers are associated with cerebrovascular disease.4 - 8 ) the most common cause is subarachnoid hemorrhage,9 - 11 ) but additional causes include head injury , meningitis and brain tumor . previous investigators has suggested that severe stress such as ischemic stroke and cerebral hemorrhage may provoke high catecholamine induced neurogenic - stunned myocardium.2)4 - 5 ) increased release of catecholamines from local nerve endings in the heart may mediate these cardiac abnormalities . transient severe coronary vasoconstriction leads to ischemia followed by postischemic ventricular failure and subendocardial myocardial damage . in addition , a direct cardiotoxic effect of catecholoamine may cause the development of subendocardial damage.4)5 ) autopsies have revealed areas of characteristics subendocardial myocardial lesions , called contraction band necrosis , in the hearts of patients with subarachnoid hemorrhage ( sah).14 - 16 ) the myocardial damage resembles lesions produced in animal experiments by infusion of norepinephrine.4 ) the characteristic pattern of myocardial lesions has suggested that damaging catecholamines are released from intramyocardial nerve endings rather than from the general circulation.17 ) despite all these studies , the precise mechanism of action is still unclear and future studies are required . when unconscious cerebral hemorrhage patients with electrocardiograms showing st segment elevation come to the emergency room , we have a tendency to misdiagnose as acute myocardial infarction and treat with multiple antiplatelet and anticoagulate agents , which can cause harmful effects . furthermore , delaying accurate diagnosis may result in catastrophic outcome.12)13 ) therefore , any neurological abnormalities including paralysis or severe headache should be dealt with careful attention and the possibility of cerebrovascular disease should be considered , prompting the need to be prudent with the use of antiplatelet agents . even if a patient is misdiagnosed as acute st elevation myocardial infarction , we should consider a cerebral cause if there is no significant stenosis in coronary angiography , and act promptly to save the life of a patient . it is well known that stress induced cardiomyopathy may develop by a cerebrovascular accident , but typical st elevation is rare . by reporting this case , we wish to share our uncommon experience and hope that it may be helpful in future cases .

without significant coronary artery stenosis , ischemic electrocardiographic change including st segment elevation , segmental wall motion abnormality and elevated serum cardiac - specific markers ( creatine kinase - mb , troponin - t ) may develop after central nervous system injuries such as subarachnoid , intracranial or subdural hemorrhage . misdiagnosing these patients as acute myocardial infarction may result in catastrophic outcomes . by reporting a case of a 55-year old female with subarachnoid hemorrhage mimicking acute st elevation myocardial infarction , we hope to underline that careful attention of neurologic abnormality is critical in making better prognosis .

fibrosing mediastinitis , also known as sclerosing mediastinitis or mediastinal fibrosis , is a rare late sequela of a thoracic inflammatory process . most cases arise from prior histoplasmosis infection , and less commonly from tuberculosis ( tb ) . fibrosing mediastinitis is characterized by the development of dense mediastinal infiltrates that obliterate normal fat planes and is best viewed through advanced imaging modalities , such as computed tomography ( ct ) or magnetic resonance imaging ( mri ) . given the rarity of this clinical entity , some cases may go unrecognized and is often misdiagnosed . we present the case of a patient with tb - associated fibrosing mediastinitis whose diagnosis was delayed . a 71-year - old man with a history of chronic obstructive pulmonary disease ( copd ) , pulmonary hypertension , and tb status posttreatment in 1985 , presented for evaluation of chronic , progressive dyspnea . the patient had previously been seen at our institution for dyspnea and had been diagnosed with and treated for numerous copd exacerbations . he had no history of tobacco use , significant alcohol consumption , or any illicit drug use . on examination , the patient was in no significant distress and was able to speak in full sentences . his vital signs were normal except for a respiratory rate of 20 breaths / min and oxygen saturation of 90% on room air at rest . transthoracic echocardiography revealed right ventricular dilatation with flattening of the interventricular septum and an estimated pulmonary artery systolic pressure of 85 mmhg . chest radiograph demonstrated bilateral perihilar soft tissue densities with right apical scarring , pleural thickening and volume loss [ figure 1 ] . contrast - enhanced chest ct revealed ill - defined , infiltrative bilateral hilar soft tissue densities with calcifications , enlargement of the main and right pulmonary artery , and irregular narrowing of the right mainstem and upper lobe bronchi [ figure 2 ] . positron emission tomography ( pet ) showed mild fluorodeoxyglucose uptake in the bilateral perihilar regions , right more prominent than left . of note , the patient had undergone a non contrast - enhanced thoracic ct three years prior , which documented relative stability all the abnormal findings , including the bronchial narrowing and pulmonary artery dilation [ figure 3 ] . a 71-year - old man with a history of chronic obstructive pulmonary disease , pulmonary hypertension , and prior pulmonary tuberculosis infection presenting with progressive dyspnea , diagnosed with tuberculosis - associated fibrosing mediastinitis . chest posteroanterior radiograph showing bilateral peri - hilar soft tissue densities ( white arrows ) with right apical , pleural thickening and volume loss ( black arrow head ) . a 71-year - old man with a history of chronic obstructive pulmonary disease , pulmonary hypertension , and prior pulmonary tuberculosis infection presenting with progressive dyspnea , diagnosed with tuberculosis - associated fibrosing mediastinitis . ( a - d ) demonstrates ill - defined , infiltrative bilateral hilar soft tissue densities with calcifications ( white arrows ) ; enlargement of the main and right pulmonary artery ( black arrow heads ) ; and irregular narrowing of the right mainstem and upper lobe bronchi ( black arrow ) . a 71-year - old man with a history of chronic obstructive pulmonary disease , pulmonary hypertension , and prior pulmonary tuberculosis infection presenting with progressive dyspnea , diagnosed with tuberculosis - associated fibrosing mediastinitis . ( a - d ) demonstrating ill - defined , infiltrative bilateral hilar soft tissue densities with calcifications ( white arrows ) ; enlargement of the main and right pulmonary artery ( black arrow heads ) ; and irregular narrowing of the right mainstem and upper lobe bronchi ( black arrow ) . the patient had previously undergone a bronchoscopy with bronchoalveolar lavage , brushings , and biopsies which were negative for fungal organisms and acid - fast bacilli . the patient 's known history of tb and findings of old granulomatous disease on imaging along and with negative bronchoscopy results established fibrosing mediastinitis as the likely cause of his mediastinal infiltrates . although the pet scan showed mild uptake in the perihilar regions consistent with an active inflammatory process , the stability noted on imaging over a prolonged course was reassuring that the mediastinal and hilar infiltrates did not represent malignancy . the patient had compression of his pulmonary artery due to fibrosing mediastinitis and findings of pulmonary hypertension on the examination and by echocardiography . he also had tracheobronchial narrowing as a result of this entity as seen on chest imaging which likely manifested as obstruction on spirometry . the patient 's respiratory symptoms stabilized on supportive medications , and no further interventions were required . the pathophysiology of fibrosing mediastinitis is postulated to stem from the chronic inflammation and associated profound fibrotic changes of mediastinal structures from the adjacent primary granulomatous disease , either via direct infiltration from granuloma rupture or indirectly via local inflammatory processes within regional mediastinal lymph nodes . the etiology of this inflammation includes granulomatous diseases ( such as histoplasmosis , tb , sarcoidosis , and behcet 's disease ) , malignancy ( such as bronchogenic cancer and lymphoma ) , trauma , and medication - induced ( methysergide ) ; however , a large number of cases remain idiopathic . a subset of idiopathic fibrosing mediastinitis now encompasses an emerging disease entity mediated by igg-4 , a presumed anti - inflammatory immunoglobulin whose exact role in inflammation modulation is yet to be elucidated but can manifest as retroperitoneal fibrosis with or without thyroiditis . the development of fibrotic infiltrates / masses has the potential to encase and compromise mediastinal structures including the airway , esophagus , and/or major vessels . airway involvement can vary widely ranging from hoarseness , if the laryngeal nerve is affected , to obstructive pneumonitis and/or atelectasis , and hemoptysis when erosion of the vascular bundle due to local inflammation into the pulmonary parenchyma occurs . vascular involvement can compromise any of the following : superior vena cava ( svc ) , aorta , pulmonary arteries , and veins through compression secondary to mass effect . , the insidious onset of vascular compromise often allows for the development of significant collaterals and the potential to remain asymptomatic . the diagnosis of fibrosing mediastinitis is established via clinical impression and imaging , and must exclude other active infiltrative processes involving the mediastinum , particularly bronchogenic carcinoma and lymphoproliferative disorders . chest radiographs are usually nonspecific and often underestimate the extent of mediastinal disease . therefore , advanced imaging modalities such as ct and mri are preferred . characteristic findings on ct or mri include soft tissue obliteration of normal mediastinal fat planes with or without encasement and invasion of adjacent structures . there are currently , no medical therapies that have shown to prevent this sequela of granulomatous disease or alter it 's natural progression . although controlled trials have not been performed , glucocorticoids do not appear to be beneficial . treatment of any underlying infectious process is still warranted for patients well - being and public health purposes . other management modalities can include percutaneous stenting of vascular structures such as the svc to relieve obstruction , or placement of endoscopic stents in cases of airway obstruction and for the management of dysphagia . surgery has a limited benefit and generally leads to poor outcomes given the extent of the fibrosis , calcifications , and the presence of collaterals . terminal outcomes with fibrosing mediastinitis include the development of cor pulmonale and respiratory compromise from recurrent infections , bronchial obstruction , or hemoptysis . although rare , fibrosing mediastinitis should be considered in the differential diagnosis of an ill - defined , calcified soft tissue mass in the mediastinum . the clinical presentation and symptomatic involvement is directly proportional to the extent of infiltration of mediastinal structures . fibrosing mediastinitis is a diagnosis of exclusion and is best established via advanced imaging modalities . it is most often a late sequela of granulomatous inflammation , however , active processes such as infection or malignancy must first be excluded . the management is primarily directed toward palliation of symptoms , if present , particularly as no medical therapy or surgical intervention has shown any benefit .

fibrosing mediastinitis is a rare condition defined by the presence of fibrotic mediastinal infiltrates that obliterate normal fat planes . it is a late complication of a previous granulomatous infection , such as histoplasmosis or tuberculosis ( tb ) . due to its rarity , fibrosing mediastinitis is often under - recognized , and the clinical presentation is variable and dependent on the extent of infiltration or encasement of structures within the mediastinum . we present a case of fibrosing mediastinitis in a man with a prior history of tb , who presented with progressive dyspnea and was found to have chronic mediastinal soft tissue opacities and pulmonary hypertension . his diagnosis was delayed due to the lack of recognition of this clinical / radiographic entity . fibrosing mediastinitis is a rare entity usually caused by granulomatous disease . most cases develop as a late complication of histoplasmosis or tb . the presence of calcified mediastinal soft tissue infiltrates on advanced chest imaging can be diagnostic of fibrosing mediastinitis in patients with a prior history of a granulomatous infection once active processes such as malignancy are excluded .

remodeling after tooth extraction results in substantial horizontal ( 3 - 4 mm ) and vertical ( 1 - 2 mm ) alveolar bone loss [ 13 ] . this postextraction alveolar bone loss can compromise or prevent subsequent implant placement , while loss of crestal support compromises the position and appearance of the soft tissues in aesthetic areas . in an effort to minimize postextraction alveolar bone remodeling and thus prevent its undesirable sequelae , alveolar ridge preservation ( arp , a form of guided bone regeneration , gbr ) was developed as a therapeutic modality . several studies have been conducted to evaluate the effectiveness of different arp surgical techniques ( e.g. , flapped versus flapless and primary intention healing versus no primary closure ) and materials ( e.g. , occlusive membranes and bone grafts ) , and several approaches have proven successful to varying degrees [ 116 ] . systematic reviews indicate that the combination of bone grafts with resorbable membranes achieved the best results [ 13 ] . however , a high incidence of membrane exposure ( potentially leading to infection ) , early membrane degradation with inadequate barrier function , postoperative discomfort with coronal flap movement , and loss of width and thickness of keratinized tissue in the alveolar ridge are among the reported complications [ 2 , 6 , 8 , 17 ] . soft tissue management is important for maintaining an appropriate soft tissue profile for future tooth- or implant - supported restorations [ 1821 ] . for example , in patients with thin biotype , a connective tissue graft may be recommended during or after arp . in this context , a resorbable barrier that preserves soft tissue attributes could be a valuable addition to arp protocols . recently , a new xenogeneic collagen matrix ( xcm ) ( mucograft , geistlich pharma ag , wolhusen , switzerland ) of porcine origin has been introduced into clinical practice that is made of non - cross - linked collagen types i and iii . the new xcm is designed with a bilayer structure to support tissue ingrowth , regeneration , and integration within the host tissue . it has been specifically designed for soft tissue regeneration and has been histologically and clinically evaluated for root coverage and keratinized tissue augmentation . studies report complete integration and revascularization with mature mucosal and submucosal tissues after 3 months , in both nonsubmerged and submerged healing environments [ 2233 ] . the structural characteristics of this xcm and the studies indicating that it maintains its barrier function for at least 30 days suggest that it could also be used as a gbr device [ 22 , 23 , 28 ] . results of clinical studies suggesting that the width and thickness of keratinized tissue can be maintained or increased , even if this matrix is left exposed , indicate that this xcm may be used without coronal advancement of flaps or periosteal - releasing incisions [ 27 , 29 ] . these are potentially significant advantages since such an approach could minimize the reported complications following gbr . the aim of this case series is to report clinical , radiographic , and histological outcomes following use of a new xcm in combination with freeze - dried bone allograft ( fdba ) for arp . nine nonsmoking patients ( aged 2174 years ; 2 males and 7 females ) were treated with arp after extraction of 18 teeth in a private practice in athens , greece , from october 2010 to october 2012 . all patients had a noncontributory medical history and required arp either prior to future implant placement or for preservation of aesthetics prior to fabrication of a maxillary anterior tooth - supported fixed restoration ( table 1 ) . a presurgical evaluation , consisting of a detailed oral and periodontal examination and full mouth radiographic assessment , was conducted on all patients . three patients presented with gingivitis , 4 presented with moderate or severe periodontitis , and 2 were on maintenance . all patients received at least one session of oral hygiene instruction and scaling prior to tooth extraction , in order to establish an oral environment more favorable to wound healing . in addition , periodontal treatment comprising of root planing under local anesthesia and access / regenerative surgery , when necessary , was completed prior to the arp procedure . the recommended treatment was thoroughly explained to each patient and written informed consent was obtained . all patients received antibiotics ( amoxicillin 500 mg three times a day for 8 days or azithromycin 250 mg once a day for 6 days ) starting 2 days preoperatively . following minimal flap elevation with soft tissue preservation , atraumatic extractions were performed , using piezosurgical instruments ( piezotome , satelec acteon , merignac , france ) . buccal bone wall defects were present in all sockets , with a buccal bony dehiscence extending > 50% of the length of the socket in seven sites . the fdba ( cortical bone ( 2501000 m ) lifenet , virginia beach , va , usa ) was rehydrated and used to completely fill the sockets and resulting bony defects . the xcm was trimmed and adapted to cover the defects and 2 - 3 mm of the adjacent bone . the flaps were repositioned ( no periosteal release was performed ) and sutured with nonabsorbable monofilament sutures ( gore - tex , w. l. gore & associates , flagstaff , az , usa ) ( figures 1 , 2 , 3 , and 6 ) . postoperatively , patients were given instructions and prescriptions for antimicrobial rinse ( chlorhexidine gluconate 0.12% ) two times a day for 3 weeks and analgesics ( acetaminophen 1000 mg or ibuprofen 400 mg ) as needed for pain . patients were seen at 1 , 2 , 4 , 8 , 12 , and 24 weeks postoperatively . radiographic examination included periapical radiographs preoperatively and 6 months postoperatively and cone - beam computed tomography ( cbct ) scans in 6 patients at 6 months . histological and immunohistochemical analysis included 9 sites from 4 patients 6 months after arp ( table 1 ) . following thorough discussion and explanation of the procedure , patients agreed to proceed , and an informed consent form was signed that was based on the helsinki declaration of 1975 , as revised in 2000 . soft tissues , approximately 3 4 mm in size , removed by soft tissue punches during guided implant placement surgery ( navigator system , biomet 3i , palm beach gardens , fl , usa ) or ridge modification for construction of ovate pontics , were not discarded but placed in 10% buffered formalin , processed , and stored for future analysis . after fixation in 10% buffered formalin , 5 m thick paraffin - embedded tissue sections were stained with hematoxylin and eosin . streptavidin - biotin - peroxidase immunohistochemistry was performed with a fully automated slide preparation system ( ventana benchmark xt , ventana medical systems inc . , tucson , az , usa ) and commercially available detection kit ( iview dab , ventana medical systems inc . antibodies used were pan - keratin ( dilution 1 : 50 ) ( clone ae1/ae3 , dako , carpinteria , ca , usa ) and cd34 ( dilution 1 : 50 ) ( clone qbend 10 , dako , carpinteria , ca , usa ) . appropriate positive and negative ( i.e. , primary antibodies substituted with nonimmune serum ) controls were used according to manufacturers ' instructions . postoperatively , patients reported only minor swelling and discomfort or pain ; in all cases , healing was uneventful . the exposed matrix portions remained intact during the first 8 postoperative weeks and were slowly replaced by mature keratinized tissue within 2 - 3 months . the clinical appearance of the soft tissue between postoperative visits at 8 weeks and 24 weeks suggested that the width and thickness had increased ( figures 4 and 5 ) . radiographic assessment on cbct scans at 24 weeks indicated adequate crestal bone width for standard - size implant placement in all sites , which was confirmed during surgery ( figures 4 , 6 , 7 , and 8) . horizontal ridge width , measured with specialized software ( simplant , materialise dental nv , belgium ) 1 mm below the most coronal aspect of the crest perpendicular to the long axis of the ridge , ranged from 5.8 to 7.6 mm . all treatment - planned implants were placed in acceptable positions and all fixed restorations fulfilled the aesthetic demands of the case without need for further soft or hard tissue augmentation procedures ( figure 5 ) ( table 1 ) . following processing of the gross specimens ( figure 9(a ) ) , microscopic examination showed that all specimens consisted of normal - appearing oral mucosa , covered by parakeratinized squamous epithelium with long interconnecting rete pegs ( figure 9(b ) ) . the lamina propria was composed of fibrous connective tissue with interlacing bands of collagen fibers , showing many fibroblasts and medium- and small - sized vessels ( figure 9(c ) ) . the full thickness of the regenerated epithelium reacted with the pan - keratin antibody ( figure 9(d ) ) , while many capillary vessels lined by cd34-positive endothelial cells were regularly distributed in the lamina propria ( figures 9(e ) and 9(f ) ) . this case series reports on the clinical , radiographic , and histological outcomes after use of a new xcm and fdba when performing arp following tooth extraction . the treatment plan called for the treated sites to subsequently receive either dental implant placement or tooth - supported fixed partial dentures . the clinical and radiographic results indicated that the xcm - fdba combination resulted in successful arp outcomes , with minimal complications or patient discomfort and pain . the xcm remained clinically intact during the first 8 postoperative weeks ; this suggests that the barrier function was maintained during the first 2 months of healing . clinically , the exposed matrix portions were slowly replaced by mature keratinized tissue within 2 - 3 months , with tissue width and thickness seemingly increasing between the postoperative visits at 8 weeks and 24 weeks . all implants were placed in acceptable positions without need for further soft or hard tissue augmentation procedures , thus minimizing possible additional discomfort and cost for the patient during placement . the histological and immunohistochemical results indicated that the soft tissue regenerated over the extraction sites has the characteristics of normal keratinized oral mucosa . these findings are consistent with some of the recent clinical [ 27 , 2931 ] and histological studies [ 24 , 27 ] suggesting that the width and thickness of keratinized tissue can be maintained or even increased when this specific matrix is left exposed . the reported complete integration and formation of mature mucosal and submucosal tissues suggested that the new xcm could also be used as a gbr device [ 22 , 23 , 28 ] and that the xcm - fdba combination could be an additional valuable option when performing arp for subsequent implant placement or fixed partial denture restorative treatment . however , the limitations of this study small and heterogeneous clinical , radiographic , and histological sample size ; lack of clinical and preoperative radiographic measurements ; and one time point of histological assessment suggest caution in interpreting the results . randomized controlled clinical trials are necessary to confirm the efficacy and predictability of this approach and to assess the long - term outcomes of implant therapy or conventional prosthodontics in sites treated with this protocol . for a successful outcome in maintaining barrier function during the early postoperative healing period , resorbable barrier membranes used in gbr must possess certain properties , including biocompatibility , preferential tissue integration , place - holder characteristics , and adequate physicochemical stability . collagen - based materials have often been explored for gbr applications because of the desirable material properties of collagen ( natural origin , rapid biodegradation rate , biocompatibility , etc . ) . however , these same characteristics may prove to be a disadvantage , since barrier function may be limited over time . to decrease the degradation rate and enhance the temporal stability of collagen - based membranes , manufacturers have used several cross - linking approaches . although cross - linking may address membrane stability in the oral or wound environment , it may also result in compromised attachment and proliferation of desirable connective tissue wound cells ( e.g. , fibroblasts ) , which could lead to delayed wound healing and possible infection as well as to undesirable tissue reaction . one such technique involves the combination of non - cross - linked native collagen iii , which undergoes relatively fast degradation , and collagen i , which is more resistant , in order to tightly control membrane degradation . in addition , the literature shows that intentional exposure of such bioresorbable membranes does not jeopardize the procedure outcomes ( alveolar bone and keratinized tissue preservation ) [ 2 , 37 ] . the new non - cross - linked xcm is composed of collagen type i and type iii without further cross - linking or chemical treatment . the xcm matrix is a bilayer : one side is thin and smooth and is of low porosity , while the other is a more porous 3-dimensional network . the xcm must be placed with the thin and smooth surface as the external layer since it is designed to allow cell attachment and host tissue integration but at the same time to remain impermeable to invading cells for 30 days . the more porous part is designed to be the internal layer since it is rapidly infiltrated by host mesenchymal cells [ 22 , 23 ] . in summary , the favorable preliminary results reported here indicate that the xcm used could be a valuable alternative for arp procedures . randomized controlled clinical trials are necessary to confirm its efficacy and predictability and to assess the long - term outcomes of implant therapy or conventional prosthodontics in sites treated with this protocol .

alveolar ridge preservation ( arp ) has been shown to prevent postextraction bone loss . the aim of this report is to highlight the clinical , radiographic , and histological outcomes following use of a bilayer xenogeneic collagen matrix ( xcm ) in combination with freeze - dried bone allograft ( fdba ) for arp . nine patients were treated after extraction of 18 teeth . following minimal flap elevation and atraumatic extraction , sockets were filled with fdba . the xcm was adapted to cover the defect and 2 - 3 mm of adjacent bone and flaps were repositioned . healing was uneventful in all cases , the xcm remained in place , and any matrix exposure was devoid of further complications . exposed matrix portions were slowly vascularized and replaced by mature keratinized tissue within 2 - 3 months . radiographic and clinical assessment indicated adequate volume of bone for implant placement , with all planned implants placed in acceptable positions . when fixed partial dentures were placed , restorations fulfilled aesthetic demands without requiring further augmentation procedures . histological and immunohistochemical analysis from 9 sites ( 4 patients ) indicated normal mucosa with complete incorporation of the matrix and absence of inflammatory response . the xcm + fdba combination resulted in minimal complications and desirable soft and hard tissue therapeutic outcomes , suggesting the feasibility of this approach for arp .

... the aim of oxygen therapy should be to increase the delivery of oxygen rather than to reach any arbitrary concentration in the arterial blood . is administration of oxygen , the most widely prescribed drug in the formulary , free of risks to nonhypoxemic patients with regional ischemia ? hyperoxia marginally increases the arterial blood oxygen content ( cao2 ) , theoretically increasing tissue oxygen delivery ( do2 ) assuming no reduction in tissue blood flow . however , oxygen causes constriction of the coronary , cerebral , renal and other key vasculatures - and if regional perfusion decreases concomitantly with blood hyperoxygenation , one would have a seemingly paradoxical situation in which the administration of oxygen may place tissues at increased risk of hypoxic stress . any tissue damage in the course of oxygen administration would plausibly be attributed to the underlying disease process . ascribing hypoxic damage to oxygen administration is counter - intuitive and is difficult to accept without a receptive mindset . considering the ubiquity of oxygen therapy , the continued low threshold for its administration , and the widespread belief that its use is justified and safe , we believe it is important to revisit the arguments made to justify the status quo . owing to the vasoconstrictor effects on the coronary , cerebral , renal and other key vasculatures , there are many scenarios in which administration of oxygen decreases the perfusion to vital organs to a greater extent than the small increase in cao2 , thereby actually reducing do2 . the calculated cao2 increases with normobaric hyperoxia ( assuming all hemoglobin is already saturated ) by only 0.03 ml / l per mmhg . with increases in alveolar pao2 from 100 to 600 mmhg , cao2 increases by 15 ml / l , or about ~7.5% assuming a hemoglobin concentration of 150 g / l . in healthy adults , administration of high oxygen concentrations is therefore likely to decrease brain do2 . despite this known effect of hyperoxia on cerebral blood flow , and the published recommendations , patients with stroke - even those with satisfactory arterial saturations - although singhal and colleagues reported transient improvement in patients with ischemic strokes , survival at 7 months for patients with mild or moderate strokes is significantly greater in those administered air than in those given 100% oxygen for the first 24 hours after the event . normobaric hyperoxia reduces coronary blood flow by 8 to 29% in normal subjects and in patients with coronary artery disease or chronic heart failure . the reduction in coronary artery flow as early as 1950 russek and colleagues reported that supplemental oxygen failed to reduce electrocardiographic signs of ischemia or reduce anginal pain in patients with myocardial infarction . in 1969 bourassa and colleagues proposed that hyperoxia - induced decreases in coronary blood flow provoke myocardial ischemia in patients with severe coronary artery disease . then in 1976 , in a double - blind randomized controlled trial , rawles and kenmure reported greater serum aspartate aminotransferase levels , indicating increased infarct size , in patients with acute myocardial infarction receiving high - flow oxygen compared with room air . they also observed a nonsignificant tripling of the death rate in those patients . given these concerns , the emergency oxygen guideline group of the british thoracic society called for ' large randomised trials of oxygen therapy for non - hypoxaemic patients with acute cardiac and cerebral ischaemia ' . conti , in a recent editorial , reminded readers that that there is only level c evidence for the administration of supplemental oxygen to patients with uncomplicated st elevation in myocardial infarction during the first 6 hours . based on currently available evidence , the uk national institute for health and clinical excellence guidelines have recently emphasized that ' supplementary oxygen should not be routinely administered to patients with acute chest pain of suspected cardiac origin , but that oxygen saturation levels should be monitored and used to guide its administration ' . similar cautions have been expressed about the use of oxygen for the treatment of traumatic brain injury . the mechanisms by which hyperoxia causes systemic vasoconstriction remain uncertain . recent work focuses on the inhibition of vasodilators ( prostaglandins , nitric oxide ) by reactive oxygen species generated as a result of the hyperoxia [ 19 - 23 ] . other work suggests that reactive oxygen species activate brainstem respiratory neurons , but this suggestion needs to be established as occurring under normobaric conditions . the role of hyperoxia - induced hypocapnia ( that is , the reverse haldane effect ) remains contentious . regardless of the underlying mechanism(s ) , the importance of considering the effects of both pao2 and paco2 on vascular tone is evident in a study in which both hyperoxia and hypocapnia independently increased cerebrovascular resistance and reduced cerebral blood flow . indeed , in some situations , the vasoconstrictive effects of hyperoxia may be predominantly due to the concomitant hypocapnia . positron emission tomography provides similar results : the reduction of cerebral blood flow and the increase in oxygen extraction during inhalation of 100% oxygen is completely reversed when subjects breathe carbogen ( 5% carbon dioxide , 95% oxygen ) . these observations emphasize the importance of independent control of arterial pco2 and po2 - possibly using dynamic forcing of alveolar gases ( for example ) or sequential gas delivery ( for example ) - when studying the independent effects of po2 and pco2 on regional perfusions . these observations also suggest that adding carbon dioxide to oxygen may offset the vasoconstriction due to hyperoxia or hypoxia - induced hypocapnia . there are other clinical situations in which the routine administration of high - concentration oxygen may lead to worse outcomes , although primarily through mechanisms other than changes in regional perfusion . austin and colleagues recently reported in a randomized controlled trial that patients with acute exacerbations of chronic obstructive pulmonary disease have a twofold to fourfold increased mortality when treated with high - flow oxygen compared with oxygen titrated to result in an arterial oxygen saturation between 88 and 92% . although several mechanisms may account for these findings , worsening respiratory failure is probably the predominant mechanism . of the patients whose arterial blood gases were measured within 30 minutes of presentation to hospital , those who received high - concentration oxygen were more likely to have hypercapnia ( mean difference paco2 34 mmhg ) or respiratory acidosis ( mean difference ph 0.12 ) . adverse outcomes with hyperoxia have also been reported in critically ill patients admitted to the intensive care unit ; a high pao2 in the first 24 hours after admission is independently associated with in - hospital mortality . in this study a u - shaped curve of mortality with pao2 was observed , illustrating the risks of both hypoxia and hyperoxia . kilgannon and colleagues recently reported that patients administered high - concentration oxygen resulting in hyperoxia ( pao2 > 300 mmhg ) following cardiac arrest have increased in - hospital mortality , a finding they attributed to increased oxidative stress associated with hyperoxia . however , because a subsequent study was unable to replicate these findings , randomized controlled trials will be required to resolve the clinical uncertainty . neonatal resuscitation is the clinical situation in which administration of 100% oxygen has most clearly been demonstrated to increase the risk of death . this has resulted in a radical change in practice whereby room air rather than oxygen is now the recommended resuscitation regime . considering the ubiquity of the administration of supplemental oxygen , there are surprisingly few randomized clinical trials that demonstrate its beneficial role when hypoxemia is absent . this may reflect the fact that its usage is so embedded in clinical practice that it is accepted as safe . nevertheless , there are some situations in which supplemental oxygen administration is useful : treatment of cluster headache , reducing the oxidative stress associated with colon surgery , and the prevention of desaturation during endoscopy . supplemental oxygen administration can , however , have the unintended side effect of delaying recognition by oximetry of hypoventilation . until recently many studies had indicated that supplementary oxygen reduced postoperative nausea and vomiting , but the current status is ambiguous ( for example [ 43 - 46 ] ) . similarly , oxygen was thought to reduce postsurgical infections - but more recent studies ( see for a partial summary ) have cast doubt on the original findings . moreover , ventilation with high inspired oxygen concentrations during surgery leads to subsequent impairment of pulmonary gas exchange [ 48 - 50 ] that may be of clinical significance . traumatic injury and compartment syndrome may appear to be obvious applications for supplementary oxygen - an increased po2 would help overcome the reductions in perfusion - but hyperbaric rather than normobaric oxygen is the treatment of choice [ 51 - 53 ] . oxygen is used for the treatment of carbon monoxide poisoning , but this is probably less effective than it should be if the accompanying hypocapnia is not prevented . in the case of breathlessness , which has long been treated with supplementary oxygen , a recent randomized double - blind controlled trial established that nasal oxygen was no better than air in relieving breathlessness and improving quality of life in palliative care patients with refractory breathlessness . in conclusion , nasa managers demanded in 1986 that their counterparts at martin - thiokol prove that it was not safe to launch the space shuttle challenger despite concerns expressed by engineers about the integrity at low temperatures of the o - rings joining the segments of the solid rocket boosters . in the case of supplementary oxygen , failure to ask the right question reinforces complacency about its use in patients who may have regional hypoxia or ischemia but are not hypoxemic . cao2 : arterial blood oxygen content ; do2 : oxygen delivery ; paco2 : arterial partial pressure of carbon dioxide ; pao2 : arterial partial pressure of oxygen ; pco2 : partial pressure of carbon dioxide ; po2 : partial pressure of oxygen . si and jaf have participated in the development of devices suitable for increasing the efficiency of oxygen delivery . the protection of the related intellectual property and distribution of income from sales ( if any ) follow the guidelines set by the university health network .

supplementary oxygen is routinely administered to patients , even those with adequate oxygen saturations , in the belief that it increases oxygen delivery . but oxygen delivery depends not just on arterial oxygen content but also on perfusion . it is not widely recognized that hyperoxia causes vasoconstriction , either directly or through hyperoxia - induced hypocapnia . if perfusion decreases more than arterial oxygen content increases during hyperoxia , then regional oxygen delivery decreases . this mechanism , and not ( just ) that attributed to reactive oxygen species , is likely to contribute to the worse outcomes in patients given high - concentration oxygen in the treatment of myocardial infarction , in postcardiac arrest , in stroke , in neonatal resuscitation and in the critically ill . the mechanism may also contribute to the increased risk of mortality in acute exacerbations of chronic obstructive pulmonary disease , in which worsening respiratory failure plays a predominant role . to avoid these effects , hyperoxia and hypocapnia should be avoided , with oxygen administered only to patients with evidence of hypoxemia and at a dose that relieves hypoxemia without causing hyperoxia .

in recent years , nursing staff shortages have become a major challenge for health care systems around the world , including iran . in 2008 , iranian hospitals needed approximately 220,000 nurses ; nonetheless , there were just about 90,000 nurses . this shortage is related to decreased satisfaction among nurses and posed a potential threat to the quality of patient care . in the study which was conducted in 12 countries in europe and the usa , the range of nurses burnout was from 10% in the netherlands to 78% in greece , job dissatisfaction was from 11% in the netherlands to 56% in greece , and intention to leave was from 14% in the usa to 49% in finland and greece . nursing shortages are a symptom of inadequate policies on recruitment and retention of nurses in the world . also , in a nationwide study , iranian nurses reported an average level of job satisfaction . another important challenge of iranian health care system is poor quality of patient care , which is influenced strongly by nurses motivation . nurses are the main group of the human resources in the health care and the quality of health care is highly dependent on an adequate recruit and supply of qualified and motivated nursing personnel . motivation is an important factor that influences nurses job satisfaction and their intention to work . therefore , understanding nurses motivators can enhance job satisfaction , quality of care , and productivity . identifying nurses motivators can help nurse mangers to find a way to motivate nursing staffs . but the focus of previous studies has been mainly on the association of job motivation with different variables such as evaluation outcomes , psychiatric nurses anger , job satisfaction , innovation , and individual and organizational factors . in general , therefore , psychologists have extensively studied about motivation and have provided theories about the reasons for motivation . motivation is defined as a process responsible for making the efforts strong , directed , and continuous to achieve the goals . in general , motivation originates from the needs that must be met . russell and swansburg believed that motivation is a concept used to describe an external condition stimulating a special behavior and internal responses revealing that behavior . many theories were applied to explain motivation at work , such as the needs theory ( maslow 1954 ; herzberg et al . 1959 ) , expectancy theory ( vroom 1964 ) , equity theory ( adams 1965 ) , and goal setting theory ( campbell and pritchard 1976 ) ; however , there is no single theory describing motivation comprehensively . it can be one of the possible reasons for the lack of consensus in an instrument to measure motivation . this study was conducted to identify the motivating factors among the hospital nurses of tehran university of medical sciences . this is a descriptive study in which the motivation of 310 nurses working at 14 hospitals of tehran university of medical sciences was evaluated in 2010 . nurses who had full - time work experience of at least 1 year in clinical practice in nursing and also had associate degree or higher educational qualification in nursing were included in the study . according to our given population size ( n = 2427 ) , however , to ensure obtaining an adequate sample size , with likelihood of 10% incomplete questionnaires , 330 questionnaires were delivered to nurses . the strata are formed based on members shared attributes or characteristics . in this study , each hospital was considered as a stratum and the samples were selected based on the proportion of the number of nurses in each hospital from the sampling frame . the researcher explained the purpose of the study and freedom for joining in the study to the potential participants . so , if the selected nurses did not wish to participate in the study or complete the delivered questionnaire , researchers selected the next nurse from the list . the analysis was done for the data of 310 nurses in the sample because 20 questionnaires were incompletely filled . demographic information questionnaire was used to measure the variables of age , gender , marital status , educational level , income status , work position , having overtime , and working in other hospitals . in spite of the availability of instruments to measure motivation , we developed a new questionnaire because of iranian hospitals context and socio - cultural differences . the instrument was developed by an extensive review of the literature including previous studies conducted in iran . after the initial draft of the instrument was developed , its content validity was evaluated by the nursing scholars who have experiences regarding the topic . in this stage , two items were omitted and a number of them were modified . also , the content validity index ( cvi ) was estimated and all items were approved based on their cvi > 0.85 . then , for face validity , the instrument was distributed to 10 nurses and their views on its simplicity and comprehensibility were taken and the required changes were made . after exploratory factor analysis , 30 items were reduced to 25 and classified into four factors : career development ( 7 items ) , job characteristics ( 9 items ) , job authority ( 5 items ) , and recognition ( 4 items ) . the factors were named after the item with the highest standardized factor loading within the domain . factor loadings and cronbach alpha coefficient for nursing motivation questionnaire for reliability , 30 nurses completed the instrument and the cronbach alpha coefficient was calculated as 0.81 . the items were scored on likert scale , with scores ranging from very low ( 1 ) to very high ( 5 ) . distribution of scores from the instrument and its factors was categorized based on the range of possible scores as follows : low ( 033% ) , medium ( 3366% ) , and high ( 66100% ) . also , to compare different factors , the mean score of each factor was obtained by dividing the sum of scores of each factor by the number of its items . statistical package for social sciences ( spss ) version 16.0 for windows ( spss inc . descriptive statistics and independent t - test , analysis of variance , tukey post - hoc test , chi - square and fisher 's exact test were used . a significance level of p < 0.05 was considered . the mean age of the participants was 35.07 years [ standard deviation ( sd ) = 7.46 ; range : 2253 ] . the length of the participants work experience ranged from 1 to 30 years , with a mean of 11.48 years ( sd = 7.25 ) . characteristics of the participants ( n=310 ) the motivation of most of the subjects in career development ( 52.6% ) and job authority ( 64.5% ) was at a medium level , while the motivation in job characteristics ( 61.3% ) was at a high level . half of the subjects had a high motivation in the factor of recognition . the findings of this study showed that the least mean of the factor score , considering the number of items , was 3.23 for career development , while the highest mean was 3.81 for job characteristics . scores of motivating factors and total motivation independent t - test showed that there was no statistically significant difference in the total motivation score between males and females ( p = 0.381 ) and in terms of being employed in other hospital or none ( p = 0.599 ) . also , independent t - test showed that total motivation of nurses who had overtime was higher than that of others ( p = 0.031 ) . also , the results of one - way analysis of variance ( anova ) showed that there was no difference in total motivation in terms of marital status and educational level . there was a statistically significant difference in the total motivation of nurses in terms of their positions ( p = 0.007 ) . tukey post - hoc test showed that the motivation of head nurses was significantly higher than that of staff nurses ( p = 0.005 ) . the mean score of total motivation among nurses who had inadequate income was significantly less than those who had adequate income ( p < 0.001 ) . the chi - square test showed no statistically significant relationship of career development with gender , working overtime , and working in other hospital . this factor had a statistically significant relationship to income ( p = 0.001 ) , age ( p = 0.035 ) , and work position ( p = 0.04 ) . fisher 's exact test showed that the factor job characteristics was significantly related to the work position ( p = 0.021 ) , job authority was only related to overtime ( p = 0.035 ) , and also recognition was significantly related to overtime ( p = 0.043 ) . the present study was conducted to identify the motivating factors among iranian nurses . in this study , the factors of career development , job characteristics , job authority , and recognition were considered as the aspects of motivation in nurses . shattuck et al . , in a systematic review , identified seven major motivational themes including financial rewards , career development , continuing education , hospital infrastructure , resource availability , hospital management , and recognition / appreciation . except two factors , career development and recognition / appreciation , which are completely similar with the themes identified in the mentioned review , the findings showed that the least mean score of motivation , considering the number of items , was related to career development , while the highest one was related to job characteristics . these results are comparable with the results of a study conducted by mahmoudi et al . , who reported the nature of work among the internal factors and supervision among the external factors as the most important factors of job motivation in iranian critical care nurses . in the mentioned study , the ability to serve the community and the value of nursing among people as work nature factors have had the highest effect on job motivation . several previous studies have identified accomplishing jobs , working independently , and attaining interpersonal relationships as the most important factors that motivate nurses . the findings showed that the motivation score of 55.5% of nurses was at a medium level . similarly , jodat et al . reported that nurses overall score for job motivation was moderate . also , this finding could be compared with the findings of the study conducted by taghavi larijani et al . , in which the motivation of 65% of iranian nurses working in medical - surgical wards was reported as low . this controversy can be explained by the difficulties confronted by nurses in the iranian health care system . iranian hospitals deal with challenges including inadequate staffing , limited equipments available to nursing care , lack of authority to change practice , and organizational cultures rewarding routine and task - based practice . low levels of motivation among nurses are important in view of the fact that the largest subgroup of human resources in the health care system consists of nurses . it becomes even more important considering that staff 's motivation is a predictor of their productivity , and the studies conducted on productivity of iranian nurses show that only 7.5% of iranian nurses have shown the desired productivity . one of the main challenges in providing good - quality nursing care in iran and around the world is shortage of nurses . studies show that this shortage has a domino effect in nurses loss of knowledge and motivation , exhaustion , burnout , and severe stress . furthermore , job stress , lack of autonomy , and nurse physician collaboration are the most important factors that contributed to nurses job dissatisfaction and retention in the nursing literature . reported that job motivation of nurses is an important factor in the intent of nurses to leave nursing . the findings of the present study showed a significant relation of age , work position , and the income status with the first factor ( career development ) , work position with the second factor ( job characteristics ) , and finally , working overtime with the third and fourth factors ( job authority and recognition , respectively ) . several researchers have shown a positive significant association between the age of nurses and their job motivation . although there was no significant association between gender and total motivation score in this study , franco et al . reported that female health workers in jordan had lower ratings to motivational determinants , and there were almost no differences related to gender or age in georgia . found that nurses younger than 30 years were more motivated than older nurses , and higher university degrees were related to higher motivation in nurses . de cooman et al . stated that male and female nurses are motivated for similar characteristics of nursing . in a study by the mixed method in which the motivation of non - medical staff of tanzania was examined , the findings showed that though non - financial factors are of great importance for motivation , financial satisfaction is a prerequisite of any intervention for increasing the motivation by non - financial motivators . also , the study of lambrou et al . showed the managerial position was associated with job characteristics among greek nurses . the importance of the supervision factor becomes less while the importance of the factor of appreciation and recognition is increased . this means that the sample covered nurses who work in public university hospitals in tehran , the capital and largest city of iran ; therefore , future study should be conducted to have a clear understanding about the motivating factors among nurses in public / private sectors of urban / remote areas . in addition , the questionnaire of this study was developed by the authors and used for the first time ; hence , its criterion validity including concurrent and predictive validity should be evaluated in future studies . our findings showed that the factor of career development had the maximum potential ability to inspire nurses in their profession . so , it is necessary that nursing managers pay more attention to use the element of mentioned factors such as effective supervision , encouragement , and job enrichment . however , other motivating factors including job characteristics , job authority , and recognition should not be neglected to motivate nurses . specifically , the findings of this study imply that the importance of the factor of job characteristics , such as the use of various and high - level nursing skills , feedback , and critical thinking , as the first ranked motivating factor in the motivation of nurses needs to be emphasized . moreover , the medium level of motivation in participants indicates the necessity of paying more attention to the motivating factors to improve motivation in nurses . the results of the current study can be used in programs designed to improve nurses work motivation .

background : one of the most important challenges of iranian health care system is quality of care , and it is assumed that motivated nurses are more ready to provide better care . there are limited studies investigating iranian nurses motivations ; however , factors which motivate them have not been studied yet . identifying the motivating factors enables nurse managers to inspire nurses for continuous quality improvement . the aim of this study was to identify motivating factors for iranian hospital nurses.materials and methods : this is a cross - sectional descriptive study in which 310 nurses working at 14 hospitals of tehran university of medical sciences were selected by proportionate stratified random sampling . data were collected in 2010 by a researcher - developed questionnaire . descriptive statistics and independent t - test , analysis of variance , tukey post - hoc test , chi - square and fisher 's exact test were used for statistical analysis by statistical package for social sciences ( spss ) version 16.results:the mean score of motivation was 90.53 10.76 ( range : 59121 ) . four motivating factors including career development ( 22.63 5.66 ) , job characteristics ( 34.29 4 ) , job authority ( 18.48 2.79 ) , and recognition ( 15.12 2.5 ) were recognized . the least mean of the motivation score , considering the number of items , was 3.23 for career development , while the highest mean was 3.81 for job characteristics.conclusions:the findings showed that motivation of nurses was at a medium level , which calls for improvement . the factors that have the greatest potential to motivate nurses were identified in this study and they can help managers to achieve the goal of continuous quality improvement .

a 4.5-year - old male was referred to our ophthalmology department , due to developmental glaucoma . the prenatal history was unremarkable . on physical examination , marked right hemihypertrophy , a protuberant abdomen containing subcutaneous tumors and lipoma , macrodactyly of the third and fourth digits of the right hand , macrodactyly in nearly all of the toes ( fig . 1 ) , hyperpigmented skin lesions on his back and legs , verrucous epidermal nevi , and asymmetry of the limbs were discovered . magnetic resonance imaging of the brain showed a temporal lobe cavernoma ( fig . however , there were no neurological symptoms related with the cavernoma . on ophthalmic examination , the patient had a history of a bilateral goniotomy operation when he was four months old . visual acuity could not be measured due to mental - motor retardation , but central , steady , maintained fixation ( csm ) was positive in both eyes . slit - lamp examination showed haab 's striae with a corneal diameter of 11 mm horizontally and 12 mm vertically in the right eye . the left eye was buphthalmic , with a corneal diameter of 12 mm horizontally and 13 mm vertically . intraocular pressures were 12 mmhg in the right eye and 14 mmhg in the left eye with latanoprost 0.005% once a day treatment . central corneal thickness measurements using ultrasonic pachymetry were 557 m in the right eye and 509 m in the left eye . cup / disc ratio was 0.5 in the right eye and 0.7 in the left eye ( fig . axial lengths were 22.8 mm in the right eye , and 25.36 mm in the left eye . best - corrected visual acuity was 20 / 40 in the right eye and 20 / 50 in the left eye . ps is thought to occur as the result of a lethal somatic gene mutation that leads to a mosaic state . most patients with ps are born without significant asymmetry , but some cases were diagnosed using prenatal ultrasonography , and rapidly progressive overgrowth could paused during puberty . the most common clinical ocular manifestations of the disease have been reported to be strabismus and epibulbar tumors . in the present case report , we defined a concordance of developmental glaucoma , pseudopapilledema , and myopia in a 4.5-year - old male patient with ps . clinical diagnosis of ps is challenging and contentious . in the early stages of the disease , it may be difficult to make differential diagnosis from other overgrowth disorders , such as neurofibromatosis , klippel - trenaunay - weber syndrome , maffucci syndrome , congenital lipomatous overgrowth , vascular malformations , and epidermal nevi ( clove ) syndrome , and bannayan syndrome . these disorders may present with similar manifestations as ps ; however , they had stringent diagnostic criteria that delineated a distinct cohort of patients who have parallel features of overgrowth . according to the literature ; the prognosis of the ps seems to labile and is correlated to the severity of neurological involvement , skeletal deformities , internal lipomatosis , and neoplastic appearance . we have defined in the present report that developmental glaucoma and pseudopapileudema in a patient with ps for the first time in the literature . the diagnosis of ps was based on the typical clinical findings including hemihypertrophy , subcutaneous tumors and lipoma , macrodactyly , hyperpigmented skin lesions , verrucous epidermal nevi , and asymmetry of the limbs . although the intraocular pressures were in normal limits with latanoprost 0.005% once a day treatment , left eye enlargement was evident . although the precise mechanism of the pathogenesis of secondary glaucoma associated with ps is unknown , the most likely explanation is the malformation of the trabecular meshwork and iris ( iridotrabeculodysgenesis ) or iridocorneal dysgenesis . hamarthomatous lesions may also be another cause of glaucoma in these individuals . in conclusion , patients with a diagnosis of ps should be carefully reviewed by an ophthalmologist to rule out ocular manifestations of the disease . timely diagnosis and treatment of the developmental glaucoma may preserve visual loss in patients with ps .

the purpose of this study was to report developmental glaucoma and pseudopapilledema in a patient with proteus syndrome . we defined the presence of developmental glaucoma , right pseudopapilledema and myopia in a 4.5-year - old patient with proteus syndrome . marked right hemihypertrophy , lipoma , macrodactyly , and asymmetry of the limbs were observed on systemic examination . a cavernoma was also detected in magnetic resonance imaging of the brain . the patient underwent bilateral goniotomy surgery due to glaucoma . the surgical outcomes were satisfactory in both eyes . in conclusions developmental glaucoma and pseudopapilledema might be associated with proteus syndrome .

initially described after treatment with flutamide , responses to withdrawal of hormonal therapies in prostate cancer patients have been documented after cessation of other antiandrogens such as nilutamide , bicalutamide , or cyproterone acetate and of megestrol acetate , diethylstilbestrol or estramustine . in the southwest oncology group trial 9426 , 21% of 210 patients had confirmed psa decreases of 50% after treatment with nonsteroidal antiandrogens with a median progression - free survival of 3 months . it has been proposed that withdrawal responses could result from mutations in the androgen receptor ( ar ) . transfection experiments revealed that ar point mutations in the hormone - binding domain allow activation by ligands other than dihydrotestosterone . mutated ar from clinical samples was shown to be activated by progesterone , estradiol , adrenal androgens , hydrocortisone or hydroxyflutamide . however , a prospective study failed to demonstrate a clear association between detectability of ar mutations and antiandrogen withdrawal responses . an improvement in overall survival has been reported with abiraterone acetate ( aa ) , a selective inhibitor of cytochrome p450c17 ( cyp17 ) , in castrate - resistant prostate cancer patients who have failed docetaxel chemotherapy . the addition of low - dose corticoids to aa is mandatory in daily practice since the combination has been shown to minimize the syndrome of secondary mineralocorticoid excess related to cyp17 inhibition . here , we report the case of a patient who had a confirmed psa decrease of 50% after stopping aa , mimicking a withdrawal syndrome . a 60-year - old patient was diagnosed with a prostate adenocarcinoma ( gleason score 8 , 4 + 4 ) with synchronous bone metastases in april 2007 . he successively received an lhrh agonist , a combined androgen blockade with lhrh agonist and bicalutamide , without subsequent response to bicalutamide withdrawal , docetaxel ( 10 cycles ) , then mitoxantrone ( 3 cycles ) and diethylstilbestrol . in april 2011 , aa was started at the standard dose of 1,000 mg daily in combination with prednisone ( 5 mg twice daily ) . psa slightly decreased to a nadir of 68 ng / ml one month after the start of treatment . in parallel , a metabolic partial response according to consensus criteria on 18-fluorodeoxyglucose positron emission tomography ( pet ) and choline pet ( suvmax = 37% ) was observed . however , aa and prednisone were stopped in august 2011 because of back pain related to vertebral metastases and concomitant psa progression ( psa 128 ng / ml ) . one month later , a confirmed psa decrease to a nadir of 62 ng / ml occurred , defining a partial biological response according to standard criteria , with a concomitant improvement in back pain . to the best of our knowledge , this is the first case ever reported of a withdrawal response with aa . currently proposed mechanisms of resistance to aa include ligandless activation of ar by constitutively active variants lacking the ligand - binding domain , cross - talk with relative signaling pathways and/or activation of amplified or promiscuous ar by nonandrogenic ligands such as corticosterone or other steroids . following the latter hypothesis , the withdrawal response observed in the present case could be related rather to prednisone than to aa itself as it was stopped at the same time .

in 2011 abiraterone acetate ( aa ) was approved for the treatment of castrate - resistant metastatic prostate cancer patients who have failed docetaxel chemotherapy . we report the case of a patient who experienced a confirmed psa decrease of 50% after stopping aa , mimicking an antiandrogen withdrawal syndrome .

expensive and time - consuming processes have forced an increase in efficiency in the research industry ; this , as well as the increasing need for documentation , introduces the problem of pipetting robots operating blind . the operator provides the reagents and substances for the system to work with according to a preprogrammed procedure , leaving results in the form of value measurements at the end of the experiment when identifying the root cause for outliers is difficult and corrective actions are no longer possible . it may therefore make sense to introduce a pipetting monitoring system to monitor individual handling procedures . the pipetting monitoring system presented here is a low - priced , rapid , and space - saving solution towards detecting extremely small amounts in wells . the monitoring results are then added to the documentation or fed back into the control system to initialise a repeat pipetting procedure . detecting fluid fill levels plays a major role in many industrial specialities , so many methods of determining fill levels have been developed and reported on in various application areas . weighing , pressure measurement on vessel bottoms , and ultrasound are a few examples of measurement principles that have been used [ 2 , 3 ] , while optical methods have also been used in a large number of applications , for example , where contact - free measurement is needed . so far , there have not been any reports on using optical methods in determining fluid fill levels in lab automation systems , but a patent filed in 1989 did describe a mechanism for manual visual control on microtitre plates ( mtps ) . using this method , mtps to be examined are laid into the device that holds them at a predefined parallel distance to a patterned surface . the light reflected from the patterned surface is refracted through the fluid in the wells of transparent mtps , allowing detection of fluid from distortions in the pattern or excess intensity compared to the empty wells . this method makes manual monitoring easy for the user , but it is still restricted to clear , colourless microtitre plates . currently , automated pipetting systems use capacitive or air pressure - sensitive pipettes to determine fill level , where the level is determined by detecting the change in capacity on contact between the tip of the pipette and the fluid or change in pressure as the pipette tip is dipped into the fluid . this capacitive measurement principle is restricted to fluids that conduct electricity , which may then have to be added to the actual sample ; this restriction does not apply to the pressure principle , however . both systems measure fill levels using gap measurement and volume calculation based on the known geometry of the wells . however , the volumes that apply here amount to 020 l for 96-well and 010 l for 384-well plates the fluid still forms a droplet on the bottom of the well ; classical fill - level measurement in these volume ranges will not yield usable results . using the methods described above , the pipettes would also need to keep to a minimum distance to the bottom of the well to avoid damage . apart from that , small off - centre droplets in the well due to adhesion effects would remain undetectable . ultrasound sensors may be used in determining volume and also support contact - free measurement . there are sensors that are small enough to allow multiple well measurements ; the restrictions named above regarding the minimum gap from the pipette to the bottom of the plate or nondetection of off - centre droplets do not apply here . the principles named above have one particular drawback measurement is time - consuming , as each sensor can only monitor one well at a time . capacitive measurement with an eight - tip pipette tool on a ninety - six - well plate would take around half a minute to complete and around two for 384 wells . ultrasound sensors are faster , but , to be used for 96-well plates , thin sensors must be used that can be arranged in a row , where each well 's width is 9 mm . since most robots approach labware ( to pick up and transport ) from above , a conveyor must be used to transport the plate below the sensory equipment . furthermore it needs a relatively large amount of space and would not be usable for 384-well plates . these fill - level detector systems could theoretically provide a way of monitoring individual pipetting steps , but the time taken would be considerably longer . the optical pipette monitoring system developed would provide an adequate way of measuring each dosing step on several wells in parallel , supporting monitoring for 384 wells at very short times of less than ten seconds . evaluation covers detecting droplets and subsequent estimation of droplet volume from the two - dimensional projection of the droplet on the image plane and the well - known geometry . camera systems provide a fast imaging method at around a second , but they are very sensitive to ambient light ; in addition , they photograph each well from a different angle depending on position . the speed benefit can not outweigh the drawbacks for image processing , as monitoring pipettes requires an extremely high degree of accuracy ( sensitivity and specificity ) . flatbed systems are an alternative , as they light each well directly from below , making the necessary image processing much easier . the contact image sensor ( cis ) system ( zts - a6 , ziath ltd . ) has a weak light source and depth of field ; the weak light source renders the scanner sensitive to alterations in ambient lighting conditions , but the low depth of field presents an advantage in that only objects on the bottom of the well are in focus , making them easier to recognise . in contrast , charge coupled device ( ccd ) flatbed scanners ( xtr-96 , fluidx ltd . ) have a strong light source and greater depth of field . the plus and minus points of each sensor type can be weighed up depending on application the software supports a variety of imaging systems . the system was designed in order to integrate the hardware needed on the pipetting robot deck ( biomek fx , beckman coulter ) and support a suitable interface to the control computer . in addition , a variety of coverings were tried out in order to determine and minimise the effects of ambient lighting . additional software needs to be installed on the computer to be controlled by the control software . the software supports a variety of sensor types connected via usb , ensuring convenience and simplicity in installing the device . the image evaluation software , which was developed by the authors , is the heart of the measuring system ; it can be used with a variety of imaging systems and can be configured for various plate types that may differ in bottom shape and material , and therefore also transparency . the image processing concept was inspired by cascade classifiers since it was not initially possible to develop an algorithm that would be equally suitable for the various plate types , droplet sizes , and fluids . cascade classifiers consist of a number of weak classifiers that combine to a single strong one . three algorithms ( the weak classifiers ; see table 1 ) evaluate an image simultaneously ; output is merged with an adaline ( adaptive linear neuron ) to calculate the result . optimum weights exist to configure the system for each plate and device combination ( see figure 1 ) . finally , a fixed threshold needs to be selected in order to use the system ; the ideal threshold topt is determined from the training data as follows : ( 1)topt = max [ tp(t)fp(t ) ] . the a priori knowledge on the plate , imaging device , and pipetted fluids is used for other points as well . the system selects the settings required for the imaging method and the algorithm parameters by reference to plate - device combination . the plates were then transferred to the optical system ; an image was taken of each with ( cis , camera ) and without covering ( cis , ccd , camera ) . the camera system was not included for evaluation for the reasons stated in section 2.2 . to generate more test data , the plates were used several times with accumulating amounts of substance inside . two pipetting approaches were used for the examinations . for the 96-well plates a certain volume was dispensed to each of the 8 wells in one row whereas the following row was left empty ( 6 rows filled , 6 rows empty ) . for the 384-well plate a certain volume was dispensed to every second well . there were also empty wells distributed across the plate for position effects to be detected as well . dosages of 140 l were taken for the 96-well mtps , but only 112 l max dosage for the 384-well plates due to the smaller well volume . the tests were run on 96-well polystyrene ( ps ) and polypropylene ( pp ) plates with v - bottoms ( v ) , a 96-well polystyrene plate with a flat bottom ( f ) , anda 384-well platepolypropylene plate with a v - bottom . in the following , we will be referring to the plates by the above abbreviations . images were taken in three to four runs each for four plates in eight to twelve volume steps in three types of setup ccd , cis with , and cis without covering . in total , more than four hundred test images were taken . a receiver operating characteristic ( roc ) function describes the detector 's behaviour depending on threshold selection setting its sensitivity . if a low threshold is set , many true positives but more false alarms would be expected . efficacy was expressed as true positives ( tps ) and false positives ( fps ) for one selected threshold ( table 3 ) . regardless of threshold , the area under the roc curve is taken to measure its efficacy . table 1 summarises the true and false positives for the plates examined for each device as a percentage . this table shows an example of one run with fixed parameters optimised for v - pp-96 plates and cis system ( without covering ) . wide - ranging examinations were performed on system sensitivity to various influences in order to gauge the usefulness of the system in real - life conditions . the tests were performed at a maximum resolution of 600 dpi ( 0.042 mm per pixel ) . comparative tests on lower resolutions of 300 dpi ( 0.085 mm per pixel ) also yielded good results . lowering resolution in the lower limit is subject to several factors , such as light distorting the image in the middle of v - bottom wells at the cylinder tip or v - tip , and the droplet needs to be larger than the bottom tip . for all plates the lower limit was found to be below 1 l . figure 2 shows how droplets tend to stick to the walls of a well in recognisably increased numbers , when growing in size . this reduces the tp rate for large volumes since the reflexions disappear and hence leads to the upper boundary of the measurement range . the ideal measuring range for 96-well plates was between 1 and 24 l , while volumes of up to 10 l were recognisable in 384-well plates . the system would be used in a variety of conditions in real - life operation ; ambient light reaching the plate varies depending on the system 's location as well as the season and time of day , so the system would have to be tested for robustness with regard to light conditions . to test this , test images were taken in three different typical lighting situations as follows : ( 1 ) full direct sunlight on the device , ( 2 ) indirect daylight , and ( 3 ) no natural lighting lab lighting . two images were taken for each run using the cis sensor to test its particular sensitivity towards ambient light . each plate was imaged once with and once without the covering ( microtitre plate lid ) in each ambient light setting and with every volume . similar overexposure also affected images made using the ccd sensor , albeit less strongly since the ccd sensor is less sensitive to ambient light . overall , no images taken with the ccd sensor were affected by direct light such that they became useless . the results for the cis scanner with lid are represented by the hashed area in figure 4 . the figure shows the improved relationship between true positives against false positives on the one hand and the smaller fluctuation range on the other , using the lid . the smaller fluctuation range is equivalent to a smaller area on the tp / fp plane . the bounded area auco was 0.132 without covering compared to aucl at 0.018 with covering ( lid)only around 13.6% . the ccd sensor yielded more robust results ; the difference in area auco , ccd was 0.034 for the ccd sensor , the same general range as with the cis sensor with covering . fluids with varying levels of viscosity and surface tension are dosed using different pipetting techniques . if the cohesion effects between the fluid and pipette are too heavy , the droplets have to be placed onto the well using techniques such as tip touch . the ideal pipetting technique for water was used for the droplets of the same shape to be placed into the middle of the well at a very high level of reproducibility . dmso was pipetted using tip touch , which is not ideal for the substance ; this increased the negative influence of droplets clinging to the well edges . dosing dmso also showed an increasing frequency of off - centre droplets at increasing volume , suggesting an operational range depending on substance . figure 5 shows how a bad pipetting technique leads to uncentered drops clinging to the walls . the accuracy decreases earlier and more rapidly for dmso than it does for water using either sensor type . using a basic flatbed scanner simplifies application for pipetting monitoring and improves results while increasing efficiency compared to the camera solution used up to now . the pipetting monitoring presented can be implemented using barcode readers based on ccd or cis flatbed scanners that the lab may already have at its disposal . efficacy with regard to sample volume and substance properties as well as robustness to ambient light was tested . depending on lab lighting conditions , further work should be done for the evaluation of all environmental variables influencing the sensor signals . additionally error analysis of the developed system and comparison to classical methods will be done . the results of the tests taken up to now have revealed a variety of possible improvements for the system ; result quality showed heavy dependence on the algorithm parameters used , so automatic parameter optimisation should be used for the reliable detection of the best parameters . additionally , this would enable the user to configure the device for new labware on his own , since all settings could then be found automatically . in addition , adaptation to ambient light should be optimised to ensure that the system can be used without covering wherever possible . there is further room for improvement at high volume ranges or for badly positioned droplets ; the potential for quantitative volume estimation from two - dimensional droplet projections , fluid properties , and well shape warrants further investigation .

parallel liquid handling systems are widely used in different applications of life sciences . in order to avoid false positive or negative results which lead to higher costs due to the replication of the experiments it is necessary to monitor the process and success of liquid delivery . an easy method for the determination of the liquid levels in microplates has been developed and evaluated . the optical method bases on the measurement of the liquid level using ccd cameras followed by special algorithms for the evaluation and visualization of the measured data . the proposed method was tested in changing environmental lighting for two different liquids . these tests confirm our approach towards optical liquid level determination for smallest volumes in microplates and also show the challenges regarding environmental lighting and different physical properties of fluids .

arthrogryposis multiplex congenita ( amc ) is a multiple joint condition which affects both lower and upper extremities and thus affects ambulation . the objective of this study is to identify the most critical residual deformity that diminishes the ambulatory status . the mean age at first surgery was 4.1 years ( range 2 - 16 years ) . the mean length of followup was 44.0 months ( range 22 - 168 months ) . type of procedures and number of operations , residual deformity and walking ability were recorded . residual deformity including hip flexion contracture more than 30 , knee flexion contracture more than 30 , scoliosis , hip dysplasia or dislocation , knee extension contracture or recurvatum , active motion of hips and knees and upper limb involvement were evaluated . statistical analysis was done to evaluate factors that were statistically significant to affect walking ability in amc patients . at the latest followup , 31 patients were community ambulators , 3 patients were household ambulators , 3 patients were nonfunctional ambulatory , and 14 patients were nonambulatory . statistical analysis of all factors was done and the results were significant with a p < 0.037 in knee flexion contracture > 30 degrees with odds ratio of 4.58 . hip flexion contracture > 30 was a trend toward significant with a p value of 0.058 and odds ratio of 4.53 . multivariate analysis showed that knee flexion contracture was significant with 4.58 ( 95% ci 1.01 - 20.6 ) . amc is a rare disease that causes disability , requiring multiple surgeries to correct deformities . our study showed that residual knee flexion contracture was associated with nonambulatory status of patients with amc . arthrogryposis multiplex congenita ( amc ) is a rare , nonprogressive congenital disorder which is characterized by multiple joint contractures with normal sensation.12345 diagnosis of amc is usually based on physical examination with characteristic deformities of upper and lower extremities , limited range of motion , clubfoot or hip dislocation . there are 150 different disorders for syndromes that have joint contractures as a part of their manifestations ; amc is diagnosed by exclusion , and precise diagnosis is very important for the evaluation of results.6 the term amyoplasia refers to the most common arthrogrypotic syndrome , which includes multiple congenital contractures , typical and symmetrical positioning of the limbs and the replacement of muscles by fibrous and fatty tissues . it is sporadic , with an unknown hereditary pattern.7 the goal of treatment is to obtain the maximum possible function for each child by an early multidisciplinary approach.78 at present the goal of treatment is to improve ambulatory status of patients and patient self - care . amc patients have multiple problems which can be improved by surgical intervention but the most helpful procedures are still undefined . this study aims to find residual deformity that affects the ambulatory status of the patient . residual deformities that are risk factors in this study include hip flexion contracture more than 30 , knee flexion contracture more than 30 , knee extension deformity or recurvatum , severe scoliosis , upper extremity contracture or weakness and development dysplasia of the hip ( ddh ) or hip dislocation . we feel that our results will guide physicians in decision making regarding treatment to promote ambulation in amc patients . this study was designed as a retrospective study of amc patients at our institute from january 1995 to december 2010 . after approval from the ethics committee , chart review was conducted in accordance with the guidelines provided from our institutional review board . we reviewed all the medical records and included only those children with amc who had a mean followup of 44 months ( range 22 - 168 months ) . the inclusion criteria were amc patients who underwent surgical procedure or treatment for deformities or dislocations of the joints in the upper or lower limbs and patients or parents who agreed to participate . the study recruited 53 patients ; two of them were excluded because of incomplete medical data . we recorded the children 's potential to ambulate at the first visit and at each of the subsequent visits until the last followup . all clinical assessment was recorded and included age , sex , associated disease , and surgical procedure carried out . ambulatory status and residual deformities which include deformities in both upper and lower extremities , scoliosis , degrees of contracture at the hips and knees , active motion of hips and knees and the presence of ddh or hip dislocation were recorded from the clinical and physiotherapy notes . thirty three patients were in walking age and twenty patients were ambulatory at the start of treatment . walking age in this study was patient age more than 18 months . all the patients who were ambulatory at the start of treatment remained ambulatory at final followup . out of thirty one patients who were nonambulatory at the start of treatment , seventeen patients could ambulate at the final followup , fourteen patients were still nonambulatory . of the thirty one patients who were nonambulatory at the start of treatment , twenty one patients had hips and knee flexion contracture of more than 30 and after proximal femoral extension osteotomy and distal femoral extension osteotomy , seventeen patients who were corrected to less than 30 of hips and knee flexion contractures could walk . for the residual deformities , seven patients had hip flexion contracture more than 30 and nine patients had knee flexion contracture more than 30. forty seven patients were able to do active range of motion of hips and knees . there were 54 upper extremities procedures and 165 lower extremities procedures [ tables 2 and 3 ] . bilateral limb surgeries were considered as two procedures , even if they were done during the same anesthesia [ tables 2 and 3 ] . the final functional outcome was assessed using hoffer 's classification of walking status [ table 4].9 thirty one patients were community ambulatory who were able to walk with aids in the community and did not need a wheel chair , three patients were household ambulatory , able to walk with aids in the house and use a wheel chair in the community whereas three patients were nonfunctional ambulators using a wheel chair and capable of transfer while 14 patients were nonambulators and were not capable of transfer [ table 4 ] . location and type of operations for the upper limbs type of operations for the lower limbs characteristics of walking at latest followup at the last followup , 37 patients were ambulatory and 14 patients were nonwalkers . there was statistical significance with p value 0.037 for knee flexion contracture more than 30 with odds of 4.58 ( 95% ci 1.01 - 20.6 ) . hip flexion contracture more than 30 was a trend toward significant with a p value 0.058 and odds ratio of 4.53 . these children are best managed by multidisciplinary teams that include an experienced geneticist , an orthopedic surgeon , a physical therapist , and a pediatric physical therapist . it should be recognized that high percentage of these children might be able to achieve some measure of functional ambulatory potential , but many will lose ambutation as they get older . the need for surgery is high in these children , and often , several procedures will be necessary . a careful discussion of realistic goals with the parents is very important , as is the ongoing focus on skills necessary for promoting independence in adulthood . hoffer et al.9 reported functional ambulation in 22 out of 36 severely affected adolescents and young adults with arthrogryposis . many series have reported varying degrees of functional ambulation in 50 to 78% of patients.1011 sells et al.11 found that 85% of children with amyoplasia were ambulatory by the age of 5 . these children had an average of 5.7 orthopedic procedures along with multiple casting , splinting of limbs and regular physical and occupational therapy . ultimately they were able to participate in activities of daily living and attend school . based on our findings we strongly believe that children with arthrogryposis may have good potential for ambulation if their knee flexion contractures have been adequately and timely corrected . kroksmark et al . has reported a group of patients with amyoplasia that are indistinguishable in the newborn period and respond dramatically to physical therapy.12 all of these series suggest an optimistic childhood , with peak function occurring by the age of 10 years and some decline in ambulation into the adult years . despite these reports assessment for this potential can be difficult , with decisions of the extent and timing of surgery hanging in balance . future multicenter studies by exploring the effects and involvement of residual deformity which affect ambulation in this population are recommended . longer followup periods should be included to verify the extent to which ambulatory gains are maintained . knee involvement is commonly seen among children with arthrogryposis , with flexion contracture of the knee being the most frequent knee deformity . knee flexion contracture in the pediatric population is particularly debilitating as it adversely affects ambulation . treatment for knee flexion contracture requires numerous orthopedic procedures and extensive followup period . according to most authors , knee flexion contracture is more frequent and more difficult to treat with conservative methods than the knee extension contracture.1314 in the literature consensus is to perform early serial casting and physiotherapy , which sometimes is sufficient to correct contracture in flexion or extension . in cases of failure of conservative treatment surgery is recommended and includes procedures like by posterior capsulotomy in addition to soft - tissue release ( including hamstring tenotomy ) . del - bello and watts recommended performing a distal femoral extension osteotomy for flexion contracture as a safe procedure even for severe contractures.15 thomas et al . used femoral osteotomies in young patients because the walking improvement is large and quick ( 32 nonambulators became community or household ambulators in their series).13 brunner et al . used the ilizarov technique as an efficient tool for knee and foot deformity corrections ; however , he noted a high recurrence rate in children younger than 10 years of age.16 thomas et al . and hoffer et al . noted the importance of having a flexion contracture less than 20 degrees in order to walk independently.913 our results support this conclusion . murray and fixsen presented functional results of 22 patients with amyoplasia followed up over an average of 7 years . patients in this series were treated by initial physiotherapy and splintage , as well as repeated posterior release and bony procedures when necessary . they reported 14 community walkers in 22 patients.14 herzenberg et al . reported 10 patients with knee flexion contractures of various different etiologies , including 2 patients with arthrogryposis , treated with ilizarov external fixator . both became community ambulators at the latest followup.17 a study by van bosse et al.18 reported a high rate of improvement in ambulation in all seven children with arthrogryposis with knee flexion contracture after ilizarov correction at latest followup , including five who were initially nonambulatory . a recent report by fassier et al . indicated that among 11 children with arthrogryposis , 7 were independent ambulators at skeletal maturity.19 however , these children had normal knee mobility or a flexion contracture of less than 15 and most had mild involvement of the hips , spine , or upper extremities . we agree with these researchers that early aggressive management of children with severe arthrogryposis is justified and recommended . in our series hip flexion contracture we observed that community ambulators presented with less than 30 degrees of hip flexion contracture . hoffer et al . also noted that less than 30 of hip flexion contracture in their independently walking patients.9 staheli et al.420 and hoffer et al.9 have categorized children with ambulatory potential as having grade 4 or greater hip extensors ; hip flexion contracture less than 20 ; grade 4 quadriceps function ; grade 3 quadriceps function with knee flexion contracture less than 20 ; and good strength and sitting balance , with shoulder depressor function and only mild upper extremity abnormalities but many studies show progressive muscle activity improvement after the recovery of a passive range of motion in a useful arc . many studies showed that independent ambulators were able to perform an increase in strength during growth . the difficulty remaining in identifying prognosis factors is , as with the case of any rare diseases , the small number of patients available to generate data . in our series , poor prognostic factors for independent or community walkers were residual knee flexion contracture more than 30. hip flexion contracture is less likely to occur in isolation , but if greater than 30 , it may affect ambulation , and if greater than 45 , it will generally require release . often , the combination of hip flexion , external rotation , and abduction contractures are present.21 in these cases , the hip abductors may function as extensors and if the hip is left in external rotation , the hip can often be adducted to neutral and extend to less than 30 of contracture without soft tissue release while preserving good hip extensor strength for standing . a distal femoral osteotomy is necessary to bring the knee and foot into alignment for ambulation . reduction of hip dislocation is recommended for unilateral dislocation in all reports.2021 long term ambulatory status at skeletal maturity is not correlated with the severity of condition at birth.19 therefore , we believe that early aggressive management of children with severe arthrogryposis is warranted and justified . the ambulatory status in children with arthrogryposis is variable and our findings seem to indicate that although knee flexion contractures have an impact on ambulation , hip flexion contracture may also influence ambulation . our findings emphasize that residual knee flexion contracture affects the ambulatory status of children with arthrogryposis . surgical interventions for knee flexion contractures in this population is warranted and support a positive prognosis .

background : arthrogryposis multiplex congenita ( amc ) is a multiple joint condition which affects both lower and upper extremities and thus affects ambulation . multiple surgeries are needed to correct limb deformity in order to promote walking . the objective of this study is to identify the most critical residual deformity that diminishes the ambulatory status.materials and methods:51 patients were included in this study , 14 patients were nonambulatory . the mean age at first surgery was 4.1 years ( range 2 - 16 years ) . the mean length of followup was 44.0 months ( range 22 - 168 months ) . type of procedures and number of operations , residual deformity and walking ability were recorded . residual deformity including hip flexion contracture more than 30 , knee flexion contracture more than 30 , scoliosis , hip dysplasia or dislocation , knee extension contracture or recurvatum , active motion of hips and knees and upper limb involvement were evaluated . statistical analysis was done to evaluate factors that were statistically significant to affect walking ability in amc patients.results:at the latest followup , 31 patients were community ambulators , 3 patients were household ambulators , 3 patients were nonfunctional ambulatory , and 14 patients were nonambulatory . there were an average of 4.3 surgeries per patient . statistical analysis of all factors was done and the results were significant with a p < 0.037 in knee flexion contracture > 30 degrees with odds ratio of 4.58 . hip flexion contracture > 30 was a trend toward significant with a p value of 0.058 and odds ratio of 4.53 . multivariate analysis showed that knee flexion contracture was significant with 4.58 ( 95% ci 1.01 - 20.6).conclusion : amc is a rare disease that causes disability , requiring multiple surgeries to correct deformities . our study showed that residual knee flexion contracture was associated with nonambulatory status of patients with amc .

charles darwin suffered illness for most of his adult life with many very differing symptoms . some of these symptoms were present when he was a university student , both in edinburgh and cambridge . in edinburgh he was known to have a weak stomach and was unable to watch surgical operations ; at cambridge he suffered from eczema of his lips and hands . when attending two recitals in 1 day at a birmingham music festival , he experienced extreme fatiguemost terribly knocked up , as he expressed in his autobiography ( barlow 1958 ) . when he was a resident in plymouth , before he sailed on hms beagle , he experienced an episode of rapid heartbeat with pain around the heart . during his voyage on the beagle , darwin suffered greatly from seasickness . this was not ordinary seasickness but a sickness that became worse throughout the 5-year voyage . when ashore , he also had periods of illness , including attacks of headache and visual disturbances . these episodes were severe enough for him to be incapacitated for days on end . before the voyage , apart from these unusual but mostly sporadic episodes of illness , darwin was a fit young man . after the voyage , however , his illness progressed and he had attacks of sickness during which he was incapacitated for weeks , even months at a time . he suffered with nausea , retching , vomiting , flatulence , episodes of abdominal pain , lumbago or backache , and symptoms of asthma . eczema , diagnosed as atopic dermatitis ( sauer 2000 ) , was at times severe and was complicated by frequent boils . he complained of numbness in his fingers ( peripheral neuropathy ) , together with shivering , sweating , and giddy turns ( dysautonomia ) . he had psychological symptoms , waking at night with intense , irrational fear and other episodes of hysterical crying . he continued to have periods of severe lethargy , with times when he could only lie on a sofa and do nothing . darwin s main symptoms are listed in table 1 ; symptoms that may be considered secondary in nature are listed in table 2 together with their proposed relationship to his primary symptoms . the two hormones are released together from the pituitary , molecule for molecule , by splitting of a large parent molecule . his attacks were characteristically brought on by any forms of stress , even by pleasurable events . darwin learned to prevent these events by restricting visitors and avoiding scientific and social occasions . in older age there was no pressure to publish and darwin could work at a pace that suited him and , evidently , his frail condition . many of the different diagnoses that have been proposed for darwin s illness are psychogenic or psychological in nature . these include repressed hatred for a dominating father , or , alternatively , as a means of bonding with his father by developing a patient doctor relationship ( colp 2008 ) . john bowlby , an english psychiatrist , propounded psychogenic causes for many illnesses , in particular mother child separation . he suggested that unresolved grief over the death of his mother when he was 8 years old was the cause of darwin s psychosomatic illness ( bowlby 1965 ) . bowlby suggested that his hypothesis could be tested by showing that darwin s symptoms were worse at anniversary dates , such as the date of his mother s death , and that his symptoms were similar to those of his mother s . colp diligently examined the state of darwin s illness on these dates and found no such association ( colp 1977 ) . it will be proposed here , however , that there was an important maternal link to darwin s illness but that it was genetic , not psychological . indeed , darwin and his mother seem to have shared a number of symptoms as would be expected for such a connection . other psychogenic causes that have been proposed include inner emotional conflict ( repressed hatred ) toward his loving and devoted wife emma and guilt over conflict with religious beliefs and his ideas of evolution ( colp 2008 ) . darwin certainly had psychological symptoms , including symptoms of a panic disorder with periods of irrational fear ( barloon and noyes 1997 ) , episodes of hysterical sobbing , and other symptoms that may be psychological such as sweating , tremors , and palpitations . other diagnoses relate to possible acquired infection during the voyage of the hms beagle ; the most persistent of these is that darwin had chagas disease ( american trypanosomiasis ) ( adler 1959 ) . despite a comprehensive rebuttal by woodruff and others this diagnosis persists ( woodruff 1965 ) . woodruff pointed out that although darwin was bitten by a known vector , and certainly bitten several times , the insect in that place and at that time would be unlikely to have been carrying the infectious agent . darwin suffered from severe incapacity but he lived to the age of 73 ; he almost certainly would not have survived to this age with advanced trypanosomal heart and intestinal disease . in addition , darwin consulted the best physicians of his time and no physical abnormality in their examinations is recorded . woodruff concluded : it is beyond credibility that severe incapacity could have been produced ( by chagas disease ) for 4050 years without the development of physical signs . intestinal disorders have also been proposed including peptic ulceration , biliary disease , crohn s disease , and the irritable bowel syndrome ( ibs ) ( shanahan 2012 ) . darwin certainly had symptoms of ibs ; he also had symptoms of another suggested diagnosis , that of paroxysmal tachycardia ( dent 1965 ) . the symptoms of ibs , panic disorder , atopic dermatitis , and paroxysmal tachycardia may all occur with darwin s proposed diagnosis . other diagnoses may be dismissed simply on the grounds that darwin had some early symptoms of his disorder before he sailed on the beagle , before he developed any ideas about evolution , and before his proposal and marriage to emma . in fairness , it should be remembered that many of these more imaginative diagnoses were put forward before there was much knowledge of mitochondrial genetic diseases . most of darwin s symptoms are similar to those seen in patients with cyclic vomiting syndrome ( cvs ) ( hayman 2009 ) , including some of the more unusual features of this rather poorly defined disorder . patients with cvs suffer from motion sickness , attacks may be brought on by pleasurable events ( positive stress ) , and patients often have relief from water exposure ( fleisher et al . only one of the many treatments that darwin tried seemed to bring him any relief and that was hydropathy or the water cure . patients with cvs today will spend hours in a bath or under a shower ( cyclic vomiting association 2010 ) . some of darwin s symptoms , however , were not symptoms experienced by patients with cvs . in his 50 s , darwin experienced episodes of transient partial paralysis , inability to speak , and memory loss ( jones 1867 ) . these symptoms , together with many of his other symptoms such as headache and visual disturbances may occur in melas syndrome ( pavlakis et al . this syndrome , usually regarded as a fatal childhood disorder , may have less severe manifestations and symptoms may first appear in adult life ( higashikata et al . 2001 ) . lactic acidosis , which is a biochemical feature of the disorder ( and part of the acronym ) may be associated with feelings of panic ( ehlers et al . eighty percent of patients with this disorder have been shown to have a particular mitochondrial dna mutation , an a - to - g transition at nucleotide 3243 in the gene for leucine transfer rna in the mitochondrial ring chromosome ( goto et al . 1990 ) . this same mutation may be associated with cardiac and vestibular symptoms , atopy ( atopic dermatitis , asthma ) , dysautonomia , and peripheral neuropathy ( finsterer 2007 ) . darwin s symptoms and their similarities to the effects created by the mtdna mutation associated with melas syndrome are summarized in table 1 . although melas syndrome as initially described was progressive and fatal in early life , patients carrying the mutation commonly associated with the condition may have lesser symptoms and a normal lifespan ( manwaring et al . 2007 ) . an examination of darwin s family history provides supporting evidence that charles darwin had such an inherited mitochondrial disorder . erasmus alvey darwin ( 18041881 ) , charles elder brother , graduated in medicine from the university of edinburgh but never practiced . instead , he spent a life in london partly as a socialite and partly as a chronic invalid ( healey 2001 ) . he suffered from abdominal pain and lethargy ; today he would probably be diagnosed as having chronic fatigue syndrome . his symptoms are consistent with his having had the same mtdna mutation as his younger brother but with a lower level of heteroplasmy . susannah ( sukey ) darwin ( wedgwood ) ( 17651817 ) , charles and erasmus mother , suffered chronic ill health and was never quite well and never very ill ( wedgwood and wedgwood 1980 ) . as a child she suffered from vomiting and boils , and had difficulties with her pregnancies , spending much time in bed and suffering from what most likely was hyperemesis . she also experienced motion sickness and preferred to ride in a phaeton rather than a carriage . her symptoms are those that may occur in cvs ; female patients frequently have hyperemesis during pregnancy ( fleisher et al . tom wedgwood ( 17711805 ) , susannah s youngest brother , was unwell for most of his short life . as a student he suffered from headaches and later severe abdominal pains and would roll around the floor in agony . on his trip to the west indies he also suffered from seasickness and was confined to his cabin for the entire voyage with both vomiting and abdominal pain ( wedgwood and wedgwood 1980 ) . his symptoms are consistent with what today would be called abdominal migraine , a disorder that may be associated with cvs and with the same mtdna mutation ( pronicki et al . 2002 ) . mary anne wedgwood ( 17781786 ) , the youngest child in the family , had short stature and was physically and mentally retarded . she died with progressive dementia at the age of eight ( wedgwood and wedgwood 1980 ) . her symptoms are typical of the severer cases of melas syndrome , as associated with the a3243 g mtdna mutation ( goto et al . 1990 ) . other siblings in the family suffered more ambiguous symptoms such as social and cognitive decline , while daughters of susannah s sisters also had similar problems . although less specific as a symptom , psychosocial abnormality may also occur with the a3243 g mutation ( finsterer 2007 ) . two brothers had tremors ; one had a lifetime tremor and the other developed classical parkinson s disease in later life . a diagram , giving symptoms of charles darwin s siblings and his maternal ancestors is shown in figure 1 . diagram showing charles darwin s siblings and his maternal ancestors , with their major symptoms . most , if not all of these symptoms may occur with the a3243 g mtdna mutation . charles darwin s 10 children were in general a sickly lot ; one died in infancy , one in childhood , and their first daughter died at the age of 10 . their illnesses do not seem to be related to one another and not related to the illness of their father . as well as other symptoms , the children suffered from various infections . their sicknesses may have at least in part been due to the consanguinity of their parents ( charles and his wife emma were first cousins ) as there may be increased susceptibility to infection in the children of such partnerships ( berra et al . darwin s illness , the illnesses of his brother , their mother , his maternal uncle tom , and a child belonging to the maternal generation as well as other family members show a pattern of maternal inheritance that is the hallmark of mitochondrial mutations , while the particular symptoms point to one specific well - characterized mitochondrial disorder , melas syndrome . the evidence is circumstantial , of course , but it is considerable and consistent . as darwin said of evolution and natural selection : let me add that there are many difficulties not satisfactorily explained by my theory of descent with modification , but i can not possibly believe that a false theory would explain so many classes of facts as i think it certainly does explain . much the same if the conclusion that darwin s illness was due to a mtdna mutation is accepted , then the detailed , lifetime history of his illness and those of family members shows us the range of symptoms that may occur with the one mtdna abnormality . further study of diseases associated with mtdna mutations may lead us to a better understanding of darwin s illness , in particular of his very diverse symptoms and the manner in which his attacks of illness were precipitated .

charles darwin s long - term illness has been the subject of much speculation . his numerous symptoms have led to conclusions that his illness was essentially psychogenic in nature . these diagnoses have never been fully convincing , however , particularly in regard to the proposed underlying psychological background causes of the illness . similarly , two proposed somatic causes of illness , chagas disease and arsenic poisoning , lack credibility and appear inconsistent with the lifetime history of the illness . other physical explanations are simply too incomplete to explain the range of symptoms . here , a very different sort of explanation will be offered . we now know that mitochondrial mutations producing impaired mitochondrial function may result in a wide range of differing symptoms , including symptoms thought to be primarily psychological . examination of darwin s maternal family history supports the contention that his illness was mitochondrial in nature ; his mother and one maternal uncle had strange illnesses and the youngest maternal sibling died of an infirmity with symptoms characteristic of mitochondrial encephalomyopathy , lactic acidosis , and stroke - like episodes ( melas syndrome ) , a condition rooted in mitochondrial dysfunction . darwin s own symptoms are described here and are in accord with the hypothesis that he had the mtdna mutation commonly associated with the melas syndrome .

the field of cosmetic facial rejuvenation has been revolutionised by the availability of facial fillers in differing densities . fillers are now a prime sought after rejuvenation procedure as they offer a youthful 3 dimensional look with minimal invasiveness . aging of human face is a complex dynamic interplay of various factors involving 3 dimensional changes in the skeletal as well as soft tissue structure along with superficial textural changes of skin wrinkling . aging individually affects all the components of skin and subcutaneous soft - tissues which comprise of fat , muscle , fascia along with structural support provided by bones and dentition . this is compounded by effects of gravity , sun insult , smoking and hormonal imbalances . the net effect has been found to be loss of facial volume and skin texture . the midface naturally commands more respect as it is central and comes to the notice first because it is the most dynamic region of the face while one interacts with others . the midfacial attractiveness is a function of synergy among the eyes , nose , lips and malar prominences what is commonly referred to as the central facial triangle . facial aging involves loss of volume in certain areas of face ( periorbital , forehead , malar , temporal , mandibular , mental , glabellar and perioral sites ) and persistence or hypertrophy of fat in others ( submental , lateral nasolabial fold and labiomental crease , jowls , infraorbital fat pouches and malar fat pad ) . a selective hypertrophy of the of the cheek pad fat also complements the ptosis leading to midface aging changes . the ptotic hypertrophied cheek fat needs to be contoured as the facial muscles hardly show changes over age . apart from the conventional facelift techniques , structural fat grafting has been attributed as an ideal facial filler . the adipose tissue having the maximum percentage of stem cells of any tissues in the body can fill large and small soft - tissue defects of the face thus acting as a permanent facial filler . a recent trend towards non - surgical techniques of facial rejuvenations has led to increase in demand for the facial fillers for enhancing facial features and symmetry with immediate results and minimal recovery time . a retrospective case series analysis study was carried out at our institute about a novel method of facial filling , the hammock method which includes building up the pillars and pyramids using a more viscous filler and connecting them using a less viscous filler . the study period spanned from 1 july 2011 to 30 june 2013 over a period of 24 months . 67 patients were included in the study which included 48 females and 19 males . a detailed history about the past medical events , medications being used , history of drug allergies , with stress on diabetic and anticoagulant medication were recorded . patients with the above medical conditions were excluded from the study . a detailed clinical examination and the patient 's expectations on the outcome were discussed and explained in detail . pre - a written informed consent was taken after having a detailed discussion on the pros and cons of the procedure including the full details about the filler to be used , expected longevity of results , its approval status , possible side effects and the cost . furthermore , the newer methods of facial filling and its advantages were explained to the patients . deep nasolabial folds procedure included cleaning the area with povidine - iodine solution and wiping the area with wet normal saline wipes . later emla cream ( eutectic mixture of lidocaine 2.5% and prilocaine 2.5% ) is applied onto the area to be injected and covered with occlusal dressing and left in place for 15 - 20 min . no local infiltration anaesthesia was given in routine cases but , in apprehensive and sensitive patient 's infraorbital blocks were given in addition . in the nasolabial folds and the infraorbital area our technique involved a novel method of laying the fillers , called the pillars pyramids and tie beams ( ppt ) technique by constructing pillars , pyramids and tie beams in the form of a hammock . here the filler was used in 3 layers the supra periosteal , the subdermal and the dermal layer [ figures 2 and 3 ] . 0.5 ml of the more viscous filler was used in erecting the pyramids 3 - 4 pyramids in each area with their base down supraperiosteally and 0.5 ml lesser viscous fillers was used in each area by connecting the pillars and pyramids dermally and subdermally by the threading method [ figures 49 ] . the technique included creating a hammock tied to the tips of the pillars and pyramids [ figure 10 ] . by this method the standard volume of filling was adhered and rejuvenation was done to patient 's satisfaction . the patient was asked for a follow - up at the end of a week . the patient was advised to avoid exposure to extreme cold or heat , avoid massaging treated areas for 6 h , avoid strenuous physical activity for 6 h , sleep with the head elevated for one night , analgesics if needed and allowed to continue the skin care products the next day . furthermore , the patient was explained that a bruise may be seen the next day with pain which will usually subside in a weeks time which can be camouflaged with skin cosmetics . since the needle manipulation was minimal the swelling of the area along with pain was limited . pyramids and pillars placed with high molecular weight fillers pillars being connected with low molecular weight filler tie beams pyramids placed using high molecular weight filler material , more on the periosteum and minimal subdermally low molecular weight filler materials placed as tiebeams across the pyramids schematic diagram of the high molecular weight filler material used as pillars schematic diagram of the low molecular weight filler material used as tie beams over pyramids schematic diagram of the high molecular weight filler material used as pillars schematic diagram of the low molecular weight filler material used as tie beams over pyramids schematic representation of the pillars pyramids and tie beams technique of facial filling . note that the filler gets hydrated over initial week to restore the lost volume all the patients were followed - up regularly at 1 week , 6 weeks and 6 months post injection . after that the patients were asked to follow - up whenever they felt that they needed a touch up to add to the area . this novel method of dermal filling has given considerably better results particularly in the midface volume restoration . as minimal amount of filler with strict adherence of the standard guidelines was done , the complication rate was negligible . immediate concerns like pain and bruising were seen in some patients but no incidence of erythema , asymmetry , bumpiness , lumpiness , anaphylaxis , oedema , acneiform eruptions was seen . no incidences of late complications like an inflammatory nodule , tyndall effect , allergic reactions , vascular occlusion and granulomas were seen . the longevity of results was found to be consistently better than the conventional filler laying methods [ figures 11a d and 12a and b ] the conventional method required later refilling sessions at 8 - 10 months whereas in the ppt technique this is at 12 - 14 months . also the amount of filler material required in subsequent sessions was found to be lesser in our technique . pre procedure front view of a 42 year lady with deep nasojugal and nasolabial folds post procedure front view of a 42 year lady with deep nasojugal and nasolabial folds pre procedure half lateral view of a 42 year lady with deep nasojugal and nasolabial folds post procedure half lateral view of a 42 year lady with deep nasojugal and nasolabial folds pre procedure picture of a 47 year lady with deep nasolabial and nasojugal folds post procedure picture of a 47 year lady with deep nasolabial and nasojugal folds a balanced distribution of superficial and deep fat conferring a 3 dimensional anatomy well - delineated by a series of arcs and convexities is a feature of a normal youthful face . the aging process is not uniform all along the face and leaves a contour abnormality resulting from volume deficiency below the dermal plane . as the subcutaneous fat of the face is not uniform and is compartmentalised and each compartment ages at a different pace in the same individual , so each compartment should be addressed individually . hyaluronic acid ( ha ) dermal fillers are the most sought after , non - permanent injectable materials available today for the correction of aging changes of the face . ha has excellent water binding capacity and also is fluid enough which offers an ease of injection . facial fat gets redistributed and appear as pockets due to the disappearing of surrounding fullness which is seen particularly in submaxillary areas and bony protuberances . furthermore the malar fat pad gradually slides forward and down bulging against the nasolabial crease , giving rise to prominence of the nasal fold . the unbalanced facial appearance with fat redistribution and loss of fullness is to be restored as a primary goal of facial rejuvenation . it involves smoothening the facial pockets and recreating the primary arcs and convexities of the youth . surgical face lift procedures includes lifting and tightening the facial skin which has sagged as a result of atrophy and loss of elasticity . recent trends in facial rejuvenation involve a paradigm shift from conventional excision and suspension procedures to conservative skin excision , deep fascial superficial musculoaponeurotic system manipulation , volume restoration and modification of facial animation . facial fillers have emerged as logical and effective modality for lifting , filling and resurfacing the facial soft tissues and can also be used along with other surgical facial rejuvenation techniques . midfacial volume restoration is not basically correcting the deficiency in tissue levels of ha but a true augmentation of the ha . the ha ratios in the foetal as well as the aged skin is nearly unaltered , so ha as the filler will only act as a mere augmentation . it has the intricate physical properties of increased longevity , filling capacity and the ease of injection making it accurate for facial rejuvenation . the longevity of the filler depends on the degree of crosslinking in ha which increases the viscosity and reduces free radical and enzymatic degradation . the more the crosslinks , more is the viscosity and cohesivity giving a sustained dermal lift but more difficult to inject through a thin needle . the lower molecular weight , higher viscous ha is slowly biodegraded as it is in excess to the naturally existing ha in the dermis . it retains water and volume , until it reaches a critical level where it rapidly disappears . in general the narrowest calibre needle that can deliver the filler subdermally with the least amount of pain sensation the amount of the filler , the type and the depth is determined by the defect . the less deep defects can be filled with less volume of fillers used superficially while the deep defects need more volume at deeper levels and lesser volume superficially . as far as the techniques for filler injection are concerned no consensus has been reached . commonly used techniques are the serial puncture , threading , fanning , crosshatching and the sandwich methods . techniques are tailored to surgeon 's expertise , defect volume and anatomy and the viscosity of the filler being used . lip augmentation and superficial defects filling are done by the serial puncture technique where small boluses are delivered along a line to be augmented with serial punctures . the threading technique , where the needle is inserted and tunnelled and the filler is deposited at a slow continuous line when the needle is withdrawn making it a better technique for nasolabial fold and lip defects . threading done in a radial fashion without withdrawing the needle is also called as a fanning technique , while series of threads injected in a perpendicular fashion is the cross - hatching technique . these are used to fill larger defects ; mixture of superficial and deep threading and serial punctures is what is described as the sandwich technique . desired results are not attained if an under correction or overcorrection of the defect is done . under correction furthermore it occurs when lesser amount of fillers are used in a larger defect due to financial constraints . lesser viscous fillers if used at a deeper plane without superficial augmentation also leads to under correction . overcorrection is seen where excess fillers are used in comparison to the volume deficiency and appear as palpable nodules . the only treatment for overcorrection is to use hyalase to breakdown the filler . in an effort to standardise the technique of dermal filling we introduced the ppt method ( ppt technique ) which uses a minimum amount of filler in a systematic method to optimise results . the logic behind the ppt technique is that laying the higher density filler material in a structurally sound manner creates a firm background over which fine tuning can effectively be done with a lighter density filler material . the use of lighter density filler material on this solid base in miniscule quantities virtually eliminates the risk of overcorrection . also we encountered that the average time interval between subsequent sittings is increased to 12 - 14 months as compared to 8 - 10 months for conventional techniques . also the volume of filler material required in subsequent sittings is reduced as the pillars and pyramids constructed with higher density material continue to provide residual support for longer periods . facial fillers being a safe , simple and effective modality of facial rejuvenation can be made to work well with this ppt technique . secret of facial rejuvenation lies in an accurate knowledge of the topography of facial aging , areas of injection , proper patient selection and a suitable technique giving optimal results with minimal complications .

context : facial fillers have revolutionized the field of cosmetic facial rejuvenation as it has become the prime sought after rejuvenation procedure offering youthful , 3-dimensional look with minimal invasiveness . fillers are expensive and need to be redone periodically hence a sound understanding of structural basis on which they are laid is important in reducing the quantity of filler required in each sitting as well as increasing the longevity of results.aim:the aim of the following study is to analyse a novel method of facial filling the pillars pyramids and tie beams ( ppt ) technique and its advantages over the conventional methods.subjects and methods : a novel technique of injecting the facial fillers was employed on 67 patients visiting our clinic . these patients were followed - up for a period of 3 years.results:we observed that the amount of filler material required in initial sitting remains the same , however the frequency of touch up visits is decreased and so is the amount of filler material required for follow - up injections.conclusion:facial contour remodelling is being revolutionised by the new filler materials for volume augmentation and no uniform consensus has been reached on the techniques currently used in clinical practice . we advocate this novel ppt technique of facial filling in facial rejuvenation to restore a youthful look as a primary goal .

hemangiomas are benign tumors and tumor like conditions.1 they are uncommon in the spinal cord.28 their source in the cord may be the meningeal coverings and the vasa nervosum.6 on the basis of their histopathologic characteristics , they have been differentiated into capillary and cavernous hemangiomas . chung et al.9 stated that capillary and cavernous hemangiomas are well - defined , slow - growing vascular tumors , if confined to closed compartments like the skull or spinal cord may behave as space occupying lesions ( sol ) , and may present with myelopathy / radiculopathy . capillary and cavernous hemangiomas at times may be friable , with presentation of sudden neurological compromise due to bleeding . cavernous angioma has recurrent bleeding tendencies ( 44% risk in intracranial location).10 the natural history of spinal cord capillary hemangiomas is not well studied . there is a significant risk of bleeding , hence enbloc excision of the same is suggested.41112 common spinal cord tumors like schwannoma and meningioma have similar magnetic resonance imaging ( mri ) features to that of capillary hemangioma.13 we report a rare case of intradural extramedullary spinal cord capillary hemangioma with a brief review of literature [ table 1 ] . a 35-year - old male presented with mid back pain , progressive weakness in both lower limbs since 4 months , with difficulty in walking since last 2 weeks . on examination of spine , there was no deformity and tenderness . on neurological examination , there was spasticity in both lower limbs , with grade 4 power in both hips and grade 2 in both knee and ankle muscle groups and hypoesthesia below l3 . mri screening showed a well - circumscribed intradural mass of 2.78 1.28 cm at the level of d12 vertebral body , which was isointense on t1-weighted images [ figures 1a and b ] and hyperintense on t2-weighted images [ figures 1c and d ] with homogenous enhancement on gadolinium t1-weighted images [ figure 1e ] . tumor mass was separated from dura , spinal cord , nerve roots and was excised completely . on gross appearance , a reddish brown , multilobular , spongy oval mass of 2.4 1.3 1.2 cm size was identified [ figure 2 ] . histologically , it was aggregates of closely packed , thin - walled capillaries , blood filled and lined by flattened endothelium and the vessels were separated by scant connective tissue stroma . there was no cellular atypia [ figure 3 ] . patient was followed over a period of 3 months where he showed neurological improvement ( of paraparesis and pain ) . on 1.5 years of followup , ( a ) t1-weighted sagittal image demonstrates isointense mass at the level of d12 vertebral body . ( b ) t2-weighted sagittal image demonstrates hyperintense oval nodular mass ( c ) t1-weighted axial image shows well - circumscribed intradural isointense mass ( d ) t2-weighted axial mr image demonstrates a hyperintense solid tumor on the right side of the thecal sac , causing cord compression ( e ) t1w sagittal mri with gadolinium contrast showing 2.78 1.28 cm , well - defined and homogenously enhancing mass at the level of d12 vertebral body peroperative photograph showing multilobular vascular tumor of 2.4 1.3 1.2 cm histological appearance of capillary hemangioma ( h and e stain ) showing small , thin - walled capillaries lined by flat endothelium ( red arrow ) and slit - like vascular space ( white arrow ) separated by fibrous septae . 15% of the cns tumors are located in the spinal cord . of these , 27% are of vascular origin.2 among these lesions , capillary hemangiomas in the spinal cord are rare and only a few cases have been reported13 [ table 1 ] . the most frequent sites of these tumors are around the cauda equina and conus.3 features of capillary hemangioma on mr images are : isointense lesion on t1-weighted images , hyperintense relative to the spinal cord on t2-weighted images , and homogenous , strong enhancement on contrast - enhanced t1-weighted images681415 ( which is similar to our case ) . the differential diagnosis for intradural extramedullary tumors includes hemangioma , meningioma , schwannoma , hemangioblastoma , metastasis and paraganglioma.1316 among these , intradural extramedullary lesions , schwannoma and meningioma are the most common neoplasms commonly occurring at the thoracic level . schwannomas are frequently seen in middle age with equal sex predilection , while meningioma is seen at the age of 5070 years with m : f=1:5 . both show similar mri features , with the exception of the following : schwannoma frequently shows cystic changes or necrosis , while meningioma shows characteristic dural attachment with dural tail sign on the contrast - enhanced study.917 abdullah et al.7 reported a similar case with mr features of enlarged perimedullary veins indicating a vascular tumor and suggested preoperative spinal angiography . spinal angiography is a useful investigation to differentiate non - vascular tumors from vascular tumors , and thus prevents the risk of intraoperative bleeding . they can be differentiated on histopathology by vessel size:13 capillary hemangioma is composed of small , closely packed capillaries , while cavernous hemangioma is composed of blood - filled sinus like spaces . both show distinct demarcation from the surrounding parenchyma , unlike other vascular lesions such as av malformations and telangiectasias which interdigitate into the parenchyma forming the differentiating features . capillary and cavernous hemangiomas show similar mr characteristics.18 they may differ in their clinical presentation . they may present in four major clinical patterns : acute episodes of step wise deterioration , slow progression , acute onset with rapid deterioration , and acute onset with gradual decline . they are common in 36 decade of life , with m : f ratio of 1:2 . capillary hemangiomas are common in 56 decade , with m : f ratio of 1:1 . they are commonly located near conus medullaris or attached to nerve roots of cauda equina with a variable onset of presentation2 ( as low back pain , myelopathy , radiculopathy or cauda equine syndrome ) . complete surgical resection is the treatment of choice for intradural extramedullary hemangioma,1419 with no recurrence.5712141720 schwannoma and meningioma are common intradural tumors of the spinal cord and it may be difficult to differentiate them clinicoradiologically from capillary hemangioma .

capillary hemangiomas are benign tumors and tumor like conditions commonly involving skin and mucus membrane of head and neck region . they are extremely rare in the spinal cord . we report a 35-year - old male presenting with gradual progressive paraparesis over a period of 4 months . magnetic resonance imaging showed a hypo- to isointense intradural mass at the level of d12 vertebral body on t1-weighted images and homogenous enhancement on gadolinium contrast . complete surgical resection revealed intradural extramedullary tumor , which on histopathologic examination showed characteristics of capillary hemangioma . at 1.5 years followup patient was asymptomatic .

a 51-year - old postmenopausal woman , admitted to hospital for a 2-week history of subacute right flank pain , was found to have right renal angiomyolipoma on computed tomography ( ct ) of the abdomen and pelvis . past medical history was significant for hypertension treated with lisinopril , allergic rhinitis , and osteoarthritis . a percutaneous transfemoral abdominal aortography was performed using ioversol ( non - ionic iodinated contrast ) for prophylactic embolization of the artery supplying the angiomyolipoma so as to prevent bleeding complications . selective angiography was performed in multiple projections including the origin of the right renal artery and infrarenal abdominal aorta to study the lower pole of the right kidney where the angiomyolipoma was located . however , embolization could not be performed owing to the inability to isolate a feeding vessel to the tumor . twelve hours after the procedure , the patient complained of progressively worsening diffuse abdominal pain and bright red rectal bleeding . on examination , she had a blood pressure of 117/63 mm hg , heart rate of 94/min , respiration of 16/min , and temperature of 98.1f . abdominal examination revealed normal bowel sounds , soft abdomen without any distention , and tenderness over the periumbilical region and left upper quadrant . digital rectal examination showed stool mixed with bright red blood but no hemorrhoids or mass . laboratory studies included : white blood cell 10,600/l with 80% granulocytes , hemoglobin 14.4 g / dl , and platelet count 232,000/l . the glucose , lactate , amylase , lipase , coagulation profile , and liver and renal function tests were all within normal limits . she was given nil - by - mouth and started on normal saline infusion , intravenous metronidazole , ciprofloxacin , and morphine as needed . she continued to have abdominal pain and multiple bloody bowel movements over the next 2 days . a ct of the abdomen and pelvis showed thickening of a long segment of colon spanning the distal transverse to the proximal sigmoid colon ( fig . a colonoscopy showed edematous , erythematous , and friable mucosa overlying the splenic flexure ( fig . biopsy of the affected area showed focal glandular dropout , small glands with mucin depletion , denudation of surface epithelium , stromal hemorrhage , and fibrosis , thus confirming a diagnosis of ischemic colitis ( fig . she remained hemodynamically stable throughout the course of her illness and continued to improve over the subsequent 45 days . she was discharged on the tenth hospital day . computed tomography scan of the abdomen ( axial view ) showing thickening of the colon wall ( short thick arrow , on the left ) as well as right kidney mass ( long thin arrow ) . low - power photomicrograph ( hematoxylin and eosin stain ) of a biopsy of splenic flexure showing focal glandular dropout , small glands with mucin depletion , denudation of surface epithelium , stromal hemorrhage , and fibrosis . aortography can be associated with distal arterial occlusion in 5.7% of cases after abdominal aortography and 18.2% after thoracic aortography ( 6 ) . embolic complications from angiographic procedures mainly involve the lower extremities , and rarely the gastrointestinal tract ( 0.30.7% cases of aortography ) ( 5 , 7 ) . however , the use of abdominal angiography and transcatheter embolization has increased rapidly in the last few decades ; hence , it is important to be aware of the potential complications . different mechanisms proposed to explain the development of the ischemic bowel injury following angiography include the toxic effect of contrast dye , injecting the dye into the intimal layer , embolization of the atheromatous debris to the mesenteric arteries , and micro - cholesterol embolization syndrome of minor vessels ( 8) . the possibility and the extent of ischemic injury depend on several factors such as the presence of preexisting arterial disease or atherosclerosis , and technical aspects of the procedure . a study has shown that the presence of the stenosis of major arteries prior to the procedure can result in complete occlusion and bowel infarction after the procedure ( 9 ) . it has also been shown that the incidence of intimal injury increases with superselective catheterization ( 10 ) . the difference in the length of the catheter , and the nature , concentration and amount of the contrast material used can also influence the incidence of arterial occlusion ( 6 , 11 ) . ischemic colitis has usually been reported in elderly patients with diffuse atherosclerotic disease and multiple underlying comorbidities , however , it has also been reported in younger patients ( 12 ) . to our knowledge , the youngest reported case was a 41-year - old patient with massive intestinal infarction after angiography ( 8) . although variable , it usually occurs 2448 hours after angiography ( 8) . even though the clinical features vary with the severity , most cases present with sudden , crampy abdominal pain , associated with diarrhea , which is usually bloody . there is mild to moderate tenderness over the affected bowel , and peritoneal signs are only seen in severe cases . the patient is usually hemodynamically stable except in advanced cases when they can be acidotic and anuric ( 2 ) . ischemic bowel injury can present diagnostic challenges ; while some patients might have a fulminant course with sepsis and death , others may be asymptomatic . although abdominal pain and diarrhea are the usual presenting symptoms , patients can present without these symptoms , thus delaying timely diagnosis . a case of postangiography ischemic bowel injury presenting with anuria and general deterioration in the absence of abdominal pain has been reported ( 13 ) . severe cases of postangiography mesenteric infarctions often have fatal outcomes . in one study , more than of the half patients died reflecting the high mortality ( 8) . therefore , a high suspicion of index and prompt investigation in the appropriate clinical context is essential for prompt diagnosis . leukocytosis is often present , which along with lactic acidosis , might indicate an advanced disease . although abdominal radiograph findings such as thumb printing , ileus , and free air may be suggestive , ct scan of the abdomen is the diagnostic imaging modality of choice . ct scan shows bowel wall thickening , and colonic fat stranding , with or without pericolic fluid collection . colonoscopic findings such as erythematous , edematous and friable mucosa , and consistent histopathological features can confirm the diagnosis , as in our patient ( 2 ) . a mild case of ischemic colitis can be managed with bowel rest , intravenous fluids , and empiric antibiotics such as ciprofloxacin and metronidazole ( 14 ) . timely initiation of therapy , as in our patient , can likely prevent further deterioration . patients requiring prolonged bowel rest , and those who are not surgical candidates should be started on parenteral nutrition ( 15 ) . worsening abdominal pain , intractable vomiting and severe bloody diarrhea , free intraperitoneal air , and extensive gangrene on colonoscopy are indications to perform surgery . a total of 20% of cases undergo surgery ; such patients have mortality as high as 6080% ( 1618 ) . the possibility of complications from the angiographic procedure warrants that it should be performed judiciously , more so in high - risk patients ( 19 ) . intimal injuries can be minimized with gentle manipulation of guide wires and catheters , use of flexible tipped wires and end - hole - only catheters ( 20 ) . finally , patient education and careful monitoring for symptoms and signs of such complications are important for timely diagnosis . postprocedural monitoring , patient education , and timely evaluation can prevent further deterioration and associated morbidity and mortality . ischemic bowel injury can have protean and atypical manifestations ; hence , a high index of suspicion is important . the authors have not received any funding or benefits from industry or elsewhere to conduct this study .

the use of abdominal angiography and transcatheter embolization has increased rapidly in the last few decades . although improvement in angiographic techniques has made the procedure safe , ischemic colitis is a rare but potentially dreadful complication . we report a case of a 51-year - old woman who developed ischemic colitis following aortography , demonstrating that such angiographic studies may produce substantial morbidity .

although hemophagocytosis is an interesting phenomenon , it is commonly overlooked during bone marrow examination . hemophagocytosis may be associated with infections , ineffective hemopoiesis , leukemia , granulocyte - macrophage colony stimulating factor therapy , or hemophagocytic lymphohistiocytosis ( hlh ) . hemophagocytosis is the phenomenon of engulfment and phagocytosis of hemopoietic cells , neutrophils , erythrocytes , or cellular debris by macrophages or histiocytes . we present this case because it emphasizes the fact that hemophagocytosis observed on bone marrow examination may provide an early hint for a thorough examination of the marrow for any latent infection . in addition , patients with histoplasmosis on bone marrow examination may present with pancytopenia , and hence , their human immunodeficiency virus ( hiv ) status should always be investigated . the patient was a 38-year - old woman residing in uttarakhand state , which is situated in the northern himalayan region of india . she had no significant travel history and presented with unexplained fever associated with chills , rigors , cough , and loss of appetite for the past 2 months . clinical examination showed that the patient had anemia and bilateral cervical lymphadenopathy with right - sided pleural effusion . hematological investigations showed that she had progressive pancytopenia ( hemoglobin , 4.7 g / dl ; total leukocyte count , 1.610/l ; and platelet count , 3010/l ) . her blood culture examination tested negative for tuberculosis and typhoid , and her rapid malarial test ( qdx malaria pv / pf ; piramal healthcare , india ) for plasmodium vivax and plasmodium falciparum also tested negative . a careful examination of the peripheral blood smear showed no evidence of malarial parasites or any other organism . the bone marrow aspirate smears were normocellular for age and showed normoblastic erythroid hyperplasia with increased plasma cells ( 12% ) , but showed no obvious pathological finding . increased number of plasma cells , we conducted a thorough examination of the smear for signs of infection . the bone marrow aspirate smear showed negative staining for acid - fast bacilli ( ziehl - neelsen stain ) . a detailed examination of the smears revealed very few fungal hyphae and oval , budding yeast - like cells that were morphologically identified as histoplasma . the yeast - like cells were spherical to oval , measured 2 - 4 m in diameter , and had a clear space or halo around them ( fig . 2 ) . staining with gomori 's methenamine silver also revealed pseudohyphae showing segmental constrictions ( fig . 3 ) . the patient was advised to undergo an evaluation of her immunological status and was found to be positive for hiv infection . hemophagocytosis results from immunological activation that may be triggered in response to various conditions such as infection , lymphoma , or hlh . in lymphomas , the enhanced macrophage proliferation and phagocytosis may be in response to the lymphokines secreted by lymphoma cells ; whereas , in hlh , the highly stimulated but ineffective immune response may be a result of defective cytotoxic function of natural killer cells and cytotoxic t - lymphocytes [ 1 , 2 ] . during an infection , phagocytosis involves binding of the fc and c3b receptors followed by engulfment and destruction of the antigen . these infections may include tuberculosis , typhoid , leishmaniasis , malaria , and fungal infections , such as histoplasmosis and candidiasis . in the present case , the possibility of tuberculosis , typhoid , leishmaniasis , and malaria were excluded by blood culture and careful examination of the peripheral blood and bone marrow aspirate smear . histoplasmosis is a rare fungal infection observed in the bone marrow , and compromised immunity due to malignancies , chemotherapy , organ transplantation , and aids are considered important predisposing factors for disseminated histoplasmosis [ 5 , 6 ] . pancytopenia may be associated with histoplasmosis , particularly in patients showing hemophagocytosis [ 7 , 8 ] . our patient presented with pancytopenia and showed the presence of hemophagocytosis in the marrow ; this was an early indicator of infection . this was followed by a thorough examination of the smears , revealing the presence of mild histoplasmosis , in which histoplasma manifested in the form of fungal hyphae and oval budding yeast - like cells . a previous report has documented the case of a newborn , who was diagnosed with histoplasmosis on the basis of peripheral blood smear analysis . although cryptococcus and blastomyces dermatitidis may resemble the yeast forms of histoplasma , they can be differentiated on the basis of the feature that cryptococci are usually carminophilic , and b. dermatitidis cells are multinucleated , thick - walled , and bud from a broad base . viral infections such as those caused by the epstein - barr virus ( ebv ) may also be associated with hemophagocytosis , but our patient was not investigated for ebv infection , because she refused to undergo further tests . because immunodeficiency is an important predisposing factor for disseminated histoplasmosis , we advised our patient to undergo testing for histoplasmosis ; she then tested positive for hiv infection . jeong et al . have also reported a case of disseminated histoplasmosis in a patient with hiv infection , where the bone marrow smear examination revealed numerous histoplasma capsulatum cells . in contrast to our case , the aforementioned case was associated with tuberculosis , and the authors suggested that histoplasmosis should be considered along with tuberculosis in immunocompromised patients , because disseminated histoplasmosis and tuberculosis have similar clinical manifestations . however , cases of histoplasmosis in immunocompetent individuals have also been reported [ 12 , 13 ] . thus , if hemophagocytosis is observed on a bone marrow examination , clinicians should immediately consider the associated conditions , and this should be followed by a thorough examination of the marrow for any subtle pathological finding , including infections . in addition , histoplasmosis with hemophagocytosis may be associated with pancytopenia , and the hiv status of the patient should always be examined .

a 38-year - old woman who presented with unexplained fever and pancytopenia was subjected to a bone marrow examination . her bone marrow aspirate smear showed no obvious pathological finding except for the presence of hemophagocytosis and mild plasmacytosis . in view of hemophagocytosis , a thorough examination of the smear was conducted and revealed the presence of histoplasmosis . she was advised to undergo evaluation of her immunological status , and she tested positive for human immunodeficiency virus ( hiv ) infection . this case highlights that hemophagocytosis in the marrow may be an early sign of underlying disease , and that careful examination of bone marrow smears may reveal subtle infections . in addition , histoplasmosis with hemophagocytosis may be associated with pancytopenia , and hence , the hiv status of the patient should always be investigated .

cryptococcus neoformans is an encapsulated opportunistic yeast which is responsible for approximately 1 million infections and over 600,000 deaths per year worldwide ( 1 ) . the patient populations most affected are those with adaptive immunity dysfunction , specifically t - cell defects . individuals suffering from aids or lymphoma or recipients of chronic immunosuppressive medication are at highest risk for developing cryptococcal infection ( 2 ) . c. neoformans is ubiquitous , but a higher rate of infection is observed in sub - saharan countries , which suggests that either there are host factors that result in a more susceptible phenotype or there are differences in the virulence of the fungal strains found in these niches . more recently , hypervirulent strains of the closely related species cryptococcus gattii have caused epidemic infections in predominantly immunocompetent individuals ( 3 ) . c. neoformans can exist as a haploid or diploid organism and divides using either an asexual budding cycle or a sexual stage with conidial forms . cryptococcus has a complete and intact life cycle in the environment but has clearly found a niche as a mammalian pathogen . the ability of c. neoformans to survive in the human phagocyte may have evolved through the interactions of the fungal cells with free - living amoebae ( 4 ) . exposure to c. neoformans is thought to typically occur following inhalation of airborne organisms . once the organisms are in the lungs , professional phagocyte populations ( e.g. , dendritic cells , macrophages , and polymorphonuclear leukocytes ) clear the majority of the organism burden and potently influence the nature and outcome of adaptive immune responses . the strong association of cd4 t - cell depletion or dysfunction with cryptococcosis is testimony to the particular importance of this immune cell to cryptococcal host defenses . for these reasons , studies aimed at understanding the interaction between professional antigen - presenting cells such as macrophages and cryptococcus will help define the steps leading to lasting immunity and correlate clinical outcome . in a recent issue of mbio , alanio et al . ( 5 ) show that the interaction of cryptococcus with host innate immunity is more complex than previously thought . using a large panel of c. neoformans organisms isolated from cerebrospinal fluid ( csf ) of patients with cryptococcal meningoencephalitis , clinical outcome was shown to rely not only on host immune factors but also on specific virulence properties of the organism . to accomplish this task , alanio et al . ( 5 ) devised an ingenious flow cytometry - based standardized macrophage assay that allowed quantification of both c. neoformans phagocytosis and intracellular replication . using a reference strain and a macrophage - like cell line , remarkably , based on these two metrics , the authors were able to segregate the cryptococcal isolates into distinct macrophage phenotypes that correlated with clinical and microbiological outcomes ( fig . patients with isolates that had both a high phagocytic index and high intracellular proliferation experienced a 5-fold - increased risk of death . on the other hand , patients with isolates exhibiting both a low phagocytic index and low intracellular proliferation had a 15-fold - increased risk of having positive csf cultures after 2 weeks of antifungal therapy . interestingly , phenotypic characteristics that have been associated with virulence in animal studies ( including capsule size , growth rate , chitin content , and urease and laccase activities ) did not correlate with clinical outcome . the intrinsic virulence of clinical isolates of cryptococcus neoformans was assessed by flow cytometry following interaction with macrophages . patients with isolates that had high phagocytic indices and increased cellular division had significantly increased mortality at 3 months . conversely , patients with isolates exhibiting low phagocytic indices and reduced cellular division were more likely to fail to sterilize their cerebrospinal fluid at 2 weeks . it is important to remember that because all the isolates in the study by alanio et al . ( 5 ) came from patients who had cryptococcal meningitis , they possess some degree of virulence . thus , rather than looking at virulence in the traditional sense , the authors have taken a fresh approach by looking at how the interaction of c. neoformans with macrophages in vitro correlates with outcomes in patients who are already infected and receiving antifungal drugs . the results suggest that a dynamic interplay between host innate cells and cryptococcus continues well after phagocytosis . in support of this concept , alanio et al . ( 5 ) also demonstrated that cryptococcus changes its gene expression profile within the macrophage phagolysosome . similarly to other intracellular pathogens , c. neoformans undergoes phenotypic and perhaps genotypic change as it adapts to life within the cell . the receptor - ligand interactions leading to phagocytosis , antifungal activity , and cytokine responses have been well characterized ( 6 ) . however , we are just beginning to understand the subsequent intracellular events occurring in the phagolysosomal compartment and the consequences of these events . it is clear that this period is not quiescent , and evidence is mounting that there is continued sampling of the pathogens by the innate immune cell . recent studies have shown that the toll - like receptors ( tlr ) , such as tlr 9 , continue to engage the fungal phagolysosome well beyond the initial surface events leading to phagocytosis ( 7 ) . data also suggest that the fungal surface evolves within the phagosomal compartment , presenting new and distinct antigens . this fact was highlighted in a study of aspergillus fumigatus conidia and hyphae where each morphotype was found to elicit a unique immune response ( 8) . ( 5 ) suggests that fungal pathogenesis is dependent not only on host response but also on the dynamic adaptations by the pathogen . other studies have also supported fungus - specific intracellular virulence factors . c. gattii isolated from the vancouver island outbreak has enhanced intracellular survival and proliferation in macrophages . in this example , microarray analysis identified the majority of the gene expression differences , as compared to control , to be centered on mitochondrial genes , which are thought to promote a better - fit state of survival in a phagolysosome ( 9 ) . our ability to understand how fungi sense and adapt to intracellular compartments will be important for deciphering the nature of the host - pathogen interaction . in order to answer these questions , new techniques will need to be developed to assess the activities within the phagosomal compartments of professional phagocytes . ( 5 ) is an excellent example of the ingenuity required to advance the field of fungal pathogenesis . moreover , the authors successful ability to correlate the macrophage phenotype of clinical isolates with patient outcomes has to - the - bedside implications . in the future , therapy for cryptococcosis may very well be individualized based on the phenotypic and genotypic characteristics of both the host and pathogen .

abstractwhile a myriad of studies have examined host factors that predispose persons to infection with the opportunistic fungal pathogen cryptococcus neoformans , comparatively little has been done to examine how virulence factor differences among cryptococcal isolates may impact outcome . in the recent report by alanio et al . ( a. alanio , m. desnos - ollivier , and f. dromer , mbio 2:e00158 - 11 , 2011 ) , novel flow cytometry - based techniques were employed to demonstrate an association between the phenotype of c. neoformans - macrophage interactions , as measured by phagocytosis and intracellular replication , and patient outcomes , as determined by positive cultures on therapy and survival . these experiments establish that the prognosis of patients with cryptococcosis is influenced by the phenotypic properties of the infecting fungal isolate .

we established and sampled 10 mark - recapture sites within and adjacent to rnbm during 20032007 . sampling of grids depended upon weather conditions , the purpose of the grid , and transitory human settlements . each mark - recapture grid consisted of an 11 11 array of trap stations spaced 10 m apart , each of which had 1 standard live trap ( h.b . sherman traps , tallahassee , fl , usa ) placed on the ground , and another in branches or vines 23 m above ground to capture arboreal species . grids were sampled for 8 nights , with at least 2 months between sampling sessions . rodents captured in the mark - recapture grids were individually marked with passive integrated transponder tags , and 100 l of blood was collected from the retroorbital sinus ( once per trapping session ) . animals were identified to species , age class , reproductive condition , sex , and weight and released . rodents were also collected in a series of traplines , each of which contained 50 traps placed 10 m apart . animals collected in traplines were killed , standard collecting information was recorded , and liver , lung , heart , kidney , muscle tissues , and blood specimens were collected . all samples were snap - frozen in liquid nitrogen , transported to the museum of texas tech university ( ttu ) , and stored at 80c . standard voucher specimens were prepared from these animals , and have or will be deposited in the museum of ttu or the museo nacional de historia natural del paraguay . all field protocols followed american society of mammologists guidelines for the use of wild mammals in research ( 6 ) , and were reviewed and approved by the ttu animal care and use committee . a total of 1,150 small mammals from > 20 species were captured , including 13 sigmodontine rodent species ( 1,140 animals ) ( technical appendix ) . the dominant rodent species in mbaracay were a. montensis ( 55.7% ) , necromys lasiurus ( hairy - tailed akodont ) ( 10.8% ) , c. callosus ( big laucha ) ( 6.5% ) , and o. fornesi ( fornes colilargo ) ( 6.3% ) . antibodies to hantavirus antigens were detected in blood specimens by using an indirect immunofluorescent antibody assay and irradiation - sterilized slides of vero e6 cells infected with andes virus as described ( 4 ) . seven species were antibody positive : a. montensis , n. lasiurus , o. fornesi , o. nigripes , oligoryzomys sp . , oryzomys megacephalus ( azara s broad - headed oryzomys sp . ) , and oxymycterus delator ( paraguayan hocicudo ) . antibodies to hantavirus antigens were 3 more abundant in blood samples from males than females ( technical appendix ) . total rna was extracted from antibody - positive blood clots from mark - recapture samples or lung tissue from killed animals . nested reverse transcription pcr was performed to amplify a 371-nt small ( s ) hantavirus rna segment ( 4 ) . hantavirus rna was detected in 23 a. montensis , 5 o. fornesi , 1 o. nigripes , and 1 oligoryzomys sp . of these animals , all but 2 a. montensis were males , which indicated that male rodents play the primary role in maintenance and transmission of hantavirus . a representative sample ( 15 a. montensis , 3 o. fornesi , 1 o. nigripes , and 1 oligoryzomys sp . pcr - amplified cdnas of a 1,014-nt amino terminus region of the s segment were purified by agarose gel electrophoresis and cloned into pcrii ( invitrogen , carlsbad , ca , usa ) ( 4,5 ) . m13 forward and reverse primers were used for sequencing . for sequence comparison and phylogenetic analysis , phylogeny reconstruction was conducted by using modeltest version 3.6 analysis ( http://darwin.uvigo.es/software/modeltest.html . ) , maximum - likelihood estimation , and bayesian inference ( figure 2 ) . phylogenetic tree based on bayesian analysis of the small ( s ) segment of american hantaviruses , paraguay , 20032007 . the tree is based on 1,014 nucleotides of partial s segment of north and south american hantaviruses . clades ( upper case letters ) , subclades ( numbers ) , and groups ( lower case letters ) are indicated on the left . alignment and editing of nucleotide sequences were conducted by using vector nti version 10.3.1 ( invitrogen , carlsbad , ca , usa ) . estimation of the suitable model of nucleotide substitution and phylogenetic analysis were conducted by using modeltest version 3.6 ( http://darwin.uvigo.es/software/modeltest.html ) , paup * 4.0b10 ( http://paup.csit.fsu.edu ) , and mrbayes version 3.1.2 ( http://mrbayes.csit.fsu.edu ) . two runs of 4 chains each ( 1 cold , 3 heated , temperature 0.20 ) were run for 1 million generations , and trees were sampled every 100 generations . convergence was assessed by using the average standard deviation in partition frequency values across independent analyses with a threshold value of 0.01 ; burn - in was set to 25% . nucleotide sequences of specimens collected at reserva natural del bosque mbaracay , departamento canindey , are indicated by acronyms of related viruses , rodent species , and collection numbers . are aai ( ape aime ) virus from paraguay [ dq345764 ] ; alpa ( alto paraguay ) virus from paraguay [ dq345762 ] ; andv_ah1 ( andes virus , strain ah-1 ) from argentina [ af324902 ] ; andv_chile ( andes virus , strain chile 9717869 ) [ af291702 ] ; andv_nort ( andes virus , strain nort ) from argentina [ af325966 ] ; arav ( araraquara virus ) from brazil [ af307325 ] ; arauv ( araucaria virus ) from brazil [ ay740633 ] ; bayv ( bayou virus ) from the united statesa [ l36929 ] ; bccv ( black creek canal virus ) from the united states [ l39949 ] ; bmjv ( bermejo virus ) from argentina [ af482713 ] ; bmjv - ebu ( bermejo virus , strain eembuc ) from paraguay [ dq345763 ] ; cajuru ( araraquara - like virus , strain cajuru ) from brazil [ ef571895 ] ; catv ( catacamas virus ) from honduras [ dq256126 ] ; cadv ( cano delgadito virus ) from venezuela [ dq285566 ] ; choclo virus from panama [ dq285046 ] ; elmcv ( el moro canyon virus ) from the united states [ u11427 ] ; htn-007 virus from peru [ af133254 ] ; ip37 ( itapa virus , strain 37 ) from paraguay [ dq345765 ] ; ip38 ( itapa virus , strain 38 ) from paraguay [ dq345766 ] ; jabor ( jab ) virus from brazil [ ef492471 ] ; juqv ( juquitiba virus ) from brazil [ ef492472 ] ; lecv ( lechiguanas virus ) from argentina [ af482714 ] ; mulv ( muleshoe virus ) from the united states [ u54575 ] ; lanv ( laguna negra virus ) from paraguay [ af005727 ] ; lscv ( limestone canyon virus ) from the united states [ af307322 ] ; mclv ( maciel virus ) from argentina [ af482716 ] ; maporal virus from venezuela [ ay267347 ] ; mglv ( monongahela virus ) from the united states [ u32591 ] ; nyv ( new york virus ) from the united states [ u47135 ] ; orov ( playa de oro virus ) from the mexico [ ef53407779 ] ; ornv ( oran virus ) from argentina [ af482715 ] ; paranoa virus from brazil [ ef576661 ] ; phv ( prospect hill virus ) from the united states [ u47136 ] ; prgv ( pergamino virus ) from argentina [ af482717 ] ; puuv from finland [ x61035 ] ; riomv ( rio mamore virus ) from bolivia [ u52136 ] ; rios ( rio segundo ) virus from costa rica [ genbank u18100 ( s segment ) ] ; snv_cc107 ( sin nombre virus , strain cc107 ) from the united states [ l33683 ] ; snv_nmr11 ( sin nombre virus , strain nmr11 ) from the united states [ l37904 ] ; and tulv ( tula virus ) from russia [ z30941 ] . olfo , oligoryzomys fornesi ; olni , o. nigripes ; olsp , oligoryzomys sp . ; akmo , akodon montensis ) . bayesian analysis based on the 1,014-nt sequence showed that all sequences from a. montensis formed a strongly supported clade , which included aaiv - related hantaviruses from itapa department , jabor virus ( jabv ) from southern brazil , and strains from rnbm in paraguay ( figure 2 , clade c1 ) . phylogenetic analyses identified 3 subclades representing virus sequences from animals in the rnbm , itapa , and southern brazil . this type of geographic clustering is similar to sin nombre related viruses in deer mice in north america ( 7 ) . all s segment sequences from a. montensis were closely related , with nucleotide sequence differences between rnbm strains and aaiv and jabv of 4% and 12% , respectively , and derived amino acid differences of 0% or 1% , respectively ( table 1 ) . * values above the diagonal are percentage nucleotide sequence similarities , and values below the diagonal are percentage amino acid sequence similarities . lanv , laguna negra virus ; riomv , rio mamore virus ; alpa , alto paraguay virus ; jabv , jabor virus ; aaiv , ape aime virus ; andv , andes virus ; bmjv - nebu , beremjo virus from eembuc ; ipv37 , itapa virus strain 37 ; juqv , juquitiba virus ; prgv , pergamino virus ; arav , araraquara virus . in contrast , all virus sequences from o. fornesi , o. nigripes , and oryzomys sp . at rnbm formed a strongly supported clade with viruses related to juquitiba virus ( juqv ) from brazil and itapa virus strain 37 , which was originally detected in o. nigripes from itapa department in eastern paraguay ( figure 2 , clade c2d ) . nucleotide sequence differences between juqv strains from rnbm and itapa virus strain 37 or juqv ( brazil ) were 5% or 4% , respectively , and derived amino acid differences were 0% ( table 1 ) . this clade is phylogenetically distinct from viruses that form the akodon montensis clade at rnbm and more closely related to andes ( clade c2b ) and bermejo - eembuc ( clade c2a ) viruses . this finding suggests that spillover infection of juqv - related viruses is actively occurring among oryzomyine rodent species at rnbm , as reported for other hantaviruses in oryzomyines ( 8) and other rodent hosts of old world hantaviruses ( 9,10 ) . additional data are needed to determine the primary oryzomyine reservoir of juqv and to better understand mechanisms by which spillover occurs . in addition to spillover infection of juqv among oryzomyine rodents , we identified 2 virus strains ( juqv and jabv ) in close proximity ( collected 20 m apart on the same grid in the same sampling session ) on 2 occasions , in sites separated by 30 km ( figure 1 ; table 2 ) . thus , these 2 distinct hantaviruses appear to be maintaining a sympatric status across a considerable expanse of landscape , rather than reflecting a temporary or localized phenomenon . we use the term sympatric to underscore that these viruses are in the same community and are near enough ( their rodent reservoirs ) to interact . * coexistence of hantaviruses in 2 rodent species at mark - recapture sites has been observed ( 1113 ) . serologic analyses in these studies would not have differentiated whether distinct strains of hantaviruses were co - circulating or active spillover infection was occurring among sympatric rodents at collection sites . recently , raboni et al . reported juqv circulating in 3 sympatric rodent species in southern brazil and 2 distinct hantaviruses ( jabora and juqv ) in 1 rodent species ( a. montensis ) ( 14 ) . we have not detected juqv in a. montensis in paraguay . to address host - jumping of hantaviruses among sympatric rodent species in rnbm and other regions in south america , such studies are critical to understanding evolutionary adaptation of hantaviruses in rodents in south america , the ability of these viruses to adapt to new rodent reservoirs , and their emergence and maintenance in the environment .

to explore geographic and host - taxonomic patterns of hantaviruses in paraguay , we established sampling sites in the mbaracay biosphere reserve . we detected jabor virus and itapa37/juquitiba related virus in locations 20 m apart in different years , which suggested sympatry of 2 distinct hantaviruses .

idiopathic osteolysis is a heterogeneous group of rare diseases in which there is a spontaneous , aggressive and extensive bone resorption . idiopathic osteolysis was first described in 1838 and again in 1872 by jackson ( 1 , 2 ) who reported a case of " boneless arm " . in 1955 , gorham and stout ( 3 ) defined a specific disease entity and reviewed 24 cases from the literature . the gorham - stout syndrome presents progressive idiopathic osteolysis of one bone or contiguous bones around one focus , without respect for joint boundaries . in 1985 , there have been a number of publications and case reports which do not appropriately fit into this classification ( 8 - 13 ) . we present a case of histologically proven massive osteolysis documented with plain radiography , ct and mri . to our knowledge , this is the first case in which multifocal , non - contiguous , osteolytic skip lesions without associated nephropathy and without a hereditary pattern is described in one extremity . a 38-year - old man is initially presented with pain and decreased strength in the left arm . laboratory results were normal including renal function tests ( urea , creatinine ) , thyroid and parathyroid hormone ( pth ) tests . the patient was treated with non - steroidal anti - inflammatory drugs but the pain was not relieved , the patient was referred for radiography 2 years later . during this time , radiography demonstrated almost complete non - contiguous osteolysis in the left elbow , proximal and distal radius , ulna , wrist , carpal bones , proximal and distal metacarpals and phalanges ( fig . static images from bone scintigraphy with 99 technecium methylene diphosphate ( 99mtc - mdp ) showed increased activities in the osteolysed regions ( fig . 1e , f ) . to define the extent of the osteolysis , ct examination was performed . mri demonstrated that the soft tissue masses and the affected bones were hypointense to isointense with muscle on t1-weighted imaging ( tr / te , 732/12 ) and were of heterogeneous signal intensity on t2-weighted imaging ( tr / te , 3986/99 ) ( fig . multi - site fine needle aspiration biopsy and tru - cut biopsy were undertaken ; bone specimens were taken from proximal , distal radius and proximal ulna for pathological examinations . this revealed fibrous tissue containing proliferated vascular structures replaced with bone trabeculae and bone marrow ( fig . the pathological specimen obtained at open biopsy of a lesion in the left proximal radius also confirmed such findings . gorham disease must be distinguished from osteolysis secondary to other pathologic processes , including the hereditary , metabolic , neoplastic , infectious and immunologic etiologies . common differential diagnoses included hereditary multicentric osteolysis , essential osteolysis with nephropathy , metastasis , osteomyelitis , and rheumatoid arthritis . the clinical findings are usually helpful when ruling out these diseases ( 5 , 6 ) . idiopathic osteolysis is a heterogeneous group of rare diseases in which there is spontaneous onset of mostly peripheral osteolysis without obvious reasons . ( 4 ) described the most commonly accepted classification with five types of idiopathic osteolysis . type i , hereditary multicentric osteolysis with dominant transmission is commonly seen at early childhood with complaints of spontaneous pain and swelling beginning in the hands and feet . type ii , hereditary multicentric osteolysis with recessive transmission is similar to type i except for possible associations with severe generalized osteoporosis . type iii , is a non - hereditary multicentric osteolysis with nephropathy appearing in childhood . type iv , gorham - stout syndrome is a monocentric syndrome which involve any part of the skeleton . rarely , two or more anatomic regions are affected , separated by normal osseous structures . apparently , any bone can be involved , including the small tubular bones of hands and feet , spine , skull and the mandible . the gorham - stout syndrome presents as progressive idiopathic osteolysis of one bone or contiguous bones around one focus without respect for joint boundaries . while contiguous bony involvement is typical , multiple foci with skip lesions have not been reported in the literature ( 14 ) . type v , winchester syndrome is a rare childhood carpotarsal osteolysis syndrome with autosomal recessive transmission . it is associated with contractures , shortness of stature , skin lesions , corneal clouding and osteoporosis without nephropathy . this patient , without any underlying conditions , was diagnosed as idiopathic osteolysis based on radiologic , morphological and clinical findings . however , our case does not readily fit in to the classification of idiopathic osteolysis according to hardegger et al . this case fits most closely into the type iv of hardegger classification , however multifocal , non - contiguous osteolysis with skip lesions differ from the usual characteristics of gorham syndrome . there have been increasing numbers of cases which can not accurately be placed within this classification ( 8 - 13 ) . white ( 8) reported four patients with multifocal osteolysis in association with severe skin lesions . beals and bird ( 9 ) observed one case of carpotarsal osteolysis without associated nephropathy and a hereditary pattern . ( 10 ) described a woman with osteolytic lesions of the metacarpal and metatarsal bones and terminal phalanges without a family history or renal involvement ; burkhard et al . ( 13 ) and tauro ( 11 ) noted cases of ' multicentric gorham - stout syndrome ' and downing et al . ( 12 ) published one case of multicentric osteolysis in both hands and feet , especially of the phalanges , associated with normal renal functions and with no genetic basis . we report a unique pattern of involvement in the upper left extremity with non - contiguous , multifocal osteolysis . this case is an addition to the enlarging group which can not be readily placed in the proposed classification of idiopathic osteolysis .

a patient with a 2-year history of pain in the left arm , and decreased strengths unrelieved by non - steroidal anti - inflammatory therapy , was being referred for repeating radiography . the radiologic examinations have demonstrated a unique pattern of non - contiguous osteolysis in the left elbow , proximal and distal radius , ulna , wrist , carpal bones , proximal and distal metacarpals and phalanges . multi - site biopsies were being performed and confirmed the diagnosis of massive osteolysis . to our knowledge , this is the first case in which multifocal , non - contiguous osteolysis with skip lesions without associated nephropathy and without a hereditary pattern is being described in one extremity .

the definitive implantation of a permanent impulse generator ( interstim 3023 , medtronic ) months after was performed after a temporary trial period of stimulation . she had regained weight , defecations continued with a good daily rhythm withouth straining or abdominal pain . the patient declared to be fully satisfied by the improvement to her quality of life . we performed an abdominal x - ray showing marked distension of the whole bowel , particularly of the colon . after a brief observation period , air fluid levels increased and the colon reached an enormous dilation . ct scan demonstrated no mechanical obstruction , there seemed to be a deteriorating intestinal pseudoocclusion ( ogilvie syndrome ) . the patient 's serious general condition and the presence of free air in the peritoneum forced us to operate on her . the length and volume of the colon were enormously increased and the wall was thin and perforated in the cecum . histological findings revealed a diffused and dense inflammatory infiltrate restricted to all myenteric plexuses ( fig . 1 , fig . 3 ) , associated with degenerative features and concurrent loss of ganglion cells . in some plexuses , ganglion cells were absent . inflammatory infiltrate was mixed in nature , being composed of lymphocytes , plasma cells and eosinophilis . 4 ) revealed that most lymphocytes were cd3 + and cd4 + and only scattered lymphocytes were cd8 + or cd20 + ; a normal number and distribution of interstitial cells of cajal stained with c - kit ( cd117 ) was demonstrated . no pathological changes were observed in the mucosa and submucosa , with the exception of a mild and specific inflammatory infiltrate in the colonic mucosa . the histological findings , and particularly the presence of the just described subclasses of lymphocytes , allowed the diagnosis of acute pseudoobstruction due to idiopathic immune - mediated myenteric ganglionitis. unfortunately surgery did not resolve the illness . after a period of relative healthiness , three months after the operation the abdomen was again dilated and the peristalsis stopped . the patient was given total parenteral nutrition and at the same time we attempted a course of pulse - dosed steroid treatment ( 100 mg i.v . we attempted a jejunostomy to obtain decompression of the small bowel , but the patient 's condition quickly worsened until she eventually died . although the cause of idiopathic severe chronic constipation has never been completely clarified , almost all pathological clues have been described to be of degenerative character and/or alterations of the neuropeptide levels . an underlying inflammatory neuropathy may be responsible for chronic constipation / megacolon , usually secondary as in chagas and paraneoplastic diseases . recently , idiopathic forms of chronic constipation / megacolon have been described with autoimmune enteric ganglionitis underlying chronic idiopathic constipation and subsequent megacolon . chronic intestinal pseudoobstruction , characterized by a loss or failure of intestinal peristalsis without organic causes occluding the lumen , appears to be characterized by frequent pseudoocclusive episodes , which can simulate mechanical occlusion . in chronic intestinal pseudoobstruction the clues affect either the myogenic and/or the neurogenic part of the intestinal wall in mitochondrial myopathies and in progressive systemic sclerosis ; more frequently an enteric ganglionitis can be secondary to different conditions , including inflammatory and paraneoplastic disease , or more rarely can be idiophatic . because of recent reports in literature [ 2 , 3 ] we speculate that in our case , ganglionitis of the myenteric plexus was present since the first observation with clinical signs of chronic constipation / megacolon with a subsequent dramatic change into an acute pseudoobstruction , because of the worsening of the autoimmune inflammation . pharmacological treatment of severe idiopathic chronic constipation ( and of chronic pseudoobstruction ) is reported in the scientific literature with various types of prokinetics : cisapride , metoclopramide , domperidone , octreotide , prostigmina , erythromycin , etc . however , the disordered motility is resistant to treatment and prokinetic drug therapy is generally disappointing . recently some encouraging results have been reported regarding the first experiences in treatment by sacral neuromodulation . if the cause of severe chronic constipation is an autoimmune ganglionitis , we can also attempt immunosuppressive therapy [ 4 , 5 ] . in hindsight , we should suspect intestinal ganglionitis as a cause of severe constipation . nowadays , a secure diagnosis concerning the existence of enteric ganglionitis can be confirmed only by histological sampling from full - thickness samples of the intestinal wall , and this is possible , except for the rectum , only in patients undergoing intestinal surgery . antineuronal circulating antibodies , such as the antineuronal antinuclear anna-1 , the anti - hu ( antineuronal nuclear antibody ) , the anti - yo ( anti purkinje cell protein cytoplasmatic antibody ) or other circulating antineuronal antibodies expressed in ganglionitis , are not reliable for diagnosis . however , in presence of any suspicion when intestinal occlusion is not secondary to mechanical causes , we should not hesitate to obtain a full - thickness biopsy of the intestinal wall , even if surgery is required . this way a short operation can avoid a long series of useless surgical procedures . once we have a firm diagnosis , patients can benefit immediately from immunosuppressive treatment with high - dosed steroids and/or immunosuppressive drugs , also in association with permanent sacral nerve stimulation , which can help patients with complete failure of intestinal motility . the reported case is exceptionally rare , in fact we found only one analogous case of mortality in a young adult due to acute intestinal pseudoocclusion with known primary visceral myopathy in the literature . however we can draw some conclusions : ( 1 ) when severe chronic constipation is present , we must consider that this can be due to an inflammatory process of the myenteric plexus and thus might evolve into severe pseudoocclusion . ( 2 ) only a full - thickness biopsy can offer a firm diagnosis : if we suspect ganglionitis we should try absolutely to obtain it . ( 3 ) with a firm diagnosis of ganglionitis we can treat the disease in time , not only during the exacerbation but also in the chronic stadium , by high doses of corticosteroids [ 4 , 5 ] , npt , etc . ( 4 ) in a part of rare perforative complications , surgery is not indicated in intestinal pseuodoocclusion , except for full - tickness biopsy or decompressive procedures .

inflammation of the myenteric plexus of the gastrointestinal tract is a very rare pathological condition , with few reports in the medical literature . this pathological condition causes atonic gut motor dysfunction and is principally secondary to other diseases , being reported nearly solely as a paraneoplastic phenomenon in neuroendocrine lung tumors , including small cell carcinomas or neuroblastomas . in addition it can also be associated with disorders of the central nervous system , although it has rarely been described in chagas disease . it has been named idiopathic myenteric ganglionitis because no apparent causes can be demonstrated . we report the clinicopathologic findings of an exceptional case of a young woman affected by severe chronic constipation suddenly changing into acute intestinal pseudoobstruction with dramatic evolution . relationships between ganglionitis , idiopathic constipation and acute intestinal pseudoobstruction as well as therapeutic implications are discussed .

in normal human epidermis , each melanocyte associates with approximately 35 keratinocytes to form an the keratinocytes in each unit exert considerable control over the behavior of the associated melanocyte , via interactions of cell - cell adhesion molecules and release of paracrine factors . ultraviolet radiation ( uvr ) uvr exposure enhances keratinocyte production of a wide variety of paracrine factors , including interleukins , growth factors , interferons , and chemokines , that may profoundly affect melanocyte and melanoma cell proliferation , migration , and gene expression [ 14 ] . within the cell , s100 proteins , in the form of heterodimers or homodimers , control the localization and activity of a variety of target proteins ; however , the s100 proteins s100a8 and a9 are also secreted from cells as calprotectin , a heterodimeric proinflammatory cytokine . calprotectin exerts its effects by binding to a variety of receptors on the surface of target cells , including toll - like receptor 4 ( tlr4 ) , the receptor for advanced glycation end - products ( rage ) , and extracellular matrix metalloproteinase inducer ( emmprin ) [ 57 ] . s100a8 and a9 are expressed at extremely low levels in unperturbed keratinocytes , but their expression is readily stimulated by a variety of insults , including uvr exposure . calprotectin is chemotactic for leukocytes and keratinocytes ; thus , it stimulates keratinocyte motility and recruits inflammatory cells to the skin . melanocytes and melanoma cells themselves do not appear to express significant levels of s100a8 and a9 , although they do express the calprotectin receptors rage , tlr4 , and emmprin [ 7 , 11 , 12 ] . based on these observations , we investigated a possible role for calprotectin in the paracrine activation of melanocytes and melanoma cells . normal human melanocytes ( nhm ) and normal human keratinocytes of neonatal origin were obtained from the american type culture collection ( manassas , va ) and were maintained in dermal basal medium supplemented with a melanocyte or keratinocyte growth kit ( atcc ) as appropriate . the wc62 melanoma cell line ( coriell institute , camden , nj ) , derived from the primary melanoma of a patient with metastatic disease , was grown in eagle 's modified essential medium ( atcc ) supplemented with 10% normal calf serum ( thermo scientific , hudson , nj ) . cells grown on coverslips were fixed briefly in paraformaldehyde and nonspecific binding was blocked with 5% bsa in tris - buffered saline containing 0.05% tween . coverslips were incubated with a rabbit polyclonal anti - rage primary antibody ( abcam , cambridge , ma ) diluted in blocking buffer for 2 hours at room temperature and then with alexa 488-labeled goat anti - rabbit fab secondary antibody ( life technologies , grand island , ny ) for 1 hour in the dark at room temperature . control slides were incubated with normal goat igg ( r&d systems , minneapolis , mn ) at a protein concentration equivalent to the primary antibody before addition of secondary antibody . cells were examined by confocal microscopy . to validate expression of rage , mrna was isolated from normal human keratinocytes , nhm , and wc62 cells using the qiagen rneasy kit followed by qiashredder treatment ( qiagen , valencia , ca ) . after reverse transcription and dnase treatment , rage and gapdh mrna levels were determined using taqman gene expression assays ( hs00542584_g1 and hs02758991_g1 , life technologies , grand island , ny ) as directed together with taqman universal master mix ( 4304437 , applied biosystems ) . amplifications were performed on a 7900ht real - time pcr analyzer ( applied biosystems ) . relative gene expression was calculated using the comparative c(t ) method , using gapdh expression to calculate delta ct and determining fold change compared to expression in normal human keratinocytes . to assay the effect of calprotectin on melanocyte and melanoma cell proliferation , we treated the cells with calprotectin , using recombinant s100a8 and s100a9 ( abnova , taiwan ) allowed to dimerize in vitro . cells were seeded at 15 10 cells per well in 96-well dishes in standard medium or medium containing calprotectin at a final concentration of 100 pg / ml s100a8 and 1 ng / ml s100a9 . on the succeeding 5 days , 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide ( mtt ) ( sigma , st . louis , mo ) dissolved in freshly prepared 0.1 n hcl in anhydrous isopropanol at a concentration of 5 mg / ml was added and cells were incubated for 3 hours . absorbance was measured at 570 nm . to evaluate the effect of calprotectin on migration , cells were plated into uncoated or matrigel - coated transwell chambers ( becton , dickinson and company biosystems , bedford , ma ) . lower chambers were filled with medium alone or with medium containing recombinant s100a8 and s100a9 . after 24 hours , upper chambers were cleaned of remaining cells and membranes were fixed and stained to visualize migrating cells ( diffquick kit , sigma , st . dye was extracted from transwell membranes using methanol and absorbance measured with a spectrophotometer at 550 nm . all migration assays were conducted in the presence of 10 g / ml mitomycin c ( sigma , st . as shown in figure 1(a ) , both cell types expressed detectable levels of surface rage , the canonical calprotectin receptor , in agreement with previous reports . expression of rage mrna was confirmed by qrt - pcr ( figure 1(b ) ) . compared to normal human keratinocytes , nhm expressed more than twice the level and wc62 cells expressed a comparable level of rage mrna . both immunofluorescence and qrt - pcr results suggest higher expression of rage in nhm than in wc62 cells . as shown in figure 2(a ) , a significant difference in cell number between control and calprotectin - treated cells appeared at 4 days of treatment in nhm and at 2 days of treatment in wc62 cells . calprotectin stimulated a maximum increase in cell number of 1.8-fold in nhm and 2.5-fold in wc62 cells compared to control cells . movement through untreated membranes ( migration ) and through matrigel - coated membranes ( invasion ) was significantly enhanced by 2- to 3-fold in both melanocytes and melanoma cells treated with calprotectin compared to control cells ( figure 2(b ) ) . it is important to note that these studies do not indicate that rage is the calprotectin receptor responsible for the effect of calprotectin on nhm and wc62 melanoma cell proliferation and migration , only that these cells express at least one calprotectin receptor . another study has shown that overexpression of rage in a human melanoma cell line is associated with not only increased migration but also reduced proliferation in contrast with our study , . other calprotectin receptors , including tlr4 and emmprin , may play important roles in mediating calprotectin effects on cells of melanocytic origin . indeed , a recent study demonstrates that s100a9 , probably also calprotectin , is a ligand for emmprin and that emmprin overexpression enhances and emmprin blockade suppresses the migration of melanoma cell lines in response to s100a9 treatment . however , it does not appear that emmprin is expressed at appreciable levels on normal human melanocytes . it is clear from these studies that exogenous calprotectin can activate melanocytes and melanoma cells to proliferate and to migrate . thus , calprotectin appears to be one of the numerous paracrine factors released by uvr - exposed keratinocytes that may promote melanomagenesis . blocking the induction , release , or activity of calprotectin may thus represent a potential preventative or therapeutic strategy for melanoma . tlrs and rages , receptors for calprotectin and for a variety of other ligands , are being considered as therapeutic targets for a wide array of diseases , including sepsis , asthma , and diabetes [ 19 , 20 ] . a number of approaches to blocking signaling through these receptors are under investigation and may prove valuable in preventing or treating melanoma . however , further studies are clearly needed to determine the importance of calprotectin in melanoma development and progression and the therapeutic benefit of blocking its activity . we have shown that melanocytes and melanoma cells express rage , the canonical calprotectin receptor , and that calprotectin stimulates these cells to proliferate and to migrate . because calprotectin activates melanocytes and melanoma cells , it is a potential target for intervention in melanomagenesis .

calprotectin , a heterodimer of s100a8 and s100a9 , is a proinflammatory cytokine released from ultraviolet radiation - exposed keratinocytes . calprotectin binds to toll - like receptor 4 , the receptor for advanced glycation end - products , and extracellular matrix metalloproteinase inducer on target cells to stimulate migration . melanocytes and melanoma cells produce little if any calprotectin , but they do express receptors for the cytokine . thus , keratinocyte - derived calprotectin has the potential to activate melanocytes and melanoma cells within the epidermis in a paracrine manner . we examined the ability of calprotectin to stimulate proliferation and migration in normal human melanocytes and melanoma cells in vitro . we first showed , by immunofluorescence and quantitative rt - pcr , that the melanocytic cells employed expressed a calprotectin receptor , the receptor for advanced end - products . we then demonstrated that calprotectin significantly enhanced proliferation , migration , and matrigel invasion in both normal human melanocytes and melanoma cells . thus , calprotectin is one of the numerous paracrine factors released by ultraviolet radiation - exposed keratinocytes that may promote melanomagenesis and is a potential target for melanoma prevention or therapy .

in this study , we gathered the total sample size is 200 of mentally retarded students in north of tehran ( districts 1 , 2 , 3 ) and the sample size was determined according to previous research ( 11 - 12 ) and also sample size for preliminary evaluation of reliability and validity test . data were analyzed by cronbach 's alpha coefficient for internal consistency and linear multivariate regression for construct validity ( since this scale has seven items and each item measures comments and feedback of the person about one area of personal well - being , the designers ( 16 ) of this scale believe that the individual score in each area plays an important role in the distribution of overall life satisfaction scores ( the first single item and separated from the other seven items ) . therefore , the designers have recommended linear multivariate regression analysis for validity assessment in which individual score in single item of overall life satisfaction as the dependent variable and the seven items scales as prediction variables are considered ) . after obtaining an authorization for the study from tehran 's exceptional education organization , we referred to sayyad shirazi girl 's exceptional school and piroozi boy 's exceptional school located in north of tehran . in these schools , a total of 200 mentally retarded students were selected of morning shift from 8 to 12 and afternoon shift from 2 to 5 and were studied in the counseling room . during this period , eight meetings with the mothers were held before research on their children and after describing the aims of the research , all mothers signed a written consent form . the test in this research was the personal well- being index- cognitive disability scale ( 16 ) that was conducted for mentally retarded students.this indicator consists of five stages . at the beginning of the test , some questions are asked about agreement responses that determine whether the student should continue the test or not . if the student succeeds , he/ she will enter the next stage which is the testing of likert scale sufficiency and the student should numerate from zero to ten.then , the student enters the total happiness scale of personal well- being index that consists of eight questions in two parts . the first part asks about life satisfaction : are you satisfied with your life ? ; and the second part consists of questions regarding the following issues : 1 ) life standards and conditions ; 2 ) health ; 3 ) achievements in life ; 4 ) relationships with others ; 5 ) safety and peace in life ; 6 ) dependence and membership among others ; 7 ) future safety.the student responses to each of the eight items with likert scale of zero to ten , with each number showing the following states : zero : completely dissatisfied and sad ; five : average ; ten : completely satisfied and happy ; between zero and five : completely dissatisfied and sad to average ; and between five and ten : average to completely satisfied and happy . if the student does not succeed at the likert scale stage , another three stage test will be used for him which ( cube test ) consists of three two cube , three- cube and five- cube stages . the fourth stage is to match with the abstract reference ( step building by cubes ) that consists of three stages : two steps , three steps and five steps . the fifth stage is to match with the abstract reference ( images stage ) in which the child shows his / her satisfaction in each item with regard to the images ( two faces , three faces and five faces ) ( 16 ) . the construct validity of this indicator questions was 0.78 with respect to satisfaction scale ; and according to 12 studies conducted in australia , the maximum changes of the reliability was 3.1 percent of personal well- being and in australia and other world regions , cronbach 's alpha coefficient was 0.70- 0.85(16).the correlation between the questions was 30%-55% and the sum of questions correlation was at least 50% in pwi - a version ( 10 ) . all the questions of personal well - being index- cognitive disability were translated and revised based on ( comqol ) and pwi protocol . then , the translated text was back translated , and the two forms were compared . finally , the translated text was revised and given to several professors holding a phd in psychology ; and their professional suggestions were included in the translations . to identify the face validity and initial survey , the persian version of the personal well - being index- cognitive disability scale in this study , we gathered the total sample size is 200 of mentally retarded students in north of tehran ( districts 1 , 2 , 3 ) and the sample size was determined according to previous research ( 11 - 12 ) and also sample size for preliminary evaluation of reliability and validity test . data were analyzed by cronbach 's alpha coefficient for internal consistency and linear multivariate regression for construct validity ( since this scale has seven items and each item measures comments and feedback of the person about one area of personal well - being , the designers ( 16 ) of this scale believe that the individual score in each area plays an important role in the distribution of overall life satisfaction scores ( the first single item and separated from the other seven items ) . therefore , the designers have recommended linear multivariate regression analysis for validity assessment in which individual score in single item of overall life satisfaction as the dependent variable and the seven items scales as prediction variables are considered ) . after obtaining an authorization for the study from tehran 's exceptional education organization , we referred to sayyad shirazi girl 's exceptional school and piroozi boy 's exceptional school located in north of tehran . in these schools , a total of 200 mentally retarded students were selected of morning shift from 8 to 12 and afternoon shift from 2 to 5 and were studied in the counseling room . during this period , eight meetings with the mothers were held before research on their children and after describing the aims of the research , all mothers signed a written consent form . the test in this research was the personal well- being index- cognitive disability scale ( 16 ) that was conducted for mentally retarded students.this indicator consists of five stages . at the beginning of the test , some questions are asked about agreement responses that determine whether the student should continue the test or not . if the student succeeds , he/ she will enter the next stage which is the testing of likert scale sufficiency and the student should numerate from zero to ten.then , the student enters the total happiness scale of personal well- being index that consists of eight questions in two parts . the first part asks about life satisfaction : are you satisfied with your life ? ; and the second part consists of questions regarding the following issues : 1 ) life standards and conditions ; 2 ) health ; 3 ) achievements in life ; 4 ) relationships with others ; 5 ) safety and peace in life ; 6 ) dependence and membership among others ; 7 ) future safety.the student responses to each of the eight items with likert scale of zero to ten , with each number showing the following states : zero : completely dissatisfied and sad ; five : average ; ten : completely satisfied and happy ; between zero and five : completely dissatisfied and sad to average ; and between five and ten : average to completely satisfied and happy . if the student does not succeed at the likert scale stage , another three stage test will be used for him which ( cube test ) consists of three two cube , three- cube and five- cube stages . the fourth stage is to match with the abstract reference ( step building by cubes ) that consists of three stages : two steps , three steps and five steps . the fifth stage is to match with the abstract reference ( images stage ) in which the child shows his / her satisfaction in each item with regard to the images ( two faces , three faces and five faces ) ( 16 ) . the construct validity of this indicator questions was 0.78 with respect to satisfaction scale ; and according to 12 studies conducted in australia , the maximum changes of the reliability was 3.1 percent of personal well- being and in australia and other world regions , cronbach 's alpha coefficient was 0.70- 0.85(16).the correlation between the questions was 30%-55% and the sum of questions correlation was at least 50% in pwi - a version ( 10 ) . all the questions of personal well - being index- cognitive disability were translated and revised based on ( comqol ) and pwi protocol . then , the translated text was back translated , and the two forms were compared . finally , the translated text was revised and given to several professors holding a phd in psychology ; and their professional suggestions were included in the translations . to identify the face validity and initial survey , the persian version of the personal well - being index- cognitive disability scale two hundred mentally retarded students had a minimum age of 9 and a maximum age of 21 years and their mean age was 14.49 2.66 . demographic characteristics of mentally retarded students cronbach 's alpha coefficient the seven items of personal well - being index- cognitive disability was between 0.56 - 0.62.besides , studying the internal consistency of these items showed that all the seven items were correlated with the total score and their scores averages were similar to each other . this indicates that the test 's questions have reliability with regard to evaluation of a common feature . cronbach 's alpha for mentally retarded students it should be mentioned that one hundred of mentally retarded students participated in test - retest reliability study . the results are presented in table 3 . also , the results of coefficients test - retest using the pearson correlation between initial and retest scores were significant at 0.001 level . coefficient alpha and test - retest results of kmo and bartlett 's test showed that the sample size was sufficient for analysis . bartlett test of sphericity resulted in a chi - square value of equal to 818.974 with 406 degrees of freedom that was significant in an alpha level of 0.001 . as previously mentioned , since this scale has seven items and each item measures comments and feedback of the person about one area of personal well - being , the designers of this scale believe that the individual score in each area plays an important role in the distribution of overall life satisfaction scores ( the first single item and separated from the other seven items ) . therefore , the designers have recommended linear multivariate regression analysis for validity assessment of personal well - being index - cognitive disability ( 16 ) in which individual score in single item of overall life satisfaction as the dependent variable and the seven items scales as prediction variables are considered . and results of linear multivariate regression analysis with enter method showed that the scale items can predict 67% of distribution of overall life satisfaction . anova - linear multivariate regression by enter method for mentally retarded students besides , there was a significant relation between the questions of part one and the questions of part two , after implementation of linear multivariate regression analysis , regression coefficients were calculated for the seven items and the results showed that the among the seven items of personal well - being index- cognitive disability scale , items 2 and 7 has significant contribution to the prediction of satisfaction with life in mentally retarded students in north of tehran . cronbach 's alpha coefficient the seven items of personal well - being index- cognitive disability was between 0.56 - 0.62.besides , studying the internal consistency of these items showed that all the seven items were correlated with the total score and their scores averages were similar to each other . this indicates that the test 's questions have reliability with regard to evaluation of a common feature . cronbach 's alpha for mentally retarded students it should be mentioned that one hundred of mentally retarded students participated in test - retest reliability study . the results are presented in table 3 . also , the results of coefficients test - retest using the pearson correlation between initial and retest scores were significant at 0.001 level . coefficient alpha and test - retest results of kmo and bartlett 's test showed that the sample size was sufficient for analysis . bartlett test of sphericity resulted in a chi - square value of equal to 818.974 with 406 degrees of freedom that was significant in an alpha level of 0.001 . as previously mentioned , since this scale has seven items and each item measures comments and feedback of the person about one area of personal well - being , the designers of this scale believe that the individual score in each area plays an important role in the distribution of overall life satisfaction scores ( the first single item and separated from the other seven items ) . therefore , the designers have recommended linear multivariate regression analysis for validity assessment of personal well - being index - cognitive disability ( 16 ) in which individual score in single item of overall life satisfaction as the dependent variable and the seven items scales as prediction variables are considered . and results of linear multivariate regression analysis with enter method showed that the scale items can predict 67% of distribution of overall life satisfaction . anova - linear multivariate regression by enter method for mentally retarded students besides , there was a significant relation between the questions of part one and the questions of part two , after implementation of linear multivariate regression analysis , regression coefficients were calculated for the seven items and the results showed that the among the seven items of personal well - being index- cognitive disability scale , items 2 and 7 has significant contribution to the prediction of satisfaction with life in mentally retarded students in north of tehran . this is the first study which evaluates the validity and reliability of the personal well - being index- cognitive disability on mentally retarded students in north of tehran . the results confirmed the reliability and validity for the personal well - being index- cognitive disability in mentally retarded students of exceptional schools in north districts of tehran . findings of this study are relatively harmonious with studies of lau and cummins ( 10 ) , miller ( 12 ) , davey ( 17 ) and davern ( 18 ) . also , the results of this study is relatively harmonious with that of diener , emmons , larsen , griffin ( 13 ) and tomas ( 14 ) , which reported a correlation of 0.78 between the satisfaction and life scale . lau and cummins ( 10 ) reported the eight domains form to be a single stable factor which accounts for about 50% of the variance in australia and other countries . overall , pwb is an important construct , as its low levels can lead to depression or social isolation ( 19 , 20 ) . in this regard , identification of factors that maintain high levels of swb such as community connectedness are important for developing strategies to prevent problems associated with low levels of swb . with regard to the extracted data from the results of this research , it can be concluded that mentally retarded students in north districts of tehran had lower emotional , mental and behavioral and , in general , improper reactions to the environmental and social desirable stimulus . therefore , using efficient and effective strategies and ability of researchers to control interfering factors have resulted in validity and reliability of this indicator in north districts of tehran . in addition , the studied children and teenagers have experienced similar mental conditions , family and economic stresses and similar environmental conditions . they accepted the facts and tried to solve their problems , engaged in group programs such as collective game , expression of events , memoirs and short stories and interacted with friends and got involved in physical activities and cognitive programs such as counting digits down , and also sports . further , they were not disappointed with undesirable attitude and response of people and society . they , with a heart full of hope , did not think about their weaknesses and disabilities and tried to see a light in the darkness and tried to be active and dynamic and to think about their capabilities . parents respect increased these children 's self- respect and created internal security and emotional immunity against cultural and social plagues . in general , it can be concluded that the personal well - being index- cognitive disability on mentally retarded students of north districts of tehran is a valid and reliable scale . therefore , we suggest that the experts of exceptional education and psychology clinics to use this index to identify the well - being of mentally retarded students . as a limited group of mentally retarded students were enrolled in this study , these findings can not be generalized .

objectivehaving a good quality of life has always been desirable for humans , and the concept of a good life and the ways of achieving it have become important over the years . personal wellbeing is the mental component of quality of life . thus , the current study was conducted to assess the reliability and validity of the personal well - being index- cognitive disability on mentally retarded students.method200 mentally retarded students in north districts of tehran ( districts 1 , 2 and 3 ) were selected by systematic random sampling . the collected data using personal well - being index- cognitive disability was analyzed by cronbach 's alpha coefficient for internal consistency and linear multivariate regression for construct validity.resultsresults confirmed the reliability and validity for the personal well - being index- cognitive disability in mentally retarded students of exceptional schools . studying the internal consistency of seven items showed that all the items were correlated with the total score and their scores averages were similar to each other . this indicates that the test 's questions have reliability with regard to evaluation of a common feature and results showed personal well - being index- cognitive disability had the most extensive coverage of construct validity.conclusionpersonal well - being index- cognitive disability scale could be applied to measure personal wellbeing in mentally retarded students .

the danish hernia database is subdivided into an inguinal hernia database and a ventral hernia database . this article refers to the danish ventral hernia database ( dvhd ) that includes repairs of all abdominal wall hernias excluding inguinal and femoral hernias . thus , the database includes all primary ( umbilical , epigastric , and others ) as well as secondary hernias ( incisional and parastomal ) . with reference to ventral hernia repair , the database is designed to provide national surveillance of current danish surgical practice and clinical postoperative outcomes . this database facilitates mapping of the incidence of surgery , aspects of surgical techniques , and postoperative complications . it is specifically intended that the data generated by the database must contribute to reduction of postoperative morbidity and hernia recurrence . moreover , it seeks to evaluate new treatment strategies and facilitate nationwide implementation of evidence - based treatment strategies . the database includes all adult ( 18 years ) danish patients operated on under elective or emergency conditions for ventral hernia in a danish surgical department ( public , n=22 or private , n=10 ) . all centers contributed with registration of hernia procedures since the launch of the database in 2007 . data entry is most often performed by the operating surgeon immediately after surgery on a secured website using the patient s unique danish civil registration number . the variables that are recorded include demographic data , detailed hernia description , and technical aspects related to the surgical repair ( table 1 ) . data entry is kept simple and uniform , and it is possible to monitor different variables depending on the type of hernia repair . in order to eliminate missing data , the system does not accept upload of insufficient registrations . data registration is mandatory and has been validated against patient files ( gold standard ) demonstrating more than 94% overall agreement on parameters , such as type of hernia , hernia size , mesh product , and mesh fixation.1 a continuous follow - up is performed by a preprogrammed and automatic merge of data from dvhd with data from the danish national patient register ( dnpr),2 which holds data from all patient contacts , to the danish health care providers ( private and public ) , including operations . this merging of data relies on the unique danish civil registration number of the patient . this combination of data is performed on a monthly basis to provide quality assessment given by four defined clinical indicators ( table 2 ) . such measures may include reoperation for hernia recurrence , specific diagnoses , and other surgical procedures . since the establishment of dvhd in 2007 , there has been an intensive scientific activity resulting in national collaboration and many international publications within the field ( http://www.herniedatabasen.dk/index.php/downloads/litteraturliste/ ) . based on the combination of the prospectively collected data from the dvhd and follow - up in the dnpr , high volume data have been analyzed and have provided evidence for surgical improvement.3,4 high complication rates have been documented for all types of elective ventral hernia repairs3,58 and after emergency repairs , which are associated with up to 15-fold increase of morbidity.8,9 the nationwide studies have pointed out several areas for surgical improvement for the different types of ventral hernias to reduce risk for early and late complications and recurrence . these include the advantageous application of a sublay mesh during open repair of an incisional hernia7 and use of a mesh for open umbilical or epigastric hernia repair to reduce recurrence.10 combining data from the dvhd with data from patient files , patient questionnaires , and clinical examinations revealed that mesh repairs reduce the risk for recurrence significantly,7 even in small repairs and without increased risk of pain.10,11 additionally , large - size data from dvhd have shown that laparoscopic intraperitoneal mesh fixation with absorbable as compared with titanium tacks is associated with an increased risk of hernia recurrence . contrary to previous expectations by manufacturers of mesh fixation devices , there was no difference in long - term pain between patients receiving absorbable tacks and patients operated on with titanium tacks.12 data from dvhd have been combined with information obtained from dnpr and clinical examinations to determine the cumulated incidence difference between a recurrent hernia diagnosed by clinical examination and reoperation for hernia recurrence . clinical recurrences were four- to fivefold higher than the number of reoperations for recurrence.13 earlier reports based on reoperation rates for hernia recurrence thus severely underestimate the real frequency of hernia recurrence . the link between specific databases according to a unique danish civil registration number for each patient allows for combining scientifically interesting data from various databases . findings were recently published combining data from dvhd with information from the danish inguinal hernia database . interestingly , patients operated on for a direct or recurrent inguinal hernia as compared with surgery for an indirect inguinal hernia were significantly more prone to ventral hernia repair suggesting a specific predisposition to herniogenesis.14 it has been suggested in small studies that abdominal aortic aneurism shares common pathological mechanisms with the development of incisional hernia . merging data from dvhd , the danish vascular surgery registry and dnpr allowed for the largest study ever in this field . it demonstrated that both obesity and aortic reconstruction due to abdominal aortic aneurism as compared with aortoiliac occlusive disease significantly increased the risk of subsequent incisional hernia repair.15 however , contrary to findings of previous low - powered studies , the presence of abdominal aortic aneurism in a large screening population was not associated with diagnosis of inguinal hernia.16 the prospective danish hernia databases were among the first in the field and the only ones requiring mandatory registration by all surgeons conducting hernia repairs . it is crucial for the quality of the databases that a high registration rate is maintained . this is facilitated by a number of ongoing initiatives , including meetings for surgeons providing feedback information twice annually . moreover , lists of unregistered procedures are generated on a monthly basis and distributed to the surgical centers . finally , a national report is published every year on main statistics and center - based reporting rates to the registries . the national rate of registration to the dvhd is 80% as compared to the rate for the danish inguinal hernia database that reaches 90% . there is an ongoing initiative from the steering committee of dvhd to motivate all surgeons to report their operations in order to increase the national registration rate . moreover , there is political focus on annual reports which are sent to the administrators and chairman of each surgical center informing on the local registration rate . however , there are no judicial options to increase the registration rate . the data collected from the hernia databases combined with information from dnpr and other specific databases provide scientific evidence for revised recommendations and guidelines following discussion between participating surgeons at regular meetings . based on the combination of the prospectively collected data from the dvhd and follow - up in the dnpr , high volume data have been analyzed and have provided evidence for surgical improvement.3,4 high complication rates have been documented for all types of elective ventral hernia repairs3,58 and after emergency repairs , which are associated with up to 15-fold increase of morbidity.8,9 the nationwide studies have pointed out several areas for surgical improvement for the different types of ventral hernias to reduce risk for early and late complications and recurrence . these include the advantageous application of a sublay mesh during open repair of an incisional hernia7 and use of a mesh for open umbilical or epigastric hernia repair to reduce recurrence.10 combining data from the dvhd with data from patient files , patient questionnaires , and clinical examinations revealed that mesh repairs reduce the risk for recurrence significantly,7 even in small repairs and without increased risk of pain.10,11 additionally , large - size data from dvhd have shown that laparoscopic intraperitoneal mesh fixation with absorbable as compared with titanium tacks is associated with an increased risk of hernia recurrence . contrary to previous expectations by manufacturers of mesh fixation devices , there was no difference in long - term pain between patients receiving absorbable tacks and patients operated on with titanium tacks.12 data from dvhd have been combined with information obtained from dnpr and clinical examinations to determine the cumulated incidence difference between a recurrent hernia diagnosed by clinical examination and reoperation for hernia recurrence . clinical recurrences were four- to fivefold higher than the number of reoperations for recurrence.13 earlier reports based on reoperation rates for hernia recurrence thus severely underestimate the real frequency of hernia recurrence . the link between specific databases according to a unique danish civil registration number for each patient allows for combining scientifically interesting data from various databases . findings were recently published combining data from dvhd with information from the danish inguinal hernia database . interestingly , patients operated on for a direct or recurrent inguinal hernia as compared with surgery for an indirect inguinal hernia were significantly more prone to ventral hernia repair suggesting a specific predisposition to herniogenesis.14 it has been suggested in small studies that abdominal aortic aneurism shares common pathological mechanisms with the development of incisional hernia . merging data from dvhd , the danish vascular surgery registry and dnpr allowed for the largest study ever in this field . it demonstrated that both obesity and aortic reconstruction due to abdominal aortic aneurism as compared with aortoiliac occlusive disease significantly increased the risk of subsequent incisional hernia repair.15 however , contrary to findings of previous low - powered studies , the presence of abdominal aortic aneurism in a large screening population was not associated with diagnosis of inguinal hernia.16 the prospective danish hernia databases were among the first in the field and the only ones requiring mandatory registration by all surgeons conducting hernia repairs . it is crucial for the quality of the databases that a high registration rate is maintained . this is facilitated by a number of ongoing initiatives , including meetings for surgeons providing feedback information twice annually . moreover , lists of unregistered procedures are generated on a monthly basis and distributed to the surgical centers . finally , a national report is published every year on main statistics and center - based reporting rates to the registries . the national rate of registration to the dvhd is 80% as compared to the rate for the danish inguinal hernia database that reaches 90% . there is an ongoing initiative from the steering committee of dvhd to motivate all surgeons to report their operations in order to increase the national registration rate . moreover , there is political focus on annual reports which are sent to the administrators and chairman of each surgical center informing on the local registration rate . the data collected from the hernia databases combined with information from dnpr and other specific databases provide scientific evidence for revised recommendations and guidelines following discussion between participating surgeons at regular meetings . the majority of core structural tasks within the database is controlled and maintained by government organizations ( regionernes kliniske kvalitetsudviklings program ) . data access : each participating center may obtain their data . in order to obtain data from external centers , approval is required from the danish data protection agency and regionernes kliniske kvalitetsudviklings program . the registration requires a limited contribution from all surgeons and is an excellent tool for observing changes over time , including adjustment of several confounders . the registration system permits post hoc subgrouping of patients at high risk and may investigate even rare clinical events . finally , this national database registry has led to a high number of scientific publications in recent years .

aimthe danish ventral hernia database ( dvhd ) provides national surveillance of current surgical practice and clinical postoperative outcomes . the intention is to reduce postoperative morbidity and hernia recurrence , evaluate new treatment strategies , and facilitate nationwide implementation of evidence - based treatment strategies . this paper describes the design and purpose of dvhd.study populationadult ( 18 years ) patients with a danish civil registration number and undergoing surgery under elective or emergency conditions for ventral hernia in a danish surgical department from 2007 and beyond . a total of 80% of all ventral hernia repairs performed in denmark were reported to the dvhd.main variablesdemographic data ( age , sex , and center ) , detailed hernia description ( eg , type , size , surgical priority ) , and technical aspects ( open / laparoscopic and mesh related factors ) related to the surgical repair are recorded . data registration is mandatory . data may be merged with other danish health registries and information from patient questionnaires or clinical examinations.descriptive datamore than 37,000 operations have been registered . data have demonstrated high agreement with patient files . the data allow technical proposals for surgical improvement with special emphasis on reduced incidences of postoperative complications , hernia recurrence , and chronic pain.conclusiondvhd is a prospective and mandatory registration system for danish surgeons . it has collected a high number of operations and is an excellent tool for observing changes over time , including adjustment of several confounders . this national database registry has impacted on clinical practice in denmark and led to a high number of scientific publications in recent years .

a 10-year - old japanese girl presented with an 8-month history of pigmented lesion on the sole of the right foot . examination showed a rhomboid - shaped brown macule with keratotic scale , 4x3 mm in size , on the lateral center side of the sole ( figure 1 ) . dermoscopic examination revealed that a number of black dots and globules were evenly distributed on the ridges of the skin , marking an area of symmetrical brown pigmentation ( figure 2 ) . on the periphery , a streak - like arrangement of black dots / globules on the brown pigmentation was observed along the ridges , simulating a starburst pattern . histological examination showed epidermal hyperplasia and a symmetrical , wedge - shaped compound melanocytic lesion ( figure 3a ) . junctional and intradermal nests were well circumscribed , and consisted of a mixture of large spindle and epithelioid cells . none of the nevus cells were atypical , and maturation of the cells with increasing depth was observed ( figure 3b ) . upward epidermal spread of a single nevus cell or small groups of cells was absent . from these findings transepidermal elimination of nevus cell nests was seen and there were small groups of degenerated melanin - laden cells in the cornified layer ( figure 3c ) . the nevus cells , including the degenerated cells in the cornified layer , were s-100 protein positive . masson fontana stain revealed fine melanin deposits in the nevus cells of the junctional and intradermal nests , as well as heavy melanin deposits in the small groups of degenerated cells in the cornified layer ( figure 3d ) . spitz nevus , also known as spindle and epithelioid cell nevus , is found primarily on the lower extremities , followed by the trunk and upper extremities . a report on japanese patients demonstrated that spitz nevus on glabrous skin represents 2% of all spitz nevi . thus , little is known about the dermoscopic findings of spitz nevus on the plantar aspect due to its rarity . dermoscopic examination of a pigmented spitz nevus on the sole of the foot by hatta et al . revealed a central black astructural area , large peripheral blue - black globules , and streaks along the ridges of the skin marking simulating starburst pattern . the dermoscopic finding in the present case of black dots and globules on the ridges in the peripheral area is similar to the finding of that previous published case . however , the number of black dots and globules in the area of diffuse brown pigmentation in the present case are very different from the dermoscopic finding of that previous case . in the present case , fine melanin deposits in the junctional and intradermal nests may correspond to the dermoscopic finding of brown pigmentation , and heavy melanin deposits in the groups of degenerated cells in the cornified layer may correspond to the black dots on dermoscopy . these two components of melanin deposits constitute the dermoscopic pattern found in the present case . the small groups of degenerated melanin - laden cells in the cornified layer may come from the junctional nevus cell nests through transepidermal elimination . transepidermal elimination is infrequently observed in spitz nevus , but this phenomenon may provide a unique pattern on dermoscopy , as seen in the present case . involution as the natural evolution of spitz nevi on the face , extremities , and trunk has been reported . in the regression of pigmented skin lesions such as melanoma , fibrosis , melanosis , and numerous telangiectasis are histopathologically observed , but the combination of these features is not found in spitz nevi . however , the transepidermal elimination observed in the present case may be related to this mechanism . dermoscopy is a useful tool for differentiating early melanomas from benign melanocytic nevi on acral volar skin . parallel ridge pattern is a highly specific dermoscopic pattern of malignant melanoma , including melanoma in situ on acral volar skin . an irregular diffuse pigmentation pattern is also highly specific to malignant melanoma on acral volar skin . in contrast , a parallel furrow pattern is the most prevalent pattern in melanocytic nevi on acral volar skin . in the present case as well as in the case of hatta thus , pigmented spitz nevus on the sole of the foot may be a differential diagnosis of malignant melanocytic lesion . however , dermoscopic patterns of the present case , including the equal and symmetrical distribution of black dots and globules in the area of the brown pigmentation , are different from the patterns of malignant melanoma on acral volar skin . the dermoscopic pattern of the present case may be novel , and this report may help in the diagnosis of melanocytic lesions on acral volar skin .

a 10-year - old japanese girl presented with a rhomboid - shaped brown macule , 4x3 mm in size , on the sole of the right foot . dermoscopic examination revealed a number of black dots and globules on the ridges of the skin , marking an area of symmetrical brown pigmentation . on the periphery , a streak - like arrangement of black dots / globules on the brown pigmentation was observed along the ridges , simulating a starburst pattern . the lesion was excised and histological examination showed a symmetrical wedge - shaped compound melanocytic lesion that consisted of junctional and intradermal nests of a mixture of large spindle and epithelioid cells . none of the cells were atypical , and maturation of the cells with increasing depth was observed . from these findings , a diagnosis of spitz nevus was made . transepidermal elimination of nevus cell nests was observed and there were small groups of degenerated melanin - laden cells in the cornified layer . masson fontana stain revealed fine melanin deposits in the nevus cells of the junctional and intradermal nests , as well as heavy melanin deposits in the small groups of degenerated cells in the cornified layer . the distribution of melanin may contribute to a unique dermoscopic finding in this case .

due to the increasing incidence of multiple sclerosis ( ms ) all over of the world and in isfahan / iran , attention , care and education to these patients in order to alleviate the disease symptoms seem to be essential . in fact , the patient education could be accounted as a major component of any health care facility . training component determines the level of patient satisfaction and quality of the patient - physician relationship . while health professionals , especially nurses , and doctors have no enough time , therefore educational program , could be involved as ( 1 ) giving brochures ( 2 ) teaching traditional education and ( 3 ) referrals to other health centers or even ( 4 ) not giving any education . it is well known that all of the four mentioned items could influence clinical outcome . electronic applications could be considered as an alternative method for improving the quality of education offered to the patient . with the increasing popularity of computer - based training methods for both the physician and the patient , these activities could be considered as a way to promote activities related to the education of the patient . research has shown that virtual method in terms of time , place and even economic conditions have better facilities for the learner . this kind of learning seems to be learner - centered , and can be tailored to learner needs and information requirements of time and place , pace , and content set . within this electronic program , in addition to text , there are things such as images , animations and sound , which can cause learning more . the virtual training data could be done at home , during traveling , or at any time when necessary to provide them with data and also could be print it out easily by the patient whenever it is needed . although e - learning has spread around the world through computer education to patients , but patient education via computer is still rare . a study performed by neafsey et al . in 2002 , and southard et al . in 2003 , confirmed that e - learning could influence patients awareness . whereas in a study performed by street et al . in 1995 , and murray et al . in 2001 , such an effect was not recognized . however , unfortunately , the medical staff in their training , communication , and education , due to many responsibilities , less emphases on education . it is possible that the content of the lecture related to patients ( e.g. , with ms ) may be forgotten . using programs based on video or computer depends could be useful in case of not understanding or forgetting things . it seems that it is necessary to health professionals that should have the necessary knowledge related to e - learning . therefore , given the importance of effective teaching methods and appropriate care for patients with ms , several methods of teaching are currently used . most of these methods particularly in the areas of health are lectures and pamphlets . in order to provide effective methods of teaching for patients with ms , due to contradictory published work , the aim of this study was to investigate and compares two teaching method ( e - learning and illustrated booklet ) on the knowledge and consent of training in patients who attended ms clinic located at the isfahan ayatollah kashani hospital . a two groups pool blind quasi - experimental investigation was carried out on 120 patients with ms . according to the formula ( n = sample volume , z = confidence level , p = expected prevalence , d = accuracy ) . due to approximately 20% loss of samples ( 10 patients ) , the final sample size of 60 patients , was calculated per each group . therefore , at the end of this study , 120 patients in each group completed the study packages . the sampling procedure was in order to the easy way and performed on those who referred to the ms clinic located at the isfahan ayatollah kashani hospital . on the day of experiment based on the lottery , the first runner - up was assigned as e - learning and the second one as illustrated booklet . inclusion criteria were as follows : ( 1 ) age between 15 and 50 years ( 2 ) consent to participate in this study ( 3 ) having a phone number to call ( 4 ) have at least literate reading and writing ( 5 ) having the ability to speak , to hear and to see and finally ( 6 ) there is a computer or video device at home and the ability to use these devices ( in both educational groups ) . exclusion criteria were as follows : ( 1 ) employees working in the medical field ( 2 ) those who attended educational classes related to ms . at first informed consent form was given to patients , and the purpose of the study was explained to them . then in the group of multimedia , after visiting the ms patients by a neurologist , a cd was given to them . the cd contained ms education through text , pictures , animation , and sound , as well as a slideshow . this 30-min software contained ms education on the following issues : ( i ) description of the disease ( ii ) causes , sign and symptom , effects of disease on health , prognosis , treatment , benefits and side effects of treatment , recommendation on how to alleviate the symptoms of diseases . access to the internet was not possible for all patients in the form of an open line in the present study , and it was found that in similar studies , the materials were taught through multimedia method . on the other hand , the internet speed is so low that it leads to low quality of sound and image in online education in iran . therefore , educational content was in the format of a web page or flash video , windows media video , and mpeg-4 ( mp4 ) , as these formats can be used in a closed line web . after the explanation was given to the patients as to how to use the cd , they were informed that they would be asked some related questions 2 weeks later . in the second group , after being visited , in the second group were given an illustrated booklet that contained text with pictures ( illustration ) . the subjects were asked to study the material , and after 2 weeks , an awareness questionnaire was again filled for them . for both groups , demographic information such as name , surname , age and disease data were filled . another questioner form including the awareness of illness in patients with ms was placed and authorized to research units . questionnaire related to ms patients awareness training included eight sides education such as : ( 1 ) explain how patient 's illness was started ( 5 items ) ( 2 ) causes ( 5 items ) ( 3 ) signs and symptoms ( 5 items ) ( 4 ) complications ( 5 items ) ( 5 ) prognosis ( 5 items ) ( 6 ) treatments ( 5 items ) ( 7 ) benefits and side effects - related to treatments ( 5 items ) ( 8) recommendations on reducing symptoms and complications ( 5 items ) . the questionnaire was included 40 questions that patients could choose one of these options : right , wrong or i do not know with a score range of 040 . due to lack of availability of a standard questionnaire in this field , so this questionnaire was designed through use of countrywide national project , references , and textbooks , and its validity was confirmed by five faculty members of the of isfahan university of medical sciences . its reliability was confirmed by use of a pilot study ( questionnaire was given to 10 patients with ms ) and calculation of cronbach 's alpha ( = 0.89 ) . data were analyzed by student 's t - test and paired t - test through version 11.5 [ spss inc . , chicago , il , usa ] with a significance level of p < 0.05 . the mean age , duration of the disease and visit of patients to ms clinic were ( 20/3 4/01 ) years and ( 2/5 2/02 ) years and ( 2.3 1.11 ) month respectively . most sources of information related to learning about the disease were as follow : television 39 ( 33% ) , book 15 ( 12% ) . to get information some patients were offered family and friends and in others were as follow : television 39 ( 33% ) , radio 26 ( 22% ) , and internet 19 ( 16% ) . two groups before intervention were homogenous , and there were no significant differences related to age , duration of disease , the mean visit of ms clinic ( p > 0.05 ) . table 1 shows that the mean knowledge score related to training diseases within two groups that is , electronic and illustrated the booklet , after the intervention in compared to before the intervention has increased significantly . comparison of patients awareness and education related to disease training before intervention and 2 weeks after intervention within two groups that is , electronic and illustrated booklet the findings show that the highest ( 5.0 2.1 , 5.0 1.12 ) and lowest ( 2.0 0.4 , 1.0 1.6 ) scores on various aspects of knowledge after the intervention in both groups that is , the electronics and the illustrated leaflets , were the signs , symptoms and prognosis of the disease respectively [ table 2 ] . comparison of patients awareness and education related to disease training before the intervention and 2 weeks after the intervention within two groups that is , electronic and illustrated booklet the result showed that there is a significant increase after the intervention in the mean knowledge score , than before the intervention within two groups of electronic learning and illustrated booklet . in other words , this increase could represent the effectiveness of both educational methods in the awareness of patients with ms . in confirming the effectiveness of education on knowledge and satisfaction of the subjects , it would be pointed out to the studies of mohamadirizi and shaygannejad , mohamadirizi et al . in this , in 2003 , on the 104 heart patients showed that 6 months after the intervention within electronic training group , the rate of cardiovascular events were lower than the illustrated booklet group ( normal training ) respectively . the results of another study performed by neafsey et al . , in 2002 , in elderly ( age : 85 years ) showed that the use of computer - based training ( 2 weeks after intervention ) increased awareness about drug interactions and improved self - efficacy in consumer of drugs . our findings showed that e - learning have been associated with increased awareness of patients with ms . among the features of this study , data collection consisted of eight different training topics that were included as : ( 1 ) explaining disease ( 2 ) causes ( 3 ) signs and symptoms ( 4 ) side effects ( 5 ) prognosis ( 6 ) different treatments ( 7 ) benefits and side effects of the treatment ( 8) recommendations on reducing signs and symptoms . sensory difficulties such as vision problems ( blurred vision or double vision ) are common in patients with ms which could stand as a barrier in front of teaching and learning . based on e - learning 's method , it is quite possible for the patient to use other senses such as hearing . in addition to the items listed , using training computer - based , study performed by gustafson et al . , found no significant differences in terms of improving knowledge of breast cancer between the two groups that is , computer - based training and brochures . our results within the population studied here , demonstrate the effectiveness of both methods that could be illustrated as pamphlets , and e - learning . table 1 shows that the significant differences were seen in the percentage change related to awareness score in both groups of e - learning and illustrated the booklet . however , the change percentage in awareness score in the intervention group ( e - learning ) , have been far greater when compared to illustrated booklets ( illustrated instruction booklet ) . therefore , it could be assumed that e - learning is more effective in improving patient awareness. a study performed by langkamp et al . , confirmed that the combination of verbal and written instructions seem to be more useful than theological education alone . in fact , based on e - learning ( multimedia ) , information in written form with speech and animation could be accessible at home , while traveling or at any time . the content of information could be printed it out easily , at any time that seem to be necessary . also for many patients who have not the habit of reading the limitations of the study were the possibility of obtaining information from other sources on research it could occur in all two groups and out - of - control researchers . another limitation of this study was that data were collected through self - report . also due the high cost of travel and time of visit to the door houses to complete the posttest the strength of this study was to compare both methods electronics and illustrated booklet while other studies were done , the only one of the two types of education . however , it is clear that in all studies , measuring the amount of learning is the score that is normally obtaining by test , but learning due to responsibility for self - learning in e - learning group seem to be deeper than other educational methods . finally , it could be imagined that within e - learning method , training focuses on knowledge construction and not necessarily on knowledge accumulation . the results obtained in this study indicated that both electronic education and illustrated booklet methods had a great impact on promoting the knowledge level of ms patients . also it conveys that the e - learning method could be more effective than the pamphlets in order to increasing awareness of the disease . therefore , due to spending lower cost and less time e - learning besides the usual training , could be used by patients and the health care team provider .

background : multiple sclerosis ( ms ) could be considered as one of the most common chronic disorders of the central nervous system . however , patient education tasks in this group are a challenge for health care provider team but due to increase in the incidence of ms , a new category of contact , care , and education seems to be useful . hence , the aim of this study was to compare the effect of electronic education and illustrated booklet on knowledge of patients with ms.methods:this was a quasi - experimental research was carried out on 120 patients with ms from january 2013 to july 2013 . all patients attended ms clinic located at the ayatollah kashani hospital conducted to isfahan neurosciences research center ( inrc ) . patients were divided randomly into two equal groups : ( 1 ) electronic education ( n = 60 ) and ( 2 ) illustrated booklet ( n = 60 ) . participants knowledge score was collected according to the researcher - made questionnaire with 40 questions . data were analyzed using student 's t - test and paired t - test through spss ( version 11.5 ) with a significance level of p < 0.05.results:although there was not any significant difference between the knowledge score of electronic education and illustrated booklet group before intervention ( 18 2.2 vs. 17.01 3.4 ( , ( p = 0.434 , t = 5.64 ) , but there was a significant difference after 2 weeks intervention ( 35.74 1.4 vs. 33.74 3.4 ) , ( p = 0.021 , t = 6.64 ) . paired t - test showed a statistically significant difference in the knowledge level in both groups after intervention as follow : ( 1 ) electronic education ( 18 2.2 vs. 35.74 1.4 ) , ( p = 0.024 , t = 7.55 ) and illustrated booklet ( 17.01 3.4 vs. 33.74 3.4 ) , ( p = 0.003 , t = 8.55).conclusion : the electronic educational program applied in this study appears increased knowledge of patients with ms . therefore , the conveyance of this program to earn time for patient and healthcare provider team is suggested as a valuable and appropriate teaching method .

with more schools utilizing prosected cadaveric specimens in the anatomy laboratory , is there still a role for dissection ? historically , dissection has been utilized as the best means for teaching anatomy to medical students . nevertheless , a systematic literature review found little objective data that actually supports this notion . more recently , the superiority of dissection over prosection has been debated , and the use of prosection as an adequate tool for learning anatomy is becoming increasingly common in medical schools . a further understanding of the usefulness of both the aforementioned techniques is important as we look to the future and attempt to optimize gross anatomy education . prior to commencing this study , our hypothesis was that first - year medical students who participate in an extracurricular thoracic dissection elective would perform better on thoracic - related anatomy examinations than those who did not . a secondary hypothesis was that the use of peer - mediated teaching would offer an added benefit to medical students learning gross anatomy . the aim of this study then was to evaluate the impact of an optional thoracic dissection elective upon anatomy subject acquisition and determine whether peer - mediated teaching has a beneficial effect . all first - year medical students ( n = 709 ) at the university of ottawa between 2002 and 2006 were taught thoracic anatomy in the cadaver lab through the use of prosected specimens as part of the standard curriculum . an optional thoracic anatomy dissection elective was offered to all students in addition to the regular curriculum . the dissection elective consisted of 12 hours in the cadaver lab , divided into 4 sessions . the focus of this elective was the dissection of specimens and a review of thoracic anatomy learned in class . two groups were separated : the control group comprising the students who only participated in the standard curriculum ; and the intervention group comprising the students who participated in the standard curriculum , and the dissection elective . evaluation of the intervention was performed by analyzing students ' results on the thoracic anatomy component of their examinations during the first year cardiology and respirology blocks . a secondary analysis compared exam results between students in the dissection elective who received peer - mediated teaching and those who did not ( figure 1 ) . from 2002 to 2004 , there were no teaching assistants and the dissection elective was self - directed with the anatomy professor present to answer questions and demonstrate proper dissection technique . from 2005 to 2006 , the role of the anatomy professor remained the same but senior medical students in their second year of study , who had taken the dissection elective previously , were also present as peer - mediators . examination results between these two groups were analyzed using a paired student 's t - test . comparison of scores on the thoracic anatomy components of the cardiology and respirology examinations between the control and intervention groups is depicted in figures 2 and 3 . however , with the exception of 2003 ( p = 0.000979 and p = 0.00113 for cardiology and respirology exams , resp . ) , no statistical significance was found when mean scores were compared . figure 4 compares performance on the thoracic anatomy component of the first - year cardiology and respirology exams between the non - peer - mediated group and peer - mediated group . student 's t - test showed that the non - peer - mediated group performed better on both examinations ( p = 0.0033 ) ; however no statistical significance was elicited . historically , dissection has been the gold standard for teaching anatomy to medical students , even though there is a dearth of objective data that does not support this notion . numerous studies have suggested that prosection is just as efficient as dissection for students learning gross anatomy [ 3 , 4 ] . our study aimed to identify whether introducing dissection of cadavers into the curriculum would offer any added educational benefit over students viewing prepared prosected specimens alone . analysis of our data did suggest that students exposed to dissection above and beyond the regular curriculum of prosection alone performed slightly better on their anatomy examinations of the thorax compared with those students who did not have the additional benefit of dissection . it is important to note , however , that no statistical significance was identified between students learning gross anatomy from prosection alone and those students who had additional exposure to dissection in the anatomy lab . this is in keeping with the literature that prosection is just as efficacious as dissection for learning gross anatomy . as far back as 1990 , nnodim showed that prosection was advantageous because it is more cost - effective and requires less time to learn the same amount of material . in fact , in a time when funding is scarce , showing that prosection is as adequate as dissection for acquisition of anatomy knowledge in medical school is important . it should be noted though that this study only analyzed dissection and prosection in terms of the acquisition and recall of thoracic anatomy knowledge . literature suggests that dissection appears to offer benefits to students concerning their attitudes towards death and the development of clinically relevant visuospatial abilities and procedural skills . considering the retrospective nature of our study , we were unable to assess these variables . this study , therefore , could lay the groundwork for future investigations into the added benefits of dissection beyond acquisition of anatomical knowledge . a second arm of this study was to determine whether the addition of peer - mediated teaching would offer an additional learning benefit to students participating in the dissection elective . our study suggests that the addition of peer - mediated teaching to the dissection elective did not influence student performance on examinations . in fact , a surprising result suggested that the addition of teaching assistants may have negatively impacted student performance . based on this interesting and unpredicted result , further exploration into this subject is warranted . worthy of note , however , is that a study by krych et al . suggests that peer teaching improves anatomy subject acquisition and communication skills for the peer - teachers themselves . this was not examined in our study and may be an area that warrants further exploration . although our study presents promising and useful data that prosection is a sufficient means by which to teach medical students gross anatomy , a number of limitations did exist within the study . the additional benefit of qualitative data from medical students via focus groups or questionnaires would likely have been of benefit and perhaps would have added strength and another dimension to the study . furthermore , this study is retrospective in nature . a greater understanding of pedagogical techniques is always an area of interest in medical education , and this study aimed to evaluate two of those techniques . first , our study suggests that prosection is as effective as dissection for acquisition of thoracic anatomy knowledge . this lays the groundwork for larger , more extensive studies to examine this notion further . second , peer - mediated teaching appeared to offer no additional benefit with regards to anatomy knowledge acquisition . considering the potential secondary benefit of creating peer - mediated teaching curricula , further exploration in this area through prospective , controlled studies is warranted .

purpose . to evaluate the impact of an optional thoracic dissection elective upon anatomy subject acquisition and determine whether peer - mediated teaching has a beneficial effect . methodology . first year medical students ' results on thoracic anatomy laboratory examinations over a five - year period were obtained . all students were taught in the laboratory using prosected specimens as part of a standard curriculum . a subset of students from each class volunteered to participate in an optional thoracic dissection . a comparison of exam performance between the two groups was made , and the results were analyzed to see if incorporating peer teaching into the elective had an impact on the students ' performance on anatomy examinations . results . with the exception of one year 's results , no significant statistical difference was found in student performance on anatomy examinations between the two groups . the addition of peer teaching did not result in superior performance . conclusion . it is believed that prosected specimens are suitable for anatomy laboratory teaching in an undergraduate medical curriculum . our study did not reveal that an opportunity for dissection offered any added benefit in terms of exam performance . in addition , peer teaching did not affect exam performance . this study strictly compared student exam results . it did not assess the possible impact of the dissection process to influence student attitudes towards death or the development of clinically relevant visuospatial abilities and procedural skills .

a 67-year - old obese man was referred for further investigation following an episode of sudden - onset left - sided loin pain that had lasted for 6 h and then resolved spontaneously . he had type 2 diabetes mellitus , but no other relevant past medical history . physical examination revealed a large left - sided irreducible , non - tender inguino - scrotal hernia , and laboratory investigation , including serum creatinine was within normal limits . an ultrasound scan of his renal tract revealed left - sided hydronephrosis , and a subsequent computed tomography scan showed left - sided hydronephrosis with a dilated ureter that was seen to enter the large inguino - scrotal hernia [ figures 1 and 2 ] . it then took a path back out of the hernia where it became non - dilated and inserted into the bladder in its usual position . non - contrast ( left ) and delayed phase ( right ) coronal computed tomography scan showing dilated left ureter entering large left inguino - scrotal hernia ( arrows ) venous phase coronal computed tomography showing left ureter after having left the inguino - scrotal hernia as it enters the bladder . note , how the ureter is now of normal calibre ( arrow ) a subsequent dimercaptosuccinic acid ( dmsa ) scan confirmed reduced function of the affected kidney , contributing 35% to overall renal function and hence he underwent a mesh repair of this hernia with careful dissection of the ureter from the hernial sac and his post - operative recovery was uneventful . uretero - inguinal hernia in patients with non - transplant kidneys is a rare phenomenon with the majority diagnosed intra - operatively when found unexpectedly during the hernia repair . two types have been described - paraperitoneal , accounting for 80% of cases , in which the ureter is pulled into the hernia alongside the peritoneal sac due to an adherent layer of posterior peritoneum ; and extraperitoneal , in which no peritoneal sac is present in the hernia and the ureter is involved alone or in combination with retroperitoneal fat . in our case , the rarer extraperitoneal form is more commonly associated with renal tract anomalies ( such as renal ptosis ) , and hence renal tract imaging should be performed even if it is incidentally found at surgery . as this condition is associated with inguinal herniation , it is more common in men , typically in the fifth or sixth decade . reported pre - disposing features include obesity and a deficiency in collagen synthesis . pre - operative diagnosis is important to reduce the significant risk of ureteral injury during surgery . although stenting of the ureter facilitates identification and protection during the hernia repair , the length and tortuosity of the herniated ureter make endourological procedures ( such as ureteric stent insertion ) difficult and hence careful dissection of the ureter from the hernial sac and replacement in the retroperitoneal space is imperative to prevent injury .

obstructive uropathy secondary to uretero - inguinal hernia is a rare phenomenon . two types have been described - the rarer extraperitoneal type is frequently associated with other renal anomalies . pre - operative diagnosis is essential in order to reduce the risk of ureteric injury intra - operatively . we describe one such case .

alternative medicine refer to a broad set of health care practices that are not part of that country s own tradition or conventional medicine and are not fully integrated into the dominant health - care system . according to who they are used interchangeably with traditional medicine in some countries . homeopathic medicine , herbal medicine and acupuncture are the most common , albeit not the unique , cam forms in european countries . homeopathy is a method of medical practice that aims to improve the level of health of an organism through the administration of medicinal products selected individually according to the principle of similarity ( see text ) . since homeopathy is strictly individualized and takes into account the physical , emotional , mental , constitutional , biographical and environmental state , it is a medicine of the whole person . the term homeopathy comes from the greek ( omoios = similar , pathos = suffering ) . integrative medicine is not simply the combination of conventional medicine with complementary and alternative medicine . the consortium of academic health centers for integrative medicine defines it as the practice of medicine that reaffirms the importance of the relationship between practitioner and patient , focuses on the whole person , is informed by evidence , and makes use of all appropriate therapeutic approaches , healthcare professionals and disciplines to achieve optimal health and healing . alternative medicine refer to a broad set of health care practices that are not part of that country s own tradition or conventional medicine and are not fully integrated into the dominant health - care system . according to who they are used interchangeably with traditional medicine in some countries . homeopathic medicine , herbal medicine and acupuncture are the most common , albeit not the unique , cam forms in european countries . homeopathy is a method of medical practice that aims to improve the level of health of an organism through the administration of medicinal products selected individually according to the principle of similarity ( see text ) . since homeopathy is strictly individualized and takes into account the physical , emotional , mental , constitutional , biographical and environmental state , it is a medicine of the whole person . the term homeopathy comes from the greek ( omoios = similar , pathos = suffering ) . integrative medicine is not simply the combination of conventional medicine with complementary and alternative medicine . the consortium of academic health centers for integrative medicine defines it as the practice of medicine that reaffirms the importance of the relationship between practitioner and patient , focuses on the whole person , is informed by evidence , and makes use of all appropriate therapeutic approaches , healthcare professionals and disciplines to achieve optimal health and healing .

some physicians have incorporated some forms of complementary and alternative medicine ( cam ) or related medicinal products in their clinical practices , suggesting that an unconventional treatment approach might be seen as an integration rather than as an alternative to standard medical practice . among the various cams , homeopathy enjoys growing popularity with the lay population , but it is not acknowledged by academia or included in medical guidelines . the major problem is to establish the effectiveness of this clinical approach using the strict criteria of evidence - based medicine . this issue of the journal of medicine and the person collects contributions from some of the most prestigious centers and research groups working in the field of homeopathy and integrative medicine . these contributions are not specialized information but are of general interest , focusing on this discipline as one of the emerging fields of personalized medical treatment .

nkt cells are distinguished type i nkt cell and type ii nkt cells according to t cell receptor ( tcr ) usage . type i nkt cells are called invariant nkt ( inkt ) cells because they express only restricted tcr chain ( v14 ) and tcr chain ( v2 , 7 and 8) , whereas type ii nkt cells express various tcr chains ( 2,3 ) . nkt cells can help activation of other lymphocytes such as , t , b , nk and dendritc cells ( 3 - 6 ) . it has been known that dedritic cells ( dcs ) play a pivotal role in antigen presentation to nkt cells ( 7 ) . in contrast , resting b cells are known poor immunogenic antigen presenting cells ( apcs ) to nkt cells ( 8) . however nkt cells provide direct and indirect help for lipid and protein - specific b cells , respectively ( 9,10 ) . direct help from inkt cells for lipid - specific b cells is dependent on il-21 secreted from inkt cells ( 11 ) . high - density -galcer loaded b cells stimulate inkt cells although the efficiency of stimulation is not comparable to dendritic cells ( 12 ) . -galcer / peptide loaded b cells can induce peptide - specific cytotoxic cd8 t cells and induced cytotoxic cd8 t cells eliminate various kinds of tumor ( 12,13 ) . in micro - environment of foreign antigen stimuli , dc and b cells cooperate to activate antigen - specific cytotoxic cd8 t cells ( 14 ) . nevertheless , it remains to be resolved unknown nkt cells response upon co - operative stimulation of b cells and dcs . in this study . we found that b cells induced th1-skewed response of nkt cells in the presence of -galcer loaded dcs , regardless of exogenous antigen loading to b cells . we also demonstrated that regulation of nkt cell response by b cells stimulation was dependent on cd1d expression of b cells . six- to eight - week - old c57bl/6 ( b6 ) , cd1d and cd1d mice ( b6 background ) were bred in facilities at korea university . the experimental protocols of this study were approved by the institutional animal care and use committee of korea university . monoclonal antibodies specific for mouse tcr ( h57 ) , ifn- ( xmg-1 ) , il-4 ( 11b11 ) and nk1.1 ( pk136 ) were purchased from bd biosciences . b cells were isolated from splenocytes via macs by using anti - b220-conjugated magnetic beads ( miltenyi biotec ) after dc had been depleted by using anti - cd11c microbeads . purified b cells and dcs were loaded 10 ng / ml -galcer for 4 hr and they were washed extensively , then were co - cultured with nkt cells for 8 hr or 48 hr . after 8 hr or 48 hr , the amount of cytokines was measured by intracellular cytokine staining and elisa . cells were washed and blocked with an anti - fcrii / iii mab ( 2.4g2 ) for 15 min and then labeled for 30 min on ice with the appropriate mabs . for intracellular cytokine staining , cells were fixed with a cytofix / cytoperm kit ( bd biosciences ) according to the manufacturer 's protocol . the stained cells were analyzed with a facscalibur flow cytometer using cellquest software ( bd biosciences ) . student 's t - tests were used to determine the statistical significance of differences between the comparison groups unless otherwise stated . six- to eight - week - old c57bl/6 ( b6 ) , cd1d and cd1d mice ( b6 background ) were bred in facilities at korea university . the experimental protocols of this study were approved by the institutional animal care and use committee of korea university . monoclonal antibodies specific for mouse tcr ( h57 ) , ifn- ( xmg-1 ) , il-4 ( 11b11 ) and nk1.1 ( pk136 ) were purchased from bd biosciences . b cells were isolated from splenocytes via macs by using anti - b220-conjugated magnetic beads ( miltenyi biotec ) after dc had been depleted by using anti - cd11c microbeads . purified b cells and dcs were loaded 10 ng / ml -galcer for 4 hr and they were washed extensively , then were co - cultured with nkt cells for 8 hr or 48 hr . after 8 hr or 48 hr , the amount of cytokines was measured by intracellular cytokine staining and elisa . cells were washed and blocked with an anti - fcrii / iii mab ( 2.4g2 ) for 15 min and then labeled for 30 min on ice with the appropriate mabs . for intracellular cytokine staining , cells were fixed with a cytofix / cytoperm kit ( bd biosciences ) according to the manufacturer 's protocol . the stained cells were analyzed with a facscalibur flow cytometer using cellquest software ( bd biosciences ) . student 's t - tests were used to determine the statistical significance of differences between the comparison groups unless otherwise stated . to test whether b cells can affect nkt cell stimulating activity of dcs , we co - cultured wt cd11c dc with nkt cells and b cells and then assessed the ability of b cells to activate nkt cells . elisa analysis and intracellular staining demonstrated that ifn- from nkt cells was significantly increased , in contrast il-4 was substantially reduced upon the addition of -galcer pulsed b cells compared to the response by dcs alone ( fig . the co - culture of nkt cells with -galcer un - pulsed b cells also led to a significantly higher production of ifn- and lower production of il-4 than that with -galcer pulsed dcs alone ( fig . 2a and 2b ) . taken together , these results show that b cells promote th1 response of nkt cells in the presence of antigen - loaded dcs , regardless of exogenous antigen pulse to b cells . although b cells promote th1 response of nkt cells in the presence of antigen - loaded dcs , it was not clear whether nkt cells and b cells form directly cell - cell contact by cd1d - tcr interaction . to test whether cd1d expression on b cells was required to promote th1 response of nkt cells in the presence of -galcer pulsed dcs , we isolated b cells from cd1d or cd1d mice and co - cultured them with dcs to activate nkt cells . co - culture of nkt cells with cd1d b cells led to a significantly higher production of ifn- and lower production of il-4 than that with cd1d b cells ( fig . this data show that th1-skewed response of nkt cells upon the addition of conventional b cells is dependent on cd1d expression of b cells . similarly , it had been reported that marginal zone ( mz ) b cells amplify dc mediated - nkt cell activation ( 15 ) . the cytokine patterns of nkt cells upon mz b cells and dcs stimulation ( 15 ) was similar to our results , except il-4 expression was also increased when -galcer loaded mzb cells was used . however , there was a contradicting report where conventional b cells could dampen inkt cells activation in the presence of dcs ( 8) . we are not sure at the moment what made these difference in nkt cell response but the density of b cells and concentration of -galcer might be causative factor since they used much higher number of b cells and higher concentration of -galcer to activate nkt cells compared to the experimental condition in this study . nkt cell - mediated cytokines milieu can be influenced by pattern of cellular composition of lymphocytes in specific inflammatory site . for example , nkt cells in tumor model promote th1-skewed cytokine milieu , in contrast nkt cells in asthma model promote th2-skewed cytokine milieu ( 4,6 ) . in asthma model , the administration of -galcer ameliorated or worsened the disease symptoms by how to inject -galcer ( 16 - 18 ) . a shift from th2 to th1-response by the administration of -galcer suppressed airway hyper - responsiveness ( ahr ) ( 17,18 ) . in this study , we demonstrated that b cells promote th1 response of nkt cells in the presence of antigen - loaded dcs . thus , the administration of -galcer pulsed b cells and dcs may be a possible approach for the treatment of ahr . eventually , the elucidation of optimal composition of apcs such as dcs and b cells to regulate finely the direction of nkt cell response will be the basis to apply nkt cell - based cell therapy .

cd1d expressing dendritic cells ( dcs ) are good glyco - lipid antigen presenting cells for nkt cells . however , resting b cells are very weak stimulators for nkt cells . although -galactosylceramide ( -galcer ) loaded b cells can activate nkt cells , it is not well defined whether b cells interfere nkt cell stimulating activity of dcs . unexpectedly , we found in this study that b cells can promote th1-skewed nkt cell response , which means a increased level of ifn- by nkt cells , concomitant with a decreased level of il-4 , in the circumstance of co - culture of dcs and b cells . remarkably , the response promoted by b cells was dependent on cd1d expression of b cells .

despite global improvements in caries status , dental caries remains to be the most common chronic childhood disease world - wide . teeth with deep pits and fissures are shown to be more vulnerable to develop caries . in the other hand , fissure sealant application is proved to be able to block pits and fissures in order to prevent occlusal caries development . any sign of microleakage in sealants is considered as the weak point eventually leading to failure as the inability to isolate pit and fissures would enhance the retention of bacteria , nutrients , and their acidic metabolic products . the necessity of tooth preparation prior to the sealant application and its effect on microleakage has different perceptions among the researchers . believes that lower microleakage rate is associated with teeth following bur preparation while some studies illustrate opposing results . pumice prophylaxis has long been used prior to the sealant application with its effect on microleakage being mostly reported as beneficial . in the other hand , the use of acid etching alone or associated with one of the other preparatory methods has shown little to no difference in microleakage level of the teeth . the aim of this investigation was to compare the degree of microleakage at the enamel - sealant interface when prepared by a fissurotomy bur or pumice prophylaxis before the acid etchant being applied . occlusal fissures of the specimens in group a were prepared with a micro stf fissurotomy bur ( ss white burs inc . , lakewood , nj , usa ) on a high - speed hand piece . for each specimen , the bur was moved along all the occlusal fissures with a gentle force applied . the occlusal surface of the specimens in the group b received a thorough prophylaxis for 20 s with water - based slurry of pumice , using a prophylaxis brush fitted on a slow - speed hand piece . all teeth were then etched for 20 s using 35% phosphoric acid gel ( 3 m espe , usa ) , washed and dried for 20 s each . each sample received an adhesive ( adper single bond plus , 3 m espe , usa ) prior to fissure sealant placement . a light - cured sealant ( clinpro sealant , 3 m espe , usa ) was then applied to all the prepared fissure through a syringe type tip . polymerization was performed using an led demetron ii ( kerr , usa ) light - curing unit with an output of 800 mw / cm for 20 s. specimens were then subjected to a thermo cycle machine with 1000 cycles between 5c and 55c with 20 s dwell time . apices of each sample tooth was then covered with a layer of sticky wax followed by the application of two layers of nail varnish to the surface of each tooth leaving 2 mm around the sealant borders . specimens were then immersed in a 3% basic fuchsin dye solution for 72 h. sample teeth were subsequently washed under the tap water for 1 min to remove excess dye from the surfaces . each was then embedded in acrylic blocks and sectioned in the bucco - lingual plane through the sealant for two identical sections using a water - cooled diamond disk on an isomet saw ( buehler ltd . three prepared sections with four surfaces from each sample were examined under 10 magnifications using the xtd series stereomicroscope ( blue light inc . all the sections were blindly subjected to an assessment process using a four point scoring system suggested by overbo and raadal . dye penetration scale employed was as : ( 0 ) no dye penetration ; ( 1 ) dye penetration restricted to the outer half of the enamel - sealant interface ; ( 2 ) dye penetration in the inner half of the enamel - sealant interface ; ( 3 ) dye penetration into the underlying fissure . data were analyzed using kruskall - wallis analysis of variance and mann - whitney u - tests for comparing microleakage levels among and between groups . mean standard deviation of microleakage score of the cases in each group was separately calculated [ table 1 ] . the highest frequency of the microleakage in all groups was for score 0 and 1 , with fissurotomy 80% , pumice prophylaxis 79.2% and control group 66.7% . surprisingly , score 3 was not observed in any of the groups [ figure 1 ] . meansd of microleakage score of different preparatory groups dye penetration scores in three different tooth preparation methods kruskall - wallis analysis of variance showed significant differences among microleakage levels of different preparation methods ( p = 0.003 ) . mann - whitney u - test indicated that teeth in fissurotomy bur and pumice prophylaxis groups had significantly reduced level of microleakage than those in acid etch alone ( p = 0.005 and p = 0.003 , respectively ) ; however , it showed no significant differences of micloleakage level between fissurotomy bur and pumice prophylaxis groups ( p = 0.83 ) . sealing pits and fissures have been proved to have an effective role on preventing teeth from fissure caries in childhood . there are several preparatory methods introduced prior to the placement of the fissure sealant with varying degrees of efficacy on the adhesiveness of material to the prepared surfaces . however , the necessity of the tooth surface preparation prior to the sealant application is still under scrutiny . as a possible choice , the currently available and specifically designed fissurotomy bur could conservatively widen the fissures providing a larger surface for the adhesion of sealant material . a similar concept has also been reported using fine diamond bur in order to reduce microleakage of the sealants . fissurotomy bur has been suggested to have a significantly high influence on sealant retention when used along with acid etch . as indicated earlier it seems that bur preparation can provide greater surface area , inducing better sealant adhesion as well as an increased chance for the flow of sealant into the depth of fissures improving its wear resistance . reported that quarter round bur preparation with acid etch has a better effect than acid etching alone in reducing microleakage ; however , several other studies are also raising doubts on the effectiveness of bur preparation . the diversity of the materials and methods used to assess the microleakage may explain the contradictions between the results along with the use of dye agents such as methylene blue or basic fuchsin . results of the current investigation indicated that pumice prophylaxis along with acid etch as superior to acid etching alone in reducing microleakage around the sealants , supporting earlier reports by ansari et al . despite the introduction of pumice prophylaxis as one of the essential steps of fissure sealing by cueto and bunocore , this application has later been proved ineffective in promoting the sealant effectiveness by lowering the microleakage . the retention of sealant is believed to be enhanced when adhesive bonding agents are applied prior to the sealant . however , there are also reports suggesting no improvement for microleakage reduction when these adhesive agents are applied . the invasive use of bur to open the fissures has not been widely accepted due to its damaging effect on the teeth requiring fissure sealant . interestingly , there was no case with score three dye penetration ( to the full depth of the fissure ) indicating reasonable flow of the sealant into the depth of fissures . findings of this study indicate that the use of fissurotomy bur along with etchant gel enhances adhesiveness of sealant to the tooth . the use of prophylaxis paste would be advantageous in microleakage reduction to the use of etching alone .

background : a prolonged life of fissure sealant has always been the target for preventing caries in vulnerable newly erupted teeth . the use of preparatory techniques including bur introduction to the fissures is considered among such improving steps.materials and methods : ninety freshly extracted healthy maxillary premolar teeth were randomly selected for this investigation . teeth were then divided into three fissure sealant preparatory groups of a : fissurotomy bur + acid etch ; b : pumice prophylaxis + acid etch and c : acid etch alone . sealant was applied to the occlusal fissures of all specimens using a plastic instrument . this was to avoid any air trap under the sealant . sample teeth were first thermocycled ( 1000 cycles , 20 s dwell time ) and then coated with two layers of nail varnish leaving 2 mm around the sealant . this was then followed by immersion in basic fuchsin 3% . processed teeth were sectioned longitudinally and examined under a stereomicroscope for microleakage assessment using a score of 0 - 3 . collected data was then subjected to kruskall - wallis analysis of variance and mann - whitney u - test . p > 0.05 was considered as significant.results:teeth in fissurotomy bur and pumice prophylaxis groups had significantly reduced level of microleakage than those in acid etch alone ( p = 0.005 and p = 0.003 , respectively).conclusion : use of fissurotomy bur and pumice prophylaxis accompanied with acid etching appears to have a more successful reduction of microleakage than acid etch alone .

pheochromocytomas are rare neuroendocrine tumors that secrete high levels of catecholamines and usually cause paroxysmal or sustained hypertension . we report a patient who was treated for recurrent transient left ventricular ( lv ) dysfunction , with the final diagnosis of a catecholamine - induced cardiomyopathy . in november of 1999 , a 62-year - old woman with a history of diabetes mellitus and hypothyroidism , was admitted to the hospital with right renal cell carcinoma . there was a 54 cm solid mass at the lower pole of the right kidney on the abdominal ct scan , suggesting a renal cell carcinoma . angioembolization of the right renal cell carcinoma was performed on the 25 of november 1999 . the preoperative blood pressure was 160/100 mmhg in the operating room , and the blood pressure increased to 230/110 mmhg after induction of anesthesia . the ecg changes included t wave inversions and st segment depression in leads v1 - 6 , which were new ecg findings . echocardiography was performed immediately and showed impaired wall motion of all basal and mid - ventricular segments of the left ventricle ( fig . the creatine kinase - mb ( ck - mb ) level was elevated to 66.4 ng / ml by the next day . the echocardiography was repeated after two weeks and showed normalization of the left ventricular wall motion . the size of the right renal cell carcinoma was markedly reduced after the interferon treatment . follow - up abdominal ct scanning was performed in april and november of 2000 ( fig . the right renal cell carcinoma and the left adrenal mass were mildly enlarged by march 2002 . the patient had no subjective symptoms and was lost to follow up . in december 2003 , the patient visited the emergency room ( er ) with dizziness . echocardiography showed impaired wall motion of the apical and mid - segments of the left ventricle and severely decreased lv systolic function ( fig . 3 ) . the peak level of cardiac troponin i was 3.1 ng / ml . technetium-99 m methoxyiso - butylisonitrile ( tc-99 m mibi ) single emission computerized tomography ( spect ) revealed no evidence of inducible ischemia . echocardiography was repeated after one week , the lv systolic function and regional wall motion abnormalities had fully recovered . in september 2004 , 2 ) and she was diagnosed with a pheochromocytoma . the 24 hour urine metanephrine was elevated at 3.478 mg / day , and the iodine-131 meta - iodobenzylguanidine ( i-131 mibg ) adrenal scan was compatible with a pheochromocytoma ( fig . the patient had a successful resection of the left adrenal tumor and right kidney in december 2004 . microscopic examination confirmed that left adrenal tumor was a pheochromocytoma and the right renal tumor was a renal cell carcinoma . catecholamine excess leads to cyclic adenosine mono - phosphate ( amp)-mediated calcium overload of the cell , with the resultant decrease in synthetic activity and viability.1 ) pheochromocytomas are derived from endocromaffin cells ; they are catecholamine - secreting neuroendocrine tumors . cardiomyopathy related to a pheochromocytoma is well known ; associated dilated cardiomyopathy has been reported.4)5 ) in addition , many cases of takotsubo cardiomyopathy have been reported.6)7 ) recent case reports have described patients with lesions involving areas other than the apex.8 - 10 ) there appears to be no unique ventricular dysfunction pattern in catecholamine - induced cardiomyopathies . in this case , the left adrenal pheochromocytoma might have been too small to identify on the initial ct scan . however , the fluctuating blood pressure ( bp ) in this patient and the growth of the left adrenal mass on the follow - up ct scan , suggested a relationship between the first event of lv dysfunction and the pheochromocytoma . this case demonstrates recurrent and variable manifestations of a catecholamine - induced cardiomyopathy in a patient with a pheochromocytoma . the cardiomyopathy was the inverted takotsubotype for the first event , and later a conventional type with the presentation of apical ballooning . in this patient the cardiomyopathy induced by catecholamine 's or stress , can be completely reversed and potentially cured with the appropriate treatment . the diagnosis of a pheochromocytoma should be considered in patients with left ventricular dysfunction and no other obvious diagnosis.3 ) if the imaging studies are negative , biochemical studies for pheochromocytoma should be performed . especially in cases with recurrent left ventricular dysfunction .

pheochromocytomas presents with variable clinical manifestations . cardiomyopathy caused by a pheochromocytoma is well known . we report the case of a 62-year - old woman with recurrent left ventricular dysfunction , who was subsequently found to have a pheochromocytoma . the patient had two different patterns of cardiomyopathy . patients with a cardiomyopathy , of non - specific origin , should have a pheochromocytoma ruled out .

takotsubo syndrome ( tts ) is a transient cardiomyopathy of unknown origin , clinically manifesting as acute coronary syndrome ( acs ) . this syndrome mainly occurs in postmenopausal women and has a temporary relationship with emotional or physical stress . tts occurred in 46-year - old female patient on the first day after renal transplantation . the predominant symptoms were connected with acs , performed with low grade troponin elevation and characteristic shape of left ventricle depicted in echocardiography . taking into consideration the risk of the development of contrast - induced nephropathy , coronary angiography ( ca ) was delayed ; myocardial perfusion scintigraphy and iodine-123 metaiodobenzylguanidine ( i - mibg ) myocardial uptake were performed to confirm the clinical suspicion . myocardial perfusion scintigraphy ( mps ) performed in rest condition showed normal perfusion but myocardial uptake of i - mibg was impaired . within 6 months after surgery , full recovery of all biochemical and functional parameters of the left ventricle were observed . at that time ca takotsubo syndrome ( tts ) is a rare cardiomyopathy of unknown origin , often manifesting as acute coronary syndrome ( acs ) . clinical features of this syndrome include sudden onset of chest symptoms , st - segment elevation on electrocardiogram ( ecg ) , reversible apical ballooning with hyper - contractile basal segments during systole on echocardiography ( echo ) , normal coronal angiogram ( ca ) and minimal elevation of cardiac enzymes [ 13 ] . tts mainly occurs in postmenopausal women and has a temporary relationship with emotional or physical stress as well as with systemic diseases . tts was at first described in japanese women as a syndrome of multivessel spasm . the name of this syndrome is connected with a shape of the left ventricle ( lv ) , which resembles a pot for trapping octopus used by japanese fishers . the subject of our report was 46-year - old female patient , who in the past underwent bilateral nephrectomy due to polycystic kidney . since then she had been hemodialysed and qualified for kidney transplantation . on the first day after surgery , the patient suddenly experienced tachycardia , anxiety and feeling hot , without typical chest pain . the ecg showed sinus tachycardia 120/min , negative t wave in most of the leads , and previously observed left ventricular hypertrophy ( figure 1 ) . in biochemical tests noradrenaline serum level was 452.0 pg / ml ( 175500 ) , adrenaline was 52.1 pg / ml ( < 90 ) and dopamine was 37.0 pg / ml ( < 90 ) . other biochemical parameters and their evolution during the patient s hospitalization and follow - up are presented in table 1 . echo revealed apical ballooning with preserved contractility of basal and middle segments and left ventricular ejection fraction ( lvef ) was reduced to 35% ( figure 2a , b ) . coronary angiogram was delayed to prevent contrast - induced nephropathy ( cin ) in the newly - transplanted kidney . the rest myocardial perfusion scintigraphy ( mps ) by gated single photon emission computed tomography ( gspect ) was performed 60 min after iv injection of 740 mbq technetium-99 m methoxy - isobutyl - isonitrile ( tc - mibi ) on a double - head , large field of view gamma camera varicam ( elscint , haifa , israel ) equipped with low - energy , high - resolution collimators . cardiac sympathetic functions were evaluated by spect and planar i - labeled meta - iodo - benzylguanidine ( i - mibg ) myocardial scintigraphy . semiquantitative analysis of i - mibg myocardial uptake was expressed as routine heart - to - mediastinum ratio ( hmr ) : 15 ( early ehmr ) and 240 min ( delayed dhmr ) post - administration as well as washout rate ( wor ) . mps revealed a characteristic shape of the left ventricle but normal perfusion without relevant perfusion defects , but left ventricular ejection fraction ( lvef ) was as low as 27% . semiquantitative i - mibg cardiac imaging assessment indicated low values of hmr ( ehmr 1.7 ; dhmr 1.43 ) and high values of wor ( 46.7 ) . during the follow - up , improvement in clinical status , biochemical function the patient was discharged in good condition 30 days after surgery . in follow - up examinations 6 months after surgery , the general health condition of the patient and , especially , the function of transplanted kidney were normal . there was full recovery of st - t in ecg ( figure 3 ) with persisting features of left ventricular hypertrophy . the cardiac echo depicted normalization of the left ventricular function with lvef equal 64% ( figure 4a , b ) . myocardial perfusion gspect stress / rest study revealed normal perfusion and shape of lv as well as normalization of lvef ( 62% ) . the i - mibg myocardial spect showed only a small defect of radiotracer uptake in inferior segments of lv . the normalizations of semiquantitative indices were also observed ( wor 20.6 ; ehmr 2.02 ; dhmr 1.8 . ) the takotsubo cardiomyopathy study group defines tts as : a disease exhibiting an acute left ventricular apical ballooning of unknown cause . as stressed in the guidelines published by this group , the exclusion of coronary stenosis by means ca is a crucial test for diagnosis of this syndrome , which is also emphasized by other authors . we believe that the diagnosis may still be made by the means of non - invasive tests : echocardiography and i - mibg myocardial uptake [ 911 ] . echocardiography is able to detect changes of lv characteristic of tts in shape and wall motion . by this method transient neurogenic myocardial stunning is the likely pathomechanism of tts , thus i - mibg myocardial uptake and serum catecholamine level were assessed . the increased sympathetic nervous system activity is associated with high myocardial i - mibg washout and low myocardial i - mibg early and delayed uptake [ 1315 ] . low myocardial i - mibg uptake is considered to be a poor prognostic factor for patients with heart failure . the semi - quantitative analysis of i - mibg myocardial uptake expressed by ehmr reflects the integrity of pre - synaptic nerve endings and uptake-1 , whereas dhmr combines information on neuronal function from uptake to release through the storage vesicle at the nerve endings , while wor is an index of the degree of sympathetic drive . in the presented case , the values of ehmr and of dhmr were lower , whereas mean value of wor was higher compared to normal values of these indices mentioned in previous studies [ 1316 ] . i - mibg myocardial uptake has also been used to diagnose tts by many other authors , who emphasized the physiological basis of tracer uptake and the semi - quantitative evaluation of hmr and wor . the cardiac sympathetic nerve endings are more susceptible to ischemia than myocytes , therefore the comparison with myocardial perfusion is essential for further diagnosis . to exclude possible influence of ischemia in our patient , performed 6 months after the acute phase of tts , relevant regression of the adrenergic nervous system was observed . the entire array of clinical symptoms of the presented patient biochemical tests , ecg changes , echocardiography , mps findings and i - mibg myocardial uptake pattern are highly suggestive of takotsubo syndrome . the complete regression of these changes and normal ca results were the final confirmation of tts in our patient . after achievement of stabile function of the transplanted kidney , there were no contraindications to ca . to our best knowledge , this is the first recognized case of tts after renal transplantation . in patients with high risk of contrast - induced nephropathy , tts can be diagnose by not nephrotoxic tests , like : cardiac sympathetic scintigraphy , myocardial perfusion scintigraphy and echocardiography , instead coronal anfiography .

summarybackgroundtakotsubo syndrome ( tts ) is a transient cardiomyopathy of unknown origin , clinically manifesting as acute coronary syndrome ( acs ) . this syndrome mainly occurs in postmenopausal women and has a temporary relationship with emotional or physical stress.case reporttts occurred in 46-year - old female patient on the first day after renal transplantation . the predominant symptoms were connected with acs , performed with low grade troponin elevation and characteristic shape of left ventricle depicted in echocardiography . taking into consideration the risk of the development of contrast - induced nephropathy , coronary angiography ( ca ) was delayed ; myocardial perfusion scintigraphy and iodine-123 metaiodobenzylguanidine ( 123i - mibg ) myocardial uptake were performed to confirm the clinical suspicion . myocardial perfusion scintigraphy ( mps ) performed in rest condition showed normal perfusion but myocardial uptake of 123i - mibg was impaired . within 6 months after surgery , full recovery of all biochemical and functional parameters of the left ventricle were observed . at that time ca was done , depicting normal coronary arteries.conclusionstts could be diagnosed by the use of non - nephrotoxic tests 123i - mibg myocardial scintigraphy , mps and echocardiography .

since the last description of rebase in the 2003 nar database issue ( 1 ) , there has been considerable growth in the size of the database primarily due to the large number of restriction modification ( rm ) genes that can be found in the sequence databases . more than 200 bacterial and archaeal genomes are available from genbank ( 2 ) and it is now clear that rm systems are much more common than had once seemed likely . mainly , this is because of the difficulty of detecting type i systems or solitary dna methyltransferases by biochemical or genetic assay . putative rm genes identified in these genomes are named systematically according to recently published nomenclature rules ( 3 ) and all have the suffix the rebase website ( http://rebase.neb.com/rebase/rebase.html ) summarizes all information known about every restriction enzyme and their associated proteins . this includes source , commercial availability , sequence data , crystal structure information , cleavage sites , recognition sequences , isoschizomers and methylation sensitivity . within the reference section of rebase , links are maintained to the full text of all papers whenever that is freely available on the web . rebase includes links to genbank and pubmed , and ncbi 's linkout utility uses rebase , pubmed and genbank record numbers to hook directly into rebase 's enzyme , sequence , reference and genome data . links to other major databases such as swissprot ( 4 ) , pdb ( 5 ) and pfam ( 6 ) are also maintained . there are currently 3681 biochemically characterized restriction enzymes in rebase and of the 3612 type ii restriction enzymes , 588 are commercially available , including 221 distinct specificities from a total of 253 total specificities known . as can be seen from figure 1 , the major growth in rebase during the previous two years has been in the number of putative genes for rm system components . more than 620 restriction enzyme genes and 2200 dna methyltransferase genes can be identified in genbank entries . the method used to identify putative rm genes in dna sequences has three fundamental components : the rebase database itself , an expert - derived set of rm system features and a computer program designed to spot these features in anonymous sequences . each sequence analyzed is checked for its overall sequence similarity to rebase gene sequences . for dna methyltransferase sequences , which are the primary indicator of an rm system , the presence , proper order and characteristic spacing of well - conserved motifs suggest the candidates . the more widely divergent genes of the restriction enzymes reside close to the genes for their cognate methyltransferases . such associations point to potential restriction enzyme genes , even when they lack any similarity to genes of known enzymes . publicly available sources of non - eukaryotic sequences are also analyzed frequently by this system . specialized information is available from the rebase lists icon and information about the sensitivity of restriction enzymes to dna methylation can be found by clicking on the rebase methylation sensitivity icon . in the latter case , the data is shown in double - strand format so that the effects of hemi - methylation and double - strand methylation are clearly differentiated . nebcutter analyzes dna sequences for the presence of restriction enzyme recognition sites ( 7 ) . rebsites will generate theoretical digests of an input dna with each of the 253 known specificities . rebpredictor is a tool for predicting restriction enzyme recognition sites that is an updated version of tables ( 8) and a specific blast ( 9 ) option permits a new sequence to be analyzed for rm genes . the rebase genomes icon leads to data for the currently sequenced 193 bacterial and 21 archaeal genomes . schematic representations of the whole genomes and the individual rm system within them are available and , from the pages showing the sequence schematics , there are links to the major database entries for these genes as well as links that will identify the closest neighboring sequences . this can be extremely useful in making predictions about the recognition sequence specificity of newly sequenced systems . this whole section of rebase provides a valuable resource for the annotation of the rm genes in a newly sequenced bacterial genome , particularly given the large numbers of rm systems that are often found . scientists interested in using the sequence information in rebase to annotate microbial genomes are encouraged to contact the rebase staff . special thanks are due to the many individuals who have so kindly contributed their unpublished results for inclusion in this compilation and to the rebase users who continue to steer our efforts with their helpful comments . this database is supported by the national library of medicine ( lm04971 ) and new england biolabs .

rebase is a comprehensive database of information about restriction enzymes , dna methyltransferases and related proteins involved in restriction modification . it contains both published and unpublished work with information about recognition and cleavage sites , isoschizomers , commercial availability , crystal and sequence data . experimentally characterized homing endonucleases are also included . additionally , rebase contains complete and up - to - date information about the methylation sensitivity of restriction endonucleases . an extensive analysis is included of the restriction modification systems that are predicted to be present in the sequenced bacterial and archaeal genomes from genbank . the contents of rebase are available by browsing from the web ( http://rebase.neb.com/rebase/rebase.html ) and through selected compilations by ftp ( ftp.neb.com ) and as monthly updates that can be requested via email .