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we compared serum polychlorinated dibenzo - p - dioxins ( pcdds ) and polychlorinated dibenzofurans ( pcdfs ) among residents of two homes to levels among age- and sex - matched comparison subjects . the residents of the two homes consumed contaminated eggs and beef from animals raised at the homes . the animals had greater soil contact than those raised with conventional commercial husbandry practices . the comparison subjects were from a similar rural area , but did not consume home - produced beef and eggs . serum levels of 2,3,7 , 8-substituted tetra- , penta- , and hexacdds and penta- , hexa- , and heptacdfs were increased between 2- and 6-fold in residents from one home ; contaminated eggs and beef were consumed by residents for 2 - 15 years . elevations were less for those in the other index home , where only home - produced eggs were consumed for 2 years ; a 3-fold elevation of 1,2,3,7,8,9-hexacdd as compared to controls was most apparent . very strong bivariate correlations among all of the 2,3,7 , 8 penta- and hexacdds / cdfs were observed . the elevations observed verify that pcdd / pcdf - contaminated food contributed to the body burden of these compounds . the blood levels among the highest exposed participants are generally higher than those observed in other studies of u.s . contaminated - fish consumers and higher than average adipose tissue levels observed in u.s . urban populations . there are sufficient animal toxicologic and human epidemiologic data to recommend that exposures be reduced . in the study area , pentachlorophenol and pentachlorophenol incineration sources have been identified , and the animal contamination and blood elevations probably reflect these sources . soil reference values and site - specific risk assessments should include estimates of exposures to contamination in home - produced animal products . such estimates can be verified with limited pcdd / pcdf sampling of animals and humans.imagesfigure 1figure 2

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a review of the literature and an extensive medline search revealed that this is the first case report of the use of guaifenesin to increase sperm motility . he reported an inability to conceive with his wife after 18 months of unprotected intercourse . a semen analysis was performed that included spermatozoa count , liquefaction , morphology , motility , viscosity and volume . two months after guaifenesin therapy the semen analysis was repeated that demonstrated marked improvement in both total sperm count and motility . evidence for the effectiveness of guaifenesin is almost entirely anecdotal . given the mechanism of action of guaifenesin , it is not clear from this case why the patient demonstrated such a large improvement in both sperm count and motility . additional studies of the effects of guaifenesin on male fertility could yield information of the medication s effect on men with normal or decreased total sperm counts . there are currently anecdotal reports and popular news media stories on the use of guaifenesin , particularly the brand name product robitussin ( pfizer , inc . , new york , ny ) , for use in treating both male and female infertility.14 guaifenesin is an expectorant medication sold over the counter and usually taken by mouth to assist expectoration of phlegm from the airways in acute respiratory tract infections . its mode of action in treating infertility is not well understood , but it appears to decrease mucus viscosity . a 32-year - old male patient presented to his primary care provider for an infertility evaluation . the patient is a nonsmoker , who consumes little or no alcohol with no known allergies . a recent screening exam for pulmonary tuberculosis was negative and the patient had recently undergone a required military service physical exam . he reported an inability to conceive with his wife after 18 months of unprotected , regular intercourse . as part of a routine infertility evaluation a semen analysis was performed that included spermatozoa count , liquefaction , morphology , motility , viscosity and volume ( cpt code 89320 ) . initial results of the semen analysis demonstrated low sperm count and motility ( table 1 ) . this sample , as well as the follow - up sample , were obtained through masturbation and provided to the lab within 30 minutes of collection . the patient s primary care provider offered treatment with guaifenesin 600 mg extended release tablets twice daily . the repeat semen analysis demonstrated marked improvement in both total sperm count and motility ( table 1 ) . the patient made no other significant lifestyle changes during the treatment course with guaifenesin . at the time of writing this case report describes the semen analysis laboratory results in a male patient who was given guaifenesin . guaifenesin is a mucolytic agent usually taken orally to assist the expectoration of phlegm from the airways in acute respiratory tract infections . scientific evidence for the effectiveness of guaifenesin is almost entirely anecdotal ; a review of medical literature revealed very limited data on use of guaifenesin for infertility.5,6 there appeared to be some improvement in a small study without controls of female infertility related to hostile cervical mucus.5 check regards guaifenesin as the simplest but least effective method of improving cervical mucus.7 given the proposed mechanism of action of guaifenesin , it is not clear from this case why the patient demonstrated such a large improvement in both sperm count and motility . additional study of the effects of guaifenesin on male fertility suggests the need to conduct a more rigorous placebo - controlled clinical trial that could yield information of the medication s effects on men with normal or decreased total sperm counts .

backgrounda review of the literature and an extensive medline search revealed that this is the first case report of the use of guaifenesin to increase sperm motility.casea 32-year - old male presented for an infertility evaluation . he reported an inability to conceive with his wife after 18 months of unprotected intercourse . a semen analysis was performed that included spermatozoa count , liquefaction , morphology , motility , viscosity and volume . initial results of the semen analysis demonstrated low sperm count and motility . the provider offered treatment with guaifenesin 600 mg extended release tablets twice daily . two months after guaifenesin therapy the semen analysis was repeated that demonstrated marked improvement in both total sperm count and motility.conclusionevidence for the effectiveness of guaifenesin is almost entirely anecdotal . given the mechanism of action of guaifenesin , it is not clear from this case why the patient demonstrated such a large improvement in both sperm count and motility . additional studies of the effects of guaifenesin on male fertility could yield information of the medication s effect on men with normal or decreased total sperm counts .

Background Case Conclusion Background Case Conclusion

because of rampant concern that estrogenic chemicals in the environment may be adversely affecting the health of humans and wildlife , reliable methods for detecting and characterizing estrogenic chemicals are needed . it is important that general agreement be reached on which tests to use and that these tests then be applied to the testing of both man - made and naturally occurring chemicals . as a step toward developing a comprehensive approach to screening chemicals for estrogenic activity , three assays for detecting estrogenicity were conducted on 10 chemicals with known or suspected estrogenic activity . the assays were 1 ) competitive binding with the mouse uterine estrogen receptor , 2 ) transcriptional activation in hela cells transfected with plasmids containing an estrogen receptor and a response element , and 3 ) the uterotropic assay in mice . the chemicals studied were 17 beta - estradiol , diethylstilbestrol , tamoxifen , 4-hydroxytamoxifen , methoxychlor , the methoxychlor metabolite 2,2-bis(p - hydroxyphenyl)-1,1,1-trichloroethane ( hpte ) , endosulfan , nonylphenol , o , p'-ddt , and kepone . these studies were conducted to assess the utility of this three - assay combination in the routine screening of chemicals , or combinations of chemicals , for estrogenic activity . results were consistent among the three assays with respect to what is known about the estrogenic activities of the chemicals tested and their requirements for metabolic activation . by providing information on three levels of hormonal activity ( receptor binding , transcriptional activation , and an in vivo effect in an estrogen - responsive tissue ) , an informative profile of estrogenic activity is obtained with a reasonable investment of resources.imagesp1296-afigure 1.figure 2.figure 3.figure 4.figure 5 .

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we have prepared two new diastereoisomeric 2-aza-5-phosphabicyclo[2.2.1]heptanes from naturally occurring trans-4-hydroxy - l - proline in six chemical operations . these syntheses are concise and highly efficient , with straightforward purification . when we used these chiral phosphines as catalysts for reactions of -substituted allenoates with imines , we obtained enantiomerically enriched pyrrolines in good yields with excellent enantioselectivities . these two diastereoisomeric phosphines functioned as pseudoenantiomers , providing their chiral pyrrolines with opposite absolute configurations .

Supplementary Material

nathan , as an oncology fellow , knew well that white blood cells fought infections . this was an experiment repeated in front of us all the time , he says : chemotherapy lowered his patients ' white blood cells and increased their risk of infections . mackaness had shown that macrophage activation did not depend on direct contact with t cells ( 1 ) , suggesting the possibility of a secreted factor . when nathan tested the supernatant from activated t cells , he saw that it did indeed induce macrophage activation ( 2 ) . nathan got a rough idea of the molecular weight ( 3 ) , but that was the best anyone could do , he says . protein separation methods were primitive , and cloned proteins and monoclonal antibodies would only become available a decade later . henry murray , one of nathan 's collaborators , sums up the feeling of frustration : we were all nibbling at the edges of the same problem . nathan therefore changed tack to take a closer look at the activated macrophages . short - lived neutrophils were known to produce hydrogen peroxide , and nathan found the same was true of longer - lived activated macrophages ( 4 ) . unlike previous signs of macrophage activation increased spreading , phagocytosis , and glucose metabolism this so - called respiratory burst ifn had been on the cover of time magazine , and recombinant murine ifn was found to induce macrophages to kill tumor cells ( 5 ) . nathan , now a faculty member in zanvil cohn 's macrophage factory at rockefeller university ( new york , ny ) , thought ifn might also activate macrophages to kill intracellular parasites . consistent with this idea , ifn was made by antigen - stimulated t cells and was associated with defense from infection . now the respiratory burst gave nathan an assay , berish rubin ( down the street at the new york blood center ) supplied an ifn monoclonal antibody , and a phone call to genentech yielded recombinant ifn. in a seminal paper published in the journal of experimental medicine in 1983 , nathan was thus able to show that depleting ifn from unpurified t cell supernatants decreased the respiratory burst activity and the killing of intracellular protozoa in human macrophages . adding back recombinant ifn into this mix restored macrophage activation ( 6 ) . i had an assay , a hunch , a history of purifying proteins that did this , and the serendipity of meeting with people nearby who had the antibody . nathan next showed that ifn worked in people . injecting recombinant ifn directly into cutaneous lesions of lepromatous leprosy patients induced macrophage infiltration , hydrogen peroxide production , and killing of the causative pathogen , mycobacterium leprae ( 7 ) . in the 1990s , the macrophages of children with ifn receptor deficiencies were shown to be defective in killing mycobacteria ( 8) . tracing the pathway from t cells to macrophages to bacteria started , for nathan , in 1967 , and he says we still haven't finished making the molecular links .

t cells tell macrophages when to start making the toxic soup of lysosomal enzymes , reactive oxygen species , and nitric oxide that destroys intracellular pathogens . in 1983 , carl nathan proved that this start signal comes in the form of the secreted cytokine ifn.

The elusive eluate Back on track

temporary henna tattoos or pseudotattoo have become increasingly widespread among children and adolescent , as a safe and economic alternative to permanent tattoos . it is well - known that allergic skin reactions to natural henna are rare , due to its extremely low rate of sensitization . in india , north of africa , china , and egypt , it is used in weddings and religious ceremonies ; in occident , it is used to dye hair and cosmetics . paraphenylenediamine ( ppd ) , a powerful allergen , is added to the henna tattoo mixtures ( black henna tattoo ) to decrease application time and intensify the color . we describe the case of a 7-year - old boy who reported erythematous papular bulls - eye shaped lesions and consolidated edema primarily in the upper and lower extremities [ figure 1 ] . he also showed an erythematous - eczematous lesion on his leg , shaped like a dolphin [ figure 2 ] , and lesions compatible with erythema multiforme - like reaction . erythematous papular lesions contact eczema in the tattoo area dolphin shaped patch tests were performed , and we observed a high sensitivity after 48 h and moderate after 96 h. we reported a positive reaction to ppd . henna has been used to paint the skin for adornment and religious reasons for 9000 years and in over 60 countries . christians , jews , muslims , hindus , and buddhists have used henna as part of their religious customs . the henna is a flowering plant native to northern africa , western and southern asia in semi - arid zones , used since antiquity to dye skin . it has a great affinity for keratinocytes , and it is used to create temporary tattoos , without it being necessary to puncture the skin . black henna contains an ingredient in addition to pure henna to achieve its ebony color . in most cases , this added ingredient is ppd , a powerful sensitizer that should not be directly applied to the skin as it may cause mild contact dermatitis . one of the most dangerous applications of this chemical is when it is added to henna because the dye is applied while the ppd is in its oxidation process , and its potential as allergen is increased . when added to henna , the concentration of ppd is often much higher than what is approved for use in hair dyes . the cause of the sensitivity to ppd is unknown ; it is believed that the mechanism involved in the pathogenesis may be a reaction mediated by type iii immune complexes and associated with type iv retarded hypersensitivity . various topicals allergens cause erythema multiforme , including topical drugs such as corticosteroids , nonsteroidal anti - inflammatory drugs , iodine povidone , imiquimod ; rubber gloves ; nickel and herbicides . three possible causes of the residual hypopigmentation have been described : a reduction in melanin synthesis , selective destruction of the melanocytes , or photoleukomelanodermitis due to pigment blocking . as henna tattoos are becoming increasingly popular , prevention requires the provision of information to consumers , especially young people and their parents . it is important for the population to be aware of this circumstance and the risk entailed by sensitization to ppd . to conclude , we believe that temporary black henna tattooing should be controlled by health authority legislation to minimize the appearance of new cases of reaction to ppd and the serious and permanent consequences we have presented . it is important for the population to be aware of the risk entailed by sensitization to ppd due to popular henna tattoos .

temporary henna tattoos or pseudotattoos have become increasingly widespread among children and adolescent . a generalized skin reaction , type erythema multiforme - like reaction is unusual , and rarely reported . we describe the case of a 7-year - old boy who reported erythematous papular bulls - eye shaped lesions and consolidated edema primarily in the upper and lower extremities . these lesions were compatibles with erythema multiforme - like reaction . he also showed an erythematous - eczematous lesion on his leg , shaped like a dolphin . in this area , a temporary henna tattoo was painted 1-month earlier . patch test was positive for paraphenylenediamine ( ppd ) . skin reactions due to henna are rare . most of the reactions are due to additives , especially ppd , an aniline derivative , which is added to speed up the process of skin dyeing and to give a darker brown to black color ( black henna ) . as henna tattoos are becoming increasingly popular , prevention requires the annual provision of information to consumers , especially young people and their parents .

Introduction Case Report Discussion

a 55 year - old man visited our emergency department because of increasing frequency of chest pain . he had undergone off - pump coronary artery bypass grafting ( cabg ) 10 years ago because of unstable angina associated with three vessel coronary artery disease . at the initial operation , the in situ right internal thoracic artery ( ita ) , in situ left ita and in situ right gastroepiploic artery ( rgea ) grafts were used to revascularize the left anterior descending coronary artery , two obtuse marginal coronary branches , and posterior descending coronary artery , respectively . an excess segment of the distal right ita was connected to the side of left ita as a y - composite graft and anastomosed to the first diagonal coronary artery . coronary angiography and myocardial single photon emission computed tomography ( spect ) were performed at 5 years after surgery as a follow - up study . the 5-year angiography showed all patent grafts and the myocardial spect demonstrated no perfusion decrease . exertional chest pain recurred at 7 years after surgery , and a repeated coronary angiography showed patent previous grafts including faint visualization of the in situ rgea graft associated with significant stenosis at the os of the celiac axis . the computed tomographic angiogram also demonstrated a 90% stenosis at the celiac os , which had been without stenosis on abdominal angiography taken before the surgery ( fig . redo off - pump cabg was performed 10 years after the initial surgery because of an increasing frequency of angina and an aggravated finding of the follow - up myocardial spect , which was a newly developed reversible perfusion decrease in the inferior wall ( fig . , the great saphenous vein was harvested from the lower leg and interposed between the middle part of in situ right ita and distal part of in situ rgea grafts used previously , to supply blood flow from the right ita graft to the posterior descending coronary artery . one year after redo surgery , the patient had no symptoms of angina and coronary angiogram was performed and revealed patent grafts , including an interposed saphenous vein graft ( fig . 3a ) . the myocardial spect test was also performed and demonstrated that there was no perfusion decrease including the inferior wall ( fig . reoperations for coronary artery disease have been increased due to the increased number of isolated cabg . the society of thoracic surgeons statistics indicated that nearly 5% of the current cabg procedures done in the us were repeat surgical revascularization . angiographic indications for reoperation are progression of native coronary atherosclerosis , previous graft failure or a combination of both . one previous study demonstrated that 4 out of 400 patients who underwent cabg using the rgea graft needed percutaneous interventions due to the rgea graft failure during postoperative follow - up of 2211 months . one of those 4 patients required an angioplasty for a newly developed stenosis of the celiac trunk . in the present case , an indication for reoperation the patient had been free of angina , and the angiographic and myocardial spect follow - up studies revealed no abnormal findings at postoperative 5 years . when the patient suffered from recurred angina at postoperative 7 years , coronary angiography showed a faint visualization of the in situ rgea graft associated with significant stenosis at the os of the celiac axis . the 10-year follow - up myocardial spect test demonstrated a newly developed reversible perfusion decrease in the inferior wall . the prevalence of celiac axis stenosis was 7.3% in a korean population although it was lower than the previously reported incidence of celiac axis stenosis in western populations ranged from 12.5% to 24% . in the present case , celiac artery stenting could be an alternative option in such a case . however , we performed a redo operation because celiac axis stenting was associated with a high incidence of late restenosis . the aorta or another in situ arterial graft could be chosen as a blood source . alternatively , patent in situ grafts used previously may be re - used as an inflow conduit . with regards to our patient , the 3 in situ arterial grafts had already been used . the saphenous vein graft was interposed between the middle part of right ita and distal part of in situ rgea grafts used previously .

we report a redo coronary artery bypass grafting ( cabg ) in a 55-year - old man . angina recurred 7 years after the initial surgery . coronary angiography showed all patent grafts except a faint visualization of the in situ right gastroepiploic artery ( rgea ) graft , which was anastomosed to the posterior descending coronary artery , associated with celiac axis stenosis . redo - cabg was performed at postoperative 10 years because of aggravated angina and decreased perfusion of the inferior wall in the myocardial single photon emission computed tomography . the saphenous vein graft was interposed between the 2 in situ grafts used previously ; the right internal thoracic artery and rgea grafts . angina was relieved and myocardial perfusion was improved .

CASE REPORT DISCUSSION

care coordination is an important aspect of nursing care especially for elderly patients admitted to an acute care setting . in singapore care coordination and transitional care nursing is a new concept of care nevertheless important but unexplored . the objective of this paper is to explore the characteristics of elderly patients receiving care coordination , determine care gaps and intervention during home visit and telephonic review . a designed questionnaire was used to collect information on the patient s demography , social and clinical profile and determine post discharge activities using eric coleman s four pillars tool . the retrospective data from the patient s index admission from the last six months ( nov 08april 09 ) was analyzed using spss version 16 . majority , 69% were above 70 years old of which 57% female and 76% lives with their children . clinical information demonstrates that 53% had 36 co - morbidities and 58% were taking more than five medications . the abbreviated mental test score were 6.2 , 6% were depressed and delirium was present in 14% of patients . only 65 patients ( 0.1% ) had home visits and telephonic review done whilst 97% of the remaining had only telephonic review done . those who had both telephonic and home visit review , medications advice and compliance were checked only in 0.8% ( at one week ) and 1.6% ( at one month ) whilst during home visit this was done in 12.2% of patients as medication discrepancy were apparent at home . as for appointment compliance and compilation were done in 0.8% at one week and 51% at four weeks of telephonic review compared to during home visit only 4.8% . caregivers education was emphasized in 14% of patients at home visit , 2% at one week and 4% at one month of telephonic review . the result showed that home visit is effective in exploring medication compliance , advice and emphasizing caregiver education , managing appointments can be effectively done through telephone review . this study demonstrates the vital role of home visit for elderly patient to safely transit between hospitals to home .

introductioncare coordination is an important aspect of nursing care especially for elderly patients admitted to an acute care setting . in singapore care coordination and transitional care nursing is a new concept of care nevertheless important but unexplored.aim/objectivesthe objective of this paper is to explore the characteristics of elderly patients receiving care coordination , determine care gaps and intervention during home visit and telephonic review.research design and samplinga designed questionnaire was used to collect information on the patient s demography , social and clinical profile and determine post discharge activities using eric coleman s four pillars tool . a pilot study of ten questionnaires was conducted . the retrospective data from the patient s index admission from the last six months ( nov 08april 09 ) was analyzed using spss version 16.resulttotal of 517 patients were recruited from october 2008 to march 2009 . majority , 69% were above 70 years old of which 57% female and 76% lives with their children . clinical information demonstrates that 53% had 36 co - morbidities and 58% were taking more than five medications . the abbreviated mental test score were 6.2 , 6% were depressed and delirium was present in 14% of patients.only 65 patients ( 0.1% ) had home visits and telephonic review done whilst 97% of the remaining had only telephonic review done . those who had both telephonic and home visit review , medications advice and compliance were checked only in 0.8% ( at one week ) and 1.6% ( at one month ) whilst during home visit this was done in 12.2% of patients as medication discrepancy were apparent at home . as for appointment compliance and compilation were done in 0.8% at one week and 51% at four weeks of telephonic review compared to during home visit only 4.8% . caregivers education was emphasized in 14% of patients at home visit , 2% at one week and 4% at one month of telephonic review.discussionthe result showed that home visit is effective in exploring medication compliance , advice and emphasizing caregiver education , managing appointments can be effectively done through telephone review.conclusionthis study demonstrates the vital role of home visit for elderly patient to safely transit between hospitals to home .

Introduction Aim/objectives Research design and sampling Result Discussion Conclusion

supported by nci 2p50 ca09825806 , nci u01 ca168394 , stand up to cancer / aacr dream team translational cancer research grant su2c - aacr - dt0209 , tcga gdac grant ( nih / nci u24 ca143883 ) to gbm ; mdacc uterine spore career development award ( nci p50ca098258 ) to lwt .

pik3r1 ( encoding the p85 subunit of phosphatidylinositol 3-kinase ) is the 11th most frequently mutated gene across tumors . we recently reported neomorphic p85 mutants that induce signaling cascades not predicted by the canonical functions of p85 , suggesting the need to functionally annotate specific mutations in cancer genes for effective genome - informed personalized therapy .

Disclosure of Potential Conflicts of Interest Funding

the laparoscopic removal of a cervical stump following a supra cervical ( subtotal ) hysterectomy was first described by nezhat et al , and they concluded that the cervical stump could be removed laparoscopically by an experienced surgeon . the advantages of the laparoscopic approach included possible stump adhesiolysis , providing adequate postoperative vault support , and assessment of the pelvic lymph nodes . the 43-year - old , presented with a history of persistent p v discharge and occasional post - coital bleeding . she had undergone subtotal hysterectomy in 1994 , due to postpartum hemorrhage following a normal delivery . a colposcopic biopsy done in january 2009 , reported severe dysplasia of the cervix , with a human papillomavirus ( hpv ) effect and crypt extension . there was a strong family history of cancer of the cervix , as her mother had succumbed to the disease . on general examination she was in fair general condition , well - built and well - nourished , with adequate hydration . the hemoglobin was 13.3 g / dl , blood sugar was 5.3 mmols / l , urea and electrolytes were normal . an initial diagnosis of abnormal pap smear was entertained and the patient opted for a laparoscopic trachelectomy , with the option of a laparotomy , after discussing all her options . there were dense adhesions in the pouch of douglas involving the bowel and the cervical stump . the pelvic lymph nodes were clearly visualized ( after intracervical methylene blue injection ) and did not appear to be enlarged . gentle adhesiolysis was undertaken using sharp dissection , bipolar cautery , and a harmonic scalpel . the vaginal vault was subsequently opened over the ceramic cup of a clermont ferrand elevator . a cystoscopy with retrograde ureteral catheterization , to confirm the integrity of the bladder and ureters , was undertaken . the cervical stump after laparoscopic trachelectomy at one week of follow - up the patient was well . a postoperative intravenous urogram ( ivu ) confirmed that both the ureters and bladder were intact . subtotal hysterectomy was developed as a procedure in the 1990s , and is regarded as a safe option to total abdominal hysterectomy in the management of benign uterine conditions and in obstetrics , due to severe postpartum hemorrhage . okaro et al , in an assessment of the long - term outcomes of laparoscopic supracervical hysterectomy analyzed the case records of 70 consecutive women undergoing the procedure . of these , 24.3% ( 17 cases ) reported symptoms related to the cervical stump , within 14 months of the original surgery . in his series 14 of these patients underwent laparoscopic trachelectomy , one had only laparoscopic adhesiolysis and two underwent a laparotomy with trachelectomy due to dense bowel adhesions on the cervical stump . histologically the stumps showed endometriosis ( 23.5% ) and mild dysplasia in 7.6% of the patients . in this case our patient presented with persistent p v discharge and occasional post - coital bleeding . the subsequent pap smears were abnormal . in a retrospective of 41 patients undergoing laparoscopic subtotal hysterectomy , van der stege et al , noted that 98% of the patients were satisfied with their procedure , with 10% of them having monthly spotting . they concluded that although laparoscopic hysterectomy for benign diseases was a satisfactory procedure , special attention should be paid to careful management of the cervical stump . hilger et al , reviewed the indications of 310 trachelectomies performed at the mayo clinic from 1974 to 2003 . they included stump prolapse ( 4% ) , fibroid mass ( 1% ) , cervical dysplasia ( 6% ) , carcinoma in situ ( 5% ) , irregular bleeding ( 2% ) , and cervicitis ( 53% ) . the complications following vaginal trachelectomies were encountered in 80% of the procedures against 37% in the abdominal procedure . in our report the cervical stump confirmed carcinoma in situ .

a 43-year - old , who underwent a subtotal hysterectomy for postpartum hemorrhage following a normal delivery , 10 years ago , presented with a history of persistent vaginal discharge and post - coital bleeding . a pap smear reported moderate dysplasia , and a subsequent colposcopic biopsy reported severe dysplasia with crypt extension . the patient underwent a laparoscopic trachelectomy , and histology of the stump reported cervical squamous carcinoma in situ , with no microinvasion .

INTRODUCTION CASE REPORT THE OPERATION DISCUSSION

established in 2003 , erste foundation has a history stretching back 190 years to the year 1819 when it was founded as the erste sterreichische spar casse in vienna . rooted in our history as a social enterprise and financial service provider , erste foundation recognises that contemporary society faces huge challenges and that for a new and united europe to work , integration is crucial and that means uniting the economic , cultural and social capital of our region . we develop ideas and concepts to increase social participation and to ensure that no - one is left out , whatever their circumstances which in turn creates stable , effective and fairer societies . we want to work against prejudice and nationalism , to integrate thinking and living across borders , and make these experiences accessible , particularly to the young generation . we intend to play an active role in giving people opportunities to increase their understanding of each other . therefore , erste foundation has supported research projects that concern themselves with the effects of societal transformation processes : in particular we have been looking at the effects that demographic changes will have on the long - term care needs of elderly people in central and eastern europe . from this , we intend to develop policy recommendations for decision makers in civil society , economy and politics .

introductionestablished in 2003 , erste foundation has a history stretching back 190 years to the year 1819 when it was founded as the erste sterreichische spar casse in vienna . rooted in our history as a social enterprise and financial service provider , erste foundation recognises that contemporary society faces huge challenges and that for a new and united europe to work , integration is crucial and that means uniting the economic , cultural and social capital of our region.descriptionwe develop ideas and concepts to increase social participation and to ensure that no - one is left out , whatever their circumstances which in turn creates stable , effective and fairer societies.european integration is important to us . we want to work against prejudice and nationalism , to integrate thinking and living across borders , and make these experiences accessible , particularly to the young generation.projectswe intend to play an active role in giving people opportunities to increase their understanding of each other . therefore , erste foundation has supported research projects that concern themselves with the effects of societal transformation processes : in particular we have been looking at the effects that demographic changes will have on the long - term care needs of elderly people in central and eastern europe . from this , we intend to develop policy recommendations for decision makers in civil society , economy and politics .

Introduction Description Projects

acute generalized exanthematous pustulosis ( agep ) is a rare acute reaction that is drug - induced in 90% of the cases , characterized by a widespread , sterile pustular rash . cefepime is a fourth generation cephalosporin antibiotic used to treat febrile neutropenia , severe infections related to the urinary tract , skin , nosocomial pneumonia , brain abscess , and intra - abdominal and septic lateral / cavernous sinus thrombosis . a 67-year - old man with renal failure who had been on dialysis during the last 2 years and with an 8-year history of cardiac insufficiency was admitted to the hospital complaining of 6 days of diarrhea . the patient was taken to the semi - intensive care unit and treated with ciprofloxacin . as a consequence , his long - term medications had not been changed and consisted of acetylsalicylic acid , furosemide , captopril , carvedilol and clonazepam . on the seventh day , the patient became dyspneic and his chest radiograph showed a left lower lobe opacity . treatment for nosocomial pneumonia was promptly initiated with cefepime ( 1 g / day ) . five days later , he presented with a pruritic , erythematous , maculopapular eruption affecting the abdomen , neck and skin folds . one day later , he developed disseminated pustular lesions ( fig . 1 ) and his temperature was 37c . laboratory exams evidenced c - reactive protein 136 mg / l , white blood cells 14,700 cells/l ( normal 3,50010,500 cells/l ) with 11,995 cells/l neutrophils ( normal 1,7008,000 cells/l ) . histology showed a toxic pustuloderma with spongiform subcorneal pustules , edema in the papillary dermis and perivascular inflammatory infiltrate consisting of neutrophils ( fig . after withdrawal of cefepime and introduction of imipenem , the disseminated skin nonfollicular pustules cleared within 4 days following a desquamation . the patient denied previous adverse reaction to other drugs and no personal or family history of psoriasis was evident . agep is a disease characterized by the rapid onset of many sterile , nonfollicular pustules usually arising on an edematous erythema and frequently accompanied by leukocytosis and fever . skin symptoms usually arise rapidly after an insult and resolve spontaneously ( within a few days ) . agep often starts predominantly in intertriginous areas or on the face , spreading rapidly to the trunk and lower limbs . the mean duration of the pustules is 9.7 days , and an annular desquamation typically follows for a few days . complications are rare [ 1 , 3 ] . the agep validation score of the euroscar study group has been used to establish the diagnosis . a score between 8 and 12 for agep is a definitive diagnosis ( table 1 ) . the case score was 11 , according to the validation score of the euroscar study group ( table 2 ) . the main differential diagnosis of agep is pustular psoriasis . because the pustules clinically and histologically resemble the lesions of pustular psoriasis and because in a number of reports patients had a history of plaque psoriasis , some authors assume that agep is nothing more than an acute exacerbation of psoriasis caused by a variety of exogenous triggers however , many studies strongly suggest that agep is not associated with psoriasis [ 1 , 5 ] . up to now agep has been attributed to a variety of causes such as viral infections , chlamydia pneumoniae infection or hypersensitivity to mercury , but the skin reaction is primarily an adverse response to drugs . antibiotics , other than cefepime , have been implicated as the causative agents in 80% of individuals . in this group , the present case of agep has well defined criteria , and because correct diagnosis generally leads to spontaneous resolution once the causative drug is withdrawn , clinicians should keep the possibility of this cutaneous drug reaction in mind .

acute generalized exanthematous pustulosis ( agep ) is a rare cutaneous rash characterized by widespread sterile nonfollicular pustules . cefepime is a fourth generation cephalosporin , used to treat severe infections . a 67-year - old man was admitted with acute gastroenterocolitis . on the seventh day , the patient developed a nosocomial pneumonia and cefepime was initiated . on the fourth day of cephalosporin treatment , he presented with a maculopapular , pruritic eruption affecting the face , neck , abdomen and limbs . one day later he developed disseminated pustular lesions and his temperature was 37c . laboratory analysis evidenced leukocytosis and skin biopsy showed subcorneal pustule , edema in the papillary dermis , perivascular inflammatory infiltrate consisting of neutrophils , leukocytoclasia and red cell extravasation in the epidermis . cefepime was suspended and within 4 days the non - follicular pustules cleared following a desquamation . agep is a disease attributed to a variety of causes , but in 90% of the cases it is due to an adverse drug reaction . antibiotics are implicated in 80% of these cases , mostly penicillins and macrolides . there are few cases associated with cephalosporins . it is very important to consider agep in cases of acute pustular rashes and drugs should be investigated as causative agents .

Introduction Case Report Discussion

canaliculitis is a common encounter in ophthalmic practice but supernumerary puncta and canaliculi ( spc ) are rare congenital disorders . in a large series a 59-year - old gentleman presented with painful swelling of the left lower lid for a week , which was associated with epiphora . the swelling was confined to the nasal aspect of the left lower lid ( 0.50.5 mm ) with inflamed overlying skin ( figure 1a ) . eversion of the lower eyelid revealed two puncta , 0.5 mm apart ( figure 1b ) . the outer punctum was situated at the normal anatomical position ; whereas the inner punctum in the caruncle . gentle pressure did not result in any regurgitation from the both puncta . the patient was treated with oral cloxacillin 500 mg , 6 hourly for 5 days . the outer punctum had a soft stop with regurgitation of fluid from the same punctum . the outer punctum - canaliculus system was a cul - de - sac ( figure 1c ) . c ) dacryocystography showed pooling of dye in the cul - de - sac ( white arrow ) . c ) dacryocystography showed pooling of dye in the cul - de - sac ( white arrow ) . most spcs ( 78% ) present with epiphora . among the 23 patients reported by satchi et al . , none presented with canaliculitis . sequestration of tear and debris in the cul - de - sac served as nidus for infection . the resultant canaliculitis with its surrounding edema caused obstruction of the lacrimal drainage ; hence epiphora . epiphora however , may develop despite patent lacrimal drainage system . the 2-compartment model for lacrimal canalicular drainage of kakizaki et al . , suggested that the muscle of duverney - horner may deviate normal flow within the accessory canaliculus and thence transport tears back to the lacrimal tear lake , leading to epiphora . a solid epithelial cord forms in the region of the medial lower eyelid ( figure 2a ) and sends projections to form the canaliculi and the nasolacrimal duct ( figure 2b ) . spc is due to extra out - budding of the solid epithelial cord ( figure 2c ) . canalization begins at 4 months of gestation with disintegration of the central ectodermal core , forming lacrimal drainage outflow system . in this case , the extra inner canalicular epithelial bud ( nearer to the main epithelial cord ) underwent complete canalization and remained connected to the main epithelial cord . the outer canalicular epithelial bud , although its punctum is located at the normal anatomical position , was separated from the main epithelial cord ; forming a cul - de - sac ( figure 2d ) . c ) extra out - budding of the solid epithelial cord in supernumerary puncta and canaliculi . d ) the outer canalicular epithelial cord was separated from the main epithelial cord , forming a cul - de - sac . c ) extra out - budding of the solid epithelial cord in supernumerary puncta and canaliculi . d ) the outer canalicular epithelial cord was separated from the main epithelial cord , forming a cul - de - sac .

we report the first case of supernumerary puncta and canaliculi presented with canaliculitis . a-59 year - old gentleman presented with painful swelling of the left lower lid for a week , which was associated with epiphora . the swelling was confined to the nasal aspect of the left lower lid ( 0.50.5 mm ) with inflamed overlying skin . two puncta ( 0.5 mm apart ) were noted . the outer punctum at the normal anatomical position was a cul - de - sac while the inner punctum it the caruncle was patent . we described the embryology leading to supernumerary puncta and canaliculi to explain the paradoxical patency of the abnormally located punctum as well as the pathomechanism leading to canaliculitis . the patient was treated with oral cloxacillin 500 mg , 6 hourly for 5 days ; the cellulitis subsided after three days .

Introduction Case Report Discussion

mypro is a software pipeline for high - quality prokaryotic genome assembly and annotation . it was validated on 18 oral streptococcal strains to produce submission - ready , annotated draft genomes . mypro installed as a virtual machine and supported by updated databases will enable biologists to perform quality prokaryotic genome assembly and annotation with ease .

Supplementary Material

we are grateful for financial support from the industrial source technology development program of the ministry of knowledge economy ( 10044909 ) , the next - generation biogreen 21 program ( ssac grant # pj01111803 ) , rda , and the kribb initiative program of south korea .

abstractbacterial volatiles protect plants either by directly inhibiting a pathogenic fungus or by improving the defense capabilities of plants . the effect of bacterial volatiles on fungal growth was dose - dependent . a low dosage did not have a noticeable effect on botrytis cinerea growth and development , but was sufficient to elicit induced resistance in arabidopsis thaliana . bacterial volatiles displayed negative effects on biofilm formation on a polystyrene surface and in in planta leaf colonization of b. cinerea . however , bacterial volatile - mediated induced resistance was the major mechanism mediating protection of plants from b. cinerea . it was responsible for more than 90% of plant protection in comparison with direct fungal inhibition . our results broaden our knowledge of the role of bacterial volatiles in plant protection .

Abbreviations Disclosure of potential conflicts of interest Funding

octane - enhancing constituents of gasoline pose a number of health hazards . this paper considers the relative risks of metallic ( lead , manganese ) , aromatic ( e.g. , benzene ) , and oxygenated additives in both industrialized and developing countries . technological advances , particularly in industrialized countries , have allowed the progressive removal of lead from gasoline and the increased control of exhaust emissions . the developing world , by contrast , has relatively lax environmental standards and faces serious public health problems from vehicle exhaust and the rapid increase in automobile use . financial obstacles to the modernization of refineries and vehicle fleets compound this problem and the developing world continues to import large quantities of lead additives and other hazardous materials . progress in decreasing environmental health problems depends both on the adoption of international public health standards as well as efforts to decrease dependence on the private automobile for urban transport.imagesfigure 1.figure 2 .

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ala - al - din abu al - hassan ali ibn abi - hazm al - qarshi al - dimashqi , known as ibn al - nafis ( 1210 - 1288 ad ) , was a muslim syrian physician primarily famous for being the first to describe the pulmonary circulation of the blood . the most voluminous of his books is alshamel fi sanaat tebbiat , which is a comprehensive medical encyclopedia . the aim of this review article , as a tribute to ibn al - nafis , was to introduce his valuable but neglected encyclopedia of materia medica . ibn al - nafis traditional approach in his alshamel fi sanaat tebbiat book is studied in the present article . alshamel fi sanaat tebbiat covers three branches of knowledge . the first category is devoted to theoretical traditional medicine . the third category is on materia medica covering the aspect of unani medicine , from which only 28 volumes of the comprehensive book on the traditional medicine have been found so far . the latter , introduces mono - ingredient medications in alphabetical order . each chapter , in several parts , is dedicated to the botanical characteristics and nature of each mono - ingredient medication . in addition , this book explains traditional pharmacokinetic of every single medication for each human body organs . based on pharmaco - mechanistic perspective on alshamel fi sanaat tebbiat , it could be considered as the main reference book on traditional medicine and pharmacy , worthy of revival .

background : ala - al - din abu al - hassan ali ibn abi - hazm al - qarshi al - dimashqi , known as ibn al - nafis ( 1210 - 1288 ad ) , was a muslim syrian physician primarily famous for being the first to describe the pulmonary circulation of the blood . the most voluminous of his books is alshamel fi sanaat tebbiat , which is a comprehensive medical encyclopedia . it comprised 300 volumes of notes , from which only 80 volumes are published . his writings are cataloged in many libraries around the world . the aim of this review article , as a tribute to ibn al - nafis , was to introduce his valuable but neglected encyclopedia of materia medica.methods:ibn al - nafis traditional approach in his alshamel fi sanaat tebbiat book is studied in the present article.results:alshamel fi sanaat tebbiat covers three branches of knowledge . the first category is devoted to theoretical traditional medicine . the second is in four sections where much of it is not available yet . the third category is on materia medica covering the aspect of unani medicine , from which only 28 volumes of the comprehensive book on the traditional medicine have been found so far . the latter , introduces mono - ingredient medications in alphabetical order . each chapter , in several parts , is dedicated to the botanical characteristics and nature of each mono - ingredient medication . in addition , this book explains traditional pharmacokinetic of every single medication for each human body organs.conclusion:based on pharmaco - mechanistic perspective on alshamel fi sanaat tebbiat , it could be considered as the main reference book on traditional medicine and pharmacy , worthy of revival .

Background: Methods: Results: Conclusion:

though both minor and major spontaneous or post - operative bleeding is the most common presentation of this rare disorder , there are several case reports of thrombotic complications also . there are few reports of myocardial infarction ( mi ) in the literature in patients of afibrinogenemia . a 33-year - old man , who was a confirmed case of congenital afibrinogenemia and was diagnosed six years back when he had excessive bleeding following trauma over face and persisted even after suturing that area , presenting to us with severe retro sternal chest pain of 10 h duration . he had a past history of myocardial infarction ( mi ) two years back and was advised dual antiplatelet therapy . he was born of second degree consanguineous marriage with history of sibling death after birth . on admission , electrocardiogram showed 2 mm st segment elevation in leads ii , iii , avf and st depression in leads i and avl [ figure 1 ] . troponin t obtained at admission was strongly positive with 1.24 ng / ml ( normal- < 0.1 ng / ml ) . coagulation profile was sent after admission and tests revealed absent fibrinogen using the clauss method , markedly reduced fibrinogen antigen level , normal platelet count and bleeding time , infinitely prolonged activated partial thromboplastin time ( aptt ) , prothrombin time ( pt ) and thrombin time . prominent q wave , st segment elevation and t wave inversion in lead ii , iii and avf with st segment depression seen in lead i and avl . right sided chest leads ( v4r - v6r ) showed < 1 mm st segment elevation as this patient had high risk for bleeding , thrombolysis or primary percutaneous transluminal coronary angioplasty ( ptca ) was not advised though he had ongoing chest pain . he was treated with dual antiplatelet therapy ( aspirin plus clopidogrel ) , statins , betablocker , angiotensin converting enzyme inhibitors and injection nitroglycerin ( ntg ) . after few hours of treatment , the chest pain subsided and st segment showed evolving changes . his admission lipid profile was normal ( low density lipoprotein 112 mg / dl , triglyceride 128 mg / dl , high density lipoprotein 40 mg / dl ) . the patient did not experience a recurrence of angina and was discharged three days after admission with dual antiplatelet therapy . fibrinogen is the major coagulation protein in blood by mass : normal fibrinogen levels vary between 1.5 and 3.5 bleeding , which usually manifests already in the neonatal period ( 85% of cases presenting umbilical cord bleeding ) , is the main complication of afibrinogenemia . paradoxically , both arterial and venous thromboembolic complications have also been reported in afibrinogenemic patients . these complications can occur in the presence of concomitant risk factors such as a co - inherited thrombophilic risk factor or after replacement therapy . first , even in the absence of fibrinogen , platelet aggregation is possible due to the action of von willebrand factor and , in contrast to patients with hemophilia , afibrinogenemic patients are able to generate thrombin , both in the initial phase of limited production and also in the secondary burst of thrombin generation . second , the increase of prothrombin activation fragments or thrombin - antithrombin complexes have been observed , reflecting enhanced thrombin generation . so , antithrombin role has also been attributed to fibrinogen because in its absence , clearance of thrombin is impaired . though there are several reports of both arterial and venous thrombosis in afibrinogenemia , only a few cases have been reported where these patients developed mi . with recurrent mi , treatment of mi in the presence of a bleeding disorder like afibrinogenemia is difficult as administration of thrombolysis and anticoagulant will increase bleeding . so , we treated with both aspirin and clopidogrel in our case . as patient stopped taking dual antiplatelet therapy he had recurrence of mi . chest pain subsided after starting injection of ntg and the area of myocardial involvement was also small , we managed the patient conservatively , and discharged him on dual antiplatelet therapy . further study is needed on this aspect to determine the best treatment that we can provide to them . until then dual antiplatelet therapyshould be recommended to all these patient with hereditary bleeding disorder with close supervision of bleeding diathesis since without this treatment they may have recurrences .

afibrinogenemia is a rare autosomal recessive bleeding disorder with an estimated prevalence of 1:1,000,000 . usual presentation of this disorder is spontaneous bleeding , bleeding after minor trauma and excessive bleeding during interventional procedures . paradoxically , few patients with afibrinogenemia may also suffer from severe thromboembolic complications . the management of these patients is particularly challenging because they are not only at risk of thrombosis but also of bleeding . we are presenting a case of 33-year - old male patient of congenital afibrinogenemia who had two episodes myocardial infarction in a span of two years . the patient was managed conservatively with antiplatelet therapy and thrombolytic therapy was not given due to high risk for bleeding .

INTRODUCTION CASE REPORT DISCUSSION

mesenteric pseudocyst is a term used to describe abdominal cystic mass without the origin of abdominal organ.(1 ) this has been classified according to embryologic , ehiologic , histologic , and ther data , causing considerable confusion . it was considered the term mesenteric cyst as merely descriptive , and apply a histologic classification such as lymphangioma , pseudocyst , enteric duplication cyst , enteric cyst , and mesothelial cyst.(2 ) we presented a case of mesenteric pseudocyst of the small bowel in a 70-year - old man . a 70-year - old man was referred to our hospital for operation of gastric cancer with a 1-month history of progressively worsening epigastric and intermittent peri - umbilical discomfort . he had no specific previous medical or surgical history including cancer . on physical examination , esophago - gastro - duodenoscopy ( egd ) showed a 3.5 cm sized excavated lesion on the posterior wall of angle . endocopic biopsy confirmed a histologic diagnosis of poorly differentiated adenocarcinoma including signet ring cell component . endoscopic ultrasonography revealed invasion of caner to the proper muscle layer . abdominal computed tomography ( ct ) scan showed a focal mucosal enhancement in posterior wall of angle of stomach , a 2.4 cm sized enhancing mass on distal small bowel loop without distant metastases or ascites in rectovesical pouch , and multiple gallbladder stones ( fig . 1 ) . these physical , laboratory , and radiological findings prompted us to diagnose early gastric cancer , and gastrointestinal stromal tumor of small bowel . laboratory testing revealed alfa - fetoprotein level of 2.88 ( normal range , 0 to 9 ng / ml ) , carcino - embryonic antigen level of 1.45 ng / ml ( normal range , 0 to 5 ng / ml ) , carbohydrate antigen ( ca ) 19 - 9 level of 6.5 u / ml ( normal range , 1 to 35 u / ml ) , and ca 72 - 4 level of 4.8 u / ml ( normal range , 0 to 4 u / ml ) . other laboratory test results were within normal limit . the patient underwent subtotal gastrectomy with gastroduodenostomy , segmental resection of small bowel , and cholecystectomy . mesenteric mass was adhered severely with greater omentum at the mesenteric side of small bowel , and mesenteric fat tissues . small bowel , mesentery , and mesenteric mass were resected en - bloc methods , and end to end anastomosis was performed . after fixation of the surgical specimen , macroscopic examination revealed a uni - locular cyst measuring 332 cm in size . pathological examination revealed 3 cm sized fibrous cystic wall without endothelial or epithelial lining and foam cell collection ( fig . 2 , 3 ) . pathologic stage of gastric cancer was t1bn1m0 ( 6th international union against cancer tnm staging system ) ; invasion to submusosa , metastases to 4 perigastric lymph nodes out of 16 retrieved nodes , and negative resection margin . mesenteric pseudocysts are very rare intraabdominal mass with an incidence of about 1 case per 100,000 hospital admissions.(3 ) ros et al.(2 ) first used the term " pseudocyst " in the classification of mesenteric cyst . mesenteric pseudocyst could be located in the small bowel , large bowel mesentery and even retroperitoneum.(1,4 ) most reports were pseudocyst of large bowel or retroperitoneum.(1 ) although most mesenteric pseudocysts are asymptomatic , symptomatic mesenteric cysts could be associated with cyst size , cyst location , and complications , including infection , rupture , hemorrhage , and intestinal obstruction.(5 ) in our patient , there was no specific symptom associated with mesenteric pseudocyst except for intermittent vague periumbilical discomfort . if egd and ct scan were not performed in this patient presenting non - specific abdominal pain , the diagnosis of mesenteric pseudocyst would be delayed . to the best of our knowledge , this is the first case report describing incidentally detected mesenteric pseudocyst of small bowel in gastric cancer patients . when clinician performed staging work up for gastric cancer , should be aware the possibility of associated intraabdominal lesions .

mesenteric pseudocyst is rare . this term is used to describe the abdominal cystic mass , without the origin of abdominal organ . we presented a case of mesenteric pseudocyst of the small bowel in a 70-year - old man . esophago - gastro - duodenoscopy showed a 3.5 cm sized excavated lesion on the posterior wall of angle . endocopic biopsy confirmed a histologic diagnosis of the poorly differentiated adenocarcinoma , which includes the signet ring cell component . abdominal computed tomography scan showed a focal mucosal enhancement in the posterior wall of angle of the stomach , a 2.4 cm sized enhancing mass on the distal small bowel loop , without distant metastases or ascites in rectal shelf , and multiple gallbladder stones . the patient underwent subtotal gastrectomy with gastroduodenostomy , segmental resection of the small bowel , and cholecystectomy . the final pathological diagnosis was mesenteric pseudocyst . this is the first case report describing incidentally detected mesenteric pseudocyst of the small bowel in gastric cancer patients .

Introduction Case Report Discussion

compromised renal functions and previous central nervous system ( cns ) disease have been shown to predispose to this neurotoxicity . we describe a case of acute transient encephalopathy in a patient treated with ceftriaxonefor enteric fever infection . the present case illustrates the diagnostic challenges and management of this rare but potentially severe side effect of one of the most commonly prescribed parenteral antibiotics . an eight - year - old male child presented with a history of diarrhea and high - grade fever . the child was conscious , cooperative , well oriented to time , place and persons . the patient was hospitalized and started on ceftriaxone ( 1 g iv daily ) and intravenous fluids . after three days of treatment with iv ceftriaxone , child became afebrile but showed altered mental status with progressive apathy and somnolence . the patient was referred to the dyanand medical college , ludhiana ( punjab ) . in the emergency department , the patient was not in acute distress , had no fever , was hemodynamically stable , but dehydrated . hb 12 g / dl [ normal range 12 to 15 g / dl ] , hct 38% [ normal range 35.0 to 49.0% ] , tlc 6 10/l l [ normal range 5 to 12 10/l l ] , dlc - n 62 [ normal range 6070% ] , l 27% [ normal range 2040% ] , plt 274 10/l l [ normal range 100 to 300 10/l ] , urea 14 mg / dl [ normal range 825 mg / dl ] , cr 0.6 mg / dl [ normal range 0.51.7 mg / dl ] , na / k 139/4 [ normal range 135147/ 3.55 meq / dl ] , urinalysis revealed no bacteriuria and pyuria , tsb / dsb 0.77/0 [ normal range 0.11.0/ < 0.2 mg / dl ] , sgot / pt 44/23 [ normal range 1147/ 753 iu / l ] , stoolr / e , 2d mri scan of brain did not reveal acute stroke . the patient 's neurological status improved and three days later he was again alert and oriented . the proposed mechanisms include a decrease in -amino butyric acid ( gaba)-mediated inhibition and cephalosporin - mediated release of cytokines . in fact , cephalosporins may decrease gaba release from nerve terminals , increase excitatory amino acid release , and exert a competitive antagonism with gaba . alternatively , cephalosporin treatment has been proposed to induce endotoxin release , which generates cytokines liberation , such as tumor necrosis factor- , a proinflammatory cytokine implicated in septic encephalopathy . pre - existing cns abnormalities have been indicated as a risk factor for -lactams encephalopathy . in this was not the case in our patient , who presented with enteric fever and dehydration corrected with intravenous fluids . in fact , the temporal association of the encephalopathy induction and resolution with ceftriaxone administration and withdrawal makes this antibiotic highly likely to be responsible for the encephalopathy . moreover , the temporal pattern is in accordance with previous publications reporting cephalosporin neurotoxicity , with a latency of one to ten days after drug initiation and regression of all neurological symptoms within two to seven days following ceftriaxone treatment suspension . we could establish a probable causal relationship between ceftriaxone and the encephalopathy ( naranjo score 6 ) . the severity assessment revealed the adr to be moderate , suggesting that required therapeutic intervention and hospitalization prolonged by 1 day but resolved in 24 h or change in drug therapy or specific treatment to prevent a further outcome . since this patient did not have a history of any such reaction due to ceftriaxone , this adverse drug reaction was unpreventable . we describe a case of ceftriaxone - induced acute reversible encephalopathy in a patient treated for enteric fever infection . early recognition of this complication is particularly relevant as discontinuation of ceftriaxone reverts the neurological syndrome .

ceftriaxone is a commonly used , third - generation cephalosporin . encephalopathy is a rare side effect of third- and fourth - generation cephalosporins . renal failure and previous disease of the central nervous system predispose to this neurotoxicity . we describe a case of acute transient encephalopathy in a patient treated with ceftriaxone for enteric fever infection . early detection of this complication is relevant given that stopping the drug usually reverts the neurological syndrome .

Introduction Case Report Discussion Conclusion

the fully differentiated cells of the rat mammary parenchyma , the ductal epithelial , alveolar , and myoepithelial cells , are distinguished by their ultrastructure and by their accumulation of immunocytochemically detectable marker proteins . the different cell types probably develop from primative ductal structures called terminal end buds , which are present in the developing rat mammary glands , and these structures contain relatively undifferentiated cells . clonal epithelial stem cell lines , obtained from normal rat mammary glands or benign mammary tumors , differentiate under appropriate conditions along a pathway to droplet - cell / doming cultures of primative alveolarlike cells . under different culture conditions , the epithelial stem cells differentiate along a separate pathway to myoepitheliallike cells . they accumulate some of the specific marker proteins of myoepithelial cells in vivo , including type iv collagen , laminin , and thy-1 antigen . in addition , these myoepitheliallike cells in culture contain an abundance of a potential calcium - binding protein , p9ka , which also occurs in myoepithelial cells of histological sections from mammary glands . the accumulation of type iv collagen , laminin , thy-1 , and p9ka occurs asynchronously along the pathway to the myoepitheliallike cells in vitro . furthermore , the steady - state levels of these different marker proteins arise by alterations in the controls at the transcriptional , the posttranscriptional processing , and the translational stages of their production . these results suggest a stepwise control of synthesis of myoepithelial cell marker proteins , and in the case of p9ka and thy-1 antigen , this altered control may arise through their possession of novel transcriptional promoters.imagesfigure 1 .

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in exposure or risk assessments , both environmental and biological measurements are often used . environmental measurements are an excellent means for evaluating regulatory compliance , but the models used to estimate body burden from these measurements are complex . unless all possible routes of exposure ( i.e. , inhalation , dermal absorption , ingestion ) are evaluated , exposure to a toxicant can be underestimated . to circumvent this problem , measurements of the internal dose of a toxicant in blood , serum , urine , or tissues can be used singularly or in combination with environmental data for exposure assessment . in three separate laboratories , carbaryl or its primary metabolite , 1-naphthol , was measured in personal air , dermal samples , blood serum , and urine from farmer applicators and their families . the usefulness of both environmental and biological data has been demonstrated . for the farmer applicator , the environmental levels of carbaryl would have been sufficient to determine that an exposure had occurred . however , biological measurements were necessary to determine the absorbed dose of each member of the applicator 's family . in addition , a correlation between serum and urinary 1-naphthol measurements has been shown ; therefore , either matrix can be used to accurately evaluate occupational carbaryl exposure.imagesfigure 1.figure 2.figure 3.figure 4.figure 5 . afigure 5 . b

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anti--tubulin mouse monoclonal antibody ( sigma - aldrich corp ) , anti - arf6 mouse monoclonal antibody ( santa cruz biotechnology , inc ) , anti - rab11 rabbit polyclonal antibody , anti - tfr mouse monoclonal antibody ( invitrogen corp ) , anti - eea-1 mouse monoclonal antibody and anti - gm130 mouse monoclonal antibody ( bd biosciences ) were obtained commercially . s2 was performed with a fluorophore - conjugated anti - tfr antibody that was generated by using the zenon antibody labeling kit ( invitrogen corp ) . using this antibody slightly enhanced the tfr signals at the plasma membrane ( figs . s1 and s2 ) . all of the procedures used to perform cell culture , immunoblotting and the immunofluorescence analyses have been described elsewhere . anti--tubulin mouse monoclonal antibody ( sigma - aldrich corp ) , anti - arf6 mouse monoclonal antibody ( santa cruz biotechnology , inc ) , anti - rab11 rabbit polyclonal antibody , anti - tfr mouse monoclonal antibody ( invitrogen corp ) , anti - eea-1 mouse monoclonal antibody and anti - gm130 mouse monoclonal antibody ( bd biosciences ) were obtained commercially . s2 was performed with a fluorophore - conjugated anti - tfr antibody that was generated by using the zenon antibody labeling kit ( invitrogen corp ) . using this antibody slightly enhanced the tfr signals at the plasma membrane ( figs . s1 and s2 ) . all of the procedures used to perform cell culture , immunoblotting and the immunofluorescence analyses have been described elsewhere .

recycling endosomes are key platforms for endocytic recycling that return internalized molecules back to the plasma membrane . to determine how recycling endosomes perform their functions , searching for proteins and lipids that specifically localized at recycling endosomes has often been performed by colocalization analyses between candidate molecules and conventional recycling endosome markers . however , it remains unclear whether all the conventional markers have identical localizations . here we report finding that three well - known recycling endosome markers , i.e. , arf6 , rab11 and transferrin receptor ( tfr ) , have different intracellular localizations in pc12 cells . the results of immunofluorescence analyses showed that the signals of endogenous arf6 , rab11 and tfr in nerve growth factor - stimulated pc12 cells generally differed , although there was some overlapping . our findings provide new information about recycling endosome markers , and they highlight the heterogeneity of recycling endosomes .

Materials and Methods Antibodies Cell culture, immunoblotting and immunofluorescence analyses Supplementary Material

bspp : bisulfite padlock probe ; charm : comprehensive high - throughput arrays for relative methylation ; cimp : cpg island methylator phenotype ; esc : embryonic stem cell ; fda : food and drug administration ; help : hpaii tiny fragment enrichment by ligation - mediated pcr ; mca : methylated cpg island amplification ; mcam : methylated cpg island amplification microarray ; medip : methylated dna immunoprecipitation ; mira : methylated - cpg island recovery assay ; mscc : methyl - sensitive cut counting ; pcr : polymerase chain reaction ; rrbs : reduced representation bisulfite sequencing . the authors are supported by the leukemia specialized program of research excellence grant p50 ca100632 .

dna methylation of promoter cpg islands is strongly associated with gene silencing and is known as a frequent cause of loss of expression of tumor suppressor genes , as well as other genes involved in tumor formation . dna methylation of driver genes is very likely outnumbered by the number of methylated passenger genes , though these can be useful as tumor markers . much of what is known about the importance of dna methylation in cancer was gained through small- and moderate - scale analysis of gene promoters and tumor samples . a much better understanding of the role of dna methylation in cancer , either as a marker of disease or as an active driver of tumorigenesis , will likely be gained from genome - wide studies of this modification in normal and malignant cells . this goal has become more attainable with the recent introduction of large - scale genome analysis methodologies and these have been modified to allow for investigation of dna methylation . several research groups have been formed to coordinate efforts and apply these methodologies to decipher the methylome of healthy and diseased tissues . in this article we review technological advances in genome - wide methylation profiling .

Abbreviations Competing interests Authors' contributions Acknowledgements

as a service to our authors and readers , this journal provides supporting information supplied by the authors . such materials are peer reviewed and may be reorganized for online delivery , but are not copyedited or typeset . technical support issues arising from supporting information ( other than missing files ) should be addressed to the authors .

abstractmacrocyclization can be used to constrain peptides in their bioactive conformations , thereby supporting target affinity and bioactivity . in particular , for the targeting of challenging protein protein interactions , macrocyclic peptides have proven to be very useful . available approaches focus on the stabilization of helices , which limits their general applicability . here we report for the first time on the use of ringclosing alkyne metathesis for the stabilization of an irregular peptide secondary structure . a small library of alkynecrosslinked peptides provided a number of derivatives with improved target affinity relative to the linear parent peptide . in addition , we report the crystal structure of the highestaffinity derivative in a complex with its protein target 1433. it can be expected that the alkynebased macrocyclization of irregular binding epitopes should give rise to new scaffolds suitable for targeting of currently intractable proteins .

Supporting information

in 2009 , a 52-year - old woman presented with a single lesion on her nose , which started as a papule , referred to sedighe tahereh clinic , isfahan , iran . the lesion had existed for a period of 14 months and was slowly increasing in size , enlarging to a plaque . the diagnosis of leishmaniasis was confirmed with a positive smear of the lesion showing leishmania bodies about 1 year before . all five members of her family had had a history of proven leishmaniasis . in the past medical history , the patient was a renal failure case since 11 years before and received a renal transplant 4 years after the diagnosis of renal failure . she was receiving oral mycophenolate mofetil ( 2 g daily ) and cyclosporine ( 100 mg daily ) . a 33 cm indurated ulcer with elevated borders was present on the tip of her nose ( figure 1 ) . her therapeutic plan was intralesional glucantime injection ( approximately 1 ml of 1.5 g vial per week , intralesional injection ) . after completing a therapeutic course of 20 sessions receiving intralesional glucantime injections , she was considered as glucantime therapy resistant . the occurrence of malignant neoplasms in sites of scars is an infrequent but well - known phenomenon.5 although the coexistence of cutaneous leishmaniasis and bcc may have been coincidental , some studies suggest that an association between these two entities does exist.6 leishmaniasis can directly or indirectly alter the diagnosis and course of different malignancies.7 there are reports of bcc in chronic leg ulcers.8 cases of bcc developing in a leishmania scar have also been documented,9 but to our knowledge , cases of both leishmaniasis and bcc in the same site and the same lesion are rare.10 however , in this case , solid organ transplantation and long term immuno suppressive therapy should be considered as risk factors for malignancy . advances in effective immuno suppression after organ transplantation have led to increased risk of malignancies , particularly skin cancers11 including squamous cell carcinoma , basal bcc and malignant melanoma.12 thus , malignancies should be considered in the differential diagnosis of leishmaniasis lesions difficult to treat . the possible role of cutaneous leishmaniasis , as a predisposing factor for skin cancer , should also be kept in mind . aa was the main therapeutic physician and helped write the manuscript . i m and pk contributed in writing the manuscript .

leishmaniasis is a protozoan infection due to organisms of the genus leishmania . the differential diagnosis of cutaneous leishmaniasis includes arthropod bites , basal cell carcinoma ( bcc ) and other malignancies . bcc is the most common form of skin cancer . we present a case of cutaneous leishmaniasis resistant to standard intralesional glucantime injection in an immunocompromised patient , which was proved to be bcc after surgical excision .

Case Report Discussion Authors Contributions

we attempted to estimate the perceived degree of urgency of the visit and to identify reasons for seeking non - urgent care in the ped by patients and parents . a prospective survey was completed by parents ( for children 17 and younger ) and patients ( 18 - 21 ) presenting to a suburban academic ped that sees approximately 15,000 patients per year . three hundred and five of 334 surveys were completed ( 91% response rate ) over a 3-month period . twenty - four percent of the chief complaints were perceived by those surveyed as emergent or possibly life - threatening , 23% were felt to be very urgent , and 52% were deemed somewhat urgent or minor . twenty - five percent of those with minor or somewhat urgent complaints arrived by ambulance . overall , 79% of those surveyed identified a primary care provider ( pcp ) for themselves or their child . of those , 54% had attempted to contact the pcp prior to coming to the ped . six percent of those who attempted to reach their primary care providers were able to contact them and 52% were told to come to the ped . more than half of patients and parents presenting to the ped believed they had minor or somewhat urgent complaints . while the majority of patients have a regular provider , limited access to timely primary care and convenience may make the ped a more attractive care option than primary care for many parents and patients .

objectives : pediatric emergency department ( ped ) patients often present with non - urgent complaints . we attempted to estimate the perceived degree of urgency of the visit and to identify reasons for seeking non - urgent care in the ped by patients and parents.methods:a prospective survey was completed by parents ( for children 17 and younger ) and patients ( 18 - 21 ) presenting to a suburban academic ped that sees approximately 15,000 patients per year . a convenience sample of participants was enrolled.results:three hundred and five of 334 surveys were completed ( 91% response rate ) over a 3-month period . twenty - four percent of the chief complaints were perceived by those surveyed as emergent or possibly life - threatening , 23% were felt to be very urgent , and 52% were deemed somewhat urgent or minor . twenty - five percent of those with minor or somewhat urgent complaints arrived by ambulance . weekend visits and minority race correlated with a lower degree of perceived urgency . overall , 79% of those surveyed identified a primary care provider ( pcp ) for themselves or their child . of those , 54% had attempted to contact the pcp prior to coming to the ped . six percent of those who attempted to reach their primary care providers were able to contact them and 52% were told to come to the ped.conclusions:more than half of patients and parents presenting to the ped believed they had minor or somewhat urgent complaints . while the majority of patients have a regular provider , limited access to timely primary care and convenience may make the ped a more attractive care option than primary care for many parents and patients .

Objectives: Methods: Results: Conclusions:

fluoro refers to both fluorescent and fluorinated compounds . despite the shared prefix , there are very few fluorescent molecules that are soluble in perfluorinated solvents . this paucity is surprising , given that optical microscopy is a ubiquitous technique throughout the physical sciences and the orthogonality of fluorous materials is a commonly exploited strategy in synthetic chemistry , materials science , and chemical biology . we have addressed this shortage by synthesizing a panel of fluorofluorophores , fluorescent molecules containing high weight percent fluorine with optical properties spanning the visible spectrum . we demonstrate the utility of these fluorofluorophores by preparing fluorescent perfluorocarbon nanoemulsions .

Supplementary Material

we developed a sensitive and accurate analytical method for quantifying methyleugenol ( me ) in human serum . our method uses a simple solid - phase extraction followed by a highly specific analysis using isotope dilution gas chromatography - high resolution mass spectrometry . our method is very accurate ; its limit of detection is 3.1 pg / g and its average coefficient of variation is 14% over a 200-pg / g range . we applied this method to measure serum me concentrations in adults in the general u.s . population . me was detected in 98% of our samples , with a mean me concentration of 24 pg / g ( range < 3.1 - 390 pg / g ) . lipid adjustment of the data did not alter the distribution . bivariate and multivariate analyses using selected demographic variables showed only marginal relationships between race / ethnicity and sex / fasting status with serum me concentrations . although no demographic variable was a good predictor of me exposure or dose , our data indicate prevalent exposure of u.s . adults to me . detailed pharmacokinetic studies are required to determine the relationship between me intake and human serum me concentrations.imagesfigure 1figure 2figure 3figure 4figure 5figure 6figure 7

Images

a mild catalytic asymmetric direct fluoro - arylation of styrenes has been developed . the palladium - catalyzed three - component coupling of selectfluor , a styrene and a boronic acid , provides chiral monofluorinated compounds in good yield and in high enantiomeric excess . a mechanism proceeding through a pd(iv)-fluoride intermediate is proposed for the transformation and synthesis of an sp3 c f bond .

Supplementary Material

to identify the possible barriers to the implementation of pharmaceutical care among community and hospital pharmacists in enugu state using nsukka and enugu metropolis as a case study . the questionnaires were distributed to community and hospital pharmacists from designated areas during one of their quarterly meeting and their practice sites in 2009 . eighty completed questionnaires were collected with 22.8% from community pharmacists , and 77.2% from hospital pharmacists . the important barriers identified were lack of space , enough personnel in pharmacy to handle routine technical tasks , time , need for too much effort , and need for payment for services . the opinions on barriers to pharmaceutical care of pharmacists from community and hospital practice areas in these two metropolises of enugu state are majorly lack of time , space and routine technical task personnel .

objective : to identify the possible barriers to the implementation of pharmaceutical care among community and hospital pharmacists in enugu state using nsukka and enugu metropolis as a case study.method:a semi structured questionnaire was designed to carry out a cross sectional descriptive study . the questionnaires were distributed to community and hospital pharmacists from designated areas during one of their quarterly meeting and their practice sites in 2009.results:eighty completed questionnaires were collected with 22.8% from community pharmacists , and 77.2% from hospital pharmacists . the important barriers identified were lack of space , enough personnel in pharmacy to handle routine technical tasks , time , need for too much effort , and need for payment for services.conclusion:the opinions on barriers to pharmaceutical care of pharmacists from community and hospital practice areas in these two metropolises of enugu state are majorly lack of time , space and routine technical task personnel .

Objective: Method: Results: Conclusion:

in the previous issue of critical care , chase and coworkers reported on their implementation into clinical practice and evaluation of the specialized relative insulin nutrition table ( sprint ) . this is an improved protocol in the form of a wheel - based system to control blood glucose levels and nutritional intakes in intensive care patients , which was developed a few years ago . blood glucose has become a key biological parameter in critical care since publication of the study conducted by van den berghe and colleagues , who demonstrated decreased mortality in surgical intensive care patients in association with tight glycaemic control ( tgc ) , based on intensive insulin therapy . however , two negative studies were recently reported , which were interrupted early because of high rates of severe hypoglycaemia , namely the visep study and the as yet unpublished glucontrol trial . hence , there is currently much debate regarding the actual benefits of such a strategy in intensive care patients in terms of outcomes . it is also uncertain whether the results of the ongoing multicentre , open label , randomized controlled trial nice sugar of the effects of blood glucose management on 90-day all - cause mortality in a heterogeneous population of intensive care unit ( icu ) patients will resolve remaining concerns about tgc in the icu . included among these concerns is the key issue of what is the most appropriate algorithm to achieve the desired blood glucose range . the major focus of the study conducted by chase and colleagues was on the method to achieve a predetermined blood glucose range by modulating both insulin infusion rate and nutritional inputs . as with the other reported studies comparing protocols , efficacy was evaluated by comparison with historical control patients . however , although the study reported by chase and coworkers was conducted with great care and rigour , it is but another case - control retrospective comparative study . nevertheless , there is a clear need to introduce efficient tools that will help clinicians and nursing staff to control blood glucose levels in icu patients , because hyperglycaemia superior to 10 mmol studies are required to provide clinicians with recommendations on the evaluation and comparison of the various protocols currently in use or that are soon to become available . benchmarking of tgc protocols must take in account all the dimensions of efficiency : performance , risk for severe hypoglycaemia , practical aspects ( ease of use , training time and required materials prior to implementation , error rate ) , integrated continuous monitoring , nursing workload ( evaluated on the mean time between controls ) . furthermore the best way to compare performance is controversial : is it the time with glucose within a common target range , the hyperglycaemia index , the recently described glycaemic penalty index , or the variability that would be associated with outcome ? this raises the question of whether the efficacy results from instructions regarding nutritional intake , allowing insulin infusion rates to be limited to a level lower than usual , or from the intrinsic quality of the algorithm used , which is based on the glucose - insulin regulatory system model ( capturing insulin utilization rate , insulin losses and saturation dynamics ) . also , sprint is apparently associated with few severe hypoglycemia events , which contrasts with the high rate of severe hypoglycaemic episodes reported in the second leuven study . finally , sprint should be relatively simple to implement in numerous icus as a paper - based protocol , presented in an original form using a wheel , without need for computational resources . weaknesses of sprint rest in its inability to monitor parameters related to the quality of glucose control as sprint is a paper - based protocol . most importantly , despite the favourable subjective opinions of care givers , sprint may not reduce workload because it requires measurements every hour or 2 hours . ultimately , evaluation of any tgc protocol must also include an assessment of its ability to be implemented easily and safely in another icu that did not participate in its development . the monocentric study of chase and coworkers may not ensure the ' exportability ' of their tgc protocol . the debate continues about the real benefits of tgc , with numerous questions being asked . what is the optimal target range ? which patients will benefit the most ? when during the icu stay should tgc be applied and to derive which benefits ? which is the best method to control glucose level intensive insulin therapy , and/or limitation of nutritional intakes during acute phase , and/or antidiabetic drugs ? however , the competition to develop the ideal tool with which to control blood glucose levels in the icu and perhaps throughout the hospital stay has begun , involving multidisciplinary teams of physicians and engineers who have specialized in control systems ( feedback control or model predictive control ) . icu = intensive care unit ; sprint = specialized relative insulin nutrition table ; tgc = tight glycaemic control . pk declares that he holds shares of lk2 ( saint - avertin , france ) .

the report by chase and coworkers in the previous issue of critical care describes the implementation into clinical practice of the specialized relative insulin nutrition table ( sprint ) for tight glycaemic control in critically ill patients . sprint is a simple , wheel - based system that modulates both insulin rate and nutritional inputs . it achieved a better glycaemic control in a severely ill critical cohort than their previous method for glycaemic control in a matched historical cohort . reductions in mortality were also observed .

None Abbreviations Competing interests

techniques for isolation and culture of fetal type ii alveolar epithelial cells , as well as the morphologic and biochemical characteristics of these histotypic cultures , are described . type ii alveolar epithelial cells can be isolated from fetal rat lungs and grown in an organotypic culture system as described in this review . the fetal type ii cells resemble differentiated rat type ii cells in morphology , biochemistry , and karyotype as they grow in culture for up to 5 weeks . the cells of the mature organotypic cultures form alveolarlike structures while growing on a gelatin sponge matrix . the type ii cells also synthesize and secrete pulmonary surfactant similar in biochemical composition to that produced in vivo . this system has been used to study the effects of hormones on surfactant production and composition . the organotypic model has many potential applications to the study of pulmonary toxicology.imagesfigure 1.figure 2 .

Images

defining alterations in signalling pathways in normal and malignant cells is becoming a major field in proteomics . a number of different approaches have been established to isolate , identify and quantify phosphorylated proteins and peptides . in the current report , a comparison between scx prefractionation versus an antibody based approach , both coupled to tio2 enrichment and applied to tmt labelled cellular lysates , is described . the antibody strategy was more complete for enriching phosphopeptides and allowed the identification of a large set of proteins known to be phosphorylated ( 715 protein groups ) with a minimum number of not previously known phosphorylated proteins ( 2 ) .

Supplementary Material

spondylolisthesis is defined as an anterior migration of a vertebral body in relation to the vertebra located immediately caudal . in 1930 junghanns was the first to describe anterior translation of a lumbar vertebra without any defect in the neural arch following this the term degenerative spondylolisthesis ( ds ) was introduced by newman in 1955 . five types of spondylolisthesis have been described including dysplastic , isthmic , traumatic , pathologic , and degenerative . there are many predisposing factors like sagittally - placed facet joint , a high iliac crest [ 4 - 6 ] , etc . ds which is characterized by an intact vertebral ring is presumed to result from degeneration of facet joints and intervertebral discs with aging and thus has traditionally been considered to represent instability of the vertebral segment . a 66-year - old gentleman , farmer by occupation , came with complaints of lower backache for 2 years which was insidious in onset , gradually progressive and non - radiating . he also complained of acute retention of urine since 15 days for which he was catheterized . he also had a history of neurogenic claudication at a distance of 100 m. there was no history of any trauma . a detailed systemic and neurological examination revealed power of flexor hallucis longus(fhl ) and flexor digitalis longus(fdl ) as 4/5 , ankle jerks were absent , sensory deficits in s1-s2 dermatome and per - rectal examination revealed decreased perianal sensations and anal tone with absent anal wink . plain radiographs of lumbo - sacral spine revealed spondylolisthesis of s1-s2 ( meyerding s grade 1 ) ( fig.1 ) . magnetic resonance imaging and computed tomography scan of the spine revealed lumbarization of s1 with spondylolisthesis of s1 over s2 , facetal hypertrophy at l5-s1 and canal stenosis at s1-s2 ( figs . 2 , and 3 ) . anteroposterior ( a ) and lateral ( b ) radiographs showing grade 1 spondylolisthesis ats1-s2b . the patient underwent posterior spine surgery where decompression was done with laminotomy of s1 bilaterally and then pedicular screw fixation was done bilaterally at l5 , s1 , and s2 ( fig.4 ) . s1 and post - operative radiographs - anteroposterior ( a ) and lateral ( b ) view . the bladder symptoms disappeared after 3 weeks and the power of fhl / fdl improved from 4/5 to 5/5 . the patient underwent posterior spine surgery where decompression was done with laminotomy of s1 bilaterally and then pedicular screw fixation was done bilaterally at l5 , s1 , and s2 ( fig.4 ) . s1 and post - operative radiographs - anteroposterior ( a ) and lateral ( b ) view . the bladder symptoms disappeared after 3 weeks and the power of fhl / fdl improved from 4/5 to 5/5 . the patient underwent posterior spine surgery where decompression was done with laminotomy of s1 bilaterally and then pedicular screw fixation was done bilaterally at l5 , s1 , and s2 ( fig.4 ) . s1 and post - operative radiographs - anteroposterior ( a ) and lateral ( b ) view . the bladder symptoms disappeared after 3 weeks and the power of fhl / fdl improved from 4/5 to 5/5 . the deformity occurs at l4 - 5 6 times more often than at other lumbar levels and four times more often above a sacralized l5 . the lumbosacral junction and middle lumbar spine are most often involved , but the lesion is also found in cervical or rarely the thoracic vertebra . to the best of our knowledge , ds of sacral vertebrae has not been reported in the available english literature till now . the prevalence of complete lumbarization is 1.8% and to get a spondylolisthesis is even rarer . there have been many publications in the literature mentioning incidence of spondylolisthesis with sacralization but hardly any on spondylolisthesis with lumbarization . further case series or longitudinal studies of such cases may help understand better the pathomechanics related to spondylolisthesis at this level . ds of s1-s2 is a very rare entity and further case reports will help us to explore the biomechanics at this level .

introduction : degenerative spondylolisthesis ( ds ) is usually seen at l4-l5 level and less frequently at l5-s1 level . this is a rare case report of spondylolisthesis of s1 over s2 with lumbarization of s1 . lumbarization of s1 is seen in just 1 - 2% of the population and to have spondylolisthesis in this segment is even rarer . the purpose is to report a rare case of ds at s1-s2 level.case report : this is a single case report of a 66-year - old gentleman who presented with complains of lower backache for 2 years and acute retention of urine to the emergency department . detailed clinical and radiological evaluation of the spine was done which revealed lumbarization of s1 with spondylolisthesis at s1-s2 and facetal hypertrophy at l5 , s1 , and s2 . he underwent decompression and stabilization at l5 , s1 , and s2 along with placement of autologous bone graft . the bladder symptoms disappeared after 3 weeks . at 1-year follow - up , patient s clinical symptoms were relieved , and he improved clinically.conclusion:to the best of our knowledge , this is probably the first case of ds of sacral vertebrae to be reported in english literature . the prevalence of complete lumbarization is around 1.8% and to get spondylolisthesis in this segment is even rarer , hence the lack of literature in this regard . since this is the first of its kind of case , further case series or longitudinal studies of such cases may help understand better the pathomechanics related to spondylolisthesis at this level .

Introduction Case report None Operative procedure Results Discussion Conclusion

ductal adenocarcinoma of the prostate was first reported by melicow and pachter in 1967 as an endometrial carcinoma prostatic utricle . since then , ductal adenocarcinoma of the prostate has been found to account for 0.27.5% of all prostate carcinomas . a 73-year - old man was referred to our hospital due to an elevated prostate - specific antigen ( psa ) level of 23.4 ng / ml . he had no remarkable medical history . the hematological and biochemical data showed no abnormal findings aside from the elevated psa levels . in february 2016 , a prostate needle biopsy detected gleason score 4 + 4 adenocarcinoma in his left prostate . computed tomography ( ct ) and magnetic resonance imaging ( mri ) showed a higher density on his left peripheral zone ( fig 1a , b ) . in may 2016 , radical prostatectomy with lymph node resection histologically , there were many large , clear - edged cells and cancer cells with low differentiation forming a circular shape . based on these findings , ductal adenocarcinoma and gleason score 4 + 4 = 8 acinar adenocarcinoma with positive surgical margin were diagnosed . the patient has not experienced recurrence or biochemical recurrence in the 10 months since radical prostatectomy . histologically , there were many large , clear - edged cells and cancer cells with low differentiation forming a circular shape . based on these findings , ductal adenocarcinoma and gleason score 4 + 4 = 8 acinar adenocarcinoma with positive surgical margin were diagnosed . no adverse perioperative events were observed . the patient has not experienced recurrence or biochemical recurrence in the 10 months since radical prostatectomy . ductal adenocarcinoma of the prostate was first reported as endometrial carcinoma of the prostatic utricle in 1967 . recent studies have suggested that ductal adenocarcinoma of the prostate developed from the ductal epithelium , based on findings from immunohistochemical and electron microscope analyses . histologically , ductal adenocarcinoma of the prostate is characterized by high cylindrical epithelium collate papillary or etat cribriform . the histological differences between ductal adenocarcinoma and acinar adenocarcinoma are thought to be clear . in this case , although the prostate needle biopsy showed acinar adenocarcinoma , the surgical specimens showed ductal adenocarcinoma . the first is a mixed type with acinar adenocarcinoma and accounts for < 75% of ductal prostate specimens . mixed - type ductal prostate adenocarcinomas account for 5.06.6% of all prostate cancer cases , and pure - type ductal prostate adenocarcinomas account for 0.40.8% of all prostate cancer cases . because ductal carcinomas account for 90% of all prostatic carcinoma cases , our case was assumed to be pure type . because of its extension toward the urethra , the tumor was not palpable on a digital rectal examination and showed a low psa level . ductal adenocarcinoma of the prostate usually extends toward the urethra and shows macrohematuria and urinary symptoms at an early stage . reported that ductal adenocarcinoma of the prostate showed a significantly poorer prognosis than acinar prostate adenocarcinoma in nonmetastatic cases . however , in metastatic cases , there were no prognostic differences between these 2 groups . other reports have found no marked differences in the 5-year survival rate between ductal adenocarcinoma and gleason score 810 acinar adenocarcinoma . reported therapies of ductal adenocarcinoma of the prostate are also the same as for acinar adenocarcinoma , including radical prostatectomy , androgen deprivation therapy , and radiation therapy or a combination of these therapies . reported that pure ductal adenocarcinoma tended to extend into the submucosal urethra ; as such , pure ductal adenocarcinoma carries a higher risk of a positive surgical margin in the urethra . although we are not performing adjuvant therapy in this patient at present , careful observation including ct , mri , or positron emission tomography - ct should be performed , as psa does not always accurately represent cancer progression .

ductal adenocarcinoma is an unusual variant of adenocarcinoma of the prostate . a 73-year - old male was referred to our hospital for the further examination of an elevated prostate - specific antigen level of 23.4 ng / ml . radical prostatectomy ( rp ) was performed based on the diagnosis obtained by a prostate needle biopsy . the rp specimen revealed ductal adenocarcinoma of the prostate with positive capsular penetration . we herein report a rare case of ductal adenocarcinoma of the prostate .

Introduction Case Presentation Operative Procedure and Pathological Findings Postoperative Course Discussion Statement of Ethics Disclosure Statement

a male neonate born to g2 p1l1 mother at term by spontaneous vaginal delivery to iii degree consanguineous marriage was found to have proximal shortening of both upper and lower limbs [ figure 1 ] . the antenatal period was uneventful and antenatal ultrasound was reportedly not done during pregnancy and the mother was referred to our hospital after the onset of labor . apart from rhizomelic shortening , the neonate also had coronal clefts of thoracic vertebrae and stippled epiphysis of femur tibia and humerus on skeletal survey radiograph [ figure 2 ] . based on the above features a provisional diagnosis of rhizomelic chondro - dysplasia punctata ( rcdp ) was made and the prognosis was explained to the parents . the baby developed progressively severe respiratory distress and was discharged at request on day 3 of life as the parents were unable to come to terms with the diagnosis . rhizomelic shortening of upper limb punctate calcification and epiphyseal abnormalities chondrodysplasia punctata is a radiological diagnosis characterized by punctate or stippled calcifications in epiphyseal cartilage and seen in peroxisomal disorders such as zellweger syndrome , neonatal adrenoleukodystrophy , and infantile refsum disease . it may also be inherited as x - linked dominant , x - linked recessive , and autosomal recessive forms . it is classically associated with pex7 gene ( peroxin family of genes ) mutation and has been reported in indian patients too . rcdp is characterized by proximal shortening of the humerus and to a lesser degree the femur , punctate calcifications in cartilage with epiphyseal and metaphyseal abnormalities , radiolucent defects ( coronal clefts ) of the vertebral bodies which represents cartilage that are not ossified , cataracts , contractures , microcephaly , characteristic skin changes of icthyosis , facial dysmorphism ( depressed nasal bridge , hypertelorism , hypoplastic midface , anteverted nostrils , full cheeks ) , and developmental impairment . this condition is considered to be lethal and most of the affected fetuses die in utero or soon after birth . only few of them survive beyond infancy with severe physical disability and profound mental retardation in whom , death usually occurs in the first decade of life . diagnosis of rcdp is based on clinical findings and confirmed by clinically available biochemical or molecular genetic testing which includes biochemical tests of peroxisomal function like red cell plasmologen concentration , plasma phytanic acid , and very long chain fatty acid estimation . this case is presented due to its rarity and failure to detect such an abnormality in utero resulting in a wasted pregnancy . the lack of resources ( both money and manpower ) is probably responsible for this tragedy to the parents which could have been prevented by early diagnosis and appropriate counseling . establishing regional genetic labs which are connected with district level hospitals can be of immense help in reducing the burden of genetic diseases by appropriate prenatal diagnosis and counseling .

a male neonate was born with rhizomelic shortening of limbs . skeletal radiograph showed punctate calcification of epiphysis of humerus , femur , and tibia . the diagnosis and a brief review of literature pertaining to the condition with emphasis on antenatal diagnosis and counseling are being reported .

Introduction

when the gallbladder is not visualized in its normal location , the possibility of its ectopic location should be considered . a case of incidentally detected anomalous position of gall bladder causing confounding problem in interpretation of pet - ct is described . a 70-year - old man , with h / o chronic liver disease and suspected of hepatocellular carcinoma [ serum alpha - fetoprotein ( afp ) 5024 ng / ml ] was subjected to fluorine-18 fluorodeoxyglucose positron emission tomography ( f-18 fdg pet)/computed tomography ( ct ) imaging . rest of the liver revealed non - fdg avid lesions in segments iii and viii . on viewing the fused pet / ct images , the radiotracer accumulation was localized to the anomalously placed suprahepatic gallbladder . magnetic resonance ( mr ) images of the same patient confirmed the presence of the suprahepatic gallbladder [ figure 1 ] . ( a ) transaxial view of pet image showing suprahepatic subdiaphragmatic gallbladder with tracer uptake ; ( b ) coronal view of pet image ; ( c ) sagittal view of pet image ; ( d ) transaxial view of ct image ; ( e ) coronal view of ct image ; ( f ) sagittal view of ct image ; ( g ) transaxial view of post - contrast t1-weighted mri image ; ( h ) coronal view of post - contrast t1-weighted mri image ; ( i ) transaxial view of t2 fat saturated mri image shows gallbladder as a bright structure routine imaging of the gallbladder demonstrates a wide array of imaging variants , including anomalies in location , number , and configuration . an awareness of these normal variants would prevent misdiagnosis and aid in the assessment of differential diagnostic possibilities . normally , the gallbladder is situated adjacent to the inferior surface of the liver , in the plane of the interlobar fissure , with the gallbladder neck maintaining a constant relationship to porta hepatis . the gallbladder is generally found in the right upper quadrant , but may be seen in other parts of the abdomen . while anomalous positions are rare , the most common of these are ( 1 ) under the left hepatic lobe , ( 2 ) intrahepatic , ( 3 ) transverse , and ( 4 ) retroplaced ( retrohepatic or retroperitoneal ) . the lesser common of these are ( 1 ) supradiaphragmatic and ( 2 ) suprahepatic . gallbladder is intrahepatic during the embryonic period and becomes extrahepatic only later . an intrahepatic gallbladder ( usually a congenital anomaly ) this poses a problem for scintigraphy , as an intrahepatic gallbladder can cause a focal defect ( pseudo space - occupying lesion ) ; ultrasonography can be helpful in these cases . the suprahepatic region is among the rarest sites , and very few reports have appeared in either the surgical or radiological literature.[35 ] of the very few reports on the suprahepatic gallbladder , one refers to a normally inserted organ that rotated 180 upward to an intrathoracic position after eventration of the diaphragm . in two other cases , an abnormally mobile gallbladder was found trapped between the chest wall and the upper border of the liver ; this became symptomatic and caught the attention of the clinician and the imageologist . faintuch et al . reported three cases of suprahepatic gallbladder with hypoplasia of the right hepatic lobe and upward migration of the gallbladder . gansbeke reported a case of suprahepatic gallbladder which was associated with hepatomegaly due to macronodular cirrhosis complicating existing hepatitis . kabaroudis reported a case of floating gallbladder associated with hypoplasia of the right hepatic lobe , whereas maeda had reported a similar case associated with hypoplasia of left hepatic lobe . pet - ct is found to be useful in diagnosing this rare anatomical variant of ectopically located gall bladder and predicting its functional implication .

the purpose of this study was to appraise the imageologists of a possible mislocalization of tracer accumulation to anomalously placed gallbladder during positron emission tomography - computed tomography ( pet / ct ) examination . pet / ct is increasingly playing an important role in staging and restaging of the disease process in cancer patients . with the advent of fusion imaging , the tracer accumulation can be correctly localized to a structure or lesion on ct . we did a staging pet / ct scan of a patient with hepatocellular carcinoma for liver transplant evaluation . fluorine-18 fluorodeoxyglucose ( f-18 fdg ) was used as a tracer and the scan was performed on seimens biograph - mct pet / ct machine . we noted the tracer accumulation at the superior surface of liver , which was localized to the anomalously placed gallbladder in suprahepatic subdiaphragmatic location . the anomalously placed gallbladder can create localization confusion . keeping the possibility of ectopically placed gallbladder in mind , the imageologist can better localize the tracer uptake .

INTRODUCTION CASE REPORT DISCUSSION CONCLUSION

this work was supported , in whole or in part , by the one hundred person project of sun yat - sen university ( xz ) , national natural science foundation 81302262 ( xz ) , the basser research center for brca ( lz ) , the national institutes of health r01ca142776 , r01ca190415 , p50ca083638 ( lz ) , the ovarian cancer research fund ( lz and xh ) , the breast cancer alliance ( lz ) , department of defense ( lz ) , and the marsha rivkin center for ovarian cancer research ( lz ) .

long non - coding rnas ( lncrnas ) are defined as rna transcripts larger than 200 nucleotides that do not appear to have protein - coding potential . accumulating evidence indicates that lncrnas are involved in tumorigenesis . our work reveals that lncrna fal1 ( focally amplified lncrna on chromosome 1 ) is frequently and focally amplified in human cancers and mediates oncogenic functions .

Disclosure of Potential Conflicts of Interest Acknowledgments Funding

additional supporting information may be found in the online version of this article at the publisher 's web site .

this report describes that a regular positive electrospray ionization mass spectrometry ( ms ) analysis of terpendoles often causes unexpected oxygen additions to form [ m + h + o]+ and [ m + h + 2o]+ , which might be a troublesome in the characterization of new natural analogues . the intensities of [ m + h + o]+ and [ m + h + 2o]+ among terpendoles were unpredictable and fluctuated largely . simple electrochemical oxidation in electrospray ionization was insufficient to explain the phenomenon . so we studied factors to form [ m + h + o]+ and [ m + h + 2o]+ using terpendole e and natural terpendoles together with some model indole alkaloids . similar oxygen addition was observed for 1,2,3,4-tetrahydrocyclopent[b]indole , which is corresponding to the substructure of terpendole e. in tandem ms experiments , a major fragment ion at m / z 130 from protonated terpendole e was assigned to the substructure containing indole . when the [ m + h + o]+ was selected as a precursor ion , the ion shifted to m / z 146 . the same 16 da shift of fragments was also observed for 1,2,3,4-tetrahydrocyclopent[b]indole , indicating that the oxygen addition of terpendole e took place at the indole portion . however , the oxygen addition was absent for some terpendoles , even whose structure resembles terpendole e. the breakdown curves characterized the tandem ms features of terpendoles . preferential dissociation into m / z 130 suggested the protonation tendency at the indole site . terpendoles that are preferentially protonated at indole tend to form oxygen addition peaks , suggesting that the protonation feature contributes to the oxygen additions in some degrees . 2014 the authors . journal of mass spectrometry published by john wiley & sons , ltd .

Supporting information

the epidermal growth factor receptor ( egfr ) is over expressed in various solid malignancies including non small cell lung cancer ( nsclc ) . however , they are associated with a dermatologic side effects , which can occasionally be responsible for discontinuation of the egfr inhibitors . hence , we report a case of metastatic adenocarcinoma of lung who developed skin ulceration with gefitinib and responded to interruption of the drug and early intervention . the present case report is about a 50-year - old female patient who had been diagnosed as having lung adenocarcinoma with multiple bone metastases was initiated on gefitinib therapy at an oral dose of 250 mg / d . after 2 weeks of initiating therapy , the patient presented with ulcer over the palm [ figure 1 ] . the ulcers improved with stopping gefitinib for 2 weeks and also with the addition of topical steroids and antibiotics . non - small - cell lung cancer ( nsclc ) with sensitive mutations of the egfr is highly responsive to gefitinib . gefitinib is a small molecule tyrosine kinase inhibitor ( tki ) of egfr . since 2004 , it was clear that a substantial proportion of nsclc obtaining objective response when treated with gefitinib harboring activating mutations in the egfr gene . the occurrence of skin disorders ( dry skin and acneiform rash ) is explained by the fact that egfr is also expressed in the basal layer of the skin ; inhibition of the receptor will disturb normal biology and result in skin rash . skin rash is notorious as an adverse event of egfr - tki and is noted in up to two - thirds of patients receiving any of these agents although severe in only 5 - 10% who can develop pyogenic granuloma like lesions . very rarely the cutaneous inflammation is so pronounced that skin necrosis with black eschar formation and ulceration is seen . the cutaneous side - effects are treated with topical steroids and antibiotics with interruption of treatment for 2 - 4 weeks as in our case .

we report a case of gefitinib - induced skin ulceration in a 50-year - old female with metastatic adenocarcinoma of lung who developed this adverse effect 2 weeks following initiation of gefitinib at a dose of 250 mg / day . the ulcer improved with stopping gefitinib for 2 weeks and also addition of topical steroids and antibiotics . we are reporting this case to create awareness among treating oncologists of this adverse effect and also prompt interruption of therapy and topical steroids / antibiotics is useful to treat this adverse event .

INTRODUCTION CASE REPORT DISCUSSION

frontometaphyseal dysplasia ( fmd ) , also called gorlin cohen syndrome , is a hereditary x - linked dominant syndrome described in 1969 with less than 30 cases described in the literature . this case report of a child with fmd is presented owing to the rarity of the syndrome and the anticipated difficult airway , which was successfully managed by using a combination of dexmedetomidine and ketamine while preserving spontaneous ventilation . a 2-year - old female child , a known case of fmd , presented for open reduction of the left hip with osteotomy of femur . physical examination revealed a slender undernourished girl of 8 kg with prominent supraorbital ridges , ocular hypertelorism , low set ears and a wide bridge nose with prominent eyes . airway examination revealed a mallampatti score of iii with significant retrognathia , high arched palate with malocclusion of teeth . in addition , she had dorsolumbar scoliosis , pectus carinatum , bowing of long bones with distal phalangeal hypoplasia and multiple joint dislocations [ figure 1 ] . pre - operative blood investigations , echocardiography and chest x - ray were within physiological limits . on arrival to the operation theatre , monitors were connected and child pre - oxygenated for 5 minutes . injection dexmedetomidine 1 g / kg was administered for 10 min and then a continuous infusion at 1 g / kg / h was set for the duration of the remaining procedure . ketamine was administered in increments of 5 mg up to 12 mg until there was no response to jaw thrust while ensuring spontaneous respiration . just before direct laryngoscopy intravenous lignocaine rigid laryngoscopy with miller 1 straight blade offered a grade iv cormack and lehane view . after optimal external laryngeal manipulation , the visible glottic chink was sprayed with topical lignocaine and tracheal intubation was successfully performed using an uncuffed 4 sized endotracheal tube . anesthesia was continued with n2o in 40% o2 along with a continuous dexmedetomidine and atracurium infusion . adequate padding was provided at pressure points and extreme caution was exercised during positioning . at the end of fmd belongs to the otopalatodigital spectrum syndromes that includes four phenotypically related conditions , otopalatodigital syndrome types 1 and 2 , fmd and melnick - needles syndrome . the most common manifestations include supraorbital hyperostosis , hypertelorism , down - slanting palpebral fissures , broad nasal bridge and micrognathia with anomalies of teeth and generalized skeletal dysplasia . congenital heart disease , subglottic tracheal narrowing and genitourinary anomalies , muscular hypotonia . micrognathia , microstomia and malocclusion of teeth may make direct laryngoscopy impossible ; therefore , a well - planned airway strategy is mandatory . ketamine was preferred in our case of anticipated difficult airway due to it 's inherent sympathomimetic actions devoid of respiratory depression alongwith provision of excellent analgesia and amnesia . dexmedetomidine a specific and selective 2-adrenoceptor agonist known for its sedative , anxiolytic , analgesic properties was used to complement ketamine . at the same time dexmedetomidine offsets the sympathomimetic effects of ketamine , this unique pharmacological combination in the present case preserved the respiratory drive , allowed maintenance of a patent airway and provided sufficient sedation , analgesia and anesthesia to allow successful airway control . in addition , topical lignocaine was used as per recommendation of aroni et al . which states that ketamine does not depress coughing or swallowing reflexes . available literature describes the use of combination of both these drugs in children during procedural anesthesia and not as a complete anesthesia protocol in a challenging case . the present experience of using this combination successfully paves the way to emerging new solutions for management of a difficult pediatric airway . hence safety profile , rapid onset of action with adequate sedation and analgesia provided by the ketamine and dexmedetomidine make them a distinctive drug combination in the pediatric difficult airway situation in a child with fmd .

frontometaphyseal dysplasia ( fmd ) , also called gorlin - cohen syndrome , is a rare hereditary x - linked dominant craniotubular bone disorder . the presentation describes the airway management of a 2-year - old child suffering from fmd with significant retrognathia , posted for major long bone corrective osteotomy . induction with a combination of dexmedetomidine and ketamine preceded a successful endotracheal intubation under spontaneous ventilation .

Introduction Case Report Discussion

for a prospective study of lead exposure and early development , we recruited pregnant women from a lead smelter town and from an unexposed town in yugoslavia and followed their children through 7 years of age . in this paper we consider associations between lifetime lead exposure , estimated by the area under the blood lead ( bpb ) versus time curve ( auc7 ) , and intelligence , with particular concern for identifying lead 's behavioral signature . the wechsler intelligence scales for children - version iii ( wisc - iii ) was administered to 309 7-year - old children , 261 of whom had complete data on intelligence , blood lead , and relevant sociodemographic covariates ( i.e. , home observation for the measurement of the environment ( home ) , birth weight , gender , sibship size , and maternal age , ethnicity , intelligence , and education ) . these showed anticipated associations with 7-year intelligence , explaining 41 - 4% of the variance in full scale , performance , and verbal iq . before covariate adjustment , auc7 was unrelated to intelligence ; after adjustment , auc7 explained a significant 2.8%-4.2% of the variance in iq . after adjustment , a change in lifetime bpb from 10 to 30 micro / dl related to an estimated decrease of 4.3 full scale iq points ; estimated decreases for verbal and performance iq were 3.4 and 4.5 points , respectively . auc7 was significantly and negatively related to three wisc - iii factor scores : freedom from distractibility , perceptual organization , and verbal comprehension ; the association with perceptual organization was the strongest . consistent with previous studies , the iq / lead association is small relative to more powerful social factors . findings offer support for lead 's behavioral signature ; perceptual - motor skills are significantly more sensitive to lead exposure than are the language - related aspects of intelligence.imagesfigure 1 . afigure 1 . bfigure 1 . cfigure 1 . dfigure 2 .

Images

non - hodgkin lymphomas ( nhls ) account for approximately 60% of all lymphomas in children and adolescents . childhood nhls are subdivided into burkitt 's lymphoma , diffuse large b - cell lymphoma ( dlbcl ) , lymphoblastic lymphoma , and anaplastic large - cell lymphoma . dlbcl is characterized by relatively more frequent extranodal presentation , seen in upto 40% of the cases . primary involvement of the lymphoma of the middle ear is rare , with only about 18 cases being reported in literature so far . here , we report a case of dlbcl , presented with features of facial palsy and otitis , who received initial symptomatic treatment and later chemotherapy after diagnosing dlbcl . a 2 years 8 months old boy visited our tertiary care hospital with complaints of ear ache ( left side ) and left facial palsy of 4 weeks duration . after initial 2 weeks of these symptoms , there was whitish serous discharge from the left ear . before referral to our hospital , he was treated for otitis media with antibiotics , details of which were not available . his complete blood picture and biochemistry investigations done in our hospital were within normal limits . as the symptoms persisted for 4 weeks , computed tomography of head and neck was done which was suggestive of solid mass lesion of 2 cm 2 cm size in the left mastoid with destruction of mastoid bone [ figure 1 ] . the disease was in stage 1 ( as per murphy 's staging ) and was completely resected . histopathological examination showed large cells of lymphoid cell proliferation immune histochemistry was positive for cd20 , bcl-2 and negative for cd3 , with low mib-1 , which confirmed dlbcl . his positron emission tomography for staging , bone marrow and cerebrospinal fluid revealed no abnormality . computed tomography head and neck suggestive of solid mass lesion of 2 cm 2 cm size in the left mastoid with destruction of mastoid bone computed tomography head and neck of right side showing no abnormality his initial clinical symptoms of earache and facial nerve palsy followed by ear discharge resolved after starting chemotherapy as per b - cell lymphoma protocol for 6 months . currently , he is 37 months off treatment , and no disease recurrence is seen clinically as well as radiologically . it is an aggressive form of lymphoma , usually curable with appropriate treatment and has high survival rate . rapid disease progression of dlbcl calls for an early , accurate diagnosis and appropriate treatment . however , unusual presentation can mislead the physician resulting in wrong diagnosis , which delays the treatment , thus promoting disease progression . extranodal presentations of childhood dlbcl are relatively uncommon in clinical practice , and much rarer are those primarily involving middle ear and mastoid . involvement of middle ear and mastoid can resemble the features of otitis media and unusual facial palsy mimicking mastoiditis . although these initial symptoms were suggestive of middle ear infection , the distinguishing factor was unresponsiveness to antibiotics . there have been very few reports of nhl with facial nerve involvement ; ogawa et al . mccabe et al . , reported a case of 2-year - old , an immunocompetent boy with spontaneous regression of an epstein - barr - virus - associated monoclonal lymphoid proliferation who presented with acute otitis media and facial palsy . have described a case of dlbcl with features of otitis media , mastoiditis , and facial palsy . as symptoms persisted even after 4 weeks of treatment , the patient was started on chemotherapy , to which he promptly responded . extranodal nhls of middle ear which is not a common clinical presentation may present as facial palsy , and misdiagnosed as otomastoiditis . there should be a high index of suspicion for primary neoplasms of the middle ear in patients with chronic otomastoiditis refractory to appropriate initial antibiotic therapy ; early diagnosis and appropriate treatment results in good therapeutic outcome and minimizes further complications .

extra nodal presentation of non hodgkins lymphoma ( nhl ) is a rare entity , and data available about the nhl that primarily involves of middle ear and mastoid is limited . we report a case of diffuse large b cell lymphoma ( dlbcl ) , in a 2 year 8 month old boy , who developed otalgia and facial palsy . computed tomography revealed a mass in the left mastoid . mastoid exploration and histopathological examination revealed dlbcl . this case highlights the importance of considering malignant lymphoma as one of the differential diagnosis in persistent otitis media and / facial palsy .

Introduction Case Report Discussion Financial support and sponsorship Conflicts of interest

acute pancreatitis due to antipsychotic treatment is rare but sometimes causes a fatal adverse effect . some atypical antipsychotic agents , including clozapine , olanzapine , quetiapine , and risperidone , are associated with acute pancreatitis.1,2 ) among them , acute pancreatitis caused by risperidone is the rarest.3,4 ) although most cases of acute pancreatitis due to atypical antipsychotic agents occur within 6 months of starting antipsychotic administration,1 ) we experienced a schizophrenic patient suffering from pancreatitis after more than 6 months of risperidone therapy . a 69-year - old japanese woman was diagnosed with schizophrenia at the age of 30 years and received outpatient care at another mental hospital . her positive symptoms were not prominent , but her cognitive level was so impaired that she could not regulate her appetite and consumed about 2,000 kcal / day in addition to three ordinary meals . she had never smoked , did not drink alcohol , and did not take any illegal drugs . blood tests ( table 1 ) , abdominal ultrasonography , and a computed tomography ( ct ) scan were performed . clinical features were accompanied by laboratory findings of hyperamylasemia ( amylase , 1,191 u / l ) , hyperlipasemia ( lipase , 1,514 u / l ) , and mild liver enzyme elevations . results of the abdominal ultrasonography were positive for gallstones in the gallbladder and distention of the common bile duct . subsequently , the amylase and lipase titers remained high ( 461 u / l and 804 u / l , respectively ) , although alanine and aspartate aminotransferases decreased gradually to normal levels . at this point , we felt that it was safe for her to start taking the risperidone again . two days after starting the risperidone , serum lipase and amylase increased again to 1,275 u / l and 745 u / l , respectively , and ck also increased ( 766 u / l ) . we decided to suspend the risperidone and introduced 10 mg intravenous haloperidol injections once per day . two days after discontinuing the risperidone , the serum amylase decreased ( 605 u / l ) , but the serum lipase level remained elevated ( 1,654 u / l ) . one week after discontinuing the risperidone , the levels of amylase and lipase decreased gradually ( 309 u / l and 542 u / l , respectively ) , and ck dropped to the normal range . as her general clinical condition and biochemical markers were stable , we changed the haloperidol injection to an oral solution of 6 mg / day aripiprazole because her mental condition worsened after stopping the risperidone treatment . her mental status improved with the aripiprazole treatment , and she was discharged without positive laboratory findings . the patient 's monthly blood tests continue to be normal , including amylase , lipase , and blood cell counts . although atypical antipsychotic - induced pancreatitis has been reported in conjunction with hyperglycemia,5 ) the pathophysiological mechanism of these adverse events remains unclear . most antipsychotic - induced pancreatitis occurs within 6 months after administration1 ) ; however , our case developed pancreatitis more than 6 months after the start of risperidone treatment . risperidone is a 5-ht2a antagonist and ameliorates diet - induced necrotic pancreatitis in mice,6 ) and reduced serum pancreatic amylase levels is observed after endoscopic retrograde cholangiopancreatography.7 ) however , there is no evidence of an association between risperidone treatment and acute pancreatitis . a thorough evaluation for pancreatitis , such as alcohol , tumor , and autoimmune causes , gallstones were present , which were due to an adverse effect of risperidone because the two separate risperidone administrations elevated serum amylase and lipase independently . aripiprazole is currently used in such cases , as aripiprazole is thought to have fewer effects on metabolism , including saccharometabolism , than other atypical antipsychotic agents . lifestyle was also a risk factor in this case . thus , it is necessary to monitor pancreatic function in addition to hyperglycemia in such cases .

acute pancreatitis with antipsychotic treatment is rare but sometimes causes a fatal adverse effect . most cases of acute pancreatitis due to atypical antipsychotic agents are reported to occur within six months of starting antipsychotic administration . acute pancreatitis caused by risperidone is rare . the patient had a high fever , stomachache and vomiting . the results of the abdominal computed tomograhpy scan were negative . the results of the abdominal ultrasonography were positive for gallstones in gallbladder and distention of the common bile duct . she had been fasting and received antibiotic intravenous injections . amylase and lipase titers were high . after risperidone discontinuation , both the levels of the amylase and the lipase were gradually decreased . three months later , the patient still maintains a good clinical balance . although atypical antipsychotic - induced pancreatitis has been reported in conjunction with hyperglycemia , the pathophysiologic mechanism of these adverse events remains unclear . this case got pancreatitis 6 month after risperidone treatment . using the antipsychotic agents , it is necessary to monitor pancreas function .

INTRODUCTION CASE DISCUSSION

an atlanto - axial synovial cyst is very rare . since the first report of this lesion by onofrio and mih1 ) in 1988 , to our knowledge . however , the current report described a patient with a large hemorrhagic cystic mass which was seen around prevertebral space of the atlantoaxial joint on the left side and the obstruction of the nasopharyngeal cavity on cervical magnetic resonance image ( mri ) . we report a symptomatic case associated with rheumatoid atlanto - axial subluxation , which regressed after the surgical management . a 72-year - old woman presented with sudden severe headache in her left occipital area with dyspnea . a laboratory examination of the patient 's blood revealed no remarkable abnormality indicative of inflammation , but high - titer of rheumatoid factor ( 95.9 iu / ml ) . seven months ago before visiting to our department , she checked brain mri due to sudden attack of severe headache on left occipital area , which revealed non - specific lesion except rheumatoid pannus with small prevertebral cyst of c1 - 2 junction ( fig . , there was a large hemorrhagic cystic mass around prevertebral space of the atlanto - axial joint on the left side , obstructing the nasopharyngeal cavity on cervical mri ( fig . the cystic mass was connected to atlanto - axial joint capsule on axial view of computed tomography ( ct ) . multiple bony erosion , rheumatoid atlanto - axial instability including left tilted c1 - 2 subluxation and cranial settling were demonstrated . and there were loss of lordosis and retrolisthesis in c 3 - 4 , 4 - 5 ( fig . 3 ) . in the first operation stage , considering patient 's dyspnea , aspiration of the cystic lesion was performed via transoral approach with otolaryngology surgeon ( fig . after 0.5 cm - sized mucosal incision on left side oropharyngeal wall , residual material of the cyst was squeezed by forceps and removed by suction tools . in the second operation stage , there were rheumatoid atlanto - axial instability and retrolisthesis in c 3 - 4 , 4 - 5 , so it was followed by posterior occipito - cervical fusion that connected from occiput to c5 , using vertex screw & rod system and iliac bone graft ( fig . 5 ) . the patient was tolerable on her postoperative course and showed good respiration and relieved headache . cervical synovial cysts are rare and located at the c1 - 2 junction or lower cervical spine . only 24 cases of synovial cysts of the c1 - 2 junction have been reported in the literature5 ) . moreover , the pathogenesis of spinal synovial cysts remains unclear but is thought to be attributable to degenerative changes of the facet joints or excessive joint motion2,3,5,7 ) . it revealed multiple bony erosions and a large pannus formation of c1 - 2 junction on this case . this patient also showed atlanto - axial instability caused by rheumatoid arthritis , such as left tilted antlanto - axial subluxation and basilar impression . the atlantoaxial articulation is a true synovial joint and is responsible for a large proportion of normal cervical mobility . the etiology of articular cysts is unclear , but they are assumed to be degenerative because minor chronic damage to articular surfaces produces a reactive proliferation of synovium or fibrocartilage that includes loculated collections of mucinous fluid . so , we hypothesized that hemorrhagic event was developed as a result of microtrauma caused by rheumatoid atlantoaxial instability . it is known that the higher titer of rheumatoid factor , the more destructive manifestations of joint occur1 ) . the patient was in the controlled state in serologic inflammatory marker , such as esr(erythrocyte sedimentation rate ) and crp ( c - reactive protein ) . however , the high titer of rheumatoid factor , in spite of long standing medication of rheumatology , was related factor of progressive destruction of joints . we report a rare case of large hemorrhagic cyst on prevertebral space of left side c1 - 2 area associated with rheumatoid arthritis causing airway obstruction and left occipital pain , successfully managed anterior and posterior approach . we suggest repeated microtrauma due to atlanto - axial subluxation associated with rheumatoid arthritis as a main cause of hemorrhagic event on the cyst .

synovial cyst on prevertebral space of c1 - 2 joint is rare but may be associated hemorrhagic event . we describe a case of a 72-year - old woman who presented with sudden severe headache in her left occipital area with dyspnea . she had rheumatoid arthritis for 14-years . large hemorrhagic cystic mass was seen around prevertebral space of the atlantoaxial joint on the left side on cervical mri ( magnetic resonance image ) and it obstructed the nasopharyngeal cavity . aspiration of the cystic lesion was performed via transoral approach , followed by posterior occipito - cervical fusion . the specimen was xanthochromic , suggesting old hemorrhage . the patient was tolerable on her postoperative course and showed good respiration and relieved headache . we suggest that repeated microtrauma due to atalantoaxial subluxation associated with rheumatoid arthritis as a main cause of hemorrhagic event on the cyst .

INTRODUCTION CASE REPORT DISCUSSION CONCLUSION

we compared bona - fide human induced pluripotent stem cells ( ipsc ) derived from umbilical cord blood ( cb ) and neonatal keratinocytes ( k ) . as a consequence of both incomplete erasure of tissue - specific methylation and aberrant de novo methylation , cb - ipsc and k - ipsc are distinct in genome - wide dna methylation profiles and differentiation potential . extended passage of some ipsc clones in culture did n't improve their epigenetic resemblance to esc , implying that some human ipsc retain a residual epigenetic memory of their tissue of origin .

Supplementary Material

to investigate the anti - ulcerogenic properties of the chloroform extract of flemingia strobilifera root in rats . other anti - ulcer related activities of the extract such as the effects on free radicals and antimicrobial activity were also evaluated . chloroform extract of flemingia strobilifera root was found to be safe up to 300 mg / kg body weight when administrated orally in female wistar rats . pretreatment with chloroform extract of flemingia strobilifera root reduced the characteristic lesions in a dose dependent manner ( p<0.001 ) when compared with the control . pretreatment with chloroform extract of flemingia strobilifera root at a dose of 15 and 30 mg / kg body wt . increased the gastric mucosal glutathione level , total protein content significantly ( p<0.001 ) as compared to control group . whereas there is significant ( p<0.05 , p<0.001 ) reduction in gastric mucosal malonaldehyde levels when compared to control . free radical scavenging activity of chloroform extract of flemingia strobilifera root was observed in the concentration range tested , the ic50 value was calculated . antimicrobial activity of the chloroform extract of flemingia strobilifera root exhibited activity against both gram positive and negative bacteria at concentration of 10 mg / ml . the root extract of flemingia strobilifera possess antiulcerogenic properties could justify folklore uses of the plant in peptic ulcer diseases .

purpose : to investigate the anti - ulcerogenic properties of the chloroform extract of flemingia strobilifera root in rats.methods:anti-ulcer effect was evaluated by water immersion induced ulcer in rats . other anti - ulcer related activities of the extract such as the effects on free radicals and antimicrobial activity were also evaluated.results:chloroform extract of flemingia strobilifera root was found to be safe up to 300 mg / kg body weight when administrated orally in female wistar rats . water immersion stress produced characteristic lesions in the glandular portion of the rat stomach . pretreatment with chloroform extract of flemingia strobilifera root reduced the characteristic lesions in a dose dependent manner ( p<0.001 ) when compared with the control . pretreatment with chloroform extract of flemingia strobilifera root at a dose of 15 and 30 mg / kg body wt . increased the gastric mucosal glutathione level , total protein content significantly ( p<0.001 ) as compared to control group . whereas there is significant ( p<0.05 , p<0.001 ) reduction in gastric mucosal malonaldehyde levels when compared to control . free radical scavenging activity of chloroform extract of flemingia strobilifera root was observed in the concentration range tested , the ic50 value was calculated . antimicrobial activity of the chloroform extract of flemingia strobilifera root exhibited activity against both gram positive and negative bacteria at concentration of 10 mg / ml.conclusion : the root extract of flemingia strobilifera possess antiulcerogenic properties could justify folklore uses of the plant in peptic ulcer diseases .

PURPOSE: METHODS: RESULTS: CONCLUSION:

ocular cysticercosis is caused by the growth of the larval form of taenia solium within ocular tissues.1,2 the cysts may be located in descending order of frequency in the subretinal space ( 35% ) , vitreous ( 22% ) , conjunctiva ( 22% ) , anterior segment ( 5% ) and orbit ( 1%).3 intraocular cysticercosis usually presents with reduced vision and ocular inflammation . it is believed that the larva reaches the subretinal space through the posterior ciliary arteries.3 - 6 as the cyst develops , it may cause exudative retinal detachment.6 as long as the cyst remains viable , it evokes little or no inflammatory response . once the cyst starts degenerating , an antigen , which may be a metabolic by - product or toxin , leaks from the cyst and induces an inflammatory reaction , manifesting as vitritis , uveitis and sometimes endophthalmitis.3 - 6 most often , the characteristic intraocular cyst can be visualized by indirect ophthalmoscopy or detected by b - scan ultrasound in the presence of hazy media.3 b - scan ultrasonography will show a curvilinear echo corresponding to the cyst wall together with an eccentric hyperechoic dot suggestive of the scolex . a - scan analysis reveals two high amplitude echoes representing the anterior and posterior walls of the cyst . mahendradas et al7 highlighted the features of intraocular cysticercus cyst employing spectral domain oct ; they clearly delineated the hyper - reflective wall of the subretinal cyst with a more hyper - reflective portion within its wall suggestive of the scolex / larva . cns involvement can be observed in approximately 90% of patients with ocular cysticercosis and mri is superior to computed tomography ( ct ) in detecting lesions of neurocysticercosis ( ncc).8 in addition , mri better illustrates cystic lesions in the base of the brain , cerebrospinal fluid ( csf ) spaces as in ventricular ncc and cisternal ncc , and also with intramedullary lesions.9 the scolex may be more readily apparent on mri than on ct . on mri , contents of live cysts ( vesicular stage ) are isointense relative to csf on t1- and t2-weighted images.10 treatment of ocular cysticercosis is mandatory since it has been reported that 80% of untreated cases result in severe ocular damage.3 antihelminthic drugs such as praziquantel or albendazole are effective in central nervous system and skin cysticercosis . . surgical removal of the cyst can also be performed through transretinal or trans - scleral routes.11 systemic corticosteroid coverage is required before and after surgical removal of the cysticercus.3

a 31-year - old man of asian descent presented with loss of vision in his right eye from 6 months earlier . best corrected visual acuity ( bcva ) was limited to light perception in the right eye and was 6/6 , n6 in the left one . slit lamp examination revealed normal anterior segments bilaterally . intraocular pressure was 8 and 14 mmhg in the right and left eyes , respectively . fundus examination in the right eye showed a large subretinal cysticercus cyst , accompanied by total retinal detachment ( rd ) , severe extensive subretinal fibrosis and membranes ( fig . 1a).b - scan ultrasound ( alcon ultrascan , alcon laboratories , fort worth , texas , usa ) images illustrated total rd with a hyperechoic area within the cystic cavity suggestive of cysticercus scolex ( fig . 1b ) . spectral domain optical coherence tomography ( oct ) ( topcon 3d oct-2000 , topcon medical systems , oakland , new jersey , usa ) demonstrated a highly reflective cyst wall and a more hyper - reflective dome - shaped structure within the wall suggestive of the scolex ( fig . 1c ) . the posterior extent of the cyst could not be visualized due to its large size . t1-weighted contrast - enhanced magnetic resonance imaging ( mri ) of the brain demonstrated a ring - shaped enhancing lesion in the left cerebellar hemisphere with perilesional brain edema suggestive of neurocysticercosis ( fig . 1d ) . the patient was referred to a neurophysician and received a three month course of oral albendazole and steroids . eventually , he was recommended for follow - up care .

DISCUSSION

epidemiologic studies of the link between particulate matter ( pm ) concentrations and mortality rates have yielded a range of estimates , leading to disagreement about the magnitude of the relationship and the strength of the causal connection . previous meta - analyses of this literature have provided pooled effect estimates , but have not addressed between - study variability that may be associated with analytical models , pollution patterns , and exposed populations . to determine whether study - specific factors can explain some of the variability in the time - series studies on mortality from particulate matter [ less than / equal to ] 10 microm in aerodynamic diameter ( pm(10 ) ) , we applied an empirical bayes meta - analysis . we estimate that mortality rates increase on average by 0.7% per 10 microg / m(3 ) increase in pm(10 ) concentrations , with greater effects at sites with higher ratios of particulate matter [ less than / equal to ] 2.5 microm in aerodynamic diameter ( pm(2.5))/pm(10 ) . this finding did not change with the inclusion of a number of potential confounders and effect modifiers , although there is some evidence that pm effects are influenced by climate , housing characteristics , demographics , and the presence of sulfur dioxide and ozone . although further analysis would be needed to determine which factors causally influence the relationship between pm(10 ) and mortality , these findings can help guide future epidemiologic investigations and policy decisions.imagesfigure 1

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he had suffered from intermittent headache for 2 months and had taken benzodiazepines and analgesics under the diagnosis of somatoform disorder at a local clinic . he had a 5-day history of diplopia and a 3-day history of blurred vision that progressed to blindness during the preceding 24 hours . on admission his blood pressure was 130/70 mmhg , pulse rate was 82/min , respiratory rate was 20/min , and body temperature was 36.3. on neurologic examination the patient was alert and exhibited no meningeal signs . only light perception was possible in both eyes , but no other neurological abnormality was noted . lumbar puncture showed the opening pressure of 160 mm h2o with clear cerebrospinal ( csf ) fluid . csf evaluation showed 30 red blood cells / mm , 80 white blood cells / mm , 80% lymphocytes , 41 mg / dl glucose , and 114 mg / dl protein . his body temperature increased to 38.8 1 day after admission , but cbc revealed no leukocytosis . brain mri showed no meningeal enhancement , parenchymal lesion , or intracranial vascular abnormality supplying the optic nerve , optic chiasm , or optic tract . the results of fundoscopic examinations were unremarkable , and visual evoked potential showed no wave formation on bilateral pathways ( fig . an india ink smear of the csf demonstrated encapsulated yeast , and cryptococcus neoformans was cultured ( fig . he was found to be seropositive for hiv with a high antibody titer ( 53.87 s / co ) . he was treated with both antiretroviraland antifungal agents , and his visual acuity had improved upon discharge . neuro - ophthalmic lesions are present in 6% of patients with hiv infection during the course of the disease , with most of them being are attributable to cryptococcal meningitis.3 cryptococcus neoformans , the cause of cryptococcal meningitis , is the fourth most common source of life - threatening infection in aids patients after infections of cytomegalovirus , pneumocystis carinii , and mycobacterium avium intracellulare.1 it is present in pigeon droppings and infects by inhalation of contaminated soil . cryptococcal meningitis is fatal in hiv - infected patients if not treated , and hence early diagnosis is very important . the signs and symptoms of cryptococcal meningitis include headache ( 80~92% of cases ) , meningeal signs ( 50~80% ) , nausea / vomiting ( 40~80% ) , fever ( 36~67% ) , and visual disturbances ( 33~47%).1 our patient presented with acute blindness without other definite clinical symptoms at the time of admission . possible mechanisms for binocular blindness due to cryptococcal meningitis include direct fungal infiltration of the optic nerve , optic chiasm , or optic tracts , adhesive arachnoiditis , cerebral vasculitis , and intracranial hypertension.4 it has been suggested that rapid - onset visual loss is caused by infiltration of the optic nerve or optic chiasm , while slow - onset visual loss is due to increased csf pressure.4 a csf opening pressure exceeding 200 mmh2o and papilledema reflect intracranial hypertension , but our patient showed a normal csf opening pressure and unremarkable fundoscopic examination findings . moreover , his visual symptoms developed very early in the course of the disease . thus , the sudden visual loss might have been due to retrobulbar fungal infiltration . whereas the prevalence of cryptococcosis is decreasing because of the widespread availability of antiretroviral therapy , cryptococcal meningitis is still a fatal complication of hiv infection . thus , both early diagnosis of cryptococcal meningitis and detection of the underlying causes are important . in our opinion , unexpected sudden binocular blindness should be considered as a possible initial manifestation of cryptococcal meningitis related to hiv infection .

ocular complications of hiv - related cryptococcal meningitis are reasonably common , but complete binocular blindness as the first manifestation of hiv is extremely rare . a 58-year - old man presented with binocular blindness . he experienced blurred vision for 3 days before the blindness . mild pleocytosis was present in the cerebrospinal fluid , from which cryptococcus neoformans was cultured . serology revealed positivity for hiv antibody . he was treated with antifungal and antiretroviral therapy . this case indicates that hiv - related cryptococcal meningitis should be taken into consideration when determining the cause of unexpected sudden binocular blindness .

CASE REPORT DISCUSSION

the russian nickel refineries located in the cities of nikel and zapolyarny close to the norwegian border are responsible for extensive sulfur dioxide and nickel pollution , as well as severe ecological damage in both countries . the aim of our study was to investigate human nickel exposure in the populations living on both sides of the norwegian - russian border . the design was a cross - sectional population - based study of adults aged 18 - 69 years residing in sor - varanger municipality , norway , and nikel and zapolyarny , russia , during 1994 and 1995 . individual exposure to nickel was assessed by measurements of nickel in urine using electrothermal atomic absorption spectrometry . for controls , urine was collected from adults in the russian cities of apatity and umba ( kola peninsula ) and the norwegian city of tromso , all of which are locations without nearby point sources of nickel . altogether 2,233 urine specimens were analysed for nickel . people living in nikel had the highest concentrations ( median 3.4 microg / l ) , followed by umba ( median 2.7 microg / l ) , zapolyarny ( median 2.0 microg / l ) , apatity ( median 1.9 microg / l ) , tromso ( median 1.2 microg / l ) , and sor - varanger ( median 0.6 microg / l ) . regardless of geographical location , the russian study groups all had a higher urinary - nickel average than those in norway ( p<0.001 ) . with the exception of nikel , neither the russian nor the norwegian urinary - nickel levels were associated with residence location near a russian nickel refinery . we concluded that industrial nickel pollution alone could not explain the observed discrepancy between norway and russia ; we also discuss other possible nickel exposure sources that may account for the high urinary levels found in russia.imagesfigure 1figure 2figure 3figure 4figure 5

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methods and any associated references are available in the online version of the paper at http://www.nature.com / naturemethods/. difference in optimal collision energies for identification and quantification supplementary note real - time filtering supplementary table 1 summary of quantification and identification results supplementary protocol implementing quantmode on commercial mass spectrometers

we describe a mass spectrometry method , quantmode , which improves the accuracy of isobaric tag based quantification by alleviating the pervasive problem of precursor interference co - isolation of impurities through gas - phase purification . quantmode analysis of a yeast sample contaminated with interfering human peptides showed substantially improved quantitative accuracy compared to a standard scan , with a small loss of spectral identifications . this technique will allow large - scale , multiplexed quantitative proteomics analyses using isobaric tagging .

METHODS Supplementary Material

the majority of swallowed indigestible foreign bodies pass through the gastrointestinal tract without complications [ 1 , 2 , 3 , 4 ] . however , there are three physiological narrowings involving the pylorus , duodenal c - loop and ileocecal valve . foreign bodies longer than 10 cm , such as a toothbrush , can not negotiate the duodenal c - loop due to its fixed retroperitoneal position . these objects should be endoscopically removed as soon as possible to avoid pressure necrosis and gastrointestinal perforation [ 5 , 6 , 7 ] . if endoscopic removal fails or there is evidence of obstruction or perforation , laparoscopic gastrotomy should be performed . an 18-year - old caucasian woman with no previous history of related medical problems was admitted to the department of internal medicine , division of gastroenterology , clinical hospital split because she had accidentally swallowed a toothbrush . the patient admitted she had been using the toothbrush to induce emesis . on presentation , 2 h after ingestion , she was asymptomatic and her vital signs were within normal limits . a plain abdominal x - ray study confirmed the presence of the foreign body in the left upper abdominal quadrant ( fig . informed written consent for upper gastrointestinal endoscopy was obtained from the patient and her parents . esophagogastroduodenoscopy revealed the toothbrush in the stomach with its head positioned against the gastric fundus . the extracted toothbrush was 20 cm long . repeated upper gastrointestinal endoscopy was performed 4 h later and showed no evidence of mucosal lesion to the stomach or the esophagus . the patient was discharged home in excellent clinical condition after being observed for 6 hours . foreign bodies in the stomach will pass uneventfully through the gastrointestinal tract in 8090% of cases [ 1 , 2 , 3 ] . however , foreign objects longer than 10 cm , such as a toothbrush , can not negotiate the duodenal c - loop due to its fixed retroperitoneal position . in such cases , these objects should be removed as soon as possible to avoid pressure necrosis and gastric perforation [ 2 , 3 , 4 , 5 ] . removal of long foreign bodies from the stomach is influenced by the patient 's clinical condition and technical abilities of the endoscopist [ 2 , 3 , 4 , 5 ] . if endoscopic removal fails or there is evidence of obstruction or perforation , surgical gastrotomy should be performed . we had no need for conscious sedation since the patient was actively participating during the procedure . special attention has to be paid during the extraction of the toothbrush to its alongside alignment with the esophagus . otherwise , this most critical and demanding part of the extraction procedure may easily result in mucosal damage or foreign body impaction . the second important phase of the extraction procedure is when the foreign body reaches the oropharynx . the patient has to extend his head backwards and the endoscopist has to reach for the toothbrush with his hand and pull it out . this case report describes a rare case in whom a toothbrush was safely extracted from the stomach endoscopically by snare extraction . the procedure is brief , does not require conscious sedation , and the patient can be discharged from hospital after a few hours . early endoscopic retrieval of the toothbrush is critical for reducing morbidity and mortality . in cases when endoscopic removal fails

most ingested foreign bodies will pass uneventfully through the gastrointestinal tract . nevertheless , long and rigid foreign bodies are associated with an increased risk of gastrointestinal impaction , perforation and bleeding . moreover , there has been no case of spontaneous passage of a toothbrush reported . therefore , the prompt removal of such ingested foreign objects is recommended before complications develop . this case report describes a case of an 18-year - old woman who accidentally swallowed her toothbrush . the toothbrush was successfully removed via flexible endoscopy using a polypectomy snare . a swallowed toothbrush is a special clinical challenge . early endoscopic retrieval of the toothbrush is critical for reducing morbidity and mortality . in cases when endoscopic removal fails , a laparoscopic surgical approach may be an alternative .

Introduction Case Report Discussion Conclusion Disclosure Statement

a 55-year - old man presented at our emergency department with sudden - onset sharp chest pain that had started two hours previously . he also complained of progressive swelling and bruising on his neck , and the development of dysphagia and dyspnea over the previous two hours . he had a history of admission with spontaneous hemothorax seven years previously , and at that time , despite several work - ups for hemothorax , its origin was not found . other than this incident , he had hypertension but no history of gastrointestinal or bleeding disorders . upon arrival at the emergency department extensive neck swelling was observed , as well as bruising on the neck and upper chest . during the examination , he suddenly vomited bright red blood with food material three times , and approximately a quarter - cup of blood was generated on each occasion . other laboratory tests , including cardiac markers and his coagulation profile , were within their normal ranges . 1b ) revealed extensive non - enhancing soft tissue lesions in the posterior mediastinum and neck , which were suspected to be hematomas . emergency gastroscopy showed many blood clots but no definite focus of gastrointestinal bleeding , such as an ulcer , mass , or perforation . instead , gastroscopy showed extrinsic esophageal compression . since the patient was hemodynamically stable , conservative management was adopted in the intensive care unit . followup ct on the third day post - admission showed a focal aneurysm in the right bronchointercostal trunk ( fig . subsequent selective bronchial arteriography revealed a 1-cm aneurysm in the right bronchial artery ( fig . since the aneurysm was considered to be the cause of the hematemesis and mediastinal hemorrhage , we decided to perform embolization to prevent recurrence . the right bronchial artery was subsequently embolized with four microcoils ( vortx-18 ; boston scientific co. , marlborough , ma , usa ) and 33% glue ( fig . 2c ) , and repeat ct showed that the mediastinal hematoma had nearly disappeared ( fig . the patient was discharged without complications . over the course of one year of follow - up spontaneous mediastinal hemorrhage can develop as a result of trauma , aortic dissection , the valsalva maneuver , or iatrogenic procedures . the rupture of a bronchial artery aneurysm ( baa ) is also known to result in mediastinal hemorrhage . when a baa ruptures into the mediastinum , most patients present with chest pain , hemothorax , or hemomediastinum . furthermore , if hematemesis is a prominent symptom of baa rupture , it can be confused with boerhaave s syndrome , variceal disease , or a perforated ulcer . to the best of our knowledge , only three cases of baa presenting with hematemesis have been reported in the literature [ 46 ] . in one case , a pinhole connection between the aneurysm and esophagus was found during an endoscopic examination , but in the present case , no evidence of communication was found between the aneurysm and the esophagus . we first suspected that the mediastinal hemorrhage and hematemesis were caused by the perforation of an esophageal ulcer , but repeated gastroscopy showed a normal esophagus . the only abnormal finding was the finding of a baa without evidence of extravasation three days after the onset of symptoms . after ruling out the possibility of mediastinal hematoma , the baa was the only remaining possible source of the mediastinal hemorrhage . since the baa was regarded as the source of the mediastinal hemorrhage and hematemesis , it was embolized to avoid recurrence . the treatment of a ruptured baa depends on the patient s hemodynamic status and the presence of cardiorespiratory compromise . if the patient is hemodynamically stable , endovascular embolization is considered to be the first - line management strategy , and surgery should only be considered when embolization is contraindicated , as in patients allergic to contrast medium or when a medullary artery is involved . in patients presenting at an emergency department with hematemesis and mediastinal hemorrhage ,

hematemesis is a rare manifestation of a ruptured bronchial artery aneurysm ( baa ) in the mediastinum . it is difficult to diagnose a ruptured baa presenting as hematemesis , because it can be confused with other diseases , such as boerhaave s syndrome , variceal disease , or a perforated ulcer . in this report , we describe a case of baa resulting in hematemesis and mediastinal hemorrhage .

CASE REPORT DISCUSSION

in the previous issue of critical care , kmpers and colleagues demonstrated a direct correlation between increased peripheral blood levels of the vascular growth factor , angiopoietin ( angpt)-2 , and mortality in 43 critically ill adults with sepsis . endothelial injury is one of the main hallmarks of sepsis , leading to capillary leak , microcirculatory dysfunction , organ failure , and eventual death in many critically ill patients . angpt-1 and angpt-2 are two of the best - characterized members of a family of endothelial - derived vascular growth factors necessary for both normal and pathologic angiogenesis and vasculogenesis . both angpt-1 and angpt-2 appear to bind to the tyrosine kinase receptor , tie-2 , found primarily on the luminal surface of endothelial cells . recent studies have also shown that the tie-2 receptor may be found on certain populations of peripheral blood monocytes , although the function and role of the tie-2 receptor in the host innate immune response remain relatively unexplored . angpt-1 is a tie-2 agonist and promotes endothelial stabilization and quiescence , whereas angpt-2 is a tie-2 antagonist and promotes endothelial activation , destabilization , and inflammation . as such , the relative balance between angpt-2 and angpt-1 at the tie-2 receptor may be more relevant to the pathobiology of sepsis than the absolute levels of the individual growth factors . several studies have demonstrated increased peripheral blood levels of angpt-2 in critically ill patients with sepsis [ 5,7 - 9 ] , multiple trauma , acute lung injury ( ali ) , and cardiopulmonary bypass when compared with healthy controls . more importantly , increased angpt-2 levels appear to be associated with adverse outcomes [ 5,6,9 - 12 ] . for example , the study of kmpers and colleagues showed that increased peripheral blood angpt-2 levels correlated with surrogate markers of tissue hypoxia , disease severity , and mortality in 43 critically ill adults with sepsis . also of note , consistent with the opposing roles of angpt-2 and angpt-1 on the tie-2 receptor , peripheral blood levels of angpt-1 were significantly lower in the patients with sepsis compared with healthy controls . unfortunately , in the study of kmpers and colleagues , similar to the aforementioned studies , the temporal kinetics of angpt-1 and angpt-2 were not assessed as blood samples were collected upon the first day of admission to the intensive care unit only . angpt-2 is stored in the weibel - palade bodies within endothelial cells in a more or less prepackaged form . it is therefore not surprising that angpt-2 levels are increased early in response to endothelial activation or injury . whether angpt-2 levels remain increased in critically ill patients with sepsis has not been directly addressed and is a question for future investigation . it is certainly tempting to speculate that peripheral blood angpt-2 levels would be an ideal biomarker of early endothelial activation and injury . similarly , whether angpt-1 levels remain decreased in critically ill patients who eventually succumb to their illness is an interesting question . angpt-1 may be a biomarker of endothelial recovery ; however , given its purported anti - inflammatory role , angpt-1 would appear to be an attractive therapeutic target as well . to this end , several studies have suggested that manipulating the ratio of angpt-2 to angpt-1 by augmenting angpt-1 levels may represent an ideal therapeutic strategy for patients with sepsis and ali . important translational laboratory studies are necessary to show that increased angpt-2 levels in critically ill patients are more than just an epiphenomenon . the role of angpt-2 in the pathobiology of sepsis and ali needs to be further elucidated by using in vitro cell - based studies and animal models of critical illness . similarly , the presence of the tie-2 receptor on certain subpopulations of peripheral blood monocytes suggests a larger role for angpt-2 in the host innate immune response . finally , manipulation of the angpt / tie-2 system may be a rational therapeutic strategy for the management of critically ill patients with sepsis and ali . all of these questions remain an active focus in several laboratories , including our own . the authors ' research is funded by the national institutes of health ( bethesda , md , usa ) ( grant numbers 5ko8gm077432 and 1r03hd058246 ) .

the early recognition and management of sepsis remain the greatest challenges in the field of critical care medicine . endothelial injury is one of the hallmarks of sepsis , leading to capillary leak , microcirculatory dysfunction , organ failure , and eventual death in many critically ill patients . the angiogenic growth factors , angiopoietin ( angpt)-1 and angpt-2 , act upon the tie-2 receptor in opposing roles . angpt-2 has been found in abundance in septic patients when compared with healthy controls . in the study by kmpers and colleagues in the previous issue of critical care , angpt-2 levels correlated with markers of tissue hypoxia , disease severity , and mortality in septic adults . however , the temporal kinetics of the angiopoietins were not assessed . it remains to be seen whether angpt-2 levels will function solely as an early marker of sepsis or whether the manipulation of the angpt / tie-2 system will become a rational therapeutic target for the management of sepsis .

None Abbreviations Competing interests Acknowledgements

plx4032 was synthesized using the general procedures previously described.6 expression and purification of b - raf , structure determination , protein kinase activity measurements , and xenograft studies were carried out as previously described.6 clinical methods have also been recently described.5 melanoma patients were selected for study using previously described taqman methodology.8 semi - quantitative immunohistochemistry for perk and ki67 was performed on 5 m - thick formalin - fixed paraffin - embedded tumor biopsies following h&e staining to determine pathologic diagnosis and tissue morphology and integrity . the degree of phospho - erk staining in the nucleus and cytoplasm was interpreted semiquantitatively by assessing the intensity and extent of staining on the slides . for ki67 staining ,

b - raf is the most frequently mutated protein kinase in human cancers.1 the finding that oncogenic mutations in braf are common in melanoma2 followed by the demonstration that these tumors are dependent on the raf / mek / erk pathway3 offered hope that inhibition of b - raf kinase activity could benefit melanoma patients . herein , we describe the structure - guided discovery of plx4032 ( rg7204 ) , a potent inhibitor of oncogenic b - raf kinase activity . preclinical experiments demonstrated that plx4032 selectively blocked the raf / mek / erk pathway in braf mutant cells and caused regression of braf mutant xenografts.4 toxicology studies confirmed a wide safety margin consistent with the high degree of selectivity , enabling phase 1 clinical trials using a crystalline formulation of plx4032.5 in a subset of melanoma patients , pathway inhibition was monitored in paired biopsy specimens collected before treatment initiation and following two weeks of treatment . this analysis revealed substantial inhibition of erk phosphorylation , yet clinical evaluation did not show tumor regressions . at higher drug exposures afforded by a new amorphous drug formulation,4,5 greater than 80% inhibition of erk phosphorylation in the tumors of patients correlated with clinical response . indeed , the phase 1 clinical data revealed a remarkably high 81% response rate in metastatic melanoma patients treated at an oral dose of 960 mg twice daily.5 these data demonstrate that braf - mutant melanomas are highly dependent on b - raf kinase activity .

METHODS SUMMARY Supplementary Material

few similar cases are reported in literature but none of them is associated with mirizzi syndrome . radiological images could help the surgeon to choose the surgical strategy and to evaluate the presence of associated diseases . in our case laparoscopic surgery showed to be an excellent approach for both the cholecystectomy and the repair of the defect of the abdominal wall . the patient was an 85 year - old man with history of hypertension , previous surgery for perforated diverticular disease ( hartmann procedure followed by reversal of colostomy ) . the physical examination showed a 5 cm mass in the right upper quadrant tender to palpation . ultrasound and ct confirmed the presence of a lithiasic gallbladder herniated through the abdominal wall ( fig.1 ) , with a dilatation of the common bile duct that measured 11 mm , due to a 17 mm obstructive infundibular stone as it happens in mirizzi syndrome type i ( fig.2 ) . lithiasic gallbladder herniated through the abdominal wall the routine complete blood test , including bilirubin level , was unremarkable . therefore the patient underwent a laparoscopic cholecystectomy and a repair of the hernia . during surgery , multiple adhesions were found and released carefully to identify the gallbladder that was fully included in the right upper quadrant abdominal wall covered by peritoneum . the gallbladder was completely released and the dissection of the pedicle showed a short cystic duct and a normal common bile duct . most of the cases reported in literature are internal hernias through the winslow foramen ( 1 ) . the herniation of the gallbladder through acquired defects of the abdominal wall ( incisional hernia ) has been much less reported . ( 2 ) presented the case of a gallbladder herniated through a fascial defect of a subcostal incision . garcia reported a patient who presented a gallbladder hernia through a parastomal defect ( 3 ) . more recently , the case of a gallbladder strangulation through an abdominal wall defect on the site of a previous colostomy was described ( 4 ) . in this case , the most remarkable thing is that herniation does not occur through a natural orifice or an acquired defect , such as respectively for the winslow foramen or for an incisional hernia , but directly into the abdominal wall . to our knowledge , there are only 3 published cases of spontaneous herniation of the gallbladder through the abdominal wall ( 5,6,7 ) . another interesting aspect of this case is the presence of a chronically distended gallbladder ( gallbladder hydrops ) , associated with extrinsic compression of the common hepatic duct by an impacted stone in the infundibulum ( mirizzi syndrome type i ) ( 8) . it is probably the gallbladder dilatation that plays an important role in the development of the hernia pressing constantly the gallbladder against the abdominal wall . usually the clinical picture is represented by a right upper quadrant pain , associated with variable degrees of a compromised general condition . in our experience the preoperative study based on computed tomography is essential for the diagnosis of the gallbladder hernia , and it provides also additional information on the abdominal wall defect . the management of this type of hernia consists in reducing the content and repairing the abdominal wall defect . in this case we suggest the laparoscopy as surgical approach of first choice because it allows to solve three problems at the same time : first , the reduction of the gallbladder s incarcerated hernia ; second , it enables to perform a cholecystectomy that was indicated for the presence of gallstones and hydrops ; third , it allows to repair the hernia defect preferably with a mesh , if the local conditions are favorable . in our experience , preoperative imaging has been proved to detect the gallbladder disease and the morphology of the fascial defect . mesh repair is the gold standard for hernias ; however , acute cholecystitis still remains a contraindication for mesh repair due to the high risk of infection .

a gallbladder incarcerated hernia associated with mirizzi syndrome is a very rare entity and to our knowledge this is the first case ever described in literature . an 85-year - old man presented at the emergency department with a tender right upper quadrant mass . computed tomography ( ct ) revealed the presence of a gallbladder lithiasis with signs of acute cholecystitis , herniated through the abdominal wall with an associated mirizzi syndrome . laparoscopic cholecystectomy and repair of the abdominal wall defect were performed . the patient recovered very well and the postoperative period was uneventful .

INTRODUCTION CASE PRESENTATION DISCUSSION

multistep skin carcinogenesis assays were performed with mice with keratinocyte - specific deletion of the cnb1 gene ( cnb1xk5-crepr1)3 in parallel with cre - negative controls ( cnb1 ) . detailed conditions for these assays as well as chromatin immunoprecipitation , immunoblotting , immunofluorescence , senescence -galactosidase staining , biotinylated dna pull down assays , and sorting can be found in the method section and supplementary figure legends .

calcineurin inhibitors such as cyclosporin a ( csa ) are the mainstay of immunosuppressive treatment for organ transplant recipients . squamous cell carcinoma ( scc ) of the skin is a major complication of treatment with these drugs , with a 65100 fold higher risk than in the normal population1 . by contrast , the incidence of basal cell carcinoma ( bcc ) , the other major keratinocyte - derived tumour of the skin , of melanoma and of internal malignancies increases to a significantly lesser extent 1 . here we report that genetic and pharmacological suppression of calcineurin / nfat function promotes tumour formation in mouse skin and in xenografts , in immune compromised mice , of h - rasv12 expressing primary human keratinocytes or keratinocyte - derived scc cells . calcineurin / nfat inhibition counteracts p53-dependent cancer cell senescence thereby increasing tumourigenic potential . atf3 , a member of the enlarged ap-1 family , is selectively induced by calcineurin / nfat inhibition , both under experimental conditions and in clinically occurring tumours , and increased atf3 expression accounts for suppression of p53-dependent senescence and enhanced tumourigenic potential . thus , intact calcineurin / nfat signalling is critically required for p53 and senescence - associated mechanisms that protect against skin squamous cancer development .

Methods summary Supplementary Material

placental polyp is a somewhat pedunculated remnant of chorionic tissue retained in the uterine cavity for an indefinite time . it may result in abnormal uterine bleeding and slightly elevated detectable titers of serum -human chorionic gonadotropin ( hcg ) . these pedunculated masses of villi are often found within days to weeks following abortion or delivery of a term placenta . since trophoblastic neoplasms especially placental site trophoblastic tumor may have similar symptoms and signs , it is important to consider placental polyp in differential diagnosis in such situations . a 34-year - old g4l3ab1 woman came with abnormal uterine bleeding since her last normal vaginal delivery 3 months ago . serum -hcg level was slightly elevated ranging from 86 to 103 iu / ml during diagnostic investigations . ultrasonography revealed enlarged uterus with an echolucent intracavitary uterine mass measuring 73 mm 55 mm 24 mm . computerized topography confirmed the presence of the mass and showed no abnormality in thorax . clinical , laboratory , and imaging findings raised the suspicion of gestational trophoblastic tumors especially those arising from intermediate trophoblastic cells . macroscopically , the uterus showed slight global enlargement resulting from the presence of a polypoid mass within the endometrial cavity . the cut surface was diffusely red with some fine streaks of a gray colored tissue . it was attached to the uterine wall in the fundal region without any macroscopic permeation into the myometrium [ figure 1 ] . microscopic study showed largely necrotic villi in a network of fibrin deposition [ figures 2 and 3 ] . a large polypoid mass with smooth outer surface has completely filled the endometrial cavity necrotic chorionic villi are seen in the background of fibrin deposition ( 40 ) nuclear debris are seen in the stroma of necrotic chorionic villi ( 400 ) placental polyp is a fragment of retained placental tissue in the uterus that has undergone neovascularization after resolution of gestation . chronic uterine inversion due to placental polyp has also been reported . a case of placental these pedunculated masses of villi are often found within days to weeks following abortion or delivery of a term placenta . rarely , they persist for months or even years after pregnancy . abnormal uterine bleeding due to placental polyp has been attributed to preserved villi , clusters of destructive villi , and isolated viable cotyledons . preservation of the brush border of syncytiotrophoblastic cells and the presence of placental phosphatase maintain the anticoagulative properties of villi . thromboplastic properties of the preserved villi play an important role in the pathogenesis of uterine bleeding when necrotic villi with epithelial remnants are prevalent . computed tomographic angiography is also useful in diagnosis and management of placental polyp with neovascularization . magnetic resonance imaging may also be used in diagnosis and follow - up of placental polyps . . a hypervascular placental polyp may lead to severe hemorrhage that requires blood transfusions , interventional radiology procedures , hysteroscopic resection , and even hysterectomy to control bleeding . evaluation of neovascularization by multimodal imaging is potentially useful in management of placental polyp in women who wish to preserve fertility . successful treatment with the use of iliac artery occlusion catheters and concomitant hysteroscopic resection has been reported . intraoperative injection of prostaglandin f2 followed by hysteroscopic resection has been successful in management of these cases . serum hcg fell to undetectable level following surgery . although the patient had completed her family and did not have any desire to preserve her fertility , a proper preoperative diagnosis with accurate interpretation of imaging findings and satisfactory curettage would have prevented hysterectomy in this patient . placental polyp should be considered in any case of parous woman with unexplained abnormal uterine bleeding and slightly elevated serum hcg level . this does not exclude the possibility of the presence of a placental polyp as the source of abnormal bleeding . all authors have contributed in designing and preparation of the first draft of the manuscript . they have read and approved the content of the manuscript and confirmed the accuracy or integrity of any part of the work .

placental polyp is retained placental tissue within the endometrial cavity , which forms a nidus for inflammation and bleeding . there are very few reported cases of the clinical placental polyp . here , we report a case of 34-year - old g4l3ab1 woman with the chief complaint of intermittent vaginal bleeding since her last normal vaginal delivery 3 months ago . serum human chorionic gonadotropin ( hcg ) titer was slightly elevated . a polypoid mass was detected within the endometrial cavity by imaging studies . history of the patient , mass lesion within the endometrial cavity and slightly elevated serum hcg titer raised the suspicion of trophoblastic neoplasms . endometrial curettage yielded unsatisfactory specimen containing only fibrin deposition and was followed by total hysterectomy . the uterus showed slight global enlargement resulting from the presence of a polypoid mass within the endometrial cavity . the red - colored mass had a smooth outer surface and fragile consistency without any permeation into the myometrium . pathology reported it as the placental polyp . although very rare , placental polyp should be kept in mind as one of the reasons of abnormal uterine bleeding in parous women . definite diagnosis is made by pathology examination .

INTRODUCTION CASE REPORT DISCUSSION AUTHORS CONTRIBUTIONS

many organs can be herniated into the scrotum such as small intestine , appendix , colon , and ovaries . ureteral herniation is extremely rare , usually asymptomatic and is reported as isolated case report or small series . we report the case of an 88-year - old man treated for inguinoscrotal hernia where the left ureter was incidentally found in the herniated retroperitoneal fat . presenting symptoms , diagnostic evaluation , and surgical management an 88-year - old man was admitted for a left moderately sized inguinoscrotal hernia . his medical history included hypertension and benign prostatic hyperplasia . the herniated parts were dislocated from the scrotum , as well as the testicle , and cord strictures . the cord was separated from the herniated parts and was partially covered from preperitoneal fat . a large amount of retroperitoneal fat surrounded from a sac - like formation was found adjacent to the cordis [ figure 1a and b ] . these adhesions , as well as a part of this fat , were excised because of the irreducibility of the mass . during the excision , 24 h later , an abdominal ultrasound was performed to rule out any structural abnormality , which may have been missed preoperatively . ( a and b ) the left extraperitoneal inguinoscrotal hernia the ureter identified into the herniated retroperitoneal fat ureteral herniation is rare , and approximately 140 cases have been reported in the literature , mainly as isolated case reports or small series . ureteric hernia is also reported as spontaneous , postoperative or as a complication of renal transplantation . ureteral herniation presents as a groin mass usually asymptomatic although many cases describe association with dysuria , hematuria , and hydronephrosis . the hernia has the classical aspect of an indirect hernia ; it is formed by the sac anteromedially that contain viscera that make up the wall of the sac , and the ureter lying posterolaterally . the ureter slides into the canal drawn by the posterior peritoneum that follows the herniated viscera . paraperitoneal hernias are more common in men , usually located on the right side , are often large in size , usually reducible and rarely symptomatic . there is not a clear association with kidney or ureteric abnormalities . on the other hand , the hernia is often accompanied by the large amount of retroperitoneal fat , is often nonreducible , usually small and commonly associated with urinary symptoms . authors consider this type of hernia congenital and related to developmental abnormalities of differentiation of the ureter from the wolffian duct . the ureter slides along with the testis into the scrotum ; a process also favored by adhesions between the ureter and genitoinguinal ligaments . many extraperitoneal hernias have a congenital association to renal or ureteral malformation such as crossed renal ectopia or nephroptosis . however , in our case the hernia was sizable , partially reducible and was no associated with urinary symptoms . the diagnosis of ureteral hernia is often missed due to lack of urinary symptoms or signs or symptoms that could lead doctors to apply an extended preoperative work up . although computed tomography may determine the type and the contents of hernias and the intravenous urography may determine abnormalities before surgery , they are not justifiable on every inguinal hernia repair . considering the fact that ureteric injuries are serious complications and require additional surgical approaches , we emphasize the high index of suspicion needed by surgeons when repairing hernias identifying gross amount of sliding fat and resecting fat trying to reduce hernia into the abdomen .

an inguinoscrotal hernia is a common disorder that usually contains intraperitoneal organs ( small intestine , colon , appendix , ovaries ) . extraperitoneal ureteral herniation into an inguinoscrotal hernia is a rare condition and often associated with congenital abnormalities or postoperative anatomic changes . a high index of suspicion is needed in order to avoid intraoperative ureteric injuries . we herein report the case of a ureteric herniation into an inguinoscrotal hernia incidentally found during a scheduled hernia repair .

INTRODUCTION CASE REPORT DISCUSSION CONCLUSION Financial support and sponsorship Conflict of interest

in the closed structure of the p2x cation channel , three -helical transmembrane domains cross the membrane obliquely : in rat p2x2 receptors , these intersect at thr339 . replacing thr339 by lysine in one , two or three subunits progressively increased chloride permeability and reduced unitary conductance . this implies that the closed - open transition involves a symmetrical separation of the three subunits , and that thr339 from each contributes symmetrically to the open channel permeation pathway .

Supplementary Material