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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

primary neuroendocrine carcinoma ( nec ) of the breast is a rare distinct clinicopathological entity , comprising 0.5 - 2% of breast carcinomas world - wide . in 2003 , primary nec of the breast was identified as a distinct entity by the world health organization ( who ) classification of tumors . the who classification defines primary nec of the breast as tumors that express 50% or more of ne markers there are no previous reports of f-18 fluorodeoxyglucose ( fdg ) positron emission tomography / computed tomography ( pet / ct ) in patients with primary nec of breast with liver and bone metastasis . here we describe a case of a 45-year - old female patient who presented with jaundice and was evaluated to have multiple liver lesions and biopsy from liver showed metastatic neuroendocrine tumor . her chromogranin level was 886 ng / ml ( normal < 78 ng / ml ) . she was referred for the whole body pet / ct for detection of the primary site . pet / ct showed an intense uptake in the soft- tissue necrotic lesion in the inner quadrant of the left breast [ figure 1a and b ] with the same charecteristic feature of multiple hypodense liver lesions [ figure 1c ] . furthermore uptake noted in a lytic lesion in the d4 vertebra [ figure 1d and e ] . patient underwent fine - needle aspiration of the breast lesion , which confirmed neuroendocrine origin [ figure 2a and b ] . a diagnosis of primary nec of the left breast with metastasis was made and she was treated with peptide receptor radionuclide therapy and is on follow - up now . whole body fluorodeoxyglucose - positron emission tomography / computed tomography ( pet / ct ) maximum intensity projection image ( a ) , axial fused pet / ct showed a intense uptake in the soft - tissue lesion in the left breast ( b ) , liver lesions ( c ) and bone lesion ( d ) , axial ct showing lytic bone lesion in d4 vertebra ( e ) immunohistochemistry staining showing positive for chromogranin ( a ) and synaptophysin ( b ) primary nec of the breast is extremely rare with the first reported case in 1983 . the most frequent reported age varies from 40 to 70 years , with a higher incidence in women greater than 60 years . as metastatic neuroendocrine tumors of the breast are more common than that of primary neuroendocrine tumors of the breast , it is , therefore , important to differentiate primary breast neuroendocrine tumor from metastatic disease to the breast because of the differences in treatment focus . primary nec of the breast can be diagnosed if the presence of a non - mammary primary site can be clinically ruled out or if an in situ component is histologically detected or both . however , findings of certain studies have revealed that ne - differentiated tumors of the breast present as dense round or irregular masses with spiculated or lobular margins on the mammogram . definitive diagnosis is made with core needle biopsy , allowing for the immunohistochemical evaluation of the specimen for the ne markers . although the use of pet for the evaluation of ne tumors has been limited , tumors with moderate or high proliferative activity can be identified by fdg pet . there are reports of fdg pet / ct in a case of neuroendocrine differentiated breast carcinoma with pleural metastases using indium-111 octreotide . there are case reports of synchronous metastases to the liver and pancreas from a primary nec of the breast . our case is the first demonstrates that 18f - fdg pet / ct provides the most significant additional information related to the accurate detection of primary nec of breast and bone metastasis and guiding treatment .

cases of primary neuroendocrine carcinoma ( nec ) of the breast have been reported , though rare . we report the case of a 45-year - old woman presented with jaundice and evaluated to have liver metastasis from neuroendocrine origin . she underwent whole body positron emission tomography / computed tomography , which showed left breast lesion and bone metastasis . fine - needle aspiration ( fna ) of breast revealed a nec . a diagnosis of a primary nec of the breast was rendered with hepatic and bone metastasis . she was treated with peptide receptor radionuclide therapy and is on follow - up .

INTRODUCTION CASE REPORT DISCUSSION

thermal spring 's microbiomes have been in attention of the scientific community since past few decades . these springs , being hub of diverse microflora , increase the probability of vast gene pool of uncultured microbiota . metagenomics have helped the microbiologist to reveal the genome of the rest of the 99% of non - cultivable microbes which further helped to better understand the global microbial ecology and also helped in meeting the current demand for novel enzymes . thus , with the advances in metagenomics all the hidden facts of the microbial ecology have been faced off . odisha being rich in bio - diversity due to seasonal / climatic variations possesses a variety of hot - springs located in different geographical locations and vary both in physio - chemical and microbial ecology parameters . mainly four major hot - springs have been reported in odisha i.e. deulajhari hot spring in angul , taptapani hot spring in ganjam , atri hot spring in khurda and tarabalo in nayagarh . deulajhari hot spring is located at about 6 km from athamallik and between 203 north latitude and 8449 east longitude . in our study , sediment sample from deulajhari hot spring ( latitude 20.74199 n , longitude 84.49206 e ) was collected from the hot spring having 69 c temperature . the v3v4 region of the 16s rrna was amplified using primers 341f , 5-cctacgggaggcagcag-3 and 518r , 5-attaccgcggctgctgg-3 with 50 ng of metagenomic dna . the amplified pcr product was purified by gel elution using minelute column ( qiagen , india ) and further leads to 150 nucleotide paired end multiplex sequencing using illumina gaiix sequencer at genotypic technology pvt . krona tool was used for plotting krona graph as depicted in fig . 1 . 2,073,312 high quality reads obtained from the hot spring with temperature of 69 c were used for further analysis . out of the total , proteobacteria ( 88.12% ) , bacteriodetes ( 10.76% ) , firmicutes ( 0.35% ) , spirochetes ( 0.18% ) , thermi ( 0.13% ) and chloroflexi ( 0.11% ) were identified at the phylum level . of the total 216 genera in this deulajhari hot spring only 53.7% were identified and 46.29% were unidentified at the genus level . since all the phylotypes , retrieved through the sequencing , do not contribute to all the taxonomic groups known till date , it indicates the significance of the diversity of deulajhari hot spring explored .

insights about the distribution of the microbial community prove to be the major goal of understanding microbial ecology which remains to be fully deciphered . hot springs being hub for the thermophilic microbiota attract the attention of the microbiologists . deulajhari hot spring cluster is located in the angul district of odisha . covered within a wooded area , deulajhari hot spring is also fed by the plant litter resulting in a relatively high amount of total organic content ( toc ) . for the first time , illumina sequencing based biodiversity analysis of microbial composition is studied through amplicon metagenome sequencing of 16s rrna targeting v3v4 region using metagenomic dna from the hot spring sediment . over 28 phyla were detected through the amplicon metagenome sequencing of which the most dominating phyla at the existing physiochemical parameters like ; temperature 69 c , ph 8.09 , electroconductivity 0.025 dsm 1 and total organic carbon 0.356% , were proteobacteria ( 88.12% ) , bacteriodetes ( 10.76% ) , firmicutes ( 0.35% ) , spirochetes ( 0.18% ) and chloroflexi ( 0.11% ) . approximately 713 species were observed at the above physiochemical parameters . the analysis of the metagenome provides the quantitative insights into microbial populations based on the sequence data in deulajhari hot spring . metagenome sequence is deposited to sra database which is available at ncbi with accession no . srx1459736 .

Direct link to deposited data Experimental design, materials and methods

the author has not received any funding or benefits from industry or elsewhere to conduct this study .

there remain tremendous opportunities to improve the stability and safety of american health care . within this context , residents and residency programs face two essential questions : how to reduce the risk to patients resulting from resident inexperience , and how to change our programs to create the safer physician of the future ? the spread of side - by - side teaching and non - teaching services creates a natural setting to study these questions and improve both services . when asked the question , would you admit your mother to the resident service ? , many of us respond , it depends . we are focusing this column on helping programs answer this question definitively in the positive , share potential best practices , and underscore community hospital 's contribution to our understanding of patient safety .

Conflict of interest and funding

hemifacial spasm is a disorder of the seventh cranial nerve , and is characterized by irregular , involuntary and recurrent tonic and clonic contractions of the ipsilateral facial expression muscles . each spontaneous motor paroxysm starts with eye twitching and progresses to involve the other muscles innervated by the facial nerve . the episode characteristically begins with a series of twitches that increase in frequency and intensity , followed by a sustained spasm . the disorder is typical during adulthood and is commonly attributed to vascular compression of the facial nerve emergence at the brain stem . altogether , posterior fossa or cerebellopontine angle tumors are rare causes of hemifacial spasm , reported in less than 1% of a large series of adult patients . in children , the association of hemifacial spasm with tumors is also rare , with very few cases reported . a 6-year - old girl without any significant past medical history was admitted with intermittent involuntary twitching of the right orbicular region ; the twitching had occurred for 18 months . over time , the spasms became more tonic , and after 4 months , the spasms also involved the right orbicularis oris area . she was noted to be in good overall condition , showing a normal physical examination without fever or any other signs of infection . her height was 133 cm , and she weighed 39 kg , with a body mass index of 22.4 . the neurological examination was noteworthy for dysarthria and right hemifacial spasm [ figure 1 ] . sustained right hemifacial spasm laboratory evaluations , including a complete blood cell count , electrolytes , blood urea nitrogen and liver enzymes were within the normal range . cranial magnetic resonance imaging ( mri ) revealed a right - sided heterogeneous lesion from the midbrain to the pons , extending to the cerebellopontine angle , with a slight mass effect on the fourth ventricle [ figure 2 ] . after the neuroimaging procedures , a cerebral biopsy was performed , which revealed a pilocytic astrocytoma . the hospital ethic commission approved this case report , and the patient 's parents gave informed consent for publication . ( a ) t2-weighted coronal and ( b ) flair axial mri images showing a right - sided heterogeneous high signal lesion from the midbrain to the pons , extending to the cerebellopontine angle , with a slight mass effect on the fourth ventricle . ( c ) t1-weighted aspect of the lesion , with heterogeneous low signal and ( d ) t1-weighted post - gadolinium sagittal image showing its enhanced pattern these causes include venous sinus thrombosis , masses of the fourth ventricle , pilocytic astrocytoma , congenital or acquired cholesteatoma , tuberculous meningitis , thickening of the arachnoid membrane , neurosurgical facial nerve injury , accommodative esotropia and mandibular prognathism . masses may directly impinge on the facial nerve depending on the size and location of the tumor . some studies described cases in which the facial nerve was compressed against bony structures or tethered to arachnoid adhesions . this case shows the importance of a thorough neurological evaluation because our patient presented with subtle clinical signs of hemifacial spasm as the initial manifestation of a pilocytic astrocytoma . children who present with hemifacial spasm , even if very mild , should undergo further investigation .

hemifacial spasm is a disorder of the seventh cranial nerve , which is characterized by irregular , involuntary and recurrent tonic and clonic contractions of the ipsilateral facial expression muscles . this disorder affects mainly adults , and there are few cases reported in childhood . the main etiologies are vascular problems , although tumors are an important cause of hemifacial spasm via a direct or an indirect mass effect . we report a 6-year - old girl who presented with right hemifacial spasm . magnetic resonance imaging showed a lesion in the cerebellopontine angle , extending from the midbrain to the pons with a slight mass effect on the fourth ventricle . the histological examination revealed a pilocytic astrocytoma .

Introduction Case Report Discussion

the common occurrence of these tumors is prevalent among males in their second or third decades of life with site predilection toward trunk and extremities , especially in the forearm . however , the incidence of al is extremely rare in the intraoral region , with only 21 reported cases in english literature . a 90-year - old woman with no significant medical history was referred to our department for evaluation of painless mass arising from oral cavity . the tumor was noticed by the patient 20 years ago as a small nodule on the right buccal mucosa and since then it gradually increased in its size . the growth reached a size , which could not accommodate in mouth , and due to constant irritation from the tumor , the patient coughed the growth for 5 years . since then on extraoral examination , a solitary , smooth , nontender and nonpulsatile pedunculated growth of size 14 cm 10 cm with variable consistency was evident with intraoral origin [ figure 1 ] . clinical image shows preoperative tumor on intraoral examination , single , smooth , firm and nontender stalk - like pedicle of diameter 2 cm was seen originating from the right buccal mucosa . based on the history and clinical examination , we provisionally diagnosed it as a benign growth . surgical excision of the tumor was done under general anesthesia [ figures 2 and 3 ] . clinical image shows excised tumor mass clinical image shows postoperative frontal view histopathology confirmed it as noninfiltrating al [ figures 46 ] . one - year follow - up of the patient revealed no evidence of recurrence . ethical approval from the institutional review board was obtained for the publication , and patient release form was signed by the patient . clinical image shows histopathology section ( 4 magnifications ) clinical image shows histopathology section ( 10 magnifications ) clinical image shows histopathology section ( 40 magnifications ) lipomas are the most frequently found soft - tissue benign tumors , but their occurrence in head and neck region is rare . al , in the oral cavity , was first documented by davis et al . as a growth on the hard palate . history of trauma , lipomatous differentiation by hormones during puberty , vascular proliferation of a congenital lipoma and fatty degeneration of a central hemangioma have been implicated as possible etiological factors . the mean diameter at the largest portions of all the 21 documented als occurring in oral region was 3 cm , and the mean onset age of the patients was about 29 years old . although diagnostic modalities such as magnetic resonance imaging , computed tomography , ultrasonography and aspiration biopsy have been used to differentiate between hemangioma , lipomas and al , the diagnosis of these tumors is confirmed only by histopathology . the standard treatment of choice is surgical excision for the noninfiltrating als and complete surgical excision with a clear surgical margin for poorly encapsulated infiltrating als to avoid recurrence . the case we have presented showed the typical clinical and histological findings of a noninfiltrating al . its most striking and unique features were its occurrence in a 90-year - old female with a 20-year long history and pedunculated mass of 14 cm 10 cm . with regard to the size and its typical pedunculated appearance , our present case can be considered to be the first of its kind in literature .

we present an extremely rare case of noninfiltrating angiolipoma ( al ) of the buccal mucosa in a 90-year - old patient reaching a size of 14 cm 10 cm . al is rare in the soft tissues of oral cavity , and till date , only 22 cases have been reported , including our case . if size be taken into consideration , our case can be considered to be the first in literature to reach this massive size . surgical excision of the tumor mass was performed . the histopathological findings confirmed the diagnosis of noninfiltrating al . follow - up for 1 year revealed no signs of recurrence .

INTRODUCTION CASE REPORT DISCUSSION Financial support and sponsorship Conflicts of interest

oral angiokeratomas are most commonly found as a component of the generalized systemic disorder in fabry 's disease or fucosidosis , where multiple angiokeratomas can be found on the skin and the oral mucosa . we report a rare case of a patient with multiple oral and scrotal angiokeratomas in the absence of a systemic disorder . a 60-year - old man presented with a 2-year history of painless red raised lesions involving the tongue . he complained of burning sensation in the mouth in the region of the papules . clinical examination revealed multiple erythematous to slightly bluish , shiny , vascular papules ranging from 1to3 mm size , discrete to grouped on the undersurface and lateral aspects of the tongue [ figure 1 a and b ] . biopsy from a vascular papule on the tongue showed acanthosis , and papillomatosis , with large , dilated spaces lined by normal - appearing endothelium which were filled with erythrocytes and organizing thrombi [ figure 1d ] . the patient was counseled about the benign nature of the disease after which he chose not to take any treatment . ( a - b ) multiple erythematous to bluish , shiny , vascular papules on the undersurface and lateral aspects of the tongue ; ( c ) similar vascular papules on the scrotum ; ( d ) acanthosis , and papillomatosis , with large , dilated spaces lined by normal - appearing endothelium which are filled with erythrocytes and organizing thrombi ( h and e , 200 ) angiokeratoma is an asymptomatic cutaneous vascular disorder of the papillary dermis characterized by dermal vasculsar ectasia with overlying hyperkeratosis of the epidermis . it is thought to be a telangiectatic lesion arising from local injury to papillary dermal capillaries , either from trauma or venous hypertension . they are ( 1 ) the generalized systemic type : angiokeratoma corporis diffusum of fabry characterized by multiple tiny red papules in a symmetrical distribution in the bathing area ; ( 2 ) angiokeratoma of mibelli , the bilateral form occurring on the dorsal areas of the fingers and toes ; ( 3 ) angiokeratoma of fordyce , the most common angiokeratoma which occurs on the scrotum ; ( 4 ) the solitary papular angiokeratoma which has a predilection for the legs ; and ( 5 ) angiokeratoma circumscriptum , the multiple papular and plaque- like form . oral mucosal angiokeratomas have also been associated , uncommonly , with angiokeratomas of the scrotum , gastrointestinal mucosa ( jejunum ) , or both . recently ranjan & mahajan have proposed a clinical classification for oral angiokeratomas , depending on the number of lesions , associated other muco - cutaneous involvement and systemic disease . oral angiokeratomas present as single / multiple , erythematous , shiny papules , which may be studded with keratotic tops . they are firm on palpation , nontender , show telangiectatic vessels on diascopy , and bleed occasionally . the tongue , with a predilection for the dorsal aspect , appears to be the most common site for isolated oral angiokeratoma . they may be mistaken for hemangiomas , lymph - hemangiomas , focal epithelial hyperplasia , or nevi . the histologic features are similar to their cutaneous counterparts ; hyperkeratosis , acanthosis and dilated capillaries in the papillary dermis , partly or completely enclosed by the papillomatous epidermis . organized or organizing thrombi are occasionally observed within the dilated capillaries . the only difference being the presence of parakeratosis in oral angiokeratomas . however , in fabry 's disease and fucosidosis , swollen and vacuolated ( lipid containing ) endothelial cells are characteristic differentiating features .

we report a 60-year - old man who presented with a 2-year history of painless red raised lesions involving the tongue and scrotum . histopathology was suggestive of angiokeratoma . oral angiokeratomas are most commonly found as a component of the generalized systemic disorder in fabry 's disease or fucosidosis . our patient had isolated mucosal angiokeratomas which is very rare .

Introduction Case Report Discussion

the collected comments and pathologic diagnoses of several pathologists are summarized for 18 cases in which lesions were induced in the upper respiratory tract of rats and mice . specific neoplastic and nonneoplastic lesions of the nose and trachea are described and discussed , and opinions regarding pathogenesis and biologic significance of the lesions are presented . the anatomic and pathophysiologic complexities of the rodent nose in relation to lesion development following inhalation or systemic exposure to xenobiotics are important considerations in the genesis of pathologic changes in this organ.imagesplate 1.plate 2.plate 3.plate 4.plate 5.plate 6.plate 7.plate 8.plate 9.plate 10.plate 11.plate 12.plate 13.plate 14.plate 15.plate 16.plate 17plate 18plate 19plate 20.plate 21.plate 22.plate 23.plate 24.plate 25.plate 26.plate 27.plate 28.plate 29.plate 30.plate 31.plate 32.plate 33.plate 34.plate 35.plate 36.plate 37.plate 38.plate 39.plate 40.plate 41.plate 42.plate 43.plate 44.plate 45.plate 46.plate 47.plate 48.plate 49.plate 50.plate 51.plate 52.plate 53 .

Images

subdural spinal hematoma is an extremely rare complication of spinal and epidural anesthesia and may lead to cauda equina syndrome , bowel bladder dysfunction or even complete permanent paraplegia . a 60-year - old female patient was diagnosed to have osteoarthritis of right knee joint and was advised knee arthroplasty . enoxaparin sodium 40 mg ( lmwh ) was started 9 h after surgery and was followed by once daily dose . foot pump and compression stockings were applied for deep vein thrombosis ( dvt ) prophylaxis . on day 2 , the epidural catheter was removed 13 h after last dose , and she was discharged on 3 postoperative day in stable condition . at the time of discharge , on 4 postoperative day , she developed sudden onset pain in the lower back which was radiating to left lower limb . the pain was followed by loss of sensation and weakness in the left lower limb . it showed a large subdural hematoma , which was compressing the thecal sac at l2-l3 level . laminectomy with decompression of spinal cord and evacuation of hematoma was done on the emergent basis . postoperatively patient recovered well with complete control over bowel and bladder functions , but foot drop on the left side persisted after 6 months of follow - up . combined spinal epidural anesthesia though safe has been associated with uncommon neurologic complications like subdural hematoma . venous stasis , endothelial injury and hypercoagulable conditions contribute to the postoperative development of dvt which can be a life - threatening complication . in surgeries as total knee and hip replacement , direct injury to the large vessels of lower limb predispose patients for increased chances of dvt especially in absence of postoperative anticoagulation prophylaxis . however , prophylaxis must be balanced against the risks for postoperative bleeding and epidural hematoma . spinal and epidural anesthetic procedures in combination with anti - coagulant therapy represent the fifth most common cause of spinal hematoma . three cases developed paraplegia due to subdural hematoma which was due to underlying coagulation disorder . and horlocker and wedel highlighted the risk of spinal hematoma which gets aggravated by concomitant administration of anticoagulants and anti - platelet drugs . fryburg et al . , reported two patients who suffered from spontaneous acute spontaneous subdural hematoma while taking fondaparinux for venous thromboembolism prophylaxis . it is recommended that lmwh should be used once daily and to be started 12 - 24 h postoperatively , especially when indwelling spinal catheter are present or when concomitant antiplatelet or oral anticoagulant medication is being given . patients who develop extra or subdural hematoma usually present with acute back or radicular pain radiating to limbs , followed by progressive sensory and motor involvement in either one or both the lower limbs along with saddle anesthesia and bowel and bladder dysfunction . in most of the cases , these symptoms usually develop shortly after the procedure with mean age of onset being 30 h after operation , but in our case , the patient developed sudden onset neurological symptoms suggestive of cauda equina syndrome on 4 postoperative day . urgent mri was done to confirm the diagnosis and patient was immediately taken to the operation theatre where laminectomy with decompression of spinal canal and evacuation of hematoma was done . , neurosurgical intervention must be sought immediately , because recovery is unlikely if surgery is postponed for more than 8 h. this case highlights that even in the absence of an existing spinal pathology and carefully administrated spinal - epidural anesthesia , cse may cause dreaded neurologic complication like subdural hematoma especially in the presence of anti - coagulant therapy . hence frequent 4 hourly neurological examination is essential for early detection of hematoma , which should be continued 24 hours postoperatively following a neuraxial block or upto 24 hours following catheter removal if patient is anticoagulated . in a case of suspected cauda equina syndrome , the patient should be investigated and urgent decompression should be done on emergent basis to prevent permanent neurological sequelae .

combined spinal - epidural anesthesia ( cse ) is considered safe in lower limb surgeries . we report a case of sudden neurological deterioration in a stable postoperative patient who was given cse for total knee replacement and low molecular weight heparin in postoperative period . on the 4th postoperative day , she developed sudden onset weakness in left lower limb along with bladder incontinence . magnetic resonance imaging spine revealed a subdural hematoma at l2-l3 level . immediate laminectomy along with cord decompression was done and patient recovered well except for a persistent foot drop on left side .

Introduction Case Report Discussion

the centers for disease control and prevention report that autism spectrum disorder ( asd ) now affects 1 in 88 children in the usa and 1 in 47 in utah . asd is 5 times more likely in boys with 1 in 54 boys identified nationally . more children will be diagnosed with asd this year than with aids , diabetes , and cancer combined . a diagnosis of autism is based on observed behavior and educational and psychological testing . currently , there is no single definitive treatment for autism , nor is there presently a cure . traditional treatments may be biomedical , sensory , behavioral , developmental , sports - related , or arts - based . the objective was to conduct qualitative research using light hands - on touch energy work with children diagnosed with asd with focus on the following behaviors : eye contact , appropriate social behavior , verbal tics , motor control and coordination , neural impulses related to the sensory organs , immune system , and ability to learn . six participants between 9 and 16 years of age were treated by teams of two practitioners in 10 sessions using light touch energy work protocol focusing on boosting the immune system and strengthening organs of the body and brain functioning . over a 15-month period , participants had an overall improvement of 70% in 5 categories evaluated . specifically , there was an improvement of 81% in eye contact , 72% in social behavior , 61% in motor control / coordination , 75% in sensory neural reorganization , and 65% in learning evolution . energy work may positively impact people living with asd and can be safely integrated with other healthcare modalities . further research needs to be conducted , and more reliable research instruments for complementary and alternative healthcare need to be developed .

focus area : pediatricsintroduction : the centers for disease control and prevention report that autism spectrum disorder ( asd ) now affects 1 in 88 children in the usa and 1 in 47 in utah . asd is 5 times more likely in boys with 1 in 54 boys identified nationally . more children will be diagnosed with asd this year than with aids , diabetes , and cancer combined . a diagnosis of autism is based on observed behavior and educational and psychological testing . currently , there is no single definitive treatment for autism , nor is there presently a cure . traditional treatments may be biomedical , sensory , behavioral , developmental , sports - related , or arts-based.objectives:the objective was to conduct qualitative research using light hands - on touch energy work with children diagnosed with asd with focus on the following behaviors : eye contact , appropriate social behavior , verbal tics , motor control and coordination , neural impulses related to the sensory organs , immune system , and ability to learn.methods or target groups : six participants between 9 and 16 years of age were treated by teams of two practitioners in 10 sessions using light touch energy work protocol focusing on boosting the immune system and strengthening organs of the body and brain functioning . assessments included parental and practitioner observations using verified and unverified research instruments.results or activities : over a 15-month period , participants had an overall improvement of 70% in 5 categories evaluated . specifically , there was an improvement of 81% in eye contact , 72% in social behavior , 61% in motor control / coordination , 75% in sensory neural reorganization , and 65% in learning evolution.conclusion or deliverables : energy work may positively impact people living with asd and can be safely integrated with other healthcare modalities . further research needs to be conducted , and more reliable research instruments for complementary and alternative healthcare need to be developed .

Introduction: Objectives: Methods or target groups: Results or activities: Conclusion or deliverables:

successful laparoscopic treatment has been described previously in only a few cases . rarely the diagnosis is suspected preoperatively when using only ultrasound . other diagnostic tests like magnetic resonance cholangiopancreatography ( mrcp ) , endoscopic retrograde cholangiopancreatography ( ercp ) and intraoperative cholangiogram can be more accurate in the diagnosis of this condition . intraoperative cholangiogram represents a powerful tool for the surgeon when dealing with double gallbladder , it help to delineate the anatomy and confirms the diagnosis . ( 1,2 ) we present a case report of a patient with symptomatic cholelithiasis with double gallbladder treated laparoscopically using intraoperative cholangiogram . a 21 year old male otherwise healthy with no previous surgical history , presented to the emergency room with the chief complaint of several hours of right upper quadrant pain that started after a large meal . the patient described a history of several weeks of right upper quadrant pain after meals but normally it would subside without any intervention . on admission , the patient had normal and stable vital signs and on physical exam there was tenderness to palpation on the right upper quadrant but no peritoneal signs . his laboratory exams were unremarkable with a normal white blood cell count and normal liver function test . the patient was admitted to the hospital and he was taken to the operating room where he underwent a laparoscopic cholecystectomy using the standard 4 port technique with intraoperative cholangiogram ( fig 1 ) . also appreciated in the image : the common bile duct , the common hepatic duct and the left and right hepatic ducts . during the operation ( fig 23 ) the intraoperative cholangiogram helped to identify each cystic duct and the operation was otherwise uneventful . he was started on clear liquid diet postoperatively and he was discharged home on postoperative day one . gallbladder duplication is a very rare diagnosis . even though the true incidence reported during autopsy is about 1:40005000 the gallbladder primordium can split and form a gallbladder duplication but this only represents a congenital anomaly of the gallbladder . true gallbladder duplication has two cystic ducts and two cystic arteries . the true double gallbladder forms from an extra primordium during the embryonic development . the symptomatic patient with two gallbladder represents a diagnostic and treatment challenge to the general surgeon.(13 ) to aid in the diagnosis the surgeon can use ultrasound , mrcp , ercp and ultrasound . none of these tools are 100% sensitive and only in little more than 50% of the cases the diagnosis is made preoperatively.(2,3 ) in our case the ultrasound was questionable but certainly prompted the use of intraoperative cholangiogram to help define the anatomy . in figure 2 two cystic ducts can clearly be seen which makes our case a true gallbladder duplication treated successfully with standard laparoscopic technique . the differential diagnosis of a gb duplication seen in us is large , but the most common diagnosis are a phrygian cap , gallbladder diverticulum or a choledochal cyst.(3 ) once the diagnosis has been made by seen two cystic ducts in the symptomatic patient , the surgical removal of both gallbladders is indicated . there are only a few case reports of double gb successfully managed laparoscopically in the literature.(3 - 7 ) our case shows that the use of intraoperative cholangiogram confirms the diagnosis and helps to identify both cystic ducts . previous literature have shown conflicting and controversial results when trying to use intraoperative cholangiogram to prevent bile duct injuries , but there no large series or randomized studies evaluating the use of intraoperative cholangiogram in patients with double gallbladder . ( 8 - 10 ) we recommend routine use of ioc when dealing with abnormal anatomy or congenital anomalies of the gallbladder . the evidence is anecdotal but as shown on this case report clearly seen two cystic ducts accurately diagnosed a gallbladder duplication and prevented the surgeon from leaving an unidentified gallbladder which later can become a diagnostic enigma .

double gallbladder is a rare finding in patients with symptomatic cholelithiasis or acute cholecystitis . the incidence has been described as 1 in every 4000 - 5000 patients during autopsy . to identify the gallbladder ( gb ) duplication prior to surgical removal of the gb is of upmost importance . it is not unusual to identify this diagnosis intraoperatively , but by using us , ercp or mrcp more than 50% of the cases are diagnosed preoperatively . the use of intraoperative cholangiogram helps to identify the anatomy and confirm the diagnosis during laparoscopic cholecystectomy in patients with gallbladder duplication .

INTRODUCTION CASE REPORT DISCUSSION

in the present issue of critical care , linder and colleagues present a new study in which they assess the clinical importance of serial measurements of heparin - binding protein ( hbp ) plasma levels in critically ill septic and nonseptic patients . they found that hbp plasma levels are significantly higher in patients with severe sepsis and septic shock in comparison with patients with a nonseptic critical condition . the authors also demonstrated that hbp plasma levels obtained at admission to the icu and during the last individual sampling are higher in nonsurvivors as compared with survivors in both the septic group and the whole study group . moreover , the high baseline hbp plasma levels in septic patients were associated with an increased 28-day mortality rate . altogether , these results indicate that serial hbp measurements might be very helpful in stratification of icu patients . however , there are some issues that should be raised before the study results can be translated into the daily routine . the study was designed to compare hbp plasma levels in patients with severe sepsis and septic shock with levels in patients with noninfectious critical illness . however , these two groups of patients were not equal in size . also , a significant proportion of patients from the nonseptic group developed infection and was treated with antibiotics . this raises the question of whether the comparison between septic and nonseptic icu patients is hindered by this treatment . nevertheless , the study design is logical because finding a biomarker that would predict development of any shock state is highly desirable . previous studies have demonstrated significant predictive values of elevated levels of lactate , cortisol and il-6 in the blood of patients with different etiologies of shock [ 2 - 4 ] . however , these biomarkers have some limitations : lactate levels are less influenced by arterial sampling , endogenous cortisol levels are downregulated by corticosteroids used in the treatment of septic shock or by relative adrenal insufficiency , and il-6 analysis is not generally available in regular hospital laboratories . other routinely measured biomarkers - such as procalcitonin , c - reactive protein , neutrophil and lymphocyte counts - have only a limited value in prognostic scoring of the critically ill patients and are mostly used in the early diagnostics of bacterial etiology of critical illness [ 6 - 8 ] . notably , hbp has antibacterial activity , which includes a direct microbicidal effect , and also helps neutrophils to migrate into the focus of infection . similarly to hbp , c - reactive protein and il-6 play an active role during the immune responses against infections : c - reactive protein is an inflammation opsonin , and the major function of il-6 is amplification as well as downregulation of inflammatory reactions , depending on the concentrations . regarding procalcitonin , there are only limited data from animal studies - which demonstrate that immunoneutralization of procalcitonin improved survival in experimental porcine sepsis . additionally , elevated cortisol levels in peripheral blood during sepsis are considered an integral part of compensatory anti - inflammatory response syndrome , leading to downregulation of exaggerated systemic immune responses . from the functional point of view , in comparison with the abovementioned biomarkers , hbp therefore plays the most complex role in severe sepsis and septic shock - highlighting its potential for clinical use . in conclusion , the serial measurements of hbp plasma levels can be a useful tool for close monitoring of critically ill septic patients . however , availability of a routine diagnostic method for hbp analysis is essential to confirm these interesting data . the authors thank dr e david mcintosh ( imperial college , london , uk ) for help with the manuscript .

heparin - binding protein ( hbp ) , also known as azurocidin , has multiple functions in the inflammatory process , especially during severe infections . beside its antimicrobial properties , hbp may induce vascular leakage leading to extravascular efflux , which is an important pathophysiologic event in the development of septic shock . not surprisingly , high hbp plasma levels are found in severe sepsis patients and in septic shock patients as well as in serious infections associated with endothelial damage . in the present issue of critical care , linder and colleagues demonstrate new aspects of hbp daily monitoring in icu patients . the authors observed that high hbp plasma levels are associated with an increased mortality rate in both septic and nonseptic critically ill patients , indicating that hbp may be a reliable prognostic biomarker . however , there are some limitations hindering rapid translation of these interesting findings into the daily routine . first , the group of nonseptic critically ill patients ( n = 28 ) enrolled in the study was rather small as compared with the septic group ( n = 151 ) . moreover , 50% of nonseptic patients developed infection while hospitalized in the icu , and to classify them as truly nonseptic patients is problematic . second , there is a lack of a routine diagnostic method for hbp analysis . nevertheless , if the results of the present study are validated in large clinical trials in different icu populations and cost - effectiveness data become available , the serial hbp measurements will have a promising future .

None Abbreviations Competing interests Acknowledgements

adrenal myelolipoma is a tumor - like lesion composed of variable amounts of mature adipose tissue and bone marrow elements . in spite of wbc and rbc precursors such as megakaryocytes giercke in 1905 first described and 24 years later , oberling coined the term myelolipoma. only two cases under the age of 16 are reported and to the best of our knowledge , this patient is the youngest pediatric case of adrenal myelolipoma reported in the english literature . an 11-year - old girl presented with recurrent pain abdomen for 1 year , which was gradually increasing in frequency and severity for last 5 months . ultrasonography ( usg ) of abdomen showed a well - encapsulated and hypo echoic lesion in right suprarenal region measuring 27.1 24.3 mm . contrast enhanced computed tomography ( cect ) scan of abdomen confirmed the lesion to be arising from right adrenal gland with fat density measuring 1.8 2.3 cm [ figure 1 ] . gross examination of the specimen showed reddish yellow colored friable mass , soft in consistency ; and on microscopy , islands of hematopoietic tissue were found scattered among the fat cells [ figure 2 ] . cect reveal small fat containing lesion in right adrenal suggestive of myelolipoma histopathology showing fat lobules ( f ) and megakaryocyte ( m ) adrenal myelolipoma is a tumor - like lesion composed of variable amounts of mature adipose tissue and bone marrow elements . in spite of wbc and rbc precursors such as megakaryocytes myelolipoma may occur in retroperitoneum around kidney and pre - sacral space or in liver ; however , adrenal gland is the most common site . most of the cases of myelolipomas are asymptomatic . usually diagnosed incidentally at imaging for other purposes and the reported incidence are reaching up to 7% of the adrenal masses . majority of incidentally discovered myelolipomas are small and asymptomatic though large symptomatic lesions are also reported but in adult population . symptoms may be due to large tumor causing the pressure effect , tumor necrosis and intralesional hemorrhage . malignant potential of adrenal myelolipoma has not been reported . in our study , the child presented with pain abdomen and , on investigation diagnosis was confirmed . the lesion is itself hormonally inactive but may be associated with metabolically active adrenal lesion like cushing syndrome , conn 's syndrome , congenital adrenal hyperplasia etc . myelolipoma can be regarded as an exception to the mandatory metabolic work - up of a newly discovered adrenal mass . large myelolipoma usually associated with hematological disorders like hereditary spherocytosis , thalassemia intermedia , thalassemia major , sickle cell anemia and usually bilateral if we get a case of large or bilateral adrenal myelolipoma we have to investigate for chronic hematological disorders . before removal the of tumor , it may be necessary for bone marrow transplantation to avoid aggravation of hemolytic anemia . most accepted theory regarding etiologies are that it arises in response to infection , stress or necrosis causing metaplasia of reticuloendothelial cells of the capillaries of adrenal gland . focal fat density , peripheral calcification and hemorrhage within the tumor can be better identified with cect scan . myelolipoma contains adipocytes with hematopoietic elements , consisting of myeloid and erthyroid precursors , as well as , megakaryocytes . these hematopoietic elements are scattered in the adrenal tissue and separated by sheets and large clusters of mature adipocytes admixed with hemorrhagic foci . though open surgery is the classical method , laparoscopic adrenalectomy has now become the standard of care for the treatment of functioning and non - functioning adrenal tumors , introduced by gagner in 1992 . small asymptomatic myelolipomas can be treated conservatively but the symptomatic one should be treated with surgical excision and/or adrenalectomy .

myelolipoma is a rare benign tumor of adrenal gland and rarer in children . myelolipoma contains adipose tissue and myeloid precursor producing white blood cells ( wbc ) , red blood cells ( rbc ) and megakaryocytes . asymptomatic tumor does not require treatment whereas symptomatic tumor needs operation . we are reporting a rare adrenal myelolipoma in a child with review of literature .

INTRODUCTION CASE REPORT DISCUSSION CONCLUSION

we did a single - center retrospective analysis of seven patients with pelvic abscess treated by eus transrectal drainage between january 2010 and august 2014 . there were four men and three women , with a median age of 50 years ( range 22 - 68 ) . a concomitant intravenous antibiotic treatment was always administered be for eus and for a minimum of 7 days after drainage . the method of drainage was done with a linear interventional echoendoscope ( pentax ) ( eg 3870utk pentax - hitachi , hambourg , germany ) . eus - doppler evaluation was first performed to exclude the presence of intercalated blood vessels before puncture with a 19-gauge access needle ( cook ) ( 19 g , echotip access needle , cook ireland ltd . , limerick , ireland ) . the puncture tract was then enlarged with a 10 french diathermic cystostomy over a tetrafluoroethylene ( tfe)-coated 0.035-inch guidewire ( cook endoscopy , winston - salem , nc , usa ) . a second guidewire was then put into the cavity , and two 7 french double pigtail plastic stents were positioned ( 4 or 7 cm length ) . eus drainages were done for a majority of abscesses post surgery ( n = 5/7 ) . the treatment was feasible and effective in 100% of cases [ figures 17 ] , without supplementary radiological or surgical intervention [ table 1 ] . the median time of hospitalization was 10 days ( range 4 - 25 days ) . the main difficulty related to this technique is the positioning of the double pigtail plastic stents , induced by pus outflow that can reduce the endoscopic visibility . two of our patients were embarrassed by the length of the double pigtail plastic stents which protruded in the anal canal . pelvic abscess before drainages pelvic abscess after drainage sagittal view of pigtail stent in pelvic abscess fluoroscopic view of first pigtail insertion endoscopic ultrasound ( eus ) view of douglas abscess eus view of abscess puncture endoscopic view with first guidewire insertion etiology and outcomes since 2003 , eus pelvic abscesses drainage is performed ; given the proximity between the rectal lumen and the abscess , with a mini - invasive technique compare to radiological or surgical drainage . moreover , percutaneous drainage may be difficult to realize and uncomfortable , especially if the collection is in deep location which needs a posterior drainage . our technique is safe , without adverse events observed ; and is actually well standardized , in analogy with 10 years of practice for eus drainage of pancreatic pseudocysts . the use of the fluoroscopy and cystostomy facilitates the procedure and can be easily used by experienced operators . the length of double pigtail plastic stents should be as short as possible , especially if drainage is done in the lower rectum , because it may cause discomfort if it touches the anal canal . we can also conceive that the length of hospital stay could be further reduced if the antibiotic treatment is continued orally in selected patients . eus transrectal drainage is a safe and an efficient method for therapeutical treatment of pelvic abscess . in our experience , we recommend eus transrectal drainage for pelvic abscess as the first - line technique for experienced hands .

background and objective : pelvic abscesses are a well - known complication of intestinal diseases or abdominal surgery . we report our case series concerning transrectal drainage by endoscopic ultrasound ( eus).methods : between january 2010 and august 2014 , seven patients received transrectal drainage by endoscopic ultrasound ( eus ) were selected and analyzed.results:two pigtails was positioned under fluoroscopic and eus control . the success rate was 100% and complication rate was 0% . the median time of hospitalization was 10 days [ range 4 - 25].conclusions : the technique appears to be safe and feasible in all etiologies . in our experience , we can considerate transrectal drainage by eus like a first - line technique in experienced hands .

INTRODUCTION MATERIALS AND METHODS RESULTS DISCUSSION CONCLUSION

lymphangioma circumscriptum ( lc ) or microcystic lymphatic malformation is a hamartomatous malformation of the lymphatic channels of the skin . treatment of lc is difficult because of the persistent nature of the disease due to deeper subcutaneous cisternal connections . we report here a case of lc treated effectively with radiofrequency ablation without any recurrence . a 16-year - old male with fitzpatrick skin type v presented to our clinic with partially fluid - filled lesions on left upper arm with slight local swelling . the patient had these lesions since the age of 2 years and had been repeatedly treated with antibiotics for local infection . examination showed a well - defined plaque on left upper arm with grouped vesicular lesions , giving the typical appearance of a a biopsy was taken from the edge of the lesion and histopathology showed multiple thin - walled , dilated lymphatic spaces in the papillary dermis and these spaces contained lymph and few erythrocytes . the overlying epidermis was thin , and there were elongated rete ridges that appeared to surround the lymphatic channels . the patient was given a systemic antiobiotic , cefadroxil 500 mg twice daily for 5 days , to treat the infection including oozing from the lesions and to decrease the inflammation . radiofrequency ablation was done a week later ( basco radiofrequency device , model rf - b2 , high frequency 2 mhz , power < 150 w ) , in cut and coagulate mode with wire loop electrode , under local anesthesia . the patient was advised to clean the area with betadine lotion and apply topical antibiotic mupirocin on the lesions . three sessions were required at weekly intervals for the lesions to clear as some deeper components were left untreated at the first two sessions . one week after last treatment , the area had partially healed with slight depigmentation . at 1 month , the lesions had completely healed and swelling had subsided [ figure 1 ] . no recurrence has occurred in the past 1 year and the patient is still under surveillance . ( a ) lc lesion on the left upper arm ; ( b ) lesions being treated with radiofrequency ablation ; ( c ) immediate post treatment red erythematous area ; ( d ) complete healing of the lesions at 1 month lc is benign ectasia with two components : the clinically obvious , dermal vesicular component , visible on the skin , and the deeper subcutaneous cisternal element . whimster described the pathogenesis and said that lc arises from the subcutaneous muscle - coated lymphatic cisterns which receive lymphatic flow from the surrounding tissue , but this is not drained to the normal lymphatic system . these dilated cisterns conduct the lymph through communicating channels into the dermal thin lymphatics , which balloon out into the epidermis . treatment modalities include surgical excision , lasers and sclerotherapy with varying success.[35 ] we tried the radiofrequency ablation to treat lc , which produced near - complete clinical ablation with coagulation of lesional and perilesional skin leading to fibrosis of the perivesicular lymphatics . the follow up was longer in our case , i.e. , 1 year and we are encouraged to do a case series to determine the efficacy of radiofrequency in this notorious condition .

lymphangioma circumscriptum ( lc ) , a hamartomatous lymphatic malformation , is a therapeutic challenge for the dermatologist . various modalities like surgical excision , lasers , and sclerotherapy have been used in the past to treat this notorious skin condition . we report the efficacy of a radiofrequency ablation in a patient with lc . the treatment efficacy of radiofrequency was satisfactory in our patient with no recurrence during 1 year follow - up period . the radiofrequency technique is a safe and economic treatment for management of lc .

Introduction Case Report Discussion

a patient was immediately referred to our department after epidural endoscopy with severe bilateral visual impairment and underwent complete ophthalmologic examination . a 45-year old man suffered from low back pain unresponsive to pharmacologic treatment , radiating to the left hip and left lower extremity , due to a back injury 4 years ago . other medical history was noncontributory and he was otherwise healthy without hypertension , diabetes mellitus , cardiovascular disease , or blood clotting abnormalities . the patient underwent an epidural endoscopy and endoscopic adhesiolysis in the level of l4l5 and o5s1 by infusion of 120 cc of normal saline . at the end of the procedure the patient received an epidural injection of 80 mg methylprednisolone . after the operation the general condition of the patient was good without clinical signs of elevated cerebrospinal pressure and blood pressure and heart rate remained stable . however , a few hours later , he became aware of a major decrease of vision in both eyes and was immediately admitted to the department of ophthalmology . at presentation , best corrected visual acuity ( bcva ) was 20/400 re and counting fingers le . the ophthalmic examination revealed the presence of extensive scattered preretinal , subhyaloid , and subretinal hemorrhages in both eyes and especially in the le ( figure 1 ) . ocular history before the operation did not reveal any ocular disease and bcva was 20/20 in both eyes . examination of the fundus showed mild vitreous hemorrhage with extensive intraretinal and subretinal hemorrhages involving the macula especially of the le . four months after the operation , bcva was 20/30 in both eyes . despite the improved vision fundus examination revealed a remarkable resolution of the retinal and subretinal hemorrhages bilaterally with mild pigmentary changes of the macula especially of the le ( figure 2 ) . intraocular hemorrhages often occur in association with acute subarachnoid hemorrhage and secondary aneurysms of the anterior communicating and internal carotid arteries ( terson 1900 ) . the present case represents an extremely rare incidence of intraocular hemorrhage following epiduroscopy and endoscopic adhesiolysis ( amirikia et al 2000 ; brian et al 2005 ) . several mechanisms have been proposed to explain the occurrence of intraocular hemorrhage ( purdy et al 1998 ) . it seems that a sudden increase of the epidural pressure after the epiduroscopy causes cerebrospinal fluid to effuse through the communication of the subarachnoid space within the optic nerve sheath and subsequently compresses the optic nerve and its vasculature . specifically , the retinochoroidal anastomosis and the central retinal vein are occluded resulting in venous stasis allowing extravasation of blood through the vessels causing subhyaloid , retinal , and subretinal hemorrhages . the different types of hemorrhages suggest an acute generalized extravasation of blood within the various layers of the posterior segment opposed to the direct tracking of blood from within the optic nerve sheath . more particularly , intracranial pressure can be directly affected if the dura is punctured and fluid is added to the subarachnoid space . the visual prognosis is considered to be good , with recovery occurring within 6 months ( tabandeh 2000 ) . the present case is rare and it represents a rare complication of a rather common operation . however , as endoscopic spinal procedures become widely established , it is anticipated that similar cases will be recognized more frequently in the future . therefore , surgeons should be aware of the possibility of possible vision loss after this procedure .

purposeto report a case of acute visual loss after endoscopic spinal surgery.methodsa patient was immediately referred to our department after epidural endoscopy with severe bilateral visual impairment and underwent complete ophthalmologic examination.resultsvisual acuity was decreased in both eyes . fundus examination revealed the presence of retinal and vitreous hemorrhages bilaterally . four months later , visual acuity increased and the hemorrhages were remarkably resolved.conclusionthe present case represents an extremely rare incidence of intraocular hemorrhage following epiduroscopy .

Purpose Methods Results Conclusion Case report Discussion

spinal epidural hemangiomas have been reported in the literature , but most of them were cavernous type hemangiomas that enable a preoperative differential diagnosis with relative ease . the limited number of spinal epidural hemangiomas and few radiological findings make an exact diagnosis difficult prior to surgery . a high vascularization of spinal epidural hemangiomas may result in an unexpected surgical situation in the case of preoperative misinterpretation . in the current case , a 51-year - old woman presented with a 3-week history of lower back pain with right anterior thigh numbness . the patient had a magnetic resonance imaging ( mri ) at a local hospital which revealed a lesion at the l3 level , located in the ventral epidural space and connected with l3/4 protruded disc material that demonstrated a heterogeneous signal at t2 weighted images and an iso- to low signal at t1 weighted image ( t1-wi ) . 1 ) . based on a presumed diagnosis of a ruptured disc with possible sequestration or granulation tissue formation , the patient underwent surgery . a right hemilamincetomy of l3 was performed , and a retracting thecal sac revealed a highly engorged vascular structure . near - infrared indocyanine green videoangiography ( icg - va ) showed a delayed mass filling . histological examination revealed a vascular lesion composed of small to medium sized veins with irregular calibers , which is consistent with an arteriovenous hemangioma ( fig . the typical symptoms of epidural lesions other than disc herniation of the lumbar region are low back pain or radiculopathy which are indistinguishable from the clinical symptoms of disc herniation diseases . moreover , spinal epidural hemangiomas are very rare . also , spinal epidural hemangiomas constitute approximately 4% of all epidural tumors and 12% of all intraspinal hemangiomas4 ) . the differential diagnosis for spinal epidural hemangiomas before surgery included schwannoma , lymphoma , meningioma , angiolipoma , disk herniation , synovial cysts , granulomatous infection , pure epidural hematoma , and extramedullary hematopoiesis9,12 ) . the cavernous type displays histologically with large number of sinusoidal channels in collagenous tissue7 ) , whereas the arteriovenous type shows with a cluster of abnormal arteries and veins and vessel walls containing elastin , and smooth muscle5 ) . a complete surgical en bloc removal is the treatment of choice for spinal epidural hemangiomas with mass effect because of the excessive vascularity of hemangioma , piece to piece resection should be avoided6 ) . an indocyanine green videoangiography can help surgeons understand the vasculature surrounding the mass and facilitate the en bloc removal of the hemangioma . fluorescence angiography with indocyanine green provides real - time information regarding the patency of vessels . an icg - va enhances the flow direction delineation capability , flow velocity and sequence of dye filling in different components of complex spinal vascular lesions3 ) . due to the high vascularization of hemangiomas , the incomplete surgical removal of a spinal hemagioma because of diffuse bleeding or minimal exposure during disk surgery might result in the persistence of clinical symptoms or recurrence . reoperation for remnant or recurrent spinal hemangioma is very difficult due to peridural or periradicular adhesion and unclear margins ; as a result , complete resection can not be guaranteed . therefore , proper preoperative planning and complete resection during the operation is essential . for this , but , like this case , an angiography may not always confirm the diagnosis of an artriovenous hemangioma . clinicians should be aware that an angiography can not provide conclusive evidence of the presence of an antriovenous hemangioma . if spinal epidural hemangiomas are unexpected encountered during surgery , an icg - va can be helpful to diagnose and surgery . this technique provides accurate information about the flow dynamics through the anatomy of vascular lesions in real time10,11,13,14 ) . further study is required to recognize and to provide a differential diagnosis of spinal epidural hemangiomas . if the lesion is like a ruptured disc in mri , we should consider spinal epidural hemangioma as one of differential diagnosis .

a spinal epidural hemangioma is rare . in this case , a 51 year - old female patient had low back pain and right thigh numbness . she was initially misdiagnosed as having a ruptured disc with possible sequestration of granulation tissue formation due to the limited number of spinal epidural hemangiomas and little - known radiological findings . because there are no effective diagnostic tools to verify the hemangioma , more effort should be put into preoperative imaging tests to avoid misdiagnosis and poor decisions ) .

INTRODUCTION CASE REPORT DISCUSSION CONCLUSION

the application of a 32p - postlabeling assay for 7-methylguanines in dna was studied either by labeling the imidazole ring - opened dinucleotide derivatives or by using strong - anion - exchange column chromatography for the adduct enrichment from normal nucleotides . data showed that 7-methylguanines can be efficiently labeled as dinucleotides when in vitro methylated dna was first imidazole ring - opened and then digested to the dinucleotide level with deoxyribonuclease i , snake venom phosphodiesterase , and prostatic acid phosphatase . when using ion exchange chromatography for the adduct enrichment , dna was digested with micrococcal nuclease and spleen phosphodiesterase . anion exchange chromatography was applied for 7-methylguanine measurements in white blood cell dna of healthy nonsmokers ( n = 17 ) and patients ( n = 4 ) treated with the methylating drugs procarbazine and decarbazine . we found that the mean level of 7-methylguanine residues in nonsmokers was 2.5 per 10(7 ) nucleotides . the corresponding level in the patient samples immediately after the drug treatment was 57 per 10(7 ) nucleotides.imagesfigure 2 .

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written informed consent was obtained from the patient for publication of this case report and accompanying images . a copy of the written consent is available for review by the editor - in - chief of this journal on request . lumbar hernias are rare and good history and general physical examination can rule out most of the differential diagnosis.ct scan should be done as routine prior to planning surgical approach unless patient is in life threatening emergency situation.even though the data available for us regarding the management of lumber hernias are limited current literature suggests laparoscopic approach is the best method of treatment.open surgery should be reserved for patients who have very large defects or failed laparoscopic approach.the operative technique should be decided on the size of the hernia , location , contents , etiology , recurrence and availability of facilities and expertise of the hospital . lumbar hernias are rare and good history and general physical examination can rule out most of the differential diagnosis . ct scan should be done as routine prior to planning surgical approach unless patient is in life threatening emergency situation . even though the data available for us regarding the management of lumber hernias are limited current literature open surgery should be reserved for patients who have very large defects or failed laparoscopic approach . the operative technique should be decided on the size of the hernia , location , contents , etiology , recurrence and availability of facilities and expertise of the hospital .

lumbar hernias are uncommon and about 300 cases have been reported till date . they commonly occur due to trauma , surgery and infection . they are increasingly being reported after motor vehicle collision injuries . however , spontaneous lumbar hernias are rare and are reported infrequently . it is treated with different surgical approaches and methods . we report a case of primary spontaneous lumbar hernia which was repaired by transperitonial laparoscopic approach using vypro ( polypropylene / polyglactin ) mesh and covered with a peritoneal flap .

Conflict of interest Funding Ethical approval Author contributions Key learning points

asbestos and silica are well - known fibrogenic dusts . however , there is no comprehensive understanding of the molecular and cellular events that lead to fibrosis as a consequence of asbestos or silica inhalation . previous studies have shown that asbestos stimulates superoxide anion production in alveolar macrophages through the phospholipase c / protein kinase c pathway . in contrast , silica does not appear to activate this pathway nor stimulate superoxide anion production , but silica does stimulate cytokine release by some undetermined pathway . therefore , using human alveolar macrophages isolated from normal healthy volunteers , we evaluated the potential involvement of intracellular calcium and tyrosine kinases as potential signal transduction pathways . in the absence of serum , crystalline silica , and to a lesser extent amorphous silica , caused a rapid and dose - dependent elevation of intracellular calcium coming from the extracellular space . however , in the presence of serum , which is required for silica - stimulated cytokine release , neither form of silica caused noticeable elevation of intracellular calcium . silica , however , did increase the extent of tyrosine phosphorylation , most notably of proteins at approximately 46 and 50 kda , suggesting activation of a tyrosine kinase pathway . preincubation of alveolar macrophages for 24 hr with silica - primed human alveolar macrophages for enhanced interleukin-1 beta ( il-1 beta ) release stimulated by endotoxin ( lps ) that was dose dependent . the enhanced lps - stimulated release of il-1 beta correlated with enhanced mitogen - activated protein kinase activity . taken together , these results indicate that a tyrosine kinase pathway is activated during silica stimulation of human alveolar macrophages.imagesfigure 4 . afigure 4 . b

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the purpose of this study was to investigate the efficacy and safety of fixed dose combination ( fdc ) of olanzapine 5 mg and fluoxetine 20 mg in indian patients with severe or treatment resistant depression . this was an open , non - comparative study of seven weeks duration with an initial placebo run in period of one week . one hundred and forty - four patients completed the study as per protocol and 151 patients were safety evaluable . one hundred and eleven patients ( 77% ) received one tablet of fdc of olanzapine 5 mg / fluoxetine 20 mg once daily for 6 weeks , in patients ( 14% ) , the dose was stepped up at the end of 2 weeks to 2 tablets of fdc of olanzapine 5 mg/ fluoxetine 20 mg once daily for a further 4 weeks and 13 patients ( 9% ) required dose to be stepped up at the end of 4 weeks to 3 tablets of fdc of olanzapine 5 mg and fluoxetine 20 mg once daily for last 2 weeks . one hundred and thirty four patients ( 93% ) responded to fdc of olanzapine and fluoxetine therapy ( a responder was defined as a patient with 50 % reduction over baseline in hdrs total score at the end of therapy).statistically significant ( p < 0.0001 ) reductions in hdrs total score , madrs total score and cgi severity scores were seen with olanzapine/ fluoxetine combination . one hundred and four patients ( 72% ) were remitters ( hdrs total score of < 7 ) after 6 weeks of therapy . treatment with fdc of olanzapine 5 mg / fluoxetine 20 mg was highly effective and well tolerated in indian patients with severe or treatment resistant depression .

objective : the purpose of this study was to investigate the efficacy and safety of fixed dose combination ( fdc ) of olanzapine 5 mg and fluoxetine 20 mg in indian patients with severe or treatment resistant depression.design : this was an open , non - comparative study of seven weeks duration with an initial placebo run in period of one week.method : one hundred and fifty three patients were enrolled . one hundred and forty - four patients completed the study as per protocol and 151 patients were safety evaluable . one hundred and eleven patients ( 77% ) received one tablet of fdc of olanzapine 5 mg / fluoxetine 20 mg once daily for 6 weeks , in patients ( 14% ) , the dose was stepped up at the end of 2 weeks to 2 tablets of fdc of olanzapine 5 mg/ fluoxetine 20 mg once daily for a further 4 weeks and 13 patients ( 9% ) required dose to be stepped up at the end of 4 weeks to 3 tablets of fdc of olanzapine 5 mg and fluoxetine 20 mg once daily for last 2 weeks . results : one hundred and thirty four patients ( 93% ) responded to fdc of olanzapine and fluoxetine therapy ( a responder was defined as a patient with 50 % reduction over baseline in hdrs total score at the end of therapy).statistically significant ( p < 0.0001 ) reductions in hdrs total score , madrs total score and cgi severity scores were seen with olanzapine/ fluoxetine combination . one hundred and four patients ( 72% ) were remitters ( hdrs total score of < 7 ) after 6 weeks of therapy.adverse experiences were reported by thirty one patients ( 20.5% ) . majority of them were mild in intensity . no serious adverse event was recorded with study therapy . three patients were withdrawn from the therapy due to adverse event.conclusion : treatment with fdc of olanzapine 5 mg / fluoxetine 20 mg was highly effective and well tolerated in indian patients with severe or treatment resistant depression .

Objective : Design : Method : Results : Conclusion :

concentrations of ambient pm2.5 ( particulate matter < 2.5 microm in aerodynamic diameter ) were associated with increased mortality in two prospective cohort studies . in this paper , i assess whether the weight of the evidence supports a causal association . i assumed the study population in each city to have the same exposure ; therefore , these are ecologic studies because exposure is at the group level . health outcome and confounding data are at the individual level . ambient pm concentrations are inadequate surrogates for personal exposure because they are at the group level and comprise only a small proportion of personal exposure , they change over time , and they constitute only a small proportion of a life span . the strength of association and exposure - response relationships can not be determined because the ecologic group - level risks of pm2.5 are overestimated 150- to 300-fold based on an analogy with individual - level exposure to inhaled cigarette smoke . risk estimates may also be high because of confounding from factors such as physical activity and lung function . the evidence is not coherent because the stronger associations are expected to be with morbidity , but instead are with mortality . for example , pm2.5 was associated with mortality but not with measurable reductions in lung function . biological plausibility is lacking because lifetime exposure of rats to combustion products at concentrations two to three orders of magnitude higher than air pollution levels cause lung overloading but no consistent reduction in survival . criteria for quantitative risk assessment are not met so the data are not useful for setting air quality standards . the weight of evidence suggests there is no substantive basis for concluding that a cause - effect relationship exists between long - term ambient pm2.5 and increased mortality.imagesfigure 1figure 2figure 3figure 4figure 5

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beryllium was released into the air from routine operations and three accidental fires at the rocky flats plant ( rfp ) in colorado from 1958 to 1989 . we evaluated environmental monitoring data and developed estimates of airborne concentrations and their uncertainties and calculated lifetime cancer risks and risks of chronic beryllium disease to hypothetical receptors . this article discusses exposure - response relationships for lung cancer and chronic beryllium disease . we assigned a distribution to cancer slope factor values based on the relative risk estimates from an occupational epidemiologic study used by the u.s . environmental protection agency ( epa ) to determine the slope factors . we used the regional atmospheric transport code for hanford emission tracking atmospheric transport model for exposure calculations because it is particularly well suited for long - term annual - average dispersion estimates and it incorporates spatially varying meteorologic and environmental parameters . we accounted for model prediction uncertainty by using several multiplicative stochastic correction factors that accounted for uncertainty in the dispersion estimate , the meteorology , deposition , and plume depletion . we used monte carlo techniques to propagate model prediction uncertainty through to the final risk calculations . we developed nine exposure scenarios of hypothetical but typical residents of the rfp area to consider the lifestyle , time spent outdoors , location , age , and sex of people who may have been exposed . we determined geometric mean incremental lifetime cancer incidence risk estimates for beryllium inhalation for each scenario . the risk estimates were < 10(-6 ) . predicted air concentrations were well below the current reference concentration derived by the epa for beryllium sensitization.imagesfigure 1figure 2figure 3figure 4figure 5figure 6

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as a scientist , administrator , and diplomat , david p. rall pioneered the effort to identify and understand the elements that make up the human environment and their consequences for human health . as an intellectual and aggressive activist , he educated scientists , governments , and the world community to the critical need to address the existence of environmental agents and their consequences for human health . as a leader he marshalled some of the best minds and hearts of his time to the cause of world health through a safe and clean environment . and as a visionary he provided the goals of environmental health science and the direction to guide both current and future generations . his death on september 28 brought to a close a chapter in the evolution of our understanding of the interconnectedness of human health and the environment , a chapter he was largely responsible for writing.imagespa538-a

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in order to select dna fragments of interest to be purified , these should be resolved in agarose or acrylamide gels gel stained with ethidium bromide by electrophoresis using 0.5x tbe buffer ( tris borate , edta ) at 120 volts for 1 hour . for this , ~ 700 ng of plasmid pproex - gdmre11s ( 6000-bp ) previously digested with ndei and hindiii was used to release a 900-bp fragment ( 560 ng of plasmid and 84 ng of fragment ) . the electroeluter tank ( figure 1 ) should be filled with 0.5x tbe equally distributed in each side of the mid plateau taking care of not spill it onto the mid plateau . the selected band ( or bands ) is cut out of the gel , and placed in sample chamber as close as possible to the v channel ( one slice per well ) . running buffer should be added to each chamber ; just enough to cover the gel slice . each v channel used must be flushed with a pasteur pipette to eliminate any air bubble trapped . then 100 ul of 10 m nh4 acetate ( to facilitate visualization a small amount of bromophenol blue is added , just enough to color it ) are gently added inside the v channel . the lid should be closed gently to prevent any resuspension of the high salt cushion . when electrolution is completed , 400 ul are removed from v - channel , and placed in a microfuge tube to be precipitated with 2 volumes of cold ethanol and glycogen ( recommended to improve dna recovery ) at 4 c for 1 hour or overnight . the recovery obtained was 75% ( 63 ng recovered when 84 ng were placed on the v - channel ) . anod an cathode are indicated on each side of tank , dna contained in gel sliced ( illustrated as a black square ) will migrate towards cathode due to its negative charge . then it will be trapped in the salt cushion ( represented as an inverted black triangle ) located in the v - channel . the duration of the run will depend highly on the size of the fragments , normally for fragments up to 20 kb 50 minutes to 1 hour is enough , while for small fragments uv light monitoring every 10 minutes is required to prevent the fragment to go through the salt cushion and consequently to the anodal buffer chamber decreasing recovery . it is important to make sure that when you set your power supply at 100 volts , there is a current at least of 10 mamp . the dna band can be monitored by using a uv - hand lamp and detect when this abandons the gel slice . this procedure allows the purification of dna or rna fragments of different sizes with good recovery ( ~80% ) to be radiolabeled , digested by restriction enzymes , processed by modifying enzymes , etc .

purified dna fragments are used for different purposes in molecular biology and they can be prepared by several procedures . most of them require a previous electrophoresis of the dna fragments in order to separate the band of interest . then , this band is excised out from an agarose or acrylamide gel and purified by using either : binding and elution from glass or silica particles , deae - cellulose membranes , " crush and soak method " , electroelution or very often expensive commercial purification kits . thus , selecting a method will depend mostly of what is available in the laboratory . the electroelution procedure allows one to purify very clean dna to be used in a large number of applications ( sequencing , radiolabeling , enzymatic restriction , enzymatic modification , cloning etc ) . this procedure consists in placing dna band - containing agarose or acrylamide slices into sample wells of the electroeluter , then applying current will make the dna fragment to leave the agarose and thus be trapped in a cushion salt to be recovered later by ethanol precipitation .

Protocol Discussion Disclosures

a 70 year old woman first visited our clinic for right hand bradykinesia and gait disturbance unresponsive to levodopa treatment . at age 67 , she started to feel clumsiness in her right hand and to walk with very short stride and festination . her gait disturbance rapidly worsened until she was unable to walk without assistance after two years . at age 69 , she was diagnosed with pd and started to take levodopa . at age 70 , she took 450 mg of levodopa by regular levodopa / carbidopa , 150 mg by controlled release form of levodopa / carbidopa , 6 mg of ropinirole , and 200 mg of amantadine per day , but felt no clinical improvement . her verbal output was markedly reduced , and she could speak only simple words . on neurological examination , she showed masked face and no rest tremor . muscle tone was moderately elevated in her right limbs and mildly in the left limbs . she could not perform hand rolling , finger tapping , and foot tapping movements with her right limbs . deep tendon reflexes were normoactive . the stimulus sensitive jerks and ideomotor apraxia were observed in her right hand . a t2-weighted brain magnetic resonance imaging ( mri ) study showed diffuse cortical atrophy which was prominent in the left fronto - tempo - parietal cortex , and moderate degree of hypersignal intensities in diffuse subcortical white matter . an [ f]-deoxyglucose positron emission tomography study showed severe hypometabolism in left fronto - temporo - parietal cortex , striatum and thalamus ( figure 1 ) . because there was no response to levodopa treatment , we started to taper off anti - parkinsonian medications . three days after abrupt discontinuation of ropinirole , amantadine , and controlled release form of levodopa except regular levodopa / carbidopa , she developed severe dysphagia and dyspnea . serum ck level was 10,632 iu / l and urine myoglobin level was 2,881 ng / ml . the dosage of levodopa was increased to 750 mg per day and antibiotics treatment was started . during the course of following seven days , body temperature and serum ck level slowly returned to the normal level . the pd patients with longer disease duration , higher motor severity and motor fluctuation are likely to develop nms after abrupt reduction of anti - parkinsonian medications.3 abrupt deterioration of dopaminergic transmission is suggested to be a common pathophysiological mechanism of nms.2,4 however , the nms can occur in atypical parkinsonisms , including progressive supranuclear palsy , multiple system atrophy , and cbd , which accompany the pathology in postsynaptic striatal neurons and poor levodopa responsiveness.2,5 these suggest that peripheral mechanism or the alteration of neurotransmitters other than dopamine may also be involved in the pathogenesis of nms.2,4 in this patient , both reduction of levodopa dosage and concurrent infection might precipitate nms . therefore , prevention of infection , a common complication of parkinson - plus syndromes , is necessary to prevent nms . additionally , dose reduction or withdrawal of anti - parkinsonian medications should be carefully performed even in the patients with cbd who are expected to be unresponsive to levodopa treatment .

parkinson s disease is a principal underlying disease of neuroleptic malignant syndrome ( nms ) occurring in parkinsonian disorders , but nms may occur in patients with progressive supranuclear palsy and multiple system atrophy . we report first patient with corticobasal degeneration ( cbd ) who developed nms after abrupt reduction of antiparkinsonian medication and concurrent infection . it should be kept in mind that the prevention of infectious illness , which is common complication in parkinson - plus syndrome , is important , and dose reduction or withdrawal of anti - parkinsonian medications should be carefully performed even in the patients with cbd who are expected to be unresponsive to levodopa treatment .

Case Discussion

kawasaki disease ( kd ) is an acute systemic vasculitis of unknown cause that occurs primarily in children and rarely in adults . in the absence of specific laboratory tests , we report an unusual case of an elderly man with several unique features of incomplete kd . a 75-year - old white man was admitted to our hospital for a 3-week history of fever and poor general condition . his past medical history included hypertension , hyperlipidemia , myocardial infarction , and a coronary artery bypass graft surgery 2 years ago . the patient was febrile ( 39c ) , and physical examination revealed bilateral nonpurulent conjunctivitis , red and cracked lips ( fig . 1 ) , and slightly edematous erythema with desquamation of the hands and feet ( fig . laboratory tests revealed anemia ( hemoglobin 8.5 g / dl ) , hypoalbuminemia ( 2.6 g / dl ) , elevated erythrocyte sedimentation rate ( esr ) and c - reactive protein ( crp ) ( 83 mm / h and 100.3 mg / l , respectively ) , elevated alanine aminotransferase ( 56 iu / l ; normal < 40 ) , and sterile leukocyturia ( 30 cells/l ) . serological assays for human immunodeficiency virus , hepatotropic viruses , epstein - barr virus , cytomegalovirus , and antinuclear antibodies were negative . the patient was subsequently treated with an intravenous immunoglobulin infusion ( 1 g / kg for 2 days ) and high - dose aspirin ( 3 g / day ) . the fever remitted within 3 days , and within 1 week , the laboratory abnormalities returned to normal and mucocutaneous lesions improved dramatically . low - dose aspirin , which the patient had taken since his bypass surgery , was then restarted . kd is defined as the presence of a fever for 5 days and 4 of the 5 major clinical features : conjunctivitis , oral mucosal changes , polymorphous rash , palmoplantar erythema with desquamation , and cervical lymphadenopathy . incomplete kd refers to patients who do not fulfill the classic criteria of 4 of the 5 findings and in whom alternative diagnoses have been ruled out . in adults , the main differential diagnoses the higher prevalence of coronary artery lesions in patients with incomplete kd reflects difficulties in diagnosis and delays in treatment . although adults are less frequently affected by coronary aneurysms compared with children ( 5 vs. 20% , respectively ) , establishing the diagnosis of incomplete kd and initiating treatment is essential . in 2004 , a multidisciplinary committee of experts proposed an algorithm to diagnose incomplete kd in children . for pediatric patients with a fever for 5 days and < 4 classical criteria of kd , laboratory tests , including crp and esr , should be obtained . in patients with elevated crp ( 30 mg / l ) and/or esr ( 40 mm / h ) levels who fulfill 3 supplemental laboratory criteria [ including albumin 3.0 g / dl , anemia , elevation of alanine aminotransferase , 450,000/mm platelets after 7 days , white blood count 15,000/mm , and sterile pyuria ( 10 cells / high - power field ) ] , intravenous immunoglobulin and aspirin should be instituted and echocardiography should be performed . our case emphasizes the importance of considering kd at any age , even among elderly individuals . this case also highlights the usefulness of the algorithm proposed for children to diagnose incomplete kd in adults .

kawasaki disease ( kd ) is a systemic vasculitis of unknown etiology , affecting predominantly young children . here , we describe an unusual case of a 75-year - old man with several unique features of incomplete kd . healthcare professionals should therefore be aware of the importance of considering kd at any age , even among elderly individuals . this case also highlights the usefulness of the algorithm proposed for children to diagnose incomplete kd in adults .

Introduction Case Presentation Discussion Disclosure Statement

estimates were made of the proportion of chemicals that were carcinogenic , anticarcinogenic , or either in 397 long - term bioassays conducted by the national toxicology program ( ntp ) . the estimates were obtained from the global pattern of p - values obtained from statistical tests applied to individual experiments . these tests accounted for multiple comparisons using a randomization procedure and were found to operate at the correct level of significance . representative estimates of the proportion of carcinogens [ with 90% confidence intervals ( ci ) ] compared to the ntp estimates were as follows : male mice , 0.32 ( ci , 0.19 - 0.44 ) , ntp = 0.29 ; female mice , 0 . 28 ( ci , 0.15 - 0.41 ) , ntp = 0.34 ; male rats , 0.35 ( ci , 0.23 - 0.47 ) , ntp = 0.36 ; female rats , 0.34 ( ci , 0.21 - 0.46 ) , ntp = 0.28 ; all sexes and species , 0.59 ( ci , 0.49 - 0.69 ) , ntp = 0.51 . representative estimates of the proportion of anticarcinogens were as follows : male mice , 0 . 34 ; female mice , 0.27 ; male rats , 0.40 ; female rats , 0.44 ; all sexes and species , 0.66 . thus , there was as much or more evidence in this study for anticarcinogenesis as carcinogenesis . even though the estimators used were negatively biased , it was estimated that 85% of the chemicals were either carcinogenic or anticarcinogenic at some site in some sex - species group . this suggests that most chemicals given at high enough doses will cause some sort of perturbation in tumor rates.imagesfigure 1figure 2figure 3figure 4figure 5

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maintaining the microsurgical field , free from flooding with irrigation fluid , is important to get good vessel approximation in microsurgery . the commonly followed practice is to keep dry gauze at the periphery of the field so as to siphon off the excessive fluid . a certain amount of the irrigation fluid still remains in the field and causes adhesion of the suture material with the anastomotic clamp or the background material or to the vessel wall and thereby frustrating the surgeon while applying the microknots . we present our technique that avoids the aforementioned , and in addition provides a good platform to perform microvascular anastomosis . this is folded over a dry gauze and then fenestrations are made in the surface and on the two margins [ figure 1 ] of the glove component so as to provide for continuous drainage of the irrigation fluid to the gauze . the tip of the infant feeding tube ( size 4 ) is then passed in to the gauze [ figure 2 ] and the whole assembly is then placed in the microsurgical field deep to the vessels to be anastomosed and thus provides a platform for the microanastomosis . the vessels to be anastomosed are laid over a background on the platform and then the proximal part of the feeding tube is connected to a suction system so as to provide continuous suctioning of the irrigation fluid that keeps the microsurgical field clean and dry and also by keeping away the tip of the feeding tube from the surgical field [ figure 3 ] . the wrist part of the glove with open ends and fenestrations on the surface to facilitate siphoning off of the irrigation fluid the tip of a size 4 infant feeding tube is passed between the layers of gauze the entire assembly is shifted to the neck for anastomosis forming a good platform for anastomosis . the proximal end of the infant feeding tube is connected to the suction tube the wrist part of the glove component has been described in the past to transfer the pedicle of the flap from the oral cavity to the neck for microanastomosis and in this report we present a technique in which the component can be used to keep the operative field clean and dry and also to provide a stable platform to perform a perfect microanastomosis . this is folded over a dry gauze and then fenestrations are made in the surface and on the two margins [ figure 1 ] of the glove component so as to provide for continuous drainage of the irrigation fluid to the gauze . the tip of the infant feeding tube ( size 4 ) is then passed in to the gauze [ figure 2 ] and the whole assembly is then placed in the microsurgical field deep to the vessels to be anastomosed and thus provides a platform for the microanastomosis . the vessels to be anastomosed are laid over a background on the platform and then the proximal part of the feeding tube is connected to a suction system so as to provide continuous suctioning of the irrigation fluid that keeps the microsurgical field clean and dry and also by keeping away the tip of the feeding tube from the surgical field [ figure 3 ] . the wrist part of the glove with open ends and fenestrations on the surface to facilitate siphoning off of the irrigation fluid the tip of a size 4 infant feeding tube is passed between the layers of gauze the entire assembly is shifted to the neck for anastomosis forming a good platform for anastomosis . the proximal end of the infant feeding tube is connected to the suction tube the wrist part of the glove component has been described in the past to transfer the pedicle of the flap from the oral cavity to the neck for microanastomosis and in this report we present a technique in which the component can be used to keep the operative field clean and dry and also to provide a stable platform to perform a perfect microanastomosis .

during microvascular anastomosis , it is important to maintain the microsurgical field irrigated yet dry so as to achieve a good view of the vessels for approximation . in this method , an infant feeding tube ( size 4 ) , with its tip sandwiched between layers of dry gauze and a surgical glove component placed in the anastomotic field and the other end connected to a suction apparatus , is used to maintain the microsurgical field free from flooding . it also has the additional advantage of providing a stable platform for microvascular anastomosis .

INTRODUCTION Technique

kerosene is refined oil belonging to the hydrocarbon group of compounds , obtained from crude petroleum . poisoning is due to inhalation of fumes or ingestion of small amounts accidentally ( children ) or most of the cases reported in the literature were self - inflicted with the intention of committing suicide which constitutes significant emergency admissions . a 34-year - old male patient presented to our out - patient department with a history of injecting about 5 ml of kerosene to his left hand at two sites following an argument with his family members 2 days prior to presentation , with an intention to commit suicide . after 2 days , the pain became intolerable leading to disturbed sleep , with multiple blisters and swelling of the left hand . no other significant medical history was noted . on examination , he was an alert middle - aged man , moderately built and nourished , and well oriented to time , place , and person . multiple vesicles and blisters were present over the left forearm and few over the dorsal aspect of the left hand . black discoloration extending from the hand up to the lower third of the arm was present . local rise of temperature and tenderness was present from the hand up to lower third of arm . refilling could not be elicited [ figures 1 and 2 ] . multiple vesicles and blisters black discoloration extending from the hand up to the lower third of the arm was present . patient was unable to flex the hand few vesicles , blisters , and erosions were present over the dorsal aspect of the left hand there were no other lesions . irritant contact dermatitis the patient was admitted to the ward ; intravenous ( iv ) amoxycillin with clavulinic acid , iv steroid , and iv fluids were started . iv or subcutaneous self - injections of commercial gasoline or kerosene with suicidal intent constitute extraordinary events in psychotic patients . the lethal dose of kerosene for a 70 kg adult is 100 ml . in 1977 , green first described a patient who survived a 3 ml iv injection of energine , a derivate of kerosene . this patient developed lethargy , drowsiness , and a sterile abscess at the injection site without other systemic effects . our patient had injected 5 ml of kerosene and developed lesions over the forearm , as described . neeld and vaziri each reported a case of iv injection of petroleum distillate that caused severe chemical pneumonitis . in both cases , pulmonary edema and hypoxemia developed , and in one , the patient suffered abrupt respiratory arrest immediately after injection . kosa reported an accidental iv injection of 10 ml of gasoline that resulted in a fatal outcome . the case strongly suggested that hydrocarbons , as low - viscosity chemical compounds , have a direct toxic effect on lung tissue , interfering with gas exchange and leading to liquid interstitial pulmonary edema and severe hypoxemia caused by impaired diffusion . other effects of hydrocarbon intoxication include acute renal damage with oliguria , hepatocellular damage , intracellular hemolysis , gastric ulcers , and cardiac toxicity with negative inotropism . a case of self - inflicted acute necrotizing fasciitis with compromised venous return secondary to injection of kerosene was reported . a study on the clinical findings and outcome in suicide attempts by iv injection of kerosene among iv drug abusers was done in iran . although kerosene is a easily available refined oil as it is used for household purposes , poisoning occurs by inhaling fumes and ingestion accidentally in children and with the intention of committing suicide in adults . kerosene injection can produce severe tissue damage , especially if prompt surgical treatment is delayed . therefore , it is important to initiate active and immediate surgical intervention in the form of complete multiple fasciotomies , incision , and surgical excision of non - viable tissue . it should also be followed by active and repeated aggressive wound debridement until healthy granulation tissue is formed .

kerosene is refined oil belonging to the hydrocarbon group of compounds , available for domestic use in developing countries . poisoning is due to inhalation , ingestion . kerosene . we report a rare case of attempted suicide by means of intravenous injection of kerosene . it has a devastating effect and it is important to initiate active and immediate surgical intervention . psychotherapy should also be an integral part of the management .

INTRODUCTION CASE REPORT DISCUSSION CONCLUSION

a 16-year - old boy visited to our neurology clinic with a 12-month history of a clicking noise in the both ears and palatal discomfort . the clicking resembled the sound of snapping fingernails and was externally audible at a distance of 50 cm . he denied any voluntary control over this movement as well as any sensation of urge before the movement . he complained of throat fullness in daytime . on neurologic and otolaryngologic examination , rhythmic contraction of whole soft palate muscles the movement was able to be suppressed for a few seconds by touching the back of his neck , but it could soon return after the voluntary suppression . in addition , the entrainment at each slow and fast finger tapping with external pace was found ( video ) . needle electromyography ( emg ) of tvp muscle showed rhythmic contractions with a frequency of 2.6 hz with amplitude of 150 v ( figure 1 ) . there were no abnormal results in other laboratory , audiologic tests , and brain magnetic resonance imaging . after diagnosis of ept , despite of medications including benzodiazepines , muscle relaxants , and anticonvulsants for 1 month , his symptoms were not changed at all . therefore , we started to inject 15 units of bta ( botox , allergan , inc . , though the success of the first bta therapy was lasted about 10 weeks , the additional injections of bta were needed for 3 times due to recurrence . the dosage of bta was finally elevated to 20 units and there were 4 times injection of bta at interval of 3 months , but the presenting symptoms showed again . his involuntary movements were clinically closed to ept because of ear click perceived as objective tinnitus , bilateral involvement , no brain lesions and involvement of tvp muscle by emg . although no single clinical finding is pathognomonic for pmds , several features are quite helpful.10 in general , pmds are characterized by distractibility , entrainment , coactivation sign , variable frequency , amplitude and direction , increase with attention , and poor response to medications.8,11 this patient also showed entrainment of soft palate muscle contraction to external paced finger tapping . furthermore , pmds have particular histories including precipitating factor or trivial trauma preceding acute onset , emotional trigger , psychological stressors and psychiatric comorbidities such as anxiety disorders.8 in this patient , mild trauma ( e.g .. voice abuse ) before onset suggest to psychogenic type of ept rather than primary type . in our case , the only difference from usual psychogenic pt is that this abnormal movement was not well responded to treatment . psychogenic pt is usually reported to have good response to non - physiological treatment or placebo.8 in summary , bilateral objective tinnitus , bilateral tvp muscles involvement , mild trauma before onset , and entrainment of soft palate contraction suggest a psychogenic ept .

essential palatal tremor ( ept ) is a rare disorder which shows rhythmic involuntary movement of the muscles of soft palate , especially tensor veli palatini muscle . ept is classified by two subtypes , which is primary and secondary ept . secondary ept includes psychogenic type . we describe a case of intractable psychogenic ept .

Case Discussion Legend to the Video

the list is based on the data available at genomenet web site http://www.genome.jp/. click here for additional data file .

carbonic anhydrase ( ca ) ( e.c . 4.2.1.1 ) is a ubiquitous enzyme catalysing interconversion between co2 and bicarbonate . the irregular distribution of the phylogenetically distinct classes of ca in procaryotic genome suggests its complex evolutionary history in procaryotes . genetic evidence regarding the dispensability of ca under high - co2 air in some model organisms indicates that ca - deficient microorganisms can persist in the natural environment by choosing high - co2 niches . in this study , we studied the distribution of ca in the genome of proteobacteria . while a large majority of the genome - sequenced proteobacteria retained a ca gene(s ) , intracellular bacterial genera such as buchnera and rickettsia contained ca - defective strains . comparison between ca - retaining and ca- deficient genomes showed the absence of whole coding sequence in some strains and the presence of frameshifted coding sequence in other strains . the evidence suggests that ca is inactivated and lost in some proteobacteria during the course of evolution based on its dispensability .

Supplementary Material

the effects of inhaled zinc oxide / hexachloroethane smoke ( 11,580 mg x min / m3 ) and intratracheally instilled zinc chloride ( 2.5 mg / kg body weight ) have been studied in rat lung . the effects of subsequent treatment with 70% oxygen have been studied after both procedures . both the inhalation of the smoke and instillation of zinc chloride produced similar effects that included pulmonary edema , alveolitis and , at a later stage , some fibrosis . after zinc chloride instillation , the pathological changes largely spared the periphery of the lung , while following smoke inhalation they were more diffuse . subsequent oxygen administration had little effect on the development or progression of the pathological changes.imagesfigure 5.figure 6.figure 7.figure 8 .

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a 54 year - old - man , presented with multiple , small , well- defined , gray - brown , papules and small papillomatous patches located on his penis , which had appeared over the last year ( figure 1 ) . genital warts , lichen planus , a verrucous nevus and bp were suspected among our clinical diagnosis . the dermoscopy revealed a pigmented papillomatous surface , brown - gray dots arranged in a linear distribution at the periphery of the lesion , and widespread dotted vessels ( figures 2 and 3 ) . a biopsy was done , and the histology showed mild hyperkeratosis , irregular acanthosis , dyskeratosis , cytological atypia and mitosis ( figures 4 and 5 ) , consistent with the diagnosis of bp . a 31-year - old male patient with no relevant medical history presented with gray - brown asymptomatic small papules on his penis that had appeared a few months before ( figure 6 ) . the dermoscopy revealed multiple areas with grey - brown dots aligned in a linear fashion and a keratotic surface . a 54 year - old - man , presented with multiple , small , well- defined , gray - brown , papules and small papillomatous patches located on his penis , which had appeared over the last year ( figure 1 ) . genital warts , lichen planus , a verrucous nevus and bp were suspected among our clinical diagnosis . the dermoscopy revealed a pigmented papillomatous surface , brown - gray dots arranged in a linear distribution at the periphery of the lesion , and widespread dotted vessels ( figures 2 and 3 ) . a biopsy was done , and the histology showed mild hyperkeratosis , irregular acanthosis , dyskeratosis , cytological atypia and mitosis ( figures 4 and 5 ) , consistent with the diagnosis of bp . a 31-year - old male patient with no relevant medical history presented with gray - brown asymptomatic small papules on his penis that had appeared a few months before ( figure 6 ) . the dermoscopy revealed multiple areas with grey - brown dots aligned in a linear fashion and a keratotic surface . the natural course of this disease is unpredictable : the lesions may increase , decrease , and even disappear spontaneously . although progression to an invasive scc is uncommon , it has been estimated in 2.6% of cases . the most important differential diagnoses are genital warts , both clinically and dermoscopically . to date and to our knowledge , no reports that specifically describe the dermoscopic findings of bp are available , and a few reports of dermoscopic examinations of this dermatosis have been published in the literature . dong et al . reported two cases of bp showing an unspecific pattern , and one of the lesions also showed dotted vessels and a keratotic surface as in our first case . in a study describing pigmented lesions of the vulva , ferrari et al . also presented 2 cases of bp : one lesion revealed brown to gray structureless areas and glomerular vessels in a clustered and linear arrangement ; the other lacked pigmentation and revealed multiple whitish - red exophytic papillary structures with central glomerular and hairpin vessels . the features of the two cases we presented were similar : brown - gray dots with a linear arrangement , located at the periphery of the lesion . these features remind us of pigmented bowen s disease , an in situ variant of cutaneous squamous cell carcinoma , which needs to be differentiated from bp at histopathological level . although more studies are needed to confirm these findings as criteria for bp , we think that in the presence of linear arrangement of brown - gray dots in a genital lesion , we should rule out bp among other diagnosis .

bowenoid papulosis ( bp ) corresponds to an in situ squamous cell carcinoma ( scc ) located in the anogenital region . it is related to hpv , and presents with gray - brown elevated papules or plaques . a biopsy is needed to confirm the diagnosis ; however , dermoscopy may be useful to differentiate this disease from other conditions , such as genital warts , seborrheic keratosis and lichen planus . in this paper we describe the dermoscopic findings in two patients with this disease .

Case report Case 1 Case 2 Discussion

however , the style of the application may induce both allergic and photoallergic contact dermatitis from the nsaids and their ingredients . we describe a case of allergic contact dermatitis with diffuse erythematous reaction caused by allergic sensitivity to a component , diisopropanolamine , of a compress used by the patient . an 87-year - old japanese man with dementia presented with a pruritic eruption following the use of compresses for lumbago . the patient had used the same compresses for three weeks . during the last ten days of use , pruritic eruptions appeared on the bilateral lower back and upper buttock where the compresses were being applied . then , diffuse erythema developed on the trunk and extremities . physical examination revealed rectangular - shaped , pruritic exudative erythematous macular lesions on the bilateral lower back and upper buttock and diffuse erythema on the chest , abdomen , back and extremities ( fig . a patch test ( international contact dermatitis research group criteria ; finn chambers on scanpor tape , epitest ltd . , tuusula , finland ) was performed with the compress ingredients and the japanese baseline series . the positive reactions at both 2 and 4 days after application were to diisopropanolamine 1% pet . , fragrance mix 8% pet . ( brial allergen gmbh , greven , germany ) , and mercuric chloride 0.05% aq . it is used in emulsifying agents for cosmetic lotions , neutralizers in cosmetics , and bath preparations . until now , eight cases of allergic contact dermatitis from diisopropanolamine , including the present case , have been described ( table 1 ) . we previously reported a case of diffuse erythematic reaction after using compresses . in the previous case , three concomitant sensitizations to diisopropanolamine , felbinac , and crotamiton supposedly caused a diffuse erythematic reaction . in the present case , a single sensitization to diisopropanolamine was associated with a diffuse erythema . thus , similar phenomena of allergic contact dermatitis with diffuse erythematous reaction may be caused by allergic sensitivity to a different component or different combinations of ingredients in the topical medicament . patch testing with full ingredients from the manufacturer is essential for detecting the sensitized allergens in each case .

compresses containing a nonsteroidal antiinflammatory drug ( nsaid ) are commonly used in japan . however , this treatment may induce both allergic and photoallergic contact dermatitis from the nsaids and their ingredients . here , we describe a case of allergic contact dermatitis with diffuse erythematous reaction due to diisopropanolamine in the applied compress . the absorption of diisopropanolamine might have been enhanced by the occlusive condition .

Introduction Case Report Discussion

torsion of uterine adnexa is an important cause of acute abdominal pain reported in the literature.1 however , isolated torsion of fimbrial cysts has rarely been described as a cause for acute abdomen.23 we report a rare case of isolated torsion of fimbrial cysts leading to acute abdomen . a 22-yr - old female presented to the hospital with acute abdomen , amenorrhea for a half month and a half , and spotting on and off . the patient provided written consent to reproduce information or photographs . on physical examination , the patient s vital signs were found to be normal . laboratory investigations including hemoglobin , total leucocyte count , differential leucocyte count , and routine and microscopic examination of the urine were found to be normal . therefore , a serum beta human chorionic gonadotropin ( hcg ) test was done to confirm pregnancy . however , serum beta hcg levels were within normal range . the ultrasound report showed a tubo - ovarian mass in the right adnexa along with fluid in the pouch of douglas , suggestive of fimbrial cysts or ectopic pregnancy ( fig . on laprotomy , multiple cystic structures attached to the fimbriae were seen , which were twisted at their pedicle . many of them had ruptured leading to collection of about 200 ml of straw colored fluid . however , the fallopian tubes and ovaries were normal on both the sides , so a cystectomy was done . multiple cystic structures varying in size from 3 3 cm to 2 2 cm were seen . the cystic structures were filled with yellow colored fluid and were twisted at the pedicle ( fig . 2 ) . histopathology showed ciliated , columnar cells with underlying stroma and few chronic inflammatory cells , and a diagnosis of fimbrial cysts was made ( fig . paraovarian cysts represent approximately 10% of adnexal masses.4 they are more common in childbearing women.5 paratubal cysts arise from mllerian or wolffian structures and are common in adult females . these are hormone sensitive and are generally asymptomatic.6 malignant neoplasms arising from paratubal cysts are very rare.7 rarely , they can be associated with torsion of fallopian tubes.7 other complications include hemorrhage , rupture , and infection.3 paratubal cysts are difficult to diagnose preoperatively , and even transvaginal ultrasound in older women has detected only about 44% of paratubal cysts preoperatively.8 in only 1 of 15 patients is the diagnosis of fimbrial cyst suspected before surgery.4 thus , acute abodomen is a rare presentation of fimbrial cysts , which needs to be considered in a female of reproductive age group . timely diagnosis and excision of these cysts may prevent the rare complications of torsion and rupture that are associated with them .

we present a case of a 22-year - old female who presented with acute abdomen and amenorrhea . emergency laprotomy was done with a clinical diagnosis of ectopic pregnancy . on laprotomy , twisted fimbrial cysts were found . thus , although fimbrial cysts are rarely twisted , they should be considered as a cause of acute abdomen in a female of reproductive age group .

Introduction Case Report Discussion

gender bias in different types of congenital defects is well know . a significant bias in sex ratio has been documented for congenital heart disease with several lesions occurring more frequently in males or in females.12 this difference may be related to differences in hormonal constitution . it has been proposed that foetal sex is partially determined by hormone levels of both parents around the time of conception has put forward35 but it is unclear whether such hormonal variations may also be responsible for sex - biasing of congenital anomalies . a literature search shows that transposition of the great arteries has been shown to have a gender bias ( table 1 ) but no explanation has been put forward in order to account for this observation . sex ratio of transposition of the great arteries in published reports in this study , we compare gender of patients with transposition with controls . in the general population , females tend to be smaller than male and in this study , we also attempt to relate gender ratios of patients with transposition with birth weight , maternal age and parental occupation . we evaluated 95 isolated livebirths with transposition of the great arteries cases referred to sicilian registry of congenital malformations from 1991 to 1998 , and compared these with a control group of 1000 consecutive newborns from the same geographic origin . all types of transposition of the great arteries were evaluated together and we excluded cases with other associated birth defects . we found a sex ratio ( male / female ) of 2.8 in transposition of the great arteries while the control group had a sex ratio of 1.04 . we did not find any statistical association between birth weights and gender bias in transposition of the great arteries and controls . stratification of our cases by gender and maternal age was not sigificant , with a mean maternal age of 29 years for both male and female cases of transposition of the great arteries ( p=1 ) . a statistically significant association both for maternal ( p=0.03 ) and paternal ( p=0.04 ) occupation related to agriculture was found for males with transposition , while none was found for affected females . moreover , in transposition of the great arteries , gender and birth weight are independent factors . hytten and leitch16 proposed that a high male sex ratio correlated with high maternal age , but james and rostron17 in a large sample of data found a decline in sex ratio of births at high maternal age . recently loffredo et al18 reported an association between transposition of the great arteries and maternal exposure to herbicides and rodenticides . . the aetiological agent / s may be chemicals used in agriculture that produce a hormonal disruptor effect . the results of the present study , despite the limitations attributable to the small number of sample and controls , suggest further studies on environmental agents and their possible teratogenic effect .

a significant bias in sex ratio has been documented for several congenital cardiac malformations . transposition of the great arteries has been associated with a such a bias but no explanation has been proposed for this bias . we evaluated 95 isolated livebirths with transposition of the great arteries cases referred to the sicilian registry of congenital malformations from 1991 to 1998 . we found a statistically significant male bias of 2.8 and this was significantly associated with both maternal and paternal occupational exposure to agricultural chemicals for male infants with transposition , but not for female infants . this study raises new questions about the possible role played by environmental chemicals in relationship to birth defects and to sex ratio imbalance .

Introduction Methods Results Discussion Conclusion Related link

we thank nih national institute of neurological disorders and stroke ( ninds ) r01ns085214 and fred hutchinson cancer research center ( fhcrc ) new development grant for financial support .

abstractcross - modal plasticity is a striking adaptive feature of the brain , whereby the loss of one sensory modality induces cortical reorganization that leads to enhanced sensory performance in remaining modalities . much is known about the macroscopic modifications in the brain that underly cross - modal plasticity and the associated changes in sensory performance . in contrast there is relatively scant information about the molecular and cellular underpinnings of this mechanism . we hypothesized that cross - modal plasticity is a fundamental feature of the nervous system . as such , it should be found in organisms with brains that are substantially less complex than our own . indeed , we discovered a cross - modal plasticity mechanism in the roundworm caenorhabditis elegans , whose nervous system is composed of only 302 neurons . taking advantage of the simplicity of the c. elegans nervous system , we were able to comprehensively study cross - modal plasticity from molecule through circuit to behavior .

Disclosure of potential conflicts of interest Funding

several randomized trials have demonstrated that breast - conserving surgery followed by radiation therapy , which is called breast - conserving therapy ( bct ) , is as effective as mastectomy and should be a standard treatment for early - stage breast cancer . recently , there has been an increase in reports of angiosarcoma ( as ) after bct [ 2 , 3 , 4 ] . lymphedema - associated cutaneous as , so - called stewart - treves syndrome , was first described in 1948 by stewart and treves . herein , we report a case of as which developed after bct and a case of stewart - treves syndrome with a focus on lymphedema . in 1997 , a 62-year - old woman underwent bct with 50 gy radiation for left - sided breast cancer , categorized as stage ia . she was started on weekly intravenous paclitaxel at a dose of 100 mg / m . in may 2009 , she presented with an erythematous purplish palpable mass on the right breast ( fig . a punch biopsy revealed the invasion of spindle - shaped cells with vascular differentiation into the subcutaneous tissue ( fig . each time , further wide excisions were performed . due to these local recurrences , at 85 cycles after the administration of weekly paclitaxel therapy , the patient was switched to monthly docetaxel at a dose of 70 mg / m . since then a 64-year - old woman was diagnosed with right - sided breast cancer that was categorized as stage ia . she received no adjuvant radiotherapy because she had already been treated with chemotherapy using a combination of paclitaxel and carboplatin for ovarian cancer . in november 2011 , the patient was admitted to our hospital for evaluation of purplish ecchymosed cutaneous lesions without a palpable mass on the right breast in the setting of chronic lymphedema ( fig . a punch biopsy revealed pleomorphic spindle - shaped cells with little vascular differentiation infiltrated into the dermis ( fig . the patient was started on monthly docetaxel at a dose of 75 mg / m . in 1997 , a 62-year - old woman underwent bct with 50 gy radiation for left - sided breast cancer , categorized as stage ia . she was started on weekly intravenous paclitaxel at a dose of 100 mg / m . in may 2009 , she presented with an erythematous purplish palpable mass on the right breast ( fig . a punch biopsy revealed the invasion of spindle - shaped cells with vascular differentiation into the subcutaneous tissue ( fig . each time , further wide excisions were performed . due to these local recurrences , at 85 cycles after the administration of weekly paclitaxel therapy , the patient was switched to monthly docetaxel at a dose of 70 mg / m . since then a 64-year - old woman was diagnosed with right - sided breast cancer that was categorized as stage ia . she received no adjuvant radiotherapy because she had already been treated with chemotherapy using a combination of paclitaxel and carboplatin for ovarian cancer . in november 2011 , the patient was admitted to our hospital for evaluation of purplish ecchymosed cutaneous lesions without a palpable mass on the right breast in the setting of chronic lymphedema ( fig . a punch biopsy revealed pleomorphic spindle - shaped cells with little vascular differentiation infiltrated into the dermis ( fig . the patient was started on monthly docetaxel at a dose of 75 mg / m . many studies have demonstrated that radiation may be a major risk factor in the development of as [ 2 , 3 , 4 ] . on the other hand , case 2 suggests that chronic lymphedema is the primary risk factor for as , which was first described in 1948 by stewart and treves . radiation therapy secondarily tends to induce the development of as , since radiation therapy induces fibrosis and proliferation of lymphatic vessels via cytokines such as vascular endothelial growth factor , which is followed by subclinical chronic edema . it is suggested that axillary lymph node dissection predisposes patients to the development of as , since it is closely associated with lymphedema . the increased use of bct is likely to lead to an increase in the number of patients with as . the prognosis of as after bct is poor , with a low 5-year overall survival ( 55% ) and a low disease - free survival at 5 years ( 35% ) . therefore , breast surgeons and radiologists should be aware of skin changes in order to improve the early detection of as during the follow - up of patients who have undergone bct , and especially those treated with axillary lymph node dissection .

several randomized trials have shown that breast - conserving therapy ( bct ) is as effective as mastectomy and should be a standard treatment for early - stage breast cancer . recently , there has been an increase in reports of angiosarcoma ( as ) after bct . herein , we report a case of as which developed after bct and a case of stewart - treves syndrome with a focus on lymphedema . chronic lymphedema is the primary risk factor for as , which was first described in 1948 by stewart and treves [ cancer 1948;1:6481 ] . radiation therapy secondarily tends to induce the development of as , since radiation therapy induces fibrosis and proliferation of lymphatic vessels via cytokines such as vascular endothelial growth factor , which is followed by subclinical chronic edema . it is suggested that axillary lymph node dissection predisposes patients to the development of as , since it is closely associated with lymphedema . breast surgeons and radiologists should be aware of skin changes in order to improve the early detection of as during the follow - up of patients who have undergone bct , and especially those treated with axillary lymph node dissection .

Introduction Case Report Case 1 Case 2 Discussion