To analyze whether gender influence survival results of kidney transplant grafts and patients.® 5.2 software, through the application of a random effects model. Recipient, donor, and donor-recipient gender comparisons were evaluated. Systematic review with meta-analysis of cohort studies available on Medline (PubMed), LILACS, CENTRAL, and Embase databases, including manual searching and in the grey literature. The selection of studies and the collection of data were conducted twice by independent reviewers, and disagreements were settled by a third reviewer. Graft and patient survival rates were evaluated as effectiveness measurements. Meta-analysis was conducted with the Review Manager : Twenty-nine studies involving 765,753 patients were included. Regarding graft survival, those from male donors were observed to have longer survival rates as compared to the ones from female donors, only regarding a 10-year follow-up period. Comparison between recipient genders was not found to have significant differences on any evaluated follow-up periods. In the evaluation between donor-recipient genders, male donor-male recipient transplants were favored in a statistically significant way. No statistically significant differences were observed in regards to patient survival for gender comparisons in all follow-up periods evaluated. The quantitative analysis of the studies suggests that donor or recipient genders, when evaluated isolatedly, do not influence patient or graft survival rates. However, the combination between donor-recipient genders may be a determining factor for graft survival. This review, by focusing on those gender-related differences in the clinical effectiveness of immunosuppressive therapies for kidney transplant maintenance, may promote better understanding, provide more efficient health care, contribute to the creation of clinical protocols, and promote better long-term results for patients.The objective of this review was to analyze whether genders influence patient and graft survival rates in kidney transplants.This review was conducted according to the recommendations from the Cochrane Collaboration Handbook.Observational cohort studies were selected. The selection included studies with patients who received kidney transplants from living or deceased donors for the first time or more than once, mentioning gender differences concerning pre-transplant characteristics, and finding survival results for grafts, patients, or for both. Studies that did not involve immunosuppressants for maintenance of kidney transplants, pharmacokinetic studies, economic evaluation studies, review studies, and studies conducted on animals were excluded, as per the exclusion criteria.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES – Coordination for the Improvement of Undergraduate Personnel), in Biblioteca Digital Brasileira de Teses e Dissertações , and in Universidade de São Paulo’s Digital Library of Theses and Dissertations. There were no restrictions regarding dates and languages of publications. An electronic search was performed for articles published until December 2013, on Medline (PubMed), Latin-American and Caribbean Center on Health Sciences Information (LILACS), Cochrane Controlled Trials Databases (CENTRAL), Embase databases. Manual searches were also conducted in the reference lists of all studies selected from the published systematic review.After duplicate studies were excluded, two independent reviewers selected the references in three phases: analysis of titles, abstracts, and full texts. The disagreements were settled by a third reviewer. The data – including methodological quality, subject information, treatment length, and patient and graft survival rates – were extracted and collected in duplicate in a Microsoft Excel 2010 spreadsheet.Methodological quality evaluations were independently conducted by the reviewers, and related disagreements were settled through the consensus among reviewers. Newcastle-Ottawa scaleIn order to be analyzed, the studies were grouped according to the comparison of results among:a)Donor genders – male donors (MD) and female donors (FD);b)Recipient genders – male recipients (MR) and female recipients (FR);c)Donor-recipient genders – male donor-male recipient transplants (MD-MR), male donor-female recipient transplants (MD-FR), female donor-female recipient transplants (FD-FR), female donor-male recipient transplants (FD-MR).The study data were combined using randomized effects model in Metaview module of Review Manager software, version 5.3. The results were presented as relative risk for dichotomous variables, with a confidence interval of 95%. Analyses with IThe outcomes that were evaluated in the meta-analysis were graft survival and patient survival per follow-up period .,A total of 5,993 publications were initially identified in the electronic databases, and seven through manual searches, all adding up to 6,000 publications. Of these, 500 publications were excluded because of the participant type, 5,251 due to study type and 177 due to the intervention. The main causes for excluded studies were: studies that did not analyze the outcome of interest , ones that did not include kidney transplants, review, pharmacokinetic, pharmacoeconomic studies, among others. After duplicate publications were eliminated and the reviewers conducted their analyses, 29 cohort studies were included, which involved 765.753 patients. Among those, six studies compared the measurements from results involving donor genders (MD and FD); eight studies, involving recipient genders (MR and FR), and for 20 others, results involving donor-recipient genders  . One stuOut of the 29 observational studies included, 28 were retrospective and one was prospective.,,,,,,,The majority of subjects  were males, for all gender comparisons. All studies included evaluated graft survival rates, but only eight of them evaluated patient survival rates.,Out of the 29 studies included, two of them were observed to have scores of six as per New-Castle Ottawa scale;-,,Out of the six studies included in the systematic review for donor gender comparison, five of them were included in the meta-analysis for graft survival outcome.2 = 70.0%), 1.03 , 1.02 , 0.89 , 0.86 , and 0.82 . Only at the 10-year follow-up period was the difference significant for graft survival, favoring male donors. Heterogeneity was high and significant for follow-up periods of one and three years , as grouped chronologically according to follow-up periods of one, two, three, five, and ten years were, respectively, 1.02 , 0.99 , 1.23 . No significant differences were found for any of the follow-up periods, and no recipient genders were highlighted among the groups. Heterogeneity was high and significant for follow-up periods of five and 10 years or more , as grouped chronologically according to follow-up periods of one, five, and 10 years or more were, respectively, 1.01   .versus FD-MR, MD-MR versus FD-FR, MD-MR versus MD-FR, MD-FR versus FD-FR, MD-FR versus FD-MR, FD-FR versus FD-MR. Regarding graft survival outcome, 13 studies were included,,,,-,,,-,In order to evaluate donor-recipient genders, six comparisons were analyzed: MD-MR ,,,,,,,The remaining studies were not found to have enough data for the quantitative analysis.The studies by Ellison et alversus FD-MR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1,03 , 1.05 , 1.06 , 1.15 , and 1.08 . The graft survival rate was significantly higher in all follow-up periods evaluated, and it favored MD-MR pair. Heterogeneity was high and significant for all periods, except for the two-year follow-up period. The patient survival analysis was only conducted for the one-year follow-up period, and no pairs were observed to be favored .In the MD-MR versus FD-FR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.02 , 1.02 , 1.05 , 1.02 , and 1.02 . The graft survival rate was significantly higher in follow-up periods of one, three, and five years, and it favored MD-MR pair. Heterogeneity only was not significant for the two-year follow-up period. The patient survival meta-analysis was observed to favor none of the pairs .In the MD-MR versus MD-FR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.01 , 1.01 , 1.03 , 1.00 , and 0.96 . The graft survival rate was only significantly higher for the one-year follow-up period, favoring the MD-MR pair. Heterogeneity only was not significant for the two-year follow-up period. The patient survival meta-analysis was observed to favor none of the pairs .In the MD-MR versus FD-FR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.01 , 1.01 , 1.01 , 1.01 , and 1.04 . The graft survival rate was significantly higher in follow-up periods of three and ten years, and it favored MD-FR pair. Heterogeneity only was not significant for the two and three-year follow-up periods. The patient survival meta-analysis was observed to favor none of the pairs .In the MD-FR versus FD-FR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.01 , 1.05 , 1.03 , 1.18 , and 1.10 . The graft survival rate was significantly higher for all follow-up periods, except for the one-year one, favoring MD-FR pair. Heterogeneity was high and significant for all periods, except for the two-year follow-up period. The patient survival meta-analysis was observed to favor none of the pairs .In the MD-FR versus FD-MR comparison, the RRs as grouped for graft survival in a chronological order of follow-up periods of one, two, three, five, and 10 years were, respectively, 1.01 , 1.03 , 1.01 , 1.14 , and 1.06 . There were no significant differences regarding graft survival considering all follow-up periods. Heterogeneity was high and significant for all periods, except for the three-year follow-up period. The patient survival meta-analysis was observed to favor none of the pairs .In the FD-FR This meta-analysis evaluated the influences of donor genders, recipient genders, and the donor-recipient combination in regards to kidney transplant patient and graft survival rates.,,,In the comparison between donor genders, 9,022 subjects were evaluated in the meta-analysis. Donor genders were not found to favor gender rates in the evaluation of one, two, three, five, and eight-year follow-up periods (p < 0.05). Ten-year follow-up period was the only observed to differ significantly, favoring male donors (p = 0.03). The study by MullerIn the comparison between recipient genders in all follow-up periods, 9,593 subjects were evaluated in the meta-analysis, and no significant differences were observed regarding graft survival. Patient survival analysis considered 747 patients. No significant differences were found among the studies. The study by Busson and Benoitversus FD-MR, MD-MR versus FD-FR, MD-MR versus MD-FR); that is, kidney transplants from male donors to male recipients were found to have the best graft survival rates. Nonetheless, FD-MR pair was found to have the worst results , except for the FD-MR versus FD-FR comparison. Those results are comparable with other reviews.,The comparison between donor-recipient genders included 471,252 patients. MD-MR pair should be highlighted for having been observed to have the best results in all comparisons , numbers of transplants, monitored periods, among others. Despite that, observational studies are observed to have the advantages of gathering a large number of patients and best representing the real world.Another limitation in the interpretation of results was the statistical heterogeneity among studies, which was found in the meta-analyses. The small number of studies included in the comparisons, and the lack of complete, accurate information in the studies made it difficult to account for heterogeneity sources. Most studies were not observed to include immunosuppressive therapies, ages (donors and recipients), or monitored periods. The sensitivity analysis, in which studies were included and excluded for each comparison, in general, has not altered the directions of outcomes, having changes of small relevance in heterogeneity values. It has not provided information on the possible causes for heterogeneity either.However, the results from this review can be considered for decision-making by medical teams responsible for transplants in the clinical practice, once it represents the best level of evidence regarding the topic.Gender incompatibilities must be avoided whenever possible. Genders must be considered as criteria in the choices regarding allocation of organs from donors and to recipients. Gender combinations may make a difference in survival rates. Nonetheless, that reality is utopic in the clinical practice, due to the scarcity of donors and the increase in the number of patients on waiting lists for transplants. A change in that scenario is required in order to improve the allocation of organs.In conclusion, recipient and donor genders, when evaluated isolatedly, do not influence patient or graft survival rates. However, combinations between donor-recipient genders may be a determining factor for graft survival, favoring MD-MR pair. ,,,,,,O transplante renal é considerado a melhor alternativa terapêutica para os portadores de doença renal crônica avançada.,A sobrevida após o transplante renal é maior entre as mulheres,Conhecer as diferenças entre gênero é necessário para identificar possíveis barreiras para obtenção dos resultados ideais e desenvolvimento de intervenções que as superem. Esta revisão, ao focalizar essas diferenças entre gênero na efetividade clínica da terapia imunossupressora de manutenção do transplante renal, poderá promover melhor compreensão, proporcionar cuidados à saúde mais eficientes, contribuir para a elaboração de protocolos clínicos e promover melhores resultados em longo prazo para os pacientes.O objetivo desta revisão foi analisar se gênero influencia a sobrevida de enxerto e paciente no transplante renal.Cochrane Collaboration Handbookv.Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA).Esta revisão foi realizada de acordo com as recomendações da Foram selecionados estudos observacionais, do tipo coorte, realizados em pacientes que receberam transplantes renais de doadores vivos ou cadáver, pela primeira vez ou por mais vezes, que abordaram as diferenças entre gênero relacionadas às características pré-transplantes e que apresentaram resultados de sobrevida do enxerto, do paciente ou de ambos. Os critérios de exclusão foram estudos não relacionados aos imunossupressores de manutenção do transplante renal, estudos farmacocinéticos, de avaliação econômica, de revisão e estudos realizados em animais.Cochrane Controlled Trials Databases , Embase. Também foi feita busca manual nas listas de referências de todos os estudos selecionados da revisão sistemática publicada.Foi realizada busca eletrônica de artigos publicados até dezembro de 2013 nas bases de dados Medline (PubMed), Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs), Excluídas todas as duplicações, dois revisores independentes selecionaram as referências, em três fases: análise de títulos, dos resumos e dos textos completos. As discordâncias foram resolvidas por um terceiro revisor. Os dados, incluindo qualidade metodológica, informações do participante, período de duração do tratamento e sobrevida do enxerto e do paciente, foram extraídos e coletados em duplicata em planilha do Microsoft Excel 2010.As avaliações da qualidade metodológica foram realizadas de forma independente por dois revisores e as divergências, por consenso. Foi utilizada a escala de Newcastle-OttawaPara serem analisados, os estudos foram agrupados de acordo com a comparação de resultados entre:a) Gênero de doador – doador masculino (DM) e doador feminino (DF);b) Gênero de receptor – receptor masculino (RM) e receptor feminino (RF);c) Gênero de doador-receptor – doador masculino-receptor masculino (DM-RM), doador masculino-receptor feminino (DM-RF), doador feminino-receptor feminino (DF-RF), doador feminino-receptor masculino (DF-RM).Metaview do softwareReview Manager versão 5.3. Os resultados foram apresentados por risco relativo para as variáveis dicotômicas com intervalo de confiança de 95%. Análises com I2 > 40,0% e p-valor do teste do Qui-quadrado < 0,10 foram consideradas como heterogeneidade significante. Análise de sensibilidade foi conduzida para investigar as causas da heterogeneidade, excluindo um estudo de cada vez e verificadas as mudanças nos valores de I2 e p.Os dados dos estudos foram combinados usando o modelo de efeitos randômicos no módulo Os desfechos avaliados na metanálise foram sobrevida do enxerto e sobrevida do paciente por tempo de seguimento .,Inicialmente foram identificadas 5.993 publicações nas bases eletrônicas e sete pela busca manual, totalizando 6.000 publicações. Foram excluídas 500 devido ao tipo do participante, 5.251 pelo tipo de estudo e 177 devido à intervenção. As principais causas das exclusões foram: estudos que não analisavam desfecho de interesse (sobrevida do enxerto e do paciente), que não contemplavam transplante renal, estudos de revisão, farmacocinéticos e farmacoeconômico, entre outros. Após a eliminação de duplicatas e análise pelos revisores, 29 estudos de coortes foram incluídos, envolvendo 765.753 pacientes. Desses, seis estudos compararam as medidas de resultados entre gênero de doador (DM e DF); oito estudos entre gênero de receptor (RM e RF); e 20 entre combinações de gênero de doador-receptor  . Foram iDos 29 estudos observacionais incluídos, 28 eram retrospectivos e um prospectivo.,,,,,,,Para todas as comparações entre gênero, a maioria dos participantes dos estudos  era do sexo masculino. Todos os estudos incluídos avaliaram sobrevida do enxerto, mas apenas oito avaliaram sobrevida do paciente.,Dos 29 estudos incluídos, dois obtiveram a pontuação seis na escala de New-Castle Ottawa;-,,Dos seis estudos incluídos na revisão sistemática para a comparação de gênero do doador, cinco foram incluídos na metanálise para o desfecho sobrevida do enxerto.2 = 70,0%), 1,03 , 1,02 , 0,89 , 0,86  e 0,82 . Apenas aos 10 anos de acompanhamento a diferença foi significativa para sobrevida do enxerto, favorecendo doadores do gênero masculino. A heterogeneidade foi alta e significante para os tempos de acompanhamento de um e três anos  agrupados em ordem por tempo de acompanhamento de um, dois, três, cinco, oito e 10 anos foram, respectivamente, 1,02 .Dos oito estudos incluídos na revisão sistemática para a comparação de gênero do receptor, seis foram incluídos na metanálise para o desfecho sobrevida do enxerto.35 (1989) comparou-se a influência da terapia imunossupressora sobre o gênero, dividido em dois grupos: Sánchez Garcia et alNa metanálise referente à sobrevida do enxerto para um ano foram incluídas quatro comparações de três estudos. No estudo de Sánchez Garcia et al,2 = 0%), 0,99 , 1,23 . Não houve diferença significante em nenhum dos tempos de acompanhamento, sem favorecimento para o gênero de receptor entre os grupos. A heterogeneidade foi alta e significante para cinco e 10 ou mais anos de acompanhamento   .versus DF-RM, DM-RM versus DF-RF, DM-RM versus DM-RF, DM-RF versus DF-RF, DM-RF versus DF-RM, DF-RF versus DF-RM. Para o desfecho sobrevida do enxerto, foram incluídos 13 estudos,,,,-,,,-,Para avaliar gênero do doador-receptor, foram analisadas seis comparações: DM-RM ,,,,,,,Os outros estudos não apresentaram dados suficientes para a análise quantitativa.Os estudos de Ellison et alversus DF-RM, os RR agrupados para a sobrevida do enxerto em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,03 , 1,05 , 1,06 , 1,15  e 1,08 . A taxa de sobrevida do enxerto foi significativamente maior em todos os tempos de acompanhamento avaliados, favorecendo o par DM-RM. A heterogeneidade foi alta e significante para todos os períodos, exceto aos dois anos de acompanhamento. A análise de sobrevida do paciente foi realizada apenas para o tempo de acompanhamento de um ano e não houve favorecimento de nenhum par .Na comparação DM-RM versus DF-RF, os RR agrupados para a sobrevida do enxerto em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,02 , 1,02 , 1,05 , 1,02  e 1,02 . A taxa de sobrevida do enxerto foi significativamente maior nos tempos de acompanhamento de um, três e cinco anos, favorecendo o par DM-RM. A heterogeneidade não foi significante apenas para dois anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par .Na comparação DM-RM versus DM-RF, os RR agrupados para a sobrevida do enxerto, em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,01 , 1,01 , 1,03 , 1,00  e 0,96 . A taxa de sobrevida do enxerto foi significativamente maior apenas no tempo de acompanhamento de um ano, favorecendo o par DM-RM. A heterogeneidade não foi significante apenas para dois anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par .Na comparação DM-RM versus DF-RF, os RR agrupados para a sobrevida do enxerto, em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,01 , 1,01 , 1,01 , 1,01  e 1,04 . A taxa de sobrevida do enxerto foi significativamente maior nos tempos de acompanhamento de três e 10 anos, favorecendo o par DM-RF. A heterogeneidade não foi significante apenas para dois e três anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par .Na comparação DM-RF versus DF-RM, os RR agrupados para a sobrevida do enxerto em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,01 , 1,05 , 1,03 , 1,18  e 1,10 . A taxa de sobrevida do enxerto foi significativamente maior em todos os tempos de seguimento, exceto em um ano, favorecendo o par DM-RF. A heterogeneidade foi alta e significante para todos os períodos, exceto aos dois anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par .Na comparação DM-RF versus DF-RM, os RR agrupados para a sobrevida do enxerto em ordem por tempo de acompanhamento de um, dois, três, cinco e 10 anos foram, respectivamente, 1,01 , 1,03 , 1,01 , 1,14  e 1,06 . Não houve diferença significante na taxa de sobrevida do enxerto nos tempos de acompanhamento. A heterogeneidade foi alta e significante para todos os períodos, exceto aos três anos de acompanhamento. A metanálise de sobrevida do paciente não mostrou favorecimento para nenhum par .Na comparação DF-RF Esta metanálise avaliou a influência do gênero de doadores, receptores e combinação doador-receptor na sobrevida do enxerto e do paciente no transplante renal.24 concluiu que enxertos renais de pacientes do gênero masculino funcionam melhor que aqueles de pacientes do gênero feminino, em longo prazo. Vários estudos sugerem que, nesses casos, os enxertos de doadoras são mais antigênicos, o que pode explicar a menor sobrevida.,,,Para a comparação entre gênero de doador, foram avaliados 9.022 pacientes na metanálise. O gênero do doador não favoreceu a sobrevida do enxerto na avaliação de um, dois, três, cinco e oito anos de acompanhamento . Apenas no tempo de acompanhamento de 10 anos houve diferença significativa favorecendo os doadores do gênero masculino . O estudo de MullerPara a comparação entre gênero de receptor, em todos os períodos de acompanhamento, foram avaliados 9.593 pacientes na metanálise e não foi observada diferença significativa na sobrevida do enxerto. Na análise de sobrevida do paciente foram avaliados 747 pacientes e não foram encontradas diferenças significativas entre os estudos. O estudo de Busson e Benoitversus DF-RM, DM-RM versus DF-RF, DM-RM versus DM-RF), ou seja, os transplantes de rins de doadores masculinos em receptores masculinos apresentaram melhores taxas para sobrevida do enxerto. Entretanto, no par DF-RM houve os piores resultados , exceto na comparação DF-RM versus DF-RF. Esses resultados são comparáveis com outras revisões.,Na comparação entre gênero de doador-receptor, participaram 471.252 pacientes. Evidencia-se que no par DM-RM houve melhores resultados em todas as comparações , número de transplantes, período de seguimento, entre outros. Apesar disso, os estudos observacionais têm a vantagem de reunir um número grande de pacientes e melhor representar o mundo real.Outra limitação na interpretação dos resultados foi a heterogeneidade estatística entre os estudos encontrada nas metanálises. O pequeno número de estudos incluídos nas comparações e a falta de informações completas e precisas nos estudos dificultaram a explicação para as fontes de heterogeneidade. A maioria dos estudos não apresentou a terapia imunossupressora, idade (doador e receptor) e tempo de seguimento. A análise de sensibilidade com inclusão e exclusão de estudos em cada comparação, no geral, não alterou a direção dos desfechos, com alterações pouco relevantes no valor da heterogeneidade, além de não fornecer informação sobre as possíveis causas para a heterogeneidade.Entretanto, os resultados desta revisão podem ser considerados para a tomada de decisão na prática clínica pelas equipes transplantadoras, uma vez que representa o melhor nível de evidência sobre o assunto.A incompatibilidade entre gênero deve ser evitada sempre que possível. O gênero deve ser considerado como um critério na escolha da alocação de órgãos dos doadores e receptores, sendo que a combinação de gênero pode fazer a diferença nas taxas de sobrevida. Entretanto, essa é uma realidade comprometida na prática clínica, devido à escassez de doadores e ao aumento do número de pacientes na lista de espera para transplante, tornando-se necessária uma mudança nesse cenário a fim de melhorar a alocação dos órgãos.Em conclusão, gênero do receptor e do doador avaliado isoladamente não influencia a sobrevida do enxerto e do paciente. Contudo, a combinação gênero doador-receptor pode ser um fator determinante para a sobrevida do enxerto, favorecendo o par DM-RM.


Fecal incontinence is a challenging condition with numerous available treatment modalities. Success rates vary across these modalities, and permanent colostomy is often indicated when they fail. For these cases, a novel potential therapeutic strategy is anorectal transplantation (ATx). We performed four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) ATx procedures. The anorectum was retrieved with a vascular pedicle containing the aorta in continuity with the inferior mesenteric artery and portal vein in continuity with the inferior mesenteric vein. In the recipient, the native anorectal segment was removed and the graft was transplanted by end-to-side aorta-aorta and porto-cava anastomoses and end-to-end colorectal anastomosis. Recipients were sacrificed at the experimental endpoint on postoperative day 30. Surviving animals resumed normal body weight gain and clinical performance within 5 days of surgery. Isografts and 42.9% of allografts achieved normal clinical evolution up to the experimental endpoint. In 57.1% of allografts, signs of immunological rejection  were observed three weeks after transplantation. Histology revealed moderate to severe rejection in allografts and no signs of rejection in isografts. We describe a feasible model of ATx in rats, which may allow further physiological and immunologic studies. Fecal incontinence, often accompanied by definitive colostomy, is one of the most psychologically and socially debilitating medical conditions. The incidence of fecal incontinence in the general population may be as high as 17%, and the number of patients undergoing colostomy for this reason is steadily increasing5Anorectal transplantations (ATx) have been described experimentally in rat89101214ad libitum. Every effort was made to minimize animal suffering, including the administration of pain medication and antibiotics.Twenty-two male rats weighing 220–280 grams were included in this study. Four isogeneic (Lewis-to-Lewis) and seven allogeneic (Wistar-to-Lewis) isolated ATx procedures were performed. All procedures followed the guidelines of the International Council for Laboratory Animal Science and received approval from the University of São Paulo Medical School ethical committee. Fasting was imposed on all rats for 24 h prior to the operation, but they were given drinking water Four Lewis and seven Wistar rats were used as isogeneic and allogeneic donors, respectively. After intaperitoneal anesthesia with ketamine (30 mg/kg) and xylazine (10 ml/kg), we performed a midline laparotomy and perianal incision to procure the anorectal graft. The perineal dissection was performed adjacent to the rectal segment, and the pudendal nerves were not preserved. The anorectal segment was then mobilized into the abdomen through the perineum, preserving the inferior mesenteric artery (IMA) . A long The graft was then removed from the abdominal cavity. The aorta was then cannulated and flushed with 20 mL of cold lactated Ringer’s solution. The colon and rectum were also flushed with the same cold solution. The composite graft was placed in a container with 50 mL of cold lactated Ringer’s solution and stored at 4 °C .Eleven Lewis rats were used as both isogeneic and allogeneic recipients. The recipients received ceftriaxone  and metronidazole . After the same anesthesia used for the donors, a combined perineal and abdominal incision, the anorectal segment was mobilized and resected as described above. Vascular reconstruction was started by an end-to-side aortic-aortic anastomosis followed by an end-to-side porto-cava anastomosis with a 10-0 nylon running suture . All micet al. for intestinal allograft rejectionClinical examination was performed by assessing surgical complications , behavioral modifications, anal aspect, body weight, and survival. Body weight loss of more than 30%, declining clinical status, and one-month animal survival were set as experimental endpoints. Samples from the proximal graft border and anal canal  were removed at the end of the study for histological examination using hematoxylin-eosin. Classification of intestinal graft rejection was graded as indeterminate, mild, moderate, and severe, as described in A trained microsurgeon performed the microsurgical technique and the whole procedure was completed in approximately 90 min. (donor: 29 ± 19 min. and recipient: 57 ± 38 min.). The mean of time consuming for end-to-side porto-cava anastomosis in recipient was 15.6 ± 3.1 min. and the entire vascular anastomosis time was 27.8 ± 5.7 min.One animal that underwent isogeneic transplantation died 5 days after transplant due to technical failure (9.1%). The cause of death was graft necrosis associated with peritonitis due to thrombosis of the PV.All surviving animals sustained mild body weight loss (<10%) within the first week and progressively regained normal body weight. Stool characteristics returned to normal by the end of the first week in most of the animals (90.1%). Six animals  retained favorable evolution until the study end-point. Four animals receiving allogeneic transplants  presented mild clinical signs of rejection approximately 20 days after transplant, including diarrhea (n = 1), abdominal distention (n = 3), and anal hyperemia and petechiaes (n = 3) . The cliAll animals were sacrificed at postoperative day 30. In every animal receiving isogeneic transplants, macroscopic examination showed a small amount of abdominal adhesions and normal graft appearance. Histopathology confirmed normal graft appearance without signs of rejection. On the other hand, in most animals receiving allogeneic transplants, a significant amount of intestinal adhesions, diffuse graft inflammation, and enlarged Peyer’s patches could be observed. Three moderate and four severe graft rejections were identified according to the criteriaet al.In this study, we described an innovative and feasible microsurgical model for isolated ATx in rats. We also showed for the first time the different immunological responses and rejection patterns between isogeneic and allogeneic ATx. In 2000, O’Bichere In this article we portrait the first experience of ATx using arterial and venous microanastomosis. This technique was inspired by our previous intestinal transplantation models in the rat1718et al.In our previous ATx experiments in rodents we compared a simulated model of autologous ATx with animals submitted to anorectal segment resection and colostomyThe disadvantage of these autologous ATx models includes a simulated transplantation technique and the impossibility to study the graft rejection. In the present model we performed the real transplantation of the graft by recovering it from one rat and reimplanted in another using vascular anastomosis. Furthermore, in the current model we can perform syngeneic transplantations  to study graft functional recovery and preservation surveys, and allogeneic transplantations (between different rat’s strain) to perform investigations about rejection and tolerance induction.et al.Araki et al. investigated the evolution of small bowel transplantation by different donor–recipient allograft combinations in 1994Tanabe et al. system are useful and relatively easily to perform because identify steady features of acute cellular rejection in the three segments of the graft . This features include crypt apoptosis, crypt epithelial injury, activated lymphocytic inflammatory infiltration in the lamina propria (rectum), epithelium and gland atrophy , epidermic and subepidermic activated lymphocytic inflammatory infiltrate, squamous epithelium atrophy (skin), arterites, necrosis, architectural distortion and ulceration. These features were similar in the three segments of anorectal graft analyzed for each degree of rejection. The activated lymphocytes mixed with some eosinophils and neutrophils in the rejection of ATx are easily differentiated from other nonspecific conditions of lymphocytes infiltration that contain nonactivated lymphocytes. The intensity of the infiltration was generally correlated with the severity of the rejection.The used four histologic features for score grading in this investigation based in Wu et al. have shown that anal resting pressure in the rat is maintained by both the external and internal anal sphincters et al. showed that rats were not rendered incontinent after bilateral pudendal nerve transectionRecently Zutshi et al.The dissection of the extraperitoneal rectum must be near the rectum serosa to avoid urinary complications and injury to the iliac vessels. The IMA and IMV were dissected far from its wall to avoid spasm and thrombosis due to their manipulation. Another important consideration was the creation of long aortic-mesenteric and porto-mesenteric conduits so the anus could be implanted in the perineum without tension on microvascular anastomoses. As observed by O’Bichere In conclusion, we described a feasible model of ATx in rats that could be useful for further anorectal physiological and immunological studies. Ultimately, the current study may increase interest not only in ATx alone but also as a combined modality therapy with intestinal and multivisceral allografts in human clinical practice.How to cite this article: Galvão, F. H. F. et al. Allogeneic anorectal transplantation in rats: technical considerations and preliminary results. Sci. Rep.6, 30894; doi: 10.1038/srep30894 (2016).


Introduction: Used routinely in maxillofacial reconstructive surgery, the chondrocostal graft is also used in hand surgery. The purpose of this overview was to analyze at long follow-up the radiological and histological evolution of this autograft, in the hand and wrist surgery.Materials and methods: Since 1992, 144 patients have benefitted from a chondrocostal autograft: 116 osteoarthritis of the thumb carpometacarpal joint, 18 radioscaphoid arthritis, six articular malunions of the distal radius, four kienbock, and four traumatic loss of cartilage of the PIP joint. Magnetic Resonance Imaging (MRI) was performed in 19 patients and histological study in 12 patients with a mean follow-up of 68 months (4–159).Results: Whatever the indication, the reconstruction by a chondrocostal or ostochondrocostal graft has allowed us to obtain satisfactory clinical results at long follow-up. The main question was the viability of the graft. The radiological study has shown the non-wear of the graft and a certain degree of ossification. The MRI confirmed a very small degree of osseous metaplasia but its viability. The biopsies showed a neo-vascularization of the cartilage.Conclusion: Despite the strong mechanical strain in the hand and wrist, the chondrocostal graft is a biological arthroplasty, trustworthy and secure at long time even if it can cause infrequent complications inherent to this type of surgery. Despite the inevitable histological modification, the cartilage remains alive and is of satisfactory quality at long term follow-up and fulfilling the requirements for interposition and reconstruction of an articular surface. The rib cartilage contains hyalin cartilage, which has the characteristics of an epiphyseal plate , 30. Sko2.4Tropet et al.  histolog3Through a horizontal incision, the anterior cartilaginous end of the 7th, 8th, or 9th rib is exposed. The osteochondral junction is easy to identify because of its different color. The deep side of the 9th rib is reamed carefully. The graft is harvested using a no. 23 scalpel blade. The rib harvest is extraperichondrial for greater safety. The perichondrium can also be harvested. If the rib is sufficiently wide, the graft can be harvested without breaking rib continuity. In collaboration with the anesthesiologist, positive pressure insufflation allows the surgeon to verify pleural integrity. After closing the intercostal muscles and subcutaneous tissues, a subcuticular suture is used to close the wound with placement of a Redon drain.4Tropet et al.  performe55.1Basal joint arthritis causes pain and reduced key pinch ability in patients who are still active , 36. TraTropet et al.  reviewed5.1.1Nineteen MRIs were performed in patients at more than 5 years of postoperative follow-up . The T1-5.1.2In the patients who underwent MRI at different follow-up times, no graft wear was noted, but it was very difficult to compare the MRI images taken over time. In patients where sagittal views were taken, there was evidence of the graft molding itself into the base of the first metacarpal.Histological analysis of ten grafts was carried out between two and 46 months postoperative, when the joint dislocated or after revision surgery. Neovascularization of the cartilage graft was noted, but there were areas of chondrocyte necrosis with fibrous tissue development and osseous metaplasia.Ossification within the graft corresponding to osseous metaplasia was probably related to the presence of fibrovascular granulation tissue formation. This ossification varied greatly from patient to patient. It appeared either at the center or periphery of the graft. On X-rays, it can take on a trapezoid appearance; at the latest follow-up, the X-rays may give the impression of a nearly completely rebuilt trapezium.5.1.3The scaphometacarpal space had narrowed to 2 mm. This was not related to any clinical outcomes in the multivariate study. It was most apparent during the first year and corresponded to the graft’s adaptation to the base of the first metacarpal. Graft lysis was found in four out of 100 cases. This lysis was present every time the trapezium had been completely excised. For this reason, Tropet deems it essential to retain a part of the trapezium when treating basal joint arthritis.5.2In cases of radiocarpal osteoarthritis , a rare Seven patients were operated using this technique. They all presented substantial wrist pain and stiffness initially. Their mean age was 49.2 years (range 22–72 years). They were reviewed at a mean follow-up of 22.5 months (range 6–38 months). Both clinical and imaging evaluations were performed. The mean Herzberg score  was 72/15.3In cases of periscaphoid osteoarthritis, wrist pain and weakness , 31 contIn this disease condition, whether nonunion or a scapholunate ligament lesion coexists with osteoarthritis, the proximal pole of the scaphoid is resected. This is logical in cases of scapholunate advanced collapse (SLAC) because this part of the scaphoid is arthritic. In scaphoid nonunion advanced collapse (SNAC), this approach has been criticized because the middle and distal part of the scaphoid are arthritic. It is critical that less than the proximal two-thirds of the scaphoid be resected and the osteochondral cartilage graft (bone part toward the scaphoid and cartilaginous part toward the radius) be attached with at least two pins. We had not used screw fixation with this graft until very recently . Now tha5.4Advanced Kienböck’s disease is treated by proximal row resection or by partial arthrodesis. Between 2007 and 2009 four patients of mean age 40 years (32–51) were operated using replacement of the lunate with a free costochondral autograft . Like ca6We wanted to take the mystery out of harvesting a rib cartilage graft, as this type of graft can be used in multiple ways in upper limb surgery. When used for reconstruction procedures, it can be easily and reliably matched to the defect size and can act as a free spacer or fixed graft. Partial and total fusions are traditional solutions for cases of degenerative disease in the hand and the wrist. Functional results after fusion are predictable in painful wrists having undergone multiple surgeries. We believe that pain can be eliminated with rib cartilage grafting while preserving whatever mobility the arthritic patient still has. Although there are alternatives to which grafting should be compared for treatment of basal joint arthritis and periscaphoid osteoarthritis, this option provides true resurfacing in cases of joint malunion. The absence of other conservative solutions to reconstruct a destroyed joint surface is the main argument in favor of this surgical technique, which we are reporting here for the first time.L. Obert is a consultant for FX Solution, Zimmer, SBI, Synthes & Depuy, Medartis, Evolutis, Biotech & wright, Argo.Every other author certifies that he has no commercial associations that might pose a conflict of interest in connection with the submitted article.Each author has no conflict of interest in connection with this article.


Errata 1“Serotonin and the bone assessment”, authors Carsote M, Radoi V, Geleriu A, Mihai A, Ferechide D, Opris D, Paun D, Poiana C, was published both in Journal of Medicine and Life, vol. VI, issue 2, pp. 151-155, 2013 in the “General Articles” category and in Journal of Medicine and Life Volume 7, Special Issue 2, pp. 49-53, 2014.Due to a regrettable error the article The above-mentioned article will only remain valid in Journal of Medicine and Life, vol. VI, issue 2, pp. 151-155, 2013, and the duplicate will be cancelled . The change should be made at all the levels: the journal’s web page – www.medandlife.ro and the databases the journal is indexed in . Errata 2“Detection of EWS/FLI-1 fusion in non-Ewing soft tissue tumors”, authors Trancau IO, Huica R, Surcel M, Munteanu A, Ursaciuc C, was published both in Journal of Medicine and Life, vol. VIII, issue 1, pp. 85-89, 2015 in the “Case Presentations” category and in Journal of Medicine and Life Volume 7, Special Issue 3, pp. 114-119, 2014. Due to a regrettable error the article The above-mentioned article will only remain valid in Journal of Medicine and Life Volume 7, Special Issue 3, pp. 114-119, 2014, and the duplicate will be cancelled . The change should be made at all the levels: the journal’s web page – www.medandlife.ro and the databases the journal is indexed in .Errata 3“Biomaterials for orbital fractures repair”,authors Totir M, Ciuluvica R, Dinu I, Careba I, Gradinaru S, was published both in Journal of Medicine and Life, vol. VIII, issue 1, pp. 41-43, 2015 in the “General Articles” category and in Journal of Medicine and Life Volume 7, Special Issue 4, pp. 62-64, 2014. Due to a regrettable error the article The above-mentioned article will only remain valid in Journal of Medicine and Life Volume 7, Special Issue 4, pp. 62-64, 2014, and the duplicate will be cancelled . The change should be made at all the levels: the journal’s web page – www.medandlife.ro and the databases the journal is indexed in . Errata 4Synergistic approach to patient dialysate”, authors Dragotoiu A, Checheriţă AI, Ciocâlteu A, Rizeanu S; “Evaluation of adherence to anti-osteoporosis treatment from the socio-economic context”, authors Abobului M, Berghea F, Vlad V, Balanescu A, Opris D, Bojinca V, Kosevoi Tichie A, Predeteanu D, Ionescu R; “Socio-economical factors that influence the perception of quality of life in patients with osteoporosis”, authors Abobului M, Berghea F, Vlad V, Balanescu A, Opris D, Bojinca V, Predeteanu D, Ionescu R and “Study regarding the survival of patients suffering a traumatic cardiac arrest”, authors Georgescu V, Tudorache O, Nicolau M, Strambu V, causing a modification of the numbers of the pages of the articles. Due to a regrettable error the following four articles were omitted from publication in the first printed version of Journal of Medicine and Life, Volume 8, Special Issue, 2015: “The above-mentioned articles are now included in the final version of the journal which will not be changed anymore. The publishers regret any inconvenience caused by these errors.


Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipient's perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2–2.9]). Moreover, we observed two novel risk factors for DGF: patient's residual diuresis ≤500 mL/d (OR = 2.3 [1.6–3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0–5.4]). Area under the curve of the ROC curve (0.77 [0.74–0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P = 0.54). However, graft survival is decreased only when rejection was associated with DGF (P < 0.001).  Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre. Delayed graft function (DGF) is a common complication most frequently defined as the need for dialysis during the first posttransplant week . DGF resIn 2003, Irish et al. developed the first multivariable logistic regression model to quantify the risk of DGF using donor and recipient characteristics at the time of transplantation . In receGiven the burden of DGF impact, many strategies are now at different stages of development, which might reduce the risk of DGF in the future, but there are no approved strategies for DGF prevention to date . Of courIn our centre, DGF incidence dropped steeply in 1992 and subsequently decreased continuously until reaching a record low since 2010, close to 5%. Our aim was to answer four questions: (1) What are the factors behind the decrease in DGF incidence in our cohort across the three past decades? (2) What role does rejection play in DGF occurrence? (3) What are the risk factors for DGF taking rejection into account or not? (4) Does DGF impact patient and graft outcome differently with and without rejection?n = 1046) or tacrolimus (n = 690) and an antiproliferative medication either azathioprine (n = 191) or mycophenolate mofetil (n = 684) and it was associated in most cases with an antilymphocyte induction therapy consisting in either a polyclonal globulin  or a monoclonal globulin directed to the CD3 receptor  or to the IL-2 receptor . A few patients received sirolimus (n = 48) and others an anti-LFA1 induction therapy (n = 13). Few transplantations (n = 32) were preemptive.From August 25, 1983, when cyclosporin was first used at our centre, to June 30, 2014, which defines the end of the study period, 1784 consecutive kidney-only transplantations from deceased donors have been carried out on 1452 adult (≥15 years old) recipients. The immunosuppressive protocol on an intent-to-treat basis included, along with corticosteroids, a calcineurin inhibitor either cyclosporin  and then from the rise in serum creatinine , and finn = 33), primary nonfunction (n = 9), or urological problems (n = 8), were not considered as DGF, as regular dialysis was not interrupted.DGF was defined as the need for dialysis in the postoperative course irrespective of its duration. Grafts that never functioned due to technical failures, arterial and/or venous thrombosis  curve was built from the results of the logistic regression in order to estimate the discriminant power of the factors which emerged from the logistic regression model. An area under the ROC curve and its 95% confidence interval were computed.Univariate survival was computed according to the Kaplan-Meier method and the Cox proportional hazard method was used in multivariate survival analyses.StatView  and StatThe study has been reviewed by the local ethics committee and has therefore been performed in accordance with the ethical standards of the Declaration of Helsinki 2000 as well as the Declaration of Istanbul 2008.P < 0.001) correlated: for instance, regrafting with peak HLA sensitization, immunosuppression and HLA mismatches with acute rejection episodes, and DGF with cold ischemia time. Grafts with missing data were predominantly encountered in the 1983–1997 period.The incidence of nearly all risk factors changed significantly in the course of time . These cP < 0.001), the median difference between both groups being 5.5 days.Altogether, DGF was observed in 382 out of 1784 transplantations (21.4%) and its duration was limited to the first two posttransplant weeks in 81.4% of the cases . TransplP < 0.001) than in those dead from other causes (P = 0.74).The cause of death was unknown in 100 transplants (5.6%). Five groups of known causes were considered: traumatism resulting from traffic accident, fall, or gunshot, cerebrovascular event (haemorrhagic or thrombotic), anoxia due to respiratory arrest induced by drugs or severe asthma, brain tumor, and other less frequent miscellaneous causes. By far, the first two causes were predominant (90.8%) and a clear relationship appeared between the cause of death and donor terminal creatinine, distinguishing traumatic from nontraumatic causes : donor'sP > 0.10  justifying the creation of a dichotomous variable: <500 (64.5% of grafts) versus ≥ 500 mL/d (35.5% of grafts). The final model included seven risk factors, all the others being excluded at P > 0.10: cold ischaemia time, recipient's residual diuresis <500 mL/d, perioperative saline loading, recipient's BMI, DCD donor, donor's terminal creatinine, and recipient's gender. These results were nearly identical whether rejection episodes occurring during the DGF period were taken into account . Restricting the analysis to the 1998–2014 period in which transplants with incomplete data were less frequent , group 2 DGF+/ARE− (n = 300), and group 3 DGF+/ARE+ (n = 82). Patient survival was similar in the three groups: at ten years it was 84.5% in group 1, 86.8% in group 2, and 86.5% in group 3 (P = 0.54). On the contrary, whereas no difference in deceased censored graft survival was observed between groups 1 and 2 (P = 0.45), survival was much lower (P < 0.001) in group 3 than in the other two groups  or absence (−) of DGF and ARE: group 1 DGF−/ARE−  to that reported in other centres. This observation prompted us to find an explanation for this discrepancy.In order to distinguish the respective role of ischemia-reperfusion injury and acute rejection occurring during the DGF period, risk factors for rejection during the DGF period were studied. Along with well known factors , perioperative saline loading significantly prevents acute rejection. As perioperative saline loading has been shown to decrease the risk of ischemia-reperfusion injury , 29 thatRisk factors for DGF are very similar whether early occurring rejection episodes are taken into account or not. All these factors except perioperative saline loading are different from those for acute rejection. This suggests that ischemia-reperfusion injury is the predominant mechanism involved in the development of DGF. Several factors contribute to increase in ischemia-reperfusion injury and thereby DGF risk. Whether their effects are additive or enhance each other is difficult to establish. Anyhow, prolonged cold ischemia time, absence of perioperative saline loading, high recipient's BMI, male gender (which is highly correlated to his cardiovascular antecedents), DCD donors, and high donor's terminal creatinine (which is highly correlated to donor's traumatic death) are all detrimental for DGF, consistent with previously reported results . A not yWhen early occurring rejection episodes are taken into account, deceased censored graft survival is lower in grafts with DGF than in those without DGF, at variance with what is observed in rejection-free grafts. Long-term graft survival depends mostly on immunologic processes inducing acute rejection  and, latArea under the ROC curves derived from our logistic regression analyses, close to 0.77, shows an excellent discriminant power of the risk factors identified in our model and compares favourably with that reported (0.70) in a large multicentric study . MoreoveThe usefulness of our model should be confirmed by internal validation in new patients using the same database as well as by external validation in patients from other databases using our model . Indeed,The current low DGF incidence in our centre, close to 5%, is, at least in part, related to systematic recipient's perioperative saline loading that efficiently prevents ischemia-reperfusion injury, the predominant cause of DGF. Along with other factors, residual function of the native kidneys is another novel important factor emerging from our study. Our model affords excellent discriminant power to predict DGF. DGF significantly reduces graft survival only when early occurring rejection episodes are taken into account, suggesting that acute rejection should be considered in any study on DGF. As they are powerful determinants of rejection, recent immunosuppressive regimens and better donor-recipient HLA match might further contribute to reduction in DGF incidence.


A thorough understanding of starch gelatinization is extremely important for precise control of starch functional properties for food processing and human nutrition. Here we reveal the molecular mechanism of starch gelatinization by differential scanning calorimetry (DSC) in conjunction with a protocol using the rapid viscosity analyzer (RVA) to generate material for analysis under conditions that simulated the DSC heating profiles. The results from DSC, FTIR, Raman, X-ray diffraction and small angle X-ray scattering (SAXS) analyses all showed that residual structural order remained in starch that was heated to the DSC endotherm end temperature in starch:water mixtures of 0.5 to 4:1 (v/w). We conclude from this study that the DSC endotherm of starch at a water:starch ratio of 2 to 4 (v/w) does not represent complete starch gelatinization. The DSC endotherm of starch involves not only the water uptake and swelling of amorphous regions, but also the melting of starch crystallites. Starch is a major component of the harvestable parts of many food crops. It occurs as water-insoluble granules, which are composed of two types of α-glucans-amylose and amylopectin, which make up 98–99% of the dry weight. The ratio of the two polysaccharides and their structures vary with the botanical origin of the starch granules. Amylose is mainly located in the amorphous core area of the starch granules, with some interspersed radially among the amylopectin clusters134567911in situ structural characterization techniques such as XRD and SAXS has indicated that residual crystallinity and lamellar organization still remain at the completion of the gelatinization endotherm172021Disruption of the multiple levels of granular organization, as occurs during hydrothermal treatment in food processing, follows hydration, swelling and solubilization of starch molecules, collectively referred to as starch gelatinization1314151618The finding that there is still considerable residual crystallinity and lamellar structure at the end of starch gelatinization endotherm17202123Wheat (Zhoumai 18) flour was kindly provided by the Institute of Crop Science, Chinese Academy of Agricultural Science. Amylose (A0512) and amylopectin (A8515) from potato starch were purchased from Sigma Chemical Co. . Other chemical reagents were all of analytical grades. Starch isolation and characterization of its chemical composition are described elsewhereDifferential scanning calorimetry (DSC) measurements were performed using a Differential Scanning Calorimeter  equipped with a thermal analysis data station. An empty aluminum pan was used as the reference. Samples of approximately 3.0 mg of native wheat starch (10.6% moisture) were weighed accurately into an aluminum sample pan. Distilled water was added with a pipette to obtain water:starch ratios (v/w) of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0 and 4.0 in the DSC pans, corresponding to water contents of 33.3, 42.9, 50.0, 60.0, 66.7, 75.0 and 80.0%, respectively. The pans were sealed and allowed to stand for 4 h at room temperature before analysis. The pans were heated from 20 to 95 °C at a heating rate of 10 °C/min. For the freeze-dried starch samples, prepared as described subsequently using an RVA instrument, a ratio of water:starch of 4 (v/w) was used in the DSC measurements.o-10, To, Tp, Tc, Tc + 10, Tc + 20 and 95 °C with the paddle immobilized , as shown in To obtain sufficient material to characterize structural changes of starch during DSC heating, samples were prepared by heating starch-water systems in a RVA instrument without stirring under the same heating profile described above for DSC measurements. Approximately 2.5 g of native starch (10.6% moisture) were weighed accurately into an RVA canister and distilled water was added with a pipette to obtain the water:starch ratios of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0 and 4.0 (v/w). The mixtures in the canister were agitated gently with a glass rod and allowed to stand for 4 h at room temperature before heating. Each water:starch mixture was heated separately to T−1, with an accumulation of 64 scans and a resolution of 4 cm−1. All spectra were automatically baseline-corrected in the range of 1200 and 800 cm−1 by OMNIC 8.0 before being deconvoluted with a half-band width of 19 cm−1 and an enhancement factor of 1.6. The ratio of absorbances at 1047/1022 cm−1 was used to estimate the short-range ordered structure of starchThe FTIR spectra of freeze-dried starch samples after RVA heating were obtained using a Tensor 27 FTIR spectrometer  equipped with a KBr beam splitter and a DLATGS detector. The spectra were scanned in the range of 4000–400 cm−1, which can be used to characterize the molecular order of starch, was calculated using the software of WiRE 2.0.Raman spectra of freeze-dried starch samples were obtained using a Renishaw Invia Raman microscope system  equipped with a Leica microscope . A 785 nm green diode laser source was used in this studyX-ray diffraction analysis was carried out using a D/max-2500kv/pc X-ray diffractometer . All of the starch samples were stored for one week in a desiccator over a saturated NaCl solution, to equilibrate samples to a constant humidity before measurementsq-range from 0.11 to 2.25 nm°. The q resolution of the instrument at the main lamellar peak at approximately 0.6 nm−1 was calculated to be 0.01 nm−1. Samples were presented in 2 mm sealed quartz capillaries as suspensions containing excess water above the sedimented sample and scattering was measured for 60 seconds. A sealed 2 mm quartz capillary filled with water was used as a background. SAXS data sets were averaged radially using Bruker AXS software 4.1.30. SAXS curves were normalized to sample transmission and background-subtracted using fit 2D.Synchrotron SAXS experiments were conducted on the beam line BL16B1 at Shanghai Synchrotron Radiation Facility . A monochromatic beam of 0.124 nm was used and the sample-to-detector distance was 1860 mm, which provided a The freeze-dried samples were mounted on a stub with double-sided adhesive tape, sputter-coated with gold before imaging using a field-emission scanning electron microscope . An accelerating voltage of 5 kV was used during imaging.Results are reported as the mean values and standard deviations of at least duplicate measurements. Analyses of variance (ANOVA) by Duncan’s test (p < 0.05) were conducted using the SPSS 19.0 Statistical Software Program .o), peak (Tp) and conclusion (Tc) transition points (thermograms not shown). The values for To, Tp and Tc increased from 55.8 to 57.5 °C, from 60.3 to 62.0 °C and from 63.8 to 67.4 °C, respectively, with increasing water content in the mixture, although the increase was not statistically significant in some cases. Enthalpy change (ΔH) increased from 1.8 to 9.6 J/g as the water/starch ratio increased from 0.5 to 2, above which ΔH remained essentially constant with further increases in water content. Similar results for thermal transition of starch as a function of water content were also reported in many previous studies2324282923o, Tp and Tc and greater ΔH due to increasing disruption of starch crystallites.The effect of water content on thermal transition parameters of wheat starch is presented in c + 20 and 95 °C. However, no endothermic transitions were observed for starch:water mixtures of 1:1 or greater pre-heated to Tc + 10 or higher. In general, To, Tp and Tc increased with increasing end temperature of RVA pre-heating , νs (C1-O-C4), νs (C1-O-C5), skeletal (C-C-O), and ν (C-H) modes, respectively−1 are sensitive to changes of ordered structure in starch232433−1 is strongly and positively related to the relative crystallinity of starch25−1. The FWHM of the various water:starch mixtures increased with increasing end temperature of RVA pre-heating. Similar to the FTIR results, the FWHM did not change greatly with RVA pre-heating below Tp, but increased substantially above Tp. The FWHM continued to increase with increasing end temperature of RVA pre-heating above Tc, showing that short-range ordered structure still remained in pre-heated starch samples, consistent with the FTIR results.As all of the starch samples presented similar LCM-Raman spectra, only those of 2:1 water:starch mixtures are presented . Severalc, all starch samples showed the typical A-type X-ray diffraction patterns, although the peak intensities decreased with increasing end temperature of RVA pre-heating. With pre-heating to Tc + 10 and above, the disappearance of diffraction peaks indicated the starch crystallites were almost completely disrupted. The relative crystallinity only decreased sharply with pre-heating to a temperature above Tp. Starch samples at various water contents after RVA pre-heating to Tc still presented a clearly discernible X-ray diffraction pattern, with residual crystallinity ranging from 10 to 14.4% , which rapidly decreased at larger angles and featured a well-resolved peak around q of 0.60 nm−1. This peak was assumed to arise from the periodic arrangement of alternating crystalline and amorphous lamellae, corresponding to lamellar d-spacing of 10.0 nmo, above which it decreased gradually. The initial increase in lamellar peak intensity indicated that the density contrast between crystalline and amorphous lamellae increased initially with increasing end temperature of RVA pre-heating. As starch is heated at a temperature below To, annealing may occur, leading to the improved quality of starch crystalliteso-10 and To. For starch samples that were pre-heated to a temperature up to Tp, the characteristic lamellar peak was clearly identified and its q value was essentially unchanged indicating the lamellar d-spacing of starch samples remained almost constant. With pre-heating temperature increasing beyond Tp, the lamellar peak intensity decreased up to Tc, indicating residual lamellar structure was still present in starch samples after pre-heating to this temperature. The peak essentially disappeared with pre-heating above Tc. Taking these results together, we can conclude that the lamellar structure of starch was little affected after pre-heating to Tp, above which it was severely disrupted.As the SAXS patterns of all starch samples were similar, only the patterns of samples at water:starch ratios of 2:1 and 4:1 are presented . The SAXp. After pre-heating to Tp, some starch granules were deformed and adhered as a result of small granule swelling followed by freeze-drying. Many starch granules were still clearly observed for all starch samples after pre-heating to Tc (c). These observations were generally consistent with the previous reports23SEM micrographs of starch samples at a water:starch ratio of 2:1 after pre-heating are shown in ng to Tc  2.0/Tc. c), and that further disruption occurred on further heating beyond Tc. At low to intermediate water content (water:starch ratio < 2:1), the DSC endothermic transition is considered to represent partial gelatinization of starch due to limited swelling and melting of starch granules23c. At a water:starch ratio of around 2:1 or higher, the DSC endotherm remained essentially unchanged, leading to the constant gelatinization parameters , but also the melting of starch crystallites (beyond Tp).Another interesting result from the present study is that when starch was pre-heated up to the temperature of Tc. We conclude that the gelatinization endotherm of starch does not represent complete starch gelatinization, and reflects more the loss of long-range crystallinity than short-range molecular order. The gelatinization endotherm involves not only the water uptake and swelling of amorphous regions, but also the melting of starch crystallites (beyond Tp).Changes in the molecular order of starch during the DSC gelatinization endotherm were investigated for a wide range of water:starch mixtures that were pre-heated in a RVA to simulate the DSC heating profiles. Multiple analyses of starch samples prepared under conditions that mimicked the DSC heating profile showed that the starch still contained appreciable amounts of long- and short-range ordered structure at the conclusion temperature of the endotherm over water:starch ratios ranging from 0.5 to 4.0. The loss of long-range crystallinity appeared to be greater than that of short-range molecular order in the DSC endotherm to THow to cite this article: Wang, S. et al. Changes of multi-scale structure during mimicked DSC heating reveal the nature of starch gelatinization. Sci. Rep.6, 28271; doi: 10.1038/srep28271 (2016).


Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN.Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1–4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively.After 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months  and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation  and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine  correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation  at diagnosis, and high PVAN stage  were associated with worse long-term graft survival rates.The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN. The human BK polyomavirus (BKV) can infect the majority of the population and subsequently remains dormant in the kidney without consequence. However, under conditions of immunosuppression, especially renal transplantation, reactivation, and replication, may occur, causing an interstitial nephritis in the renal allograft. Polyomavirus-associated nephropathy (PVAN) was first diagnosed in Pittsburgh in 1993 by Dr. Randhawa in a renal transplant recipient suspected of having acute rejection . PVAN prGiven the small number of published interventional studies, the clinician is often faced with uncertainty in predicting the clinical outcome of the graft. Clinical factors reported to be associated with worse prognosis include deceased donor, female recipient, high serum creatinine at diagnosis, late diagnosis, and plasma peak viral load –9.Although the biopsy findings at diagnosis are proposed to be a predictive tool for assessing prognosis , 11, theIn the current investigation, we used quantitative PCR for BKV DNA load in urine and plasma and quantitative urine cytology to evaluate BKV infection in kidney transplant (KTx) recipients who received renal graft biopsies concurrently to identify PVAN. Moreover, we followed up PVAN patients after modification of maintenance immunosuppression to observe the clinical course hoping to identify prognostic variables of PVAN.From March 2006 to August 2014, 615 renal transplant recipients at our institution who underwent an allograft biopsy with an immunohistochemistry assay for polyomavirus were screened for BKV reactivation concomitantly, which consisted of urine cytological evaluation and quantitative PCR of both urine and plasma for BKV DNA. Forty-eight kidney transplant (KTx) recipients diagnosed with definitive PVAN were included in this study.Study approval was obtained from the Ethics Committee of the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. All patients gave their written informed consent to participate in the study, which was conducted in accordance with the Helsinki Declaration.Urinary cytology smears were stained by the Papanicolaou method and evaluated for the presence of cells with intranuclear viral inclusions (decoy cells), which were counted [number per 10 high-power fields] as described elsewhere –14.VP1 gene, amplification protocols, PCR precautions, and quality assurance have been described elsewhere . Prednisone was not changed.All patients were followed for at least 1 years post-diagnosis with regular monitoring of serum creatinine (Scr), trough Tac/CsA levels, and BKV replication every week for the first month followed by 2~4 weeks for next 3 months and then every 3–6 months.Delayed graft function (DGF) was defined as the need for dialysis within the first week after transplantation, except when only one session was performed immediately after surgery due to hyperkalemia or fluid overload. Severe pneumonia was defined as pneumonia occurring in the first year accompanied with acute respiratory distress syndrome.The mean graft follow-up period of BKVN patients after diagnosis was 32.1±26.4 months. The study endpoint was date of return to dialysis, or most recent clinical record. The following adverse outcomes were assessed for each patient: (a) Graft loss: patient death or return to dialysis. (b) Any graft functional decline: Graft loss or sustained increase in Scr >30% compared to the value at PVAN diagnosis.Analysis was performed using SPSS software . Continuous variables were expressed as mean ± standard deviation (SD) or as median  and compared using the t-test or Wilcoxon signed-rank test. Pearson’s chi-square test, Fisher’s exact test, and the Mann-Whitney-U test were used to analyze the data, as appropriate.The 1, 3, 5 year-graft survival rates rate were calculated by Kaplan-Meier curves and compared among groups by Log rank test.Univariate logistic and Cox regression analysis were performed to determine which risk factors affected clinical outcome and graft loss respectively. After univariate regression, recipient, transplant characteristics, and specific variables associated with p-values <0.05 by univariate analysis were entered into multivariate analysis to determine which factor affected graft outcome independently. Results were expressed as odds ratios (OR) with respective 95% confidence intervals. Cox’s proportional hazard regression analysis was used to assign relative risk (RR) to factors predictive of graft loss. A P-value <0.05 was considered significant.9 copies/ml, range (8.10×105−1.20×1012copies/ml)], and plasma BK viral load , compared to class A and C PVAN  and 13 (27.1%) patients. For those (n = 42) patients with a functioning graft at 1 year post-diagnosis, the mean level of Scr at 1 years was 200.5 ± 108.1μmol/L (range 90–531μmol/L). At last available follow-up, the frequencies of graft loss and any functional decline were 25% (12/48) and 33.3% (16/48) respectively. The 1, 3, 5 year graft survival rates rates were 100%, 80.5% and 69.1%, respectively. The frequency of graft loss, any functional decline, and the mean level of Scr at 1 year post-diagnosis and last available follow-up was higher in class C PVAN compared to class A and B . Long-teMore patients with PVAN class A had reduction of BKV replication by 90% and cleared BKV after modification of maintenance immunosuppression . There wThirty-three of 41 (80.5%) BK viremia patients with clearance of viremia on follow-up showed better graft survival rates than the 8 patients (19.5%) without viral clearance p<0.001, . The med6 copies/ml , and clearance of BKV DNAuria as well as viremia could be documented in only in 10 cases. Thirty-eight of 46 (82.6%) BK BKV DNAuria patients with 90% reduction of BKV load on follow-up showed better graft survival rates  continued to excrete virus in urine for 25.6 ± 25.5 months with a median viral load of 4.42x10p<0.001, . The medPresuming an exponential multiplication of viral load during infection, a significant viral load reduction was defined as a reduction of at least 90% (1 log is 10 fold) ; the devLogistic regression analyses of different clinical parameters on any graft functional decline at 1 year post-diagnosis are shown in On multivariate logistic regression analysis only severe interstitial inflammation  was as an independent predictor of poor graft function at 12 months post-diagnosis (p = 0.042). Rapid reduction of BKV DNAuria and clearance of viremia were associated with a trend towards improvement of graft function .On univariate analyses using Cox’s regression model , factorsThis study reveals factors associated with graft functional decline and long-term outcome in KTx recipients with PVAN. These potential factors include patient characteristics, immunosuppressive regimen, complications posttransplant, characteristics at diagnosis of PVAN, viral response to modification of maintenance immunosuppression, and histologic findings at diagnosis.Based on histologic classification, there are some characteristics in every PVAN class at diagnosis, which have the potential to influence graft outcome. The majority of patients in class A (9/11) received graft biopsy for BKV surveillance and not for a rise of the Scr. This was less frequently the case for class B 7/31) and class C (0/6). Patients with class B were characterized by the highest BKV load at diagnosis. The mean level of Scr, and scores for cy, i, ci, and ct were the highest in the patients with class C. However, except the histologic lesions, other factors of baseline did not influence graft outcome independently in our study, which is not consistent with some previous reports. For example, Masutani et al  reported/31 and cAlthough with early diagnosis the majority of patients can respond favorably, approximately 15% of still progress to graft loss. The actual consequence of the disease is more serious since 38% of patients continue to show decline in graft function, while 24% show a major decline characterized by sustained increase in serum creatinine of ≥ 50% compared to the value at the time of PVAN diagnosis. The data above is based on a 20±11 months follow-up study [On multivariate Cox’s regression analysis, histological classification was an independent factor for long-term graft outcome due to advanced interstitial fibrosis and tubular atrophy in class C at diagnosis. Our data indicate that definitive PVAN can still occur with stable allograft function and only detectable by surveillance biopsies. 81.8% patients in class A fall into this category. Detection of PVAN in the early stage is very likely the key step for the success of immunosuppression reduction strategies. Indeed, all studies—including ours—that report favorable outcomes of immunosuppression reduction, detected BKV-viremia early posttransplant allowing for timely therapeutic intervention , 20–22. A composite system to classify the disease based on viral cytopathic effect, extent of interstitial inflammation, tubular atrophy, and severity of interstitial fibrosis were also involved in the analysis. Extensive interstitial inflammation can influence adversely on both graft function at 1 year post-diagnosis and long-term graft survival rates. This is in agreement with Randhawa et al. , who demIf the frequency of viral reduction and clearance is introduced to the analysis, thirty-three of 41 (80.5%) BK viremia patients with clearance of viremia on follow-up showed better graft survival rates than the 8 patients 19.5%) without viral clearance p<0.001, . This is.5% withoAccording to the mathematical model about BKV replication developed by Funk et al , optimalIt is noteworthy that the urine cytology is a very convenient and useful method for diagnosis of PVAN and predicting viremia, especially for the developing countries where PCR may not be easily available. Our previous study, which included 338 recipients with renal transplant biopsies showed that using decoy cells without quantitation had a sensitivity of 95.8% and a specificity of 83.1% for PVAN. If the amount of decoy cells used as positive diagnostic standard was increased, the specificity for prediction of viruia, viremia, and PVAN was increased too. If the amount of decoy cells used as positive diagnostic standard was increased to more than 20 per 10 HPF, the specificity for prediction of viruia, viremia, and PVAN was 100%, 99.7%, and 99.7%, respectively .In summary, we present data suggesting that the extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. Stage of PVAN, viral reduction time, and viral clearance also can be used as prognostic markers in PVAN.


We present the case of successful repair of an exposed glaucoma drainage tube by cornea graft fixation with tissue adhesive, and without subsequent coverage by adjacent conjunctiva or donor tissues. Patient with history of keratoglobus with thin cornea and sclera, and phthisical contralateral eye, underwent three unsuccessful corneal grafts followed by Boston type 1 keratoprosthesis in the right eye. Ahmed drainage device with sclera patch graft was implanted to control the intraocular pressure. Two years later the tube eroded through sclera graft and conjunctiva. Repair was performed by covering the tube with a corneal patch graft secured by tissue adhesive after the conjunctiva in this area was dissected away. The cornea graft was left uncovered due to fragility of adjacent conjunctiva. The healing of ocular and graft surfaces was complete prior to the 1 month follow-up. Conjunctival epithelium covered the corneal patch graft. At 12 months follow-up, the graft and the tube remained stable. Our report suggests that corneal patch graft fixation to the sclera by means of tissue adhesive, without closing the conjunctiva, can be considered as an effective alternative surgical approach for managing exposed glaucoma drainage tube, accompanied by adjacent conjunctiva tissue deficiency.How to cite this article: Berezina TL, Fechtner RD, Cohen A, Kim EE, Chu DS. New Technique of Exposed Glaucoma Drainage Tube Repair: Report of a Case. J Curr Glaucoma Pract 2015;9(2):62-64. This technique may be challenging in eyes that previously underwent multiple surgeries because of scar formation and partial immobility of conjunctival tissue. The aim of this publication is to present a novel way of repairing an exposed glaucoma drainage tube when deficiency and fragility of conjunctiva prevented coverage over the patch.Erosion of the tube through graft material and conjunctiva, after glaucoma drainage device surgery, is a serious complication that may lead to local infection and endophthalmitis. The frequency of erosion varies from 2.5 to 7%.A 57-year-old patient with keratoglobus and phthisical left eye underwent three unsuccessful corneal grafts, followed by Boston type 1 keratoprosthesis and Ahmed drainage device with sclera patch graft in the right eye. Glaucoma drainage implant plate was placed 9 mm posterior to the corneal limbus and fixed to the sclera using 8-0 nylon sutures. The tube was passed through a short scleral tunnel just posterior to the corneal limbus. The anterior extraocular portion of the tube was covered with preserved human donor scleral graft that was secured to host sclera with 10-0 nylon suture. At 24 months after glaucoma surgery, the patient developed erosion of the Ahmed glaucoma tube through conjunctiva and sclera graft. Sclera graft covering the tube melted, and 2 mm segment of tube was exposed . A revisThe epithelium around the erosion (6 mm in diameter) was removed by a blade . A 6 mm During 12 months after the surgery, the intraocular pressure (IOP) was maintained by latanoprost 0.005% eyedrops. Eye examination was performed frequently postoperatively, then every few months and included: IOP measurement (pneumotonometry), visual acuity measurement and slit-lamp examination. The IOP did not exceed 15 mm Hg. Visual acuity remained stable (20/200). No infections or other complications were recorded. Covering of the corneal patch graft by native conjunctival epithelium was noticed prior to the 1 month follow-up visit . At the 13 In our case, we used donor corneal graft for coverage of a revised glaucoma tube, as cornea may be the preferable material to provide stable tube coverage.11 Different methods to close conjunctival defects that may occur after glaucoma drainage device surgery have been reported. In certain situations, conjunctival tissue cannot be advanced to cover the graft. The use of amniotic membrane, free conjunctival graft or buccal tissue have been proposed to cover the conjunctival defect.16 Cornea used for transplant is known to be a reasonable substrate for re-epithelialization. Our case was remarkable for the large conjunctival deficit and fragile thin sclera, partially due to keratoglobus, as well as numerous previous surgeries. We wished to minimize suturing to avoid scleral injury. Under this circumstance, a minimally invasive technique was used to secure corneal patch, that eventually epithe-lialized. We observed that a corneal patch graft with a smooth transition zone to sclera could be secured with tissue adhesive and successfully re-epithelialized. The described technique may be particularly useful in eyes with scleromalacia and/or multiple conjunctival surgeries with scarring.For repair of an exposed tube, use of different patch graft materials have been described, such as autologous fascia lata, donor pericardium, sclera, cornea, acellular dermis graft, and bioengineered collagen implant.Our case illustrates that primary conjunctival coverage of corneal patch graft, secured by tissue adhesive, is not mandatory. Conjunctival epithelium has the ability to cover the corneal patch during the first several weeks after surgery. This technique provides an additional surgical option for complex eyes with deficient sclera and conjunctiva.


Croatian Medical Journal is a general medical journal and although it might seem at first that lacking a specific field is mainly a weakness   . One of Croatian Medical Journal can aspire “to move the Earth” of biomedicine. At a new interdisciplinary stage of the biomedical future, the Croatian Medical Journal must be ready to respond to the emerging challenges of the new research pattern and publish relevant science.If multiple disciplinary effort is the right place to stand, then the


Risk prediction is an important area of clinical application of statistical methods. Angela Wood, assisted by Ian White and Simon Thompson, organized a three‐day international workshop on Statistical Challenges in Risk Prediction in Cambridge, UK, on November 19–21, 2012, with 21 invited academic statisticians  discuss decision curve analysis. Discussion during the workshop concluded that more methods development is needed to advance the evaluation of risk models in the clinical context in which the models will be used, and hence to evaluate the patient benefit and economic benefit of using the risk models in clinical practice.Biometrical Journal and its editors and reviewers for allowing us to publish the papers together in the journal.We hope you will enjoy reading these papers and contributing to the development of this important area of biostatistical methodology. We thank the Angela Wood, Ian WhiteGuest Editors


A very warm welcome to you all!I am happy to extend warm greetings to all of you as the new Editor-in-Chief. This year marks the 35th anniversary of Epidemiology and Health, the journal of the Korean Society of Epidemiology.epiH), altering the language from Korean to English. Thanks to the devoted efforts of Professor BoYoul Choi, former Editor-in-Chief, and enthusiastic member support, our journal is currently listed in the databases of PubMed, PubMed Central, KoreaMed, Korea Journal Citation Index, CINAHAL, EBSCO host, and CABI. We have redoubled our efforts to have the journal listed in Scopus and SCI as soon as possible so that it can play a more pivotal role as an international journal.The Korean Society of Epidemiology was founded in 1979. In October 2009, on the society’s 30th anniversary, the Korean Journal of Epidemiology was relaunched as an open-access online journal under the new name of Epidemiology and Health (epiH.This year, to achieve this goal, we have introduced the following seven editorial changes for First, our journal is published in English, but submissions in Korean are also accepted. The submitted Korean manuscripts, after being reviewed and revised, will be translated and published.Second, all costs, including those incurred during publication, reviewing, translation, and editing, will be assumed by the Society; authors submitting their papers are not required to assume any financial burden. Further, readers worldwide will have free access to the papers continuously.Third, besides the existing original papers, editorial, reviews, outbreak investigation, and briefs, a variety of new sections, such as cohort profiles, data resource profiles, invited lectures, invited editorials, and book reviews, will enrich the journal.Fourth, the primary emphases of each paper will be condensed into two to three lines, written in Korean, as key messages. This will allow Korean readers to quickly glimpse the paper’s content. Such key messages will be notified to all members by e-mail.epiH website.Fifth, all the published papers in our journal, from the inaugural issue to the latest issue, will be uploaded in full length to the Sixth, the online submission system was introduced to facilitate the submission process and enable authors to track the review process.Finally, we launched a fast-track review to accelerate the publication of your valuable manuscripts. If you wish to profit from this fast-track review, simply let us know when submitting your manuscript.epiH, and we rely on your active participation during the process of converging productive opinions.We are currently exploring various improvement measures for the development of epiH editorial board will do its utmost to ensure that your valuable papers are read and cited by target audiences worldwide at the earliest possible time.Our journal publishes a wide spectrum of epidemiological papers related to medicine and public health. The epiH is waiting for your esteemed manuscripts.On behalf of the editorial board, I wish you all good health and success in all your undertakings.Moran KiEditor-in-ChiefThank you.


There is an error in the “Ethics statement” section of this article. The correct statement is: All mice were housed, treated and handled under permission and in accordance with the guidelines of the Animal Care Committee of the University of Leipzig and the Regional Board of Animal Care for the district of Leipzig . The Animal Care Committee of the University of Leipzig and the Regional Board of Animal Care for the district of Leipzig specifically approved this study.


Journal of Eating Disorders editorial team would like to thank all reviewers who have contributed to the journal in 2015.The  Samir Al-AdawiOmanKarina AllenAustraliaJon ArcelusUnited KingdomEvelyn AttiaUnited StatesRachel Bachner-MelmanIsraelRoni BarakIsraelCarolyn BeckerUnited StatesCarl BirminghamCanadaChris BoyatzisUnited StatesCaroline BraetBelgiumJuleen BuserUnited StatesSusan ByrneLebanonIain CampbellUnited KingdomTerry CarneyAustraliaJue ChenChinaSimon ClarkeAustraliaAngelica ClaudinoBrazilLoa ClausenDenmarkJennifer CoelhoCanadaMyra CooperUnited KingdomRoss CrosbyUnited StatesRiccardo Dalle GraveItalyMartina de ZwaanGermanyLinley DensonAustraliaIvan EislerUnited KingdomManfred FichterGermanySarah FogartyAustraliaDavid ForbesAustraliaKatrin GielGermanyScott GriffithsAustraliaKjersti Solhaug GulliksenNorwayPhillipa HayAustraliaAnja HilbertGermanyVincent HoAustraliaHans HoekNetherlandsFrank HumeAustraliaCarokine HuntAustraliaMimi IsraelCanadaDavid JimersonUnited StatesAllan KaplanCanadaMichael KohnAustraliaHubert LaceyUnited KingdomJanet LatnerUnited StatesYael LatzerIsraelAnna LavisUnited KingdomDaniel Le GrangeUnited StatesTanja LegenbauerGermanySau Fong LeungHong KongPaolo MachadoPortugalSloane MaddenAustraliaSarah MaguireAustraliaSian McLeanAustraliaPhilip MehlerUnited StatesJennifer MillsCanadaDeborah MitchisonAustraliaAdith MohanAustraliaStuart MurrayAustraliaRichard NewtonAustraliaMarion OlmstedCanadaSusan PaxtonAustraliaKevin PileAustraliaCarolyn PlateauUnited KingdomCecile Rausch HerscoviciArgentinaDeborah ReasNorwayGaby ResmarkGermanyPaul RhodesAustraliaLina RicciardelliAustraliaP Scott RichardsUnited StatesElizabeth RiegerAustraliaMelissa RouelAustraliaPratap SharanIndiaFinns SkarderudNorwayEvelyn SmithAustraliaNerissa SohAustraliaKristin StedalNorwayDaniel SteinUnited StatesEsben StrodlAustraliaLois SurgenorNew ZealandAmy TalbotAustraliaMartin TeufelGermanyMichael TheodorosAustraliaTracey WadeAustraliaGlenn WallerUnited KingdomYan-Fang WangChinaHunna WatsonAustraliaMartin WeltmanAustraliaSteve WonderlichUnited StatesBlake WoodsideCanadaSarah YoungAustraliaFlorian ZepfAustraliaStephan ZipfelGermany


We read with great interest the recent correspondence from Topf et al  regardinimpressions" data as a reported outcome measure and provide a well-explained example of how this metric is dynamic. Further, they correctly note that "spam" accounts associated with the journal clubs (JC) artificially increase the total impressions for a Twitter journal club. Despite this, when used appropriately, we believe there is some value to impressions as a performance metric given the paucity of comparative outcome measures in the early Twitter-based journal club era. This education tool is unique and traditional analysis methods typically used in systematic reviews and meta-analytical studies are clearly not suitable. The  "impression:tweet ratio"  reported in the initial manuscript was a metric applied only to the Twitter user account to assess the following and “impression” of the journal club, thus reducing the influence of such "spam" accounts to a degree. We believe this modified calculation is a useful quantifiable measure of publicity and potential viewership of the discussion. However, for trend analysis, such as that performed for the top five performing journal clubs, the identification and exclusion of such accounts  was performed as they were not only statistical outliers but also known spam accounts. This helped us to provide highly accurate data in this analysis.Topf et al note the limitation associated with the dynamic nature of the "The dynamic nature of Twitter-based JC was pertinently raised by the authors, as evidenced by the commencement of recent JCs. We support the notion of a "living" systematic review, not currently possible given the publication using traditional peer-reviewed methods and associated delays. The suggested method of “Storifying” the chat is an appealing method for consolidation and formalization of the conversation for later review. The value of these conversations for scholarly activity is gaining momentum, with some institutions promoting Altmetric scores for affiliated publications. Furthermore, Symplur in this context as a real-time aggregate database is an invaluable tool in appreciating the changes in journal club discussions. We anticipate that with further time and refinement, more sophisticated methods for measuring journal club performance will be devised. The ongoing success of current and future journal clubs will be determined by appropriate identification and recommendation from experienced participants with advice for successes and pitfalls from established JCs.Given the current opportunity to present updated data six-months following the previous review , 6 more


In a unique collaboration between The Seventh Hospital of Hangzhou, the International Society for Traumatic Stress Studies (ISTSS), and the Zhejiang Behavior Medicine Association, the international conference “Posttraumatic stress: state-of-the-art research and clinical implications for China” was organized in Hangzhou, China, on 17–19 October 2014.The organizational team was led by Dr Zhonglin Tan, a psychiatrist from The Seventh Hospital of Hangzhou, who has spent a year with Professor Olff's research team in Amsterdam, The Netherlands. With the support of Dr Zhang, Director of The Seventh Hospital of Hangzhou, and with guidance from Professor Olff, Dr Zhonglin Tan successfully created a full program. Over 300 participants, the majority of them from China, enjoyed one full day in both English and Chinese (with simultaneous translation) and the rest of the meeting in Chinese only.global meetings program (see www.istss.org). Recognizing that trauma is a global issue (Schnyder, The renowned board members of ISTSS (Kaysen, Stappenbeck, Rhew, & Simpson, Next to the international speakers, a strong representation of Chinese PTSD experts was seen who gave keynotes on topics ranging from biological stress systems (Bao & Swaab, European Journal of Psychotraumatology (Cao, Wang, Wang, Qing, & Zhang, Apart from keynote lectures, this collection contains the abstracts of a selection of over 100 submissions, the authors of which were awarded for their excellent contribution to the field with a certificate and abstract publication in the Miranda OlffEditor-in-ChiefZhonglin TanHangzhou Mental Health CenterHangzhou Seventh Peoples’ HospitalHangzhou, People's Republic of China