Mutações novas no gene CFTR de pacientes brasileiros portadores de agenesia dos vasos deferentes: dificuldades no aconselhamento

PURPOSE: Screening for mutations in the entire Cystic Fibrosis gene (CFTR) of Brazilian infertile men with congenital absence of vas deferens, in order to prevent transmission of CFTR mutations to offspring with the use of assisted reproductive technologies. METHOD: Specific polymerase chain reaction (PCR) primers were designed to each of the 27 exons and splicing sites of interest followed by single strand conformational polymorphism and Heteroduplex Analysis (SSCP-HA) in precast 12.5% polyacrylamide gels at 7ºC and 20ºC. Fragments with abnormal SSCP migration pattern were sequenced. RESULTS: Two novel missense mutations (S753R and G149W) were found in three patients (two brothers) together with the IVS8-5T allele in hetrozygosis. CONCLUSION: The available screenings for CF mutations do not include the atypical mutations associated to absence of vas deferens and thus, when these tests fail to find mutations, there is still a genetic risk of affected children with the help of assisted reproduction. We recommend the screening of the whole CFTR gene for these infertile couples, as part of the work-up before assisted reproduction.OBJETIVO: Pesquisar mutações em toda a extensão do gene que causa a Fibrose Cística (CFTR) de homens brasileiros inférteis por agenesia congênita dos vasos deferentes, com a finalidade de prevenir a transmissão de mutações em CFTR à prole com o uso das tecnologias de reprodução assistida. MÉTODOS: Foram desenhados oligonucleotídeos específicos para realização de reação de polimerização em cadeia (PCR) para cada um dos 27 exons e sítios de processamento de interesse no gene CFTR. O PCR foi seguido pela técnica de SSCP-HA (polimorfismos de conformação no DNA de fita simples e na formação de heteroduplexes) em géis pré-fabricados de poliacrilamida a 12,5% em duas temperaturas, 7ºC e 20ºC. Os fragmentos com padrão alterado na migração do SSCP foram submetidos a seqüenciamento automatizado. RESULTADOS: Foram identificadas duas mutações novas com alteração de aminoácidos (S753R and G149W) em 3 pacientes (dois irmãos) juntamente com o alelo IVS8-5T em heterozigose. CONCLUSÕES: O rastreamento básico de mutações típicas da Fibrose Cística não inclui as mutações atípicas associadas à ausência dos deferentes. Desta forma, quando esses testes resultam normais, ainda assim existe um risco genético de crianças afetadas serem geradas com auxílio das Assisted Reproduction Technologies. Por este motivo, recomenda-se que a pesquisa de mutações em todo o gene CFTR seja o exame a ser oferecido para todos os casais inférteis em que o homem seja portador de agenesia dos vasos deferentes, antes da realização de reprodução assistida

Novel CFTR missense mutations in Brazilian patients with congenital absence of vas deferens: counseling issues

PURPOSE: Screening for mutations in the entire Cystic Fibrosis gene (CFTR) of Brazilian infertile men with congenital absence of vas deferens, in order to prevent transmission of CFTR mutations to offspring with the use of assisted reproductive technologies. METHOD: Specific polymerase chain reaction (PCR) primers were designed to each of the 27 exons and splicing sites of interest followed by single strand conformational polymorphism and Heteroduplex Analysis (SSCP-HA) in precast 12.5% polyacrylamide gels at 7ºC and 20ºC. Fragments with abnormal SSCP migration pattern were sequenced. RESULTS: Two novel missense mutations (S753R and G149W) were found in three patients (two brothers) together with the IVS8-5T allele in hetrozygosis. CONCLUSION: The available screenings for CF mutations do not include the atypical mutations associated to absence of vas deferens and thus, when these tests fail to find mutations, there is still a genetic risk of affected children with the help of assisted reproduction. We recommend the screening of the whole CFTR gene for these infertile couples, as part of the work-up before assisted reproduction.OBJETIVO: Pesquisar mutações em toda a extensão do gene que causa a Fibrose Cística (CFTR) de homens brasileiros inférteis por agenesia congênita dos vasos deferentes, com a finalidade de prevenir a transmissão de mutações em CFTR à prole com o uso das tecnologias de reprodução assistida. MÉTODOS: Foram desenhados oligonucleotídeos específicos para realização de reação de polimerização em cadeia (PCR) para cada um dos 27 exons e sítios de processamento de interesse no gene CFTR. O PCR foi seguido pela técnica de SSCP-HA (polimorfismos de conformação no DNA de fita simples e na formação de heteroduplexes) em géis pré-fabricados de poliacrilamida a 12,5% em duas temperaturas, 7ºC e 20ºC. Os fragmentos com padrão alterado na migração do SSCP foram submetidos a seqüenciamento automatizado. RESULTADOS: Foram identificadas duas mutações novas com alteração de aminoácidos (S753R and G149W) em 3 pacientes (dois irmãos) juntamente com o alelo IVS8-5T em heterozigose. CONCLUSÕES: O rastreamento básico de mutações típicas da Fibrose Cística não inclui as mutações atípicas associadas à ausência dos deferentes. Desta forma, quando esses testes resultam normais, ainda assim existe um risco genético de crianças afetadas serem geradas com auxílio das Assisted Reproduction Technologies. Por este motivo, recomenda-se que a pesquisa de mutações em todo o gene CFTR seja o exame a ser oferecido para todos os casais inférteis em que o homem seja portador de agenesia dos vasos deferentes, antes da realização de reprodução assistida

II Consenso Brasileiro de Câncer Gástrico realizado pela Associação Brasileira de Câncer Gástrico

Background: Since the publication of the first Brazilian Consensus on Gastric Cancer (GC) in 2012 carried out by the Brazilian Gastric Cancer Association, new concepts on diagnosis, staging, treatment and follow-up have been incorporated. Aim: This new consensus is to promote an update to professionals working in the fight against GC and to provide guidelines for the management of patients with this condition. Methods: Fiftynine experts answered 67 statements regarding the diagnosis, staging, treatment and prognosis of GC with five possible alternatives: 1) fully agree; 2) partially agree; 3) undecided; 4) disagree and 5) strongly disagree A consensus was adopted when at least 80% of the sum of the answers “fully agree” and “partially agree” was reached. This article presents only the responses of the participating experts. Comments on each statement, as well as a literature review, will be presented in future publications. Results: Of the 67 statements, there was consensus in 50 (74%). In 10 declarations, there was 100% agreement. Conclusion: The gastric cancer treatment has evolved considerably in recent years. This consensus gathers consolidated principles in the last decades, new knowledge acquired recently, as well as promising perspectives on the management of this disease.Racional: Desde a publicação do primeiro Consenso Brasileiro sobre Câncer Gástrico em 2012 realizado pela Associação Brasileira de Câncer Gástrico (ABCG), novos conceitos sobre o diagnóstico, estadiamento, tratamento e seguimento foram incorporados. Objetivo: Promover uma atualização aos profissionais que atuam no combate ao câncer gástrico (CG) e fornecer diretrizes quanto ao manejo dos pacientes portadores desta afecção. Métodos: Cinquenta e nove especialistas responderam 67 declarações sobre o diagnóstico, estadiamento, tratamento e prognóstico do CG com cinco alternativas possíveis: 1) concordo plenamente; 2) concordo parcialmente; 3) indeciso; 4) discordo e 5) discordo fortemente. Foi considerado consenso a concordância de pelo menos 80% da soma das respostas “concordo plenamente” e “concordo parcialmente”. Este artigo apresenta apenas as respostas dos especialistas participantes. Os comentários sobre cada declaração, assim como uma revisão da literatura serão apresentados em publicações futuras. Resultados: Das 67 declarações, houve consenso em 50 (74%). Em 10 declarações, houve concordância de 100%. Conclusão: O tratamento do câncer gástrico evoluiu consideravelmente nos últimos anos. Este consenso reúne princípios consolidados nas últimas décadas, novos conhecimentos adquiridos recentemente, assim como perspectivas promissoras sobre o manejo desta doença

Protective Effect of Prolactin against Methylmercury-Induced Mutagenicity and Cytotoxicity on Human Lymphocytes

Mercury exhibits cytotoxic and mutagenic properties as a result of its effect on tubulin. This toxicity mechanism is related to the production of free radicals that can cause DNA damage. Methylmercury (MeHg) is one of the most toxic of the mercury compounds. It accumulates in the aquatic food chain, eventually reaching the human diet. Several studies have demonstrated that prolactin (PRL) may be differently affected by inorganic and organic mercury based on interference with various neurotransmitters involved in the regulation of PRL secretion. This study evaluated the cytoprotective effect of PRL on human lymphocytes exposed to MeHg in vitro, including observation of the kinetics of HL-60 cells (an acute myeloid leukemia lineage) treated with MeHg and PRL at different concentrations, with both treatments with the individual compounds and combined treatments. All treatments with MeHg produced a significant increase in the frequency of chromatid gaps, however, no significant difference was observed in the chromosomal breaks with any treatment. A dose-dependent increase in the mitotic index was observed for treatments with PRL, which also acts as a co-mitogenic factor, regulating proliferation by modulating the expression of genes that are essential for cell cycle progression and cytoskeleton organization. These properties contribute to the protective action of PRL against the cytotoxic and mutagenic effects of MeHg.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)IFPA Itaituba, Fed Inst Educ Sci & Technol Para, BR-68180000 Campinas, Para, BrazilFed Univ Para, Inst Biol Sci, BR-66075110 Belem, Para, BrazilIFPA, Educ Fed Inst Sci & Technol Para, BR-66645240 Belem, Para, BrazilUniv Para, Ctr Biol & Hlth Sci, BR-66050540 Belem, Para, BrazilFed Univ Western Para, UFOPA, BR-68040470 Santarem, Para, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, BR-04021001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Morphol & Genet, BR-04021001 São Paulo, BrazilWeb of Scienc

5to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

El V Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2019, realizado del 6 al 8 de febrero de 2019 y organizado por la Universidad Politécnica Salesiana, ofreció a la comunidad académica nacional e internacional una plataforma de comunicación unificada, dirigida a cubrir los problemas teóricos y prácticos de mayor impacto en la sociedad moderna desde la ingeniería. En esta edición, dedicada a los 25 años de vida de la UPS, los ejes temáticos estuvieron relacionados con la aplicación de la ciencia, el desarrollo tecnológico y la innovación en cinco pilares fundamentales de nuestra sociedad: la industria, la movilidad, la sostenibilidad ambiental, la información y las telecomunicaciones. El comité científico estuvo conformado formado por 48 investigadores procedentes de diez países: España, Reino Unido, Italia, Bélgica, México, Venezuela, Colombia, Brasil, Estados Unidos y Ecuador. Fueron recibidas un centenar de contribuciones, de las cuales 39 fueron aprobadas en forma de ponencias y 15 en formato poster. Estas contribuciones fueron presentadas de forma oral ante toda la comunidad académica que se dio cita en el Congreso, quienes desde el aula magna, el auditorio y la sala de usos múltiples de la Universidad Politécnica Salesiana, cumplieron respetuosamente la responsabilidad de representar a toda la sociedad en la revisión, aceptación y validación del conocimiento nuevo que fue presentado en cada exposición por los investigadores. Paralelo a las sesiones técnicas, el Congreso contó con espacios de presentación de posters científicos y cinco workshops en temáticas de vanguardia que cautivaron la atención de nuestros docentes y estudiantes. También en el marco del evento se impartieron un total de ocho conferencias magistrales en temas tan actuales como la gestión del conocimiento en la universidad-ecosistema, los retos y oportunidades de la industria 4.0, los avances de la investigación básica y aplicada en mecatrónica para el estudio de robots de nueva generación, la optimización en ingeniería con técnicas multi-objetivo, el desarrollo de las redes avanzadas en Latinoamérica y los mundos, la contaminación del aire debido al tránsito vehicular, el radón y los riesgos que representa este gas radiactivo para la salud humana, entre otros

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research