CYP21A2 gene mutations, its nature and frequency in a paediatric Portuguese cohort with congenital adrenal hyperplasia

Introduction: The most common cause of congenital adrenal hyperplasia (CAH) is 21-hydroxylase deficiency (21-OHD) caused by alterations in CYP21A2 gene. The clinical phenotypes of this autosomal recessive disease are classified as classic (saltwasting and simple virilizing) and non-classic forms of CAH. The severity of the disease is directly related with the impairment of the 21-OH enzymatic activity. Genetic testing can confirm the disease and is crucial for familial studies and genetic counseling. Aim: The aim of this work was to perform the clinical and molecular characterization of the patients observed at the Hospital Pediátrico de Coimbra (Portugal) with the clinical suspecion of CAH. Methods: Retrospective analysis of patient medical records of all cases observed in our hospital with suspicion of CAH and detailed literature comparison. CYP21A2 molecular analysis had been performed in 81 unrelated Portuguese patients (51 female, 30 males) with clinical and endocrine laboratorial findings suggestive of CAH, using mini-sequencing, restriction enzyme digestion, Sanger sequencing or/and multiplex ligation-dependent probe amplification (MLPA). Results: CYP21A2 variants were identified in 74/81 (91%) of the patients. Homozygosity for CYP21A2 was found in 39.2% (29/74) of the patients while 55.4% (41/74) were compound heterozygous and, in 5.4% of the cases (4/74), only one pathogenic variant was identified. The most frequent alterations were p.Val281Leu, g.655A/C>G (splicing variant) and p.Ile172Asn, that account for more than 50% of the alleles of this patient’s cohort. All variants were already described except a novel missense variant identified in a salt-wasting patient, g.1173T>C(p.Trp201Arg). The rare variant p.Gly424Ser which was detected in one patient had been previously associated with a possible founder effect in Brazil and the splicing variant g.391G>A, only described in the Portuguese population. Conclusion: Our study provides a detailed clinical and molecular characterization of a large cohort of CAH Portuguese patients. The overall concordance between the clinical phenotype and the inferred phenotype (based on genotype) was 90%.info:eu-repo/semantics/publishedVersio

INCIDÊNCIA DE CONSUMO DE BEBIDA ALCOÓLICA ENTRE AS VÍTIMAS DE SUICÍDIO NO DISTRITO FEDERAL

Suicide is motivated by multiple causes, and the abusive consumption of alcoholic beverages can be an important sign that individuals do not have physical and emotional control of themselves. To estimate the incidence of alcohol consumption, immediately before suicide, among people who died in 2018 in the Brazilian Federal District. This is a population-based study, of a descriptive and exploratory nature, of all deaths which occurred in the Brazilian Federal District from January 1 to December 31, 2018. Data were collected from the Mortality Information System and Police reports. The incidence and respective 95% confidence intervals were calculated. This study was approved by the Research Ethics Committee. The incidence of alcohol consumption just before the suicide was 18.6% (CI 95%: 18.56% to 18.62%). Males, blacks, trade workers, those without a partner, young people, and individuals with less than 8 years of study had the highest indicators. There was a greater percentage of alcohol consumption in the fall/winter, at the end of the month, in rural areas, in people who had never attempted suicide before and when the modus operandi was choking or hanging. The consumption of drugs, such as methamphetamine, ecstasy, amphetamine, and cannabis, was observed together with alcoholic beverages. The results of this research signaled an important public health problem, which is the use of alcohol to potentially encourage suicide. Effective public policies to tackle the abusive consumption of alcoholic beverages and suicide are necessary.O suicídio é motivado por múltiplas causas e o consumo abusivo de bebidas alcoólicas pode ser um sinal importante de que os indivíduos não têm controle físico e emocional de si mesmos. Estimar a incidência do consumo de álcool, imediatamente antes do suicídio, entre as pessoas que morreram em 2018 no Distrito Federal. Trata-se de um estudo de base populacional, de caráter descritivo e exploratório, de todos os óbitos ocorridos no Distrito Federal de 1º de janeiro a 31 de dezembro de 2018. Os dados foram coletados do Sistema de Informações sobre Mortalidade e relatórios policiais. Foram calculados os intervalos de confiança de 95%. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa. A incidência de consumo de álcool pouco antes do suicídio foi de 18,6% (IC 95%: 18,56% a 18,62%). Homens, negros, trabalhadores do comércio, aqueles sem parceiro, jovens e indivíduos com menos de 8 anos de estudo apresentaram os maiores indicadores. Houve maior percentual de consumo de álcool no outono/inverno, no final do mês, em áreas rurais, em pessoas que nunca haviam tentado suicídio antes e quando o modus operandi estava engasgando ou pendurado. O consumo de drogas, como metanfetamina, ecstasy, anfetamina e cannabis, foi observado juntamente com bebidas alcoólicas. Os resultados desta pesquisa sinalizaram um importante problema de saúde pública, que é o uso de álcool para potencialmente incentivar o suicídio. São necessárias políticas públicas eficazes para enfrentar o consumo abusivo de bebidas alcoólicas e o suicídio.El suicidio está motivado por múltiples causas, y el consumo abusivo de bebidas alcohólicas puede ser una señal importante de que las personas no tienen control físico y emocional de sí mismos. Estimar la incidencia del consumo de alcohol, inmediatamente antes del suicidio, entre las personas que murieron en 2018 en el Distrito Federal de Brasil. Se trata de un estudio poblacional, de carácter descriptivo y exploratorio, de todas las muertes ocurridas en el Distrito Federal de Brasil del 1 de enero al 31 de diciembre de 2018. Los datos se recopilaron del Sistema de Información de Mortalidad y de los informes de la Policía. Se calcularon la incidencia y los respectivos intervalos de confianza del 95%. Este estudio fue aprobado por el Comité de ética de la investigación. La incidencia del consumo de alcohol justo antes del suicidio fue del 18,6% (CI 95%: 18,56% a 18,62%). Los hombres, los negros, los trabajadores del comercio, los que no tienen pareja, los jóvenes y los individuos con menos de 8 años de estudio tenían los indicadores más altos. Había un mayor porcentaje de consumo de alcohol en otoño/invierno, a finales de mes, en las zonas rurales, en personas que nunca habían intentado suicidarse antes y cuando el modus operandi se estaba asfixiando o ahorcando. El consumo de drogas, como la metanfetamina, el éxtasis, la anfetamina y el cannabis, se observó junto con las bebidas alcohólicas. Los resultados de esta investigación indicaron un importante problema de salud pública, que es el uso del alcohol para fomentar potencialmente el suicidio. Las políticas públicas eficaces para hacer frente al consumo abusivo de bebidas alcohólicas y el suicidio so

INCIDÊNCIA DE CONSUMO DE BEBIDA ALCOÓLICA ENTRE AS VÍTIMAS DE SUICÍDIO NO DISTRITO FEDERAL

Suicide is motivated by multiple causes, and the abusive consumption of alcoholic beverages can be an important sign that individuals do not have physical and emotional control of themselves. To estimate the incidence of alcohol consumption, immediately before suicide, among people who died in 2018 in the Brazilian Federal District. This is a population-based study, of a descriptive and exploratory nature, of all deaths which occurred in the Brazilian Federal District from January 1 to December 31, 2018. Data were collected from the Mortality Information System and Police reports. The incidence and respective 95% confidence intervals were calculated. This study was approved by the Research Ethics Committee. The incidence of alcohol consumption just before the suicide was 18.6% (CI 95%: 18.56% to 18.62%). Males, blacks, trade workers, those without a partner, young people, and individuals with less than 8 years of study had the highest indicators. There was a greater percentage of alcohol consumption in the fall/winter, at the end of the month, in rural areas, in people who had never attempted suicide before and when the modus operandi was choking or hanging. The consumption of drugs, such as methamphetamine, ecstasy, amphetamine, and cannabis, was observed together with alcoholic beverages. The results of this research signaled an important public health problem, which is the use of alcohol to potentially encourage suicide. Effective public policies to tackle the abusive consumption of alcoholic beverages and suicide are necessary.O suicídio é motivado por múltiplas causas e o consumo abusivo de bebidas alcoólicas pode ser um sinal importante de que os indivíduos não têm controle físico e emocional de si mesmos. Estimar a incidência do consumo de álcool, imediatamente antes do suicídio, entre as pessoas que morreram em 2018 no Distrito Federal. Trata-se de um estudo de base populacional, de caráter descritivo e exploratório, de todos os óbitos ocorridos no Distrito Federal de 1º de janeiro a 31 de dezembro de 2018. Os dados foram coletados do Sistema de Informações sobre Mortalidade e relatórios policiais. Foram calculados os intervalos de confiança de 95%. Este estudo foi aprovado pelo Comitê de Ética em Pesquisa. A incidência de consumo de álcool pouco antes do suicídio foi de 18,6% (IC 95%: 18,56% a 18,62%). Homens, negros, trabalhadores do comércio, aqueles sem parceiro, jovens e indivíduos com menos de 8 anos de estudo apresentaram os maiores indicadores. Houve maior percentual de consumo de álcool no outono/inverno, no final do mês, em áreas rurais, em pessoas que nunca haviam tentado suicídio antes e quando o modus operandi estava engasgando ou pendurado. O consumo de drogas, como metanfetamina, ecstasy, anfetamina e cannabis, foi observado juntamente com bebidas alcoólicas. Os resultados desta pesquisa sinalizaram um importante problema de saúde pública, que é o uso de álcool para potencialmente incentivar o suicídio. São necessárias políticas públicas eficazes para enfrentar o consumo abusivo de bebidas alcoólicas e o suicídio.El suicidio está motivado por múltiples causas, y el consumo abusivo de bebidas alcohólicas puede ser una señal importante de que las personas no tienen control físico y emocional de sí mismos. Estimar la incidencia del consumo de alcohol, inmediatamente antes del suicidio, entre las personas que murieron en 2018 en el Distrito Federal de Brasil. Se trata de un estudio poblacional, de carácter descriptivo y exploratorio, de todas las muertes ocurridas en el Distrito Federal de Brasil del 1 de enero al 31 de diciembre de 2018. Los datos se recopilaron del Sistema de Información de Mortalidad y de los informes de la Policía. Se calcularon la incidencia y los respectivos intervalos de confianza del 95%. Este estudio fue aprobado por el Comité de ética de la investigación. La incidencia del consumo de alcohol justo antes del suicidio fue del 18,6% (CI 95%: 18,56% a 18,62%). Los hombres, los negros, los trabajadores del comercio, los que no tienen pareja, los jóvenes y los individuos con menos de 8 años de estudio tenían los indicadores más altos. Había un mayor porcentaje de consumo de alcohol en otoño/invierno, a finales de mes, en las zonas rurales, en personas que nunca habían intentado suicidarse antes y cuando el modus operandi se estaba asfixiando o ahorcando. El consumo de drogas, como la metanfetamina, el éxtasis, la anfetamina y el cannabis, se observó junto con las bebidas alcohólicas. Los resultados de esta investigación indicaron un importante problema de salud pública, que es el uso del alcohol para fomentar potencialmente el suicidio. Las políticas públicas eficaces para hacer frente al consumo abusivo de bebidas alcohólicas y el suicidio so

Avaliação ultrassonográfica de variações anatômicas entre vasos femorais realizada por estudantes de medicina

Introduction: Central vein puncture is a medical procedure traditionally done following anatomical landmarks as a reference to successfully achieving the vessel. However, this traditional technique is commonly unsuccessful due to anatomical variations that may be found. Point of care ultrasonography (POC-US) is used to assist central catheterization by directly visualizing the vessel, increasing procedure security and minimizing risks. Objectives: Evaluate anatomical variations prevalence in femoral vessels, utilizing POC-US, done by medical students submitted to a short period of time training in ultrasonography. Methods: Five medical students, without previous experience on the use of ultrasonography, were submitted to an eight-hour theorical practical training in POC-US. The students evaluated one hundred femoral vessels of volunteers. Results: The right limb femoral vein was found more frequently in the medial position (43%) in comparison to the right limb femoral artery. On the left limb, the posteromedial position was the most found (45%). Conclusion: The insertion of a central catheter following the traditional technique is based on anatomical landmarks, and does not take into account existing anatomical variations. With a short period of training, POC-US is capable of qualifying professionals to acknowledge the real location of the vessel and avoid inadvertent punctures and complications.Introdução: A punção venosa central é um procedimento médico tradicionalmente realizado seguindo os marcadores anatômicos como referência para atingir o vaso, às cegas. No entanto, nem sempre o sucesso nessa técnica é alcançado, fato que se deve principalmente às variações anatômicas. A ultrassonografia point of care (US-POC) é utilizada para auxiliar a cateterização central por visualização direta do vaso, aumentando a segurança do procedimento. Objetivo: Avaliar a prevalência das variações anatômicas de vasos femorais através da utilização da US-POC por estudantes de medicina submetidos a curto período de treinamento. Materiais e Métodos: Cinco estudantes de medicina, sem experiência prévia em US-POC, foram submetidos a oito horas de treinamento teórico-prático. Foram avaliados os vasos femorais de cem voluntários. Resultados: A veia femoral direita foi encontrada mais frequentemente na posição medial (43%) em relação à artéria femoral direita. À esquerda, a posição posteromedial foi a mais observada (45%). Conclusão: A técnica tradicional de punção de acesso central se baseia em marcadores anatômicos e não leva em consideração as variações anatômicas existentes. Um treinamento de curto período para uso da US-POC é capaz de capacitar o profissional para reconhecer o posicionamento real dos vasos e evitar punções inadvertidas

Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production

Genetic diversity of Mycobacterium tuberculosis affects immune responses and clinical outcomes of tuberculosis (TB). However, how bacterial diversity orchestrates immune responses to direct distinct TB severities is unknown. Here we study 681 patients with pulmonary TB and show that M. tuberculosis isolates from cases with mild disease consistently induce robust cytokine responses in macrophages across multiple donors. By contrast, bacteria from patients with severe TB do not do so. Secretion of IL-1β is a good surrogate of the differences observed, and thus to classify strains as probable drivers of different TB severities. Furthermore, we demonstrate that M. tuberculosis isolates that induce low levels of IL-1β production can evade macrophage cytosolic surveillance systems, including cGAS and the inflammasome. Isolates exhibiting this evasion strategy carry candidate mutations, generating sigA recognition boxes or affecting components of the ESX-1 secretion system. Therefore, we provide evidence that M. tuberculosis strains manipulate host-pathogen interactions to drive variable TB severities

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Ageing and dementia in low and middle income countries - Using research to engage with public and policy makers

Abstract While two thirds of the 24 million people with dementia worldwide live in low and middle income countries, very little research has been conducted to support policy making in these regions. Among the non-communicable diseases, dementia (in common with other chronic NCDs linked more to long-term disability than to mortality) has been relatively under-prioritized. International agreements, plans and policy guidelines have called for an end to ageist discrimination and a focus upon reducing disadvantage arising from poverty and the consequences of ill health. Social protection, access to good quality age-appropriate healthcare and addressing the problem of disability are all key issues. However, as yet, little progress has been made in addressing these concerns. In this review we outline the current international policy agenda for older individuals, and its specific relevance to those with dementia and other disabling non-communicable diseases. We consider the potential for epidemiological research to raise awareness, refine the policy agenda, and promote action, using the example of the dissemination strategy developed by the 10/66 Dementia Research Group

A picture of medically assisted reproduction activities during the COVID-19 pandemic in Europe

STUDY QUESTION: How did coronavirus disease 2019 (COVID-19) impact on medically assisted reproduction (MAR) services in Europe during the COVID-19 pandemic (March to May 2020)? SUMMARY ANSWER: MAR services, and hence treatments for infertile couples, were stopped in most European countries for a mean of 7 weeks. WHAT IS KNOWN ALREADY: With the outbreak of COVID-19 in Europe, non-urgent medical care was reduced by local authorities to preserve health resources and maintain social distancing. Furthermore, ESHRE and other societies recommended to postpone ART pregnancies as of 14 March 2020. STUDY DESIGN, SIZE, DURATION: A structured questionnaire was distributed in April among the ESHRE Committee of National Representatives, followed by further information collection through email. PARTICIPANTS/MATERIALS, SETTING, METHODS: The information was collected through the questionnaire and afterwards summarised and aligned with data from the European Centre for Disease Control on the number of COVID-19 cases per country. MAIN RESULTS AND THE ROLE OF CHANCE: By aligning the data for each country with respective epidemiological data, we show a large variation in the time and the phase in the epidemic in the curve when MAR/ART treatments were suspended and restarted. Similarly, the duration of interruption varied. Fertility preservation treatments and patient supportive care for patients remained available during the pandemic. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Data collection was prone to misinterpretation of the questions and replies, and required further follow-up to check the accuracy. Some representatives reported that they, themselves, were not always aware of the situation throughout the country or reported difficulties with providing single generalised replies, for instance when there were regional differences within their country. WIDER IMPLICATIONS OF THE FINDINGS: The current article provides a basis for further research of the different strategies developed in response to the COVID-19 crisis. Such conclusions will be invaluable for health authorities and healthcare professionals with respect to future similar situations.peer-reviewe

O impacto da pandemia de COVID-19 na população indígena: uma análise científica

A pandemia de COVID-19, desencadeada pelo coronavírus SARS-CoV-2, tem sido um desafio global, afetando diversas comunidades, com destaque para as populações indígenas, historicamente marginalizadas e vulneráveis devido a desigualdades estruturais. O presente artigo trata-se de uma pesquisa bibliográfica, através de uma revisão integrativa da literatura. A análise epidemiológica revela que fatores como superlotação em moradias, falta de acesso a água potável e saneamento básico, além de altas taxas de comorbidades, contribuem para a propagação e impactos severos da doença nessas comunidades. A falta de acesso a serviços de saúde adequados é agravada pela escassez de infraestrutura e profissionais de saúde em áreas remotas, somada a barreiras linguísticas e culturais. Apesar dos desafios, as populações indígenas têm demonstrado resiliência, implementando medidas proativas de prevenção, promovendo solidariedade comunitária e preservando práticas tradicionais de cura. Estratégias de longo prazo incluem a diversificação econômica e o fortalecimento dos sistemas de saúde indígenas. A conclusão ressalta a importância de reconhecer e valorizar os conhecimentos e direitos das comunidades indígenas, promovendo ações colaborativas para construir sociedades mais inclusivas e resilientes

Uso de telas pela população pediátrica e seus impactos oftalmológicos a curto e a longo prazo: uma revisão sistemática : Use of screens by the pediatric population and its short and long-term ophthalmological impacts: a systematic review

Ao se discorrer sobre a formação e formatação da nossa sociedade, pode-se notar que cada vez mais esta está permeada pela tecnologia e pelos sistemas integrativos, processo esse benéfico para comunicação, gestão e tomada de decisões para além de ser uma ferramenta de trabalho e entretenimento, porém, com a progressiva quantidade de horas que ficamos expostos a este tipo de tecnologia também podem acarretar prejuízos a acuidade visual dos usuários. Juntamente a isso, nota-se que as crianças estão tendo cada vez mais precocemente acesso os equipamentos eletrônicos e deixando de lado as brincadeiras, desta forma a partir de uma pesquisa qualitativa, feita a partir de um levantamento bibliográfico, pode-se dispor que esta busca compreender quais são os sintomas e efeitos do uso excessivo deste tipo de ferramenta e algumas formas de tratamento e profilaxia que podem ser dispostas sobre o tema, com enfoque na população pediátrica