66 research outputs found

    Antibody levels following vaccination against SARS-CoV-2: associations with post-vaccination infection and risk factors

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    SARS-CoV-2 antibody levels can be used to assess humoral immune responses following SARS-CoV-2 infection or vaccination, and may predict risk of future infection. From cross-sectional antibody testing of 9,361 individuals from TwinsUK and ALSPAC UK population-based longitudinal studies (jointly in April-May 2021, and TwinsUK only in November 2021-January 2022), we tested associations between antibody levels following vaccination and: (1) SARS-CoV-2 infection following vaccination(s); (2) health, socio-demographic, SARS-CoV-2 infection and SARS-CoV-2 vaccination variables. Within TwinsUK, single-vaccinated individuals with the lowest 20% of anti-Spike antibody levels at initial testing had 3-fold greater odds of SARS-CoV-2 infection over the next six to nine months, compared to the top 20%. In TwinsUK and ALSPAC, individuals identified as at increased risk of COVID-19 complication through the UK "Shielded Patient List" had consistently greater odds (2 to 4-fold) of having antibody levels in the lowest 10%. Third vaccination increased absolute antibody levels for almost all individuals, and reduced relative disparities compared with earlier vaccinations. These findings quantify the association between antibody level and risk of subsequent infection, and support a policy of triple vaccination for the generation of protective antibodies

    Association between anthropometry and lifestyle factors and risk of B cell lymphoma: an exposome wide analysis.

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    To better understand the role of individual and lifestyle factors in human disease, an exposome-wide association study was performed to investigate within a single study anthropometry measures and lifestyle factors previously associated with B-cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2,402 incident BCL cases were diagnosed from 475,426 participants that were followed-up on average 14 years. Standard and penalized Cox regression models as well as principal component (PC) analysis were used to evaluate 84 exposures in relation to BCL risk. Standard and penalized Cox regression models showed a positive association between anthropometric measures and BCL and multiple myeloma/plasma cell neoplasm (MM). The penalized Cox models additionally showed the association between several exposures from categories of physical activity, smoking status, medical history, socioeconomic position, and diet and BCL and/or the subtypes. PC analyses confirmed the individual associations but also showed additional observations. The PC5 including anthropometry, was positively associated with BCL, diffuse large B-cell lymphoma (DLBCL), and MM. There was a significant positive association between consumption of sugar and confectionary (PC11) and follicular lymphoma risk, and an inverse association between fish and shellfish and Vitamin D (PC15) and DLBCL risk. The PC1 including features of the Mediterranean diet and diet with lower inflammatory score showed an inverse association with BCL risk, while the PC7, including dairy, was positively associated with BCL and DLBCL risk. Physical activity (PC10) was positively associated with DLBCL risk among women. This study provided informative insights on the etiology of BCL

    The Cardiac Transcription Network Modulated by Gata4, Mef2a, Nkx2.5, Srf, Histone Modifications, and MicroRNAs

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    The transcriptome, as the pool of all transcribed elements in a given cell, is regulated by the interaction between different molecular levels, involving epigenetic, transcriptional, and post-transcriptional mechanisms. However, many previous studies investigated each of these levels individually, and little is known about their interdependency. We present a systems biology study integrating mRNA profiles with DNA–binding events of key cardiac transcription factors (Gata4, Mef2a, Nkx2.5, and Srf), activating histone modifications (H3ac, H4ac, H3K4me2, and H3K4me3), and microRNA profiles obtained in wild-type and RNAi–mediated knockdown. Finally, we confirmed conclusions primarily obtained in cardiomyocyte cell culture in a time-course of cardiac maturation in mouse around birth. We provide insights into the combinatorial regulation by cardiac transcription factors and show that they can partially compensate each other's function. Genes regulated by multiple transcription factors are less likely differentially expressed in RNAi knockdown of one respective factor. In addition to the analysis of the individual transcription factors, we found that histone 3 acetylation correlates with Srf- and Gata4-dependent gene expression and is complementarily reduced in cardiac Srf knockdown. Further, we found that altered microRNA expression in Srf knockdown potentially explains up to 45% of indirect mRNA targets. Considering all three levels of regulation, we present an Srf-centered transcription network providing on a single-gene level insights into the regulatory circuits establishing respective mRNA profiles. In summary, we show the combinatorial contribution of four DNA–binding transcription factors in regulating the cardiac transcriptome and provide evidence that histone modifications and microRNAs modulate their functional consequence. This opens a new perspective to understand heart development and the complexity cardiovascular disorders

    Ações de Prevenção da Deficiência Mental, dirigidas a Gestantes e Recém-Nascidos, no âmbito da Saúde Pública da Grande Vitória-ES

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    The accomplishment of prevention in Public Health requires a systematized knowledge for the proposition of a program and its evaluation. When it comes to the prevention of Mental Deficiency, which afflicts around 10% of the population, little is known in Brazil. By adopting a methodology for cataloging MD preventive actions in hospitals and health units, with pregnant women and newborns, it was possible to describe and analyze the actions of the public health system in Greater Vitoria/ES, indicating the levels of prevention which were most covered. Preventive actions (PA) of five large public hospitals, nine health units and six health offices, from 1996 to 1997 were studied. Data from 25 interviews show that these places made 51.5% of the 433 possible PA (57.4% of primary prevention and 45.5% of the secondary). Along with the particularization of the action of each municipality and place researched, the obtained data was useful for analyses and possible changes in maternal-infantile health indicators.Faire de la prévention dans la santé publique est conditionné par une très bonne connaissance afin de proposer des programmes et les évaluer. Au Brésil, on sait peu de choses sur la prévention de la déficience mentale, qui atteint pourtant 10 % de la population. Adoptant une méthodologie et pour faire un catalogue des actions préventives de déficience mentale dans les hôpitaux et les unités de santé, pour les femmes enceintes et les nouveau-nés, on a pu décrire et analyser les actions de santé publique dans la ville de Grande Vitoria (État du Espirito Santo), indiquant le niveau de prévention les plus couverts. On a regroupé les actions de prévention de cinq hôpitaux publics importants, neuf (31 %) unités de santé et six bureaux centralisateurs, entre 1996 et 97. Les données de vingt-cinq entrevues montrent que ces locaux réalisent 51,5 % des 433 actions de prévention possibles (57,4 % de prévention primaire et 45,5 % de secondaire). En détaillant les réalisations de chaque municipalité et local étudié, les chiffres fournissent des ressources pour des analyses et les modifications possibles dans les indicateurs de santé maternelle et infantile.Fazer prevenção em Saúde Pública implica em conhecimento sistematizado para a proposição de programas e sua avaliação. Quanto à prevenção de Deficiência Mental, que atinge cerca de 10% da população, pouco se conhece no país. Adotando uma metodologia para levantamento de ações preventivas de DM em hospitais e unidades de saúde, junto a gestantes e recém-nascidos, fo i possível descrever e analisar a atuação da rede pública de saúde da Grande Vitória/ES, indicando os níveis de prevenção mais atendidos. Foram levantadas as ações de prevenção (AP) de cinco hospitais públicos de grande porte, nove (31%) unidades de saúde e seis secretarias de saúde, entre 1996-97. Os dados de 25 entrevistas mostram que esses locais realizavam 51,5% das 433 AP possíveis (57,4% da prevenção primária e 45,5% da secundária). Particularizando a atuação de cada município e local pesquisado, os dados fornecem subsídios para análises e possíveis mudanças nos indicadores de saúde materno-infantil

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