Incidence of and causes for all-cause hospitalizations in patients with atrial fibrillation

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in clinical practice, and its prevalence is expected to further increase in the future. AF patients not only have a high number of comorbidities, but they also have an increased risk of hospital admissions compared to individuals without AF. Nevertheless, predicting hospital admission risk among patients with AF remains difficult, and possible preventive strategies unclear. Based on these gaps in knowledge, the overall goal of this PhD thesis was to investigate the incidence of and causes for all-cause hospital admission in patients with AF. The specific aims were (1) to perform a systematic review and meta-analysis summarizing the current evidence of the incidence of and associated risk factors for hospital admissions in AF patients; (2) to identify risk factors for hospital admissions in our own cohorts and subsequently use this knowledge to develop and validate a risk score for predicting hospital admissions; (3) to identify psychosocial factors associated with hospital admissions in patients with AF. Methods: For the meta-analysis, we performed a comprehensive literature search in PubMed, EMBASE and CENTRAL, and pooled incidence rates for hospital admissions using random-effects models. Factors associated with observed between-study heterogeneity were identified using meta-regression analysis. For the second and third study, we used data of two ongoing, prospective observational cohort studies, the Basel Atrial Fibrillation Cohort Study (BEAT-AF) and the Swiss Atrial Fibrillation Cohort Study (Swiss-AF) in which 3,968 patients with diagnosed AF were enrolled. Unplanned hospital admissions were defined as any unpredicted admission leading to at least one overnight stay. For the second study, we used the Swiss-AF data set as the derivation cohort and performed a variable selection using the least absolute shrinkage and selection operator (LASSO) method. Multivariable adjusted Cox regression analyses were performed to assess the effect of the selected variables on all-cause hospitalization. Based on regression coefficients we constructed a risk score and subsequently validated the score in the external validation cohort (BEAT-AF). For the third study, we used psychosocial factors, such as marital status, education, level of depression and health perception, and investigated their effects on risk of hospital admission. Cox regression analyses adjusted for conventional risk factors for hospital admission were performed to calculate hazard ratio (HR). Results: We included 35 studies of 311’314 AF patients in the meta-analysis. The pooled incidence of all-cause hospital admissions was 43.7 per 100 person-years. AF patients were more often admitted for cardiovascular causes (26.3 per 100 person-years), but the risk of non-cardiovascular hospitalizations was substantial (15.7 per 100 person-years). Associated factors for hospital admission were older age, longer follow-up time and prevalent chronic pulmonary disease or cancer. In the second study we found that the most important predictors for all-cause hospital admission were age (75-79 years: adjusted hazard ratio [aHR], 1.33; 95% confidence interval [95% CI], 1.00-1.77; 80-84 years: aHR, 1.51; 95% CI, 1.12-2.03; 85 years: aHR, 1.88; 95% CI, 1.35-2.61), prior pulmonary vein isolation (aHR, 0.74; 95% CI, 0.60-0.90), hypertension (aHR, 1.16; 95% CI, 0.99-1.36), diabetes (aHR, 1.38; 95% CI, 1.17-1.62), coronary heart disease (aHR, 1.18; 95% CI, 1.02-1.37), prior stroke/TIA (aHR, 1.28; 95% CI, 1.10-1.50), heart failure (aHR, 1.21; 95% CI, 1.04-1.41), peripheral artery disease (aHR, 1.31; 95% CI, 1.06-1.63), cancer (aHR, 1.33; 95% CI, 1.13-1.57), renal failure (aHR, 1.18, 95% CI, 1.01-1.38), and previous falls (aHR, 1.44; 95% CI, 1.16-1.78). A risk score with these variables was well calibrated, and achieved a C statistic of 0.64 (95% CI, 0.61-0.66) in the derivation and 0.59 (95% CI, 0.56-0.63) in the external validation cohort. In the third study including patients from Swiss-AF, 1582 (67.1%) were married, 156 (6.6%) were single, 287 (12.2%) were divorced, and 333 (14.1%) were widowed. Two hundred and seventy six patients (11.7%) had at most a primary education, 1171 (49.7) had secondary education, and 911 (38.6%) had a college or university degree. Depression or depressive symptoms was present in 99 (4.2%) patients. Median health perception was 75 (interquartile range [IQR], 60-85) on a scale ranging from 0-100, with higher scores indicated better health perception. The highest risk of all-cause hospital admission was observed in single (aHR, 1.35; 95% CI, 1.05-1.75) or divorced patients (aHR, 1.26; 95% CI, 1.03-1.54), and in those who reported low health perception (aHR for <75 points, 1.40; 95% CI, 1.21-1.61). Conclusions: The overall incidence of hospital admissions in patients with AF is high. The risk of hospital admissions is related to multiple cardiovascular and non-cardiovascular risk factors, including several psychosocial factors and subjective health perception. Outlook: Given the high risk among AF patients of being admitted to the hospital and the high burden of associated risk factors, new multidisciplinary preventive strategies are needed with the goal to reduce hospital admissions, unfavorable patient outcomes and healthcare costs

Genomic insights into early-onset obesity

The biological causes of childhood obesity are complex. Environmental factors, such as massive marketing campaigns for food leading to over-nutrition and snacking and the decline in physical activity, have undoubtedly contributed to the increased prevalence of overweight and obesity in children, but these cannot be considered as the only causes. Susceptibility to obesity is also determined to a great extent by genetic factors. Furthermore, molecular mechanisms involved in the regulation of gene expression, such as epigenetic mechanisms, can increase the risk of developing early-onset obesity. There is evidence that early-onset obesity is a heritable disorder, and a range of genetic factors have recently been shown to cause monogenic, syndromic and polygenic forms of obesity, in some cases interacting with environmental exposures. Modifications of the transcriptome can lead to increased adiposity, and the gut microbiome has recently been shown to be key to the genesis of obesity. These new genomic discoveries complement previous knowledge on the development of early-onset obesity and provide new perspectives for research on the complex molecular and physiological mechanisms involved in this disease. Personalized preventive strategies and genomic medicine may become possible in the near future

ENPP1, premier exemple d’un déterminant génétique commun à l’obésité et au diabète de type 2

L’obésité, en particulier ses formes sévères, est l’un des principaux facteurs de risque de diabète de type 2. Par ailleurs, l’explosion de l’épidémie d’obésité infantile s’accompagne de l’apparition de formes précoces de diabète de type 2, avec un syndrome métabolique et une intolérance au glucose détectables dès l’adolescence. Ces données suggèrent l’existence de déterminants moléculaires primitifs communs entre obésité sévère et précoce et diabète de type 2, qui partageraient une insulinorésistance génétiquement déterminée. Dans ce contexte, l’identification, sur la région chromosomique 6q liée à la « diabésité », du gène ENPP1 codant pour un inhibiteur du récepteur de l’insuline, dont des variants codants et non codants contribuent au risque génétique de cette affection, est un pas vers la dissection génétique des obésités les plus diabétogènes. Ces résultats ouvrent des perspectives nouvelles vers le profilage génétique et biologique des adolescents obèses, dans une optique de prévention et de traitement de la « diabésité » et de ses complications vasculaires.Clinical studies have established the strong link between obesity and type 2 diabetes, especially in children, where the rising prevalence of childhood severe obesity has preceded the recent emergence of early-onset forms of “diabesity”. These data suggested a common genetic background shared by both conditions, which was also supported by the identification by genome scans of several diabesity chromosomal regions of linkage. The genetic investigation of early-onset form of familial obesity linkage to chromosome 6q led to the identification of ENPP1, an inhibitor of the insulin receptor, as a possible molecular mechanism behind both obesity and type 2 diabetes. Analysis of the DNA variations of ENPP1 in 6,147 subjects showed association between a combination of variants and both childhood obesity, morbid or moderate obesity in adults and also with type 2 diabetes. This study provides a first molecular basis for the physiopathologic association between severe insulin resistance and obesity, and further type 2 diabetes, and offers a new perspective for prevention and treatment of these conditions

Liberando a Vuyazi: oralidad y subjetividad femenina en la ficción de Paulina Chiziane

Oral stories often maintain societal structures through the teaching of cultural norms. By bringing oral stories into her written text, Chiziane positions the elders as the resources of the village, the pillars, and the center of a fragmented world where things have started to change. As sites of memory, elder women establish a balance when the community needs to face modernity. However, as Chiziane deconstructs oral tales, she also subverts the colonial language. Here, I examine how the author utilizes a feminist and Africanist aesthetics, through oral tales, myths and proverbs often told by elder women, to reinvent the Portuguese language and literature while subverting myths and legends which reinforce gender hierarchies.Las historias orales mantienen a menudo las estructuras sociales, a través de la enseñanza de normas culturales. Al incorporar historias orales en su obra escrita, Chiziane sitúa a los mayores como recursos de la aldea, como pilares y centro de un mundo fragmentado en el que las cosas han empezado a cambiar. Como sedes de la memoria, las mujeres mayores aportan un equilibrio cuando la comunidad necesita afrontar la modernidad. Sin embargo, al tiempo que Chiziane deconstruye los cuentos orales, subvierte igualmente la lengua colonial. En este trabajo examino cómo la autora recurre a una estética feminista y africanista, a través de cuentos, mitos y proverbios orales, frecuentemente transmitidos por mujeres mayores, para reinventar la lengua portuguesa, al tiempo que subvierte los mitos y leyendas que refuerzan las jerarquías de género

Molecular Basis of Obesity: Current Status and Future Prospects

Obesity is a global health problem that is gradually affecting each continent of the world. Obesity is a heterogeneous disorder, and the biological causes of obesity are complex. The rapid increase in obesity prevalence during the past few decades is due to major societal changes (sedentary lifestyle, over-nutrition) but who becomes obese at the individual level is determined to a great extent by genetic susceptibility. In this review, we evidence that obesity is a strongly heritable disorder, and provide an update on the molecular basis of obesity. To date, nine loci have been involved in Mendelian forms of obesity and 58 loci contribute to polygenic obesity, and rare and common structural variants have been reliably associated with obesity. Most of the obesity genes remain to be discovered, but promising technologies, methodologies and the use of “deep phenotyping” lead to optimism to chip away at the ‘missing heritability’ of obesity in the near future. In the longer term, the genetic dissection of obesity will help to characterize disease mechanisms, provide new targets for drug design, and lead to an early diagnosis, treatment, and prevention of obesity

Genetics of Obesity: What have we Learned?

Candidate gene and genome-wide association studies have led to the discovery of nine loci involved in Mendelian forms of obesity and 58 loci contributing to polygenic obesity. These loci explain a small fraction of the heritability for obesity and many genes remain to be discovered. However, efforts in obesity gene identification greatly modified our understanding of this disorder. In this review, we propose an overlook of major lessons learned from 15 years of research in the field of genetics and obesity. We comment on the existence of the genetic continuum between monogenic and polygenic forms of obesity that pinpoints the role of genes involved in the central regulation of food intake and genetic predisposition to obesity. We explain how the identification of novel obesity predisposing genes has clarified unsuspected biological pathways involved in the control of energy balance that have helped to understand past human history and to explore causality in epidemiology. We provide evidence that obesity predisposing genes interact with the environment and influence the response to treatment relevant to disease prediction

Demographic, clinical and functional profile of elderly participants and non-participants in community activities of church

INTRODUÇÃO: Atividades sociais e comunitárias são referidas na literatura científica como estratégias para promoção de saúde e de qualidade de vida no envelhecimento. OBJETIVO: Traçar e comparar o perfil demográfico, clínico e funcional de idosas participantes e não-participantes de atividades comunitárias ligadas à igreja. Métodos: Dezenove idosas, sendo 10 participantes e 9 não-participantes de atividades ligadas à igreja, submeteram-se à avaliação sócio-demográfica, cognitiva (Mini-Exame do Estado Mental) e funcional (Timed Get Up and Go e Short Physical Performance Battery). RESULTADOS: As idosas participantes destas atividades apresentaram um tempo médio de atuação de 23,62 anos. Essas idosas apresentaram idade menor, mais anos de estudo, melhor desempenho cognitivo, menor prevalência de doenças auto-relatadas, de quedas e de medo de cair, e melhor desempenho funcional quando comparadas às não-participantes. Observou-se correlação significativa entre anos de participação nas atividades com a idade (r=-0,579) e com o desempenho cognitivo (r=0,467). CONCLUSÃO: As idosas participantes de atividades ligadas à igreja apresentaram perfil mais favorável ao envelhecimento ativo, incluindo melhor desempenho cognitivo e funcional, quando comparadas às não-participantes. A participação nessas atividades parece ser benéfica para manutenção da capacidade funcional para o envelhecimento ativo e saudável, e, desta forma, deve ser incentivada para complementar os programas de promoção de saúde e prevenção de doenças. ___________________________________________________________________________________________________________ABSTRACTINTRODUCTION: the social and community activities are referred in scientific literature as strategies to promote health and quality of life during aging. Objective: To describe and compare the demographic, clinical and functional status of participants and non-participants elderly in community activities of the church. METHODS: Nineteen elderly, being 10 participants and 9 non-participants in church activities, underwent socio-demographic, cognitive (Mini-Mental State Examination) and functional (Timed Get Up and Go and Short Physical Performance Battery) assessment. RESULTS: The elderly participants in these activities had an average time of 23.62 years of activity. These elderly were younger age, more years of education, better cognitive performance, lower prevalence of self-reported falls and fear of falling, and better functional performance when compared to non-participants. There was a significant correlation between years of participation in activities with age (r=-0.579) and with cognitive performance (r=0.467). Conclusion: The elderly participants in church activities showed clinical and demographic profile more favorable for active aging and better cognitive and functional performance when compared to non-participants. Participation in these activities seems to be beneficial for maintaining the functional capacity, to have active and healthy aging, and thins this way should be encouraged to complement the programs of health promotion and disease prevention

O depósito de Au-Ag-barita Zacarias, Orógeno Brasília, Brasil Central : mineralização vulcanogênica Toniana associada ao Arco Magmático Goiás

Dissertação (mestrado) — Universidade de Brasília, Instituto de Geociências, Programa de Pós-Graduação em Geologia, 2022.O depósito de Au-Ag-barita Zacarias (com reserva total em 650.000 t a 4,4 g/t Au, 48 g/t Ag e 10% de barita) é definido por mineralização de sulfetos vulcanogênica rica em ouro (Au-VMS) hospedada em rochas neoproterozoicas da sequência meta-vulcanossedimentar Mara Rosa, Arco Magmático Goiás, Brasil Central. Esse depósito faz parte de um importante orógeno acrescionário com evolução tectônica entre ca. 900 e 600 Ma durante a orogenia Brasiliana-Pan Africana. Neste trabalho, apresentamos um quadro detalhado da geologia do depósito bem como informações da química mineral de filossilicatos e da geoquímica isotópica de enxofre, além da geocronologia U-P em zircão. O depósito de Au-Ag-barita Zacarias possui geometria lenticular concordante com encaixantes representadas por anfibolitos, metavulcânicas félsicas, gnaisses tonalíticos, gonditos e pegmatitos. A zona mineralizada é caracterizada por lentes de barita quartzito e barita-muscovita quartzito com sulfetos disseminados representados por pirita, esfalerita, calcopirita e galena. Texturas identificadas nos sulfetos são caracterizadas por recristalização/annealing, incluindo crescimento dos grãos de cristais euédricos, formadas em resposta aos processos deformacionais dúcteis-rúpteis no metamorfismo regional. Apesar do depósito ter sofrido intensa deformação e metamorfismo de fácies anfibolito, sobreposto do retrometamorfismo de fácies xisto verde, foram definidas as seguintes assembleias de alteração: (i) quartzo-biotita com a presença de pirita disseminada; (ii) cianita-muscovita-flogopitaquartzo com pirita ± calcopirita disseminada; (iii) clorita-flogopita-quartzo com pirita ± calcopirita disseminada e agregados (blebs) de pirita; (iv) flogopita-clorita-quartzo com gahnita +pirita ± calcopirita-pirrotita-esfalerita disseminadas. Nesse contexto, essas assembleias foram interpretadas como produtos de alteração hidrotermal ricos em Al2O3 e MgO, similares a alterações sinvulcânicas fílica-clorítica e, possivelmente, argílica. Os dados de U-Pb LA-ICPMS em zircão fornecem idade de 908,3±7,4 para metavulcânica félsica (granada-biotita gnaisse de granulação fina), sugerindo que a mineralização está associada ao magmatismo Toniano do estágio Intra-Oceânico do Arco Magmático Goiás. Zircões obtidos em amostra de intrusiva félsica (quartzo-diorito gnaisse) no depósito apresentou idade de cristalização de 634,2 ± 5,4 Ma. Esta idade é associada aos últimos eventos deformacionais e metamórficos ocorridos no Orógeno Brasília. Além da presença de barita, informações da química das micas do depósito Zacarias exibem concentrações elevadas de bário em muscovita (5,75-6,96 % BaO) e flogopita (2,20-3,36 % BaO), comuns em ambientes hidrotermais de assoalho oceânico. As composições isotópicas de enxofre (δ34S) da pirita em barita quartzito (2,8-3,3‰) e barita-muscovita quartzito (4,4-7,2‰) são consistentes com enxofre derivados da redução termoquímica do sulfato (RST) e lixiviados de rochas magmáticas e/ou fluidos magmático-hidrotermal. Ao combinar esses novos dados com estudos anteriores, propomos que a mineralização do depósito Zacarias provavelmente ocorreu durante o período extensional nos estágios iniciais de sinsubducção que formou o Sistema Arco Intra-Oceânico Mara Rosa, parte do Arco magmático Goiás. O depósito de Au-Ag-barita Zacarias passou por processos de deformação e metamorfismo similares a vários depósitos VMS mundiais. Nesse sentido, os resultados apresentados aqui são relevantes não apenas para o depósito Au-Ag-barita Zacarias, mas também para outros depósitos Au-VMS globalmente.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).The Zacarias Au-Ag-barite deposit (with total reserve of 650,000 t at 4.4 g/t Au, 48 g/t Ag and 10% barite) is gold-rich volcanogenic sulfide mineralization (Au-VMS) hosted in Neoproterozoic rocks of the Mara Rosa metavolcano-sedimentary sequence, Goiás Magmatic Arc, central Brazil. This arc is part of Brasília accretionary Orogen, with a tectonic evolution between ca. 900 and 600 Ma during the Brasiliano Orogeny. In this study, we combine mineral chemistry, zircon U-Pb geochronology, and sulfur isotopes geochemistry to constraints the nature and evolution of the Zacarias deposit. The Zacarias Au-Ag-barite deposit has a lenticular geometry, concordant with the country rocksrepresented by amphibolites, felsic metavolcanics, tonalitic gneisses, gondites, and pegmatites. The orebodies comprise barite-quartzite and baritemuscovite quartzite lenses with fine-grained sulfides disseminations (pyrite, sphalerite, chalcopyrite, and galena). The sulfides textures are results of recrystallization/annealing, including increase in grain size growth of euhedral crystals, probably formed in response to ductile-brittle deformation processes associated with regional metamorphism. Despite deformation and metamorphism under amphibolite and superimposed by greenschist facies, the following hydrothermal assemblages are identified in the deposit: (i) quartz-biotite assemblage with disseminated pyrite, (ii) kyanite-muscovite-phlogopite-quartz with disseminated pyrite ± chalcopyrite, (iii) chlorite-phlogopite-quartz with disseminated pyrite ± chalcopyrite and blebs of pyrite, and (iv) garnet-phlogopite-chlorite-quartz with disseminated pyrite ± chalcopyritepyrrhotite-sphalerite. In this context, these mineral assemblages are interpreted as Al2O3 and MgO-rich hydrothermal alterations, analogous to the phyllic-chloritic and, possibly argillic, in synvolcanic alterations. Zircons from a felsic metavolcanic rock (fine-grained garnet-biotite gneiss) yielded a U–Pb crystallization age of 908.3±7.4 Ma, suggesting that mineralization is associated with the Tonian Intra-Oceanic Arc magmatism. A felsic intrusive rock (quartzdiorite gneiss) yielded a crystallization age of 634.2 ± 5.4 Ma, associated with the last deformational and metamorphic events that took place in the Brasília Orogen. In addition to barite, mineral chemistry analyses of micas reveal significant concentrations of barium in muscovite (5.75-6.96 wt.% BaO) and phlogopite (2.20-3.36 wt.% BaO), common in seafloor hydrothermal environments. The δ34S sulfur isotopic compositions of pyrite from barite quartzite (2.8-3.3‰) and barite-muscovite quartzite (4.4-7.2‰) are consistent with sulfur derived from thermochemical sulfate reduction (TSR) and sulfur leached from igneous wall rock and/or derived from magmatic-hydrothermal fluids. By combining these new insights with those of previous studies, we propose that the Au-Ag-barite Zacarias deposit mineralization developed during the extensional period in the initial stages of syn-subduction (possible forearc basin) that formed the Mara Rosa Intra-Oceanic Arc System, Goiás Magmatic Arc. The Zacarias Au-Ag-barite deposit underwent deformation and metamorphism processes similar to several VMS deposits worldwide. In this context, the results are not only relevant for the Zacarias Au-Ag-barite deposit but also other Au-VMS deposits globally

CONSTRUINDO O DIREITO À MORAR E TRABALHAR: DESAFIOS DA REFORMA PSIQUIÁTRICA BRASILEIRA

Resumo O artigo apresenta reflexões de pesquisadores assistentes sociais do Brasil sobre o campo do cuidado em saúde mental na perspectiva da Reforma Psiquiátrica antimanicomial. O efetivo exercício de cidadania e a garantia de direitos humanos dos usuários com transtorno mental e seus familiares são abordados a partir da temática da residência e do trabalho e são desafios importantes na construção do modo de cuidado psicossocial

Congos do Carmo, fé e devoção na festa de Nossa Senhora do Rosário

The feast of Nossa Senhora do Rosário is permeated by numerous devotional manifestations, and in view of this, the study emerged from the need for greater knowledge involving a secular tradition of the Congos in the festive context of the feast. In this sense, one of the pillars of this project is to value the cultural manifestations of Monte do Carmo – TO, directly linked to the devotion and lineage of the Congo in the festivity of Senhora do Rosário. Its main objective is to support and underpin the traditional culture of the congada in the feast of Nossa Senhora do Rosário in Monte do Carmo, in how the tradition is filled with love and devotion for the Congos in their entirety since the generations. Having as methodological procedures the execution of a thorough bibliographic review with topics such as cultural geography, which is one of the pillars for the production of this project, and an interview conducted by the academic of this project to the Congos of Monte do Carmo - TO. Therefore, it can be concluded that the traditional and festive journey of the Congos rescued a strong cultural matrix, with many signs of a rich culture in dance, singing and in the elaboration of the plot, and that tradition and devotion are passed from generation to generation.A festa de Nossa Senhora do Rosário, em Monte do Carmo, é permeada por inúmeras manifestações devocionais e, por isso, este estudo surgiu da necessidade de obter maior conhecimento envolvendo uma tradição considerada secular, a dos Congos, no contexto da festa. Tem por objetivo principal resgatar a cultura tradicional da congada na festa de Nossa Senhora do Rosário, tendo por finalidade compreender como a tradição é mantida de dedicação e devoção pelos congadeiros desde as gerações. Tendo como procedimentos metodológicos uma revisão bibliográfica sobre o tema e os fundamentos da geografia cultural e das religiões, e a realização de entrevistas aos congadeiros de Monte do Carmo - TO. Assim sendo, pode-se concluir que essa tradição dos congos possui uma matriz cultural afrobrasileira de caráter híbrido na sua apresentação que são passadas de geração em geração