Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Diabetes mellitus: pathophysiological changes and therap

O caso da Rede Universitária de Telemedicina: análise da entrada da telessaúde na agenda política brasileira The case of Telemedicine University Network: analysis of telehealth entry in the Brazilian political agenda

Estudo de abordagem qualitativa sobre a concepção da política de telessaúde no Brasil baseado em modelos de avaliação em saúde e na análise de políticas públicas, mais especificamente na proposta analítica de múltiplos fluxos e no modelo lógico de avaliação de programas em saúde. As fontes de dados consistiram em documentos relacionados à criação da Rede Universitária de Telemedicina (Rute), artigos disponíveis na literatura sobre telessaúde e avaliação em saúde, atas e participações em reuniões de variados fóruns. O modelo de múltiplos fluxos se concentra nas fases iniciais do ciclo da política pública: a construção da agenda governamental e a escolha de alternativas de políticas. Buscou-se delinear a composição da Rute e responder quais condicionantes levaram os gestores federais de diversos setores a reconhecer a qualidade do sistema como problema na saúde pública e a escolha da implantação de programas de telessaúde como uma das alternativas para a solução. Os processos analisados demonstraram que, na convergência do fluxo de problemas com ambiente político favorável, abriu-se uma janela de oportunidade para a implantação da telessaúde como alternativa vir a ascender como política na agenda de decisão governamental. Porém, para isso, urge a necessidade de inclusão digital no território e identificar as tecnologias da informação e comunicação como inovação para o SUS.<br>A qualitative study on the policy design of telehealth in Brazil based on valuation models in health and public policy analysis, specifically the proposed multiple streams of analytical and logical model for evaluating health programs. Data sources consisted of documents related to the creation of Telemedicine University Network (Rute), articles available in the literature on telehealth and health evaluation, minutes of meetings and participating in various forums. The model focuses multiple streams in the early stages of the cycle of public policy: the construction of the government agenda and choice of alternative policies. We sought to delineate the composition of Rute and answer constraints which led federal managers from various sectors to recognize the quality of the system as a public health problem and the choice of implementing telehealth programs as one of the alternatives. The cases analyzed showed that in the flux convergence problems with favorable political environment, a window of opportunity opened up for the deployment of telehealth to eventually ascend as an alternative in the political agenda of the government decision. But for this, there is urgent need for digital inclusion in the territory and identify the technologies of information and communication as an innovation for SUS

Isolamento e identificação da microbiota periodontal de cães da raça Pastor Alemão Isolate and identify of periodontal microbiota of German Shepherd dogs

A microbiota indígena gengival de cães não está totalmente descrita, sendo sua identificação uma etapa importante no estabelecimento da etiopatogenia e terapia da doença periodontal. O objetivo deste trabalho foi isolar e identificar a microbiota periodontal de cães da raça Pastor Alemão, considerando sítios saudáveis e com doença periodontal. Foram utilizados 29 cães, com idade variando de três a seis anos, sendo analisados espécimes clínicos de sítios periodontais saudáveis de 12 cães e sítios com periodontite de outros 17. Foram isoladas 672 amostras microbianas, com predomínio dos gêneros Pasteurella, Staphylococcus, Porphyromonas e Fusobacterium. A microbiota dos sítios saudáveis equiparou-se à dos sítios doentes, tratando-se de uma microbiota indígena. A microbiota dos sítios doentes apresentou-se aumentada em relação a dos sítios saudáveis, indicando mudança do ambiente do sítio periodontal.<br>The indigenous gingival microbiota of dogs is not totally described, although such identification is an important step to establish the etiopathogenesis and adequate therapy for the periodontal disease. The aims of this study were to isolate and identify the periodontal microbiota of German Shepherd dogs from healthy and with periodontal desease sites. Twenty nine German Shepherd dogs from three to six years of age were used in this study. Clinical specimens were analysed from healthy periodontal sites of 12 dogs and sites presenting gingivitis of 17 dogs. A total amount of 672 microbial samples, were isolated where the predominant genera were Pasteurella spp., Staphylococcus spp., Porphyromonas spp. and Fusobacterium spp. The microbiological population of the affected sites was similar to the healthy sites, consisting on an indigenous microbiota. The microbiota on the affecteded sites was higher in number than on the healthy sites, showing change in the environment of the periodontal sites

Desempenho, características de carcaça, qualidade da carne e condição sanitária de suínos criados nas fases de crescimento e terminação nos sistemas confinado convencional e de cama sobreposta Performance, carcass characteristics, meat quality and health condition of growing and finishing pigs raised in conventional and deep litter housing systems

O objetivo deste trabalho foi avaliar o efeito do sistema de alojamento sobre o desempenho zootécnico, as características da carcaça, a qualidade da carne e a condição sanitária de suínos criados em seis diferentes sistemas. Foram usados 803 suínos mestiços MS58 x (Landrace x Large White) em sete lotes seqüenciais no tempo, avaliando as fases de creche e de crescimento-terminação. Na creche, foram avaliados três tipos de alojamento: confinado convencional (CO); cama sobreposta-(CS); e sistema intensivo de suínos criados ao ar livre (SISCAL). No crescimento-terminação, foram avaliados apenas dois tipos de alojamento (CO e CS), sendo o último subdividido em três substratos (palha de trigo-PT, casca de arroz-CA e serragem-SE). Para a análise estatística foi considerado no modelo os efeitos de lote, o tratamento (combinação de tipos de alojamento na creche e no crescimento-terminação), idade dos suínos (84, 105, 126, 147 e 160 dias) e a interação tratamento x idade. Suínos alojados no sistema CO apresentaram maior (P<0,05) ganho de peso diário (824 vs. 779g), maior peso de carcaça quente (75 vs. 69kg) e maior espessura de toucinho (18, vs. 17mm) do que os criados sobre cama todavia estes suínos apresentaram peso do conteúdo estomacal significativamente (P<0,05) maior (360 vs. 204g) e menor grau de lesão do estômago do que aqueles alojados em tratamento convencional, embora com maior prevalência de espirro. O sistema de alojamento não afetou os aspectos sanitários avaliados, contudo, suínos alojados em cama sobreposta no crescimento-terminação apresentaram desempenho e características de carcaça inferiores àqueles do sistema convencional, independentemente do sistema de alojamento utilizado na creche.<br>The objective of this study was to evaluate the effect of housing system on live performance, carcass characteristics, meat quality, and the sanitary condition of pigs raised in six different systems. A total of 803 MS58 x (Landrace x Large White) hybrid type pigs was used in seven subsequent lots, during the nursery and growing-finishing phases. At the nursery period, the systems evaluated were: conventional (CO), deep litter (CS), and intensive free range (SISCAL), while during the growing-finishing phase only the CO and CS systems were evaluated, being the CS system subdivided into three substrates (wheat straw, rice hulls and wood shaving). The factors considered on the statistical analysis were lot, treatment (combination of housing type used during nursery and growing-finishing phases), age (84, 105, 126, 147 e 160 days), and the interaction treatment x age. A significant effect of housing type was observed on weight gain, carcass characteristics, and weight of heart, liver, full stomach and stomach content. Animals housed on conventional treatment had higher (P<0.05) weight gain (824 vs. 779g), higher hot carcass weight (75 vs. 69kg) and higher fat thickness (18 vs. 17mm) than the ones raised on deep litter, however, these, on the other hand, presented larger (P<0.05) gut content (360 vs. 204g) and less degree of gut lesion than those of the conventional treatment, eventhough with higher sneeze prevalence. The housing system did not influence the health, however pigs housed on deep litter system during the growing-finishing phase presented lower performance and carcass values than the ones housed in the conventional housing system despite the housing system used during the nursery phase