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Even though the impact of COVID-19 in metropolitan areas has been extensively studied, the geographic spread to smaller cities is also of great concern. We conducted an ecological study aimed at identifying predictors of early introduction, incidence rates of COVID-19 and mortality (up to 8 May 2020) among 604 municipalities in inner São Paulo State, Brazil. Socio-demographic indexes, road distance to the state capital and a classification of regional relevance were included in predictive models for time to COVID-19 introduction (Cox regression), incidence and mortality rates (zero-inflated binomial negative regression). In multivariable analyses, greater demographic density and higher classification of regional relevance were associated with both early introduction and increased rates of COVID-19 incidence and mortality. Other predictive factors varied, but distance from the State Capital (São Paulo City) was negatively associated with time-to-introduction and with incidence rates of COVID-19. Our results reinforce the hypothesis of two patterns of geographical spread of SARS-Cov-2 infection: one that is spatial (from the metropolitan area into the inner state) and another which is hierarchical (from urban centres of regional relevance to smaller and less connected municipalities). Those findings may apply to other settings, especially in developing and highly heterogeneous countries, and point to a potential benefit from strengthening non-pharmaceutical control strategies in areas of greater risk.

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We described the clinical evolution of patients with structural heart disease presenting at the emergency room with syncope. Patients were stratified according to their syncope etiology and available scores for syncope prognostication. Cox proportional hazard models were used to investigate the relationship between etiology of the syncope and event-free survival. Of the 82,678 emergency visits during the study period, 160 (0.16%) patients were there due to syncope, having a previous diagnosis of structural heart disease. During the median follow-up of 33.8±13.8 months, mean age at the qualifying syncope event was 68.3 years and 40.6% of patients were male. Syncope was vasovagal in 32%, cardiogenic in 57%, orthostatic hypotension in 6%, and of unknown causes in 5% of patients. The primary composite endpoint death, readmission, and emergency visit in 30 days was 39.4% in vasovagal syncope and 60.6% cardiogenic syncope (P<0.001). Primary endpoint-free survival was lower for patients with cardiogenic syncope (HR=2.97, 95%CI=1.94-4.55; P<0.001). The scores were analyzed for diagnostic performance with area under the curve (AUC) and did not help differentiate patients with an increased risk of adverse events. The differential diagnosis of syncope causes in patients with structural heart disease is important, because vasovagal and postural hypotension have better survival and less probability of emergency room or hospital readmission. The available scores are not reliable tools for prognosis in this specific patient population.

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Zooarchaeological collections from shell mounds in Rio de Janeiro (2,470-4,632 cal BP) contain a high prevalence of swollen fish bones belonging to the Atlantic spadefish (Chaetodipterus faber), crevalle jack (Caranx hippos) and fat snook (Centropomus parallelus). Given the lack of knowledge of the bone degenerative process in senile fishes, this study analysed hyperostotic bone in zooarchaeological and modern specimens to obtain high-resolution morphology and microstructure reconstruction. We used microCT as well as X-ray diffraction to characterize the crystallographic changes associated with fish senility. Our results showed that trabecular microstructures in hyperostotic bones were consistent with estimated values of the per cent bone volume-to-total volume ratio (BV/TV) and were greater than 60% in cortical bone. Hyperostotic bones indicated a high radiograph density, and X-ray diffractograms showed a decrease in hydroxyapatite [Ca10 (PO4 )6 (OH)2 ] and calcite (CaCO3 ) neocrystallization. These crystalline and density changes revealed an advanced stage of fish senile and indicate the vulnerability of ageing fish populations.

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Lesoes do ligamento cruzado anterior (LCA) podem resultar em instabilidade funcional em alguns individuos, enquanto outros retornam ao nivel funcional pre-lesao. A relacao da propriocepcao com desempenho funcional de individuos com LCA lesado nao esta bem evidenciada na literatura. Os objetivos deste estudo foram: 1)comparar a propriocepcao de individuos com e sem lesaodo LCA por meio da avaliacao do senso posicional e limiar de percepcao de movimento e 2) verificar se ha associacao entre o desempenho funcional e a acuidade proprioceptiva desses individuos. Participaram do estudo dez sujeitos (idade media=24 anos) com lesao unilateral do LCA tratada conservadoramente e dez sem historia de lesao. A propriocepcao foi avaliada por meio dos testes de senso posicional e limiar de percepcao de movimento. O desempenho funcional foi avaliado pela Escala Funcional de Cincinatti, Hop Index e razao figura oito/linha reta. Os dados foram avaliados por uma anlise de variancia fatorial com fator de medida repetida, testes T e por modelos de regressao Stepwise. Os resultados demonstraram que os sujeitos com lesao apresentaram pontuacao na escala de Cincinatti significativamente inferior ao grupo controle (p=0,001). Nao foi observada diferenca significativa entre grupos ou entre pernas para senso posicional e limiar de percepcao de movimento. Nenhuma diferenca significativa foi encontrada entre grupos para o Hop Index e razao figura oito/linha reta. Apenas variavel limiar de percepcao de movimento foi selecionada pelo modelo de regressao para explicar o Hop Index (r=0,643, R2=0,413, p=0,045). Os resultados mostram que individuos com LCA lesado nao operado e com bom desempenho funcional nao apresentam deficit proprioceptivo, sugerindo que mecanorrecptores ligamentares nao exercem papel primario na propriocepcao. Alem disso, a propriocepcao parece nao ter impacto direto no desempenho funcional desses individuos i

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AIM/HYPOTHESIS: By acting in the brain, insulin suppresses food intake. However, little is known with regard to insulin signalling in the hypothalamus in insulin-resistant states. METHODS: Western blotting, immunohistochemistry and polymerase chain reaction assays were combined to compare in vivo hypothalamic insulin signalling through the PI3-kinase and MAP kinase pathways between lean and obese Zucker rats. RESULTS: Intracerebroventricular insulin infusion reduced food intake in lean rats to a greater extent than that observed in obese rats, and pre-treatment with PI3-kinase inhibitors prevented insulin-induced anorexia. The relative abundance of IRS-2 was considerably higher than that of IRS-1 in hypothalamus of both lean and obese rats. Insulin-stimulated phosphorylation of IR, IRS-1/2, the associations of PI 3-kinase to IRS-1/2 and phosphorylation of Akt in hypothalamus were decreased in obese rats compared to lean rats. These effects seem to be mediated by increased phosphoserine content of IR, IRS-1/2 and decreased protein levels of IRS-1/2 in obese rats. In contrast, insulin stimulated the phosphorylation of MAP kinase equally in lean and obese rats. CONCLUSION/INTERPRETATION: This study provides direct measurements of insulin signalling in hypothalamus, and documents selective resistance to insulin signalling in hypothalamus of Zucker rats. These findings provide support for the hypothesis that insulin could have anti-obesity actions mediated by the PI3-kinase pathway, and that impaired insulin signalling in hypothalamus could play a role in the development of obesity in this animal model of insulin-resistance.

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We observe for the first time a structural phase transition in the oxyborate Fe3O2BO3 which occurs along three leg ladders present in this material. X-ray diffraction shows that this transition at 283 K is associated with a new phase where atomic displacements occur in alternate directions perpendicular to the axis and within the plane of the ladders. Magnetic data show that these displacements lead to the formation of singlet pairs which dissociate close to the structural transition. Anomalies in the transport properties also occur close to 283 K showing that the structural transition is related to a charge ordering phenomenon in a low dimensional structure.

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The hypothalamic serotonergic system is involved in the regulation of food ingestion and energy metabolism. Since disturbances of both energy intake and expenditure can contribute to obesity, the objective of the present study was to evaluate the serotonergic response stimulated by food ingestion in two different models of obesity: the hyperphagic Zucker and the hypophagic and hypometabolic, monosodium glutamate (MSG) obese Wistar rat. For this we used microdialysis to examine the release of 5-hydroxytryptamine (serotonin, 5HT) and 5-hydroxyindoleacetic acid (5HIAA) in the lateral hypothalamus. Daily intake of MSG-obese rats was 40% lower while that of Zucker obese rats was 60% higher than that of the respective lean controls. In overnight-fasted animals, 20-min microdialysate samples were collected before (basal release) and during a 2-h period of access to a balanced palatable food mash. The animals began to eat during the first 20 min of food access, and food consumption was similar among the four groups in all six individual 20-min periods recorded. Ingestion of food increased 5HT release in all groups. In MSG-obese and lean Wistar rats, 5HT levels were similarly elevated during the whole experimental period. In the Zucker strain, 5HT increments of basal release tended to be higher in obese than in lean rats at 20 and 40 min, and a significantly higher increment was observed at 60 min after food access (40 and 135% for lean and obese, respectively). The area under the curve relating serotonin levels to the 120 min of food availability was significantly higher in Zucker obese (246.7 +/- 23.3) than MSG-obese (152.7 +/- 13.4), lean Wistar (151.9 +/- 11.1), and lean Zucker (173.5 +/- 24.0) rats. The present observation, of a food-induced serotonin release in the lateral hypothalamus of lean Wistar and Zucker rats, evidences that 5HT in the lateral hypothalamus is important in the normal response to feeding. In obese animals, the serotonin response was similar to (in the hypophagic-hypometabolic MSG model) or even higher than (in the hyperphagic Zucker model) that seen in the respective lean controls. This result indicates that the energy homeostasis disturbances of both these obesity models may not be ascribed to an impairment of the acute lateral hypothalamic serotonin response to a dietary stimulus.

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