Risk factors for death due to COVID-19, in the state of Acre, Brazil, 2020: a retrospective cohort study. / Fatores de risco para óbito por COVID-19 no Acre, 2020: coorte retrospectiva.

OBJECTIVE: To analyze risk factors for death in individuals with severe acute respiratory syndrome due to COVID-19. METHODS: This was a retrospective cohort study, comprised of adult individuals with COVID-19, from March to September 2020, notified by the Epidemiological Surveillance System in the state of Acre, Brazil. Cox regression was used. RESULTS: Among 57,700 individuals analyzed, the incidence was 2,765.4/100,000 inhabitants, and mortality was, 61.8/100,000 inhabitants. The risk factors for death were: being male (HR=1.48 -95% CI 1.25;1.76), age ≥60 years (HR=10.64 -95% CI 8.84;12.81), symptom of dyspnea (HR=4.20 -95% CI 3.44;5.12) and multimorbidity (HR=2.23 -95% CI 1.77;2.81), with emphasis on heart disease and diabetes mellitus. 'Sore throat' and 'headache' were symptoms present in mild cases of COVID-19. CONCLUSION: Being male, elderly, having heart disease, diabetes mellitus and dyspnea were characteristics associated with death due to COVID-19.

Fatores de risco para óbito por COVID-19 no Acre, 2020: coorte retrospectiva / Factores de riesgo de muerte por COVID-19, en Acre, Brasil, 2020: cohorte retrospectiva / Risk factors for death due to COVID-19, in the state of Acre, Brazil, 2020: a retrospective cohort study

Objetivo: Analisar fatores de risco para óbito em indivíduos com síndrome respiratória aguda grave por COVID-19. Métodos: Coorte retrospectiva, constituída de indivíduos adultos com COVID-19, de março a setembro de 2020, notificados pelo sistema de vigilância epidemiológica do estado do Acre, Brasil. Empregou-se regressão de Cox. Resultados: Entre 57.700 indivíduos analisados, a incidência foi de 2.765,4/100 mil habitantes, e a mortalidade, de 61,8/100 mil hab. Os fatores de risco para o óbito foram ser do sexo masculino (HR=1,48 - IC95% 1,25;1,76), ter idade ≥60 anos (HR=10,64 - IC95% 8,84;12,81), sintoma de dispneia (HR=4,20 - IC95% 3,44;5,12) e apresentar multimorbidade (HR=2,23 - IC95% 1,77;2,81), com destaque para cardiopatas e diabetes mellitus. Os sintomas 'dor de garganta' e 'cefaleia' estavam presentes nos casos leves da doença. Conclusão: Ser homem, idoso, apresentar cardiopatia, diabetes mellitus e dispneia foram características associadas ao óbito pela COVID-19.

Objetivo: Analizar los factores de riesgo de muerte en individuos con Síndrome Respiratorio Agudo Grave por COVID-19. Métodos: Cohorte retrospectiva, con individuos adultos con COVID-19, entre marzo y septiembre 2020, notificado pelo Sistema de Vigilancia Epidemiológica en el estado de Acre, Brasil. Se utilizó la regresión de Cox. Resultados: 57.700 individuos evaluados, la incidencia fue de 2.765,4/100.000 habitantes y la mortalidad 61,8/100.000 habitantes. Los factores de riesgo de muerte fueron: sexo masculino (HR=1,48 - IC95% 1,25;1,76), edad ≥60 años (HR=10,64 - IC95% 8,84;12,81), disnea (HR=4,20 - IC95% 3,44;5,12), multimorbidad (HR=2,23 - IC95% 1,77;2,81), incluidos problemas cardíacos y diabetes. Los síntomas dolor de garganta y de cabeza estuvieron presentes en casos leves de la enfermedad. Conclusión: Hombres, ancianos, personas com enfermedades cardíacas, diabetes y disnea fueron características asociadas com la muerte por COVID-19.

Objective: To analyze risk factors for death in individuals with severe acute respiratory syndrome due to COVID-19. Methods: This was a retrospective cohort study, comprised of adult individuals with COVID-19, from March to September 2020, notified by the Epidemiological Surveillance System in the state of Acre, Brazil. Cox regression was used. Results: Among 57,700 individuals analyzed, the incidence was 2,765.4/100,000 inhabitants, and mortality was, 61.8/100,000 inhabitants. The risk factors for death were: being male (HR=1.48 -95% CI 1.25;1.76), age ≥60 years (HR=10.64 -95% CI 8.84;12.81), symptom of dyspnea (HR=4.20 -95% CI 3.44;5.12) and multimorbidity (HR=2.23 -95% CI 1.77;2.81), with emphasis on heart disease and diabetes mellitus. 'Sore throat' and 'headache' were symptoms present in mild cases of COVID-19. Conclusion: Being male, elderly, having heart disease, diabetes mellitus and dyspnea were characteristics associated with death due to COVID-19.

The role of Na+/K+-ATPase during chick skeletal myogenesis.

The formation of a vertebrate skeletal muscle fiber involves a series of sequential and interdependent events that occurs during embryogenesis. One of these events is myoblast fusion which has been widely studied, yet not completely understood. It was previously shown that during myoblast fusion there is an increase in the expression of Na+/K+-ATPase. This fact prompted us to search for a role of the enzyme during chick in vitro skeletal myogenesis. Chick myogenic cells were treated with the Na+/K+-ATPase inhibitor ouabain in four different concentrations (0.01-10 µM) and analyzed. Our results show that 0.01, 0.1 and 1 µM ouabain did not induce changes in cell viability, whereas 10 µM induced a 45% decrease. We also observed a reduction in the number and thickness of multinucleated myotubes and a decrease in the number of myoblasts after 10 µM ouabain treatment. We tested the involvement of MEK-ERK and p38 signaling pathways in the ouabain-induced effects during myogenesis, since both pathways have been associated with Na+/K+-ATPase. The MEK-ERK inhibitor U0126 alone did not alter cell viability and did not change ouabain effect. The p38 inhibitor SB202190 alone or together with 10 µM ouabain did not alter cell viability. Our results show that the 10 µM ouabain effects in myofiber formation do not involve the MEK-ERK or the p38 signaling pathways, and therefore are probably related to the pump activity function of the Na+/K+-ATPase.

Differences in the expression and distribution of flotillin-2 in chick, mice and human muscle cells.

Myoblasts undergo a series of changes in the composition and dynamics of their plasma membranes during the initial steps of skeletal muscle differentiation. These changes are crucial requirements for myoblast fusion and allow the formation of striated muscle fibers. Membrane microdomains, or lipid rafts, have been implicated in myoblast fusion. Flotillins are scaffold proteins that are essential for the formation and dynamics of lipid rafts. Flotillins have been widely studied over the last few years, but still little is known about their role during skeletal muscle differentiation. In the present study, we analyzed the expression and distribution of flotillin-2 in chick, mice and human muscle cells grown in vitro. Primary cultures of chick myogenic cells showed a decrease in the expression of flotillin-2 during the first 72 hours of muscle differentiation. Interestingly, flotillin-2 was found to be highly expressed in chick myogenic fibroblasts and weakly expressed in chick myoblasts and multinucleated myotubes. Flotillin-2 was distributed in vesicle-like structures within the cytoplasm of chick myogenic fibroblasts, in the mouse C2C12 myogenic cell line, and in neonatal human muscle cells. Cryo-immunogold labeling revealed the presence of flotillin-2 in vesicles and in Golgi stacks in chick myogenic fibroblasts. Further, brefeldin A induced a major reduction in the number of flotillin-2 containing vesicles which correlates to a decrease in myoblast fusion. These results suggest the involvement of flotillin-2 during the initial steps of skeletal myogenesis.

Induction of skeletal muscle differentiation in vitro by therapeutic ultrasound.

Therapeutic ultrasound (TU) has been used for the last 50 y in rehabilitation, including treatment of soft tissues. Ultrasound waves can be employed in two different modes of operation, continuous and pulsed, which produce both thermal and non-thermal effects. Despite the large-scale use of TU, there are few scientific studies on its biologic effects during skeletal muscle differentiation. To better analyze the cellular effects of TU, we decided to follow cells in vitro. The main purpose of this study was to evaluate the effects of TU in primary chick myogenic cell cultures using phase contrast optical microscopy and immunofluorescence microscopy, followed by image analysis and quantification. Our results indicate that TU can stimulate the differentiation of skeletal muscle cells in vitro, as measured by the thickness of multinucleated myotubes, the ratio of mononucleated cells to multinucleated cells and expression of the muscle-specific protein desmin. This study is a first step toward a metrologic and science-based protocol for cell treatment under different ultrasound field exposures.

Sciatic nerve regeneration is accelerated in galectin-3 knockout mice.

The success of peripheral nerve regeneration depends on intrinsic properties of neurons and a favorable environment, although the mechanisms underlying the molecular events during degeneration and regeneration are still not elucidated. Schwann cells are considered one of the best candidates to be closely involved in the success of peripheral nerve regeneration. These cells and invading macrophages are responsible for clearing myelin and axon debris, creating an appropriate route for a successful regeneration. After injury, Schwann cells express galectin-3, and this has been correlated with phagocytosis; also, in the presence of galectin-3, there is inhibition of Schwann-cell proliferation in vitro. In the present study we explored, in vivo, the effects of the absence of galectin-3 on Wallerian degeneration and nerve-fiber regeneration. We crushed the sciatic nerves of galectin-3 knockout and wild-type mice, and followed the pattern of degeneration and regeneration from 24 h up to 3 weeks. We analyzed the number of myelinated fibers, axon area, fiber area, myelin area, G-ratio and immunofluorescence for beta-catenin, macrophages and Schwann cells in DAPI counterstained sections. Galectin-3 knockout mice showed earlier functional recovery and faster regeneration than the wild-type animals. We concluded that the absence of galectin-3 allowed faster regeneration, which may be associated with increased growth of Schwann cells and expression of beta-catenin. This would favor neuron survival, followed by faster myelination, culminating in a better morphological and functional outcome.