Short-Term Efficacy Outcomes of Tenecteplase versus Alteplase for Acute Ischemic Stroke: A Meta-Analysis of 5 Randomized Trials.

Tenecteplase (TNK) has been shown to be noninferior to Alteplase (ALT) for long term efficacy and safety outcomes. Whether this also applies to short term efficacy outcomes such as early clinical improvement and recanalization is unknown. To compare TNK and ALT regarding the short term efficacy outcomes: early neurological improvement and recanalization. The PRISMA was used to conduct a meta analysis, adapted to noninferiority analysis. The primary outcome was early (24-72 h) neurological improvement, defined as either NIHSS score 0 or reduction of at least 8 points compared to baseline. Recanalization was a secondary outcome. The noninferiority margin was set at 6.5%. Search strategy yielded 5 randomized clinical trials (1585 patients: 828 TNK, 757 ALT). Mean age was 70.8, 58.8% were men, mean baseline NIHSS was 7, and mean onset to treatment time was 148 min. Patients in intervention group received TNK at doses of 0.1 mg/kg (6.8%), 0.25 mg/kg (24.6%), and 0.4 mg/kg (68.6%), while all ALT patients received 0.9 mg/kg. In random effects meta analysis, TNK was noninferior to ALT for the primary outcome, early major neurological improvement (risk difference 8% in favor of TNK, 95% CI 1%-15%). Recanalization was also noninferior for the TNK compared to the ALT group (risk difference 9% in favor of TNK, 95% CI 6% to 23%). Fixed effects models yielded similarly noninferior results and signaled for a possible TNK superiority for both early neurological improvement and recanalization. TNK is noninferior to ALT at the short term efficacy outcomes: early neurological improvement and recanalization.

Th17 cell-linked mechanisms mediate vascular dysfunction induced by testosterone in a mouse model of gender-affirming hormone therapy.

Clinical data point to adverse cardiovascular events elicited by testosterone replacement therapy. Testosterone is the main hormone used in gender-affirming hormone therapy (GAHT) by transmasculine people. However, the cardiovascular impact of testosterone in experimental models of GAHT remains unknown. Sex hormones modulate T-cell activation, and immune mechanisms contribute to cardiovascular risk. The present study evaluated whether testosterone negatively impacts female cardiovascular function by enhancing Th17 cell-linked effector mechanisms. Female (8 wk old) C57BL/6J mice received testosterone (48 mg/kg/wk) for 8 wk. Male mice were used for phenotypical comparisons. The hormone treatment in female mice increased circulating testosterone to levels observed in male mice. Testosterone increased lean body mass and body mass index, and decreased perigonadal fat mass, mimicking clinical findings. After 8 wk, testosterone decreased endothelium-dependent vasodilation and increased peripheral Th17 cells. After 24 wk, testosterone increased blood pressure in female mice. Ovariectomy did not intensify phenotypical or cardiovascular effects by testosterone. Female mice lacking T and B cells [Rag1 knockout (-/-)], as well as female mice lacking IL-17 receptor (IL-17Ra-/-), did not exhibit vascular dysfunction induced by testosterone. Testosterone impaired endothelium-dependent vasodilation in female mice lacking γδ T cells, similarly to the observed in wild-type female mice. Adoptive transfer of CD4+ T cells restored testosterone-induced vascular dysfunction in Rag1-/- female mice. Together, these data suggest that CD4+ T cells, most likely Th17 cells, are central to vascular dysfunction induced by testosterone in female mice, indicating that changes in immune-cell balance are important in the GAHT in transmasculine people.NEW & NOTEWORTHY Sex hormone-induced cardiovascular events are important undesirable effects in transgender people under GAHT. Studies addressing the cardiovascular impact of GAHT will certainly contribute to improve healthcare services offered to this population. Our study showing that vascular dysfunction, via Th17 cell-related mechanisms, precedes increased blood pressure induced by testosterone in a GAHT mouse model, reveals potential mechanisms involved in GAHT-related cardiovascular events and may provide new markers/targets for clinical practices in transmasculine people.

Maternal vitamin D deficiency affects the morphology and function of glycolytic muscle in adult offspring rats.

BACKGROUND: Fetal stage is a critical developmental window for the skeletal muscle, but little information is available about the impact of maternal vitamin D (Vit. D) deficiency (VDD) on offspring lean mass development in the adult life of male and female animals. METHODS: Female rats (Wistar Hannover) were fed either a control (1000 IU Vit. D3/kg) or a VDD diet (0 IU Vit. D3/kg) for 6 weeks and during gestation and lactation. At weaning, male and female offspring were randomly separated and received a standard diet up to 180 days old. RESULTS: Vitamin D deficiency induced muscle atrophy in the male (M-VDD) offspring at the end of weaning, an effect that was reverted along the time. Following 180 days, fast-twitch skeletal muscles [extensor digitorum longus (EDL)] from the M-VDD showed a decrease (20%; P < 0.05) in the number of total fibres but an increase in the cross-sectional area of IIB (17%; P < 0.05), IIA (19%; P < 0.05) and IIAX (21%; P < 0.05) fibres. The fibre hypertrophy was associated with the higher protein levels of MyoD (73%; P < 0.05) and myogenin (55% %; P < 0.05) and in the number of satellite cells (128.8 ± 14 vs. 91 ± 7.6 nuclei Pax7 + in the M-CTRL; P < 0.05). M-VDD increased time to fatigue during ex vivo contractions of EDL muscles and showed an increase in the phosphorylation levels of IGF-1/insulin receptor and their downstream targets related to anabolic processes and myogenic activation, including Ser 473 Akt and Ser 21/9 GSK-3ß. In such muscles, maternal VDD induced a compensatory increase in the content of calcitriol (two-fold; P < 0.05) and CYP27B1 (58%; P < 0.05), a metabolizing enzyme that converts calcidiol to calcitriol. Interestingly, most morphological and biochemical changes found in EDL were not observed in slow-twitch skeletal muscles (soleus) from the M-VDD group as well as in both EDL and soleus muscles from the female offspring. CONCLUSIONS: These data show that maternal VDD selectively affects the development of type-II muscle fibres in male offspring rats but not in female offspring rats and suggest that the enhancement of their size and fatigue resistance in fast-twitch skeletal muscle (EDL) is probably due to a compensatory increase in the muscle content of Vit. D in the adult age.

Vulnerability of the micro-regions of the South of Brazil to the new coronavirus (SARS-CoV-2) pandemic / Vulnerabilidade das microrregiões da Região Sul do Brasil à pandemia do novo coronavírus (SARS-CoV-2)

This is the first report of the 'Observatório COVID191 - Grupo: Redes de Contágio ­ Laboratório de Estudos de Defesa' for the South region of Brazil. We have combined data of confirmed cases of the new coronavirus (SARS-CoV-2) for the South available up to 17/04/2020, with structural analyses of road networks, from within and between states, to estimate the vulnerability and potential influence of the South micro-regions to propagate the disease.

Este é o primeiro relatório do Observatório COVID19 - Grupo: Redes de Contágio ­ Laboratório de Estudos de Defesa para a região Sul do Brasil. Combinamos dados de casos confirmados do novo coronavírus (SARS-CoV-2) para o Sul, disponíveis até o dia 17/04/2020, com análises estruturais da rede de rotas rodoviárias intra e interestaduais para estimarmos a vulnerabilidade e potencial influência das microrregiões sulinas na propagação da doença.

Perfil bioquímico sérico de bezerros de origem leiteira aleitados com dietas líquidas alternativas / Serum biochemistry profile of dairy calves fed with alternative liquid diets

O perfil metabólico é utilizado como monitoramento rotineiro para o diagnóstico de transtornos metabólicos, deficiências nutricionais e como preventivo de transtornos subclínicos, além da pesquisa de problemas de saúde e de desempenho de um rebanho. Neste contexto, o objetivo do presente trabalho foi avaliar a influência de diferentes dietas líquidas contendo soro de queijo e colostro sobre os perfis dos metabólitos séricos de bezerros durante a fase de aleitamento. Foram utilizados 24 bezerros mestiços provenientes de rebanhos leiteiros da região, distribuídos em delineamento inteiramente casualizado com três tratamentos e oito repetições: LI = Leite integral (controle); LS = 50% Leite integral + 50% de Soro de queijo in natura; SC = 70% de Soro de queijo in natura + 30% Colostro. Semanalmente foram coletadas amostras de sangue por punção jugular externa, no período da manhã, antes do fornecimento da dieta líquida e duas horas após a ingestão desta. As concentrações dos parâmetros séricos avaliados diferiram entre os tratamentos, porém sem comprometer o desempenho dos animais. Desse modo, a utilização de soro de queijo associado ao colostro apresenta-se como forma viável de redução de custos com aleitamento de bezerros, visto que possíveis déficits causados pelas diferenças nutricionais das dietas líquidas são supridos pelos alimentos sólidos, não afetando os perfis dos metabólitos séricos relacionados ao status protéico e energético.(AU)

Metabolic profile is used as routine monitoring for the diagnosis of metabolic disorders, nutritional deficiencies, and as a preventive of subclinical disorders, in addition to research health issues and performance of a herd. In this context, the aim of this study was to evaluate the influence of different liquid diets containing whey cheese and colostrum on the serum biochemistry profile of calves. Twenty-four crossbred calves from dairy herds in the region, distributed in a completely randomized design with three treatments and eight replicates: LI = Whole milk (control); LS = 50% Whole milk + 50% cheese whey in nature; SC = 70% of cheese whey in natura + 30% Colostrum. Weekly blood samples by jugular puncture were collected in the morning, before the supply of liquid diet and two hours after eating this. The serum concentrations of the evaluated parameters differ between treatments, but without compromising animal performance. Thus, the use of whey associated with colostrum presents itself as a viable cost reduction with feeding calves, since possible nutritional deficits caused by differences in liquid diets are supplied by solid food form, not affecting the profiles of the metabolites related to serum protein and energy status.(AU)