The unequal impact of the pandemic at subnational levels and educational attainment-related inequalities in COVID-19 mortality, Brazil, 2020-2021.

OBJECTIVES: We estimated COVID-19 mortality indicators in 2020-2021 to show the epidemic's impact at subnational levels and to analyze educational attainment-related inequalities in COVID-19 mortality in Brazil. STUDY DESIGN: This was an ecological study with secondary mortality information. METHODS: Crude and age-standardized COVID-19 mortality rates were calculated by gender, major regions, and states. The COVID-19 proportional mortality (percentage) was estimated by gender and age in each region. Measures of education-related inequalities in COVID-19 mortality were calculated per state, in each of which the COVID-19 maternal mortality rate (MMR) was estimated by the number of COVID-19 maternal deaths per 100,000 live births (LBs). RESULTS: The analysis of mortality rates at subnational levels showed critical regional differences. The North region proved to be the most affected by the pandemic, followed by the Center-West, with age-standardized COVID-19 mortality rates above 2 per 1000 inhabitants. The peak of COVID-19 mortality occurred in mid-March/April 2021 in all regions. Great inequality by educational level was found, with the illiterate population being the most negatively impacted in all states. The proportional mortality showed that males and females aged 50-69 years were the most affected. The MMR reached critical values (>100/100,000 LB) in several states of the North, Northeast, Southeast, and Center-West regions. CONCLUSIONS: This study highlights stark regional and educational disparities in COVID-19 mortality in Brazil. Exacerbated by the pandemic, these inequalities reveal potential areas for intervention to reduce disparities. The results also revealed high MMRs in certain states, underscoring pre-existing healthcare access challenges that worsened during the pandemic.

Assessment of aerobic capacity during swimming exercise in ob/ob mice.

Obesity is a highly prevalent condition associated with several diseases. Physical exercise has been considered as a non-pharmacological tool in the treatment of obesity. However, several aspects underlying exercise evaluation and prescription in obesity and associated pathologies are still under investigation. Although many research involving exercise have been performed in animal models, there is a lack of protocols for aerobic capacity assessment in obese animals, such as the ob/ob mice. This study aimed the following: (i) to verify the possibility of determining the lactate threshold (LT) on swimming exercise in ob/ob mice and in non-obese heterozygote mice (ob/OB), through visual inspection (vLT) and polynomial adjustment (pLT); and (ii) to verify if the LT determined through these protocols corresponds to the maximal lactate steady state (MLSS). Eight ob/ob and ten ob/OB mice performed an incremental exercise test to determine vLT and pLT as well as constant-load exercise bouts to determine MLSS. There were no within-group differences between vLT, pLT and MLSS [ob/ob: ~5.3% body weight (BW); ob/OB: ~3·6%BW] with a high agreement among protocols. In conclusion, the identification of the LT and MLSS intensities was possible for both groups. These data suggest that the proposed protocols may be used in new research on the effects of different exercise intensities on some aspects of obesity.

Effect of type 2 diabetes on plasma kallikrein activity after physical exercise and its relationship to post-exercise hypotension.

AIM: The present study was undertaken to determine the effects of type 2 diabetes (T2D) on plasma kallikrein activity (PKA) and postexercise hypotension (PEH). METHODS: Ten T2D patients (age: 53.6±1.3 years; body mass index: 30.6±1.0kg/m(2); resting blood glucose: 157.8±40.2mgdL(-1)) and 10 non-diabetic (ND) volunteers (age: 47.5±1.0 years; body mass index: 28.3±0.9kg/m(2); resting blood glucose: 91.2±10.5mgdL(-1)) underwent two experimental sessions, consisting of 20min of rest plus 20min of exercise (EXE) at an intensity corresponding to 90% of their lactate threshold (90LT) and a non-exercise control (CON) session. Blood pressure (BP; Microlife BP 3AC1-1 monitor) and PKA were measured during rest and every 15min for 135min of the postexercise recovery period (RP). RESULTS: During the RP, the ND individuals presented with PEH at 30, 45 and 120min (P<0.05) while, in the T2D patients, PEH was not observed at any time. PKA increased at 15min postexercise in the ND (P<0.05), but not in the T2D patients. CONCLUSION: T2D individuals have a lower PKA response to exercise, which probably suppresses its hypotensive effect, thus reinforcing the possible role of PKA on PEH.

Escherichia coli lipopolysaccharide inhibits renin activity in human mesangial cells.

Hyperactivation of systemic renin-angiotensin system (RAS) during sepsis is well documented. However, the behavior of intrarenal RAS in the context of endotoxemia is yet to be defined. The present study evaluates the direct effect of Escherichia coli lipopolysaccharide (LPS) on immortalized human mesangial cell (HMC) RAS. Quiescent HMC were incubated with vehicle or LPS (1-100 microg/ml), and levels of angiotensin I and II (Ang I and II) and their metabolites were analyzed by high-performance liquid chromatography. In addition, angiotensin-converting enzyme (ACE) and renin activity were also investigated. Cell lysate and extracellular medium levels of Ang II were rapidly reduced (1 h) in a time- and concentration-dependent manner, reaching a significant -9 fold-change (P<0.001) after 3 h of LPS incubation. Similar results were obtained for Ang I levels (-3 fold-change, P<0.001). We ruled out Ang I and II degradation, as levels of their metabolic fragments were also significantly decreased by LPS. ACE activity was slightly increased following LPS incubation. On the other hand, renin activity was significantly inhibited, as Ang I concentration elevation following exogenous angiotensinogen administration was blunted by LPS (-60% vs vehicle, P<0.001). Renin and angiotensinogen protein levels were not affected by LPS according to Western blot analysis. Taken together, these data demonstrate for the first time that LPS significantly downregulates HMC RAS through inhibition of renin or renin-like activity. These findings are potentially related to the development of and/or recovery from acute renal failure in the context of sepsis.