Effect Of Aerobic Exercise Training On Regional Blood Flow And Vascular Resistance In Diabetic Rats

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Background: Hyperglycemia has been associated with decreased blood flow in various organs, leading to tissue damage and dysfunctions. Exercise training (ET) is known to promote beneficial changes in the autonomic nervous system and may have effects on circulation. The aim of this study was to evaluate coronary and renal blood flows and vascular resistances after ET in diabetic rats. Methods: Thirty-two rats were divided into four groups (n = 8): sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD). Diabetes was induced by an injection of streptozotocin (STZ, 50 mg/kg). The ET was performed on a treadmill for 10 weeks. The blood flows were measured using colored microspheres. Results: The diabetic groups presented hyperglycemia (blood glucose >350 mg/dL) and ET did not change this parameter. The SD group showed reduced renal blood flow when compared to SC group, and ET was able to normalize this parameter in TD rats (SC: 4.3 +/- 0.5; TC: 2.9 +/- 0.3; SD: 1.9 +/- 0.4; TD: 3.2 +/- 0.4 mL/min/g). TD group presented increased coronary blood flow in relation to SD group (SC: 2.3 +/- 0.23; TC: 2.8 +/- 0.5; SD: 1.2 +/- 0.4; TD: 3.0 +/- 0.4 mL/min/g). The heart and kidneys vascular resistance were increased in SD group when compared to SC group, and ET was able to reverse these changes. Conclusions: Given the relevance of cardiomyopathy and nephropathy in mortality of diabetics, our results demonstrated that ET is effective in improving coronary and renal blood flows and vascular resistances in STZ-diabetic rats, reinforcing the positive role of this approach in preventing hyperglycemia-induced long-term organ damage.7Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)CAPES [88881.062178/2014-01]FAPESP [2012/20141-5, 2007/52419-4]CNPq [563961/2010-4, 457200/2014-6

Dexmedetomidina versus outros sedativos na prevenção de Delirium nos adultos em ventilação mecânica

Delirium é uma síndrome neurocognitiva aguda relativamente comum e grave que se caracteriza por desatenção, consciência alterada, disfunção cognitiva e curso flutuante, e pode levar à mortalidade, declínio funcional, institucionalização e demência, com maior incidência nos pacientes mais velhos. Pacientes hospitalizados na Unidade de Terapia Intensiva (UTI) e em uso de ventilação mecânica (VM), quando sedados em excesso, possuem maior duração de permanência na UTI, aumento da duração da VM, maior incidência de delirium e mortalidade. Estudos apontam que a dexmedetomidina reduz a incidência de delirium em pacientes adultos hospitalizados na UTI e em uso de ventilação mecânica quando comparada com outros sedativos. Desse modo, o objetivo do estudo é comparar a dexmedetomidina e outros sedativos na prevenção de delirium nos adultos em ventilação mecânica. Trata-se de uma revisão bibliográfica integrativa, do tipo quantitativa, que utilizou as plataformas do PubMed, SciELO e Cochrane Library como bases de dados para seleção dos artigos, todos na língua inglesa. Foram utilizadas literaturas publicadas com recorte temporal de 2017 a 2022. De acordo com as literaturas analisadas, conclui-se que, quando comparado com outros sedativos gabaminérgicos, como os benzodiazepínicos e o propofol, a dexmedetomidina diminui significativamente a incidência de delirium nos pacientes adultos em ventilação mecânica na UTI, com melhora da capacidade de despertar do paciente, preservação do desempenho cognitivo e redução do risco de depressão respiratória. Desse modo, pesquisas futuras sobre as propriedades farmacológicas da dexmedetomidina podem ajudar a determinar se esta droga possui propriedades neuroprotetoras intrínsecas, sendo assim, tal descoberta facilitaria o desenvolvimento de análogos com menos efeitos colaterais cardiorrespiratórios, tendo em vista seu efeito hemodinâmico, com bradicardia e possível hipotensão associadas

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Effect Of Aerobic Exercise Training On Regional Blood Flow And Vascular Resistance In Diabetic Rats.

Hyperglycemia has been associated with decreased blood flow in various organs, leading to tissue damage and dysfunctions. Exercise training (ET) is known to promote beneficial changes in the autonomic nervous system and may have effects on circulation. The aim of this study was to evaluate coronary and renal blood flows and vascular resistances after ET in diabetic rats. Thirty-two rats were divided into four groups (n = 8): sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD). Diabetes was induced by an injection of streptozotocin (STZ, 50 mg/kg). The ET was performed on a treadmill for 10 weeks. The blood flows were measured using colored microspheres. The diabetic groups presented hyperglycemia (blood glucose >350 mg/dL) and ET did not change this parameter. The SD group showed reduced renal blood flow when compared to SC group, and ET was able to normalize this parameter in TD rats (SC: 4.3 ± 0.5; TC: 2.9 ± 0.3; SD: 1.9 ± 0.4; TD: 3.2 ± 0.4 mL/min/g). TD group presented increased coronary blood flow in relation to SD group (SC: 2.3 ± 0.23; TC: 2.8 ± 0.5; SD: 1.2 ± 0.4; TD: 3.0 ± 0.4 mL/min/g). The heart and kidneys vascular resistance were increased in SD group when compared to SC group, and ET was able to reverse these changes. Given the relevance of cardiomyopathy and nephropathy in mortality of diabetics, our results demonstrated that ET is effective in improving coronary and renal blood flows and vascular resistances in STZ-diabetic rats, reinforcing the positive role of this approach in preventing hyperglycemia-induced long-term organ damage

Effect of aerobic exercise training on regional blood flow and vascular resistance in diabetic rats

Hyperglycemia has been associated with decreased blood flow in various organs, leading to tissue damage and dysfunctions. Exercise training (ET) is known to promote beneficial changes in the autonomic nervous system and may have effects on circulation. The aim of this study was to evaluate coronary and renal blood flows and vascular resistances after ET in diabetic rats. Thirty-two rats were divided into four groups (n = 8): sedentary control (SC), trained control (TC), sedentary diabetic (SD), trained diabetic (TD). Diabetes was induced by an injection of streptozotocin (STZ, 50 mg/kg). The ET was performed on a treadmill for 10 weeks. The blood flows were measured using colored microspheres. The diabetic groups presented hyperglycemia (blood glucose >350 mg/dL) and ET did not change this parameter. The SD group showed reduced renal blood flow when compared to SC group, and ET was able to normalize this parameter in TD rats (SC: 4.3 +/- 0.5; TC: 2.9 +/- 0.3; SD: 1.9 +/- 0.4; TD: 3.2 +/- 0.4 mL/min/g). TD group presented increased coronary blood flow in relation to SD group (SC: 2.3 +/- 0.23; TC: 2.8 +/- 0.5; SD: 1.2 +/- 0.4; TD: 3.0 +/- 0.4 mL/min/g). The heart and kidneys vascular resistance were increased in SD group when compared to SC group, and ET was able to reverse these changes. Given the relevance of cardiomyopathy and nephropathy in mortality of diabetics, our results demonstrated that ET is effective in improving coronary and renal blood flows and vascular resistances in STZ-diabetic rats, reinforcing the positive role of this approach in preventing hyperglycemia-induced long-term organ damage7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQCOORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP563961/2010-4; 457200/2014-688881.062178/2014-012012/20141-5; 2007/52419-

Diabetic hyperglycemia attenuates sympathetic dysfunction and oxidative stress after myocardial infarction in rats

Background: Previous research has demonstrated that hyperglycemia may protect the heart against ischemic injury. The aim of the present study was to investigate the association between hyperglycemia and myocardial infarction on cardiovascular autonomic modulation and cardiac oxidative stress profile in rats. Male Wistar rats were divided into: control (C), diabetic (D), myocardial infarcted (MI) and diabetic infarcted rats (DMI). Methods: Diabetes was induced by streptozotocin (STZ, 50 mg/Kg) at the beginning of the protocol and MI was induced by left coronary occlusion 15 days after STZ. Thirty days after streptozocin-induced diabetes, cardiovascular autonomic modulation was evaluated by spectral analysis, and oxidative stress profile was determined by antioxidant enzyme activities and superoxide anion, together with protein carbonylation and redox balance of glutathione (GSH/GSSG). Results: The diabetic and infarcted groups showed decreased heart rate variability and vagal modulation (p < 0.05); however, sympathetic modulation decreased only in diabetic groups (p < 0.05). Sympatho/vagal balance and vascular sympathetic modulation were increased only in the MI group (p < 0.05). Diabetes promoted an increase in catalase concentration (p < 0.05). Glutathione peroxidase activity was increased only in DMI when compared to the other groups (p < 0.05). Superoxide anion and protein carbonylation were increased only in MI group (p < 0.05). Cardiac redox balance, as evaluated by GSH/GSSG, was lower in the MI group (p < 0.05). Conclusions: These data suggest that hyperglycemia promotes compensatory mechanisms that may offer protection against ischemia, as demonstrated by increased antioxidants, decreased pro-oxidants and protein damage, possibly related to the improvements in both redox balance and sympathetic modulation to the heart