O papel da inervação do tecido adiposo retroperitoneal na ativação simpática sistêmica e alterações cardiovasculares e metabólicas em modelo de obesidade experimental

The predominance of obesity and overweight has been constantly increasing in developed and emerging countries due to the intake of high-fat foods and a sedentary lifestyle of choice, which makes obesity one of the most concerning public health issues worldwide. Obese people have a higher risk of developing comorbidities, such as type 2 diabetes, atherosclerosis, arterial hypertension, chronic kidney diseases and increase of cardiovascular morbidity and mortality rates. It is suggested that 65-75% of arterial hypertension diagnosis cases are associated with overweight, bringing even more attention to the importance of comprehending obesity and its comorbidities development’s underlying mechanisms. Thus, this project aimed to evaluate the influence of the retroperitoneal white adipose tissue (rWAT) innervation on sympathetic activity, cardiovascular and metabolic changes in high-fat diet-induced obese rats. For such, male Wistar rats, weighting 250-300g, were used, separated into groups treated with high-fat diet (HFD) (5,18 kcal/g, 36,5% fat) or conventional diet (2,69 kcal/g, 4,6% fat) for 8 weeks and that underwent or not rWAT denervation at 6 weeks. Our results have shown that animals treated with HFD presented higher serum levels of leptin and glucose, a discreet increase in mean arterial pressure (MAP) and a significant increase in splanchnic sympathetic nervous activity (sSNA); after rWAT denervation, these parameters were all normalized. We have also verified an increase in pro- and anti-inflammatory cytokines gene and protein expression levels, as well as tissue renin-angiotensin-aldosterone system (RAAS) components protein expression in retroperitoneal, mesenteric and epididymal white adipose tissue in HFD-treated animals; rWAT denervation has significantly altered these parameters. Therefore, the model of obesity induced by HFD was able to promote increased levels of serum leptin and blood glucose, MAP, sSNA, inflammatory and tissue RAAS activation markers. Besides, rWAT denervation has improved and even normalized most of these factors, suggesting that the adipose tissue signaling is capable of regulating tissue responses, as well as systemic, that are most likely involved in obesity’s comorbidities development.A prevalência da obesidade e sobrepeso tem aumentado muito em países desenvolvidos e subdesenvolvidos, tornando-se cada vez mais um problema de saúde pública devido ao alto risco de desenvolvimento de doença associadas, dentre elas, a diabetes, aterosclerose, hipertensão arterial, doença renal crônica e aumento de morbidade e mortalidade cardiovascular. Sugere-se que 65-75% do diagnóstico de hipertensão arterial é atribuído ao excesso de peso corporal, evidenciando a importância de compreender os mecanismos responsáveis pelo desenvolvimento destas doenças associadas à obesidade. Sendo assim, o objetivo do presente trabalho foi avaliar o papel da inervação do tecido adiposo retroperitoneal (RET) na ativação simpática, alterações cardiometabólicas em ratos submetidos à dieta hiperlipídica. Para tanto, foram utilizados ratos wistar (250-300g) tratados com dieta hiperlipídica (5,18 Kcal/g e 36,5% de gordura) ou dieta padrão (2,69 Kcal/g e 4,6% de gordura) durante 8 semanas, e submetidos ou não à denervação do tecido adiposo RET. Nossos resultados mostraram que os animais tratados com dieta hiperlipídica apresentaram aumento na concentração sérica de leptina e glicose, bem como um pequeno aumento na pressão arterial média (PAM) e significante elevação na atividade nervosa simpática esplâncnica (ANSe), e, após a denervação do tecido adiposo RET, estes parâmetros foram normalizados. Verificamos também aumento na expressão gênica e proteica de citocinas pró-inflamatórias e na expressão gênica de componentes do sistema renina-angiotensina-aldosterona (SRAA) tecidual (RET e mesentérico) nos animais tratados com dieta hiperlipídica; após a denervação do RET, observamos uma importante redução nessas citocinas e nos componentes do SRAA. Além disso, a dieta hiperlipídica modificou a atividade das enzimas antioxidante no soro, tecido adiposo RET e mesentérico e a denervação do tecido adiposo RET reverteu estas alterações. Portanto, podemos concluir que a obesidade induzida pela dieta hiperlipídica promoveu aumento na atividade nervosa simpática, PAM, leptina sérica e glicemia, assim como, em marcadores envolvidos no processo inflamatório, na ativação do SRAA e estresse oxidativo tecidual. Além disso, a denervação do tecido adiposo RET melhorou de forma significante a maior parte destes parâmetros, sugerindo que a sinalização proveniente da inervação do tecido adiposo é capaz de regular respostas sistêmicas e teciduais provavelmente envolvidas no desenvolvimento das comorbidades presentes na obesidade.Dados abertos - Sucupira - Teses e dissertações (2019

Long-term respiratory follow-up of ICU hospitalized COVID-19 patients: Prospective cohort study.

BackgroundCoronavirus disease (COVID-19) survivors exhibit multisystemic alterations after hospitalization. Little is known about long-term imaging and pulmonary function of hospitalized patients intensive care unit (ICU) who survive COVID-19. We aimed to investigate long-term consequences of COVID-19 on the respiratory system of patients discharged from hospital ICU and identify risk factors associated with chest computed tomography (CT) lesion severity.MethodsA prospective cohort study of COVID-19 patients admitted to a tertiary hospital ICU in Brazil (March-August/2020), and followed-up six-twelve months after hospital admission. Initial assessment included: modified Medical Research Council dyspnea scale, SpO2 evaluation, forced vital capacity, and chest X-Ray. Patients with alterations in at least one of these examinations were eligible for CT and pulmonary function tests (PFTs) approximately 16 months after hospital admission. Primary outcome: CT lesion severity (fibrotic-like or non-fibrotic-like). Baseline clinical variables were used to build a machine learning model (ML) to predict the severity of CT lesion.ResultsIn total, 326 patients (72%) were eligible for CT and PFTs. COVID-19 CT lesions were identified in 81.8% of patients, and half of them showed mild restrictive lung impairment and impaired lung diffusion capacity. Patients with COVID-19 CT findings were stratified into two categories of lesion severity: non-fibrotic-like (50.8%-ground-glass opacities/reticulations) and fibrotic-like (49.2%-traction bronchiectasis/architectural distortion). No association between CT feature severity and altered lung diffusion or functional restrictive/obstructive patterns was found. The ML detected that male sex, ICU and invasive mechanic ventilation (IMV) period, tracheostomy and vasoactive drug need during hospitalization were predictors of CT lesion severity(sensitivity,0.78±0.02;specificity,0.79±0.01;F1-score,0.78±0.02;positive predictive rate,0.78±0.02; accuracy,0.78±0.02; and area under the curve,0.83±0.01).ConclusionICU hospitalization due to COVID-19 led to respiratory system alterations six-twelve months after hospital admission. Male sex and critical disease acute phase, characterized by a longer ICU and IMV period, and need for tracheostomy and vasoactive drugs, were risk factors for severe CT lesions six-twelve months after hospital admission

Data_Sheet_1_Data-driven, cross-disciplinary collaboration: lessons learned at the largest academic health center in Latin America during the COVID-19 pandemic.PDF

IntroductionThe COVID-19 pandemic has prompted global research efforts to reduce infection impact, highlighting the potential of cross-disciplinary collaboration to enhance research quality and efficiency.MethodsAt the FMUSP-HC academic health system, we implemented innovative flow management routines for collecting, organizing and analyzing demographic data, COVID-related data and biological materials from over 4,500 patients with confirmed SARS-CoV-2 infection hospitalized from 2020 to 2022. This strategy was mainly planned in three areas: organizing a database with data from the hospitalizations; setting-up a multidisciplinary taskforce to conduct follow-up assessments after discharge; and organizing a biobank. Additionally, a COVID-19 curated collection was created within the institutional digital library of academic papers to map the research output.ResultsOver the course of the experience, the possible benefits and challenges of this type of research support approach were identified and discussed, leading to a set of recommended strategies to enhance collaboration within the research institution. Demographic and clinical data from COVID-19 hospitalizations were compiled in a database including adults and a minority of children and adolescents with laboratory confirmed COVID-19, covering 2020–2022, with approximately 350 fields per patient. To date, this database has been used in 16 published studies. Additionally, we assessed 700 adults 6 to 11 months after hospitalization through comprehensive, multidisciplinary in-person evaluations; this database, comprising around 2000 fields per subject, was used in 15 publications. Furthermore, thousands of blood samples collected during the acute phase and follow-up assessments remain stored for future investigations. To date, more than 3,700 aliquots have been used in ongoing research investigating various aspects of COVID-19. Lastly, the mapping of the overall research output revealed that between 2020 and 2022 our academic system produced 1,394 scientific articles on COVID-19.DiscussionResearch is a crucial component of an effective epidemic response, and the preparation process should include a well-defined plan for organizing and sharing resources. The initiatives described in the present paper were successful in our aim to foster large-scale research in our institution. Although a single model may not be appropriate for all contexts, cross-disciplinary collaboration and open data sharing should make health research systems more efficient to generate the best evidence.</p