Lacking conventional lymphatic system, the central nervous system requires alternative clearance systems, such as the glymphatic system, which promotes clearance of interstitial solutes. Aquaporin-4 water channels (AQP4) are an integral part of this system and related to neuropathologies, such as Alzheimer’s disease (AD). The clearance of Alzheimer’s associated proteins amyloid β and tau is diminished by glymphatic system impairment, due to lack of AQP4. Even though AQP4 mislocalisation (which affects its activity) is a phenotype of AD, it remains a controversial topic, as it is still unclear if it is a phenotype-promoting factor or a consequence of this pathology. This review provides important and updated knowledge about glymphatic system, AQP4 itself, and their link with Alzheimer’s disease. Finally, AQP4 as a therapeutic target is proposed to ameliorate Alzheimer’s Disease and other neuropathologies AQP4-related.

O objetivo desta pesquisa é analisar a percepção dos estudantes quanto à utilidade da técnica role-play no desenvolvimento de habilidades e competências, requeridas ao profissional da área contábil no primeiro estágio do Ensino Embasado na Estrutura Conceitual. A percepção sobre o uso da técnica foi identificada por meio de levantamento e grupo focal com os estudantes matriculados na disciplina Contabilidade Introdutória. Os resultados sugerem que, na percepção dos estudantes, o role-play auxilia no desenvolvimento de habilidades e competências de todas as categorias do domínio cognitivo da Taxonomia de Bloom (Conhecimento, Compreensão, Aplicação, Análise, Síntese e Avaliação), superando as expectativas do Ensino Embasado na Estrutura Conceitual de desenvolvimento apenas das três primeiras categorias.

Diabetes is a known risk factor for severe coronavirus disease 2019 , the disease caused by the new coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. We aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of patients with and without diabetes hospitalized for COVID-19. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of the SARS-CoV-2 main receptor system (ACE2/TMPRSS2), and for the main molecule of the leukotriene B 4 (LTB 4 ) pathway (ALOX5). We found that diabetes activates the LTB 4 pathway and that during COVID-19 it increases ACE2/TMPRSS2 as well as ALOX5 expression. Diabetes was also associated with COVID-19-related disorders, such as reduced oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen (FiO 2 ) and arterial partial pressure of oxygen/FiO 2 levels, and increased disease duration. In addition, the expressions of ACE2 and ALOX5 are positively correlated, with increased expression in patients with diabetes and COVID-19 requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB 4 is significantly increased in individuals with diabetes. In addition, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB 4 and IL-6 systemic levels, as well as ACE2/ALOX5 blood expression, could be early markers of severe COVID-19 in individuals with diabetes.As of 17 May 2021, >162 million confirmed cases of coronavirus disease 19 (COVID-19) and >3.3 million deaths worldwide from the pandemic had been recorded (1). The disease is caused by the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged in China and rapidly spread around the world (2). Estimates indicate that $80% of infected individuals are asymptomatic or develop mild symptoms. The other 20% can develop moderate to severe disease, occasionally

Background and Aims End-stage chronic kidney disease is associated with the condition of chronic inflammation, impacting increased cardiovascular mortality in this specific population. Patients on hemodialysis are known to be predisposed to several factors that predispose to inflammation: dialysis membranes, central venous catheters, oxidative stress, fluid overload, sodium overload, uraemic toxins. Propolis, a natural resin produced by bees from plant materials, has anti-inflammatory, immunomodulatory, and anti-oxidant properties. The aim of this study was to evaluate the impact of Brazilian green propolis extract on inflammation in hemodialysis patients. Here we present preliminary results of the trial NCT04072341. Method We performed a prospective trial, open-label 9-week crossover study examining the effect of Brazilian green propolis (250mg/day, in capsules) on inflammation in hemodialysis patients. We included patients over 18 years, under intermittent hemodialysis (thrice per week), on hemodialysis for at least 1 month and until now 37 patients were included. We excluded pregnant women, cancer carried and patients who developed infection or underwent any surgical procedure during the study period. Each period was 4 weeks in duration with a 1-week washout period in between. The primary end point was change in serum level of high-sensitivity c-reactive protein (HsCRP). Secondary end point evaluated the safety of propolis use in hemodialysis patients. Results Their mean age was 58.6 ± 15.2 years (mean ± SD), and 22 (59.4%) were men. The proportion of patients with hypertension was 14 (37.8%) and diabetes was 9 (24.3%). The number of patients using arteriovenous fistula were 26 (70.2%). The HsCRP presented (mean ± SE) 5.31 ± 1.02 mg/L at baseline, 4.26 ± 0.76 mg/L after propolis period and 4.56 ± 1.32 mg/L in control period, p = 0.0042. Safety parameters were analyzed such as amylase, aspartate aminotransferase (AST) and creatine phosphokinase (CPK); there was no difference between them before and after the use of propolis. None of the participants reported any adverse effects or allergic reactions during the treatment. Conclusion Patients on hemodialysis have an increased inflammatory state. For the best of our knowledge it was the first clinical trial who demonstrated the safety of propolis in hemodialysis patients. Brazilian green propolis demonstrated a tendency to reduce inflammation in these patients.

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AimsPre-existing conditions, such as age, hypertension, obesity, and diabetes, constitute known risk factors for severe COVID-19. However, the impact of prediabetes mellitus (PDM) on COVID-19 severity is less clear. This study aimed to evaluate the influence of PDM in the acute and long-term phases of COVID-19.Materials and methodsWe compared inflammatory mediators, laboratory and clinical parameters and symptoms in COVID-19 patients with prediabetes (PDM) and without diabetes (NDM) during the acute phase of infection and at three months post-hospitalization.ResultsPatients with PDM had longer hospital stays and required intensive care unit admission more frequently than NDM. Upon hospitalization, PDM patients exhibited higher serum levels of interleukin 6 (IL-6), which is related to reduced partial pressure of oxygen (PaO2) in arterial blood, oxygen saturation (SpO2) and increased COVID-19 severity. However, at three months after discharge, those with PDM did not exhibit significant alterations in laboratory parameters or residual symptoms; however, PDM was observed to influence the profile of reported symptoms.ConclusionsPDM seems to be associated with increased risk of severe COVID-19, as well as higher serum levels of IL-6, which may constitute a potential biomarker of severe COVID-19 risk in affected patients. Furthermore, while PDM correlated with more severe acute-phase COVID-19, no long-term worsening of sequelae was observed.

Data showed that in vitro combination of carboplatin and piroxicam produced a more potent antiproliferative effect when compared to single drugs.

Diabetes is a known risk factor for severe COVID-19, the disease caused by the new coronavirus SARS-CoV-2. However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. Therefore, we aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of hospitalized patients for COVID-19, with diabetes and without diabetes. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of SARS-CoV-2 main receptor system (<i>ACE2/TMPRSS2</i>) and main molecule of LTB₄ pathway (<i>ALOX5</i>). We found that diabetes activates LTB₄ pathway, and during COVID-19, it increases <i>ACE2/TMPRSS2</i> as well as <i>ALOX5</i> expression. Diabetes was also associated with COVID-19-related disorders, such as reduced SpO2/FiO2 and PaO2/FiO2 levels, and increased disease duration. In addition, the expression of <i>ACE2</i> and <i>ALOX5</i> are positively correlated, with increased expression in COVID-19 patients with diabetes requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB₄ is significantly increased in individuals with diabetes. Besides, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB₄ and IL-6 systemic levels, as well as, <i>ACE2</i><i>/ALOX5</i> blood expression could be early markers of severe COVID-19 in individuals with diabetes.