Residues in the Fructose Binding Pocket Are Required for Ketohexokinase-A Activity.

Excessive fructose consumption is a primary contributor to the global surges in obesity, cancer, and metabolic syndrome. Fructolysis is not robustly regulated and is initiated by ketohexokinase (KHK). In this study, we determined the crystal structure of KHK-A, one of two human isozymes of KHK, in the apo-state at 1.85 Å resolution, and we investigated the roles of residues in the fructose-binding pocket by mutational analysis. Introducing alanine at D15, N42, or N45 inactivated KHK-A, whereas mutating R141 or K174 reduced activity and thermodynamic stability. Kinetic studies revealed that the R141A and K174A mutations reduced fructose affinity by 2- to 4-fold compared to WT KHK-A, without affecting ATP affinity. Molecular dynamics simulations provided mechanistic insights into the potential roles of the mutated residues in ligand coordination and the maintenance of an open state in one monomer and a closed state in the other. Protein-protein interactome analysis indicated distinct expression patterns and downregulation of partner proteins in different tumor tissues, warranting a re-evaluation of KHK's role in cancer development and progression. The connections between different cancer genes and the KHK signaling pathway suggest that KHK is a potential target for preventing cancer metastasis. This study enhances our understanding of KHK-A's structure and function and offers valuable insights into potential targets for developing treatments for obesity, cancer, and metabolic syndrome.

Social determinants of respiratory health from birth: still of concern in the 21st century?

Respiratory symptoms are ubiquitous in children and, even though they may be the harbinger of poor long-term outcomes, are often trivialised. Adverse exposures pre-conception, antenatally and in early childhood have lifetime impacts on respiratory health. For the most part, lung function tracks from the pre-school years at least into late middle age, and airflow obstruction is associated not merely with poor respiratory outcomes but also early all-cause morbidity and mortality. Much would be preventable if social determinants of adverse outcomes were to be addressed. This review presents the perspectives of paediatricians from many different contexts, both high and low income, including Europe, the Americas, Australasia, India, Africa and China. It should be noted that there are islands of poverty within even the highest income settings and, conversely, opulent areas in even the most deprived countries. The heaviest burden of any adverse effects falls on those of the lowest socioeconomic status. Themes include passive exposure to tobacco smoke and indoor and outdoor pollution, across the entire developmental course, and lack of access even to simple affordable medications, let alone the new biologicals. Commonly, disease outcomes are worse in resource-poor areas. Both within and between countries there are avoidable gross disparities in outcomes. Climate change is also bearing down hardest on the poorest children. This review highlights the need for vigorous advocacy for children to improve lifelong health. It also highlights that there are ongoing culturally sensitive interventions to address social determinants of disease which are already benefiting children.

Use of elexacaftor+tezacaftor+ivacaftor in individuals with cystic fibrosis and at least one F508del allele: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the effect of treatment with the combination of three cystic fibrosis transmembrane conductance regulator (CFTR) modulators-elexacaftor+tezacaftor+ivacaftor (ETI)-on important clinical endpoints in individuals with cystic fibrosis. METHODS: This was a systematic review and meta-analysis of randomized clinical trials that compared the use of ETI in individuals with CF and at least one F508del allele with that of placebo or with an active comparator such as other combinations of CFTR modulators, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) methodology. We searched the following databases: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov from their inception to December 26th, 2022. The risk of bias was assessed using the Cochrane risk-of-bias tool, and the quality of evidence was based on the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: We retrieved 54 studies in the primary search. Of these, 6 met the inclusion criteria and were analyzed (1,127 patients; 577 and 550 in the intervention and control groups, respectively). The meta-analysis revealed that the use of ETI increased FEV1% [risk difference (RD), +10.47%; 95% CI, 6.88-14.06], reduced the number of acute pulmonary exacerbations (RD, -0.16; 95% CI, -0.28 to -0.04), and improved quality of life (RD, +14.93; 95% CI, 9.98-19.89) and BMI (RD, +1.07 kg/m2; 95% CI, 0.90-1.25). Adverse events did not differ between groups (RD, -0.03; 95% CI, -0.08 to 0.01), and none of the studies reported deaths. CONCLUSIONS: Our findings demonstrate that ETI treatment substantially improves clinically significant, patient-centered outcomes.

Aplicativos móveis sobre segurança do paciente idoso no ambiente cirúrgico: uma prospecção tecnológica / Mobile applications on the safety of elderly patients in the surgical environment: a technological prospecting

OBJETIVO: Descrever os aplicativos voltados para a segurança do paciente idoso cirúrgico nos períodos pré e pós-operatório. MÉTODO: Prospecção tecnológica com abordagem qualitativa realizada nas lojas virtuais Apple Store, Google Play e aplicativo web. Como estratégia de busca utilizou-se os termos: 'autocuidado idoso', 'pré-operatório', 'pós-operatório', 'segurança do paciente', 'segurança do paciente idoso'. RESULTADOS: Foram identificados 12 aplicativos na loja virtual Apple Store, 17 na Google Play e um web app, os quais estavam voltados a gamificação de profissionais da saúde e da população; aplicativos educacionais aos profissionais de saúde e usuários do sistema de saúde; aplicativos relacionados como ferramenta de trabalho para os profissionais de saúde; aplicativos como ferramenta de autocuidado para usuários do sistema de saúde; e, aplicativos voltados para pós-operatório de usuários do sistema de saúde. CONCLUSÃO: Não foram encontradas tecnologias voltadas para o autocuidado e segurança do paciente idoso nos períodos pré e pós-operatório

OBJECTIVE: To describe applications focused on the safety of elderly surgical patients in the pre- and postoperative periods. METHOD: Technology prospecting with a qualitative approach in the Apple Store, Google Play virtual stores, and web application. As a search strategy, the following terms were used: 'elderly self-care', 'preoperative', 'postoperative', 'patient safety', 'elderly patient safety'. RESULTS: 12 applications were identified in the Apple Store, 17 in Google Play, and a web app, which focused on the gamification of health and population professionals; educational applications to health professionals and health system users; related applications as a work tool for health professionals; applications as a self-care tool for health system users; and, post-operative applications for health system users. CONCLUSION: Technologies aimed at self-care and the safety of elderly patients were not found in the pre- and postoperative periods.

Impact of the immune profiles of hypertensive patients with and without obesity on COVID-19 severity.

BACKGROUND: Comorbidities such as obesity, hypertension, and diabetes are associated with COVID-19 development and severity, probably due to immune dysregulation; however, the mechanisms underlying these associations are not clear. The immune signatures of hypertensive patients with obesity with COVID-19 may provide new insight into the mechanisms of immune dysregulation and progression to severe disease in these patients. METHODS: Hypertensive patients were selected prospectively from a multicenter registry of adults hospitalized with COVID-19 and stratified according to obesity (BMI ≥ 30 kg/m²). Clinical data including baseline characteristics, complications, treatment, and 46 immune markers were compared between groups. Logistic regression was performed to identify variables associated with the risk of COVID-19 progression in each group. RESULTS: The sample comprised 213 patients (89 with and 124 without obesity). The clinical profiles of patients with and without obesity differed, suggesting potential interactions with COVID-19 severity. Relative to patients without obesity, patients with obesity were younger and fewer had cardiac disease and myocardial injury. Patients with obesity had higher EGF, GCSF, GMCSF, interleukin (IL)-1ra, IL-5, IL-7, IL-8, IL-15, IL-1ß, MCP 1, and VEGF levels, total lymphocyte counts, and CD8+ CD38+ mean fluorescence intensity (MFI), and lower NK-NKG2A MFI and percentage of CD8+ CD38+ T cells. Significant correlations between cytokine and immune cell expression were observed in both groups. Five variables best predicted progression to severe COVID-19 in patients with obesity: diabetes, the EGF, IL-10, and IL-13 levels, and the percentage of CD8+ HLA-DR+ CD38+ cells. Three variables were predictive for patients without obesity: myocardial injury and the percentages of B lymphocytes and HLA-DR+ CD38+ cells. CONCLUSION: Our findings suggest that clinical and immune variables and obesity interact synergistically to increase the COVID-19 progression risk. The immune signatures of hypertensive patients with and without obesity severe COVID-19 highlight differences in immune dysregulation mechanisms, with potential therapeutic applications.

Prospective, randomized, controlled trial assessing the effects of a driving pressure-limiting strategy for patients with acute respiratory distress syndrome due to community-acquired pneumonia (STAMINA trial): protocol and statistical analysis plan / Estudo randomizado prospectivo e controlado de avaliação dos efeitos de uma estratégia de limitação da driving pressure em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade (estudo STAMINA): protocolo e plano de análise estatística

ABSTRACT Background: Driving pressure has been suggested to be the main driver of ventilator-induced lung injury and mortality in observational studies of acute respiratory distress syndrome. Whether a driving pressure-limiting strategy can improve clinical outcomes is unclear. Objective: To describe the protocol and statistical analysis plan that will be used to test whether a driving pressure-limiting strategy including positive end-expiratory pressure titration according to the best respiratory compliance and reduction in tidal volume is superior to a standard strategy involving the use of the ARDSNet low-positive end-expiratory pressure table in terms of increasing the number of ventilator-free days in patients with acute respiratory distress syndrome due to community-acquired pneumonia. Methods: The ventilator STrAtegy for coMmunIty acquired pNeumoniA (STAMINA) study is a randomized, multicenter, open-label trial that compares a driving pressure-limiting strategy to the ARDSnet low-positive end-expiratory pressure table in patients with moderate-to-severe acute respiratory distress syndrome due to community-acquired pneumonia admitted to intensive care units. We expect to recruit 500 patients from 20 Brazilian and 2 Colombian intensive care units. They will be randomized to a driving pressure-limiting strategy group or to a standard strategy using the ARDSNet low-positive end-expiratory pressure table. In the driving pressure-limiting strategy group, positive end-expiratory pressure will be titrated according to the best respiratory system compliance. Outcomes: The primary outcome is the number of ventilator-free days within 28 days. The secondary outcomes are in-hospital and intensive care unit mortality and the need for rescue therapies such as extracorporeal life support, recruitment maneuvers and inhaled nitric oxide. Conclusion: STAMINA is designed to provide evidence on whether a driving pressure-limiting strategy is superior to the ARDSNet low-positive end-expiratory pressure table strategy for increasing the number of ventilator-free days within 28 days in patients with moderate-to-severe acute respiratory distress syndrome. Here, we describe the rationale, design and status of the trial.

RESUMO Contexto: Em estudos observacionais sobre a síndrome do desconforto respiratório agudo, sugeriu-se que a driving pressure é o principal fator de lesão pulmonar induzida por ventilador e de mortalidade. Não está claro se uma estratégia de limitação da driving pressure pode melhorar os desfechos clínicos. Objetivo: Descrever o protocolo e o plano de análise estatística que serão usados para testar se uma estratégia de limitação da driving pressure envolvendo a titulação da pressão positiva expiratória final de acordo com a melhor complacência respiratória e a redução do volume corrente é superior a uma estratégia padrão envolvendo o uso da tabela de pressão positiva expiratória final baixa do protocolo ARDSNet, em termos de aumento do número de dias sem ventilador em pacientes com síndrome do desconforto respiratório agudo devido à pneumonia adquirida na comunidade. Métodos: O estudo STAMINA (ventilator STrAtegy for coMmunIty acquired pNeumoniA) é randomizado, multicêntrico e aberto e compara uma estratégia de limitação da driving pressure com a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet em pacientes com síndrome do desconforto respiratório agudo moderada a grave devido à pneumonia adquirida na comunidade internados em unidades de terapia intensiva. Esperamos recrutar 500 pacientes de 20 unidades de terapia intensiva brasileiras e duas colombianas. Eles serão randomizados para um grupo da estratégia de limitação da driving pressure ou para um grupo de estratégia padrão usando a tabela de pressão positiva expiratória final baixa do protocolo ARDSnet. No grupo da estratégia de limitação da driving pressure, a pressão positiva expiratória final será titulada de acordo com a melhor complacência do sistema respiratório. Desfechos: O desfecho primário é o número de dias sem ventilador em 28 dias. Os desfechos secundários são a mortalidade hospitalar e na unidade de terapia intensiva e a necessidade de terapias de resgate, como suporte de vida extracorpóreo, manobras de recrutamento e óxido nítrico inalado. Conclusão: O STAMINA foi projetado para fornecer evidências sobre se uma estratégia de limitação da driving pressure é superior à estratégia da tabela de pressão positiva expiratória final baixa do protocolo ARDSnet para aumentar o número de dias sem ventilador em 28 dias em pacientes com síndrome do desconforto respiratório agudo moderada a grave. Aqui, descrevemos a justificativa, o desenho e o status do estudo.

The II Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19 Joint Guidelines of the Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia and Sociedade Brasileira de Reumatologia.

OBJECTIVE: To update the recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. METHODS: Experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. RESULTS: Twenty-one recommendations were generated, including strong recommendations for the use of corticosteroids in patients using supplemental oxygen and conditional recommendations for the use of tocilizumab and baricitinib for patients on supplemental oxygen or on noninvasive ventilation and anticoagulants to prevent thromboembolism. Due to suspension of use authorization, it was not possible to make recommendations regarding the use of casirivimab + imdevimab. Strong recommendations against the use of azithromycin in patients without suspected bacterial infection, hydroxychloroquine, convalescent plasma, colchicine, and lopinavir + ritonavir and conditional recommendations against the use of ivermectin and remdesivir were made. CONCLUSION: New recommendations for the treatment of hospitalized patients with COVID-19 were generated, such as those for tocilizumab and baricitinib. Corticosteroids and prophylaxis for thromboembolism are still recommended, the latter with conditional recommendation. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and to promote resource economy.

Effects of atelectatic areas on the surrounding lung tissue during mechanical ventilation in an experimental model of acute lung injury induced by lipopolysaccharide / Efeitos das áreas atelectásicas no tecido pulmonar circundante durante a ventilação mecânica em um modelo experimental de lesão pulmonar aguda induzida por lipopolissacarídeo

ABSTRACT Objective: To assess the effect of atelectasis during mechanical ventilation on the periatelectatic and normal lung regions in a model of atelectasis in rats with acute lung injury induced by lipopolysaccharide. Methods: Twenty-four rats were randomized into the following four groups, each with 6 animals: the Saline-Control Group, Lipopolysaccharide Control Group, Saline-Atelectasis Group, and Lipopolysaccharide Atelectasis Group. Acute lung injury was induced by intraperitoneal injection of lipopolysaccharide. After 24 hours, atelectasis was induced by bronchial blocking. The animals underwent mechanical ventilation for two hours with protective parameters, and respiratory mechanics were monitored during this period. Thereafter, histologic analyses of two regions of interest, periatelectatic areas and the normally-aerated lung contralateral to the atelectatic areas, were performed. Results: The lung injury score was significantly higher in the Lipopolysaccharide Control Group (0.41 ± 0.13) than in the Saline Control Group (0.15 ± 0.51), p < 0.05. Periatelectatic regions showed higher lung injury scores than normally-aerated regions in both the Saline-Atelectasis (0.44 ± 0.06 x 0.27 ± 0.74 p < 0.05) and Lipopolysaccharide Atelectasis (0.56 ± 0.09 x 0.35 ± 0.04 p < 0.05) Groups. The lung injury score in the periatelectatic regions was higher in the Lipopolysaccharide Atelectasis Group (0.56 ± 0.09) than in the periatelectatic region of the Saline-Atelectasis Group (0.44 ± 0.06), p < 0.05. Conclusion: Atelectasis may cause injury to the surrounding tissue after a period of mechanical ventilation with protective parameters. Its effect was more significant in previously injured lungs.

RESUMO Objetivo: Avaliar o efeito da atelectasia durante a ventilação mecânica nas regiões periatelectáticas e pulmonares normais em um modelo de atelectasia em ratos com lesão pulmonar aguda induzida por lipopolissacarídeo. Métodos: Foram distribuídos aleatoriamente 24 ratos em quatro grupos, cada um com 6 animais: Grupo Salina-Controle, Grupo Lipopolissacarídeo-Controle, Grupo Salina-Atelectasia e Grupo Lipopolissacarídeo-Atelectasia. A lesão pulmonar aguda foi induzida por injeção intraperitoneal de lipopolissacarídeo. Após 24 horas, a atelectasia foi induzida por bloqueio brônquico. Os animais foram submetidos à ventilação mecânica por 2 horas com parâmetros ventilatórios protetores, e a mecânica respiratória foi monitorada durante esse período. Em seguida, foram realizadas análises histológicas de duas regiões de interesse: as áreas periatelectásicas e o pulmão normalmente aerado contralateral às áreas atelectásicas. Resultados: O escore de lesão pulmonar foi significativamente maior no Grupo Controle-Lipopolissacarídeo (0,41 ± 0,13) do que no Grupo Controle-Solução Salina (0,15 ± 0,51), com p < 0,05. As regiões periatelectásicas apresentaram escores maiores de lesão pulmonar do que as regiões normalmente aeradas nos Grupos Atelectasia-Solução Salina (0,44 ± 0,06 versus 0,27 ± 0,74, p < 0,05) e Atelectasia-Lipopolissacarídeo (0,56 ± 0,09 versus 0,35 ± 0,04, p < 0,05). O escore de lesão pulmonar nas regiões periatelectásicas foi maior no Grupo Atelectasia-Lipopolissacarídeo (0,56 ± 0,09) do que na região periatelectásica do Grupo Atelectasia-Solução Salina (0,44 ± 0,06), p < 0,05. Conclusão: A atelectasia pode causar lesão no tecido circundante após um período de ventilação mecânica com parâmetros ventilatórios protetores. Seu efeito foi mais significativo em pulmões previamente lesionados.

Risk factors associated to incisional hernia in stoma site after stoma closure: A systematic review and meta-analysis.

BACKGROUND: This study aims to identify which risk factors are associated with the appearance of an incisional hernia in a stoma site after its closure. This in the sake of identifying which patients would benefit from a preventative intervention and thus start implementing a cost-effective protocol for prophylactic mesh placement in high-risk patients. METHODS: A systematic review of PubMed, Cochrane library, and ScienceDirect was performed according to PRISMA guidelines. Studies reporting incidence, risk factors, and follow-up time for appearance of incisional hernia after stoma site closure were included. A fixed-effects and random effects models were used to calculate odds ratios' estimates and standardized mean values with their respective grouped 95% confidence interval. This to evaluate the association between possible risk factors and the appearance of incisional hernia after stoma site closure. RESULTS: Seventeen studies totaling 2899 patients were included. Incidence proportion between included studies was of 16.76% (CI95% 12.82; 21.62). Out of the evaluated factors higher BMI (p = 0.0001), presence of parastomal hernia (p = 0.0023), colostomy (p = 0,001), and end stoma (p = 0.0405) were associated with the appearance of incisional hernia in stoma site after stoma closure, while malignant disease (p = 0.0084) and rectum anterior resection (p = 0.0011) were found to be protective factors. CONCLUSIONS: Prophylactic mesh placement should be considered as an effective preventative intervention in high-risk patients (obese patients, patients with parastomal hernia, colostomy, and end stoma patients) with the goal of reducing incisional hernia rates in stoma site after closure while remaining cost-effective.

The II Brazilian Guidelines for the pharmacological treatment of patients hospitalized with COVID-19 Joint Guidelines of the Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia and Sociedade Brasileira de Reumatologia / II Diretrizes Brasileiras para o tratamento farmacológico de pacientes hospitalizados com COVID-19 Diretriz conjunta da Associação Brasileira de Medicina de Emergência, Associação de Medicina Intensiva Brasileira, Associação Médica Brasileira, Sociedade Brasileira de Angiologia e Cirurgia Vascular, Sociedade Brasileira de Infectologia, Sociedade Brasileira de Pneumologia e Tisiologia e Sociedade Brasileira de Reumatologia

ABSTRACT Objective: To update the recommendations to support decisions regarding the pharmacological treatment of patients hospitalized with COVID-19 in Brazil. Methods: Experts, including representatives of the Ministry of Health and methodologists, created this guideline. The method used for the rapid development of guidelines was based on the adoption and/or adaptation of existing international guidelines (GRADE ADOLOPMENT) and supported by the e-COVID-19 RecMap platform. The quality of the evidence and the preparation of the recommendations followed the GRADE method. Results: Twenty-one recommendations were generated, including strong recommendations for the use of corticosteroids in patients using supplemental oxygen and conditional recommendations for the use of tocilizumab and baricitinib for patients on supplemental oxygen or on noninvasive ventilation and anticoagulants to prevent thromboembolism. Due to suspension of use authorization, it was not possible to make recommendations regarding the use of casirivimab + imdevimab. Strong recommendations against the use of azithromycin in patients without suspected bacterial infection, hydroxychloroquine, convalescent plasma, colchicine, and lopinavir + ritonavir and conditional recommendations against the use of ivermectin and remdesivir were made. Conclusion: New recommendations for the treatment of hospitalized patients with COVID-19 were generated, such as those for tocilizumab and baricitinib. Corticosteroids and prophylaxis for thromboembolism are still recommended, the latter with conditional recommendation. Several drugs were considered ineffective and should not be used to provide the best treatment according to the principles of evidence-based medicine and to promote resource economy.

RESUMO Objetivo: Atualizar as recomendações para embasar as decisões para o tratamento farmacológico de pacientes hospitalizados com COVID-19 no Brasil. Métodos: A elaboração desta diretriz foi feita por especialistas, incluindo representantes do Ministério da Saúde e metodologistas. O método utilizado para o desenvolvimento rápido de diretrizes baseou-se na adoção e/ou adaptação de diretrizes internacionais existentes (GRADE ADOLOPMENT) e contou com o apoio da plataforma e-COVID-19 RecMap. A qualidade das evidências e a elaboração das recomendações seguiram o método GRADE. Resultados: Chegaram-se a 21 recomendações, incluindo recomendações fortes quanto ao uso de corticosteroides em pacientes em uso de oxigênio suplementar e recomendações condicionais para o uso de tocilizumabe e baricitinibe, em pacientes com oxigênio suplementar ou ventilação não invasiva, e de anticoagulantes, para prevenção de tromboembolismo. Devido à suspensão da autorização de uso, não foi possível fazer recomendações para o tratamento com casirivimabe + imdevimabe. Foram feitas recomendações fortes contra o uso de azitromicina em pacientes sem suspeita de infecção bacteriana, hidroxicloroquina, plasma convalescente, colchicina e lopinavir + ritonavir, além de recomendações condicionais contra o uso de ivermectina e rendesivir. Conclusão: Foram criadas novas recomendações para o tratamento de pacientes hospitalizados com COVID-19, como as recomendações de tocilizumabe e baricitinibe. Ainda são recomendados corticosteroides e profilaxia contra tromboembolismo, esta em caráter condicional. Vários medicamentos foram considerados ineficazes e não devem ser usados, no intuito de proporcionar o melhor tratamento segundo os princípios da medicina baseada em evidências e promover a economia de recursos.

New Insights on the Mechanisms of Myocardial Injury in Hypertensive Patients With COVID-19.

PURPOSE: Myocardial injury is common in hypertensive patients with 2019 coronavirus disease (COVID-19). Immune dysregulation could be associated to cardiac injury in these patients, but the underlying mechanism has not been fully elucidated. METHODS: All patients were selected prospectively from a multicenter registry of adults hospitalized with confirmed COVID-19. Cases had hypertension and myocardial injury, defined by troponin levels above the 99th percentile upper reference limit, and controls were hypertensive patients with no myocardial injury. Biomarkers and immune cell subsets were quantified and compared between the two groups. A multiple logistic regression model was used to analyze the associations of clinical and immune variables with myocardial injury. RESULTS: The sample comprised 193 patients divided into two groups: 47 cases and 146 controls. Relative to controls, cases had lower total lymphocyte count, percentage of T lymphocytes, CD8+CD38+ mean fluorescence intensity (MFI), and percentage of CD8+ human leukocyte antigen DR isotope (HLA-DR)+ CD38-cells and higher percentage of natural killer lymphocytes, natural killer group 2A (NKG2A)+ MFI, percentage of CD8+CD38+cells, CD8+HLA-DR+MFI, CD8+NKG2A+MFI, and percentage of CD8+HLA-DR-CD38+cells. On multivariate regression, the CD8+HLA-DR+MFI, CD8+CD38+MFI, and total lymphocyte count were associated significantly with myocardial injury. CONCLUSION: Our findings suggest that lymphopenia, CD8+CD38+MFI, and CD8+HLA-DR+MFI are immune biomarkers of myocardial injury in hypertensive patients with COVID-19. The immune signature described here may aid in understanding the mechanisms underlying myocardial injury in these patients. The study data might open a new window for improvement in the treatment of hypertensive patients with COVID-19 and myocardial injury.

Brazilian guidelines for the pharmacological treatment of the pulmonary symptoms of cystic fibrosis. Official document of the Sociedade Brasileira de Pneumologia e Tisiologia (SBPT, Brazilian Thoracic Association).

Cystic fibrosis (CF) is a genetic disease that results in dysfunction of the CF transmembrane conductance regulator (CFTR) protein, which is a chloride and bicarbonate channel expressed in the apical portion of epithelial cells of various organs. Dysfunction of that protein results in diverse clinical manifestations, primarily involving the respiratory and gastrointestinal systems, impairing quality of life and reducing life expectancy. Although CF is still an incurable pathology, the therapeutic and prognostic perspectives are now totally different and much more favorable. The purpose of these guidelines is to define evidence-based recommendations regarding the use of pharmacological agents in the treatment of the pulmonary symptoms of CF in Brazil. Questions in the Patients of interest, Intervention to be studied, Comparison of interventions, and Outcome of interest (PICO) format were employed to address aspects related to the use of modulators of this protein (ivacaftor, lumacaftor+ivacaftor, and tezacaftor+ivacaftor), use of dornase alfa, eradication therapy and chronic suppression of Pseudomonas aeruginosa, and eradication of methicillin-resistant Staphylococcus aureus and Burkholderia cepacia complex. To formulate the PICO questions, a group of Brazilian specialists was assembled and a systematic review was carried out on the themes, with meta-analysis when applicable. The results obtained were analyzed in terms of the strength of the evidence compiled, the recommendations being devised by employing the GRADE approach. We believe that these guidelines represent a major advance to be incorporated into the approach to patients with CF, mainly aiming to favor the management of the disease, and could become an auxiliary tool in the definition of public policies related to CF.

Incidental tomographic findings in patients with a Confirmed Diagnosis of COVID-19: An Observational Study / Achados Tomográficos Incidentais em Pacientes com Diagnóstico Confirmado de COVID-19: Estudo Observacional

Objective: Describe incidental tomographic in the sample, correlating them with risk factors for chest diseases and sociodemographic data. Methods: This is a retrospective and observational study covering 162 patients admitted to the COVID sector of the HU/UFJF, from April 1, 2020, to July 7, 2021, with a confirmed laboratory diagnosis of COVID-19. The variables were described in absolute and relative frequencies. The comparison of the correlation between the outcome variable (the tomographic findings) for independent samples was performed using Pearson's chi-square test (without correction) or Fisher's test when relevant. Results: Of the 162 patients, 15.4% had a solitary pulmonary nodule; 14.8% had multiple pulmonary nodules; 1.8%, lung mass; 3.1%, mediastinal mass, and 9.3% had mediastinal adenomegaly. Findings such as excavations, pleural effusion, emphysema, PTE, pneumothorax, chronic interstitial disease, cavitation, aneurysms, and significant atheromatosis, classified in this study in the "Other" category showed impressive results, with an overall prevalence of 81.5%. This study demonstrated that 34% of patients had two or more types of incidental CT findings and that 88.3% of patients had at least some type of incidental CT finding. Conclusion: The pandemic of SARS-CoV-2 infections has brought a series of challenges and lessons learned to healthcare teams around the world. The massive implementation of highly sensitive diagnostic methods, such as chest tomography, ends up bringing an additional challenge, which is to deal with incidental findings, making good clinical reasoning necessary to avoid unnecessary investigations and not leave without diagnosis and treatment of diseases in early and asymptomatic stages (AU)

Objetivo: Descrever os achados incidentais tomográficos na amostra, correlacionando-os com fatores de risco para doenças torácicas e dados sociodemográficos. Método: Trata-se de um estudo retrospectivo e observacional, abrangendo 162 pacientes admitidos no setor COVID do HU/UFJF, no período de 1º de abril de 2020 a 7 de julho de 2021, com diagnóstico laboratorial confirmado de COVID-19. As variáveis em frequências absolutas e relativas foram descritas. A comparação da correlação entre a variável desfecho (os achados tomográficos) para amostras independentes foi realizada por meio do teste qui-quadrado de Pearson (sem correção) ou Fisher quando pertinente. Resultado: Dos 162 pacientes, 15,4% apresentavam nódulo pulmonar solitário; 14,8%, nódulos pulmonares múltiplos; 1,8%, massa pulmonar; 3,1%, massa mediastinal e 9,3%, adenomegalia mediastinal. Achados como escavações, derrame pleural, enfisema, TEP, pneumotórax, intersticiopatia crônica, cavitação, aneurismas e ateromatose significativa, classificados, neste estudo, na categoria "Outros", apresentaram resultados impactantes, com uma prevalência global de 81,5%. Este estudo demonstrou que 34% dos pacientes apresentavam 2 ou mais tipos de achados tomográficos incidentais e que 88,3% dos pacientes apresentavam pelo menos algum tipo de achado tomográfico incidental. Conclusão: A pandemia de infecções pelo SARS-CoV-2 trouxe uma série de desafios e aprendizados para as equipes de saúde em todo o mundo. A realização maciça de métodos diagnósticos de elevada sensibilidade, como a tomográfica de tórax, acaba por trazer um desafio adicional, que é o de lidar com achados incidentais, fazendo-se necessário um bom raciocínio clínico para evitar investigações desnecessárias e não deixar sem diagnóstico e tratamento doenças em fases iniciais e assintomáticas

Condições de trabalho, adoecimento e enfrentamento da enfermagem na pandemia de covid-19 em uma capital brasileira / Working conditions, illness and nursing coping in the covid-19 pandemic in a brazilian capital / Condiciones de trabajo, enfermedades y enfermería enfrentando la pandemia del covid-19 en una capital brasileña

Objetivo: Descrever as condições de trabalho, adoecimento e o enfrentamento da enfermagem na pandemia de COVID-19 em uma capital brasileira. Métodos: Trata-se de um estudo descritivo, transversal, com abordagem quantitativa. Os dados foram coletados entre agosto e setembro de 2021, de forma on-line. A análise foi realizada por meio do BioEstat 5.0, com técnicas de estatística descritiva e analítica a partir do teste Qui-quadrado de Pearson e do Exato de Fisher, sendo calculado o Odds Ratio nas variáveis em que houve associação significativa. Resultados: Dos 121 participantes do estudo, 106 eram do sexo feminino e mais de 50% possuíam dois vínculos de trabalho. 102 profissionais referiram receber baixos salários pela complexidade do trabalho desenvolvido e 46 apontaram condições precárias para o exercício profissional. Foi encontrada associação estatística na variável referente às orientações de como inspecionar as máscaras N95/PFF2 ou equivalente (p=0.017; OR=0.31; IC 95%=0.13-0.77) e na variável acerca dos profissionais que já apresentaram sintomas de COVID-19 e/ou tiveram diagnóstico confirmado (p=0.047; OR=0.43; IC 95%=0.20-0.93). Conclusão: O presente estudo aponta a necessidade de melhor organização e condições de trabalho nos serviços de saúde de forma que os profissionais de enfermagem possam prestar uma assistência de qualidade. (AU)

Objective: To describe the working conditions, illness and nursing coping in the COVID-19 pandemic in a Brazilian capital. Methods: This is a descriptive, cross-sectional study with a quantitative approach. Data were collected between August and September 2021, online. The analysis was performed using BioEstat 5.0, with descriptive and analytical statistical techniques from Pearson's chi-square test and Fisher's exact test, with the Odds Ratio being adequate for the variables in which there was a linked association. Results: Of the 121 study participants, 106 were female and more than 50% had two jobs. 102 professionals reported salaries earned due to the complexity of the work performed and 46 indicated precarious conditions for professional practice. A statistical association was found regarding the guidelines on how to inspect with masks N95 / PFF2 or equivalent (p = 0.017; OR = 0.31; 95% CI = 0.13-0.77) and the relative variable of professionals who are already associated students of COVID-19 and/or had a confirmed diagnosis (p = 0.047; OR = 0.43; 95% CI = 0.20-0.93). Conclusion: This study points to the need for better organization and working conditions in health services so that nursing professionals must provide quality care. (AU)

Objetivo: Describir las condiciones de trabajo, enfermedad y afrontamiento de enfermería en la pandemia de COVID-19 en una capital brasileña. Métodos: Se trata de un estudio descriptivo, transversal con enfoque cuantitativo. Los datos se recopilaron entre agosto y septiembre de 2021, en línea. El análisis se realizó mediante BioEstat 5.0, con técnicas estadísticas descriptivas y analíticas de la prueba chi-cuadrado de Pearson y la prueba exacta de Fisher, siendo la Odds Ratio adecuada para las variables en las que existía asociación ligada. Resultados: De los 121 participantes del estudio, 106 eran mujeres y más del 50% tenían dos trabajos. 102 profesionales reportaron sueldos percibidos por la complejidad del trabajo realizado y 46 señalaron condiciones precarias para el ejercicio profesional. Se encontró asociación estadística con respecto a las guías sobre cómo inspeccionar con mascarilla N95 / PFF2 o equivalente (p = 0.017; OR = 0.31; IC 95% = 0.13-0.77) y la variable relativa de profesionales que ya son estudiantes asociados de COVID- 19 y / o tenían un diagnóstico confirmado (p = 0,047; OR = 0,43; IC 95% = 0,20-0,93). Conclusión: Este estudio apunta a la necesidad de una mejor organización y condiciones de trabajo en los servicios de salud para que los profesionales de enfermería deban brindar una atención de calidad. (AU)

Grupo de Trabalho em Práticas Corporais e Atividades Físicas na APS da SBAFS: criação, atividades e perspectivas / Working Group on Body Practices and Physical Activities in PHC of BSPAH: creation, activities, and perspectives

A Sociedade Brasileira de Atividade Física e Saúde (SBAFS) exerce papel importante no desenvolvimento e na disseminação do conhecimento científico, além de promover a articulação entre pesquisadores, estudantes, gestores e profissionais dos serviços de saúde nos cenários nacional e internacional. Nos últimos anos, estimulou-se a elaboração e a manutenção de Grupos de Trabalhos (GT) em diferentes temáticas na área de atividade física e saúde. Em 2021, foi instituído o GT em Práticas Corporais e Atividades Físicas na Atenção Primária à Saúde (PCAF-APS), o qual busca desenvolver ações para fortalecer a área temática, por meio da realização de encontros e debates com profissionais, gestores e acadêmicos, além do desenvolvimento de pesquisas. Desse modo, o objetivo deste manuscrito é descrever as ações relacionadas à criação, trajetória e perspectivas do GT PCAF-APS

The Brazilian Society of Physical Activity and Health (BSPAH) is essential in developing and disseminat-ing scientific knowledge and promoting articulation between researchers, students, stakeholders, and health service professionals in national and international scenarios. Developing and maintaining Working Groups ( WG) on different physical activity and health topics has been encouraged in recent years. In 2021, the Body Practices and Physical Activities in Primary Health Care (BPPA-PHC) WG was established, which seeks to develop actions to strengthen the thematic area through meetings and debates with professionals, stakeholders, and academics, in addition to research development. Thus, the paper aims to describe the actions related to the creation, trajectory, and perspectives of the BPPA-PHC

Changes in cerebral autoregulation and vasoreactivity after surgical aortic valve replacement: a prospective study.

NEW FINDINGS: What is the central question of this study? How are dynamic cerebral autoregulation and brain vasoreactivity influenced by severe aortic stenosis and its surgical treatment? What are the main findings and their importance? Dynamic cerebral autoregulation is preserved in the long term in patients with severe aortic stenosis and does not change after surgical aortic valve replacement. However, carbon dioxide vasoreactivity is impaired in these patients. ABSTRACT: Surgical aortic valve replacement (SAVR) alters the natural course of severe aortic stenosis (AS). In this study, we aimed to determine the effects of the disease on dynamic cerebral autoregulation and vasoreactivity (VR) and to assess their changes after SAVR. We recruited 23 patients diagnosed with severe AS eligible for SAVR and 15 healthy matched controls. AS patients had lower mean VR to CO2 (P = 0.005) than controls, but dynamic cerebral autoregulation was preserved. Cerebral haemodynamics showed no significant change after SAVR. Patients with smaller baseline aortic valve areas presented with smaller low frequency phase changes after surgery (P = 0.016). Severe AS does not seem to impact dynamic cerebral autoregulation but does reduce VR to CO2 . SAVR does not alter cerebral autoregulation nor vasoreactivity.

pH profiles of 3-chymotrypsin-like protease (3CLpro) from SARS-CoV-2 elucidate its catalytic mechanism and a histidine residue critical for activity.

3-Chymotrypsin-like protease (3CLpro) is a promising drug target for coronavirus disease 2019 and related coronavirus diseases because of the essential role of this protease in processing viral polyproteins after infection. Understanding the detailed catalytic mechanism of 3CLpro is essential for designing effective inhibitors of infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular dynamics studies have suggested pH-dependent conformational changes of 3CLpro, but experimental pH profiles of SARS-CoV-2 3CLpro and analyses of the conserved active-site histidine residues have not been reported. In this work, pH-dependence studies of the kinetic parameters of SARS-CoV-2 3CLpro revealed a bell-shaped pH profile with 2 pKa values (6.9 ± 0.1 and 9.4 ± 0.1) attributable to ionization of the catalytic dyad His41 and Cys145, respectively. Our investigation of the roles of conserved active-site histidines showed that different amino acid substitutions of His163 produced inactive enzymes, indicating a key role of His163 in maintaining catalytically active SARS-CoV-2 3CLpro. By contrast, the H164A and H172A mutants retained 75% and 26% of the activity of WT, respectively. The alternative amino acid substitutions H172K and H172R did not recover the enzymatic activity, whereas H172Y restored activity to a level similar to that of the WT enzyme. The pH profiles of H164A, H172A, and H172Y were similar to those of the WT enzyme, with comparable pKa values for the catalytic dyad. Taken together, the experimental data support a general base mechanism of SARS-CoV-2 3CLpro and indicate that the neutral states of the catalytic dyad and active-site histidine residues are required for maximum enzyme activity.