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.

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.

Untargeted Metabolomics Reveals Lipid Impairment in the Liver of Adult Zebrafish (Danio rerio) Exposed to Carbendazim.

Carbendazim is a systemic fungicide used in several countries, particularly in Brazil. However, studies suggest that it is related to the promotion of tumors, endocrine disruption, and toxicity to organisms, among other effects. As a result, carbendazim is not allowed in the United States, Australia, and some European Union countries. Therefore, further studies are necessary to evaluate its effects, and zebrafish is a model routinely used to provide relevant information regarding the acute and long-term effects of xenobiotics. In this way, zebrafish water tank samples (water samples from aquari containing zebrafish) and liver samples from animals exposed to carbendazim at a concentration of 120 µg/L were analyzed by liquid chromatography coupled to high-resolution mass spectrometry, followed by multivariate and univariate statistical analyses, using the metabolomics approach. Our results suggest impairment of lipid metabolism with a consequent increase in intrahepatic lipids and endocrine disruption. Furthermore, the results suggest two endogenous metabolites as potential biomarkers to determine carbendazim exposure. Finally, the present study showed that it is possible to use zebrafish water tank samples to assess the dysregulation of endogenous metabolites to understand biological effects. Environ Toxicol Chem 2023;42:437-448. © 2022 SETAC.

Efeitos da suplementação com hidroximetilbutirato na sarcopenia em idosos sem exercício físico: revisão sistemática da literatura / Effects of hydroxymethylbutyrate supplementation on sarcopenia in non-exercising older adults: a systematic literature review / Efectos de la suplementación con hidroximetilbutirato sobre la sarcopenia en ancianos sin ejercicio físico: una revisión sistemática de la literatura

Observa-se um aumento percentual da população de idosos, e a prevalência de comorbidades específicas dessa população gera impactos sociais e nos gastos em saúde. Entre essas comorbidades, identifica-se a sarcopenia, relacionada a declínio funcional, incapacidade física e redução da qualidade de vida. Assim, tornam-se importantes estudos que avaliem a melhoria da força muscular com ênfase no processo de envelhecimento. Considerando a limitação física encontrada em parte dessa população, surgem evidências que avaliaram o efeito independente de suplementos nutricionais em marcadores de sarcopenia, força muscular e funcionalidade. Esta revisão sistemática tem como objetivo avaliar o efeito do hidroximetilbutirato (HMB) na sarcopenia em idosos na ausência de exercício físico. Foi feita uma revisão sistemática de estudos randomizados publicados em inglês, português ou espanhol, entre 2004 e 2021, avaliando o efeito do HMB em marcadores de sarcopenia em idosos. O estudo foi conduzido utilizando Medline, Cochrane, Cinahl, Lilacs e Periódicos Capes. A pesquisa inicial encontrou um total de 201 artigos. A análise final incluiu quatro artigos com amostra de 958 pacientes idosos sarcopênicos. Variabilidade significativa foi encontrada nas definições de sarcopenia, nos métodos utilizados para avaliar o efeito da intervenção e na composição do suplemento nutricional utilizado. Resultados estatisticamente significantes em relação à preservação de massa magra foram encontrados, sem benefício associado de marcadores de força muscular e funcionalidade. A suplementação com HMB, apesar de controlar a perda de massa magra em idosos, não foi capaz de gerar aumento de força muscular e marcadores de funcionalidade.

The population of older adults has shown a percentage increase worldwide, and the prevalence of comorbidities specific to this population generates social impacts and affects health expenditures. Among these comorbidities is sarcopenia, a condition related to functional decline, physical disability, and reduced quality of life. Hence the importance of evaluation studies on muscle strength improvement with emphasis on the aging process. Considering the physical limitations found in part of this population, recent clinical research evaluated the independent effect of nutritional supplements on sarcopenia markers, muscle strength, and functionality. This systematic literature review seeks to evaluate the effect of hydroxymethibultyrate (HMB) on sarcopenia in non-exercising older adults. Bibliographic search on randomized studies published between 2004 and 2021 in English, Portuguese, or Spanish evaluating the effect of HMB on sarcopenia markers was conducted on the MEDLINE, Cochrane, CINAHL, LILACS and CAPES databases. Of the 201 articles identified, only four were included in the review, totaling a sample of 958 sarcopenic aged patients. Results showed significant variability regarding the definitions of sarcopenia, the methods used to assess intervention effects, and the composition of the nutritional supplement used. Lean mass preservation presented statistically significant results, with no associated benefits of muscle strength and functionality markers. Despite decreasing the loss of lean mass in the aged, HMB supplementation was not able to increase muscle strength and functionality markers.

Dado el aumento porcentual de la población anciana, existe una prevalencia de comorbilidades específicas en esta población que generan impactos sociales y gastos en salud. Entre estas comorbilidades se identifica la sarcopenia, relacionada con deterioro funcional, discapacidad física y reducción de la calidad de vida. Así, cobran importancia los estudios que evalúan la mejora de la fuerza muscular con énfasis en el proceso de envejecimiento. Considerando la limitación física encontrada en parte de esta población, aparece evidencia que evalúa el efecto independiente de los suplementos nutricionales sobre los marcadores de sarcopenia, la fuerza muscular y la funcionalidad. Esta revisión sistemática tiene como objetivo evaluar el efecto del hidroximetiletibultirato (HMB) sobre la sarcopenia en ancianos en ausencia de ejercicio físico. Se realizó una revisión sistemática de estudios aleatorizados, publicados entre 2004 y 2021 en inglés, portugués o español y que evaluaron el efecto del HMB en marcadores de sarcopenia en adultos mayores. Se utilizaron las bases de datos Medline, Cochrane, Cinahl, Lilacs y Capes. La búsqueda inicial encontró un total de 201 artículos. El análisis final incluyó cuatro artículos con una muestra de 958 pacientes ancianos sarcopénicos. Se encontró una variabilidad significativa en las definiciones de sarcopenia, los métodos utilizados para evaluar el efecto de la intervención y la composición del suplemento nutricional utilizado. Hubo resultados estadísticamente significativos en cuanto a la preservación de la masa magra, sin beneficio asociado de los marcadores de fuerza muscular y funcionalidad. La suplementación con HMB, si bien disminuye la pérdida de masa magra en los ancianos, no fue capaz de generar un aumento de los marcadores de fuerza y funcionalidad muscular.

TLR-9 Plays a Role in Mycobacterium leprae-Induced Innate Immune Activation of A549 Alveolar Epithelial Cells.

The respiratory tract is considered the main port of entry of Mycobacterium leprae, the causative agent of leprosy. However, the great majority of individuals exposed to the leprosy bacillus will never manifest the disease due to their capacity to develop protective immunity. Besides acting as a physical barrier, airway epithelium cells are recognized as key players by initiating a local innate immune response that orchestrates subsequent adaptive immunity to control airborne infections. However, to date, studies exploring the interaction of M. leprae with the respiratory epithelium have been scarce. In this work, the capacity of M. leprae to immune activate human alveolar epithelial cells was investigated, demonstrating that M. leprae-infected A549 cells secrete significantly increased IL-8 that is dependent on NF-κB activation. M. leprae was also able to induce IL-8 production in human primary nasal epithelial cells. M. leprae-treated A549 cells also showed higher expression levels of human ß-defensin-2 (hßD-2), MCP-1, MHC-II and the co-stimulatory molecule CD80. Furthermore, the TLR-9 antagonist inhibited both the secretion of IL-8 and NF-κB activation in response to M. leprae, indicating that bacterial DNA sensing by this Toll-like receptor constitutes an important innate immune pathway activated by the pathogen. Finally, evidence is presented suggesting that extracellular DNA molecules anchored to Hlp, a histone-like protein present on the M. leprae surface, constitute major TLR-9 ligands triggering this pathway. The ability of M. leprae to immune activate respiratory epithelial cells herein demonstrated may represent a very early event during infection that could possibly be essential to the generation of a protective response.

Socioeconomic disparities in obstructive sleep apnea: a systematic review of empirical research.

BACKGROUND: Considering socioeconomic status (SES) in the diagnosis of obstructive sleep apnea (OSA) will enhance our understanding of socioeconomic disparities in clinical practice of sleep medicine. This systematic review analyzes the relations between SES and OSA measures. METHODOLOGY: Eleven articles were identified through the Pubmed database. The National Institute of Health's Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to rate the quality of these studies. RESULTS: This systematic review revealed that associations between socioeconomic status and OSA measures are similar for both adults, children, and adolescents. Our findings showed that: (1) A lower SES is associated with an increased risk of OSA, both in adults and children/adolescents as well as for men and women. (2) Several studies assessed sleep outcomes with a single question, an approach that is unable to capture the multi-dimensionality and day-to-day variability of sleep in general or OSA in particular, (3) Low SES has detrimental effects on sleep health. (4) Sleep questionnaires are more commonly used than objective measure to assess OSA. CONCLUSIONS: Interaction between SES and OSA must be better understood to improve current clinical guidelines. Living conditions influence the trajectory of OSA with unknown speed and for an, undetermined period, pointing to the need for more studies on this topic. Future work should identify the effect of SES on the development and progression of OSA, determine the effect of behavioral intervention and local public health programs to reduce social inequalities associated with OSA.

Epidemiologia e ônus da depressão resistente ao tratamento no Brasil: análise do subgrupo brasileiro do estudo de observação multicêntrico TRAL / Epidemiology and burden of treatment-resistant depression in Brazil: analysis of the Brazilian subset of multicenter observational TRAL study

Objetivos: A epidemiologia da depressão resistente ao tratamento (DRT) varia mundialmente, mas é incerta na América Latina. Este artigo relata a epidemiologia e o ônus da DRT em pacientes com transtorno depressivo maior (TDM) no Brasil, no estudo observacional multinacional, multicêntrico, de DRT na América Latina (TRAL). Métodos: Trezentos e noventa e seis pacientes adultos com TDM (tratados ou não) no Brasil, com diagnóstico de TDM usando o Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) e confirmado por MINI Entrevista Neuropsiquiátrica Internacional v7.0.2, foram incluídos em 10 centros. Os pacientes forneceram consentimento e concluíram as avaliações. Os critérios de exclusão incluíram pacientes com psicose, esquizofrenia, transtorno bipolar, transtorno esquizoafetivo, demência, transtorno de uso de substância ou participação atual em outro estudo. A MADRS foi usada para gravidade da doença. Escalas de depressão e instrumentos classificados pelos pacientes foram usados para medir os resultados. Resultados: A prevalência de DRT em pacientes com TDM na América Latina corresponde a 29,1% (IC 95% [26,8%; 31,4%]), embora no Brasil corresponda a 40,4% (IC 95%: 35,6%-45,2%), a mais alta no estudo TRAL. Os pacientes com DRT são mais velhos e apresentam maior proporção de divórcios e menor nível educacional, com pontuação mais alta na Escala de Classificação da Depressão de Montgomery-Asberg (MADRS), comparados a pacientes sem DRT. Os custos de saúde foram maiores em pacientes com DRT, com menor qualidade de vida e maiores custos de saúde e comprometimento laboral. Conclusões: Estes achados confirmam que a DRT apresenta alta prevalência no Brasil, consistentemente com estudos anteriores sobre transtornos depressivos. Globalmente, os pacientes com DRT apresentam maior ônus da doença, sugerindo a necessidade de melhorar os cuidados para pacientes com DRT no Brasil

Objectives: Treatment-resistant depression (TRD) epidemiology varies worldwide, but uncertain in Latin America (LatAm). This paper reports on the epidemiology and burden of TRD in major depressive disorder (MDD) patients in Brazil from the TRD in America Latina (TRAL) multicenter, multinational, observational study. Methods: 396 adult patients (treated or untreated) with MDD diagnosis in Brazil using Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and confirmed by MINI International Neuropsychiatric Interview v7.0.2 were consecutively enrolled from 10 clinical sites in Brazil. Patients provided consent and complete assessments. Exclusion criteria included patients with psychosis, schizophrenia, bipolar disorder, schizoaffective disorder, dementia, with substance use disorder or currently participating in another clinical trial. Montgomery-Asberg Depression Rating Scale (MADRS) was used for disease severity. Depression scales and patient rated instruments were used to measure outcomes. Results: The prevalence of TRD in MDD patients in LatAm is 29.1% (95%CI [26.8%; 31.4%]), though the values for Brazil are 40.4% (95%CI: 35.6%-45.2%), the highest in the TRAL study. TRD patients are older, have higher proportion of divorce and lower education, with higher MADRS score compared to non-TRD patients. Healthcare costs were higher in TRD patients, with lower quality of life (QoL) and higher work impairment and healthcare costs. Conclusions: Present findings confirms that TRD is highly prevalent in Brazil, which is consistent with previous studies concerning depressive disorders. Globally, TRD patients experience higher burden of the disease. These findings suggest the need to improve care among TRD patients in Brazil

TLR-9 Plays a Role in Mycobacterium leprae-Induced Innate Immune Activation of A549 Alveolar Epithelial Cells

The respiratory tract is considered the main port of entry of Mycobacterium leprae, the causative agent of leprosy. However, the great majority of individuals exposed to the leprosy bacillus will never manifest the disease due to their capacity to develop protective immunity. Besides acting as a physical barrier, airway epithelium cells are recognized as key players by initiating a local innate immune response that orchestrates subsequent adaptive immunity to control airborne infections. However, to date, studies exploring the interaction of M. leprae with the respiratory epithelium have been scarce. In this work, the capacity of M. leprae to immune activate human alveolar epithelial cells was investigated, demonstrating that M. leprae-infected A549 cells secrete significantly increased IL-8 that is dependent on NF-kB activation. M. leprae was also able to induce IL-8 production in human primary nasal epithelial cells. M. leprae-treated A549 cells also showed higher expression levels of human b-defensin-2 (hbD-2), MCP-1, MHC-II and the co-stimulatory molecule CD80. Furthermore, the TLR-9 antagonist inhibited both the secretion of IL-8 and NF-kB activation in response to M. leprae, indicating that bacterial DNA sensing by this Toll-like receptor constitutes an important innate immune pathway activated by the pathogen. Finally, evidence is presented suggesting that extracellular DNA molecules anchored to Hlp, a histone-like protein present on the M. leprae surface, constitute major TLR-9 ligands triggering this pathway. The ability of M. leprae to immune activate respiratory epithelial cells herein demonstrated may represent a very early event during infection that could possibly be essential to the generation of a protective response.(AU)

Adult primary liver sarcoma: systematic review.

INTRODUCTION: primary liver sarcoma is a rare type of tumor, more common in children. Among adults, it represents a spectrum of neoplasms with reserved prognosis. There is no consensus on the treatment of choice of these lesions, justifying a systematic review of the literature on treatment options, prognostic factors, and survival. MATERIAL/METHODS: a systematic review of articles published in Pubmed, Medline, LiLacs e SciElo, from 1966 to March/2019, presenting the keywords: primary-liver-sarcoma and primary-hepatic-sarcoma was undertaken. Studies including patients older than 18 years, and published in English, Portuguese and Spanish were included. Case reports, metastatic tumors and multiple oncologic diagnosis were excluded. The initial search listed 1,318 articles. 1,206 did not meet the inclusion criteria. After reviewing 112 eligible articles, 15 were selected (14 case series and 1 retrospective-cohort). RESULTS: proposed treatment modalities for primary liver sarcoma included surgery and/or chemotherapy and/or radiotherapy or liver transplantation. The most common histological types were angiosarcoma (32%), leiomyosarcoma (29%), epithelioid hemangioendothelioma (15%) and embryonal sarcoma (7%). Histology, degree of differentiation and R0 resection were mentioned positive prognostic factors. Median survival ranged from two to 23 months. Five-year survival rate varied from 0% to 64%, on average 21%. CONCLUSION: surgical resection (R0 resection) is the main treatment for primary liver sarcomas. Development of effective systemic therapies are required to improve prognosis of patients harboring this type of tumor.

Capacitar a pessoa com défice respiratório em contexto comunitário / Empowering the person with respiratory deficit in community settings

O envelhecimento da população e o aumento de hábitos de vida prejudiciais à saúde, levou ao aumento das doenças de evolução prolongada, como as doenças respiratórias, criando dependência na pessoa. A elaboração deste relatório pretende dar conta do desenvolvimento de competências de mestre e de especialista em reabilitação durante o curso, com particular relevo para o Estágio final. Pretende também descrever os resultados do programa de intervenção de como capacitar a pessoa com défice respiratório no contexto comunitário, aplicado numa Unidade de Cuidados na Comunidade (UCC). Foram 6 os participantes que cumpriram os critérios de inclusão. Após a implementação do programa, observamos e registamos melhorias na dispneia, funcionalidade e realização das técnicas respiratórias. Podemos concluir que teve um impacto positivo na realização das atividades de vida diárias (AVD's) de forma independente. O desenvolvimento das competências foi analisado à luz das gerais, especificas e de mestre, ilustrando-se com experiências de aprendizagem concretas esse processo. Concluímos que não é um processo acabado no términus do curso, em que teve origem. O agir profissional permitirá continuar na senda da excelência do cuidar em enfermagem de Reabilitação, na preocupação com a saúde dos cidadãos, mas com apoio na investigação alimentando a prática baseada na evidência.

The ageing population and the increase or harmful health life habits, led to a growth in long-term diseases, such as respiratory diseases, creating dependency on the person. This report elaboration intends to account for the development of competences of master and specialist competences in rehabilitation during the course, with particular emphasis on the final internship. It also intends to describe the results of the intervention programme on how to empower the person with respiratory deficit in the community contexto, applied in a Care Unit in the Community (UCC). There were 6 participants who fulfilled the inclusion criteria. After the programme implementation, we observed and recorded improvements in dyspnea, functionality and respiratory techniques performance. We can conclude that it had a positive impact in carrying out daily life activities (ADLs) autonomously. The competences development was analyzed in general light, specific and master, illustrating this process with particular learning experiences. We conclude that is not a finished process at the end of the course, from which it was originated. Professional action will allow us to continue on the path of excellence in rehabilitation nursing care, concerning for citizens, but with backup powered by evidence-based practice.