Biomarkers are valuable tools in clinical practice. In 2001, the National Institutes of Health (NIH) standardized the definition of a biomarker as a characteristic that is objectively measured and ...evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacological responses to a therapeutic intervention. A biomarker has clinical relevance when it presents precision, standardization and reproducibility, suitability to the patient, straightforward interpretation by clinicians, and high sensitivity and/or specificity by the parameter it proposes to identify. Thus, serum biomarkers should have advantages related to the simplicity of the procedures and to the fact that venous blood collection is commonplace in clinical practice. We described the potentiality of cfDNA as a general clinical biomarker and focused on endothelial dysfunction. Circulating cell-free DNA (cfDNA) refers to extracellular DNA present in body fluid that may be derived from both normal and diseased cells. An increasing number of studies demonstrate the potential use of cfDNA as a noninvasive biomarker to determine physiologic and pathologic conditions. However, although still scarce, increasing evidence has been reported regarding using cfDNA in cardiovascular diseases. Here, we have reviewed the history of cfDNA, its source, molecular features, and release mechanism. We also show recent studies that have investigated cfDNA as a possible marker of endothelial damage in clinical settings. In the cardiovascular system, the studies are quite new, and although interesting, stronger evidence is still needed. However, some drawbacks in cfDNA methodologies should be overcome before its recommendation as a biomarker in the clinical setting.
Introduction: predictive equations to estimate body fat based on simple anthropometric parameters are easy to use in the clinical practice.
Objective: to evaluate the relationship between predictive ...equations based on anthropometric parameters and bioelectrical impedance to estimate body fat in individuals undergoing bariatric surgery.
Methods: a prospective and longitudinal study carried out with individuals undergoing bariatric surgery. Body weight, body mass index, waist circumference and body fat percentage estimated by anthropometric parameters and by impedance were evaluated at three moments, one month before, two and six months after surgery. Data were analyzed by one-way ANOVA for repeated measures with Holm-Sidak´s post hoc or Friedman test with Tukey´s post hoc, and Pearson or Spearman correlations, according to data distribution. Significance level adopted 5%.
Results: twenty-five subjects composed the final sample. All anthropometric parameters reduced significantly over time (p<0.001). Except for Lean et al equation before surgery, the body fat percentage estimated by other formulas showed a strong correlation with impedance in all moments, with the highest correlation strength observed in Gómez-Ambrosi et al. equation.
Conclusion: in the present study, the equations used showed a good correlation with bioelectrical impedance, and the Gómez-Ambrosi et al. equation as a better option to the use of bioimpedance to assess changes in body fat percentage of patients undergoing bariatric surgery for the treatment of severe obesity.
Impaired cardiomyocyte contractility and calcium handling are hallmarks of left ventricular contractile dysfunction. Exercise training has been used as a remarkable strategy in the treatment of heart ...disease. The microRNA-1, which targets sodium/calcium exchanger 1 (NCX), and microRNA-214, which targets sarcoplasmic reticulum calcium ATPase-2a (Serca2a), are involved in cardiac function regulation. Thus, the aim of this study was to evaluate the effect of exercise training on cardiac microRNA-1 and -214 expression after myocardial infarction.
Wistar rats were randomized into four groups: sedentary sham (S-SHAM), sedentary infarction (S-INF), trained sham (T-SHAM), and trained infarction (T-INF). Exercise training consisted of 60 min/days, 5 days/week for 10 weeks with 3 % of body weight as overload beginning four weeks after myocardial infarction.
MicroRNA-1 and -214 expressions were, respectively, decreased (52 %) and increased (54 %) in the S-INF compared to the S-SHAM, while exercise training normalized the expression of these microRNAs. The microRNA targets NCX and Serca-2a protein expression were, respectively, decreased (55 %) and increased (34 %) in the T-INF group compared to the S-INF group.
These results suggest that exercise training restores microRNA-1 and -214 expression levels and prevents change in both NCX and Serca-2a protein and gene expressions. Altogether, our data suggest a molecular mechanism to restore ventricular function after exercise training in myocardial infarction rats.
Abstract
Early diagnosis of COVID-19 in suspected patients is essential for contagion control and damage reduction strategies. We investigated the applicability of attenuated total reflection (ATR) ...Fourier transform infrared (FTIR) spectroscopy associated with machine learning in oropharyngeal swab suspension fluid to predict COVID-19 positive samples. The study included samples of 243 patients from two Brazilian States. Samples were transported by using different viral transport mediums (liquid 1 or 2). Clinical COVID-19 diagnosis was performed by the RT-PCR. We built a classification model based on partial least squares (PLS) associated with cosine k-nearest neighbours (KNN). Our analysis led to 84% and 87% sensitivity, 66% and 64% specificity, and 76.9% and 78.4% accuracy for samples of liquids 1 and 2, respectively. Based on this proof-of-concept study, we believe this method could offer a simple, label-free, cost-effective solution for high-throughput screening of suspect patients for COVID-19 in health care centres and emergency departments.
Despite the important role of iron in cellular homeostasis, iron overload (IO) is associated with systemic and tissue deposits which damage several organs. In order to reduce the impact caused by IO, ...invasive diagnosis exams (e.g., biopsies) and minimally invasive methods were developed including computed tomography and magnetic resonance imaging. However, current diagnostic methods are still time-consuming and expensive. A cost-effective solution is using Fourier-transform infrared spectroscopy (FTIR) for real-time and molecular-sensitive biofluid analysis during conventional laboratory exams. In this study, we performed the first evaluation of the accuracy of FTIR for IO diagnosis. The study was performed by collecting FTIR spectra of plasma samples of five rats intravenously injected with iron-dextran and five control rats. We developed a classification model based on principal component analysis and supervised methods including J48, random forest, multilayer perceptron, and radial basis function network. We achieved 100% accuracy for the classification of the IO status and provided a list of possible biomolecules related to the vibrational modes detected. In this preliminary study, we give a first step towards real-time diagnosis for acute IO or intoxication. Furthermore, we have expanded the literature knowledge regarding the pathophysiological changes induced by iron overload.
One of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. ...N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin I-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, P=0.0003) and reduced Ac-SDKP levels (by 50%, P<0.0001). T2 increased the number of hematopoietic stem cells (HSCs; ∼200%, P=0.0008), early erythroid progenitor colonies (∼300%, P<0.0001) and reticulocytes (∼500%, P=0.0007), and reduced erythrocyte lifespan (∼50%, P=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril (Cap) treatment: 10 mg.kg-1.day-1). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated with increased ACE NH2-terminal activity and reduction in the hematopoietic inhibitor Ac-SDKP.
Early life adversity has been linked with a higher probability of developing behavioral impairments and environmental manipulation is a strategy that may reduce the negative effects of exposure to ...adversity in early life. Here, we focused on exploring the influence of environmental enrichment (EE) as a protective factor in the context of early life adversity. We hypothesized that 24 hours of maternal deprivation (MD), in the second week of life, could induce anxiety-like behavior alterations and that exposure to EE could induce resilience to these behaviors due to alterations in the serotonergic system. Male Wistar rats were exposed to MD, on postnatal days 11 and 13, and to EE, after weaning. In adulthood, we performed a series of behavioral tests for fear, anxiety, and locomotor activity. We also measured the levels of serotonin in the amygdala and dorsal raphe nucleus. Our results revealed that MD does not impact fear behavior or the levels of serotonin, while EE decreases locomotor activity in a novel environment and enhances exploration in the predator odor test. EE also decreases serotonin in the amygdala and increases its turnover rate levels. Our findings provide insights into the critical timeframe during which stress exposure impacts the development and confirm that exposure to EE has an independent and protective effect for anxiety-like behaviors later in life.
•Maternal deprivation on postnatal days 11 and 13 showed no impact on fear extinction or anxiety.•Environmental enrichment (EE) reduces locomotion and increases exploration time.•EE influences the amygdala, but not dorsal raphe nucleus serotonergic levels.
To determine the effects of resistance training (RT) on the expression of microRNA (miRNA)-214 and its target in sarcoplasmic reticulum Ca2+-ATPase (SERCA2a), and on the morphological and mechanical ...properties of isolated left ventricular myocytes.
Male Wistar rats were divided into two groups (n = 7/group): Control (CO) or trained (TR). The exercise-training protocol consisted of: 4 × 12 bouts, 5×/week during 8 weeks, with 80% of one repetition maximum.
RT increased the left ventricular myocyte width by 15% and volume by 12%, compared with control animals (p < 0.05). The time to half relaxation and time to peak were 8.4% and 4.4% lower, respectively, in cells from TR group as compared to CO group (p < 0.05). RT decreased miRNA-214 level by 18.5% while its target SERCA2a expression were 18.5% higher (p < 0.05).
Our findings showed that RT increases single left ventricular myocyte dimensions and also leads to faster cell contraction and relaxation. These mechanical adaptations may be related to the augmented expression of SERCA2a which, in turn, may be associated with the epigenetic modification of decreased miRNA-214 expression.
Sepsis survivors are at higher risk for cardiovascular events. Lipopolysaccharide (LPS) activates Toll-like receptor 4 (TLR4) in sepsis. Activation of TLR4 modulates vascular smooth muscle cells ...(VSMCs) phenotype and contributes to cardiovascular changes after sepsis.
Investigate changes in VSMCs phenotype caused by LPS-induced TLR4 activation.
Rat VSMCs were incubated with LPS. Two incubation conditions were used in cell contraction and migration assays: acute stimulation — LPS stimulus was initiated at the beginning of the assay and maintained throughout; and preconditioning — LPS stimulation was applied prior to the assay then discontinued. Nitric oxide (NO) production, mRNA expression of cytokines and phenotype markers, and interleukin (IL)-6 production were evaluated.
LPS increased gene expression of IL-1β, IL-6, TNFα and MCP-1 (p < .001), of secretory phenotype markers collagen and vimentin (p < .0479) and of the contractile marker smooth muscle 22α (SM22α) (p = .0067). LPS exposure increased IL-6 secretion after 24 and 48 h (p < .0001), and NO at 8 and 24 h (p < .0249) via inducible nitric oxide synthase (iNOS), as demonstrated by a decrease in NO after incubation with aminoguanidine. Acute stimulation with LPS reduced migration and contraction in a NO-dependent manner, while preconditioning with LPS increased both in an IL-6-dependent manner.
LPS affects VSMCs by modulating their secretory, contractile and migratory phenotypes. LPS acute stimulation of VSMCs promoted a NO-dependent reduction in migration and contraction, while preconditioning with LPS promoted IL-6-dependent increases in migration and contraction, evidencing that VSMCs can present phenotype modifications that persist after sepsis, thereby contributing to postsepsis cardiovascular events.
Resumo Objetivo Analisar a associação entre determinantes sociais e morbidades para os desfechos de internação, internação em unidade de terapia intensiva e óbito por COVID-19 no Espírito Santo, ...Brasil. Métodos Estudo transversal, com dados secundários de casos confirmados de COVID-19 notificados no Sistema de Informação de Agravos de Notificação. Utilizou-se regressão de Poisson para estimar as razões de prevalências. Resultados Foram estudados 104.384 casos, notificados entre 28 de fevereiro e 1º de setembro de 2020. Os desfechos em estudo foram mais frequentes entre indivíduos do sexo masculino, idosos, de raça/cor da pele amarela ou preta, sem escolaridade, com multimorbidade. Todas as morbidades associaram-se a maior risco de desfechos desfavoráveis. Observou-se maior risco de óbito entre pessoas com idade superior a 60 anos (RP=56,31 - IC95% 34,24;92,61), multimorbidades (RP=3,63 - IC95% 3,16;4,17), doença renal (RP=3,42 - IC95% 2,81;4,15) e neoplasias (RP=3,15 - IC95% 2,41;4,13). Conclusão Evidencia-se o efeito dos determinantes sociais e morbidades em internação e óbitos por COVID-19.
Resumen Objetivo Analizar la asociación entre determinantes sociales y morbilidad para los resultados de hospitalización, ingreso en unidad de cuidados intensivos y muerte por COVID-19 en el Estado de Espírito Santo, Brasil. Métodos Estudio transversal con datos secundarios de casos confirmados de COVID-19, reportados en el Sistema de Información de Enfermedades Notificables. Se utilizó la regresión de Poisson para estimar las razones de prevalencia. Resultados Se estudiaron 104.384 casos notificados entre el 28 de Febrero y el 1 de Septiembre de 2020. Los desenlaces en estudio fueron más frecuentes entre hombres, ancianos, amarillos, seguidos de negros, no educados y con multimorbilidad. Hubo un mayor riesgo de muerte entre las personas mayores de 60 años (RP=56,31 - IC95% 34,24;92,61), multimorbilidades (RP=3,63 - IC95% 3,16;4,17), enfermedad renal (RP=3,42 - IC95% 2,81;4,15) y neoplasias (RP=3,15 - IC95% 2,41;4,13). Conclusión El efecto de los determinantes sociales y las morbilidades sobre la hospitalización y las muertes por COVID-19 es evidente.
Abstract Objective To analyze the association between social determinants and morbidities for the outcomes of hospitalization, intensive care unit admission and death by COVID-19 in Espírito Santo State, Brazil. Methods Cross-sectional study with secondary data from confirmed cases of COVID-19, reported in the Notifiable Diseases Information System. Poisson regression was used to estimate the prevalence ratios. Results 104,384 cases reported between February 28th and September 1st, 2020 were studied. The outcomes under study were more frequent among male, elderly, yellow, followed by black, uneducated and with multimorbidity. There was a higher risk of death among people over the age of 60 (PR=56.31 - 95%CI 34.24;92.61), multimorbidities (PR=3.63 - 95%CI 3.16;4.17), kidney disease (PR=3.42 - 95%CI 2.81;4.15) and neoplasms (PR=3.15 - 95%CI 2.41;4.13). Conclusion The effect of social determinants and morbidities on hospitalization and deaths by COVID-19 is evident.
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