Distinguishing pathophysiological features of heart failure with reduced and preserved ejection fraction: A comparative analysis of two mouse models.

Heart failure (HF) is a heterogeneous condition that can be categorized according to the left ventricular ejection fraction (EF) into HF with reduced (HFrEF) or preserved (HFpEF) EF. Although HFrEF and HFpEF share some common clinical manifestations, the mechanisms underlying each phenotype are often found to be distinct. Identifying shared and divergent pathophysiological features might expand our insights on HF pathophysiology and assist the search for therapies for each HF subtype. In this study, we evaluated and contrasted two new murine models of non-ischaemic HFrEF and cardiometabolic HFpEF in terms of myocardial structure, left ventricular function, gene expression, cardiomyocyte calcium handling, mitochondrial polarization and protein acetylation in a head-to-head fashion. We found that in conditions of similar haemodynamic stress, the HFrEF myocardium underwent a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation was greater in the HFpEF myocardium. We observed opposing features on calcium release, which was diminished in the HFrEF cardiomyocyte but enhanced in the HFpEF cardiomyocyte. Mitochondria were less polarized in both HFrEF and HFpEF cardiomyocytes, reflecting similarly impaired metabolic capacity. Hyperacetylation of cardiac proteins was observed in both models, but it was more accentuated in the HFpEF heart. Despite shared features, unique triggering mechanisms (neurohormonal overactivation in HFrEF vs. inflammation in HFpEF) appear to determine the distinct phenotypes of HF. The findings of the present research stress the need for further exploration of the differential mechanisms underlying each HF subtype, because they might require specific therapeutic interventions. KEY POINTS: The mechanisms underlying heart failure with either reduced (HFrEF) or preserved (HFpEF) ejection fraction are often found to be different. Previous studies comparing pathophysiological traits between HFrEF and HFpEF have been conducted on animals of different ages and strains. The present research contrasted two age-matched mouse models of non-ischaemic HFrEF and cardiometabolic HFpEF to uncover divergent and shared features. We found that upon similar haemodynamic stress, the HFrEF heart experienced a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation appeared to be greater in the HFpEF myocardium. Calcium release was diminished in the HFrEF cardiomyocyte and enhanced in the HFpEF cardiomyocyte. Mitochondria were comparably less polarized in both HFrEF and HFpEF myocytes. Hyperacetylation of proteins was common to both models, but stronger in the HFpEF heart. Casting light on common and distinguishing features might ease the quest for phenotype-specific therapies for heart failure patients.

Relationship of Circulating Irisin with Body Composition, Physical Activity, and Cardiovascular and Metabolic Disorders in the Pediatric Population.

Exercise-induced irisin, a recently discovered myokine, has been linked to insulin resistance, obesity, and other diseases in adults; however, information in children is scarce and contradictory. We analyzed the limited evidence of irisin's effects in children and adolescents, and its association with body composition, exercise training, cardiovascular risk factors, and metabolic diseases, as well as the results of dietetic interventions. Both positive and negative correlations between irisin concentrations and body mass index, fat mass, fat-free mass, and other anthropometric parameters were found. Likewise, contradictory evidence was shown associating irisin plasma levels with cardiovascular and metabolic parameters such as glucose, insulin resistance, and cholesterol and other lipid and fatty acid plasma levels in healthy children, as well as in those with obesity and the metabolic syndrome. Gender, puberty, and hormonal differences were also examined. Furthermore, important contradictory findings according to the type and duration of exercise and of dietetic interventions in healthy and unhealthy subjects were demonstrated. In addition, correlations between mother⁻infant relations and circulating irisin were also identified. This review discusses the potential role of irisin in health and disease in the pediatric population.

Seasonal Variation in Vitamin D in Association with Age, Inflammatory Cytokines, Anthropometric Parameters, and Lifestyle Factors in Older Adults.

Vitamin D deficiency is present even in sunny regions. Ageing decreases pre-vitamin D production in the skin and is associated with altered cytokine profile. We performed a multivariate analysis considering lifestyle factors, anthropometric, and inflammatory markers according to seasonal variation in Mexican healthy older adults. The same cohort was followed during 12 months. Vitamin D deficiency/insufficiency was found in 91.3% of the subjects despite living in appropriate latitude (25°40'0″N). 25(OH)D levels remained below <30 ng/mL through all seasons. Vitamin D deficiency did not correlate to sun exposure or dietary intake. Gender was the strongest associated factor, explaining a variance of 20%. Waist circumference (WC) greater than 88 cm was a risk factor for vitamin D deficiency. Age (>74 years) combined with WC (>88 cm) and BMI (>32.7) showed a high probability (90%) of vitamin D deficiency. Remarkably, an increase in one centimeter in WC decreased 25(OH)D by 0.176 ng/mL, while an increase in one point BMI decreased 25(OH)D by 0.534 ng/mL. A cutoff point of 74 years of age determined probability of vitamin D hipovitaminosis. Vitamin D deficiency was correlated with TNF-α serum levels, possibly increasing the susceptibility of older adults to a proinflammatory state and its related diseases.

Analysis of the Mitochondrial Density and Longitudinal Distribution in Rat Live-Skeletal Muscle Fibers by Confocal Microscopy.

The mitochondrion is an organelle that can be elongated, fragmented, and renovated according to the metabolic requirements of the cells. The remodeling of the mitochondrial network allows healthy mitochondria to meet cellular demands; however, the loss of this capacity has been related to the development or progression of different pathologies. In skeletal muscle, mitochondrial density and distribution changes are observed in physiological and pathological conditions such as exercise, aging, and obesity, among others. Therefore, the study of the mitochondrial network may provide a better understanding of mechanisms related to those conditions. Here, a protocol for mitochondria imaging of live-skeletal muscle fibers from rats is described. Fibers are manually dissected in a relaxing solution and incubated with a fluorescent live-cell imaging indicator of mitochondria (tetramethylrhodamine ethyl ester, TMRE). The mitochondria signal is recorded by confocal microscopy using the XYZ scan mode to obtain confocal images of the intermyofibrillar mitochondrial (IMF) network. After that, the confocal images are processed by thresholding and binarization. The binarized confocal image accounts for the positive pixels for mitochondria, which are then counted to obtain the mitochondrial density. The mitochondrial network in skeletal muscle is characterized by a high density of IMF population, which has a periodic longitudinal distribution similar to that of T-tubules (TT). The Fast Fourier Transform (FFT) is a standard analysis technique performed to evaluate the distribution of TT that allows finding the distribution frequency and the level of their organization. In this protocol, the implementation of the FFT algorithm is described for the analysis of the longitudinal mitochondrial distribution in skeletal muscle.

Role of mitochondria-associated endoplasmic reticulum membranes in insulin sensitivity, energy metabolism, and contraction of skeletal muscle.

Skeletal muscle has a critical role in the regulation of the energy balance of the organism, particularly as the principal tissue responsible for insulin-stimulated glucose disposal and as the major site of peripheral insulin resistance (IR), which has been related to accumulation of lipid intermediates, reduced oxidative capacity of mitochondria and endoplasmic reticulum (ER) stress. These organelles form contact sites, known as mitochondria-associated ER membranes (MAMs). This interconnection seems to be involved in various cellular processes, including Ca2+ transport and energy metabolism; therefore, MAMs could play an important role in maintaining cellular homeostasis. Evidence suggests that alterations in MAMs may contribute to IR. However, the evidence does not refer to a specific subcellular location, which is of interest due to the fact that skeletal muscle is constituted by oxidative and glycolytic fibers as well as different mitochondrial populations that appear to respond differently to stimuli and pathological conditions. In this review, we show the available evidence of possible differential responses in the formation of MAMs in skeletal muscle as well as its role in insulin signaling and the beneficial effect it could have in the regulation of energetic metabolism and muscular contraction.

Impact and future of telemedicine amidst the COVID-19 pandemic: a systematic review of the state-of-the-art in Latin America.

Significant progress has been made in using information and communication technologies in medicine, by impacting the quality of health-care delivery system and patient care, and paving the way for ground-breaking tools for e-health and clinical decision-support systems. This study investigates the extent to which the evolution of telemedicine applications has been used to support patient care in Latin America (LATAM) amidst the pandemic. Theoretically, the study applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to identify the impact of telemedicine in the region. Practically, the paper provides a systematic mapping study of the different domain areas and methodological progress in Telemedicine that occurred during the pandemic, and applied a text mining technique to understand the intensities of the terms expressed by the analyzed studies. The results show that while telemedicine has not been extensively used, a greater percentage of the studies report that telemedicine was effective. Approximately 70% positive emotional valence score was found. The paper also provides an empirical discussion and recommendations for the next steps in ample adoption of telemedicine.

Intermittent Fasting as Possible Treatment for Heart Failure.

Western-style diet often leads to food overconsumption, which triggers the development of comorbidities, such as obesity, insulin resistance, hypercholesterolemia, hypertriglyceridemia, type 2 diabetes, and heart failure (HF). Several studies suggest that intermittent fasting (IF) protects against the development of those morbidities. This study presents evidence of the beneficial effects of IF on HF. Based on the current evidence, we discuss the potential molecular mechanisms by which IF works and where liver ketone bodies (KBs) play important roles. There is evidence that IF promotes a metabolic switch in highly metabolic organs, such as the heart, which increases the use of KBs during fasting. However, besides their role as energy substrates, KBs participate in the signaling pathways that control the expression of genes involved in oxidative stress protection and metabolism. Several molecular factors, such as adenosine monophosphate-activated protein kinase (AMPK), peroxisome proliferatoractivated receptor, fibroblast growth factor 21 (FGF21), sirtuins, and nuclear factor erythroid 2-related factor 2 (Nrf2) are involved. Furthermore, IF appears to maintain circadian rhythm, which is essential for highly metabolically active organs. Finally, we highlight the important research topics that need to be pursued to improve current knowledge and strengthen the potential of IF as a preventive and therapeutic approach to HF.

A single session of physical activity restores the mitochondrial organization disrupted by obesity in skeletal muscle fibers.

BACKGROUND: Several studies have proved that physical activity (PA) regulates energetic metabolism associated with mitochondrial dynamics through AMPK activation in healthy subjects. Obesity, a condition that induces oxidative stress, mitochondrial dysfunction, and low AMPK activity leads to mitochondrial fragmentation. However, few studies describe the effect of PA on mitochondrial dynamics regulation in obesity. AIM: The present study aimed to evaluate the effect of a single session of PA on mitochondrial dynamics regulation as well as its effect on mitochondrial function and organization in skeletal muscles of obese rats (Zucker fa/fa). MAIN METHODS: Male Zucker lean and Zucker fa/fa rats aged 12 to 13 weeks were divided into sedentary and subjected-to-PA (single session swimming) groups. Gastrocnemius muscle was dissected into isolated fibers, mitochondria, mRNA, and total proteins for their evaluation. KEY FINDINGS: The results showed that PA increased the Mfn-2 protein level in the lean and obese groups, whereas Drp1 levels decreased in the obese group. OMA1 protease levels increased in the lean group and decreased in the obese group. Additionally, AMPK analysis parameters (expression, protein level, and activity) did not increase in the obese group. These findings correlated with the partial restoration of mitochondrial function in the obese group, increasing the capacity to maintain the membrane potential after adding calcium as a stressor, and increasing the transversal organization level of the mitochondria analyzed in isolated fibers. SIGNIFICANCE: These results support the notion that obese rats subjected to PA maintain mitochondrial function through mitochondrial fusion activation by an AMPK-independent mechanism.

Impact and future of telemedicine amidst the COVID-19 pandemic: a systematic review of the state-of-the-art in Latin America / Impacto e futuro da telemedicina em meio à pandemia de COVID-19: uma revisão sistemática do estado da arte na América Latina

Abstract Significant progress has been made in using information and communication technologies in medicine, by impacting the quality of health-care delivery system and patient care, and paving the way for ground-breaking tools for e-health and clinical decision-support systems. This study investigates the extent to which the evolution of telemedicine applications has been used to support patient care in Latin America (LATAM) amidst the pandemic. Theoretically, the study applied the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to identify the impact of telemedicine in the region. Practically, the paper provides a systematic mapping study of the different domain areas and methodological progress in Telemedicine that occurred during the pandemic, and applied a text mining technique to understand the intensities of the terms expressed by the analyzed studies. The results show that while telemedicine has not been extensively used, a greater percentage of the studies report that telemedicine was effective. Approximately 70% positive emotional valence score was found. The paper also provides an empirical discussion and recommendations for the next steps in ample adoption of telemedicine.

Resumo Foram feitos progressos significativos na utilização de tecnologias de informação e comunicação na medicina, com impacto no sistema de prestação de cuidados de saúde e nos cuidados aos doentes, e abrindo caminho a ferramentas inovadoras para sistemas eletrônicos de saúde e de apoio à decisão clínica. O presente estudo investiga até que ponto o crescimento das aplicações da telemedicina tem sido utilizado para apoiar os cuidados aos doentes na América Latina (LATAM) em meio da pandemia. Teoricamente, o estudo aplicou a metodologia Preferred Reporting Items for Systematic Reviews e Meta-Analyses (PRISMA) para identificar o impacto da telemedicina na região. Na prática, o artigo apresenta um estudo de mapeamento sistemático das diferentes áreas de domínio e progresso metodológico em telemedicina que ocorreram durante a pandemia, e aplicou uma técnica de text mining para compreender as intensidades dos termos expressos pelos pesquisas analisadss. Os resultados mostram que, embora a telemedicina não tenha sido amplamente utilizada, um maior percentual de estudos informa que a telemedicina foi eficaz. Foi encontrada uma pontuação de valência emocional positiva de aproximadamente 70%. O documento também traz uma discussão empírica para os próximos passos na adoção da telemedicina.

Gynecologic and Obstetric Consequences of Obesity in Adolescent Girls.

In the past few decades, there has been an overwhelming increase in childhood and adolescent obesity worldwide. Besides the well recognized cardiometabolic complications and other physical conditions associated with obesity, during adolescence, it causes psychological and social distress in a period of life that is already sensitive for a girl. This in turn increases their risk of low self-esteem and depression. Furthermore, obesity diminishes health-related quality of life and years of life. Overweight and obese teenagers are more likely to have gynecologic and obstetric complications, during adolescence and also later in life. Consequences of obese and overweight childhood and adolescence include sexual maturation and reproductive dysfunction, alterations in menstruation, dysmenorrhea, risky sexual behavior, and inefficient use of contraception, polycystic ovary syndrome, bone density abnormalities, macromastia, and an increased risk of breast and endometrial cancer. Obese adolescents are at greater risk of pregnancy and perinatal complications, such as preeclampsia, gestational hypertension and preeclampsia, gestational diabetes mellitus, primary cesarean delivery, and induction of labor, to mention a few. Evidence shows that infants born to obese teenagers are also more likely to have complications including preterm or post-term delivery, small-for-gestational age newborns, macrosomia, meconium aspiration, respiratory distress, and even stillbirth, among others. This comprehensive review focuses on the gynecological and obstetric consequences of obesity in adolescent girls.

High hydrostatic pressure processing reduces the glycemic index of fresh mango puree in healthy subjects.

Dietary guidelines recommend the daily consumption of fruits; however, healthy and type 2 diabetes mellitus (T2DM) subjects receive conflicting messages regarding ingestion of fruits, such as mango, because of its sugar content. We investigated the effects of high hydrostatic pressure (HHP) processing of fresh mango puree (MP) on the glycemic indexes (GIs) and postprandial glycemic responses of 38 healthy Mexican subjects in a randomized cross-over clinical trial. Physicochemical characterization of MP included sugar profiles by HPLC-ELSD, starch, fibers, moisture, viscosity, swelling capacity and solubility properties of alcohol insoluble residue (AIR). The mean GI for HHP-MP was significantly lower (32.7 ± 13.4) than that of unprocessed-MP (42.7 ± 19.5). A significantly higher proportion of subjects showed a low GI following the consumption of HHP-MP compared to unprocessed-MP and none of them showed a high GI for the HHP-MP, compared to a significantly higher proportion for the unprocessed-MP. The viscosity and AIR solubility values of HHP-MP samples were significantly higher, which influenced glucose peaking later (Tmax) at 45 minutes and induced 20% lower AUC values than unprocessed-MP, corresponding to greater retardation indexes. The study findings support data stating that low GI fruits are appropriate for glycemic control and that mango may be included as part of healthy subjects' diets and potentially T2DM subjects' diets. Furthermore, HHP processing of mango may offer additional benefits for glycemic control, as its performance regarding GI, AUC and Tmax was significantly better than that of the unprocessed-MP. To our knowledge, this is the first report on the impact of this commercial non-thermal pasteurization technology on glucose metabolism.