RBPMS and RBPMS2 Cooperate to Safeguard Cardiac Splicing.

Background: Mutations in cardiac splicing factors (SFs) cause cardiomyopathy and congenital heart disease, underscoring the critical role of SFs in cardiac development and disease. Cardiac SFs are implicated to cooperatively regulate the splicing of essential cardiac genes, but the functional importance of their collaboration remains unclear. RNA Binding Protein with Multiple Splicing (RBPMS) and RBPMS2 are SFs involved in heart development and exhibit similar splicing regulatory activities , but it is unknown whether they cooperate to regulate splicing .

Parent-Led Applied Behavior Analysis to Impact Clinical Outcomes for Individuals on the Autism Spectrum: Retrospective Chart Review.

Background: Autism spectrum disorder (ASD) can have traits that impact multiple domains of functioning and quality of life, which can persevere throughout life. To mitigate the impact of ASD on the long-term trajectory of an individual's life, it is imperative to seek early and adequate treatment via scientifically validated approaches, of which applied behavior analysis (ABA) is the gold standard. ABA treatment must be delivered via a behavior technician with oversight from a board-certified behavior analyst.

Protein tyrosine phosphatase 1B in metabolic and cardiovascular diseases: from mechanisms to therapeutics.

Protein Tyrosine Phosphatase 1B (PTP1B) has emerged as a significant regulator of metabolic and cardiovascular disease. It is a non-transmembrane protein tyrosine phosphatase that negatively regulates multiple signaling pathways integral to the regulation of growth, survival, and differentiation of cells, including leptin and insulin signaling, which are critical for development of obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. Given PTP1B's central role in glucose homeostasis, energy balance, and vascular function, targeted inhibition of PTP1B represents a promising strategy for treating these diseases.

Machine Learning Approach for Improved Longitudinal Prediction of Progression from Mild Cognitive Impairment to Alzheimer's Disease.

Mild cognitive impairment (MCI) is cognitive decline that can indicate future risk of Alzheimer's disease (AD). We developed and validated a machine learning algorithm (MLA), based on a gradient-boosted tree ensemble method, to analyze phenotypic data for individuals 55-88 years old ( = 493) diagnosed with MCI. Data were analyzed within multiple prediction windows and averaged to predict progression to AD within 24-48 months.

Carbohydrate ingestion attenuates the reduction in complex cognitive function and cerebral blood flow during prolonged passive heat stress in humans.

Purpose: To determine whether carbohydrate ingestion would reduce cognitive dysfunction in humans following long duration passive heat stress (PHS) versus consuming electrolytes alone.

Methods: Fifteen young (27 ± 4 y) healthy adults were exposed to 120 min of PHS through the use of a liquid perfused suit (50 °C) on two randomized visits. Subjects consumed fluids supplemented with electrolytes (E) or electrolytes + carbohydrates (E + C).

Machine learning determination of applied behavioral analysis treatment plan type.

Background: Applied behavioral analysis (ABA) is regarded as the gold standard treatment for autism spectrum disorder (ASD) and has the potential to improve outcomes for patients with ASD. It can be delivered at different intensities, which are classified as comprehensive or focused treatment approaches. Comprehensive ABA targets multiple developmental domains and involves 20-40 h/week of treatment.

Daily blueberry consumption for 12 weeks improves endothelial function in postmenopausal women with above-normal blood pressure through reductions in oxidative stress: a randomized controlled trial.

Estrogen-deficient postmenopausal women have oxidative stress-mediated suppression of endothelial function that is exacerbated by high blood pressure. Previous research suggests blueberries may improve endothelial function through reductions in oxidative stress, while also exerting other cardiovascular benefits. The objective of this study was to examine the efficacy of blueberries to improve endothelial function and blood pressure in postmenopausal women with above-normal blood pressure, and to identify potential mechanisms for improvements in endothelial function.

Rho-kinase inhibition improves haemodynamic responses and circulating ATP during hypoxia and moderate intensity handgrip exercise in healthy older adults.

Skeletal muscle haemodynamics and circulating adenosine triphosphate (ATP) responses during hypoxia and exercise are blunted in older (OA) vs. young (YA) adults, which may be associated with impaired red blood cell (RBC) ATP release. Rho-kinase inhibition improves deoxygenation-induced ATP release from OA isolated RBCs.

Carbohydrate ingestion attenuates cognitive dysfunction following long-duration exercise in the heat in humans.

Introduction: To determine if electrolyte or carbohydrate supplementation vs. water would limit the magnitude of dehydration and decline in cognitive function in humans following long-duration hyperthermic-exercise.

Methods: 24 subjects performed 3 visits of 2 h walking (3mph/7% grade) in an environmental chamber (33 °C/10% relative humidity).

Comprehensive assessment of cardiovascular structure and function and disease risk in middle-aged ultra-endurance athletes.

Background And Aims: Recent studies suggest that long-term endurance training may be damaging to the heart, thus increasing cardiovascular disease (CVD) risk. However, studies utilizing cardiac imaging are conflicting and lack measures of central and peripheral vascular structure and function, which are also independently predictive of CVD events.

Methods: We performed a comprehensive assessment of cardiovascular structure and function in long-term (≥ 10 years) ultra-endurance athletes (ATH, 14 M/11 F, 50 ± 1 y) and physically active controls (CON, 9 M/9 F, 49 ± 2 y).

Self-selected fluid volume and flavor strength does not alter fluid intake, body mass loss, or physiological strain during moderate-intensity exercise in the heat.

Introduction: The purpose of this study was to determine the effects of ad libitum flavor and fluid intake on changes in body mass (BM) and physiological strain during moderate intensity exercise in the heat.

Methods: Ten subjects (24±3yrs, 7M/3F) performed 60 min of treadmill walking at 1.3 m/s and 7% grade in an environmental chamber set to 33 °C and 10% relative humidity while carrying a 22.

K channel activation links local vasodilatation with muscle fibre recruitment during exercise in humans.

Key Points: During exercise, blood flow to working skeletal muscle increases in parallel with contractile activity such that oxygen delivery is sufficient to meet metabolic demand. K released from active skeletal muscle fibres could facilitate vasodilatation in proportion to the degree of muscle fibre recruitment. Once released, K stimulates inwardly rectifying K (K ) channels on the vasculature to elicit an increase in blood flow.

Augmentation of endothelium-dependent vasodilatory signalling improves functional sympatholysis in contracting muscle of older adults.

Key Points: The ability of contracting skeletal muscle to attenuate sympathetic vasoconstriction (functional sympatholysis) is critical for maintaining blood flow during exercise-mediated sympathoexcitation. Functional sympatholysis and endothelial function are impaired with ageing, resulting in compromised blood flow and oxygen delivery to contracting skeletal muscle during exercise. In the present study, intra-arterial infusion of ACh or ATP to augment endothelium-dependent signalling during exercise attenuated α -adrenergic vasoconstriction in the contracting muscle of older adults.

Rapid-onset vasodilator responses to exercise in humans: Effect of increased baseline blood flow.

New Findings: What is the central question of this study? What is the effect of an elevated baseline blood flow, induced by high-dose intra-arterial infusion of either adenosine or ATP, on the rapid-onset vasodilatory response to a single forearm muscle contraction? What is the main finding and its importance? The peak response to a single contraction is unaffected by augmented baseline blood flow, and thus, is likely to be attributable to a feedforward vasodilatory mechanism.

Abstract: The hyperaemic responses to single muscle contractions are proportional to exercise intensity, which, in turn, is proportional to tissue metabolic demand. Hence, we tested the hypothesis that the rapid-onset vasodilatory response after a single muscle contraction would be unaffected when baseline blood flow was increased via high-dose intra-arterial infusion of either adenosine (ADO) or ATP.

Acute differences in pulse wave velocity, augmentation index, and central pulse pressure following controlled exposures to cookstove air pollution in the Subclinical Tests of Volunteers Exposed to Smoke (SToVES) study.

Household air pollution emitted from solid-fuel cookstoves used for domestic cooking is a leading risk factor for morbidity and premature mortality globally. There have been attempts to design and distribute lower emission cookstoves, yet it is unclear if they meaningfully improve health. Using a crossover design, we assessed differences in central aortic hemodynamics and arterial stiffness following controlled exposures to air pollution emitted from five different cookstove technologies compared to a filtered air control.

Reduced deformability contributes to impaired deoxygenation-induced ATP release from red blood cells of older adult humans.

Key Points: Red blood cells (RBCs) release ATP in response to deoxygenation, which can increase blood flow to help match oxygen supply with tissue metabolic demand. This release of ATP is impaired in RBCs from older adults, but the underlying mechanisms are unknown. In this study, improving RBC deformability in older adults restored deoxygenation-induced ATP release, whereas decreasing RBC deformability in young adults reduced ATP release to the level of that of older adults.

Escape, lysis, and feedback: endothelial modulation of sympathetic vasoconstriction.

The sympathetic nervous system exerts a vasoconstrictor influence over peripheral vascular beds that is counter-regulated by local vascular signaling mechanisms (i.e. sympathetic escape, sympatholysis, and myoendothelial feedback).

Sustained exercise hyperemia during prolonged adenosine infusion in humans.

The contribution of Adenosine (ADO) to exercise hyperemia remains controversial and it is unknown whether ADO can evoke the prolonged vasodilation seen during exercise bouts. Therefore, we tested hypotheses in the human forearm during 3 h of intra-arterial high dose ADO infusion: (1) skeletal muscle blood flow would wane over time; (2) exercise hyperemic responses during ADO administration would be unaffected compared to baseline. Using sodium nitroprusside (SNP), we tested parallel hypotheses regarding nitric oxide (NO) in a separate group of participants.

Amplification of endothelium-dependent vasodilatation in contracting human skeletal muscle: role of K channels.

Key Points: In humans, the vasodilatory response to skeletal muscle contraction is mediated in part by activation of inwardly rectifying potassium (K ) channels. Evidence from animal models suggest that K channels serve as electrical amplifiers of endothelium-dependent hyperpolarization (EDH). We found that skeletal muscle contraction amplifies vasodilatation to the endothelium-dependent agonist ACh, whereas there was no change in the vasodilatory response to sodium nitroprusside, an endothelium-independent nitric oxide donor.

Elevated extracellular potassium prior to muscle contraction reduces onset and steady-state exercise hyperemia in humans.

The increase in interstitial potassium (K) during muscle contractions is thought to be a vasodilatory signal that contributes to exercise hyperemia. To determine the role of extracellular K in exercise hyperemia, we perfused skeletal muscle with K before contractions, such that the effect of any endogenously-released K would be minimized. We tested the hypothesis that local, intra-arterial infusion of potassium chloride (KCl) at rest would impair vasodilation in response to subsequent rhythmic handgrip exercise in humans.

Inhibition of Na /K -ATPase and K channels abolishes hypoxic hyperaemia in resting but not contracting skeletal muscle of humans.

Key Points: Increasing blood flow (hyperaemia) to exercising muscle helps match oxygen delivery and metabolic demand. During exercise in hypoxia, there is a compensatory increase in muscle hyperaemia that maintains oxygen delivery and tissue oxygen consumption. Nitric oxide (NO) and prostaglandins (PGs) contribute to around half of the augmented hyperaemia during hypoxic exercise, although the contributors to the remaining response are unknown.

Acute ingestion of dietary nitrate increases muscle blood flow via local vasodilation during handgrip exercise in young adults.

Dietary nitrate (NO3-) is converted to nitrite (NO2-) and can be further reduced to the vasodilator nitric oxide (NO) amid a low O environment. Accordingly, dietary NO3- increases hind limb blood flow in rats during treadmill exercise; however, the evidence of such an effect in humans is unclear. We tested the hypothesis that acute dietary NO3- (via beetroot [BR] juice) increases forearm blood flow (FBF) via local vasodilation during handgrip exercise in young adults (n = 11; 25 ± 2 years).

Sympatholytic effect of intravascular ATP is independent of nitric oxide, prostaglandins, Na /K -ATPase and K channels in humans.

Key Points: Intravascular ATP attenuates sympathetic vasoconstriction (sympatholysis) similar to what is observed in contracting skeletal muscle of humans, and may be an important contributor to exercise hyperaemia. Similar to exercise, ATP-mediated vasodilatation occurs via activation of inwardly rectifying potassium channels (K ), and synthesis of nitric oxide (NO) and prostaglandins (PG). However, recent evidence suggests that these dilatatory pathways are not obligatory for sympatholysis during exercise; therefore, we tested the hypothesis that the ability of ATP to blunt α -adrenergic vasoconstriction in resting skeletal muscle would be independent of K , NO, PGs and Na /K -ATPase activity.