Exploring the quality of participation and strategies to support meaningful engagement in an adapted paddleboard program among individuals with disabilities.

Aim: Adapted paddleboard provides an outdoor leisure-time physical activities (LTPA) opportunity with many health benefits (e.g., physical activity, reduced stress, social engagement).

User perceptions about resources based on the Wheelchair Skills Training Program for training indoor and community wheelchair skills in pediatrics: a descriptive qualitative study.

Purpose: The Wheelchair Skills Training Program (WSTP) is underutilized in pediatrics for training manual wheelchair skills because the voluminous manual lacks pediatric specificity and no materials adapted for pediatric manual wheelchair users (PMWUs) are available. A set of resources (storybook, posters, training workbook) based on the WSTP has previously been developed for training basic indoor wheelchair skills with five to 15-year-old PMWUs. Occupational therapists (OTs) and PMWUs expressed a need for additional resources addressing higher-level skills.

Ischemia promotes acyl-CoAs dephosphorylation and propionyl-CoA accumulation.

Introduction: Our untargeted metabolic data unveiled that Acyl-CoAs undergo dephosphorylation, however little is known about these novel metabolites and their physiology/pathology relevance.

Objectives: To understand the relationship between acyl-CoAs dephosphorylation and energy status as implied in our previous work, we seek to investigate how ischemia (energy depletion) triggers metabolic changes, specifically acyl-CoAs dephosphorylation in this work.

Methods: Rat hearts were isolated and perfused in Langendorff mode for 15 min followed by 0, 5, 15, and 30 minutes of global ischemia.

p38α MAPK proximity assay reveals a regulatory mechanism of alternative splicing in cardiomyocytes.

The p38 mitogen-activated protein kinase (MAPK) signaling pathway is essential for normal heart function. However, p38 also contributes to heart failure pathogenesis by affecting cardiomyocytes contractility and survival. To unravel part of the complex role of p38 in cardiac function, we performed an APEX2-based proximity assay in cultured neonatal rat ventricular myocytes and identified the protein interaction networks (interactomes) of two highly expressed p38 isoforms in the heart.

Identification of Metabolic Changes in Ileum, Jejunum, Skeletal Muscle, Liver, and Lung in a Continuous I.V. Pseudomonas aeruginosa Model of Sepsis Using Nontargeted Metabolomics Analysis.

Sepsis is a multiorgan disease affecting the ileum and jejunum (small intestine), liver, skeletal muscle, and lung clinically. The specific metabolic changes in the ileum, jejunum, liver, skeletal muscle, and lung have not previously been investigated. Live Pseudomonas aeruginosa, isolated from a patient, was given via i.

MURC/CAVIN-4 facilitates store-operated calcium entry in neonatal cardiomyocytes.

Intact store-operated calcium entry (SOCE) mechanisms ensure the maintenance of Ca homeostasis in cardiomyocytes while their dysregulation promotes the development of cardiomyopathies. To better understand this calcium handling process in cardiomyocytes, we sought to identify unknown protein partners of stromal interaction molecule 1 (STIM1), a main regulatory protein of SOCE. We identified the muscle-related coiled-coil protein (MURC), also known as Cavin-4, as a candidate and showed that MURC interacts with STIM1 in cardiomyocytes.

A Mixed-Methods Study Examining Adherence to and Acceptability of Intravaginal Rings for HIV Prevention: Behavioral Results of MTN-027.

Intravaginal rings (IVR) containing antiretroviral drugs are a promising method for HIV prevention. We triangulated quantitative and qualitative assessments to evaluate the acceptability of four IVRs used continuously for 28 days as part of a Phase I trial (N = 48 HIV-negative women; ages 18-45). Adherence was high throughout the trial, yet 30% of participants reported involuntary IVR expulsions followed by re-insertion.

Phase 1 Safety and Pharmacokinetics Study of MK-2048/Vicriviroc (MK-4176)/MK-2048A Intravaginal Rings.

Background: Vaginal rings (VR) containing antiretroviral (ARV) drugs can be utilized for prevention of human immunodeficiency virus (HIV) with potential for improved adherence compared to daily pills. Combination ARV VRs could improve efficacy.

Methods: MTN-027, a single-blind, randomized, placebo-controlled trial in 48 women, evaluated VRs containing MK-2048 (30 mg) and vicriviroc (VCV, 182 mg), alone or in combination, and placebo used continuously for 28 days.

ADAP1 limits neonatal cardiomyocyte hypertrophy by reducing integrin cell surface expression.

The ArfGAP with dual PH domains 1 (ADAP1) regulates the activation of the hypertrophic mitogen-activated protein kinase ERK1/2 pathway in non-cardiomyocytes. However, its role in cardiomyocytes is unknown. Our aim was to characterize the role of ADAP1 in the hypertrophic process of cardiomyocytes.

Dietary Fructose Increases the Sensitivity of Proximal Tubules to Angiotensin II in Rats Fed High-Salt Diets.

Dietary fructose causes salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the filtered NaCl. Angiotensin II (Ang II), atrial natriuretic peptide (ANP) and norepinephrine (NE) regulate this process.

Tumor necrosis factor receptor-associated factor 6 as a nuclear factor kappa B-modulating therapeutic target in cardiovascular diseases: at the heart of it all.

Inflammatory and immune signaling has been documented as a root cause of many cardiovascular pathologies. In this review, we explore the emerging role of tumor necrosis factor receptor-associated factor 6 (TRAF6)-nuclear factor kappa B (NF-κB) signaling axis in atherosclerosis, ischemic heart disease, pathologic cardiac hypertrophy or heart failure, myocarditis, and sepsis-induced cardiomyopathy. We discuss the current understanding of cardiac inflammation in heart disease, present the TRAF6 signaling axis in the heart, then summarize what is known about TRAF6 in pathophysiology of heart disease including proof-of-concept studies that identify the utility of blocking TRAF6 to attenuate cardiac dysfunction, which suggests that TRAF6 is a novel, druggable target in treating cardiovascular disease incurred by inflammatory processes.

Mitochondrial NAD/NADH Redox State and Diabetic Cardiomyopathy.

Diabetic cardiomyopathy (DCM) is a frequent complication occurring even in well-controlled asymptomatic diabetic patients, and it may advance to heart failure (HF). The diabetic heart is characterized by a state of "metabolic rigidity" involving enhanced rates of fatty acid uptake and mitochondrial oxidation as the predominant energy source, and it exhibits mitochondrial electron transport chain defects. These alterations promote redox state changes evidenced by a decreased NAD/NADH ratio associated with an increase in acetyl-CoA/CoA ratio.

Dietary Fructose Enhances the Ability of Low Concentrations of Angiotensin II to Stimulate Proximal Tubule Na⁺ Reabsorption.

Fructose-enriched diets cause salt-sensitive hypertension. Proximal tubules (PTs) reabsorb 70% of the water and salt filtered through the glomerulus. Angiotensin II (Ang II) regulates this process.

Diet-Induced Ketosis Protects Against Focal Cerebral Ischemia in Mouse.

Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective.

Methylene blue decreases mitochondrial lysine acetylation in the diabetic heart.

Diabetic cardiomyopathy is preceded by mitochondrial alterations, and progresses to heart failure. We studied whether treatment with methylene blue (MB), a compound that was reported to serve as an alternate electron carrier within the mitochondrial electron transport chain (ETC), improves mitochondrial metabolism and cardiac function in type 1 diabetes. MB was administered at 10 mg/kg/day to control and diabetic rats.

Use of a Vaginal Ring Containing Dapivirine for HIV-1 Prevention in Women.

Background: Antiretroviral medications that are used as prophylaxis can prevent acquisition of human immunodeficiency virus type 1 (HIV-1) infection. However, in clinical trials among African women, the incidence of HIV-1 infection was not reduced, probably because of low adherence. Longer-acting methods of drug delivery, such as vaginal rings, may simplify use of antiretroviral medications and provide HIV-1 protection.

MuRF1 mono-ubiquitinates TRα to inhibit T3-induced cardiac hypertrophy in vivo.

Thyroid hormone (TH) is recognized for its role in cellular metabolism and growth and participates in homeostasis of the heart. T3 activates pro-survival pathways including Akt and mTOR. Treatment with T3 after myocardial infarction is cardioprotective and promotes elements of physiological hypertrophic response after cardiac injury.

Role of Receptor Protein Tyrosine Phosphatase γ in Sensing Extracellular CO2 and HCO3.

Regulation of blood pH-critical for virtually every facet of life-requires that the renal proximal tubule (PT) adjust its rate of H(+) secretion (nearly the same as the rate of HCO3 (-) reabsorption, JHCO3 ) in response to changes in blood [CO2] and [HCO3 (-)]. Yet CO2/HCO3 (-) sensing mechanisms remain poorly characterized. Because receptor tyrosine kinase inhibitors render JHCO3 in the PT insensitive to changes in CO2 concentration, we hypothesized that the structural features of receptor protein tyrosine phosphatase-γ (RPTPγ) that are consistent with binding of extracellular CO2 or HCO3 (-) facilitate monitoring of blood CO2/HCO3 (-) concentrations.

Mitochondrial complex I defect and increased fatty acid oxidation enhance protein lysine acetylation in the diabetic heart.

Aims: Cardiomyopathy is a major complication of diabetes. Our study was aimed to identify the sites of mitochondrial dysfunction and delineate its consequences on mitochondrial metabolism in a model of type 1 diabetes.

Methods And Results: Diabetes was induced by streptozotocin injection to male Lewis rats.

Catabolism of (2E)-4-hydroxy-2-nonenal via ω- and ω-1-oxidation stimulated by ketogenic diet.

Oxidative stress triggers the peroxidation of ω-6-polyunsaturated fatty acids to reactive lipid fragments, including (2E)-4-hydroxy-2-nonenal (HNE). We previously reported two parallel catabolic pathways of HNE. In this study, we report a novel metabolite that accumulates in rat liver perfused with HNE or 4-hydroxynonanoic acid (HNA), identified as 3-(5-oxotetrahydro-2-furanyl)propanoyl-CoA.

Cardioprotective effects of dietary lipids evident in the time-dependent alterations of cardiac function and gene expression following myocardial infarction.

We have previously shown that prolonged high-saturated fat feeding (SAT) for 8 weeks after myocardial infarction (MI) improves ventricular function and prevents the metabolic remodeling commonly observed in heart failure. The current study was designed to delineate the interplay between markers of energy metabolism and indices of cardiac remodeling with 2 and 4 weeks of post-MI SAT in male Wistar rats. By 2 weeks, less remodeling was noted in MI-SAT evidenced by diminished chamber dilation and greater ejection fraction assessed by echocardiography and hemodynamic measures.

Novel approach in LC-MS/MS using MRM to generate a full profile of acyl-CoAs: discovery of acyl-dephospho-CoAs.

A metabolomic approach to selectively profile all acyl-CoAs was developed using a programmed multiple reaction monitoring (MRM) method in LC-MS/MS and was employed in the analysis of various rat organs. The programmed MRM method possessed 300 mass ion transitions with the mass difference of 507 between precursor ion (Q1) and product ion (Q3), and the precursor ion started from m/z 768 and progressively increased one mass unit at each step. Acyl-dephospho-CoAs resulting from the dephosphorylation of acyl-CoAs were identified by accurate MS and fragmentation.

4-Hydroxy-2(E)-nonenal (HNE) catabolism and formation of HNE adducts are modulated by β oxidation of fatty acids in the isolated rat heart.

We previously reported that a novel metabolic pathway functionally catabolizes 4-hydroxy-2(E)-nonenal (HNE) via two parallel pathways, which rely heavily on β-oxidation pathways. The hypothesis driving this report is that perturbations of β oxidation will alter the catabolic disposal of HNE, favoring an increase in the concentrations of HNE and HNE-modified proteins that may further exacerbate pathology. This study employed Langendorff perfused hearts to investigate the impact of cardiac injury modeled by ischemia/reperfusion and, in a separate set of perfusions, the effects of elevated lipid (typically observed in obesity and type II diabetes) by perfusing with increased fatty acid concentrations (1mM octanoate).

The relationship of hospital quality and cost per case in Hawaii.

One of the leading questions of our time is whether high-quality care leads to lower health care costs. Using data from Hawaii hospitals, this paper addresses the relationship of overall cost per case to a composite measure of the quality of inpatient care and a 30-day readmission rate. We found that low-cost hospitals tend to have the highest quality but the worst readmission performance.