Cardiovascular responses to static handgrip exercise and postexercise ischemia in heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) is characterized by reduced ability to sustain physical activity that may be due partly to disease-related changes in autonomic function that contribute to dysregulated cardiovascular control during muscular contraction. Thus, we used a combination of static handgrip exercise (HG) and postexercise ischemia (PEI) to examine the pressor response to exercise and isolate the skeletal muscle metaboreflex, respectively. Mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were assessed during 2-min of static HG at 30 and 40% of maximum voluntary contraction (MVC) and subsequent PEI in 16 patients with HFpEF and 17 healthy, similarly aged controls.

Tetrahydrobiopterin Administration Augments Exercise-Induced Hyperemia and Endothelial Function in Patients With Systemic Sclerosis.

Systemic sclerosis (SSc) is a rare, auto-immune disease with variably progressive fibrosis of the skin and internal organs, as well as vascular dysfunction. Recently, we demonstrated a decrement in exercising skeletal muscle blood flow and endothelium-dependent vasodilation in SSc, but the mechanisms responsible for these impairments have not been investigated. Thus, we sought to determine if acute administration of tetrahydrobiopterin (BH), an essential cofactor for endothelial nitric oxide synthase (eNOS), would improve hyperemia and brachial artery vasodilation during progressive handgrip exercise in SSc.

A Novel Method to Measure Transient Impairments in Cognitive Function During Acute Bouts of Hypoxia.

Exposure to low oxygen environments (hypoxia) can impair cognitive function; however, the time-course of the transient changes in cognitive function is unknown. In this study, we assessed cognitive function with a cognitive test before, during, and after exposure to hypoxia. Nine participants (28 4 yr, 7 women) completed Conners Continuous Performance Test (CCPT-II) during three sequential conditions: 1) baseline breathing room air (fraction of inspired oxygen, Fo₂ 0.

Cardiovascular responses to rhythmic handgrip exercise in heart failure with preserved ejection fraction.

Although the contribution of noncardiac complications to the pathophysiology of heart failure with preserved ejection fraction (HFpEF) have been increasingly recognized, disease-related changes in peripheral vascular control remain poorly understood. We utilized small muscle mass handgrip exercise to concomitantly evaluate exercising muscle blood flow and conduit vessel endothelium-dependent vasodilation in individuals with HFpEF ( = 25) compared with hypertensive controls (HTN) ( = 25). Heart rate (HR), stroke volume (SV), cardiac output (CO), mean arterial pressure (MAP), brachial artery blood velocity, and brachial artery diameter were assessed during progressive intermittent handgrip (HG) exercise [15-30-45% maximal voluntary contraction (MVC)].

Skeletal Muscle Mitochondrial Adaptations to Maximal Strength Training in Older Adults.

Maximal strength training (MST) results in robust improvements in skeletal muscle force production, efficiency, and mass. However, the effects of MST on muscle mitochondria are still unknown. Accordingly, the purpose of this study was to examine, from the molecular level to whole-muscle, mitochondrial adaptations induced by 8 weeks of knee-extension MST in the quadriceps of 10 older adults using immunoblotting, spectrophotometry, high-resolution respirometry in permeabilized muscle fibers, in vivo 31P magnetic resonance spectroscopy (31P-MRS), and gas exchange.

Cost-Effectiveness of a Weight Loss Intervention: An Adaptation of the Look AHEAD Lifestyle Intervention in the US Military.

Objective: This study aimed to assess whether a counselor-initiated (CI) adaptation of the Look AHEAD (Action for Health in Diabetes) intensive lifestyle intervention in a military setting was cost-effective relative to a self-paced (SP) adaptation.

Methods: A cost-effectiveness analysis from a payer perspective was performed alongside a 2014-2017 randomized behavioral weight loss trial among 248 active-duty military personnel stationed at a US Air Force base in Texas. Incremental cost-effectiveness ratios were calculated for weight loss, reductions in waist circumference, and quality-adjusted life-years (QALYs).

Impact of acute antioxidant administration on inflammation and vascular function in heart failure with preserved ejection fraction.

Although it is now well established that heart failure with preserved ejection fraction (HFpEF) is associated with marked inflammation and a prooxidant state that is accompanied by vascular dysfunction, whether acute antioxidant (AO) administration can effectively target these disease-related decrements has not been evaluated. Thus, the present study sought to evaluate the efficacy of an acute over-the-counter AO cocktail (600 mg α-lipoic acid, 1,000 mg vitamin C, and 600 IU vitamin E) to mitigate inflammation and oxidative stress, and subsequently improve nitric oxide (NO) bioavailability and vascular function, in patients with HFpEF. Flow-mediated dilation (FMD) and reactive hyperemia (RH) were evaluated to assess conduit vessel and microvascular function, respectively, 90 min after administration of either placebo (PL) or AO in 16 patients with HFpEF (73 ± 10 yr, EF 54-70%) using a double-blind, crossover design.

A clinical pathway to minimize computed tomography for suspected nephrolithiasis in children.

Introduction: Ultrasound (US) imaging is preferred in the initial evaluation for children with suspected nephrolithiasis; however, computed tomography (CT) continues to be used in this setting with resultant unnecessary ionizing radiation exposure. The study institution implemented a standardized clinical pathway to reduce rates of CT utilization for children with nephrolithiasis.

Objective: The aim of this study was to evaluate the impact of this pathway on initial imaging strategies for children with suspected nephrolithiasis.

Verbal Fluency Is Affected by Altered Brain Lateralization in Adults Who Were Born Very Preterm.

Language difficulties have been reported in children and adolescents who were born very preterm (<32 weeks' gestation) and associated with an atypical lateralization of language processing, i.e., increased right-hemispheric engagement.

Cholinergic basal forebrain neurons regulate fear extinction consolidation through p75 neurotrophin receptor signaling.

Cholinergic basal forebrain (cBF)-derived neurotransmission plays a crucial role in regulating neuronal function throughout the cortex, yet the mechanisms controlling cholinergic innervation to downstream targets have not been elucidated. Here we report that removing the p75 neurotrophin receptor (p75) from cBF neurons induces a significant impairment in fear extinction consolidation. We demonstrate that this is achieved through alterations in synaptic connectivity and functional activity within the medial prefrontal cortex.

Maximal strength training increases muscle force generating capacity and the anaerobic ATP synthesis flux without altering the cost of contraction in elderly.

Aging is associated with a progressive decline in skeletal muscle function, then leading to impaired exercise tolerance. Maximal strength training (MST) appears to be a practical and effective intervention to increase both exercise capacity and efficiency. However, the underlying physiological mechanisms responsible for these functional improvements are still unclear.

Oxygen availability and skeletal muscle oxidative capacity in patients with peripheral artery disease: implications from in vivo and in vitro assessments.

Evidence suggests that the peak skeletal muscle mitochondrial ATP synthesis rate ( V) in patients with peripheral artery disease (PAD) may be attenuated due to disease-related impairments in O supply. However, in vitro assessments suggest intrinsic deficits in mitochondrial respiration despite ample O availability. To address this conundrum, Doppler ultrasound, near-infrared spectroscopy, phosphorus magnetic resonance spectroscopy, and high-resolution respirometry were combined to assess convective O delivery, tissue oxygenation, V, and skeletal muscle mitochondrial capacity (complex I + II, state 3 respiration), respectively, in the gastrocnemius muscle of 10 patients with early stage PAD and 11 physical activity-matched healthy control (HC) subjects.

Attenuated nitric oxide bioavailability in systemic sclerosis: Evidence from the novel assessment of passive leg movement.

New Findings: What is the central question of this study? Do systemic sclerosis patients exhibit impaired nitric oxide-mediated vascular function of the lower limb and are these decrements correlated with plasma biomarkers for inflammation and oxidative stress? What is the main finding and its importance? Findings indicate impaired nitric oxide-mediated vascular function, linked to the incidence of digital ulcers and a milieu of inflammation and oxidative stress. However, the absence of significant correlations between individual biomarkers and blood flow responses suggests that the vasculopathy observed in systemic sclerosis may not be solely the result of derangements in the redox balance or inflammatory signalling.

Abstract: Systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy, which may be the consequence of inflammation and oxidative stress that ultimately leads to a reduced nitric oxide (NO) bioavailability.

Outcomes of a Clinical Pathway to Standardize Use of Maintenance Intravenous Fluids.

Objectives: Improper use of maintenance intravenous fluids (IVFs) may cause serious hospital-acquired harm. We created an evidence-based clinical pathway to guide providers on the indications for IVF, its preferred composition, and appropriate clinical monitoring.

Methods: Pathway implementation was supported by the creation of an electronic order set (PowerPlan) and hospital-wide education.

Acute oral tetrahydrobiopterin administration ameliorates endothelial dysfunction in systemic sclerosis.

Objectives: Systemic sclerosis (SSc) is a rare, autoimmune disease characterised by endothelial dysfunction, which is associated with peripheral vasculopathy, such as digital ulcers (DU). We sought to determine if acute oral administration of tetrahydrobiopterin (BH4), an essential cofactor for endothelial nitric oxide synthase, would augment endothelial function in patients with SSc.

Methods: Twelve SSc patients, of whom a majority had a history of DU, were studied 5 hours after oral BH4 administration (10 mg/kg body mass) or placebo on separate days using controlled, counterbalanced, double-blind, crossover experimental design.

Reliable Pregnancy Testing Before Intravenous Cyclophosphamide: A Quality Improvement Study.

Background And Objective: Cyclophosphamide is a teratogenic medication used in the treatment of adolescents with autoimmune disorders. This adolescent population is sexually active, does not receive adequate contraceptive care, and is at risk for unintended pregnancy. We undertook a quality improvement initiative to improve rates of pregnancy screening before intravenous cyclophosphamide administration in our adolescent girl patients.

Exercise-induced brachial artery blood flow and vascular function is impaired in systemic sclerosis.

Systemic sclerosis (SSc) is a rare autoimmune disease characterized by debilitating fibrosis and vascular dysfunction; however, little is known about the circulatory response to exercise in this population. Therefore, we examined the peripheral hemodynamic and vasodilatory responses to handgrip exercise in 10 patients with SSc (61 ± 4 yr) and 15 age-matched healthy controls (56 ± 5 yr). Brachial artery diameter, blood flow, and mean arterial pressure (MAP) were determined at rest and during progressive static-intermittent handgrip exercise.

Nicotinic acid is a common regulator of heat-sensing TRPV1-4 ion channels.

Nicotinic acid (NA, a.k.a.

Stratification of children by medical complexity.

Objective: To stratify children using available software, Clinical Risk Groups (CRGs), in a tertiary children's hospital, Seattle Children's Hospital (SCH), and a state's Medicaid claims data, Washington State (WSM), into 3 condition groups: complex chronic disease (C-CD); noncomplex chronic disease (NC-CD), and nonchronic disease (NC).

Methods: A panel of pediatricians developed consensus definitions for children with C-CD, NC-CD, and NC. Using electronic medical record review and expert consensus, a gold standard population of 700 children was identified and placed into 1 the 3 groups: 350 C-CD, 100 NC-CD, and 250 NC.

TRPV1 channels are involved in niacin-induced cutaneous vasodilation in mice.

Niacin is effective in treating dyslipidemias but causes cutaneous vasodilation or flushing, a side effect that limits its clinical use. Blocking prostaglandins in humans reduces but does not consistently eliminate flushing, indicating additional mechanisms may contribute to flushing. The transient receptor potential vanilloid 1 (TRPV1) channel, when activated, causes cutaneous vasodilation and undergoes tachyphylaxis similar to that seen with niacin.

Nicotinic acid activates the capsaicin receptor TRPV1: Potential mechanism for cutaneous flushing.

Objective: Nicotinic acid (also known as niacin or vitamin B3), widely used to treat dyslipidemias, represents an effective and safe means to reduce the risk of mortality from cardiovascular disease. Nonetheless, a substantial fraction of patients discontinue treatment because of a strong side effect of cutaneous vasodilation, commonly termed flushing. In the present study, we tested the hypothesis that nicotinic acid causes flushing partially by activating the capsaicin receptor TRPV1, a polymodal cellular sensor that mediates the flushing response on consumption of spicy food.

Predictive Analytics In Healthcare: Medications as a Predictor of Medical Complexity.

Children with special healthcare needs (CSHCN) require health and related services that exceed those required by most hospitalized children. A small but growing and important subset of the CSHCN group includes medically complex children (MCCs). MCCs typically have comorbidities and disproportionately consume healthcare resources.

Inpatient growth and resource use in 28 children's hospitals: a longitudinal, multi-institutional study.

Objective: To compare inpatient resource use trends for healthy children and children with chronic health conditions of varying degrees of medical complexity.

Design: Retrospective cohort analysis.

Setting: Twenty-eight US children's hospitals.