Increased Muc5AC and Decreased Ciliated Cells in Severe Asthma Partially Restored by Inhibition of IL-4Rα Receptor.

The role of IL-13 on the airway epithelium in severe asthma leading to airway remodeling remains poorly understood. To study IL-13-induced airway remodeling on goblet cells and cilia in the airway epithelium in severe asthma and the impact of an anti-IL4Rα antibody, dupilumab, . Quantitative computed tomography of the lungs and endobronchial biopsies and brushings were obtained in 51 participants (22 with severe asthma, 11 with nonsevere asthma, and 18 healthy participants) in SARPIII (Severe Asthma Research Program III) and measured for mucin and cilia-related proteins.

Dissemination and implementation research coordination and training to improve cardiovascular health in people living with HIV in sub-Saharan Africa: the research coordinating center of the HLB-SIMPLe Alliance.

As global adoption of antiretroviral therapy extends the lifespan of People Living with HIV (PLHIV) through viral suppression, the risk of comorbid conditions such as hypertension has risen, creating a need for effective, scalable interventions to manage comorbidities in PLHIV. The Heart, Lung, and Blood Co-morbiditieS Implementation Models in People Living with HIV (HLB-SIMPLe) Alliance has been funded by the National Heart, Lung, and Blood Institute (NHLBI) and the Fogarty International Center (FIC) since September 2020. The Alliance was created to conduct late-stage implementation research to contextualize, implement, and evaluate evidence-based strategies to integrate the diagnosis, treatment, and control of cardiovascular diseases, particularly hypertension, in PLHIV in low- and middle-income countries (LMICs).

Azithromycin therapy in infants hospitalized for respiratory syncytial virus bronchiolitis: Airway matrix metalloproteinase-9 levels and subsequent recurrent wheeze.

Background: Early life respiratory syncytial virus (RSV) bronchiolitis is a significant risk factor for childhood asthma. In vitro and in vivo studies suggested that decreasing levels of airway matrix metalloproteinase (MMP)-9 during RSV bronchiolitis may be associated with clinical benefits.

Objective: To investigate whether azithromycin therapy during severe RSV bronchiolitis reduces upper airway MMP-9 levels, whether upper airway MMP-9 levels correlate with upper airway interleukin IL-8 levels, and whether MMP-9 level reduction is associated with reduced post-RSV recurrent wheeze (RW).

A Pilot Randomized Controlled Trial of De Novo Belatacept-based Immunosuppression After Lung Transplantation.

Background: Chronic lung allograft dysfunction (CLAD) is the leading cause of death beyond the first year after lung transplantation. The development of donor-specific antibodies (DSA) is a recognized risk factor for CLAD. Based on experience in kidney transplantation, we hypothesized that belatacept, a selective T-cell costimulatory blocker, would reduce the incidence of DSA after lung transplantation, which may ameliorate the risk of CLAD.

The inorganic NItrate and eXercise performance in Heart Failure (iNIX-HF) phase II clinical trial: Rationale and study design.

Background: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF).

Parents, but not their children, demonstrate greater delay discounting with resource scarcity.

Background: Individuals with obesity tend to discount the future (delay discounting), focusing on immediate gratification. Delay discounting is reliably related to indicators of economic scarcity (i.e.

Family-Based Behavioral Treatment for Childhood Obesity Implemented in Pediatric Primary Care: A Randomized Clinical Trial.

Importance: Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics. Evidence is lacking on their effectiveness in pediatric primary care settings.

Objective: To evaluate the effects of family-based treatment for overweight or obesity implemented in pediatric primary care on children and their parents and siblings.

Relationships examined: Parent and child readiness to change and sociodemographic characteristics in family based weight loss treatment.

Background: Family based treatment is an effective, multipronged approach to address obesity as it plagues families.

Objective: To investigate the relationships among sociodemographic characteristics (e.g.

Recombinant Human Perlecan DV and Its LG3 Subdomain Are Neuroprotective and Acutely Functionally Restorative in Severe Experimental Ischemic Stroke.

Despite recent therapeutic advancements, ischemic stroke remains a major cause of death and disability. It has been previously demonstrated that  ~ 85-kDa recombinant human perlecan domain V (rhPDV) binds to upregulated integrin receptors (α2β1 and α5β1) associated with neuroprotective and functional improvements in various animal models of acute ischemic stroke. Recombinant human perlecan laminin-like globular domain 3 (rhPDV), a 21-kDa C-terminal subdomain of rhPDV, has been demonstrated to more avidly bind to the α2β1 integrin receptor than its parent molecule and consequently was postulated to evoke significant neuroprotective and functional effects.

Effect of excessive gestational weight gain on insulin sensitivity and insulin kinetics in women with overweight/obesity.

Objective: Obesity increases the risk for pregnancy complications and maternal hyperglycemia. The Institute of Medicine developed guidelines for gestational weight gain (GWG) targets for women with overweight/obesity, but it is unclear whether exceeding these targets has adverse effects on maternal glucose metabolism.

Methods: Insulin sensitivity (assessed using the Matsuda Insulin Sensitivity Index), β-cell function (assessed as insulin secretion rate in relation to plasma glucose), and plasma insulin clearance rate were evaluated using a frequently sampled oral glucose tolerance test at 15 and 35 weeks of gestation in 184 socioeconomically disadvantaged African American women with overweight/obesity.

High rates of undiagnosed and uncontrolled hypertension upon a screening campaign in rural Rwanda: a cross-sectional study.

Background: Hypertension remains the major risk factor for cardiovascular diseases (CVDs) worldwide with a prevalence and mortality in low- and middle-income countries (LMICs) among the highest. The early detection of hypertension risk factors is a crucial pillar for CVD prevention.

Design And Method: This cross-sectional study included 4284 subjects, mean age 46 ± 16SD, 56.

Azithromycin to Prevent Recurrent Wheeze Following Severe Respiratory Syncytial Virus Bronchiolitis.

Background: Early-life severe respiratory syncytial virus (RSV) bronchiolitis is a risk factor for childhood asthma. Because azithromycin may attenuate airway inflammation during RSV bronchiolitis, we evaluated whether it would reduce the occurrence of post-RSV recurrent wheeze.

Methods: We prospectively enrolled 200 otherwise healthy 1- to 18-month-old children hospitalized with RSV bronchiolitis in this single-center, double-blind, placebo-controlled study and randomly assigned them to receive oral azithromycin (10 mg/kg daily for 7 days, followed by 5 mg/kg daily for 7 days) or placebo.

A pilot randomized controlled trial of de novo belatacept-based immunosuppression following anti-thymocyte globulin induction in lung transplantation.

The development of donor-specific antibodies (DSA) after lung transplantation is common and results in adverse outcomes. In kidney transplantation, Belatacept has been associated with a lower incidence of DSA, but experience with Belatacept in lung transplantation is limited. We conducted a two-center pilot randomized controlled trial of de novo immunosuppression with Belatacept after lung transplantation to assess the feasibility of conducting a pivotal trial.

SARS-CoV-2 active infection prevalence and seroprevalence in the adult population of St. Louis County.

Background: The true prevalence of COVID-19 is difficult to estimate due to the absence of random population-based testing. To estimate current and past COVID-19 infection prevalence in a large urban area, we conducted a population-based survey in St. Louis County, Missouri.

Exploring contextual factors influencing the implementation of evidence-based care for hypertension in Rwanda: a cross-sectional study using the COACH questionnaire.

Importance: Hypertension is the largest contributor to the Global Burden of Disease. In Rwanda, as in most low-income and middle-income countries, an increasing prevalence of hypertension and its associated morbidity and mortality is causing major healthcare and economic impact. Understanding healthcare systems context in hypertension care is necessary.

Implementing family-based behavioral treatment in the pediatric primary care setting: Design of the PLAN study.

Family-based behavioral treatment (FBT) is an evidence-based treatment for pediatric obesity. FBT has primarily been implemented in specialty clinics, with highly trained interventionists. The goal of this study is to assess effectiveness of FBT implemented in pediatric primary care settings using newly trained interventionists who might implement FBT in pediatric practices.

The azithromycin to prevent wheezing following severe RSV bronchiolitis-II clinical trial: Rationale, study design, methods, and characteristics of study population.

Severe respiratory syncytial virus (RSV) bronchiolitis in early life is a significant risk factor for future recurrent wheeze (RW) and asthma. The goal of the Azithromycin to Prevent Wheezing following severe RSV bronchiolitis II (APW-RSV II) clinical trial is to evaluate if azithromycin treatment in infants hospitalized with RSV bronchiolitis reduces the occurrence of RW during the preschool years. The APW-RSV II clinical trial is a double-blind, placebo-controlled, parallel-group, randomized trial, including otherwise healthy participants, ages 30 days-18 months, who are hospitalized due to RSV bronchiolitis.

A multi-center trial of exercise and testosterone therapy in women after hip fracture: Design, methods and impact of the COVID-19 pandemic.

Background: Up to 75% of hip fracture patients never recover to their pre-fracture functional status. Supervised exercise that includes strength training can improve functional recovery after hip fracture. The role of testosterone replacement for augmenting the effects of exercise in older women after hip fracture is unknown.

Lung function trajectories and bronchial hyperresponsiveness during childhood following severe RSV bronchiolitis in infancy.

Background: Children with severe respiratory syncytial virus (RSV) bronchiolitis in infancy have increased risks of asthma and reduced lung function in later life. There are limited studies on the longitudinal changes of lung function and bronchial hyperreactivity from early to late childhood in infants hospitalized for RSV bronchiolitis.

Methods: In a prospective cohort of 206 children with their first episode of RSV-confirmed bronchiolitis in the first year of life, 122 had spirometry performed at least twice between 5-16 years of age.

Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes.

Background: Some studies have suggested that in people with type 2 diabetes, Roux-en-Y gastric bypass has therapeutic effects on metabolic function that are independent of weight loss.

Methods: We evaluated metabolic regulators of glucose homeostasis before and after matched (approximately 18%) weight loss induced by gastric bypass (surgery group) or diet alone (diet group) in 22 patients with obesity and diabetes. The primary outcome was the change in hepatic insulin sensitivity, assessed by infusion of insulin at low rates (stages 1 and 2 of a 3-stage hyperinsulinemic euglycemic pancreatic clamp).

Impaired tumor necrosis factor-α secretion by CD4 T cells during respiratory syncytial virus bronchiolitis associated with recurrent wheeze.

Background: Infants with severe respiratory syncytial virus (RSV) bronchiolitis have an increased risk of recurrent wheezing and asthma. We aimed to evaluate the relationships between regulatory T cell (Treg) percentage and cytokine production of in vitro-stimulated CD4+ T cells during acute bronchiolitis and the development of recurrent wheezing in the first 3 years of life.

Methods: We obtained peripheral blood from 166 infants hospitalized with their first episode of RSV-confirmed bronchiolitis.

Effect of Fresh vs Standard-issue Red Blood Cell Transfusions on Multiple Organ Dysfunction Syndrome in Critically Ill Pediatric Patients: A Randomized Clinical Trial.

Importance: The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial.

Objective: To determine if the transfusion of fresh red blood cells (stored ≤7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children.

Design, Setting, And Participants: The Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers.

Clinical significance of the bronchodilator response in children with severe asthma.

Background: Our objective was to determine those characteristics associated with reversibility of airflow obstruction and response to maximal bronchodilation in children with severe asthma through the Severe Asthma Research Program (SARP).

Methods: We performed a cross-sectional analysis evaluating children ages 6 to 17 years with nonsevere asthma (NSA) and severe asthma (SA). Participants underwent spirometry before and after 180 µg of albuterol to determine reversibility (≥12% increase in FEV ).

Low dose chloroquine decreases insulin resistance in human metabolic syndrome but does not reduce carotid intima-media thickness.

Background: Metabolic syndrome, an obesity-related condition associated with insulin resistance and low-grade inflammation, leads to diabetes, cardiovascular diseases, cancer, osteoarthritis, and other disorders. Optimal therapy is unknown. The antimalarial drug chloroquine activates the kinase ataxia telangiectasia mutated (ATM), improves metabolic syndrome and reduces atherosclerosis in mice.