Do Pulmonary Ionocytes Absorb Chloride or Secrete Chloride?

Pulmonary ionocytes express high levels of cystic fibrosis transmembrane conductance regulator (CFTR) channels. When studied using the short-circuit current technique, ionocytes produce CFTR-dependent short-circuit currents consistent with Cl secretion. However, when studied without a voltage-clamp, data indicate that ionocytes absorb Cl.

Initiation of home noninvasive ventilation in hypercapnic chronic obstructive pulmonary disease: when, where, and how?

Purpose Of Review: This review aims to highlight the importance of timely initiation of home noninvasive ventilation (homeNIV) for patients with chronic hypercapnic respiratory failure (CHRF) due to chronic obstructive pulmonary disease (COPD). As emerging evidence continues to show substantial benefits in reducing mortality and hospitalizations, it's crucial to identify which patients will benefit most and to provide clear guidance on implementing homeNIV effectively.

Recent Findings: Recent research supports the use of high intensity homeNIV for CHRF secondary to COPD, showing marked reductions in hospitalizations and mortality.

Risk Factors for Pediatric Bystander-Related Riding Lawnmower Injuries: A Qualitative Study.

Riding lawnmowers are the most frequent cause of major limb amputation in children in the United States. Our study objective was to investigate the circumstances of child bystander-related riding lawnmower injuries and identify behaviors leading to these events. Followers/members of lawnmower injury-related Facebook pages, who were aware of children that had suffered a lawnmower injury, were invited to complete a survey.

Impact of high spinal anesthesia in pediatric congenital heart surgery on postoperative recovery: a retrospective propensity score-matched study.

Background: High spinal anesthesia (HSA) has been utilized in cardiac surgery; however, there is limited evidence on its impact on facilitating postoperative recovery. This study aimed to evaluate the impact of HSA in pediatric congenital heart surgery on postoperative recovery.

Methods: A single center, propensity score-matched retrospective cohort study was designed using data from pediatric patients under 18 years old, who underwent congenital heart surgeries classified as Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) score 3 or less.

Structure and assembly of the dystrophin glycoprotein complex.

The dystrophin glycoprotein complex (DGC) has a crucial role in maintaining cell membrane stability and integrity by connecting the intracellular cytoskeleton with the surrounding extracellular matrix. Dysfunction of dystrophin and its associated proteins results in muscular dystrophy, a disorder characterized by progressive muscle weakness and degeneration. Despite the important roles of the DGC in physiology and pathology, its structural details remain largely unknown, hindering a comprehensive understanding of its assembly and function.

Supplementary oxygen efficacy for chronic pulmonary disorders and exertion desaturation.

Introduction: Exertion-induced desaturation (EID) is a common complication of numerous pulmonary disorders and often treated with supplementary oxygen during exertion. We performed a systematic review and meta-analysis of randomised clinical trials (RCTs) to evaluate the efficacy of supplementary oxygen for EID in pulmonary disorders.

Material And Methods: Medline and Embase were systematically searched from July 2022 to June 2023 following PRISMA guidelines.

Comparison of outcomes by race among a population-based matched sample of multiple myeloma patients.

Purpose: It is important to understand racial inequities in multiple myeloma treatment and survival, particularly in the Midwest where clear differences exist in cancer incidence and mortality. Since age and geographic location can greatly impact treatment and prognosis, matching patients on these characteristics can help identify reasons for outcome differences.

Methods: Retrospective data from the Iowa Cancer Registry's Surveillance, Epidemiology, and End Results database were analyzed for adult patients diagnosed with first primary MM between 1/1/2010-12/31/2019.

Spinal afferent neurons: emerging regulators of energy balance and metabolism.

Recent advancements in neurophysiology have challenged the long-held paradigm that vagal afferents serve as the primary conduits for physiological signals governing food intake and energy expenditure. An expanding body of evidence now illuminates the critical role of spinal afferent neurons in these processes, necessitating a reevaluation of our understanding of energy homeostasis regulation. This comprehensive review synthesizes cutting-edge research elucidating the multifaceted functions of spinal afferent neurons in maintaining metabolic equilibrium.

Shear stress-stimulated AMPK couples endothelial cell mechanics, metabolism and vasodilation.

Endothelial cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that the application of force to endothelial cells stimulates VE-cadherin to activate liver kinase B1 (LKB1; also known as STK11) and AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin-stimulated AMPK increases eNOS (also known as NOS3) activity and localization to the plasma membrane, reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake.

Widespread pain phenotypes impact treatment efficacy results in randomized clinical trials for interstitial cystitis/bladder pain syndrome: a Multidisciplinary Approach to the Study of Chronic Pelvic Pain network study.

Pain clinical trials are notoriously complex and often inefficient in demonstrating efficacy, even for known efficacious treatments. A major issue is the difficulty in the a priori identification of specific phenotypes to include in the study population. Recent work has identified the extent of widespread pain as an important determinant of the likelihood of response to therapy, but it has not been tested in clinical trials for the treatment of interstitial cystitis/bladder pain syndrome (IC/BPS).

Patient, facility, and environmental factors associated with obesity treatment in US Veterans.

Background: Identifying patient-, facility-, and environment-level factors that influence the initiation and retention of comprehensive lifestyle management interventions (CLMI) for urban and rural Veterans could improve obesity treatment and reach at Veterans Affairs (VA) facilities.

Aims: This study identified factors at these various levels that predicted treatment engagement, retention, and weight management among urban and rural Veterans.

Methods: A retrospective cohort study of 631,325 Veterans was designed using VA databases to identify Veterans with class II and III obesity during 2015-2017.

Immediate change following valve deployment in left ventricular systolic and diastolic functions in transcatheter aortic valve replacement: a retrospective cohort study.

Background: Transcatheter aortic valve replacement (TAVR) is an effective treatment for aortic valve disorder. Several studies have reported improvements in systolic and diastolic function following TAVR. However, few studies have addressed immediate post-deployment changes.

Overnutrition causes insulin resistance and metabolic disorder through increased sympathetic nervous system activity.

The mechanisms underlying obesity-induced insulin resistance remain incompletely understood, as impaired cellular insulin signaling, traditionally considered the primary driver of insulin resistance, does not always accompany impaired insulin action. Overnutrition rapidly increases plasma norepinephrine (NE), suggesting overactivation of the sympathetic nervous system (SNS). However, the role of the SNS in obesity is controversial, as both increased and decreased SNS activity (SNA) have been reported.

Saturation mutagenesis-reinforced functional assays for disease-related genes.

Interpretation of disease-causing genetic variants remains a challenge in human genetics. Current costs and complexity of deep mutational scanning methods are obstacles for achieving genome-wide resolution of variants in disease-related genes. Our framework, saturation mutagenesis-reinforced functional assays (SMuRF), offers simple and cost-effective saturation mutagenesis paired with streamlined functional assays to enhance the interpretation of unresolved variants.

BATokines in metabolic liver disease: good cops or bad cops?

The systemic regulation of metabolic dysfunction-associated liver disease remains poorly understood. In this issue, Hsiao et al (2024) identify PCPE-1 as a brown-adipose tissue-derived mediator of hepatic fibrosis, integrating context-dependent ER stress-signaling.

Amphiphilic shuttle peptide delivers base editor ribonucleoprotein to correct the CFTR R553X mutation in well-differentiated airway epithelial cells.

Base editing could correct nonsense mutations that cause cystic fibrosis (CF), but clinical development is limited by the lack of delivery methods that efficiently breach the barriers presented by airway epithelia. Here, we present a novel amphiphilic shuttle peptide based on the previously reported S10 peptide that substantially improved base editor ribonucleoprotein (RNP) delivery. Studies of the S10 secondary structure revealed that the alpha-helix formed by the endosomal leakage domain (ELD), but not the cell penetrating peptide (CPP), was functionally important for delivery.

IL-13 induces loss of CFTR in ionocytes and reduces airway epithelial fluid absorption.

The airway surface liquid (ASL) plays a crucial role in lung defense mechanisms, and its composition and volume are regulated by the airway epithelium. The cystic fibrosis transmembrane conductance regulator (CFTR) is abundantly expressed in a rare airway epithelial cell type called an ionocyte. Recently, we demonstrated that ionocytes can increase liquid absorption through apical CFTR and basolateral barttin/chloride channels, while airway secretory cells mediate liquid secretion through apical CFTR channels and basolateral NKCC1 transporters.