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.

The pH-sensitive translocation of V-ATPase in the small airway of cystic fibrosis pigs.

In contrast to pig large airways, the pH of airway surface liquid (ASL) in pig small airways is regulated by CFTR-mediated HCO secretion and the vacuolar-type H ATPase (V-ATPase) proton secretion. We hypothesized that, in cystic fibrosis (CF), the ASL pH of small airways is acidic, and the V-ATPase is internalized. We quantified proton secretion during the addition of an alkaline test solution by measuring changes in a pH-dependent fluorescent dye generated by porcine small airway epithelia in the absence and presence of bafilomycin A1.

Needlessly Treated: Evaluation of Prehospital Needle Thoracostomy.

Background: Needle thoracostomy is a potentially life-saving intervention for tension pneumothorax but may be overused, potentially leading to unnecessary morbidity.

Objective: To review prehospital needle thoracostomy indications, effectiveness, and adverse outcomes.

Methods: A retrospective cohort study was conducted based on registry data for a United States Midwestern Level I trauma center for a 7.

A national study of firearm exposure and safety training among rural youth.

Background: Data regarding rural youths' experience with firearms, including safety training, is highly limited despite their frequent presence in homes. Our objective was to investigate rural adolescents' use of firearms and whether they had received formal firearm training.

Methods: A convenience sample of 2021 National FFA (formerly Future Farmers of America) Convention & Expo attendees were given an anonymous survey at the University of Iowa Stead Family Children's Hospital injury prevention booth.

Update on Antisocial Personality Disorder.

Purpose Of Review: Antisocial personality disorder (ASPD) is a characterized by lifelong or recurrent behavioral problems that begin in childhood or early adolescence. This communication provides an overview on ASPD including findings from recent reviews and new research.

Recent Findings: With regard to DSM-5's Section III Alternative Model of Personality Disorder criteria for ASPD, advocates point to the broader symptom coverage and harmonization with ICD-11; yet critics point to the lack of evidence for improved outcomes.

Development and Initial Characterization of Pigs with Mutations and Primary Ciliary Dyskinesia.

Mutations in more than 50 different genes cause primary ciliary dyskinesia (PCD) by disrupting the activity of motile cilia that facilitate mucociliary transport (MCT). Knowledge of PCD has come from studies identifying disease-causing mutations, characterizing structural cilia abnormalities, finding genotype-phenotype relationships, and studying the cell biology of cilia. Despite these important findings, we still lack effective treatments and people with PCD have significant pulmonary impairment.

Management of pediatric patients admitted for colonic disimpaction: A scoping review protocol.

Objectives: Chronic constipation is a common condition in pediatric patients worldwide and is associated with decreased quality of life. Inpatient management of constipation is required when outpatient therapy fails and a child becomes obstipated, and unable to pass stool or gas. There is a growing body of evidence regarding different management strategies for pediatric obstipation.

Mucociliary clearance is impaired in small airways of cystic fibrosis pigs.

Cystic fibrosis (CF) is a genetic disorder characterized by recurrent airway infections, inflammation, impaired mucociliary clearance, and progressive decline in lung function. The disease may start in the small airways; however, this is difficult to prove due to the limited accessibility of the small airways with the current single-photon mucociliary clearance assay. Here, we developed a dynamic positron emission tomography assay with high spatial and temporal resolution.

A Teach-the-Teacher Module for Human Trafficking Bedside Instruction.

Introduction: Human trafficking (HT) is a public health issue that adversely affects patients' well-being. Despite the prevalence of trafficked persons in health care settings, a lack of educational modules exists for use in clinical contexts. We developed a 50-minute train-the-trainer module on HT.

Prevalence of Bronchodilator Responsiveness: A Comparison of Old Versus New Criteria.

Background: In 2021, the European Respiratory Society (ERS)/American Thoracic Society (ATS) guidelines issued a new definition of bronchodilator responsiveness, which is now defined as an increase in FEV or FVC by ≥ 10% of the predicted FEV or FVC. The impact of this revised definition on bronchodilator responsiveness prevalence has been relatively understudied.

Methods: We retrospectively analyzed data from 2,696 subjects who performed pulmonary function testing at the University of Iowa from 1997 to 2018.

The association between county ordinances allowing off-road vehicles on public roads and crash rates.

Background: Legislative bodies across the country have increasingly allowed off-road vehicles (ORVs) including all-terrain vehicles (ATVs) and utility task vehicles (UTVs) on public roads, an environment for which they are not designed. In 2004, Iowa gave individual counties the discretion to pass ordinances allowing ORVs on public roadways. The objective of this study was to evaluate the relationship between the passage of ORV ordinances and ORV crash rates, especially on public roads.

Respiratory Therapist-Driven Mechanical Ventilation Protocol Is Associated With Increased Lung Protective Ventilation.

Background: Mechanical ventilation is a common life-saving procedure but can lead to serious complications, including ARDS and oxygen toxicity. Nonadherence to lung-protective ventilation guidelines is common. We hypothesized that a respiratory therapist-driven mechanical ventilation bundle could increase adherence to lung-protective ventilation and decrease the incidence of pulmonary complications in the ICU.

Unlocking opioid neuropeptide dynamics with genetically encoded biosensors.

Neuropeptides are ubiquitous in the nervous system. Research into neuropeptides has been limited by a lack of experimental tools that allow for the precise dissection of their complex and diverse dynamics in a circuit-specific manner. Opioid peptides modulate pain, reward and aversion and as such have high clinical relevance.

IL-13 decreases susceptibility to airway epithelial SARS-CoV-2 infection but increases disease severity in vivo.

Treatments available to prevent progression of virus-induced lung diseases, including coronavirus disease 2019 (COVID-19) are of limited benefit once respiratory failure occurs. The efficacy of approved and emerging cytokine signaling-modulating antibodies is variable and is affected by disease course and patient-specific inflammation patterns. Therefore, understanding the role of inflammation on the viral infectious cycle is critical for effective use of cytokine-modulating agents.