Magnetic microwire rheometer reveals differences in hydrogel degradation disulfide reducing agents.

Mucus is composed of a complex network of mucin polymers connected by disulfide bonds. In muco-obstructive diseases, an increase in mucin disulfide crosslinks contributes to pathologic mucus formation, characterized by an increase in mucus viscosity and stiffness. Reducing agents that break down the disulfide bonds between mucins can be used to treat pathologic mucus and restore healthy mucus flow properties.

Dextromethorphan inhibits collagen and collagen-like cargo secretion to ameliorate lung fibrosis.

Excessive deposition of fibrillar collagen in the interstitial extracellular matrix (ECM) of human lung tissue causes fibrosis, which can ultimately lead to organ failure. Despite our understanding of the molecular mechanisms underlying the disease, no cure for pulmonary fibrosis has yet been found. We screened a drug library and found that dextromethorphan (DXM), a cough expectorant, reduced the amount of excess fibrillar collagen deposited in the ECM in cultured primary human lung fibroblasts, a bleomycin mouse model, and a cultured human precision-cut lung slice model of lung fibrosis.

Targeting neutrophil serine proteases in bronchiectasis.

Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis (BE). Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase, cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung destruction, mucosal-related defects, further susceptibility to infection and worsening of clinical outcomes can occur.

Longitudinal microcomputed tomography detects onset and progression of pulmonary fibrosis in conditional deficient mice.

Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease, which is usually diagnosed late in advanced stages. Little is known about the subclinical development of IPF. We previously generated a mouse model with conditional deficiency () that develops IPF-like lung disease.

Management of Busulfan-Induced Lung Injury in Pediatric Patients with High-Risk Neuroblastoma.

: Integrating the cytotoxic drug busulfan into a high-dose chemotherapy regimen prior to autologous hematopoietic stem cell rescue in patients with high-risk neuroblastoma has improved the survival of children battling this deadly disease. Busulfan-induced toxicities can, however, be severe. Here, we describe the diagnosis and successful treatment of acute pulmonary injury by total-body-weight-adjusted busulfan therapy in two children with high-risk neuroblastoma.

Longitudinal Magnetic Resonance Imaging of Changes in Lung Morphology and Perfusion in Children with Cystic Fibrosis From Infancy through Adolescence.

Rationale: The progression of lung changes in cystic fibrosis (CF) from infancy through adolescence remains poorly understood due to limited longitudinal imaging data.

Objectives: To assess changes in lung morphology and perfusion in children with CF through the pediatric age range by longitudinal chest magnetic resonance imaging (MRI).

Methods: 1112 annual chest MRI were performed in 226 patients with CF aged 0-18yr.

Lentiviral Gene Therapy for Cystic Fibrosis: A Promising Approach and First-in-Human Trial.

Cystic fibrosis (CF) is a genetic disease caused by mutations in the (cystic fibrosis transmembrane conductance regulator) gene. Although CF is a multiorgan disease, the leading causes of morbidity and mortality are related to progressive lung disease. Current understanding of the effects of the broad spectrum of mutations on CFTR function has allowed for the development of CFTR modulator therapies.

A systematic literature review of the clinical and socioeconomic burden of bronchiectasis.

Background: The overall burden of bronchiectasis on patients and healthcare systems has not been comprehensively described. Here, we present the findings of a systematic literature review that assessed the clinical and socioeconomic burden of bronchiectasis with subanalyses by aetiology (PROSPERO registration: CRD42023404162).

Methods: Embase, MEDLINE and the Cochrane Library were searched for publications relating to bronchiectasis disease burden (December 2017-December 2022).

Long-Term Impact of Lumacaftor/Ivacaftor Treatment on Cystic Fibrosis Disease Progression in Children 2-5 Years of Age Homozygous for : A Phase 2, Open-Label Clinical Trial.

Clinical trials show that lumacaftor/ivacaftor (LUM/IVA) treatment has the potential to modify early cystic fibrosis (CF) disease progression in children as young as 2 years of age. To assess the long-term impact of LUM/IVA treatment on CF disease progression in children aged 2-5 years. This phase 2 trial had two parts: part 1, a 48-week, randomized, double-blind, placebo-controlled study of LUM/IVA in children aged 2-5 years (previously reported) was followed by a 48-week open-label treatment period in which all children received LUM/IVA (part 2; reported here).

Cystic fibrosis.

Cystic fibrosis is a rare genetic disease caused by mutations in CFTR, the gene encoding cystic fibrosis transmembrane conductance regulator (CFTR). The discovery of CFTR in 1989 has enabled the unravelling of disease mechanisms and, more recently, the development of CFTR-directed therapeutics that target the underlying molecular defect. The CFTR protein functions as an ion channel that is crucial for correct ion and fluid transport across epithelial cells lining the airways and other organs.

COVID-19 in Pediatric Populations.

The COVID-19 pandemic reshaped the landscape of respiratory viral illnesses, causing common viruses to fade as SARS-CoV-2 took precedence. By 2023, more than 96% of the children in the United States were estimated to have been infected with SARS-CoV-2, with certain genetic predispositions and underlying health conditions posing risk factors for severe disease in children. Children, in general though, exhibit immunity advantages, protecting against aspects of the SARS-CoV-2 infection known to drive increased severity in older adults.

Thiolated polyglycerol sulfate as potential mucolytic for muco-obstructive lung diseases.

Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale.

Contrast agent-free functional magnetic resonance imaging with matrix pencil decomposition to quantify abnormalities in lung perfusion and ventilation in patients with cystic fibrosis.

Background: Previous studies showed that contrast-enhanced (CE) morpho-functional magnetic resonance imaging (MRI) detects abnormalities in lung morphology and perfusion in patients with cystic fibrosis (CF). Novel matrix pencil decomposition MRI (MP-MRI) enables quantification of lung perfusion and ventilation without intravenous contrast agent administration.

Objectives: To compare MP-MRI with established morpho-functional MRI and spirometry in patients with CF.

Comprehensive Characterization of the Viscoelastic Properties of Bovine Submaxillary Mucin (BSM) Hydrogels and the Effect of Additives.

This study presents a comprehensive characterization of the viscoelastic and structural properties of bovine submaxillary mucin (BSM), which is widely used as a commercial source to conduct mucus-related research. We conducted concentration studies of BSM and examined the effects of various additives, NaCl, CaCl, MgCl, lysozyme, and DNA, on its rheological behavior. A notable connection between BSM concentration and viscoelastic properties was observed, particularly under varying ionic conditions.

Ileal mucus viscoelastic properties differ in Crohn's disease.

Crohn's disease (CD) is an inflammatory bowel disease that can affect any part of the gastrointestinal tract, frequently involving the terminal ileum. While colonic mucus alterations in CD patients have been described, terminal ileal mucus and its mechanobiological properties have been neglected. Our study is the first of its kind to decipher the viscoelastic and network properties of ileal mucus.

Health-related quality of life and impact of socioeconomic status among primary and secondary school students after the third COVID-19 wave in Berlin, Germany.

In the earlier phases of the COVID-19 pandemic, studies in Germany and elsewhere found an overall reduction in health-related quality of life (HRQoL) among students. However, there is little evidence on later pandemic stages as well as socioeconomic influencing factors. We aimed to (1) describe HRQoL in a Berlin student cohort at two time points in mid-2021, and to (2) analyze the effects of household income and education.