Pseudomonas aeruginosa is oxygen-deprived during infection in cystic fibrosis lungs, reducing the effectiveness of antibiotics.

Pseudomonas aeruginosa infects the lungs of patients with cystic fibrosis. Sputum expectorated from the lungs of patients contains low levels of oxygen, indicating that P. aeruginosa may be oxygen-deprived during infection.

Exercise and motivational text messaging to support physical activity behaviour change in a population with obstructive sleep apnoea: a feasibility study.

Introduction Patients with obstructive sleep apnoea (OSA) commonly present in primary care. Increasing physical activity reduces symptoms and severity of OSA. Low motivation is a barrier to physical activity in adults with OSA.

Embryonic medial ganglionic eminence cells survive and integrate into the inferior colliculus of adult mice.

Acoustic overexposure can lead to decreased inhibition in auditory centers, including the inferior colliculus (IC), and has been implicated in the development of central auditory pathologies. While systemic drugs that increase GABAergic transmission have been shown to provide symptomatic relief, their side effect profiles impose an upper-limit on the dose and duration of use. A treatment that locally increases inhibition in auditory nuclei could mitigate these side effects.

Genome evolution drives transcriptomic and phenotypic adaptation in during 20 years of infection.

The opportunistic pathogen chronically infects the lungs of patients with cystic fibrosis (CF). During infection the bacteria evolve and adapt to the lung environment. Here we use genomic, transcriptomic and phenotypic approaches to compare multiple isolates of collected more than 20 years apart during a chronic infection in a CF patient.

Perceived versus objective sleep quality in long-stay hospitalised older adults-a mixed methods study.

Background: Hospital inpatients experience substantial sleep problems that have been linked with worse health outcomes, poor quality of life and the post-hospital syndrome. However, little is known about assessing sleep issues in older hospitalised patients.

Objective: To conduct an in-depth investigation on hospitalised older adults' sleep challenges and methods of sleep assessment.

Physical activity behaviour and barriers to activity in adults at high risk of obstructive sleep apnoea.

INTRODUCTION Physical inactivity is a risk factor for disease severity among people with obstructive sleep apnoea. AIM To determine physical activity levels in patients at risk of obstructive sleep apnoea and explore their perceptions about barriers to participation in physical activity. METHODS This was a cross-sectional observational study.

Biallelic variants in EFEMP1 in a man with a pronounced connective tissue phenotype.

Connective tissue disorders are a spectrum of diseases that affect the integrity of tissues including skin, vasculature, and joints. They are often caused by variants that disrupt genes encoding components of extracellular matrix (ECM). The fibulin glycoproteins are ECM proteins important for integrity of tissues including dermis, retina, fascia, and vasculature.

Mucosal-associated invariant T cells and Vδ2 γδ T cells in community acquired pneumonia: association of abundance in sputum with clinical severity and outcome.

Mucosal-associated invariant T (MAIT) cells and Vδ2 γδ T cells are anti-bacterial innate-like lymphocytes (ILLs) that are enriched in blood and mucosa. ILLs have been implicated in control of infection. However, the role of ILLs in community-acquired pneumonia (CAP) is unknown.

Genomic and phenotypic comparison of environmental and patient-derived isolates of suggest that antimicrobial resistance is rare within the environment.

Patient-derived isolates of the opportunistic pathogen are frequently resistant to antibiotics due to the presence of sequence variants in resistance-associated genes. However, the frequency of antibiotic resistance and of resistance-associated sequence variants in environmental isolates of has not been well studied. Antimicrobial susceptibility testing (ciprofloxacin, ceftazidime, meropenem, tobramycin) of environmental (=50) and cystic fibrosis (=42) isolates was carried out.

Phase 1 trial of intrapleural LTI-01; single chain urokinase in complicated parapneumonic effusions or empyema.

Background: Current dosing of intrapleural fibrinolytic therapy (IPFT) in adults with complicated parapneumonic effusion (CPE) / empyema is empiric, as dose-escalation trials have not previously been conducted. We hypothesized that LTI-01 (scuPA), which is relatively resistant to PA inhibitor-1 (PAI-1), would be well-tolerated.

Methods: This was an open-label, dose-escalation trial of LTI-01 IPFT at 50,000-800,000 IU daily for up to 3 days in adults with loculated CPE/empyema and failed pleural drainage.

Comparison of Electrocardiographic Biomarkers for Differentiating Drug-Induced Single vs. Multiple Cardiac Ion Channel Block.

Since introduction of the International Conference on Harmonization proarrhythmia guidelines in 2005, no new marketed drugs have been associated with unacceptable risk of Torsade de Pointes. Although cardiac safety improved, these guidelines had the unintended consequence of eliminating potentially beneficial drugs from pipelines early in development. More recently, it has been shown that a corrected QT (QTc) prolonging drug may be safe if it impacts multiple ion channels vs.

Treatable traits can be identified in a severe asthma registry and predict future exacerbations.

Background And Objective: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk.

Methods: The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma.

Expression of Pseudomonas aeruginosa Antibiotic Resistance Genes Varies Greatly during Infections in Cystic Fibrosis Patients.

The lungs of individuals with cystic fibrosis (CF) become chronically infected with that is difficult to eradicate by antibiotic treatment. Two key antibiotic resistance mechanisms are the AmpC β-lactamase that degrades β-lactam antibiotics and MexXYOprM, a three-protein efflux pump that expels aminoglycoside antibiotics from the bacterial cells. Levels of antibiotic resistance gene expression are likely to be a key factor in antibiotic resistance but have not been determined during infection.

Comparison of one- and three-lead ECG to measure cardiac intervals and differentiate drug-induced multi-channel block.

Introduction: FDA has established initiatives to characterize clinical and non-clinical biomarkers to enable more precise prediction of proarrhythmia risk based upon knowledge of drug effect on multiple cardiac ion channels (Colatsky et al., 2016). The FDA has recently demonstrated superiority of early ventricular repolarization interval (JTp) in differentiating pure hERG block from multi-channel block in human subjects.

Working while unwell: Workplace impairment in people with severe asthma.

Background: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood.

Objective: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma.

Methods: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore.

Effect of Obstructive Sleep Apnea Treatment on Renal Function in Patients with Cardiovascular Disease.

Rationale: Obstructive sleep apnea (OSA) is associated with impaired renal function, but uncertainty exists over whether OSA treatment can influence renal outcomes.

Objectives: To determine the effects of continuous positive airway pressure (CPAP) on renal function in subjects with coexisting OSA and cardiovascular disease.

Methods: This was a substudy of the international SAVE (Sleep Apnea Cardiovascular Endpoints) trial, in which 2,717 patients with moderate to severe OSA and established coronary or cerebrovascular disease were randomized to receive either CPAP plus usual care or usual care alone.

Rare SOX2 Airway Progenitor Cells Generate KRT5 Cells that Repopulate Damaged Alveolar Parenchyma following Influenza Virus Infection.

Recent studies have implicated keratin 5 (KRT5) cells in repopulation of damaged lung tissue following severe H1N1 influenza virus infection. However, the origins of the cells repopulating the injured alveolar region remain controversial. We sought to determine the cellular dynamics of lung repair following influenza infection and define whether nascent KRT5 cells repopulating alveolar epithelium were derived from pre-existing alveolar or airway progenitor cells.

Effect of Inhaled β2-Agonist on Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease.

The fractional exhaled nitric oxide measured at an expiratory flow of 50mL/s (FENO50) is a marker of airway inflammation, and high levels are associated with greater response to steroid treatment. In asthma, FENO50 increases with bronchodilation and decreases with bronchoconstriction, the latter potentially causing an underestimate of the degree of airway inflammation when asthma worsens. It is unknown whether the same effect occurs in chronic obstructive lung disease (COPD).

Intrapleural tissue plasminogen activator and deoxyribonuclease for pleural infection. An effective and safe alternative to surgery.

Rationale: Intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) therapy for pleural infection given at the time of diagnosis has been shown to significantly improve radiological outcomes. Published cases are limited to only a single randomized controlled trial and a few case reports.

Objectives: Multinational observation series to evaluate the pragmatic "real-life" application of tPA/DNase treatment for pleural infection in a large cohort of unselected patients.

Epithelial clara cell injury occurs in bronchiolitis obliterans syndrome after human lung transplantation.

Bronchiolitis obliterans syndrome (BOS) is a condition of progressive airflow obstruction that affects a majority of lung transplant recipients and limits long-term posttransplant survival. Although epithelial injury appears central to the development of BOS, little is known regarding the specific epithelial cell types that are affected in this condition. We hypothesized that BOS would involve preferential injury to the secretory Clara cells that function in innate defense and epithelial repair.

Airway epithelial progenitors are region specific and show differential responses to bleomycin-induced lung injury.

Mechanisms that regulate regional epithelial cell diversity and pathologic remodeling in airways are poorly understood. We hypothesized that regional differences in cell composition and injury-related tissue remodeling result from the type and composition of local progenitors. We used surface markers and the spatial expression pattern of an SFTPC-GFP transgene to subset epithelial progenitors by airway region.

β-Catenin-SOX2 signaling regulates the fate of developing airway epithelium.

Wnt-β-catenin signaling regulates cell fate during organ development and postnatal tissue maintenance, but its contribution to specification of distinct lung epithelial lineages is still unclear. To address this question, we used a Cre recombinase (Cre)-LoxP approach to activate canonical Wnt signaling ectopically in developing lung endoderm. We found that persistent activation of canonical Wnt signaling within distal lung endoderm was permissive for normal development of alveolar epithelium, yet led to the loss of developing bronchiolar epithelium and ectasis of distal conducting airways.