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        Ca-EDTA restores the activity of ceftazidime-avibactam or aztreonam against carbapenemase-producing Klebsiella pneumoniae infections

        Developing an effective therapy to overcome carbapenemase-positive Klebsiella pneumoniae (CPKp) is an important therapeutic challenge that must be addressed urgently. Here, we explored a Ca-EDTA combination with aztreonam or ceftazidime-avibactam in vitro and in vivo against diverse CPKp clinical isolates. ...

        Research

        Substrate-dependent metabolomic signatures of myeloperoxidase activity in airway epithelial cells: Implications for early cystic fibrosis lung disease

        Myeloperoxidase is released by neutrophils in inflamed tissues. MPO oxidizes chloride, bromide, and thiocyanate to produce hypochlorous acid, hypobromous acid, and hypothiocyanous acid, respectively. These oxidants are toxic to pathogens, but may also react with host cells to elicit biological activity and potential toxicity. In cystic fibrosis and related diseases, increased neutrophil inflammation leads to increased airway MPO and airway epithelial cell exposure to its oxidants. ...

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        Official ERS technical standard: Global Lung Function Initiative reference values for static lung volumes in individuals of European ancestry

        Measurement of lung volumes across the life course is critical to the diagnosis and management of lung disease. The aim of the study was to use the Global Lung Function Initiative methodology to develop all-age multi-ethnic reference equations for lung volume indices determined using body plethysmography and gas dilution techniques. ...

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        Inhaled corticosteroids to improve lung function in children (aged 6–12 years) who were born very preterm (PICSI): a randomised, double-blind, placebo-controlled trial

        Despite the substantial burden of lung disease throughout childhood in children who were born very preterm, there are no evidence-based interventions to improve lung health beyond the neonatal period. We tested the hypothesis that inhaled corticosteroid improves lung function in this population. ...

        Research

        Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy

        Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus, but whether stretches of differentially methylated regions can also be identified in adolescent GDM offspring is unknown. ...

        Research

        Pseudomonas aeruginosa modulates neutrophil granule exocytosis in an in vitro model of airway infection

        A population of neutrophils recruited into cystic fibrosis (CF) airways is associated with proteolytic lung damage, exhibiting high expression of primary granule exocytosis marker CD63 and reduced phagocytic receptor CD16. Causative factors for this population are unknown, limiting intervention. Here we present a laboratory model to characterize responses of differentiated airway epithelium and neutrophils following respiratory infection. ...

        Research

        Protocol for establishing a core outcome set for evaluation in studies of pulmonary exacerbations in people with cystic fibrosis

        Pulmonary exacerbations are associated with increased morbidity and mortality in people with cystic fibrosis (CF). There is no consensus about which outcomes should be evaluated in studies of pulmonary exacerbations or how these outcomes should be measured. ...

        Research

        The role of exome sequencing in childhood interstitial or diffuse lung disease

        Children’s interstitial and diffuse lung disease (chILD) is a complex heterogeneous group of lung disorders. Gene panel approaches have a reported diagnostic yield of ~ 12%. No data currently exist using trio exome sequencing as the standard diagnostic modality. ...

        Research

        Characterisation of lung function trajectories and associated early-life predictors in an Australian birth cohort study

        There is growing evidence that lung function in early-life predicts later lung function. Adverse events over the lifespan might influence an individual’s lung function trajectory, resulting in poor respiratory health. The aim of this study is to identify early-life risk factors and their impact on lung function trajectories to prevent long-term lung impairments. ...

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