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Louise, J.

Publications and source records attributed to Louise, J..

3 recordsLinked to original sources

A longitudinal evaluation of localised chronic Pseudomonas aeruginosa infection in cystic fibrosis rat models

Recurrent bacterial infections with Pseudomonas aeruginosa result in chronic airway inflammation, lung damage and eventual respiratory failure, and are the major cause of morbidity and mortality in people with cystic fibrosis (CF). Animal models are essential for understanding disease progression and assessing potential treatments in the presence of infection. Previously reported P. aeruginosa lung infection rodent models for CF research have some weakness, including acute infection rather than chronic, associated mortality, use of laboratory strains of P. aeruginosa and the use of non-CF rodents. The aim of this study was to create a localised P. aeruginosa infection in wildtype and two CF rat models, by delivering bacteria embedded agar beads using a miniature bronchoscope. The resulting infection was well tolerated by all animals of all genotypes with no mortality associated with the procedure or infection. Histologically the affected regions were localised to the right lung, with bronchopneumonia present. Bacteria persisted for 9 weeks (63 days) in all genotypes, with lung function changes observed by day 63 of the infection.

pathology↗

Functional lung imaging identifies peripheral ventilation changes in mice with muco-obstructive lung disease

{beta}-ENaC-Tg mice serve as a relevant model of muco-obstructive lung disease, with impaired mucociliary clearance, mucus obstruction, chronic airway inflammation, structural lung damage, and altered lung function. The aim of this study was to undertake a comprehensive lung function and mechanics analysis of the adult {beta}-ENaC-Tg model. {beta}-ENaC-Tg and wild-type littermates underwent X-ray Velocimetry (XV) scans using a Permetium XV scanner (4DMedical, Melbourne, Australia). For comparative lung mechanics, lung function assessments were conducted with a flexiVent system. XV imaging demonstrated elevated ventilation defect percentage, mean specific ventilation, and ventilation heterogeneity in {beta}-ENaC-Tg mice. Spatial analysis of ventilation maps indicated increased ventilation variability in the peripheral lung regions, as well as an increased proportion of under-ventilated areas. The flexiVent analysis indicated that compared to wild-types, {beta}-ENaC-Tg mice have a significantly more compliant lungs with increased inspiratory capacity, reduced tissue elastance and increased hysteresivity (heterogeneity), suggesting loss of parenchymal integrity. This research highlights the utility of XV imaging in evaluating ventilation defects in the {beta}-ENaC-Tg model and provides a comprehensive lung function analysis.

physiology↗

Data Processing Choices Can Affect Findings in Differential Methylation Analyses: An Investigation Using Data from the LIMIT RCT

ObjectiveA wide array of methods exist for processing and analysing DNA methylation data. We aimed to perform a systematic comparison of the behaviour of these methods, using cord blood DNAm from the LIMIT RCT, in relation to detecting hypothesised effects of interest (intervention and pre-pregnancy maternal BMI) as well as effects known to be spurious, and known to be present. MethodsDNAm data, from 645 cord blood samples analysed using Illumina 450K BeadChip arrays, were normalised using three different methods (with probe filtering undertaken pre- or post-normalisation). Batch effects were handled with a supervised algorithm, an unsupervised algorithm, or adjustment in the analysis model. Analysis was undertaken with and without adjustment for estimated cell type proportions. The effects estimated included intervention and BMI (effects of interest in the original study), infant sex and randomly assigned groups. Data processing and analysis methods were compared in relation to number and identity of differentially methylated probes, rankings of probes by p value and log-fold-change, and distributions of p values and log-fold-change estimates. ResultsThere were differences corresponding to each of the processing and analysis choices. Importantly, some combinations of data processing choices resulted in a substantial number of spurious significant findings. We recommend greater emphasis on replication and greater use of sensitivity analyses. Clinical Trials RegistrationACTRN12607000161426

bioinformatics↗