Comparison of Cochet-Bonnet, Dental Floss, and Cotton Wisp With Applications to Corneal Sensation Testing.

Purpose: The measurement of corneal sensation can be useful in the diagnosis of corneal neuropathies. Although the Cochet-Bonnet esthesiometer (CB) is the gold standard, cotton wisp (CW) and dental floss are commonly used in clinical practice.

Methods: We assessed the steady-state force of thick dental floss (tkDF), thin dental floss (tnDF), and CW compared with that of CB.

Gene expression responses of CF airway epithelial cells exposed to elexacaftor/tezacaftor/ivacaftor suggest benefits beyond improved CFTR channel function.

The combination of elexacaftor/tezacaftor/ivacaftor (ETI, Trikafta) reverses the primary defect in cystic fibrosis (CF) by improving CFTR-mediated Cl and HCO secretion by airway epithelial cells (AECs), leading to improved lung function and less frequent exacerbations and hospitalizations. However, studies have shown that CFTR modulators like ivacaftor, a component of ETI, have numerous effects on CF cells beyond improved CFTR channel function. Because little is known about the effect of ETI on CF AEC gene expression, we exposed primary human AEC to ETI for 48 h and interrogated the transcriptome by RNA-seq and qPCR.

E.PathDash, pathway activation analysis of publicly available pathogen gene expression data.

Unlabelled: E.PathDash facilitates re-analysis of gene expression data from pathogens clinically relevant to chronic respiratory diseases, including a total of 48 studies, 548 samples, and 404 unique treatment comparisons. The application enables users to assess broad biological stress responses at the KEGG pathway or gene ontology level and also provides data for individual genes.

Lung-Kidney Axis in Cystic Fibrosis: Early Urinary Markers of Kidney Injury Correlate with Neutrophil Activation and Worse Lung Function.

Background: Adult people with cystic fibrosis (PwCF) have a higher risk of end-stage kidney disease than the general population. The nature and mechanism of kidney disease in CF are unknown. This study quantifies urinary kidney injury markers and examines the hypothesis that neutrophil activation and lung infection are associated with early kidney injury in CF.

Gene expression responses of CF airway epithelial cells exposed to elexacaftor/tezacaftor/ivacaftor (ETI) suggest benefits beyond improved CFTR channel function.

Unlabelled: The combination of elexacaftor/tezacaftor/ivacaftor (ETI, Trikafta) reverses the primary defect in Cystic Fibrosis (CF) by improving CFTR mediated Cl and HCO secretion by airway epithelial cells (AEC), leading to improved lung function and less frequent exacerbations and hospitalizations. However, studies have shown that CFTR modulators like ivacaftor, a component of ETI, has numerous effects on CF cells beyond improved CFTR channel function. Because little is known about the effect of ETI on CF AEC gene expression we exposed primary human AEC to ETI for 48 hours and interrogated the transcriptome by RNA-seq and qPCR.

Rethinking Tuberculosis Morbidity Quantification: A Systematic Review and Critical Appraisal of TB Disability Weights in Cost-Effectiveness Analyses.

Background: The disability-adjusted life year (DALY), a key metric for health resource allocation, encompasses morbidity through disability weights. Widely used in tuberculosis cost-effectiveness analysis (CEAs), DALYs play a significant role in informing intervention adopt/reject decisions. This study reviews the values and consistency of disability weights applied in tuberculosis-related CEAs.

tRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in cystic fibrosis.

Although tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of () in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is not completely understood. Here, we demonstrate that tobramycin increases 5' tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by laboratory and CF clinical isolates of . The 5' tRNA-fMet halves are transferred from OMVs into primary CF human bronchial epithelial cells (CF-HBEC), decreasing OMV-induced IL-8 and IP-10 secretion.

transcriptome analysis of metal restriction in cystic fibrosis sputum.

Chronic lung infections are a feature of cystic fibrosis (CF) that many patients experience even with the advent of highly effective modulator therapies. Identifying factors that impact in the CF lung could yield novel strategies to eradicate infection or otherwise improve outcomes. To complement published studies using laboratory models or RNA isolated from sputum, we analyzed transcripts of strain PAO1 after incubation in sputum from different CF donors prior to RNA extraction.

tRNA-fMet halves secreted in outer membrane vesicles suppress lung inflammation in Cystic Fibrosis.

Unlabelled: Although tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is not completely understood. Here, we demonstrate that tobramycin increases 5' tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by laboratory and CF clinical isolates of . The 5' tRNA-fMet halves are transferred from OMVs into primary CF human bronchial epithelial cells (CF-HBEC), decreasing OMV-induced IL-8 and IP-10 secretion.

An medium for modeling gut dysbiosis associated with cystic fibrosis.

The gut physiology of pediatric and adult persons with cystic fibrosis (pwCF) is altered relative to healthy persons. The CF gut is characterized, in part, as having excess mucus, increased fat content, acidic pH, increased inflammation, increased antibiotic perturbation, and the potential for increased oxygen availability. These physiological differences shift nutritional availability and the local environment for intestinal microbes, thus likely driving significant changes in microbial metabolism, colonization, and competition with other microbes.

APPLICATION OF QUANTILE DISCRETIZATION AND BAYESIAN NETWORK ANALYSIS TO PUBLICLY AVAILABLE CYSTIC FIBROSIS DATA SETS.

The availability of multiple publicly-available datasets studying the same phenomenon has the promise of accelerating scientific discovery. Meta-analysis can address issues of reproducibility and often increase power. The promise of meta-analysis is especially germane to rarer diseases like cystic fibrosis (CF), which affects roughly 100,000 people worldwide.

Rocket-miR, a translational launchpad for miRNA-based antimicrobial drug development.

Antimicrobial-resistant infections contribute to millions of deaths worldwide every year. In particular, the group of bacteria collectively known as ESKAPE ( and sp) pathogens are of considerable medical concern due to their virulence and exceptional ability to develop antibiotic resistance. New kinds of antimicrobial therapies are urgently needed to treat patients for whom existing antibiotics are ineffective.

Trial of Affordable Bone Conduction Headphones to Support a Deaf Child's Education in Malawi.

A 13-year-old child with hearing loss secondary to chronic serous otitis media and bilateral tympanic perforations had been unable to hear the teacher at school and unable to pass end-of-year exams. In 2020, she trialed a bone conduction headset paired by Bluetooth to a remote microphone and used this to support her hearing at school, socializing with friends and in the family home. Due to the COVID (COronaVIrus Disease) pandemic and a cholera epidemic, she was followed up 3 years later.

Smartphone applications for measuring noise in the intensive care unit: A feasibility study.

Purpose: This study aims to explore the suitability of using smartphone applications with low-cost external microphones in measuring noise levels in intensive care units.

Methods: Four apps and two external microphones were tested in a laboratory by generating test signals at five noise levels. The average noise levels were measured using the apps and a professional device (i.

Analysis of transcription in an cystic fibrosis sputum model identifies metal restriction as a gene expression stimulus.

Chronic lung infections are a distinctive feature of cystic fibrosis (CF) pathology, that challenge adults with CF even with the advent of highly effective modulator therapies. Characterizing transcription in the CF lung and identifying factors that drive gene expression could yield novel strategies to eradicate infection or otherwise improve outcomes. To complement published gene expression studies in laboratory culture models designed to model the CF lung environment, we employed an ex vivo sputum model in which laboratory strain PAO1 was incubated in sputum from different CF donors.

An In Vitro Medium for Modeling Gut Dysbiosis Associated with Cystic Fibrosis.

The gut physiology of pediatric and adult persons with cystic fibrosis (pwCF) is altered relative to healthy persons. The CF gut is characterized, in part, as having excess mucus, increased fat content, acidic pH, increased inflammation, increased antibiotic perturbation and the potential for increased oxygen availability. These physiological differences shift nutritional availability and the local environment for intestinal microbes, thus likely driving significant changes in microbial metabolism, colonization and competition with other microbes.

Comparative effects of CFTR modulators on phagocytic, metabolic and inflammatory profiles of CF and nonCF macrophages.

Macrophage dysfunction has been well-described in Cystic Fibrosis (CF) and may contribute to bacterial persistence in the lung. Whether CF macrophage dysfunction is related directly to Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) in macrophages or an indirect consequence of chronic inflammation and mucostasis is a subject of ongoing debate. CFTR modulators that restore CFTR function in epithelial cells improve global CF monocyte inflammatory responses but their direct effects on macrophages are less well understood.

Development of the intestinal microbiome in cystic fibrosis in early life.

Cystic fibrosis (CF) is a heritable disease that causes altered physiology at mucosal sites; these changes result in chronic infections in the lung, significant gastrointestinal complications as well as dysbiosis of the gut microbiome, although the latter has been less well explored. Here, we describe the longitudinal development of the gut microbiome in a cohort of children with CF (cwCF) from birth through early childhood (0-4 years of age) using 16S rRNA gene amplicon sequencing of stool samples as a surrogate for the gut microbiota. Similar to healthy populations, alpha diversity of the gut microbiome increases significantly with age, but diversity plateaus at ~2 years of age for this CF cohort.

PlmCas12e (CasX2) cleavage of CCR5: impact of guide RNA spacer length and PAM sequence on cleavage activity.

Gene editing using CRISPR/Cas (clustered regularly interspaced palindromic repeats/CRISPR-associated) is under development as a therapeutic tool for the modification of genes in eukaryotic cells. While much effort has focused on CRISPR/Cas9 systems from and , alternative CRISPR systems have been identified from non-pathogenic microbes, including previously unknown class 2 systems, adding to a diverse toolbox of CRISPR/Cas enzymes. The Cas12e enzymes from non-pathogenic Deltaproteobacteria (CasX1, DpeCas12e) and Planctomycetes (CasX2, PlmCas12e) are smaller than Cas9, have a selective protospacer adjacent motif (PAM), and deliver a staggered cleavage cut with a 5-7 nucleotide overhang.

An rRNA fragment in extracellular vesicles secreted by human airway epithelial cells increases the fluoroquinolone sensitivity of .

Lung infections caused by antibiotic-resistant strains of are difficult to eradicate in immunocompromised hosts such as those with cystic fibrosis. We previously demonstrated that extracellular vesicles (EVs) secreted by primary human airway epithelial cells (AECs) deliver microRNA let-7b-5p to to suppress biofilm formation and increase sensitivity to beta-lactam antibiotics. In this study, we show that EVs secreted by AECs transfer multiple distinct short RNA fragments to that are predicted to target the three subunits of the fluoroquinolone efflux pump MexHI-OpmD, thus increasing antibiotic sensitivity.

Recurrent croup is a good indicator of underlying paediatric airway issues: A 10-year retrospective cohort study of airway endoscopy.

Objective: Children with a history of recurrent croup alert the ENT clinician to the potential for underlying laryngotracheal pathology. There is equipoise about the likelihood of identifying any underlying structural issues or subglottic stenosis in those children who undergo airway assessment.

Methods: A retrospective cohort study in a tertiary UK paediatric hospital of a decade of children with recurrent croup who underwent a rigid laryngo-tracheo-bronchoscopy (airway endoscopy).

Foreign body impaction of the hard palate: tabletop party confetti mimicking button batteries in two infants.

We present the first two cases in the literature of tabletop party confetti mimicking button batteries in two infants. Both patients presented to the Emergency Department with an incidentally noticed shiny, metallic appearing, disc-shaped foreign body impacted in the hard palate. Both objects were understandably misdiagnosed as button batteries.