A Three-year Longitudinal Assessment of Pseudomonas aeruginosa Antibiotic Susceptibility in Children With Cystic Fibrosis in the Era of Cystic Fibrosis Transmembrane Conductance Regulator Modulator Therapy.

fibrosis is a genetic disease characterized by chronic lung infection, often with Pseudomonas aeruginosa, requiring repeated antibiotic treatment for pulmonary exacerbations. In the era of cystic fibrosis transmembrane conductance regulator modulator therapy, we assessed susceptibility to antipseudomonal antibiotics in modulator-eligible and modulator-ineligible children over 3 years and found that P. aeruginosa isolates largely remained susceptible to standard parenteral but not oral antimicrobial agents.

Bacteriophage Therapy of Multidrug-resistant Achromobacter in an 11-Year-old Boy With Cystic Fibrosis Assessed by Metagenome Analysis.

Background: Cystic fibrosis (CF) is a genetic disease associated with lung disease characterized by chronic pulmonary infection, increasingly caused by multiple drug-resistant pathogens after repeated antibiotic exposure, limiting antibiotic treatment options. Bacteriophages can provide a pathogen-specific bactericidal treatment used with antibiotics to improve microbiologic and clinical outcomes in CF.

Methods: Achromobacter species isolates from sputum of a chronically infected person with CF, were assessed for susceptibility to bacteriophages: 2 highly active, purified bacteriophages were administered intravenously every 8 hours, in conjunction with a 14-day piperacillin/tazobactam course for CF exacerbation.

Bicarbonate Effects on Antibacterial Immunity and Mucus Glycobiology in the Cystic Fibrosis Lung: A Review With Selected Experimental Observations.

The primary defect in cystic fibrosis (CF) is abnormal chloride and bicarbonate transport in the cystic fibrosis transmembrane conductance regulator (CFTR) epithelial ion channel. The apical surface of the respiratory tract is lined by an airway surface liquid layer (ASL) composed of mucin comprising mainly MUC5A and MUC5B glycoproteins. ASL homeostasis depends on sodium bicarbonate secretion into the airways and secretion deficits alter mucus properties leading to airway obstruction, inflammation, and infections.

Leveraging Electronic Health Records for Guideline-Based Asthma Documentation.

Background: Asthma is the most common pediatric chronic disease; thus, clinical guidelines have been developed for its assessment and management, which rely on systematic symptom documentation. Electronic health records (EHR) have the potential to record clinical data systematically; however, variability in documentation persists.

Objective: To identify if the use of a structured asthma template is associated with increased guideline-based asthma documentation and clinical outcomes when compared with the use of nonstructured ones.

Persistent recovery of pancreatic function in patients with cystic fibrosis after ivacaftor.

Exocrine pancreatic insufficiency (EPI), which leads to malabsorption and poor weight gain, is seen in 85% of patients with cystic fibrosis (CF). EPI is treated with pancreatic enzyme replacement therapy taken with each meal. The highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator, ivacaftor, restores CFTR function in patients with responsive mutations.

Hypoxia-inducible factor-1α inhibition modulates airway hyperresponsiveness and nitric oxide levels in a BALB/c mouse model of asthma.

Unlabelled: Hypoxia-inducible factor (HIF)-1α is a master regulator of inflammation and is upregulated in alveolar macrophages and lung parenchyma in asthma. HIF-1α regulates select pathways in allergic inflammation, and thus may drive particular asthma phenotypes. This work examines the role of pharmacologic HIF-1α inhibition in allergic inflammatory airway disease (AIAD) pathogenesis in BALB/c mice, which develop an airway hyperresponsiveness (AHR) asthma phenotype.

Putting the model to the test: are APC proteins essential for neuronal polarity, axon outgrowth, and axon targeting?

The highly polarized architecture of neurons is important for their function. Experimental data based on dominant-negative approaches suggest that the tumor suppressor adenomatous polyposis coli (APC), a regulator of Wnt signaling and the cytoskeleton, regulates polarity of neuroectodermal precursors and neurons, helping specify one neurite as the axon, promoting its outgrowth, and guiding axon pathfinding. However, such dominant-negative approaches might affect processes in which APC is not essential.

Novel roles for APC family members and Wingless/Wnt signaling during Drosophila brain development.

Construction of the brain is one of the most complex developmental challenges. Wnt signals shape all tissues, including the brain, and the tumor suppressor adenomatous polyposis coli (APC) is a key negative regulator of Wnt/Wingless (Wg) signaling. We carried out the first assessment of the role of APC proteins in brain development, simultaneously inactivating both APC1 and APC2 in clones of cells in the Drosophila larval optic lobe.

Drosophila APC2 and APC1 play overlapping roles in wingless signaling in the embryo and imaginal discs.

The regulation of signal transduction plays a key role in cell fate choices, and its disregulation contributes to oncogenesis. This duality is exemplified by the tumor suppressor APC. Originally identified for its role in colon tumors, APC family members were subsequently shown to negatively regulate Wnt signaling in both development and disease.

Drosophila APC2 and APC1 have overlapping roles in the larval brain despite their distinct intracellular localizations.

The tumor suppressor APC and its homologs, first identified for a role in colon cancer, negatively regulate Wnt signaling in both oncogenesis and normal development, and play Wnt-independent roles in cytoskeletal regulation. Both Drosophila and mammals have two APC family members. We further explored the functions of the Drosophila APCs using the larval brain as a model.