Background: Melatonin is widely used to promote sleep in both normally developing children and adolescents and those with neurodevelopmental disorders. It has an evidence base as both hypnotic and chronobiotic although the optimum dose and timing remain unclear. There are now a wide variety of different preparations of melatonin both immediate and prolonged release.
View Article and Find Full Text PDFBackground: Pulmonary exacerbations (PExs) are clinically important in people with cystic fibrosis (CF). Multiple definitions have been used for PEx, and this scoping review aimed to identify the different definitions reported in the literature and to ascertain which signs and symptoms are commonly used to define them.
Methods: A search was performed using Embase, MEDLINE, Cochrane Library, Scopus and CINAHL.
Building an immune system is a monumental task critical to the survival of the fetus and newborn. A functional fetal immune system must complement the maternal immune system in handling in utero infection; abstain from damaging non-self-reactions that would compromise the materno-fetal interface; mobilize in response to infection and equip mucosal tissues for pathogen exposure at birth. There is growing appreciation that immune cells also have noncanonical roles in development and specifically may contribute to tissue morphogenesis.
View Article and Find Full Text PDFBackground: Cystic fibrosis (CF) is a genetic condition caused by variants in the ) gene that primarily impacts the lungs. Treatments historically have been symptomatic to improve airway clearance and treat infection. However, CFTR modulator drugs have recently been developed that target the underlying defect.
View Article and Find Full Text PDFConjunctival epithelial cells, which express viral-entry receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type 2 (TMPRSS2), constitute the largest exposed epithelium of the ocular surface tissue and may represent a relevant viral-entry route. To address this question, we generated an organotypic air-liquid-interface model of conjunctival epithelium, composed of basal, suprabasal, and superficial epithelial cells, and fibroblasts, which could be maintained successfully up to day 75 of differentiation. Using single-cell RNA sequencing (RNA-seq), with complementary imaging and virological assays, we observed that while all conjunctival cell types were permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome expression, a productive infection did not ensue.
View Article and Find Full Text PDFPharmgenomics Pers Med
February 2022
Cystic fibrosis (CF) is an autosomal recessive genetic condition that is caused by variants in the gene. This causes multisystem disease due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel at the apical surface of epithelia. Until recently, treatment was directed at managing the downstream effects in affected organs, principally improving airway clearance and treating infection in the lungs and improving malabsorption in the gastrointestinal tract.
View Article and Find Full Text PDFThe nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue.
View Article and Find Full Text PDFCystic fibrosis is a monogenic disease considered to affect at least 100 000 people worldwide. Mutations in CFTR, the gene encoding the epithelial ion channel that normally transports chloride and bicarbonate, lead to impaired mucus hydration and clearance. Classical cystic fibrosis is thus characterised by chronic pulmonary infection and inflammation, pancreatic exocrine insufficiency, male infertility, and might include several comorbidities such as cystic fibrosis-related diabetes or cystic fibrosis liver disease.
View Article and Find Full Text PDFMost patients with cystic fibrosis (CF) suffer from acute and chronic pulmonary infections with bacterial pathogens, which often determine their life quality and expectancy. Previous studies have demonstrated a downregulation of the acid ceramidase in CF epithelial cells resulting in an increase of ceramide and a decrease of sphingosine. Sphingosine kills many bacterial pathogens, and the downregulation of sphingosine seems to determine the infection susceptibility of cystic fibrosis mice and patients.
View Article and Find Full Text PDFBackground: The presence of co-morbidities, including underlying respiratory problems, has been identified as a risk factor for severe COVID-19 disease. Information on the clinical course of SARS-CoV-2 infection in children with cystic fibrosis (CF) is limited, yet vital to provide accurate advice for children with CF, their families, caregivers and clinical teams.
Methods: Cases of SARS-CoV-2 infection in children with CF aged less than 18 years were collated by the CF Registry Global Harmonization Group across 13 countries between 1 February and 7 August 2020.
Am J Physiol Lung Cell Mol Physiol
February 2021
Cystic fibrosis (CF) arises from mutations in the CF transmembrane conductance regulator () gene, resulting in progressive and life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterized. Our aims were to describe the clinical and molecular phenotypes associated with R751L.
View Article and Find Full Text PDFNontuberculous mycobacteria (NTM) infection is of growing concern in cystic fibrosis (CF). UK CF Registry data were analyzed from 2016 to 2018. Prevalence of infection stabilized in the pediatric age-group during this period but remained substantially higher than in 2010.
View Article and Find Full Text PDFAm J Respir Crit Care Med
October 2020
In cystic fibrosis the major cause of morbidity and mortality is lung disease characterized by inflammation and infection. The influence of sphingolipid metabolism is poorly understood with a lack of studies using human airway model systems. To investigate sphingolipid metabolism in cystic fibrosis and the effects of treatment with recombinant human acid ceramidase on inflammation and infection.
View Article and Find Full Text PDFIn recent years, the importance of mucosal surface pH in the airways has been highlighted by its ability to regulate airway surface liquid (ASL) hydration, mucus viscosity and activity of antimicrobial peptides, key parameters involved in innate defense of the lungs. This is of primary relevance in the field of chronic respiratory diseases such as cystic fibrosis (CF) where these parameters are dysregulated. While different groups have studied ASL pH both in vivo and in vitro, their methods report a relatively wide range of ASL pH values and even contradictory findings regarding any pH differences between non-CF and CF cells.
View Article and Find Full Text PDFExpert Opin Pharmacother
September 2017
Cystic fibrosis (CF) is one of the most common genetically-acquired life-limiting conditions worldwide. The underlying defect is dysfunction of the cystic fibrosis transmembrane-conductance regulator (CFTR) which leads to progressive lung disease and other multi-system effects. Around 10% of people with CF have a class I nonsense mutation that leads to production of shortened CFTR due to a premature termination codon (PTC).
View Article and Find Full Text PDFTransepithelial bicarbonate secretion by human airway submucosal glands and surface epithelial cells is crucial to maintain the pH-sensitive innate defence mechanisms of the lung. cAMP agonists stimulate HCO secretion via coordinated increases in basolateral HCO influx and accumulation, as well as CFTR-dependent HCO efflux at the luminal membrane of airway epithelial cells. Here, we investigated the regulation of a basolateral located, DIDS-sensitive, Cl/HCO exchanger, anion exchanger 2 (AE2; SLC4A2) which is postulated to act as an acid loader, and therefore potential regulator of HCO secretion, in human airway epithelial cells.
View Article and Find Full Text PDFObjectives: To address the limited long-term outcome data for catheter ablation (CA) of persistent atrial fibrillation (PeAF), we analysed consecutive ablations performed at our centre from 1 January 2008 to 31 December 2010 and followed patients prospectively until January 2014.
Methods: Both arrhythmia recurrence and symptom relief were assessed. Follow-up data were collected from hospital records, supplemented by data from general practitioners and referring hospitals.
Cystic fibrosis (CF) is a life-limiting disease characterised by recurrent respiratory infections, inflammation and lung damage. The volume and composition of the airway surface liquid (ASL) are important in maintaining ciliary function, mucociliary clearance and antimicrobial properties of the airway. In CF, these homeostatic mechanisms are impaired, leading to a dehydrated and acidic ASL.
View Article and Find Full Text PDFCystic fibrosis is the most common genetically determined, life-limiting disorder in populations of European ancestry. The genetic basis of cystic fibrosis is well established to be mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that codes for an apical membrane chloride channel principally expressed by epithelial cells. Conventional approaches to cystic fibrosis care involve a heavy daily burden of supportive treatments to combat lung infection, help clear airway secretions and maintain nutritional status.
View Article and Find Full Text PDFIntroduction: The most frequent complications of AF ablation (AFA) are related to vascular access, but there is little evidence as to how these can be minimized.
Methods: Consecutive patients undergoing AFA at a high-volume center received either standard care (Group S) or routine ultrasound-guided vascular access (Group U). Vascular complications were assessed before hospital discharge and by means of postal questionnaire 1 month later.
Gastroschisis is a common congenital abdominal wall defect requiring surgical correction in early neonatal life. The time to full enteral feeds among infants with gastroschisis is variable. Gastroschisis remains a common surgical cause of intestinal failure in neonates.
View Article and Find Full Text PDFHigh flow nasal cannula (HFNC) devices deliver an adjustable mixture of heated and humidified oxygen and air at a variable flow rate. Over recent years HFNC devices have become a frequently used method of non-invasive respiratory support in infants and preterm neonates that is generally popular amongst clinicians and nursing staff due to ease of use and being well tolerated by patients. Despite this rapid adoption relatively little is known about the exact mechanisms of action of HFNC however and only recently have data from randomised controlled trials started to become available.
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