Extensive carrier testing and CF birth prevalence: evidence for a negative correlation

Aim of the study was to evaluate if extensive CF carrier testing may be connected with the progressive decrease of CF birth incidence recorded in North Eastern Italy. From 1993 to 2007 an average 52,000 newborns per year underwent Neonatal Screening (NS), and 198 newborns with CF were detected (1/3937). A time related contraction in birth prevalence was confirmed, with an average annual percent decrease of 0.15 per 10,000 neonates (Poisson regression analysis p 0.003). In the NS area two sections were identified: the Western Region (WR), where CF carrier testing is not offered to couples from the general population, and the Eastern Region (ER), where CF carrier testing is widely offered to couples from the general population. In ER from 1995 to 2007 such testing practice has been steadily expanding, with a total of 87,721 CF carrier tests performed, 3460 carriers identified, and 238 carrier couples detected (data collection in progress). The prevalence of CF decreased by time (p<0.001) but the rate of decrease was more enhanced in ER as suggested by the existence of a statistically significant (p = 0.014) interaction term between time and region in the Poisson regression model. The overall negative trend in North Eastern Italy is due to a contraction of CF births in its Eastern part. In ER a negative correlation was found between CF incidence and the number of carrier tests (p 0.012). Prenatal diagnosis data collection is in progress. These data support the hypothesis that carrier screening may modify the incidence of CF

Impact of MIF Gene Promoter Polymorphism on F508del Cystic Fibrosis Patients

Macrophage migration Inhibitory Factor (MIF) is a pro-inflammatory cytokine sustaining the acute response to gram-negative bacteria and a regulatory role for MIF in Cystic Fibrosis has been suggested by the presence of a functional, polymorphic, four-nucleotide repeat in this gene's promoter at position -794, with the 5-repeat allele displaying lower promoter activity. We aimed at assessing the association of this polymorphism with disease severity in a group of Cystic Fibrosis patients homozygous for F508del CFTR gene mutation. Genotype frequencies were determined in 189 Cystic Fibrosis and 134 control subjects; key clinical features of patients were recorded and compared among homozygous 5-allele patients and the other MIF genotypes. Patients homozygous for the 5-repeat allele of MIF promoter displayed a slower rate of lung function decline (p\u200a=\u200a0.027) at multivariate survival analysis. Multiple regression analysis on age-normalized respiratory volume showed no association of the homozygous 5-repeat genotype with lung function under stable conditions and no correlation with P.aeruginosa chronic colonization. Therefore, only the Homozygous 5-repeat genotype at MIF -794 is associated with milder disease in F508del Cystic Fibrosis patients

Size limits the formation of liquid jets during bubble bursting

A bubble reaching an air–liquid interface usually bursts and forms a liquid jet. Jetting is relevant to climate and health as it is a source of aerosol droplets from breaking waves. Jetting has been observed for large bubbles with radii of R≫100 μm. However, few studies have been devoted to small bubbles (R<100 μm) despite the entrainment of a large number of such bubbles in sea water. Here we show that jet formation is inhibited by bubble size; a jet is not formed during bursting for bubbles smaller than a critical size. Using ultrafast X-ray and optical imaging methods, we build a phase diagram for jetting and the absence of jetting. Our results demonstrate that jetting in bubble bursting is analogous to pinching-off in liquid coalescence. The coalescence mechanism for bubble bursting may be useful in preventing jet formation in industry and improving climate models concerning aerosol production

Preliminary Evidence for Cell Membrane Amelioration in Children with Cystic Fibrosis by 5-MTHF and Vitamin B12 Supplementation: A Single Arm Trial

Cystic fibrosis (CF) is one of the most common fatal autosomal recessive disorders in the Caucasian population caused by mutations of gene for the cystic fibrosis transmembrane conductance regulator (CFTR). New experimental therapeutic strategies for CF propose a diet supplementation to affect the plasma membrane fluidity and to modulate amplified inflammatory response. The objective of this study was to evaluate the efficacy of 5-methyltetrahydrofolate (5-MTHF) and vitamin B12 supplementation for ameliorating cell plasma membrane features in pediatric patients with cystic fibrosis.A single arm trial was conducted from April 2004 to March 2006 in an Italian CF care centre. 31 children with CF aged from 3 to 8 years old were enrolled. Exclusion criteria were diabetes, chronic infections of the airways and regular antibiotics intake. Children with CF were supplemented for 24 weeks with 5-methyltetrahydrofolate (5-MTHF, 7.5 mg /day) and vitamin B12 (0.5 mg/day). Red blood cells (RBCs) were used to investigate plasma membrane, since RBCs share lipid, protein composition and organization with other cell types. We evaluated RBCs membrane lipid composition, membrane protein oxidative damage, cation content, cation transport pathways, plasma and RBCs folate levels and plasma homocysteine levels at baseline and after 24 weeks of 5-MTHF and vitamin B12 supplementation. In CF children, 5-MTHF and vitamin B12 supplementation (i) increased plasma and RBC folate levels; (ii) decreased plasma homocysteine levels; (iii) modified RBC membrane phospholipid fatty acid composition; (iv) increased RBC K(+) content; (v) reduced RBC membrane oxidative damage and HSP70 membrane association.5-MTHF and vitamin B12 supplementation might ameliorate RBC membrane features of children with CF.ClinicalTrials.gov NCT00730509

Aztreonam inhalation solution for suppressive treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis.

An aerosol form of aztreonam lysinate has recently been developed as a treatment for cystic fibrosis patients suffering from chronic Pseudomonas aeruginosa lung colonization. Local administration means the drug can reach mucus concentrations in the order of hundreds of times the MIC(50) of Pseudomonas associated with severe lung disease in cystic fibrosis, resulting in a significant reduction in airway bacterial density and a parallel improvement in lung function. These advantages are maintained over prolonged periods of treatments. Administration of the drug is optimized by the use of a specific eFlow(\uae) system, resulting in considerable reductions in treatment times when compared with conventional nebulizers. The drug has been proven safe and no concomitant induction of resistance to Pseudomonas was found during the clinical trial period of 18 months. Aztreonam lysinate has been shown to ameliorate pulmonary function in cystic fibrosis patients with chronic airway Pseudomonas infection and this is paralleled by a reduction in bacterial density in the lungs. The increased availability of new aerosolized antibiotics for cystic fibrosis will lead to new scenarios in the treatment of the disease