Explore the vast range of titles available.

Functional exercise capacity assessment is recommended in children with cystic fibrosis (CF). The six-minute walk test (6MWT) is a valid evaluation of exercise capacity but can be technically complex. Inversely, the sit-to-stand test (STST) is a simple method to evaluate exercise capacity, and is validated in healthy children and adults with CF. This study aimed to evaluate STST measurement properties in children and adolescents with CF. In this multicenter study, children with CF (6 to 18 years) performed two iterations of both the STST and the 6MWT in a randomized order. Criterion validity was determined by assessing correlations between STST repetitions and 6MWT distance (6MWD). Intra-rater reliability, test-retest repeatability, mean bias and limits of agreement were also assessed. Relationships with other outcomes (i.e. respiratory and quadriceps muscle strength) and cardio-respiratory responses were analysed for both tests. Thirty-six children with CF were included (mean age 12.0 ±3.5 years and FEV1 95.8 ±25.0%). On average, 39.6 ±10.5 repetitions were performed during the STST and mean 6MWD was 596.0 ±102.6 meters. STST number of repetitions was significantly correlated with 6MWD (r = 0.48; p<0.01). Both tests had very good intra-rater reliability (ICCSTST = 0.91 (95%CI 0.76-0.96) and ICC6MWT = 0.94 (95%CI 0.85-0.97)), and a significant test-retest learning effect. The number of STST repetitions was not correlated with quadriceps or respiratory muscle strength test, and the STST induced fewer cardio-respiratory responses than the 6MWT. The STST is an easy-to-use functional test with moderate criterion validity when compared to the 6MWT in children with CF, probably because both tests measure different components of functional exercise capacity. The STST is useful when the 6MWT is unfeasible, however further investigations are required to explore the clinical implications of STST results in children with CF. NCT03069625.

Chronic colonization by filamentous fungi in patients with cystic fibrosis (pwCF) is linked to declines in lung function and quality of life. To better assess indoor mold exposure, 23 French dwellings of pwCF from CF care centers in Normandy and Maine & Loire, France were visited. Bioaerosols collected using Coriolis® µ and Coriolis® compact biocollectors and dust were cultured on four different media: Potato Dextrose Agar (PDA), Malt Extract Agar (MEA), Sabouraud Chloramphenicol Gentamicin (SCG) and Sabouraud Chloramphenicol Gentamicin Actidione (S +). A total of 164 fungal species were identified (44 in both air and dust, 77 in air only and 43 in dust only), with no significant difference in average species count between air and dust samples ( p  = 0.353). The Coriolis® µ biocollector yielded significantly higher species recovery and fungal load from air samples compared to the Coriolis® compact biocollector ( p  < 0.001 and p  < 0.0001, respectively). Higher CFU/m 3 for Aspergillus , Fusarium , Mucor and Rhizopus were found on MEA, PDA and SCG media compared to S + ( p  = 0.037, p  = 0.005 and p  = 0.030, respectively). Alpha diversity was also greater on MEA, PDA and SCG media than on S + medium ( p  = 0.001, p  < 0.0001 for PDA and SCG) and PDA than on MEA ( p  = 0.008). The distribution of common fungal genera was consistent with literature, except for higher frequencies of Fusarium and Talaromyces in our study. In conclusion, air sampling with the Coriolis® µ biocollector and inoculation on PDA or MEA media is recommended for this type of field study.

Background A major breakthrough in cystic fibrosis (CF) therapy was achievedAQ1 with CFTR modulators. The lumacaftor/ivacaftor combination is indicated for the treatment of CF in pediatric patients above 6 years old. Pharmacokinetic (PK) studies of lumacaftor/ivacaftor in these vulnerable pediatric populations are AQ2crucial to optimize treatment protocols. Objectives and Methods The objectives of this study were to describe the population PK (PPK) of lumacaftor and ivacaftor in children with CF, and to identify factors associated with interindividual variability. The association between drug exposure and clinical response was also investigated. Results A total of 75 children were included in this PPK study, with 191 concentrations available for each compound and known metabolites (lumacaftor, ivacaftor, ivacaftor-M1, and ivacaftor-M6). PPK analysis was performed using Monolix software. A large interindividual variability was observed. The main sources of interpatient variability identified were patient bodyweight and hepatic function (aspartate aminotransferase). Forced expiratory volume in the first second (FEV1) was statistically associated with the level of exposure to ivacaftor after 48 weeks of treatment. Conclusions This study is the first analysis of lumacaftor/ivacaftor PPK in children with CF. These data suggest that dose adjustment is required after identifying variability factors to optimize efficacy. The use of therapeutic drug monitoring as a basis for dose adjustment in children with CF may be useful.

Highly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI impact on glucose tolerance remains controversial.BACKGROUNDHighly effective CFTR modulators, such as elexacaftor/tezacaftor/ivacaftor (ETI), herald a new era in therapeutic strategy of cystic fibrosis (CF). ETI impact on glucose tolerance remains controversial.All the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and 12 months (M12), and at 24 months if possible. The cohort was stratified in two subgroups based on the baseline OGTT: normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) defined by impaired fasting glucose or impaired glucose tolerance or diabetes not requiring insulin treatment.METHODSAll the participants underwent a baseline oral glucose tolerance test (OGTT) before ETI initiation (M0) and 12 months (M12), and at 24 months if possible. The cohort was stratified in two subgroups based on the baseline OGTT: normal glucose tolerance (NGT) and abnormal glucose tolerance (AGT) defined by impaired fasting glucose or impaired glucose tolerance or diabetes not requiring insulin treatment.We included 106 adolescents with CF (age 14.1±1.5 years), 75 with NGT, 31 with AGT. The baseline characteristics of the two groups were similar except for a higher glucose level at 1 and 2-h OGTT in the AGT group. ETI induced an increase in BMIz-score and in Forced Expiratory Volume in 1 second (FEV1) (p<0.001). After 12 months, participants with NGT did not experience any change of 1-h and 2-h glucose. By contrast, those with AGT displayed a reduction of 2-h glucose at M12 (p=0.006). 15out of the 31 (48%) adolescents in the AGT group reversed to NGT but 9/75 (17%) in the NGT group progressed to AGT. 3 participants with CF related diabetes at baseline reversed to AGT. 1-hour glucose concentrations at or above 8.7 mmol/L (157mg/dL) during baseline OGTT had 80% sensitivity to identify those with AGT at 12 months (OR 1.51 [1.20, 1.92], p=0.001). 20 participants had a 24-month OGTT that confirmed preserved insulin secretion.RESULTSWe included 106 adolescents with CF (age 14.1±1.5 years), 75 with NGT, 31 with AGT. The baseline characteristics of the two groups were similar except for a higher glucose level at 1 and 2-h OGTT in the AGT group. ETI induced an increase in BMIz-score and in Forced Expiratory Volume in 1 second (FEV1) (p<0.001). After 12 months, participants with NGT did not experience any change of 1-h and 2-h glucose. By contrast, those with AGT displayed a reduction of 2-h glucose at M12 (p=0.006). 15out of the 31 (48%) adolescents in the AGT group reversed to NGT but 9/75 (17%) in the NGT group progressed to AGT. 3 participants with CF related diabetes at baseline reversed to AGT. 1-hour glucose concentrations at or above 8.7 mmol/L (157mg/dL) during baseline OGTT had 80% sensitivity to identify those with AGT at 12 months (OR 1.51 [1.20, 1.92], p=0.001). 20 participants had a 24-month OGTT that confirmed preserved insulin secretion.ETI may improve glucose tolerance in adolescents with CF by preserving insulin secretion. 1-hour glucose during the OGTT helps to detect risk for AGT after ETI treatment.CONCLUSIONETI may improve glucose tolerance in adolescents with CF by preserving insulin secretion. 1-hour glucose during the OGTT helps to detect risk for AGT after ETI treatment.

Pseudomonas aeruginosa ( Pa ) and Methicillin susceptible Staphylococcus aureus ( MSSA ) are the predominant bacteria found in the airways of people with cystic fibrosis (pwCF), significantly contributing to lung disease progression. While various factors influencing the initial acquisition (IA) of these pathogens are known, the impact of environmental conditions remains understudied. This epidemiological study assessed the risk of MSSA and Pa initial acquisitions in relation to seasonality and climatic zones among 1,184 French pwCF under 18 years old. The age at IA for Pa ( Pa -IA) and MSSA ( MSSA -IA) was estimated using the Kaplan–Meier method. Seasonality and climatic zones were analysed as risk factors using time-varying Cox regression models. The median age at MSSA -IA was notably earlier (2.0 years) than that at Pa -IA (5.1 years). MSSA -IA occurred increasingly younger in more recent birth cohorts, while the age at Pa -IA remained stable over time. The risk of Pa -IA was consistently higher in all seasons compared with spring, peaking in autumn (HR = 1.53), irrespective of climatic zones. In Oceanic and Continental climates, the highest risk for MSSA -IA was in winter (HRs = 1.45 and 1.20 respectively). In the Mediterranean climate, the risk of MSSA -IA was lower in winter compared to spring (HRs = 0.68 and 0.61 respectively), and the median age at MSSA -IA later than for Pa -IA. This study demonstrates that seasonality and meteorological factors may influence acquisition of MSSA and Pa in pwCF. These findings suggest that environmental factors play a role in pathogen acquisition dynamics in CF and could inform the development of preventive strategies.

Incidence of resistance to erythromycin at our institution reached 53% in 122 Staphylococcus aureus isolates obtained from patients with cystic fibrosis (CF) from 1997 to 1999. Macrolide-resistance genes were sought for in 20 erythromycin-resistant isolates from 9 patients with CF by use of polymerase chain reaction; 13 strains did not contain any known macrolide-resistance genes. Sequence of ribosomal genes rrl (23S rRNA), rplD (L4 protein), and rplV (L22 protein) revealed the presence of mutations in the target site of macrolides in 15 of the 20 isolates. A higher proportion of hypermutator strains was observed in a group of 89 CF staphylococcal isolates, compared with that in the 74 non-CF control isolates (13/89 vs. 1/74 with resistance to rifampin [P=.0045]; 9/89 vs. 1/74 with resistance to streptomycin [P=.04]). Various mutations or deletions of the mutator mutS gene were found not only in 5 of 11 hypermutable strains but also in 3 nonhypermutable strains harboring a large number of ribosomal mutations. The presence of a high proportion of hypermutable strains might explain the adaptation of certain strains in the patients, as well as the emergence of macrolide resistance as a result of antibiotic selective pressure in CF

Until recently, the roles of plant MADS-box genes have mainly been characterized during inflorescence and flower differentiation. In order to precise the roles of AGAMOUS-LIKE 12, one of the few MADS-box genes preferentially expressed in roots, we placed its cDNA under the control of the double 35S CaMV promoter to produce transgenic walnut tree and Arabidopsis plants. In Juglans sp., transgenic somatic embryos showed significantly higher germination rates but abnormal development of their shoot apex prevented their conversion into plants. In addition, a wide range of developmental abnormalities corresponding to ectopic root-like structures affected the transgenic lines suggesting partial reorientations of the embryonic program toward root differentiation. In Arabidopsis, AtAGL12 overexpression lead to the production of faster growing plants presenting dramatically wider and shorter root phenotypes linked to increased meristematic cell numbers within the root apex. In the upper part of the roots, abnormal cell divisions patterns within the pericycle layer generated large ectopic cell masses that did not prevent plants to grow. Taken together, our results confirm in both species that AGL12 positively regulates root meristem cell division and promotes overall root vascular tissue formation. Genetic engineering of AGL12 expression levels could be useful to modulate root architecture and development.