Elexacaftor/tezacaftor/ivacaftor efficacy in intestinal organoids with rare CFTR variants in comparison to CFTR-F508del and CFTR-wild type controls.

Cystic fibrosis is a life-shortening genetic disease caused by pathological variants of the cystic fibrosis transmembrane conductance regulator gene. The CFTR modulator therapy elexacaftor, tezacaftor and ivacaftor (ETI) rescues CFTR protein function and has made a significant impact on the lives of many people with CF. In Europe, ETI is currently available for people with CF who have at least one F508del mutation whilst the effect of ETI on rare CFTR variants remains unknown, albeit that many of such variants may be restored through ETI.

Physical Activity Levels, Cardiorespiratory Fitness, and Physical Literacy in Children With a Chronic Medical Condition.

Purpose: This study investigated differences in cardiorespiratory fitness (CRF) and other physical literacy domains between children with a chronic medical condition (CMC) who adhered to with the physical activity guideline and those who did not.

Method: Forty children with a CMC (7-12 years) wore an accelerometer for 7 days to measure moderate-to-vigorous physical activity. CRF and muscle power were assessed with a maximal cardiopulmonary exercise test, and motor performance was measured with an exercise course.

Early-Life Risk Factors for Carotid Intima-Media Thickness and Carotid Stiffness in Adolescence.

Importance: Atherogenesis starts during childhood, making childhood and adolescence an important window of opportunity to prevent atherosclerotic cardiovascular disease later in life.

Objective: To identify early-life risk factors for preclinical atherosclerosis in adolescence.

Design, Setting, And Participants: This cohort study is part of the ongoing Wheezing Illness Study in Leidsche Rijn (WHISTLER) prospective birth cohort study, which includes 3005 healthy newborns born between December 2001 and December 2012 in the Leidsche Rijn area of Utrecht, the Netherlands.

Physical activity, sedentary behaviour, and childhood asthma: a European collaborative analysis.

Objectives: To investigate the associations of physical activity (PA) and sedentary behaviour in early childhood with asthma and reduced lung function in later childhood within a large collaborative study.

Design: Pooling of longitudinal data from collaborating birth cohorts using meta-analysis of separate cohort-specific estimates and analysis of individual participant data of all cohorts combined.

Setting: Children aged 0-18 years from 26 European birth cohorts.

Centralized intestinal organoid generation is a feasible and safe approach for personalized medicine as demonstrated in the HIT-CF Europe Organoid Study.

Background: Patient-derived intestinal organoids (PDIOs) show great potential as in vitro drug testing platform for personalised medicine in Cystic Fibrosis and oncology. PDIOs can be generated by culturing adult stem cells obtained through rectal forceps biopsy or suction biopsy, but the safety of these procedures and the success rates of generating organoids after shipment to a centralized lab using these procedures has not been studied in this context. We here report the safety and success rates of both biopsy procedures and the subsequent generation of PDIOs in the international multicentre HIT-CF Organoid Study.