Originalarbeiten / Original Articles. Die protektive Rolle von Selbstregulation für die gesundheitsbezogene Lebensqualität bei Jugendlichen mit einer chronisch körperlichen Erkrankung / The Protective Role of Self-Regulation for HRQOL of Adolescents with a Chronic Physical Health Condition.

The Protective Role of Self-Regulation for HRQOL of Adolescents with a Chronic Physical Health Condition A physical chronic condition comes with many challenges and negatively impacts the healthrelated quality of life (HRQOL) of those affected. Self-regulation plays an important role in successfully coping with the demands of a chronic condition. In line with a resource-oriented approach, this study aimed to investigate themoderating effect of self-regulation on the relationship between disease severity andHRQOL. For this, 498 adolescents with cystic fibrosis, juvenile idiopathic arthritis, or type-1 diabetes aged of 12-21 years (M= 15.43, SD= 2.07) were recruited through three patient registers. Subjective disease severity, self-regulation (Brief Self-Control- Scale), andHRQOL (DISABKIDSChronicGenericMeasure)were examined at two time points (T1 and T2, one year apart). Cross-sectional analysis showed significant effects of subjective disease severity and self-regulation on HRQOL. Prospective analysis, in which HRQOL at T1 was controlled for, revealed that disease severity only predicted emotion-related HRQOL at T2; selfregulation emerged as a predictor for HRQOL subscales independence, emotion, inclusion, exclusion, and treatment. A significantmoderation effect of self-regulation was found on the relationship between disease severity and HRQOL emotion. Our results highlight the positive impact of self-regulation on quality of life, specifically in the context of chronic conditions and represent a starting point for prevention and intervention approaches.

Stability and longitudinal association between Body Mass Index and maladaptive eating behaviors in older adults: Results from the NutriAct Family Study (NFS).

PURPOSE: Due to the increasing prevalence of overweight and obesity with age and associated health risks, older adults are an important target group to promote healthy weight. Evidence indicates that maladaptive eating behaviors are associated with higher BMI. However, older adults are often neglected in this research field. This prospective study aims to clarify the temporal relationship between BMI and maladaptive eating behaviors among older adults. METHODS: In total, 964 participants of the NutriAct Family Study (Mage = 63.34 years) completed web-based questionnaires two times (M = 3.33 years apart). BMI was assessed via self-reported height and weight, and maladaptive eating behaviors with the Dutch Eating Behavior Questionnaire (DEBQ). The stability and longitudinal associations were analyzed using cross-lagged models. RESULTS: Cross-sectional analysis showed positive correlations between BMI and emotional (r = 0.218), external (r = 0.101), as well as restrictive eating (r = 0.160). All maladaptive eating behaviors (ß > 0.684) and BMI (ß > 0.922) were longitudinally stable. No significant bidirectional relationships were found between BMI and maladaptive eating behaviors over time, except for BMI predicting restrictive eating (ß = 0.133). CONCLUSION: The observed cross-sectional, but not longitudinal associations between BMI and maladaptive eating behaviors underline the need for prospective study designs to deepen the understanding of the role of maladaptive eating behaviors in weight management among the general population. Maladaptive eating behaviors among older adults may have already consolidated and play a smaller role in explaining weight course, compared to early life like childhood.

Exon junction complex-associated multi-adapter RNPS1 nucleates splicing regulatory complexes to maintain transcriptome surveillance.

The exon junction complex (EJC) is an RNA-binding multi-protein complex with critical functions in post-transcriptional gene regulation. It is deposited on the mRNA during splicing and regulates diverse processes including pre-mRNA splicing and nonsense-mediated mRNA decay (NMD) via various interacting proteins. The peripheral EJC-binding protein RNPS1 was reported to serve two insufficiently characterized functions: suppressing mis-splicing of cryptic splice sites and activating NMD in the cytoplasm. The analysis of transcriptome-wide effects of EJC and RNPS1 knockdowns in different human cell lines supports the conclusion that RNPS1 can moderately influence NMD activity, but is not a globally essential NMD factor. However, numerous aberrant splicing events strongly suggest that the main function of RNPS1 is splicing regulation. Rescue analyses revealed that the RRM and C-terminal domain of RNPS1 both contribute partially to regulate RNPS1-dependent splicing events. We defined the RNPS1 core interactome using complementary immunoprecipitations and proximity labeling, which identified interactions with splicing-regulatory factors that are dependent on the C-terminus or the RRM domain of RNPS1. Thus, RNPS1 emerges as a multifunctional splicing regulator that promotes correct and efficient splicing of different vulnerable splicing events via the formation of diverse splicing-promoting complexes.

Celsr1 and Celsr2 exhibit distinct adhesive interactions and contributions to planar cell polarity.

Cadherin EGF LAG seven-pass G-type receptor (Celsr) proteins 1-3 comprise a subgroup of adhesion GPCRs whose functions range from planar cell polarity (PCP) signaling to axon pathfinding and ciliogenesis. Like its Drosophila ortholog, Flamingo, mammalian Celsr1 is a core component of the PCP pathway, which, among other roles, is responsible for the coordinated alignment of hair follicles across the skin surface. Although the role of Celsr1 in epidermal planar polarity is well established, the contribution of the other major epidermally expressed Celsr protein, Celsr2, has not been investigated. Here, using two new CRISPR/Cas9-targeted Celsr1 and Celsr2 knockout mouse lines, we define the relative contributions of Celsr1 and Celsr2 to PCP establishment in the skin. We find that Celsr1 is the major Celsr family member involved in epidermal PCP. Removal of Celsr1 function alone abolishes PCP protein asymmetry and hair follicle polarization, whereas epidermal PCP is unaffected by loss of Celsr2. Further, elimination of both Celsr proteins only minimally enhances the Celsr1 -/- phenotype. Using FRAP and junctional enrichment assays to measure differences in Celsr1 and Celsr2 adhesive interactions, we find that compared to Celsr1, which stably enriches at junctional interfaces, Celsr2 is much less efficiently recruited to and immobilized at junctions. As the two proteins seem equivalent in their ability to interact with core PCP proteins Vangl2 and Fz6, we suggest that perhaps differences in homophilic adhesion contribute to the differential involvement of Celsr1 and Celsr2 in epidermal PCP.

New mouse models for high resolution and live imaging of planar cell polarity proteins in vivo.

The collective polarization of cellular structures and behaviors across a tissue plane is a near universal feature of epithelia known as planar cell polarity (PCP). This property is controlled by the core PCP pathway, which consists of highly conserved membrane-associated protein complexes that localize asymmetrically at cell junctions. Here, we introduce three new mouse models for investigating the localization and dynamics of transmembrane PCP proteins: Celsr1, Fz6 and Vangl2. Using the skin epidermis as a model, we characterize and verify the expression, localization and function of endogenously tagged Celsr1-3xGFP, Fz6-3xGFP and tdTomato-Vangl2 fusion proteins. Live imaging of Fz6-3xGFP in basal epidermal progenitors reveals that the polarity of the tissue is not fixed through time. Rather, asymmetry dynamically shifts during cell rearrangements and divisions, while global, average polarity of the tissue is preserved. We show using super-resolution STED imaging that Fz6-3xGFP and tdTomato-Vangl2 can be resolved, enabling us to observe their complex localization along junctions. We further explore PCP fusion protein localization in the trachea and neural tube, and discover new patterns of PCP expression and localization throughout the mouse embryo.

Celsr1 adhesive interactions mediate the asymmetric organization of planar polarity complexes.

To orchestrate collective polarization across tissues, planar cell polarity (PCP) proteins localize asymmetrically to cell junctions, a conserved feature of PCP that requires the atypical cadherin Celsr1. We report that mouse Celsr1 engages in both trans- and cis-interactions, and organizes into dense and highly stable punctate assemblies. We provide evidence suggesting that PCP-mutant variant of Celsr1, Celsr1Crsh, selectively impairs lateral cis-interactions. Although Celsr1Crsh mediates cell adhesion in trans, it displays increased mobility, diminishes junctional enrichment, and fails to engage in homophilic adhesion with the wild-type protein, phenotypes that can be rescued by ectopic cis-dimerization. Using biochemical and super-resolution microscopy approaches, we show that although Celsr1Crsh physically interacts with PCP proteins Frizzled6 and Vangl2, it fails to organize these proteins into asymmetric junctional complexes. Our results suggest mammalian Celsr1 functions not only as a trans-adhesive homodimeric bridge, but also as an organizer of intercellular Frizzled6 and Vangl2 asymmetry through lateral, cis-interactions.

Cystic fibrosis newborn screening: the importance of bloodspot sample quality.

OBJECTIVE: Wales has an immunoreactive trypsin (IRT)-DNA cystic fibrosis (CF) newborn screening (NBS) programme. Most CF NBS false negative cases are due to an IRT concentration below the screening threshold. The accuracy of IRT results is dependent on the quality of the dried bloodspot (DBS) sample. The aim of this study was to determine the cause of false negative cases in CF NBS and their relationship to DBS quality. DESIGN: Longitudinal birth cohort. SETTING: Wales 1996-2016. PATIENTS: Children with CF. INTERVENTIONS: Identification of all CF patients with triangulation of multiple data sources to detect false negative cases. MAIN OUTCOME MEASURES: False negative cases. RESULTS: Over 20 years, 673 952 infants were screened and 239 were diagnosed with CF (incidence 1:2819). The sensitivity of the programme was 0.958, and positive predictive value was 0.476. Eighteen potential false negatives were identified, of whom eight were excluded: four screened outside Wales, two had complex comorbidities, no identified cystic fibrosis transmembrane conductance regulator (CFTR) variants on extended analysis and thus not considered to have CF and two were diagnosed after their 16th birthday. Of the 10 false negatives, 9 had a low DBS IRT and at least one common CFTR variant and thus should have received a sweat test under the programme. DBS cards were available for inspection for five of the nine false negative cases-all were classified as small/insufficient or poor quality. CONCLUSIONS: The majority of false negatives had a low bloodspot IRT, and this was associated with poor quality DBS. The optimal means to improve the sensitivity of our CF NBS programme would be to improve DBS sample quality.

HYGIENIC SUBSTANTIATION OF NECESSITY FOR MONITORING IN THE ENVIRONMENTAL OBJECTS OF SDHI FUNGICIDES CONSIDERING THEIR POSSIBLE IMPACT ON THE THYROID GLAND.

OBJECTIVE: The aim: Was hygienic substantiation of necessity for monitoring in the environmental objects of SDHI fungicides considering their possible impact on the thyroid gland. PATIENTS AND METHODS: Materials and methods: To test the proposed selection criteria for hygienic monitoring of pesticides that affect the thyroid gland, we evaluated 4 new SDHI fungicides from the chemical class of pyrazolecarboxamides (isopyrazam, pentiopyrad, sedaxan, fluxapyroxad). RESULTS: Results: Based on the results obtained, all studied compounds are assigned to the second pesticide group, hygienic monitoring of which is desirable but not required. This is due, on the one hand, to their low toxicity, to the other, to low environmental sustainability. CONCLUSION: Conclusions: It was shown, that compared to other classes of pesticides, the studied are much less dangerous in terms of groundwater contamination.

A Day in the Life of the Exon Junction Complex.

The exon junction complex (EJC) is an abundant messenger ribonucleoprotein (mRNP) component that is assembled during splicing and binds to mRNAs upstream of exon-exon junctions. EJCs accompany the mRNA during its entire life in the nucleus and the cytoplasm and communicate the information about the splicing process and the position of introns. Specifically, the EJC's core components and its associated proteins regulate different steps of gene expression, including pre-mRNA splicing, mRNA export, translation, and nonsense-mediated mRNA decay (NMD). This review summarizes the most important functions and main protagonists in the life of the EJC. It also provides an overview of the latest findings on the assembly, composition and molecular activities of the EJC and presents them in the chronological order, in which they play a role in the EJC's life cycle.

A Live-Cell Screen for Altered Erk Dynamics Reveals Principles of Proliferative Control.

Complex, time-varying responses have been observed widely in cell signaling, but how specific dynamics are generated or regulated is largely unknown. One major obstacle has been that high-throughput screens are typically incompatible with the live-cell assays used to monitor dynamics. Here, we address this challenge by screening a library of 429 kinase inhibitors and monitoring extracellular-regulated kinase (Erk) activity over 5 h in more than 80,000 single primary mouse keratinocytes. Our screen reveals both known and uncharacterized modulators of Erk dynamics, including inhibitors of non-epidermal growth factor receptor (EGFR) receptor tyrosine kinases (RTKs) that increase Erk pulse frequency and overall activity. Using drug treatment and direct optogenetic control, we demonstrate that drug-induced changes to Erk dynamics alter the conditions under which cells proliferate. Our work opens the door to high-throughput screens using live-cell biosensors and reveals that cell proliferation integrates information from Erk dynamics as well as additional permissive cues.

Minimal change in structural, functional and inflammatory markers of lung disease in newborn screened infants with cystic fibrosis at one year.

BACKGROUND: With the widespread introduction of newborn screening for cystic fibrosis (CF), there has been considerable emphasis on the need to develop objective markers of lung health that can be used during infancy. We hypothesised that in a newborn screened (NBS) UK cohort, evidence of airway inflammation and infection at one year would be associated with adverse structural and functional outcomes at the same age. METHODS: Infants underwent lung function testing, chest CT scan and bronchoscopy with bronchoalveolar lavage (BAL) at 1 year of age when clinically well. Microbiology cultures were also available from routine cough swabs. RESULTS: 65 infants had lung function, CT and BAL. Mean (SD) lung clearance index and forced expiratory volume in 0.5 s z-scores were 0.9(1.2) and -0.6(1.1) respectively; median Brody II CF-CT air trapping score on chest CT =0 (interquartile range 0-1, maximum possible score 27). Infants isolating any significant pathogen by 1 yr of age had higher LCI z-score (mean difference 0.9; 95%CI:0.4-1.4; p = 0.001) and a trend towards higher air trapping scores on CT (p = 0.06). BAL neutrophil elastase was detectable in 23% (10/43) infants in whom BAL supernatant was available. This did not relate to air trapping score on CT. CONCLUSIONS: In this UK NBS cohort at one year of age, lung and airway damage is much milder and associations between inflammation, abnormal physiology and structural changes were at best weak, contrary to our hypothesis and previously published reports. Continued follow-up will clarify longer term implications of these very mild structural, functional and inflammatory changes.

Non-pulsed Sinusoidal Electromagnetic Field Rescues Animals From Severe Ischemic Stroke via NO Activation.

Despite the high prevalence and devastating outcome, only a few treatment options for cerebral ischemic stroke exist. Based on the nitric oxide (NO)-stimulating capacity of Non-pulsed Sinusoidal Electromagnetic Field (NP-SEMF) and the possible neuroprotective role of NO in ischemic stroke, we hypothesized that NP-SEMF is able to enhance survival and neurological outcome in a rat model of cerebral ischemia. The animals, in which ischemic injury was induced by occlusion of both common carotid arteries, received 20 min of NP-SEMF of either 10 or 60 Hz daily for 4 days. NP-SEMF dramatically increased survival, reduced the size of the infarcted brain area and significantly improved the neurological score of the surviving rats. Corresponding to previous reports, NP-SEMF was able to induce NO production in vitro. The importance of NO as a key signaling molecule was highlighted by inhibition of the NP-SEMF beneficial effects in the rat stroke model after blocking NO synthase (NOS). Our results indicate for the first time that NP-SEMF exposure (13.5 mT at 60 and 10 Hz) improves the survival and neurological outcome of rats subjected to cerebral ischemia and that this effect is mediated by NO, underlining the great therapeutic potential of NP-SEMF as a therapy for ischemic stroke.

Test of the Einstein Equivalence Principle near the Galactic Center Supermassive Black Hole.

During its orbit around the four million solar mass black hole Sagittarius A* the star S2 experiences significant changes in gravitational potential. We use this change of potential to test one part of the Einstein equivalence principle: the local position invariance (LPI). We study the dependency of different atomic transitions on the gravitational potential to give an upper limit on violations of the LPI. This is done by separately measuring the redshift from hydrogen and helium absorption lines in the stellar spectrum during its closest approach to the black hole. For this measurement we use radial velocity data from 2015 to 2018 and combine it with the gravitational potential at the position of S2, which is calculated from the precisely known orbit of S2 around the black hole. This results in a limit on a violation of the LPI of |ß_{He}-ß_{H}|=(2.4±5.1)×10^{-2}. The variation in potential that we probe with this measurement is six magnitudes larger than possible for measurements on Earth, and a factor of 10 larger than in experiments using white dwarfs. We are therefore testing the LPI in a regime where it has not been tested before.

The CF-Sputum Induction Trial (CF-SpIT) to assess lower airway bacterial sampling in young children with cystic fibrosis: a prospective internally controlled interventional trial.

BACKGROUND: Pathogen surveillance is challenging but crucial in children with cystic fibrosis-who are often non-productive of sputum even if actively coughing-because infection and lung disease begin early in life. The role of sputum induction as a diagnostic tool for infection has not previously been systematically addressed in young children with cystic fibrosis. We aimed to assess the pathogen yield from sputum induction compared with that from cough swab and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage. METHODS: This prospective internally controlled interventional trial was done at the Children's Hospital for Wales (Cardiff, UK) in children with cystic fibrosis aged between 6 months and 18 years. Samples from cough swab, sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage were matched for within-patient comparisons. Primary outcomes were comparative pathogen yield between sputum induction and cough swab for stage 1, and between sputum induction, and single-lobe, two-lobe, and six-lobe bronchoalveolar lavage for stage 2. Data were analysed as per protocol. This study is registered with the UK Clinical Research Network (14615) and with the International Standard Randomised Controlled Trial Network Registry (12473810). FINDINGS: Between Jan 23, 2012, and July 4, 2017, 124 patients were prospectively recruited to the trial and had 200 sputum induction procedures for stage 1. 167 (84%) procedures were successful and the procedure was well tolerated. Of the 167 paired samples, 63 (38%) sputum-induction samples were pathogen positive compared with 24 (14%) cough swabs (p<0·0001; odds ratio [OR] 7·5; 95% CI 3·19-17·98). More pathogens were isolated from sputum induction than cough swab (79 [92%] of 86 vs 27 [31%] of 86; p<0·0001). For stage 2, 35 patients had a total of 41 paired sputum-induction and bronchoalveolar lavage procedures. Of the 41 paired samples, 28 (68%) were positive for at least one of the concurrent samples. 39 pathogens were isolated. Sputum induction identified 27 (69%) of the 39 pathogens, compared with 22 (56%; p=0·092; OR 3·3, 95% CI 0·91-12·11) on single-lobe, 28 (72%; p=1·0; OR 1·1, 95% CI 0·41-3·15) on two-lobe, and 33 (85%; p=0·21; OR 2·2, 95% CI 0·76-6·33) on six-lobe bronchoalveolar lavage. INTERPRETATION: Sputum induction is superior to cough swab for pathogen detection, is effective at sampling the lower airway, and is a credible surrogate for bronchoalveolar lavage in symptomatic children. A substantial number of bronchoscopies could be avoided if sputum induction is done first and pathogens are appropriately treated. Both sputum induction and six-lobe bronchoalveolar lavage provide independent, sizeable gains in pathogen detection compared with the current gold-standard two-lobe bronchoalveolar lavage. We propose that sputum induction and six-lobe bronchoalveolar lavage combined are used as standard of care for comprehensive lower airway pathogen detection in children with cystic fibrosis. FUNDING: Health and Care Research Wales-Academic Health Science Collaboration and Wellcome Trust Institutional Strategic Support Fund.

Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient.

With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants.Forced expiratory volume in 0.5 s (FEV0.5), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls.By 2 years there was no significant difference in FEV0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45-1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV0.5 on all test occasions, precluding the ability to identify "high-risk" infants in early life.In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up.

Spatially patterned matrix elasticity directs stem cell fate.

There is a growing appreciation for the functional role of matrix mechanics in regulating stem cell self-renewal and differentiation processes. However, it is largely unknown how subcellular, spatial mechanical variations in the local extracellular environment mediate intracellular signal transduction and direct cell fate. Here, the effect of spatial distribution, magnitude, and organization of subcellular matrix mechanical properties on human mesenchymal stem cell (hMSCs) function was investigated. Exploiting a photodegradation reaction, a hydrogel cell culture substrate was fabricated with regions of spatially varied and distinct mechanical properties, which were subsequently mapped and quantified by atomic force microscopy (AFM). The variations in the underlying matrix mechanics were found to regulate cellular adhesion and transcriptional events. Highly spread, elongated morphologies and higher Yes-associated protein (YAP) activation were observed in hMSCs seeded on hydrogels with higher concentrations of stiff regions in a dose-dependent manner. However, when the spatial organization of the mechanically stiff regions was altered from a regular to randomized pattern, lower levels of YAP activation with smaller and more rounded cell morphologies were induced in hMSCs. We infer from these results that irregular, disorganized variations in matrix mechanics, compared with regular patterns, appear to disrupt actin organization, and lead to different cell fates; this was verified by observations of lower alkaline phosphatase (ALP) activity and higher expression of CD105, a stem cell marker, in hMSCs in random versus regular patterns of mechanical properties. Collectively, this material platform has allowed innovative experiments to elucidate a novel spatial mechanical dosing mechanism that correlates to both the magnitude and organization of spatial stiffness.

Bitter Gentian Teas: Nutritional and Phytochemical Profiles, Polysaccharide Characterisation and Bioactivity.

As a result of the wide distribution of herbal teas the data on nutritional characterisation, chemical profile and biological activity of these products are required. The decoctions of Gentiana algida, G. decumbens, G. macrophylla and G. triflora herb teas were nutritionally characterized with respect to their macronutrients, demonstrating the predominance of polysaccharides and low lipid content. Gentian decoctions were also submitted to a microcolumn RP-HPLC-UV analysis of phytochemicals demonstrating a high content of iridoids (177.18-641.04 µg/mL) and flavonoids (89.15-405.71 µg/mL). Additionally, mangiferin was detected in samples of G. triflora tea (19.89 µg/mL). Five free sugars (fructose, glucose, sucrose, gentiobiose, gentianose) were identified in all gentian teas studied, as well as six organic acids (malic, citric, tartaric, oxalic, succinic, quinic). Pectic polysaccharides with a high content of rhamnogalacturonans and arabinogalactans were also identified and characterized in gentian decoctions for the first time. Gentian tea decoctions and their specific compounds (gentiopicroside, loganic acid-6'-O-ß-d-glucoside, isoorientin, isoorientin-4'-O-ß-d-glucoside, mangiferin, water-soluble polysaccharides) showed a promising antimicrobial, anti-inflammatory and antioxidant potentials. Evidences obtained indicate the prospective use of gentian herb teas as food products and medicines.

Evolution of lung function during the first year of life in newborn screened cystic fibrosis infants.

RATIONALE: Newborn screening (NBS) for cystic fibrosis (CF) allows early intervention. Design of randomised controlled trials (RCT) is currently impeded by uncertainty regarding evolution of lung function, an important trial end point in such infants. OBJECTIVE: To assess changes in pulmonary function during the first year of life in CF NBS infants. METHODS: Observational longitudinal study. CF NBS infants and healthy controls were recruited between 2009 and 2011. Lung Clearance Index (LCI), plethysmographic lung volume (plethysmographic functional residual capacity (FRCpleth)) and forced expired volume (FEV0.5) were measured at 3 months and 1 year of age. MAIN RESULTS: Paired measurements were obtained from 72 CF infants and 44 controls. At 3 months, CF infants had significantly worse lung function for all tests. FEV0.5 improved significantly (0.59 (95% CI 0.18 to 0.99) z-scores; p<0.01) in CF infants between 3 months and 1 year, and by 1 year, FEV0.5 was only 0.52 (0.89 to 0.15) z-scores less than in controls. LCI and FRCpleth remained stable throughout the first year of life, being on average 0.8 z-scores higher in infants with CF. Pulmonary function at 1 year was predicted by that at 3 months. Among the 45 CF infants with entirely normal LCI and FEV0.5 at 3 months, 80% remained so at 1 year, while 74% of those with early abnormalities remained abnormal at 1 year. CONCLUSIONS: This is the first study reporting improvements in FEV0.5 over time in stable NBS CF infants treated with standard therapy. Milder changes in lung function occurred by 1 year than previously reported. Lung function at 3 months predicts a high-risk group, who should be considered for intensification of treatment and enrolment into RCTs.

Is chest CT useful in newborn screened infants with cystic fibrosis at 1 year of age?

RATIONALE: Sensitive outcome measures applicable in different centres to quantify and track early pulmonary abnormalities in infants with cystic fibrosis (CF) are needed both for clinical care and interventional trials. Chest CT has been advocated as such a measure yet there is no validated scoring system in infants. OBJECTIVES: The objectives of this study were to standardise CT data collection across multiple sites; ascertain the incidence of bronchial dilatation and air trapping in newborn screened (NBS) infants with CF at 1 year; and assess the reproducibility of Brody-II, the most widely used scoring system in children with CF, during infancy. METHODS: A multicentre observational study of early pulmonary lung disease in NBS infants with CF at age 1 year using volume-controlled chest CT performed under general anaesthetic. MAIN RESULTS: 65 infants with NBS-diagnosed CF had chest CT in three centres. Small insignificant variations in lung recruitment manoeuvres but significant centre differences in radiation exposures were found. Despite experienced scorers and prior training, with the exception of air trapping, inter- and intraobserver agreement on Brody-II score was poor to fair (eg, interobserver total score mean (95% CI) κ coefficient: 0.34 (0.20 to 0.49)). Only 7 (11%) infants had a total CT score ≥ 12 (ie, ≥ 5% maximum possible) by either scorer. CONCLUSIONS: In NBS infants with CF, CT changes were very mild at 1 year, and assessment of air trapping was the only reproducible outcome. CT is thus of questionable value in infants of this age, unless an improved scoring system for use in mild CF disease can be developed.