Pediatric Patients with Eosinophilic Esophagitis and Their Parents Identify Symptoms as the Most Important Treatment Outcome.

INTRODUCTION: Given the lack of data, we aimed to explore which therapeutic endpoints pediatric patients with eosinophilic esophagitis (EoE) and their parents consider to be relevant. METHODS: We created an educational brochure on EoE and a questionnaire, both of which were content-validated by pediatric patients and parents. Validated documents were sent to 112 patients and parents. They ranked the importance (5 levels) of short (during next 3 months) and long-term (≥1 year) treatment effect on symptoms, quality of life, endoscopic inflammation, stricture formation, histological inflammation, and fibrosis. RESULTS: A total of 45 parents and 30 pediatric patients ≥11 years completed the questionnaires. Pediatric patients identified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (73% vs. 77%), QoL (53% vs. 57%), histologic inflammation (47% vs. 50%), histologic fibrosis (40% vs. 33%), endoscopic inflammation (47% vs. 40%), and strictures (33% vs. 40%). Parents of children ≥11 years old classified improvement in the following domains as most important in the short- and long-term, respectively: symptoms (70% vs. 83%), QoL (63% vs. 80%), histologic inflammation (67% vs. 77%), histologic fibrosis (47% vs. 63%), endoscopic inflammation (77% vs. 80%), and strictures (40% vs. 53%). Agreement between caregiver and children on the short-term importance of treatment outcomes was as follows: symptoms (77%), QoL (40%), histologic inflammation and fibrosis (47% and 43%), endoscopic inflammation and strictures (50% and 40%). CONCLUSION: Pediatric patients and parents attributed most importance to improvement in symptoms and QoL. Agreement between parents and patients regarding therapy goals is limited.

On efficient modelling of radical production in cavitation assisted reactors.

Process intensification by cavitation is gaining widespread attention due to the benefits that the intense bubble collapse conditions can provide, yet, several knowledge gaps exist in the modelling of such systems. This work studies the numerical prediction of single bubble dynamics and the various approaches that can be employed to estimate the changes in the chemical composition of cavitating bubbles. Specific emphasis is placed on the prediction of the radical production rates during bubble collapse and the computational performance, with the aim of coupling the single bubble dynamics to flow models for reactor hydrodynamics. The results reveal that the choice of chemical reaction approach has virtually no effect on the bubble dynamics, whereas the predicted radical production rates can differ substantially. It is found that evaluating the radical production only on temperature peaks, an approach commonly followed in literature, may result in the most erroneous estimations (on average 12.8 times larger than those of the full kinetic model), while a simplified kinetic model yields more accurate predictions (2.3 times larger) at the expense of increased computational times. Continuous evaluation of the bubble content by assuming equilibrium when the bubble temperature is above a certain threshold (≈1500K) is shown to be capable of predicting total radical production values close to those estimated by solving the kinetics of a detailed reaction model (19.8% difference), as well as requiring only 22.2% more computational costs compared to simulations without chemical reaction modelling. Such an equilibrium approach is therefore recommended for future studies aiming to couple flow simulations with single bubble dynamics to accurately predict radical production rates in cavitation devices, involving numerous bubbles following different flow trajectories. Furthermore, an algebraic expression that successfully approximates the full kinetic simulation results is proposed as a function of the initial nucleus size and the time integral of the liquid pressure when it is under vapor pressure. Such a model can be applied in modelling efforts that do not require local instantaneous radical concentrations, and paves the way for efficient closure modelling of radical production in CFD simulations of hydrodynamic reactors.

Epidemiology, clinical features and management of autoimmune hepatitis in Switzerland: a retrospective and prospective cohort study.

BACKGROUND AND AIMS: The Swiss Autoimmune Hepatitis Cohort Study is a nationwide registry, initiated in 2017, that collects retrospective and prospective clinical data and biological samples from patients of all ages with autoimmune hepatitis treated at Swiss hepatology centres. Here, we report the analysis of the first 5 years of registry data. RESULTS: A total of 291 patients with autoimmune hepatitis have been enrolled, 30 of whom were diagnosed before 18 years of age and composed the paediatric cohort. Paediatric cohort: median age at diagnosis 12.5 years (range 1-17, interquartile range (IQR) 8-15), 16 (53%) girls, 6 (32%) with type 2 autoimmune hepatitis, 8 (27%) with autoimmune sclerosing cholangitis, 1 with primary biliary cholangitis variant syndrome, 4 (15%) with inflammatory bowel disease and 10 (41%) with advanced liver fibrosis at diagnosis. Adult cohort: median age at diagnosis 54 years (range 42-64, IQR 18-81), 185 (71%) women, 51 (20%) with primary biliary cholangitis variant syndrome, 22 (8%) with primary sclerosing cholangitis variant syndrome, 9 (4%) with inflammatory bowel disease and 66 (32%) with advanced liver fibrosis at diagnosis. The median follow-up time for the entire cohort was 5.2 years (IQR 3-9.3 years). Treatment in children: 29 (97%) children were initially treated with corticosteroids, 28 of whom received combination treatment with azathioprine. Budesonide was used in four children, all in combination with azathioprine. Mycophenolate mofetil was used in five children, all of whom had previously received corticosteroids and thiopurine. Treatment in adults (data available for 228 patients): 219 (96%) were treated with corticosteroids, mostly in combination with azathioprine. Predniso(lo)ne was the corticosteroid used in three-quarters of patients; the other patients received budesonide. A total of 78 (33%) patients received mycophenolate mofetil, 62 of whom had previously been treated with azathioprine. Complete biochemical response was achieved in 13 of 19 (68%) children and 137 of 182 (75%) adults with available follow-up data. All children were alive at the last follow-up, and none had undergone liver transplantation. Five (2%) adults underwent liver transplantation, two of whom had a fulminant presentation. Four (2%) adults with autoimmune hepatitis died (two from liver-associated causes). CONCLUSION: Patients with autoimmune hepatitis in Switzerland had clinical features similar to those in other cohorts. The proportion of patients diagnosed with primary biliary cholangitis variant syndrome was higher than expected. Autoimmune hepatitis was managed according to guidelines, except for the use of budesonide in a small proportion of paediatric patients. The outcomes were excellent, but the findings must be confirmed over a longer follow-up period.

Early warning for SpO2 decrease by the oxygen reserve index in neonates and small infants.

INTRODUCTION: Continuously assessing the oxygenation levels of patients to detect and prevent hypoxemia can be advantageous for safe anesthesia, especially in neonates and small infants. The oxygen reserve index (ORI) is a new parameter that can assess oxygenation through a relationship with arterial oxygen partial pressure (PaO2 ). The aim of this study was to examine whether the ORI provides a clinically relevant warning time for an impending SpO2 (pulse oximetry hemoglobin saturation) reduction in neonates and small infants. METHODS: ORI and SpO2 were measured continuously in infants aged <2 years during general anesthesia. The warning time and sensitivity of different ORI alarms for detecting impending SpO2 decrease were calculated. Subsequently, the agreement of the ORI and PaO2 with blood gas analyses was assessed. RESULTS: The ORI of 100 small infants and neonates with a median age of 9 months (min-max, 0-21 months) and weight of 8.35 kg (min-max, 2-13 kg) were measured. For the ORI/PaO2 correlation, 54 blood gas analyses were performed. The warning time and sensitivity of the preset ORI alarm during the entire duration of anesthesia were 84 s (25th-75th percentile, 56-102 s) and 55% (95% CI 52%-58%), and those during anesthesia induction were 63 s (40-82 s) and 56% (44%-68%), respectively. The positive predictive value of the preset ORI alarm were 18% (95% CI 17%-20%; entire duration of anesthesia) and 27% (95% CI 21%-35%; during anesthesia induction). The agreement of PaO2 intervals with the ORI intervals was poor, with a kappa of 0.00 (95% CI = [-0.18; 0.18]). The weight (p = .0129) and height (p = .0376) of the infants and neonates were correlated to the correct classification of the PaO2 interval with the ORI interval. CONCLUSIONS: The ORI provided an early warning time for detecting an impending SpO2 decrease in small infants and neonates in the defined interval in this study. However, the sensitivity of ORI to forewarn a SpO2 decrease and the agreement of the ORI with PaO2 intervals in this real-life scenario were too poor to recommend the ORI as a useful early warning indicator for this age group.

Vegan Diet in Young Children.

The prevalence of restrictive diets, mainly vegetarian and vegan, is markedly on the increase in Europe and other Western countries. In young children and adolescents, not only weight and height but also neurocognitive and psychomotor development are all strongly influenced by the source, quantity, and quality of their nutrition. In studies done mainly in adult populations, a plant-based diet showed benefits in the reduced risk of chronic diseases such as obesity, type 2 diabetes, cardiovascular diseases, and some types of cancer. However, there is no clear evidence that a vegan diet started in early childhood confers a lasting health benefit. On the other hand, a vegan diet can be potentially critical for young children with risks of inadequate supply in terms of protein quality and energy as well as long-chain fatty acids, iron, zinc, vitamin D, iodine, calcium, and particularly vitamin B12. Deficiencies in these nutrients can lead to severe and sometimes irreversible developmental disorders. If such a diet is chosen for ethical, ecological, or health reasons, a well-planned, diversified diet with additional supplementation of vitamin B12, vitamin D, iodine, and potentially other micronutrients is crucial to ensure a healthy and nutritious intake during childhood.

Impact of Different Combinations of Water Treatment Processes on the Concentration of Disinfection Byproducts and Their Precursors in Swimming Pool Water.

To mitigate microbial activity in swimming pools and to ensure hygienic safety for bathers, pool systems have a recirculating water system ensuring continuous water treatment and disinfection by chlorination. A major drawback associated with the use of chlorine as disinfectant is its potential to react with precursor substances present in pool water to form harmful disinfection byproducts (DBPs). In this study, different combinations of conventional and advanced treatment processes were applied to lower the concentration of DBPs and their precursors in pool water by using a pilot-scale swimming pool model operated under reproducible and fully controlled conditions. The quality of the pool water was determined after stationary concentrations of dissolved organic carbon (DOC) were reached. The relative removal of DOC (Δc cin-1) across the considered treatment trains ranged between 0.1  ±  2.9% and 7.70  ±  4.5%, where conventional water treatment (coagulation and sand filtration combined with granular activated carbon (GAC) filtration) was revealed to be the most effective. Microbial processes in the deeper, chlorine-free regions of the GAC filter have been found to play an important role in the degradation of organic substances. Almost all treatment combinations were capable of removing trihalomethanes to some degree and trichloramine and dichloroacetonitrile almost completely. However, the results demonstrated that effective removal of DBPs across the treatment train does not necessarily result in low DBP concentrations in the basin of a pool. This raises the importance of the DBP formation potential of the organic precursors, which has been shown to depend strongly on the treatment concept applied. Irrespective of the filtration technique employed, treatment combinations employing UV irradiation as a second treatment step revealed higher concentrations of volatile DBPs in the pool compared to those employing GAC filtration as a second treatment step. In the particular case of trichloramine, results confirm that its removal across the treatment train is not a feasible mitigation strategy because it cannot compensate for the fast formation in the basin.

[Vegan diet in children : what potential deficits to monitor ?] / Alimentation végétalienne de l'enfant : quels déficits surveiller ? Revue pratique pour le médecin.

The vegan diet, although beneficial for adults in the prevention of metabolic diseases, raises questions about its benefits for a growing child : adequate caloric and protein intake, quality of essential amino acids, presence of essential fatty acids, inhibition of absorption of trace elements (including iodine, iron and zinc) and supply of various vitamins. Whereas vegan food is vitamin B12 deprived, the biggest challenge remains the vitamin B12 substitution in pregnant women, breastfeeding mothers and children at any age. Specific management by pediatricians using dietetic support and blood analyzes are required for children under vegan diet with respect of moral and ethical values related to this lifestyle choice.

L'alimentation végétalienne, bien que bénéfique pour les adultes dans la prévention de maladies métaboliques, pose des questions quant à ses bénéfices pour un enfant en croissance : apports caloriques et protéiques suffisants, qualité en acides aminés essentiels et présence d'acides gras, inhibition de l'absorption des vitamines (notamment la D) et des éléments traces (par exemple, iode, fer, et zinc). Elle pose surtout la question de la supplémentation en vitamine B12 des futures mamans, des mères allaitantes et des enfants de chaque âge, alors que leur alimentation en est dépourvue. Des mesures particulières de surveillance diététiques et biologiques, ainsi qu'un accompagnement pédiatrique nutritionnel sont à proposer tout en respectant les valeurs morales et éthiques sous-jacentes à ce choix de vie.

[Diagnosis and Treatment of Familial Hypercholesterolemia]. / Familiäre Hypercholesterinämie ­ Diagnose und Therapie.

Diagnosis and Treatment of Familial Hypercholesterolemia Abstract. Familial hypercholesterolemia secondary to heterozygous mutations in the LDL receptor, Apolipoprotein B or PCSK9 gene is characterized by 2- to 3-fold elevated LDL cholesterol levels, premature atherosclerosis and extravascular cholesterol deposits (tendon xanthomata, corneal arcus). The same phenotype may occur if a person carries several LDL cholesterol rising polymorphisms (polygenic FH). Primary prevention with statins has been shown to dramatically reduce the cardiovascular burden in patients with the disease. However, it is estimated that less than 10 % of affected subjects in Switzerland have received the diagnosis, and undertreatment is frequent. Thus, clinical cardiovascular events are still the first manifestation of the disease in many cases. A correct diagnosis in index patients and cascade screening of families are mandatory to identify and treat patients before they suffer the sequelae of untreated severe hypercholesterolemia. In patients with clinical cardiovascular disease combination lipid lowering treatment with potent statins, ezetimibe and the newly available PCSK9 inhibitors will successfully lower LDL cholesterol to normal or even target levels.

Nutrient intake of Swiss toddlers.

PURPOSE: During the first years of life, food preferences are shaped that might last throughout a person's entire life affecting his/her health in the long term. However, knowledge on early feeding habits is still limited for toddlers. Therefore, the goal of the present study was to: (1) assess toddlers' nutrient intake; (2) compare the findings to past studies as well as to national feeding recommendations and (3) identify major food sources for energy and macronutrients. METHODS: A food survey using a 4-day diary was conducted. The dietary software nut.s® was used to analyse the data. RESULTS: A cohort of 188 healthy toddlers (aged 1-3 years) was analysed. The energy intake of most toddlers was below the recommended daily intake (RDI) but in accordance with earlier studies. Protein intake was three- to fourfold higher than the RDI and reached the proposed upper limit of 15% of total energy intake. Fat intake was in accordance with the RDI, but the balance of saturated and unsaturated fatty acids should be improved. Carbohydrate intake met the RDI. For the micronutrients, iron and vitamin D intakes showed critical values. CONCLUSION: As in other European countries, the diet of Swiss toddlers in general seems adequate but does not meet all nutritional requirements. In particular, the quality of the fats and vitamin D supplementation should be improved. For proteins and iron, additional research is needed to gain more confidence in the recommendations.

Pulmonary Function Test Abnormalities in Pediatric Inflammatory Bowel Disease.

BACKGROUND: Pulmonary involvement in adult patients with inflammatory bowel disease (IBD) seems more common than previously appreciated. Its prevalence and development over time in pediatric IBD patients are largely unknown. OBJECTIVES: The aim was to study lung function including fraction of exhaled nitric oxide (FeNO) and transfer capacity for carbon monoxide (TLCO) in pediatric IBD patients and to describe the longitudinal development in a subset of patients with lung function abnormalities. METHODS: Sixty-six measurements were made in 48 IBD patients (30 patients with Crohn's disease and 18 with ulcerative colitis) and 108 matched controls. Patients with abnormal TLCO or elevated residual volume/total lung capacity (RV/TLC) ratios were invited for a follow-up. Statistical comparisons were made by nonparametric tests and ANOVA. RESULTS: TLCO was decreased in IBD patients [median: 88% predicted (interquartile range, IQR, 22) vs. 99% predicted (IQR 19) in controls]. RV/TLC ratios were mildly elevated in patients with ulcerative colitis [32% (IQR 9) vs. 27% (IQR 8) in controls], and maximum expiratory flows at 50 and 25% of vital capacity were mildly reduced in patients with Crohn's disease. FeNO and disease activity did not correlate with lung function abnormalities. Abnormalities did not consistently persist over a median follow-up period of 34 months. CONCLUSIONS: This study supports evidence that variable and fluctuating pulmonary involvement also occurs in pediatric IBD patients. Its clinical significance is unclear.

Wrinkling of random and regular semiflexible polymer networks.

We investigate wrinkling of two-dimensional random and triangular semiflexible polymer networks under shear. Both types of semiflexible networks exhibit wrinkling above a small critical shear angle, which scales with an exponent of the bending modulus between 1.9 and 2.0. Random networks exhibit hysteresis at the wrinkling threshold. Wrinkling lowers the total elastic energy by up to 20% and strongly affects the elastic properties of all semiflexible networks such as the crossover between bending and stretching dominated behavior. In random networks, we also find evidence for metastable wrinkled configurations. While the disordered microstructure of random networks affects the scaling behavior of wrinkle amplitudes, it has little effect on wrinkle wavelength. Therefore, wrinkles represent a robust, microstructure-independent assay of shear strain or elastic properties.

In silico-guided target identification of a scaffold-focused library: 1,3,5-triazepan-2,6-diones as novel phospholipase A2 inhibitors.

A collection of 2150 druggable active sites from the Protein Data Bank was screened by high-throughput docking to identify putative targets for five representative molecules of a combinatorial library sharing a 1,3,5-triazepan-2,6-dione scaffold. Five targets were prioritized for experimental evaluation by computing enrichment in individual protein entries among the top 2% scoring targets. Out of the five proposed proteins, secreted phospholipase A2 (sPLA2) was shown to be a true target for a panel of 1,3,5-triazepan-2,6-diones which exhibited micromolar affinities toward two human sPLA2 members.

sc-PDB: an annotated database of druggable binding sites from the Protein Data Bank.

The sc-PDB is a collection of 6 415 three-dimensional structures of binding sites found in the Protein Data Bank (PDB). Binding sites were extracted from all high-resolution crystal structures in which a complex between a protein cavity and a small-molecular-weight ligand could be identified. Importantly, ligands are considered from a pharmacological and not a structural point of view. Therefore, solvents, detergents, and most metal ions are not stored in the sc-PDB. Ligands are classified into four main categories: nucleotides (< 4-mer), peptides (< 9-mer), cofactors, and organic compounds. The corresponding binding site is formed by all protein residues (including amino acids, cofactors, and important metal ions) with at least one atom within 6.5 angstroms of any ligand atom. The database was carefully annotated by browsing several protein databases (PDB, UniProt, and GO) and storing, for every sc-PDB entry, the following features: protein name, function, source, domain and mutations, ligand name, and structure. The repository of ligands has also been archived by diversity analysis of molecular scaffolds, and several chemoinformatics descriptors were computed to better understand the chemical space covered by stored ligands. The sc-PDB may be used for several purposes: (i) screening a collection of binding sites for predicting the most likely target(s) of any ligand, (ii) analyzing the molecular similarity between different cavities, and (iii) deriving rules that describe the relationship between ligand pharmacophoric points and active-site properties. The database is periodically updated and accessible on the web at http://bioinfo-pharma.u-strasbg.fr/scPDB/.

Comparative evaluation of eight docking tools for docking and virtual screening accuracy.

Eight docking programs (DOCK, FLEXX, FRED, GLIDE, GOLD, SLIDE, SURFLEX, and QXP) that can be used for either single-ligand docking or database screening have been compared for their propensity to recover the X-ray pose of 100 small-molecular-weight ligands, and for their capacity to discriminate known inhibitors of an enzyme (thymidine kinase) from randomly chosen "drug-like" molecules. Interestingly, both properties are found to be correlated, since the tools showing the best docking accuracy (GLIDE, GOLD, and SURFLEX) are also the most successful in ranking known inhibitors in a virtual screening experiment. Moreover, the current study pinpoints some physicochemical descriptors of either the ligand or its cognate protein-binding site that generally lead to docking/scoring inaccuracies.

Recovering the true targets of specific ligands by virtual screening of the protein data bank.

The Protein Data Bank (PDB) has been processed to extract a screening protein library (sc-PDB) of 2148 entries. A knowledge-based detection algorithm has been applied to 18,000 PDB files to find regular expressions corresponding to either protein, ions, co-factors, solvent, or ligand atoms. The sc-PDB database comprises high-resolution X-ray structures of proteins for which (i) a well-defined active site exists, (ii) the bound-ligand is a small molecular weight molecule. The database has been screened by an inverse docking tool derived from the GOLD program to recover the known target of four unrelated ligands. Both the database and the inverse screening procedures are accurate enough to rank the true target of the four investigated ligands among the top 1% scorers, with 70-100 fold enrichment with respect to random screening. Applying the proposed screening procedure to a small-sized generic ligand was much less accurate suggesting that inverse screening shall be reserved to rather selective compounds.

Evaluation of a noise reduction system for the assessment of click-evoked otoacoustic emissions.

A recently proposed noise reduction system intended to facilitate the assessment of click-evoked otoacoustic emission (CEOAE) in noisy environments [Comput. Biol. Med. 30, 341 (2000)] is evaluated using 13 normally hearing ears and 9 ears with a sensorineural hearing loss. The noise reduction system is based on an adaptive noise canceller design using an additional noise-only reference microphone and intended to reduce externally generated noise. The system is tested in quiet and at different levels of white noise. The three main design parameters of the noise reduction system (adaptation time constant, length of the adaptive filter, and position of the noise reference microphone) are varied systematically in different experiments. With the noise reduction system active, CEOAE can be assessed correctly at noise levels which are 5 to 9 dB higher than without the noise reduction system. For the range of adaptation time constants considered (65.6 to 656 ms), no statistically significant effect on the amount of noise reduction is observed. Noise reduction is highest when the reference microphone is positioned close to the ear probe. Using this reference microphone position and adaptive filters of 6.56 ms in length, average noise reductions of 7.17 to 8.50 dB are achieved.