Incidence and Paris Classification of pediatric inflammatory bowel disease

New epidemiological data suggest that the incidence of inflammatory bowel disease (IBD) is increasing. As a result the burden of disease accounts for more strains to the health care system. The clinical variability queries whether disease characteristics are related to clinical outcome. Our aim was to delineate the latest results of incidence trends in pediatric IBD and to compare the first experiences with Paris Classification. Incidence of pediatric IBD has been increasing in Western Europe and in Eastern Europe. To better characterize IBD, Paris Classification was introduced and validated recently. Ileocolonic involvement is the most characteristic disease location in Crohn's disease (CD) based on applying Paris Classification. The rate of perianal disease and complicated behaviour in CD was similar. It is of interest that CD patients with colonic involvement were less likely to have stricturing disease compared with patients with ileal involvement. In addition, pancolitis dominated in ulcerative colitis (UC). However, most countries lack prospective, nationwide epidemiological studies to estimate incidence trends. This review emphasizes the importance of nationwide registries that enroll all pediatric IBD cases serving reliable data for "everyday practice." These first reports have shown that Paris Classification is a useful tool to determine the pediatric IBD phenotype

Foreign body impaction in the sigmoid colon

Foreign body ingestion is a common clinical problem in early childhood. However, it may occur even in adults, unknowingly. Most ingested foreign bodies entering the stomach pass through the gastrointestinal tract uneventfully. Here we report on a 13-year-old boy who presented with chronic abdominal pain, weight loss and occult gastrointestinal bleeding for 6 mo. Colonoscopy was negative; however, a ballpoint pen was impacted in the sigmoid region. Subsequently, the child admitted swallowing a pen as a 20-euro bet 6 mo previously. Crohn's disease is a chronic relapsing inflammatory gastrointestinal disease. It is often difficult to diagnose due to the fact that there is no single pathognomonic sign or symptom. This case is a description of an adolescent with chronic gastrointestinal symptoms due to a foreign body. Therefore, an ingested foreign body should be included in the differential diagnostic procedure related to gastrointestinal symptoms

Micellák szénhidrogén/víz határrétegének és héjszerkezetének tanulmányozása statikus kisszögű- és dinamikus szórással = Investigation of the structure of the hydrocarbon/water interface and of the shell of micelles by static small-angle and dynamic scattering

(1) Az alkáli-alkil-szulfátok H2O- és D2O micelláris oldatából származó kisszögű röntgenszórási spektrumok izotópeffektusát a micella szórási kontraszteloszlásának újszerű modellezésével és illesztésével értelmeztük. Az illesztéssel nem dönthető el, hogy a micellák elnyújtott vagy összenyomott ellipszoidok; egy közelítő termodinamikai modell azonban az elnyújtott formát valószínűsíti. A modell pontosítása céljábó meghatároztuk az intramicelláris szórócentrumok struktúra-faktorát. (2) Az intermicelláris struktúra-faktorok elemzése azt mutatta, hogy a micelláris magot egy ~1 nm vastag "merev" vízréteg veheti körül. Kvázi-elasztikus neutronszórással az oldószerben kimutattunk egy lassan diffundáló komponenst, amely megfeleltethető volt a "merev" vízrétegnek. Az eredményeket gradiens NMR technikával megerősítettük, és valószínűsítettük, hogy a jelenséget a vízmolekulák és a lassú tenzid-monomerek fejcsoportjai között kialakult hidrogénkötés okozza. (3) Az etoxilált nonil-fenol micellák transzporttulajdonságainak tanulmányozása arra a konklúzióra vezetett, hogy az etoxiszám függvényében a hidrofil etoxiláncok konformációja fázisátalakulásra emlékeztető változást szenved. Az ABA és BAB szekvenciájú triblokk kopolimermicellák kisszögű neutron- és röntgenszórásképének összehasonlításából megállapítottuk, hogy a hidrofil láncok a blokkszekvenciától függetlenül azonos statisztikus tulajdonságokkal rendelkeznek. | (1) Solvent isotope effect was observed in small-angle X-ray scattering patterns from H2O and D2O solutions of alkali alkyl sulphate micelles and was interpreted in terms of a novel model fitted to the scattering patterns in a novel way. The fit could not decide whether the micelles are prolate or oblate ellipsoids; an approximate thermodynamic model, however, renders the prolate shape more probable. As a first step to improve the model, the structure factor of the intramicellar scatterers also has been calculated. (2) Parameters of the intermicellar structure factors suggest that the cores may be covered by 'stiff' water layers of ~1 nm thickness. A slowly diffusing water component was found by quasi-elastic neutron scattering and was confirmed by gradient NMR technique. This component could be identified as the 'stiff' layer and its formation was explained by hydrogen bonds formed between the water molecules and the head-groups of the slow, micelle forming, monomers. (3) Studying the transport properties of ethoxylated nonil phenol micelles led to the conclusion that, in function of the ethoxy number, the conformation of the hydrophilic ethoxy chains exerts a change resembling phase transition. By comparing small-angle neutron- and X-ray scattering patterns from solutions of ABA and BAB type triblock copolymer micelles we concluded that, regardless of the block sequence, the hydrophilic chains have the same statistical properties

New serological markers in pediatric patients with inflammatory bowel disease

The spectrum of serological markers associated with inflammatory bowel disease (IBD) is rapidly growing. Due to frequently delayed or missed diagnoses, the application of non-invasive diagnostic tests for IBD, as well as differentiation between ulcerative colitis (UC) and Crohn's disease (CD), would be useful in the pediatric population. In addition, the combination of pancreatic autoantibodies and antibodies against Saccharomyces cerevisiae antibodies/perinuclear cytoplasmic antibody (pANCA) improved the sensitivity of serological markers in pediatric patients with CD and UC. Some studies suggested that age-associated differences in the patterns of antibodies may be present, particularly in the youngest children. In CD, most patients develop stricturing or perforating complications, and a significant number of patients undergo surgery during the disease course. Based on recent knowledge, serum antibodies are qualitatively and quantitatively associated with complicated CD behavior and CD-related surgery. Pediatric UC is characterized by extensive colitis and a high rate of colectomy. In patients with UC, high levels of anti-CBir1 and pANCA are associated with the development of pouchitis after ileal pouch-anal anastomosis. Thus, serologic markers for IBD can be applied to stratify IBD patients into more homogeneous subgroups with respect to disease progression. In conclusion, identification of patients at an increased risk of rapid disease progression is of great interest, as the application of early and more aggressive pharmaceutical intervention could have the potential to alter the natural history of IBD, and reduce complications and hospitalizations

The mutational signatures of formalin fixation on the human genome

Clinical archives of patient material near-exclusively consist of formalin-fixed and paraffin-embedded (FFPE) blocks. The ability to precisely characterise mutational signatures from FFPE-derived DNA has tremendous translational potential. However, sequencing of DNA derived from FFPE material is known to be riddled with artefacts. Here we derive genome-wide mutational signatures caused by formalin fixation. We show that the FFPE-signature is highly similar to signature 30 (the signature of Base Excision Repair deficiency due to NTHL1 mutations), and chemical repair of DNA lesions leads to a signature highly similar to signature 1 (clock-like signature due to spontaneous deamination of methylcytosine). We demonstrate that using uncorrected mutational catalogues of FFPE samples leads to major mis-assignment of signature activities. To correct for this, we introduce FFPEsig, a computational algorithm to rectify the formalin-induced artefacts in the mutational catalogue. We demonstrate that FFPEsig enables accurate mutational signature analysis both in simulated and whole-genome sequenced FFPE cancer samples. FFPEsig thus provides an opportunity to unlock additional clinical potential of archival patient tissues.Peer reviewe

Granulomák előfordulási gyakorisága és szerepe 368 Crohn-beteg gyermekben

Bevezetés: A granulomák kulcsszerepet töltenek be a gyulladásos bélbetegségek diagnosztikájában. Nem tisztázott azonban jelentőségük a Crohn-betegség patogenezisében és klinikai megjelenésében. Célkitűzés: A szerzők célul tűzték ki a granulomák gyakoriságának és jelentőségének meghatározását a Magyar Gyermekkori Gyulladásos Bélbetegség Regiszter alapján. Módszer: 2007. január 1. és 2010. december 31. között 368 Crohn-beteg adatait elemezték. Eredmények: A granulomák gyakorisága a diagnóziskor 31,4% (111/353) volt. A granulomák izolált megjelenése a felső gastrointestinalis rendszerben 2,5%, a terminalis ileumban 5% volt. A granulomás és a nem granulomás csoport között nem volt eltérés a fenotípusban és aktivitási indexben. Az immunmoduláns és a biológiai kezelés gyakorisága hasonló volt a két csoportban. Következtetések: A granulomák gyakorisága hazánkban megegyezik a nemzetközi tapasztalatokkal. Kiemelendő, hogy a terminalis ileumban vagy a felső gastrointestinalis rendszerben izoláltan talált granulomák 13 Crohn-beteg gyermekből egynél járultak hozzá a diagnózis felállításához. Ezek az adatok felhívják a figyelmet arra, hogy a béltraktus minden szegmenséből vett többszörös biopsziás mintavétel a diagnózis felállításához nélkülözhetetlen. Orv. Hetil., 2013, 154, 1702–1708

MEANS: python package for Moment Expansion Approximation, iNference and Simulation.

MOTIVATION: Many biochemical systems require stochastic descriptions. Unfortunately these can only be solved for the simplest cases and their direct simulation can become prohibitively expensive, precluding thorough analysis. As an alternative, moment closure approximation methods generate equations for the time-evolution of the system's moments and apply a closure ansatz to obtain a closed set of differential equations; that can become the basis for the deterministic analysis of the moments of the outputs of stochastic systems. RESULTS: We present a free, user-friendly tool implementing an efficient moment expansion approximation with parametric closures that integrates well with the IPython interactive environment. Our package enables the analysis of complex stochastic systems without any constraints on the number of species and moments studied and the type of rate laws in the system. In addition to the approximation method our package provides numerous tools to help non-expert users in stochastic analysis. AVAILABILITY AND IMPLEMENTATION: https://github.com/theosysbio/means CONTACTS: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Multivariate moment closure techniques for stochastic kinetic models.

Stochastic effects dominate many chemical and biochemical processes. Their analysis, however, can be computationally prohibitively expensive and a range of approximation schemes have been proposed to lighten the computational burden. These, notably the increasingly popular linear noise approximation and the more general moment expansion methods, perform well for many dynamical regimes, especially linear systems. At higher levels of nonlinearity, it comes to an interplay between the nonlinearities and the stochastic dynamics, which is much harder to capture correctly by such approximations to the true stochastic processes. Moment-closure approaches promise to address this problem by capturing higher-order terms of the temporally evolving probability distribution. Here, we develop a set of multivariate moment-closures that allows us to describe the stochastic dynamics of nonlinear systems. Multivariate closure captures the way that correlations between different molecular species, induced by the reaction dynamics, interact with stochastic effects. We use multivariate Gaussian, gamma, and lognormal closure and illustrate their use in the context of two models that have proved challenging to the previous attempts at approximating stochastic dynamics: oscillations in p53 and Hes1. In addition, we consider a larger system, Erk-mediated mitogen-activated protein kinases signalling, where conventional stochastic simulation approaches incur unacceptably high computational costs