Sindbisactivated ISRE-binding complexes in mice- and chickencells

Um die Verdteidigungsmechanismen der Wirtszelle gegen Sindbisvirusinfektion zu charakterisieren, haben wir in den Extrakten infizierter Zellen. Interferon(IFN)- stimulated- response- element (ISRE)- Bindungsproteine untersucht, welche in der transkriptionellen Induktion von IFN Typ I induzierter Gene beteiligt sind. Mittels Gelretentionsanalyse in der ein humanes Interferon-stimuliertes Gen 15 ( ISG15 ) Verwendung fand, wiesen wir in Extrakten von sindbisinfizierten L-929 Zellen verschiedene Proteinkomplexe nach, die nicht in Extrakten uninfizierter Zellen nachweisbar waren. Übereinstimmung im Laufverhalten mit Extrakten NDV-infizierter Zellen, und in Antikörperversuchen zeigt, dass die sindbisinduzierten Komplexe in L-929 Zellen den bekannten DRAF1 und ISGF3 entsprechen. DRAF1 konnte nach in Sindbisinfektion in Mäuseembryofibroblasten, welche keinen Interferonrezeptor mehr besaßen, nachgewiesen werden.To elucidate the host cell defense mechanisms in response to Sindbis viral infection, we have started to characterize interferon (IFN)-stimulated response element (ISRE)-binding proteins activated in infected cells that are involved in the transcriptional induction of IFN type I-inducible genes. Using electromobility shift assays (EMSA), we detected several protein complexes with a human IFN-stimulated gene 15 (ISG15) ISRE in extracts from virus-infected L929 cells that were absent in extracts from uninfected cells. Comigration with Newcastle disease virus-activated ISRE-binding complexes, supershift experiments, and conditions of formation indicate that the complexes activated by Sindbis viral infection in L929 cells correspond to DRAF1 and ISG factor 3 (ISGF3) ISGF3. DRAF1 could be detected in Sindbis virus-infected mouse embryo fibroblasts derived from IFNR type I and type II KO mice

Catheter interventional treatment of congenital portosystemic venous shunts in childhood

OBJECTIVES: The study aimed on the catheter interventional treatment of congenital portosystemic venous shunt (CPSVS) in childhood and the impact on vascular growth of hypoplastic portal veins. Clinical course and follow up of partial or complete closure of CPSVS are described. BACKGROUND: CPSVS is a very rare vascular malformation of the portal venous drainage resulting in potentially life threatening abdominal, pulmonary, cerebral, and cardiac complications. The anatomic type, clinical course, and diagnosis must be determined for optimal management. METHODS: Single centre case series. RESULTS: Eight (6 female) children with extrahepatic (n = 5) and intrahepatic (n = 3) CPSVS were diagnosed invasively by catheterization, including test balloon occlusion of the shunt and simultaneous retrograde angiography, and treated by catheter interventions (n = 5) with partial (n = 2) and complete (n = 3) occlusion of CPSVS at a median age of 3.9 years (range 0.7-21). Congenital heart disease (CHD) was the most frequent associated organ manifestation (n = 5) followed by mild to severe pulmonary arterial hypertension (n = 4), hepatopulmonary syndrome (n = 2), and portosystemic encephalopathy (n = 1). CHD was simple (n = 3) or complex type (n = 2). Three patients were untreated so far, because they were in excellent clinical condition at an age <1 year, refused treatment, or planned for later treatment. CONCLUSIONS: Accurate invasive diagnosis of CPSVS with test balloon occlusion of the shunt is mandatory to depict the anatomic situation. Catheter interventional treatment of CPSVS offers a feasible and safe approach with complete or partial closure of the vascular malformation inducing potentially significant vascular growth of a former hypoplastic portal venous system. © 2015 Wiley Periodicals, Inc

Coping is excellent in Swiss Children with inflammatory bowel disease: Results from the Swiss IBD cohort study

BACKGROUND: Inflammatory bowel disease (IBD) starting during childhood has been assumed to impair quality of life (QoL) of affected children. As this aspect is crucial for further personality development, the health-related quality of life (HRQOL) was assessed in a Swiss nationwide cohort to obtain detailed information on the fields of impairment. METHODS: Data were prospectively acquired from pediatric patients included in the Swiss IBD Cohort Study. IBD activity was evaluated by PCDAI and PUCAI. The age adapted KIDSCREEN questionnaire was evaluated for 110 children with IBD (64 with Crohn's disease 46 with ulcerative colitis). Data were analyzed with respect to established reference values of healthy controls. RESULTS: In the KIDSCREEN index a moderate impairment was only found for physical wellbeing due to disease activity. In contrast, mental well-being and social support were even better as compared to control values. A subgroup analysis revealed that this observation was restricted to the children in the German speaking part of Switzerland, whereas there was no difference compared to controls in the French part of Switzerland. Furthermore, autonomy and school variables were significantly higher in the IBD patients as compared to controls. CONCLUSIONS: The social support for children with IBD is excellent in this cohort. Only physical well-being was impaired due to disease activity, whereas all other KIDSCREEN parameters were better as compared to controls. This indicates that effective coping and support strategies may be able to compensate the burden of disease in pediatric IBD patients

Similar occurrence of febrile episodes reported in non-atopic children at three to five years of age after prebiotics supplemented infant formula

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday

Similar occurrence of febrile episodes reported in non-atopic children at three to five years of age after prebiotics supplemented infant formula

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday

Somatic mosaicism and common genetic variation contribute to the risk of very-early-onset inflammatory bowel disease

Very-early-onset inflammatory bowel disease (VEO-IBD) is a heterogeneous phenotype associated with a spectrum of rare Mendelian disorders. Here, we perform whole-exome-sequencing and genome-wide genotyping in 145 patients (median age-at-diagnosis of 3.5 years), in whom no Mendelian disorders were clinically suspected. In five patients we detect a primary immunodeficiency or enteropathy, with clinical consequences (XIAP, CYBA, SH2D1A, PCSK1). We also present a case study of a VEO-IBD patient with a mosaic de novo, pathogenic allele in CYBB. The mutation is present in ~70% of phagocytes and sufficient to result in defective bacterial handling but not life-threatening infections. Finally, we show that VEO-IBD patients have, on average, higher IBD polygenic risk scores than population controls (99 patients and 18,780 controls; P &lt; 4 × 10-10), and replicate this finding in an independent cohort of VEO-IBD cases and controls (117 patients and 2,603 controls; P &lt; 5 × 10-10). This discovery indicates that a polygenic component operates in VEO-IBD pathogenesis