Transcription Factor Binding Site Enrichment Analysis In Co-Expression Modules In Celiac Disease

The aim of this study was to construct celiac co-expression patterns at a whole genome level and to identify transcription factors (TFs) that could drive the gliadin-related changes in coordination of gene expression observed in celiac disease (CD). Differential co-expression modules were identified in the acute and chronic responses to gliadin using expression data from a previous microarray study in duodenal biopsies. Transcription factor binding site (TFBS) and Gene Ontology (GO) annotation enrichment analyses were performed in differentially co-expressed genes (DCGs) and selection of candidate regulators was performed. Expression of candidates was measured in clinical samples and the activation of the TFs was further characterized in C2BBe1 cells upon gliadin challenge. Enrichment analyses of the DCGs identified 10 TFs and five were selected for further investigation. Expression changes related to active CD were detected in four TFs, as well as in several of their in silico predicted targets. The activation of TFs was further characterized in C2BBe1 cells upon gliadin challenge, and an increase in nuclear translocation of CAMP Responsive Element Binding Protein 1 (CREB1) and IFN regulatory factor-1 (IRF1) in response to gliadin was observed. Using transcriptome-wide co-expression analyses we are able to propose novel genes involved in CD pathogenesis that respond upon gliadin stimulation, also in non-celiac models.The authors thank the technical and human support provided by SGIker of the UPV/EHU. The work was funded by ISCIII Research Project Grants PI13/01201 and PI16/00258, cofunded by the European Union ERDF/ESF "A way to make Europe" and by Basque Department of Health project 2011/111034 to JRB and Basque Department of Health project 2015/111068 to I.S., N.F.-J. was supported by an IARC Postodctoral Fellowship (FP7 Marie Curie Actions-People-COFUND) and a Postdoctoral Fellowship from the Basque Department of Education. I.R.-G. and A.J.-M. are supported by predoctoral fellowship grants from the UPV/EHU and the Basque Department of Education, respectively

A Novel Noninvasive Method Based on Salivary Inflammatory Biomarkers for the Screening of Celiac Disease

This study was supported by a grant from theSpanish Ministry of Science, Universities andInnovation (SAF2017-91873-EXP), a grant fromthe Department of Health from the BasqueGovernment (EJ-2017111082), and a researchfellowship from the Asociación de Celiacos ySensibles al Gluten de Madrid (A.C.R.). Alsosupported by a predoctoral fellowship from theUniversity of the Basque Country (M.S.dlC.) andthe Basque Government (A.O.G.)

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Nuevos criterios diagnósticos de la enfermedad celiaca: valoración de los marcadores genéticos e inmunológicos

166 p

Nuevos criterios diagnósticos de la enfermedad celiaca: valoración de los marcadores genéticos e inmunológicos

166 p

Bloqueo Perirrectal En Cirugía Anorrectal

Proctological pathologies affect approximately 5% of the entire population and have a negative impact on the effective performance of basic life activities, which is why the prevention, diagnosis and prompt management are a fundamental part of medical care provided by care staff. Anorectal surgery has evolved over the years due to the need to implement fast, effective and specific techniques that guarantee the timely and total recovery of patients for early hospital discharge, therefore, today the type of anesthesia that is used is the main focus of attention. Local anesthesia such as perirectal nerve block alone or combined with intravenous sedation has been the chosen approach because it guarantees patient comfort by significantly reducing side effects, pain and prolonged hospital stays. In this paper you will find a systematic review of specific data on perirectal blockade in anorectal surgery as an effective alternative to general or regional anesthesia in order to expand the associated knowledge and promote the optimization of the results achieved.Las patologías de origen proctológico afectan aproximadamente al 5% de toda la población y repercuten de manera negativa en la realización efectiva de las actividades básicas de la vida diaria por lo que su prevención, diagnóstico y manejo oportuno son pilar fundamental de la atención médica brindada por el personal asistencial. La cirugía anorrectal ha evolucionado a través de los años debido a la necesidad de implementar técnicas rápidas, eficaces y específicas que permitan garantizar la recuperación oportuna y total de los pacientes para el egreso hospitalario temprano por lo que, en la actualidad, el tipo de anestesia a emplear es de igual manera foco de atención principal. La anestesia local como el bloqueo perirrectal solo o combinado con analgosedación intravenosa ha sido el abordaje preferido debido a que logra garantizar la comodidad del paciente reduciendo de manera significativa los efectos secundarios, el dolor y las estancias hospitalarias prolongadas. En este documento se encontrará una revisión sistemática de datos específicos sobre el bloqueo perirrectal en cirugía anorrectal como alternativa eficaz de la anestesia general o regional con el fin de ampliar el conocimiento asociado y promover la optimización de los resultados alcanzados

Métodos de innovación docente aplicados a los estudios de Ciencias de la Comunicación

Se analiza el fenómeno de la implantación del Espacio Europeo de Educación Superior (EEES) a los estudios de Ciencias de la Comunicación, desde el punto de vista del profesorado. En este sentido se analizan experiencias educativas como: cuadernos de visionado para la iniciación de los alumnos en el comentario fílmico; la utilización didáctica de recursos audiovisuales; el uso de películas como herramientas en la educación de estudiantes; el uso de la televisión informativa; y la aplicación de técnicas de aprendizaje colaborativo entre otras propuestas. Asimismo, se estudia el estado de implantación del EEES en España y se describen propuestas de aplicación del mismo a diferentes áreas de los estudios de Ciencias de la Comunicación. También se dedican estudios a la descripción de nuevas estrategias docentes en el marco del EEES y se proponen fórmulas de evaluación de los aprendizajes. Por último se presta atención a la aplicación de las Tecnologías de la Información y la Comunicación a los citados estudios y se definen nuevas herramientas para apoyar a los estudiantes en su labor.MadridBiblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín 5 -3 Planta; 28014 Madrid; Tel. +34917748000; [email protected]

Natural History of Liver Disease in a Large International Cohort of Children with Alagille syndrome: Results from The <scp>GALA</scp> Study

Background: Alagille syndrome (ALGS) is a multisystem disorder, characterized by cholestasis. Existing outcome data are largely derived from tertiary centers and real-world data are lacking. This study aimed to elucidate the natural history of liver disease in a contemporary, international, cohort of children with ALGS. Methods: Multicenter retrospective study of children with a clinically and/or genetically confirmed ALGS diagnosis, born Jan-1997 - Aug-2019. Native liver survival (NLS) and event-free survival rates were assessed. Cox models were constructed to identify early biochemical predictors of clinically evident portal hypertension (CEPH) and NLS. Results: 1433 children (57% male) from 67 centers in 29 countries were included. 10 and 18-years NLS rates were 54.4% and 40.3%. By 10 and 18-years, 51.5% and 66.0% of ALGS children experienced ≥1 adverse liver-related event (CEPH, transplant or death). Children (>6 and ≤12 months) with median total bilirubin (TB) levels between ≥5.0 and 10.0 mg/dL were associated with a 4.8 (95% CI 2.4 - 9.7) and 15.6 (95% CI 8.7 - 28.2) increased risk of transplantation relative to <5.0 mg/dL. Median TB <5.0 mg/dL were associated with higher NLS rates relative to ≥5.0 mg/dL, with 79% reaching adulthood with native liver (p<0.001). Conclusions: In this large international cohort of ALGS, only 40.3% of children reach adulthood with their native liver. A TB <5.0 mg/dL between 6-and-12-months of age is associated with better hepatic outcomes. These thresholds provide clinicians with an objective tool to assist with clinical decision-making and in the evaluation of novel therapies

Optimization of adsorptive removal of α-toluic acid by CaO2 nanoparticles using response surface methodology

The present work addresses the optimization of process parameters for adsorptive removal of α-toluic acid by calcium peroxide (CaO2) nanoparticles using response surface methodology (RSM). CaO2 nanoparticles were synthesized by chemical precipitation method and confirmed by Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analysis which shows the CaO2 nanoparticles size range of 5–15 nm. A series of batch adsorption experiments were performed using CaO2 nanoparticles to remove α-toluic acid from the aqueous solution. Further, an experimental based central composite design (CCD) was developed to study the interactive effect of CaO2 adsorbent dosage, initial concentration of α-toluic acid, and contact time on α-toluic acid removal efficiency (response) and optimization of the process. Analysis of variance (ANOVA) was performed to determine the significance of the individual and the interactive effects of variables on the response. The model predicted response showed a good agreement with the experimental response, and the coefficient of determination, (R2) was 0.92. Among the variables, the interactive effect of adsorbent dosage and the initial α-toluic acid concentration was found to have more influence on the response than the contact time. Numerical optimization of process by RSM showed the optimal adsorbent dosage, initial concentration of α-toluic acid, and contact time as 0.03 g, 7.06 g/L, and 34 min respectively. The predicted removal efficiency was 99.50%. The experiments performed under these conditions showed α-toluic acid removal efficiency up to 98.05%, which confirmed the adequacy of the model prediction