Interleukin 18 maintains a long-standing inflammation in coeliac disease patients

Producción CientíficaDietary gluten induces an early response in the intestine of coeliac disease patients (CD), within a few hours, and this is driven by high levels of proinflammatory cytokines, including IFNg and IL-15, as has been thoroughly shown by gluten stimulation of biopsy explants. Our aim was to identify the immune mediators involved in the long-standing inflammation in untreated CD patients at diagnosis. mRNA and protein levels of TNFa, IL-12(p35), IL-12(p40), IL-15, IL-18 and IL-23(p19) were quantified in biopsies from active CD patients, CD patients on a gluten-free diet (GFD), healthy controls, and patients with non-CD inflammation and mild histological changes in the intestine. Biopsies from CD patients on a GFD were also stimulated in vitro with gliadin, and protein expression of IL-15 and IL-18 was analysed. Levels of IL-12 and IL-23 mRNA are nearly absent, and TNFa levels remain unchanged among different groups. Both the active and inactive forms of IL-18 protein have been found in all samples from active CD, and protein expression was only localized within the crypts. Levels of IL-15 mRNA remain unchanged, and protein expression, localized within the lamina propria, is found in a small number of samples. In vitro stimulation with gluten induces the expression of IL-15 and IL-18. In active CD, the early response following gluten intake characterized by high IFNg levels is driven by IL-18, and probably IL-15, and this alternates with periods of long-standing inflammation with moderate IFNg levels, maintained by IL-18 alone

Interleukin 18 maintains a long-standing inflammation in coeliac disease patients

Producción CientíficaDietary gluten induces an early response in the intestine of coeliac disease patients (CD), within a few hours, and this is driven by high levels of proinflammatory cytokines, including IFNg and IL-15, as has been thoroughly shown by gluten stimulation of biopsy explants. Our aim was to identify the immune mediators involved in the long-standing inflammation in untreated CD patients at diagnosis. mRNA and protein levels of TNFa, IL-12(p35), IL-12(p40), IL-15, IL-18 and IL-23(p19) were quantified in biopsies from active CD patients, CD patients on a gluten-free diet (GFD), healthy controls, and patients with non-CD inflammation and mild histological changes in the intestine. Biopsies from CD patients on a GFD were also stimulated in vitro with gliadin, and protein expression of IL-15 and IL-18 was analysed. Levels of IL-12 and IL-23 mRNA are nearly absent, and TNFa levels remain unchanged among different groups. Both the active and inactive forms of IL-18 protein have been found in all samples from active CD, and protein expression was only localized within the crypts. Levels of IL-15 mRNA remain unchanged, and protein expression, localized within the lamina propria, is found in a small number of samples. In vitro stimulation with gluten induces the expression of IL-15 and IL-18. In active CD, the early response following gluten intake characterized by high IFNg levels is driven by IL-18, and probably IL-15, and this alternates with periods of long-standing inflammation with moderate IFNg levels, maintained by IL-18 alone

Natural history of irritable bowel syndrome

Producción CientíficaIBS). The aim of this study was to investigate the presence of chronic functional digestive symptoms in childhood, interviewing adult patients diagnosed with IBS, in an attempt to establish a relationship between them. METHODS: By means of a questionnaire, the history of colic, chronic diarrhea, functional abdominal pain, constipation and migraine in childhood, was analyzed in patients diagnosed with IBS according to the current Rome III criteria, and in control patients without known chronic digestive disorders. Fisher's exact test was used for comparison of frequencies. RESULTS: The IBS study group was made up of 40 patients (24 women; average age, 33.03 years), and the control group by 40 adults (22 women; average age, 29.62 years). IBS-diagnosed adults spoke about a significantly higher prevalence of chronic diarrhea (32.5/7.5%; odds ratio [OR], 7.01; 95% confidence interval [CI]: 26.84-1.80), and FAP (37.5/15%; OR, 4.30; 95%CI: 12.67-1.43) in their childhood, than the control group. There were no differences in the presence of other childhood functional symptoms. Interestingly, the present patients, when asked about the onset of symptoms that led to the diagnosis of IBS, referred to them mostly beginning in adulthood, not linking their current diagnosis of IBS with their background in childhood. In a proportion of adults with IBS the natural history of their symptoms probably began during their childhood.(IBS). The aim of this study was to investigate the presence of chronic functional digestive symptoms in childhood, interviewing adult patients diagnosed with IBS, in an attempt to establish a relationship between them. By means of a questionnaire, the history of colic, chronic diarrhea, functional abdominal pain, constipation and migraine in childhood, was analyzed in patients diagnosed with IBS according to the current Rome III criteria, and in control patients without known chronic digestive disorders. Fisher's exact test was used for comparison of frequencies. The IBS study group was made up of 40 patients (24 women; average age, 33.03 years), and the control group by 40 adults (22 women; average age, 29.62 years). IBS-diagnosed adults spoke about a significantly higher prevalence of chronic diarrhea (32.5/7.5%; odds ratio [OR], 7.01; 95% confidence interval [CI]: 26.84-1.80), and FAP (37.5/15%; OR, 4.30; 95%CI: 12.67-1.43) in their childhood, than the control group. There were no differences in the presence of other childhood functional symptoms. Interestingly, the present patients, when asked about the onset of symptoms that led to the diagnosis of IBS, referred to them mostly beginning in adulthood, not linking their current diagnosis of IBS with their background in childhood. In a proportion of adults with IBS the natural history of their symptoms probably began during their childhood

Accuracy of urea breath test performed immediately after emergency endoscopy in peptic ulcer bleeding

Producción CientíficaThe aim of this work is to investigate the accuracy of the urea breath test (UBT) performed immediately after emergency endoscopy in peptic ulcer bleeding (PUB). METHODS: Urea breath test was carried out right after emergency endoscopy in patients with PUB. The accuracy of this early UBT was compared to a delayed one after hospital discharge that was considered the gold standard. Clinical and epidemiological factors were analyzed in order to study their influence on the accuracy of the early UBT. RESULTS: Early UBT was collected without any complication and good acceptance from all the 74 patients included. In 53 of the patients (71.6%), a delayed UBT was obtained. Comparing concordance between the two tests we have calculated an accuracy of 83% for the early UBT. Sensibility and specificity were 86.36 and 66%, respectively, with a positive predictive value of 92.68% and negative predictive value of 50% (Kappa index = 0.468; p = 0.0005; CI: 95%). We found no influence of epidemiological factors, clinical presentation, drugs, times to gastroscopy, Forrest classification, endoscopic therapy, hemoglobin, and urea levels over the accuracy of early UBT. CONCLUSIONS: Urea breath test carried out right after emergency endoscopy in PUB is an effective, safe, and easy-to-perform procedure. The accuracy of the test is not modified by clinical or epidemiological factors, ulcer stage, or by the type of therapy applied. However, we have found a low negative predictive value for early UBT, so a delayed test is mandatory for all negative cases

Is it true coeliacs do not digest gliadin ?. Degradation pattern of gliadin in coeliac disease small intestinal mucosa

Prolyl-endopeptidase supplementation has been proposed to favour gliadin degradation as an alternative treatment for coeliac disease (CD), although the real usefulness of this therapy in vivo is still under discussion. 1 However, our data point to alternative treatments aiming to modify the intestinal microbiota in patients with CD by the use of probiotics and/or prebiotics. We propose that the induction of gliadin proteolysis in the human gut might not be the solution but the origin of CD

Implementación Multi-FPGA de modelos articiales del cerebro

Proyecto de investigación (Código: 1360013) Instituto Tecnológico de Costa Rica. Vicerrectoría de Investigación y Extensión (VIE). Escuela de Ingeniería Electrónica, 2019A research and development project has been completed. The project has been nanced and supported by Vicerrector a de Investigaci on y Extensi on, Vicerrector a de Docencia and Escuela de Ingenier a Electr onica from Tecnológico de Costa Rica, and the Neuroscience Department at Erasmus Medical Center, Rotterdam, the Netherlands This project intended to develop the base of a massive FPGA-based simulation network for biologically-meaningful brain modeling. The network is able to model di erent models of biologically-accurate arti cial neural networks. An accessible Web-based platform provides access for researchers interested in using the platform for their studies Neuroscience, and related elds. The nal result of the project is a exible, scalable, Multi-FPGA board platform, accessible via a web graphic interface, including three neural models tipically used in neuroscience. The project has produced three Scopus-indexed publications. Published results show that the platform is competitive against similar platforms recently reported in the literature.Se ha concluido un proyecto de investigación y desarrollo financiado y apoyado por la Vicerrectoría de Investigación y Extensión, la Vicerrectoría de Docencia y la Escuela de Ingeniería Electrónica del Tecnológico de Costa Rica, el Departamento de Neurociencia del Centro Médico Erasmus en Rotterdam, Países Bajos. Este proyecto pretendía desarrollar una red masiva basada en FPGAs para simulaciones biológicamente significativas de modelos cerebrales. La red debía ser capaz de modelar distintos modelos de redes neuronales biológicamente precisas. Una interfaz Web proveería de acceso a investigadores en el mundo entero que quieran usar la plataforma para sus estudios en neurociencia. El resultado final incluye una plataforma flexible y escalable de varias tarjetas con sistemas FPGA, accesible vía una interfaz gráfica, y que trae ya integrados los tres modelos neuronales usados típicamente por los investigadores en neurociencia. El proyecto ha producido tres publicaciones indexadas Scopus. Los resultados publicados muestras que la plataforma es competitiva cuando se compara con plataformas similares recientemente reportadas en la literatura

Five Patients with Disorders of Calcium Metabolism Presented with GCM2 Gene Variants

The GCM2 gene encodes a transcription factor predominantly expressed in parathyroid cells that is known to be critical for development, proliferation and maintenance of the parathyroid cells. A cohort of 127 Spanish patients with a disorder of calcium metabolism were screened for mutations by Next-Generation Sequencing (NGS). A targeted panel for disorders of calcium and phosphorus metabolism was designed to include 65 genes associated with these disorders. We observed two variants of uncertain significance (p.(Ser487Phe) and p.Asn315Asp), one likely pathogenic (p.Val382Met) and one benign variant (p.Ala393_Gln395dup) in the GCM2 gene in the heterozygous state in five families (two index cases had hypocalcemia and hypoparathyroidism, respectively, and three index cases had primary hyperparathyroidism). Our study shows the utility of NGS in unravelling the genetic origin of some disorders of the calcium and phosphorus metabolism, and confirms the GCM2 gene as an important element for the maintenance of calcium homeostasis. Importantly, a novel variant in the GCM2 gene (p.(Ser487Phe)) has been found in a patient with hypocalcemia.This study was supported by three grants from the Department of Health (2017111014, 2018111097 and 2019111052) and one grant from the Department of Education (IT1281-19) of the Basque Government. This work is generated within the Endocrine European Reference Network (Project ID number of Endo-ERN: 739527). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Paleoecología y cultura material en el complejo tumular prehistórico de Castillejo del Bonete (Terrinches, Ciudad Real)

Castillejo del Bonete es un complejo tumular situado en el borde meridional de la Meseta Ibérica, ocupado en fechas calcolíticas y de la Edad del Bronce, vinculado a la Cultura de las Motillas. Materiales arqueológicos muy diversos han sido recuperados asociados a las arquitecturas del lugar (túmulos, corredores, potentes muros, etc.). Se presenta un avance de la investigación paleoecológica sobre las colecciones de carbón, polen y microvertebrados. Además se presentan cuentas de piedra y madera, colgantes de concha, material lítico, la colección cerámica, nuevas metalografías e industria metálica y botones de marfil. El conjunto de estas evidencias arqueológicas pone de manifiesto la celebración ritual de banquetes y ofrendas durante la Prehistoria Reciente en una cueva monumentalizada mediante túmulos en el interior de la Península Ibérica

Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain. MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients. ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 +/- 12 vs. 54 +/- 16 years, p < 0.001), had been diagnosed younger (31 +/- 12 vs. 36 +/- 15 years, p < 0.001), and had a shorter disease duration (14 +/- 7 vs. 18 +/- 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92-2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0-1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses. ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe

Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

The authors wish to make the following corrections to this paper [...]