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Background: Iron deficiency (ID) without anaemia is a common comorbidity associated with inflammatory bowel disease (IBD) that has a negative impact on health-related quality of life (HRQoL). Methods: This multicentre, prospective, observational study examined the response to, safety of and impact on HRQoL of a single 500 mg dose of intravenous ferric carboxymaltose (FCM) in patients with IBD and ID without anaemia. The diagnostic criteria for ID were low serum ferritin (

La celebración de campañas de sensibilización sobre discapacidad nace para visibilizar en la sociedad las dificultades que afrontan diariamente personas con condiciones diferentes a las de las personas de desarrollo normotípico. El objetivo del presente estudio es analizar el impacto en Twitter de diez campañas españolas sobre discapacidad, celebradas entre 2013 y 2020. Para ello, se ha utilizado Trendinalia para determinar la cantidad, posición y duración de los trending topic (TT) generados; y una herramienta de análisis de sentimientos en Twitter para determinar la valencia positiva, neutra o negativa de los tuits. Los resultados demuestran el éxito cuantitativo de las campañas en Twitter, aunque su impacto no es uniforme para todas las campañas. A nivel cualitativo, aunque de manera general los tuits de todas las campañas presentan más connotaciones positivas que negativas, en algunas conversaciones la mayor cantidad de mensajes presentan un tono neutro. El análisis de los resultados permite concluir que la discapacidad es un tema interesante para la comunidad de Twitter y que es importante llevar a cabo iniciativas como estas campañas para proporcionar voz a las personas con discapacidad. Los resultados obtenidos pueden ser de utilidad para orientar la implementación de estrategias de éxito para futuras campañas.

AIM: Stricture is one of the main complications of Crohn's disease (CD). Among the main conservative therapeutic alternatives, endoscopic balloon dilation (EBD) of the strictures stands out, which can improve the symptoms and delay or even avoid the need for more surgeries. The main aim of this study was to evaluate the efficacy of the EBD in CD patients with post-surgical anastomotic strictures from a previous surgery. PATIENTS AND METHODS: An observational study of a cohort of 32 patients with CD who underwent EBD due to uncomplicated strictures at a tertiary hospital, since 2009. Demographic, clinical and disease variables, medical treatments and previous surgeries and types, analytical variables at the time of dilation, number of dilations, complications and need for subsequent surgery were collected by searching data in clinical records. RESULTS: Thirty-two patients were included, performing a total of 63 endoscopic dilations. A technical success of 63.5%, a therapeutic success by dilation of 58.75% and a therapeutic success per patient of 62.5% were achieved. Regarding complications, the percentage of post-dilation adverse events was 3.2% and post-dilation incidents were 4.8%. Thirty EBD did not need any medical treatment modification, 9 EBD remained untreated and 12 EBD required further surgery. The length of the strictures, but not the ongoing treatment, was the only statistically significant factor of therapeutic success by dilation and per patient. CONCLUSIONS: EBD seems a safe technique in short post-surgical strictures, can avoid the need for new surgery and prevents unnecessary immunosuppression in patients with CD anastomotic strictures.

We aim to describe the incidence and source of contagion of COVID-19 in patients with IBD, as well as the risk factors for a severe course and long-term sequelae. This is a prospective observational study of IBD and COVID-19 included in the ENEIDA registry (53,682 from 73 centres) between March-July 2020 followed-up for 12 months. Results were compared with data of the general population (National Centre of Epidemiology and Catalonia). A total of 482 patients with COVID-19 were identified. Twenty-eight percent were infected in the work environment, and 48% were infected by intrafamilial transmission, despite having good adherence to lockdown. Thirty-five percent required hospitalization, 7.9% had severe COVID-19 and 3.7% died. Similar data were reported in the general population (hospitalisation 19.5%, ICU 2.1% and mortality 4.6%). Factors related to death and severe COVID-19 were being aged >= 60 years (OR 7.1, 95% CI: 1.8-27 and 4.5, 95% CI: 1.3-15.9), while having >= 2 comorbidities increased mortality (OR 3.9, 95% CI: 1.3-11.6). None of the drugs for IBD were related to severe COVID-19. Immunosuppression was definitively stopped in 1% of patients at 12 months. The prognosis of COVID-19 in IBD, even in immunosuppressed patients, is similar to that in the general population. Thus, there is no need for more strict protection measures in IBD. This study is funded by the Carlos III Health Institute (COV20/00227: Co-IP Dra. Maria Esteve and Dra. Yamile Zabana), FEDER (Fondo Europeo de Desarrollo Regional) and supported by GETECCU. The ENEIDA Registry of GETECCU is supported by Takeda, Pfizer, Galapagos, AbbVie and Biogen.

Background Optimal thresholds for golimumab concentrations during maintenance for important outcomes are lacking. Aim The aim of the study was to investigate the association of golimumab trough concentrations during maintenance with key outcomes, including endoscopic and histologic remission, and long-term event-free persistence with golimumab, in patients with UC. Methods This multicentre, cross-sectional study included UC patients on golimumab maintenance recruited either in remission or during a flare. Colonoscopy was scheduled, and study-specific rectocolonic biopsies were taken for blind central histologic reading. Samples for golimumab trough concentrations were collected close to colonoscopy. Results Fifty-two patients were included. Median golimumab trough concentrations (mu g/ml) were significantly higher in patients who had clinical remission (2.01 vs. 0.72, p = 0.047), combined clinical-biochemical remission (PMS

BACKGROUND: Studies to evaluate the use of mycophenolate mofetil (MMF) in inflammatory bowel disease (IBD) are limited after the appearance of biological treatments. AIMS: Our primary objective was to evaluate the effectiveness and safety of MMF in IBD. METHODS: IBD patients who had received MMF were retrieved from the ENEIDA registry. Clinical activity as per the Harvey-Bradshaw Index (HBI), partial Mayo score (pMS), physician global assessment (PGA) and C-reactive protein (CRP) were reviewed at baseline, at 3 and 6 months, and at final follow-up. Adverse events and causes of treatment discontinuation were documented. RESULTS: A total of 83 patients were included (66 Crohn's disease, 17 ulcerative colitis), 90% of whom had previously received other immunosuppressants. In 61% of patients systemic steroids were used at initiation of MMF, and in 27.3% biological agents were co-administered with MMF. Overall clinical effectiveness was observed in 64.7% of the population. At the end of treatment, 45.6% and 19.1% of subjects showed remission and clinical response, respectively. MMF treatment was maintained for a median of 28.9 months (IQR: 20.4-37.5). CONCLUSION: Our study suggests, in the largest cohort to date, that MMF may be an effective alternative to thiopurines and methotrexate in IBD.

Background Methotrexate can be used to maintain remission in Crohn's disease patients who are intolerant to thiopurines. Data on its use as monotherapy in other scenarios are limited. Aim To assess the effectiveness of methotrexate monotherapy in Crohn's disease patients after previous failure to anti-tumour necrosis factor (anti-TNF alpha) drugs. Methods A retrospective, observational multicentre study of data from the Spanish ENEIDA registry. Participants were patients with active Crohn's disease and previous failure to anti-TNF alpha started on methotrexate monotherapy. Short-term effectiveness was assessed at 12-16 weeks based on Harvey-Bradshaw index (HBI): clinical remission as HBI = 3 points over baseline. Long-term effectiveness was defined as steroid-free methotrexate persistence from 12 to 16 weeks until maximum follow up. Adverse events were recorded. Results Data were compiled for 110 patients treated with methotrexate after a failed response to one (39%) or two (55.6%) anti-TNF alpha agents. Short-term clinical response and remission rates were 60% and 30.9% respectively. Of 74 patients who continued after week 16, long-term effectiveness was achieved in 82% and 74% at 12 and 24 months respectively. In the multivariate analysis, non-remission at short term (vs remission) was associated with long-term failure (HR 2.58, 95%CI 1.95-3.68, P = 0.028). Adverse events (evaluated in 100 patients) were recorded in 44%, and in 30.4% of these patients, they led to methotrexate discontinuation. Conclusions The benefits observed suggest methotrexate monotherapy could be a valid option in Crohn's disease patients with previous failure to anti-TNF alpha.

Inflammatory bowel disease (IBD) is a complex multifactorial disorder in which external and environmental factors have a large influence on its onset and development, especially in genetically susceptible individuals. Crohn's disease (CD), one of the two types of IBD, is characterized by transmural inflammation, which is most frequently located in the region of the terminal ileum. Oxidative stress, caused by an overabundance of reactive oxygen species, is present locally and systemically in patients with CD and appears to be associated with the well-described imbalanced immune response and dysbiosis in the disease. Oxidative stress could also underlie some of the environmental risk factors proposed for CD. Although the exact etiopathology of CD remains unknown, the key role of oxidative stress in the pathogenesis of CD is extensively recognized. Epigenetics can provide a link between environmental factors and genetics, and numerous epigenetic changes associated with certain environmental risk factors, microbiota, and inflammation are reported in CD. Further attention needs to be focused on whether these epigenetic changes also have a primary role in the pathogenesis of CD, along with oxidative stress.

¿Qué hace un/a docente cuando la realidad educativa es más potente que la teoría? Aquí se presentan ocho trabajos de innovación educativa presentados por docentes de la Región de Apurímac (Perú) que dan respuesta a esta pregunta. Se trata, en líneas generales, de respuestas creativas y comprometidas, de acercamiento pedagógico a la realidad del aula, problemática, compleja y, con ello, también potente y diversa. Son trabajos que más que aplicar una norma, una regla o un algoritmo, con su singularidad, han encarado la complejidad de sus aulas desde la praxis educativa para ofrecer, con esfuerzo y valor, una respuesta innovadora. Son trabajos innovadores pedagógica y socialmente comprometidos con una idea que va más allá del reto laboral y que empata con el espíritu del Objetivo de Desarrollo Sostenible (ODS) Nº4.

Background: Effectiveness of vedolizumab in real world clinical practice is unknown. Aim: To evaluate the short and long-term effectiveness of vedolizumab in patients with inflammatory bowel disease (IBD). Methods: Patients who received at least 1 induction dose of vedolizumab were included. Effectiveness was defined based on Harvey-Bradshaw index (HBI) in Crohn's disease (CD) and Partial Mayo Score (PMS) in ulcerative colitis (UC). Short-term response was assessed at week 14. Variables associated with short-term remission were identified by logistic regression analysis. The Kaplan-Meier method was used to evaluate the long-term durability of vedolizumab treatment. Cox model was used to identify factors associated with discontinuation of treatment and loss of response. Results: 521 patients were included (median follow-up 10 months [interquartile range 5-18 months]). At week 14, 46.8% had remission and 15.7% clinical response. CD (vs UC), previous surgery, higher CRP concentration and disease severity at baseline were significantly associated with impaired response. The rate of vedolizumab discontinuation was 37% per patient-year of follow-up (27.6% in UC and 45.3% in CD, P < 0.01). CD (vs UC), anaemia at baseline, steroids during induction and CRP concentration were associated with lower durability of treatment. Seven per cent of patients developed adverse events, infections being the most frequent. Conclusions: Over 60% of IBD patients respond to vedolizumab. Many patients discontinue treatment over time. CD and disease burden impair both short- and long-term response. Vedolizumab seems to be safe in clinical practice.

Aims The aims of this study were (a) to know the kinetics of antitumor necrosis factor (TNF) drug serum levels during the induction phase in patients with Crohn's disease; (b) to identify variables associated with these levels; and (c) to assess the relation between these levels and short-term effectiveness in Crohn's disease patients. Methods Patients with Crohn's disease naive to anti-TNF treatment were prospectively included. Remission was defined as a Crohn's disease activity index (CDAI) score 150 at study entry. At week 14, 52 out of 71 patients with CDAI > 150 at baseline (73%) had clinical remission. There were no differences in infliximab levels between patients with and without remission (8 vs. 9.1 mu g/mL, P > 0.05) or with and without response (7 vs. 11 mu g/mL, P > 0.05) at week 14. There was a trend to higher levels of adalimumab concentration in responders in comparison with nonresponders (13 vs. 6.7 mu g/mL, P = 0.05) and in patients who achieved remission in comparison with nonremitters (13.5 vs. 8.4 mu g/mL, P = 0.06). In the multivariate analysis, no variable was predictive of short-term remission, including infliximab and adalimumab serum levels. Conclusion Determining anti-TNF serum levels during the induction phase is not useful for predicting short-term remission in patients with Crohn's disease.

Cytokines emerge as possible biomarkers of response in Crohn's disease (CD). We aimed to determine the plasmatic cytokine profiles of active CD patients who started infliximab (IFX) treatment and their capacity to predict the response to IFX.

Golimumab has demonstrated its long-term efficacy and safety in ulcerative colitis in clinical trials, but no data of long-term persistence has been published from real world. To estimate long-term persistence of golimumab, as well as factors associated with longer persistence, in patients with ulcerative colitis in real life. Observational multicentre study including adult patients with ulcerative colitis treated with golimumab and with at least twelve months of follow-up. We included 190 patients, 105 (55.26%) naive to anti-TNF, with mean disease duration of 9.32 +/- 8.09 years. Probability of persistence was 63%, 46%, 39% and 27% at 1, 2, 3 and 4 years, respectively. Persistence was lower in patients with primary failure to previous anti-TNF. Eighty-two (43.16%) patients needed dose intensification during follow-up, with a mean time until intensification of 8.03 +/- 8.64 months. Dose intensification and lower disease duration predicted higher persistence with golimumab (p=0.037 and p=0.008, respectively). During a follow-up of 17.25 +/- 15.83 months, 32 (16.5%) patients needed hospitalisation and 11 (6%) underwent colectomy. No unexpected adverse events were reported. Golimumab has demonstrated good persistence and safety profile for long treatment in ulcerative colitis patients.

Primary sclerosing cholangitis (PSC) is usually associated with inflammatory bowel disease (IBD). An increased risk of malignancies, mainly colorectal cancer (CRC) and cholangiocarcinoma (CCA), has been reported in PSC-IBD patients. Our aim was to determine the clinical characteristics and management of PSC in IBD patients, and the factors associated with malignancies.

Background and Aims: To evaluate the clinical outcomes in patients with IBD after switching from Remicade (R) to CT-P13 in comparison with patients who maintain Remicade (R). Methods: Patients under Remicade (R) who were in clinical remission with standard dosage at study entry were included. The 'switch cohort' [SC] comprised patients who made the switch from Remicade (R) to CT-P13, and the 'non-switch' cohort [NC] patients remained under Remicade (R). Results: A total of 476 patients were included: 199 [42%] in the SC and 277 [58%] in the NC. The median follow-up was 18 months in the SC and 23 months in the NC [p < 0.01]. Twenty-four out of 277 patients relapsed in the NC; the incidence of relapse was 5% per patient-year. The cumulative incidence of relapse was 2% at 6 months and 10% at 24 months in this group. Thirty-eight out of 199 patients relapsed in the SC; the incidence rate of relapse was 14% per patient-year. The cumulative incidence of relapse was 5% at 6 months and 28% at 24 months. In the multivariate analysis, the switch to CT-P13 was associated with a higher risk of relapse (HR = 3.5, 95% confidence interval [CI] = 2-6). Thirteen percent of patients had adverse events in the NC, compared with 6% in the SC [p < 0.05]. Conclusions: Switching from Remicade (R) to CT-P13 might be associated with a higher risk of clinical relapse, although this fact was not supported in our study by an increase in objective markers of inflammation. The nocebo effect might have influenced this result. Switching from Remicade (R) to CT-P13 was safe.

The aims of this study were to characterize the immune response profile in patients with Crohn's disease (CD) and early postoperative recurrence (POR), to identify predictive biomarkers, and to develop a noninvasive predictive tool for individual estimation of POR risk.

Background There are limited data of ustekinumab administered according to the doses recommended in the UNITI studies. Aim To assess the real-world, short-term effectiveness of ustekinumab in refractory Crohn's disease (CD) Methods Multicentre study of CD patients starting ustekinumab after June 2017 at the recommend dose (260, 390 or 520 mg based on weight ~6 mg/kg IV week 0 and 90 mg subcutaneously week 8). Values for Harvey-Bradshaw Index (HBI), C-reactive protein (CRP) and faecal calprotectin (FC) were recorded at baseline and at weeks 8 and 14. Demographic and clinical data, previous treatments, AEs and hospitalisations were documented. Possible predictors of clinical remission were examined. Results Three hundred and five patients were analysed (>= 2 previous anti-TNF alpha therapies 64% and vedolizumab 29%). At baseline, 217 (72%) had an HBI >4 points. Of these, 101 (47%) and 126 (58%) achieved clinical remission at weeks 8 and 14, respectively. FC levels returned to normal (

DNA methylation is an epigenetic mechanism that regulates gene expression and represents an important link between genotype, environment, and disease. It is a reversible and inheritable mechanism that could offer treatment targets. We aimed to assess the methylation changes on specific genes previously associated with Crohn's disease (CD) and to study their possible associations with the pathology.

Aims: To establish recommendations for the management of psychological problems affecting patients with inflammatory bowel disease (IBD). Methods: A meeting of a group of IBD experts made up of doctors, psychologists, nurses and patient representatives was held. The following were presented: 1) Results of a previous focal group, 2) Results of doctor and patient surveys, 3) Results of a systematic review of tools for detecting anxiety and depression. A guided discussion was then held about the most important psychological and emotional problems associated with IBD, appropriate referral criteria and situations to be avoided. The validated instrument most applicable to clinical practice was selected. A recommendations document and a Delphi survey were designed. The survey was sent to the group and to a scientific committee of the GETECCU group in order to establish the level of agreement with these recommendations. Results: Fifteen recommendations were established linked to 3 key processes: 1) What steps should be taken to identify psychological problems at an IBD appointment; 2) What are the criteria for referring patients to a mental health specialist; 3) How to approach psychological problems. Conclusions: Resources should be made available to healthcare professionals so that they can treat these problems during consultations, identify the disorders which could affect the clinical course of the disease and determine their impact on the patient's life in order that these can be treated and followed up by the most suitable professional. These recommendations could serve as a basis for redesigning IBD services or processes and as justification for the training of healthcare personnel. (C) 2017 Elsevier Espana, S.L.U. All rights reserved.

Ethanol (EtOH) research has focused on stages of dependence. It is of paramount importance to more deeply understand the neurobehavioral factors promoting increased risk for EtOH binge drinking during the early stages of the addiction cycle. The first objective of this study was to evaluate whether C57BL/6J mice showing high drinking in the dark (DID) exhibit neurobehavioral traits known to contribute to EtOH binge-drinking disorders. Comparing high vs. low drinkers (HD/LD), we evaluated different types of basal anxiety-like responses, EtOH preference and sensitivity to the reinforcing properties of EtOH, and basal mRNA expression of the OX1/OX2 receptors (OX1r/OX2r) within the prefrontal cortex (PFC) and the nucleus accumbens (NAcc). Additionally, we tested binge drinking by LD/HD in response to a selective OX1r antagonist following intermittent episodes of DID (iDID). We report that DID consistently segregates two neurobehavioral endophenotypes, HD vs. LD, showing differences in neophobia and/or impulsivity/compulsivity traits. Additionally, HD mice show decreased basal OX1r and OX2r mRNA expression within the NAcc and elevated OX1r within the PFC. Exposure to several intermittent episodes of EtOH DID triggered a rapid increase in EtOH intake over time in LD mice matching that observed in HD mice. Despite HD/LD endophenotypes did not show differences in EtOH intake, they still predicted the response to a pharmacological challenge with a selective OX1r antagonist. The present data underscore the relevance of HD/LD endophenotypes stemming from DID procedures for exploring neurobehavioral processes underlying the early stages of the addiction cycle and EtOH binge-drinking disorders.

El Trastorno del Espectro Autista (TEA) constituye un diagnóstico encuadrado en el DSM-5 (APA, 2013) dentro de los trastornos del neurodesarrollo que se caracteriza fundamentalmente por la presencia de dificultades en la comunicación e interacción social, así como por la presencia de patrones repetitivos y restringidos de conductas, actividades e intereses. Tiene su inicio en la infancia, afecta a todas las áreas del desarrollo de la persona y sigue un patrón evolutivo diferente en cada caso, que dependerá tanto de factores internos como externos. Las familias de las personas con TEA por lo general presentan un perfil con unas necesidades y características particulares que es necesario investigar en aras al diseño de posibles intervenciones encaminadas a mejorar las condiciones y la calidad de vida de estas familias. Los estudios sobre calidad de vida y bienestar en familias de personas con TEA se han centrado en diversos aspectos tales como el estrés parental, el impacto familiar, las diversas estrategias y recursos que utilizan, el apoyo social percibido y la resiliencia que presentan estas familias. Asimismo, se han identificado, por un lado, como factores de riesgo las características propias del niño como la severidad de los síntomas autísticos, los problemas conductuales, las conductas desadaptativas, el grado de discapacidad intelectual y la edad cronológica. Por otro lado, las investigaciones sobre el impacto del TEA en el ámbito familiar ponen de manifiesto otros factores relativos a las características de los padres y cuidadores como puedan ser características de personalidad y salud mental, condiciones económicas, estrategias de afrontamiento utilizadas, así como características psicológicas y psicosociales, de manera que se han investigado los procesos de adaptación y reequilibrio del sistema familiar ante la aparición de un estresor. El estrés parental se considera como uno de los factores que influyen de manera más significativa en el comportamiento de los padres y es una variable importante para la disfunción en la crianza de los hijos y los estudios sobre padres de niños con TEA El principal objetivo de nuestra investigación es analizar los estilos y estrategias frente al estrés de los padres de niños con TEA, el apoyo social percibido, la resiliencia que presentan, la cohesión y la adaptabilidad familiar, así como su relación con el estrés parental y el impacto familiar que conlleva el nacimiento y crianza de un niño con TEA. La muestra participante estaba formada por un total de 74 padres y madres de niños entre 5 y 8 años de edad, distribuidos en dos grupos: un grupo TEA - cuyos niños presentaban diagnóstico clínico del trastorno y asistían a aulas CyL - y un grupo con desarrollo típico (DT), de las aulas de referencia de los niños pertenecientes al grupo TEA. Se administró por parte del orientador a los padres de los alumnos que componían ambos grupos varios cuestionarios, el cuestionario para recoger las variables sociodemográficas, el Parenting Stress Index (PSI) (Abidin, 1995; traducción de Grau, 2007), el Cuestionario de Impacto Familiar (Donnenberg y Baker, 1993), el Cuestionario de Estilos y Estrategias de Afrontamiento al Estrés (Fernández-Abascal, 1997), la Escala de Resiliencia (Wagnild y Young, 1993), el Cuestionario de Apoyo Social DUKE-UNC (Broadhead et al, 1988) y la Escala de Cohesión y Adaptación Familiar (Olson, Russell y Sprenkle, 1983). Para analizar la información extraída de los cuestionarios se realizaron análisis de varianza multivariantes (MANOVAs), análisis de varianza univariante (ANOVAs) y comparación entre grupos para estudiar las comparaciones entre los dos grupos en las diferentes variables cuantitativas El grupo de padres de niños con TEA de nuestro trabajo presentó niveles de estrés superiores a los de los otros padres, estrés que potencialmente y con el tiempo, podría afectar a la salud mental de los cuidadores y a la desestabilización del sistema familiar, producir una limitación considerable del tiempo disponible para sí mismos, un incremento considerable de gastos, fatiga por sobrecarga en cuidados, una falta de estrategias de afrontamiento frente al estrés que sean activas y resolutivas, una percepción negativa del apoyo percibido, aislamiento de los padres y por consiguiente de la familia al completo y una percepción de falta de cohesión de la familia. A partir de los resultados que hemos obtenido en este estudio, al compararlos con el grupo de padres de niños con DT, se evidencia que la mayor parte de todas estas consecuencias ya se produce en los padres del grupo TEA de nuestra muestra. Todo ello son condiciones que subrayan la importancia del trabajo con estas familias en su conjunto, y en particular con los padres, ayudándoles a encontrar una visión positiva, mejorar su autoestima, ser conscientes de sus fortalezas y debilidades, e incrementar su autoeficacia haciéndoles sentir seguros de sus conocimientos, recursos y decisiones, así como que contemplen la necesidad de apoyo y enseñarles a solicitarlo. The Autism Spectrum Disorder (ASD) is a diagnosis framed in the DSM-5 (APA, 2013) within the neurodevelopmental disorders that is characterized mainly by the presence of difficulties in communication and social interaction, as well as by the presence of repetitive and restricted patterns of behaviors, activities, and interests. It has its beginning in childhood, affects all areas of the development of the person and follows a different evolutionary pattern in each case, which will depend on both internal and external factors. Families of people with ASD usually present a profile with particular needs and characteristics that need to be investigated in order to design possible interventions aimed at improving the conditions and quality of life of these families. Studies on quality of life and well-being in families of people with ASD have focused on various aspects such as parental stress, family impact, coping styles and resources they use, perceived social support and the resilience of these families. Likewise, the characteristics of the child, such as severity of autistic symptoms, behavioral problems, maladaptive behaviors, degree of intellectual disability and chronological age have been identified as risk factors. On the other hand, research on the impact of ASD on the family reveals other factors related to the characteristics of parents and caregivers such as personality and mental health characteristics, economic conditions, coping strategies used, as well as characteristics Psychological and psychosocial, so that the processes of adaptation and rebalancing of the family system have been investigated in the presence of a stressor. Parental stress is considered as one of the most significant factors influencing parental behavior and is an important variable for dysfunction in parenting and studies on parents of children with ASD The main objective of our research is to analyze the styles and strategies regarding the stress of the parents of children with ASD, perceived social support, the resilience they present, family cohesion and adaptability, as well as their relationship with parental stress and Family impact that leads to the birth and upbringing of a child with ASD. The participant sample consisted of a total of 74 fathers and mothers of children between 5 and 8 years of age, divided into two groups: a ASD group - whose children presented clinical diagnosis of the disorder and attended CyL classrooms - and a group with Typical Development (TD) of the reference classrooms of children belonging to the ASD group. The evaluation instruments were administered to the parents of the students composing both groups: Questionnaire ad hoc to collect the sociodemographic variables, the Parenting Stress Index (PSI) (Abidin, 1995; Grau translation, 2007), the Impact Questionnaire, (Donnenberg and Baker, 1993), the Styles and Strategies of Coping with Stress Questionnaire (Fernández-Abascal, 1997), the Resilience Scale (Wagnild and Young, 1993), the DUKE-UNC Social Support Questionnaire Al, 1988) and the Family Cohesion and Adaptation Scale (Olson, Russell and Sprenkle, 1983). In order to analyze the information extracted from the questionnaires, multivariate analysis of variance (MANOVAs), univariate analysis of variance (ANOVAs) and comparison between groups were performed to study the comparisons between the two groups in the different quantitative variables The group of parents of children with ASD in our work had higher levels of stress than other parents, stress that potentially and over time, could affect the mental health of caregivers and destabilization of the family system, produce a limitation in the time available for themselves, a considerable increase in expenses, fatigue due to overload in care, a lack of coping strategies that are active, a negative perception of the perceived support, isolation of the parents and, consequently, the whole family and a perception of lack of family cohesion. From the results we have obtained in this study, when compared to the group of parents of children with TD, it is evident that most of all these consequences are already produced in the parents of the ASD group of our sample. All of these are conditions that emphasizes the importance of working with these families as a whole, and particularly with parents, helping them to find a positive vision, improve their self-esteem, be aware of their strengths and weaknesses, and increase their self-efficacy by making them feel confident about their knowledge, resources and decisions, and to consider the need for support and teach them how to apply

Crohn's disease (CD) is an inflammatory disorder characterised by a transmural inflammation of the intestinal wall. Although the physiopathology of the disease is not yet fully understood, it is clear that the immune response plays an important role in it. This hyperreactive immune system is accompanied by the presence of unregulated reactive oxygen species (ROS). These elements are modulated in normal conditions by different elements, including enzymes that function as antioxidant defences preventing the harmful effects of ROS. However, in CD there is an imbalance between ROS production and these antioxidant elements, resulting in oxidative stress (OxS) phenomena. In fact, now OxS is being considered more a potential etiological factor for Crohn's disease rather than a concomitant effect in the disease. The persistence of the OxS can also be influencing the evolution of the disease. Furthermore, the epigenetic mechanisms, above all microRNAs, are being considered key elements in the pathogenesis of CD. These elements and the presence of OxS have also been linked to several diseases. We, therefore, describe in this review the most significant findings related to oxidative stress and microRNAs profiles in the peripheral blood of CD patients.

Background: Psoriasis induced by anti-tumor necrosis factor-alpha (TNF) therapy has been described as a paradoxical side effect. Aim: To determine the incidence, clinical characteristics, and management of psoriasis induced by anti-TNF therapy in a large nationwide cohort of inflammatory bowel disease patients. Methods: Patients with inflammatory bowel disease were identified from the Spanish prospectively maintained Estudio Nacional en Enfermedad Inflamatoria Intestinal sobre Determinantes geneticos y Ambientales registry of Grupo Espanol de Trabajo en Enfermedad de Croh y Colitis Ulcerosa. Patients who developed psoriasis by anti-TNF drugs were the cases, whereas patients treated with anti-TNFs without psoriasis were controls. Cox regression analysis was performed to identify predictive factors. Results: Anti-TNF-induced psoriasis was reported in 125 of 7415 patients treated with anti-TNFs (1.7%; 95% CI, 1.4-2). The incidence rate of psoriasis is 0.5% (95% CI, 0.4-0.6) per patient-year. In the multivariate analysis, the female sex (HR 1.9; 95% CI, 1.3-2.9) and being a smoker/former smoker (HR 2.1; 95% CI, 1.4-3.3) were associated with an increased risk of psoriasis. The age at start of anti-TNF therapy, type of inflammatory bowel disease, Montreal Classification, and first anti-TNF drug used were not associated with the risk of psoriasis. Topical steroids were the most frequent treatment (70%), achieving clinical response in 78% of patients. Patients switching to another anti-TNF agent resulted in 60% presenting recurrence of psoriasis. In 45 patients (37%), the anti-TNF therapy had to be definitely withdrawn. Conclusions: The incidence rate of psoriasis induced by anti-TNF therapy is higher in women and in smokers/former smokers. In most patients, skin lesions were controlled with topical steroids. More than half of patients switching to another anti-TNF agent had recurrence of psoriasis. In most patients, the anti-TNF therapy could be maintained.

Biomarkers have gained increasing attention for the diagnosis and follow-up of inflammatory bowel disease (IBD). Endoscopy remains the gold standard for assessing disease activity. Biomarkers are rapid, inexpensive, and noninvasive, and can be used in different stages of the disease with high sensitivity and specificity. Calprotectin and tests for C-reactive protein are used to assess the disease activity, predict relapse, and monitor treatment response. New noninvasive tests are being studied. This review discusses current evidence for these surrogate markers, their potential clinical applications, and limitations in disease management. We highlight recent advances in IBD biomarkers and future uses.

Background: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. Methods: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54 weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. Results: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. AntiIFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3 nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10 nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10 nM) during the observation period (54 weeks). Serum concentration of ATI higher than 10 nM dramatically increased the probability (OR = 51.1; 95% CI: 20.4-128.0; p < 0.0001) of presenting low levels of IFX (

Treballs Finals de Grau d'Enginyeria Química, Facultat de Química, Universitat de Barcelona, Curs: 2014-2015, Tutor: Fidel Cunill García, Alkyl levulinates are biomass derived chemicals with a large spectrum of applications. They have the potential to substitute compounds currently derived from petro-chemical routes as components of conventional diesel or gasoline because of their physicochemical properties. Alkyl levulinates are synthesized most often from levulinic acid, but also from furfuryl alcohol or directly from cellulose and monosaccharide sugars. Levulinic acid is a platform chemical formed from hydrolysis of lignocellulose, the most readily available form of biomass, using the Biofine process. The most widely studied alkyl levulinate is ethyl levulinate, both its synthesis pathways and possible applications have been explored thoroughly. Comparatively, the potential of butyl levulinate has been left untapped. As an additive for automotive diesel fuel, butyl levulinate is even more promising than ethyl levulinate: butyl levulinate remains in diesel solution down to the diesel cloud point; butyl levulinate blends have very small particulate matter emissions; it has a lower solubility in water than ethyl levulinate; good lubricity and conductivity; and a low but better cetane number. Esterification of levulinic acid with butanol over several types of catalysts such as zeolites, lipases and heteropolyacids (HPA) supported on acid-treated clay montmorillonite (K10) has been described in literature, but the catalysis with acidic ion-exchange resins has never been attempted to the best of our knowledge. The present work studies the behavior of different sulfonated polystyrene-divinylbenzene resins in the synthesis of butyl levulinate from levulinic acid. The conducted experiments confirm that acidic polymer catalysts can be used in order to obtain very high conversion and selectivity in the esterification of levulinic acid with butanol to butyl levulinate. Selectivity toward butyl levulinate remains always over 98% for all tested catalysts in the range of temperatures studied, and the most relevant by-product is dibutyl ether. The catalyst with highest activity was Dowex 50Wx2, and overall, gel-type resins presented better yields than macroporous ones. Because of the high polarity of levulinic acid and the formation of water, resins with greater capacity for swelling would favor levulinic acid esterification. Thus resins with a lesser degree of cross-linking present higher reaction rates.Globally, reaction rates improve as the degree of polymer cross-linking diminishes and roughly correspond with large specific volume of swollen polymer.

Background:Magnetic resonance enterography (MRE) is an effective method of assessing small bowel Crohn's disease (CD). Fecal calprotectin (FC) correlates well with endoscopic disease activity. We aimed to evaluate the correlation between FC and disease activity according to MRE and surgical pathology in small bowel CD.Methods:One hundred twenty consecutive patients with ileal CD who underwent MRE assessment were included. Clinical data, C-reactive protein and FC, radiological and histological variables were obtained. Clinical activity was evaluated by the Harvey-Bradshaw Index and FC by enzyme-linked immunosorbent assay. MRE activity was assessed by means of the Magnetic Resonance Index of Activity score. Chiorean's score was used to grade pathological inflammation in surgical specimens.Results:Seventy-five patients (62.5%) were in clinical remission (Harvey-Bradshaw Index < 5) and 45 (37.5%) had active disease (Harvey-Bradshaw Index 5). The Magnetic Resonance Index of Activity score was significantly associated with FC levels (P < 0.01), with a moderate overall correlation (Spearman's r = 0.56, P < 0.001). FC reflected MRE inflammatory activity with an area under the receiver operating characteristic curve of 0.914 (confidence interval, 0.849-0.958; P < 0.001). A cutoff value of 166.50 g/g had 90% sensitivity, 74% specificity, 89% positive predictive value, and 76% negative predictive value for diagnosis of inflammation. Twenty-eight of 120 patients were operated. Surgical pathology showed a good agreement with FC for moderate (P = 0.03) and severe (P = 0.01) Chiorean's index. No relationship was detected for C-reactive protein.Conclusions:FC correlates with the degree of MRE inflammatory activity and with surgical pathology damage in ileal CD. Thus, FC could be a surrogate marker of disease control used to select patients for MRE assessment and therapeutic adjustment.

Crohn's disease (CD) is characterized by transmural inflammation that is most frequently located in the region of the terminal ileum. Although the physiopathological mechanisms of the disease are not yet well defined, the unregulated immune response is associated with high production of reactive oxygen species (ROS). These elements are associated with complex systems known as antioxidant defenses, whose function is ROS regulation, thereby preventing the harmful effects of these elements. However, the presence of an imbalance between ROS production and ROS elimination by antioxidants has been widely described and leads to oxidative stress. In this article, we describe the most significant findings on oxidative stress in the intestinal mucosa and peripheral blood. (C) 2013 Elsevier Espana, S.L. and AEEH y AEG. All rights reserved.

AIM: To investigate the influence of thiopurines and biological drugs on the presence of small intestinal bacterial overgrowth (SIBO) in patients with inactive Crohn's disease (CD). METHODS: This was a prospective study in patients with CD in remission and without corticosteroid treatment, included consecutively from 2004 to 2010. SIBO was investigated using the hydrogen glucose breath test. RESULTS: One hundred and seven patients with CD in remission were included. Almost 58% of patients used maintenance immunosuppressant therapy and 19.6% used biological therapy. The prevalence of SIBO was 16.8%. No association was observed between SIBO and the use of thiopurine Immunosuppressant (12/62 patients), administration of biological drugs (2/21 patients), or with double treatment with an anti-tumor necrosis factor drugs plus thiopurine (1/13 patients). Half of the patients had symptoms that were suggestive of SIBO, though meteorism was the only symptom that was significantly associated with the presence of SIBO on univariate analysis (P < 0.05). Multivariate analysis revealed that the presence of meteorism and a fistulizing pattern were associated with the presence of SIBO (P < 0.05). CONCLUSION: Immunosuppressants and/or biological drugs do not induce SIBO in inactive CD. Fistulizing disease pattern and meteorism are associated with SIBO. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

The first step in biomarkers discovery is to identify the best protocols for their purification and analysis. This issue is critical when considering peripheral blood samples (plasma and serum) that are clinically interesting but meet several methodological problems, mainly complexity and low biomarker concentration. Analysis of small molecules, such as circulating microRNAs, should overcome these disadvantages. The present study describes an optimal RNA extraction method of microRNAs from human plasma samples. Different reagents and commercially available kits have been analyzed, identifying also the best pre-analytical conditions for plasma isolation. Between all of them, the column-based approaches were shown to be the most effective. In this context, miRNeasy Serum/Plasma Kit (from Qiagen) rendered more concentrated RNA, that was better suited for microarrays studies and did not require extra purification steps for sample concentration and purification than phenol based extraction methods. We also present evidences that the addition of low doses of an RNA carrier before starting the extraction process improves microRNA purification while an already published carrier dose can result in significant bias over microRNA profiles. Quality controls for best protocol selection were developed by spectrophotometry measurement of contaminants and microfluidics electrophoresis (Agilent 2100 Bioanalyzer) for RNA integrity. Selected donor and patient plasma samples and matched biopsies were tested by Affymetrix microarray technology to compare differentially expressed microRNAs. In summary, this study defines an optimized protocol for microRNA purification from human blood samples, increasing the performance of assays and shedding light over the best way to discover and use these biomarkers in clinical practice.

To evaluate the effectiveness of adalimumab in preventing recurrence after intestinal resection for Crohn's disease in high-risk patients.

There is increasing interest in oxidative stress being a potential aetiological factor and/or a triggering factor in Crohn's disease, rather than a concomitant occurrence during the pathogenesis of the disease. Recent research has shown that the immune mononuclear cells of Crohn's disease patients are induced to produce hydrogen peroxide (H2O2). Similarly, the regulation of antioxidant enzymes during disease in these cells has been unravelled, showing that SOD (superoxide dismutase) activity and GPx (glutathione peroxidase) activity is increased during active disease and returns to normal in remission phases. However, catalase remains constantly inhibited which supports the idea that catalase is not a redox-sensitive enzyme, but a regulator of cellular processes. ROS (reactive oxygen species) can be produced under the stimulus of different cytokines such as TNFa (tumour necrosis factor a). It has been shown in different experimental models that they are also able to regulate apoptosis and other cellular processes. The status of oxidative stress elements in Crohn's disease and their possible implications in regulating cellular processes are reviewed in the present paper.

Treatment with antitumor necrosis factor-alpha (anti-TNF-a) offers a significant improvement in several immune-based diseases, including Crohn's disease (CD) and psoriasis. Different cutaneous side effects have been described for anti-TNF-a therapy such as psoriasis. Previous reports showed that inhibition of TNF-a can induce over expression of cutaneous IFN-a, which in turn caused a predisposition to psoriasis. We report a 31-year-old woman with extensive CD and perianal lesions, without response to conventional treatment. She paradoxically developed a cutaneous eruption with psoriasiform morphology and distribution during treatment with both anti-TNF-a approved in Europe for CD, infliximab and adalimumab. These lesions cleared after topical application of corticosteroids and cessation of the anti-TNF-a treatment. Due to uneffectiveness of pharmacological treatment on disease, the patient had to undergo surgery. TNF-induced psoriasis in patients with CD is rare and has been previously documented with infliximab or adalimumab. The reason for this apparently paradoxical effect of the therapy is still unclear. This is the first case of psoriasis induced first by infliximab and later by adalimumab in the same CD patient. We would like to review and to draw attention about psoriasis as a cutaneous side effect with anti-TNF-a treatments.

Oxidative stress is considered a potential etiological factor for Crohn's disease (CD). We characterized the reactive oxygen species (ROS) generated in immune peripheral cells of CD patients, as well as their antioxidant enzyme status and the presence of oxidative damage. In addition, mitochondrial function (DeltaPsim) was analyzed to detect the possible origin of ROS.

The incidence and clinical importance of infectious gastroenteritis was studied in 67 consecutive relapses of inflammatory bowel disease (IBD). A stool culture was done in every case before starting treatment. Stool culture was positive in 6 relapses (8.9%): Four were exacerbations of ulcerative colitis and two of Crohn's disease (8.8% in ulcerative colitis vs 9% in Crohn's disease; NS). The microorganisms isolated were Campylobacter jejuni in three cases, Salmonella enteritidis in two and Staphylococcus aureus in one case. There were not clinical differences between patients with positive and negative stool culture. Treated with antibiotics, stool cultures became negative in all of them but only in three the disease was controlled. The other three had to be treated with corticosteroids to achieve remission. We conclude that stool culture should be practised in all relapses of IBD and in case of positivity, antibiotic therapy should be started. With this approach the use of corticosteroids can be avoided in some patients.