Impacto del entrenamiento cognitivo NEXXO sobre la atención y funciones ejecutivas en edad escolar

El origen de esta tesis se remonta a la propia práctica clínica con niños con Trastorno por Déficit de Atención e Hiperactividad (TDAH). Abordando la intervención psicoeducativa y neuropsicológica de este trastorno observé la necesidad de implementar un programa de intervención que tratase aspectos básicos de la atención y de las funciones ejecutivas, como son la vigilancia y la inhibición (Figueroa y Youmans, 2012; Rueda, Posner y Rothbart, 2005), con el objetivo final de entrenar el control atencional y el control ejecutivo. Un programa que, además, fuese dirigido por profesionales donde, además, se aplicasen pautas y estrategias metacognitivas que consolidasen y generalizasen la intervención. Como se ha dicho anteriormente, la idea inicial fue abordar el entrenamiento de la vigilancia y de la inhibición, aspectos deficitarios para estos pacientes en las reconocidas pruebas de ejecución continua como Conners Continous Performance Test II (CPT-II) (Conners et al., 2000), Conners Kiddie Continuous Performance Test (K-CPT V.5) (Conners y Staff, 2001) o CSAT-R tarea de atención sostenida en la infanciarevisada (Servera y Llabrés, 2015). Al diseñar el entrenamiento, nos centramos en elcontrol atencional y ejecutivo, y los procesos relacionados con los mismos. Entre otrascosas, por ello, entrenamiento debía estar acompañado de ciertas pautas y estrategias quepudieran ayudar a asimilar de forma más adecuada el entrenamiento, estrategiasmetacognitivas. El entrenamiento “Nexxo” surgió de una necesidad: entrenar procesosbásicos de atención y funciones ejecutivas con un enfoque determinado (desde laneuropsicología infantil), un programa que además incorporase estrategiasmetacognitivas para su consolidación; un programa inexistente en el mercado, y, portanto, inaccesible en ese momento. Parasuraman y Giambra (1991) consideran la vigilancia y la atención sostenida como la misma habilidad, una habilidad en la que el observador debe mantener su foco de atención y su estado de alerta durante tiempos prolongados. La principal distinción es que en las tareas de vigilancia la frecuencia con la que el observador debe detectar un estímulo relevante es baja (Hauke et al., 2011). Esta habilidad se considera crucial para el desempeño de tareas de atención sostenida y de atención dividida, aspectos relevantes para la vida diaria (Figueroa y Youmans, 2012). La vigilancia se ha visto afectada en trastornos como el Trastorno por Déficit de Atención e Hiperactividad (TDAH) (Huang- Pollock, Karalunas, Tam, y Moore, 2012; Michelini et al., 2016), ansiedad (Price et al., 2013) y autismo (Christakou et al., 2013) entre otros. Por su parte la inhibición es uno de los aspectos principales de las funciones ejecutivas (Miyake y Friedman, 2012; Miyake et al., 2000). La inhibición supone dos habilidades básicas, por un lado, la habilidad de suprimir una respuesta automática o una tendencia en favor de otra, lo que se conoce como inhibición de respuesta, por otro, la selección de la información relevante en presencia de distractores, conocido como control de la interferencia (Miyake et al., 2000; Tamm y Nakonezny, 2015). Déficits en inhibición se encuentran en trastornos como TDAH, (Barkley, 1997), trastorno obsesivo-compulsivo y autismo (Ozonoff y Jensen,1999). Se consideran por tanto aspectos relevantes a incorporar en un entrenamiento de la atención y las funciones ejecutivas..

Schoolchildren’s compensatory strategies and skills in relation to attention and executive function app training

Background: Given the importance of attention and executive functions (EF) in children’s behavior, programs aimed at improving these processes are of special interest. Nexxo-training combines the use of the Nexxo touchscreen application (inhibition and vigilance tasks) with procedural metacognitive strategies (imparted by an instructor) for all the individuals using the app, regardless of their level of ability, plus compensatory strategies based on individual child performance. This study presents an analysis of the compensatory strategies that schoolchildren (aged 6–8 years old) receive when experiencing difficulties with EF tasks, in addition to an analysis of the developmental factors and cognitive skills that may modulate EF task performance. Methods: For this study, we use data from a previous randomized active-controlled study (under review), in which forty-six typically developing children aged between 6 and 8 years old (24 girls/22 boys) were enrolled in the training group. The selected children were in the 1st grade (n = 28, Nx = 78.32 4.037 months) and 3rd grade of primary education (n = 18, Nx = 102.11 3.445). We collected data on EF training performance, compensatory strategies needed and neuropsychological assessments. Results: A total of 80.43% participants required some form of compensatory strategy during training. Regarding required compensatory strategies, those who had lower scores in EF training needed more compensatory strategies, in particular, instructional comprehension (r = -0.561, p < 0.001 for inhibition-tasks; r = -0.342, p < 0.001 for vigilance-tasks). Concerning developmental factors, age significantly predicted better performance in both EF tasks (b = 0.613, p < 0.001 for inhibition; b = 0.706, p < 0.001 for attention). As regards task performance, those with better performance in inhibition tasks also had better performance in vigilance tasks (r = 0.72, p < 0.001). Finally, regarding cognitive skills, participants with higher performance in fluid intelligence (Q1, n = 12) had higher scores (U = 14.5, p < 0.05) than the group with the lowest performance (Q4, n = 11) in vigilance Conclusion: As previous literature suggests, inhibition is one of the core processes of EF. Therefore, we should focus training on the core EF processes. Inhibition and vigilance are closely related processes. In terms of the use of compensatory strategies, these are more needed for participants with lower levels of performance in inhibition or vigilance. Regarding strategy analysis, instructional comprehension and self-instruction (goal setting and planning) seem to be the most useful strategies for those with difficulties in inhibitory and vigilance task performance. Regarding development, as expected, age moderates task performance in inhibition and attention. Finally, cognitive skills, such as fluid intelligence and cognitive flexibility, predicted better results in attention. EF training using not only an app, but also compensatory strategies based on user performance, is a new research direction offering more opportunities to generalize EF training in everyday lif

Oxidative Stress and Antioxidant Activity in Hypothermia and Rewarming. Can RONS Modulate the Beneficial Effects of Therapeutic Hypothermia?

Hypothermia is a condition in which core temperature drops below the level necessary to maintain bodily functions. The decrease in temperature may disrupt some physiological systems of the body, including alterations in microcirculation and reduction of oxygen supply to tissues. The lack of oxygen can induce the generation of reactive oxygen and nitrogen free radicals (RONS), followed by oxidative stress, and finally, apoptosis and/or necrosis. Furthermore, since the hypothermia is inevitably followed by a rewarming process, we should also consider its effects. Despite hypothermia and rewarming inducing injury, many benefits of hypothermia have been demonstrated when used to preserve brain, cardiac, hepatic, and intestinal function against ischemic injury. This review gives an overview of the effects of hypothermia and rewarming on the oxidant/antioxidant balance and provides hypothesis for the role of reactive oxygen species in therapeutic hypothermia

Satellitome analysis of Rhodnius prolixus, one of the main Chagas disease vector species

The triatomine Rhodnius prolixus is the main vector of Chagas disease in countries such as Colombia and Venezuela, and the first kissing bug whose genome has been sequenced and assembled. In the repetitive genome fraction (repeatome) of this species, the transposable elements represented 19% of R. prolixus genome, being mostly DNA transposon (Class II elements). However, scarce information has been published regarding another important repeated DNA fraction, the satellite DNA (satDNA), or satellitome. Here, we offer, for the first time, extended data about satellite DNA families in the R. prolixus genome using bioinformatics pipeline based on low-coverage sequencing data. The satellitome of R. prolixus represents 8% of the total genome and it is composed by 39 satDNA families, including four satDNA families that are shared with Triatoma infestans, as well as telomeric (TTAGG)n and (GATA)n repeats, also present in the T. infestans genome. Only three of them exceed 1% of the genome. Chromosomal hybridization with these satDNA probes showed dispersed signals over the euchromatin of all chromosomes, both in autosomes and sex chromosomes. Moreover, clustering analysis revealed that most abundant satDNA families configured several superclusters, indicating that R. prolixus satellitome is complex and that the four most abundant satDNA families are composed by different subfamilies. Additionally, transcription of satDNA families was analyzed in different tissues, showing that 33 out of 39 satDNA families are transcribed in four different patterns of expression across samples

Differentiating Iberoformica and Formica (Serviformica) with Description of the Sexual Castes of Formica (Serviformica) gerardi Bondroit, 1917 stat. rev.

A list of morphological characters to separate Iberoformica and Formica (Serviformica) (F. fusca species group) is provided. Sexual forms of Formica gerardi Bondroit are described based on Iberian material and reinstated into the subgenus Serviformica based on genetic data and morphological characters. The status of †F.horrida Wheeler, 1915 is assessed

Physiology and Pathology of Immune Dysregulation: Regulatory T Cells and Anergy

The immune system is responsible for the defense of the organism. It controls what is introduced into it and identifies it as self from non-self. The defensive mechanisms activated by the immune system are directed against pathological microbes and toxic or allergenic proteins, and it must avoid responses that produce excessive damage of self-tissues, inducing tolerance to avoid autoimmunity and other immunopathologies. Regulatory T cells play an essential role in these active processes, using several distinct suppressive mechanisms. The immune dysregulatory diseases result from defects affecting regulatory T cell development and/or function, including the impact of essential genes mutations for T regulatory cell functions and the associated autoimmune syndromes

Preconditioning-Like Properties of Short-Term Hypothermia in Isolated Perfused Rat Liver (IPRL) System

Hypothermia may attenuate the progression of ischemia-induced damage in liver. Here, we determined the effects of a brief cycle of hypothermic preconditioning applied before an ischemic/reperfusion (I/R) episode in isolated perfused rat liver (IPRL) on tissue damage and oxidative stress. Rats (male, 200-250 g) were anaesthetised with sodium pentobarbital (60 mg·kg-1 i.p) and underwent laparatomy. The liver was removed and perfused in a temperature-regulated non-recirculating system. Livers were randomly divided into two groups (n = 6 each group). In the hypothermia-preconditioned group, livers were perfused with hypothermic buffer (cycle of 10 min at 22 °C plus 10 min at 37 °C) and the other group was perfused at 37 °C. Both groups were then submitted to 40 min of warm ischemia and 20 min of warm reperfusion. The level of tissue-damage indicators (alanine amino transferase, ALT; lactate dehydrogenase, LDH; and proteins), oxidative stress markers (thiobarbituric acid-reactive substances, TBARS; advanced oxidation protein products, AOPP; and glutathione, GSH) were measured in aliquots of perfusate sampled at different time intervals. Histological determinations and oxidative stress biomarkers in homogenized liver (AOPP; TBARS; nitric oxide derivatives, NOx; GSH and glutathione disulphide, GSSG) were also made in the tissue at the end. Results showed that both damage and oxidant indicators significantly decreased while antioxidant increased in hypothermic preconditioned livers. In addition, homogenized liver determinations and histological observations at the end of the protocol corroborate the results in the perfusate, confirming the utility of the perfusate as a non-invasive method. In conclusion, hypothermic preconditioning attenuates oxidative damage and appears to be a promising strategy to protect the liver against IR injury

Immune Checkpoints as a Novel Source for Diagnostic and Therapeutic Target in Celiac Disease

Celiac disease, as an autoimmune disorder, is a disease which appears in sensing and immune reaction responses to gluten. It has been confirmed that both genetic and environmental factors are involved. CD is strongly associated with the HLA alleles DQB1*02 (serological DQ2) or DQB1*0302 (serological DQ8). These HLA alleles are necessary but not sufficient for the development of CD and non-HLA risk genes also contribute to disease susceptibility. Several studies have identified linkage or association of CD with the 2q33 locus, a region harboring the candidate genes CD28, CTLA4 and ICOS, important immune checkpoints regulators of T-cell activity. Immune checkpoints are crucial to maintain self-tolerance and protect self-tissue from damage during an ongoing immune response

EoE CONNECT, the European Registry of Clinical, Environmental, and Genetic Determinants in Eosinophilic Esophagitis: rationale, design, and study protocol of a large-scale epidemiological study in Europe

Background: The growing prevalence of eosinophilic esophagitis (EoE) represents a considerable burden to patients and health care systems. Optimizing cost-effective management and identifying mechanisms for disease onset and progression are required. However, the paucity of large patient cohorts and heterogeneity of practice hinder the defining of optimal management of EoE. Methods: EoE CONNECT is an ongoing, prospective registry study initiated in 2016 and currently managed by EUREOS, the European Consortium for Eosinophilic Diseases of the Gastrointestinal Tract. Patients are managed and treated by their responsible specialists independently. Data recorded using a web-based system include demographic and clinical variables; patient allergies; environmental, intrapartum, and early life exposures; and family background. Symptoms are structurally assessed at every visit; endoscopic features and histological findings are recorded for each examination. Prospective treatment data are registered sequentially, with new sequences created each time a different treatment (active principle, formulation, or dose) is administered to a patient. EoE CONNECT database is actively monitored to ensure the highest data accuracy and the highest scientific and ethical standards. Results: EoE CONNECT is currently being conducted at 39 centers in Europe and enrolls patients of all ages with EoE. In its aim to increase knowledge, to date EoE CONNECT has provided evidence on the effectiveness of first- and second-line therapies for EoE in clinical practice, the ability of proton pump inhibitors to induce disease remission, and factors associated with improved response. Drug effects to reverse fibrous remodeling and endoscopic features of fibrosis in EoE have also been assessed. Conclusion: This prospective registry study will provide important information on the epidemiological and clinical aspects of EoE and evidence as to the real-world and long-term effectiveness and safety of therapy. These data will potentially be a vital benchmark for planning future EoE health care services in Europe

Accurate and timely diagnosis of Eosinophilic Esophagitis improves over time in Europe. An analysis of the EoE CONNECT Registry

BACKGROUND: Poor adherence to clinical practice guidelines for eosinophilic esophagitis (EoE) has been described and the diagnostic delay of the disease continues to be unacceptable in many settings. OBJECTIVE: To analyze the impact of improved knowledge provided by the successive international clinical practice guidelines on reducing diagnostic delay and improving the diagnostic process for European patients with EoE. METHODS: Cross‐sectional analysis of the EoE CONNECT registry based on clinical practice. Time periods defined by the publication dates of four major sets of guidelines over 10 years were considered. Patients were grouped per time period according to date of symptom onset. RESULTS: Data from 1,132 patients was analyzed and median (IQR) diagnostic delay in the whole series was 2.1 (0.7‐6.2) years. This gradually decreased over time with subsequent release of new guidelines (p < 0.001), from 12.7 years up to 2007 to 0.7 years after 2017. The proportion of patients with stricturing of mixed phenotypes at the point of EoE diagnosis also decreased over time (41.3% vs. 16%; p < 0.001), as did EREFS scores. The fibrotic sub‐score decreased from a median (IQR) of 2 (1‐2) to 0 (0‐1) when patients whose symptoms started up to 2007 and after 2017 were compared (p < 0.001). In parallel, symptoms measured with the Dysphagia Symptoms Score reduced significantly when patients with symptoms starting before 2007 and after 2012 were compared. A reduction in the number of endoscopies patients underwent before the one that achieved an EoE diagnosis, and the use of allergy testing as part of the diagnostic workout of EoE, also reduced significantly over time (p = 0.010 and p < 0.001, respectively). CONCLUSION: The diagnostic work‐up of EoE patients improved substantially over time at the European sites contributing to EoE CONNECT, with a dramatic reduction in diagnostic delay