EDU-EX: a tool for auto-regulated IntelligentTutoring systems development based on models

In recent years there has been an upsurge in forms of instruction that envisage a permanent and ongoing involvement in education of novel concepts such as planned and personalised instruction and autonomous learning. A large number of problems that arise ineducation today may be solved by introducing new technologies into the educational environment, as they allow the form and content of tutoring systems to be tailored to each individual.The application of Artificial Intelligence techniques is helping open up new prospects in the field of teaching and learning. Using Artificial Intelligence techniques in education has the advantage of making it possible to represent expert reasoning and knowledge skills, and to take advantage of this experience in education.This study has involved the development of a tool to generate auto-regulated intelligent tutoring systems based on models. This form of representation makes it possible to break down, organise and represent information so as to enable the easy creation of functionalintelligent computerised tutoring systems. Information about the subject in question, about inference mechanisms, and of a pedagogical nature (independent of any one strategy) is allseparated. The tool also enables knowledge acquired by a student to be constantly monitored with a view to auto-regulating the course contents

Efficacy of biosecurity measures in the control of microorganisms associated to endometritis in sows. Preliminary study

Biosecurity can be defined as all the applied measurements that take as a target to minimize the sanitary risks in a stock farm, and include measurements related to the facilities and the management. The efficacy of these measurements must be reflected in a decrease of the microorganism in different productive phases. A study was carried out to evaluate if the set of applied measurements influences the microbial uterine contamination after farrowing of healthy sows. Two swine farms were been completed about biosecurity measurements was completed and a microbiological study of uterine swabs of sows after the farrowing was carried out. A total of 60 animals were studied, and 27 (45%, 95% CI [33.3%, 56.7%]) resulted positive. Significant differences between production and selection and multiplication farms were detected (OR = 3.44, IC 95%, 1.135-11.047). The colonization frequency was 65% CI [51.3%, 78.6%] and 35% CI [21%, 49%] in production and selection farm, respectively (P = 0.02). A total of 66 isolates were obtained, represented mainly by Staphylococcus spp. (33.33%) and Aerococcus spp. (27.27%), although other species included in the genus Streptococcus (9.09%), Enterococcus (6.06%) and Pseudomonas (4.55%), as well as different fungi species were also isolated. The frequency of isolation of different microorganisms was similar in both farms, with the exception of the genus Enterococcus that was not isolated in the production farm (P = 0.01). The questionnaire showed some differences in biosecurity measures in the selection and multiplication farm when it is compared to the production farm, which together with the increased uterine microbial contamination observed in the latter leads us to propose a preliminary hypothesis about the possible risk factors associated with this process, highlighting the absence of measures to avoid the presence of vectors and the establishment of strict protocols for cleaning and disinfectio

The Need for the Closer Monitoring of Novel Drugs in MS: A Siponimod Retrospective Cohort Study (Realhes Study)

Lymphopenia; Multiple sclerosis; PharmacovigilanceLinfopenia; Esclerosis múltiple; FarmacovigilanciaLimfopènia; Esclerosi múltiple; FarmacovigilànciaBackground: Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile. Objective: We aimed to evaluate the incidence of lymphopenia following the initiation of siponimod treatment in clinical practice. The secondary objectives included the analysis of factors predisposing to and the clinical relevance of lymphopenia events. Methods: In this multicenter retrospective cohort study, information collected from the medical records of 129 patients with MS from 15 tertiary hospitals in Spain who initiated treatment with Siponimod were followed-up for at least 3 months, including at least one lymphocyte count evaluation per patient. Results: Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade ≤ 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for grade ≤ 3 and grade 4 lymphopenia, respectively). The study included an unexpectedly high proportion of male subjects (72.9%), which might have led to an underestimation of the actual magnitude of the risk. Conclusions: In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for the closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow-up studies to properly characterize this risk

A TRAF2 binding independent region of TNFR2 is responsibl for TRAF2 depletion and enhancement of cytotoxicity driven b TNFR1

Tumor Necrosis Factor (TNF) interacts with two receptors known as TNFR1 and TNFR2. TNFR1 activation may result in either cell proliferation or cell death. TNFR2 activates Nuclear Factor-kappaB (NF-kB) and c-Jun N-terminal kinase (JNK) which lead to transcriptional activation of genes related to cell proliferation and survival. This depends on the binding of TNF Receptor Associated Factor 2 (TRAF2) to the receptor. TNFR2 also induces TRAF2 degradation. In this work we have investigated the structural features of TNFR2 responsible for inducing TRAF2 degradation and have studied the biological consequences of this activity. We show that when TNFR1 and TNFR2 are co-expressed, TRAF2 depletion leads to an enhanced TNFR1 cytotoxicity which correlates with the inhibition of NF-kB. NF-kB activation and TRAF2 degradation depend of different regions of the receptor since TNFR2 mutants at amino acids 343-349 fail to induce TRAF2 degradation and have lost their ability to enhance TNFR1-mediated cell death but are still able to activate NF-kB. Moreover, whereas NF-kB activation requires TRAF2 binding to the receptor, TRAF2 degradation appears independent of TRAF2 binding. Thus, TNFR2 mutants unable to bind TRAF2 are still able to induce its degradation and to enhance TNFR1-mediated cytotoxicity. To test further this receptor crosstalk we have developed a system stably expressing in cells carrying only endogenous TNFR1 the chimeric receptor RANK-TNFR2, formed by the extracellular region of RANK (Receptor activator of NF-kB) and the intracellular region of TNFR2.This has made possible to study independently the signals triggered by TNFR1 and TNFR2. In these cells TNFR1 is selectively activated by soluble TNF (sTNF) while RANK-TNFR2 is selectively activated by RANKL. Treatment of these cells with sTNF and RANKL leads to an enhanced cytotoxicity

Application of a Pharmacogenetics-Based Precision Medicine Model (5SPM) to Psychotic Patients That Presented Poor Response to Neuroleptic Therapy

[EN] Antipsychotics are the keystone of the treatment of severe and prolonged mental disorders. However, there are many risks associated with these drugs and not all patients undergo full therapeutic profit from them. The application of the 5 Step Precision Medicine model(5SPM), based on the analysis of the pharmacogenetic profile of each patient, could be a helpful tool to solve many of the problematics traditionally associated with the neuroleptic treatment. In order to solve this question, a cohort of psychotic patients that showed poor clinical evolution was analyzed. After evaluating the relationship between the prescribed treatment and pharmacogenetic profile of each patient, a great number of pharmacological interactions and pharmacogenetical conflicts were found. After reconsidering the treatment of the conflictive cases, patients showed a substantial reduction on mean daily doses and polytherapy cases, which may cause less risk of adverse effects, greater adherence, and a reduction on economic costs

Long-term cardiac reverse remodeling after cardiac resynchronization therapy

Introduction: The benefit of cardiac resynchronization therapy (CRT) in heart failure (HF) patients with reduced left ventricular ejection fraction (LVEF) have been observed in the first year. However, there are few data on long-term follow-up and the effect of changes of LVEF on mortality. This study aimed to assess the LV remodeling after CRT implantation and the probable effect of changes in LVEF with repeated measures on mortality over time in a real-world registry. Methods: Among our cohort of 328 consecutive CRT patients, mixed model effect analysis have been made to describe the temporal evolution of LVEF and LVESV changes over time up with several explanatory variables. Besides, the effect of LVEF along time on the probability of mortality was evaluated using joint modeling for longitudinal and survival data. Results: The study population included 328 patients (253 men; 70.2 ± 9.5 years) in 4.2 (2.9) years follow-up. There was an increase in LVEF of 11% and a reduction in LVESV of 42 mL during the first year. These changes are more important during the first year, but slight changes remain during the follow-up. The largest reduction in LVESV occurred in patients with left bundle branch block (LBBB) and the smallest reduction in patients with NYHA IV. The smallest increase in LVEF was an ischemic etiology, longer QRS, and LV electrode in a nonlateral vein. Besides, the results showed that the LVEF profiles taken during follow-up after CRT were associated with changes in the risk of death. Conclusion: Reverse remodeling of the left ventricle is observed especially during the first year, but it seems to be maintained later after CRT implantation in a contemporary cohort of patients. Longitudinal measurements could give us additional information at predicting the individual mortality risk after adjusting by age and sex compared to a single LVEF measurement after CRTS

La estructura argumental y su aplicación a la enseñanza de ELE: El caso de los pronombres átonos de complemento

[ES] En la enseñanza de ELE, el docente se encuentra con un buen número de aspectos gramaticales complejos ante los que debe ofrecer una descripción coherente con el uso, y fácil de asimilar por parte de un estudiante que no suele tener formación lingüística previa. Para lograrlo, defendemos en este trabajo que la formación gramatical del profesor es esencial y, en ese sentido, mostramos un caso ilustrativo: cómo la estructura argumental de un predicado y la teoría de las valencias derivada de L. Tesnière pueden ayudar en el aprendizaje del uso de los pronombres átonos de complemento.[EN] In the teaching of ELE, the teacher encounters a good number of complex grammatical aspects before which he must offer a description that is coherent with the use, and easy to assimilate by a student who usually does not have any previous linguistic training. To achieve this, we defend in this work that the teacher’s grammar training is essential and, in this sense, we show an illustrative case: how the argument structure of a predicate and the theory of valences derived from L. Tesnière can help in learning the use of unstressed complement pronouns

Effectiveness and tolerability of dolutegravir/lamivudine for the treatment of HIV-1 infection in clinical practice

Objectives: To assess the effectiveness and tolerability of dolutegravir (DTG)/lamivudine (3TC) among treatment-naive and virologically suppressed treatment-experienced individuals in the multicentre cohort of the Spanish HIV/AIDS Research Network (CoRIS) during the years 2018-2021. Methods: We used multivariable regression models to compare viral suppression (VS) [HIV RNA viral load (VL) <50 copies/mL] and the change in CD4 cell counts at 24 and 48 (±12) weeks after initiation with dolutegravir/lamivudine or other first-line ART regimens. Results: We included 2160 treatment-naive subjects, among whom 401 (18.6%) started with dolutegravir/lamivudine. The remaining subjects started bictegravir (BIC)/emtricitabine (FTC)/tenofovir alafenamide (TAF) (n = 949, 43.9%), DTG + FTC/tenofovir disoproxil fumarate (TDF) (n = 282, 13.1%), DTG/3TC/abacavir (ABC) (n = 255, 11.8%), darunavir (DRV)/cobicistat(COBI)/FTC/TAF (n = 147, 6.8%) and elvitegravir (EVG)/COBI/FTC/TAF (n = 126, 5.8%). At 24 and 48 weeks after starting dolutegravir/lamivudine, 91.4% and 93.8% of the subjects, respectively, achieved VS. The probability of achieving VS with dolutegravir/lamivudine was not significantly different compared with any other regimen at 24 or 48 weeks, with the exception of a lower chance of achieving VS at 24 weeks for DRV/COBI/FTC/TAF (adjusted OR: 0.47; 95% CI: 0.30-0.74) compared with dolutegravir/lamivudine.For the analysis of treatment-experienced virally suppressed subjects we included 1456 individuals who switched to dolutegravir/lamivudine, among whom 97.4% and 95.5% maintained VS at 24 and 48 weeks, respectively. During the first 48 weeks after dolutegravir/lamivudine initiation, 1.0% of treatment-naive and 1.5% of treatment-experienced subjects discontinued dolutegravir/lamivudine due to an adverse event. Conclusions: In this large multicentre cohort, effectiveness and tolerability of dolutegravir/lamivudine were high among treatment-naive and treatment-experienced subjects.This work was supported by (i) the Instituto de Salud Carlos III through the Red Temática de Investigación Cooperativa en Sida (RD06/006, RD12/0017/0018 and RD16/0002/0006) as part of the Plan Nacional I + D + i and co-financed by Instituto de Salud Carlos III-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), and (ii) ViiV Healthcare. The funders did not play any decision making role in the design, execution, analysis or reporting of the research.S

Alfabetización tecnológica

Introduction: The social, economic and cultural environment is undergoing a transformation caused by computer technologies, becoming almost indispensable in our lives. However, the elderly can present problems of adaptation, triggering a lack of technological literacy that in the health field could have an impact on their quality of life. The objective is to observe how new technologies affect the elderly, and propose nursing interventions that favor their adaptation to this new era. Material and Methods: Articles published since 2009, from anywhere in the world, have been consulted free of charge, in Spanish and English. The databases consulted have been PubMed, Google Scholar, Mesh, ScienceDirect, Trip Database, IBECS and DeCS. Results: Currently, technologies are adapting and evolving differently around the world, assuming progress in all places. A positive effect has been observed regarding the relationship and communication between the elderly and their environment, being advisable to provide greater cognitive stimulation with respect to these. Discussion: Most of the evidence found points to the benefit that technology brings regarding the connection of the elderly with their social environment. In healthcare, telecare has proven to improve the quality of life of the elderly. Just as the electronic prescription helps with pharmacological adherence and provides comfort for chronic and / or multipathological patients, the telematic appointment reduces long waiting times. Conclusion: The technologies, associated with social isolation, telecare and electronic prescriptions, have a positive effect on the quality of life of the elderly population. Providing them with an exercise of their brain activity, greater selfesteem and comfort, solving their health problems from home without having to approach a health center.Introducción: El entorno social, económico y cultural está sufriendo una transformación causada por las tecnologías informáticas, convirtiéndose casi indispensables en nuestras vidas. Sin embargo, la edad anciana puede presentar problemas de adaptación, desencadenando una falta de alfabetización tecnológica que en el ámbito sanitario podría repercutir en su calidad de vida. El objetivo es observar cómo afectan las nuevas tecnologías a los ancianos, y proponer intervenciones enfermeras que favorezcan su adaptación a esta nueva era. Material y Métodos: Se han consultado artículos publicados a partir de 2009, de cualquier parte del mundo, de extensión completa gratuita, en español e inglés. Las bases de datos consultadas han sido PubMed, Google Académico, Mesh, ScienceDirect, Trip Database, IBECS y DeCS. Resultados: Actualmente las tecnologías están adaptándose y evolucionando de forma diferente por el mundo, suponiendo un avance en todos los lugares. Se ha observado un efecto positivo en cuanto a la relación y comunicación entre los ancianos y su entorno,siendo recomendable proporcionar una mayor estimulación cognitiva con respecto a estas. Discusión: La mayor parte de la evidencia encontrada apunta al beneficio que la tecnología aporta respecto a la conexión de los ancianos con su entorno social. En sanidad, la teleasistencia ha demostrado mejorar la calidad de vida de los ancianos. Así como la receta electrónica ayuda con la adherencia farmacológica y supone comodidad para pacientes crónicos y/o pluripatológicos, la cita telemática disminuye las largas esperas de consulta. Conclusión: Las tecnologías, asociadas al aislamiento social, teleasistencia y receta electrónica, tienen efecto positivo en la calidad de vida de la población anciana. Proporcionándoles una ejercitación de su actividad cerebral, una mayor autoestima y comodidad, solucionando sus problemas de salud desde casa sin tener que acercarse a un centro sanitario