Maternal separation increases alcohol-drinking behaviour and reduces endocannabinoid levels in the mouse striatum and prefrontal cortex

Altres ajuts: This study was supported by Plan Nacional sobre Drogas (2014/020) i UE Medbioinformatic project (grant number 634143).Childhood adversity is associated with an increased risk of mood, anxiety and substance use disorders. Maternal separation is a reliable rodent model of early life adversity that leads to depression-like symptoms, which may increase the vulnerability to alcohol consumption during adolescence. However, the specific alterations in the pattern of alcohol consumption induced by maternal separation and the underlying molecular mechanisms are still unclear. The purpose of this study is to evaluate the long-term effects of maternal separation with early weaning (MSEW) on emotional and social behaviour, alcohol rewarding properties, and alcohol consumption, abstinence and relapse in adolescent male C57BL/6 mice. In addition, endocannabinoid and monoamine levels were analysed in discrete brain areas. Results showed that MSEW mice presented emotional alterations related to depressive-like behaviour and modified endocannabinoid levels in the striatum and the prefrontal cortex. MSEW mice also showed impairments in alcohol-induced conditioned place preference and higher alcohol intake in a model of binge drinking. Moreover, MSEW animals displayed a higher propensity to relapse in the two-bottle choice paradigm following a period of alcohol abstinence associated with reduced monoamine levels in the striatum. Such results indicate that exposure to early life stress increased the vulnerability to alcohol binge-drinking during adolescence, which may be partially explained by decreased sensitivity to alcohol rewarding properties and the ability to potentiate alcohol intake following a period of abstinence

Herramientas virtuales en el nivel de cumplimiento de tareas autónomas en el bachillerato en la unidad educativa Dr. Luis Célleri Aviles

This research article details all the work related to the use of virtual tools at the level of fulfillment of autonomous tasks in high school. This investigation lasted 5 months and was carried out with the help of the entire educational community that was the object of study; Teachers and students of the Baccalaureate of the Educational Unit Dr. Luis Célleri Avilés of the La Libertad Canton in the province of Santa Elena participated, which corresponds to 1008 students and 45 teachers. The problem that was under discussion was the low level of fulfillment of autonomous tasks. This inconvenience was expected to be solved through the interaction between teacher - student through a virtual platform that has the advantage of promoting autonomous work with the help of didactic resources. Information was obtained through scientific journals with the bibliographic method and pedagogical strategies that were needed for students to complete extra tasks with the help of technology, and thus improve their academic performance, with all this information it was possible to develop the proposal. which was the structuring of a learning environment. In this proposal, a virtual platform in Moodle was selected for all the advantages and resources that can be used for online classes, sending and receiving activities and the follow-up that the teacher can do with their students. After its implementation, the platform was tested and validated by some teachers and students, obtaining a positive and accepted response.Este artículo de investigación detalla todo el trabajo referente al uso de herramientas virtuales en el nivel de cumplimiento de tareas autónomas en el bachillerato. Esta indagación duro 5 meses y se llevó a cabo con la ayuda de toda la comunidad educativa que fue objeto de estudio; participaron docentes y estudiantes del Bachillerato de la Unidad Educativa Dr. Luis Célleri Avilés del Cantón La Libertad en la provincia de Santa Elena, que corresponde a 1008 estudiantes y 45 docentes. El problema que estuvo en discusión era el bajo nivel de cumplimiento de las tareas autónomas. Este inconveniente se esperaba solucionar a través de la interacción entre docente - estudiante mediante una plataforma virtual que tiene ventajas de promover a realizar los trabajos autónomos con la ayuda de recursos didácticos. Se obtuvo información mediante revista científicas con el método bibliográfico y estrategias pedagógicas que se necesitaba para que los estudiantes cumplan con las tareas extra con la ayuda de la tecnología, y de esa manera mejorar su rendimiento académico, con toda esta información fue posible desarrollar la propuesta que fue la estructuración de un entorno de aprendizaje. En esta propuesta se seleccionó una plataforma virtual en Moodle por todas las ventajas y recursos que se pueden utilizar para las clases online, envió y recepción de actividades y el seguimiento que el docente puede hacer a sus estudiantes. Después de su implementación, la plataforma fue probada y validada por algunos docentes y estudiantes, obteniendo una respuesta positiva y aceptada

Machine Learning Improves Risk Stratification in Myelofibrosis: An Analysis of the Spanish Registry of Myelofibrosis

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with heterogeneous clinical course. Allogeneic hematopoietic cell transplantation remains the only curative therapy, but its morbidity and mortality require careful candidate selection. Therefore, accurate disease risk prognostication is critical for treatment decision-making. We obtained registry data from patients diagnosed with MF in 60 Spanish institutions (N = 1386). These were randomly divided into a training set (80%) and a test set (20%). A machine learning (ML) technique (random forest) was used to model overall survival (OS) and leukemia-free survival (LFS) in the training set, and the results were validated in the test set. We derived the AIPSS-MF (Artificial Intelligence Prognostic Scoring System for Myelofibrosis) model, which was based on 8 clinical variables at diagnosis and achieved high accuracy in predicting OS (training set c-index, 0.750; test set c-index, 0.744) and LFS (training set c-index, 0.697; test set c-index, 0.703). No improvement was obtained with the inclusion of MPN driver mutations in the model. We were unable to adequately assess the potential benefit of including adverse cytogenetics or high-risk mutations due to the lack of these data in many patients. AIPSS-MF was superior to the IPSS regardless of MF subtype and age range and outperformed the MYSEC-PM in patients with secondary MF. In conclusion, we have developed a prediction model based exclusively on clinical variables that provides individualized prognostic estimates in patients with primary and secondary MF. The use of AIPSS-MF in combination with predictive models that incorporate genetic information may improve disease risk stratification

Clinical Presentation and Outcomes of Kawasaki Disease in Children from Latin America: A Multicenter Observational Study from the REKAMLATINA Network

Objetivos: Describir la presentación clínica, el manejo y los resultados de la enfermedad de Kawasaki (EK) en Latinoamérica y evaluar los indicadores pronósticos tempranos de aneurisma de la arteria coronaria (AAC). Diseño del estudio: Se realizó un estudio observacional basado en el registro de la EK en 64 centros pediátricos participantes de 19 países latinoamericanos de forma retrospectiva entre el 1 de enero de 2009 y el 31 de diciembre de 2013, y de forma prospectiva desde el 1 de junio de 2014 hasta el 31 de mayo de 2017. Se recopilaron datos demográficos, clínicos y de laboratorio iniciales. Se utilizó una regresión logística que incorporaba factores clínicos y la puntuación z máxima de la arteria coronaria en la presentación inicial (entre 10 días antes y 5 días después de la inmunoglobulina intravenosa [IGIV]) para desarrollar un modelo pronóstico de AAC durante el seguimiento (>5 días después de la IGIV). Resultados: De 1853 pacientes con EK, el ingreso tardío (>10 días tras el inicio de la fiebre) se produjo en el 16%, el 25% tuvo EK incompleta y el 11% fue resistente a la IGIV. Entre los 671 sujetos con puntuación z de la arteria coronaria notificada durante el seguimiento (mediana: 79 días; IQR: 36, 186), el 21% presentaba AAC, incluido un 4% con aneurismas gigantes. Un modelo pronóstico simple que utilizaba sólo una puntuación z de la arteria coronaria máxima ≥2,5 en la presentación inicial fue óptimo para predecir la AAC durante el seguimiento (área bajo la curva: 0,84; IC del 95%: 0,80, 0,88). Conclusiones: De nuestra población latinoamericana, la puntuación z de la arteria coronaria ≥2,5 en la presentación inicial fue el factor pronóstico más importante que precedió a la AAC durante el seguimiento. Estos resultados resaltan la importancia de la ecocardiografía temprana durante la presentación inicial de la EK. © 2023 Los autoresObjectives: To describe the clinical presentation, management, and outcomes of Kawasaki disease (KD) in Latin America and to evaluate early prognostic indicators of coronary artery aneurysm (CAA). Study design: An observational KD registry-based study was conducted in 64 participating pediatric centers across 19 Latin American countries retrospectively between January 1, 2009, and December 31, 2013, and prospectively from June 1, 2014, to May 31, 2017. Demographic and initial clinical and laboratory data were collected. Logistic regression incorporating clinical factors and maximum coronary artery z-score at initial presentation (between 10 days before and 5 days after intravenous immunoglobulin [IVIG]) was used to develop a prognostic model for CAA during follow-up (>5 days after IVIG). Results: Of 1853 patients with KD, delayed admission (>10 days after fever onset) occurred in 16%, 25% had incomplete KD, and 11% were resistant to IVIG. Among 671 subjects with reported coronary artery z-score during follow-up (median: 79 days; IQR: 36, 186), 21% had CAA, including 4% with giant aneurysms. A simple prognostic model utilizing only a maximum coronary artery z-score ≥2.5 at initial presentation was optimal to predict CAA during follow-up (area under the curve: 0.84; 95% CI: 0.80, 0.88). Conclusion: From our Latin American population, coronary artery z-score ≥2.5 at initial presentation was the most important prognostic factor preceding CAA during follow-up. These results highlight the importance of early echocardiography during the initial presentation of KD. © 2023 The Author(s

Safety and efficacy of intra-arterial bone marrow mononuclear cell transplantation in patients with acute ischaemic stroke in Spain (IBIS trial): a phase 2, randomised, open-label, standard-of-care controlled, multicentre trial

[Background] Pilot clinical trials have shown the safety of intra-arterial bone marrow mononuclear cells (BMMNCs) in stroke. However, the efficacy of different doses of intra-arterial BMMNCs in patients with acute stroke has not been tested in a randomised clinical trial. We aimed to show safety and efficacy of two different doses of autologous intra-arterial BMMNC transplantation in patients with acute stroke.[Methods] The IBIS trial was a multicentre phase 2, randomised, controlled, investigator-initiated, assessor-blinded, clinical trial, in four stroke centres in Spain. We included patients (aged 18–80 years) with a non-lacunar, middle cerebral artery ischaemic stroke within 1–7 days from stroke onset and with a National Institutes of Health Stroke Scale score of 6–20. We randomly assigned patients (2:1:1) with a computer-generated randomisation sequence to standard of care (control group) or intra-arterial injection of autologous BMMNCs at one of two different doses (2 × 106 BMMNCs/kg or 5 × 106 BMMNCs/kg). The primary efficacy outcome was the proportion of patients with modified Rankin Scale scores of 0–2 at 180 days in the intention-to-treat population, comparing each BMMNC dose group and the pooled BMMNC group versus the control group. The primary safety endpoint was the proportion of serious adverse events. This trial was registered at ClinicalTrials.gov, NCT02178657 and is completed.[Findings] Between April 1, 2015, and May 20, 2021, we assessed 114 patients for eligibility. We randomly assigned 77 (68%) patients: 38 (49%) to the control group, 20 (26%) to the low-dose BMMNC group, and 19 (25%) the high-dose BMMNC group. The mean age of participants was 62·4 years (SD 12·7), 46 (60%) were men, 31 (40%) were women, all were White, and 63 (82%) received thrombectomy. The median NIHSS score before randomisation was 12 (IQR 9–15), with intra-arterial BMMNC injection done a median of 6 days (4–7) after stroke onset. The primary efficacy outcome occurred in 14 (39%) patients in the control group versus ten (50%) in the low-dose group (adjusted odds ratio 2·08 [95% CI 0·55–7·85]; p=0·28), eight (44%) in the high-dose group (1·89 [0·52–6·96]; p=0·33), and 18 (47%) in the pooled BMMNC group (2·22 [0·72–6·85]; p=0·16). We found no differences in the proportion of patients who had adverse events or dose-related events, but two patients had a groin haematoma after cell injection in the low-dose BMMNC group.[Interpretation] Intra-arterial BMMNCs were safe in patients with acute ischaemic stroke, but we found no significant improvement at 180 days on the mRS. Further clinical trials are warranted to investigate whether improvements might be possible at different timepoints.The Andalusian Network for the Design and Translation of Advanced Therapies through the Andalusian Progress and Health Public Foundation is the study sponsor. We acknowledge all the participants of the trial and the investigators. We thank the funding bodies Instituto de Salud Carlos III through the projects PI18/01414, PI15/01197, RD16/0019/0015 (INVICTUS+), and RD21/0006/0015 (co-funded by the European Regional Development Fund “A way to make Europe” and by the European Social Fund [FSE] “The FSE invests in your future”), Mutua Madrileña grant, and the Regional Ministry of Health of Andalusia, who financed the costs incurred by participating hospitals and the Andalusian Network for the Design and Translation of Advanced Therapies through the Andalusian Progress and Health Public Foundation. MM-R has a Rio Hortega grant (CM21/00096). We acknowledge the Methodological and Statistical Support Unit from the Andalusian Public Foundation for Health Research Management in Seville (FISEVI) for their support in the statistical analysis.Peer reviewe

Optical properties of nanostructured sol-gel thin films doped with Fe2O3 and the study of their ferromagnetic properties by Mössbauer spectroscopy

Sol–gel thin films containing Fe2O3 were deposited onto glass substrates by the dip-coating method at room temperature. Fe2O3 enriched with the isotope 57Fe was embedded in two kinds ofmatr ices: zinc oxide (ZnO) and silica (SiO2). X-ray diffraction (XRD) was used for morphology and structure determination ofthe nanostructures and showed that the ZnO exhibit a wurtzite form when the film is annealed at 450 C for 20 min. SiO2 thin films at C16H33PEO20:Fe2O3 = 1:2.7×10−1 molar concentration exhibit a hexagonal nanophase produced by the diblock copolymer Brij58 (C16H33PEO20). Optical absorption and infrared spectroscopy techniques were used to evaluate the optical quality ofthe films. In order to determine ifthe Fe2O3 was incorporated into the matrices, room temperature Mössbauer spectra ofboth samples were obtained. In both cases the hematite spectrum was obtained, corroborating that the incorporation ofthe Fe2O3 to the matrices was done without chemical reaction whatsoever

Herramientas virtuales en el nivel de cumplimiento de tareas autónomas en el bachillerato en la unidad educativa Dr. Luis Célleri Aviles

This research article details all the work related to the use of virtual tools at the level of fulfillment of autonomous tasks in high school. This investigation lasted 5 months and was carried out with the help of the entire educational community that was the object of study; Teachers and students of the Baccalaureate of the Educational Unit Dr. Luis Célleri Avilés of the La Libertad Canton in the province of Santa Elena participated, which corresponds to 1008 students and 45 teachers. The problem that was under discussion was the low level of fulfillment of autonomous tasks. This inconvenience was expected to be solved through the interaction between teacher - student through a virtual platform that has the advantage of promoting autonomous work with the help of didactic resources. Information was obtained through scientific journals with the bibliographic method and pedagogical strategies that were needed for students to complete extra tasks with the help of technology, and thus improve their academic performance, with all this information it was possible to develop the proposal. which was the structuring of a learning environment. In this proposal, a virtual platform in Moodle was selected for all the advantages and resources that can be used for online classes, sending and receiving activities and the follow-up that the teacher can do with their students. After its implementation, the platform was tested and validated by some teachers and students, obtaining a positive and accepted response.Este artículo de investigación detalla todo el trabajo referente al uso de herramientas virtuales en el nivel de cumplimiento de tareas autónomas en el bachillerato. Esta indagación duro 5 meses y se llevó a cabo con la ayuda de toda la comunidad educativa que fue objeto de estudio; participaron docentes y estudiantes del Bachillerato de la Unidad Educativa Dr. Luis Célleri Avilés del Cantón La Libertad en la provincia de Santa Elena, que corresponde a 1008 estudiantes y 45 docentes. El problema que estuvo en discusión era el bajo nivel de cumplimiento de las tareas autónomas. Este inconveniente se esperaba solucionar a través de la interacción entre docente - estudiante mediante una plataforma virtual que tiene ventajas de promover a realizar los trabajos autónomos con la ayuda de recursos didácticos. Se obtuvo información mediante revista científicas con el método bibliográfico y estrategias pedagógicas que se necesitaba para que los estudiantes cumplan con las tareas extra con la ayuda de la tecnología, y de esa manera mejorar su rendimiento académico, con toda esta información fue posible desarrollar la propuesta que fue la estructuración de un entorno de aprendizaje. En esta propuesta se seleccionó una plataforma virtual en Moodle por todas las ventajas y recursos que se pueden utilizar para las clases online, envió y recepción de actividades y el seguimiento que el docente puede hacer a sus estudiantes. Después de su implementación, la plataforma fue probada y validada por algunos docentes y estudiantes, obteniendo una respuesta positiva y aceptada

Pressure algometry is a useful tool to quantify pain in the medial part of the knee: An intra- and inter-reliability study in healthy subjects.

PURPOSE: Pain quantification is essential for diagnostic and pain monitoring purposes in disorders around the knee. Pressure algometry is a method described to determine pressure pain threshold (PPT) by applying controlled pressure to a given body point. The purpose of this study was to determine the reliability of this method when it was applied to the medial part of the proximal tibia metaphysis and to evaluate the PPT levels between genders. METHODS: Fifty healthy (mean age; 46.9) volunteers were recruited, 25 men and 25 women. Pressure algometry was applied to a 1 cm(2)-probe area on the medial part of the knee by 2 raters. Intra- and interclass correlation (ICC) was obtained and differences between genders were evaluated. Bland-Altman plots were performed to evaluate the variability of the measures. RESULTS: The mean values of PPT obtained by rater 1 and 2 were 497.5 Kpa and 489 Kpa respectively. The intrarater reliability values (95% IC) for rater 1 and 2 were 0.97 (0.95-0.98) and 0.84 (0.73-0.90) respectively. With regard to interrater reliability, the ICC (95% IC) for the first measurement was 0.92 (0.87-0.95) and 0.86 (0.78-0.92) for the second one. Women showed significant lower values of PPT than men. The Bland-Altmand plots showed excellent agreement. CONCLUSIONS: Pressure algometry has excellent reliability when it is applied to the medial part of the proximal metaphysis of the tibia. Women have lower values of PTT than men. The high reliability of the PA in an individual volunteer makes it a more valuable tool for longitudinal assessment of a given patient than for comparison between them. LEVEL OF EVIDENCE:/nLevel III. Prospective study

Distorsiones, equívocos y ambigüedades. Las ilusiones ópticas en el arte

La muestra plantea un recorrido pensado para motivar la reflexión y el estudio sobre el potencial creativo que han supuesto las ilusiones ópticas a través de la historia del arte y su significación en el arte contemporáneo

Method for removing contaminants from beeswax

[ES] Procedimiento de eliminación de contaminantes de cera de abeja. La presente invención se refiere a un procedimiento para el tratamiento de cera de abeja procedente de explotaciones apícolas, contaminada con restos de tratamientos veterinarios y fitosanitarios mediante un proceso de extracción de la cera fundida con metanol y las posteriores etapas para la adecuación de la cera obtenida para fabricar, a partir de ella, colmenas que son aceptadas por las abejas, además de poder utilizarse en formulaciones galénicas. Por tanto, el marco tecnológico en el que se engloba esta invención es el de la apicultura y más concretamente en el de procesos y dispositivos de extracción de cera de abeja.[EN] The present invention relates to a process for the treatment of beeswax from beekeeping farms, contaminated with residues of veterinary and phytosanitary treatments by means of a process of extraction of the molten wax with methanol and the subsequent steps for the adaptation of the wax obtained to manufacture hives therefrom that are accepted by the bees, and that can also be used in galenic formulations. Therefore, the technological framework in which this invention is included is that of beekeeping and, more specifically, beeswax extraction processes and devices.Peer reviewedUniversidad de Almería, Universidad de Córdoba, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Universidad de AlcaláB2 Patente con examen previ