Using pluripotent stem cells to understand normal and leukemic hematopoietic development

Several decades have passed since the generation of the first embryonic stem cell (ESC) lines both in mice and in humans. Since then, stem cell biologists have tried to understand their potential biological and clinical uses for their implementation in regenerative medicine. The hematopoietic field was a pioneer in establishing the potential use for the development of blood cell products and clinical applications; however, early expectations have been truncated by the difficulty in generating bonafide hematopoietic stem cells (HSCs). Despite some progress in understanding the origin of HSCs during embryonic development, the reproduction of this process in vitro is still not possible, but the knowledge acquired in the embryo is slowly being implemented for mouse and human pluripotent stem cells (PSCs). In contrast, ESC-derived hematopoietic cells may recapitulate some leukemic transformation processes when exposed to oncogenic drivers. This would be especially useful to model prenatal leukemia development or other leukemia-predisposing syndromes, which are difficult to study. In this review, we will review the state of the art of the use of PSCs as a model for hematopoietic and leukemia development

Características clínico- epidemiológicas de pacientes con esclerosis múltiple en dos hospitales de alta complejidad

Objetive: To know the clinical-epidemiological characteristics of patients with multiple sclerosis of two high complexity hospitals in the Lambayeque region between 2012-2017. Material and methods. reviewed 84 medical records of patients diagnosed with multiple sclerosis at Almanzor Aguinaga Asenjo National Hospital and Lambayeque Regional Hospital. The data obtained were recorded in a data collection sheet composed of 17 items. We worked with the database in SPSS v 22, for the descriptive analysis we used absolute and relative frequency. Results: The most common form of presentation was the progressive primary form, with an average age of 44 years; among the most frequent clinical manifestations, limb weakness was found, followed by retro ocular pain. The total number of patients diagnosed with multiple sclerosis was performed, nuclear magnetic resonance as a diagnostic test. Conclusions: The most frequent clinical manifestations were weakness of upper and lower limbs, retro ocular pain, paraesthesia, ataxia and fatigue. They were mostly men with an average age of 44 years. Most of them came from the coast and had no infections prior to diagnosis. Magnetic resonance imaging was performed as a complementary test in all patients.Objetivo: Conocer las características clínico- epidemiológicas de pacientes con esclerosis múltiple de dos hospitales de alta complejidad de la región Lambayeque entre los años 2012-2017. Material y Métodos: Revisaron 84 historias clínicas de pacientes con diagnóstico de Esclerosis múltiple en Hospital nacional Almanzor Aguinaga Asenjo y Hospital Regional Lambayeque. Los datos obtenidos fueron registrados en una ficha de recolección de datos compuesta por 17 ítems. Se trabajó con la base de datos en SPSS v 22, para el análisis descriptivo se utilizó frecuencia absoluta y relativa. Resultados: La forma de presentación más común fue la forma primaria progresiva, con una edad promedio de 44 años; entre las manifestaciones clínicas más frecuentes, se encontró la debilidad de miembros, seguida del dolor retro ocular. Al total de pacientes diagnosticados con esclerosis múltiple se le realizó, resonancia magnética nuclear como examen diagnóstico. Conclusiones: Las manifestaciones clínicas más frecuentes fueron debilidad de miembros superiores e inferiores, dolor retro ocular, parestesias, ataxia y fatiga. En su mayoría fueron varones con edad promedio de 44 años. La mayor parte procedían de la costa y no presentaban infecciones previas al diagnóstico. La resonancia magnética se realizó como examen complementario en todos los pacientes

Chromatin-linked and NF-kB independent IkBa function in embryonic stem cell pluripotency exit and differentation

Pluripotent stem cells (PSCs) have the ability to self-renew and give rise to almost every somatic cell type. Because of their enormous potential as a tool for regenerative medicine, understanding molecular mechanisms that drive and maintain pluripotency identity is crucial not only to obtain somatic cell products but also to better know how pluripotency dysregulation can lead to diseases such as cancer. In this regard, NF-κB constitutes a key pathway which mediates immune response and inflammation, although its implication in pluripotency has not yet been elucidated. Specifically, the main inhibitor of NF-κB, IκBα, has been reported to have nuclear and alternative functions independent to NF-κB which are linked to developmental gene regulation in adult stem cells. In this doctoral thesis, I study the functional implication of nuclear IκBα in the context of pluripotency, and how it can regulate gene regulation upon differentiation of mouse embryonic stem cells. I demonstrated that IκBα is essential for pluripotency exit after mESCs differentiation in vitro and in vivo. Mechanistically, loss of IκBα in mESCs induces a global loss of DNA methylation which persists upon differentiation. Interestingly, identification of separation-of-function IκBα mutants has allowed to demonstrate for the first time that pluripotency blockade in IκBα-/- mESCs is.Las células madre pluripotentes (por sus siglas en ingles PSCs) tienen la habilidad de mantenerse en cultivo de manera indiferenciada establemente y, activando diferentes programas de diferenciación, puedes originar casi todos los tipos de células diferenciadas. Debido al gran potencial que las PSCs tienen como herramienta en medicina regenerativa, entender los mecanismos moleculares que controlan la pluripotencia es crucial no sólo para obtener mejores productos celulares sino también para conocer mejor cómo la desregulación en la red de pluripotencia puede originar enfermedades como el cáncer. En este sentido, la vía de NF-κB es clave para mediar una respuesta inmune y regular la inflamación, aunque la implicación de esta vía en la pluripotencia no se conoce muy bien. Específicamente, el principal inhibidor de of NF-κB, IκBα, tiene una función nuclear y alternativa independiente a NF-κB que está ligada a regulación génica durante el desarrollo en células madre adultas. En esta tesis doctoral, estudio el papel funcional de este IκBα nuclear en el contexto de pluripotencia, y cómo IκBα puede regular genes durante la diferenciación de células madre embrionarias. Más en detalle, demuestro que IκBα es esencial para la salida de pluripotencia tras la diferenciación de PSCs de ratón in vivo e in vitro. A nivel mecanístico, la falta de IκBα en PSCs induce una perdida global de metilación en el DNA que persiste tras la diferenciación. Además, la identificación de mutantes de IκBα que pueden separar la función cromatínica de la función ligada a NF-κB ha permitido demostrar por primera vez que el bloqueo de pluripotencia en IκBα-/- PSCs es dependiente de la función de cromatina de IκBα, mientras que no depende de la vía de NF-κB

Excessive Drinking Among Men Who Have Sex With Men Recruited From Web-Based Resources : Cross-sectional Questionnaire Study

Background: US and Northern European studies have found a higher prevalence of alcohol-related problems among men who have sex with men (MSM) than among the general population of men (GPM). However, most of them relied on traditional sampling methods, not profiting from MSM dating apps and websites for recruitment. Besides, analogous comparisons in Southern Europe are lacking. Objective: This study aimed to compare several indicators of excessive drinking between MSM and GPM in Spain. Methods: Overall, 5862 MSM were recruited through dating apps or websites for the Méthysos Project, and 10,349 GPM were recruited using probability sampling via the Household Survey on Alcohol and Drugs in Spain from 2018 to 2020. The outcomes were the prevalence of hazardous or harmful drinking (Alcohol Use Disorders Identification Test [AUDIT] ≥8), hazardous drinking (AUDIT-Consumption ≥4), harmful drinking (AUDIT-Problem ≥4), regular hazardous drinking (>14 standard drinks per week), and monthly binge drinking. The prevalence of excessive drinking indicators was calculated for MSM and GPM and compared using the adjusted prevalence ratio (aPR). Two different aPRs and their 95% CIs were estimated using Poisson regression models with robust variance. The first was adjusted for sociodemographic characteristics, and the second was adjusted for the aforementioned covariates plus other drug use. Results: The prevalence of hazardous or harmful drinking was 15.6% (913/5862) among MSM versus 7.7% (902/10,349) among GPM. After adjusting for sociodemographic covariates, the risk was higher in MSM than in GPM for harmful or hazardous drinking (aPR 1.8, 95% CI 1.6-2.0), harmful drinking (aPR 2.3, 95% CI 2.0-2.7), and binge drinking (aPR 1.7, 95% CI 1.5-1.9); the same in both populations for hazardous drinking (aPR 0.9, 95% CI 0.9-1.0); and higher in GPM than in MSM for regular hazardous drinking (aPR 0.7, 95% CI 0.6-0.9). The relative excess risk of harmful drinking and binge drinking among MSM tended to increase with increasing education level and size of the place of residence, and the opposite was true for the deficit risk in regular hazardous drinking. Additional adjustment for other drug use greatly buffered the relative excess risk in harmful drinking and binge drinking in MSM, while it deepened its deficit risk in regular hazardous drinking. Conclusions: The use of web-based resources allowed recruiting a large sample of MSM. The risk of hazardous or harmful drinking was 80% greater in MSM than in GPM, which was mainly because of the higher risk of harmful drinking and binge drinking among MSM. Nearly 1 in 6 MSM would benefit from early brief alcohol intervention procedures. The subgroup with harmful or binge drinking combined with other drug use is an important contributor to excess MSM risk in hazardous or harmful drinking and must be a priority target for harm reduction interventions

Promoción turística sostenible de la reserva de la biosfera Tajo-Tejo Internacional

Convocatoria proyectos de innovación de Extremadura 2020/2021Se describe un proyecto llevado acabo por varios centros educativos ubicados en la zona de la Reserva de la Biosfera Tajo-Tejo Internacional (RBTTI) que pretendía contribuir a la transformación sostenible del entorno mediante su conocimiento y promoción, implementando las competencias digital, social y ciudadana y la cultura emprendedora mediante metodologías activas como el aprendizaje servicio. Entre los objetivos principales del proyecto destacan: dar a conocer las implicaciones de la RBTTI; diseñar una campaña de promoción de la RBTTI mediante trípticos y vídeos promocionales; conocer la Reserva a través de las principales vías pecuarias y caminos que comunican los pueblos; descubrir los principales elementos socioculturales, históricos y tradicionales de la Reserva; valorar la importancia del territorio para conservar la biodiversidad: paisajes, ecosistemas, fauna y flora representativa; relacionar la trashumancia y las vías pecuarias como rasgos identificativos de la Reserva, vinculándolo con la historia y rasgos culturales de los pueblos y valorar el emprendimiento y la iniciativa personal, el asosiacionismo y creación de redes de cooperación en y entre pueblos como motor de desarrolloExtremaduraES