Neural stem cell quiescence and stemness are molecularly distinct outputs of the notch3 signalling cascade in the vertebrate adult brain

International audienceNeural stem cells (NSCs) in the adult vertebrate brain are found in a quiescent state and can preserve long-lasting progenitor potential (stemness). Whether and how these two properties are linked, and to what extent they can be independently controlled by NSC maintenance pathways, is unresolved. We have previously identified Notch3 signalling as a major quiescence-promoting pathway in adult NSCs of the zebrafish pallium. We now show that Notch3 also controls NSC stemness. Using parallel transcriptomic characterizations of notch3 mutant NSCs and adult NSC physiological states, we demonstrate that a set of potentially direct Notch3 target genes distinguishes quiescence and stemness control. As a proof of principle, we focus on one 'stemness' target, encoding the bHLH transcription factor Hey1, that has not yet been analysed in adult NSCs. We show that abrogation of Hey1 function in adult pallial NSCs in vivo, including quiescent NSCs, leads to their differentiation without affecting their proliferation state. These results demonstrate that quiescence and stemness are molecularly distinct outputs of Notch3 signalling, and identify Hey1 as a major Notch3 effector controlling NSC stemness in the vertebrate adult brain

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

Background: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. Methods: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine’s registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. Results: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. Conclusions: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Empleo de sitio web en la asignatura Estomatología Integral II

It was carried out an educational investigation, from January 2008 to July 2009 in the University Of Medical Sciences in the University Of Medical Sciences Of Villa Clara, with the objective to identify the learning cores of the subject Integral Dentistry II, to conform a material aid with the educational main topics. It was carried out a documental revision, the opinion of a nominal group was obtained and theoretical methods were used. As a result a website was elaborated using the software Macromedia Flash version 7 and the work was valued by experts and students. There were identified as theoretical cores: the dentist office, the dentist appliances and the dental materials. The judgment of the experts, obtained by means of a focal group, coincides in that the website is favorably related with the didactics and relevancy of the objectives of the subject program that is why the material was very useful for the independent study.Se realizó una investigación educativa, entre los meses de enero del 2008 a julio del 2009 en la Universidad de Ciencias Médicas de Villa Clara, con el objetivo de identificar los núcleos cognitivos de la asignatura Estomatología Integral II, para conformar un material de apoyo a la docencia que supla las carencias bibliográficas de los estudiantes y emplee modernas tecnologías de la información  digitalizada, el cual fue sometido a la valoración de los expertos. Se utilizó la revisión documental, se obtuvo la opinión de los miembros de un grupo nominal y se emplearon métodos teóricos. Como resultado se elaboró un sitio web usando el software Macromedia Flash versión 7 y se valoró su aceptación por expertos y estudiantes. Fueron identificados como núcleos teóricos: el consultorio dental, instrumental y los materiales dentales. El juicio de los expertos, obtenido mediante un grupo focal, coincide en que el sitio creado se relaciona favorablemente con la didáctica y pertinencia de los objetivos del programa de la asignatura, por lo que el material resultó ser de utilidad para el estudio independiente

Factores motivacionales que influyeron en estudiantes de primer año para elegir la carrera de Estomatología

Type of study: descriptive study in fresh more students of the Villa Clara Odontology Faculty in the academic year2011- 2012. Objective: to determine the motivational factors that influenced upon fresh more students to select the Odontology career. Universe: All the students registered in the central site. Sample: conglomerated and randomized sampling of 50% of the students of the groups. Method: a survey was applied to the students. Results: 50.9 % of the students are from Santa Clara , and 49% come from the pre- university, the rest entered through contest. 51.6% referred they had received orientation lectures in Santa Clara municipality and only one student participated in a special training and orientation group, the rest of the municipalities haven�t received any orientation. The identified motivational factors that the students referred were the social recognition 22(41.5%) and the family or friendships 21(39.6) Conclusions: most of the students entered coming from the pre-university and the ones from Santa Clara municipality are predominant. It is stated the presence of motivational factors such as the social recognition and the affective influence, it is also stated the lack of orientation, vocational formation and in a greater extent the participation in special training and orientation groups.Tipo de estudio: descriptivo en estudiantes de primer año de la Facultad de Estomatología de Villa Clara en el curso 2011-2012. Objetivo: determinar los factores motivacionales que influyeron en estos estudiantes para elegir la carrera. Universo: constituido por todos los estudiantes matriculados en la sede central. Muestra: se obtuvo mediante un muestreo aleatorio simple con el 50 % de los alumnos. Métodos: teóricos, empíricos y matemáticos. Resultados: el 50.9% de los ingresados a la carrera fueron del municipio Santa Clara; de éstos, el 49% acceden por preuniversitario, el resto por concurso. Entre ellos, el 51.6% declaran haber recibido conferencias orientadoras y solamente un estudiante del propio municipio señala participación en círculo de interés, el resto de los municipios no refieren haber recibido alguna orientación. Los factores motivacionales identificados en los estudiantes fueron el reconocimiento social representado por 22 (41.5%) y la familia o amistades 21 (39.6). Conclusiones: la mayoría de los estudiantes ingresaron por vía preuniversitario, y predominaron los del municipio Santa Clara. Se identificaron como factores influyentes el reconocimiento social y la influencia afectiva, la escasez de orientación y formación vocacional, y en mayor medida, la casi nula participación en círculo de interés. Por lo que proponemos el análisis en las enseñanzas media superior y superior, de factores como los ya descritos para que se desarrollen acciones con el fin de lograr una mayor motivación en los estudiantes

Progresión curricular en la didáctica de las matemáticas entre segundo nivel de transición (NT2) de educación parvularia y primer nivel de educación básica (NB1)

Tesis (Educadora de Párvulos y Licenciado en Educación)El impacto que tienen los primeros años de vida en el desarrollo del ser humano es considerado un aspecto clave en las distintas políticas públicas a nivel país. Del mismo modo, se ha instalado en el conocimiento colectivo, la idea central que la adecuada intervención en la primera infancia impacta considerablemente en el desarrollo de la inteligencia, la personalidad y el comportamiento social del ser humano. El desarrollo temprano del niño(a) y sus aprendizajes están, a su vez, condicionados por factores que contribuyen a explicar su nivel de avance biopsicosocial. En este sentido, los factores socioeconómicos, características familiares y el acceso a la Educación Parvularia, tienen un efecto decisivo en el resultado escolar, tanto en asociación con otros factores, como de forma aislada. Ahora bien, el impacto beneficioso que tiene la Educación Parvularia en el desarrollo de la personalidad de los niños (as) en sus primeros años de vida, y el posterior aporte a su proceso escolar en la Educación General Básica, requiere de acciones conjuntas entre ambos ciclos educativos. El proceso de progresión curricular, que involucra a las Educadoras de Párvulos y a los profesores de Educación General Básica, pretende una mayor focalización de los aprendizajes relevantes alcanzados por los niños que egresan de Educación Parvularia. Para que el trabajo colaborativo prospere entre ambos niveles, se debe trabajar en conjunto como agentes educativos mediadores en el aprendizaje de los niños y niñas, para facilitarles una exitosa transición. Este trabajo colaborativo requiere de regulación y sistematización, a modo de establecer lineamientos comunes entre los distintos niveles educativos, orientando, a través de acciones concretas, la adecuada progresión curricular. Para alcanzar los propósitos pedagógicos, los marcos curriculares de Educación Parvularia y Educación General Básica, definen los aprendizajes que deberán alcanzar los niños y niñas en ambos ciclos. Transversalmente contienen el principio de que los niños y niñas son capaces de adquirir contenidos y habilidades progresivamente más complejas, en todas las disciplinas que contiene el currículo nacional, tanto por la acumulación y consolidación de sus conocimientos previos, como por su creciente desarrollo físico, cognitivo y socio afectivo. A nivel nacional, el informe resultados SIMCE 2012 ratifica que los establecimientos particulares pagados obtienen puntajes promedios significativamente superiores que los establecimientos de las otras dependencias administrativas, en las tres pruebas. Mientras que los establecimientos particulares subvencionados, obtienen puntajes promedio más altos que los municipales, MINEDUC (2012). Matemática, por otra parte, es el área que representa mayores desafíos para Chile, principalmente por las evidencias internacionales que ubican el aprendizaje de nuestros niños en los niveles de logro más bajos, como en el caso de PISA. El resultado de nuestros estudiantes está más distante del promedio OCDE en matemáticas, que en las otras áreas. Debido a la relevancia que adquieren de las matemáticas en la formación del ser social, el presente estudio centrará su foco en la problemática de cómo se desarrolla el proceso de progresión curricular, entre el Segundo Nivel de Transición (NT2) de Educación Parvularia y Primer Nivel de Educación General Básica (NB1) en la didáctica de las matemáticas. Esta problemática será abordada a partir del trabajo de campo realizado en tres establecimientos educacionales. Cada uno de ellos se denominará de la siguiente manera; Institución A, perteneciente a una red de establecimientos administrados por una sociedad educacional sin fin de lucro, institución B, de administración particular subvencionado e institución C, de administración municipal, ubicados en Chile, Región Metropolitana, en las comunas de San Ramón y Santiago

BINOL-amino acid conjugates as triggerable carriers of DNA-targeted potent photocytotoxic agents

Mild photoactivation of new BINOL-amino acid and -amino ester conjugates (BINOLAMs) yielded alkylating and DNA cross-linking agents with high photoefficiency and superior cytotoxicity. Detection of the transient electrophile, by laser flash photolysis (LFP), suggests that BINOL-quinone methides (QMs) are key intermediates in the process. QMs trapping by water, monitored in a time-dependent product distribution analysis, demonstrated that the phototriggered reactivity of BINOLAMs as bis-alkylating agents is the result of a two-step process involving sequential photogeneration of monoalkylating QMs. Light activation of the BINOL-L-amino esters produced cytotoxic QMs very effective against human tumor LoVo cells with EC50 in the 130-230 nM range. Trimethylpsoralen (PS) is about 4 times less potent than our newly tested compounds. BINOL-L-proline methyl ester showed notable photoselectivity because it displayed cytotoxic effects upon irradiation only and was able to efficiently reach the target DNA inside the cells, where it forms both alkylated and cross-linked species