Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation

Here we explored the role of interleukin-1β (IL-1β) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent in acute myeloid leukemia (AML) patients and represents a prognostic marker of reduced survival. Treatments with IL-1RN and the IL-1β monoclonal antibody canakinumab reduce the expansion of leukemic cells, including CD34+ progenitors, in AML xenografts. In vivo deletion of IL-1rn induces hematopoietic stem cell (HSC) differentiation into the myeloid lineage and hampers B cell development via transcriptional activation of myeloid differentiation pathways dependent on NFκB. Low IL-1rn is present in an experimental model of pre-leukemic myelopoiesis, and IL-1rn deletion promotes myeloproliferation, which relies on the bone marrow hematopoietic and stromal compartments. Conversely, IL-1rn protects against pre-leukemic myelopoiesis. Our data reveal that HSC differentiation is controlled by balanced IL-1β/IL-1rn levels under steady-state, and that loss of repression of IL-1β signaling may underlie pre-leukemic lesion and AML progression

Endogenous IL-1 receptor antagonist restricts healthy and malignant myeloproliferation.

Here we explored the role of interleukin-1β (IL-1β) repressor cytokine, IL-1 receptor antagonist (IL-1rn), in both healthy and abnormal hematopoiesis. Low IL-1RN is frequent in acute myeloid leukemia (AML) patients and represents a prognostic marker of reduced survival. Treatments with IL-1RN and the IL-1β monoclonal antibody canakinumab reduce the expansion of leukemic cells, including CD34+ progenitors, in AML xenografts. In vivo deletion of IL-1rn induces hematopoietic stem cell (HSC) differentiation into the myeloid lineage and hampers B cell development via transcriptional activation of myeloid differentiation pathways dependent on NFκB. Low IL-1rn is present in an experimental model of pre-leukemic myelopoiesis, and IL-1rn deletion promotes myeloproliferation, which relies on the bone marrow hematopoietic and stromal compartments. Conversely, IL-1rn protects against pre-leukemic myelopoiesis. Our data reveal that HSC differentiation is controlled by balanced IL-1β/IL-1rn levels under steady-state, and that loss of repression of IL-1β signaling may underlie pre-leukemic lesion and AML progression.We thank K. Tasken, J. Saarela and the NCMM at the University of Oslo (UiO), S. Kanse (UiO) and B. Smedsrød (UiT), for access to facilities. We acknowledge Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital (Bergen, Norway) and R. Hovland for karyotyping, FISH, translocation and DNA analyses of AML and MDS patients included in this study, and Department of Pathology, Oslo University Hospital (Oslo, Norway) and S. Spetalen for deep sequencing. L.M. Gonzalez, L.T. Eliassen, X. Zhang, M. Ristic and other members of L. Arranz group, O.P. Rekvig, R. Doohan, L.D. Håland, M.I. Olsen, A. Urbanucci, J. Landskron, K.B. Larsen, R.A. Lyså and UiT Advanced Microscopy Core Facility, UiO and UiT Comparative Medicine Units, for assistance. P. Garcia and S. Mendez-Ferrer for providing NRASG12D and Nes-gfp mice, respectively. P. Garcia and L. Kurian for careful reading of the manuscript. E. Tenstad (Science Shaped) for artwork in schematics. We would also like to thank the AML and MDS patients, and healthy volunteers, who donated biological samples. Our work is supported by a joint meeting grant of the Northern Norway Regional Health Authority, the University Hospital of Northern Norway (UNN) and UiT (Strategisk-HN06-14), Young Research Talent grants from the Research Council of Norway, (Stem Cell Program, 247596; FRIPRO Program, 250901), and grants from the Norwegian Cancer Society (6765150), the Northern Norway Regional Health Authority (HNF1338-17), and the Aakre-Stiftelsen Foundation (2016/9050) to L.A. Vav-Cre NRASG12D experiments were supported by NIH grant R01CA152108 to J.Z.S

Competencia digital, alfabetización mediática y formación del profesorado: vinculación de la teoría y la práctica a través de la colaboración inter-nivelar

Depto. de Estudios EducativosFac. de EducaciónFALSEsubmitte

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

IMPREsION a DOS

Si en la vida cotidiana el libro se suele identificar con una lectura dirigida y lineal del lenguaje escrito, que en ocasiones está ilustrado con imágenes visuales, ahora, con la visión nueva aportada por los artistas, asume una diversidad infinita, gracias a la cual se puede utilizar cualquier lenguaje que dé cabida a los cinco sentidos; así, nos permite adoptar la postura que deseemos, tanto de receptores pasivos como de observadores con actitud interactiva plena, en un sinfín de juegos lectores abiertos a descubrir, observar y conocer cualquier nuevo lenguaje y fórmula de expresión artística. La historia, a través de figuras excepcionales como Seghers, Blake, Gauguin y Picasso, entre otros, nos ha mostrado que todas las etapas del proceso creativo pueden contribuir de forma indiscutible a la configuración definitiva del objeto artístico. Así pues, la actitud que el artista adopta, los medios que elige y la acción que desarrolla son determinantes; él nunca olvida que es fundamental la libertad de acción y de elección, que debe correr el riesgo de experimentar nuevas opciones y trazar nuevos caminos buscando su propia, única y original identidad. El libro concebido con esta libertad, goza de la fuerza expresiva que le otorga su inequívoca cualidad de objeto artístico

RedTIC- The Network for Advanced Schools in the use of ICT

La Red de Centros Educativos Avanzados en el uso de las TIC, redTIC, surge en 2004 como una iniciativa nacional impulsada conjuntamente desde la Administración Central, a través de la Entidad Pública Empresarial red.es, y desde las Administraciones Educativas de 11 Comunidades Autónomas: Aragón, Principado de Asturias, Illes Balears, Canarias, Cantabria, Castilla-La Mancha, Castilla y León, Cataluña, La Rioja, Región de Murcia y Comunidad Valenciana. Esta Red nace con el principal objetivo de dar respuesta a los interrogantes que aparecen cuando se pretende integrar las TIC en los procesos de enseñanza y aprendizaje de forma efectiva. Este artículo surge con el fin de dar a conocer la iniciativa y su recorridoThe Network for Advanced Schools in the use of ICT, redTIC, emerges in 2004 as a national initiative driven jointly from the central government, through the Public Entity red.es, and from the education authorities of 11 Autonomous Communities: Aragon, Asturias, Balearic Islands, Canary Islands, Cantabria, Castilla-La Mancha, Castilla y Leon, Catalonia, La Rioja, Murcia and Valencia. This network was created with the main objective of responding to the questions that appear when trying to integrate ICT in teaching and learning in an effective manner. This article arises in order to publicize the initiative and its rout

RedTIC - Red de Centros Educativos Avanzados en el uso de las TIC

The Network for Advanced Schools in the use of ICT, redTIC, emerges in 2004 as a national initiative driven jointly from the central government, through the Public Entity red.es, and from the education authorities of 11 Autonomous Communities: Aragon, Asturias, Balearic Islands, Canary Islands, Cantabria, Castilla-La Mancha, Castilla y Leon, Catalonia, La Rioja, Murcia and Valencia. This network was created with the main objective of responding to the questions that appear when trying to integrate ICT in teaching and learning in an effective manner. This article arises in order to publicize the initiative and its route.La Red de Centros Educativos Avanzados en el uso de las TIC, redTIC, surge en 2004 como una iniciativa nacional impulsada conjuntamente desde la Administración Central, a través de la Entidad Pública Empresarial red.es, y desde las Administraciones Educativas de 11 Comunidades Autónomas: Aragón, Principado de Asturias, Illes Balears, Canarias, Cantabria, Castilla-La Mancha, Castilla y León, Cataluña, La Rioja, Región de Murcia y Comunidad Valenciana. Esta Red nace con el principal objetivo de dar respuesta a los interrogantes que aparecen cuando se pretende integrar las TIC en los procesos de enseñanza y aprendizaje de forma efectiva. Este artículo surge con el fin de dar a conocer la iniciativa y su recorrido

RED. Revista de educación a distancia

Número especial con trabajos del V Simposio pluridisciplinar sobre diseño y evaluación de contenidos educativos reutilizables (SPDECE 2008), Salamanca Octubre 2008.Resumen basado en el de la publicaciónLa Red de Centros Educativos Avanzados en el uso de las TIC, redTIC, surge en 2004 como una iniciativa nacional impulsada conjuntamente desde la Administración Central, a través de la Entidad Pública Empresarial red.es, y desde las Administraciones Educativas de 11 Comunidades Autónomas: Aragón, Principado de Asturias, Illes Balears, Canarias, Cantabria, Castilla-La Mancha, Castilla y León, Cataluña, La Rioja, Región de Murcia y Comunidad Valenciana. Esta Red nace con el objetivo de dar respuesta a los interrogantes que aparecen cuando se pretende integrar las TIC en los procesos de enseñanza y aprendizaje de forma efectiva. Se analiza la iniciativa y su recorrido para darla a conocer.MurciaES

The role of negative affects as mediators in the relationship between stress and mental health in Ecuadorian adolescents

Background Stress and negative emotions have adverse consequences for the mental health of adolescents, an area that deserves further examination. These attributes are associated with each other and regularly interact in different ways. The way they exert an influence can be both direct and indirect, so the general objective is to elucidate the potential mediating effect of negative affects in the relationship between stress and mental health in Ecuadorian adolescents. Participants and procedure An explanatory and mediation design based on structural equation modeling (SEM) was applied with 1154 high school students from Ecuador (67.7% women) aged 14 to 19 years (M = 15.69). Results In our sample, the presence of stress and negative affect is moderate, while that of mental health problems is low. Accord-ing to our final model, these variables covary with and influence each other in the following way: stress (X) has a direct effect on mental health (Y) and also an indirect effect mediated by negative affect (M). The structural regression model pro-posed explains 63% of the variance in mental health. Conclusions Stress exerts a relevant impact on mental health, both through direct and indirect pathways. The indirect pathway, mediat-ed by negative affect, opens the door to novel interventional strategies to foster mental health