Hyperphosphatemia Promotes Senescence of Myoblasts by Impairing Autophagy Through Ilk Overexpression, A Possible Mechanism Involved in Sarcopenia

In mammalians, advancing age is associated with sarcopenia, the progressive and involuntary loss of muscle mass and strength. Hyperphosphatemia is an aging-related condition involved in several pathologies. The aim of this work was to assess whether hyperphosphatemia plays a role in the age-related loss of mass muscle and strength by inducing cellular senescence in murine myoblasts and to explore the intracellular mechanism involved in this effect. Cultured mouse C2C12 cells were treated with 10 mM beta-glycerophosphate (BGP] at different periods of time to induce hyperphosphatemia. BGP promoted cellular senescence after 24 h of treatment, assessed by the increased expression of p53, acetylated-p53 and p21 and senescence associated beta-galactosidase activity. In parallel, BGP increased ILK expression and activity, followed by mTOR activation and autophagy reduction. Knocking-down ILK expression increased autophagy and protected cells from senescence induced by hyperphosphatemia. BGP also reduced the proliferative capacity of cultured myoblasts. Old mice (24months-old] presented higher serum phosphate concentration, lower forelimb strength, higher expression of p53 and ILK and less autophagy in vastus muscle than young mice (5-months-old]. In conclusion, we propose that hyperphosphatemia induces senescence in cultured myoblasts through ILK overexpression, reducing their proliferative capacity, which could be a mechanism involved in the development of sarcopenia, since old mice showed loss of muscular strength correlated with high serum phosphate concentration and increased levels of ILK and p53

Consenso sobre la vacunación frente a la gripe en el personal sanitario

Health care workers (HCW) are included each year among risk groups for vaccination against influenza. However, vaccination coverage among this group in our country is very low, not exceeding 25%. Convinced that one of the best tools to increase this coverage among professionals in our country are the scientific evidence, 19 scientific societies and associations professionals bringing together health professionals more directly related to influenza as an health problem, and the General Nursing Council, met to discuss and develop this consensus document in order to inform HCW about the appropriateness of their vaccination against influenza and the benefits that flow from it for themselves, for their patients and for the rest of the population. This recommendation is based on 3 pillars: argument of necessity, ethics and exemplary

Conocimientos tradicionales relativos a la biodiversidad agrícola

La biodiversidad agrícola, a diferencia de la silvestre, requiere la acción continuada de los agricultores para su conservación, ya que las plantas cultivadas dependen de la intervención humana, con actividades como la selección, la siembra, el abonado, la poda u otras prácticas agrícolas para su supervivencia. Desde la revolución agrícola del Neolítico hasta la actualidad, estas prácticas y conocimientos han ido generando y conservando una gran diversidad, amenazada a partir de la segunda mitad del siglo XX por las causas que se han indicado anteriormente.Peer reviewe

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Ejemplos de unidades didácticas en Educación Física para la Educación Secundaria Obligatoria

El objetivo es crear hábitos de Educación Física en conexión con valores socioculturales dentro de la E.S.O. La obra consta de varios ejemplos de unidades didácticas que se distribuyen teniendo en cuenta los objetivos, los contenidos, y las orientaciones de evaluación. El contenido de dichas unidades se organiza en juegos y deportes populares, la educación física para la salud, los juegos y deportes alternativos, la resistencia, la condición física y la salud. Concluye con un epígrafe dedicado a la alimentación, control de peso y ejercicio..MadridES

La salud con alegría

Experiencia que entiende la salud no sólo como 'ausencia de enfermedad', sino también como un estado de bienestar físico, mental y social. Por ello, todo lo que contribuya a lograr este estado en la comunidad educativa será objetivo de este proyecto. Se tratará el tema de la salud con vistas a desarrollar la autoestima, y el respeto por los demás y el medio ambiente. El plan de trabajo se basará en clases teóricas en las horas lectivas, prácticas de laboratorio, apoyo de los medios audiovisuales, coordinación de cursos y seminarios, y charlas con los padres. No se adjunta memoria..Madrid (Comunidad Autónoma). Consejería de Sanidad y Servicios SocialesMadridNo disponibleES

Rincón matemático 2000

Con el proyecto se quieren sacar las matemáticas del aula y abrirlas a toda la comunidad. Los objetivos son la participación en el Año Mundial de las Matemáticas de modo activo tanto por profesores como por alumnos; dar a conocer otros aspectos de las matemáticas que no se trabajan en los periodos lectivos; y conocer el desarrollo de las matemáticas a través de sus principales personajes. El proyecto consiste en la elaboración y mantenimiento de un tablón de actividades matemáticas en la entrada de los institutos implicados. Se organiza en los apartados Problema de la semana; Adivina ¿quién es?, donde se esconde un personaje matemático misterioso; Curiosidades, citas, adivinanzas, chistes y anécdotas de carácter matemático; Noticias y convocatorias de concursos, exposiciones y otras actividades que tienen lugar en Madrid; Colaboraciones donde se recogen y exponen los materiales elaborados; y Concurso de Grafitis, realizado en un muro cedido por el ayuntamiento. Cada actividad tiene periodicidad distinta y puede cambiar para cada ciclo. En la evaluación los alumnos valoran los materiales y las actividades realizadas. Participan los Institutos de Educación Secundaria Tierno Galván, José de Churriguera, María Zambrano, Octavio Paz y San Nicasio.Madrid (Comunidad Autónoma). Consejería de EducaciónMadridMadrid (Comunidad Autónoma). Subdirección General de Formación del Profesorado. CRIF Las Acacias; General Ricardos 179 - 28025 Madrid; Tel. + 34915250893ES

Biological features and prognostic impact of bone marrow infiltration in patients with diffuse large B-cell lymphoma

This article belongs to the Special Issue Personalized Medicine: Recent Progress in Cancer Therapy.The biology and clinical impact of bone marrow (BM) infiltration in patients with diffuse large B-cell lymphoma (DLBCL) remains unclear in the rituximab era. We retrospectively analyzed 232 patients diagnosed with DLBCL at our center between 1999 and 2014. Concordant-presence of large cells similar to those of the lymph node biopsy- and discordant-infiltration by small cells forming lymphoid aggregates, lacking cytological atypia-BM infiltration was defined by histological criteria and further characterized by flow cytometry (FCM). Cell of origin (COO) was determined using Hans’ algorithm. For the clonal relationship between tumor and discordant BM, the VDJH rearrangement was analyzed. Survival analyses were restricted to 189 patients treated with rituximab and chemotherapy. Thirty-six (16%) had concordant, and 37 (16%) discordant BM infiltration. FCM described different indolent lymphomas among discordant cases, clonally related with DLBCL in 10/13 available samples. Median follow-up was 58 months. 5-year-progression-free survival (PFS) for non-infiltrated, discordant and concordant groups was 68%, 65% and 30%, respectively (p < 0.001). Combining COO and BM infiltration, patients with discordant BM and non-germinal center B-cell COO also had decreased 5-year-PFS (41.9%). In multivariate analysis, concordant BM had an independent effect on PFS (HR 2.5, p = 0.01). Five-year cumulative incidence of central nervous system (CNS) relapse was 21%, 4% and 1% in concordant, discordant and non-infiltrated groups, respectively (p < 0.001). In conclusion, concordant BM infiltration represents a subset with poor prognosis, whereas the prognostic impact of discordant BM infiltration could be limited to non-CGB cases.This work was partially supported by the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness PI13/02644, PI15/01393, RD12/0036/0069, CIBERONC-CB16/12/00233, and “Una manera de hacer Europa” (Innocampus; CEI-2010-1-0010)”, the Health Council of the Junta de Castilla y León (GRS 850/A/13, GRS 1180/A/15, GRS 1350/A/16, GRS 1846/A/18, GRS 2035/A/19, and BIO/SA78/15), and Gilead Sciences (GLD17/00334). All Spanish funding is co-sponsored by the European Union FEDER program.Peer reviewe

Cristales y minerales

[ES] Trata sobre la formación de los minerales y la cristalografía.[EN] This work is about the minerals and the crystallography