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Muscle atrophy and functional decline (sarcopenia) are common manifestations of frailty and are critical contributors to morbidity and mortality in older people1. Deciphering the molecular mechanisms underlying sarcopenia has major implications for understanding human ageing2. Yet, progress has been slow, partly due to the difficulties of characterizing skeletal muscle niche heterogeneity (whereby myofibres are the most abundant) and obtaining well-characterized human samples3,4. Here we generate a single-cell/single-nucleus transcriptomic and chromatin accessibility map of human limb skeletal muscles encompassing over 387,000 cells/nuclei from individuals aged 15 to 99 years with distinct fitness and frailty levels. We describe how cell populations change during ageing, including the emergence of new populations in older people, and the cell-specific and multicellular network features (at the transcriptomic and epigenetic levels) associated with these changes. On the basis of cross-comparison with genetic data, we also identify key elements of chromatin architecture that mark susceptibility to sarcopenia. Our study provides a basis for identifying targets in the skeletal muscle that are amenable to medical, pharmacological and lifestyle interventions in late life.

Tissue regeneration requires coordination between resident stem cells and local niche cells1,2. Here we identify that senescent cells are integral components of the skeletal muscle regenerative niche that repress regeneration at all stages of life. The technical limitation of senescent-cell scarcity3was overcome by combining single-cell transcriptomics and a senescent-cell enrichment sorting protocol. We identified and isolated different senescent cell types from damaged muscles of young and old mice. Deeper transcriptome, chromatin and pathway analyses revealed conservation of cell identity traits as well as two universal senescence hallmarks (inflammation and fibrosis) across cell type, regeneration time and ageing. Senescent cells create an aged-like inflamed niche that mirrors inflammation associated with ageing (inflammageing4) and arrests stem cell proliferation and regeneration. Reducing the burden of senescent cells, or reducing their inflammatory secretome through CD36 neutralization, accelerates regeneration in young and old mice. By contrast, transplantation of senescent cells delays regeneration. Our results provide a technique for isolating in vivo senescent cells, define a senescence blueprint for muscle, and uncover unproductive functional interactions between senescent cells and stem cells in regenerative niches that can be overcome. As senescent cells also accumulate in human muscles, our findings open potential paths for improving muscle repair throughout life.

The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p= 0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p= 0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p= 0.01) and the anterior insula (7.56 vs. 7.70; p= 0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p= 0.022) and the posterior insula (1.77 vs. 2.00; p= 0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p= 0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p= 0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD= 2.95 vs. 34.40, SD= 0.6; p= 0.005), depression measured by the Hamilton Depression Scale (7.70, SD = 0.81 vs. 7.56, SD= 0.68; p= 0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD= 0.96 vs. 5.31, SD= 1.12; p= 0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia.

This paper presents different examples of automatic generation of queries to be implemented in a b-learning platform. Queries can be used as complementary contents and self-assessment by students in Manufacturing Processes subjects. They are useful when the available time for classroom teaching is reduced and also in blended applications, allowing students the consolidation of in-person received knowledge. Firstly, some considerations about the teaching of Manufacturing Processes subjects and about the types of queries to be generated automatically are explored. Secondly, a list of potential manufacturing topics for which this methodology is suitable is proposed, selecting three of them. Finally, and by means of non-specialized computer tools, an example of application is developed and the obtained results are presented in each topic.

El infarto agudo de miocardio es en los países desarrollados la causa más importante de mortalidad, así como de un gran número de ingresos hospitalarios. Concretamente, en España cada año se producen alrededor de 140.000 muertes y 5 millones de hospitalizaciones a causa de infarto agudo de miocardio, lo cual corresponde a unos costes de asistencia sanitaria que suponen un 15% de los gastos totales. En este artículo se presenta, pues, un análisis exhaustivo del infarto agudo de miocardio y el pronóstico que comporta en cuanto a recurrencia y mortalidad.

El objetivo del trabajo es identificar variables que permitan diferenciar el dolor torácico de causa no cardiológica (DTCNC) de la enfermedad coronaria (EC). Se realizó un estudio observacional, de casos (pacientes con DTCNC, n = 40) y controles (pacientes con EC, n = 40). Se analizaron variables sociodemográficas, médicas y psicológicas. No existían diferencias en personalidad, excepto en el rasgo «control emocional», menor en DTCNC. Estos enfermos presentaron mayor alexitimia y empleaban más frecuentemente dos estrategias de afrontamiento: la religión y la búsqueda de ayuda médica. Cuando se realizó un análisis multivariable, el modelo compuesto por las siguientes cuatro variables: alexitimia, calidad de vida y afrontamientos basados en la religión y en la búsqueda de ayuda médica muestra una sensibilidad del 85,4% y una especificidad del 80%. Este modelo predictivo podría emplearse como test de screeningpara diferenciar ambos trastornos.

La mortalidad y morbilidad de la cardiopatía isquémica siguen una distribución geográfica heterogénea entre diferentes países e incluso dentro de cada país. El objetivo del presente estudio es analizar si hay diferencias en la distribución geográfica del síndrome metabólico en la población laboral española y su relación con la mortalidad por cardiopatía isquémica. Analizamos datos clínicos y analíticos (n=17.837) procedentes de los exámenes de salud realizados a trabajadores durante el año 2003.

Analizar el perfil de riesgo cardiovascular de una muestra de jóvenes varones españoles de los años ochenta, cohorte inicial del estudio AGEMZA, y compararla con otra muestra de similares características, tras el 2000.

RESUMENEl trabajo presenta un análisis exploratorio usando el criterio BIC para diferenciar empresas entre grupos que establecen relaciones entre el precio de las acciones y variables de información contable como el cash flowy el Valor Patrimonial en Libros. Los grupos obtenidos son analizados sobre medidas características como tamaño, política de dividendos y de inversión, rentabilidad y rotación de activos con el fin de extraer las diferencias de las empresas existentes en cada uno de dichos grupos. Los resultados empíricos obtenidos son consistentes con la teoría del ciclo de vida de la empresa. En particular, el valor de mercado de las empresas pequeñas tiende a estar más influido por el cash flowmientras que el de las empresas grandes tiende a estarlo por el valor en libros.

Los pacientes jóvenes diagnosticados de infarto agudo de miocardio tienen diferente perfil de riesgo cardiovascular, presentación clínica, hallazgos angiográficos y pronóstico que los demás pacientes. En este estudio se analizan las características y la evolución de los pacientes diagnosticados de infarto agudo de miocardio con edad < 46 años.

No randomised, controlled trials have been conducted to date on the efficacy of psychological and pharmacological treatments of pain catastrophising (PC) in patients with fibromyalgia. Our aim in this study was to assess the effectiveness of cognitive-behaviour therapy (CBT) and the recommended pharmacological treatment (RPT) compared with treatment as usual (TAU) at the primary care level for the treatment of PC in fibromyalgia patients.

Introduction The aim of this paper was to compare the efficacy of the treatments for fibromyalgia currently available in both primary care and specialised settings.Methods Published reports of randomised controlled trials (RCTs) researching pharmacological and non-pharmacological treatments in patients with fibromyalgia were found in the MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials and PsychInfo databases. The most recent electronic search was undertaken in June 2006.Results We identified a total of 594 articles. Based on titles and abstracts, 102 full articles were retrieved, 33 of which met the inclusion criteria. These RCTs assessed 120 treatment interventions in 7789 patients diagnosed with primary fibromyalgia. Of them, 4505 (57.8%) were included in the primary care group of our study and 3284 (42.2%) in the specialised intervention group. The sample was mostly made up of middle-aged women, who have had fibromyalgia for a mean period of 6 to 10 years. The mean effect size of the efficacy of the 120 treatment interventions in patients with fibromyalgia compared with controls was 0.49 (95% confidence interval [CI] = 0.39 to 0.58; p < 0.001). In the primary care group it was 0.46 (95% CI = 0.33 to 0.58) while in specialised care it was 0.53 (95% CI = 0.38 to 0.69), with no statistical significance in the differences. We analysed the efficacy of treatments by comparing primary and specialised care in the different fibromyalgia groups and there were no significant differences. The variables of the studies that affected the improvements in the efficacy of fibromyalgia treatment were low quality of the studies and a shorter duration of treatment. However, both factors were biased by the heterogeneity of the studies. Other variables that also improved outcome and were not biased by the heterogeneity of the studies, were younger age of the patients and shorter duration of the disorder. On the contrary, gender and type of treatment (pharmacological vs. psychological) did not affect outcome.Conclusion Based on this meta-analysis and despite the heterogeneity of specialised care studies and of the other limitations described in this article, treating fibromyalgia in specialised care offers no clear advantages.