Early-life adversity accelerates cellular ageing and affects adult inflammation: experimental evidence from the European starling

Early-life adversity is associated with accelerated cellular ageing during development and increased inflammation during adulthood. However, human studies can only establish correlation, not causation, and existing experimental animal approaches alter multiple components of early-life adversity simultaneously. We developed a novel hand-rearing paradigm in European starling nestlings (Sturnus vulgaris), in which we separately manipulated nutritional shortfall and begging effort for a period of 10 days. The experimental treatments accelerated erythrocyte telomere attrition and increased DNA damage measured in the juvenile period. For telomere attrition, amount of food and begging effort exerted additive effects. Only the combination of low food amount and high begging effort increased DNA damage. We then measured two markers of inflammation, high-sensitivity C-reactive protein and interleukin-6, when the birds were adults. The experimental treatments affected both inflammatory markers, though the patterns were complex and different for each marker. The effect of the experimental treatments on adult interleukin-6 was partially mediated by increased juvenile DNA damage. Our results show that both nutritional input and begging effort in the nestling period affect cellular ageing and adult inflammation in the starling. However, the pattern of effects is different for different biomarkers measured at different time points

Impacto del trabajo de extensión social y comunitaria que realiza URACCAN - IEPA, en la comunidad mestiza de el Hormiguero e Indígena de Wasakin, Municipios de Siuna y Rosita R.A.A.N periodo 1997 -2007.

El presente estudio se realizó en la comunidad de El Hormiguero, y en la comunidad de Wasakin, Municipios de Siuna y Rosita respectivamente del año 1997 al 2007. Este se hizo con el objetivo primordial de valorar el impacto del trabajo de extensión social y comunitaria que realiza el Instituto de Estudio y Promoción de la Autonomía (IEPA), determinar los beneficios que obtienen los beneficiarios y beneficiarias del acompañamiento comunitario, además conocer la percepción de comunitarios y comunitarias sobre la contribución de la extensión social comunitaria. La metodología empleada para este trabajo fue la aplicación de entrevistas a beneficiarios y beneficiarias del acompañamiento, de igual forma se realizó la técnica de grupo focal, entrevista, en cada una de las comunidades de estudio, como también la observación directa y pláticas informales, esta investigación es de tipo descriptiva con un enfoque cualitativo. A continuación se mencionan algunos de los principales hallazgos obtenidos de ésta investigación: como una manera de llevar a cabo las actividades establecidas hacia las comunidades, el IEPA implementa metodologías sobre distintas temáticas abordadas, entre las que se destacan la ley de Autonomía, gestión local, ley de medio ambiente, demarcación territorial, derechos indígenas entre otras, que se desarrollan cada trimestre. Por medio de este acompañamiento se han generado beneficios en ambas comunidades, ya que a través de esto la universidad URACCAN gestionó a la Corte Suprema de Justicia un centro de mediación y resolución de conflictos en el Hormiguero y como principal logro los comunitarios y comunitarias han desarrollo sus habilidades por medio de sus propias gestiones para su comunidad. En Wasakin los comunitarios y comunitarios obtuvieron la construcción de un puente de hamaca, con la ayuda de también otro de los logros es que se ha incrementado la capacidad de gestión de los mismos, además ambos comunidades cuentan con una muy buena organización. Por otro lado los beneficiarios y beneficiarias de ambas comunidades de estudio perciben que el trabajo del IEPA a través del acompañamiento ha contribuido en gran medida en su desarrollo individual y comunitario. Este estudio servirá como insumo para que la universidad URACCAN en conjunto con las Institutos y Centros Estudios pueda valorar el impacto que ha tenido en el desarrollo de sus funciones y en beneficio a esto puedan continuar con este proceso

Continuous Positive Airway Pressure Treatment in Patients with Alzheimer's Disease: A Systematic Review

Background: Epidemiological studies have suggested a pathophysiological relationship between obstructive sleep apnea syndrome (OSAS) and Alzheimer's disease (AD). The aim of this study is to evaluate the treatment of obstructive sleep apnea with continuous positive airway pressure (CPAP) in AD and its relationship with neurocognitive function improvement. Methods: Systematic review conducted following PRISMA's statements. Relevant studies were searched in MEDLINE, PEDro, SCOPUS, PsycINFO, Web of Science, CINAHL and SportDicus. Original studies in which CPAP treatment was developel in AD patients have been included. Results: 5 studies, 3 RCTs (Randomized controlled trials) and 2 pilot studies. In all RCTs the CPAP intervention was six weeks; 3 weeks of therapeutic CPAP vs. 3 weeks placebo CPAP (pCPAP) followed by 3 weeks tCPAP in patients with AD and OSA. The two pilot studies conducted a follow-up in which the impact on cognitive impairment was measured. Conclusions: CPAP treatment in AD patients decreases excessive daytime sleepiness and improves sleep quality. There are indications that cognitive deterioration function measured with the Mini Mental Scale decreases or evolves to a lesser extent in Alzheimer's patients treated with CPAP. Caregivers observe stabilization in disease progression with integration of CPAP. More research is needed on the topic presented

CathepsinKCre mediated deletion of βcatenin results in dramatic loss of bone mass by targeting both osteoclasts and osteoblastic cells

It is well established that activation of Wnt/βcatenin signaling in the osteoblast lineage leads to an increase in bone mass through a dual mechanism: increased osteoblastogenesis and decreased osteoclastogenesis. However, the effect of this pathway on the osteoclast lineage has been less explored. Here, we aimed to examine the effects of Wnt/βcatenin signaling in mature osteoclasts by generating mice lacking βcatenin in CathepsinK-expressing cells (Ctnnb1;CtsKCre mice). These mice developed a severe low-bone-mass phenotype with onset in the second month and in correlation with an excessive number of osteoclasts, detected by TRAP staining and histomorphometric quantification. We found that WNT3A, through the canonical pathway, promoted osteoclast apoptosis and therefore attenuated the number of M-CSF and RANKL-derived osteoclasts in vitro. This reveals a cell-autonomous effect of Wnt/βcatenin signaling in controlling the life span of mature osteoclasts. Furthermore, bone Opg expression in Ctnnb1;CtsKCre mice was dramatically decreased pointing to an additional external activation of osteoclasts. Accordingly, expression of CathepsinK was detected in TRAP-negative cells of the inner periosteal layer also expressing Col1. Our results indicate that the bone phenotype of Ctnnb1;CtsKCre animals combines a cell-autonomous effect in the mature osteoclast with indirect effects due to the additional targeting of osteoblastic cells.This work was supported by grant ISCIII PI12/01405 to JGM and grant BFU2014-57216-P to MAR from the Spanish Government and R01AR056679 from NIAMS/NIH to MA.Peer Reviewe

Diseño sísmico para una vivienda multifamiliar de 5 pisos con la implementación de la metodología BIM en ADUS-Sullana-Piura- 2021

El presente Proyecto de Investigación denominada “Diseño sísmico para una vivienda multifamiliar de 5 pisos con la Implementación de la Metodología BIM en ADUS-Sullana-Piura-2021” el cual tuvo por objetivo realizar el diseño sísmico para una vivienda multifamiliar de 5 pisos con la Metodología BIM. Esta investigación fue de enfoque cuantitativo de nivel descriptivo, tipo aplicativo y diseño no experimental, la población estuvo constituida por los edificios multifamiliares de ADUS y la muestra fue la edificación de la Mz D11. Lote 09. Se obtuvo como resultados que la edificación de acuerdo a su ubicación tiene un factor de Zona 4, Z= 0.45, el estudio de suelos indico que tiene un suelo Tipo S2 y se desarrolló con un sistema estructural aporticado. Finalmente se concluye, que el modelado en 3D de la vivienda multifamiliar de 5 pisos en ADUS fue realizado el Software Revit 2021, asimismo en el programa SketchUp donde se dieron los toques finales de diseño y presentación y en el Software Robot Structural 2021 se realizó el análisis sísmico donde los desplazamientos, masas participantes, cortantes basales de la edificación, cumplen con lo estipulado en la Norma Técnica Peruana E.030

The newcastle 85+ study

Funding Information: Funding: The Newcastle 85+ study was jointly funded by the Medical Research Council and Biotechnology and Biomedical Science Research Council (G0500997), now part of UK Research and Innovation (UKRI) in addition to the Newcastle Healthcare Charity. The following waves were funded by the Dunhill Medical Trust (R124/0509), Newcastle University, UK Medical Research Council and the British Heart Foundation. Overall, the project was supported by National Institute for Health Research Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. This particular analysis (vitamin D and telomere length) received no additional external funding. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.(1) Introduction: vitamin D may maintain the telomere length, either directly or via the inflammation effect and/or modulating the rate of cell proliferation. Whilst results from crosssectional studies investigating the association between 25(OH)D concentration and telomere length have been mixed, there is a dearth of data from prospective studies which have assessed these associations. This study aimed to examine the association between 25(OH)D concentration in plasma and telomere length in blood cells in very-old adults (≥85 years old) at baseline, 18 months and 36 months by controlling for related lifestyle factors. (2) Methodology: our prospective cohort study comprised 775 participants from the Newcastle 85+ Study who had 25(OH)D measurements at baseline. Plasma 25(OH)D was stratified as 50 nmol/L (high). Peripheral blood mononuclear cell telomere length was measured by quantitative real-time polymerase chain reaction at baseline, 18 and 36 months from baseline. (3) Results: a positive significant association was found between 25(OH)D concentration and telomere length amongst very-old participants at baseline (95% CI = 12.0–110.3, B = 61.2 ± 5.0, p = 0.015). This association was negative at 18 months (95% CI = −59.9–−7.5, B = −33.7 ± 13.3, p = 0.012) but was non-significant at 36 months. (4) Conclusion: Circulating 25(OH)D concentration shows inconsistent relationships with telomere length over time in very-old (85+ year old) adults.publishersversionpublishe

Evaluación formativa del TFG del Grado de Psicologia. Diseño de Rubricas para diferentes modalidades, fases y acciones

El Trabajo de Fin de Grado (TFG), es una asignatura novedosa y de elevada complejidad que ha necesitado el desarrollo de un marco normativo por las Universidades y sus Centros (Reglamentos y Guías Docentes específicas). Tras varios cursos de implantación en el Grado en Psicología de la Universidad de Málaga, este equipo docente consideró necesario revisar el sistema de evaluación de las competencias adquiridas por los alumnos. Para ello se eligió el sistema de evaluación por rúbricas por los beneficios que de ellas se derivan (Alsina, 2010; Del Pozo, 2012; Fernández, 2010; García y Terrón, 2010; Mertler, 2001), especialmente por su valor formativo y evaluador (Blanco, 2008; Cano, 2015; Fernández, 2010), tanto para los estudiantes como para el profesorado. Por tanto, el objetivo de este trabajo fue el diseño de rúbricas para facilitar a todos los implicados (estudiantes, tutores y tribunales) el desarrollo del TFG y la evaluación formativa de los resultados de aprendizaje vinculados a cada una de sus fases, para cada modalidad (Trabajo de Investigación, desarrollo y/o innovación; Análisis y propuesta de resolución de casos prácticos reales; Trabajo de revisión y actualización teórica y/o metodológica y Proyecto de emprendimiento). Para ello se eligió un tipo de rúbrica analítica (Blanco, 2008) y su diseño y elaboración se llevó a cabo según los pasos establecidos por Mertler (2005), de acuerdo al consenso del equipo docente, bajo la supervisión y guía de una profesora experta en evaluación. Fueron evaluadas cualitativamente por el equipo docente, estando prevista la validación de las mismas en cursos posteriores. Se presenta aquí la primera de las rúbricas realizadas para la evaluación de los Trabajos de Fin de Grado en Psicología de la Universidad de Málaga según la modalidad Trabajo de Investigación, desarrollo y/o innovación, sobre un tema determinado relacionado con la Psicología en cualquiera de sus ámbitos de aplicación. Palabras clave: Trabajo de fin de grado, rúbricas, evaluación formativa, enseñanza superior.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Myocardial Ischemia and Reperfusion Leads to Transient CD8 Immune Deficiency and Accelerated Immunosenescence in CMV-Seropositive Patients

Rationale: There is mounting evidence of a higher incidence of coronary heart disease (CHD) in cytomegalovirus (CMV) seropositive individuals. Objective: The aim of this study was to investigate whether acute MI triggers an inflammatory T-cell response that might lead to accelerated immunosenescence in CMV-seropositive patients. Methods and Results: Thirty-four patients with acute MI undergoing primary PCI (PPCI) were longitudinally studied within 3 months following reperfusion (Cohort A). In addition, 54 patients with acute and chronic MI were analyzed in a cross-sectional study (Cohort B). CMV-seropositive patients demonstrated a greater fall in the concentration of terminally differentiated CD8 effector memory T cells (TEMRA) in peripheral blood during the first 30 min of reperfusion compared with CMV-seronegative patients (-192 vs. -63 cells/µl; p=0.008), correlating with the expression of programmed cell death-1 (PD-1) before PPCI (r=0.8; p=0.0002). A significant proportion of TEMRA cells remained depleted for at least 3 months in CMV-seropositive patients. Using high-throughput 13-parameter flow cytometry and HLA class I CMV-specific dextramers, we confirmed an acute and persistent depletion of terminally differentiated TEMRA and CMV-specific CD8+ cells in CMV-seropositive patients. Long-term reconstitution of the TEMRA pool in chronic CMV-seropositive post-MI patients was associated with signs of terminal differentiation including an increase in KLRG1 and shorter telomere length in CD8+ T cells (2225 bp vs. 3397 bp; p<0.001). Conclusions: Myocardial ischemia and reperfusion in CMV-seropositive patients undergoing PPCI leads to acute loss of antigen-specific, terminally differentiated CD8 T-cells, possibly through PD-1-dependent programmed cell death. Our results suggest that acute MI and reperfusion accelerate immunosenescence in CMV-seropositive patients

Literature review on the Council Framework Decision 2008/947/JHA of 27 November 2008 and the Council Framework Decision 2009/829/JHA of 23 October 2009

This report, which addresses a literature review above the Council Framework Decision (FD) 2008/947/JHA and Council Framework Decision (FD) 2009/829/JHA, forms part of the Probation Observatory. Training and Network (PONT) project. This European project is funded by the Directorate General of Justice, coordinated by the University of Bucharest (coordinated by Ioan Durnescu) and implemented in partnership with University Loyola Andalucía, University of Latvia, Bremen Ministry of Justice and Constitution and the Confederation of European Probation (CEP). The main objectives of this project are to offer training to the competent authorities on the two FDs and to create a sustainable network of experts in this field2. To this end, the project team has produced this report to conduct a literature review on the above-mentioned FDs, covering academic papers, grey literature and previous training content. This review has focused on collecting interesting data and information related to the implementation of the mentioned FDs (947 and 829) in order to highlight the most important learning points. From here, PONT will develop an e-manual on good practices and to develop a training package, our project goals. Therefore, articles, books, project reports and other kind of documentation have been taken into account, paying special attention to the training materials developed in prior projects or reports coming from international entities (organisations and EU institutions) related to the practical implementation of the FDs 947 and 829

Rate of telomere shortening and cardiovascular damage: a longitudinal study in the 1946 British Birth Cohort.

AIM: Cross-sectional studies reported associations between short leucocyte telomere length (LTL) and measures of vascular and cardiac damage. However, the contribution of LTL dynamics to the age-related process of cardiovascular (CV) remodelling remains unknown. In this study, we explored whether the rate of LTL shortening can predict CV phenotypes over 10-year follow-up and the influence of established CV risk factors on this relationship. METHODS AND RESULTS: All the participants from the MRC National Survey of Health and Development (NSHD) with measures of LTL and traditional CV risk factors at 53 and 60-64 years and common carotid intima-media thickness (cIMT), cardiac mass and left ventricular function at 60-64 years were included. LTL was measured by real-time polymerase chain reaction and available at both time points in 1033 individuals. While LTL at 53 years was not linked with any CV phenotype at 60-64 years, a negative association was found between LTL and cIMT at 60-64 years (β = -0.017, P = 0.015). However, the strongest association was found between rate of telomere shortening between 53 and 60-64 years and values of cIMT at 60-64 years (β = -0.020, P = 0.006). This association was not affected by adjustment for traditional CV risk factors. Cardiac measurements were not associated with cross-sectional or longitudinal measures of LTL. CONCLUSION: These findings suggest that the rate of progression of cellular ageing in late midlife (reflected by the rate of LTL attrition) relates to vascular damage, independently from contribution of CV risk factor exposure