Envejecimiento: ADN mitocondrial y nuclear

La longevidad ha sido durante años el último deseo de la humanidad, por esta razón, la búsqueda del “elixir de la vida” ha atormentado al hombre durante siglos. Posteriormente, cuando los campos de la ciencia y la tecnología comenzaban a extenderse y los avances conseguidos mejoraron la calidad de vida, tanto en ricos como en pobres, la reducción de la mortalidad y morbilidad en ancianos y la presencia de “supercentenarios” llevaría a pensar que la esperanza de vida seguiría aumentando de manera gradual y lentamente. En el siglo XXI, el hombre ha dejado atrás la búsqueda de la inmortalidad y se ha centrado en conseguir una mayor supervivencia en las mejores condiciones físicas y mentales. Para ello se recurre a la genómica buscando el descubrimiento de los factores genéticos que afectan al mecanismo del envejecimiento y a enfermedades relacionadas con él. Aunque se conocen todavía poco sobre los diversos factores que afectan a la longevidad en los seres humanos, en los últimos años se han publicado numerosos trabajos que evidencian la dependencia de la longevidad respecto al fondo genético

Improved metal-graphene contacts for low-noise, high-density microtransistor arrays for neural sensing

Poor metal contact interfaces are one of the main limitations preventing unhampered access to the full potential of two-dimensional materials in electronics. Here we present graphene solution-gated field-effect-transistors (gSGFETs) with strongly improved linearity, homogeneity and sensitivity for small sensor sizes, resulting from ultraviolet ozone (UVO) contact treatment. The contribution of channel and contact region to the total device conductivity and flicker noise is explored experimentally and explained with a theoretical model. Finally, in-vitro recordings of flexible microelectrocorticography (μ-ECoG) probes were performed to validate the superior sensitivity of the UVO-treated gSGFET to brain-like activity. These results connote an important step towards the fabrication of high-density gSGFET μ-ECoG arrays with state-of-the-art sensitivity and homogeneity, thus demonstrating the potential of this technology as a versatile platform for the new generation of neural interfaces

Evaluation of aminoglycoside and non-aminoglycoside compounds for stop-codon readthrough therapy in four lysosomal storage diseases

Nonsense mutations are quite prevalent in inherited diseases. Readthrough drugs could provide a therapeutic option for any disease caused by this type of mutation. Geneticin (G418) and gentamicin were among the first to be described. Novel compounds have been generated, but only a few have shown improved results. PTC124 is the only compound to have reached clinical trials. Here we first investigated the readthrough effects of gentamicin on fibroblasts from one patient with Sanfilippo B, one with Sanfilippo C, and one with Maro- teaux-Lamy. We found that ARSB activity (Maroteaux-Lamy case) resulted in an increase of 2 - 3 folds and that the amount of this enzyme within the lysosomes was also increased, after treatment. Since the other two cases (Sanfilippo B and Sanfilippo C) did not respond to gentamicin, the treatments were extended with the use of geneticin and five non-aminogly- coside (PTC124, RTC13, RTC14, BZ6 and BZ16) readthrough compounds (RTCs). No recovery was observed at the enzyme activity level. However, mRNA recovery was observed in both cases, nearly a two-fold increase for Sanfilippo B fibroblasts with G418 and around 1.5 fold increase for Sanfilippo C cells with RTC14 and PTC124. Afterwards, some of the products were assessed through in vitro analyses for seven mutations in genes responsible for those diseases and, also, for Niemann-Pick A/B. Using the coupled tran- scription/translation system (TNT), the best results were obtained for SMPD1 mutations with G418, reaching a 35% recovery at 0.25 μ g/ml, for the p.W168X mutation. The use of COS cells transfected with mutant cDNAs gave positive results for most of the mutations with some of the drugs, although to a different extent. The higher enzyme activity recovery, of around two-fold increase, was found for gentamicin on the ARSB p.W146X mutation. Our results are promising and consistent with those of other groups. Further studies of novelcompounds are necessary to find those with more consistent efficacy and fewer toxic effect

Els treballs de fi de grau a la Universitat de Barcelona

Podeu consultar la versió castellana al camp recurs relacionat.La implantació dels títols de grau ha suposat un repte per a les universitats, que han hagut d'adaptar els seus projectes formatius a les directrius de l’Espai Europeu d’Educació Superior. Un dels aspectes importants d’aquest procés ha estat l'obligació d’incorporar els treballs de fi de grau (TFG) a l’estructura curricular dels plans d’estudis. Aquesta tasca ha estat complexa i, a més, s’ha vist dificultada per la poca tradició que la majoria de facultats i escoles universitàries tenien en el disseny, l'organització i l'avaluació d’aquest tipus de treball. Uns quants cursos després d’haver-se posat en marxa els TFG, l’Institut de Ciències de l’Educació (ICE) de la Universitat de Barcelona va voler oferir als diferents centres de la UB una plataforma de reflexió i debat on poguessin compartir experiències, plantejar dubtes, analitzar models de bones pràctiques i recollir idees per millorar els seus projectes. A tal efecte, des de la Secció d’Universitat de l’ICE, es va organitzar la jornada «Els treballs de fi de grau a la UB». Aquest quadern recull les comunicacions presentades, sintetitza el debat que van generar i presenta les conclusions a què es va arribar

High IGKC-Expressing Intratumoral Plasma Cells Predict Response to Immune Checkpoint Blockade.

Este artículo ha sido publicado en la revista International Journal of Molecular Sciences. Esta versión tiene Licencia Creative Commons CC-BYResistance to Immune Checkpoint Blockade (ICB) constitutes the current limiting factor for the optimal implementation of this novel therapy, which otherwise demonstrates durable responses with acceptable toxicity scores. This limitation is exacerbated by a lack of robust biomarkers. In this study, we have dissected the basal TME composition at the gene expression and cellular levels that predict response to Nivolumab and prognosis. BCR, TCR and HLA profiling were employed for further characterization of the molecular variables associated with response. The findings were validated using a single-cell RNA-seq data of metastatic melanoma patients treated with ICB, and by multispectral immunofluorescence. Finally, machine learning was employed to construct a prediction algorithm that was validated across eight metastatic melanoma cohorts treated with ICB. Using this strategy, we have unmasked a major role played by basal intratumoral Plasma cells expressing high levels of IGKC in efficacy. IGKC, differentially expressed in good responders, was also identified within the Top response-related BCR clonotypes, together with IGK variants. These results were validated at gene, cellular and protein levels; CD138+ Plasma-like and Plasma cells were more abundant in good responders and correlated with the same RNA-seq-defined fraction. Finally, we generated a 15-gene prediction model that outperformed the current reference score in eight ICB-treated metastatic melanoma cohorts. The evidenced major contribution of basal intratumoral IGKC and Plasma cells in good response and outcome in ICB in metastatic melanoma is a groundbreaking finding in the field beyond the role of T lymphocytes

Impact of a Primary Care Antimicrobial Stewardship Program on Bacterial Resistance Control and Ecological Imprint in Urinary Tract Infections

Antimicrobial stewardship programs (ASPs) are a central component in reducing the overprescription of unnecessary antibiotics, with multiple studies showing benefits in the reduction of bacterial resistance. Less commonly, ASPs have been performed in outpatient settings, but there is a lack of available data in these settings. We implemented an ASP in a large regional outpatient setting to assess its feasibility and effectiveness. Over a 5-year post-implementation period, compared to the pre-intervention period, a significant reduction in antibiotic prescription occurred, with a reduction in resistance in E. coli urinary isolates. ASP activities also were found to be cost-effective, with a reduction in medication prescription

Los trabajos de fin de grado en la Universidad de Barcelona

Podeu consultar la versió catalana al camp recurs relacionat.[spa] La implantación de los títulos de grado ha supuesto un reto para las universidades, que han tenido que adaptar sus proyectos formativos a las directrices del Espacio Europeo de Educación Superior. Uno de los aspectos importantes de este proceso ha sido la obligación de incorporar los trabajos de fin de grado (TFG) a la estructura curricular de los planes de estudios. Esta tarea ha sido compleja y, además, se ha visto dificultada por la poca tradición que la mayoría de facultades y escuelas universitarias tenían en el diseño, organización y evaluación de esta clase de trabajo. Después de varios cursos de haberse puesto en marcha los TFG, el Instituto de Ciencias de la Educación (ICE) de la Universidad de Barcelona quiso ofrecer a los diferentes centros de la UB una plataforma de reflexión y debate donde pudieran compartir experiencias, plantear dudas, analizar modelos de buenas prácticas y recoger ideas para mejorar sus proyectos. A tal efecto, desde la Sección de Universidad del ICE se organizó la jornada «Los trabajos de fin de grado en la UB». Este cuaderno recoge las comunicaciones presentadas, sintetiza el debate que generaron y presenta las conclusiones a que se llegó.[eng] The phase-in of undergraduate degrees conforming to the guidelines of the European Higher Education Area has been a challenge for universities as far as their training projects are concerned. An important aspect of this process was the need to incorporate the Bachelor’s Degree Final Project (TFG) to the structure of their curricula. This task has been complex and been hampered also by the lack of tradition that most faculties and university colleges had in the design, organization and evaluation of these types of project. Several years after launching the TFG, the Institute of Education Sciences (ICE) of the University of Barcelona (UB) organized the «The Bachelor’s Degree Final Project» conference to offer different centres of the UB a space for reflection and debate to be able to share experiences, ask questions, analyse models of good practices and gather ideas for improving their projects. The present booklet includes papers, summarizes the debate that many and varied contributions generated and outlines the final conclusions reached at this conference

Plan de Acción Tutorial para nuevos estudiantes de la Facultad de Economía y Empresa

Memoria ID-010. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2021-2022

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe