El concepto de la confianza como valor social que sostiene el sistema sanitario público en España

The public health system is the result of the interaction of social, economic, political and cultural factors, in close relation to social values. Although it is true that times of healthcare shortage and the pandemic caused by the recent Covid 19 Coronavirus have highlighted the management problems of the healthcare organization worldwide. One of the least studied factors is the relationship of trust of the population towards the healthcare system, when, in fact, it is a fundamental dimension for understanding its functioning. This article discusses the concept of trust building between patients and their environment. Contrary to widespread assertions that continue to prioritize doctor- patient relationships, our research data show that the complex concept of trust requires a comprehensive approach by all actors in the public health sector.El sistema sanitario público es el resultado de la interacción de factores sociales, económicos, políticos y culturales, en estrecha relación con los valores sociales. Si bien es cierto que en tiempos de recorte sanitario y de la pandemia reciente provocada por el nuevo coronavirus, COVID-19, se han puesto de manifiesto los problemas de gestión de la organización sanitaria en todo el mundo. Uno de los factores menos estudiados es la relación de confianza de la población hacia el sistema sanitario, cuando, realmente, es una dimensión fundamental para comprender el funcionamiento del mismo. Este artículo analiza el concepto de generación de confianza entre los pacientes y su entorno. En contra de las afirmaciones generalizadas que siguen priorizando las relaciones de médico-paciente, los datos de nuestra investigación evidencian que el complejo concepto de la confianza requiere un abordaje integral de todos los agentes del sector público sanitario

Human umbilical cord-derived mesenchymal stem cells utilise activin-A to suppress interferon-gamma production by natural killer cells

Following allogeneic hematopoietic stem cell transplantation (HSCT), interferon (IFN)-γ levels in the recipient's body can strongly influence the clinical outcome. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) are lucrative as biological tolerance inducers in HSCT settings. Hence, we studied the molecular mechanism of how UC-MSCs influence natural killer (NK) cell-mediated IFN-γ production. Allogeneic NK cells were cultured in direct contact with UC-MSCs or cell free supernatants from MSC cultures (MSC conditioned media). We found that soluble factors secreted by UC-MSCs strongly suppressed IL-12/IL-18-induced IFN-γ production by NK cells by reducing phosphorylation of STAT4, NF-κB as well as T-bet activity. UC-MSCs secreted considerable amounts of Activin-A, which could suppress IFN-γ production by NK cells. Neutralisation of Activin-A in MSC conditioned media significantly abrogated their suppressive abilities. Till date, multiple groups have reported that prostaglandin (PG)-E2 produced by MSCs can suppress NK cell functions. Indeed, we found that inhibition of PGE2 production by MSCs could also significantly restore IFN-γ production. However, the effects of Activin-A and PGE2 were not cumulative. To the best of our knowledge, we are first to report the role of Activin-A in MSC mediated suppression of IFN-γ production by NK cells.DFG/SFB738/A5Hannover Biomedical Research School (HBRS)DFG/REBIRTHNiedersächsische Krebsgesellschaf

Role of gamma-secretase in human umbilical-cord derived mesenchymal stem cell mediated suppression of NK cell cytotoxicity

Background: Mesenchymal stem cells (MSCs) are increasingly considered to be used as biological immunosuppressants in hematopoietic stem cell transplantation (HSCT). In the early reconstitution phase following HSCT, natural killer (NK) cells represent the major lymphocyte population in peripheral blood and display graft-vs-leukemia (GvL) effects. The functional interactions between NK cells and MSCs have the potential to influence the leukemia relapse rate after HSCT. Until date, MSC-NK cell interaction studies are largely focussed on bone marrow derived (BM)-MSCs. Umbilical cord derived (UC)-MSCs might be an alternative source of therapeutic MSCs. Thus, we studied the interaction of UC-MSCs with unstimulated allogeneic NK cells.Results: UC-MSCs could potently suppress NK cell cytotoxicity in overnight cultures via soluble factors. The main soluble immunosuppressant was identified as prostaglandin (PG)-E2. Maximal PGE2 release involved IL-1β priming of MSCs after close contact between the NK cells and UC-MSCs. Interestingly, blocking gamma-secretase activation alleviated the immunosuppression by controlling PGE2 production. IL-1 receptor activation and subsequent downstream signalling events were found to require gamma-secretase activity.Conclusion: Although the role of PGE2 in NK cell-MSC has been reported, the requirement of cell-cell contact for PGE2 induced immunosuppression remained unexplained. Our findings shed light on this puzzling observation and identify new players in the NK cell-MSC crosstalk.DFG/SFB738/A5Hannover Biomedical Research School (HBRS)REBIRTH Cluster of ExcellenceNiedersächsische Krebsgesellschaft e.V

A Social Return on Investment Analysis of Improving the Management of Chronic Obstructive Pulmonary Disease Within the Spanish National Healthcare System

Purpose: To define a set of proposals that would improve the current management of chronic obstructive pulmonary disease (COPD) within the Spanish National Healthcare System (SNHS) from a comprehensive multidisciplinary perspective and to assess the impact of its implementation from clinical, healthcare, economic, and social perspectives. Patients and Methods: A group of 20 stakeholders related to COPD (healthcare professionals, patients, and informal caregivers, among others) participated in an online Delphi process to agree on a set of 15 proposals that would improve the current management of COPD within the SNHS in four areas: diagnosis, risk stratification, management of exacerbations, and management of stable COPD. A one-year forecast-type social return on investment (SROI) analysis was used to estimate the impact that implementing the set of proposals would have in relation to the investment required. A sensitivity analysis was used to test the strength of the model when varying assumption-based data-points. Results: The hypothetical implementation of the complete set of 15 proposals would require a €668 million investment and would generate a €2079 million social impact concerning savings for the SNHS and quality of life improvements for patients and their informal caregivers, among others. Accordingly, for every euro invested in the set of proposals, a social return of €3.11 would be generated (€2.71 in the worst-case scenario and €3.62 in the best-case scenario) of both tangible (32.56%) and intangible nature (67.44%). Conclusion: Altogether, implementing this set of 15 proposals would generate a positive social impact, threefold the required investment. The results may inform decisions relative to healthcare policy and practice regarding COPD management within the SNHS, further contributing to reduce the large burden of COP

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

Daily Impact of COPD in Younger and Older Adults: Global Online Survey Results from over 1,300 Patients

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