La imagen y La narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Municipios Arauquita, Fortul del departamento de Arauca y Soatá, departamento de Boyacá.

Colombia ha experimentado décadas de violencia, una realidad que muchos de sus ciudadanos han llegado a considerar como parte normal de su día a día. En diversas regiones del país, las masacres, desapariciones y desplazamientos forzados son lamentablemente comunes, imponiendo un peso constante en la vida de los habitantes de esos territorios. Entre los numerosos testimonios, destaca el caso de Amparo, quien tuvo que afrontar la desaparición de su esposo y se vio obligada al exilio. En su nueva realidad, se enfrentó a cambios significativos, una situación compartida por relatos similares, como el de Yulery en El Salado. Estas historias revelan un panorama de inseguridad, miedo, temor, ansiedad, vergüenza, desesperación y un desequilibrio mental y emocional, así como daños físicos y rupturas en los tejidos sociales, además de sufrir torturas. Además, se llevó a cabo un análisis de diversas experiencias en el municipio de Arauca, donde la violencia perpetrada por grupos armados al margen de la ley ha sumido a la población en un dolor profundo y desesperanza. Asimismo, se examina la violencia relacionada con el consumo de sustancias psicoactivas en el municipio de Soatá, observando cómo afecta principalmente al núcleo familiar ya sus miembros. Es evidente que la narrativa se ha convertido en una herramienta crucial para aquellos que buscan liberar sus emociones y superar las difíciles etapas de duelo por estas experiencias traumáticas. Estos relatos no solo documentan el sufrimiento, sino que también resaltan la resiliencia de aquellos que buscan reconstruir sus vidas a pesar de las adversidades.Colombia has experienced decades of violence, a reality that many of its citizens have come to consider as a normal part of their daily lives. In various regions of the country, massacres, disappearances and forced displacements are unfortunately common, imposing a constant burden on the lives of the inhabitants of those territories. Among the numerous testimonies, the case of Amparo stands out, who had to face the disappearance of her husband and was forced into exile. In his new reality, he faced significant changes, a situation shared by similar stories, such as that of Yulery in El Salado. These stories reveal a panorama of insecurity, fear, fear, anxiety, shame, despair and a mental and emotional imbalance, as well as physical damage and ruptures in social fabrics, in addition to suffering torture. In addition, an analysis was carried out of various experiences in the municipality of Arauca, where violence perpetrated by armed groups outside the law has plunged the population into deep pain and hopelessness. Likewise, violence related to the consumption of psychoactive substances in the municipality of Soatá is examined, observing how it mainly affects the family nucleus and its members. It is evident that narrative has become a crucial tool for those seeking to release their emotions and overcome the difficult stages of grieving these traumatic experiences. These stories not only document suffering, but also highlight the resilience of those seeking to rebuild their lives despite adversity

Generation of a novel model of bioengineered human oral mucosa with increased vascularization potential

Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I) of the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III), Grant/Award Number: FIS PI18/331, FIS PI21/00980, FIS PI18/332 and ICI19/00024; Consejeria de Salud y Familias, Junta de Andalucia, Spain, Grant/Award Number: PI-0442--2019; FEDER funds, European UnionObjective: The aim of this study was to generate novel models of bioartificial human oral mucosa with increased vascularization potential for future use as an advanced therapies medicinal product, by using different vascular and mesenchymal stem cell sources. Background: Oral mucosa substitutes could contribute to the clinical treatment of complex diseases affecting the oral cavity. Although several models of artificial oral mucosa have been described, biointegration is a major issue that could be favored by the generation of novel substitutes with increased vascularization potential once grafted in vivo. Methods: Three types of mesenchymal stem cells (MSCs) were obtained from adipose tissue, bone marrow, and dental pulp, and their in vitro potential was evaluated by inducing differentiation to the endothelial lineage using conditioning media. Then, 3D models of human artificial oral mucosa were generated using biocompatible fibrin-agarose biomaterials combined with human oral mucosa fibroblasts and each type of MSC before and after induction to the endothelial lineage, using human umbilical vein endothelial cells (HUVEC) as controls. The vascularization potential of each oral mucosa substitute was assessed in vitro and in vivo in nude mice. Results: In vitro induction of MSCs kept in culture was able to increase the expression of VEGF, CD31, and vWF endothelial markers, especially in bone marrow and dental pulp-MSCs, and numerous proteins with a role in vasculogenesis become overexpressed. Then, in vivo grafting resulted in a significant increase in blood vessels formation at the interface area between the graft and the host tissues, with significantly positive expression of VEGF, CD31, vWF, and CD34 as compared to negative controls, especially when pre-differentiated MSCs derived from bone marrow and dental pulp were used. In addition, a significantly higher number of cells committed to the endothelial lineage expressing the same endothelial markers were found within the bioartificial tissue. Conclusion: Our results suggest that the use of pre-differentiated MSCs could contribute to a rapid generation of a vascular network that may favor in vivo biointegration of bioengineered human oral mucosa substitutes.Spanish Plan Nacional de Investigacion Cientifica, Desarrollo e Innovacion Tecnologica (I+D+I) of the Spanish Ministry of Science and Innovation (Instituto de Salud Carlos III) FIS PI18/331 FIS PI21/00980 FIS PI18/332 ICI19/00024Junta de Andalucia PI-0442-2019European Commissio

Exploring the link between MORF4L1 and risk of breast cancer.

INTRODUCTION: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. METHODS: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. RESULTS: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to γ-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, Ptrend = 0.45 and 0.05, P2df = 0.51 and 0.14, respectively; and rs10519219, Ptrend = 0.92 and 0.72, P2df = 0.76 and 0.07, respectively. CONCLUSIONS: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Fomento de la inserción laboral desde el aprendizaje servicio y emprendimiento social en los estudiantes del grado de trabajo social

Este proyecto ha seguido las principales líneas definidas en anteriores proyectos de innovación entre los que se encuentran: 1. El Proyecto de Innovación y Mejora de la Calidad Docente de la Convocatoria 2016/2017, con el nº 109, con el tema: “El impulso del emprendimiento como competencia transversal en los estudiantes del Grado de Trabajo Social”, premiado en la VII EDICIÓN de PREMIOS EMPRENDEDOR UNIVERSITARIO UCM, en la 4ª modalidad de Premio Innova docente. 2. El Proyecto de innovación y Mejora de la Calidad Docente de la Convocatoria 2017/2018, con el nº 54, con el tema: “ Red de Empleabilidad y Emprendimiento en los estudiantes del Grado de Trabajo Social” Se ha seguido investigando sobre el emprendimiento social como competencia transversal “iniciativa y espíritu emprendedor” en las asignaturas de: 1. Bases Teóricas del Trabajo Social, 2º Practicum (donde debe realizarse un Proyecto Social); 3. en el Trabajo Fin de Grado (TFG), ayudando a configurar el perfil profesional del alumnado, visualizando nuevas formas de dar respuesta a las necesidades de la población. En otras universidades españolas estos proyectos de innovación, son definidos en sus convocatorias como proyectos de investigación en innovación ya que la innovación conlleva un previo trabajo de investigación. Estas universidades reconocen la investigación que se realiza. En esta línea se encuentran universidades como la Universidad de Alicante, la Universidad Nacional de Educación a Distancia (UNED), la Universidad de Barcelona, etc., que definen la convocatoria como redes de investigación e innovación. Este reconocimiento y acreditación ha sido solicitado a la Universidad Complutense el 30 de Junio de 2016 por email. La existencia de emprendedores sociales como referentes históricos que vincularon su actividad universitaria con la innovación social y el progreso de la humanidad, justifican esta línea de trabajo. En este sentido se ha continuado con el Proyecto de Aprendizaje Servicio “UCM_MEDIMAYOR_ ALUMNI”, de formación en mediación a un grupo de mayores pertenecientes al Centro de Día Peñagrande del Ayuntamiento de Madrid. La responsabilidad social de la universidad, puede encontrase en esta función ya que se ha potenciado la adquisición de competencias profesionales a través de la colaboración en la sociedad Se ha continuado trabajando el fortalecimiento del emprendimiento social relacionado con el desarrollo social y humano, para la realización de una sociedad más equitativa y participativa desde distintas iniciativas que motiven la participación y la cooperación en esta sociedad desde sus instituciones. Entre los resultados obtenidos está la presentación a los estudiantes de buenas prácticas de emprendedores sociales y de estudiantes que han conseguido su inserción laboral, con el fin de incentivar la generación de nuevas experiencias en los estudiantes del Grado de Trabajo Social. Se destaca el hecho de que 12 estudiantes han terminado con un contrato de trabajo en su centro de practicas externas

Assessing associations between the AURKAHMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers

While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood appr

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

An original phylogenetic approach identified mitochondrial haplogroup T1a1 as inversely associated with breast cancer risk in BRCA2 mutation carriers

Introduction: Individuals carrying pathogenic mutations in the BRCA1 and BRCA2 genes have a high lifetime risk of breast cancer. BRCA1 and BRCA2 are involved in DNA double-strand break repair, DNA alterations that can be caused by exposure to reactive oxygen species, a main source of which are mitochondria. Mitochondrial genome variations affect electron transport chain efficiency and reactive oxygen species production. Individuals with different mitochondrial haplogroups differ in their metabolism and sensitivity to oxidative stress. Variability in mitochondrial genetic background can alter reactive oxygen species production, leading to cancer risk. In the present study, we tested the hypothesis that mitochondrial haplogroups modify breast cancer risk in BRCA1/2 mutation carriers. Methods: We genotyped 22,214 (11,421 affected, 10,793 unaffected) mutation carriers belonging to the Consortium of Investigators of Modifiers of BRCA1/2 for 129 mitochondrial polymorphisms using the iCOGS array. Haplogroup inference and association detection were performed using a phylogenetic approach. ALTree was applied to explore the reference mitochondrial evolutionary tree and detect subclades enriched in affected or unaffected individuals. Results: We discovered that subclade T1a1 was depleted in affected BRCA2 mutation carriers compared with the rest of clade T (hazard ratio (HR) = 0.55; 95% confidence interval (CI), 0.34 to 0.88; P = 0.01). Compared with the most frequent haplogroup in the general population (that is, H and T clades), the T1a1 haplogroup has a HR of 0.62 (95% CI, 0.40 to 0.95; P = 0.03). We also identified three potential susceptibility loci, including G13708A/rs28359178, which has demonstrated an inverse association with familial breast cancer risk. Conclusions: This study illustrates how original approaches such as the phylogeny-based method we used can empower classical molecular epidemiological studies aimed at identifying association or risk modification effects.Peer reviewe

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe