La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamento de Santander

El presente informe, tiene como fin poder desarrollar un análisis contextual sobre diversos casos enfocados en el proceso narrativo del conflicto armado, a través de la articulación de escenarios reales contados por sus principales actores. De esta forma, se tiene en cuenta que el proceso del conflicto armado, ha dejado grandes secuelas que atentan contra la salud mental fundamental de las personas que tienen que vivir este flagelo. En consideración con lo anterior, “es importante reconocer que en conflicto armado ha dejado grandes secuelas en el contexto colombiano y en las comunidades, tanto de manera directa como de manera indirecta; teniendo en cuenta de que el conflicto armado también recae sobre las comunidades rurales y urbanas que están alejados de las realidades y los conflictos qué se desarrollan en primera persona” (Rodríguez, J.; De la Torre, A.; Miranda, C. pg. 9. 2002). A partir de lo anterior dicho, se realiza un análisis crítico de dos casos relacionados con la violencia que se ha desarrollado en Colombia, así como con el proceso del desplazamiento forzado que ha tenido que vivir la población a raíz del proceso de la violencia que se ha propinado en las comunidades a raíz de procesos políticos, internos y de dominación del territorio.The purpose of this report is to be able to develop a contextual analysis of various cases focused on the narrative process of the armed conflict, through the articulation of real scenarios told by its main actors. In this way, it is taken into account that the process of the armed conflict has left great consequences that threaten the fundamental mental health of the people who have to live this scourge. In consideration of the above, “it is important to recognize that the armed conflict has left great consequences in the Colombian context and in the communities, both directly and indirectly; taking into account that the armed conflict also falls on rural and urban communities that are far from the realities and conflicts that take place in the first person” (Rodríguez, J.; De la Torre, A.; Miranda, C. pg 9 2002). Based on the foregoing, a critical analysis of two cases related to the violence that has developed in Colombia is carried out, as well as the process of forced displacement that the population has had to experience as a result of the process of violence that took place. it has inflicted on the communities as a result of political, internal and territorial domination processes

Generación de materiales y recursos para la implantación del Plan de Lenguas para la Internacionalización PLI en la Facultad de Óptica y Optometría

Depto. de Optometría y VisiónFac. de Óptica y OptometríaFALSEsubmitte

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury.Acknowledgements: This work was supported by Ministerio de Ciencia, Innovación y Universidades MICINN: PID2020-117116RB-I00 integrado en el Plan Estatal de Investigación Cientifica y Técnica y Innovación, cofinanciado con Fondos FEDER (to MLM-C), Ministerio de Ciencia e Innovación CONSOLIDER-INGENIO 2010 Program Grant CSD2008-00005 (to LAMC); Spanish Ministry of Economy and Competitiveness Grant BFU2013-47531-R, BFU2016-77408-R, PID2019-109055RB-100 (to L.A.M.-C.) (MINECO/FEDER, UE); Asociación Española contra el Cáncer (MLM-C, TC-D), Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M.-C.), La Caixa Foundation Program (to M.L.M.-C.), Fundacion BBVA UMBRELLA project (to M.L.M.-C.), Ayuda RYC2020-029316-I financiada por MICIN/AEI/10.13039/501100011033 (to TC-D), Plataforma de Investigación Clínica-SCReN (PT17 0017 0020) (to M.I.-L.), programa retos RTC2019-007125-1 (to M.L.M.-C, J.S.), Proyectos Investigacion en Salud DTS20/00138 (to M.L.M.-C., J.S), ERA-Net E-Rare EJP RD Joint Translational Call for Rare Diseases FIGHT-CNNM2 (EJPRD19-040) and from Instituto Carlos III, Spain (REF G95229142) (to L.A.M.-C.), US National Institutes of Health under grant CA217817 (to D.B.), Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thankMINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644) and PhD fellowship fromMINECO (REF BES-2017-080435) awarded to I.G.-R. The collection and storage of patients tissues was supported by the Newcastle Biomedicine Biobank and the European Community’s Seventh Framework Programme (FP7/2001–2013) and Cancer Research UK awards Cancer Research UK grants C18342/A23390; C9380/A18084 and C9380/A26813. Finally, we would like to acknowledge Begoña Rodríguez Iruretagoyena for the technical support provided

Mitochondrial bioenergetics boost macrophage activation, promoting liver regeneration in metabolically compromised animals

Background and aims: Hepatic ischemia-reperfusion injury (IRI) is the leading cause of early posttransplantation organ failure as mitochondrial respiration and ATP production are affected. A shortage of donors has extended liver donor criteria, including aged or steatotic livers, which are more susceptible to IRI. Given the lack of an effective treatment and the extensive transplantation waitlist, we aimed at characterizing the effects of an accelerated mitochondrial activity by silencing methylation-controlled J protein (MCJ) in three preclinical models of IRI and liver regeneration, focusing on metabolically compromised animal models. Approach and results: Wild-type (WT), MCJ knockout (KO), and Mcj silenced WT mice were subjected to 70% partial hepatectomy (Phx), prolonged IRI, and 70% Phx with IRI. Old and young mice with metabolic syndrome were also subjected to these procedures. Expression of MCJ, an endogenous negative regulator of mitochondrial respiration, increases in preclinical models of Phx with or without vascular occlusion and in donor livers. Mice lacking MCJ initiate liver regeneration 12 h faster than WT and show reduced ischemic injury and increased survival. MCJ knockdown enables a mitochondrial adaptation that restores the bioenergetic supply for enhanced regeneration and prevents cell death after IRI. Mechanistically, increased ATP secretion facilitates the early activation of Kupffer cells and production of TNF, IL-6, and heparin-binding EGF, accelerating the priming phase and the progression through G1 /S transition during liver regeneration. Therapeutic silencing of MCJ in 15-month-old mice and in mice fed a high-fat/high-fructose diet for 12 weeks improves mitochondrial respiration, reduces steatosis, and overcomes regenerative limitations. Conclusions: Boosting mitochondrial activity by silencing MCJ could pave the way for a protective approach after major liver resection or IRI, especially in metabolically compromised, IRI-susceptible organs.Funding information: Supported by grants from Ministerio de Ciencia, Innovación y Universidades MICINN (PID2020-117116RB-100, RTI2018-096759-A-100, RTI2018-095114-B-I00, PID2019-108977RB-100 and RTI2018-095700-B100, integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER, to M.L.M.-C., T.C.D., C.P., P.M.-S., and N.G.A.A., respectively), Subprograma Retos Colaboración RTC2019-007125-1; Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M.-C.); Asociación Española contra el Cáncer (to T.C.D. and M.S.-M); La Caixa Foundation Program (HR17-00601, to M.L.M.-C.), Proyectos Investigación en Salud DTS20/00138 (to M.L.M.-C.); Departamento de Industria del Gobierno Vasco (to M.L.M.-C.); Departamento de Educación del Gobierno Vasco (to N.G.-U. and J.S.); Acción Estratégica Ciber Emergentes 2018 (Ciberehd-ISCIII) and Gilead Sciences International Research Scholars Program in Liver Disease (to M.V.-R.); Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos IIIAcknowledgments: We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644). We acknowledge Begoña Rodríguez Iruretagoyena for the technical support provided

Handbook for Moving towards Multiprofessional Work

This handbook was supposed to be a choral artwork and the result is a very choral and artistic patchwork. In the process of building up the project ‘MOMU – Moving towards Multiprofessional Work’, we sewed, we combined patterns to define new ones. We knew our shapes were different as were our fabrics but we learned to measure and cut in order to create a larger design. The results of this is what you can see in this handbook. We hope you’ll agree that the whole is greater than the sum of the parts. It has not been easy to piece this together. These types of processes bring with them discussions, arguments, discoveries, hopes, despair and bureaucratic requirements; all inevitable parts of such a complex process. However, it is honest to say that the process has been exciting and paves the way for future and productive collaborations. Along the way some of the participants left us: Carola Boehm and Esther Mercado; some others joined us: Pedro de la Paz. Some changes took place in our universities, new roles were assumed. This is also part of the richness of the tapestry. We are very thankful to all of them for their contribution. We thank the European Union for funding this project. For all of us it was the first time we had developed an Erasmus+ KA2 project and we had to apply the ‘learning by doing formula’, but we managed. We are very thankful to teachers who volunteered to participate in the training sessions, to practitioners who gave us important input and feedback and showed us how to improve and make our teaching more practical. Thanks also to our national steering groups for their clarity and recommendations. Importantly, our gratitude extends to our students: social work and art students, who were open to new perspectives and ways of exploring their place in the world and the job market. Youth unemployment in Europe continues to be an issue, but projects like MOMU aim to address this challenge in creative ways. However, we are at the very starting point and further steps are needed to make the new competence framework we have created a reality. This handbook intends to suggest and inspire instead of guiding the reader. It offers training packages to be adapted depending on contexts, whilst highlighting our successes and failures. We suggest it is read, considered and adapted. In other words, each person willing to put it into practice will have to assume that they will have to make their own patchwork

Restoring cellular magnesium balance through Cyclin M4 protects against acetaminophen-induced liver damage

Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes. Herein, we identify that among all magnesium transporters, only Cyclin M4 expression is upregulated in the liver of patients with acetaminophen overdose, with disturbances in magnesium serum levels. In the liver, acetaminophen interferes with the mitochondrial magnesium reservoir via Cyclin M4, affecting ATP production and reactive oxygen species generation, further boosting endoplasmic reticulum stress. Importantly, Cyclin M4 mutant T495I, which impairs magnesium flux, shows no effect. Finally, an accumulation of Cyclin M4 in endoplasmic reticulum is shown under hepatoxicity. Based on our studies in mice, silencing hepatic Cyclin M4 within the window of 6 to 24 h following acetaminophen overdose ingestion may represent a therapeutic target for acetaminophen overdose induced liver injury

Neddylation inhibition ameliorates steatosis in NAFLD by boosting hepatic fatty acid oxidation via the DEPTOR-mTOR axis

Objective: Neddylation is a druggable and reversible ubiquitin-like post-translational modification upregulated in many diseases, including liver fibrosis, hepatocellular carcinoma, and more recently, non-alcoholic fatty liver disease (NAFLD). Herein, we propose to address the effects of neddylation inhibition and the underlying mechanisms in pre-clinical models of NAFLD. Methods: Hepatic neddylation measured by immunohistochemical analysis and NEDD8 serum levels measured by ELISA assay were evaluated in NAFLD clinical and pre-clinical samples. The effects of neddylation inhibition by using a pharmacological small inhibitor, MLN4924, or molecular approaches were assessed in isolated mouse hepatocytes and pre-clinical mouse models of diet-induced NAFLD, male adult C57BL/6 mice, and the AlfpCre transgenic mice infected with AAV-DIO-shNedd8. Results: Neddylation inhibition reduced lipid accumulation in oleic acid-stimulated mouse primary hepatocytes and ameliorated liver steatosis, preventing lipid peroxidation and inflammation in the mouse models of diet-induced NAFLD. Under these conditions, increased Deptor levels and the concomitant repression of mTOR signaling were associated with augmented fatty acid oxidation and reduced lipid content. Moreover, Deptor silencing in isolated mouse hepatocytes abolished the anti-steatotic effects mediated by neddylation inhibition. Finally, serum NEDD8 levels correlated with hepatic neddylation during the disease progression in the clinical and pre-clinical models. Conclusions: Overall, the upregulation of Deptor, driven by neddylation inhibition, is proposed as a novel effective target and therapeutic approach to tackle NAFLDThis work was supported by grants from Gobierno Vasco-Departamento de Salud 2013111114 (to M.L.M.-C), ELKARTEK 2016, Departamento de Industria del Gobierno Vasco (to M.L.M−C), Ministerio de Ciencia, Innovación y Universidades MICINN: SAF2017-87301-R, and RTI2018-096759-A-100 integrado en el Plan Estatal de Investigación Científica y Técnica y Innovación, cofinanciado con Fondos FEDER (to M.L.M− T.C.D respectively); MCIU/AEI/FEDER, UE (RTI2018-095134-B-100) (to P.A.), AECC Bizkaia (M.S-M); Asociación Española contra el Cáncer (T.C.D), Fundación Científica de la Asociación Española Contra el Cáncer (AECC Scientific Foundation) Rare Tumor Calls 2017 (to M.L.M, J.M.B., M.A.A., J.J.G.M.), La Caixa Foundation Program (to M.L.M and J.M.B.), 2018 BBVA Foundation Grants for Scientific Research Teams (to M.L.M.-C.), Ayudas para apoyar grupos de investigación del sistema Universitario Vasco IT971-16 (P.A.). MyFirst Grant AIRC n.16888, Ricerca Finalizzata Ministero della Salute RF-2016-02364358, Ricerca corrente Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico (to LV), the European Union (EU) Programme Horizon 2020 (under grant agreement No. 777377) for the project LITMUS- “Liver Investigation: Testing Marker Utility in Steatohepatitis” (to LV), Fondazione IRCCS Ca’ Granda “Liver BIBLE” PR-0391, Fondazione IRCCS Ca’ Granda core COVID-19 Biobank (RC100017A) (to LV). This research was funded by the CIBERehd (EHD15PI05/2016) and “Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III”, Spain (PI16/00598 and PI19/00819, co-funded by European Regional Development Fund/European Social Fund, “Investing in your future”); Spanish Ministry of Economy, Industry and Competitiveness (SAF2016-75197-R); “Junta de Castilla y Leon” (SA063P17); AECC Scientific Foundation (2017/2020), Spain; “Centro Internacional sobre el Envejecimiento” (OLD-HEPAMARKER, 0348_CIE_6_E), Spain; University of Salamanca Foundation, Spain (PC-TCUE18-20_051), and Fundació Marato TV3 (Ref. 201916–31), Spain. RB acknowledges BFU2017-84653-P (MINECO/FEDER, EU), SEV-2016-0644 (Severo Ochoa Excellence Program), 765445-EU (UbiCODE Program), SAF2017-90900-REDT (UBIRed Program), and IT1165-19 (Basque Country Government). Ciberehd_ISCIII_MINECO is funded by the Instituto de Salud Carlos III. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)S

Beef Nutritional Characteristics, Fat Profile and Blood Metabolic Markers from Purebred Wagyu, Crossbred Wagyu and Crossbred European Steers Raised on a Fattening Farm in Spain

19 Pág.A high intramuscular fat content characterizes Wagyu (WY) cattle breed. Our objective was to compare beef from WY, WY-by-Angus, or Wangus (WN) steers with European, Angus-by-Charolais-Limousine crossbred steers (ACL), considering metabolic biomarkers pre-slaughtering and nutritional characteristics, including health-related indexes of the lipid fraction. The fattening system with olein-rich diets and no exercise restriction included 82 steers, 24 WY, 29 WN, and 29 ACL. The slaughter ages and weights were (median and interquartile range) 38.4 mo.-old (34.9-40.3 mo.) and 840 kg (785-895 kg) for WY; for WN, 30.6 mo. (26.9-36.5 mo.) and 832 kg (802-875 kg), and for ACL steers, 20.3 mo.-old (19.0-22.7 mo.) and 780 kg (715-852 kg). Blood lipid-related metabolites, except for non-esterified fatty acids (NEFA) and low-density level cholesterol (LDL), were higher in WY and WN than in ACL, while glucose was lower in WY and WN. Leptin was higher in WN than in ACL. Pre-slaughtering values of plasma HDL underscored as a possible metabolic biomarker directly related to beef quality. The amino-acid content in beef did not differ among experimental groups, except for more crude protein in ACL. Compared to ACL, WY steers showed higher intramuscular fat in sirloin (51.5 vs. 21.9%) and entrecote (59.6 vs. 27.6%), more unsaturated fatty acids in entrecote (55.8 vs. 53.0%), and more oleic acid in sirloin (46 vs. 41.3%) and entrecote (47.5 vs. 43.3%). Compared to ACL entrecote, WY and WN showed better atherogenic (0.6 and 0.55 vs. 0.69), thrombogenicity (0.82 and 0.92 vs. 1.1), and hypocholesterolemic/hypercholesterolemic index (1.9 and 2.1 vs. 1.7). Therefore, beef's nutritional characteristics depend on breed/crossbred, slaughtering age and cut, with WY and WN entrecote samples showing a healthier lipid fraction.This research was funded by the Centre for the Development of Industrial Technology from the Spanish Ministry of Science and Innovation, grant number CDTI-IDI-20180254.Peer reviewe

Inhibition of ATG3 ameliorates liver steatosis by increasing mitochondrial function

Non-alcoholic fatty liver disease (NAFLD) is a major health threat in both developed and developing countries and is a precursor of the more advanced liver diseases, including non-alcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. Currently, understanding the multiple and complex molecular pathways implicated in NAFLD onset and progression is a major priority. The transcription factor p63, which belongs to a family comprising p53, p63, and p73,1 is one of many factors that contributes to the development of liver steatosis. The role of p63 as a tumor suppressor and in cell maintenance and renewal is well studied, but we have recently reported that it is also relevant in the control of lipid metabolism.2 p63 encodes multiple isoforms that can be grouped into 2 categories; isoforms with an acidic transactivation domain (TA) and those without this domain (domain negative). The TAp63α isoform is elevated in the liver of animal models of NAFLD as well as in liver biopsies from obese patients with NAFLD. Furthermore, downregulation of p63α in the liver attenuates liver steatosis in diet-induced obese (DIO) mice, while the activation of TAp63α increases hepatic fat content, mediated by the activation of IKKβ and endoplasmic reticulum stress.2 A specialized form of autophagy that degrades lipid droplets, termed “lipophagy”, is a major pathway of lipid mobilization in hepatocytes. Lipophagy is elevated in hepatoma cells upon exposure to free fatty acids,3 and reduces the fatty acid load in mouse hepatocytes.4 Its impairment has been associated with the development of fatty liver and insulin resistance3,5; in contrast, the autophagic flux is increased during the activation of hepatic stellate cells.6 In the present study, we used an unbiased proteomics approach to gain insight into novel proteins modulating lipid metabolism in the liver of mice with genetic knockdown or overexpression of TAp63α. We found that autophagy-related gene 3 (ATG3) was upregulated by TAp63α activation and downregulated after p63α inhibition. ATG3 is elevated in several animal models of NAFLD and in the liver of patients with NAFLD. Genetic overexpression of ATG3 increased the lipid load in hepatocytes, while its repression alleviated TAp63α- and diet-induced steatosis. ATG3 exerted its role in lipid metabolism by regulating SIRT1 and mitochondrial function. Collectively, these findings identify ATG3 as a novel factor implicated in the development of steatosisThis work has been supported by grants from FEDER/Ministerio de Ciencia, Innovación y Universidades-Agencia Estatal de Investigación (PA: RTI2018-095134-B-100; DS and LH: SAF2017-83813-C3-1-R; MLMC: RTC2019-007125-1; CD: BFU2017-87721; ML: RTI2018–101840-B-I00; GS; PID2019-104399RB-I00; RN: RTI2018-099413-B-I00 and RED2018-102379-T; MLMC: SAF2017-87301-R; TCD: RTI2018-096759-A-100), FEDER/Instituto de Salud Carlos III (AGR: PI19/00123), Xunta de Galicia (ML: 2016-PG068; RN: 2015-CP080 and 2016-PG057), Fundación BBVA (RN, GS and MLM), Proyectos Investigación en Salud (MLMC: DTS20/00138), Sistema Universitario Vasco (PA: IT971-16); Fundación Atresmedia (ML and RN), Fundación La Caixa (M.L., R.N. and M.C.), Gilead Sciences International Research Scholars Program in Liver Disease (MVR), Marató TV3 Foundation (DS: 201627), Government of Catalonia (DS: 2017SGR278) and European Foundation for the Study of Diabetes (RN and GS). This research also received funding from the European Community’s H2020 Framework Programme (ERC Synergy Grant-2019-WATCH- 810331, to RN, VP and MS). Centro de Investigación Biomédica en Red (CIBER) de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Centro de Investigación Biomédica en Red (CIBER) de Enfermedades Hepáticas y Digestivas (CIBERehd) and CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERdem). CIBERobn, CIBERehd and CIBERdem are initiatives of the Instituto de Salud Carlos III (ISCIII) of Spain which is supported by FEDER funds. We thank MINECO for the Severo Ochoa Excellence Accreditation to CIC bioGUNE (SEV-2016-0644)S