Detoxifying enzymes at the cross-roads of inflammation, oxidative stress, and drug hypersensitivity: role of glutathione transferase P1-1 and aldose reductase

9 p.-2 figPhase I and II enzymes are involved in the metabolism of endogenous reactive compounds as well as xenobiotics, including toxicants and drugs. Genotyping studies have established several drug metabolizing enzymes as markers for risk of drug hypersensitivity. However, other candidates are emerging that are involved in drug metabolism but also in the generation of danger or costimulatory signals. Enzymes such as aldo-keto reductases (AKR) and glutathione transferases (GST) metabolize prostaglandins and reactive aldehydes with proinflammatory activity, as well as drugs and/or their reactive metabolites. In addition, their metabolic activity can have important consequences for the cellular redox status, and impacts the inflammatory response as well as the balance of inflammatory mediators, which can modulate epigenetic factors and cooperate or interfere with drug-adduct formation. These enzymes are, in turn, targets for covalent modification and regulation by oxidative stress, inflammatory mediators, and drugs. Therefore, they constitute a platform for a complex set of interactions involving drug metabolism, protein haptenation, modulation of the inflammatory response, and/or generation of danger signals with implications in drug hypersensitivity reactions. Moreover, increasing evidence supports their involvement in allergic processes. Here, we will focus on GSTP1-1 and aldose reductase (AKR1B1) and provide a perspective for their involvement in drug hypersensitivityThis work has been supported by grants SAF2012-36519 from MINECO and SAF-2015-68590-R from MINECO/FEDER and ISCIII RETIC RIRAAF RD12/0013/0008 to DP,and RD12/0013/0002 to J A.Peer reviewe

Evaluation of air conditioning in commercial buildings, integrating thermography techniques, simulation and modeling Finite Element. Case Snail Shop

En el trabajo se integran técnicas utilizadas para analizar problemas asociados a la climatización que por sí solas no son capaces de evaluar todo un sistema de acondicionamiento de aire. Se utiliza la termografía para obtener el perfil de temperatura en el área de incidencia del aire climatizado y los focos calientes en el interior del local. Mediante la simulación con el software Trnsys se obtiene el comportamiento de la temperatura interior y se estima el perfil de carga térmica. Con el diseño asistido por computador se crea un modelo espacial de la zona térmica y con el Método de los Elementos Finitos (MEF) se modela la circulación del aire y la distribución de la temperatura en el espacio. Finalmente se propone un nuevo esquema para el sistema de frío a partir de los resultados obtenidos con las herramientas anteriores.At work are integrated techniques used to analyze problems associated with the climate which alone are unable to assess an entire air conditioning system. Thermography is used to obtain the temperature profile in the area of incidence of conditioned air and the hot spots inside the premises. By simulating the behavior of software Trnsys indoor temperature is obtained and the thermal load profile is estimated. With computer aided design a spatial model of the thermal zone is created and the finite element method (FEM) air flow and temperature distribution in space is modeled. Finally a new scheme for the cooling system is proposed based on the results obtained with previous tools.Eje: Evaluación y certificación de sustentabilidad (actas).Facultad de Arquitectura y Urbanism

NSAIDs-hypersensitivity often induces a blended reaction pattern involving multiple organs

Las reacciones de hipersensibilidad inducidas por medicamentos antiinflamatorios no esteroideos (AINE) están clasificadas por la Red Europea de Alergia a los Medicamentos (ENDA) como reacciones cruzadas o selectivas. La primera es el tipo más frecuente e incluye a los pacientes con síntomas exclusivamente respiratorios (AINE - enfermedad respiratoria exacerbada, ENDA) o exclusivamente cutáneos: urticaria/angioedema inducido por AINEs (NIUA); y enfermedad cutánea exacerbada por AINEs (NECD). Sin embargo, aunque no se refleja en el esquema de clasificación actual (ENDA), en la práctica clínica se observa con frecuencia una combinación de síntomas tanto cutáneos como respiratorios o incluso de otros órganos, como los síntomas del tracto gastrointestinal (reacciones mixtas o combinadas). Esta entidad no ha sido suficientemente caracterizada. Nuestro objetivo era caracterizar clínicamente las reacciones mixtas a los AINEs, comparando sus características clínicas con las del NERD y la NIUA. Evaluamos a los pacientes con síntomas que sugerían hipersensibilidad a los AINEs que acudieron a la Unidad de Alergia del Hospital Universitario Regional de Málaga (Málaga, España) entre 2008 y 2015. Se incluyeron 880 pacientes con reacción cruzada confirmada en base a la historia clínica, prueba de provocación nasal positiva con acetilsalicilato de lisina (NPT-LASA) y/o prueba de provocación de drogas positiva (DPT) con ácido acetilsalicílico (ASA), que se clasificaron como mezclados (261; 29,6%), NERD (108; 12,3%) o NIUA (511; 58,1%). Se compararon los síntomas, los medicamentos, las enfermedades subyacentes y los métodos de diagnóstico dentro de los grupos y entre ellos. Entre los pacientes mezclados, el subgrupo más común comprendía aquellos que desarrollaban urticaria/angioedema más rinitis/asma (n = 138), que tenían un mayor porcentaje de rinitis subyacente (p < 0,0001) y asma (p < 0,0001) que los pacientes de NIUA, mostrando similitudes con la NERD. Estas diferencias no se encontraron en el subgrupo de pacientes mezclados que desarrollaron síntomas respiratorios como el edema de la glotis; estos eran más similares a la NIUA. El porcentaje de NPT-LASA positivo fue similar para los grupos de mezcla (77%) y NERD (78,7%). Concluimos que las reacciones mixtas son reacciones de hipersensibilidad a los AINEs que afectan al menos a dos órganos. Además de la clásica afectación cutánea y respiratoria, en nuestra población algunos pacientes también desarrollan síntomas gastrointestinales. Dada la alta tasa de respuestas positivas al NPT-LASA en el NERD así como las reacciones mixtas, sugerimos que todos los pacientes que reporten síntomas respiratorios, independientemente de si tienen otros síntomas asociados, deben ser evaluados inicialmente usando el NPT-LASA, lo cual representa menos riesgo que el DPT.Non-steroidal anti-inflammatory drugs (NSAIDs)-induced hypersensitivity reactions are classified by the European Network on Drug Allergy (ENDA) as either cross-reactive or selective. The former is the most frequent type and includes patients with exclusively respiratory symptoms (NSAIDs-exacerbated respiratory disease, NERD) or exclusively cutaneous symptoms: NSAIDs-induced urticaria/angioedema (NIUA); and NSAIDs-exacerbated cutaneous disease (NECD). However, although not reflected in the current classification scheme (ENDA), in clinical practice a combination of both skin and respiratory symptoms or even other organs such as gastrointestinal tract symptoms (mixed or blended reactions) is frequently observed. This entity has not been sufficiently characterised. Our aim was to clinically characterize blended reactions to NSAIDs, comparing their clinical features with NERD and NIUA. We evaluated patients with symptoms suggestive of hypersensitivity to NSAIDs who attended the Allergy Unit of the Regional University Hospital of Malaga (Malaga, Spain) between 2008 and 2015. We included 880 patients confirmed as cross-reactive based on clinical history, positive nasal provocation test with lysine acetylsalicylate (NPT-LASA), and/or positive drug provocation test (DPT) with acetylsalicylic acid (ASA), who were classified as blended (261; 29.6%), NERD (108; 12.3%) or NIUA (511; 58.1%). We compared symptoms, drugs, underlying diseases and diagnostic methods within and between groups. Among blended patients the most common sub-group comprised those developing urticaria/angioedema plus rhinitis/asthma (n = 138), who had a higher percentage of underlying rhinitis (p < 0.0001) and asthma (p < 0.0001) than NIUA patients, showing similarities to NERD. These differences were not found in the sub-group of blended patients who developed such respiratory symptoms as glottis oedema; these were more similar to NIUA. The percentage of positive NPT-LASA was similar for blended (77%) and NERD groups (78.7%). We conclude that blended reactions are hypersensitivity reactions to NSAIDs affecting at least two organs. In addition to classical skin and respiratory involvement, in our population a number of patients also develop gastrointestinal symptoms. Given the high rate of positive responses to NPT-LASA in NERD as well as blended reactions, we suggest that all patients reporting respiratory symptoms, regardless of whether they have other associated symptoms, should be initially evaluated using NPT-LASA, which poses less risk than DPT.• Gobierno de Andalucía. Ayuda PI-0463-2013 • Instituto de Salud Carlos III y Fondo Europeo Regional de Desarrollo. Ayuda RETIC ARADyAL RD16/0006/0001 y PI17/1253 • Sociedad Española de Alergología. Fondo de Investigación de la Fundación de la SEAIC 2016 • Instituto de Salud Carlos III, Ministerio de Economía y Competitividad y Fondo Europeo Social. Contrato de investigación Juan Rodes JR15/00036, para Inmaculada Doña Díaz. Contrato Río Hortega CM16/0067, para Gádor Bogas Herrera. Programa Miguel Servet CP14/00034, para José Antonio Cornejo García. Programa Sara Borrell CD14/00242, para James Richard Perkins.peerReviewe

Ensayos para un nuevo paradigma en la política de drogas

El conjunto de ensayos que componen este Occasional Paper del ICEI es el resultado de la reflexión final de la mayoría de los integrantes del Proyecto I+D+i DER2016-74872-R. Fiscalización internacional de las drogas: problemas y soluciones (AEI/ FEDER, UE). https://www.ucm.es/catedradrogas21/fiscalizacion-internacional-de-drogas-problemas-y-soluciones-der-201674872-r-programa-retos-ministerio-de-economia-y-competitividad El Proyecto de investigación I+D+i DER2016-74872-R. Fiscalización internacional de las drogas: problemas y soluciones (AEI/ FEDER, UE), ha partido de la premisa general de que el régimen jurídico internacional en materia de drogas –regulado por tres convenios concluidos en el seno de las Naciones Unidas en 1961, 1971 y 1988- no es el adecuado pues, aparte de que existen cada vez más drogas y más baratas, los efectos negativos del régimen de su fiscalización y represión, son enormes. Por todo ello, los miembros del grupo de investigación, bajo el liderazgo de la Profesora Manjón-Cabeza, parten de la creencia en la necesidad de un cambio de paradigma en la política de drogas que i) sustituya la prohibición/represión por la regulación/control estatal, ii) tenga en cuenta tres enfoques fundamentales ignorados por el actual régimen, que son el enfoque de derechos humanos, el enfoque de salud pública y el enfoque de evidencia científica. Para poner en marcha ese nuevo paradigma, urge una base científica que pueda orientar los cambios

Medical students maintain their humanistic and patient‑centred vocation throughout Medicine Degree in Spain: a study based on narratives

Narrative medicine has great educational potential in the degree of medicine. This study explores for the frst time the use of narrative medicine in relation to longitudinal evolution of medical vocation for the same group of students. In the context of the Degree in Medicine at the Universidad Autónoma de Madrid (Spain), students wrote narratives about what it meant to them to be a doctor at the beginning and end of their studies. The narratives of 338 students of the academic years 2012/13– 2017/18 and 2013/14–2018/19 were analysed and compared. Students mostly pursued a degree in medicine on account of humanistic motivations, which are reinforced throughout their degree. In contrast, up to 10% of students reference to have experienced vocational crises and sufered frustration, with up to 25% of the references pertaining to having made signifcant sacrifces. Students maintain and evolve their humanistic, patient-centred vision throughout their degree studies, despite the difculties they appear to encounter. We suggest that eforts must be made to include more humanistic perspectives in the medical degree to keep this trend, which may improve both the educational experience created in universities and the health care given to patient

El debate académico de competición como instrumento para el aprendizaje de cuestiones de derecho, ciencia política y criminología

Memoria ID-0032. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2016-2017

Plan de cobertura educativa local : guía metodológica

La guía metodológica para las instancias involucradas en la prestación del servicio público educativo, en especial el nivel central, las Direcciones Locales de Educación, las instituciones educativas distritales y se concibe como un referente de consulta para todos los agentes educativos convocados en el ejercicio de la planeación de la cobertura local. La formulación del Plan de Cobertura Educativa Local 2016-2019, inicia con el diagnóstico y la caracterización de la localidad y continúa con el análisis del comportamiento de la demanda y la oferta educativa territorial, desde un enfoque integra

The ecology of peace : preparing Colombia for new political and planetary climates

ABSTRACT: Colombia, one of the world’s most species-rich nations, is currently undergoing a profound social transition: the end of a decadeslong conflict with the Revolutionary Armed Forces of Colombia, known as FARC. The peace agreement process will likely transform the country’s physical and socioeconomic landscapes at a time when humans are altering Earth’s atmosphere and climate in unprecedented ways. We discuss ways in which these transformative events will act in combination to shape the ecological and environmental future of Colombia. We also highlight the risks of creating perverse development incentives in these critical times, along with the potential benefits – for the country and the world – if Colombia can navigate through the peace process in a way that protects its own environment and ecosystems

Intermediate Molecular Phenotypes to Identify Genetic Markers of Anthracycline-Induced Cardiotoxicity Risk.

Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (n = 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (n = 71) and women with breast cancer (n = 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.J.P.L.’s lab is sponsored by Grant PID2020-118527RB-I00 funded by MCIN/AEI/10.13039/ 501100011039; Grant PDC2021-121735-I00 funded by MCIN/AEI/10.13039/501100011039 and by the “European Union Next Generation EU/PRTR”, the Regional Government of Castile and León (CSI144P20). J.P.L. and P.L.S. are supported by the Carlos III Health Institute (PIE14/00066). AGN laboratory and human patients’ studies are supported by an ISCIII project grant (PI18/01242). The Human Genotyping unit is a member of CeGen, PRB3, and is supported by grant PT17/0019 of the PE I + D + i 2013–2016, funded by ISCIII and ERDF. SCLl is supported by MINECO/FEDER research grants (RTI2018-094130-B-100). CH was supported by the Department of Defense (DoD) BCRP, No. BC190820; and the National Cancer Institute (NCI) at the National Institutes of Health (NIH), No. R01CA184476. Lawrence Berkeley National Laboratory (LBNL) is a multi-program national laboratory operated by the University of California for the DOE under contract DE AC02-05CH11231. The Proteomics Unit belongs to ProteoRed, PRB3-ISCIII, supported by grant PT17/0019/0023 of the PE I + D +i, 2017–2020, funded by ISCIII and FEDER. RCC is funded by fellowships from the Spanish Regional Government of Castile and León. NGS is a recipient of an FPU fellowship (MINECO/FEDER). hiPSC-CM studies were funded in part by the “la Caixa” Banking Foundation under the project code HR18-00304 and a Severo Ochoa CNIC Intramural Project (Exp. 12-2016 IGP) to J.J.S