Dual-Specificity Phosphatase 1 (DUSP1) Has a Central Role in Redox Homeostasis and Inflammation in the Mouse Cochlea.

Stress-activated protein kinases (SAPK) are associated with sensorineural hearing loss (SNHL) of multiple etiologies. Their activity is tightly regulated by dual-specificity phosphatase 1 (DUSP1), whose loss of function leads to sustained SAPK activation. Dusp1 gene knockout in mice accelerates SNHL progression and triggers inflammation, redox imbalance and hair cell (HC) death. To better understand the link between inflammation and redox imbalance, we analyzed the cochlear transcriptome in Dusp1-/- mice. RNA sequencing analysis (GSE176114) indicated that Dusp1-/- cochleae can be defined by a distinct profile of key cellular expression programs, including genes of the inflammatory response and glutathione (GSH) metabolism. To dissociate the two components, we treated Dusp1-/- mice with N-acetylcysteine, and hearing was followed-up longitudinally by auditory brainstem response recordings. A combination of immunofluorescence, Western blotting, enzymatic activity, GSH levels measurements and RT-qPCR techniques were used. N-acetylcysteine treatment delayed the onset of SNHL and mitigated cochlear damage, with fewer TUNEL+ HC and lower numbers of spiral ganglion neurons with p-H2AX foci. N-acetylcysteine not only improved the redox balance in Dusp1-/- mice but also inhibited cytokine production and reduced macrophage recruitment. Our data point to a critical role for DUSP1 in controlling the cross-talk between oxidative stress and inflammation

La “diversidad contextual” de las palabras como facilitador de la lectura

Eva M. Rosa, Marta Vergara-Martínez, Manuel Perea (miembros de la ERI-Lectura de la Universitat de València) y Jose L. Tapia (profesor de la Universidad Católica de Valencia San Vicente Mártir) presentan los resultados de su investigación sobre la “diversidad contextual” de las palabras como facilitador de la lectura en las Jornades Lectura Fàcil de la Generalitat Valenciana organizadas por la ERI-Lectura de la Universitat de València el 18-19 mayo de 2018. http://ir.uv.es/4zhj7I

mcr-9, An inducible gene encoding an acquired phosphoethanolamine transferase in Escherichia coli, and its origin

The plasmid-located mcr-9 gene, encoding a putative phosphoethanolamine transferase, was identified in a colistin-resistant human fecal Escherichia coli strain belonging to a very rare phylogroup, the D-ST69-O15:H6 clone. This MCR-9 protein shares 33% to 65% identity with the other plasmid-encoded MCR-type enzymes identified (MCR-1 to -8) that have been found as sources of acquired resistance to polymyxins in Enterobacteriaceae. Analysis of the lipopolysaccharide of the MCR-9- producing isolate revealed a function similar to that of MCR-1 by adding a phosphoethanolamine group to lipid A and subsequently modifying the structure of the lipopolysaccharide. However, a minor impact on susceptibility to polymyxins was noticed once the mcr-9 gene was cloned and produced in an E. coli K-12-derived strain. Nevertheless, we showed here that subinhibitory concentrations of colistin induced the expression of the mcr-9 gene, leading to increased MIC levels. This inducible expression was mediated by a two-component regulatory system encoded by the qseC and qseB genes located downstream of mcr-9. Genetic analysis showed that the mcr-9 gene was carried by an IncHI2 plasmid. In silico analysis revealed that the plasmid-encoded MCR-9 shared significant amino acid identity (ca. 80%) with the chromosomally encoded MCR-like proteins from Buttiauxella spp. In particular, Buttiauxella gaviniae was found to harbor a gene encoding MCR-BG, sharing 84% identity with MCR-9. That gene was neither expressed nor inducible in its original host, which was fully susceptible to polymyxins. This work showed that mcr genes may circulate silently and remain undetected unless induced by colistin

Propuesta de mejora del Sistema Interno de Garantía de Calidad de la Facultad de Medicina

La garantía de calidad en el ámbito universitario puede considerarse como la atención sistemática, estructurada y continua a las titulaciones ofertadas. La garantía de calidad se compromete a poner en marcha los medios que aseguren y demuestren la calidad de los programas formativos que se desarrollan en cada una de las titulaciones ofrecidas por la Universidad y así cumplir con la obligación que tiene con la sociedad. El presente proyecto nace como fruto de la responsabilidad adquirida para el cumplimiento de las funciones encomendadas y, con el objetivo de seguir adoptando una estrategia de mejora continua de la calidad de la docencia y satisfacción de los colectivos implicados en el proceso de enseñanza-aprendizaje (Profesorado, Estudiantes y PAS)

The impact of surgical practice on oncological outcomes in robot-assisted radical hysterectomy for early-stage cervical cancer, Spanish National Registry

Minimal invasive surgery (MIS) has been associated with lower disease-free survival than open surgery among women who underwent radical hysterectomy for early-stage cervical cancer. However, the mechanisms by which MIS increases mortality in cervical cancer remain uncertain. We aimed to determine if surgical practice among centers using robotic surgery has an impact on oncological outcomes. We evaluated 215 women with early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009) who underwent robot-assisted radical hysterectomy in five Spanish tertiary centers between 2009 and 2018. A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed for the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes in all surgical approaches. Abstract: This study aimed to assess whether surgical practice had a significant impact on oncological outcomes among women who underwent robot-assisted radical hysterectomy for early-stage cervical cancer (≤IB1 or IIA1, FIGO 2009). The secondary objective was to audit the pre-surgical quality indicators (QI) proposed by the European Society of Gynaecological Oncology (ESGO). The top 5 of 10 centers in Spain and Portugal were included in the analysis. The hospitals were divided into group A (n = 118) and group B (n = 97), with recurrence rates of 10%, respectively. After balancing both groups using the propensity score, the ORs for all events were higher and statistically significant for group B (recurrences OR = 1.23, 95% CI = 1.13-1.15, p-value = 0.001; death OR = 1.10, 95% CI = 1.02-1.18, p-value = 0.012; disease-specific mortality ORr = 1.11, 95% CI = 1.04-1.19, p-value = 0.002). A higher surgical volume, higher participation in clinical trials, higher rate of MRI use for diagnosis, greater use of sentinel lymph node biopsies, and a favorable learning curve with low rates of early recurrences were observed among the centers with better oncological outcomes. These factors might have a significant impact on oncological outcomes not only after robot-assisted surgery, but also after laparoscopies and open surgeries in the treatment of cervical cancer

Reseñas de libros

Carrasca Hortal, José y Millán Gómez, Antonio. La Estructura Gótica Catalana. Sobre los conceptos de media y espacio. El problema de la forma en la cubierta (Por Antonio Millán) pp. 4.-- Verd Herrero, Antonio. Dibujo del natural. Manual de texto docente universitario (Por Antonio Verd) pp.5-6.-- Caninva, Luigi. L'Architettura romana (Por Carlos de San Antonio Gómez) pp.6-7.-- Villalobos Alonso, Daniel. La mirada de Fisac (Por Alberto Grijalba Bengoetxea)pp.8.-- Jiménez Martín, Alfonso et al. La catedral gótica de Sevilla. Fundación y fábrica de la obra nueva (Por Enrique Rabasa Díaz) pp.8-9.-- García-Gutiérrez Mosteiro, Javier. Narciso Pascual y Colomer (1808-1870). Arquitecto del Madrid isabelino (Por Enrique Rabasa Díaz) pp.9-10.-- Valladolid. Bellido Blanco, Santiago. Cuaderno de apuntes (Por Fernando Lmares García) pp.10-11.-- Lopez-Peláez, José Manuel. Maestros cercanos de un arquitecto (Por Javier García-Gutiérrez Masteiro) pp.12.-- Garcia Bueno, Antonio. Dibujando la Alhambra (Por Joaquín Casado de Amezúa Vázquez) pp.13-14.-- Chías Navarro, Pilar y Abad Balboa, Tomás. Eduardo Torroja. Obras y proyectos (Por Jorge Llopis Verdú) pp.14-15.-- Gómez i Serrano, Josep y Font, Juan. La forma de la Villa de Madrid. Soporte gráfico para la información histórica de la ciudad (Por Jorge Llopis Verdú) pp.15-16.-- Nagore, Fernando. Geometría métrica y descriptiva para arquitectos (Por José Antonio Ruiz de le Rosa) pp.16-17.-- Rabasa Diaz, Enrique y el Centro de los Oficios de LeónGuía práctica de la estereotomía de la piedra (Por José CalvoLópez) pp.18-19.-- Hernández Iviartinez, Ascensión. La clonación arquitectónica (Por José Joaquín Parra 8añón) pp.20-21.-- Gentil Baldrich, José María y Yanguas Álvarez de Toledo, Ana. Fernando Barquín y Barón Joaquín Barquín y Barón Imágenes de su archivo en los fondos FIDAS (Por José Manuel Pala) pp.21-22.-- Escoda Pastor, Carmen. El magnetismo del lugar en la arquitectura pp.23.-- Herrero Vázquez, Eduardo Alejandro. Compases de mano, compases de ojo: la Geometrización de la Realidad según Laussedat (POr Adrien Javary) pp.24-25.-- Castaño Perea, Enrique. Arquitectura y música: Policoralidad en la Capilla Real del Alcázar de Madrid pp.25-26.-- Piquer Cases, Juan Carlos. Los modelos digitales en la arquitectura, desarrollo del proyecto e investigación patrimonial. Palacio Real de Valencia (1239-1810): análisis y reconstrucción virtual sobre la planta de Vicente Gascó de 1761 (Por Juan Carlos Piquer Cases) pp.26-28.-- Pérez Naya, Antonia. Arquitectura del silencio y la memoria. Análisis de los cementerios de la Costa da Morte gallega (Por JAfT) pp. 28-29.-- Falcón Meraz, José Manuel. La expresión de una línea museística singular (Por Juan Puebla) pp.29-30.-- 11Seminario Internacional "Color en el Diseño y la Arquitectura" pp.32.-- Taller de Pintura con Antonio López E.T.S. de Pamplona, septiembre de 2006 y 2007 (Por Inmacu/ada .liméne: Cabal/ero) pp.32-35.-- Arquitectura y autopsia: análisis gráficos de algunos restos de la inexistente Universidad laboral de Sevilla (Por José Joaquín Parra Bañón) pp.36-37Milán Gómez, A.; Verd Herrero, A.; De San Antonio Gomez, JC.; Grijalba Bengoetxea, A.; Rabasa Díaz, E.; Linares García, F.; García-Gutiérrez Mosteiro, J.... (2008). Reseñas de libros. EGA Expresión Gráfica Arquitectónica. 13(13):4-37. https://doi.org/10.4995/ega.2008.10266OJS437131

Investigación en Matemáticas, Economía, Ciencias Sociales y Agronomía

Cada trabajo del libro incluye conclusiones para los interesados en las temáticas aludidas y en ellos nos enteramos de aspectos como los siguientes: - El mayor incremento del precio de los insumos como el maíz, sorgo y en menor medida desperdicio de pan, en relación con el menor crecimiento del precio del ganado en pie, dará como consecuencia un desabasto de carne bovina. - El agua es un recurso primordial en las zonas áridas y semiáridas de México, en tanto que su aporte limita la producción de la agricultura. En este estudio se observó que el precio real del agua es muy bajo en relación a otras zonas agrícolas del mundo. - Hoy en día en el país se consumen alrededor de 718 mil barriles diarios de gasolinas, un aproximado de 113.7 millones de litros, una cantidad tan grande que nuestro país se ve en la necesidad de importar cerca del 39 % de las gasolinas que consumimos. - Los jaliscienses radicados en Estados Unidos tienen una mayor capacidad de financiamiento del bienestar en la entidad, que el propio gobierno de ese estado. - México continuará basando sus finanzas públicas y su política de desarrollo económico en la extracción de combustibles fósiles (petróleo). Este modelo acelerará el deterioro y agotamiento de los recursos naturales. -La importancia de la agricultura orgánica radica en que retoma los tres ámbitos de la sustentabilidad; el ámbito ambiental, el económico y el social. - Es fundamental motivar la organización de los productores de haba para que ellos puedan captar una mayor proporción de los altos márgenes de precios que los consumidores están dispuestos a pagar. - Las condiciones del clima afectan a la producción agraria. Debido al fenómeno de cambio climático, es necesario contar con herramientas informáticas que proporcionen información climatológica para poder tomar medidas preventivas a favor de una mayor cantidad y calidad de producción. La herramienta de software permite la consulta del clima por localidades evitando la necesidad de contar con una estación meteorológica

LAG3 genotype of the donor and clinical outcome after allogeneic transplantation from HLA-identical sibling donors

IntroductionThe association of polymorphisms in molecules involved in the immune response (checkpoint inhibitors) with the clinical outcome after allogeneic transplantation (alloHSCT) has been described. Lymphocyte Activation 3 (LAG3) is a surface protein that plays a regulatory role in immunity as an inhibitory immune checkpoint molecule.MethodsTo determine its role in the alloHSCT setting, we analyzed 797 patients transplanted from HLA-identical sibling donors. The LAG3 rs870849 C>T polymorphism was genotyped in donors.ResultsWe detected a higher incidence of severe acute GVHD in patients transplanted from donors with TT genotype (p: 0.047, HR 1.64; 95% CI 1.01 – 2.67). Overall survival (OS) was worse for patients transplanted from donors with the rs870849 CT/TT genotype (0.020; HR, 1.44; 95% CI 1.06 – 1.96), as well as disease-free survival (DFS) (p: 0.002; HR 1.58, 95%CI: 1.18 – 2.14) and transplant-related mortality (TRM) (p< 0.001; HR: 1.88, 95% CI 1.29 – 2.74). When combining the LAG3 rs870849 and the PDCD1 rs36084323 genotypes of the donor, three genetic groups were well defined, allowing a good stratification of the risk of acute GVHD, TRM, OS and DFS.DiscussionWe conclude that the LAG3 genotype of the donor may be considered in donors’ selection. As this selection may be limited in the HLA-identical sibling donor scenario, further studies exploring the impact of LAG3 genotype of the donor in unrelated transplantation are warranted

Higher versus lower nut consumption and changes in cognitive performance over two years in a population at risk of cognitive decline: a cohort study

Background: Tree nuts and peanuts (henceforth, nuts) are nutrient-dense foods rich in neuroprotective components; thus, their consumption could benefit cognitive health. However, evidence to date is limited and inconsistent regarding the potential benefits of nuts for cognitive function. Objective: To prospectively evaluate the association between nut consumption and 2-y changes in cognitive performance in older adults at cognitive decline risk. Methods: A total of 6,630 participants aged 55 to 75 y (mean age 65.0±4.9 y, 48.4% women) with overweight/obesity and metabolic syndrome completed a validated semi-quantitative food frequency questionnaire and a comprehensive battery of neuropsychological tests at baseline and a 2-y follow-up. Composite cognitive scores were used to assess global, general, attention, and executive function domains. Nut consumption was categorized as Results: Nut consumption was positively associated with 2-y changes in general cognitive function (P-trend Conclusion: Frequent nut consumption was associated with a smaller decline in general cognitive performance over 2 y in older adults at risk of cognitive decline. Randomized clinical trials to verify our findings are warranted