IFNL3 rs12980275 Polymorphism Predicts Septic Shock-Related Death in Patients Undergoing Major Surgery: A Retrospective Study

Interferon lambda 3 (IFNL3, previously called IL-28B) is a cytokine with effects against viral and bacterial pathogens. We aimed to analyze the IFNL3 rs12980275 SNP in patients who underwent major surgery, in order to establish its relationship with susceptibility to septic shock and septic shock-related death in these patients. We performed a case-control study on 376 patients to establish the association between IFNL3 rs12980275 SNP and the susceptibility to develop septic shock. Besides, we performed a longitudinal study among 172 septic shock patients using survival analysis with one censoring point of 28-days mortality. The IFNL3 rs12980275 polymorphism was genotyped by Agena Bioscience's MassARRAY platform. IFNL3 rs12980275 polymorphism was not associated with higher susceptibility to infection and septic shock development. Regarding survival analysis, the Kaplan-Meier analysis showed that patients with IFNL3 rs12980275 AA genotype had higher survival than patients with GG genotype (p = 0.003). The Cox regression analysis adjusted by the most relevant clinical and epidemiological characteristics showed that the GG genotype (recessive model) and the presence of the G allele (additive model) were associated with higher risk of death [adjusted hazard ratio (aHR) = 2.15, p = 0.034; aHR = 1.50, p = 0.030, respectively]. In conclusion, IFNL3 rs12980275 polymorphism was associated with septic shock-related death in patients who underwent major surgery. The A allele was linked to protection, and the G allele was associated with an increased risk of death. This is a first preliminary study that suggests for the first time a role of IFNL3 polymorphisms in the prognosis of septic shock.This work has been supported by grants given by Instituto de Salud Carlos III (grant numbers PI15/01451 to ET), Gerencia de Salud, Consejería de Sanidad, Junta de Castilla y Leon (grant number GRS 463/A/10 and 773/A/13 to ET), and PFIZER (grant number CT25-ESP01-01 to SR). MJ-S and AF-R are supported by Instituto de Salud Carlos III (grant numbers CP17CIII/00007 and CP14CIII/00010, respectively).S

Differential Effects of IGF-1R Small Molecule Tyrosine Kinase Inhibitors BMS-754807 and OSI-906 on Human Cancer Cell Lines

We have determined the effects of the IGF-1R tyrosine kinase inhibitors BMS-754807 (BMS) and OSI-906 (OSI) on cell proliferation and cell-cycle phase distribution in human colon, pancreatic carcinoma, and glioblastoma cell lines and primary cultures. IGF-1R signaling was blocked by BMS and OSI at equivalent doses, although both inhibitors exhibited differential antiproliferative effects. In all pancreatic carcinoma cell lines tested, BMS exerted a strong antiproliferative effect, whereas OSI had a minimal effect. Similar results were obtained on glioblastoma primary cultures, where HGUE-GB-15, -16 and -17 displayed resistance to OSI effects, whereas they were inhibited in their proliferation by BMS. Differential effects of BMS and OSI were also observed in colon carcinoma cell lines. Both inhibitors also showed different effects on cell cycle phase distribution, BMS induced G2/M arrest followed by cell death, while OSI induced G1 arrest with no cell death. Both inhibitors also showed different effects on other protein kinases activities. Taken together, our results are indicative that BMS mainly acts through off-target effects exerted on other protein kinases. Given that BMS exhibits a potent antiproliferative effect, we believe that this compound could be useful for the treatment of different types of tumors independently of their IGF-1R activation status.This research was funded by a Grant from Instituto de Salud Carlos III Grant PI012/02025 co-supported by FEDER funds and PRECIPITA crowdfunding platform from Fundación Española para la Ciencia y la Tecnología (Fecyt) to M. Saceda and AMACMED (Asociación de mujeres afectadas por cáncer de mama de Elche y Comarca) and Monica Moraleda donation to M. Saceda. The Spanish Ministry of Economy and Competitiveness (MINECO, Project RTI2018-096724-B-C21) and the Generalitat Valenciana (PROMETEO/2016/006) supported the work in the Encinar laboratory

CEACAM7 polymorphisms predict genetic predisposition to mortality in post-surgical septic shock patients

We carried out a retrospective exploratory study on 173 patients who underwent major surgery and developed septic shock after surgery. Our findings suggest that CEACAM7 rs1001578, rs10409040, and rs889365 polymorphisms could influence septic shock-related death in individuals who underwent major surgery.This work has been supported by grants given by Instituto de Salud Carlos III (grant number PI15/01451 to ET), “Gerencia de Salud, Consejería de Sanidad, Junta de Castilla y Leon” [grant number GRS 463/A/10 and 773/A/13 to ET], and PFIZER [grant number CT25-ESP01-01 to SR]. MAJS and AFR are supported by “Instituto de Salud Carlos III” [grant numbers CP17CIII/00007 and CP14CIII/00010, respectively]S

Adaptación de las asignaturas básicas de primer curso de la ETSI Navales de la UPM: Actividades 2008-2009

En el marco de la reforma de las titulaciones con motivo del Espacio Europeo de Educación un grupo de profesores hemos coordinado, durante el curso 2008-2009, todas las asignaturas básicas de primer curso y una más de segundo curso en la Escuela Técnica Superior de Ingenieros Navales. Las actividades realizadas son: a) Coordinación de todas las asignaturas básicas de primer curso, con reuniones periódicas de coordinación horizontal y el establecimiento de una página web de moodle para profesores como espacio para el trabajo cooperativo. Particularmente importante es el establecimiento de un calendario conjunto de pruebas de evaluación continua. b) Redacción de guías de aprendizaje, con un formato común para todas las asignaturas, incluyendo los objetivos formativos, los contenidos, las actividades formativas, los enlaces y la bibliografía. c) Establecimiento de una plataforma de teleeducación común para todas las asignaturas, uno de los objetivos fundamentales del proyecto, ya que coexistían dos plataformas distintas. Igualmente importante ha sido reforzar los contenidos y las actividades que se podían realizar en la plataforma. d) Seguimiento del tiempo dedicado por los alumnos, hemos ido siguiendo el tiempo dedicado por los alumnos a las distintas asignaturas, para detectar si el tiempo que se dedica está en los márgenes establecidos en los créditos ECTS. Igualmente, hemos hecho dos encuestas a la mitad de cada semestre, para recoger las opiniones de los alumnos sobre las asignaturas y sobre los aspectos relevantes del proyecto. e) Organización de actividades de nivelación, para los alumnos de nuevo ingreso, con la organización de cursos cero y la participación y coordinación en la Plataforma de Punto de inicio de la UPM. f) Organización de actividades formativas, para poder llevar a cabo estas tareas, hemos organizado, en colaboración con el Centro y el Gabinete de Tele-Educación (GATE) actividades formativas relacionadas con la plataforma moodle, métodos de evaluación y de formación en competencias.En la presentación haremos una descripción de las actividades realizadas, así como una primera evaluación de las mismas. Por último, describiremos las tareas a desarrollar en los próximos cursos

Adaptación de las asignaturas básicas de primer curso de la ETSI Navales de la UPM: Primeras experiencias

En el marco de la reforma de las titulaciones con motivo de la puesta en marcha del Espacio Europeo de Educación Superior, un grupo de profesores hemos decidido coordinar todas las asignaturas básicas de primer curso y una asignatura de segundo curso en la Escuela Técnica Superior de Ingenieros Navales de la Universidad Politécnica de Madrid con el fin de dar una visión mas homogénea y compacta al alumno de lo que debe ser la formación básica del ingeniero. Para llevar a cabo dicho fin, la Universidad nos ha concedido un Proyecto de Innovación Educativa en la convocatoria 2008 para poder alcanzar una serie de objetivos en el curso 2008-2009, como son la coordinación de todas las asignaturas básicas de primer curso, la aplicación de nuevas metodologías en la práctica educativa, y una mejor adaptación de los alumnos de nuevo ingreso

Monitorización y seguimiento del esfuerzo realizado por los estudiantes y de su asistencia a actividades presenciales

Este artículo documenta el planteamiento, la metodología y los primeros resultados de un plan de monitorización detallada del esfuerzo y de asistencia a actividades presenciales por parte de los estudiantes de las titulaciones ofertadas por la Escuela Técnica Superior de Ingenieros Navales de la Universidad Politécnica de Madrid durante el segundo cuatrimestre del curso 2011-2012. Se ha establecido un sistema mecánico de recogida de datos de esfuerzo por parte de los estudiantes utilizando una hoja tipo test especialmente configurada al efecto. Se pasa una hoja en todas y cada una de las actividades presenciales realizadas y en la hoja se solicita información sobre el trabajo "fuera de clase". Se documenta en este artículo cómo se ha estructurado esa hoja, qué tipo de datos se recogen, cómo se tratan mediante una base de datos creada al efecto, qué tipo de análisis se puede realizar y qué resultados preliminares obtenemos de dichos análisis

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

Novel genes and sex differences in COVID-19 severity

[EN] Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10−8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10−22 and P = 8.1 × 10−12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10−8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10−8) and ARHGAP33 (P = 1.3 × 10−8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10−8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.S