Mejoras en el sistema MOIRA para su aplicación a los emplazamientos nucleares fluviales españoles

Entre las posibles secuelas de un accidente nuclear hay que contar con la contaminación radiactiva a medio y largo plazo de los sistemas acuáticos de agua dulce. Frente a ese problema, es fundamental disponer de una evaluación realista del impacto radiológico, ecológico, social y económico de las posibles estrategias de gestión, para poder adoptar las decisiones más convenientes de forma racional. MOIRA es un sistema de ayuda a la decisión desarrollado en el curso de los Programas Marco Europeos con participación de la UPM, que ha sido mejorado y adaptado a los emplazamientos nucleares españoles en los últimos años en el contexto del Proyecto ISIDRO, patrocinado por el Consejo de Seguridad Nuclear, con la participación del CIEMAT y la UPM. El trabajo se centra en esos avances, principalmente relacionados con los sistemas hidráulicos complejos como los de los ríos Tajo, Ebro y Júcar, en los que se ubican varias centrales nucleares españolas

Método del Grado de Intervención: Modelo Empírico de Predimensionado del Coste en Rehabilitación de Edificios

La idea que dirige el Método de Análisis y Estimación Rápida, que se plantea, se fundamenta en: a) Expresar la cantidad e Intensidad de la Intervención necesaria en el edificio estudiado, expresándola en el parámetro denominado: Grado de Intervención (Gi). b) Ponderar dicho Grado de Intervención con un Coeficiente de Mayoración de Ejecución de Obra (Cm), que tiene en cuenta las circunstancias de la Edificación y de la Realización de las Obras de Adecuación. c) Imputar al Grado de Intervención Mayorado (Gi x Cm), una equivalencia en euros, aplicando un Modulo Actualizado (Ma) a dicho producto. Estas variables nos permiten conocer el Coste de los Trabajos de Intervención (Cti), mediante la Expresión

Corioamnionitis clínica e histológica. Revisión bibliográfica.

The chorioamnionitis is a condition of pregnancy itself, which manifests itself through a variety of symptoms, both the mother and fetus. While his previous state intraamniotic infection no symptoms.  The main criterion for the diagnosis of chorioamnionitis is the clinic. Before the diagnosis, it is es-sential that happen delivery, independent of gestational age, it administer antibiotics to the mother, from the time of diagnosis, this is the mainstay of treatment and the future of the patient. Corioamnionitis is usually often clinically silent and isdiagnosed by the pathologist after birth. Clinical diagnosis of chorioamnionitis presents low sensitivityand high specificity in relation to histological chorioamnionitis. Clinical suspicion of ovular infectionis highly suggestive of advanced infection with histological fetal response. Histological choriamnionitis is statistically associated with preterm labor and early clinical sepsis. Histological chorioamnionitis with fetal response is statistically associated with bronchopulmonary dysplasia and necrotizingenterocolitis.La corioamnionitis es una patología propia del embarazo, que se manifiesta por medio de diferentes síntomas, tanto en la madre como en el feto; en su estado previo la infección intraamniótica no da síntomas. El principal criterio para el diagnóstico de corioamnionitis es la clínica. Ante el diagnóstico, es esencial que ocurra el parto, independiente de la edad gestacional, conjuntamente se le administrara a la madre antibióticos, desde el momento del diagnóstico, esto constituye la base del tratamiento y el futuro de la paciente. El diagnóstico clínico de corioamnionitis se correlaciona con la lesión histológica con baja sensibilidad y elevada especificidad. Se trata de una lesión que con mayor frecuencia es clínicamente silenciosa y que se diagnostica por el patólogo luego del nacimiento. La sospecha clínica de infección ovular es altamente sugestiva de lesión histológica avanzada con respuesta fetal. La corioamnionitis histológica se asocia a trabajo de parto pretérmino y sepsis clínica temprana. Cuando hay respuesta fetal histológica en el estudio de la placenta, se asocia a broncodisplasia pulmonar y enterocolitis necrotizante

CPEB alteration and aberrant transcriptome-polyadenylation lead to a treatable SLC19A3 deficiency in Huntington's disease

Huntington’s disease (HD) is a hereditary neurodegenerative disorder of the basal ganglia for which disease-modifying treatments are not yet available. Although gene-silencing therapies are currently being tested, further molecular mechanisms must be explored to identify druggable targets for HD. Cytoplasmic polyadenylation element binding proteins 1 to 4 (CPEB1 to CPEB4) are RNA binding proteins that repress or activate translation of CPE-containing transcripts by shortening or elongating their poly(A) tail. Here, we found increased CPEB1 and decreased CPEB4 protein in the striatum of patients and mouse models with HD. This correlated with a reprogramming of polyadenylation in 17.3% of the transcriptome, markedly affecting neurodegeneration-associated genes including PSEN1, MAPT, SNCA, LRRK2, PINK1, DJ1, SOD1, TARDBP, FUS, and HTT and suggesting a new molecular mechanism in neurodegenerative disease etiology. We found decreased protein content of top deadenylated transcripts, including striatal atrophy–linked genes not previously related to HD, such as KTN1 and the easily druggable SLC19A3 (the ThTr2 thiamine transporter). Mutations in SLC19A3 cause biotin-thiamine–responsive basal ganglia disease (BTBGD), a striatal disorder that can be treated with a combination of biotin and thiamine. Similar to patients with BTBGD, patients with HD demonstrated decreased thiamine in the cerebrospinal fluid. Furthermore, patients and mice with HD showed decreased striatal concentrations of thiamine pyrophosphate (TPP), the metabolically active form of thiamine. High-dose biotin and thiamine treatment prevented TPP deficiency in HD mice and attenuated the radiological, neuropathological, and motor HD-like phenotypes, revealing an easily implementable therapy that might benefit patients with HD

Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all nonredundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the metaanalysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNPsThis work was supported by the Instituto de Salud Carlos III (ISCIII, Spain) through grants PI14/01651, PI17/01606 and RD16/0012/0014 to AG and PI12/01909 to JJG-R. These grants are partially financed by the European Regional Development Fund of the EU (FEDER

Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNP

Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis

Introduction: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. Methods: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. Results: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. Conclusion: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes

Prediction of absolute risk of fragility fracture at 10 years in a Spanish population: validation of the WHO FRAX ™ tool in Spain

<p>Abstract</p> <p>Background</p> <p>Age-related bone loss is asymptomatic, and the morbidity of osteoporosis is secondary to the fractures that occur. Common sites of fracture include the spine, hip, forearm and proximal humerus. Fractures at the hip incur the greatest morbidity and mortality and give rise to the highest direct costs for health services. Their incidence increases exponentially with age.</p> <p>Independently changes in population demography, the age - and sex- specific incidence of osteoporotic fractures appears to be increasing in developing and developed countries. This could mean more than double the expected burden of osteoporotic fractures in the next 50 years.</p> <p>Methods/Design</p> <p>To assess the predictive power of the WHO FRAX™ tool to identify the subjects with the highest absolute risk of fragility fracture at 10 years in a Spanish population, a predictive validation study of the tool will be carried out. For this purpose, the participants recruited by 1999 will be assessed. These were referred to scan-DXA Department from primary healthcare centres, non hospital and hospital consultations. Study population: Patients attended in the national health services integrated into a FRIDEX cohort with at least one Dual-energy X-ray absorptiometry (DXA) measurement and one extensive questionnaire related to fracture risk factors. Measurements: At baseline bone mineral density measurement using DXA, clinical fracture risk factors questionnaire, dietary calcium intake assessment, history of previous fractures, and related drugs. Follow up by telephone interview to know fragility fractures in the 10 years with verification in electronic medical records and also to know the number of falls in the last year. The absolute risk of fracture will be estimated using the FRAX™ tool from the official web site.</p> <p>Discussion</p> <p>Since more than 10 years ago numerous publications have recognised the importance of other risk factors for new osteoporotic fractures in addition to low BMD. The extension of a method for calculating the risk (probability) of fractures using the FRAX™ tool is foreseeable in Spain and this would justify a study such as this to allow the necessary adjustments in calibration of the parameters included in the logarithmic formula constituted by FRAX™.</p

Risk factors for infections caused by carbapenem-resistant Enterobacterales: an international matched case-control-control study (EURECA)

© 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).[Background] Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials.[Methods] An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors.[Findings] Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-β-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74–15.53; <0.001), urinary catheter (1.78; 1.03–3.07; 0.038) and exposure to broad spectrum antibiotics, as categorical (2.20; 1.25–3.88; 0.006) and time-dependent (1.04 per day; 1.00–1.07; 0.014); chronic renal failure (2.81; 1.40–5.64; 0.004) and admission from home (0.44; 0.23–0.85; 0.014) were significant only for CSE controls. Subgroup analyses provided similar results.[Interpretation] The main risk factors for CRE infections in hospitals with high incidence included previous colonization, urinary catheter and exposure to broad spectrum antibiotics.The study was funded by the Innovative Medicines Initiative Joint Undertaking (https://www.imi.europa.eu/) under Grant Agreement No. 115620 (COMBACTE-CARE).Peer reviewe