Enfermedad de Paget extramamaria

Background and objective: Extramammary Paget disease (EMPD) has seldom been studied in Mediterranean populations. We aimed to review the characteristics of our patients with EMPD, the presence of a neoplasm in continuity, and the long-term course of the disease. Patients and methods: Retrospective observational study of 27 patients diagnosed with EMPD between 1990 and 2015. All clinical and pathology findings related to clinical course and outcomes were retrieved for analysis. Results: Twenty patients were women and 7 were men. Ages ranged from 42 to 88 years (median, 76 years). Lesions were in the following locations: vulva (16 cases), pubis-groin (5), perianal region (4), and axilla (2). Time from onset to diagnosis ranged from 1 to 60 months (median, 12 months) and maximum lesion diameter from 20 to 140mm (median, 55mm). In 3 cases (11.1%) EMPD was a secondary condition. None of the lesions developed on a previous cutaneous adnexal adenocarcinoma. Ten of the 24 primary EMPDs (41.7%) invaded the dermis. Eight of the 27 patients (29.6%) experienced local recurrence after the initial surgical treatment.Three patients (11.1%) died as a consequence of metastasis from the EMPD. Conclusions: The presence of an underlying cutaneous adnexal adenocarcinoma is uncommon, but it is not unusual to find an extracutaneous adenocarcinoma in continuity. Although EMPD is a slow-growing tumor, dermal invasion is frequent and metastasis is not uncommon. Local recurrence is common even after excision with wide margins and may be delated, so long term follow-up is essential

A multi-scale and multi-physics simulation methodology with the state-of-the-art tools for safety analysis in light water reactors applied to a turbine trip scenario (PART I)

[EN] The simulation of transient events is a requirement in the evaluation of the safety of Nuclear Power Plants. The Nuclear Authority request the operators to report the prediction of the evolution of the corresponding safety variables using simulation codes and methodologies that have proved to be validated against real data, whether experiments or plant measurements. Moreover, these simulation codes are used in the engineering work that a Nuclear Power Plant needs for planning a competitive and safe operation strategy. The available resources in simulation tools make possible complex analysis that can be used to predict realistic results. The consequence is the opportunity of making a safe and cost-efficient evaluation of the safety margins. Operators can use these tools for licensing to the Nuclear Authority and for calculation support of the operation of the reactor in whichever considered case. This paper presents a methodology that takes advantage of different simulation tools to join the capabilities in the Best Estimate (BE) simulation of transients for Light Water Reactors. This methodology works in different steps to account all the physics using the proper scale in a multi-physics and multi-scale approach. An automatic tool manages the data pre- and post-processing the corresponding input and output files. The purpose is to simulate the transient case in a coarse mesh and generate the boundary conditions for a simulation in more detailed scale with a finer mesh in the next step. Therefore, this methodology works generating the corresponding nodal cross section data to be used in coupled 3D thermal-hydraulics and neutron kinetics simulations run with system codes. A channel-by-channel core model is used in order to identify the critical fuel channel. Finally, the boundary conditions of the critical fuel channel are loaded in a pin-by-pin thermal-hydraulic model to perform the definitive Safety Analysis of the target variable, that is selected by the user. The methodology presented in this paper, is applied to a real fast transient case, a Turbine Trip event of fuel cycle 18 in Kernkraftwerk Leibstadt, KKL. The results of each step of this methodology have been validated against the available plant data and the selected target safety variable, the Critical Power Ratio at pin level, has been code-to-code verified. The results show good agreement proving the effectivity of this methodology.The authors of this paper acknowledge the interest and economical and technical support of KKL to undertake the development of this project. This acknowledgement is extended to the collaboration of KKL in the research tasks by sharing plant measurements to validate the methodology and to use their software resources to generate useful data for the code-to-code verification.Hidalga-García-Bermejo, P.; Abarca Giménez, A.; Miró Herrero, R.; Sekhri, A.; Verdú Martín, GJ. (2019). A multi-scale and multi-physics simulation methodology with the state-of-the-art tools for safety analysis in light water reactors applied to a turbine trip scenario (PART I). Nuclear Engineering and Design. 350:195-204. https://doi.org/10.1016/j.nucengdes.2019.05.008S19520435

ISG15 Is Upregulated in Respiratory Syncytial Virus Infection and Reduces Virus Growth through Protein ISGylation

UNLABELLED: Human respiratory syncytial virus (RSV), for which neither a vaccine nor an effective therapeutic treatment is currently available, is the leading cause of severe lower respiratory tract infections in children. Interferon-stimulated gene 15 (ISG15) is a ubiquitin-like protein that is highly increased during viral infections and has been reported to have an antiviral or a proviral activity, depending on the virus. Previous studies from our laboratory demonstrated strong ISG15 upregulation during RSV infection in vitro. In this study, an in-depth analysis of the role of ISG15 in RSV infection is presented. ISG15 overexpression and small interfering RNA (siRNA)-silencing experiments, along with ISG15 knockout (ISG15(-/-)) cells, revealed an anti-RSV effect of the molecule. Conjugation inhibition assays demonstrated that ISG15 exerts its antiviral activity via protein ISGylation. This antiviral activity requires high levels of ISG15 to be present in the cells before RSV infection. Finally, ISG15 is also upregulated in human respiratory pseudostratified epithelia and in nasopharyngeal washes from infants infected with RSV, pointing to a possible antiviral role of the molecule in vivo. These results advance our understanding of the innate immune response elicited by RSV and open new possibilities to control infections by the virus. IMPORTANCE: At present, no vaccine or effective treatment for human respiratory syncytial virus (RSV) is available. This study shows that interferon-stimulated gene 15 (ISG15) lowers RSV growth through protein ISGylation. In addition, ISG15 accumulation highly correlates with the RSV load in nasopharyngeal washes from children, indicating that ISG15 may also have an antiviral role in vivo. These results improve our understanding of the innate immune response to RSV and identify ISG15 as a potential target for virus control.This work was supported by grant PI11/00590 from Fondo de Investigación Sanitaria to I.M.S

Macroloides for the treatment of severe respiratory illness caused by novel H1N1 swine influenza viral strains

Producción CientíficaThe current outburst of a new H1N1 swine influenza strain(s) in México and the United States is causing great concern in health authorities and in the general population [1]. With the World Health Organization (WHO) reporting the pandemic potential of the new strain, it is necessary to determine which therapeutic options are available until a specific vaccine is available. Based on information from the Centre for Disease Control (CDC), the virus is sensitive to oseltamivir and zanamivir. Antivirals are strongly affected by viral mutations; thus their efficiency could be lost as the virus changes

Genetic polymorphisms located in TGFB1, AGTR1, and VEGFA genes are associated to chronic renal allograft dysfunction

Background: Persistent inflammation and fibrosis have been related to active progression of renal deterioration and reduced survival of kidney transplant. The aim of this study was to determine the impact of single-nucleotide polymorphisms (SNPs) located in regions related to inflammatory and immune processes on the development of chronic renal allograft dysfunction (CRAD). Methods: A retrospective study was carried out on 276 patients who received kidney transplant (KT). SNPs were genotyped via the SNPlex platform. Statistical analysis was performed with SNPstat and regression logistic analyses were adjusted by age and gender of recipients and donors, cold ischemia time and the number of human leukocyte antigen (HLA) mismatches. Results: From 276 patients with KT, 118 were non-CRAD and 158 were CRAD. Three SNPs showed significant associations with CRAD development: rs1800471 in transforming growth factor beta 1 (TGFB1), rs5186 in angiotensin II receptor type 1 (AGTR1), and rs699947 in vascular endothelial growth factor A (VEGFA). GC genotype of rs1800471 was associated with increased odds of CRAD compared to GG genotype (OR=2.65 (95% confidence interval (CI)=1.09; 6.47), p=0.025), as well as AC and AA genotype of rs699947 assuming a dominant model (OR=1.80 (95% CI=1.02; 3.20), p=0.044). Besides, AC and CC genotypes of rs5186 were associated with reduced odds of CRAD assuming a dominant model (OR=0.56 (95% CI=0.33; 0.96), p=0.033). Conclusion: Our findings suggest that three genes related to immunity and inflammation (rs1800471, rs5186 and rs699947) are associated to susceptibility or protection to CRAD, and might have diagnostic utility in predicting the likelihood of developing CRAD.This work was supported by two Grants from Instituto de Salud Carlos III (Ref: PI08/0738 and PI11/00245) and from Junta de Castilla y León (Ref: GRS 234/A/08). MAJs, AFR and MGF are supported by Grants from Instituto de Salud Carlos III, CM10/00105, UIPY-1377/08 and CM09/00031, respectively.S

Ventilator-associated pneumonia is an important risk factor for mortality after major cardiac surgery

Producción CientíficaVentilator-associated pneumonia (VAP) is the main infectious complication in cardiac surgery patients and is associated with an important increase in morbidity and mortality. The aim of our study was to analyze the impact of VAP on mortality excluding other comorbidities and to study its etiology and the risk factors for its development. MATERIALS AND METHODS: This prospective cohort study included 1610 postoperative cardiac surgery patients' status post cardiopulmonary bypass (CPB) between July 2004 and January 2008. The primary outcome measures were the development of VAP and in-hospital mortality. RESULTS: Ventilator-associated pneumonia was observed in 124 patients (7.7%). Patients with VAP had a longer length of hospitalization (40.7 ± 35.1 vs 16.1 ± 30.1 days, P <.0001) and greater in-hospital mortality (49.2% [61/124] vs 2.0% [30/1486], P =.0001) in comparison with patients without VAP. After performing the Cox multivariant analysis adjustment, VAP was identified as the most important independent mortality risk factor (adjusted hazard ratio [HR], 8.53; 95% confidence interval, 4.21-17.30; P =.0001). Other independent risk factors of in-hospital mortality were chronic renal failure (HR, 2.56), diabetes mellitus (HR, 1.90), CPB time (HR, 1.51), respiratory failure (HR, 2.13), acute renal failure (HR, 2.39), and mediastinal bleeding of at least 1000 mL (HR, 1.81)

Biological differences between in vitro produced bovine embryos and parthenotes

Parthenotes may represent an alternate ethical source of stem cells, once biological differences between parthenotes and embryos can be understood. In this study, we analyzed development, trophectoderm (TE) differentiation, apoptosis/necrosis, and ploidy in parthenotes and in vitro produced bovine embryos. Subsequently, using real-time PCR, we analyzed the expression of genes expected to underlie the observed differences at the blastocyst stage. In vitro matured oocytes were either fertilized or activated with ionomycin C6-DMAP and cultured in simple medium. Parthenotes showed enhanced blastocyst development and diploidy and reduced TE cell counts. Apoptotic and necrotic indexes did not vary, but parthenotes evidenced a higher relative proportion of apoptotic cells between inner cell mass and TE. The pluripotence-related POU5F1 and the methylation DNMT3A genes were downregulated in parthenotes. Among pregnancy recognition genes, TP-1 was upregulated in parthenotes, while PGRMC1 and PLAC8 did not change. Expression of p66shc and BAX/BCL2 ratio were higher, and p53 lower, in parthenotes. Among metabolism genes, SLC2A1 was downregulated, while AKR1B1, PTGS2, H6PD, and TXN were upregulated in parthenotes, and SLC2A5 did not differ. Among genes involved in compaction/blastulation, GJA1 was downregulated in parthenotes, but no differences were detected within ATP1A1 and CDH1.Within parthenotes, the expression levels of SLC2A1, TP-1, and H6PD, and possibly AKR1B1, resemble patterns described in female embryos. The pro-apoptotic profile is more pronounced in parthenotes than in embryos, which may differ in their way to channel apoptotic stimuli, through p66shc and p53 respectively, and in their mechanisms to control pluripotency and de novo methylation

High performance multiphysics platform for nuclear safety analysis

[ES] En los últimos años, paralelamente a los avances en tecnología informática, se están desarrollando herramientas informáticas mediante las que es posible obtener una descripción detallada de los fenómenos que tienen lugar en el núcleo de los reactores nucleares. El objeto de estas nuevas herramientas es el de realizar análisis de seguridad en reactores nucleares utilizando técnicas de mejor estimación. Las técnicas de mejor estimación, en contraposición con las conservadoras, permiten la operación del reactor con márgenes de seguridad más estrechos y, por tanto, mayor economía del núcleo. En este contexto se desarrolla una plataforma informática que integra códigos informáticos que cubren la mayor parte de las físicas que tienen lugar en los reactores nucleares. Para la integración de los diferentes fenómenos de realimentación entre termohidráulica, neutrónica, mecánica y transmisión de calor se han desarrollado una serie de acoplamientos entre los códigos que componen la plataforma. Todos los desarrollos realizados tienen por objetivo representar de forma realista el diseño y comportamiento de la instalación nuclear, incluyendo el sistema de control, los elementos y las varillas de combustible.[EN] In recent years, in parallel with advances in computer technology, computer tools have been developed through which it is possible to obtain a detailed description of the phenomena occurring in the core of nuclear reactors. The final objective of these new tools is to perform safety analysis using best estimate techniques. The best estimate techniques, as opposed to the conservative ones, allow the operation of the reactor with narrower safety margins, and thus greater core economy. In this context, it has been developed a multiphysics computer platform that integrates simulation codes that cover most of the physics that take place in nuclear reactors. For the integration of the different feedback phenomena between thermal-hydraulics, neutronics and heat transfer, a series of couplings have been developed between the codes that compose the platform. All the developments carried out are intended to realistically represent the design and behavior of the nuclear facility, including the control system, fuel elements and fuel rods.Este trabajo se enmarca dentro de la línea de investigación financiada por el Ministerio de Economía y Competitividad en el proyecto NUC-MULTPHYS (ENE2012-34585) y los proyectos de colaboración interdisciplinar de la Universitat Politècnica de Valencia COBRA_PAR (PAID - 05 -11-2810) y Open-NUC (PAID-05-12)Abarca Giménez, A.; Miró Herrero, R.; Verdú Martín, GJ.; Melara-San Román, J.; Concejal-Bermejo, A. (2018). Plataforma Multifísica de Altas Prestaciones para Análisis de Seguridad en Ingeniería Nuclear. Nuclear España. mayo:1-6. http://hdl.handle.net/10251/120921S16may