Influence of Sex on Stroke Prognosis: A Demographic, Clinical, and Molecular Analysis

Identifying the complexities of the effect of sex on stroke risk, etiology, and lesion progression may lead to advances in the treatment and care of ischemic stroke (IS) and non-traumatic intracerebral hemorrhage patients (ICH). We studied the sex-related discrepancies on the clinical course of patients with IS and ICH, and we also evaluated possible molecular mechanisms involved. The study's main variable was the patient's functional outcome at 3-months. Logistic regression models were used in order to study the influence of sex on different inflammatory, endothelial and atrial dysfunction markers. We recruited 5,021 patients; 4,060 IS (54.8% male, 45.2% female) and 961 ICH (57.1% male, 42.9% female). Women were on average 5.7 years older than men (6.4 years in IS, 5.1 years in ICH), and more likely to have previous poor functional status, to suffer atrial fibrillation and to be on anticoagulants. IS patients showed sex-related differences at 3-months regarding poorer outcome (55.6% women, 43.6% men, p < 0.0001), but this relationship was not found in ICH (56.8% vs. 61.9%, p = 0.127). In IS, women had higher levels of NT-proBNP and 3-months worse outcome in both cardioembolic and non-cardioembolic stroke patients. Stroke patients showed sex-related differences in pre-hospital data, clinical variables and molecular markers, but only IS patients presented independent sex-related differences in 3-months poor outcome and mortality. There was a relationship between the molecular marker of atrial dysfunction NT-proBNP and worse functional outcome in women, resulting in a possible indicator of increased dysfunction

Regulatory T cells participate in the recovery of ischemic stroke patients

BACKGROUND: Recent preclinical studies have shown that regulatory T cells (Treg) play a key role in the immune response after ischemic stroke (IS). However, the role of Treg in human acute IS has been poorly investigated. Our aim was to study the relationship between circulating Treg and outcome in human IS patients. METHODS: A total of 204 IS patients and 22 control subjects were recruited. The main study variable was good functional outcome at 3 months (modified Rankin scale </=2) considering infarct volume, Early Neurological Deterioration (END) and risk of infections as secondary variables. The percentage of circulating Treg was measured at admission, 48, 72 h and at day 7 after stroke onset. RESULTS: Circulating Treg levels were higher in IS patients compared to control subjects. Treg at 48 h were independently associated with good functional outcome (OR, 3.5; CI: 1.9-7.8) after adjusting by confounding factors. Patients with lower Treg at 48 h showed higher frequency of END and risk of infections. In addition, a negative correlation was found between circulating Treg at 48 h (r = - 0.414) and 72 h (r = - 0.418) and infarct volume. CONCLUSIONS: These findings suggest that Treg may participate in the recovery of IS patients. Therefore, Treg may be considered a potential therapeutic target in acute ischemic stroke

Fatty acid composition and age estimation of wild Octopus vulgaris paralarvae

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Intra- and extra-hospital improvement in ischemic stroke patients: influence of reperfusion therapy and molecular mechanisms

Neuroprotective treatments in ischemic stroke are focused to reduce the pernicious effect of excitotoxicity, oxidative stress and inflammation. However, those cellular and molecular mechanisms may also have beneficial effects, especially during the late stages of the ischemic stroke. The objective of this study was to investigate the relationship between the clinical improvement of ischemic stroke patients and the time-dependent excitotoxicity and inflammation. We included 4295 ischemic stroke patients in a retrospective study. The main outcomes were intra and extra-hospital improvement. High glutamate and IL-6 levels at 24 hours were associated with a worse intra-hospital improvement (OR:0.993, 95%CI: 0.990-0.996 and OR:0.990, 95%CI: 0.985-0.995). High glutamate and IL-6 levels at 24 hours were associated with better extra-hospital improvement (OR:1.13 95%CI, 1.07-1.12 and OR:1.14, 95%CI, 1.09-1.18). Effective reperfusion after recanalization showed the best clinical outcome. However, the long term recovery is less marked in patients with an effective reperfusion. The variations of glutamate and IL6 levels in the first 24 hours clearly showed a relationship between the molecular components of the ischemic cascade and the clinical outcome of patients. Our findings suggest that the rapid reperfusion after recanalization treatment blocks the molecular response to ischemia that is associated with restorative processes

Arquitecturas multiprocesador en computación de alto desempeño: software, métricas, modelos y aplicaciones

Caracterizar las arquitecturas multiprocesador distribuidas enfocadas especialmente a cluster y cloud computing, con énfasis en las que utilizan procesadores de múltiples núcleos (multicores, GPUs y Xeon Phi), con el objetivo de modelizarlas, estudiar su escalabilidad, analizar y predecir performance de aplicaciones paralelas, estudiar el consumo energético y su impacto en la perfomance así como desarrollar esquemas para detección y tolerancia a fallas en las mismas. Profundizar el estudio de arquitecturas basadas en GPUs y su comparación con clusters de multicores, así como el empleo combinado de GPUs y multicores en computadoras de alta perfomance. Iniciar investigación experimental con arquitecturas paralelas basadas en FPGAs. En particular estudiar perfomance en Clusters “híbridos”. Analizar y desarrollar software de base para clusters, tratando de optimizar el rendimiento. Investigar arquitecturas multicore asimétricas, desarrollar algoritmos de planificación en el software de sistema operativo para permitir la optimización del rendimiento y consumo energético en aplicaciones de propósito general. Estudiar clases de aplicaciones inteligentes en tiempo real, en particular el trabajo colaborativo de robots conectados a un cloud y procesamiento de Big Data. Es de hacer notar que este proyecto se coordina con otros proyectos en curso en el III-LIDI, relacionados con Computación de Alto Desempeño, Algoritmos Paralelos, Sistemas Distribuidos y Sistemas de Tiempo Real.Eje: Procesamiento Distribuido y Paralelo.Red de Universidades con Carreras en Informática (RedUNCI

Arquitecturas multiprocesador en HPC: software, métricas, modelos y aplicaciones

La línea presentada en este trabajo tiene como eje central las arquitecturas paralelas para Cómputo de Altas Prestaciones, con los siguientes objetivos: - Caracterizar las arquitecturas multiprocesador orientadas a computación de alto desempeño, analizando técnicas para el desarrollo de código eficiente sobre las mismas y métricas de rendimiento computacional y energético. Principalmente teniendo en cuenta aquellas arquitecturas que son combinaciones de cluster, multicores, aceleradores (GPUs, FPGAs, Xheon Phi), placas de bajo costo (Raspberry PI, Odroid). - Estudiar la conformación de clusters y clouds a partir de configuraciones homogéneas e híbridas de multiprocesadores. Y analizar la performance de aplicaciones sobre los mismos, considerando eficiencia computacional/energética y escalabilidad, así como la tolerancia a fallos. - Analizar y desarrollar software de base para estas arquitecturas con el objetivo de optimizar del rendimiento y consumo energético en aplicaciones de propósito general. - Estudiar clases de aplicaciones inteligentes en tiempo real, en particular el trabajo colaborativo de robots conectados a un cloud y procesamiento de Big Data. Es de hacer notar que este proyecto se coordina con otros proyectos en curso en el III-LIDI, relacionados con Computación de Alto Desempeño, Algoritmos Paralelos, Sistemas Distribuidos y Sistemas de Tiempo Real.Eje: Procesamiento Distribuido y Paralelo.Red de Universidades con Carreras en Informátic

Arquitecturas multiprocesador en HPC: software, métricas, modelos y aplicaciones

La línea presentada en este trabajo tiene como eje central las arquitecturas paralelas para Cómputo de Altas Prestaciones, con los siguientes objetivos: - Caracterizar las arquitecturas multiprocesador orientadas a computación de alto desempeño, analizando técnicas para el desarrollo de código eficiente sobre las mismas y métricas de rendimiento computacional y energético. Principalmente teniendo en cuenta aquellas arquitecturas que son combinaciones de cluster, multicores, aceleradores (GPUs, FPGAs, Xheon Phi), placas de bajo costo (Raspberry PI, Odroid). - Estudiar la conformación de clusters y clouds a partir de configuraciones homogéneas e híbridas de multiprocesadores. Y analizar la performance de aplicaciones sobre los mismos, considerando eficiencia computacional/energética y escalabilidad, así como la tolerancia a fallos. - Analizar y desarrollar software de base para estas arquitecturas con el objetivo de optimizar del rendimiento y consumo energético en aplicaciones de propósito general. - Estudiar clases de aplicaciones inteligentes en tiempo real, en particular el trabajo colaborativo de robots conectados a un cloud y procesamiento de Big Data. Es de hacer notar que este proyecto se coordina con otros proyectos en curso en el III-LIDI, relacionados con Computación de Alto Desempeño, Algoritmos Paralelos, Sistemas Distribuidos y Sistemas de Tiempo Real.Eje: Procesamiento Distribuido y Paralelo.Red de Universidades con Carreras en Informátic

p21 as a Transcriptional Co-Repressor of S-Phase and Mitotic Control Genes

It has been previously described that p21 functions not only as a CDK inhibitor but also as a transcriptional co-repressor in some systems. To investigate the roles of p21 in transcriptional control, we studied the gene expression changes in two human cell systems. Using a human leukemia cell line (K562) with inducible p21 expression and human primary keratinocytes with adenoviral-mediated p21 expression, we carried out microarray-based gene expression profiling. We found that p21 rapidly and strongly repressed the mRNA levels of a number of genes involved in cell cycle and mitosis. One of the most strongly down-regulated genes was CCNE2 (cyclin E2 gene). Mutational analysis in K562 cells showed that the N-terminal region of p21 is required for repression of gene expression of CCNE2 and other genes. Chromatin immunoprecipitation assays indicated that p21 was bound to human CCNE2 and other p21-repressed genes gene in the vicinity of the transcription start site. Moreover, p21 repressed human CCNE2 promoter-luciferase constructs in K562 cells. Bioinformatic analysis revealed that the CDE motif is present in most of the promoters of the p21-regulated genes. Altogether, the results suggest that p21 exerts a repressive effect on a relevant number of genes controlling S phase and mitosis. Thus, p21 activity as inhibitor of cell cycle progression would be mediated not only by the inhibition of CDKs but also by the transcriptional down-regulation of key genes

Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon?

Raquel Sabino was not included as an author in the published article. It was corrected a posteriori.Erratum in - Corrigendum: Azole-Resistance in Aspergillus terreus and Related Species: An Emerging Problem or a Rare Phenomenon? [Front Microbiol. 2018] Front Microbiol. 2019 Jan 14;9:3245. doi: 10.3389/fmicb.2018.03245. eCollection 2018.Disponível em: https://www.frontiersin.org/articles/10.3389/fmicb.2018.03245/fullFree PMC Article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5882871/ | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6340063/Objectives: Invasive mold infections associated with Aspergillus species are a significant cause of mortality in immunocompromised patients. The most frequently occurring aetiological pathogens are members of the Aspergillus section Fumigati followed by members of the section Terrei. The frequency of Aspergillus terreus and related (cryptic) species in clinical specimens, as well as the percentage of azole-resistant strains remains to be studied. Methods: A global set (n = 498) of A. terreus and phenotypically related isolates was molecularly identified (beta-tubulin), tested for antifungal susceptibility against posaconazole, voriconazole, and itraconazole, and resistant phenotypes were correlated with point mutations in the cyp51A gene. Results: The majority of isolates was identified as A. terreus (86.8%), followed by A. citrinoterreus (8.4%), A. hortai (2.6%), A. alabamensis (1.6%), A. neoafricanus (0.2%), and A. floccosus (0.2%). One isolate failed to match a known Aspergillus sp., but was found most closely related to A. alabamensis. According to EUCAST clinical breakpoints azole resistance was detected in 5.4% of all tested isolates, 6.2% of A. terreus sensu stricto (s.s.) were posaconazole-resistant. Posaconazole resistance differed geographically and ranged from 0% in the Czech Republic, Greece, and Turkey to 13.7% in Germany. In contrast, azole resistance among cryptic species was rare 2 out of 66 isolates and was observed only in one A. citrinoterreus and one A. alabamensis isolate. The most affected amino acid position of the Cyp51A gene correlating with the posaconazole resistant phenotype was M217, which was found in the variation M217T and M217V. Conclusions:Aspergillus terreus was most prevalent, followed by A. citrinoterreus. Posaconazole was the most potent drug against A. terreus, but 5.4% of A. terreus sensu stricto showed resistance against this azole. In Austria, Germany, and the United Kingdom posaconazole-resistance in all A. terreus isolates was higher than 10%, resistance against voriconazole was rare and absent for itraconazole.This work was supported by ECMM, ISHAM, and EFISG and in part by an unrestricted research grant through the Investigator Initiated Studies Programof Astellas, MSD, and Pfizer. This study was fundet by the Christian Doppler Laboratory for invasive fungal infections.info:eu-repo/semantics/publishedVersio

Comparison of seven prognostic tools to identify low-risk pulmonary embolism in patients aged <50 years

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