16 research outputs found

    Analysis of variants in the HCN4 gene and in three single nucleotide polymorphisms of the CYP3A4 gene for association with ivabradine reduction in heart rate: A preliminary report

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    Background: Ivabradine, a selective bradycardic drug, inhibits the If. In patients with heart failure (HF), ivabradine reduces the risk of rehospitalization and mortality. The average heart rate (HR) reduction is 8–10 beats, although clinical trials reveal interindividual variability. The aim of the study is to identify variants associated with HR reduction produced by ivabradine in genes involved in the drug metabolism (CYP3A4) or related to the drug target (HCN4). Methods: In an exploratory cohort (n = 11), patients started on ivabradine were genotyped and the HR reduction was studied. Results: The mean HR reduction after the treatment was 18.10 ± 12.26 bpm. The HR reduction was ≥ 15 bpm in 3 patients and > 5 and < 15 bpm in 7 patients. Four synonymous variants, L12L, L520L, P852P, and P1200P, were detected in the HCN4 gene (frequency = 0.045, 0.045, and 0.681, respectively). Moreover, the CYP3A4*1F and CYP3A4*1B were found in one patient each and CYP3A4*1G was presented in 3 patients. Conclusions: This is the first study using an exploratory pharmacogenetic approach that attempts to explain interindividual variability in ivabradine HR reduction. However, more research must be undertaken in order to determine the role of variants in HCN4 and CYP3A4 genes in response to ivabradine

    Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project

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    Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score ? 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score

    Risk Factors and Predictive Score for Bacteremic Biliary Tract Infections Due to Enterococcus faecalis and Enterococcus faecium: a Multicenter Cohort Study from the PROBAC Project

    Get PDF
    Biliary-tract bloodstream infections (BT-BSI) caused by Enterococcus faecalis and E. faecium are associated with inappropriate empirical treatment and worse outcomes compared to other etiologies. The objective of this study was to investigate the risk factors for enterococcal BT-BSI. Patients with BT-BSI from the PROBAC cohort, including consecutive patients with BSI in 26 Spanish hospitals between October 2016 and March 2017, were selected; episodes caused by E. faecalis or E. faecium and other causes were compared. Independent predictors for enterococci were identified by logistic regression, and a predictive score was developed. Eight hundred fifty episodes of BT-BSI were included; 73 (8.5%) were due to target Enterococcus spp. (48 [66%] were E. faecium and 25 [34%] E. faecalis). By multivariate analysis, the variables independently associated with Enterococcus spp. were (OR; 95% confidence interval): cholangiocarcinoma (4.48;1.32 to 15.25), hospital acquisition (3.58;2.11 to 6.07), use of carbapenems in the previous month (3.35;1.45 to 7.78), biliary prosthesis (2.19;1.24 to 3.90), and moderate or severe chronic kidney disease (1.55;1.07 to 2.26). The AUC of the model was 0.74 [95% CI0.67 to 0.80]. A score was developed, with 7, 6, 5, 4, and 2 points for these variables, respectively, with a negative predictive value of 95% for a score # 6. A model, including cholangiocarcinoma, biliary prosthesis, hospital acquisition, previous carbapenems, and chronic kidney disease showed moderate prediction ability for enterococcal BT-BSI. Although the score will need to be validated, this information may be useful for deciding empirical therapy in biliary tract infections when bacteremia is suspected. IMPORTANCE Biliary tract infections are frequent, and a significant cause of morbidity and mortality. Bacteremia is common in these infections, particularly in the elderly and patients with cancer. Inappropriate empirical treatment has been associated with increased risk of mortality in bacteremic cholangitis, and the probability of receiving inactive empirical treatment is higher in episodes caused by enterococci. This is because many of the antimicrobial agents recommended in guidelines for biliary tract infections lack activity against these organisms. To the best of our knowledge, this is the first study analyzing the predictive factors for enterococcal BT-BSI and deriving a predictive score.8 página

    Sperm Competition, Sperm Numbers and Sperm Quality in Muroid Rodents

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    Sperm competition favors increases in relative testes mass and production efficiency, and changes in sperm phenotype that result in faster swimming speeds. However, little is known about its effects on traits that contribute to determine the quality of a whole ejaculate (i.e., proportion of motile, viable, morphologically normal and acrosome intact sperm) and that are key determinants of fertilization success. Two competing hypotheses lead to alternative predictions: (a) sperm quantity and quality traits co-evolve under sperm competition because they play complementary roles in determining ejaculate's competitive ability, or (b) energetic constraints force trade-offs between traits depending on their relevance in providing a competitive advantage. We examined relationships between sperm competition levels, sperm quantity, and traits that determine ejaculate quality, in a comparative study of 18 rodent species using phylogenetically controlled analyses. Total sperm numbers were positively correlated to proportions of normal sperm, acrosome integrity and motile sperm; the latter three were also significantly related among themselves, suggesting no trade-offs between traits. In addition, testes mass corrected for body mass (i.e., relative testes mass), showed a strong association with sperm numbers, and positive significant associations with all sperm traits that determine ejaculate quality with the exception of live sperm. An “overall sperm quality” parameter obtained by principal component analysis (which explained 85% of the variance) was more strongly associated with relative testes mass than any individual quality trait. Overall sperm quality was as strongly associated with relative testes mass as sperm numbers. Thus, sperm quality traits improve under sperm competition in an integrated manner suggesting that a combination of all traits is what makes ejaculates more competitive. In evolutionary terms this implies that a complex network of genetic and developmental pathways underlying processes of sperm formation, maturation, transport in the female reproductive tract, and preparation for fertilization must all evolve in concert

    Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain : Large-Scale Epidemiological Study

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    (1) Aims: To assess the incidence of inflammatory bowel disease (IBD) in Spain, to describe the main epidemiological and clinical characteristics at diagnosis and the evolution of the disease, and to explore the use of drug treatments. (2) Methods: Prospective, population-based nationwide registry. Adult patients diagnosed with IBD-Crohn's disease (CD), ulcerative colitis (UC) or IBD unclassified (IBD-U)-during 2017 in Spain were included and were followed-up for 1 year. (3) Results: We identified 3611 incident cases of IBD diagnosed during 2017 in 108 hospitals covering over 22 million inhabitants. The overall incidence (cases/100,000 person-years) was 16 for IBD, 7.5 for CD, 8 for UC, and 0.5 for IBD-U; 53% of patients were male and median age was 43 years (interquartile range = 31-56 years). During a median 12-month follow-up, 34% of patients were treated with systemic steroids, 25% with immunomodulators, 15% with biologics and 5.6% underwent surgery. The percentage of patients under these treatments was significantly higher in CD than UC and IBD-U. Use of systemic steroids and biologics was significantly higher in hospitals with high resources. In total, 28% of patients were hospitalized (35% CD and 22% UC patients, p < 0.01). (4) Conclusion: The incidence of IBD in Spain is rather high and similar to that reported in Northern Europe. IBD patients require substantial therapeutic resources, which are greater in CD and in hospitals with high resources, and much higher than previously reported. One third of patients are hospitalized in the first year after diagnosis and a relevant proportion undergo surgery

    Correction : Chaparro et al. Incidence, Clinical Characteristics and Management of Inflammatory Bowel Disease in Spain: Large-Scale Epidemiological Study. J. Clin. Med. 2021, 10, 2885

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    The authors wish to make the following corrections to this paper [...]

    La psicología histórica de Ignace Meyerson

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    Ce travail présente la psychologie historique de Ignace Meyerson (1888-1983); c'est une approche qui est restée presque inconnue, y compris dans l'histoire de la psychologie française, où elle a pourtant été conçue et développée. Venu de la médecine et bietôt nommé co-directeur du laboratoire de psychologie physiologique de la Sorbonne (de H. Piéron), Meyerson formule son projet pour une psychologie historique après plus de trente ans de recherches, dans un texte bref mais d'une grande densité théorique: "Les fonctions psychologiques et les oeuvres" (1948). Meyerson y met en question le cadre conceptuel sur lequel la psychologie est assise- héritier de la métaphysique et son dogmatisme de la permanence - et revendique non seulement l'historicité de l'esprit mais son inachèvement essentiel. Dans le but d'éclairicir les abses théoriques et méthodologiques sur lesquelles ce projet est fondé, les rapports qu'il garde avec d'autres approches génétiques et socio-historiques de l'esprit, ainsi que les difficultés qu'il pose et ses possibles apports dans les débats contemporains, nous avons entamé une exploration de ses archives personnelles, où il a conservé toute sa correspondance, les notes de ses cours, de ses conférences et toute la documentation concernant sa thèse. A partir de ces écrits, nous avons suivi la trajectoire intellectuelle de Meyerson depuis ses débuts dans la neuropsychiatrie et la psychophysiologie jusqu'à la formulation du projet pour une psychologie historique et comparée. Ensuite, nous nous concentrons sur ce projet: sur les conditions dans lesquelles il a été rédigé, sur la forme sous laquelle il réunit les nombreux aspects dont il avait traité depuis des années, et sur les réactions qu'il suscite. Enfin, nous parcourons le devenir de Meyerson et de sa psychologie historique, aussi bien sur le plan institutionnel que sur le plan théorique et méthodologique, où à la différence d'une psychologie génétique qui cherche une architecture cognitive, stabilisée au long de la phylogénèse, vise à dévoiler les incessantes transformations auxquelles l'activité psychologique est toujours soumise.This paper introduces the historical psychology of Ignace Meyerson (1888-1983), an approach that has remained marginal, even in the history of French psychology, where it was conceived and developed. Soon after finishing his medical studies Meyerson is named co-director of the laboratory of physiological psychology at the Sorbone.His research work during the next thirty years will bring him to the formulation of his historical psychology. He does that in a brief but extremely dense text, entitled "Les fonctions psychologiques et les oeuvres" (1948). Here he questions the conceptual framework that psychology has been based upon, which he considers to be inherited from metaphysics and its dogmatism of permanence. Meyerson invokes not only the mind's historicity but also the mind's essentiel incompletion. This PhD work attempts to clarify: a) the theoretical and methodological based Meyerson's project has been funded upon, b) its relations with other genetic and socio-historical approaches to the mind, and c) the difficulties it raises and its possible contributions. In order to achieve this, we have analyzed his personal archives, where he has kept all his correspondance, his courses, conferences and documentation related to his thesis. Based on these writings, we have followed Meyerson's intellectual path from his beginnings in the field of psychophysiology and neuropsychiatry until the formulation of this historical psychology's project. Next, we focus on the project itself: on the conditions under which it has been written, the form it was adopted by putting together various issues he had worked on for a long time, and the reactions it provoked. Finally, we follow Meyerson and the latest development of his historical psychology, at the institutional, theoretical and methodological level. Contrary to a genetic psychology which looks for a cognitive architecture, stabilised through the phylogenesis, Meyerson's historical psychology aims at unveiling the incessant transformation psychological activity is always subjected to.BOULOGNE-BU Psych. Henri Pieron (920125201) / SudocSudocFranceF

    Monitoreador de tráfico ip para redes ethernet

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    El sistema “Monitoreador de Tráfico IP para redes Ethernet1” ha sido diseñado con el propósito de facilitar a los administradores de redes una herramienta capaz de monitorear el tráfico que pasa por una red específica. Esta herramienta proporciona gráficos de tipo comparativo sobre el tráfico de una red, además permite la administración de recursos y de usuarios, así como también la configuración del mismo. El software desarrollado ha sido dividido en tres módulos: el monitoreador del tráfico, la Interfase con el usuario y la base de datos. El monitoreador del tráfico constituye la parte del sistema destinada a recopilar, seleccionar y guardar la información que resulta relevante para las consultas. La Interfase se encarga de la interacción con el usuario. El administrador del sistema podrá por medio de ella manejar los recursos y realizar las consultas; mientras que, el usuario común podrá realizar solamente las consultas deseadas. La base de datos resulta ser la conexión entre la interfase y el monitoreador de tráfico. Se utiliza para guardar la información en forma clasificada por medio de tablas. INTRODUCCIÓN Este proyecto tiene como precedentes dos aplicaciones anteriores, la primera realizada en Borland C++ 3.0 para Windows95. La otra aplicación fue desarrollada en el mismo lenguaje de programación para la captura, pero el acceso y administración se lo hacía vía web aplicando el paradigma Cliente/Servidor utilizando e lenguaje JAVA. Ambas aplicaciones sólo capturaban el tráfico correspondiente a ciertas direcciones IP y se guardaba en un archivo denominado “Archivo de Configuración”. Bajo esta perspectiva la segunda aplicación tenía un mejor ambiente de trabajo y podía ser administrado desde cualquier sitio conectado a la red donde se hallaba el sistema. El sistema “Monitoreador de Tráfico IP para redes Ethernet” constituye una herramienta más sofisticada que las versiones anteriores, puesto que es capaz de: • Mostrar gráficamente el tráfico TCP/IP existente en una red Ethernet • Permitir el análisis comparativo entre las diferentes aplicaciones y/o protocolos de comunicación. • Administrarlo y ejecutarlo desde un Navegador, facilitando el acceso desde cualquier punto de la red. • Atender requerimientos de usuarios concurrentes. • Brindar una interfaz amigable al usuario. CONTENIDO 1. Descripción General El sistema consta de 5 componentes principales: 1. Base de datos 2. Monitor de Tráfico 3. Servidor Monitoreo General 4. servidor de monitoreo en línea 5. Clientes JAVA. La comunicación entre los componentes se ilustra en la figura 1. 2. Componentes del Sistema 2.1. Base de Datos El Almacenamiento de la información capturada y de los datos de configuración se lo realiza en una base de datos, pues dada la cantidad de información que se va a manejar en cuanto al tráfico por estación de trabajo, resulta más conveniente por la rapidez de acceso y la facilidad de manejo
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