26 research outputs found

    Sensitivity of hematopoietic stem cells to mitochondrial dysfunction by SdhD gene deletion

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    It is established that hematopoietic stem cells (HSC) in the hypoxic bone marrow have adapted their metabolism to oxygen-limiting conditions. This adaptation includes suppression of mitochondrial activity, induction of anerobic glycolysis, and activation of hypoxia-inducible transcription factor 1α (Hif1α)-dependent gene expression. During progression of hematopoiesis, a metabolic switch towards mitochondrial oxidative phosphorylation is observed, making this organelle essential for determining cell fate choice in bone marrow. However, given that HSC metabolism is essentially oxygen-independent, it is still unclear whether functional mitochondria are absolutely required for their survival. To assess the actual dependency of these undifferentiated cells on mitochondrial function, we have performed an analysis of the hematopoiesis in a mouse mutant, named SDHD-ESR, with inducible deletion of the mitochondrial protein-encoding SdhD gene. This gene encodes one of the subunits of the mitochondrial complex II (MCII). In this study, we demonstrate that, in contrast to what has been previously established, survival of HSC, and also myeloid and B-lymphoid progenitors, depends on proper mitochondrial activity. In addition, gene expression analysis of these hematopoietic lineages in SDHD-ESR mutants calls into question the proposed activation of Hif1α in response to MCII dysfunction.Ministerio de Ciencia e Innovación SAF2009-06970Junta de Andalucía CTS-4589Instituto de Salud Carlos III PI-0355-201

    Prognostic factors of Infective Endocarditis in Patients on Hemodialysis: A Case Series from a National Multicenter Registry.

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    Background: Infective endocarditis (IE) is a severe complication associated with high mortality. Objectives: To examine the clinical characteristics of IE in hemodialysis (HD) patients and to determine prognostic factors related to HD. Methods: From January 2008 to April 2015, 2,488 consecutive patients with definite IE were included. Clinical characteristics of IE patients on HD were compared with those of IE patients who were not on HD. Results: A total of 126 patients (63% male, median age: 66 years; IQR: 54-74 years) with IE (5.1%) were on HD. Fifty-two patients died during hospitalization (41%) and 17 additional patients (14%) died during the first year. The rate of patients who underwent surgery during hospitalization was lower in HD patients (38 patients, 30%) than in non-HD patients (1,177 patients, 50%; p 70 years (OR: 4.1, 95% CI: 1.7-10), heart failure (OR: 3.3, 95% CI: 1.4-7-6), central nervous system (CNS) vascular events (OR: 6.7, 95% CI: 2.1-22) and septic shock (OR: 4.1, 95% CI: 1.4-12.1) were independently associated with fatal outcome in HD patients. Of the 38 patients who underwent surgery, 15 (39.5%) died during hospitalization. Conclusions. HD patients with IE present a high mortality. Advanced age and complications, such as heart failure, CNS stroke or septic shock, are associated with mortality.pre-print714 K

    Role of age and comorbidities in mortality of patients with infective endocarditis

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    [Purpose]: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. [Methods]: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. [Results]: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32–3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39–1.88),and non-performed surgery (HR:1.64;95% CI:11.16–1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. [Conclusion]: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group

    Outpatient Parenteral Antibiotic Treatment vs Hospitalization for Infective Endocarditis: Validation of the OPAT-GAMES Criteria

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    Search for top squark production in fully hadronic final states in proton-proton collisions at root s=13 TeV

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    A search for production of the supersymmetric partners of the top quark, top squarks, is presented. The search is based on proton-proton collision events containing multiple jets, no leptons, and large transverse momentum imbalance. The data were collected with the CMS detector at the CERN LHC at a center-of-mass energy of 13 TeV, and correspond to an integrated luminosity of 137 fb(-1). The targeted signal production scenarios are direct and gluino-mediated top squark production, including scenarios in which the top squark and neutralino masses are nearly degenerate. The search utilizes novel algorithms based on deep neural networks that identify hadronically decaying top quarks and W bosons, which are expected in many of the targeted signal models. No statistically significant excess of events is observed relative to the expectation from the standard model, and limits on the top squark production cross section are obtained in the context of simplified supersymmetric models for various production and decay modes. Exclusion limits as high as 1310 GeVare established at the 95% confidence level on the mass of the top squark for direct top squark production models, and as high as 2260 GeV on the mass of the gluino for gluino-mediated top squark production models. These results represent a significant improvement over the results of previous searches for supersymmetry by CMS in the same final state.Peer reviewe

    Efectividad de una intervención sobre inteligencia emocional en enfermeras especialistas en salud mental.

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    En los últimos años se ha producido un aumento en el número de pacientes diagnosticados de Trastorno Límite de la Personalidad (TLP). De hecho, es el trastorno de personalidad más frecuente. El TLP consiste en un patrón persistente de inestabilidad en las relaciones interpersonales, afecto y autoimagen con escaso control de impulsos. Estos rasgos, sumados a los de poca tolerancia a la frustración, autolesiones, ideas de muerte, intentos suicidas, inestabilidad afectiva, impulsividad, ambivalencia, ira inapropiada, pobre autoconcepto con sentimientos de inadecuación o inferioridad, baja autoestima; hacen que esta entidad presente una elevada dificultad en su manejo. Todo ello evoca fuertes reacciones contratransferenciales a los terapeutas, que reaccionan de forma evitativa y que, en muchas ocasiones, les genera estrés. Es en esta situación donde la relación terapéutica se ve amenazada. El desarrollo de una relación terapéutica es esencial para enfermería y se debe desarrollar antes de que uno empiece a participar en una fase de trabajo con cualquier paciente. Por lo tanto, para participar de manera efectiva, las enfermeras deben comprender sus propias emociones y reacciones hacia el paciente diagnosticado de TLP. Para ser un buen profesional y cuidador es básico trabajar la capacidad para gestionar los propios sentimientos y emociones de forma adaptativa e inteligente. Este conjunto de habilidades forma parte del concepto de Inteligencia Emocional. El proyecto que se presenta es un estudio cuasi-experimental con un programa formativo sobre Inteligencia Emocional, dirigido a las enfermeras de Salud Mental, que trabajan con pacientes diagnosticados de TLP, de las áreas de los Hospitales de Valme y Virgen del Rocío para mejorar la relación terapéutica con estos pacientes. El objetivo principal del estudio es analizar la efectividad del programa para mejorar la relación terapéutica con estos pacientes, aumentando los niveles de Inteligencia Emocional de las enfermeras, disminuyendo el estrés de las mismas y aumentando la satisfacción tanto de las enfermeras como de los pacientes.   Abstract: In recent years there has been an increase in the number of patients diagnosed with Borderline Personality Disorder (BPD). In fact, it is the most prevalent personality disorder. The BPD is a pervasive pattern of instability in interpersonal relationships, affection, and self-image with low impulse control. These features, combined with the low frustration tolerance, self-harm, thoughts of death, suicide attempts, affective instability, impulsivity, ambivalence, inappropriate anger, poor self-concept with feelings of inadequacy or inferiority, low self esteem, make this entity to disclose an high difficulty in handling. All this evokes strong countertransference reactions to therapists, which react avoidant and, in many cases, they create stress. It is in this situation where the therapeutic relationship is threatened. The development of a therapeutic relationship is essential to nursing and must be developed before one begins to participate in one operation with any patient. Therefore, to participate effectively, nurses must understand their own emotions and reactions to the patient diagnosed with BPD. To be a good professional and basic working caregiver is the ability to manage one´s feelings and emotions in an adaptive and intelligent. This skill set is part of the concept of Emotional Intelligence. The project presented is a quasi-experimental study with Emotional Intelligence training program aimed at mental health nurses, who work with patients diagnosed with BPD, in the areas of Hospitals Virgen del Rocío and Valme and to improve the therapeutic relationship with those patients. The main objective of the study is to analyze the effectiveness of the program to improve the therapeutic relationship with these patients, increasing emotional intelligence levels of nurses, reducing stress and increasing the same satisfaction of both nurses and patients.   Palabra Clave: Trastorno Límite de la Personalidad; Enfermería Salud Mental; Inteligencia Emocional; Relación Terapéutica; Contratransferencia. Key Words: Borderline Personality Disorder; Mental Health Nursing; Emotional Intelligence; Therapeutic Relationship; Countertransference.

    Genotoxicity of tetrahydrofolic acid to hematopoietic stem and progenitor cells.

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    Metabolically reactive formaldehyde is a genotoxin and a carcinogen. Mice lacking the main formaldehyde-detoxifying gene Adh5 combined with the loss of the Fanconi anemia (FA) DNA repair pathway rapidly succumbed to bone marrow failure (BMF) primarily due to the extensive ablation of the hematopoietic stem cell (HSC) pool. However, the mechanism by which formaldehyde mediates these toxic effects is still unknown. We uncover a detrimental role of tetrahydrofolic acid (THF) in cells lacking Adh5 or the FA repair pathway. We show that Adh5- or FA-deficient cells are hypersensitive to formaldehyde and to THF, presenting DNA damage and genome instability. THF cytotoxicity involved imbalance of the nucleotide pool by deregulation of the thymidylate synthase (TYMS) enzyme, which stalled replication forks. In mice, THF exposure had widespread effects on hematopoiesis, affecting the frequency and the viability of myeloid- and lymphoid-committed precursor cells. Moreover, the hematopoietic stem and progenitor cells (HSPC) showed genomic instability, reduced colony-forming capacity and increased frequency of cycling and apoptotic HSCs upon THF exposure. Overall, our data reveal that the physiological pool of THF and formaldehyde challenge the stability of the genome of HSPCs that might lead to blood disorders

    Diseño y elaboración de un portal virtual interactivo de prácticas odontológicas

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    Memoria ID-0176. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2009-2010.La formación práctica es fundamental en la enseñanza de la Odontología ya que se emplean técnicas psicomotrices con carácter asistencial. El alumno tiene que desarrollar unas habilidades manuales y psicomotrices que no posee y debe de ensayar en prácticas simuladas sobre fantomas antes de las prácticas con pacientes. En general, la práctica complementa los conocimientos teóricos y estimula la búsqueda de nuevos conocimientos de aplicación práctica. Así se creo un portal que pudiera auxiliar los alumnos con conocimientos teóricos-prácticos de deontología
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