120 research outputs found
Encoding algebraic power series
The division algorithm for ideals of algebraic power series satisfying Hironaka’s box condition is shown to be finite when expressed suitably in terms of the defining polynomial codes of the series. In particular, the codes of the reduced standard basis of the ideal can be constructed effectively.MECUniversidad Complutense de MadridMinisterio de Ciencia e InnovaciónFondo Europeo de Desarrollo RegionalAustrian Science Fund FW
Attention Deficit Disorder and Hyperactivity (ADHD): therapeutic controversies
Emilia Alonso: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República. Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Lucía Diz: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República. Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- María Amparo Fernández: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República. Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Leonardo García: Estudiante de Medicina, Ciclo de Metodología Científica II, Facultad de Medicina, Universidad de la República. Uruguay. La contribución en la realización del trabajo fue equivalente a la de los demás estudiantes.-- Gustavo Giachetto: Docente supervisor: Clínica Pediátrica “C”, Departamento de Pediatría, Centro Hospitalario Pereira Rossell. Facultad de Medicina, Universidad de la República. Montevideo, Uruguay. Contacto: Gustavo Giachetto. E-mail: [email protected] Trastorno por Déficit de Atención e Hiperactividad (TDAH) es el trastorno neuropsiquiátrico más común en niños. Se carece de tratamiento curativo. Los beneficios y riesgos de las medidas farmacológicas y no farmacológicas disponibles son controvertidos. Esta revisión pretende aportar en la toma de decisiones clínicas para el tratamiento de este trastorno. Se hizo un análisis crítico de literatura médica publicada en PubMed, la que se complementó con entrevistas a profesionales calificados. Se encontró que los psicoestimulantes, especialmente metilfenidato, son fármacos de primera línea. Sus principales beneficios son: control de síntomas, mejora del rendimiento neurocognitivo y de la calidad de vida. Los efectos adversos más frecuentes son leves y transitorios. La toxicidad cardiovascular y la disminución del crecimiento son efectos adversos graves pero raros. El entrenamiento a padres disminuye significamente los síntomas y el entrenamiento cognitivo mejora además las capacidades cognitivas. Se concluye que los psicoestimulantes, en especial el metilfenidato, son la base del tratamiento sintomático del trastorno. A largo plazo es necesario monitorizar sus posibles efectos sobre el crecimiento y el riesgo cardiovascular. Se recomienda combinar con terapia no farmacológica (entrenamiento a
padres y cognitivo) para potenciar beneficios y disminuir riesgos.The Attention Deficit Disorder and Hyperactivity (ADHD) is the most common neuropsychiatric disorder in children. There is no curative treatment. The benefits and risks of pharmacological and nonpharmacological measures available are controversial. This review aims to contribute to clinical decision making in the treatment of this disorder. A critical analysis of literature published in PubMed was done, which was supplemented by interviews with qualified professionals. We found that the benfits of psychostimulants, especially methylphenidate, are: symptom control, improved neurocognitive performance and quality of life. The most common side effects are mild and transient. Cardiovascular toxicity and decreased growth are serious but rare side effects. Parent
training significantly reduces symptoms and cognitive training also improves cognitive abilities. For which we conclude that psychostimulants, especially methylphenidate, are symptomatic firstline treatment. In the long term it is necessary to monitor the growth and cardiovascular risk. It is recommended to combine with non-pharmacological therapy (parent and cognitive training) to enhance benefits and reduce risks
Sobre compactificaciones de Wallman-Frink de espacios discretos
Dado un espacio T3α (X,T), es posible obtener una compactificación T2 del mismo, mediante ultrafiltros asociados a ciertas bases distinguidas de cerrados de (X,T) (Frink [4]). Se plantea así el problema siguiente: ¿Puede obtenerse toda compactificación T2 de (X,T) por este método? Desde el año 1964 en que Frink lo planteó, este interrogante ha tenido respuestas afirmativas parciales. Sin embargo, la solución definitiva es negativa
On the Bezout theorem in the real case
Depto. de Álgebra, Geometría y TopologíaFac. de Ciencias MatemáticasTRUEpu
Decreased incidence of pressure ulcers in intensive care: a program goal of improving care
INTRODUCCIÓN. En sanidad, la aparición de úlceras por presión (upp), es considerado un fracaso asistencial y un gran reto al que se enfrenta el profesional de Enfermería. En cuidados intensivos, objetivamos una serie de factores que aumentan el riesgo de aparición y desarrollo de upp. Como enfermeros, tomamos conciencia de nuestro papel en la prevención y tratamiento de las upp en nuestra unidad de cuidados intensivos (UCI-1, Hospital Universitario Central de Asturias) y emprendimos medidas para disminuirlas y mejorar la calidad asistencial proporcionada. OBJETIVOS. Aumentar la calidad asistencial Disminuir las tasas de úlceras por presión MATERIAL Y MÉTODO. Estudio descriptivo, prospectivo. Muestra, N: 1265 enfermos. Realizándose seguimiento diario de enfermos a través de hoja de valoración específica. Los enfermos valorados presentaban riesgo medio- alto de padecer upp por escala Braden y riesgo bajo por dicha escala pero con condiciones particulares de riesgo objetivables. Se introducen medidas preventivas consensuadas por el equipo investigador (descritas en el trabajo de investigación). RESULTADOS. Bajada significativa de las tasas de incidencia a los cuatro meses de introducir medidas estandarizadas de prevención y mejora asistencial. CONCLUSIONES. La concienciación y unificación de criterios preventivos y de tratamiento resultó ser decisiva en la bajada significativa de la incidencia de upp y en el logro de aumento de la calidad asistencial real percibida por todo el equipo interdisciplinar.INTRODUCTION. In health, the occurrence of pressure ulcers (PU) is considered a failure of care and major challenge facing the nursing professional. In intensive care, objectify a series of factors that increase the risk of occurrence and development of PU. As nurses, we realize our role in the prevention and treatment of pressure ulcers in our intensive care unit (ICU-1, Hospital Universitario Central de Asturias) and we took measures to reduce and improve quality of care provided. OBJECTIVES. To augment quality of care To diminish rates of pressure ulcers MATERIALS AND METHODS. Prospective descriptive study. Sample, n = 1265 patients. Performing daily monitoring of patients through specific assessment sheet. The patients had rated medium-high risk of developing upp by Braden scale and low risk for this scale but with risk conditions to measure. Agreed preventive measures are introduced by the research team (described in the research). RESULTS. Llower incidence rates for four months to introduce standardized measures of prevention and improved care. CONCLUSIONS. The unification of awareness and prevention and treatment criteria proved to be instrumental in the significant decline in the incidence of PU and the achievement of increased quality of care received by all real interdisciplinary team
The association between the tumor immune microenvironments and clinical outcome in low-grade, early-stage endometrial cancer patients
Endometrial tumors show substantial heterogeneity in their immune microenvironment. This heterogeneity could be used
to improve the accuracy of current outcome prediction tools. We assessed the immune microenvironment of 235 patients
diagnosed with low-grade, early-stage endometrial cancer. Multiplex quantitative immunofluorescence was carried out
tomeasure CD8, CD68, FOXP3, PD-1,and PD-L1markers, aswell as cytokeratin (CK), on tissuemicroarrays. Clustering results
revealed five robust immune response patterns, each associated with specific immune populations, cell phenotypes, and cell
spatial clustering.Most samples (69%) belonged to theimmune-desert subtype, characterized by lowimmune cell densities.
Tumor-infiltrating lymphocyte (TIL)-rich samples (4%) displayed high CD8+ T-cell infiltration, as well as a high percentage
of CD8/PD-1+ cells. Immune-exclusion samples (19%) displayed the lowest CD8+ infiltration combined with high PD-L1
expression levels in CK+ tumor cells. In addition, they demonstrated high tumor cell spatial clustering as well as increased
spatial proximity of CD8+/PD-1+ andCK/PD-L1+ cells.FOXP3andmacrophage-rich phenotypes (3%and 4% of total samples) displayed relatively high levels of FOXP3+ regulatory T-cells and CD68+ macrophages, respectively. These phenotypes
correlated with clinical outcomes, with immune-exclusion tumors showing an association with tumor relapse.
When compared with prediction models built using routine pathological variables, models optimized with immune variables
showed increased outcome prediction capacity (AUC = 0.89 versus 0.78) and stratification potential. The improved
prediction capacity was independent of mismatch repair protein status and adjuvant radiotherapy treatment. Further,
immunofluorescence results could be partially recapitulated using single-marker immunohistochemistry (IHC) performed
on whole tissue sections. TIL-rich tumors demonstrated increased CD8+ T-cells by IHC, while immune-exclusion tumors
displayed a lack of CD8+ T-cells and frequent expression of PD-L1 in tumor cells. Our results demonstrate the capability
of the immune microenvironment to improve standard prediction tools in low-grade, early-stage endometrial carcinomasCEA and IgM were funded by Fundación La Marató de
TV3. This project was supported by grants from Partners of Choice Network from AstraZeneca and by the
Instituto de Salud Carlos III (ISCIII) (PI17/01723 and
PI21/00920), co-financed by the European Regional
Development Fund ‘A way to achieve Europe’
(FEDER). We thank Marco Cassano (Lunaphore Technologies) for his help in writing the manuscrip
Zalypsis has in vitro activity in acute myeloid blasts and leukemic progenitor cells through the induction of a DNA damage response.
Background: Although the majority of patients with acute myeloid leukemia initially respond to conventional chemotherapy, relapse is still the leading cause of death, probably because of the presence of leukemic stem cells that are insensitive to current therapies. We investigated the antileukemic activity and mechanism of action of zalypsis, a novel alkaloid of marine origin.
Design and methods: The activity of zalypsis was studied in four acute myeloid leukemia cell lines and in freshly isolated blasts taken from patients with acute myeloid leukemia before they started therapy. Zalypsis-induced apoptosis of both malignant and normal cells was measured using flow cytometry techniques. Gene expression profiling and western blot studies were performed to assess the mechanism of action of the alkaloid.
Results: Zalypsis showed a very potent antileukemic activity in all the cell lines tested and potentiated the effect of conventional antileukemic drugs such as cytarabine, fludarabine and daunorubicin. Interestingly, zalypsis showed remarkable ex vivo potency, including activity against the most immature blast cells (CD34(+) CD38(-) Lin(-)) which include leukemic stem cells. Zalypsis-induced apoptosis was the result of an important deregulation of genes involved in the recognition of double-strand DNA breaks, such as Fanconi anemia genes and BRCA1, but also genes implicated in the repair of double-strand DNA breaks, such as RAD51 and RAD54. These gene findings were confirmed by an increase in several proteins involved in the pathway (pCHK1, pCHK2 and pH2AX).
Conclusions: The potent and selective antileukemic effect of zalypsis on DNA damage response mechanisms observed in acute myeloid leukemia cell lines and in patients' samples provides the rationale for the investigation of this compound in clinical trials.Funding: this work was supported by a grant from the Ministry of Science and Innovation of Spain (BFU2006-01813/BMC and RD06/0020/ 0041).The CIC receives support from the European Community through the regional development funding program (FEDER).This work was also supported by the ‘AcciónTransversal del Cáncer’ project, through an agreement between the Instituto de Salud Carlos III (ISCIII), the Spanish Ministry of Science and Innovation, and the Cancer Research Foundation of Salamanca University. Our group also receives support from the Junta de Castilla y Léon through ‘Ayudas destinadas a financiar programas de actividad investigadora a realizar por grupos de investigación de excelencia de Castilla y León’
Deciphering CHFR role in pancreatic ductal adenocarcinoma
Checkpoint with forkhead-associated and ring finger domains (CHFR) has been proposed as a predictive and prognosis biomarker for different tumor types, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was two-pronged: to review the role of CHFR in PDAC and evaluating CHFR as a potential predictive biomarker in this disease. For this purpose, we first explored the CHFR messenger (m)RNA expression and promoter methylation through the TCGA database. Secondly, the CHFR expression and promoter methylation were prospectively evaluated in a cohort of patients diagnosed with borderline (n = 19) or resectable (n = 16) PDAC by immunohistochemistry (IHC), methylation specific-PCR (MSP), and pyrosequencing. The results from the TCGA database showed significant differences in terms of progression-free survival (PFS) and overall survival (OS) based on the CHFR mRNA expression, which was likely independent from the promoter methylation. Importantly, our results showed that in primarily resected patients and also the entire cohort, a higher CHFR expression as indicated by the higher IHC staining intensity might identify patients with longer disease-free survival (DFS) and OS, respectively. Similarly, in the same cohorts, patients with lower methylation levels by pyrosequencing showed significantly longer OS than patients without this pattern. Both, the CHFR expression intensity and its promoter methylation were established as independent prognostic factors for PFS and OS in the entire cohort. In contrast, no significant differences were found between different methylation patterns for CHFR and the response to taxane-based neoadjuvant treatment. These results suggest the potential role of the higher expression of CHFR and the methylation pattern of its promoter as potential prognostic biomarkers in PDAC, thus warranting further comprehensive studies to extend and confirm our preliminary findings.This work was funded by grants from the Department of Health from the Government of Navarra (Ref. 008-2018), REFBIO II Pyrenees Biomedical Network from Programa INTERREG V-A España-Francia-Andorra (Ref. BMK_PANC) and Sociedad Española de Oncología Médica (SEOM) to AV. IG-B was supported by a predoctoral fellowship from the Department of Economic Development Government of Navarre Ayudas para la contratación de doctorandos y doctorandas por empresas y organismos de investigación y difusión de conocimientos: doctorados industriales 2018–2020. Intensification Programme Navarrabiomed 2017-2021 Obra Social La Caixa Fundación Caja Navarra. This work has also been supported by the Spanish Ministry of Economy [MINECO; BFU2016-80360-R (to JC)] and the Ministry of Science and Innovation [MICINN; PID2019-105201RB-I00 (to JC)]. Instituto de Salud Carlos III, co-funded by European Union (ERDF/ESF, Investing in your future) [Predoctoral contract FI17/00282 (to EA-P)]. Junta de Andalucía (BIO-0139); GETNE2016 and GETNE2019 Research grants (to JC); and CIBERobn
Unraveling the effect of silent, intronic and missense mutations on VWF splicing : contribution of next generation sequencing in the study of mRNA
Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. identifier:02869074
Innovaciones y mejoras en el proyecto tutoría entre compañeros. Curso 2015-2016
Memoria ID-0137. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2015-2016
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