289 research outputs found

    Monogenic Diabetes Modeling: In Vitro Pancreatic Differentiation From Human Pluripotent Stem Cells Gains Momentum.

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    The occurrence of diabetes mellitus is characterized by pancreatic β cell loss and chronic hyperglycemia. While Type 1 and Type 2 diabetes are the most common types, rarer forms involve mutations affecting a single gene. This characteristic has made monogenic diabetes an interesting disease group to model in vitro using human pluripotent stem cells (hPSCs). By altering the genotype of the original hPSCs or by deriving human induced pluripotent stem cells (hiPSCs) from patients with monogenic diabetes, changes in the outcome of the in vitro differentiation protocol can be analyzed in detail to infer the regulatory mechanisms affected by the disease-associated genes. This approach has been so far applied to a diversity of genes/diseases and uncovered new mechanisms. The focus of the present review is to discuss the latest findings obtained by modeling monogenic diabetes using hPSC-derived pancreatic cells generated in vitro. We will specifically focus on the interpretation of these studies, the advantages and limitations of the models used, and the future perspectives for improvement

    Linking Chronic Otitis Media and Nasal Obstruction: A CFD Approach

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    Objectives To investigate a possible relationship between altered nasal flow and chronic otitis media (COM) using computational fluid dynamics (CFD). Study Design Retrospective case series. Methods Retrospective cohort sample of CT scans from patients with COM and controls without COM to compare the results of various nasal airflow parameters determined by CFD between a group of patients with COM (N = 60) and a control group of subjects without any evidence of ear disease (N = 81). The CT were subjected to various procedures to carry out CFD studies, determining the resistance to nasal flow, the proportion of flow through the right and left nasal cavity, and two nondimensional estimators. The results of CFD studies between patients with COM and controls were compared. Results Whereas only 12.3% of the controls had CFD alteration (10 out of 81), 43.3% of the patients suffering COM displayed alterations of our nondimensional parameters urn:x-wiley:0023852X:media:lary29882:lary29882-math-0001 (26 out of 60). Conclusions According to our results, the incidence of alterations in nasal airflow by studying with CFD is significantly higher in patients with COM than in controls. To our knowledge, this is the first article linking nasal cavity and COM using a CFD approach. Our results support the hypothesis that nasal flow alterations could be implicated in the etiopathogenesis of the COM

    Investigación cualitativa en mujeres víctimas de violencia de género

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    ObjetivoAnalizar la experiencia de mujeres víctimas de la violencia de género atendidas en centros de atención primaria desde el punto de vista de las mujeres.DiseñoInvestigación cualitativa interpretativa. Perspectiva fenomenológica.EmplazamientoEstudio multicéntrico en centros de salud urbanos.ParticipantesMujeres víctimas de la violencia de género (física, psíquica, sexual)atendidas en los centros de salud. Muestreo intencional y teórico hasta el punto de saturación. Criterios de segmentación: edad (jóvenes-edad media-ancianas); maltrato actual o pasado; detección en urgencies-consultas.Mediciones principalesRelatos biográficos y análisis de contenido de la transcripción literal de las grabaciones. Codificación mediante programa NUD-IST. Utilización para la interpretación de la Teoría Fundamentada.LimitacionesComplejidad del fenómeno de estudio. Proyección de la perspectiva del investigador. Volumen ingente de datos. Se proponen estrategias para mejorar la credibilidad, la conformabilidad y la transferibilidad.Aplicabilidad prácticaMejorar el conocimiento de la situación de las mujeres víctimas de la violencia doméstica desde una perspectiva no directiva, lo que permitirá mejorar la calidad de las intervenciones.ObjectiveTo analyse, from the point of view of the women, the experience of women who are victims of male violence and attended at primary care centres.DesignInterpretative, qualitative research. Phenomenological perspective.SettingMulti-centre study in urban health centres.ParticipantsWomen victims of male violence (physical, psychological, or sexual) seen at health centres. Intention andtheoretical sampling to saturation point.Segmentation criteria: age (young/middle-aged/elderly); current or past ill-treatment; detection in casualty/consultations.Main measurementsBiographical accounts and content analysis of recordings’ literal transcription. Coding through the NUDIST programme. Use for interpreting Well-Founded Theory.LimitationsComplexity of the phenomenon under study. Projection of researcher’s perspective. Huge amount of data. Strategies are proposed for increasing credibility, conformity and transferability.Practical useTo improve understanding of the situation of women who are victims of domestic violence, from a non-directive perspective that enables the quality of interventions to be improved

    NECESIDADES HÍDRICAS Y PROGRAMACIÓN DE RIEGO EN LOS CULTIVOS DE MAÍZ, SOYA Y SORGO EN LA LOCALIDAD DE SALTO, URUGUAY

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    El uso eficiente y eficaz del agua en el riego, es la clave de la sostenibilidad y la rentabilidad de cualquier cultivo. El objetivo de este estudio fue determinar la necesidad hídrica y programación de riego de los cultivos de maíz, sorgo y soya en diferentes fecha de siembra y estimar el decrecimiento del rendimiento en condición de secano. El estudio fue conducido en la localidad de Salto, ubicado en la Región Norte del Uruguay. El intervalo de la siembra fue mensual, en los meses de septiembre, octubre, noviembre y diciembre. Se efectuó análisis de consistencia de las variables climáticas para un periodo de observación de 46 años, seleccionando 36 años para el estudio. Los datos de suelo fueron obtenidos por determinaciones efectuadas en campo y mediante ensayos de laboratorio. Para estimar las láminas de riego y la evapotranspiración de los cultivos, fue utilizado el modelo WinISAREG®. Para el análisis estadístico se aplicó un diseño experimental completamente al azar, donde los factores son cultivo y fecha de siembra y los años son las repeticiones.                        Las necesidades hídricas media maíz, soya y sorgo es de 612, 643 y 597 mm, respectivamente. La lámina de riego media en maíz, soya y sorgo es 308, 329 y 291 mm en intervalo de 9, 8 y 10 días, respectivamente. El decrecimiento del rendimiento medio en maíz, soya y sorgo 0,4, 0,3 y 0,3, respectivamente. Realizar la siembra en octubre o noviembre, representaría la mayor demanda de evapotranspiración

    Unraveling the extracellular matrix-tumor cell interactions to aid better targeted therapies for neuroblastoma

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    Treatment in children with high-risk neuroblastoma remains largely unsuccessful due to the development of metastases and drug resistance. The biological complexity of these tumors and their microenvironment represent one of the many challenges to face. Matrix glycoproteins such as vitronectin act as bridge elements between extracellular matrix and tumor cells and can promote tumor cell spreading. In this study, we established through a clinical cohort and preclinical models that the interaction of vitronectin and its ligands, such as αv integrins, are related to the stiffness of the extracellular matrix in high-risk neuroblastoma. These marked alterations found in the matrix led us to specifically target tumor cells within these altered matrices by employing nanomedicine and combination therapy. Loading the conventional cytotoxic drug etoposide into nanoparticles significantly increased its efficacy in neuroblastoma cells. We noted high synergy between etoposide and cilengitide, a high-affinity cyclic pentapeptide αv integrin antagonist. The results of this study highlight the need to characterize cell-extracellular matrix interactions, to improve patient care in high-risk neuroblastoma

    Spatial distribution and community structure of megabenthic bivalves in the subtidal area of the Gulf of Cádiz (SW Spain)

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    VENUSEstudio integral de los bancos naturales de moluscos bivalvos en el Golfo de Cádiz para su gestión sostenible y la conservación de sus hábitats asociado

    Spatial distribution patterns of the striped venus clam (Chamelea gallina, L. 1758) natural beds in the Gulf of Cádiz (SW Spain)

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    VENUSEstudio integral de los bancos naturales de moluscos bivalvos en el Golfo de Cádiz para su gestión sostenible y la conservación de sus hábitats asociado

    Ecuaciones de referencia de la capacidad aeróbica máxima ciclo-ergoespirometría para la población española adulta

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    [EN] Background: Frequently used reference values for clinical exercise testing have been derived from non-random samples and some with poorly defined maximal criteria. Our objective was to obtain population based reference values for peak oxygen uptake ( ̇VO2 ) and work rate (WR) for cardiopulmonary exercise testing in a representative sample of Caucasian Spanish men and women. Methods: 182 men and women, 20–85 years old, were included and exercised on cycle-ergometer to exhaustion. ( ̇VO2 ) and WR were measured. The equations obtained from this sample were validated in an independent cohort of 69 individuals, randomly sampled form the same population. Then a final equation merging the two cohorts (=251) was produced. Results: Height, sex and age resulted predictive of both ̇VO2 peak and WR. Weight and physical activity added very little to the accuracy to the equations. The formulas ̇VO2 peak = 0.017 · height (cm) − 0.023 · age (years) + 0.864 · sex (female = 0/male = 1) ± 179 l min−1 , and peak WR = 1.345 · height (cm) − 2.074 · age (years) + 76.54 · sex (female = 0/male = 1) ± 21.2 W were the best compromise between accuracy and parsimony. Conclusions: This study provides new and accurate ̇VO2 peak and WR rate reference values for individuals of European Spanish descent[ES] Antecedentes: Los valores de referencia utilizados con frecuencia para las pruebas de esfuerzo clínicas derivan de muestras no aleatorias y los criterios máximos para algunos de ellos están mal definidos. Nuestro objetivo fue obtener valores de referencia basados en la población general para el consumo máximo de oxígeno (VO 2 ) y la carga de trabajo (CT) para las pruebas de ejercicio cardiopulmonar a partir de una muestra representativa de varones y mujeres caucásicos españoles. Métodos: Se incluyeron 182 varones y mujeres, de entre 20 y 85 a ̃nos, que realizaron ejercicio en el cicloergómetro hasta el agotamiento. Se midieron el VO 2 y la CT. Las ecuaciones obtenidas de esta muestra se validaron en una cohorte independiente de 69 individuos, seleccionados aleatoriamente de la misma población. A continuación, se creó una ecuación final que fusionó las dos cohortes (n = 251). Resultados: La altura, el sexo y la edad resultaron predictivos tanto del ̇VO2 máximo como de la CT. El peso y la actividad física contribuyeron muy poco a la precisión de las ecuaciones. Las fórmulas ̇VO2 máximo = 0,017 × altura (cm) − 0,023 × edad (a ̃nos) + 0,864 × sexo (mujer = 0/varón = 1) ± 179 L × min−1 ; y CT máxima = 1,345 × altura (cm) − 2,074 × edad (a ̃nos) + 76,54 × sexo (mujer = 0/varón = 1) ± 21,2 W fueron el mejor equilibrio entre precisión y parsimonia. Conclusiones: Este estudio proporciona valores de referencia del ̇VO 2 máximo y la CT nuevos y precisos para personas de ascendencia espa ̃nola europea.This study was supported by a SEPAR (Sociedad Española de Neumología y Cirugía Torácica/Spanish society of Pulmonology and Thoracic Surgery) grant and NEUMOMADRD (Sociedad Madrileña de Neumología y Cirugía Torácica/Madrilenian Society of Pulmonology and Thoracic Surgery) research award

    Analysis of solar direct irradiance models under clear-skies: Evaluation of the improvements for locally adapted models

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    Direct solar irradiance has to be determined for the design of many energy applications such as photovoltaic systems and concentration systems, and the generation of solar potential maps for energy use. Knowledge of the accurate values of radiation components in a local area will allow optimal sizing of solar energy conversion systems. The estimated values of direct solar irradiance from models are still necessary at those sites where no measurements are available. In this work, different models used for the estimation of the direct component of solar irradiance are analyzed. First, an evaluation of the performance of eight existing original models was performed from which three were selected. Second, the selected models were calibrated to adapt them to our studied geographical area, which is the important aspect of this work, and an assessment of performance improvements for locally adapted models is reported. Experimental data consisted of hourly horizontal global, direct, and diffuse solar irradiance values, provided by the National Meteorological Agency in Spain (AEMET) for Madrid. Long-term data series, corresponding to a total period of time of 32 years (1980–2011), have been used in this study. Only clear sky models were treated at present. The three selected models were adapted to the specific location of Madrid, and root mean square error (RMSE) and mean-biased error were determined. By comparing the performance in the direct horizontal irradiance estimation from existing original and the corresponding locally adapted models, it is found that the values of RMSE decreased from 9.9% to 5.7% for the Louche model, from 7.8% to 7.4% for the Robledo-Soler model, and finally from 8.8% to 6.7% for the European Solar Radiation Atlas model. Thus, significant improvements can be reached when parametric models are locally adapted. In our case, it is up to approximately 4% for the Louche model. It is expected that calibrated algorithms presented in this work will be applicable to regions of similar climatic characteristics.Spanish Government (grant ENE2011-27511) and the Department of Culture and Education of the Regional Government of Castilla y León, Spain (grant BU358A12-2
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