Gene Expression Profiling in Limb-Girdle Muscular Dystrophy 2A

Limb-girdle muscular dystrophy type 2A (LGMD2A) is a recessive genetic disorder caused by mutations in calpain 3 (CAPN3). Calpain 3 plays different roles in muscular cells, but little is known about its functions or in vivo substrates. The aim of this study was to identify the genes showing an altered expression in LGMD2A patients and the possible pathways they are implicated in. Ten muscle samples from LGMD2A patients with in which molecular diagnosis was ascertained were investigated using array technology to analyze gene expression profiling as compared to ten normal muscle samples. Upregulated genes were mostly those related to extracellular matrix (different collagens), cell adhesion (fibronectin), muscle development (myosins and melusin) and signal transduction. It is therefore suggested that different proteins located or participating in the costameric region are implicated in processes regulated by calpain 3 during skeletal muscle development. Genes participating in the ubiquitin proteasome degradation pathway were found to be deregulated in LGMD2A patients, suggesting that regulation of this pathway may be under the control of calpain 3 activity. As frizzled-related protein (FRZB) is upregulated in LGMD2A muscle samples, it could be hypothesized that β-catenin regulation is also altered at the Wnt signaling pathway, leading to an incorrect myogenesis. Conversely, expression of most transcription factor genes was downregulated (MYC, FOS and EGR1). Finally, the upregulation of IL-32 and immunoglobulin genes may induce the eosinophil chemoattraction explaining the inflammatory findings observed in presymptomatic stages. The obtained results try to shed some light on identification of novel therapeutic targets for limb-girdle muscular dystrophies

Detecting reliable gene interactions by a hierarchy of Bayesian network classifiers

The main purpose of a gene interaction network is to map the relationships of the genes that are out of sight when a genomic study is tackled. DNA microarrays allow the measure of gene expression of thousands of genes at the same time. These data constitute the numeric seed for the induction of the gene networks. In this paper, we propose a new approach to build gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling. The interactions induced by the Bayesian classifiers are based both on the expression levels and on the phenotype information of the supervised variable. Feature selection and bootstrap resampling add reliability and robustness to the overall process removing the false positive findings. The consensus among all the induced models produces a hierarchy of dependences and, thus, of variables. Biologists can define the depth level of the model hierarchy so the set of interactions and genes involved can vary from a sparse to a dense set. Experimental results show how these networks perform well on classification tasks. The biological validation matches previous biological findings and opens new hypothesis for future studies

Comparison of metaheuristic strategies for peakbin selection in proteomic mass spectrometry data

Mass spectrometry (MS) data provide a promising strategy for biomarker discovery. For this purpose, the detection of relevant peakbins in MS data is currently under intense research. Data from mass spectrometry are challenging to analyze because of their high dimensionality and the generally low number of samples available. To tackle this problem, the scientific community is becoming increasingly interested in applying feature subset selection techniques based on specialized machine learning algorithms. In this paper, we present a performance comparison of some metaheuristics: best first (BF), genetic algorithm (GA), scatter search (SS) and variable neighborhood search (VNS). Up to now, all the algorithms, except for GA, have been first applied to detect relevant peakbins in MS data. All these metaheuristic searches are embedded in two different filter and wrapper schemes coupled with Naive Bayes and SVM classifiers.

A ferrous oxalate mediated photo-Fenton system: Toward an increased biodegradability of indigo dyed wastewaters

This study assessed the applicability of a ferrous oxalate mediated photo-Fenton pretreatment for indigo-dyed wastewaters as to produce a biodegradable enough effluent, likely of being derived to conventional biological processes. The photochemical treatment was performed with ferrous oxalate and hydrogen peroxide in a Compound Parabolic Concentrator (CPC) under batch operation conditions. The reaction was studied at natural pH conditions (5–6) with indigo concentrations in the range of 6.67–33.33 mg L−1, using a fixed oxalate-to-iron mass ratio (C2O42−/Fe2+ = 35) and assessing the system's biodegradability at low (257 mg L−1) and high (1280 mg L−1) H2O2 concentrations. In order to seek the optimal conditions for the treatment of indigo dyed wastewaters, an experimental design consisting in a statistical surface response approach was carried out. This analysis revealed that the best removal efficiencies for Total Organic Carbon (TOC) were obtained for low peroxide doses. In general it was observed that after 20 kJ L−1, almost every treated effluent increased its biodegradability from a BOD5/COD value of 0.4. This increase in the biodegradability was confirmed by the presence of short chain carboxylic acids as intermediate products and by the mineralization of organic nitrogen into nitrate. Finally, an overall decrease in the LC50 for Artemia salina indicated a successful detoxification of the effluent.

Diabetes gestacional : el rol del ejercicio físico en su prevención

Introducción. La prevalencia de la Diabetes Gestacional (DG) varía en todo el mundo, así como entre los grupos raciales y étnicos del mismo país. Hasta la fecha actual, no se ha llegado a un consenso en el criterio diagnóstico, y eso dificulta una estimación veraz de prevalencia entre países. A pesar de ello, es ineludible obviar el incremento en la incidencia de esta complicación en todo el mundo, y la trascendencia de sus riesgos a la salud pública. En España, según los criterios clásicos –del National Diabetes Data Group- existe una alta prevalencia en un 8,8 % de DG en gestantes. Es importante encontrar la mejor vía para la prevención de la DG y, uno de los factores de riesgo parece ser el aumento excesivo de peso durante el embarazo. El ejercicio es un elemento fundamental para el control del metabolismo de la glucosa y para reducir los niveles de hiperlipidemia. Sin embargo, existe controversia para definir el tipo de sesiones, duración e intensidad que puedan contribuir a su prevención. Objetivo. Conocer en qué medida el ejercicio físico programado durante el embarazo, combinado en agua y tierra, con ejercicios aeróbicos y de tonificación muscular, puede actuar como un factor de prevención de la DG. Al mismo tiempo, valorar si exceder las recomendaciones de peso puede influir el diagnóstico de la DG. Material y Métodos. Este estudio se desarrolló mediante una colaboración entre la Universidad Politécnica de Madrid y los Servicios de Ginecología y Obstetricia del Hospital Universitario de Puerta de Hierro, el Hospital Universitario de Torrelodones y el Centro de Salud de Torrelodones. Se obtuvo la aprobación del Comité Ético de Investigación Clínica (CEIC). Se realizó un ensayo clínico, aleatorizado, controlado, no enmascarado. 272 mujeres gestantes sanas dieron su consentimiento informado para la inclusión en el estudio. De las cuáles, finalmente 257 (edad= 33,2±4,4 años) fueron analizadas, 101 de ellas correspondientes al grupo intervención (GI, n=101) y 156 al grupo control (GC, n=156). El inicio del programa correspondió a la semana 10-14 del embarazo hasta el final, la 38-40. Con una frecuencia de 3 sesiones semanales y una duración de 60 y 50 minutos, en tierra y agua, respectivamente. Resultados. Se halló diferencias significativas en los valores en los 180 min del test de tolerancia oral a la glucosa [GI: 98,00±29,48 mg/dl vs. GC: 116,25±29,90 mg/dl (t64= 2,37; p= 0,021)] y, de igual modo, el GI mostró menor prevalencia de la DG [GI: 1 %, Ejercicio y DG n= 1 vs. GC: 8,8 %, n= 13 (2 1= 6,84; p= 0,009)] y una estimación de riesgo significativa (OR= 9,604; 95 % CI: 1,23-74,66). La excesiva ganancia de peso fue menor en el GI [GI: 22,8 %, n= 23 vs. GC: 34,9 %, n= 53 (2 1= 4,22; p= 0,040)], pero no existió una correlación con la incidencia de DG (ϕ= -0,007; p= 0,910). Conclusiones. El programa de ejercicio desarrollado durante el embarazo mostró efectividad en la reducción de la prevalencia de la DG, preservó la tolerancia a la glucosa y redujo la excesiva ganancia de peso materno. Background. The prevalence of Gestational Diabetes (GD) varies around the world, as well as between racial and ethnic groups within the same country. Currently, there is not a consensus about the diagnostic criteria, and that makes it difficult to obtain accurate estimates of prevalence between countries. The increased trend in the prevalence across the globe and the risks for public health cannot be ignored. In Spain, according to the diagnostic criteria of National Diabetes Data Group, there is a prevalence of 8.8 % for GD in pregnant women. It is important to look for the best way to prevent GD and one of the risk factors seems to be excessive weight gained during pregnancy. Exercise is an essential element for glucose metabolic control and reducing hyperlipidemia levels. However, there is controversy to define the type of activity, duration and intensity to prevent GD. Objective. To assess the effectiveness of an exercise programme carried out during pregnancy (land/aquatic activities), both aerobic and muscular conditioning can help to the prevent GD. Also, to assess if excessive maternal weight gain influences the GD diagnosis. Material and methods. Collaboration between the Technical University of Madrid and the Gynecology and Obstetrics Department of Puerta de Hierro University Hospital, Torrelodones University Hospital and Health Center of Torrelodones supported the study. It was approved by the Clinical Research Ethics Committee (CEIC). A clinical, randomized controlled trial recruited 272 pregnant women without obstetric contraindications and gave informed consent for inclusion in the study. Of these women, 257 were studied (age= 33,2±4,4 years), 101 in intervention group (IG, n= 101) and 156 in control group (CG, n= 156). A physical exercise program three times per week during pregnancy was developed. The duration of the sessions was 60 minutes and 50 minutes in land and water, respectively. Results. The IG showed lower maternal values in the Oral Glucose Tolerance Test (OGTT) at 180 minutes [IG: 98,00±29,48 mg/dl vs. CG: 116,25±29,90 mg/dl (t64= 2,37; p= 0,021)] and the IG reduced the prevalence of GD [IG: 1%, n= 1 vs. CG: 8,8 %, n= 13 (2 1= 6,84; p= 0,009)] with a significance risk estimate (OR= 9,604; 95 % CI: 1,23- 74,66). Excessive maternal weight gain was less in the IG [IG: 22,8 %, n= 23 vs. CG: Exercise and GD 34,9 %, n= 53 (2 1= 4,22; p= 0,040)] but there was no correlation with the prevalence of GD (ϕ= -0,007; p= 0,910). Conclusions. The exercise programme performed during pregnancy reduced the prevalence of GD, preserved glucose tolerance and reduced excessive maternal weight gain.

¿Puede el ejercicio físico moderado durante el embarazo actuar como un factor de prevención de la Diabetes Gestacional?

El presente trabajo pretendió conocer la eficacia de un programa de ejercicio físico moderado desarrollado durante todo el embarazo en el control de la excesiva ganancia de peso materno, la tolerancia materna a la glucosa y el desarrollo de la Diabetes Gestacional (DG). Se realizó un ensayo clínico, aleatorizado, no apareado, no enmascarado mediante una colaboración entre el Servicio de Ginecología y Obstetricia del Centro de Salud de Torrelodones y la Universidad Politécnica de Madrid. 55 gestantes sin contraindicaciones obstétricas fueron estudiadas, (edad=32,9±3,9 años), todas ellas caucásicas, 25 en el grupo de tratamiento y 30 en el de control. Se desarrolló un programa de ejercicio físico (seco/agua) durante todo el embarazo con una frecuencia de tres sesiones semanales. Nuestros resultados muestran que grupo de tratamiento presentó una menor ganancia de peso materno que en el de control (12,8±3,6 kg y 14,7±3,4 kg respectivamente, p=0,03), los valores en el Test de O'Sullivan (sobrecarga oral de glucosa) fueron inferiores en el grupo de tratamiento que en el de control 102,9±17,7 gr/dL vs 125,6±30,8 gr/dL respectivamente, p=0,002). No se diagnosticó ningún caso de DG en el grupo de tratamiento mientras que en el grupo de control se diagnosticaron 2 casos. El ejercicio físico desarrollado durante el embarazo reduce la ganancia de peso materno, los valores del Test de O'Sullivan y actúa aparentemente como un factor de prevención de la DG.

Diversity and Equitability Ordering Profiles Applied to the Study of Forest Structure

Diversity and Equitability Ordering Profiles Applied to the Study of Forest Structure

Efectos de un programa de ejercicio físico supervisado sobre la estructura cardíaca durante la gestación. Ensayo clínico aleatorizado

Objetivo: Analizar la seguridad del ejercicio aeróbico para el sistema cardiovascular de las mujeres gestantes y valorar las posibles mejoras cardiovasculares producidas. Sujetos y métodos: Se diseñó un ensayo clínico aleatorizado, no apareado, no enmascarado. El registro de datos se realizó en las semanas 20 y 34 de gestación. En la semana 20, se estudió a 45 gestantes del grupo de ejercicio (GE), de las cuales completaron el estudio 35. Del grupo de control (GC), en la semana 20 participaron 14, y completaron el estudio 9. Resultados: En la semana 20 hubo mejoras en el índice de masa corporal (GE: 25,1 4,3/GC: 27,9 4,5) (p = 0,04) y en la presión arterial sistólica (GE: 104,7 10,9/GC: 112,5 11,3) (p = 0,02). En el GC hubo presencia de hipertrofia concéntrica (n = 2, 14,3%). En la semana 34, el GE presentó un mayor volumen sistólico (GE: 52,33 10,42/GC: 43,69 9,48) (p = 0,03). Conclusión: El ejercicio aeróbico durante el embarazo es seguro para el sistema cardiovascular, mejorando incluso algunos parámetros.

Cáncer de mama y ejercicio físico: Estudio piloto

El cáncer de mama (CM) es el más común entre las mujeres occidentales, con un alto porcentaje de supervivencia, la cual no está exenta de numerosos efectos secundarios tanto por los tratamientos como por la enfermedad, afectando a la calidad de vida de estas mujeres. El objetivo de este proyecto es conocer el efecto de un programa de ejercicio físico conducido en la calidad de vida de mujeres afectadas por cáncer de mama. Método. El programa de ejercicio físico consistió en 24 sesiones (doce semanas) y se desarrolló íntegramente en la Facultad de Ciencias de la Actividad Física y del Deporte-INEF (UPM), donde se estudió a 31 mujeres afectadas. Resultados. Se muestra una mejora en la calidad de vida (p= 0,034), así como en diferentes aspectos de autoestima y depresión (p = 0,029 y p = 0,003 para el primero y p = 0,018 y p = 0,015 para el segundo). También se observó una mejora en el índice de fuerza general (p = 0,009) y en la capacidad funcional (p = 0,005). Conclusiones. Estos resultados permiten asociar un programa de ejercicio físico regular con posibles mejoras en la calidad de vida de las mujeres afectadas por cáncer de mama.

Fortalecimiento del suelo pélvico y gestación

Cerca de un tercio de las mujeres tienen incontinencia urinaria, y hasta la décima parte tiene incontinencia fecal después del parto. Cada vez con más frecuencia se recomienda el entrenamiento de la musculatura del suelo pélvico durante el embarazo y después del nacimiento para la prevención y el tratamiento de la incontinencia. En este artículo se repasa el estado de la cuestión sobre este tema, a partir de la bibliografía relacionada con el efecto del fortalecimiento del suelo pélvico sobre la continencia y el parto. A la vista de las revisiones sobre los ejercicios de foralecimiento del suelo pélvico en el transcurso el embarazo y su efecto sobre la incontinencia urinaria y fecal durante el mismo y en el posparto, se puede afirmar que el entrenamiento es efectivo. Sin embargo, este efecto beneficioso desaparece a largo plazo si se interrumpe el entrenamiento. No se han descrito efectos adversos de estos ejercicios, y además pueden facilitar el parto

Exercise during pregnancy reduces the rate of cesarean and instrumental deliveries: results of a randomized controlled trial

Objective: In this study, the authors assessed the effects of a structured, moderate-intensity exercise program during the entire length of pregnancy on a woman’s method of delivery. Methods: A randomized controlled trial was conducted with 290 healthy pregnant Caucasian (Spanish) women with a singleton gestation who were randomly assigned to either an exercise (n=138) or a control (n=152) group. Pregnancy outcomes, including the type of delivery, were measured at the end of the pregnancy. Results: The percentage of cesarean and instrumental deliveries in the exercise group were lower than in the control group (15.9%, n=22; 11.6%, n=16 vs. 23%, n=35; 19.1%, n=29, respectively; p=0.03). The overall health status of the newborn as well as other pregnancy outcomes were unaffected. Conclusions: Based on these results, a supervised program of moderate-intensity exercise performed throughout pregnancy was associated with a reduction in the rate of cesarean sections and can be recommended for healthy women in pregnancy.

Exercise during pregnancy improves maternal glucose screen at 24-28 weeks: a randomised controlled trial

Objective. The influence of an exercise programme performed by healthy pregnant women on maternal glucose tolerance was studied. Study design. A physical activity (PA, land/aquatic activities) programme during the entire pregnancy (three sessions per week) was conducted by a qualified instructor. 83 healthy pregnant women were randomly assigned to either an exercise group (EG, n=40) or a control (CG, n=43) group. 50 g maternal glucose screen (MGS), maternal weight gain and several pregnancy outcomes were recorded. Results. Significant differences were found between study groups on the 50 g MGS. Values corresponding to the EG (103.8±20.4 mg/dl) were better than those of the CG (126.9±29.5 mg/dl), p=0.000. In addition, no differences in maternal weight gain and no cases of gestational diabetes in EG versus 3 in CG (7%) (p>0.05) were found. Conclusion. A moderate PA programme performed during pregnancy improves levels of maternal glucose tolerance.

Identification of a biomarker panel for colorectal cancer diagnosis

Background:Malignancies arising in the large bowel cause the second largest number of deaths from cancer in the Western World. Despite progresses made during the last decades, colorectal cancer remains one of the most frequent and deadly neoplasias in the western countries. Methods: A genomic study of human colorectal cancer has been carried out on a total of 31 tumoral samples, corresponding to different stages of the disease, and 33 non-tumoral samples. The study was carried out by hybridisation of the tumour samples against a reference pool of non-tumoral samples using Agilent Human 1A 60-mer oligo microarrays. The results obtained were validated by qRT-PCR. In the subsequent bioinformatics analysis, gene networks by means of Bayesian classifiers, variable selection and bootstrap resampling were built. The consensus among all the induced models produced a hierarchy of dependences and, thus, of variables. Results: After an exhaustive process of pre-processing to ensure data quality--lost values imputation, probes quality, data smoothing and intraclass variability filtering--the final dataset comprised a total of 8, 104 probes. Next, a supervised classification approach and data analysis was carried out to obtain the most relevant genes. Two of them are directly involved in cancer progression and in particular in colorectal cancer. Finally, a supervised classifier was induced to classify new unseen samples. Conclusions: We have developed a tentative model for the diagnosis of colorectal cancer based on a biomarker panel. Our results indicate that the gene profile described herein can discriminate between non-cancerous and cancerous samples with 94.45% accuracy using different supervised classifiers (AUC values in the range of 0.997 and 0.955).

Aplicación de metodologías participativas en los planes de prevención de incendios

Se denuncia el exceso de estudios sobre el riesgo de incendios y la escasez de estudios motodológicos sobre la ejecución de un proyecto de incendios y la exigencia de tener en cuenta a las comunidades afectadas.

Tiempos y rendimientos del método de resinación mediante pica tradicional ascendente

Se analizan los tiempos y rendimientos de los trabajos de resinación con el sistema de pica tradicional ascendente