Assessment of inflammation in patients with rheumatoid arthritis using thermography and machine learning: a fast and automated technique

Objectives Sensitive detection of joint inflammation in rheumatoid arthritis (RA) is crucial to the success of the treat-to-target strategy. In this study, we characterise a novel machine learning-based computational method to automatically assess joint inflammation in RA using thermography of the hands, a fast and non-invasive imaging technique. Methods We recruited 595 patients with arthritis and osteoarthritis, as well as healthy subjects at two hospitals over 4 years. Machine learning was used to assess joint inflammation from the thermal images of the hands using ultrasound as the reference standard, obtaining a Thermographic Joint Inflammation Score (ThermoJIS). The machine learning model was trained and tuned using data from 449 participants with different types of arthritis, osteoarthritis or without rheumatic disease (development set). The performance of the method was evaluated based on 146 patients with RA (validation set) using Spearman's rank correlation coefficient, area under the receiver-operating curve (AUROC), average precision, sensitivity, specificity, positive and negative predictive value and F1-score. Results ThermoJIS correlated moderately with ultrasound scores (grey-scale synovial hypertrophy=0.49, p<0.001; and power Doppler=0.51, p<0.001). The AUROC for ThermoJIS for detecting active synovitis was 0.78 (95% CI, 0.71 to 0.86; p<0.001). In patients with RA in clinical remission, ThermoJIS values were significantly higher when active synovitis was detected by ultrasound. Conclusions ThermoJIS was able to detect joint inflammation in patients with RA, even in those in clinical remission. These results open an opportunity to develop new tools for routine detection of joint inflammation

DNA methylation patterns in newborns exposed to tobacco in utero

[Background] Maternal smoking during pregnancy is a major risk factor for adverse health outcomes. The main objective of the study was to assess the impact of in utero tobacco exposure on DNA methylation in children born at term with appropriate weight at birth.[Methods] Twenty mother-newborn dyads, after uncomplicated pregnancies, in the absence of perinatal illness were included. All mothers were healthy with no cardiovascular risk factors, except for the associated risks among those mothers who smoked. Umbilical cord blood and maternal peripheral venous blood were collected and an epigenome-wide association study was performed using a 450 K epigenome-wide scan (Illumina Infinium HumanMethylation 450BeadChip) with adjustment to normalize the DNA methylation for data cell variability in whole blood.[Results] The maternal plasmatic cotinine levels ranged from 10.70-115.40 ng/ml in the exposed group to 0-0.59 ng/ml in the non-exposed group. After adjusting for multiple comparisons in 427102 probes, statistically significant differences for 31 CpG sites, associated to 25 genes were observed. There was a greater than expected proportion of statistically-significant loci located in CpG islands (Fisher’s exact test, p = 0.029) and of those CpG islands, 90.3% exhibit higher methylation levels in the exposed group. The most striking and significant CpG site, cg05727225, is located in the chromosome 11p15.4, within the adrenomedullin gene.[Conclusions] In utero tobacco exposure, even in the absence of fetal growth restriction, may alter the epigenome, contributing to global DNA hypomethylation. Therefore, DNA status can be used as a biomarker of prenatal insults. Considering the possibility to reverse epigenetic modifications, a window of opportunity exists to change the programmed chronic disease.The study was partially funded by grant number PI11/00144, Instituto de Salud Carlos III, Spain and CIBER Fisiopatología Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain.Peer reviewe

Evaluación docente de las clases impartidas con la pizarra táctil en Expresión Gráfica en la Ingeniería

En la última década las asignaturas de Expresión Gráfica han sufrido un profundo cambio motivado por la imposición de los sistemas CAD. Estos cambios han ocasionado la sustitución de la pizarra convencional por los monitores de las estaciones de trabajo. Sin embargo, la pizarra sigue siendo un elemento imprescindible en el desarrollo de las clases. La pizarra táctil constituye una técnica novedosa de gran utilidad en la tarea docente de las asignaturas relacionadas con el área de Expresión Gráfica, permitiendo la proyección de imágenes, figuras y dibujos de forma simultanea al proceso explicativo, de manera cómoda y sencilla. En el presente estudio se describe el trabajo realizado por los profesores del Departamento de Expresión Gráfica y Cartografía de la Universidad de Alicante, utilizando la pizarra táctil en las clases de las asignaturas de Expresión Gráfica. Se ha la evaluación del trabajo efectuado teniendo en cuenta: la facilidad de aprendizaje, la flexibilidad, la capacidad de interacción que permite, los recursos de ayuda y forma en que el usuario puede utilizarlos, el contenido científico en cuanto a exactitud, actualidad y adecuación, intenciones formativas, conocimientos previos, comunicación, formas de dar el mensaje en su aspecto estético, integración y densidad, la organización de los contenidos, secuenciación y distribución de tiempos. De este estudio se pueden deducir las ventajas e inconvenientes del uso de la pizarra táctil en las clases de Expresión Gráfica en la Ingeniería.Ingegra

Effect of osteoprotegerin and Dickkopf-related protein 1 on radiological progression in tightly controlled rheumatoid arthritis.

OBJECTIVE: To analyze the association between circulating osteoprotegerin (OPG) and Dickkopf-related protein 1 (DKK-1) and radiological progression in patients with tightly controlled rheumatoid arthritis (RA). METHODS: Serum levels of OPG and DKK-1 were measured in 97 RA patients who were treated according to a treat-to-target strategy (T2T) aimed at remission (DAS28<2.6). Radiologic joint damage progression was assessed by changes in the total Sharp-van der Heijde score (SHS) on serial radiographs of the hands and feet. The independent association between these biomarker levels and the structural damage endpoint was examined using regression analysis. RESULTS: The mean age of the 97 RA patients (68 women) at the time of the study was 54 ± 14 years, and the median disease duration was 1.6 ± 1.5 years. Most patients were seropositive for either RF or ACPA, and the large majority (76%) were in remission or had low disease activity. After a median follow-up time of 3.3 ± 1.5 years (range, 1-7.5 yrs.), the mean total SHS annual progression was 0.88 ± 2.20 units. Fifty-two percent of the patients had no progression (defined as a total SHS of zero). The mean serum OPG level did not change significantly over the study period (from 3.9 ± 1.8 to 4.07 ± 2.23 pmol/L), whereas the mean serum DKK-1 level decreased, although not significantly (from 29.9 ± 10.9 to 23.6 ± 18.8 pmol/L). In the multivariate analysis, the predictive factors increasing the likelihood of total SHS progression were age (OR per year = 1.10; p = 0.003) and a high mean C-reactive protein level over the study period (OR = 1.29; p = 0.005). Circulating OPG showed a protective effect reducing the likelihood of joint space narrowing by 60% (95% CI: 0.38-0.94) and the total SHS progression by 48% (95% CI: 0.28-0.83). The DKK-1 levels were not associated with radiological progression. CONCLUSION: In patients with tightly controlled RA, serum OPG was inversely associated with progression of joint destruction. This biomarker may be useful in combination with other risk factors to improve prediction in patients in clinical remission or low disease activity state

Innovación docente en ingeniería

El objetivo del presente trabajo consiste en comparar la estructura de enseñanza-aprendizaje empleada en los cursos 2012-2013 y 2013-2014. Esta comparación se realizará tanto a nivel metodológico como mediante el estudio de los resultados obtenidos en la evaluación realizada a los alumnos. De esta manera se pretende determinar si los cambios realizados han supuesto una mejora significativa en el proceso de aprendizaje en función de los rendimientos obtenidos por los alumnos. El trabajo se va a llevar a cabo para la asignatura de Ingeniería Grafica que se imparte en la titulación de Grado en Ingeniería Química en segundo curso. Con los datos cuantitativos sobre la forma de evaluación y participación de los alumnos, junto con los resultados parciales y finales, se realizará un análisis estadístico para valorar la mejora del método y las conclusiones que se obtienen al respecto. Estos resultados nos permitirán emprender acciones futuras en cuanto a organización de las clases y metodología a emplear

The nutrigenetic influence of the interaction between dietary vitamin E and TXN and COMT gene polymorphisms on waist circumference: a case control study

Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Abdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS). The objective of this work was to investigate whether the interaction between antioxidant vitamin intake and OS-related polymorphisms modulates gene-associated anthropometry in a Spanish population. METHODS A total of 246 subjects with AO, and 492 age and gender matched non-AO subjects were included in the study. Anthropometric, biochemical, and OS parameters, and antioxidant dietary intake data were assessed using validated procedures. DNA from white blood cells was isolated and the genotype of seven polymorphisms from genes involved in OS (pro-oxidant and antioxidant) were analyzed using the SNPlex system. The effects of the c.-793T > C polymorphism on promoter activity and thus thioredoxin (TXN) activity were examined using reporter assays. RESULTS The AO group had higher 8-Oxo-2'-deoxyguanosine levels and took in less vitamin A and vitamin E compared to the non-AO group. Logistic regression analysis revealed that the rs2301241 polymorphism in TXN and rs740603 in catechol-O-methyltransferase (COMT) were associated with waist circumference (WC) and AO. Moreover, these polymorphisms were more strongly associated with variations in WC in subjects with low vitamin E intakes. A promoter assay revealed that the T to C conversion at c.-793 (rs2301241) induced a more than two fold increase in reporter gene expression. CONCLUSIONS WC is associated both with dietary vitamin E intake and genetic variants of TXN and COMT suggesting that existence of a complex nutrigenetic pathway that involves regulation of AO.This work was co-funded with European Funds for Regional Development (FEDER), the Spanish Science and Technology Ministry [SAF2005-02883]; the health research fund from the Carlos III Health Institute [PI070497], CIBER Fisiopatología Obesidad y Nutrición (CIBERobn) [CB06/03], and CIBER de Diabetes y Enfermedades Metabólicas Relacionadas (CIBERDEM). CIBEROB and CIBERDEM are initiatives by the Carlos III Health Institute in Madrid and the Spanish Health Ministry. Funding also came from GRUPOS 03/101, PROMETEO/2009/029 and 2005/027, AMP07/075, and ACOMP/2009/201 from the Valencian Government and European Network of Excellence InGenious HyperCare (EPSS-037093) from the European Commission.Ye

Curso sobre el desarrollo de las competencias de protección civil en la Generalitat Valenciana

En esta obra se recogen las aportaciones de diversos autores, que en algunos casos son profesionales dedicados a la actividad de Protección Civil o, en otros, son profesionales del mundo académico, con conocimientos especializados en este campo, y cuyas aportaciones, en conjunto, dan una visión panorámica respecto a la configuración actual del Sistema Nacional de Protección Civil, y resuelven la cuestión de cómo las competencias autonómicas se insertan en el mismo, con tratamiento particularizado del contenido normativo vigente en la Comunidad Autónoma Valenciana. Se hace referencia también, a cómo el Sistema Nacional de Protección Civil se encuadra en el Mecanismo Europeo de Protección Civil, que supone un nivel competencial más, pero organizado en base a los mismos principios de coordinación, cooperación y solidaridad de los territorios, y que al insertarse aquel como sistema integrado en el plano europeo, respeta completamente la distribución competencial, sin que esta participación en la dimensión competencias autonómicas.Esta edición se ha financiado mediante la concesión de la subvención de la Generalitat Valenciana, a través de la Conselleria de Governació i Justícia, aprobada por Resolución de 12 de marzo de 2015, con la cual se financiaron también las Jornadas sobre el desarrollo de las competencias de Protección Civil en la Generalitat Valenciana

Bortezomib decreases Rb phosphorylation and induces caspase-dependent apoptosis in Imatinib-sensitive and -resistant Bcr-Abl1-expressing cells

The use of c-abl-specific inhibitors such as Imatinib (IM) or Dasatinib has revolutionized the treatment of chronic myeloid leukemia (CML). However, a significant percentage of patients become resistant to IM. In this report, we have analyzed the possibility of using the proteasome as a molecular target in CML. Our results show that cells that express Bcr-Abl1 are more sensitive to the inhibition of the proteasome with Bortezomib (Btz) than control cells. This treatment reduces the proliferation of Bcr-Abl1- expressing cells, by inactivating NF-jB2 and decreasing the phosphorylation of Rb, eventually leading to an increase in caspase-dependent apoptosis. Furthermore, we show that Btz also induces cell-cycle arrest and apoptosis in cells expressing Bcr-Abl1 mutants that are resistant to IM. These results unravel a new molecular target of Btz, that is the Rb pathway, and open new possibilities in the treatment of CML especially for patients that become resistant to IM because of the presence of the T315I mutation

Adquisición de competencias como ingenieros, del título de Grado en Ingeniería Química

Estamos en pleno proceso de establecimiento de los títulos de grado, donde además de implantarse bajo condiciones seguramente no óptimas del todo, debido principalmente a las circunstancias económicas de la época, surge la necesidad de analizar si la formación que reciben nuestro alumnado es suficiente para integrarse laboralmente en el mundo industrial. En concreto analizaremos el caso de la titulación de graduado en Ingeniería Química. El objetivo se centra en analizar a nivel español si en el cómputo de los estudios que se realizan, nos acercamos más a su formación como ingenieros o a su formación como químicos. Para ello se presenta un análisis sobre diferentes Universidades españolas donde se imparte esta titulación, y la clasificación de sus asignaturas en dos grandes ramas, formación en la rama química y formación en la rama ingenieril, para poderla comparar y analizar la similitud o diferencias entre ellas. También se comparan estos estudios con la orden CIN/351/2009 donde se establecen los requisitos para la verificación de los títulos universitarios que habiliten para el ejercicio de la profesión de Ingeniero Técnico Industrial. Este estudio nos permitirá en caso de realizar futuras modificaciones poder realizar cambios que busquen la excelencia de nuestros titulados

Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans

El pdf del artículo es la versión pre-print.-- et al-There are no effective antifibrotic therapies for patients with liver diseases. We performed an experimental and translational study to investigate whether ghrelin, an orexigenic hormone with pleiotropic properties, modulates liver fibrogenesis. Recombinant ghrelin was administered to rats with chronic (bile duct ligation) and acute (carbon tetrachloride) liver injury. Hepatic gene expression was analyzed by way of microarray analysis and quantitative polymerase chain reaction. The hepatic response to chronic injury was also evaluated in wild-type and ghrelin-deficient mice. Primary human hepatic stellate cells were used to study the effects of ghrelin in vitro. Ghrelin hepatic gene expression and serum levels were assessed in patients with chronic liver diseases. Ghrelin gene polymorphisms were analyzed in patients with chronic hepatitis C. Recombinant ghrelin treatment reduced the fibrogenic response, decreased liver injury and myofibroblast accumulation, and attenuated the altered gene expression profile in bile duct-ligated rats. Moreover, ghrelin reduced the fibrogenic properties of hepatic stellate cells. Ghrelin also protected rats from acute liver injury and reduced the extent of oxidative stress and inflammation. Ghrelin-deficient mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis, and ghrelin gene hepatic expression correlated with expression of fibrogenic genes. In patients with chronic hepatitis C, polymorphisms of the ghrelin gene (994CT and 604GA) influenced the progression of liver fibrosis. Conclusion: Ghrelin exerts antifibrotic effects in the liver and may represent a novel antifibrotic therapy. Copyright © 2010 by the American Association for the Study of Liver Diseases.Supported by grants from the Ministerio de Ciencia e Investigación (SAF2005-06245), from the Instituto de Salud Carlos III (FIS2005-050567, FIS 2008-PI08/0237 and PI070497), and from the European Community FP6 (LSHB-CT-2007-036644 - DIALOK) and by fellowships from Institut d’Investigacions Biomèdiques August Pi i Sunyer (to M. M. and M. D.), the Fundación Bilbao Vizcaya Argentaria (to M. D.) and the Fundació Clínic (to P. S. B.).Peer Reviewe