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Diaz-Castroverde S.,Complutense University of Madrid | Diaz-Castroverde S.,Health Institute Carlos III ISCIII | Baos S.,Complutense University of Madrid | Luque M.,Complutense University of Madrid | And 9 more authors.
Diabetologia | Year: 2016

Aims/hypothesis: In the postprandial state, the liver regulates glucose homeostasis by glucose uptake and conversion to glycogen and lipids. Glucose and insulin signalling finely regulate glycogen synthesis through several mechanisms. Glucose uptake in hepatocytes is favoured by the insulin receptor isoform A (IRA), rather than isoform B (IRB). Thus, we hypothesised that, in hepatocytes, IRA would increase glycogen synthesis by promoting glucose uptake and glycogen storage. Methods: We addressed the role of insulin receptor isoforms on glycogen metabolism in vitro in immortalised neonatal hepatocytes. In vivo, IRA or IRB were specifically expressed in the liver using adeno-associated virus vectors in inducible liver insulin receptor knockout (iLIRKO) mice, a model of type 2 diabetes. The role of IR isoforms in glycogen synthesis and storage in iLIRKO was subsequently investigated. Results: In immortalised hepatocytes, IRA, but not IRB expression induced an increase in insulin signalling that was associated with elevated glycogen synthesis, glycogen synthase activity and glycogen storage. Similarly, elevated IRA, but not IRB expression in the livers of iLIRKO mice induced an increase in glycogen content. Conclusions/interpretation: We provide new insight into the role of IRA in the regulation of glycogen metabolism in cultured hepatocytes and in the livers of a mouse model of type 2 diabetes. Our data strongly suggest that IRA is more efficient than IRB at promoting glycogen synthesis and storage. Therefore, we suggest that IRA expression in the liver could provide an interesting therapeutic approach for the regulation of hepatic glucose content and glycogen storage. © 2016 Springer-Verlag Berlin Heidelberg


Gomez-Barroso D.,CIBER ISCIII | Gomez-Barroso D.,Health Institute Carlos III ISCIII | Herrador Z.,National Center for Tropical Medicine | San Martin J.V.,Fuenlabrada University Hospital | And 6 more authors.
Eurosurveillance | Year: 2015

Since July 2009, there has been a community outbreak of leishmaniasis in south-west Madrid, Spain. The present study used the spatial distribution of cases to investigate the connection between the outbreak and a recently built peri-urban park. We included 157 cases of cutaneous (CL) and 90 cases of visceral (VL) leishmaniasis diagnosed at Fuenlabrada University Hospital between July 2009 and April 2013. CL and VL cases were geo-referenced and incidence rates by census tract were calculated. To identify high-risk areas, the spatial autocorrelation between individual cases was estimated. In a next step, areas where risk of disease was significantly increased were identified by cluster analysis. Higher incidence rates and the areas with highest intensity of CL and VL were located in the north-western part of the municipality. The most likely cluster of CL comprised three census tracks with relative risk (RR) = 11.5 (95% confidence interval (CI): 9.2–13.6). Two additional significant VL clusters were detected, the most likely one with RR = 9.2 (95% CI: 7.3–11.1). In addition, we found one significant VL cluster in the immigrant population (RR = 12.8; 95% CI: 9.3–16.1). The spatial pattern of leishmaniasis transmission revealed a relation between the outbreak and the suspected risk area. © 2015, European Centre for Disease Prevention and Control (ECDC). All rights reserved.


Munoz P.,Aragon Institute of Engineering Research | Trigo J.D.,Aragon Institute of Engineering Research | Martinez I.,Aragon Institute of Engineering Research | Munoz A.,Health Institute Carlos III ISCIII | And 2 more authors.
Journal of Healthcare Engineering | Year: 2011

The standardization of Electronic Health Records (EHR) is a crucial factor for ensuring interoperable sharing of health data. During recent decades, a plethora of initiatives - driven by international organizations - has emerged to define the required models describing the exchange of information between EHRs. These models cover different essential characteristics for building interoperable EHRs, such as architecture, methodology, communication, safety or terminology, among others. In this context, the European reference frame for the standardized exchange of EHR is the recently approved ISO/EN 13606 standard. This multi-part standard provides the syntactic and semantic capabilities (through a dual model approach) as well as terminology, security and interface considerations for the standardized exchange of EHR. This paper provides (a) an introduction to the different standardization efforts related to the interoperable exchange of EHR around the world, and (b) a description of how the ISO/EN 13606 standard provides interoperable sharing of clinical information.


Martinez I.,Aragon Institute of Engineering Research | Del Valle P.,Aragon Institute of Engineering Research | Munoz P.,Aragon Institute of Engineering Research | Trigo J.D.,Aragon Institute of Engineering Research | And 5 more authors.
2010 Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBC'10 | Year: 2010

The new paradigm of e-Health demands open sensors and middleware components that permit transparent integration and end-to-end interoperability of new personal health devices. The use of standards seems to be the internationally adopted way to solve these problems. This paper presents the implementation of an end-to-end standardsbased e-Health solution. This includes ISO/IEEE11073 standard for the interoperability of the medical devices in the patient environment and EN13606 standard for the interoperable exchange of the Electronic Healthcare Record. The design strictly fulfills all the technical features of the most recent versions of both standards. The implemented prototype has been tested in a laboratory environment to demonstrate its feasibility for its further transfer to the healthcare system. © 2010 IEEE.


Sanchez-de-Madariaga R.,Health Institute Carlos III ISCIII | Munoz A.,Health Institute Carlos III ISCIII | Caceres J.,Health Institute Carlos III ISCIII | Somolinos R.,University Hospital Puerta Of Hierro Majadahonda | And 4 more authors.
Journal of the American Medical Informatics Association | Year: 2013

Objective The objective of this paper is to introduce a new language called ccML, designed to provide convenient pragmatic information to applications using the ISO/EN13606 reference model (RM), such as electronic health record (EHR) extracts editors. EHR extracts are presently built using the syntactic and semantic information provided in the RM and constrained by archetypes. The ccML extra information enables the automation of the medico-legal context information edition, which is over 70% of the total in an extract, without modifying the RM information. Materials and Methods ccML is defined using a W3C XML schema file. Valid ccML files complement the RM with additional pragmatics information. The ccML language grammar is defined using formal language theory as a single-type tree grammar. The new language is tested using an EHR extracts editor application as proof-of-concept system.


Herrador Z.,Institute of Tropical Medicine | Siles-Lucas M.,CSIC - Institute of Natural Resources and Agriculture Biology of Salamanca | Aparicio P.,Institute of Tropical Medicine | Lopez-Velez R.,Ramon y Cajal Hospital | And 3 more authors.
PLoS Neglected Tropical Diseases | Year: 2016

Background: Cystic echinococcosis (CE) is a parasitic disease caused by the tapeworm Echinococcus granulosus. Although present throughout Europe, deficiencies in the official reporting of CE result in under-reporting and misreporting of this disease, which in turn is reflected in the wrong opinion that CE is not an important health problem. By using an alternative data source, this study aimed at describing the clinical and temporal-spatial characteristics of CE hospitalizations in Spain between 1997 and 2012. Methodology/Principal Findings: We performed a retrospective descriptive study using the Hospitalization Minimum Data Set (CMBD in Spanish). All CMBD’s hospital discharges with echinococcosis diagnosis placed in first diagnostic position were reviewed. Hospitalization rates were computed and clinical characteristics were described. Spatial and temporal distribution of hospital discharges was also assessed. Between 1997 and 2012, 14,010 hospitalizations with diagnosis of CE were recorded, 55% were men and 67% were aged over 45 years. Pediatric hospitalizations occurred during the whole study period. The 95.2% were discharged at home, and only 1.7% were exitus. The average cost was 8,439.11 €. The hospitalization rate per 100,000 per year showed a decreasing trend during the study period. All the autonomous communities registered discharges, even those considered as non-endemic. Maximum rates were reached by Extremadura, Castilla-Leon and Aragon. Comparison of the CMBD data and the official Compulsory Notifiable Diseases (CND) reports from 2005 to 2012 showed that official data were lower than registered hospitalization discharges. Conclusions: Hospitalizations distribution was uneven by year and autonomous region. Although CE hospitalization rates have decreased considerably due to the success of control programs, it remains a public health problem due to its severity and economic impact. Therefore, it would be desirable to improve its oversight and surveillance, since officially reported data are underestimating the real burden of CE in Spain. © 2016 Herrador et al.


Esteban S.,Rey Juan Carlos University | Llamas P.M.,Rey Juan Carlos University | Garcia-Cortes H.,Rey Juan Carlos University | Catala M.,Rey Juan Carlos University | Catala M.,Health Institute Carlos III ISCIII
Environmental Pollution | Year: 2016

In recent years, there is a growing concern among the scientific community about the presence of the so-called emergent pollutants in waters of different countries, especially endocrine-disrupting compounds (EDCs) that have the ability to alter the hormonal system. One of the substances found almost ubiquitously and in higher concentrations is the alkylphenol nonylphenol. Albeit this compound is included in priority lists as a probable risk for human health and the environment, little is known about its effects on developing plants. The aim of this work is to assess the acute and sub-chronic toxicity of environmental concentrations of nonylphenol in riparian vascular plant development using spores of the fern Polystichum setiferum and a biomarker-based approach: mitochondrial activity (cell viability), chlorophyll (plant physiology) and DNA content (growth). Mitochondrial activity and DNA content show that nonylphenol induces acute and sub-chronic toxicity at 48 h and after 1 week, respectively. Significant effects are observed in both parameters in fern spores at ng L−1 but chlorophyll autofluorescence shows little changes. The inhibition of germination by natural allelochemicals has been reported to be related with the active hydroxyl group of phenolic compounds and largely independent of the structural nucleus to which it is attached. Results presented in this study suggest that environmental concentrations of nonylphenol could interfere with higher plant germination development by mimicking natural allelochemicals and/or phytohormones acting as a “phytoendocrine disruptor” likely posing ecophysiological risks. © 2016 Elsevier Ltd


Jimenez-Sousa M.A.,Health Institute Carlos III ISCIII | Fernandez-Rodriguez A.,Health Institute Carlos III ISCIII | Guzman-Fulgencio M.,Health Institute Carlos III ISCIII | Garcia-Alvarez M.,Health Institute Carlos III ISCIII | Resino S.,Health Institute Carlos III ISCIII
BMC Medicine | Year: 2013

Background: Since 2009, several studies have identified single-nucleotide polymorphisms (SNPs) near the gene encoding for interleukin (IL)-28 (IL28B) that are strongly associated with spontaneous and treatment-induced hepatitis C virus (HCV) clearance. Because this large amount of data includes some inconsistencies, we consider assessment of the global estimate for each SNP to be essential.Methods: Relevant studies assessing IL28B polymorphisms associated with sustained virologic response (SVR) and spontaneous clearance (SC) were identified from a literature search of PubMed up to 9 July, 2012. Studies were eligible studies if they included patients infected with HCV or HCV/HIV, or assessed any SNP located within or near the IL28B gene, SVR data available under standard treatment, and/or SC data in patients with acute HCV infection. Pooled odds ratios were estimated by fixed or random effects models when appropriate. Variables such as HCV genotype, ethnicity, and type of co-infection were studied.Results: Of 282 screened studies, 67 were selected for SVR and 10 for SC. In total, 20,163 patients were studied for SVR and 3,554 for SC. For SVR, we found that all SNPs showed strong associations in patients with HCV genotypes 1 and 4, whereas the pooled ORs were almost three times lower for genotypes 2 and 3 (rs12979860 and rs8099917). Regarding ethnicity, the SNP most associated with SVR was rs12979860 in white patients, whereas in East Asians it seemed to be rs8099917. The most studied SNP (rs12979860) showed similar results for patients co-infected with HCV/HIV, as for those infected with HCV only. Finally, rs12979860 and rs8099917 both appeared to be associated with SC.Conclusions: IL28B polymorphisms influence both the outcome of interferon treatment and the natural clearance of HCV. However we did not identify a universal predictor SNP, as the best genetic markers differed depending on patient ethnicity, genotype, and type of infection. Nevertheless, our results may be useful for more precise treatment decision-making. © 2013 Jiménez-Sousa et al; licensee BioMed Central Ltd.


Sanchez-De-Madariaga R.,Health Institute Carlos III ISCIII | Munoz A.,Health Institute Carlos III ISCIII | Somolinos R.,Health Institute Carlos III ISCIII | Castro A.,Health Institute Carlos III ISCIII | And 5 more authors.
Studies in Health Technology and Informatics | Year: 2015

A new mark-up programming language is introduced in order to facilitate and improve the visualization of ISO/EN 13606 dual model-based normalized medical information. This is the first time that visualization of normalized medical information is addressed and the programming language is intended to be used by medical non-IT professionals. © 2015 European Federation for Medical Informatics (EFMI).


PubMed | Health Institute Carlos III ISCIII
Type: Journal Article | Journal: Journal of the American Medical Informatics Association : JAMIA | Year: 2013

The objective of this paper is to introduce a new language called ccML, designed to provide convenient pragmatic information to applications using the ISO/EN13606 reference model (RM), such as electronic health record (EHR) extracts editors. EHR extracts are presently built using the syntactic and semantic information provided in the RM and constrained by archetypes. The ccML extra information enables the automation of the medico-legal context information edition, which is over 70% of the total in an extract, without modifying the RM information.ccML is defined using a W3C XML schema file. Valid ccML files complement the RM with additional pragmatics information. The ccML language grammar is defined using formal language theory as a single-type tree grammar. The new language is tested using an EHR extracts editor application as proof-of-concept system.Seven ccML PVCodes (predefined value codes) are introduced in this grammar to cope with different realistic EHR edition situations. These seven PVCodes have different interpretation strategies, from direct look up in the ccML file itself, to more complex searches in archetypes or system precomputation.The possibility to declare generic types in ccML gives rise to ambiguity during interpretation. The criterion used to overcome ambiguity is that specificity should prevail over generality. The opposite would make the individual specific element declarations useless.A new mark-up language ccML is introduced that opens up the possibility of providing applications using the ISO/EN13606 RM with the necessary pragmatics information to be practical and realistic.

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