Santiago de Compostela, Spain
Santiago de Compostela, Spain

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Davalos A.,Hospital Universitari Germans Trias i Pujol | Alvarez-Sabin J.,Hospital Universitari Of La Vall Dhebron | Castillo J.,Hospital Clinico Universitario Of Santiago | Diez-Tejedor E.,Hospital Universitario La Paz | And 8 more authors.
The Lancet | Year: 2012

Background Citicoline is approved in some countries for the treatment of acute ischaemic stroke. The drug has shown some evidence of efficacy in a pooled analysis. We sought to confirm the efficacy of citicoline in a larger trial. Methods We undertook a randomised, placebo-controlled, sequential trial in patients with moderate-to-severe acute ischaemic stroke admitted at university hospitals in Germany, Portugal, and Spain. Using a centralised minimisation process, patients were randomly assigned in a 1:1 ratio to receive citicoline or placebo within 24 h after the onset of symptoms (1000 mg every 12 h intravenously during the first 3 days and orally thereafter for a total of 6 weeks [2×500 mg oral tablets given every 12 h]). All study participants were masked. The primary outcome was recovery at 90 days measured by a global test combining three measures of success: National Institutes of Health Stroke Scale ≤1, modified Rankin score ≤1, and Barthel Index ≥95. Safety endpoints included symptomatic intracranial haemorrhage in patients treated with recombinant tissue plasminogen activator, neurological deterioration, and mortality. This trial is registered, NCT00331890. Results 2298 patients were enrolled into the study from Nov 26, 2006, to Oct 27, 2011. 37 centres in Spain, 11 in Portugal, and 11 in Germany recruited patients. Of the 2298 patients who gave informed consent and underwent randomisation, 1148 were assigned to citicoline and 1150 to placebo. The trial was stopped for futility at the third interim analysis on the basis of complete data from 2078 patients. The final randomised analysis was based on data for 2298 patients: 1148 in citicoline group and 1150 in placebo group. Global recovery was similar in both groups (odds ratio 1.03, 95% CI 0.86-1.25; p=0.364). No significant differences were reported in the safety variables nor in the rate of adverse events. Interpretation Under the circumstances of the ICTUS trial, citicoline is not efficacious in the treatment of moderateto-severe acute ischaemic stroke.

Guglielmi O.,Sleep Unit | Jurado-Gamez B.,University of Cordoba, Spain | Gude F.,Hospital Clinico Universitario Of Santiago | Buela-Casal G.,Sleep Unit
Sleep and Breathing | Year: 2015

Purpose: The aim of this systematic literature review was to assess the impact of obstructive sleep apnea syndrome (OSAS) on patients’ occupational health. Methods: We selected 19 studies that dealt with issues related to job performance and productivity, absenteeism, and psychosocial health of patients with OSAS and assessed the risk of bias in their conclusions. Results: Although methodologically rigorous studies are needed to confirm these findings, the results obtained suggest the existence of multiple relationships between OSAS and work limitations of patients (i.e., difficulties maintaining attention, learning new tasks, or performing monotonous tasks). The studies reviewed reached more scientifically consistent conclusions about such patients’ risk of taking more days of sick leave or having work disability, particularly if they reported excessive daytime sleepiness. Very few studies have explored the relationship between OSAS and psychosocial occupational health of patients. Thus, there is a need for research to clarify these aspects of occupational medicine. Conclusions: OSAS has numerous effects on patients’ occupational health, yet, in general, results should be confirmed by studies with sufficiently large samples in which OSAS is diagnosed with reliable methods and occupational variables are assessed with standardized and validated questionnaires. © 2014, Springer-Verlag Berlin Heidelberg.

Martinon-Torres F.,Hospital Clinico Universitario Of Santiago | Martinon-Torres F.,University of Santiago de Compostela
Journal of Critical Care | Year: 2012

Most existing literature on noninvasive ventilation (NIV) in combination with helium-oxygen (HELIOX) mixtures focuses on its use in adults, basically for treatment of acute exacerbations of chronic obstructive pulmonary disease. This article reviews and summarizes the theoretical basis, existing clinical evidence, and practical aspects of the use of NIV with HELIOX in children. There is only a small body of literature on HELIOX in pediatric NIV but with positive results. The reported experience focuses on treatment for patients with severe acute bronchiolitis who cannot be treated with standard therapies. The inert nature of helium adds no biological risk to NIV performance. Noninvasive ventilation with HELIOX is a promising therapeutic option for children with various respiratory pathologies who do not respond to conventional treatment. Further controlled studies should be warranted. © 2012 Elsevier Inc.

Rodriguez D.,Hospital Clinico Universitario Of Santiago | Gutierrez-de-Teran H.,Hospital Clinico Universitario Of Santiago
Proteins: Structure, Function and Bioinformatics | Year: 2012

The recent crystallographic structures of the human chemokine CXC Receptor 4 (CXCR4) provide experimental evidence of a human G Protein-Coupled Receptor (GPCR) dimer in atomic detail. The CXCR4 homodimers reveal an unexpected dimerization mode involving transmembrane helices TM5 and TM6, which is examined here using all-atom molecular dynamics (MD) simulations in the physiological environment of a lipid bilayer. The bacteriophage T4 lysozyme (T4L), which was fused to the crystallized protein but absent in our simulations, is found to slightly affect the observed relative position of the protomers in the two dimers studied here, and consequently some rearrangements of the dimerization interface are proposed. In addition, the simulations provide further evidence about the role of the two stabilizing single point mutations introduced to crystallize the receptor. Finally, this work analyzes the structural and dynamic role of key residues involved both in ligand binding and in the infection process of HIV. In particular, the different side chain conformations of His1133.39 are found to influence the dynamics of the surrounding functional hotspot region being evaluated both in the presence and in the absence of the co-crystallized ligand IT1t. The analysis reported here adds valuable knowledge for future structure-based drug design (SBDD) efforts on this pharmacological target. © 2012 Wiley Periodicals, Inc.

Gutierrez-De-Teran H.,Hospital Clinico Universitario Of Santiago | Gutierrez-De-Teran H.,Uppsala University | Bello X.,Hospital Clinico Universitario Of Santiago | Rodriguez D.,Hospital Clinico Universitario Of Santiago | Rodriguez D.,University of Stockholm
Biochemical Society Transactions | Year: 2013

The recent advances in membrane protein crystallography have provided extremely valuable structural information of the superfamily of GPCRs (G-protein-coupled receptors). This has been particularly true for a few receptors whose structure was solved several times under different biochemical conditions. It follows that the mechanisms of receptor conformational equilibrium and related dynamic events can be explored by computational simulations. In the present article, we summarize our recent understanding of several dynamic features of GPCRs, accomplished through the use of MD (molecular dynamics) simulations. Our pipeline for the MD simulations of GPCRs, implemented in the web service, is updated in the present paper and illustrated by recent applications. Special emphasis is put on the A2A adenosine receptor, one of the selected cases where crystal structures in several conformations and conditions exist, and on the dimerization process of the CXCR4 (CXC chemokine receptor 4). © 2013 Biochemical Society.

Barreiro-De Acosta M.,Hospital Clinico Universitario Of Santiago
Medicine (Spain) | Year: 2016

Introduction Ulcerative colitis is a chronic inflammatory bowel disease unknown origin whose main symptoms of chronic diarrhea and the presence of rectal bleeding. Clinical course In its course alternating periods of remission and activity (flares), although a minority can have a fulminant course and, in others, present a chronic continuous activity. It can affect the rectum, the left colon or substantially all of the colon (large). Complications Local complications include toxic megacolon, bleeding, perforation and cancer. Diagnosis In its diagnosis mainly we employ colonoscopy biopsias. La intensity of flares can be variable, and it depends on the treatment. Treatment Oral and rectal aminosalicylates are the mainstay of treatment in mild forms. Corticosteroids are used only in acute phases. Immunosuppressive and biologic therapies are used in the most severe forms. Sometimes surgery at the failure of medical treatment will be necessary.

Viso E.,Complexo Hospitalario Of Pontevedra | Rodriguez-Ares M.T.,University of Santiago de Compostela | Gude F.,Hospital Clinico Universitario Of Santiago
Ophthalmic Epidemiology | Year: 2010

Purpose: To estimate the prevalence of Pseudoexfoliation syndrome (PXF) and to investigate its relationship with systemic and ocular diseases and lifestyle factors in a general adult population in north-western Spain. Methods: An age-stratified random sample of 1155 subjects was drawn from the population aged 40 years and over of O Salnés (Spain). From 937 eligible subjects, 619 (66.1%) participated (mean age (Standard Deviation [SD]): 63.4 (14.5) years, range: 40-96, 37.0% males). An interview to collect past history of ocular and systemic diseases and lifestyle details, and a comprehensive ophthalmic evaluation were performed. Study subjects with typical pseudoexfoliative material on the anterior capsule or in the pupil margin were labelled as having PXF. A design based analysis was performed and all calculations were weighted to give unbiased estimates. Results: The prevalence of PXF was 6.5% (95% confidence interval [CI]:4.9-8.1). PXF rates increased significantly with age (P = 0.000). No cases of PXF were detected in subjects between 40 and 60 years. Prevalence of PXF was 8.0% (95% C I5.4-11.6) in men and 5.4% (95% CI 3.8-7.6) in women (P = ns). The prevalence of glaucoma in subjects with PXF was 19.6% (95% CI 8.2-40.0). After controlling for age and sex, glaucoma, cataract surgery, rose bengal staining and diabetes were associated with PXF but only glaucoma and rose bengal staining associations remained significant in a multivariate model. Conclusions: PXF is common among older individuals in north-western Spain. Subjects with pseudoexfoliation have a significantly higher prevalence of glaucoma than subjects without. An abnormal ocular surface detected by rose bengal staining is highly prevalent among subjects with pseudoexfoliation. © 2010 Informa UK Ltd.

Morey M.,Hospital Clinico Universitario Of Santiago | Fernandez-Marmiesse A.,Hospital Clinico Universitario Of Santiago | Castineiras D.,Hospital Clinico Universitario Of Santiago | Fraga J.M.,University of Santiago de Compostela | And 2 more authors.
Molecular Genetics and Metabolism | Year: 2013

Current advances in DNA sequencing technologies are dropping down sequencing cost while increasing throughput at a pace never shown before. Past-decade great milestones, as the establishment of a reference human genome (amongst others) and large-scale human genetic variation study in the 1000 Genome project are, in conjunction with the use of these techniques, triggering advances in many areas of basic and applied science. These tools, stored in and combined with the vast amount of information present in biological online databases are, with the use of automated interpretation and analysis tools, allowing the fulfillment of increasingly ambitious studies in many areas and also are democratizing the access to information, interpretation and technologies, being the first opportunity for researchers to assess the influence of genetics in complex events as multifactorial diseases, evolutionary studies, metagenomics, transcriptomics, etc. In this review, we present the current state of the art of these technologies, focusing on second generation sequencing, from sample and library preparation to sequencing chemistries and bioinformatic software available for final data analysis and visualisation, with its possible applications. We also make an overview of first and third generation, due to its historical importance and for being the upcoming future tools for genetic analysis, respectively. © 2013 Elsevier Inc.

Viso E.,Complexo Hospitalario Of Pontevedra | Gude F.,Hospital Clinico Universitario Of Santiago | Rodriguez-Ares M.T.,Hospital Clinico Universitario Of Santiago | Rodriguez-Ares M.T.,University of Santiago de Compostela
Cornea | Year: 2011

PURPOSE: To investigate the relationship of meibomian gland dysfunction (MGD) and other prevalent ocular diseases with dry eye (DE) in a general adult population. METHODS: An age-stratified random sample of 1155 subjects aged ≤ 40 years was selected in O Salnés, Spain. From 937 eligible subjects, 654 (69.8%) participated (mean age (SD): 63.6 (14.4) years; range: 40-96; and 37.2% males). A standardized DE questionnaire was administered. Objective evaluation included the Schirmer test, tear film breakup time (TBUT), fluorescein staining, and rose bengal staining. DE was defined as the simultaneous presence of symptoms and at least one sign. The relationship of MGD and other ocular diseases with DE was investigated. A design-based analysis was performed, and all calculations were weighted to give unbiased estimates. RESULTS: DE and MGD prevalence were 11.0% [95% confidence interval (CI), 8.6-13.3] and 30.5% (95% CI, 26.9-34.1), respectively. MGD was present in 45.8% (95% CI, 34.8-57.2) of subjects with DE and was associated, after controlling for age and sex, with DE [adjusted odds ratios (ORa), 1.81]; with symptoms (ORa, 2.26); and with TBUT (ORa, 1.97), fluorescein staining (ORa, 2.09) and rose bengal staining (ORa, 3.25). The remaining ocular diseases were not associated with symptoms. However, pterygium was significantly associated with fluorescein staining (ORa, 1.89); cataract surgery with TBUT (ORa, 2.79); trauma and pseudoexfoliation with rose bengal staining (ORa, 2.75 and ORa, 4.04); and glaucoma with TBUT (ORa, 3.26), fluorescein staining (ORa, 3.40), and rose bengal staining (ORa, 3.46). CONCLUSIONS: DE and MGD are common diseases in this population. MGD is strongly associated with symptoms and signs of DE. Nearly half of the subjects with DE have MGD. Pterygium, trauma, cataract surgery, pseudoexfoliation, and glaucoma are associated with signs of DE. Copyright © 2010 by Lippincott Williams & Wilkins.

Pardo-Seco J.,University of Santiago de Compostela | Martinon-Torres F.,University of Santiago de Compostela | Martinon-Torres F.,Hospital Clinico Universitario Of Santiago | Salas A.,University of Santiago de Compostela
BMC Genomics | Year: 2014

Background: There is a growing interest among geneticists in developing panels of Ancestry Informative Markers (AIMs) aimed at measuring the biogeographical ancestry of individual genomes. The efficiency of these panels is commonly tested empirically by contrasting self-reported ancestry with the ancestry estimated from these panels.Results: Using SNP data from HapMap we carried out a simulation-based study aimed at measuring the effect of SNP coverage on the estimation of genome ancestry. For three of the main continental groups (Africans, East Asians, Europeans) ancestry was first estimated using the whole HapMap SNP database as a proxy for global genome ancestry; these estimates were subsequently compared to those obtained from pre-designed AIM panels. Panels that consider >400 AIMs capture genome ancestry reasonably well, while those containing a few dozen AIMs show a large variability in ancestry estimates. Curiously, 500-1,000 SNPs selected at random from the genome provide an unbiased estimate of genome ancestry and perform as well as any AIM panel of similar size. In simulated scenarios of population admixture, panels containing few AIMs also show important deficiencies to measure genome ancestry.Conclusions: The results indicate that the ability to estimate genome ancestry is strongly dependent on the number of AIMs used, and not primarily on their individual informativeness. Caution should be taken when making individual (medical, forensic, or anthropological) inferences based on AIMs. © 2014 Pardo-Seco et al.; licensee BioMed Central Ltd.

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