COSMIC (Cohort Studies of Memory in an International Consortium): An international consortium to identify risk and protective factors and biomarkers of cognitive ageing and dementia in diverse ethnic and sociocultural groups
Sachdev P.S.,University of New South Wales |
Lipnicki D.M.,University of New South Wales |
Kochan N.A.,University of New South Wales |
Crawford J.D.,University of New South Wales |
And 48 more authors.
BMC Neurology | Year: 2013
Background: A large number of longitudinal studies of population-based ageing cohorts are in progress internationally, but the insights from these studies into the risk and protective factors for cognitive ageing and conditions like mild cognitive impairment and dementia have been inconsistent. Some of the problems confounding this research can be reduced by harmonising and pooling data across studies. COSMIC (Cohort Studies of Memory in an International Consortium) aims to harmonise data from international cohort studies of cognitive ageing, in order to better understand the determinants of cognitive ageing and neurocognitive disorders.Methods/Design: Longitudinal studies of cognitive ageing and dementia with at least 500 individuals aged 60 years or over are eligible and invited to be members of COSMIC. There are currently 17 member studies, from regions that include Asia, Australia, Europe, and North America. A Research Steering Committee has been established, two meetings of study leaders held, and a website developed. The initial attempts at harmonising key variables like neuropsychological test scores are in progress.Discussion: The challenges of international consortia like COSMIC include efficient communication among members, extended use of resources, and data harmonisation. Successful harmonisation will facilitate projects investigating rates of cognitive decline, risk and protective factors for mild cognitive impairment, and biomarkers of mild cognitive impairment and dementia. Extended implications of COSMIC could include standardised ways of collecting and reporting data, and a rich cognitive ageing database being made available to other researchers. COSMIC could potentially transform our understanding of the epidemiology of cognitive ageing, and have a world-wide impact on promoting successful ageing. © 2013 Sachdev et al.; licensee BioMed Central Ltd.
Ascaso F.J.,Hospital Clinico Universitario Lozano Blesa |
Ascaso F.J.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
Ascaso F.J.,University of Zaragoza |
Rodriguez-Jimenez R.,Institute Investigacion Hospital 12 Of Octubre I12 Madrid |
And 25 more authors.
Psychiatry Research | Year: 2015
Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. We aimed to study retinal OCT measures of patients with schizophrenia with respect to healthy controls, and to evaluate possible differences between recent illness episode (RIE) and non-recent illness episode (NRIE) patients. Thirty schizophrenia patients were classified as RIE (. n=10) or NRIE (. n=20), and compared with 30 matched controls. Statistical analyses included linear mixed-effects models to study the association between OCT measures and group membership. Multivariate models were used to control for potential confounders. In the adjusted linear mixed-effects regression model, patients had a significantly thinner retinal nerve fiber layer (RNFL) in overall measurements, and in the nasal, superior and inferior quadrants. Macular inner ring thickness and macular volume were also significantly smaller in patients than controls. Compared with controls, in the adjusted model only NRIE (but not RIE) patients had significantly reduced RNFL overall measures, superior RNFL, nasal RNFL, macular volume, and macular inner ring thickness. No significant correlation was found between illness duration and retinal measurements after controlling for age. In conclusion, retinal parameters observed using OCT in schizophrenia patients could be related to clinical status and merit attention as potential state biomarkers of the disorder. © 2015 Elsevier Ireland Ltd.
Zavala-Mendoza D.,University of Zaragoza |
Zavala-Mendoza D.,Cuauhtémoc University |
Grasa L.,University of Zaragoza |
Grasa L.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
And 5 more authors.
Molecules | Year: 2016
The Chrysactinia mexicana A. Gray (C. mexicana) plant is used in folk medicine to treat fever and rheumatism; it is used as a diuretic, antispasmodic; and it is used for its aphrodisiac properties. This study investigates the effects of the essential oil of C. mexicana (EOCM) on the contractility of rabbit ileum and the mechanisms of action involved. Muscle contractility studies in vitro in an organ bath to evaluate the response to EOCM were performed in the rabbit ileum. EOCM (1-100 μg·mL-1) reduced the amplitude and area under the curve of spontaneous contractions of the ileum. The contractions induced by carbachol 1 μM, potassium chloride (KCl) 60 mM or Bay K8644 1 μM were reduced by EOCM (30 μg·mL-1). Apamin 1 μM and charybdotoxin 0.01 μM decreased the inhibition induced by EOCM. The d-cAMP 1 μM decreased the inhibition induced by EOCM. L-NNA 10 μM, Rp-8-Br-PET-cGMPS 1 μM, D,L-propargylglycine 2 mM, or aminooxyacetic acid hemihydrochloride 2 mM did not modify the EOCM effect. In conclusion, EOCM induces an antispasmodic effect and could be used in the treatment of intestinal spasms or diarrhea processes. This effect would be mediated by Ca2+, Ca2+-activated K+ channels and cAMP. © 2016 by the authors; licensee MDPI.
Forcen R.,University of Zaragoza |
Latorre E.,University of Zaragoza |
Pardo J.,University of Zaragoza |
Pardo J.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
And 8 more authors.
Experimental Physiology | Year: 2016
What is the central question of this study? The action of Toll-like receptors (TLRs) 2 and 4 on the motor response to serotonin in mouse colon has not previously been reported. What is the main finding and its importance? Toll-like receptors 2 and 4 modulate the serotonin-induced contractile response in mouse colon by modifying the expression of serotonin (5-HT) receptors. Alterations in 5-HT2A and 5-HT2C receptors explain the increase of the response to serotonin in TLR2−/− mice. Alterations in 5-HT2C and 5-HT4 receptors explain the suppression of the response to serotonin in TLR4−/− mice. The microbiota, through Toll-like receptors (TLRs), may regulate gastrointestinal motility by activating neuroendocrine mechanisms. We evaluated the influence of TLR2 and TLR4 in spontaneous contractions and in the serotonin (5-HT)-induced motor response in mouse colon, and assessed the 5-HT receptors involved. Muscle contractility studies to evaluate the intestinal spontaneous motility and the response to 5-HT were performed in the colon from wild-type (WT), TLR2−/−, TLR4−/− and TLR2/4 double knockout (DKO) mice. The 5-HT receptor mRNA expression was determined by real-time PCR. The amplitude and frequency of the spontaneous contractions of the colon were smaller in TLR4−/− and TLR2/4 DKO mice with respect to WT mice. In WT, TLR2−/− and TLR2/4 DKO mice, 100 μm 5-HT evoked a contractile response. The contractile response induced by 5-HT was significantly higher in TLR2−/− than in WT mice. In TLR4−/− mice, 5-HT did not evoke any contractile response. The mRNA expression of 5-HT2A was increased in TLR2−/− and TLR2/4 DKO mice. The 5-HT2C and 5-HT4 mRNA expressions were increased in TLR4−/− and TLR2/4 DKO mice. The 5-HT2C mRNA expression was diminished in TLR2−/− mice. The 5-HT3 mRNA expression was increased in TLR2−/−, TLR4−/− and TLR2/4 DKO mice. The 5-HT7 mRNA expression was diminished in TLR2/4 DKO mice. In WT, TLR2−/− and TLR2/4 DKO mice, 5-HT2, 5-HT3, 5-HT4 and 5-HT7 receptor antagonists reduced or blocked the contractile response evoked by 5-HT. We postulate that TLR2 and TLR4 modulate the serotonin contractile motor response in mouse colon in an opposing manner by modifying the expression of several serotonin receptors. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society
Lanas A.,University of Zaragoza |
Lanas A.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
Lanas A.,CIBER ISCIII |
Polo-Tomas M.,CIBER ISCIII |
And 3 more authors.
American Journal of Gastroenterology | Year: 2012
OBJECTIVES: Patients with gastrointestinal (GI) risk factors who take non-steroidal anti-inflammatory drugs (NSAIDs) should also take gastroprotective agents (GPAs). No studies have evaluated adherence and reasons for non-adherence to GPA and NSAID therapies. METHODS: This was a prospective, multicenter, observational, longitudinal study. Patients attending rheumatology/orthopedic clinics who were co-prescribed NSAID plus GPA for at least 15 days and had risk factors for GI complications were followed up by telephone call. Optimal adherence was defined as taking the drug for ≥80% of prescribed days. Multivariate logistic regression analysis was used to determine factors associated with non-adherence. RESULTS: Of 1,232 patients interviewed, 192 were excluded because of inaccurate data. Of the remaining 1,040 patients, 74% were prescribed low-dose NSAIDs and 99.8% were prescribed a standard or high-dose GPA. In all, 70% of NSAIDs and 63.1% of GPA prescriptions were short term (<30 days). The majority of patients who were prescribed either an NSAID (92.5%) or GPA (85.9%) started therapy. Optimal adherence to GPA or NSAIDs was reported by 79.7% (95% confidence interval (CI): 76.9-82.2%) and 84.1% (95% CI: 81.7-86.3%) of patients, respectively. More adverse events occurred among patients who reported non-optimal adherence than among patients with optimal adherence to GPA (22.1 vs. 1.9%, P<0.0001). As reasons for non-adherence, patients most frequently cited infrequent/low-intensity rheumatic pain (NSAIDs) or forgetfulness (GPAs). Adverse events and short-term treatment were independent factors associated with poor adherence for both NSAIDs and GPAs. History of uncomplicated peptic ulcer and frequent dosing were additional factors associated with non-adherence to NSAIDs. CONCLUSIONS: Most frequent reasons for non-adherence are infrequent/low-intensity rheumatic pain (NSAIDs) or forgetfulness (GPAs). Short-term treatment and adverse events were associated with poor adherence for both therapies. © 2012 by the American College of Gastroenterology.
Alvarez-Jarreta J.,University of Zaragoza |
Ruiz-Pesini E.,University of Zaragoza |
Ruiz-Pesini E.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
Ruiz-Pesini E.,CIBER ISCIII
BMC Bioinformatics | Year: 2016
Background: Molecular evolution studies involve many different hard computational problems solved, in most cases, with heuristic algorithms that provide a nearly optimal solution. Hence, diverse software tools exist for the different stages involved in a molecular evolution workflow. Results: We present MEvoLib, the first molecular evolution library for Python, providing a framework to work with different tools and methods involved in the common tasks of molecular evolution workflows. In contrast with already existing bioinformatics libraries, MEvoLib is focused on the stages involved in molecular evolution studies, enclosing the set of tools with a common purpose in a single high-level interface with fast access to their frequent parameterizations. The gene clustering from partial or complete sequences has been improved with a new method that integrates accessible external information (e.g. GenBank's features data). Moreover, MEvoLib adjusts the fetching process from NCBI databases to optimize the download bandwidth usage. In addition, it has been implemented using parallelization techniques to cope with even large-case scenarios. Conclusions: MEvoLib is the first library for Python designed to facilitate molecular evolution researches both for expert and novel users. Its unique interface for each common task comprises several tools with their most used parameterizations. It has also included a method to take advantage of biological knowledge to improve the gene partition of sequence datasets. Additionally, its implementation incorporates parallelization techniques to enhance computational costs when handling very large input datasets. © 2016 The Author(s).
Santabarbara J.,University of Zaragoza |
Gracia-Garcia P.,University of Zaragoza |
Pirez G.,University of Zaragoza |
Pirez G.,Center Assistencial Sant Joan Of Deu Dalmacelles |
And 14 more authors.
American Journal of Geriatric Psychiatry | Year: 2016
Objective To explore the possibility that the mortality risk of mild cognitive impairment (MCI) as diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria (DSM-5–MCI) will be higher than using Petersen's criteria (P-MCI) and to report the population-attributable fraction (PAF) of mortality due to MCI. Methods A representative community sample of 4,803 individuals aged 55 or more years was interviewed and then followed for 17 years. Standardized instruments were used in the assessment, including the Geriatric Mental State-AGECAT, and research psychiatrists diagnosed P-MCI and DSM-5–MCI cases following operationalized criteria. Mortality information was obtained from the official population registry. Kaplan-Meier age-adjusted survival curves were built for the MCI diagnostic groups, and Cox proportional hazards regression models were used to calculate the hazard ratio of death in participants with MCI relative to those without. We also estimated the PAF of mortality due to specific MCI diagnostic groups. Results Compared with noncases, the mortality rate ratio was approximately double in DSM-5–MCI individuals (2.3) than in P-MCI individuals (1.2). In the multivariate statistical analysis, a significant association between each diagnostic category and mortality was observed but was only maintained in the final model in DSM-5–MCI cases (hazard ratio: 1.24). The PAF of mortality due to MCI was approximately 1% in both MCI categories. Conclusion The mortality risk in comparison with noncases was higher in DSM-5–MCI than in P-MCI. The PAF of mortality in DSM-5–MCI individuals was ~ 1% over a 17-year period. © 2016
Sant'Anna R.,Autonomous University of Barcelona |
Gallego P.,Autonomous University of Barcelona |
Robinson L.Z.,Scripps Research Institute |
Pereira-Henriques A.,Abel Salazar Biomedical Sciences Institute |
And 13 more authors.
Nature Communications | Year: 2016
Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson's disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. These data indicate that tolcapone, already in clinical trials for familial amyloid polyneuropathy, is a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for which no small-molecule therapy exists. © 2016, Nature Publishing Group. All rights reserved.
Sanchez-Marteles M.,Hospital Clinico Universitario Lozano Blesa |
Sanchez-Marteles M.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
Rubio Gracia J.,Hospital Clinico Universitario Lozano Blesa |
Rubio Gracia J.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
And 2 more authors.
Revista Clinica Espanola | Year: 2016
Our understanding of the pathophysiological mechanisms of heart failure (HF) has changed considerably in recent years, progressing from a merely haemodynamic viewpoint to a concept of systemic and multifactorial involvement in which numerous mechanisms interact and concatenate. The effects of these mechanisms go beyond the heart itself, to other organs of vital importance such as the kidneys, liver and lungs. Despite this, the pathophysiology of acute HF still has aspects that elude our deeper understanding. Haemodynamic overload, venous congestion, neurohormonal systems, natriuretic peptides, inflammation, oxidative stress and its repercussion on cardiac and vascular remodelling are currently considered the main players in acute HF. Starting with the concept of acute HF, this review provides updates on the various mechanisms involved in this disease. © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI).
Prognostic value of measuring the diameter and inspiratory collapse of the inferior vena cava in acute heart failure [Valor pronóstico de la medición del diámetro y colapso inspiratorio de la vena cava inferior en la insuficiencia cardiaca aguda]
Josa-Laorden C.,Hospital Clinico Universitario Lozano Blesa |
Josa-Laorden C.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
Gimenez-Lopez I.,Instituto Aragones Of Ciencias Of La Salud Iacs |
Gimenez-Lopez I.,Institute Investigacion Sanitaria Of Aragon Iis Aragon |
And 8 more authors.
Revista Clinica Espanola | Year: 2016
Objectives To assess the utility of measuring the diameter and collapse of the inferior vena cava (IVC) in acute heart failure (AHF), its relationship with the prognosis and serum biomarkers of congestion. Patients and methods An observational prospective study was conducted that included 85 patients with AHF, classifying them into 4 groups according to IVC diameter (≤ or > 20 mm) and inspiratory collapse (< or ≥ 50%) at admission. The endpoints were mortality due to HF and the combined event of mortality and readmission for HF at 180 days. Results Some 24.7% of the patients had an undilated IVC and ≥ 50% collapse (group 1); 20% had an undilated IVC and < 50% collapse (group 2), 5.9% had a dilated IVC and ≥ 50% collapse (group 3); and 49.4% had a dilated IVC and < 50% collapse (group 4). The lack of inspiratory collapse but not IVC dilation was related to higher concentrations of urea (P =.007), creatinine (P =.004), uric acid (P =.008), NT-proBNP (P =.009) and CA125 (P =.005). Survival free of the combined event at 180 days was lower in those patients with no IVC collapse. Conclusions Dilation and the absence of the inspiratory collapse of the IVC are common in the context of AHF. The lack of inspiratory collapse of the IVC during the decompensation phase identifies a subgroup of patients with poorer prognosis at 6 months. © 2015 Elsevier España, S.L.U. y Sociedad Española de Medicina Interna (SEMI).