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Roswall N.,Danish Cancer Society | Angquist L.,Bispebjerg and Frederiksberg Hospitals The Capital Region | Ahluwalia T.S.,Novo Nordisk AS | Ahluwalia T.S.,Copenhagen University | And 19 more authors.
American Journal of Clinical Nutrition | Year: 2014

Background: Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics.Objective: We investigated whether FTO rs9939609 and TCF7L2 rs7903146 modified the association between the MDS and Nordic diet score (NDS) and changes in weight (Δweight), waist circumference (ΔWC), and waist circumference adjusted for body mass index (BMI) (ΔWCBMI).Design: We conducted a case-cohort study with a median followup of 6.8 y that included 11,048 participants from 5 European countries; 5552 of these subjects were cases defined as individuals with the greatest degree of unexplained weight gain during followup. A randomly selected subcohort included 6548 participants, including 5496 noncases. Cases and noncases were compared in analyses by using logistic regression. Continuous traits (ie, Δweight, ΔWC, and ΔWCBMI) were analyzed by using linear regression models in the random subcohort. Interactions were tested by including interaction terms in models.Results: A higher MDS was significantly inversely associated with case status (OR: 0.98; 95% CI: 0.96, 1.00), ΔWC (β = -0.010 cm/ y; 95% CI: -0.020, -0.001 cm/y), and ΔWCBMI(β = -0.008; 95% CI:-0.015, -0.001) per 1-point increment but not Δweight (P = 0.53). The NDS was not significantly associated with any outcome. There was a borderline significant interaction between the MDS and TCF7L2 rs7903146 on weight gain (P = 0.05), which suggested a beneficial effect of the MDS only in subjects who carried 1 or 2 risk alleles. FTO did not modify observed associations.Conclusions: A high MDS is associated with a lower ΔWC and ΔWCBMI, regardless of FTO and TCF7L2 risk alleles. For Δweight, findings were less clear, but the effect may depend on the TCF7L2 rs7903146 variant. The NDS was not associated with anthropometric changes during follow-up. © 2014 American Society for Nutrition.


Euba B.,Research Center Biomedica En Red Of Enfermedades Respiratorias Ciberes | Euba B.,Public University of Navarra | Moleres J.,Public University of Navarra | Segura V.,University of Navarra | And 10 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2015

Therapies that are safe, effective, and not vulnerable to developing resistance are highly desirable to counteract bacterial infections. Host-directed therapeutics is an antimicrobial approach alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by using host-directed drugs. In this study, we identified and evaluated the efficacy of a panel of host-directed drugs against respiratory infection by nontypeable Haemophilus influenzae (NTHi). NTHi is an opportunistic pathogen that is an important cause of exacerbation of chronic obstructive pulmonary disease (COPD). We screened for host genes differentially expressed upon infection by the clinical isolate NTHi375 by analyzing cell whole-genome expression profiling and identified a repertoire of host target candidates that were pharmacologically modulated. Based on the proposed relationship between NTHi intracellular location and persistence, we hypothesized that drugs perturbing host pathways used by NTHi to enter epithelial cells could have antimicrobial potential against NTHi infection. Interfering drugs were tested for their effects on bacterial and cellular viability, on NTHi-epithelial cell interplay, and on mouse pulmonary infection. Glucocorticoids and statins lacked in vitro and/or in vivo efficacy. Conversely, the sirtuin-1 activator resveratrol showed a bactericidal effect against NTHi, and the PDE4 inhibitor rolipram showed therapeutic efficacy by lowering NTHi375 counts intracellularly and in the lungs of infected mice. PDE4 inhibition is currently prescribed in COPD, and resveratrol is an attractive geroprotector for COPD treatment. Together, these results expand our knowledge of NTHi-triggered host subversion and frame the antimicrobial potential of rolipram and resveratrol against NTHi respiratory infection. Copyright © 2015, American Society for Microbiology. All Rights Reserved.


Campanero-Rhodes M.A.,CSIC - Institute of Physical Chemistry "Rocasolano" | Campanero-Rhodes M.A.,Research Center Biomedica En Red Of Enfermedades Respiratorias Ciberes | Llobet E.,Research Center Biomedica En Red Of Enfermedades Respiratorias Ciberes | Llobet E.,Institute Investigacion Sanitaria Of Palma | And 4 more authors.
RSC Advances | Year: 2015

We describe a protocol for the generation and validation of bacteria microarrays and their application to the study of specific features of the pathogen's surface and interactions with host receptors. Bacteria were directly printed on nitrocellulose-coated glass slides, using either manual or robotic arrayers, and printing quality, immobilization efficiency and stability of the arrays were rigorously controlled by incorporating a fluorescent dye into the bacteria. A panel of wild type and mutant strains of the human pathogen Klebsiella pneumoniae, responsible for nosocomial and community-acquired infections, was selected as model bacteria, and SYTO-13 was used as dye. Fluorescence signals of the printed bacteria were found to exhibit a linear concentration-dependence in the range of 1 × 108 to 1 × 109 bacteria per ml. Similar results were obtained with Pseudomonas aeruginosa and Acinetobacter baumannii, two other human pathogens. Successful validation of the quality and applicability of the established microarrays was accomplished by testing the capacity of the bacteria array to detect recognition by anti-Klebsiella antibodies and by the complement subcomponent C1q, which binds K. pneumoniae in an antibody-independent manner. The biotin/AlexaFluor-647-streptavidin system was used for monitoring binding, yielding strain- and dose-dependent signals, distinctive for each protein. Furthermore, the potential of the bacteria microarray for investigating specific features, e.g. glycosylation patterns, of the cell surface was confirmed by examining the binding behaviour of a panel of plant lectins with diverse carbohydrate-binding specificities. This and other possible applications of the newly developed arrays, as e.g. screening/evaluation of compounds to identify inhibitors of host-pathogen interactions, make bacteria microarrays a useful and sensitive tool for both basic and applied research in microbiology, biomedicine and biotechnology. © 2015 The Royal Society of Chemistry.


Miravitlles M.,CIBER ISCIII | Barrecheguren M.,CIBER ISCIII | Romain-Rodriguez M.,Institute Investigacion Sanitaria Of Palma
International Journal of Tuberculosis and Lung Disease | Year: 2015

SETTING: Clinical phenotypes of chronic obstructive pulmonary disease (COPD) identify patients with common characteristics. OBJ E CTIVE S : To investigate the distribution of four different COPD phenotypes: non-exacerbators, patients with asthma-COPD overlap syndrome (ACOS), exacerbators with chronic bronchitis and those without, we analysed the impact of COPD on quality of life (HRQoL), and on anxiety and depression in these phenotypes. DESIGN: Observational, multicentre study conducted among 3125 COPD patients recruited from out-patient clinics in Barcelona, Spain. Phenotyping was performed based on the clinical information available. The COPD Assessment Test and EuroQoL-5 Dimensions questionnaire were used to evaluate HRQoL; patient mood was evaluated using the Hospital Anxiety and Depression Scale (HADS). R ES U LT S : The distribution of phenotypes was as follows: 60.6% non-exacerbators, 15.9% ACOS patients, 19.3% exacerbators with chronic bronchitis and 4.3% exacerbators without chronic bronchitis. Nonexacerbators had milder COPD, whereas exacerbators presented with the most severe disease, with little difference between those with and those without chronic bronchitis. ACOS patients were more frequently female with better lung function, but more impaired HRQoL and greater anxiety and depression, than non-exacerbators. CONCLUS IONS : Almost two thirds of COPD patients are non-exacerbators, and 15.9% have ACOS. Different phenotypes showed different demographic and clinical characteristics as well as impact on HRQoL and mood. © 2015 The Union.


Elsley J.V.,Bournemouth University | Parmentier F.B.R.,University of the Balearic Islands | Parmentier F.B.R.,Institute Investigacion Sanitaria Of Palma | Parmentier F.B.R.,University of Western Australia
Quarterly Journal of Experimental Psychology | Year: 2015

Verbal–spatial bindings are integral to routine cognitive operations (e.g., reading), yet the processes supporting them in working memory are little understood. Campo and colleagues [Campo, P., Poch, C., Parmentier, F. B. R., Moratti, S., Elsley, J. V., Castellanos, N., … Maestú, F. (2010). Oscillatory activity in prefrontal and posterior regions during implicit letter-location binding. Neuroimage, 49, 2807–2815] recently reported data suggesting obligatory letter–location binding when participants were directed to remember the letters in a display (of letters in locations), but no evidence for binding when instructed to remember the filled locations. The present study contrasted two explanations for this binding asymmetry. First, it may result from an obligatory dependence on “where” during the representation of “what” information, while “where” information may be held independently of its contents (the strong asymmetry hypothesis). Second, it may constitute a snapshot of a dynamic feature inhibition process that had partially completed by test: the asymmetrical inhibition hypothesis. Using Campo and colleagues’ task with a variable retention interval between display and test, we presented four consonants in distinct locations and contrasted performance between “remember letters” and “remember locations” instructions. Our data supported the strong asymmetry hypothesis through demonstrating binding in the verbal task, but not in the spatial task. Critically, when present, verbal–spatial bindings were remarkably stable, enduring for at least 15 seconds. © 2014, © 2014 The Author(s). Published by Taylor & Francis.


Parmentier F.B.R.,University of the Balearic Islands | Parmentier F.B.R.,University of Western Australia | Parmentier F.B.R.,Institute Investigacion Sanitaria Of Palma | Beaman C.P.,University of Reading
Canadian Journal of Experimental Psychology | Year: 2015

Across 5 experiments, the temporal regularity and content of an irrelevant speech stream were varied and their effects on a serial recall task examined. Variations of the content, but not the rhythm, of the irrelevant speech stimuli reliably disrupted serial recall performance in all experiments. Bayesian analyses supported the null hypothesis over the hypothesis that irregular rhythms would disrupt memory to a greater extent than regular rhythms. Pooling the data in a combined analysis revealed that regular presentation of the irrelevant speech was significantly more disruptive to serial recall than irregular presentation. These results are consistent with the idea that auditory distraction is sensitive to both intraitem and interitem relations and challenge an orienting-based account of auditory distraction. © 2014 Canadian Psychological Association.


Satue M.,University of the Balearic Islands | Satue M.,Institute Investigacion Sanitaria Of Palma | Ramis J.M.,University of the Balearic Islands | Ramis J.M.,Institute Investigacion Sanitaria Of Palma | And 2 more authors.
Journal of Biomaterials Applications | Year: 2016

Vitamin D metabolites are essential for bone regeneration and mineral homeostasis. The Vitamin D precursor 7-dehydrocholesterol can be used after UV irradiation to locally produce active Vitamin D by osteoblastic cells. Furthermore, UV-irradiated 7-dehydrocholesterol is a biocompatible coating for titanium implants with positive effects on osteoblast differentiation. In this study, we examined the impact of titanium implants surfaces coated with UV-irradiated 7-dehydrocholesterol on the osteogenic differentiation of human umbilical cord mesenchymal stem cells. First, the synthesis of cholecalciferol (D3) was achieved through the incubation of the UV-activated 7-dehydrocholesterol coating for 48 h at 23°C. Further, we investigated in vitro the biocompatibility of this coating in human umbilical cord mesenchymal stem cells and its potential to enhance their differentiation towards the osteogenic lineage. Human umbilical cord mesenchymal stem cells cultured onto UV-irradiated 7-dehydrocholesterol-coated titanium implants surfaces, combined with osteogenic supplements, upregulated the gene expression of several osteogenic markers and showed higher alkaline phosphatase activity and calcein blue staining, suggesting increased mineralization. Thus, our results show that the use of UV irradiation on 7-dehydrocholesterol -treated titanium implants surfaces generates a bioactive coating that promotes the osteogenic differentiation of human umbilical cord mesenchymal stem cells, with regenerative potential for improving osseointegration in titanium-based bone anchored implants. © SAGE Publications.


Vicens C.,Institute Investigacion Sanitaria Of Palma | Sempere E.,Conselleria Of Sanitat Universal lut Publica | Bejarano F.,Institute Catala Of La Salut | Socias I.,Manacor Health Care Center | And 9 more authors.
British Journal of General Practice | Year: 2016

Background Primary care interventions that promote cessation of benzodiazepine (BZD) use in longterm users are effective at 1 year, but their efficacy at 3 years is uncertain. Aim To assess the 3-year efficacy of two primary care interventions delivered by GPS on cessation of BZD use in long-term users. Design and setting Multicentre, three-arm, cluster randomised, controlled trial, with random allocation at the GP level. Method Seventy-five GPS and 532 patients were randomly allocated to three groups: usual care (control), structured intervention with steppeddose reduction and follow-up visits (SIF), or structured intervention with written steppeddose reduction (SIW). The primary outcome was BZD use at 36 months. Results At 36 months, 66/168 patients (39.2%) in the SIW group, 79/191 patients (41.3%) in the SIF group, and 45/173 patients (26.0%) in the control group had discontinued BZD use. The relative risks (RR) adjusted by cluster were 1.51 (95% CI = 1.10 to 2.05; P = 0.009) in the SIW group and 1.59 (95% CI = 1.15 to 2.19; P = 0.005) in the SIF group. A total of 131/188 patients (69.7%) who successfully discontinued BZD use at 12 months remained abstinent at 36 months. The groups showed no significant differences in anxiety, depression, or sleep dissatisfaction at 36 months. Conclusion The interventions were effective on cessation of BZD use; most patients who discontinued at 12 months remained abstinent at 3 years. Discontinuation of BZD use did not have a significant effect on anxiety, depression, or sleep quality.


PubMed | Institute Investigacion Sanitaria Of Palma, Son Serra La Vileta Health Care Center, Catalonia Health Services Institute Catala Of La Salut, Valencian Health Service Conselleria Of Sanitat Universal lut Publica and Manacor Health Care Center
Type: Journal Article | Journal: The British journal of general practice : the journal of the Royal College of General Practitioners | Year: 2016

Primary care interventions that promote cessation of benzodiazepine (BZD) use in long-term users are effective at 1 year, but their efficacy at 3 years is uncertain.To assess the 3-year efficacy of two primary care interventions delivered by GPs on cessation of BZD use in long-term users.Multicentre, three-arm, cluster randomised, controlled trial, with random allocation at the GP level.Seventy-five GPs and 532 patients were randomly allocated to three groups: usual care (control), structured intervention with stepped-dose reduction and follow-up visits (SIF), or structured intervention with written stepped-dose reduction (SIW). The primary outcome was BZD use at 36 months.At 36 months, 66/168 patients (39.2%) in the SIW group, 79/191 patients (41.3%) in the SIF group, and 45/173 patients (26.0%) in the control group had discontinued BZD use. The relative risks (RR) adjusted by cluster were 1.51 (95% CI = 1.10 to 2.05; P = 0.009) in the SIW group and 1.59 (95% CI = 1.15 to 2.19; P = 0.005) in the SIF group. A total of 131/188 patients (69.7%) who successfully discontinued BZD use at 12 months remained abstinent at 36 months. The groups showed no significant differences in anxiety, depression, or sleep dissatisfaction at 36 months.The interventions were effective on cessation of BZD use; most patients who discontinued at 12 months remained abstinent at 3 years. Discontinuation of BZD use did not have a significant effect on anxiety, depression, or sleep quality.


PubMed | Institute Investigacion Sanitaria Of Palma, Institute Investigacion Sanitaria, University of Zaragoza and University of the Balearic Islands
Type: | Journal: Journal of affective disorders | Year: 2016

Obesity, metabolic syndrome (MetS) and low adherence to Mediterranean diet are frequent in major depression patients and have been separately related with prognosis. The aim of this study is to analyse their predictive power on major depression outcome, at 6 and 12 months.273 Major depressive patients completed the Beck Depression Inventory for depressive symptoms and the 14-item Mediterranean diet adherence score. MetS was diagnosed according to the International Diabetes Federation (IDF).At the baseline Mediterranean diet adherence was inversely associated with depressive symptoms (p=0.007). Depression response was more likely in those patients with normal weight (p=0.006) and not MetS (p=0.013) but it was not associated with Mediterranean diet adherence (p=0.625). Those patients with MetS and obesity were less likely to improve symptoms of depression than patients with obesity but not MetS.Obesity and MetS, but not low adherence to the Mediterranean diet at baseline, predicted a poor outcome of depression at 12 months. Our study suggests that MetS is the key factor that impacts negatively in depression prognosis, rather than obesity or diet. If this finding is confirmed, clinicians should be aware about MetS diagnosis and treatment in overweight depressed patients, especially if outcome is not being satisfactory enough.

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