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Peralta V.,Plaza de la Paz s n | Peralta V.,Institute Investigacion Sanitaria Of Navarra Idisna | Cuesta M.J.,Complejo Hospitalario de Navarra | Cuesta M.J.,Institute Investigacion Sanitaria Of Navarra Idisna
Schizophrenia Research | Year: 2016

This study aimed at examining the clinical correlates of dimensions of delusional experience in schizophrenia and delusional disorder. One-hundred and forty six subjects with schizophrenia and the same number of subjects with delusional disorder were assessed for dimensions of delusional experience including conviction, extension, bizarreness, disorganization and pressure, and for a number of clinical variables including familial liability to psychotic and mood disorders, illness characteristics, index episode symptoms, response to treatment and one-year psychosocial functioning. The associations between delusional dimensions and clinical variables were examined in each diagnostic group by means of linear regression analyses. Compared with subjects with delusional disorder, those with schizophrenia displayed higher levels of disorganization and bizarreness and lower levels of conviction, extension and pressure. Dimensions of delusional experience showed a rather different pattern of associations with clinical features both within and between diagnoses, with much more significant associations in schizophrenia than delusional disorder. Unlike schizophrenia in that dimensions of delusional experience showed a variety of associations with clinical features, most of the associations in delusional disorder were confined to the dimensions of extension and bizarreness. In schizophrenia, disorganization was the most central characteristic of delusions in that it showed associations with at least one validator within each clinical domain; furthermore all delusional dimensions but bizarreness impacted on some measure of psychosocial functioning. These findings point out the very complexity of delusions and their multidimensional character along with their distinct clinical correlates in schizophrenia and delusional disorder. © 2016. Source


Arriazu E.,University of Navarra | Pippa R.,University of Dundee | Odero M.D.,University of Navarra | Odero M.D.,Institute Investigacion Sanitaria Of Navarra Idisna
Frontiers in Oncology | Year: 2016

Acute myeloid leukemia (AML) is a heterogeneous malignant disorder of hematopoietic progenitor cells in which several genetic and epigenetic aberrations have been described. Despite progressive advances in our understanding of the molecular biology of this disease, the outcome for most patients is poor. It is, therefore, necessary to develop more effective treatment strategies. Genetic aberrations affecting kinases have been widely studied in AML; however, the role of phosphatases remains underexplored. Inactivation of the tumor-suppressor protein phosphatase 2A (PP2A) is frequent in AML patients, making it a promising target for therapy. There are several PP2A inactivating mechanisms reported in this disease. Deregulation or specific post-translational modifications of PP2A subunits have been identified as a cause of PP2A malfunction, which lead to deregulation of proliferation or apoptosis pathways, depending on the subunit affected. Likewise, overexpression of either SET or cancerous inhibitor of protein phosphatase 2A, endogenous inhibitors of PP2A, is a recurrent event in AML that impairs PP2A activity, contributing to leukemogenesis progression. Interestingly, the anticancer activity of several PP2A-activating drugs (PADs) depends on interaction/sequestration of SET. Preclinical studies show that pharmacological restoration of PP2A activity by PADs effectively antagonizes leukemogenesis, and that these drugs have synergistic cytotoxic effects with conventional chemotherapy and kinase inhibitors, opening new possibilities for personalized treatment in AML patients, especially in cases with SET-dependent inactivation of PP2A. Here, we review the role of PP2A as a druggable tumor suppressor in AML. © 2016 Arriazu, Pippa and Odero. Source


Heymans S.,Maastricht University | Gonzalez A.,University of Navarra | Gonzalez A.,Institute Investigacion Sanitaria Of Navarra Idisna | Pizard A.,University of Lorraine | And 7 more authors.
European Journal of Heart Failure | Year: 2015

Myocardial fibrosis is the result of excessive fibrillar collagen synthesis and deposition without reciprocally balanced degradation. It causes cardiac dysfunction, arrhythmias, and ischaemia, and thereby determines the clinical course and outcome of cardiac patients even when adequately treated. Therefore, further research is needed to identify and better understand the factors that trigger and maintain the myocardial fibrotic response against different injuries in a variety of cardiac diseases. Here, we will focus on the following major areas of research: molecules that stimulate the differentiation of fibroblasts into myofibroblasts and subsequently alter collagen turnover (e.g. cardiotrophin-1, galectin-3, NADPH oxidases, and neutrophil gelatinase-associated lipocalin), microRNA-induced alterations of collagen gene expression, and matricellular protein- and lysyl oxidase-mediated alterations of collagen cross-linking and deposition. © 2015 The Authors. European Journal of Heart Failure © 2015 European Society of Cardiology. Source


Lopez B.,University of Navarra | Lopez B.,Institute Investigacion Sanitaria Of Navarra Idisna | Gonzalez A.,University of Navarra | Gonzalez A.,Institute Investigacion Sanitaria Of Navarra Idisna | And 11 more authors.
Journal of the American College of Cardiology | Year: 2015

Myocardial fibrosis impairs cardiac function, in addition to facilitating arrhythmias and ischemia, and thus influences the evolution and outcome of cardiac diseases. Its assessment is therefore clinically relevant. Although tissue biopsy is the gold standard for the diagnosis of myocardial fibrosis, a number of circulating biomarkers have been proposed for the noninvasive assessment of this lesion. A review of the published clinical data available on these biomarkers shows that most of them lack proof that they actually reflect the myocardial accumulation of fibrous tissue. In this "call to action" article, we propose that this absence of proof may lead to misinterpretations when considering the incremental value provided by the biomarkers with respect to traditional diagnostic tools in the clinical handling of patients. We thus argue that strategies are needed to more strictly validate whether a given circulating biomarker actually reflects histologically proven myocardial fibrosis before it is applied clinically. © 2015 American College of Cardiology Foundation. Source


Zelaya M.V.,Institute Investigacion Sanitaria Of Navarra Idisna | Perez-Valderrama E.,Institute Investigacion Sanitaria Of Navarra Idisna | De Morentin X.M.,Institute Investigacion Sanitaria Of Navarra Idisna | Tunon T.,Institute Investigacion Sanitaria Of Navarra Idisna | And 4 more authors.
Oncotarget | Year: 2015

Olfactory dysfunction is present in up to 90% of Alzheimer's disease (AD) patients. Although deposition of hyperphosphorylated tau and β-amyloid substrates are present in olfactory areas, the molecular mechanisms associated with decreased smell function are not completely understood. We have applied mass spectrometry-based quantitative proteomics to probe additional molecular disturbances in postmortem olfactory bulbs (OB) dissected from AD cases respect to neurologically intact controls (n=20, mean age 82.1 years). Relative proteome abundance measurements have revealed protein interaction networks progressively disturbed across AD stages suggesting an early imbalance in splicing factors, subsequent interrupted cycling of neurotransmitters, alteration in toxic and protective mechanisms of β-amyloid, and finally, a mitochondrial dysfunction together with disturbance in neuron-neuron adhesion. We also present novel molecular findings in the OB in an autopsy cohort composed by Lewy body disease (LBD), frontotemporal lobar degeneration (FTLD), mixed dementia, and progressive supranuclear palsy (PSP) cases (n = 41, mean age 79.7 years). Olfactory mediators deregulated during the progression of AD such as Visinin-like protein 1, RUFY3 protein, and Copine 6 were also differentially modulated in the OB in LBD, FTLD, and mixed dementia. Only Dipeptidyl aminopeptidase-like protein 6 showed a specific down-regulation in AD. However, no differences were observed in the olfactory expression of this protein panel in PSP subjects. This study demonstrates an olfactory progressive proteome modulation in AD, unveiling cross-disease similarities and differences especially for specific proteins involved in dendritic and axonic distributions that occur in the OB during the neurodegenerative process. Source

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