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Find video protocols related to scientific articles indexed in Pubmed.
Cognitive impairment and resting-state network connectivity in Parkinson's disease.
Hum Brain Mapp
PUBLISHED: 08-28-2014
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The purpose of this work was to evaluate changes in the connectivity patterns of a set of cognitively relevant, dynamically interrelated brain networks in association with cognitive deficits in Parkinson's disease (PD) using resting-state functional MRI. Sixty-five nondemented PD patients and 36 matched healthy controls were included. Thirty-four percent of PD patients were classified as having mild cognitive impairment (MCI) based on performance in attention/executive, visuospatial/visuoperceptual (VS/VP) and memory functions. A data-driven approach using independent component analysis (ICA) was used to identify the default-mode network (DMN), the dorsal attention network (DAN) and the bilateral frontoparietal networks (FPN), which were compared between groups using a dual-regression approach controlling for gray matter atrophy. Additional seed-based analyses using a priori defined regions of interest were used to characterize local changes in intranetwork and internetwork connectivity. Structural group comparisons through voxel-based morphometry and cortical thickness were additionally performed to assess associated gray matter atrophy. ICA results revealed reduced connectivity between the DAN and right frontoinsular regions in MCI patients, associated with worse performance in attention/executive functions. The DMN displayed increased connectivity with medial and lateral occipito-parietal regions in MCI patients, associated with worse VS/VP performance, and with occipital reductions in cortical thickness. In line with data-driven results, seed-based analyses mainly revealed reduced within-DAN, within-DMN and DAN-FPN connectivity, as well as loss of normal DAN-DMN anticorrelation in MCI patients. Our findings demonstrate differential connectivity changes affecting the networks evaluated, which we hypothesize to be related to the pathophysiological bases of different types of cognitive impairment in PD. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.
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An exome study of Parkinson's disease in Sardinia, a Mediterranean genetic isolate.
Neurogenetics
PUBLISHED: 07-21-2014
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Parkinson's disease (PD) is a common neurodegenerative disorder of complex aetiology. Rare, highly penetrant PD-causing mutations and common risk factors of small effect size have been identified in several genes/loci. However, these mutations and risk factors only explain a fraction of the disease burden, suggesting that additional, substantial genetic determinants remain to be found. Genetically isolated populations offer advantages for dissecting the genetic architecture of complex disorders, such as PD. We performed exome sequencing in 100 unrelated PD patients from Sardinia, a genetic isolate. SNPs absent from dbSNP129 and 1000 Genomes, shared by at least five patients, and of functional effects were genotyped in an independent Sardinian case-control sample (n?=?500). Variants associated with PD with nominal p value <0.05 and those with odds ratio (OR) ?3 were validated by Sanger sequencing and typed in a replication sample of 2965 patients and 2678 controls from Italy, Spain, and Portugal. We identified novel moderately rare variants in several genes, including SCAPER, HYDIN, UBE2H, EZR, MMRN2 and OGFOD1 that were specifically present in PD patients or enriched among them, nominating these as novel candidate risk genes for PD, although no variants achieved genome-wide significance after Bonferroni correction. Our results suggest that the genetic bases of PD are highly heterogeneous, with implications for the design of future large-scale exome or whole-genome analyses of this disease.
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Lung cancer in never-smokers: a case-control study in a radon-prone area (Galicia, Spain).
Eur. Respir. J.
PUBLISHED: 07-17-2014
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The aim of the study was to assess the effect of residential radon exposure on the risk of lung cancer in never-smokers and to ascertain if environmental tobacco smoke modifies the effect of residential radon. We designed a multicentre hospital-based case-control study in a radon-prone area (Galicia, Spain). All participants were never-smokers. Cases had an anatomopathologically confirmed primary lung cancer and controls were recruited from individuals undergoing minor, non-oncological surgery. Residential radon was measured using alpha track detectors. We included 521 individuals, 192 cases and 329 controls, 21% were males. We observed an odds ratio of 2.42 (95% CI 1.45-4.06) for individuals exposed to ?200 Bq·m(-3) compared with those exposed to <100 Bq·m(-3). Environmental tobacco smoke exposure at home increased lung cancer risk in individuals with radon exposure>200 Bq·m(-3). Individuals exposed to environmental tobacco smoke and to radon concentrations>200 Bq·m(-3) had higher lung cancer risk than those exposed to lower radon concentrations and exposed to environmental tobacco smoke. Residential radon increases lung cancer risk in never-smokers. An association between residential radon exposure and environmental tobacco smoke on the risk of lung cancer might exist.
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Correlates of cerebrospinal fluid levels of oligomeric- and total-?-synuclein in premotor, motor and dementia stages of Parkinson's disease.
J. Neurol.
PUBLISHED: 07-04-2014
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High-oligomeric and low-total-?-synuclein cerebrospinal fluid (CSF) levels have been found in Parkinson's disease (PD), but with inconsistent or limited data, particularly on their clinical and structural correlates in earliest (premotor) or latest (dementia) PD stages. We determined CSF oligomeric- and total-?-synuclein in 77 subjects: 23 with idiopathic REM-sleep behaviour disorder (iRBD, a condition likely to include a remarkable proportion of subjects in the premotor stage of PD) and 41 with PD [21 non-demented (PDND) + 20 demented (PDD)], intended to reflect the premotor-motor-dementia PD continuum, along with 13 healthy controls. The study protocol also included the Unified PD Rating Scale motor-section (UPDRS-III), mini mental state examination (MMSE), neuropsychological cognitive testing, 3T brain MRI for cortical-thickness analyses, CSF ? and CSF A?. CSF oligomeric-?-synuclein was higher in PDND than iRBD and in PDD than iRBD and controls, and correlated with UPDRS-III, MMSE, semantic fluency and visuo-perceptive scores across the proposed premotor-motor-dementia PD continuum (iRBD + PDND + PDD). CSF total-?-synuclein positively correlated with age, CSF A?, and, particularly, CSF ?, tending towards lower levels in PD (but not iRBD) vs. controls only when controlling for CSF ?. Low CSF total-?-synuclein was associated with dysfunction in phonetic-fluency (a frontal-lobe function) in PD and with frontal cortical thinning in iRBD and PDND independently of CSF ?. Conversely, the associations of high (instead of low) CSF total-?-synuclein with posterior-cortical neuropsychological deficits in PD and with posterior cortical thinning in PDD were driven by high CSF ?. These findings suggest that CSF oligomeric- and total-?-synuclein have different clinical, neuropsychological and MRI correlates across the proposed premotor-motor-dementia PD continuum. CSF total-?-synuclein correlations with CSF ? and A? support the hypothesis of an interaction among these proteins in PD, with CSF ? probably influencing the presence of high (instead of low) CSF total-?-synuclein and its correlates mostly in the setting of PD-related dementia.
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Application of BRET for studying G protein-coupled receptors.
Mini Rev Med Chem
PUBLISHED: 04-15-2014
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G protein-coupled receptors (GPCRs) constitute one of the largest classes of cell surface receptors. GPCR biology has been a subject of widespread interest owing to the functional relevance of these receptors and their potential importance in the development of new drugs. At present, over 30% of all launched drugs target these receptors. GPCRs have been considered for a long time to function as monomeric entities and the idea of GPCR dimerization and oligomerization was initially accepted with disbelief. However, a significant amount of experimental and molecular modeling evidence accumulated during the last several years suggests that the process of GPCRs dimer or oligomer formation is a general phenomenon, in some cases even essential for receptor function. Among the many methods to study GPCR dimerization and oligomerization, modern biophysical techniques such as those based on resonance energy transfer (RET) and particularly bioluminescence resonance energy transfer (BRET) have played a leading role. RET methods are commonly applied as non-destructive indicators of specific protein-protein interactions (PPIs) in living cells. Data from numerous BRET experiments support the idea that the process of GPCR oligomerization may be relevant in many physiological and pathological conditions. The application of BRET to the study of GPCRs is not only limited to the assessment of receptor oligomerization but also expands to the investigation of the interactions of GPCRs with other proteins, including G proteins, G protein-coupled receptor kinases, ?-arrestins or receptor tyrosine kinases, as well as to the characterization of GPCR activation and signaling. In this review, we briefly summarize the fundaments of BRET, discuss new trends in this technology and describe the wide range of applications of BRET to study GPCRs.
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Integrative knowledge management to enhance pharmaceutical R&D.
Nat Rev Drug Discov
PUBLISHED: 04-02-2014
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Information technologies already have a key role in pharmaceutical research and development (R&D), but achieving substantial advances in their use and effectiveness will depend on overcoming current challenges in sharing, integrating and jointly analysing the range of data generated at different stages of the R&D process.
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Effect of deletion and overexpression of tryptophan metabolism genes on growth and fermentation capacity at low temperature in wine yeast.
Biotechnol. Prog.
PUBLISHED: 04-01-2014
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Low-temperature fermentations produce wines with greater aromatic complexity, but the success of these fermentations greatly depends on the adaptation of yeast cells to cold. Tryptophan has been previously reported to be a limiting amino acid during Saccharomyces cerevisiae growth at low temperature. The objective of this study was to determine the influence of the tryptophan metabolism on growth and fermentation performance during low-temperature wine fermentation. To this end, we constructed the deletion mutants of the TRP1 and TAT2 genes in a derivative haploid of a commercial wine strain, and the TAT2 gene was overexpressed in the prototroph and auxotroph (?trp1) backgrounds. Then we characterized growth and fermentation activity during wine fermentation at low and optimum temperatures. Our results partially support the role of this amino acid in cold yeast growth. Although deletion of TRP1 impaired amino acid uptake and the growth rate at low temperature in synthetic must, this growth impairment did not affect the fermentation rate. Deletion of TAT2 endorsed this strain with the highest nitrogen consumption capacity and the greatest fermentation activity at low temperature. Our results also evidenced reduced ammonium consumption in all the strains at low temperature.
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Cortical thinning associated with mild cognitive impairment in Parkinson's disease.
Mov. Disord.
PUBLISHED: 03-17-2014
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The aim of this study was to investigate patterns of cortical atrophy associated with mild cognitive impairment in a large sample of nondemented Parkinson's disease (PD) patients, and its relation with specific neuropsychological deficits. Magnetic resonance imaging (MRI) and neuropsychological assessment were performed in a sample of 90 nondemented PD patients and 32 healthy controls. All underwent a neuropsychological battery including tests that assess different cognitive domains: attention and working memory, executive functions, memory, language, and visuoperceptual-visuospatial functions. Patients were classified according to their cognitive status as PD patients without mild cognitive impairment (MCI; n?=?43) and PD patients with MCI (n?=?47). Freesurfer software was used to obtain maps of cortical thickness for group comparisons and correlation with neuropsychological performance. Patients with MCI showed regional cortical thinning in parietotemporal regions, increased global atrophy (global cortical thinning, total gray matter volume reduction, and ventricular enlargement), as well as significant cognitive impairment in memory, executive, and visuospatial and visuoperceptual domains. Correlation analyses showed that all neuropsychological tests were associated with cortical thinning in parietotemporal regions and to a lesser extent in frontal regions. These results provide neuroanatomic support to the concept of MCI classified according to Movement Disorders Society criteria. The posterior pattern of atrophy in temporoparietal regions could be a structural neuroimaging marker of cognitive impairment in nondemented PD patients. All of the neuropsychological tests reflected regional brain atrophy, but no specific patterns were seen corresponding to impairment in distinct cognitive domains.
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Transanal evisceration caused by rectal laceration.
Ann Coloproctol
PUBLISHED: 02-28-2014
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Transrectal evisceration caused by colorectal injury is an unusual entity. This pathology is more frequent in elderly patients and it is usually produced spontaneously. Rectal prolapse is the principal predisposing factor. An 81-year-old woman was taken to the hospital presenting exit of intestinal loops through the anus. After first reanimation measures, an urgent surgery was indicated. We observed the absence of almost every small intestine loop in the abdominal cavity; these had been moved to the pelvis. After doing the reduction, a 3 to 4 cm linear craniocaudal perforation in upper rectum was objectified, and Hartmann's procedure was performed. We investigated and knew that she frequently manipulate herself to extract her faeces. The fast preoperative management avoided a fatal conclusion or an extensive intestinal resection. Reasons that make us consider rectal self-injury as the etiologic factor are explained.
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Leisure time activities related to carcinogen exposure and lung cancer risk in never smokers. A case-control study.
Environ. Res.
PUBLISHED: 02-12-2014
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We aim to assess the relationship between leisure time activities related to exposure to carcinogenic substances and lung cancer risk in a hospital-based case-control study performed in never smokers. We included never smoking cases with anatomopathologically confirmed lung cancer and never smoking controls undergoing trivial surgery, at 8 Spanish hospitals. The study was conducted between January 2011 and June 2013. Participants were older than 30 and had no previous neoplasms. All were personally interviewed focusing on lifestyle, environmental tobacco smoke exposure, occupational history and leisure time activities (including duration of such activities). Results were analyzed through logistic regression and adjusted also by residential radon and education level. We included 513 never smokers, 191 cases and 322 controls. The OR for those performing the studied leisure time activities was 1.43 (95%CI 0.78-2.61). When we restricted the analysis to those performing do-it-yourself activities for more than 10 years the OR was 2.21 (95%CI 0.93-5.27). Environmental tobacco smoke exposure did not modify this association. The effect for the different lung cancer histological types was very close to significance for adenocarcinoma but only when these activities were performed for more than 10 years. We encourage health professionals to recommend protective measures for those individuals while performing these hobbies to reduce the risk of lung cancer.
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Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson's disease.
J. Neurosci. Res.
PUBLISHED: 01-21-2014
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Blood-cell-free circulating micro-RNAs (miRNAs) have been proposed as potential accessible biomarkers for neurodegenerative diseases such as Parkinson's disease (PD). Here we analyzed the serum levels of 377 miRNAs in a discovery set of 10 idiopathic Parkinson's disease (IPD) patients, 10 PD patients carriers of the LRRK2 G2019S mutation (LRRK2 PD), and 10 controls by using real-time quantitative PCR-based TaqMan MicroRNA arrays. We detected candidate differentially expressed miRNAs, which were further tested in a first validation set consisting of 20 IPD, 20 LRRK2 PD, and 20 control samples. We found four statistically significant miRNAs that were downregulated in either LRRK2 or IPD (miR-29a, miR-29c, miR-19a, and miR-19b). Subsequently, we validated these findings in a third set of samples consisting of 65 IPD and 65 controls and confirmed the association of downregulated levels of miR-29c, miR-29a, and miR-19b in IPD. Differentially expressed miRNAs are predicted to target genes belonging to pathways related to ECM-receptor interaction, focal adhesion, MAPK, Wnt, mTOR, adipocytokine, and neuron projection. Results from our exploratory study indicate that downregulated levels of specific circulating serum miRNAs are associated with PD and suggest their potential use as noninvasive biomarkers for PD. Future studies should further confirm the association of these miRNAs with PD.
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Functional brain networks and cognitive deficits in Parkinson's disease.
Hum Brain Mapp
PUBLISHED: 01-10-2014
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Graph-theoretical analyses of functional networks obtained with resting-state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are associated with changes in global and local network measures. Thirty-six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting-state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long-range connections as well as increased local interconnectedness manifested as higher measures of clustering, small-worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker.
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Novel insights on the structural determinants of clozapine and olanzapine multi-target binding profiles.
Eur J Med Chem
PUBLISHED: 01-10-2014
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The clinical efficacy of antipsychotic drugs has been associated with a certain binding profile for a set of G protein-coupled receptors (GPCR)s. In this work, we use the structurally-related clozapine-olanzapine pair to progress in the understanding of the structural properties that determine their divergent binding profiles and, thereby, their differing therapeutic efficacy. First, we present novel site-directed mutagenesis results that confirm our previous hypothesis on the importance of ligand interaction with positions 5.42 and 5.46 in transmembrane helix 5. Then, we use refined models of ligand-receptor complexes, built from recently published GPCR crystal structures, to gain further insight into the molecular mechanisms responsible for the observed experimental outcomes. In particular, we observe that preventing or potentiating hydrogen bonding with position 5.46, could allow obtaining ligands with, respectively, clozapine or olanzapine-like affinities. Results presented in this study could guide the design of antipsychotic candidates with tailored binding profiles.
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The Horizontal Denture: A Prosthodontic Alternative for Patients with Severe Maxillary Atrophy. A technical note.
J Oral Implantol
PUBLISHED: 01-10-2014
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Abstract Objective: To describe the Horizontal Denture®, a new implant-supported prosthetic alternative for edentulous patients with atrophied edentulous maxillae, designed to combine the advantages of conventional removable overdentures and hybrid fixed prostheses. Two cases treated following this prosthetic approach are presented. Materials and Method: The Horizontal Denture® is an implant-supported removable horizontal slide-in prosthesis. The overdenture superstructure slides horizontally in antero-posterior direction onto an implant-supported primary structure and is retained by friction. Two patients with atrophic upper maxillae were rehabilitated following this technique. Eight implants were inserted in the first case and six in the second. Prosthetic and implant complications and patient satisfaction were analyzed over a 12-month follow-up.Results: Neither prosthetic nor implant complications were observed during the follow-up period. Patient satisfaction with the slide-in prostheses was very high. Conclusions: The Horizontal Denture® prosthetic design was described and two patients were rehabilitated. This technique allowed, like conventional overdentures, camouflage of the fixing screw access holes and a good hygiene, while providing a biomechanical behavior equivalent to a fixed prosthesis. Both patients were highly satisfied with the treatment.
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Multiple organ involvement by alpha-synuclein pathology in Lewy body disorders.
Mov. Disord.
PUBLISHED: 01-02-2014
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Lewy body (LB) diseases are characterized by alpha-synuclein (AS) aggregates in the central nervous system (CNS). Involvement of the peripheral autonomic nervous system (pANS) is increasingly recognized, although less studied. The aim of this study was to systematically analyze the distribution and severity of AS pathology in the CNS and pANS. Detailed postmortem histopathological study of brain and peripheral tissues from 28 brain bank donors (10 with Parkinson's disease [PD], 5 with dementia with LB [DLB], and 13 with non-LB diseases including atypical parkinsonism and non-LB dementia). AS aggregates were found in the pANS of all 15 LB disease cases (PD, DLB) in stellate and sympathetic ganglia (100%), vagus nerve (86.7%), gastrointestinal tract (86.7%), adrenal gland and/or surrounding fat (53.3%), heart (100%), and genitourinary tract (13.3%), as well as in 1 case of incidental Lewy body disease (iLBD). A craniocaudal gradient of AS burden in sympathetic chain and gastrointestinal tract was observed. DLB cases showed higher amounts of CNS AS aggregates than PD cases, but this was not the case in the pANS. No pANS AS aggregates were detected in Alzheimer's disease (AD) cases with or without CNS AS aggregates. All pathologically confirmed LB disease cases including 1 case of iLBD had AS aggregates in the pANS with a craniocaudal gradient of pathology burden in sympathetic chain and gastrointestinal tract. AS was not detected in the pANS of any AD case. These findings may help in the search of peripheral AS aggregates in vivo for the early diagnosis of PD.
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Character strengths and well-being across the life span: data from a representative sample of German-speaking adults living in Switzerland.
Front Psychol
PUBLISHED: 01-01-2014
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Character strengths are positive, morally valued traits of personality. This study aims at assessing the relationship between character strengths and subjective well-being (i.e., life satisfaction, positive and negative affect) in a representative sample of German-speaking adults living in Switzerland (N = 945). We further test whether this relationship is consistent at different stages in life. Results showed that hope, zest, love, social intelligence and perseverance yielded the highest positive correlations with life satisfaction. Hope, zest, humor, gratitude and love presented the highest positive correlations with positive affect. Hope, humor, zest, honesty, and open-mindedness had the highest negative correlations with negative affect. When examining the relationship between strengths and well-being across age groups, in general, hope, zest and humor consistently yielded the highest correlations with well-being. Additionally, in the 27-36 years group, strengths that promote commitment and affiliation (i.e., kindness and honesty) were among the first five positions in the ranking of the relationship between strengths and well-being. In the 37-46 years group, in addition to hope, zest and humor, strengths that promote the maintenance of areas such as family and work (i.e., love, leadership) were among the first five positions in the ranking. Finally, in the 47-57 years group, in addition to hope, zest and humor, strengths that facilitate integration and a vital involvement with the environment (i.e., gratitude, love of learning) were among the first five positions in the ranking. This study partially supports previous findings with less representative samples on the association between character strengths and well-being, and sheds light on the relative importance of some strengths over others for well-being across the life span.
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Nonmotor Symptoms in LRRK2 G2019S Associated Parkinson's Disease.
PLoS ONE
PUBLISHED: 01-01-2014
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Idiopathic Parkinson's disease (IPD) and LRRK2-associated PD (LRRK2-PD) might be expected to differ clinically since the neuropathological substrate of LRRK2-PD is heterogeneous. The range and severity of extra-nigral nonmotor features associated with LRRK2 mutations is also not well-defined.
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A dynamic view of molecular switch behavior at serotonin receptors: implications for functional selectivity.
PLoS ONE
PUBLISHED: 01-01-2014
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Functional selectivity is a property of G protein-coupled receptors that allows them to preferentially couple to particular signaling partners upon binding of biased agonists. Publication of the X-ray crystal structure of serotonergic 5-HT1B and 5-HT2B receptors in complex with ergotamine, a drug capable of activating G protein coupling and ?-arrestin signaling at the 5-HT1B receptor but clearly favoring ?-arrestin over G protein coupling at the 5-HT2B subtype, has recently provided structural insight into this phenomenon. In particular, these structures highlight the importance of specific residues, also called micro-switches, for differential receptor activation. In our work, we apply classical molecular dynamics simulations and enhanced sampling approaches to analyze the behavior of these micro-switches and their impact on the stabilization of particular receptor conformational states. Our analysis shows that differences in the conformational freedom of helix 6 between both receptors could explain their different G protein-coupling capacity. In particular, as compared to the 5-HT1B receptor, helix 6 movement in the 5-HT2B receptor can be constrained by two different mechanisms. On the one hand, an anchoring effect of ergotamine, which shows an increased capacity to interact with the extracellular part of helices 5 and 6 and stabilize them, hinders activation of a hydrophobic connector region at the center of the receptor. On the other hand, this connector region in an inactive conformation is further stabilized by unconserved contacts extending to the intracellular part of the 5-HT2B receptor, which hamper opening of the G protein binding site. This work highlights the importance of considering receptor capacity to adopt different conformational states from a dynamic perspective in order to underpin the structural basis of functional selectivity.
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Confluence of ?-Synuclein, Tau, and ?-Amyloid Pathologies in Dementia With Lewy Bodies.
J. Neuropathol. Exp. Neurol.
PUBLISHED: 11-15-2013
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Dementia with Lewy bodies (DLB) is pathologically characterized by ?-synuclein aggregates in the brain. Most patients with DLB also show cerebral Alzheimer disease-type pathology (i.e. ?-amyloid plaques and hyperphosphorylated tau deposits). It is unclear whether this overlap is coincidental or driven by specific regional or cellular interactions. The aims of this study were to investigate the regional convergence of ?-synuclein, tau, and ?-amyloid and to identify patterns of cellular co-occurrence of tau and ?-synuclein in DLB. The study group consisted of 22 patients who met clinical and neuropathologic criteria for DLB. Protein aggregates were assessed semiquantitatively in 17 brain areas. APOE and MAPT genotypes were determined. Cellular co-occurrence of tau and ?-synuclein was evaluated by double immunofluorescence. We found that total ?-amyloid pathology scores correlated positively with total ?-synuclein pathology scores (? = 0.692, p = 0.001). The factors that correlated best with the amount of ?-synuclein pathology were the severity of ?-amyloid pathology and presence of the MAPT H1 haplotype. Tau and ?-synuclein frequently colocalized in limbic areas, but no correlation between total pathology scores was observed. This study confirms and extends the role of ?-amyloid deposition and the MAPT H1 haplotype as contributing factors in DLB pathogenesis and demonstrates the confluence of multiple agents in neurodegenerative diseases.
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Cell- and stimulus type-specific intracellular free Ca2+ signals in Arabidopsis.
Plant Physiol.
PUBLISHED: 09-11-2013
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Appropriate stimulus-response coupling requires that each signal induces a characteristic response, distinct from that induced by other signals, and that there is the potential for individual signals to initiate different downstream responses dependent on cell type. How such specificity is encoded in plant signaling is not known. One possibility is that information is encoded in signal transduction pathways to ensure stimulus- and cell type-specific responses. The calcium ion acts as a second messenger in response to mechanical stimulation, hydrogen peroxide, NaCl, and cold in plants and also in circadian timing. We use GAL4 transactivation of aequorin in enhancer trap lines of Arabidopsis (Arabidopsis thaliana) to test the hypothesis that stimulus- and cell-specific information can be encoded in the pattern of dynamic alterations in the concentration of intracellular free Ca(2+) ([Ca(2+)]i). We demonstrate that mechanically induced increases in [Ca(2+)]i are largely restricted to the epidermal pavement cells of leaves, that NaCl induces oscillatory [Ca(2+)]i signals in spongy mesophyll and vascular bundle cells, but not other cell types, and detect circadian rhythms of [Ca(2+)]i only in the spongy mesophyll. We demonstrate stimulus-specific [Ca(2+)]i dynamics in response to touch, cold, and hydrogen peroxide, which in the case of the latter two signals are common to all cell types tested. GAL4 transactivation of aequorin in specific leaf cell types has allowed us to bypass the technical limitations associated with fluorescent Ca(2+) reporter dyes in chlorophyll-containing tissues to identify the cell- and stimulus-specific complexity of [Ca(2+)]i dynamics in leaves of Arabidopsis and to determine from which tissues stress- and circadian-regulated [Ca(2+)]i signals arise.
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Regional vulnerability of hippocampal subfields and memory deficits in Parkinsons disease.
Hippocampus
PUBLISHED: 03-29-2013
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Neuropathological studies show the hippocampus is affected in Parkinsons disease (PD), with the second subfield of the cornu armonis (CA2) being the most involved. Our aims were to assess in vivo volumes of different hippocampal subfields in patients with PD with and without visual hallucinations using MRI and test their association with verbal learning and long-term recall. A total of 18 nondemented PD patients, 18 nondemented PD patients with visual hallucinations and 18 neurologically unimpaired elderly controls matched by age and gender were enrolled in this study. We assessed the volumes of seven hippocampal subfields on MRI, including the cornu armonis (CA) sectors, subiculum, presubiculum, and the dentate gyrus (DG) using a novel technique that enables automated volumetry. The CA2-3 and CA4-DG subfields were significantly smaller in both groups of patients, while the subiculum was only reduced in PD patients with visual hallucinations, compared to controls. Significant correlations were found between learning performance and CA2-3 as well as CA4-DG volumes in the whole patient sample. These data show there is regional atrophy of specific hippocampal subfields in PD, which is more severe and further extends to the subiculum in patients with visual hallucinations. Our findings indicate that learning deficits are associated with volume loss in subfields that act as input regions in the hippocampal circuit, suggesting that degeneration in these regions could be responsible for cognitive dysfunction in PD.
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Buccal bone crest dynamics after immediate implant placement and ridge preservation techniques: review of morphometric studies in animals.
Implant Dent
PUBLISHED: 03-07-2013
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To review morphometric studies performed in animals assessing the dynamics of the buccal bone crest after immediate implant placement and ridge preservation techniques.
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Combined dementia-risk biomarkers in Parkinsons disease: a prospective longitudinal study.
Parkinsonism Relat. Disord.
PUBLISHED: 03-05-2013
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Neuropsychological (mostly posterior-cortical) deficits, quantitative magnetic resonance imaging (MRI) atrophy patterns, and low cerebrospinal fluid (CSF) levels of amyloid-? have been separately related to worsening cognition in Parkinsons disease (PD). However, these biomarkers have not been longitudinally assessed in combination as PD-dementia predictors. In this prospective longitudinal study, 27 non-demented PD patients underwent CSF, neuropsychological and 3-T brain-MRI studies at baseline and were re-assessed 18 months later in terms of progression to dementia (primary outcome) and longitudinal neuropsychological and cortical thickness changes (secondary outcomes). At follow-up 11 patients (41%) had progressed to dementia. Lower CSF amyloid-?, worse verbal learning, semantic fluency and visuoperceptual scores, and thinner superior-frontal/anterior cingulate and precentral regions were significant baseline dementia predictors in binary logistic regressions as quantitative and/or dichotomised traits. All participants without baseline biomarker abnormalities remained non-demented whereas all with abnormalities in each biomarker type progressed to dementia, with intermediate risk for those showing abnormalities in a single to two biomarker types (p = 0.006). Both the dementia-outcome and low baseline CSF amyloid-? were prospectively associated with limbic and posterior-cortical neuropsychological decline and frontal, limbic and posterior-cortical thinning from baseline to follow-up. These findings suggest that the combination of CSF amyloid-?, neuropsychological and cortical thickness biomarkers might provide a basis for dementia-risk stratification and progression monitoring in PD.
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Cortical thinning is associated with disease stages and dementia in Parkinsons disease.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 03-05-2013
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To investigate the pattern of cortical thinning in Parkinsons disease (PD) across different disease stages and to elucidate to what extent cortical thinning is related to cognitive impairment.
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Novel insights into biased agonism at G protein-coupled receptors and their potential for drug design.
Curr. Pharm. Des.
PUBLISHED: 02-08-2013
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G-protein coupled receptors (GPCRs) are the most important class of current pharmacological targets. However, it is now widely acknowledged that their regulation is more complex than previously thought: the evidence that GPCRs can couple to several effector pathways, and the existence of biased agonists able to activate them differentially, has introduced a new level of complexity in GPCR drug research. Considering bias represents a challenge for the research of new GPCR modulators, because it demands a detailed characterization of compound properties for several effector pathways. Still, biased ligands could provide an opportunity to modulate GPCR function in a finer way and to separate therapeutic from side effects. Nowadays, a variety of agonists for GPCRs have been described, which differ in their ability to promote receptor coupling to different Gprotein families or even subunits, recruit signal transducers such as arrestins, activate a variety of downstream molecular pathways and induce certain phosphorylation signatures or gene expression patterns. In this review, we will cover some of the experimental techniques currently used to understand and characterize biased agonism and discuss their strengths and limitations. Additionally, we will comment on the computational efforts that are being devoted to study ligand-induced bias and on the potential they hold for rationalizing its structural determinants. Finally, we will discuss which of these strategies could be used for the rational design of biased ligands and give some examples of the potential therapeutic value of this class of compounds.
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Favorable outcome of patients with acute myeloid leukemia harboring a low-allelic burden FLT3-ITD mutation and concomitant NPM1 mutation: relevance to post-remission therapy.
Blood
PUBLISHED: 02-01-2013
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Risk associated to FLT3 internal tandem duplication (FLT3-ITD) in patients with acute myeloid leukemia (AML) may depend on mutational burden and its interaction with other mutations. We analyzed the effect of FLT3-ITD/FLT3 wild-type (FLT3wt) ratio depending on NPM1 mutation (NPM1mut) in 303 patients with intermediate-risk cytogenetics AML treated with intensive chemotherapy. Among NPM1mut patients, FLT3wt and low ratio (<0.5) subgroups showed similar overall survival, relapse risk, and leukemia-free survival, whereas high ratio (?0.5) patients had a worse outcome. In NPM1wt AML, FLT3-ITD subgroups showed a comparable outcome, with higher risk of relapse and shortened overall survival than FLT3wt patients. Allogeneic stem cell transplantation in CR1 was associated with a reduced relapse risk in all molecular subgroups with the exception of NPM1mut AML with absent or low ratio FLT3-ITD. In conclusion, effect of FLT3 burden is modulated by NPM1 mutation, especially in patients with a low ratio.
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Impact of time-of-flight and point-spread-function in SUV quantification for oncological PET.
Clin Nucl Med
PUBLISHED: 01-22-2013
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Accuracy in the quantification of the SUV is a critical point in PET because proper quantification of tumor uptake is essential for therapy monitoring and prognosis evaluation. Recent advances such as time-of-flight (TOF) and point-spread-function (PSF) reconstructions have dramatically improved detectability. However, first experiences with these techniques have shown a consistent tendency to measure markedly high SUV values, bewildering nuclear medicine physicians and referring clinicians.
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Dissecting the integrative antioxidant and redox systems in plant mitochondria. Effect of stress and S-nitrosylation.
Front Plant Sci
PUBLISHED: 01-01-2013
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Mitochondrial respiration provides the energy needed to drive metabolic and transport processes in cells. Mitochondria are a significant site of reactive oxygen species (ROS) production in plant cells, and redox-system components obey fine regulation mechanisms that are essential in protecting the mitochondrial integrity. In addition to ROS, there are compelling indications that nitric oxide can be generated in this organelle by both reductive and oxidative pathways. ROS and reactive nitrogen species play a key role in signaling but they can also be deleterious via oxidation of macromolecules. The high production of ROS obligates mitochondria to be provided with a set of ROS scavenging mechanisms. The first line of mitochondrial antioxidants is composed of superoxide dismutase and the enzymes of the ascorbate-glutathione cycle, which are not only able to scavenge ROS but also to repair cell damage and possibly serve as redox sensors. The dithiol-disulfide exchanges form independent signaling nodes and act as antioxidant defense mechanisms as well as sensor proteins modulating redox signaling during development and stress adaptation. The presence of thioredoxin (Trx), peroxiredoxin (Prx) and sulfiredoxin (Srx) in the mitochondria has been recently reported. Cumulative results obtained from studies in salt stress models have demonstrated that these redox proteins play a significant role in the establishment of salt tolerance. The Trx/Prx/Srx system may be subjected to a fine regulated mechanism involving post-translational modifications, among which S-glutathionylation and S-nitrosylation seem to exhibit a critical role that is just beginning to be understood. This review summarizes our current knowledge in antioxidative systems in plant mitochondria, their interrelationships, mechanisms of compensation and some unresolved questions, with special focus on their response to abiotic stress.
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LRRK2 haplotype-sharing analysis in Parkinsons disease reveals a novel p.S1761R mutation.
Mov. Disord.
PUBLISHED: 10-28-2011
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Mutations in the Leucine-Rich Repeat Kinase 2 (LRRK2) gene at chromosome 12q12 are the most common genetic cause of sporadic and familial late-onset Parkinsons disease. Our aim was to identify novel LRRK2 mutations in late-onset Parkinsons disease families.
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Influence of fruit ripening stage and harvest period on the antioxidant content of sweet pepper cultivars.
Plant Foods Hum Nutr
PUBLISHED: 07-28-2011
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Pepper (Capsicum annuum L.) fruits are highly appreciated by producers and consumers for their economical and nutritional value. Four different cultivars of coloured peppers in immature and mature stages were harvested throughout the spring and examined for their content of phenolic compounds, ascorbic acid and total antioxidant capacity (TAA) as well as for lipid peroxidation and carbonyl proteins as index of oxidative stress. Ripening and harvest period influenced the antioxidants and the development of oxidative processes in the cultivars differently: lipid peroxidation increased in mature peppers except in one cultivar (Y1075), while no changes in protein oxidation or in TAA were produced, except in Y1075 in which both parameters increased. Each cultivar presented differences in antioxidant compounds depending on the harvest period, but we could recommend May as the optimal if all cultivars have to be harvested at the same time, when levels of ascorbate, phenols and TAA were not decreased, fresh weight and proteins were elevated, and levels of oxidation were not as high as in June (except for Y1075). A previous study of the response of each cultivar to different environmental conditions results essential to establish a good program of selection of cultivars with high quality and productivity.
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Peri-implantitis: associated microbiota and treatment.
Med Oral Patol Oral Cir Bucal
PUBLISHED: 07-15-2011
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Peri-implantitis is a late complication of dental implant treatment, induced by microbiological changes. Since the disorder is frequent, a review is indicated of the microorganisms that influence it and of the existing treatment options.
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Voxel-based analysis of dual-time-point 18F-FDG PET images for brain tumor identification and delineation.
J. Nucl. Med.
PUBLISHED: 05-13-2011
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We have investigated dual-time-point (18)F-FDG PET for the detection and delineation of high-grade brain tumors using quantitative criteria applied on a voxel basis.
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An Infection Control Program for a 2009 influenza A H1N1 outbreak in a university-based summer camp.
J Am Coll Health
PUBLISHED: 04-19-2011
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Describe two 2009-H1N1 influenza outbreaks in university-based summer camps and the implementation of an infection control program.
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Microarray expression analysis in idiopathic and LRRK2-associated Parkinsons disease.
Neurobiol. Dis.
PUBLISHED: 04-14-2011
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LRRK2 mutations are the most common genetic cause of Parkinsons disease (PD). We performed a whole-genome RNA profiling of putamen tissue from idiopathic PD (IPD), LRRK2-associated PD (G2019S mutation), neurologically healthy controls and one asymptomatic LRRK2 mutation carrier, by using the Genechip Human Exon 1.0-ST Array. The differentially expressed genes found in IPD revealed an alteration of biological pathways related to long-term potentiation (LTP), GABA receptor signalling, and calcium signalling pathways, among others. These pathways are mainly related with cell signalling cascades and synaptic plasticity processes. They were also altered in the asymptomatic LRRK2 mutation carrier but not in the LRRK2-associated PD group. The expression changes seen in IPD might be attributed to an adaptive consequence of a dysfunction in the dopamine transmission. The lack of these altered molecular pathways in LRRK2-associated PD patients suggests that these cases could show a different molecular response to dopamine transmission impairment.
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Rapidly progressive diffuse Lewy body disease.
Mov. Disord.
PUBLISHED: 04-11-2011
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Lewy body syndromes (mainly Parkinsons disease and dementia with Lewy bodies) share many clinical features and usually have a slowly progressive course. Some patients may show rapid symptoms progression.
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Response of mitochondrial thioredoxin PsTrxo1, antioxidant enzymes, and respiration to salinity in pea (Pisum sativum L.) leaves.
J. Exp. Bot.
PUBLISHED: 04-02-2011
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Mitochondria play an essential role in reactive oxygen species (ROS) signal transduction in plants. Redox regulation is an essential feature of mitochondrial function, with thioredoxin (Trx), involved in disulphide/dithiol interchange, playing a prominent role. To explore the participation of mitochondrial PsTrxo1, Mn-superoxide dismutase (Mn-SOD), peroxiredoxin (PsPrxII F), and alternative oxidase (AOX) under salt stress, their transcriptional and protein levels were analysed in pea plants growing under 150 mM NaCl for a short and a long period. The activities of mitochondrial Mn-SOD and Trx together with the in vivo activities of the alternative pathway (AP) and the cytochrome pathway (CP) were also determined, combined with the characterization of the plant physiological status as well as the mitochondrial oxidative indicators. The analysis of protein and mRNA levels and activities revealed the importance of the post-transcriptional and post-translational regulation of these proteins in the response to salt stress. Increases in AOX protein amount correlated with increases in AP capacity, whereas in vivo AP activity was maintained under salt stress. Similarly, Mn-SOD activity was also maintained. Under all the stress treatments, photosynthesis, stomatal conductance, and CP activity were decreased although the oxidative stress in leaves was only moderate. However, an increase in lipid peroxidation and protein oxidation was found in mitochondria isolated from leaves under the short-term salinity conditions. In addition, an increase in mitochondrial Trx activity was produced in response to the long-term NaCl treatment. The results support a role for PsTrxo1 as a component of the defence system induced by NaCl in pea mitochondria, providing the cell with a mechanism by which it can respond to changing environment protecting mitochondria from oxidative stress together with Mn-SOD, AOX, and PrxII F.
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Cerebral basis of visual hallucinations in Parkinsons disease: structural and functional MRI studies.
J. Neurol. Sci.
PUBLISHED: 04-01-2011
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The presence of visual hallucinations (VH) is a significant predictor of dementia in Parkinsons disease (PD) and it is associated with a more rapid cognitive decline. Non-demented PD patients with VH present greater neuropsychological impairment than those without VH in domains such as verbal and visual memory, language comprehension, and visuospatial and visuoperceptive functions. Frontal dysfunction has also been described in PD with VH, including deficits in verbal fluency, sustained attention, and inhibition. In PD with VH, structural and functional abnormalities within the primary visual system and visual association areas, including ventral and dorsal pathways, have been reported. Structural MRI studies have shown that non-demented PD patients with VH present grey matter reduction in parieto-occipital areas and the hippocampal head. A follow-up study performed at a mean of 30 months revealed that unlike PD patients without VH, PD patients with VH frequently develop dementia associated with progressive atrophy in limbic, paralimbic and neocortical areas. Functional MRI (fMRI) studies have revealed altered activation in occipito-temporal and frontal areas in response to simple and complex visual stimuli in PD patients with VH, suggesting a marked impairment in bottom-up visual processing, as well as an attentional deficit in the pathophysiology of VH in PD.
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Brain structural MRI correlates of cognitive dysfunctions in Parkinsons disease.
J. Neurol. Sci.
PUBLISHED: 03-29-2011
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Cognitive dysfunction occurs at early stages of Parkinsons disease (PD). Initial studies reported that cognitive dysfunction in early PD only affected fronto-striatal circuits, provoking a marked executive dysfunction. Memory impairment in PD was thought to depend on a problem in retrieving stored information, therefore also reflecting a fronto-striatal dysfunction. However, there is increasing structural MRI evidence of medial temporal lobe atrophy in PD, which may be responsible for memory dysfunction. Other neuropsychological functions usually impaired in PD are semantic fluency, visuoperceptual and visuospatial functions, decision-making and recognition of facial emotions; and impairments in these functions are associated with cortical structural changes assessed by MRI. Overall, although the literature on the topic is scarce, there is increasing evidence of brain structural changes, detectable by MRI, which can explain the neuropsychological deficits early in the clinical disease course before dementia develops. In this review, we summarize the papers that have used structural MRI to study the neuroanatomical correlates of cognitive dysfunctions in PD.
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Amyloid-? and ? biomarkers in Parkinsons disease-dementia.
J. Neurol. Sci.
PUBLISHED: 03-14-2011
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Dementia is a frequent and devastating non-motor complication of advanced Parkinsons disease (PD). There is growing evidence of a synergistic role of Alzheimers-type brain lesions containing ? and amyloid-? (A?) proteins and cortical Lewy aggregates in PD-related dementia (PDD). Therefore, biomarkers of both ? and A? may be seen as diagnostic and predictive markers of PDD. Here, we review the available studies in PD and PDD using cerebrospinal fluid (CSF) total ?, phospho-?, and/or A? levels, and PET probes targeting Alzheimers-type lesions. Overall, high CSF ? and phospho-? levels and/or low CSF A? levels have been found in part of PDD patients, and a longitudinal study has found greater worsening in cognitive performance over time in non-demented PD patients with low baseline CSF A? levels. Few studies are available on the use of PET imaging in PD, all of them using the Pittsburgh B compound (PIB), and with figures of about 30% of scans with PIB uptake in the AD-range in PDD. We conclude that these CSF and PET markers deserve further evaluation as candidate biomarkers of dementia in PD. According to this, we are currently undertaking a longitudinal project on the predictive value of dementia of the combined use of CSF ? and A? and (18)F-FDDNP PET in PD.
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Dysfunctions of cerebral networks precede recognition memory deficits in early Parkinsons disease.
Neuroimage
PUBLISHED: 03-09-2011
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We aimed to investigate changes in the verbal recognition memory network in patients with early Parkinsons disease (PD) without overt recognition memory alteration. Verbal recognition memory was assessed in 24 PD patients in early stages of the disease and a control group of 24 healthy subjects during fMRI data acquisition. Participants were presented with a list of 35 words before imaging, and later during fMRI scanning they were required to recognize these previously presented words. Both model-based (FEAT) and model-free (MELODIC) analyses of the fMRI data were carried out with FSL software. Memory was also assessed by means of Reys Auditory Verbal Learning Test (RAVLT). PD patients showed no difference in the fMRI recognition memory task and recognition memory assessed by the RAVLT compared to healthy controls. Model-based analysis did not show significant differences between groups. On the other hand, model-free analysis identified components that fitted the task-model and were common to all the participants, as well as components that differed between PD and healthy controls. PD patients showed decreased task-related activations in areas involved in the recognition memory network and decreased task-related deactivations in the default mode network in comparison with controls. In conclusion, model-free fMRI analysis detected alterations in functional cerebral networks involved in a verbal memory task in PD patients without evident recognition memory deficit.
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Assessment of cortical degeneration in patients with Parkinsons disease by voxel-based morphometry, cortical folding, and cortical thickness.
Hum Brain Mapp
PUBLISHED: 01-17-2011
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Noninvasive brain imaging methods provide useful information on cerebral involution and degenerative processes. Here we assessed cortical degeneration in 20 nondemented patients with Parkinsons disease (PD) and 20 healthy controls using three quantitative neuroanatomical approaches: voxel-based morphometry (VBM), cortical folding (BrainVisa), and cortical thickness (FreeSurfer). We examined the relationship between global and regional gray matter (GM) volumes, sulcal indices, and thickness measures derived from the previous methods as well as their association with cognitive performance, age, severity of motor symptoms, and disease stage. VBM analyses showed GM volume reductions in the left temporal gyrus in patients compared with controls. Cortical folding measures revealed significant decreases in the left frontal and right collateral sulci in patients. Finally, analysis of cortical thickness showed widespread cortical thinning in right lateral occipital, parietal and left temporal, frontal, and premotor regions. We found that, in patients, all global anatomical measures correlated with age, while GM volume and cortical thickness significantly correlated with disease stage. In controls, a significant association was found between global GM volume and cortical folding with age. Overall these results suggest that the three different methods provide complementary and related information on neurodegenerative changes occurring in PD, however, surface-based measures of cortical folding and especially cortical thickness seem to be more sensitive than VBM to identify regional GM changes associated to PD.
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123I-MIBG cardiac uptake and smell identification in parkinsonian patients with LRRK2 mutations.
J. Neurol.
PUBLISHED: 01-08-2011
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Reduced uptake of (123)I- metaiodobenzylguanidine (MIBG) on cardiac gammagraphy and impaired odor identification are markers of neurodegenerative diseases with Lewy bodies (LB) as a pathological hallmark, such as idiopathic Parkinsons disease (IPD). LRRK2 patients present with a clinical syndrome indistinguishable from IPD, but LB have not been found in some cases. Patients with such mutations could behave differently than patients with IPD with respect to MIBG cardiac uptake and olfaction. We studied 14 LRRK2 patients, 14 IPD patients matched by age, gender, disease duration and severity, and 13 age and gender matched control subjects. Olfaction was analyzed through the University of Pennsylvania Smell Identification Test (UPSIT). MIBG cardiac uptake was evaluated through the H/M ratio. The late H/M was 1.44 ± 0.31 for LRRK2 patients, 1.19 ± 0.15 for PD patients, and 1.67 ± 0.16 for control subjects. LRRK2 patients presented lower but not statistically significant MIBG cardiac uptake than controls (p = 0.08) and significant higher uptake than PD patients (p = 0.04). UPSIT mean scores were 21.5 ± 7.3 for LRRK2 patients, 18.7 ± 6.2 for IPD patients and 29.7 ± 5.7 for control subjects. UPSIT score was lower in both LRRK2 and PD than in controls. In LRRK2 patients a positive correlation was found between myocardial MIBG uptake and UPSIT scores, (R = 0.801, p < 0.001). In LRRK2 patients, MIBG cardiac uptake was less impaired than in PD; a positive correlation between MIBG cardiac uptake and UPSIT scores was observed. As MIBG cardiac reduced uptake and impaired odor identification are markers of LB pathology, this findings may represent neuropathological heterogeneity among LRRK2 patients.
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Interleukins IL-6, IL-8, IL-10, IL-12 and periimplant disease. An update.
Med Oral Patol Oral Cir Bucal
PUBLISHED: 01-03-2011
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A study is made of the usefulness of cytokines (such as interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and interleukin-12 (IL-12)) as markers of periimplant disease (mucositis and periimplantitis). An increase in the levels of these cytokines in dental implant crevicular fluid may give rise to a lack of osteointegration, bone loss or implant failure.
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Dental implants in patients with oral mucosal alterations: An update.
Med Oral Patol Oral Cir Bucal
PUBLISHED: 01-03-2011
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To determine whether a series of diseases of the oral mucosa - Sjögren syndrome, ectodermal dysplasia, epidermolysis bullosa and lichen planus - reduce the survival rate of dental implants.
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Identifying the genetic components underlying the pathophysiology of movement disorders.
Appl Clin Genet
PUBLISHED: 01-01-2011
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Movement disorders are a heterogeneous group of neurological conditions, few of which have been classically described as bona fide hereditary illnesses (Huntingtons chorea, for instance). Most are considered to be either sporadic or to feature varying degrees of familial aggregation (parkinsonism and dystonia). In the late twentieth century, Mendelian monogenic mutations were found for movement disorders with a clear and consistent family history. Although important, these findings apply only to very rare forms of movement disorders. Already in the twenty-first century, and taking advantage of the modern developments in genetics and molecular biology, growing attention is being paid to the complex genetics of movement disorders. The search for risk genetic variants (polymorphisms) in large cohorts and the identification of different risk variants across different populations and ethnic groups are under way, with the most relevant findings to date corresponding to recent genome wide association studies in Parkinsons disease. These new approaches focusing on risk variants may enable the design of screening tests for early or even preclinical disease, and the identification of likely therapeutic targets.
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The effects of counting blessings on subjective well-being: a gratitude intervention in a Spanish sample.
Span J Psychol
PUBLISHED: 10-28-2010
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This study examined a gratitude intervention repeating Emmons and McCullough study (2003) in a Spanish sample, Participants were randomly assigned to one of three conditions (gratitude, hassles and any event) and kept daily records during 2 weeks of gratitude, affect, quality of relationships, physical and subjective well-being. We added design features to assess the intervention long-term impact (follow-up measures), and to improve the design control (pre-treatment measures). Following the cited authors analysis, i.e., comparing groups only in the post-test, we replicated their results, finding differences in positive affect and gratitude between the gratitude condition and the hassles condition. However, when including both the pre and the follow-up measures in the analysis, results were replicated only partially, as the difference in gratitude disappeared. Moreover, the difference in positive affect between groups in the post-test seemed to be influenced mainly by a decrease in positive affect in the hassles group. Post-test differences between groups in positive affect disappeared in the follow-up. Gratitude interventions may have an effect on well-being, but we consider other methods to promote gratitude besides gratitude journals should be tested.
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Antioxidant system and protein pattern in peach fruits at two maturation stages.
J. Agric. Food Chem.
PUBLISHED: 09-29-2010
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Peach fruits were selected to study the protein pattern and antioxidant system as well as oxidative parameters such as superoxide radical and hydrogen peroxide accumulation, at two maturity stages, which were chosen for being suitable for the processing industry and fresh consumption. The proteins phosphoenolpyruvate carboxylase, sucrose synthase, and 1-aminocyclopropane-1-carboxylate oxidase, as well as the antioxidants glutathione synthetase and ascorbate peroxidase, appeared as new in the mature peach fruits. Activities of superoxide dismutase (SOD) and components of the ascorbate-glutathione cycle were also measured to explore their role in the two maturity stages studied. Changes in the SOD isoenzyme pattern and an increase in the activities of ascorbate peroxidase, monodehydroascorbate reductase, and glutathione reductase were observed in mature fruits, revealing an efficient system to cope with the oxidative process accompanying ripening.
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Rapid analysis of procyanidins and anthocyanins in plasma by microelution SPE and ultra-HPLC.
J Sep Sci
PUBLISHED: 08-24-2010
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In the analysis of biological samples, such as plasma or serum, the quantity of sample available is a critical parameter in most cases. A good approach is the use of the microelution SPE (?SPE) plates as sample pre-treatment technique in which the loaded sample volume is low. An off-line ?SPE and ultra-performance LC-ESI-MS/MS (UPLC-ESI-MS/MS) method was developed and validated to determine procyanidins and anthocyanins in spiked plasma samples. The sample pre-treatment ?SPE allowed the simultaneous determination of procyanidins and anthocyanins from plasma by using a small sample volume (350 ?L) and without an evaporation step previous to the chromatographic analysis. Moreover, the use of UPLC technique allowed to determine the studied compounds at low concentration levels in a short analysis time (12.5 min approximately). Then, the developed method was applied to determine the studied compounds, procyanidins and anthocyanins, and their metabolites in rat plasma samples. Previously, the rats had consumed 5000 mg/kg of a grape pomace extract and the plasma was extracted 4 h after administration. The procyanidins catechin and epicatechin glucuronide, methyl catechin and epicatechin glucuronide, and methyl catechin and epicatechin sulphate were detected at ?M concentration level, and the parent anthocyanins at nM.
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Olfactory impairment in Parkinsons disease and white matter abnormalities in central olfactory areas: A voxel-based diffusion tensor imaging study.
Mov. Disord.
PUBLISHED: 07-30-2010
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Olfactory dysfunction is known to occur before the appearance of the classical motor signs in Parkinsons disease (PD) and diffusion tensor imaging (DTI) studies in PD have reported fractional anisotropy (FA) reductions in the early disease stages. We aimed to investigate the relationship between olfactory dysfunction and white matter (WM) FA of central olfactory areas in early PD. Twenty-four patients at Hoehn and Yahr stages I and II and 24 healthy controls matched by age, gender and years of education participated in this study. DTI was acquired at a 3 Tesla scanner and odor identification was assessed using the University of Pennsylvania Smell Identification Test (UPSIT). We performed FA voxelwise group comparisons in the central olfactory structures using tract-based spatial statistics (TBSS) and correlation analyses between FA values in these central olfactory areas and UPSIT scores. Patients with severe microsmia (UPSIT between 19 and 25) and anosmia (UPSIT lower or equal to 18) had lower FA values than PD patients with mild/moderate or no olfactory dysfunction (UPSIT between 26 and 40) and healthy controls in the WM adjacent to gyrus rectus. In addition, patients with anosmia had reduced FA in the WM surrounding primary olfactory areas in comparison with healthy controls. FA values in the WM adjacent to primary olfactory cortex and right gyrus rectus correlated with UPSIT scores in the PD group. This study demonstrates, for the first time, that microstructural WM reductions are present in the central olfactory system of early stage PD patients and that these reductions are associated with reduced ability to smell.
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High cerebrospinal tau levels are associated with the rs242557 tau gene variant and low cerebrospinal ?-amyloid in Parkinson disease.
Neurosci. Lett.
PUBLISHED: 07-21-2010
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Cerebrospinal fluid (CSF) tau and phospho-tau levels have been associated with certain tau gene variants and low CSF amyloid-? (A?) levels in Alzheimer disease (AD), constituting potential biomarkers of molecular mechanisms underlying neurodegeneration. We aimed to assess whether such CSF-genetic endophenotypes are also present in Parkinson disease (PD). CSF tau, phospho-tau and A? levels were obtained from 38 PD patients (19 with dementia) using specific ELISA techniques. All cases were genotyped for a series of tau gene polymorphisms (rs1880753, rs1880756, rs1800547, rs1467967, rs242557, rs2471738 and rs7521). The A-allele rs242557 polymorphism was the only tau gene variant significantly associated with higher CSF tau and phospho-tau levels, under both dominant and dose-response model. This association depended on the presence of dementia, and was only observed in individuals with low (<500pg/mL) CSF A? levels. Such genetic-CSF endophenotypes are probably a reflection of the presence of AD-like molecular changes in part of PD patients in the setting of dementia.
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Effect of oligogalacturonides on root length, extracellular alkalinization and O??-accumulation in alfalfa.
J. Plant Physiol.
PUBLISHED: 06-14-2010
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The effects of an oligogalacturonic acid (OGA) pool on root length of intact alfalfa seedlings (Medicago sativa L.), on extracellular pH and on both extracellular and intracellular O?? dynamics were examined in this study. Lower OGA concentrations (25, 50 and 75 ?g mL?¹)promoted root length, but 50 ?g mL?¹ had a stronger effect in promoting growth, while the higher OGA concentration (100 ?g mL?¹)had no significant effect. Extracellular alkalinization was tested only at concentrations higher than 50 ?g mL?¹ OGA, showing that the response is determined not only by the specific size of OGA, but also by the concentration of OGA. The promoting effect of OGA on root growth at 25, 50 and 75 ?g mL?¹ OGA concentrations in alfalfa root appeared to be unrelated to extracellular alkalinization. A possible explanation could be the induction of an O?? burst at non-toxic levels, which could drive directly or indirectly several processes associated with root elongation in 25, 50 and 75 ?g mL?¹ OGA-treated seedlings. Analyses using confocal microscopy showed that the increase in the O?? generation, mainly in the epidermal cells, induced by 50 ?g mL?¹ OGA could be related to the promoting effect on root growth. The combination of OGA with DPI allowed us to demonstrate that there are different O??-generating sources in the epidermal cells of the meristematic zone, likely NADPH oxidase and oxidases or oxido-reductase enzymes, insensitive to DPI, that maintain detectable O?? accumulation at 60 and 120 min of treatment. These results suggest that OGA induce an oxidative burst by several O??-generating sources in the active growth zones.
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Late-stage Parkinsons disease: the Barcelona and Lisbon cohort.
J. Neurol.
PUBLISHED: 02-09-2010
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Studies of late stages of Parkinsons disease (LS-PD) are limited. To provide an adequate health plan for patients in these most advanced stages, accurate information on their clinical condition is necessary. We characterize clinical features and medication use of LS-PD. A cross-sectional study of LS-PD stage 4 or 5 of Hoehn and Yahr during on states is presented in this paper. Demographics, clinical features and medication data were obtained using a structured questionnaire and physical examination. Patients were asked to grade the perceived impact of symptoms on their health status. Fifty patients (mean age 74.1 years and mean disease duration 17.9 years) were studied. Severe akinetic symmetric parkinsonism was present in most, with negligible rigidity and tremor, and most patients were wheelchair-bound. Severe postural instability and freezing of gait, causing frequent falls and fractures, and prominent dysarthria and dysphagia dominated the motor syndrome. Levodopa remained effective in most patients in relieving motor symptoms including tremor. Motor fluctuations and dyskinesias were present in 78 and 62% of patients, respectively, but were not perceived as disabling. All had neuropsychiatric and dysautonomic symptoms. Visual hallucinations were present in 44%, depression in 62% and dementia in 50%. Lack of tremor (p < 0.01) and absence of depression (p < 0.01) were independently associated with dementia (R(2) = 45%). Symptoms causing greatest impact on perceived health status were falls, gait unsteadiness, urinary dysfunction and sweats. Motor and non-motor non-levodopa responsive problems were frequent and the main cause of disability. Fluctuations and dyskinesias were frequent though not disabling. Dementia is not unavoidable in these very late stages.
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The pathogenicity determinant of Citrus tristeza virus causing the seedling yellows syndrome maps at the 3-terminal region of the viral genome.
Mol. Plant Pathol.
PUBLISHED: 01-19-2010
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Citrus tristeza virus (CTV) (genus Closterovirus, family Closteroviridae) causes some of the more important viral diseases of citrus worldwide. The ability to map disease-inducing determinants of CTV is needed to develop better diagnostic and disease control procedures. A distinctive phenotype of some isolates of CTV is the ability to induce seedling yellows (SY) in sour orange, lemon and grapefruit seedlings. In Florida, the decline isolate of CTV, T36, induces SY, whereas a widely distributed mild isolate, T30, does not. To delimit the viral sequences associated with the SY syndrome, we created a number of T36/T30 hybrids by substituting T30 sequences into different regions of the 3 half of the genome of an infectious cDNA of T36. Eleven T36/T30 hybrids replicated in Nicotiana benthamiana protoplasts. Five of these hybrids formed viable virions that were mechanically transmitted to Citrus macrophylla, a permissive host for CTV. All induced systemic infections, similar to that of the parental T36 clone. Tissues from these C. macrophylla source plants were then used to graft inoculate sour orange and grapefruit seedlings. Inoculation with three of the T30/T36 hybrid constructs induced SY symptoms identical to those of T36; however, two hybrids with T30 substitutions in the p23-3 nontranslated region (NTR) (nucleotides 18 394-19 296) failed to induce SY. Sour orange seedlings infected with a recombinant non-SY p23-3 NTR hybrid also remained symptomless when challenged with the parental virus (T36), demonstrating the potential feasibility of using engineered constructs of CTV to mitigate disease.
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Differential progression of brain atrophy in Parkinsons disease with and without visual hallucinations.
J. Neurol. Neurosurg. Psychiatr.
PUBLISHED: 12-03-2009
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To determine the course of cognitive deficits and the regional progression of brain atrophy in patients with Parkinsons disease (PD) with and without visual hallucinations (VH).
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MRI and cognitive impairment in Parkinsons disease.
Mov. Disord.
PUBLISHED: 10-31-2009
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Patients with Parkinsons disease (PD) may present impairment in cognitive functions even at early stages of the disease. When compared with the general population, their risk of dementia is five to six times higher. Recent investigations using structural MRI have shown that dementia in PD is related to cortical structural changes and that specific cognitive dysfunctions can be attributed to atrophy in specific structures. We review the structural MRI studies carried out in PD using either a manual region of interest (ROI) approach or voxel-based morphometry (VBM). ROI studies have shown that hippocampal volume is decreased in patients with PD with and without dementia; in addition, hippocampal atrophy correlated with deficits in verbal memory. VBM studies have demonstrated that dementia in PD involves structural changes in limbic areas and widespread cortical atrophy. Findings in nondemented patients with PD are less conclusive, possibly because cognitively heterogeneous groups of patients have been studied. Patients with PD with cognitive impairment and/or visual hallucinations present greater brain atrophy than patients without these characteristics. These findings suggest that cortical atrophy is related to cognitive dysfunction in PD and precedes the development of dementia. Structural MRI might therefore provide an early marker for dementia in PD.
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Cerebrospinal hypocretin, daytime sleepiness and sleep architecture in Parkinsons disease dementia.
Brain
PUBLISHED: 10-25-2009
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Excessive daytime sleepiness is common in Parkinsons disease and has been associated with Parkinsons disease-related dementia. Narcoleptic features have been observed in Parkinsons disease patients with excessive daytime sleepiness and hypocretin cell loss has been found in the hypothalamus of Parkinsons disease patients, in association with advanced disease. However, studies on cerebrospinal fluid levels of hypocretin-1 (orexin A) in Parkinsons disease have been inconclusive. Reports of sleep studies in Parkinsons disease patients with and without excessive daytime sleepiness have also been disparate, pointing towards a variety of causes underlying excessive daytime sleepiness. In this study, we aimed to measure cerebrospinal fluid hypocretin-1 levels in Parkinsons disease patients with and without dementia and to study their relationship to dementia and clinical excessive daytime sleepiness, as well as to describe potentially related sleep architecture changes. Twenty-one Parkinsons disease patients without dementia and 20 Parkinsons disease patients with dementia, along with 22 control subjects without sleep complaints, were included. Both Epworth sleepiness scale, obtained with the help of the caregivers, and mini-mental state examination were recorded. Lumbar cerebrospinal fluid hypocretin-1 levels were measured in all individuals using a radio-immunoassay technique. Additionally, eight Parkinsons disease patients without dementia and seven Parkinsons disease patients with dementia underwent video-polysomnogram and multiple sleep latencies test. Epworth sleepiness scale scores were higher in Parkinsons disease patients without dementia and Parkinsons disease patients with dementia than controls (P < 0.01) and scores >10 were more frequent in Parkinsons disease patients with dementia than in Parkinsons disease patients without dementia (P = 0.04). Cerebrospinal fluid hypocretin-1 levels were similar among groups (controls = 321.15 +/- 47.15 pg/ml; without dementia = 300.99 +/- 58.68 pg/ml; with dementia = 309.94 +/- 65.95 pg/ml; P = 0.67), and unrelated to either epworth sleepiness scale or mini-mental state examination. Dominant occipital frequency awake was slower in Parkinsons disease patients with dementia than Parkinsons disease patients without dementia (P = 0.05). Presence of slow dominant occipital frequency and/or loss of normal non-rapid eye movement sleep architecture was more frequent among Parkinsons disease patients with dementia (P = 0.029). Thus, excessive daytime sleepiness is more frequent in Parkinsons disease patients with dementia than Parkinsons disease patients without dementia, but lumbar cerebrospinal fluid hypocretin-1 levels are normal and unrelated to severity of sleepiness or the cognitive status. Lumbar cerebrospinal fluid does not accurately reflect the hypocretin cell loss known to occur in the hypothalamus of advanced Parkinsons disease. Alternatively, mechanisms other than hypocretin cells dysfunction may be responsible for excessive daytime sleepiness and the sleep architecture alterations seen in these patients.
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Cerebrospinal tau, phospho-tau, and beta-amyloid and neuropsychological functions in Parkinsons disease.
Mov. Disord.
PUBLISHED: 10-02-2009
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Alzheimers disease (AD)-pathology may play a role in Parkinsons disease (PD)-related dementia (PDD). The aim of this study was to assess cerebrospinal fluid (CSF) levels of tau, phospho-tau, and beta-amyloid, proposed AD biomarkers, and their relationship with cognitive function in PD. Forty PD patients [20 nondemented (PDND); 20 PDD] and 30 controls underwent CSF tau, phospho-tau, and beta-amyloid analysis using specific ELISA techniques. All PD patients and 15 controls underwent neuropsychological testing of fronto-subcortical (attention, fluency) and neocortical (memory, naming, visuoperceptive) functions. CSF markers levels were compared between groups, and compared and correlated with neuropsychological measures in PDND and PDD separately and as a continuum (PD). CSF tau and phospho-tau were higher in PDD than in PDND and controls (P < 0.05). CSF beta-amyloid ranged from high (controls) to intermediate (PDND) and low (PDD) levels (P < 0.001). In all PD and PDD patients, high CSF tau and phospho-tau were associated with impaired memory and naming. In PDND, CSF beta-amyloid was related with phonetic fluency. These findings suggest underlying AD-pathology in PDD in association with cortical cognitive dysfunction, and that low CSF beta-amyloid in PDND patients with impaired phonetic fluency can constitute an early marker of cognitive dysfunction.
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Neuroanatomical correlates of impaired decision-making and facial emotion recognition in early Parkinsons disease.
Eur. J. Neurosci.
PUBLISHED: 09-04-2009
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Decision-making and recognition of emotions are often impaired in patients with Parkinsons disease (PD). The orbitofrontal cortex (OFC) and the amygdala are critical structures subserving these functions. This study was designed to test whether there are any structural changes in these areas that might explain the impairment of decision-making and recognition of facial emotions in early PD. We used the Iowa Gambling Task (IGT) and the Ekman 60 faces test which are sensitive to the integrity of OFC and amygdala dysfunctions in 24 early PD patients and 24 controls. High-resolution structural magnetic resonance images (MRI) were also obtained. Group analysis using voxel-based morphometry (VBM) showed significant and corrected (P < 0.05 FEW-small volume correction) gray matter (GM) loss in the right amygdala and bilaterally in the OFC in PD patients. Volumetric analyses were also performed but did not yield significant differences between groups. Left lateral GM volume in OFC showed a slight correlation with the IGT, and bilateral OFC GM was strongly correlated with Ekman test performance in PD patients. We conclude that: (i) impairment in decision-making and recognition of facial emotions occurs at the early stages of PD, (ii) these neuropsychological deficits are accompanied by degeneration of OFC and amygdala, and (iii) bilateral OFC reductions are associated with impaired recognition of emotions, and GM volume loss in left lateral OFC is related to decision-making impairment in PD.
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Bacteremia caused by an Enterococcus faecalis isolate with high-level linezolid resistance in a teenager with Crohns disease.
Pediatr. Infect. Dis. J.
PUBLISHED: 05-20-2009
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Linezolid is an antibiotic used to treat highly resistant infections, including vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Enterococcus faecalis bacteremia occurs in pediatric patients. We present a teenager admitted for bacteremia caused by E faecalis with a distinctive pattern of resistance to linezolid. This organism has the highest MIC to linezolid reported in the literature to date.
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Neuroanatomical substrate of visuospatial and visuoperceptual impairment in Parkinsons disease.
Mov. Disord.
PUBLISHED: 05-05-2009
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To determine magnetic resonance imaging patterns of gray matter (GM) atrophy underlying visuospatial and visuoperceptual impairment in Parkinsons disease (PD), we applied voxel-based morphometry to 36 nondemented PD patients and correlated their whole brain GM density with performance on three visuospatial and visuoperceptual tests. In addition, group comparisons between patients and 20 healthy controls were also performed. Correlations between visuospatial performance and GM density were found in the superior parietal lobules and the superior occipital gyrus of PD patients. Poor performance on visuoperceptual tests was also found to be significantly associated with GM decreases in the fusiform, the parahippocampus, and the middle occipital gyrus. Finally, group comparisons between controls and patients showed widespread GM cortical reductions in PD, involving posterior temporal and parietal regions. Taken together, these findings suggest that visuospatial and visuoperceptual dysfunctions reflect structural GM changes in temporo-parietal cortical regions of PD patients.
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Mitochondrial and nuclear localization of a novel pea thioredoxin: identification of its mitochondrial target proteins.
Plant Physiol.
PUBLISHED: 04-10-2009
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Plants contain several genes encoding thioredoxins (Trxs), small proteins involved in the regulation of the activity of many enzymes through dithiol-disulfide exchange. In addition to chloroplastic and cytoplasmic Trx systems, plant mitochondria contain a reduced nicotinamide adenine dinucleotide phosphate-dependent Trx reductase and a specific Trx o, and to date, there have been no reports of a gene encoding a plant nuclear Trx. We report here the presence in pea (Pisum sativum) mitochondria and nuclei of a Trx isoform (PsTrxo1) that seems to belong to the Trx o group, although it differs from this Trx type by its absence of introns in the genomic sequence. Western-blot analysis with isolated mitochondria and nuclei, immunogold labeling, and green fluorescent protein fusion constructs all indicated that PsTrxo1 is present in both cell compartments. Moreover, the identification by tandem mass spectrometry of the native mitochondrial Trx after gel filtration using the fast-protein liquid chromatography system of highly purified mitochondria and the in vitro uptake assay into isolated mitochondria also corroborated a mitochondrial location for this protein. The recombinant PsTrxo1 protein has been shown to be reduced more effectively by the Saccharomyces cerevisiae mitochondrial Trx reductase Trr2 than by the wheat (Triticum aestivum) cytoplasmic reduced nicotinamide adenine dinucleotide phosphate-dependent Trx reductase. PsTrxo1 was able to activate alternative oxidase, and it was shown to interact with a number of mitochondrial proteins, including peroxiredoxin and enzymes mainly involved in the photorespiratory process.
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Structural brain correlates of verbal fluency in Parkinsons disease.
Neuroreport
PUBLISHED: 04-08-2009
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Verbal fluency tests are often used to assess cognitive dysfunction in Parkinsons disease. These tests have been found to be impaired even in initial stages of this illness. We applied voxel-based morphometry to investigate the neuroanatomic substrates of semantic and phonemic fluency impairment. Correlations between gray matter density and semantic as well as phonemic fluency performance were performed in 32 nondemented Parkinsons disease patients. We found that gray matter of temporal, frontal and cerebellar areas correlated with semantic fluency scores. In contrast, no gray matter correlations were found for phonemic fluency or for general cognitive functions. These results suggest that semantic fluency impairment is reflecting structural gray matter changes in regions involved in language networks.
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Different MAPT haplotypes are associated with Parkinsons disease and progressive supranuclear palsy.
Neurobiol. Aging
PUBLISHED: 02-23-2009
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The H1 MAPT haplotype in the 17q21 chromosomal region has been associated with several neurodegenerative diseases. Some reports have suggested that there is an association between genetic variants within the H1 haplotype with Parkinsons disease (PD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Here we report a genetic association study using seven SNPs located along the 17q21 region, in PD patients and controls. In addition, we compared these results with a dataset of previously published PSP/CBD patients from the same population. Our results show that the H1-rs242557(G) allele sub-haplotype is increased in PD (p=0.005), while the H1-rs242557(A) allele sub-haplotype is increased in PSP/CBD (p=0.0002), comparing to controls. The rs242557 polymorphism could act modulating the phenotypic expressivity of the H1 risk on these parkinsonisms. The location of this polymorphism in the 5 regulatory region of MAPT gene suggests the presence of a functional mechanism involved in the variation of MAPT expression levels.
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Sub-cellular distribution of glutathione in an Arabidopsis mutant (vtc1) deficient in ascorbate.
J. Plant Physiol.
PUBLISHED: 02-06-2009
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Glutathione and ascorbate are considered the major redox buffers in plant cells. They are implicated in many reactions at the sub-cellular level. However, information about the location and quantification of glutathione in the different sub-cellular compartments is very scarce and it has been obtained mainly using organelle purification and chemical quantification. We have used a glutathione antibody to immunolabel and quantify the total glutathione in leaves from wild-type Arabidopsis thaliana (Col-0) and an A. thaliana mutant (vtc1) deficient in ascorbate. Spectrophotometrical quantification has shown that this mutant has a higher content of glutathione during plant development compared with Col-0 [Pavet V, Olmos E, Kiddle G, Mowla S, Kumar S, Antoniw J, et al. Ascorbic acid deficiency activates cell death and disease resistance responses in Arabidopsis. Plant Physiology 2005;139:1291-03]. We have observed, using immunolabelling techniques, that mitochondria showed the highest density of glutathione labelling in both Col-0 and vtc1 plants during all developmental stages and that the lowest density occurred in the chloroplasts, for both lines. However, the distribution of glutathione in the different sub-cellular compartments indicates that the chloroplasts contain about 62-75% of the total cellular glutathione and that the mitochondria represent the second greatest pool, with about 15-25% of the total cellular glutathione. It has been observed previously that the vtc1 mutant exhibits an induction of cell death and disease resistance in the face of pathogen attack. The differing distributions and concentrations of glutathione in the mitochondria of wild-type A. thaliana and the vtc1 mutant is discussed.
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G2019S LRRK2 mutation causing Parkinsons disease without Lewy bodies.
BMJ Case Rep
PUBLISHED: 01-23-2009
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The G2019S leucine-rich repeat kinase 2 gene (LRRK2) mutation has been identified in a significant proportion of familial and sporadic cases of Parkinsons disease (PD). Until now, information on the neuropathological changes associated with the G2019S LRRK2 mutation has been sparse. We report a 77-year-old patient who presented with a 14 year history of PD but, unexpectedly, histopathological examination disclosed mild neuronal loss in the substantia nigra without ?-synuclein, tau or ubiquitin cytoplasmic inclusions. A G2019S LRRK2 mutation was eventually detected. The present case confirms that clinical PD caused by G2019S mutations can be associated with non-specific nigral degeneration without Lewy.
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Survey of practices employed by neurologists for the definition and management of secondary non-response to botulinum toxin in cervical dystonia.
Funct. Neurol.
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Secondary non-response (SNR) to botulinum toxin (BoNT) in cervical dystonia (CD) lacks a universal definition. We conducted a retrospective survey to develop a definition based on clinicians practice. Fifty-seven neurologists completed a 17-item questionnaire. In defining SNR, insufficiently improved posture was considered to be more relevant (98% of physicians) than insufficiently improved pain (86%). The most frequently used diagnostic test for SNR was the frontalis test (68%); antibody testing was performed by only 13% of physicians. Three consecutive unsuccessful injection cycles were considered the most appropriate indicator of SNR (55% of physicians). Physicians reported that 5.9% (median) of patients treated in 2008 became secondary non-responders to BoNT-A. The most common strategy for SNR was optimization of physiotherapy, considered by 98% of the physicians. On the basis of our findings, SNR can be defined as insufficiently improved posture after ?3 unsuccessful injection cycles in CD patients previously achieving satisfactory results.
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[Levodopa in the treatment of Parkinsons disease: myths and realties].
Rev Neurol
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In recent years we have witnessed a growing tendency to opt for the use of dopamine agonists (DA) as treatment for Parkinsons disease (PD), with the aim of delaying as far as possible the development of fluctuations and dyskinesias. Yet, levodopa continues to be the most effective antiparkinson drug and is probably the one that improves the greatest number of symptoms of the disease. This article reports on the results of a comprehensive review of the literature dealing with the benefits and risks of levodopa treatment in patients with PD which was conducted by a group of expert neurologists and members of the Spanish Neurology Societys Movement Disorder Group. The main conclusion reached in this article is that levodopa continues to be the most effective treatment for PD. Although the risk and incidence of developing dyskinesias remains at a lower level in the group initially treated with DA, the number of patients who develop disabling dyskinesias is very low in all the studies and is similar for DA and for levodopa. Scores on the quality of life scales are also similar in the two groups, which casts some doubt on the impact that these motor complications have on the quality of life of patients with PD. In view of these findings, we should consider whether there is any real justification for depriving patients of the good control of their symptoms offered by levodopa owing to the fear of developing dyskinesias or mild motor fluctuations that are not really going to have any negative effect on their quality of life. There is also the possibility of their developing severe side effects, which are more frequent with the use of DA.
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Progression of cortical thinning in early Parkinsons disease.
Mov. Disord.
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The aim of this study was to investigate the progression of cortical thinning and gray-matter (GM) volume loss in early Parkinsons disease (PD). MRI and neuropsychological assessment were obtained at baseline and follow-up (mean ± standard deviation = 35.50 ± 1.88 months) in a group of 16 early-PD patients (H & Y stage ?II and disease duration ?5 years) and 15 healthy controls matched for age, gender, and years of education. FreeSurfer software was used for the analysis of cortical thickness as well as for cortical and subcortical volumetric analyses. Voxel-based morphometry analysis was performed using SPM8. Compared to controls, PD patients showed greater regional cortical thinning in bilateral frontotemporal regions as well as greater over-time total GM loss and amygdalar volume reduction. PD patients and controls presented similar over-time changes in cognitive functioning. In early-PD patients, global GM loss, amygdalar atrophy, and cortical thinning in frontotemporal regions are specifically associated with the PD-degenerative process.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.