43 research outputs found

    Cognitive and neuroanatomical correlates of neuropsychiatric symptoms in Parkinson's disease: A systematic review

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    Introduction Neuropsychiatric symptoms are one of the most common non-motor symptoms in Parkinson's disease (PD). These symptoms have a negative impact on daily living activities and cognitive abilities. This review will be centred on published articles which focused on clarifying the cognitive and neuroanatomical features associated with the appearance of specific neuropsychiatric symptoms in this disease. Methods All articles indexed in the Web of Science and PubMed databases were reviewed for potential inclusion in October 2014. In the first stage of the review, we identified 41 articles that investigated neuropsychiatric symptoms and cognitive impairments in PD. In the second stage, there were 26 published articles on the neural bases of neuropsychiatric symptoms in PD. Results The main findings revealed that executive dysfunctions were common in patients with depression, apathy, visual hallucinations (VH), impulse control disorders (ICDs) and anxiety, whereas, memory deficits were associated mainly with depression and VH. Imaging studies have shown that frontal lobe atrophy was frequently observed in patients with depression, apathy, VH and ICDs. Conclusion This review gives a snapshot of those cognitive and neural correlates of neuropsychiatric symptoms in PD. Methodological shortcoming in the available studies were identified, however, of which the most critical appeared neglecting the presence of multiple neuropsychiatric symptoms in some of the patients included in studies of specific individual symptoms. Additionally, in most studies only patients in the moderate to severe stages were included which limits possible inferences to the early stage of the disease

    Global Methylation Patterns in Idiopathic Pulmonary Fibrosis

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    BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is characterized by profound changes in the lung phenotype including excessive extracellular matrix deposition, myofibroblast foci, alveolar epithelial cell hyperplasia and extensive remodeling. The role of epigenetic changes in determining the lung phenotype in IPF is unknown. In this study we determine whether IPF lungs exhibit an altered global methylation profile.\ud \ud METHODOLOGY/PRINCIPAL FINDINGS: Immunoprecipitated methylated DNA from 12 IPF lungs, 10 lung adenocarcinomas and 10 normal histology lungs was hybridized to Agilent human CpG Islands Microarrays and data analysis was performed using BRB-Array Tools and DAVID Bioinformatics Resources software packages. Array results were validated using the EpiTYPER MassARRAY platform for 3 CpG islands. 625 CpG islands were differentially methylated between IPF and control lungs with an estimated False Discovery Rate less than 5%. The genes associated with the differentially methylated CpG islands are involved in regulation of apoptosis, morphogenesis and cellular biosynthetic processes. The expression of three genes (STK17B, STK3 and HIST1H2AH) with hypomethylated promoters was increased in IPF lungs. Comparison of IPF methylation patterns to lung cancer or control samples, revealed that IPF lungs display an intermediate methylation profile, partly similar to lung cancer and partly similar to control with 402 differentially methylated CpG islands overlapping between IPF and cancer. Despite their similarity to cancer, IPF lungs did not exhibit hypomethylation of long interspersed nuclear element 1 (LINE-1) retrotransposon while lung cancer samples did, suggesting that the global hypomethylation observed in cancer was not typical of IPF.\ud \ud CONCLUSIONS/SIGNIFICANCE: Our results provide evidence that epigenetic changes in IPF are widespread and potentially important. The partial similarity to cancer may signify similar pathogenetic mechanisms while the differences constitute IPF or cancer specific changes. Elucidating the role of these specific changes will potentially allow better understanding of the pathogenesis of IPF.\ud \u

    Prediction of adeno-associated virus neutralizing antibody activity for clinical application

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    Patients with neutralizing antibodies (Nab) against adeno-associated virus (AAV) are usually excluded from treatment with AAV vectors. To develop a standard assay for detecting Nab inhibition activity, we systematically studied current AAV Nab assays in vitro and in vivo. Several factors were found that influence the Nab titers based on the in vitro assay, including: sera volume, AAV dose/cell, cell number and choice of transgenes. When the Nab titer assay was performed in vivo via intramuscular (IM) or systemic administration, a 4-fold increase in sensitivity for measurement of Nab titers was observed compared to an identical in vitro test. To better mimic the clinical setting, after passively transferring human Nabs into mice, blood was collected before systemic injection of AAV vector and used for Nab titer analysis in vitro or via IM injection. The results showed that AAV delivered via IM injection had a similar inhibition pattern to systemic administration. These studies indicate critical parameters necessary for optimizing Nab sensitivity and that an in vivo Nab assay is more sensitive than an in vitro assay for inclusion/exclusion criteria. The variables identified by this study may explain some of the compounding clinical data seen to date with respect to efficiency of AAV transduction in various Phase I clinical trials

    The POLARBEAR Cosmic Microwave Background Polarization Experiment

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    The polarbear cosmic microwave background (CMB) polarization experiment has been observing since early 2012 from its 5,200 m site in the Atacama Desert in Northern Chile. polarbear’s measurements will characterize the expected CMB polarization due to gravitational lensing by large scale structure, and search for the possible B-mode polarization signature of inflationary gravitational waves. polarbear’s 250 mK focal plane detector array consists of 1,274 polarization-sensitive antenna-coupled bolometers, each with an associated lithographed band-defining filter and contacting dielectric lenslet, an architecture unique in current CMB experiments. The status of the polarbear instrument, its focal plane, and the analysis of its measurements are presented
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