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https://www.readbyqxmd.com/read/28935965/aromatic-side-chain-conformational-switch-on-the-surface-of-the-rna-recognition-motif-enables-rna-discrimination
#1
Nana Diarra Dit Konté, Miroslav Krepl, Fred F Damberger, Nina Ripin, Olivier Duss, Jiří Šponer, Frédéric H-T Allain
The cyclooxygenase-2 is a pro-inflammatory and cancer marker, whose mRNA stability and translation is regulated by the CUG-binding protein 2 interacting with AU-rich sequences in the 3' untranslated region. Here, we present the solution NMR structure of CUG-binding protein 2 RRM3 in complex with 5'-UUUAA-3' originating from the COX-2 3'-UTR. We show that RRM3 uses the same binding surface and protein moieties to interact with AU- and UG-rich RNA motifs, binding with low and high affinity, respectively. Using NMR spectroscopy, isothermal titration calorimetry and molecular dynamics simulations, we demonstrate that distinct sub-states characterized by different aromatic side-chain conformations at the RNA-binding surface allow for high- or low-affinity binding with functional implications...
September 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/28934996/balancing-the-demands-of-two-tasks-an-investigation-of-cognitive-motor-dual-tasking-in-relapsing-remitting-multiple-sclerosis
#2
Emma Butchard-MacDonald, Lorna Paul, Jonathan J Evans
BACKGROUND: People with relapsing remitting multiple sclerosis (PwRRMS) suffer disproportionate decrements in gait under dual-task conditions, when walking and a cognitive task are combined. There has been much less investigation of the impact of cognitive demands on balance. OBJECTIVES: This study investigated whether: (1) PwRRMS show disproportionate decrements in postural stability under dual-task conditions compared to healthy controls, and (2) dual-task decrements are associated with everyday dual-tasking difficulties...
September 22, 2017: Journal of the International Neuropsychological Society: JINS
https://www.readbyqxmd.com/read/28933672/cognitive-impairment-and-the-regional-distribution-of-cerebellar-lesions-in-multiple-sclerosis
#3
Sean M Tobyne, Wilson B Ochoa, J Daniel Bireley, Victoria Mj Smith, Jeroen Jg Geurts, Jeremy D Schmahmann, Eric C Klawiter
BACKGROUND: Cerebellar lesions are often reported in relapsing-remitting multiple sclerosis (RRMS) and have been associated with impaired motor function and cognitive status. However, prior research has primarily focused on summary measures of cerebellar involvement (e.g. total lesion load, gray/white matter volume) and not on the effect of lesion load within specific regions of cerebellar white matter. OBJECTIVE: Spatially map the probability of cerebellar white matter lesion (CWML) occurrence in RRMS and explore the relationship between cognitive impairment and lesion (CWML) location within the cerebellum...
September 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28932291/neurological-safety-of-fingolimod-an-updated-review
#4
REVIEW
Fumihito Yoshii, Yusuke Moriya, Tomohide Ohnuki, Masafuchi Ryo, Wakoh Takahashi
Fingolimod (FTY) is the first oral medication approved for treatment of relapsing-remitting multiple sclerosis (RRMS). Its effectiveness and safety were confirmed in several phase III clinical trials, but proper evaluation of safety in the real patient population requires long-term post-marketing monitoring. Since the approval of FTY for RRMS in Japan in 2011, it has been administered to approximately 5000 MS patients, and there have been side-effect reports from 1750 patients. Major events included infectious diseases, hepatobiliary disorders, nervous system disorders and cardiac disorders...
August 2017: Clinical & Experimental Neuroimmunology
https://www.readbyqxmd.com/read/28923927/mif-and-d-dt-are-potential-disease-severity-modifiers-in-male-ms-subjects
#5
Gil Benedek, Roberto Meza-Romero, Kelley Jordan, Ying Zhang, Ha Nguyen, Gail Kent, Jia Li, Edwin Siu, Jenny Frazer, Marta Piecychna, Xin Du, Antoine Sreih, Lin Leng, Jack Wiedrick, Stacy J Caillier, Halina Offner, Jorge R Oksenberg, Vijayshree Yadav, Dennis Bourdette, Richard Bucala, Arthur A Vandenbark
Little is known about mechanisms that drive the development of progressive multiple sclerosis (MS), although inflammatory factors, such as macrophage migration inhibitory factor (MIF), its homolog D-dopachrome tautomerase (D-DT), and their common receptor CD74 may contribute to disease worsening. Our findings demonstrate elevated MIF and D-DT levels in males with progressive disease compared with relapsing-remitting males (RRMS) and female MS subjects, with increased levels of CD74 in females vs. males with high MS disease severity...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28914229/clinical-effectiveness-and-cost-effectiveness-of-beta-interferon-and-glatiramer-acetate-for-treating-multiple-sclerosis-systematic-review-and-economic-evaluation
#6
G J Melendez-Torres, Peter Auguste, Xavier Armoiry, Hendramoorthy Maheswaran, Rachel Court, Jason Madan, Alan Kan, Stephanie Lin, Carl Counsell, Jacoby Patterson, Jeremy Rodrigues, Olga Ciccarelli, Hannah Fraser, Aileen Clarke
BACKGROUND: At the time of publication of the most recent National Institute for Health and Care Excellence (NICE) guidance [technology appraisal (TA) 32] in 2002 on beta-interferon (IFN-β) and glatiramer acetate (GA) for multiple sclerosis, there was insufficient evidence of their clinical effectiveness and cost-effectiveness. OBJECTIVES: To undertake (1) systematic reviews of the clinical effectiveness and cost-effectiveness of IFN-β and GA in relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and clinically isolated syndrome (CIS) compared with best supportive care (BSC) and each other, investigating annualised relapse rate (ARR) and time to disability progression confirmed at 3 months and 6 months and (2) cost-effectiveness assessments of disease-modifying therapies (DMTs) for CIS and RRMS compared with BSC and each other...
September 2017: Health Technology Assessment: HTA
https://www.readbyqxmd.com/read/28912625/cognitive-impairment-in-relapsing-remitting-multiple-sclerosis-patients-with-very-mild-clinical-disability
#7
S Migliore, A Ghazaryan, I Simonelli, P Pasqualetti, F Squitieri, G Curcio, D Landi, M G Palmieri, F Moffa, M M Filippi, F Vernieri
Cognitive dysfunction affects 40-65% of multiple sclerosis (MS) patients and can occur in the early stages of the disease. This study aimed to explore cognitive functions by means of the Italian version of the minimal assessment of cognitive function in MS (MACFIMS) in relapsing-remitting MS (RRMS) patients with very mild clinical disability to identify the primarily involved cognitive functions. Ninety-two consecutive RRMS patients with Expanded Disability Status Scale (EDSS) scores ≤ 2.5 and forty-two healthy controls (HC) were investigated...
2017: Behavioural Neurology
https://www.readbyqxmd.com/read/28911257/fatigue-in-multiple-sclerosis-the-contribution-of-resting-state-functional-connectivity-reorganization
#8
Alvino Bisecco, Federica Di Nardo, Renato Docimo, Giuseppina Caiazzo, Alessandro d'Ambrosio, Simona Bonavita, Rocco Capuano, Leonardo Sinisi, Mario Cirillo, Fabrizio Esposito, Gioacchino Tedeschi, Antonio Gallo
OBJECTIVES: To investigate resting-state functional connectivity (RS-FC) of the default-mode network (DMN) and of sensorimotor network (SMN) network in relapsing remitting (RR) multiple sclerosis (MS) patients with fatigue (F) and without fatigue(NF). METHODS: In all, 59 RRMS patients and 29 healthy controls (HC) underwent magnetic resonance imaging (MRI) protocol including resting-state fMRI (RS-fMRI). Functional connectivity of the DMN and SMN was evaluated by independent component analysis (ICA)...
September 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28906152/relapse-outcomes-safety-and-treatment-patterns-in-patients-diagnosed-with-relapsing-remitting-multiple-sclerosis-and-initiated-on-subcutaneous-interferon-%C3%AE-1a-or-dimethyl-fumarate-a-real-world-study
#9
Frank R Ernst, Peri Barr, Riad Elmor, Schiffon L Wong
OBJECTIVE: To estimate real-world treatment patterns, safety, and relapse outcomes of subcutaneous (sc) interferon (IFN) β-1a (Rebif®) versus dimethyl fumarate (DMF; Tecfidera(®)), to treat relapsing-remitting multiple sclerosis (RRMS). METHODS: A U.S. retrospective chart review of 450 randomly selected adults newly diagnosed with RRMS who received sc IFN β-1a (n = 143) or DMF (n = 307) was conducted. Patients were either (a) treatment-naïve, initiating first-line treatment with sc IFN β-1a or DMF, or (b) previously treated, switching to sc IFN β-1a or DMF...
September 14, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28900067/-dimethyl-fumarate-in-multiple-sclerosis
#10
Masami Tanaka, Yuko Shimizu
At the end of 2016, dimethyl fumarate (DMF) was approved as the sixth disease-modifying drug for multiple sclerosis by the Pharmaceuticals and Medical Devices Agency of Japan. Two randomized, placebo-controlled, phase III studies (DEFINE and CONFIRM) showed beneficial effects in patients in Western countries, with relapsing-remitting multiple sclerosis (RRMS). Some of the benefits included a decreased annual relapse rate, inhibition of disease activity (shown using brain magnetic resonance imaging), and a decreased proportion of patients with confirmed disease progression...
September 2017: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/28890199/distinct-cognitive-impairments-in-different-disease-courses-of-multiple-sclerosis-a-systematic-review-and-meta-analysis
#11
REVIEW
Andreas Johnen, Nils C Landmeyer, Paul-Christian Bürkner, Heinz Wiendl, Sven G Meuth, Heinz Holling
Cognitive impairment (CI) is common and debilitating in patients with multiple sclerosis. However, little is known about how different disease courses affect CI, impeding prognosis and disease management. Here, we contrasted the magnitude and profile of CI measured with standardized neuropsychological tests in patients with primary progressive multiple sclerosis (PPMS) against relapsing-remitting multiple sclerosis (RRMS) while considering potentially confounding demographic and clinical differences. Systematic literature review and meta-analysis was performed finding 47 eligible studies (N=4460 patients)...
September 8, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28882107/statistical-classifiers-for-diagnosing-disease-from-immune-repertoires-a-case-study-using-multiple-sclerosis
#12
Jared Ostmeyer, Scott Christley, William H Rounds, Inimary Toby, Benjamin M Greenberg, Nancy L Monson, Lindsay G Cowell
BACKGROUND: Deep sequencing of lymphocyte receptor repertoires has made it possible to comprehensively profile the clonal composition of lymphocyte populations. This opens the door for novel approaches to diagnose and prognosticate diseases with a driving immune component by identifying repertoire sequence patterns associated with clinical phenotypes. Indeed, recent studies support the feasibility of this, demonstrating an association between repertoire-level summary statistics (e.g., diversity) and patient outcomes for several diseases...
September 7, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28873979/the-recruitment-of-the-saccharomyces-cerevisiae-poly-a-binding-protein-into-stress-granules-new-insights-into-the-contribution-of-the-different-protein-domains
#13
Marco Brambilla, Francesca Martani, Paola Branduardi
The Saccharomyces cerevisiae poly(A)-binding protein Pab1 is a modular protein composed of four RNA recognition motifs (RRM), a proline-rich domain (P) and a C-terminus. Thanks to this modularity, Pab1 is involved in different interactions that regulate many aspects of mRNA metabolism, including the assembly of stress granules. In this work, we analyzed the contribution of each domain for the recruitment of the protein within stress granules by comparing the intracellular distribution of synthetic Pab1-GFP variants, lacking one or more domains, with the localization of the endogenous mCherry-tagged Pab1...
September 1, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28870573/cxcl10-and-cxcl13-chemokines-in-patients-with-relapsing-remitting-and-primary-progressive-multiple-sclerosis
#14
Piotr Iwanowski, Jacek Losy, Lucyna Kramer, Marlena Wójcicka, Elżbieta Kaufman
OBJECTIVES: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system characterized by a variable clinical course. Different pathogenic mechanisms responsible for relapsing remitting (RRMS) and primary progressive multiple sclerosis (PPMS) are modulated by immunological process with important role of chemokine network. CXCL10 and CXCL13 chemokines act as chemoattractants and modulators of proinflammatory reactions promoting process of demyelination...
September 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28865414/interleukin-7-receptor-alpha-gene-variants-are-correlated-with-gene-expression-in-patients-with-relapsing-remitting-multiple-sclerosis
#15
Arezou Sayad, Mir Davood Omrani, Ghasem Solgi, Rezvan Noroozi, Shahram Arsang-Jang, Hidetoshi Inoko, Mohammad Taheri
The association of single nucleotide polymorphisms (SNPs) of the IL-7Rα gene with multiple sclerosis (MS) have been documented in various populations. This study aimed to evaluate the genotype distributions of two SNPs, rs6897932 and rs201084372, and the functional association of rs6897932 in relation to IL-7Rα gene expression in a group of Iranian relapsing-remitting MS (RRMS) patients.  Genotyping for both SNPs in the IL7Rα gene and relative quantification of mRNA expression for both isoforms of IL-7Rα were performed in 100 RRMS patients and 100 ethnic-matched healthy controls...
August 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28859672/safety-and-in-vivo-immune-assessment-of-escalating-doses-of-oral-laquinimod-in-patients-with-rrms
#16
Tjalf Ziemssen, Hayrettin Tumani, Tony Sehr, Katja Thomas, Friedemann Paul, Nils Richter, Emil Samara, Ofer Spiegelstein, Ella Sorani, Oren Bar-Ilan, Dorit Mimrod, Liat Hayardeny
BACKGROUND: Laquinimod is an oral immunomodulator in clinical development to treat relapsing-remitting multiple sclerosis (RRMS). Laquinimod is in clinical development for the treatment of multiple sclerosis and Huntington Disease (HD). The objective of this study is to assess the safety, tolerability, pharmacokinetics (PK) and cytoimmunologic effects following escalating doses of laquinimod in patients with RRMS. METHODS: One hundred twelve patients were randomly assigned to laquinimod/placebo in a series of separate dose-escalating cohorts starting from a daily oral dose of 0...
August 31, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28842450/neuroinflammation-drives-anxiety-and-depression-in-relapsing-remitting-multiple-sclerosis
#17
Silvia Rossi, Valeria Studer, Caterina Motta, Serena Polidoro, Jacopo Perugini, Giulia Macchiarulo, Ambra Mara Giovannetti, Lorena Pareja-Gutierrez, Andrea Calò, Isabella Colonna, Roberto Furlan, Gianvito Martino, Diego Centonze
OBJECTIVE: To explore the inflammatory processes in the pathogenesis of psychiatric symptoms and the prognostic value of psychiatric comorbidities in multiple sclerosis (MS). METHODS: Four hundred five patients with relapsing-remitting (RR) MS underwent psychiatric evaluation by means of Beck Depression Inventory II (BDI-II) and State/Trait Anxiety Inventory (STAI-Y). The inflammatory activity level was assessed by MRI. In a subset of 111 treatment-naive patients, CSF levels of proinflammatory cytokines were determined...
August 25, 2017: Neurology
https://www.readbyqxmd.com/read/28835741/preferences-for-multiple-sclerosis-treatments-using-a-discrete-choice-experiment-to-examine-differences-across-subgroups-of-us-patients
#18
Carol Mansfield, Nina Thomas, David Gebben, Maria Lucas, A Brett Hauber
BACKGROUND: The growing number of treatments for relapsing multiple sclerosis (MS) provides opportunities to consider patient preferences in treatment decisions. METHODS: We designed a Web-based, discrete-choice experiment survey to analyze treatment preferences in patients with relapsing-remitting MS (RRMS). The survey presented hypothetical MS treatments defined by six attributes: risk of MS progression, time between relapses, risk of serious infection, treatment-related flu-like symptoms and gastrointestinal symptoms, and route and frequency of administration...
July 2017: International Journal of MS Care
https://www.readbyqxmd.com/read/28835401/alemtuzumab-care-ms-i-5-year-follow-up-durable-efficacy-in-the-absence-of-continuous-ms-therapy
#19
RANDOMIZED CONTROLLED TRIAL
Eva Havrdova, Douglas L Arnold, Jeffrey A Cohen, Hans-Peter Hartung, Edward J Fox, Gavin Giovannoni, Sven Schippling, Krzysztof W Selmaj, Anthony Traboulsee, D Alastair S Compston, David H Margolin, Karthinathan Thangavelu, Claudio E Rodriguez, Darlene Jody, Richard J Hogan, Panos Xenopoulos, Michael A Panzara, Alasdair J Coles
OBJECTIVE: To evaluate 5-year efficacy and safety of alemtuzumab in treatment-naive patients with active relapsing-remitting MS (RRMS) (CARE-MS I; NCT00530348). METHODS: Alemtuzumab-treated patients received treatment courses at baseline and 12 months later; after the core study, they could enter an extension (NCT00930553) with as-needed alemtuzumab retreatment for relapse or MRI activity. Assessments included annualized relapse rate (ARR), 6-month confirmed disability worsening (CDW; ≥1-point Expanded Disability Status Scale [EDSS] score increase [≥1...
September 12, 2017: Neurology
https://www.readbyqxmd.com/read/28831635/a-multicenter-observational-prospective-study-of-self-and-parent-reported-quality-of-life-in-adolescent-multiple-sclerosis-patients-self-administering-interferon-%C3%AE-1a-using-rebismart%C3%A2-the-future-study
#20
A Ghezzi, A Bianchi, D Baroncini, A Bertolotto, S Malucchi, V Bresciamorra, R Lanzillo, N Milani, V Martinelli, F Patti, C Chisari, M Rottoli, M Simone, D Paolicelli, A Visconti
Besides the impact of disease per se, the use of immunomodulatory therapies in adolescents with relapsing-remitting multiple sclerosis (RRMS) may have an effect on quality of life (QL). The FUTURE (Quality of liFe in adolescent sUbjecTs affected by mUltiple sclerosis treated with immunomodulatoRy agEnt using self-injecting device) study was designed to evaluate the changes in QL of Italian adolescents with RRMS receiving treatment with IFN-β1a (Rebif; 22 μg), administered subcutaneously three times weekly using the RebiSmart™ electronic autoinjection device over a 52-week period...
August 22, 2017: Neurological Sciences
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