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Multi sclerosis

Jun Wei, Roberta G Marangoni, Feng Fang, Wenxia Wang, Jingang Huang, Joerg H W Distler, John Varga
The mechanisms underlying persistent fibroblast activation and myofibroblast phenoconversion in underlying multi-organ fibrosis in systemic sclerosis (SSc) remain incompletely understood, hindering effective therapies to slow or reverse the process. Cyclin-dependent kinase 5 (CDK5) is a pleiotropic member of the CDK family originally identified in neuronal cells. In contrast to other CDKs, CDK5 activity depends on its CDK5R1 subunit p35. Here we demonstrate that expression of p35 and CDK5 activity are induced by TGF-ß in fibroblasts and adipocytic cell types...
February 13, 2018: Oncotarget
Letizia Castelli, Luca Prosperini, Carlo Pozzilli
We performed a dual-task experiment to explore the effect of nabiximols on postural control in 22 patients with multiple sclerosis. They were assessed with static posturography and Stroop test in single- and dual-task conditions at treatment start and after 1, 3 and 12 months. At follow-up, we found more impaired postural control in single-task ( F = 3.07, p = 0.044) and dual-task ( F = 4.90, p = 0.005) conditions in patients who continued treatment (continuers, n = 11) compared with those who discontinued (quitters, n = 11)...
March 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Diana Ferraro, Valentina Camera, Eleonora Baldi, Veria Vacchiano, Erica Curti, Angelica Guareschi, Susanna Malagù, Sara Montepietra, Silvia Strumia, Mario Santangelo, Luisa Caniatti, Matteo Foschi, Alessandra Lugaresi, Franco Granella, Ilaria Pesci, Luisa Motti, Walter Neri, Paolo Immovilli, Enrico Montanari, Francesca Vitetta, Anna Maria Simone, Patrizia Sola
OBJECTIVE: The introduction of oral disease-modifying drugs (DMDs) in addition to the available, injectable, ones for Relapsing-Remitting Multiple Sclerosis (RRMS) could be expected to improve medication persistence due to a greater acceptability of the route of administration. Aim of the study was to compare the proportion of patients discontinuing injectable DMDs (interferon beta 1a/1b, pegylated interferon, glatiramer acetate) with those discontinuing oral DMDs (dimethylfumarate and teriflunomide) during an observation period of at least 12 months...
March 10, 2018: Current Medical Research and Opinion
Gilles Defer, Florian Le Caignec, Sophie Fedrizzi, François Montastruc, Damien Chevanne, Jean-Jacques Parienti, Laure Peyro-Saint-Paul
BACKGROUND: The reporting of adverse drug reactions (ADR) by patients represents an interesting challenge in the field of pharmacovigilance, but the reporting system is not adequately implemented in France. In 2015, only 20 MS patients in France reported ADR due to first-line disease-modifying drugs (DMD), while more than 3000 patients were initiated on DMD. The aim of this study is to validate a proof-of-concept as to whether the use of a mobile application (App) increases ADR reporting among patients with relapsing-remitting multiple sclerosis (RR-MS) receiving DMD...
March 9, 2018: Trials
Raed Alroughani, Alexey Boyko
BACKGROUND: Pediatric-onset multiple sclerosis (POMS) prevalence and incidence rates are increasing globally. No disease-modifying therapy are approved for MS pediatric population. Hence, we aim to review the literature on POMS to guide treating physicians on the current understanding of diagnosis and management of pediatric MS. METHODS: The authors performed a literature search and reviewed the current understanding on risk factors and disease parameters in order to discuss the challenges in assessing and implementing diagnosis and therapy in clinical practice...
March 9, 2018: BMC Neurology
Stephanie L Harrison, Kate E Laver, Kayla Ninnis, Cherie Rowett, Natasha A Lannin, Maria Crotty
PURPOSE: To examine in people with neurological disorders, which method/s of providing external cues to improve task performance are most effective. METHODS: Medline, EMBASE, and PsycINFO were systematically searched. Two reviewers independently screened, extracted data, and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Twenty six studies were included. Studies examined a wide-range of cues including visual, tactile, auditory, verbal, and multi-component cues...
March 9, 2018: Disability and Rehabilitation
Dorothea Buck, Till Fm Andlauer, Wilmar Igl, Eva-Maria Wicklein, Mark Mühlau, Frank Weber, Karl Köchert, Christoph Pohl, Barry Arnason, Giancarlo Comi, Stuart Cook, Massimo Filippi, Hans-Peter Hartung, Douglas Jeffery, Ludwig Kappos, Frederik Barkhof, Gilles Edan, Mark S Freedman, Xavier Montalbán, Bertram Müller-Myhsok, Bernhard Hemmer
BACKGROUND: Treatment of multiple sclerosis (MS) with interferon β can lead to the development of antibodies directed against interferon β that interfere with treatment efficacy. Several observational studies have proposed different HLA alleles and genetic variants associated with the development of antibodies against interferon β. OBJECTIVE: To validate the proposed genetic markers and to identify new markers. METHODS: Associations of genetic candidate markers with antibody presence and development were examined in a post hoc analysis in 941 patients treated with interferon β-1b in the Betaferon® Efficacy Yielding Outcomes of a New Dose (BEYOND) and BEtaseron® /BEtaferon® in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) prospective phase III trials...
March 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Barbara Ogórek, Hilaire C Lam, Damir Khabibullin, Heng-Jia Liu, Julie Nijmeh, Robinson Triboulet, David J Kwiatkowski, Richard I Gregory, Elizabeth P Henske
Tuberous Sclerosis Complex (TSC) is an autosomal dominant disease caused by germline inactivating mutations of TSC1 or TSC2. In TSC-associated tumors of the brain, heart, skin, kidney, and lung, inactivation of both alleles of TSC1 or TSC2 leads to hyperactivation of the mTORC1 pathway. The TSC/mTORC1 pathway is a key regulator of cellular processes related to growth, proliferation and autophagy. We and others have previously found that mTORC1 regulates microRNA biogenesis, but the mechanisms are not fully understood...
March 2, 2018: Human Molecular Genetics
Sherif M Hamdy, Maged Abdel-Naseer, Nevin M Shalaby, Alaa Elmazny, Marian Girgis, Mona A Nada, Amr Hassan, Husam S Mourad, Mohamed I Hegazy, Ahmed Abdelalim, Nirmeen A Kishk, Noha T Abokrysha, Shaimaa A Genedy, Ehab A Essawy, Hatem S Shehata
Introduction: Although the frequency of pediatric-onset multiple sclerosis (POMS) has increased in recent decades, it is still highly uncommon, which creates a need for the involvement of more registries from various clinical centers. Objective: To characterize the demographic, clinical, and paraclinical features of Egyptian patients with POMS. Patients and methods: A retrospective chart review study was undertaken on 237 Egyptian patients with demyelinating events which started before the age of 18 years who attended one of five tertiary referral centers in Cairo, Egypt...
2018: Neuropsychiatric Disease and Treatment
Carmen Navarrete, Francisco Carrillo-Salinas, Belén Palomares, Miriam Mecha, Carla Jiménez-Jiménez, Leyre Mestre, Ana Feliú, Maria L Bellido, Bernd L Fiebich, Giovanni Appendino, Marco A Calzado, Carmen Guaza, Eduardo Muñoz
BACKGROUND: Multiple sclerosis (MS) is characterized by a combination of inflammatory and neurodegenerative processes variously dominant in different stages of the disease. Thus, immunosuppression is the goal standard for the inflammatory stage, and novel remyelination therapies are pursued to restore lost function. Cannabinoids such as9 Δ-THC and CBD are multi-target compounds already introduced in the clinical practice for multiple sclerosis (MS). Semisynthetic cannabinoids are designed to improve bioactivities and druggability of their natural precursors...
March 1, 2018: Journal of Neuroinflammation
Yayoi Shimazu, Tatsuki Uchiyama, Chisaki Mizumoto, Tomoharu Takeoka, Masaaki Tsuji, Kenjiro Tomo, Koji Takaori, Naoki Sakai, Tomoko Okuno, Tatsuharu Ohno
IgG4-related disease (IgG4RD) is a multi-organ disorder characterized by an elevated serum IgG4 level and IgG4-positive plasma cell infiltration of the affected organs, accompanied by tissue fibrosis and sclerosis. Although it can affect any organ, to our knowledge, no cases involving concurrent autoimmune neutropenia and thrombocytopenia have been reported. A 62-year-old man visited our hospital and was diagnosed with IgG4RD accompanied by interstitial pneumonitis, lymphadenopathy, and interstitial nephritis...
February 28, 2018: Internal Medicine
Daniah Alshowaeir, Con Yiannikas, Clare Fraser, Alexander Klistorner
To test the hypothesis that latency delay in the fellow eyes of optic neuritis (ON) patients and to compensate for delayed transmission of visual information, latency change of multi-focal visual evoked potential (mfVEP) traces in fellow eyes of 15 ON patients were analyzed. Patients with low risk (LR) for developing multiple sclerosis (MS) were examined separately from MS patients to isolate effect of cortical plasticity from potential pathological changes in disseminated disease. The small increase in latency in fellow eyes of LR group was statistically not significant...
2018: International Journal of Ophthalmology
Juan A Paez, Nuria E Campillo
The discovery of cannabinoid receptors at the beginning of the 1990s, CB1 being cloned in 1990 and CB2 cloned in 1993, and the availability of selective and potent cannabimimetics could only be justified by the existence of endogenous ligands that are capable of binding to them. Thus, the characterisation and cloning of the first cannabinoid receptor (CB1) led to the isolation and characterisation of the first endocannabinoid, arachidonoylethanolamide (AEA), two years later and the subsequent identification of a family of lipid transmitters known as the fatty acid ester 2-arachidonoylglycerol (2-AG)...
February 25, 2018: Current Medicinal Chemistry
Alexa K Stuifbergen, Heather Becker, Francisco Perez, Janet Morrison, Adama Brown, Vicki Kullberg, Wenhui Zhang
BACKGROUND: The effects of multiple sclerosis (MS) on cognition have gained increasing recognition as one of the major disabling symptoms of the disease. Despite the prevalence of these symptoms and their impact on quality of life, limited attention has been given to strategies that might help manage the cognitive changes commonly experienced by persons with MS. OBJECTIVE: The primary purpose of this study was to determine the effectiveness of a novel computer-assisted cognitive rehabilitation intervention MAPSS-MS (Memory, Attention, Problem Solving Skills in MS) in a multi-site trial with persons with MS...
February 16, 2018: Disability and Health Journal
John D Pauling, Robyn T Domsic, Lesley A Saketkoo, Celia Almeida, Jane Withey, Hilary Jay, Tracy M Frech, Francesca Ingegnoli, Emma Dures, Joanna Robson, Neil J McHugh, Ariane L Herrick, Marco Matucci-Cerinic, Dinesh Khanna, Sarah Hewlett
OBJECTIVES: Raynaud's phenomenon (RP) is the commonest manifestation of systemic sclerosis (SSc). RP is an episodic phenomenon, not easily assessed in the clinic, leading to reliance on self-report. A thorough understanding of the patient experience of SSc-RP is essential to ensuring patient-reported outcome (PRO) instruments capture domains important to the target patient population. We report the findings of an international qualitative research study investigating the patient experience of SSc-RP...
November 21, 2017: Arthritis Care & Research
Jack D Wilkinson, Sarah A Leggett, Elizabeth J Marjanovic, Tonia L Moore, John Allen, Marina E Anderson, Jason Britton, Maya H Buch, Francesco Del Galdo, Christopher P Denton, Graham Dinsdale, Bridgett Griffiths, Frances Hall, Kevin Howell, Audrey MacDonald, Neil J McHugh, Joanne B Manning, John D Pauling, Christopher Roberts, Jacqueline A Shipley, Ariane L Herrick, Andrea K Murray
BACKGROUND: Objective and reliable outcome measures to facilitate clinical trials of novel treatments for systemic sclerosis (SSc)-related Raynaud's phenomenon (RP) are badly needed. Laser speckle contrast imaging (LSCI) and thermography are non-invasive measures of perfusion that show excellent potential. The purpose of this multi-centre study was to determine the reliability and validity of a hand cold challenge protocol using LSCI, standard thermography and low-cost mobile phone-based thermography...
February 18, 2018: Arthritis & Rheumatology
Brandi E Stevens, Kathryn S Torok, Suzanne C Li, Nicole Hershey, Megan Curran, Gloria C Higgins, Katharine F Moore, C Egla Rabinovich, Samuel Dodson, Anne M Stevens
OBJECTIVE: To investigate clinical manifestations of juvenile systemic sclerosis (jSSc), including disease characteristics and patient quality of life, through the multinational Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry. METHODS: Subjects with jSSc were prospectively enrolled between 2010 and 2013. Diagnosis of jSSc was determined by the enrolling pediatric rheumatologist, with disease onset required prior to age 18. Collected data included demographics, disease characteristics, medication exposure, and quality of life metrics...
February 18, 2018: Arthritis Care & Research
Maxime Jeanjean, Marie-Abele Bind, Jonathan Roux, Jean-Claude Ongagna, Jérôme de Sèze, Denis Bard, Emmanuelle Leray
BACKGROUND: Triggers of multiple sclerosis (MS) relapses are essentially unknown. PM10 exposure has recently been associated with an increased risk of relapses. OBJECTIVES: We further explore the short-term associations between PM10, NO2, benzene (C6H6), O3, and CO exposures, and the odds of MS relapses' occurrence. METHODS: Using a case-crossover design, we studied 424 MS patients living in the Strasbourg area, France between 2000 and 2009 (1783 relapses in total)...
February 6, 2018: Environmental Research
Xin Xu, Liwei Zheng, Quan Yuan, Gehua Zhen, Janet L Crane, Xuedong Zhou, Xu Cao
TGF-β 1-3 are unique multi-functional growth factors that are only expressed in mammals, and mainly secreted and stored as a latent complex in the extracellular matrix (ECM). The biological functions of TGF-β in adults can only be delivered after ligand activation, mostly in response to environmental perturbations. Although involved in multiple biological and pathological processes of the human body, the exact roles of TGF-β in maintaining stem cells and tissue homeostasis have not been well-documented until recent advances, which delineate their functions in a given context...
2018: Bone Research
Leila Bond, Kamren Bernhardt, Priyank Madria, Katherine Sorrentino, Hailee Scelsi, Cassie S Mitchell
Oxidative stress, induced by an imbalance of free radicals, incites neurodegeneration in Amyotrophic Lateral Sclerosis (ALS). In fact, a mutation in antioxidant enzyme superoxide dismutase 1 (SOD1) accounts for 20% of familial ALS cases. However, the variance among individual studies examining ALS oxidative stress clouds corresponding conclusions. Therefore, we construct a comprehensive, temporal view of oxidative stress and corresponding antioxidant therapy in preclinical ALS by mining published quantitative experimental data and performing metadata analysis of 41 studies...
2018: Frontiers in Neuroscience
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