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https://www.readbyqxmd.com/read/28340352/human-epistatic-interaction-controls-il7r-splicing-and-increases-multiple-sclerosis-risk
#1
Gaddiel Galarza-Muñoz, Farren B S Briggs, Irina Evsyukova, Geraldine Schott-Lerner, Edward M Kennedy, Tinashe Nyanhete, Liuyang Wang, Laura Bergamaschi, Steven G Widen, Georgia D Tomaras, Dennis C Ko, Shelton S Bradrick, Lisa F Barcellos, Simon G Gregory, Mariano A Garcia-Blanco
Multiple sclerosis (MS) is an autoimmune disorder where T cells attack neurons in the central nervous system (CNS) leading to demyelination and neurological deficits. A driver of increased MS risk is the soluble form of the interleukin-7 receptor alpha chain gene (sIL7R) produced by alternative splicing of IL7R exon 6. Here, we identified the RNA helicase DDX39B as a potent activator of this exon and consequently a repressor of sIL7R, and we found strong genetic association of DDX39B with MS risk. Indeed, we showed that a genetic variant in the 5' UTR of DDX39B reduces translation of DDX39B mRNAs and increases MS risk...
March 23, 2017: Cell
https://www.readbyqxmd.com/read/28338393/contraception-for-women-with-multiple-sclerosis-guidance-for-healthcare-providers
#2
Maria K Houtchens, Lauren B Zapata, Kathryn M Curtis, Maura K Whiteman
Family planning is essential for any comprehensive treatment plan for women of reproductive age with multiple sclerosis (MS), including counseling on using effective contraception to optimally time desired and prevent unintended pregnancies. This topical review summarizes the first evidence-based recommendations on contraception safety for women with MS. In 2016, evidence-based recommendations for contraceptive use by women with MS were included in US Medical Eligibility Criteria for Contraceptive Use. They were developed after review of published scientific evidence on contraception safety and consultation with experts...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28337550/common-genetic-etiology-between-multiple-sclerosis-like-single-gene-disorders-and-familial-multiple-sclerosis
#3
Anthony L Traboulsee, A Dessa Sadovnick, Mary Encarnacion, Cecily Q Bernales, Irene M Yee, Maria G Criscuoli, Carles Vilariño-Güell
Several single-gene disorders with clinical and radiological characteristics similar to those observed in multiple sclerosis (MS) patients have been described. To evaluate whether this phenotypic overlap can be ascribed to a common genetic etiology, 28 genes known to present pathogenic mutations for 24 of these disorders were sequenced in 270 MS patients. All identified variants were genotyped in 2131 MS cases and 830 healthy controls, and those exclusively observed in patients were assessed for segregation within families...
March 23, 2017: Human Genetics
https://www.readbyqxmd.com/read/28334724/incidence-of-multiple-sclerosis-in-puerto-rico-2014-a-population-based-study
#4
Angel Chinea, Carlos F Ríos-Bedoya, Cristina Rubi, Ivonne Vicente, Eduardo R Estades, Yatzka G Hernandez-Silvestrini
BACKGROUND: Multiple sclerosis (MS) affects millions of people worldwide. The estimates for MS incidence are difficult to obtain but are important for understanding MS etiology, developing prevention strategies, and service planning. This study is aimed at estimating the 2014 incidence of MS in Puerto Rico (PR). METHODS: The PR MS Foundation's registry was used as the data source. Neurologists, specialty pharmacies, MRI centers, health insurance companies, and the PR Department of Health identified MS cases missed by the registry...
March 24, 2017: Neuroepidemiology
https://www.readbyqxmd.com/read/28327374/discovery-and-molecular-interaction-studies-of-a-highly-stable-tarantula-peptide-modulator-of-acid-sensing-ion-channel-1
#5
REVIEW
Sing Yan Er, Ben Cristofori-Armstrong, Pierre Escoubas, Lachlan D Rash
Acute pharmacological inhibition of acid-sensing ion channel 1a (ASIC1a) is efficacious in rodent models in alleviating symptoms of neurological diseases such as stroke and multiple sclerosis. Thus, ASIC1a is a promising therapeutic target and selective ligands that modulate it are invaluable research tools and potential therapeutic leads. Spider venoms have provided an abundance of voltage-gated ion channel modulators, however, only one ASIC modulator (PcTx1) has so far been isolated from this source. Here we report the discovery, characterization, and chemical stability of a second spider venom peptide that potently modulates ASIC1a and ASIC1b, and investigate the molecular basis for its subtype selectivity...
March 18, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28327094/finger-tapping-impairments-are-highly-sensitive-for-evaluating-upper-motor-neuron-lesions
#6
Afsaneh Shirani, Braeden D Newton, Darin T Okuda
BACKGROUND: Identifying highly sensitive and reliable neurological exam components are crucial in recognizing clinical deficiencies. This study aimed to investigate finger tapping performance differences between patients with CNS demyelinating lesions and healthy control subjects. METHODS: Twenty-three patients with multiple sclerosis or clinically isolated syndrome with infratentorial and/or cervical cord lesions on MRI, and 12 healthy controls were videotaped while tapping the tip of the index finger against the tip and distal crease of the thumb using both the dominant and non-dominant hand...
March 21, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28322606/cognitive-impairment-in-pediatric-onset-multiple-sclerosis-is-detected-by-the-brief-international-cognitive-assessment-for-multiple-sclerosis-and-computerized-cognitive-testing
#7
Leigh E Charvet, Michael Shaw, Ariana Frontario, Dawn Langdon, Lauren B Krupp
BACKGROUND: Cognitive impairment is a common and troubling feature of pediatric-onset multiple sclerosis (POMS). Brief cognitive assessment in the outpatient setting can identify and longitudinally monitor cognitive involvement so that early intervention is possible. OBJECTIVES: The goal of this study was to measure the sensitivity of two cognitive assessment approaches that are brief, repeatable, and suitable for clinical practice and for multicenter investigation...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28320798/interventions-to-improve-the-self-management-support-health-professionals-provide-for-people-with-progressive-neurological-conditions-protocol-for-a-realist-synthesis
#8
Freya Davies, Fiona Wood, Alison Bullock, Carolyn Wallace, Adrian Edwards
INTRODUCTION: Supporting self-management among people with long-term conditions is recognised as an important component of healthcare. Progressive neurological conditions (PNCs), for example, Parkinson's disease and multiple sclerosis are associated with problems such as fatigue and cognitive impairment which may make self-management more challenging. Health professionals may need to develop specific skills in order to provide effective self-management support for these patients. The review aims to develop explanatory theories about how health professional-targeted interventions to improve self-management support provision for people with PNCs operate in different circumstances...
March 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28320194/acquired-pendular-nystagmus
#9
REVIEW
Sarah Kang, Aasef G Shaikh
Acquired pendular nystagmus is comprised of quasi-sinusoidal oscillations of the eyes significantly affecting gaze holding and clarity of vision. The most common causes of acquired pendular nystagmus include demyelinating disorders such as multiple sclerosis and the syndrome of ocular palatal tremor. However, several other deficits, such as pharmacological intoxication, metabolic and genetic disorders, and granulomatous disorders can lead to syndromes mimicking acquired pendular nystagmus. Study of the kinematic features of acquired pendular nystagmus has suggested a putative pathophysiology of an otherwise mysterious neurological disorder...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320130/spg2-mimicking-multiple-sclerosis-in-a-family-identified-using-next-generation-sequencing
#10
Anna Rubegni, Carla Battisti, Alessandra Tessa, Alfonso Cerase, Stefano Doccini, Alessandro Malandrini, Filippo M Santorelli, Antonio Federico
Several single gene disorders can potentially be overlooked in the differential diagnostic evaluation of patients with multiple sclerosis (MS). Pelizaeus-Merzbacher disease and spastic paraplegia type 2 are allelic X-linked disorders associated with defective myelination of the central nervous system and mutations in PLP1. Neurological symptoms are occasionally observed in female carriers of these mutations. Two women - the proposita (Pt1) and her mother (Pt2) - reported walking difficulties since adolescence and showed progressive cognitive decline...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320120/seasonal-variations-of-25-oh-vitamin-d-serum-levels-are-associated-with-clinical-disease-activity-in-multiple-sclerosis-patients
#11
Christina Hartl, Viola Obermeier, Lisa Ann Gerdes, Mathias Brügel, Rüdiger von Kries, Tania Kümpfel
Low 25-hydroxy vitamin D (25-[OH]-D) serum concentrations have been associated with higher disease activity in multiple sclerosis (MS) patients. In a large cross-sectional study we assessed the vitamin D status in MS patients in relation to seasonality and relapse rate. 415 MS-patients (355 relapsing-remitting MS and 60 secondary-progressive, 282 female, mean age 39.1years) of whom 25-(OH)-D serum concentrations were determined at visits between 2010 and 2013 were included in the study. All clinical data including relapse at visit and expanded disability status scale were recorded in a standardized manner by an experienced neurologist...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28320113/alzheimer-s-disease-elevated-pigment-epithelium-derived-factor-in-the-cerebrospinal-fluid-is-mostly-of-systemic-origin
#12
Veronika Lang, Marietta Zille, Carmen Infante-Duarte, Sven Jarius, Holger Jahn, Friedemann Paul, Klemens Ruprecht, Ana Luisa Pina
Pigment-epithelium derived factor (PEDF) is a neurotrophic factor with neuroprotective, anti-tumorigenic, and anti-angiogenic effects. Elevated levels of PEDF have previously been proposed as a cerebrospinal fluid (CSF) biomarker for Alzheimer's disease. However, the origin of PEDF in CSF, i.e. whether it is derived from the brain or from the systemic circulation, and the specificity of this finding hitherto remained unclear. Here, we analyzed levels of PEDF in paired CSF and serum samples by ELISA in patients with Alzheimer's disease (AD, n=12), frontotemporal dementia (FTD, n=6), vascular dementia (n=4), bacterial meningitis (n=8), multiple sclerosis (n=32), pseudotumor cerebri (n=36), and diverse non-inflammatory neurological diseases (n=19)...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319417/alterations-in-serum-levels-of-il-17-in-contrast-to-tnf-alpha-correspond-to-disease-modifying-treatment-in-relapsing-remitting-multiple-sclerosis
#13
Anastasiya Georgieva Trenova, Georgi Svetoslavov Slavov, Maria Georgieva Manova, Milena Nenkova Draganaova-Filipova, Nonka Georgieva Mateva, Lyuba Dineva Miteva, Spaska Angelova Stanilova
Cytokines of different types play an important role in multiple sclerosis (MS) pathogenesis as mediators and regulators of the immune processes in the central nervous system. The aim of the study was to determine the effect of interferon-beta and glatiramer acetate on serum concentrations of TNF-alpha and IL-17 A and their correlation with the degree of disability in clinically stable patients with relapsing-remitting MS. A cross-sectional, case-control study of 220 patients (68 treatment naïve; 152 treated with interferon-beta or glatiramer acetate) and 99 clinically healthy age-gender-body mass index-matched subjects were performed...
March 20, 2017: Scandinavian Journal of Clinical and Laboratory Investigation
https://www.readbyqxmd.com/read/28317084/dietary-interventions-and-multiple-sclerosis
#14
REVIEW
Ghadah Altowaijri, Allison Fryman, Vijayshree Yadav
Multiple Sclerosis (MS) is a chronic, disabling neurologic disease that has its onset in young adulthood. While the knowledge about underlying pathogenesis of MS has improved significantly over the last few decades, the exact cause still eludes us. Despite the availability of several United States Food and Drug Administration-approved disease-modifying therapies (DMT) for MS in the last two decades, the disease remains disabling for many. DMT use is limited by its partial effectiveness, significant side effects in many cases, and high cost that leads people with MS (PwMS) to look for alternative management options...
March 2017: Current Neurology and Neuroscience Reports
https://www.readbyqxmd.com/read/28315956/axonal-transport-deficits-in-multiple-sclerosis-spiraling-into-the-abyss
#15
REVIEW
Robert van den Berg, Casper C Hoogenraad, Rogier Q Hintzen
The transport of mitochondria and other cellular components along the axonal microtubule cytoskeleton plays an essential role in neuronal survival. Defects in this system have been linked to a large number of neurological disorders. In multiple sclerosis (MS) and associated models such as experimental autoimmune encephalomyelitis (EAE), alterations in axonal transport have been shown to exist before neurodegeneration occurs. Genome-wide association (GWA) studies have linked several motor proteins to MS susceptibility, while neuropathological studies have shown accumulations of proteins and organelles suggestive for transport deficits...
March 18, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28303450/dr%C3%AE-1-mog-35-55-treatment-reduces-lesion-volumes-and-improves-neurological-deficits-after-traumatic-brain-injury
#16
Liu Yang, Zhijia Liu, Honglei Ren, Lei Zhang, Siman Gao, Li Ren, Zhi Chai, Roberto Meza-Romero, Gil Benedek, Arthur A Vandenbark, Halina Offner, Minshu Li
Traumatic brain injury (TBI) results in severe neurological impairments without effective treatments. Inflammation appears to be an important contributor to key pathogenic events such as secondary brain injury following TBI and therefore serves as a promising target for novel therapies. We have recently demonstrated the ability of a molecular construct comprised of the human leukocyte antigen (HLA)-DRα1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRα1-MOG-35-55 construct) to reduce CNS inflammation and tissue injury in animal models of multiple sclerosis and ischemic stroke...
March 16, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28302008/mitochondria-targeted-antioxidants-as-a-prospective-therapeutic-strategy-for-multiple-sclerosis
#17
Elena K Fetisova, Boris V Chernyak, Galina A Korshunova, Maria S Muntyan, Vladimir P Skulachev
BACKGROUND: Multiple sclerosis (MS) is one of the most widespread chronic neurological diseases that manifests itself by progressive demyelination in the central nervous system. The study of MS pathogenesis begins with the onset of the relapsing-remitting phase of the disease, which becomes apparent due to microglia activation, neuroinflammation and demyelination/remyelination in the white matter. The following progressive phase is accompanied by severe neurological symptoms when demyelination and neurodegeneration are spread to both gray and white matter...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28299403/effects-of-ifn-%C3%AE-1a-and-ifn-%C3%AE-1b-treatment-on-the-expression-of-cytokines-inducible-nos-nos-type-ii-and-myelin-proteins-in-animal-model-of-multiple-sclerosis
#18
Natalia Lubina-Dąbrowska, Adam Stepień, Grzegorz Sulkowski, Beata Dąbrowska-Bouta, Józef Langfort, Małgorzata Chalimoniuk
The aim of this study was to investigate the effects of interferon (IFN)-β1a and IFN-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund's complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra)...
March 15, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28298899/decision-making-in-multiple-sclerosis-the-role-of-aversion-to-ambiguity-for-therapeutic-inertia-among-neurologists-discutir-ms
#19
Gustavo Saposnik, Angel P Sempere, Daniel Prefasi, Daniel Selchen, Christian C Ruff, Jorge Maurino, Philippe N Tobler
OBJECTIVES: Limited information is available on physician-related factors influencing therapeutic inertia (TI) in multiple sclerosis (MS). Our aim was to evaluate whether physicians' risk preferences are associated with TI in MS care, by applying concepts from behavioral economics. DESIGN: In this cross-sectional study, participants answered questions regarding the management of 20 MS case scenarios, completed 3 surveys, and 4 experimental paradigms based on behavioral economics...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28298841/etiological-profile-of-noncompressive-myelopathies-in-a-tertiary-care-hospital-of-northeast-india
#20
Ashok Kumar Kayal, Munindra Goswami, Marami Das, Lakhshya Jyoti Basumatary, Suvorit Subhas Bhowmick, Baiakmenlang Synmon
BACKGROUND: The discovery of antibodies against aquaporin-4 and evolving concepts of noncompressive myelopathies in the 21(st) century have made a major impact on the etiological profile of these diseases, with few cases turning out to be idiopathic. OBJECTIVE: To find causes of noncompressive myelopathy in a tertiary care hospital of Northeast India. MATERIALS AND METHODS: An observational study was carried out in the Neurology Department of Gauhati Medical College, Guwahati, from September 2013 to February 2016...
January 2017: Annals of Indian Academy of Neurology
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