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https://www.readbyqxmd.com/read/28634006/testosterone-differentially-affects-t-cells-and-neurons-in-murine-and-human-models-of-neuroinflammation-and-neurodegeneration
#1
Megan G Massa, Christina David, Stefanie Jörg, Johannes Berg, Barbara Gisevius, Sarah Hirschberg, Ralf A Linker, Ralf Gold, Aiden Haghikia
The high female-to-male sex ratio of multiple sclerosis (MS) prevalence has continuously confounded researchers, especially in light of male patients' accelerated disease course at later stages of MS. Although multiple studies have concentrated on estrogenic mechanisms of disease modulation, fairly little attention has been paid to androgenic effects in a female system, and even fewer studies have attempted to dissociate hormonal effects on the neurodegenerative and neuroinflammatory processes of MS. Herein, we demonstrate the differential effects of hormone treatment on the acute inflammatory and chronic neurodegenerative phases of murine experimental autoimmune encephalomyelitis...
July 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28627962/plasma-neurofilament-light-chain-levels-in-patients-with-ms-switching-from-injectable-therapies-to-fingolimod
#2
Fredrik Piehl, Ingrid Kockum, Mohsen Khademi, Kaj Blennow, Jan Lycke, Henrik Zetterberg, Tomas Olsson
BACKGROUND: Neurofilament light chain (NFL) is a cerebrospinal fluid (CSF) marker of neuroaxonal damage in multiple sclerosis (MS). OBJECTIVE: To determine the correlation of NFL in CSF and serum/plasma, and in plasma after switching from injectable MS therapies to fingolimod. METHODS: A first cohort consisted of MS patients ( n = 39) and neurological disease controls ( n = 27) where CSF and plasma/serum had been collected for diagnostic purposes...
June 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28618066/assessment-of-ferritin-content-in-multiple-sclerosis-brains-using-temperature-induced-r-2-changes
#3
Christoph Birkl, Daniele Carassiti, Fariha Hussain, Christian Langkammer, Christian Enzinger, Franz Fazekas, Klaus Schmierer, Stefan Ropele
PURPOSE: Current MRI techniques cannot reliably assess iron content in white matter due to the confounding diamagnetic effect of myelin. The purpose of this study was to validate with histology a novel iron mapping technique that uses the temperature dependency of the paramagnetic susceptibility in multiple sclerosis (MS) brains, where white matter has been reported to show significant variations in iron content. METHODS: We investigated post mortem brain tissue from three MS patients and one control subject...
June 15, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/28617363/-diagnostic-value-of-immunoglobulin-free-light-chains-at-the-debut-of-multiple-sclerosis
#4
V D Nazarov, G S Makshakov, A V Mazing, E A Surkova, V S Krasnov, M V Shumilina, N A Totolyan, E P Evdoshenko, S V Lapin, V L Emanuel, A A Skoromets
AIM: To evaluate the diagnostic value of determination of free immunoglobulin light chains (IgG) in the debut of multiple sclerosis (MS). MATERIAL AND METHODS: Data from 226 patients, including 111 patients with clinically isolated syndrome with conversion to multiple sclerosis within the first 2 years of the disease (group 1), 49 patients with clinically isolated syndrome who did not develop multiple sclerosis within the first 2 years of the disease (group 2), 20 patients with other inflammatory diseases of the central nervous system (group 3) were analyzed...
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
https://www.readbyqxmd.com/read/28605269/physical-activity-sedentary-behavior-and-physical-function-in-older-adults-with-multiple-sclerosis
#5
Katie L Cederberg, Robert W Motl, Edward McAuley
Older adults with multiple sclerosis(MS) experience the combined effects of aging and a chronic, disabling neurological disease on physical activity, sedentary behavior, and physical function. OBJECTIVE: This study examined associations among light and moderate-to-vigorous physical activity(LPA and MVPA), sedentary behavior, and physical function in older adults with MS. METHOD: Forty older adults with MS(median age=60 years) who had a median Expanded Disability Status Scale score of 4...
June 12, 2017: Journal of Aging and Physical Activity
https://www.readbyqxmd.com/read/28601282/kflc-index-utility-in-multiple-sclerosis-diagnosis-further-confirmation
#6
M Pieri, M Storto, S Pignalosa, R Zenobi, F Buttari, S Bernardini, D Centonze, M Dessi
The Multiple Sclerosis (MS) diagnosis is based on dissemination of focal lesions in time and space. The free light chains (FLCs) determination might be a sensitive alternative to oligoclonal bands assay. The study aim was to redefine sensitivity, specificity of the kFLC Index cut-off. We analyzed serum and cerebrospinal fluid of 176 patients, with different neurological disorders. We obtained a cut off of 12,3 for kFLC Index with a sensitivity and specificity of 93% and 100% respectively. Our data confirm that the kFLC Index is a valid tool in the diagnosis of MS...
August 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28566288/point-mutations-in-transactive-response-dna-binding-protein-43-tdp-43-s-n-terminal-domain-compromise-its-stability-dimerization-and-functions
#7
Miguel Mompeán, Valentina Romano, David Pantoja-Uceda, Cristiana Stuani, Francisco E Baralle, Emanuele Buratti, Douglas V Laurents
Transactive response DNA-binding protein 43 (TDP-43) performs multiple tasks in mRNA processing, transport and translational regulation, but it also forms aggregates implicated in amyotrophic lateral sclerosis (ALS). TDP-43's N-terminal domain (NTD) is important for these activities and dysfunctions; however, there is an open debate about whether or not it adopts a specifically folded, stable structure. Here, we studied NTD mutations designed to destabilize its structure utilizing NMR and fluorescence spectroscopies, analytical ultracentrifugation, splicing assays and in cell microscopy...
May 31, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28560747/can-assessment-of-afferent-thermal-sensitivity-shed-light-into-multiple-sclerosis-diagnosis-and-disease-progression
#8
R Matthew Brothers
Multiple Sclerosis (MS) is a disabling disease effecting approximately 2.5 million people worldwide. Common symptomology experienced by MS patients include complications with: vision, motor control, fatigue, bladder control, and sensory function. This article is protected by copyright. All rights reserved.
May 31, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28560740/acutely-damaged-axons-are-remyelinated-in-multiple-sclerosis-and-experimental-models-of-demyelination
#9
Verena Schultz, Franziska van der Meer, Claudia Wrzos, Uta Scheidt, Erik Bahn, Christine Stadelmann, Wolfgang Brück, Andreas Junker
Remyelination is in the center of new therapies for the treatment of multiple sclerosis to resolve and improve disease symptoms and protect axons from further damage. Although remyelination is considered beneficial in the long term, it is not known, whether this is also the case early in lesion formation. Additionally, the precise timing of acute axonal damage and remyelination has not been assessed so far. To shed light onto the interrelation between axons and the myelin sheath during de- and remyelination, we employed cuprizone- and focal lysolecithin-induced demyelination and performed time course experiments assessing the evolution of early and late stage remyelination and axonal damage...
August 2017: Glia
https://www.readbyqxmd.com/read/28537100/cerebrospinal-fluid-neurofilament-light-levels-mark-grey-matter-volume-in-clinically-isolated-syndrome-suggestive-of-multiple-sclerosis
#10
Carla Tortorella, Vita Direnzo, Maddalena Ruggieri, Stefano Zoccolella, Mariangela Mastrapasqua, Mariangela D'Onghia, Damiano Paolicelli, Franca Di Cuonzo, Claudio Gasperini, Maria Trojano
BACKGROUND: Brain atrophy is a known marker of irreversible tissue damage in multiple sclerosis (MS). Cerebrospinal fluid (CSF) osteopontin (OPN) and neurofilament light chain (NF-L) have been proposed as candidate surrogate markers of inflammatory and neurodegenerative processes in MS. OBJECTIVE: To evaluate the relationship between CSF NF-L and OPN levels and brain grey and white matter volumes in patients with clinically isolated syndrome (CIS) suggestive of MS...
May 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28521040/cortical-remyelination-is-heterogeneous-in-multiple-sclerosis
#11
Eva M M Strijbis, Evert-Jan Kooi, Paul van der Valk, Jeroen J G Geurts
Cortical lesions (CLs) are an important component of multiple sclerosis (MS) pathology; they correlate better with physical disability and cognitive impairment than white matter lesions (WMLs). Because remyelination can be extensive in CLs, we quantified remyelination in gray matter (GM) and white matter (WM), addressing oligodendrocyte (OGD) maturation state and clinical relevance of remyelination. Brain tissue samples from 21 chronic MS patients were immunohistochemically stained for myelin proteolipid protein, Olig2, which is strongly expressed in OGD precursor cells (OPCs), but weakly expressed in mature OGDs and other OGD markers...
May 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28516256/-skin-diseases-associated-with-environmental-factors
#12
REVIEW
Vera Mahler
BACKGROUND: Multiple environmental exposures may derange the regulatory and repair mechanisms of the skin and lead to dermatological disease. OBJECTIVES: Provide an overview of non-allergic skin diseases associated with environmental factors. MATERIALS AND METHODS: Review of current scientific evidence for associations of non-allergic skin diseases with environmental exposures: irritation, chemicals, infection, UV-radiation, temperature. RESULTS: Predisposition (constitution e...
June 2017: Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz
https://www.readbyqxmd.com/read/28512753/serum-neurofilament-light-a-biomarker-of-neuronal-damage-in-multiple-sclerosis
#13
Giulio Disanto, Christian Barro, Pascal Benkert, Yvonne Naegelin, Sabine Schädelin, Antonella Giardiello, Chiara Zecca, Kaj Blennow, Henrik Zetterberg, David Leppert, Ludwig Kappos, Claudio Gobbi, Jens Kuhle
OBJECTIVE: Neurofilament light chains (NfL) are unique to neuronal cells, are shed to the CSF and are detectable at low concentrations in peripheral blood. Various diseases causing neuronal damage have resulted in elevated CSF concentrations. We explored the value of an ultrasensitive single-molecule array (Simoa) serum NfL (sNfL) assay in MS. METHODS: sNfL levels were measured in healthy controls (HC, n=254) and two independent MS cohorts: (1) cross-sectional with paired serum and CSF samples (n=142); (2) longitudinal with repeated serum sampling (n=246, median (IQR) follow-up 3...
May 16, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28470769/how-human-iggs-against-myelin-basic-protein-mbp-recognize-oligopeptides-and-mbp
#14
Sergey Belov, Valentina N Buneva, Georgy A Nevinsky
Myelin basic protein (MBP) is a major protein of myelin-proteolipid shell of axons, and it plays an important role in pathogenesis of multiple sclerosis. In the literature, there are no data on how antibodies recognize different protein antigens including MBP. A stepwise increase in ligand complexity was used to estimate the relative contributions of virtually every amino acid residue (AA) of a specific 12-mer LSRFSWGAEGQK oligopeptide corresponding to immunodominant sequence of MBP to the light chains and to intact anti-MBP IgGs from sera of patients with multiple sclerosis...
May 4, 2017: Journal of Molecular Recognition: JMR
https://www.readbyqxmd.com/read/28466383/photopheresis-advances-and-use-in-systemic-sclerosis
#15
REVIEW
Xiaolong Alan Zhou, Jaehyuk Choi
PURPOSE OF REVIEW: Extracorporeal photochemotherapy (photopheresis, ECP) is a cell-based immunomodulatory treatment that separates leukocytes from peripheral blood, exposes them to a photosensitizing agent followed by ultraviolet A light, and then reinfuses them back into the patient. ECP has been found to be effective for graft versus host disease, transplant rejection, and various autoimmune diseases. The mechanism is not well understood but studies have shown clinical benefit in the treatment of systemic sclerosis (SSc)...
June 2017: Current Rheumatology Reports
https://www.readbyqxmd.com/read/28457198/effectiveness-of-cognitive-rehabilitation-for-people-with-multiple-sclerosis-a-meta-synthesis-of-patient-perspectives
#16
Olga A Klein, Avril Drummond, Jacqueline R Mhizha-Murira, Laura Mansford, Roshan dasNair
While previous randomised controlled trials and meta-analyses offer only limited evidence for the effectiveness of cognitive rehabilitation, qualitative studies examining patient perspectives report more positive outcomes. This meta-synthesis of qualitative studies examined patient perspectives of cognitive rehabilitation for memory, attention, and executive function problems in people with multiple sclerosis. Using set eligibility criteria, we screened electronic databases, reference lists, and academic networks for relevant papers...
May 1, 2017: Neuropsychological Rehabilitation
https://www.readbyqxmd.com/read/28444311/expression-of-als-ftd-linked-mutant-ccnf-in-zebrafish-leads-to-increased-cell-death-in-the-spinal-cord-and-an-aberrant-motor-phenotype
#17
Alison L Hogan, Emily K Don, Stephanie L Rayner, Albert Lee, Angela S Laird, Maxinne Watchon, Claire Winnick, Ingrid S Tarr, Marco Morsch, Jennifer A Fifita, Serene Gwee, Isabel Formella, Elinor Hortle, Kristy Yuan, Mark P Molloy, Kelly L Williams, Garth A Nicholson, Roger S Chung, Ian P Blair, Nicholas J Cole
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal neurodegenerative disease characterised by the death of upper and lower motor neurons. Approximately 10% of cases have a known family history of ALS and disease-linked mutations in multiple genes have been identified. ALS-linked mutations in CCNF were recently reported, however the pathogenic mechanisms associated with these mutations are yet to be established. To investigate possible disease mechanisms, we developed in vitro and in vivo models based on an ALS-linked missense mutation in CCNF...
April 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28444098/the-cerebrospinal-fluid-in-multiple-sclerosis-far-beyond-the-bands
#18
Renan Barros Domingues, Gustavo Bruniera Peres Fernandes, Fernando Brunale Vilela de Moura Leite, Charles Peter Tilbery, Rodrigo Barbosa Thomaz, Gisele Sampaio Silva, Cristóvão Luis Pitangueira Mangueira, Carlos Augusto Senne Soares
The cerebrospinal fluid analysis has been employed for supporting multiple sclerosis diagnosis and ruling out the differential diagnoses. The most classical findings reflect the inflammatory nature of the disease, including mild pleocytosis, mild protein increase, intrathecal synthesis of immunoglobulin G, and, most typically, the presence of oligoclonal bands. In recent years, new biomarkers have emerged in the context of multiple sclerosis. The search for new biomarkers reflect the need of a better evaluation of disease activity, disease progression, and treatment efficiency...
January 2017: Einstein
https://www.readbyqxmd.com/read/28415071/lower-physical-activity-in-persons-with-multiple-sclerosis-at-increased-fall-risk-a-cross-sectional-study
#19
Emerson Sebastião, Yvonne C Learmonth, Robert W Motl
Persons with multiple sclerosis (MS) often report being afraid of falling, and this may have effects on physical activity (PA) engagement. This study investigated PA levels in persons with MS as a function of fall risk categories. Forty-seven persons with MS participated in the study and were categorized into either increased fall risk (IFR; n = 21; 55.5 ± 9.0 years) or normal fall risk (NFR; n = 26; 51.2 ± 12.9 years) groups based on scores from the Activities-Balance Confidence scale. PA was measured by accelerometer and expressed as average steps per day, and time spent in sedentary behavior, light PA, and moderate to vigorous physical activity over the course of 7 consecutive days...
May 2017: American Journal of Physical Medicine & Rehabilitation
https://www.readbyqxmd.com/read/28412046/the-epigenetic-mechanism-for-discordance-of-autoimmunity-in-monozygotic-twins
#20
REVIEW
Zhongyuan Xiang, Yuanqing Yang, Christopher Chang, Qianjin Lu
Monozygotic twins share an identical DNA sequence but are not truly "identical". In fact, when it comes to health and disease, they may often display some level of phenotypic discordance. The cause of this discordance is often unknown. Epigenetic modifications such as DNA methylation, histone modification, and microRNAs-mediated regulation regulate gene expression and are sensitive to external stimuli. These modifications may be seen to bridge the gap between genetics and the environment. Over the years, the importance of epigenetics as a primary mechanism for the role that the environment plays in defining phenotype has been increasingly appreciated...
April 12, 2017: Journal of Autoimmunity
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