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Xiao-Dong Zhang, Chun-Xia He, Jun Cheng, Jing Wen, Peng-Yun Li, Na Wang, Guang Li, Xiao-Rong Zeng, Ji-Min Cao, Yan Yang
Background: We previously have proved that sodium tanshinone II-A sulfonate (DS-201), a derivative of traditional Chinese medicinal herb Danshen (Salvia miltiorrhiza), is an opener and vasodilator of BKCa channel in the vascular smooth muscle cells (VSMCs). Vascular tension is closely associated with Ca2+ dynamics and activation of BKCa channel may not be the sole mechanism for the relaxation of the vascular tension by DS-201. Therefore, we hypothesized that the vasorelaxing effect of DS-20 may be also related to Ca2+ channel and cytoplasmic Ca2+ level in the VSMCs...
2018: Frontiers in Pharmacology
Irene Eriksson, Joris Komen, Fredrik Piehl, Rickard E Malmström, Björn Wettermark, Mia von Euler
PURPOSE: The purpose of this study is to describe the utilization of disease-modifying treatments (DMTs) in relapsing-remitting multiple sclerosis (MS) and assess the impact of both the introduction of new drugs and treatment recommendations (local recommendation on rituximab use issued at the largest MS clinic in Stockholm and regional Drug and Therapeutics Committee (DTC) recommendation on how dimethyl fumarate should be used). METHODS: Interrupted time series analyses using monthly data on all MS patients treated with DMTs in the Stockholm County, Sweden, from January 2011 to December 2017...
February 10, 2018: European Journal of Clinical Pharmacology
Zsigmond Tamas Kincses, László Vécsei
MRI is the cornerstone of the diagnosis of multiple sclerosis (MS), and in recent years it was advocated for the follow up of the efficacy of the ever-growing number of disease modifying treatments (DMT). While in the clinical practice the most important biomarkers are still the T2 and T1 enhancing lesion burden, clinical studies are already utilising atrophy estimation. These measures cover a vast majority of MS pathology, namely the perivenular inflammation and gliosis in the white matter lesions as well as grey matter pathology...
February 10, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Jennifer S Graves, Lisa F Barcellos, Steve Simpson, Anita Belman, Rui Lin, Bruce V Taylor, Anne-Louise Ponsonby, Terence Dwyer, Lauren Krupp, Emmanuelle Waubant, Ingrid A F van der Mei
BACKGROUND: While common variant non-HLA (human leukocyte antigen) alleles have been associated with MS risk, their role in disease course is less clear. We sought to determine whether established multiple sclerosis (MS) genetic susceptibility factors are associated with relapse rate in children and an independent cohort of adults with MS. METHODS: Genotyping was performed for 182 children with MS or clinically isolated syndrome with high risk for MS from two Pediatric MS Centers...
January 2018: Multiple Sclerosis and related Disorders
Tomoyasu Bunai, Tatsuhiro Terada, Satoshi Kono, Masamichi Yokokura, Etsuji Yoshikawa, Masami Futatsubashi, Hiroaki Miyajima, Yasuomi Ouchi
INTRODUCTION: Chronic activation of microglia accelerates the neurodegenerative process in multiple sclerosis (MS). Although disease modifying therapy (DMT) is reportedly effective for neuroinflammatory responses in MS, the progression of neuroinflammation after DMT remains unclear. METHODS: We evaluated microglial activation in six clinically stable relapsing-remitting MS patients after DMT by quantifying changes in translocator protein (TSPO) density using PET with [11C]DPA713, a selective TSPO tracer for microglial activation...
February 15, 2018: Journal of the Neurological Sciences
Emmanuel Coudeyre, Christelle Nguyen, Aurore Chabaud, Bruno Pereira, Johann Beaudreuil, Jean-Marie Coudreuse, Philippe Deat, Frédéric Sailhan, Alain Lorenzo, François Rannou
OBJECTIVE: To develop a decision-making tool (DMT) to facilitate the prescription of knee orthoses for patients with osteoarthritis (OA) in daily practice. METHODS: A steering committee gathered a multidisciplinary task force experienced in OA management/clinical research. Two members performed a literature review with qualitative analysis of the highest-quality randomized controlled trials and practice guidelines to confirm evidence concerning knee orthosis for OA...
February 2, 2018: Annals of Physical and Rehabilitation Medicine
Stephan Schmidt, Jürgen Koehler, Christine Winterstein, Petra Schicklmaier, Boris Kallmann
Background: In relapsing-remitting multiple sclerosis (RRMS), 'no evidence of disease activity' (NEDA) is regarded as a key treatment goal. The increasing number of treatments allows for individualized treatment optimization in patients with suboptimal response to first-line disease-modifying therapies (DMTs). Therefore, monitoring of clinical and subclinical disease activity on DMTs has been recognized as an important component of long-term patient management. Methods: EPIDEM was a multicenter non-interventional retrospective study in a large cohort of RRMS patients receiving injectable DMTs for at least 2 years in outpatient centers throughout Germany...
2018: Therapeutic Advances in Neurological Disorders
Floriane Calocer, Olivier Dejardin, Karine Droulon, Guy Launoy, Gilles Defer
OBJECTIVE: In MS, Socio-Economic status (SES) may influence healthcare and access to disease-modifying treatments (DMTs). Optimising delays to switch patients to a second-line DMT may hamper disease progression most effectively and achieve long term disease control. The objective of this study is to identify the influence of SES on the delay between first and second line DMT in RRMS patients, in Western-Normandy, France. METHODS: The association between SES and the delay to access a second-line DMT were studied using data from the MS registry of Western-Normandy including 733 patients with a diagnosis of RRMS during the period in question [1982-2011]...
2018: PloS One
Yu Qiang Soh, Jodhbir S Mehta
PURPOSE: Fuchs endothelial corneal dystrophy (FECD) is an acquired corneal endotheliopathy and is one of the most common indications for corneal transplantation surgery worldwide. Endothelial keratoplasty (EK) is the most popular form of corneal transplantation for FECD. In standard EK surgery, the patient's corneal endothelium and basement membrane [ie, Descemet membrane (DM)] are first removed, followed by transplantation of donor tissue that comprises allogenic corneal endothelial cells, DM, and corneal stroma of variable thickness...
January 30, 2018: Cornea
Jonathan Hamill, Jaime Hallak, Serdar M Dursun, Glen Baker
Ayahuasca, a traditional Amazonian decoction with psychoactive properties, is made from bark of the Banisteriopsis caapi vine (contains beta-carboline alkaloids) and leaves of the Psychotria viridis bush (supply the hallucinogen N,N-dimethyltryptamine (DMT)). Originally used by indigenous shamans for the purposes of spirit communication, magical experiences, healing, and religious rituals, across several South American countries ayahuasca has been incorporated into folk medicine and spiritual healing, and several Brazilian churches use it routinely to foster spiritual experience...
January 24, 2018: Current Neuropharmacology
X Armoiry, A Kan, G J Melendez-Torres, R Court, P Sutcliffe, P Auguste, J Madan, C Counsell, A Clarke
BACKGROUND: Beta-interferon (IFN-β) and glatiramer acetate (GA) have been evaluated in people with clinically isolated syndrome (CIS) with the aim to delay a second clinical attack and a diagnosis of clinically definite multiple sclerosis (CDMS). We systematically reviewed trials evaluating the short- and long-term clinical effectiveness of these drugs in CIS. METHODS: We searched multiple electronic databases. We selected randomised controlled studies (RCTs) conducted in CIS patients and where the interventions were IFN-β and GA...
January 22, 2018: Journal of Neurology
Oscar Fernández, Mario Delvecchio, Gilles Edan, Sten Fredrikson, Gavin Giovannoni, Hans-Peter Hartung, Eva Havrdova, Ludwig Kappos, Carlo Pozzilli, Per Soelberg Soerensen, Björn Tackenberg, Patrick Vermersch, Giancarlo Comi
BACKGROUND AND PURPOSE: The European Charcot Foundation supported development of a set of surveys to understand current practice patterns for diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarises survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. METHODS: A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe...
January 21, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Benjamin MacCormick, Thu V Vuong, Emma R Master
A chemo-enzymatic pathway was developed to transform 4-O-methylglucuronic acid (MeGlcpA) containing xylo-oligosaccharides from beechwood into clickable monomers capable of polymerizing at room temperature and in aqueous conditions to form unique polytriazoles. While the gluco-oligosaccharide oxidase (GOOX) from Sarocladium strictum was used to oxidize C6-propargylated oligosaccharides, the acid-amine coupling reagents EDAC and DMT-MM were employed and compared for their ability to append click functionalities to carboxylic acid groups of enzyme-treated oligosaccharides...
January 17, 2018: Biomacromolecules
Michał Gładysz, Piotr Ruszkowski, Jan Milecki
We describe synthesis of novel acyclic nucleoside analogues which are building blocks for CuAAC reaction and their activity against two types of human cancer cell lines (HeLa, KB). Three of chosen compounds show promising cytotoxic activity. Synthesis pathway starting from simple and easily accessible substrates employing DMT or TBDPS protective groups is described. Adenosine and thymidine analogues containing alkyne moiety and adenosine analogue containing azido group were synthesized. The obtained units showed ability of forming triazole motif under the CuAAC reaction conditions...
January 16, 2018: Nucleosides, Nucleotides & Nucleic Acids
N N Ledentsov, V A Shchukin, V P Kalosha, N N Ledentsov, J-R Kropp, M Agustin, Ł Chorchos, G Stępniak, J P Turkiewicz, J-W Shi
Oxide-confined vertical cavity surface emitting lasers (VCSELs) with anti-waveguiding AlAs-rich core presently attract a lot of attention. Anti-waveguiding cavity enables the maximum possible optical confinement of the VCSEL mode ("λ/2 design"), increases its oscillator strength and reduces dramatically the optical power accumulated in the VCSEL mesa regions outside the aperture. VCSEL designs are suggested that favor single transverse mode operation. Modeling including current-induced and absorption-induced overheating shows that the preference for the transverse fundamental mode persists up to 10 mA current at 5 µm aperture diameter...
January 8, 2018: Optics Express
Lu Zhang, Xuezhi Hong, Xiaodan Pang, Oskars Ozolins, Aleksejs Udalcovs, Richard Schatz, Changjian Guo, Junwei Zhang, Fredrik Nordwall, Klaus M Engenhardt, Urban Westergren, Sergei Popov, Gunnar Jacobsen, Shilin Xiao, Weisheng Hu, Jiajia Chen
We experimentally demonstrate the transmission of a 200 Gbit/s discrete multitone (DMT) at the soft forward error correction limit in an intensity-modulation direct-detection system with a single C-band packaged distributed feedback laser and traveling-wave electro absorption modulator (DFB-TWEAM), digital-to-analog converter and photodiode. The bit-power loaded DMT signal is transmitted over 1.6 km standard single-mode fiber with a net rate of 166.7 Gbit/s, achieving an effective electrical spectrum efficiency of 4...
January 15, 2018: Optics Letters
Edward J D Webb, David Meads, Ieva Eskyte, Natalie King, Naila Dracup, Jeremy Chataway, Helen L Ford, Joachim Marti, Sue H Pavitt, Klaus Schmierer, Ana Manzano
BACKGROUND: Multiple sclerosis (MS) is a chronic disabling, inflammatory, and degenerative disease of the central nervous system that, in most cases, requires long-term disease-modifying treatment (DMT). The drugs used vary in efficacy and adverse effect profiles. Several studies have used attribute-based stated-preference methods, primarily to investigate patient preferences for initiating or escalating DMT. OBJECTIVES: To conduct a systematic review of attribute-based stated-preference studies in people with MS to identify common methods employed and to assess study quality, with reference to the specific challenges of this disease area...
January 8, 2018: Patient
Mathias Granqvist, Malin Boremalm, Amyar Poorghobad, Anders Svenningsson, Jonatan Salzer, Thomas Frisell, Fredrik Piehl
Importance: Comparative real-world effectiveness studies of initial disease-modifying treatment (DMT) choices for relapsing-remitting multiple sclerosis (RRMS) that include rituximab are lacking. Objective: To assess the effectiveness and drug discontinuation rates of rituximab among patients with newly diagnosed RRMS compared with injectable DMTs, dimethyl fumarate, fingolimod, or natalizumab. Design, Setting, and Patients: This retrospective cohort study used prospectively collected data to examine specialized care of 2 Swedish county-based community samples of patients with RRMS...
January 8, 2018: JAMA Neurology
Julien Billières, Hermès Miozzari, Anne Lübbeke, Didier Hannouche
Degenerative meniscal tears (DMT) are common, often asymptomatic, and are associated with early-stage knee osteoarthritis in patients over 35 years of age. Conservative treatment, including exercise, physiotherapy and pain medication, should be offered as a first management approach for patients with symptomatic DMT. The indication for partial arthroscopic meniscectomy should be considered carefully, and based on specific criteria. Recently, several randomized controlled studies comparing partial medial meniscectomy to conservative treatment or to a sham procedure have questioned the effectiveness of surgical treatment of these lesions...
December 13, 2017: Revue Médicale Suisse
James John Marriott, Hui Chen, Randall Fransoo, Ruth Ann Marrie
BACKGROUND: Severe relapses that required treatment were important outcomes in the sentinel trials of disease-modifying therapy (DMT). Identifying such relapses in administrative data would allow comparative-effectiveness studies of DMTs to be conducted in real-world clinical settings. METHODS: All relapsing-remitting (RRMS) and secondary-progressive (SPMS) patients living in Manitoba between 1999 and 2015 were identified using a validated case definition and linkage to the Manitoba MS Clinic database...
December 2, 2017: Multiple Sclerosis and related Disorders
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