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Symptoms relating to spasticity are common in multiple sclerosis (MS) and can be difficult to treat. We have investigated the efficacy, safety and tolerability of a standardized oromucosal whole plant cannabis-based medicine (CBM) containing delta-9 tetrahydrocannabinol (THC) and cannabidiol (CBD), upon spasticity in MS. A total of 189 subjects with(More)
Mutations in leucine-rich repeat kinase 2 (LRRK2) are strongly associated with late-onset autosomal dominant Parkinson's disease. We employed a new, parallel, compound-centric approach to identify a potent and selective LRRK2 inhibitor, LRRK2-IN-1, and demonstrated that inhibition of LRRK2 induces dephosphorylation of Ser910 and Ser935 and accumulation of(More)
An Arg present in the third transmembrane domain of all rhodopsin-like G-protein-coupled receptors is required for efficient signal transduction. Mutation of this Arg in the gonadotropin-releasing hormone receptor to Gln, His, or Lys abolished or severely impaired agonist-stimulated inositol phosphate generation, consistent with Arg having a role in(More)
BACKGROUND   Spasticity is a disabling complication of multiple sclerosis, affecting many patients with the condition. We report the first Phase 3 placebo-controlled study of an oral antispasticity agent to use an enriched study design. METHODS   A 19-week follow-up, multicentre, double-blind, randomized, placebo-controlled, parallel-group study in(More)
The outcome of pediatric ependymomas is difficult to predict based on clinical and histological parameters. To address this issue, we have performed a comparative genomic hybridization screen of 42 primary and 11 recurrent pediatric ependymomas and correlated the genetic findings with clinical outcome. Three distinct genetic patterns were identified in the(More)
The Vps34 (vacuolar protein sorting 34) class III PI3K (phosphoinositide 3-kinase) phosphorylates PtdIns (phosphatidylinositol) at endosomal membranes to generate PtdIns(3)P that regulates membrane trafficking processes via its ability to recruit a subset of proteins possessing PtdIns(3)P-binding PX (phox homology) and FYVE domains. In the present study, we(More)
A winner of the Nobel Prize, Werner Heisenberg was born in 1901 in Wurzberg, Germany. He studied physics at the University of Munich and for his Ph.D. wrote a dissertation on turbulence in fluid streams. Interested in Niels Bohrs account of the planetary atom, Heisenberg studied under Max Born at the University of Gottingen and then, in 1924, went to the(More)
BACKGROUND Muscle spasticity is common in multiple sclerosis (MS), occurring in more than 60% of patients. OBJECTIVE To compare Sativex with placebo in relieving symptoms of spasticity due to MS. METHODS A 15-week, multicenter, double-blind, randomized, placebo-controlled, parallel-group study in 337 subjects with MS spasticity not fully relieved with(More)
BACKGROUND Open-label studies are not ideal for providing robust evidence for long-term maintenance of efficacy of medicines, especially where medicines provide symptom relief and where long-term use of a placebo may be problematic and not ethical. OBJECTIVE To evaluate the maintenance of efficacy of Sativex in subjects who have gained long-term(More)
AIMS To determine the likelihood of finding an antivaccination site on the world wide web and to characterise their explicit claims and rhetorical appeals. METHODS Using "vaccination" and "immunisation", examining the first 10 sites displayed on seven leading search engines. Detailed examination of content of 100 antivaccination sites found on Google. (More)