Neuropathic-like pain features and cross-sectional associations in rheumatoid arthritis

Introduction: Increasing evidence indicates that features suggestive of neuropathic pain may also be present in patients with common rheumatic conditions. The objective of this study was to examine neuropathic-like pain symptoms and associated factors in patients with rheumatoid arthritis. Methods: We used the painDETECT screening tool to identify possible or likely neuropathic pain in 159 outpatients with rheumatoid arthritis. Patients additionally completed other self-reported measures, while clinical measures were assessed to calculate the 28-joint Disease Activity Score. Univariate analyses and multivariable logistic regression were used to identify factors associated with neuropathic pain features. Results: According to the painDETECT, 27 patients (17.0 %) were classified as having likely neuropathic pain and 34 patients (21.4 %) as having possible neuropathic pain. Besides reporting more severe pain, patients with likely or possible neuropathic pain were more likely to meet the diagnostic criteria for fibromyalgia, to use analgesics, and to have more tender joints and a worse physical and mental health status as measured by the 36-item Short-Form health survey. In multivariable analysis, physical (P < 0.001) and mental health status (P = 0.006) remained significantly associated with neuropathic pain features, even after controlling for pain severity. Conclusions: These findings suggest that a sizeable proportion of patients with relatively well-controlled rheumatoid arthritis report symptoms suggestive of neuropathic pain. Neuropathic-like pain symptoms are independently associated with worse self-reported physical and mental health

Genomic basis of deep-water adaptation in Arctic Charr (Salvelinus alpinus) morphs

Funding information Natural Sciences and Engineering Research Council of Canada; Department of Fisheries and Oceans Canada Genomic Research and Development Initiative ACKNOWLEDGEMENTS Thanks to Parks Canada, the Nunatsiavut Government, the NunatuKavut Community Council, the Sivunivut Inuit Community Corporation, the Innu Nation, the Labrador Hunting and Fishing Association, and Newfoundland DFO Salmonids section, for sup- port of this study and tissue collection. Significant portions of labo- ratory work for genotyping were conducted by staff at Aquatic Biotechnology Laboratory at the Bedford Institute of Oceanography. Computing resources for bioinformatic analyses were provided by Compute Canada. Support for this study was provided by the Ocean Frontier Institute, a Genomics Research and Development Initiative (GRDI) Grant, a Natural Sciences and Engineering Research Council (NSERC) Discovery Grant and Strategic Project Grant to I.R.B., the Weston Family Award for research at the Torngat Mountains Base Camp and an Atlantic Canada Opportunities Agency and Department of Tourism, Culture, Industry and Innovation grant al- located to the Labrador Institute.Peer reviewedPostprin

Mono-allelic KCNB2 variants lead to a neurodevelopmental syndrome caused by altered channel inactivation

International audienceIon channels mediate voltage fluxes or action potentials that are central to the functioning of excitable cells such as neurons. The KCNB family of voltage-gated potassium channels (Kv) consists of two members (KCNB1 and KCNB2) encoded by KCNB1 and KCNB2, respectively. These channels are major contributors to delayed rectifier potassium currents arising from the neuronal soma which modulate overall excitability of neurons. In this study, we identified several mono-allelic pathogenic missense variants in KCNB2, in individuals with a neurodevelopmental syndrome with epilepsy and autism in some individuals. Recurrent dysmorphisms included a broad forehead, synophrys, and digital anomalies. Additionally, we selected three variants where genetic transmission has not been assessed, from two epilepsy studies, for inclusion in our experiments. We characterized channel properties of these variants by expressing them in oocytes of Xenopus laevis and conducting cut-open oocyte voltage clamp electrophysiology. Our datasets indicate no significant change in absolute conductance and conductance-voltage relationships of most disease variants as compared to wild type (WT), when expressed either alone or co-expressed with WT-KCNB2. However, variants c.1141A>G (p.Thr381Ala) and c.641C>T (p.Thr214Met) show complete abrogation of currents when expressed alone with the former exhibiting a left shift in activation midpoint when expressed alone or with WT-KCNB2. The variants we studied, nevertheless, show collective features of increased inactivation shifted to hyperpolarized potentials. We suggest that the effects of the variants on channel inactivation result in hyper-excitability of neurons, which contributes to disease manifestations

FIRST RESULTS FROM DELCO AT PEPCalifornia Institute of Technology-Stanford Linear Accelerator Center and Stanford University Collaboration

No abstract availabl