Data_Sheet_1_Participants’ perspectives of “NeuroSask: Active and Connect”—a virtual chronic disease management program for individuals with a neurological condition.docx

IntroductionNeurological conditions account from more than half of Canadians requiring chronic care. Both physical activity and the development of a self-management skillset are critical components supporting individuals with chronic health conditions. “NeuroSask: Active and Connected” is a virtual chronic disease management program offering twice weekly neuro-physiotherapist directed “active” exercise sessions, followed by weekly knowledge-exchange “connect” sessions with invited guest experts. NeuroSask was launched April 2020 in response to the restricted services and supports for people with neurological conditions. The program aimed to provide seated physical activity, social interaction, and access to expertise in neurological conditions and neurorehabilitation. A program evaluation of NeuroSask was conducted to gain participants’ perspectives.MethodsAll participants registered for the NeuroSask program were invited to complete optional online surveys (SurveyMonkey) circulated by email at 3 occasions post-program launch: 10 weeks, 1 year, and 2 years. Participants could complete any one or all of the surveys, at their discretion. The number of potential respondents changed dependent on the total number of participants registered for NeuroSask at the time the survey was circulated. Questions were co-designed by multi-stakeholder team members. Descriptive statistics were used for closed-ended questions and a reflexive thematic analysis was completed with coding conducted in NVivo 12 Plus for open-ended text.ResultsResponse rates (participants/registrants) were as follows: 10-week survey 260/793, one year survey 326/1224, and 2-year survey 434/1989. 90% of participants reported being in either the age categories of 40–59 years or above 60 years. 75% of both survey respondents and program registrants were female. 70% of both survey respondents and program registrants reported a diagnosis of multiple sclerosis and 30% reported other neurological conditions. Survey respondents were from all ten Canadian provinces, with 45% reporting living outside of large cities. Respondents reported preferring online vs. in person format for this type of programming. Three main themes, and eight corresponding subthemes were identified highlighting the perceived impact and key components of the NeuroSask program: Theme 1 “together in a positive and encouraging environment” (subthemes 1a: connection, 1b: empowerment); Theme 2 “access to enthusiastic qualified leaders from home” (subthemes 2a: leader characteristics, 2b: accessibility, 2c: program logistics); Theme 3 “being able to enjoy everyday life” (subthemes 3a: symptom benefits and beyond, 3b: carry-over, 3c: keep going, please do not cancel).ConclusionNeuroSask is an example of an accessible and meaningful virtual approach to providing ongoing support for some individuals with neurological conditions. It was perceived as beneficial for fostering community and connection in a positive environment with perceived benefits extending beyond symptom management to participant reported improvements in function, daily life, and disease experience.</p

Analysis of Nuclear Export Sequence Regions of FUS-Related RNA-Binding Proteins in Essential Tremor

<div><p>Background and Objective</p><p>Genes encoding RNA-binding proteins, including FUS and TDP43, play a central role in different neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Recently, a mutation located in the nuclear export signal (NES) of the <i>FUS</i> gene has been reported to cause an autosomal dominant form of familial Essential tremor.</p><p>Material and Methods</p><p>We sequenced the exons coding the NES domains of five RNA-binding proteins (<i>TARDBP</i>, <i>hnRNPA2B1</i>, <i>hnRNPA1</i>, <i>TAF15</i> and <i>EWSR1</i>) that have been previously implicated in neurodegeneration in a series of 257 essential tremor (ET) cases and 376 healthy controls. We genotyped 404 additional ET subjects and 510 healthy controls to assess the frequency of the EWSR1 p.R471C substitution.</p><p>Results</p><p>We identified a rare EWSR1 p.R471C substitution, which is highly conserved, in a single subject with familial ET. The pathogenicity of this substitution remains equivocal, as DNA samples from relatives were not available and the genotyping of 404 additional ET subjects did not reveal any further carriers. No other variants were observed with significant allele frequency differences compared to controls in the NES coding regions.</p><p>Conclusions</p><p>The present study demonstrates that the NES domains of RNA-binding proteins are highly conserved. The role of the EWSR1 p.R471C substitution needs to be further evaluated in future studies.</p></div

Demographic data of Discovery and Replication Samples.

<p>Fam ET = familial essential tremor; Spo ET = sporadic essential tremor; Cont = Healthy controls; y = years; AAO = age at onset; SD = standard deviation; NA = data not applicable.</p><p>*Age was not available for 57 subjects (6 familial, 17 sporadic cases and 34 controls) from Replication Sample 1 and for 11 subjects (1 familial, 3 sporadic cases and 7 controls) from Replication Sample 2.</p>§<p>AAO was not available for 22 subjects (10 familial and 12 sporadic cases) from the Discovery Sample, for 27 subjects (14 familial and 13 sporadic cases) from the Replication Sample 1 and for 6 subjects (4 familial and 2 sporadic cases) from Replication Sample 2.</p><p>Demographic data of Discovery and Replication Samples.</p

Nuclear export signal (NES) prediction of candidate proteins based on the NetNES 1.1 prediction tool [16].

<p>NN = neural network algorithm; HMM = hidden Markov Model algorithm; NES score = combination of NN and HMM algorithms; QGSY-rich = glutamine, glycine, serine, tyrosine rich region; G-rich = glycine rich region; RRM = RNA recognition motif; RGG = Arg-Gly-Gly rich domain; Zn = zinc finger domain; The ? denotes that the NES predicted location does not surpass the NetNES established threshold. The thin black line denotes the prion-like domain location and the thick black line represents the highest score core region according to the Alberti algorithm <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0111989#pone.0111989-Alberti1" target="_blank">[20]</a>.</p