Medicine and Health Sciences Commons^™

A Randomized Placebo-Controlled Phase 3 Trial Of An Antisense Oligonucleotide, Drisapersen, In Duchenne Muscular Dystrophy, Nathalie Goemans, Eugenio Mercuri, Elena Belousova, Hirofumi Komaki, Alberto Dubrovsky, Craig M Mcdonald, John E Kraus, Afrodite Lourbakos, Zhengning Lin, Giles Campion, Susanne X Wang, Craig Campbell, Demand Iii Study Group

Paediatrics Publications

This 48-week, randomized, placebo-controlled phase 3 study (DMD114044; NCT01254019) evaluated efficacy and safety of subcutaneous drisapersen 6 mg/kg/week in 186 ambulant boys aged ≥5 years, with Duchenne muscular dystrophy (DMD) resulting from an exon 51 skipping amenable mutation. Drisapersen was generally well tolerated, with injection-site reactions and renal events as most commonly reported adverse events. A nonsignificant treatment difference (P = 0.415) in the change from baseline in six-minute walk distance (6MWD; primary efficacy endpoint) of 10.3 meters in favor of drisapersen was observed at week 48. Key secondary efficacy endpoints (North Star Ambulatory Assessment, 4-stair climb ascent velocity, and …

Peripheral Blood Epi-Signature Of Claes-Jensen Syndrome Enables Sensitive And Specific Identification Of Patients And Healthy Carriers With Pathogenic Mutations In Kdm5c., Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

Background: Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the KDM5C gene. Kdm5c is a histone lysine demethylase involved in histone modifications and chromatin remodeling. Males with hemizygous mutations in KDM5C present with intellectual disability and facial dysmorphism, while most heterozygous female carriers are asymptomatic. We hypothesized that loss of KDM5C function may influence other components of the epigenomic machinery including DNA methylation in affected patients.

Results: Genome-wide DNA methylation analysis of 7 male patients affected with Claes-Jensen syndrome and 56 age- and sex-matched controls identified a specific DNA methylation defect (epi-signature) in the peripheral blood …

Genomic Dna Methylation-Derived Algorithm Enables Accurate Detection Of Malignant Prostate Tissues., Erfan Aref-Eshghi, Laila C Schenkel, Peter Ainsworth, Hanxin Lin, David I Rodenhiser, Jean-Claude Cutz, Bekim Sadikovic

Paediatrics Publications

Introduction: The current methodology involving diagnosis of prostate cancer (PCa) relies on the pathology examination of prostate needle biopsies, a method with high false negative rates partly due to temporospatial, molecular, and morphological heterogeneity of prostate adenocarcinoma. It is postulated that molecular markers have a potential to assign diagnosis to a considerable portion of undetected prostate tumors. This study examines the genome-wide DNA methylation changes in PCa in search of genomic markers for the development of a diagnostic algorithm for PCa screening.

Methods: Archival PCa and normal tissues were assessed using genomic DNA methylation arrays. Differentially methylated sites and regions …

Disruption To Functional Networks In Neonates With Perinatal Brain Injury Predicts Motor Skills At 8 Months, Annika C Linke, Conor Wild, Leire Zubiaurre-Elorza, Charlotte Herzmann, Hester Duffy, Victor K Han, David S C Lee, Rhodri Cusack

Paediatrics Publications

Objective

Functional connectivity magnetic resonance imaging (fcMRI) of neonates with perinatal brain injury could improve prediction of motor impairment before symptoms manifest, and establish how early brain organization relates to subsequent development. This cohort study is the first to describe and quantitatively assess functional brain networks and their relation to later motor skills in neonates with a diverse range of perinatal brain injuries.

Methods

Infants (n = 65, included in final analyses: n = 53) were recruited from the neonatal intensive care unit (NICU) and were stratified based on their age at birth (prematurevs. term), and on whether neuropathology …

Infants Born Large For Gestational Age And Developmental Attainment In Early Childhood, Cairina E Frank, Kathy N Speechley, Jennifer J Macnab, M Karen Campbell

Paediatrics Publications

Objectives

To investigate if an association exists between being born large for gestational age (LGA) and verbal ability or externalizing behaviour problems at ages 4-5 years.

Method

A secondary analysis was conducted using the National Longitudinal Survey of Children and Youth, including singleton births in 2004-2005 followed till 4-5 years (

Results

Infants born LGA were not found to be at increased risk for poor verbal ability (aOR: 1.16 [0.49,2.72] and aOR: 0.83 [0.37,1.87] for girls and boys, resp.) or externalizing behaviour problems (aOR: 1.24 [0.52,2.93] and aOR: 1.24 [0.66,2.36] for girls and boys, resp.). Social factors were found to …

Disturbed Eeg Sleep, Paranoid Cognition And Somatic Symptoms Identify Veterans With Post-Traumatic Stress Disorder, Harvey Moldofsky, Lorne Rothman, Robert Kleinman, Shawn G. Rhind, Don Richardson

MacDonald Franklin OSI Research Centre

Background

Chronic post-traumatic stress disorder (PTSD) behavioural symptoms and medically unexplainable somatic symptoms are reported to occur following the stressful experience of military combatants in war zones. Aims

To determine the contribution of disordered EEG sleep physiology in those military combatants who have unexplainable physical symptoms and PTSD behavioural difficulties following war-zone exposure. Method

This case-controlled study compared 59 veterans with chronic sleep disturbance with 39 veterans with DSM-IV and clinician-administered PTSD Scale diagnosed PTSD who were unresponsive to pharmacological and psychological treatments. All had standardised EEG polysomnography, computerised sleep EEG cyclical alternating pattern (CAP) as a measure of sleep …

Understanding Parkinson’S Through Visual Narratives: “I’M Not Mrs. Parkinson’S”, S. G. Lutz, Jeffrey D. Holmes, D. Rudman, A. M. Johnson, K. Ladonna, M. E. Jenkins

Occupational Therapy Publications

Although it is accepted that individuals with Parkinson’s disease (PD) must navigate challenges such as receiving their diagnosis, and changing daily occupations, little is known about how they navigate. The purpose of this study is to deepen the current understanding of the experience of living with PD and its implications for occupation through a narrative visual methodology (photo-elicitation). Methods: Six individuals with PD were asked to take photographs and share verbal narrative accounts to illustrate their experience of living with PD. Findings: Results highlight the interrelationship between occupation and identity, as many of the participants stories were interpreted as foregrounding …

Expanding Beyond Individualism: Engaging Critical Perspectives On Occupation., Alison J Gerlach, Gail Teachman, Debbie Rudman, Rebecca M Aldrich, Suzanne Huot

Occupational Therapy Publications

BACKGROUND: Perspectives that individualize occupation are poorly aligned with socially responsive and transformative occupation-focused research, education, and practice. Their predominant use in occupational therapy risks the perpetuation, rather than resolution, of occupational inequities.

AIM: In this paper, we problematize taken-for-granted individualistic analyses of occupation and illustrate how critical theoretical perspectives can reveal the ways in which structural factors beyond an individual's immediate control and environment shape occupational possibilities and occupational engagement.

METHOD: Using a critically reflexive approach, we draw on three distinct qualitative research studies to examine the potential of critical theorizing for expanding beyond a reliance on individualistic analyses …

Designing Effective Point Of Choice Prompts To Promote Active Transportation And Staircase Use At A Canadian University, Hieu Ly, Jennifer Irwin

Health Studies Publications

Objective: The purpose of this study was to determine the most suitable health messages and designs to create point-of-choice prompts for promoting active transportation and stair- case use that would appeal to undergraduate students. Participants: Undergraduate students (N 1⁄4 21; 71% women) were recruited during Fall (2016) and Winter (2017) semesters. Methods: Focus groups (50–80minutes each) were organized to obtain students’ feedback on the kind of messages and poster designs they found motivational. Inductive content analysis was performed on verbatim transcripts. Descriptive statistics were calculated to summarize demographic characteristics of participants. Results: The major themes revealed that participants: preferred simple …

Mathematical Abilities In Children With Developmental Language Disorder, Alexandra M. Cross, Lisa M.D. Archibald, Marc F. Joanisse

Health and Rehabilitation Sciences Publications

Purpose. The present paper provides a scoping review of the literature on mathematical abilities in developmental language disorder (DLD). Children with DLD typically struggle with learning in school, however the mechanism by which DLD impacts academic success is unclear. Mathematics involves demands in the multiple domains, and therefore holds potential for examining the relationship between language and academic performance on tasks mediated by verbal and non-verbal demands.

Methods. A scoping review was performed via computerized database searching to examine literature on mathematics and DLD. The 21 papers meeting inclusion criteria compared children with typical development or DLD on various tasks …

Feasibility And Fit Of A Mental Health Promotion Program For Lgbtq+ Youth, Alicia A. Lapointe, Caely I. Dunlop, Claire Crooks

Journal Articles

This study evaluated the feasibility and fit of a mental health promotion and violence prevention program adapted for LGBTQ+ youth (ages 14-18). The pilot program included 16 30-minute sessions and was implemented in 8 gender and sexuality alliances (GSAs) and one community youth group setting. Extensive feedback was collected from 11 facilitators via session tracking sheets, ongoing email communication, an implementation survey, and a focus group; and from 7 youth who participated in a variety of feedback activities during a 2-day post-program workshop. Results indicated a strong interest in formalized programming, challenges related to its delivery in GSAs, and significant …

Research Snapshot: Changes In Depression And Positive Mental Health Among Youth In A Healthy Relationships Program, Centre For School Mental Health

Research Snapshots

This study explored and identified meaningful groups of youth based on their depression symptoms over time. Researchers found that youth who reported high levels of depression prior to the program experienced a significant decline in depressive symptoms and improved mental well-being following the program.

Comparing The Anterior, Posterior And Lateral Approach: Gait Analysis In Total Hip Arthroplasty, Stephen Petis, James Howard, Brent Lanting

Bone and Joint Institute

No abstract provided.

Corrigendum To: Erbium-Based Perfusion Contrast Agent For Small-Animal Microvessel Imaging (Contrast Media And Molecular Imaging (2017) 2017 (7368384) Doi: 10.1155/2017/7368384), Justin J. Tse, P. Joy Dunmore-Buyze, Maria Drangova, David W. Holdsworth

Bone and Joint Institute

Copyright © 2018 Justin J. Tse et al. In the article titled "Erbium-Based Perfusion Contrast Agent for Small-Animal Microvessel Imaging" [1], there were errors in the scale bars in Figure 3, which should be corrected as follows: (Figure Presented).

Intervention With Citrus Flavonoids Reverses Obesity And Improves Metabolic Syndrome And Atherosclerosis In Obese Ldlr / Mice, Amy C. Burke, Brian G. Sutherland, Dawn E. Telford, Marisa R. Morrow, Cynthia G. Sawyez, Jane Y. Edwards, Maria Drangova, Murray W. Huff

Bone and Joint Institute

Copyright © 2018 Burke et al. Obesity and its associated metabolic dysfunction and cardiovascular disease risk represent a leading cause of adult morbidity worldwide. Currently available pharmacological therapies for obesity have had limited success in reversing existing obesity and metabolic dysregulation. Previous prevention studies demonstrated that the citrus flavonoids, naringenin and nobiletin, protect against obesity and metabolic dysfunction in Ldlr/ mice fed a high-fat cholesterol-containing (HFHC) diet. However, their effects in an intervention model are unknown. In this report, we show that, in Ldlr/ mice with diet-induced obesity, citrus flavonoid supplementation to a HFHC diet reversed existing obesity and adipocyte …

Appraisal Of: Management Of Neck Pain And Associated Disorders: A Clinical Practice Guideline From The Ontario Protocol For Traffic Injury Management (Optima) Collaboration, Saravanan Esakki, Joy C. Macdermid

Bone and Joint Institute

No abstract provided.

Pain-Quilt: A User-Friendly Tool For The Self-Report And Tracking Of Pain, Chitra Lalloo, Joy Macdermid

Bone and Joint Institute

No abstract provided.

Psychometric Properties Of The Zephyr Bioharness Device: A Systematic Review, Goris Nazari, Pavlos Bobos, Joy C. Macdermid, Kathryn E. Sinden, Julie Richardson, Ada Tang

Bone and Joint Institute

© 2018 The Author(s). Background: Technological development and improvements in Wearable Physiological Monitoring devices, have facilitated the wireless and continuous field-based monitoring/capturing of physiologic measures in healthy, clinical or athletic populations. These devices have many applications for prevention and rehabilitation of musculoskeletal disorders, assuming reliable and valid data is collected. The purpose of this study was to appraise the quality and synthesize findings from published studies on psychometric properties of heart rate measurements taken with the Zephyr Bioharness device. Methods: We searched the Embase, Medline, PsycInfo, PuMed and Google Scholar databases to identify articles. Articles were appraised for quality using …

Influence Of Crown Design And Material On Chipping-Resistance Of All-Ceramic Molar Crowns: An In Vitro Study, Majed Alsarani, Grace De Souza, Amin Rizkalla, Omar El-Mowafy

Bone and Joint Institute

© 2018 by Wroclaw Medical University and Polish Dental Society. Background. All-ceramic restorations have become popular and the trend is ongoing. However, the incidence of chipping within the veneering layer has been a commonly reported failure in clinical practice. Objectives. The aim of this in vitro study was to evaluate the effect of ceramic crown design (monolithic vs bi-layered) and material on the chipping resistance of molar crowns submitted to compressive cyclic loading. Material and methods. Fifty identical epoxy resin replicas of a mandibular first molar with crown preparation were divided into 5 groups (n = 10) as follows: the …

Biomechanical Analysis Using Fea And Experiments Of Metal Plate And Bone Strut Repair Of A Femur Midshaft Segmental Defect, Jason Coquim, Joseph Clemenzi, Mohsen Salahi, Abdurahman Sherif, Pouria Tavakkoli Avval, Suraj Shah, Emil H. Schemitsch, Z. Shaghayegh Bagheri, Habiba Bougherara, Radovan Zdero

Bone and Joint Institute

© 2018 Jason Coquim et al. This investigation assessed the biomechanical performance of the metal plate and bone strut technique for fixing recalcitrant nonunions of femur midshaft segmental defects, which has not been systematically done before. A finite element (FE) model was developed and then validated by experiments with the femur in 15 deg of adduction at a subclinical hip force of 1 kN. Then, FE analysis was done with the femur in 15 deg of adduction at a hip force of 3 kN representing about 4 x body weight for a 75 kg person to examine clinically relevant cases, …

Developing Stem Cell-Based Therapeutic Strategies In Orthopaedic Surgery, Kivanc Atesok, Mitsuo Ochi, Nicola Baldini, Emil Schemitsch, Meir Liebergall

Bone and Joint Institute

No abstract provided.

Wound Irrigation Does Not Affect Healthrelated Quality Of Life After Open Fractures: Results Of A Randomized Controlled Trial, S. Sprague, B. Petrisor, K. Jeray, P. Mckay, D. Heels-Ansdell, E. Schemitsch, S. Liew, G. Guyatt, S. D. Walter, M. Bhandari

Bone and Joint Institute

© 2018 Sprague et al. Aims The Fluid Lavage in Open Fracture Wounds (FLOW) trial was a multicentre, blinded, randomized controlled trial that used a 2 3 factorial design to evaluate the effect of irrigation solution (soap versus normal saline) and irrigation pressure (very low versus low versus high) on health-related quality of life (HRQL) in patients with open fractures. In this study, we used this dataset to ascertain whether these factors affect whether HRQL returns to pre-injury levels at 12-months post-injury. Patients and Methods Participants completed the Short Form-12 (SF-12) and the EuroQol-5 Dimensions (EQ-5D) at baseline (pre-injury recall), …

Optimizing Outpatient Total Hip Arthroplasty: Perspectives Of Key Stakeholders, L Churchill, M Pollock, Y Lebedeva, N Pasic

Bone and Joint Institute

Background Advances in surgical techniques combined with multimodal analgesia and early rehabilitation have potentiated early mobilization in patients undergoing total hip arthroplasty (THA). Given an increasing push from patients to accelerate recovery and health care budgetary limitations, there has been growing interest in the implementation of outpatient THA in selected patients. Understanding the patient and primary caregiver experience of outpatient THA is important to optimize care. We aimed to gain insight into patient and caregiver perspectives regarding the perceived advantages and disadvantages of same-day discharge to identify areas of care that can be improved. Method Using a qualitative descriptive approach, …

Validity And Internal Consistency Of The New Knee Society Knee Scoring System, Se Culliton, Dm Bryant, Sj Macdonald, Kathryn Hibbert

Bone and Joint Institute

BackgroundIn 2012, a new Knee Society Knee Scoring System (KSS) was developed and validated to address the needs for a scoring system that better encompasses the expectations, satisfaction, and physical involvement of a younger, more active population of patients undergoing TKA. Revalidating this tool in a separate population by individuals other than the developers of the scoring system seems important, because such replication would tend to confirm the generalizability of this tool.Questions/purposesThe purposes of this study were (1) to validate the KSS using a separate sample of patients undergoing primary TKA; and (2) to evaluate the internal consistency of the …

Human Neuroimaging Reveals The Subcomponents Of Grasping, Reaching And Pointing Actions., Cristiana Cavina-Pratesi, Jason D Connolly, Simona Monaco, Teresa D Figley, A David Milner, Thomas Schenk, Jody C Culham

Brain and Mind Institute Researchers' Publications

Although the neural underpinnings of visually guided grasping and reaching have been well delineated within lateral and medial fronto-parietal networks (respectively), the contributions of subcomponents of visuomotor actions have not been explored in detail. Using careful subtraction logic, here we investigated which aspects of grasping, reaching, and pointing movements drive activation across key areas within visuomotor networks implicated in hand actions. For grasping tasks, we find activation differences based on the precision required (fine > coarse grip: anterior intraparietal sulcus, aIPS), the requirement to lift the object (grip + lift > grip: aIPS; dorsal premotor cortex, PMd; and supplementary motor area, SMA), …

Cross-Script Orthographic And Phonological Preview Benefits, Olessia Jouravlev, Debra Jared

Brain and Mind Institute Researchers' Publications

The present experiment examined the use of parafoveally presented first-language (LI) orthographic and phonological codes during reading of second-language (L2) sentences in proficient Russian-English bilinguals. Participants read English sentences containing a Russian preview word that was replaced by the English target word when the participant’s eyes crossed an invisible boundary located before the preview word. The use of English and Russian allowed us to manipulate orthographic and phonological preview effects independently of one another. The Russian preview words overlapped with English target words in (a) orthography (ВЕЛЮР [vʲɪˈlʲʉr]–BERRY), (b) phonology (БЛАНК [blank]–BLOOD), or (c) had no orthographic or phonological overlap …

Registered Reports: Introducing A New Article Format In Developmental Science, Daniel Ansari, Judit Gervain

Brain and Mind Institute Researchers' Publications

No abstract provided.

Understanding The Effects Of Education Through The Lens Of Biology, H Moriah Sokolowski, Daniel Ansari

Brain and Mind Institute Researchers' Publications

Early educational interventions aim to close gaps in achievement levels between children. However, early interventions do not eliminate individual differences in populations and the effects of early interventions often fade-out over time, despite changes of the mean of the population immediately following the intervention. Here, we discuss biological factors that help to better understand why early educational interventions do not eliminate achievement gaps. Children experience and respond to educational interventions differently. These stable individual differences are a consequence of biological mechanisms that support the interplay between genetic predispositions and the embedding of experience into our biology. Accordingly, we argue that …

Recording Neuronal Activity Using Miniscopes, Brainscan , Western University, Marco Prado, Sylvian Williams, Vania Prado, Salah El Mestikawy

Project Summaries

Our overarching goal is to understand how the striatum can select between competing options to favor goal-directed behaviors or the establishment of habitual control. This will provide fundamental and transformational insights into the regulation of cognitive functions by co-transmission.

Investigating Vta, Snc And Dopamine Projections In The Brain Using Mri, Brainscan , Western University, Penny Macdonald, Ali Khan, Adrian Owen, Ravi Menon

Project Summaries

By using a multi-modal imaging approach - combining a number of different imaging techniques - we will seek to understand the dopaminergic pathways of the brain. While all neurons depend on neurotransmitters such as dopamine to communicate (since neurotransmitters are responsible for transmitting signals between neurons in the brain), very few neurons actually produce dopamine.