Digital Commons Network^™

Investigating Microenvironmental Regulation Of Human Chordoma Cell Behaviour, Priya Patel, Courtney Brooks, Ayesh Seneviratne, David A. Hess, Cheryle A. Séguin

Paediatrics Publications

The tumour microenvironment is complex and composed of many different constituents, including matricellular proteins such as connective tissue growth factor (CCN2), and is characterized by gradients in oxygen levels. In various cancers, hypoxia and CCN2 promote stem and progenitor cell properties, and regulate the proliferation, migration and phenotype of cancer cells. Our study was aimed at investigating the effects of hypoxia and CCN2 on chordoma cells, using the human U-CH1 cell line. We demonstrate that under basal conditions, U-CH1 cells express multiple CCN family members including CCN1, CCN2, CCN3 and CCN5. Culture of U-CH1 cells in either hypoxia or in …

Low Birth Weight Followed By Postnatal Over-Nutrition In The Guinea Pig Exposes A Predominant Player In The Development Of Vascular Dysfunction, Jennifer A. Thompson, Ousseynou Sarr, Karolina Piorkowska, Robert Gros, Timothy R.H. Regnault

Paediatrics Publications

The association between intrauterine growth restriction (IUGR) and hypertension is well established, yet the interaction between IUGR and other pathogenic contributors remains ill-defined. This study examined the independent and interactive effects of fetal growth reduction resulting in low birth weight (LBW), and postnatal Western diet (WD) on vascular function. Growth reduction was induced in pregnant guinea pigs by uterine artery ablation. LBW and normal birth weight (NBW) offspring were randomly assigned to a control diet (CD) or a WD. In young adulthood, length-tension curves were generated in aortic rings and responses to methacholine (MCh) were evaluated in the carotid and …

Low Birth Weight Followed By Postnatal Over-Nutrition In The Guinea Pig Exposes A Predominant Player In The Development Of Vascular Dysfunction., Jennifer A Thompson, Ousseynou Sarr, Karolina Piorkowska, Robert Gros, Timothy Regnault

Paediatrics Publications

The association between intrauterine growth restriction (IUGR) and hypertension is well established, yet the interaction between IUGR and other pathogenic contributors remains ill-defined. This study examined the independent and interactive effects of fetal growth reduction resulting in low birth weight (LBW), and postnatal Western diet (WD) on vascular function. Growth reduction was induced in pregnant guinea pigs by uterine artery ablation. LBW and normal birth weight (NBW) offspring were randomly assigned to a control diet (CD) or a WD. In young adulthood, length-tension curves were generated in aortic rings and responses to methacholine (MCh) were evaluated in the carotid and …

Oral Administration Of Morphine Versus Ibuprofen To Manage Postfracture Pain In Children: A Randomized Trial, Naveen Poonai, Gina Bhullar, Kangrui Lin, Adam Papini, David Mainprize, Jocelyn Howard, John Teefy, Michelle Bale, Cindy Langford, Rodrick Lim, Larry Stitt, Michael J. Rieder, Samina Ali

Paediatrics Publications

Background: Recent warnings from Health Canada regarding codeine for children have led to increased use of nonsteroidal anti-inflammatory drugs and morphine for common injuries such as fractures. Our objective was to determine whether morphine administered orally has superior efficacy to ibuprofen in fracture-related pain.

Parent-To-Parent Support For Parents With Children Who Are Deaf Or Hard Of Hearing: A Conceptual Framework, Rebecca J. Henderson, Andrew Johnson, Sheila Moodie, Sheila Moodie

Paediatrics Publications

Background: Parent-to-parent support for parents with children who are deaf or hard of hearing (D/HH) is identified as an important component of Early Hearing Detection and Intervention (EHDI) programs for children with hearing loss.

Propranolol Therapy For Infantile Hemangioma Is Less Toxic But Longer In Duration Than Corticosteroid Therapy, Kathryn Sawa, Arjang Yazdani, Michael J. Rieder, Guido Filler

Paediatrics Publications

BACKGROUND: Infantile hemangioma is the most common benign, self-limiting tumour of childhood. Treatment is reserved for hemangiomas that obstruct vital structures or cause significant disfigurement. Traditionally, corticosteroids have been the medical treatment of choice. Since 2008, however, propranolol has been rapidly adopted as an effective pharmacological treatment for infantile hemangioma. Published data regarding the long-term side effects of propranolol are currently lacking. OBJECTIVE: To describe the long-term effects of propranolol and corticosteroids on anthropometric measurements (height, body mass index [BMI]) and blood pressure in children. METHODS: A prospective database analysis of all infantile hemangioma patient visits to the pediatric vascular …

The Sport Concussion Education Project. A Brief Report On An Educational Initiative: From Concept To Curriculum, Paul S. Echlin, Andrew M. Johnson, Jeffrey D. Holmes, Annalise Tichenoff, Sarah Gray, Heather Gatavackas, Joanne Walsh, Tim Middlebro, Angelique Schachar, Jennifer Crosbie, Paul Arnold, Elizabeth Kelley, Muhammad Ayub, Robert Nicolson, Stelios Georgiades, Jason P. Lerch, Evdokia Anagnostou

Paediatrics Publications

Current research on concussion is primarily focused on injury identification and treatment. Prevention initiatives are, however, important for reducing the incidence of brain injury. This report examines the development and implementation of an interactive electronic teaching program (an e-module) that is designed specifically for concussion education within an adolescent population. This learning tool and the accompanying consolidation rubric demonstrate that significant engagement occurs in addition to the knowledge gained among participants when it is used in a school curriculum setting.

Brca2 Inhibition Enhances Cisplatin-Mediated Alterations In Tumor Cell Proliferation, Metabolism, And Metastasis, Mateusz Rytelewski, Jessica G. Tong, Adrian Buensuceso, Hon S. Leong, Saman Maleki Vareki, Rene Figueredo, Christine Di Cresce, Sherry Y. Wu, Shelley M. Herbrich, Keith A. Baggerly, Larissa Romanow, Trevor Shepherd, Bonnie J. Deroo, Anil K. Sood, Ann F. Chambers, Mark Vincent, Peter J. Ferguson, James Koropatnick

Paediatrics Publications

Tumor cells have unstable genomes relative to non-tumor cells. Decreased DNA integrity resulting from tumor cell instability is important in generating favorable therapeutic indices, and intact DNA repair mediates resistance to therapy. Targeting DNA repair to promote the action of anti-cancer agents is therefore an attractive therapeutic strategy. BRCA2 is involved in homologous recombination repair. BRCA2 defects increase cancer risk but, paradoxically, cancer patients with BRCA2 mutations have better survival rates. We queried TCGA data and found that BRCA2 alterations led to increased survival in patients with ovarian and endometrial cancer. We developed a BRCA2-targeting second-generation antisense oligonucleotide (ASO), which …

Case 3: Stridor And Cough In A Young Child, Shruti Mehrotra, Jennifer Kilgar, Rodrick Lim

Paediatrics Publications

No abstract provided.

The Health Initiative Program For Kids (Hip Kids): Effects Of A 1-Year Multidisciplinary Lifestyle Intervention On Adiposity And Quality Of Life In Obese Children And Adolescents -- A Longitudinal Pilot Intervention Study, Dirk E. Bock, Tracy Robinson, Jamie A Seabrook, Meghan Rombeek, Kambiz Norozi, Guido Filler, Ralf Rauch, Cheril L Clarson

Paediatrics Publications

BACKGROUND: Though recent data suggest that multidisciplinary outpatient interventions can have a positive effect on childhood obesity, it is still unclear which program components are most beneficial and how they affect quality of life (QoL). The aim of this study was to determine if a 1-year multidisciplinary, family-centered outpatient intervention based on social cognitive theory would be effective in (i) preventing further increases in BMI and BMI z-score, and (ii) improving QoL in obese children and adolescents.

METHODS: Obese children and adolescents 8-17 years of age and their families participated in this 1-year longitudinal pilot intervention study. The intervention consisted …

Early Aggressive Therapy For Patients With Juvenile Idiopathic Arthritis: Are We There Yet?, Roberta A. Berard, Ronald M. Laxer

Paediatrics Publications

No abstract provided.

A Novel Mc4r Mutation Associated With Childhood-Onset Obesity: A Case Report, Manpreet Doulla, Adam D. Mcintyre, Robert A. Hegele, Patricia H. Callego

Paediatrics Publications

The melanocortin-4-receptor gene (MC4R) is a key regulator of energy homeostasis, food intake and body weight. MC4R gene mutations are associated with early-onset severe obesity. Most patients are heterozygotes, with some reports of homozygotes and compound het-erozygotes. The authors report a case involving an eight-year-old girl with progressive weight gain from infancy, body mass index 44 kg/m: (>97th percentile), hyperphagia, hvperinsulinemia and increased linear growth. There was no phenotvpe of morbid obesity in the parents or sibling. Coding regions and intron-exon boundaries of the genes encoding leptin, Ieptin receptor, pro-opiomelanocortin and MC4R were analyzed. Two heterozygous coding mutations in …

Health Related Quality Of Life Measure In Systemic Pediatric Rheumatic Diseases And Its Translation To Different Languages: An International Collaboration, Nandini N. Moorthy, Elizabeth Roy, Vamsi Kurra, Margaret G.E. Peterson, Afton L. Hassett, Thomas J.A. Lehman, Christiaan Scott, Dalia El-Ghoneimy, Shereen Saad, Reem El Feky, Sulaiman Al-Mayouf, Pavla Dolezalova, Hana Malcova, Troels Herlin, Susan Nielsen, Nico Wulffraat, Annet Van Royen, Stephen D. Marks, Alexandre Belot, Jurgen Brunner, Christian Huemer, Ivan Foeldvari, Gerd Horneff, Traudel Saurenman, Silke Schroeder, Polyxeni Pratsidou-Gertsi, Maria Trachana, Yosef Uziel, Amita Aggarwal

Paediatrics Publications

Background: Rheumatic diseases in children are associated with significant morbidity and poor health-related quality of life (HRQOL). There is no health-related quality of life (HRQOL) scale available specifically for children with less common rheumatic diseases. These diseases share several features with systemic lupus erythematosus (SLE) such as their chronic episodic nature, multi-systemic involvement, and the need for immunosuppressive medications. HRQOL scale developed for pediatric SLE will likely be applicable to children with systemic inflammatory diseases. Findings: We adapted Simple Measure of Impact of Lupus Erythematosus in Youngsters (SMILEY) to Simple Measure of Impact of Illness in Youngsters (SMILY-Illness) and had …

The Author Responds, Michael Rieder

Paediatrics Publications

No abstract provided.

Atrx Is Required For Maintenance Of The Neuroprogenitor Cell Pool In The Embryonic Mouse Brain, Kieran Ritchie, L Ashley Watson, Benjamin Davidson, Yan Jiang, Nathalie G. Bérubé

Paediatrics Publications

Mutations in the alpha-thalassemia mental retardation X-linked (ATRX) gene cause a spectrum of abnormalities including intellectual disability, developmental delay, seizures, and microcephaly. The ATRX protein is highly enriched at heterochromatic repetitive sequences adjacent to the centromere, and ATRX depletion results in chromosome congression, segregation, and cohesion defects. Here, we show that Cre-mediated inactivation of Atrx in the embryonic mouse (Mus musculus) brain results in expansion of cerebral cortical layer VI, and a concurrent thinning of layers II-IV. We observed increased cell cycle exit during early-mid neurogenesis, and a depletion of apical progenitors by late neurogenesis in the Atrx-null neocortex, explaining …

Development Of A Novel Classification System For Anatomical Variants Of The Puboprostatic Ligaments With Expert Validation, Michael Kim, Shawna L. Boyle, Alfonso Fernandez, Edward D. Matsumoto, Kenneth T. Pace, Maurice Anidjar, Gregory N. Kozak, Sumit Davé, Blayne K. Welk, Marjorie I. Johnson, Stephen E. Pautler

Paediatrics Publications

Introduction: We propose a novel classification system with a validation study to help clinicians identify and typify commonly seen variants of the puboprostatic ligaments (PPL). Methods: A preliminary dissection of 6 male cadavers and a prospective dataset of over 300 robotic-assisted laparoscopic radical prostatectomies (RARP) recorded on video were used to identify 4 distinct ligament types. Then the prospectively collected database of surgical videos was used to isolate images of the PPL from RARP. Over 300 surgical videos were reviewed and classified with 1 to 5 pictures saved for reference of the type of PPL. To validate the new classification …

T Helper Type 2-Polarized Invariant Natural Killer T Cells Reduce Disease Severity In Acute Intra-Abdominal Sepsis, R. V. Anantha, D. M. Mazzuca, S. X. Xu, S. A. Porcelli, D. D. Fraser, C. M. Martin, I. Welch, T. Mele, S. M.M. Haeryfar, J. K. Mccormick

Paediatrics Publications

Summary: Sepsis is characterized by a severe systemic inflammatory response to infection that is associated with high morbidity and mortality despite optimal care. Invariant natural killer T (iNKT) cells are potent regulatory lymphocytes that can produce pro- and/or anti-inflammatory cytokines, thus shaping the course and nature of immune responses; however, little is known about their role in sepsis. We demonstrate here that patients with sepsis/severe sepsis have significantly elevated proportions of iNKT cells in their peripheral blood (as a percentage of their circulating T cells) compared to non-septic patients. We therefore investigated the role of iNKT cells in a mouse …

Pregnancy Complications In Women With Heart Disease Conceiving With Fertility Therapy, Natalie Dayan, Carl A. Laskin, Karen Spitzer, Jennifer Mason, Jacob A. Udell, Rachel M. Wald, Samuel C. Siu, Theodora Iten-Scott, Candice K. Silversides

Paediatrics Publications

No abstract provided.

Atrx Promotes Gene Expression By Facilitating Transcriptional Elongation Through Guanine-Rich Coding Regions, Michael A. Levy, Kristin D. Kernohan, Yan Jiang, Nathalie G. Bérubé

Paediatrics Publications

ATRX is a chromatin remodeling protein involved in deposition of the histone variant H3.3 at telomeres and pericentromeric heterochromatin. It also influences the expression level of specific genes; however, deposition of H3.3 at transcribed genes is currently thought to occur independently of ATRX. We focused on a set of genes, including the autism susceptibility gene Neuroligin 4 (Nlgn4), that exhibit decreased expression in ATRX-null cells to investigate the mechanisms used by ATRX to promote gene transcription. Overall TERRA levels, as well as DNA methylation and histone modifications at ATRX target genes are not altered and thus cannot explain transcriptional dysregulation.We …

Case Of Multiple Sulfatase Deficiency And Ocular Albinism: A Diagnostic Odyssey, Chitra Prasad, C. Anthony Rupar, Craig Campbell, Melanie Napier, David Ramsay, K. Y. Tay, Sapna Sharan, Asuri N. Prasad

Paediatrics Publications

Background: Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of lysosomal metabolism. The clinical phenotypic spectrum encompasses overlapping features of variable severity and is suggestive of individual single sulfatase deficiencies (i.e., metachromatic leukodystrophy, mucopolysaccharidosis, and X-linked ichthyosis). Case Report: We describe a 3-year-old male with severe hypotonia, developmental regression and progressive neurodegeneration, coarse facial features, nystagmus (from ocular albinism), and dysmyelinating motor sensory neuropathy. Ethics approval was obtained from the Western University Ontario. Results: Extensive investigative work-up identified deficiencies of multiple sulfatases: heparan sulfate sulfamidase: 6.5 nmoles/mg/protein/17 hour (reference 25.0-75.0), iduronate-2-sulfate sulfatase: 9 nmol/mg/protein/4 hour (reference 31-110), …

A Comparison Of The Epidemiology Of Ice Hockey Injuries Between Male And Female Youth In Canada, Karen E. Forward, Jamie A. Seabrook, Tim Lynch, Rodrick Lim, Naveen Poonai, Gurinder S. Sangha

Paediatrics Publications

BACKGROUND: Hockey is played by youth across Canada, and its popularity has increased dramatically among females in the past decade. Despite this, there has been little epidemiological research comparing the injury patterns of young female and male hockey players. OBJECTIVE: To describe and compare injuries sustained by female and male youth hockey players using the Canadian Hospitals Injury Reporting and Prevention Program database. METHODS: In the present cross-sectional, retrospective comparison study, the Canadian Hospitals Injury Reporting and Prevention Program database was used to identify all hockey-related injuries sustained by children seven to 17.5 years of age over a 15-year period …

Ataluren Treatment Of Patients With Nonsense Mutation Dystrophinopathy, Katharine Bushby, Richard Finkel, Brenda Wong, Richard Barohn, Craig Campbell, Giacomo P. Comi, Anne M. Connolly, John W. Day

Paediatrics Publications

Introduction: Dystrophinopathy is a rare, severe muscle disorder, and nonsense mutations are found in 13% of cases. Ataluren was developed to enable ribosomal readthrough of premature stop codons in nonsense mutation (nm) genetic disorders. Methods: Randomized, double-blind, placebo-controlled study; males ≥5 years with nm-dystrophinopathy received study drug orally 3 times daily, ataluren 10, 10, 20 mg/kg (N=57); ataluren 20, 20, 40 mg/kg (N=60); or placebo (N=57) for 48 weeks. The primary endpoint was change in 6-Minute Walk Distance (6MWD) at Week 48. Results: Ataluren was generally well tolerated. The primary endpoint favored ataluren 10, 10, 20 mg/kg versus placebo; the …

The Role Of Untreated Psychosis In Neurodegeneration: A Review Of Hypothesized Mechanisms Of Neurotoxicity In First-Episode Psychosis, Kelly K. Anderson, Aristotle Voineskos, Benoit H. Mulsant, Tony P. George, Kwame J. Mckenzie

Paediatrics Publications

For over 20 years, studies have tried to measure the association between the duration of untreated psychosis (DUP) and changes in brain morphology. A hypothesis that untreated psychosis is neurotoxic has been postulated, but the mechanisms of that toxicity have not been described. We re-analyzed papers collected for a systematic review to extract data on the hypotheses that have been generated on the potential mechanisms by which DUP could impact brain morphology in first-episode psychosis. Dopaminergic hyperactivity, prolonged hypothalamic-pituitary-adrenal activation, and persistent activity of catecholamines have been hypothesized as mechanisms to explain these associations. However, the question remains as to …

A Transgenic Zebrafish Model Expressing Kit-D816v Recapitulates Features Of Aggressive Systemic Mastocytosis, Tugce B. Balci, Sergey V. Prykhozhij, Evelyn M. Teh, Sahar I. Da'as, Eileen Mcbride, Robert Liwski, Ian C. Chute, Daniel Leger, Stephen M. Lewis, Jason N. Berman

Paediatrics Publications

Summary: Systemic mastocytosis (SM) is a rare myeloproliferative disease without curative therapy. Despite clinical variability, the majority of patients harbour a KIT-D816V mutation, but efforts to inhibit mutant KIT with tyrosine kinase inhibitors have been unsatisfactory, indicating a need for new preclinical approaches to identify alternative targets and novel therapies in this disease. Murine models to date have been limited and do not fully recapitulate the most aggressive forms of SM. We describe the generation of a transgenic zebrafish model expressing the human KIT-D816V mutation. Adult fish demonstrate a myeloproliferative disease phenotype, including features of aggressive SM in haematopoeitic tissues …

Population Pk Modelling And Simulation Based On Fluoxetine And Norfluoxetine Concentrations In Milk: A Milk Concentration-Based Prediction Model, Reo Tanoshima, Facundo G.Arcia Bournissen, Yusuke Tanigawara, Judith H. Kristensen, Anna Taddio, Kenneth F. Ilett, Evan J. Begg, Izhar Wallach, Shinya Ito

Paediatrics Publications

AIMS: Population pharmacokinetic (pop PK) modelling can be used for PK assessment of drugs in breast milk. However, complex mechanistic modelling of a parent and an active metabolite using both blood and milk samples is challenging. We aimed to develop a simple predictive pop PK model for milk concentration-time profiles of a parent and a metabolite, using data on fluoxetine (FX) and its active metabolite, norfluoxetine (NFX), in milk.

Infrared Thermography To Assess Proliferation And Involution Of Infantile Hemangiomas: A Prospective Cohort Study, Javed Ayoub Mohammed, Alexandra Balma-Mena, Ajith Chakkittakandiyil, Florentina Matea, Elena Pope

Paediatrics Publications

IMPORTANCE Infantile hemangiomas (IHs) are common benign tumors of infancy that have the potential to interfere with vital organ function and cause permanent disfigurement. Currently, few objective and validated measures exist to assess IHs. Copyright 2014 American Medical Association. All rights reserved.

Postresuscitation Debriefing In The Pediatric Emergency Department: A National Needs Assessment, Naminder Sandhu, Walter Eppich, Angelo Mikrogianakis, Vincent Grant, Traci Robinson, Adam Cheng, Rod Lim, Allan Shefrin

Paediatrics Publications

Results: Data were analyzed from 183 participants (48.7% response rate). Although 88.8% of the participants believed that debriefing is an important process, 52.5% indicated that debriefing after real resuscitations occurs less than 25% of the time and 68.3% indicated that no expectation exists for PRD at their institution. Although 83.7% of participants believed that facilitators should have a specific skill set developed through formal training sessions, 63.4% had no previous training in debriefing. Seventy-two percent felt that medical and crisis resource management issues are dealt with adequately when PRD occurs, and 90.4% indicated that ED workload and time shortages are …

Second Bacteremia During Antibiotic Treatment In Children With Acute Myeloid Leukemia: A Report From The Canadian Infections In Acute Myeloid Leukemia Research Group, Thai Hoa Tran, Rochelle Yanofsky, Donna L. Johnston, David Dix, Biljana Gillmeister, Marie Chantal Ethier, Carol Portwine, Vicky Price, David Mitchell, Sonia Cellot, Victor Lewis, Shayna Zelcer, Mariana Silva, Bruno Michon, Lynette Bowes, Kent Stobart, Josée Brossard, Joseph Beyene, Lillian Sung

Paediatrics Publications

Background: The risk of second bacteremia during antibiotic treatment for initial bacteremia is unknown in high-risk populations. Our objectives were to describe the prevalence of second bacteremia during treatment and identify risk factors in children with acute myeloid leukemia (AML). Methods: We conducted a retrospective, population-based cohort study that included children and adolescents with de novo, non-M3 AML who were diagnosed and treated between January 1, 1995 and December 31, 2004 at 15 Canadian centers. Patients were monitored for bacteremia during chemotherapy until completion of treatment, hematopoietic stem cell transplantation, relapse, refractory disease, or death. Results: There were 290 episodes …

A Multi-Method Approach To Studying Activity Setting Participation: Integrating Standardized Questionnaires, Qualitative Methods And Physiological Measures, Barbara E. Gibson, Gillian King, Azadeh Kushki, Bhavnita Mistry, Laura Thompson, Gail Teachman, Beata Batorowicz, Margot Mcmain-Klein

Paediatrics Publications

Purpose: This study investigated the feasibility of integrating three diverse methods for studying disabled youth's experiences of activity settings: standardized questionnaires, qualitative methods and physiological measures. The article describes a case study of data collection in a real-life setting to outline the opportunities, challenges and lessons learned for future research. Methods: The methods included (a) two newly developed quantitative measures of qualities of home and community activity settings (MEQAS) and youth experiences (SEAS); (b) youth-friendly qualitative methods, including photo-elicitation, observations, electronic interviews and face-to-face interviews; and (c) an innovative system to collect physiological data (the HEART system) that provided insight …

An Integrated Methods Study Of The Experiences Of Youth With Severe Disabilities In Leisure Activity Settings: The Importance Of Belonging, Fun, And Control And Choice, Gillian King, Barbara E. Gibson, Bhavnita Mistry, Madhu Pinto, Freda Goh, Gail Teachman, Laura Thompson

Paediatrics Publications

Purpose: The aim was to examine the leisure activity setting experiences of two groups of youth with severe disabilities-those with complex continuing care (CCC) needs and those who have little functional speech and communicate using augmentative and alternative communication (AAC). Method: Twelve youth took part in a mixed methods study, in which their experiences were ascertained using qualitative methods (observations, photo elicitation and interviews) and the measure of Self-Reported Experiences of Activity Settings (SEAS). Data integration occurred using a "following a thread" technique and case-by-case analysis. Results: The analysis revealed several highly valued aspects of leisure activity setting experiences for …