Medical Specialties Commons^™

Circulating Leptin Levels Are Associated With Adiposity In Survivors Of Childhood Brain Tumors., E Danielle Sims, William J. Jennings, Brianna Empringham, Adam Fleming, Carol Portwine, Donna L. Johnston, Shayna M. Zelcer, Shahrad Rod Rassekh, Sarah Burrow, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

Survivors of Childhood Brain Tumors (SCBT) are at a higher risk of developing cardiovascular disease and type 2 diabetes compared to the general population. Adiposity is an important risk factor for the development of these outcomes, and identifying biomarkers of adiposity may help the stratification of survivors based on their cardiovascular risk or allow for early screening and interventions to improve cardiometabolic outcomes. Leptin is an adipokine that positively correlates with the adipose mass in the general population and is a predictor of adverse cardiometabolic outcomes, yet its association with adiposity in SCBT has not been studied. The aim of …

New Horizons In The Genetic Etiology Of Systemic Lupus Erythematosus And Lupus-Like Disease: Monogenic Lupus And Beyond, Erkan Demirkaya, Sezgin Sahin, Micol Romano, Qing Zhou, Ivona Aksentijevich

Paediatrics Publications

Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 >years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus …

Evaluation Of Dna Methylation Episignatures For Diagnosis And Phenotype Correlations In 42 Mendelian Neurodevelopmental Disorders., Erfan Aref-Eshghi, Jennifer Kerkhof, Victor P Pedro, Mouna Barat-Houari, Nathalie Ruiz-Pallares, Jean-Christophe Andrau, Didier Lacombe, Julien Van-Gils, Patricia Fergelot, Christèle Dubourg, Valerie Cormier-Daire, Sophie Rondeau, François Lecoquierre, Pascale Saugier-Veber, Gaël Nicolas, Gaetan Lesca, Nicolas Chatron, Damien Sanlaville, Antonio Vitobello, Laurence Faivre, Christel Thauvin-Robinet, Frederic Laumonnier, Martine Raynaud, Mariëlle Alders, Marcel Mannens, Peter Henneman, Raoul C Hennekam, Guillaume Velasco, Claire Francastel, Damien Ulveling, Andrea Ciolfi, Simone Pizzi, Marco Tartaglia, Solveig Heide, Delphine Héron, Cyril Mignot, Boris Keren, Sandra Whalen, Alexandra Afenjar, Thierry Bienvenu, Philippe M Campeau, Justine Rousseau, Michael A Levy, Lauren Brick, Mariya Kozenko, Tugce B Balci, Victoria Mok Siu, Alan Stuart, Mike Kadour, Jennifer Masters, Kyoko Takano, Tjitske Kleefstra, Nicole De Leeuw, Michael Field, Marie Shaw, Jozef Gecz, Peter J Ainsworth, Hanxin Lin, David I Rodenhiser, Michael J Friez, Matt Tedder, Jennifer A Lee, Barbara R Dupont, Roger E Stevenson, Steven A Skinner, Charles E Schwartz, David Genevieve, Bekim Sadikovic

Paediatrics Publications

Genetic syndromes frequently present with overlapping clinical features and inconclusive or ambiguous genetic findings which can confound accurate diagnosis and clinical management. An expanding number of genetic syndromes have been shown to have unique genomic DNA methylation patterns (called "episignatures"). Peripheral blood episignatures can be used for diagnostic testing as well as for the interpretation of ambiguous genetic test results. We present here an approach to episignature mapping in 42 genetic syndromes, which has allowed the identification of 34 robust disease-specific episignatures. We examine emerging patterns of overlap, as well as similarities and hierarchical relationships across these episignatures, to highlight …

Predictors Of Bicuspid Aortic Valve-Associated Aortopathy In Childhood: A Report From The Mibava Consortium, Michael Grattan, Andrea Prince, Rawan K Rumman, Conall Morgan, Michele Petrovic, Amanda Hauck, Luciana Young, Anders Franco-Cereceda, Bart Loeys, Salah A Mohamed, Harry Dietz, Seema Mital, Chun-Po Steve Fan, Cedric Manlhiot, Gregor Andelfinger, Luc Mertens

Paediatrics Publications

BACKGROUND: Bicuspid aortic valve (BAV) is the most prevalent congenital heart defect affecting 1% to 2% of the population. It is associated with ascending aorta dilatation. Valve morphology, aortic stenosis (AS), and aortic insufficiency (AI) have been proposed as potential risk factors; however, evaluating their role is difficult, as these factors are inherently related. The aim of this study was to determine whether BAV morphology and dysfunction are independent determinants for ascending aorta dilatation in pediatric patients.

METHODS: A multicenter, retrospective, cross-sectional study of pediatric BAV patients followed since 2004 was performed. Imaging data were assessed for BAV morphology, severity …

Bulging Anterior Fontanelle And Dense Bones In An Infant., Camilla Raya Halgren, Jenna Lakhani, Samantha Colaiacovo, Chitra Prasad

Paediatrics Publications

No abstract provided.

Blau Syndrome And Early-Onset Sarcoidosis: A Six Case Series And Review Of The Literature., Ayşenur Paç Kisaarslan, Betül Sözeri̇, Nihal Şahi̇n, Sümeyra Özdemi̇r Çi̇çek, Zübeyde Gündüz, Erkan Demi̇rkaya, Afig Berdeli̇, Serdal Sadet Özcan, Hakan Porazoğlu, Ruhan Düşünsel

Paediatrics Publications

Objectives: This study aims to discuss the clinical, laboratory and genetic findings, and treatment options for six patients who were diagnosed with Blau syndrome (BS)/early-onset sarcoidosis (EOS).

Patients and methods: The study included four patients (2 males,2 females; mean age 7 years; range 4 to 10 years) with EOS and two siblings (1 male, 1 female; mean age 10 years; range, 9 to 11 years) with BS. Age, age of initial symptoms, age of diagnosis; articular involvement, presence of uveitis, dermatitis, or fever, other organ involvement, laboratory findings, results of metabolic tests for mucopolysaccharidosis and mucolipidosis, results of genetic, pathologic, …

Osteochondritis Dissecans In Pediatric Patients With Juvenile Idiopathic Arthritis., Bradley C Jackson, Debra L Bartley, Roberta A Berard

Paediatrics Publications

No abstract provided.

Impressions On Reliability And Students’ Perceptions Of Learning In A Peer-Based Osce, Rishad Khan, Saad Chahine, Steven Macaluso, Ricardo Viana, Caitlin Cassidy, Thomas Miller, Debra Bartley, Michael Payne

Paediatrics Publications

Background: Peer assessment of performance in the objective structured clinical examination (OSCE) is emerging as a learning instrument. While peers can provide reliable scores, there may be a trade-off with students’ learning. The purpose of this study is to evaluate a peer-based OSCE as a viable assessment instrument and its potential to promote learning and explore the interplay between these two roles. Methods: A total of 334 medical students completed an 11-station OSCE from 2015 to 2016. Each station had 1–2 peer examiners (PE) and one faculty examiner (FE). Examinees were rated on a 7-point scale across 5 dimensions: Look, …

Labour Progression In Obese Women: Are Women With Increased Body Mass Index Having Unnecessary Cesarean Sections?, Caroline Shenouda, Aloka Wijesooriya, Amanda Toufeili, Michael R Miller, Debbie Penava, Barbra De Vrijer

Obstetrics & Gynaecology Publications

OBJECTIVE: This study sought to determine whether obese pregnant women undergo cesarean sections without an adequate trial of labour. This may affect future birth and pregnancy outcomes.

METHODS: A retrospective analysis was done on 526 parturients at Victoria Hospital in London, Ontario. Women were categorized according to parity and pre-pregnancy body mass index (BMI; normal weight, BMI 18.5-24.9 kg/m

RESULTS: Obese class II and III primiparous women required an additional 1.62 and 2.67 hours (P = 0.012), respectively, to reach a dilation of 10 cm compared with their normal weight counterparts; obese class II and III multiparous women required an …

Treatment De-Escalation For Hpv-Associated Oropharyngeal Squamous Cell Carcinoma With Radiotherapy Vs. Trans-Oral Surgery (Orator2): Study Protocol For A Randomized Phase Ii Trial., Anthony C Nichols, Pencilla Lang, Eitan Prisman, Eric Berthelet, Eric Tran, Sarah Hamilton, Jonn Wu, Kevin Fung, John R De Almeida, Andrew Bayley, David P Goldstein, Antoine Eskander, Zain Husain, Houda Bahig, Apostolos Christopoulous, Michael Hier, Khalil Sultanem, Keith Richardson, Alex Mlynarek, Suren Krishnan, Hien Le, John Yoo, S Danielle Macneil, Adrian Mendez, Eric Winquist, Nancy Read, Varagur Venkatesan, Sara Kuruvilla, Andrew Warner, Sylvia Mitchell, Martin Corsten, Murali Rajaraman, Stephanie Johnson-Obaseki, Libni Eapen, Michael Odell, Shamir Chandarana, Robyn Banerjee, Joseph Dort, T Wayne Matthews, Robert Hart, Paul Kerr, Samuel Dowthwaite, Michael Gupta, Han Zhang, Jim Wright, Christina Parker, Bret Wehrli, Keith Kwan, Julie Theurer, David A Palma

Paediatrics Publications

BACKGROUND: Patients with human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma (OPC) have substantially better treatment response and overall survival (OS) than patients with HPV-negative disease. Treatment options for HPV+ OPC can involve either a primary radiotherapy (RT) approach (± concomitant chemotherapy) or a primary surgical approach (± adjuvant radiation) with transoral surgery (TOS). These two treatment paradigms have different spectrums of toxicity. The goals of this study are to assess the OS of two de-escalation approaches (primary radiotherapy and primary TOS) compared to historical control, and to compare survival, toxicity and quality of life (QOL) profiles between the two approaches. …

Feeling Green, Aisha Ghare, Kristopher D. Langdon, Ruba Kiwan, Andrea Andrade, Adrianna Ranger, Robert Hammond

Paediatrics Publications

No abstract provided.

Insights Image For "Evidence Of Increased Hypoxia Signalling In Fetal Liver From Maternal Nutrient Restriction In Mice"., Bethany N Radford, Victor K M Han

Paediatrics Publications

No abstract provided.

Evidence Of Increased Hypoxia Signaling In Fetal Liver From Maternal Nutrient Restriction In Mice., Bethany N Radford, Victor K M Han

Paediatrics Publications

BACKGROUND: Intrauterine growth restriction (IUGR) is a pregnancy condition where fetal growth is reduced, and offspring from IUGR pregnancies are at increased risk for type II diabetes as adults. The liver is susceptible to fetal undernutrition experienced by IUGR infants and animal models of growth restriction. This study aimed to examine hepatic expression changes in a maternal nutrient restriction (MNR) mouse model of IUGR to understand fetal adaptations that influence adult metabolism.

METHODS: Liver samples of male offspring from MNR (70% of ad libitum starting at E6.5) or control pregnancies were obtained at E18.5 and differential expression was assessed by …

Prioritization And Management Recommendations Of Pediatric Urology Conditions During The Covid-19 Pandemic, Daniel T. Keefe, Mandy Rickard, Peter Anderson, Darius Bagli, Anne Sophie Blais, Stéphane Bolduc, Luis H. Braga, Natasha Brownrigg, Michael Chua, Sumit Dave, Joana Dos Santos, Luis Guerra, Allen H. Hayashi, Mélise A. Keays, Soojin Kim, Martin A. Koyle, Linda C. Lee, Armando J. Lorenzo, Dawn Maclellan, Landan Macdonald, Andrew E. Macneily, Peter D. Metcalfe, Katherine Moore, Rodrigo L.P. Romao, Peter Z.T. Wang

Paediatrics Publications

No abstract provided.

Outcomes In Pediatric Studies Of Medium-Chain Acyl-Coa Dehydrogenase (Mcad) Deficiency And Phenylketonuria (Pku): A Review., Michael Pugliese, Kylie Tingley, Andrea Chow, Nicole Pallone, Maureen Smith, Alvi Rahman, Pranesh Chakraborty, Michael T Geraghty, Julie Irwin, Laure Tessier, Stuart G Nicholls, Martin Offringa, Nancy J Butcher, Ryan Iverson, Tammy J Clifford, Sylvia Stockler, Brian Hutton, Karen Paik, Jessica Tao, Becky Skidmore, Doug Coyle, Kathleen Duddy, Sarah Dyack, Cheryl R Greenberg, Shailly Jain Ghai, Natalya Karp, Lawrence Korngut, Jonathan Kronick, Alex Mackenzie, Jennifer Mackenzie, Bruno Maranda, John J Mitchell, Murray Potter, Chitra Prasad, Andreas Schulze, Rebecca Sparkes, Monica Taljaard, Yannis Trakadis, Jagdeep Walia, Beth K Potter

Paediatrics Publications

BACKGROUND: Inherited metabolic diseases (IMDs) are a group of individually rare single-gene diseases. For many IMDs, there is a paucity of high-quality evidence that evaluates the effectiveness of clinical interventions. Clinical effectiveness trials of IMD interventions could be supported through the development of core outcome sets (COSs), a recommended minimum set of standardized, high-quality outcomes and associated outcome measurement instruments to be incorporated by all trials in an area of study. We began the process of establishing pediatric COSs for two IMDs, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and phenylketonuria (PKU), by reviewing published literature to describe outcomes reported by authors, …

Fatigue In Young People With Duchenne Muscular Dystrophy, Basmah El-Aloul, Kathy N Speechley, Yi Wei, Piotr Wilk, Craig Campbell

Paediatrics Publications

AIM: To describe fatigue in Duchenne muscular dystrophy (DMD) from patients' and parents' perspectives and to explore risk factors for fatigue in children and adolescents with DMD.

METHOD: A multicentre, cross-sectional study design was used. Seventy-one patients (all males; median age 12y, age range 5-17y) identified via the Canadian Neuromuscular Disease Registry, and their parents completed questionnaires. Subjective fatigue was assessed using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale by child self-report and parent proxy-report.

RESULTS: Patients with DMD across ages and disease stages experienced greater fatigue compared to typically developing controls from published data. Sleep disturbance symptoms …

Growth Hormone Deficiency In Megalencephaly-Capillary Malformation Syndrome: An Association With Activating Mutations In Pik3ca, Shanlee Davis, Meredith A Ware, Jordan Zeiger, Matthew A Deardorff, Katheryn Grand, Adda Grimberg, Stephanie Hsu, Megan Kelsey, Shideh Majidi, Revi P Matthew, Melanie Napier, Natalie Nokoff, Chitra Prasad, Andrew C Riggs, Margaret L Mckinnon, Ghayda Mirzaa

Paediatrics Publications

Megalencephaly-capillary malformation syndrome (MCAP) is a brain overgrowth disorder characterized by cortical malformations (specifically polymicrogyria), vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (PIK3CA). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multicenter study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had …

The Pancreas-Specific Form Of Secretory Pathway Calcium Atpase 2 Regulates Multiple Pathways Involved In Calcium Homeostasis, Melissa Fenech, Mckenzie M Carter, Peter B Stathopulos, Christopher Pin

Paediatrics Publications

Acinar cell exocytosis requires spatiotemporal Ca²⁺ signals regulated through endoplasmic reticulum (ER) stores, Ca²⁺ATPases, and store-operated Ca²⁺ entry (SOCE). The secretory pathway Ca²⁺ATPase 2 (SPCA2) interacts with Orai1, which is involved in SOCE and store independent Ca²⁺ entry (SICE). However, in the pancreas, only a C-terminally truncated form of SPCA2 (termed SPAC2C) exists. The goal of this study was to determine if SPCA2C effects Ca²⁺ homeostasis in a similar fashion to the full-length SPCA2. Using epitope-tagged SPCA2C (SPCA2C^FLAG) expressed in HEK293A cells and Fura2 imaging, cytosolic [Ca²⁺] was …

Intranasal Dexmedetomidine For Procedural Distress In Children: A Systematic Review., Naveen Poonai, Joseph Spohn, Ben Vandermeer, Samina Ali, Maala Bhatt, Shawn Hendrikx, Evelyne D Trottier, Vikram Sabhaney, Amit Shah, Gary Joubert, Lisa Hartling

Paediatrics Publications

CONTEXT: Intranasal dexmedetomidine (IND) is an emerging agent for procedural distress in children.

OBJECTIVE: To explore the effectiveness of IND for procedural distress in children.

DATA SOURCES: We performed electronic searches of Medline (1946-2019), Embase (1980-2019), Google Scholar (2019), Cumulative Index to Nursing and Allied Health Literature (1981-2019), and Cochrane Central Register.

STUDY SELECTION: We included randomized trials of IND for procedures in children.

DATA EXTRACTION: Methodologic quality of evidence was evaluated by using the Cochrane Collaboration's risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation system, respectively. The primary outcome was the proportion of participants …

Brain Metabolite Levels In Sedentary Women And Non-Contact Athletes Differ From Contact Athletes., Amy L Schranz, Gregory A Dekaban, Lisa Fischer, Kevin Blackney, Christy Barreira, Timothy J Doherty, Douglas Fraser Md, Phd, Frcpc, Arthur Brown, Jeff Holmes, Ravi S Menon, Robert Bartha

Paediatrics Publications

White matter tracts are known to be susceptible to injury following concussion. The objective of this study was to determine whether contact play in sport could alter white matter metabolite levels in female varsity athletes independent of changes induced by long-term exercise. Metabolite levels were measured by single voxel proton magnetic resonance spectroscopy (MRS) in the prefrontal white matter at the beginning (In-Season) and end (Off-Season) of season in contact (

Mtorc1 Transcriptional Regulation Of Ribosome Subunits, Protein Synthesis, And Molecular Transport In Primary Human Trophoblast Cells., Fredrick J Rosario, Theresa L Powell, Madhulika B Gupta, Laura Cox, Thomas Jansson

Paediatrics Publications

Mechanistic Target of Rapamycin Complex 1 (mTORC1) serves as positive regulator of placental nutrient transport and mitochondrial respiration. The role of mTORC1 signaling in modulating other placental functions is largely unexplored. We used gene array following silencing of raptor to identify genes regulated by mTORC1 in primary human trophoblast (PHT) cells. Seven hundred and thirty-nine genes were differentially expressed; 487 genes were down-regulated and 252 up-regulated. Bioinformatic analyses demonstrated that inhibition of mTORC1 resulted in decreased expression of genes encoding ribosomal proteins in the 60S and 40S ribosome subunits. Furthermore, down-regulated genes were functionally enriched in genes involved in eIF2, …

The Cost-Utility Of Measles-Mumps-Rubella Immunization Strategies During A Mumps Outbreak, Kikanwa Anyiwe, David Naimark, Oliver Baclic, Vinita Dubey, Marina Salvadori, Man Wah Yeung, Matthew Tunis, Beate Sander

Paediatrics Publications

No abstract provided.

Improving Access And Mental Health For Youth Through Virtual Models Of Care, Cheryl Forchuk, Sandra Fisman, Jeffrey P. Reiss, Kerry Collins, Julie Eichstedt, Abraham Rudnick, Wanrudee Isaranuwatchai, Jeffrey S. Hoch, Xianbin Wang, Daniel Lizotte, Shona Macpherson, Richard Booth

Paediatrics Publications

The overall objective of this research is to evaluate the use of a mobile health smartphone application (app) to improve the mental health of youth between the ages of 14–25 years, with symptoms of anxiety/depression. This project includes 115 youth who are accessing outpatient mental health services at one of three hospitals and two community agencies. The youth and care providers are using eHealth technology to enhance care. The technology uses mobile questionnaires to help promote self-assessment and track changes to support the plan of care. The technology also allows secure virtual treatment visits that youth can participate in through …

Nox2 Is Critical To Endocardial To Mesenchymal Transition And Heart Development, Hoda Moazzen, Yan Wu, Anish Engineer, Xiangru Lu, Simran Aulakh, Qingping Feng

Paediatrics Publications

NADPH oxidases (NOX) are a major source of reactive oxygen species (ROS) production in the heart. ROS signaling regulates gene expression, cell proliferation, apoptosis, and migration. However, the role of NOX2 in embryonic heart development remains elusive. We hypothesized that deficiency of Nox2 disrupts endocardial to mesenchymal transition (EndMT) and results in congenital septal and valvular defects. Our data show that 34% of Nox2-/- neonatal mice had various congenital heart defects (CHDs) including atrial septal defects (ASD), ventricular septal defects (VSD), atrioventricular canal defects (AVCD), and malformation of atrioventricular and aortic valves. Notably, Nox2-/- embryonic hearts show abnormal development of …

Estimation Of Gfr In Patients With Cystic Fibrosis: A Cross-Sectional Study, Andrea Wallace, April Price, Erin Fleischer, Michael Khoury, Guido Filler

Paediatrics Publications

Background: Patients with cystic fibrosis (CF) have frequent infectious complications requiring nephrotoxic medications, necessitating monitoring of renal function. Although adult studies have suggested that cystatin C (CysC)-based estimated glomerular filtration rate (eGFR) may be preferable due to reduced muscle mass of patients with CF, pediatric patients remain understudied. Objective: Our objective was to determine which eGFR formula is best for estimating glomerular filtration rate (GFR) in pediatric patients with CF. Methods: A total of 17 patients with CF treated with nephrotoxic antibiotics were recruited from the Children’s Hospital at London Health Sciences Centre, London, Ontario, Canada. 99Tc DTPA GFR (measured …

Presence Of Benznidazole Conjugated Metabolites In Urine Identified By Β-Glucuronidase Treatment, María Elena Marson, Facundo García Bournissen, Jaime Altcheh, Guillermo Moscatelli, Samantha Moroni, Guido Enrique Mastrantonio

Paediatrics Publications

Chagas disease is a serious public health problem in Latin America and, due to migration, in other non-endemic regions. Benznidazole (BNZ) is first choice drug in pediatric therapeutics. However, little is known regarding its metabolism in humans. The aim of the study was to isolate and identify products of human BZN metabolism in urine samples obtained from a pediatric Chagas patient and a healthy adult volunteer both treated with BZN. Urine samples were collected after dose of BNZ. Urine was treated with β-glucuronidase followed by an extraction procedure under two different pH conditions and a HPLC/UV and MS/MS identification of …

Endothelial Injury And Glycocalyx Degradation In Critically Ill Coronavirus Disease 2019 Patients: Implications For Microvascular Platelet Aggregation, Douglas Fraser

Data and Test Instruments

No abstract provided.

Inflammation Profiling Of Critically Ill Coronavirus Disease 2019 Patients, Douglas Fraser

Data and Test Instruments

No abstract provided.

Novel Outcome Biomarkers Identified With Targeted Proteomic Analyses Of Plasma From Critically Ill Coronavirus Disease 2019 Patients, Douglas Fraser

Data and Test Instruments

No abstract provided.

Composite Outcomes For Clinical Trials In Critical Care: The Devil Is In The Detail, Saptharishi Lalgudi Ganesan, Narayanan Parameswaran

Data and Test Instruments

No abstract provided.