Medical Specialties Commons^™

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 …

Erratum: Correction To: Does Specialist Physician Supply Affect Pediatric Asthma Health Outcomes? (Bmc Health Services Research (2018) 18 1 (247)), Guido Filler, Tom Kovesi, Erik Bourdon, Sarah Ann Jones, Laurentiu Givelichian, Cheryl Rockman-Greenberg, Jason Gilliland, Marion Williams, Elaine Orrbine, Bruno Piedboeuf

Paediatrics Publications

In the original publication of this article [1], the institutional author's name needs to be revised from The Paediatric Chairs of Canada Mark Bernstein to The Paediatric Chairs of Canada.

The Transcription Factor Pu.1 Mediates Enhancer-Promoter Looping That Is Required For Il-1 Erna And Mrna Transcription In Mouse Melanoma And Macrophage Cell Lines, Soon-Duck Ha, Woohyun Cho, Rodney P. Dekoter, Sung Ouk Kim

Paediatrics Publications

The DNA-binding protein PU.1 is a myeloid lineage– determining and pioneering transcription factor due to its ability to bind “closed” genomic sites and maintain “open” chromatin state for myeloid lineage–specific genes. The precise mechanism of PU.1 in cell type–specific programming is yet to be elucidated. The melanoma cell line B16BL6, although it is nonmyeloid lineage, expressed Toll-like receptors and activated the transcription factor NF-B upon stimulation by the bacterial cell wall component lipopolysaccharide. However, it did not produce cytokines, such as IL-1 mRNA. Ectopic PU.1 expression induced remodeling of a novel distal enhancer (located 10 kbp upstream of the IL-1 …

Immunoreactive Trypsinogen Levels In Newborn Screened Infants With An Inconclusive Diagnosis Of Cystic Fibrosis., Chee Y Ooi, Rosie Sutherland, Carlo Castellani, Katherine Keenan, Margaret Boland, Joe Reisman, Candice Bjornson, Mark A Chilvers, Richard Van Wylick, Steven Kent, April Price, Dimas Mateos-Corral, Daniel Hughes, Melinda Solomon, Peter Zuberbuhler, Janna Brusky, Peter R Durie, Felix Ratjen, Tanja Gonska

Paediatrics Publications

BACKGROUND:
Newborn screening (NBS) for cystic fibrosis (CF) not only identifies infants with a diagnosis of CF, but also those with an uncertain diagnosis of cystic fibrosis (CF), i.e. CF transmembrane conductance regulator (CFTR)-related metabolic syndrome (CRMS) or CF screen positive inconclusive diagnosis (CFSPID). These infants have an uncertain long-term outcome and it is currently unclear around time of diagnosis, which infants are at higher risk of later fulfilling a CF diagnosis. In this study, we hypothesised that immunoreactive trypsinogen (IRT) levels, used in NBS as a marker of pancreatic disease and function, may reflect the degree of CFTR dysfunction …

Asthma Exacerbation Trajectories And Their Predictors In Children With Incident Asthma., Sharifa Nasreen, Piotr Wilk, Tara Mullowney, Igor Karp

Paediatrics Publications

BACKGROUND:
Asthma exacerbation trajectories in children after incident asthma diagnosis are understudied.

OBJECTIVE:
To identify trajectories of asthma exacerbation and predictors of these trajectories in children with incident asthma.

METHODS:
Children from the National Longitudinal Survey of Children and Youth, Canada, with incident asthma were followed-up for up to 12 years during childhood. Latent class growth modeling was used to identify distinct asthma exacerbation trajectory groups. Multinomial logistic regression was performed to identify predictors of trajectory group membership.

RESULTS:
The mean age at asthma diagnosis among 403 children was 5.9 years. Three distinct trajectories were identified: low increasing (21.3% of …

Utility Of Clinical Features With Fine Needle Aspiration Biopsy For Diagnosis Of Warthin Tumor., Thomas So, Axel Sahovaler, Anthony Nichols, Kevin Fung, John Yoo, Michele M Weir, S Danielle Macneil

Paediatrics Publications

BACKGROUND:
Conservative management of Warthin tumor (WT) may be a viable alternative to surgery, but there are concerns of missed malignancies on fine needle aspiration biopsy (FNAB). The purpose of this study is to measure the sensitivity and positive predictive value of FNAB for WT, and to identify clinical features associated with WT that can aid in this diagnosis.

METHODS:
Retrospective analysis of patients from January 1, 2006 to April 30, 2017 at a tertiary care center in London, Ontario, Canada. All patients with a diagnosis of WT on FNAB or resection were included. Electronic medical records were identified for …

Offspring From Maternal Nutrient Restriction In Mice Show Variations In Adult Glucose Metabolism Similar To Human Fetal Growth Restriction., B N Radford, V K M Han

Paediatrics Publications

Fetal growth restriction (FGR) is a pregnancy condition in which fetal growth is suboptimal for gestation, and this population is at increased risk for type 2 diabetes as adults. In humans, maternal malnutrition and placental insufficiency are the most common causes of FGR, and both result in fetal undernutrition. We hypothesized that maternal nutrient restriction (MNR) in mice will cause FGR and alter glucose metabolism in adult offspring. Pregnant CD-1 mice were subjected to MNR (70% of average ad libitum) or control (ad libitum) from E6.5 to birth. Following birth, mice were fostered by mothers on ad libitum feeds. Weight, …

Classification Criteria For Autoinflammatory Recurrent Fevers., Marco Gattorno, Michael Hofer, Silvia Federici, Federica Vanoni, Francesca Bovis, Ivona Aksentijevich, Jordi Anton, Juan Ignacio Arostegui, Karyl Barron, Eldad Ben-Cherit, Paul A Brogan, Luca Cantarini, Isabella Ceccherini, Fabrizio De Benedetti, Fatma Dedeoglu, Erkan Demirkaya, Joost Frenkel, Raphaela Goldbach-Mansky, Ahmet Gul, Veronique Hentgen, Hal Hoffman, Tilmann Kallinich, Isabelle Kone-Paut, Jasmin Kuemmerle-Deschner, Helen J Lachmann, Ronald M Laxer, Avi Livneh, Laura Obici, Seza Ozen, Dorota Rowczenio, Ricardo Russo, Yael Shinar, Anna Simon, Nataša Toplak, Isabelle Touitou, Yosef Uziel, Marielle Van Gijn, Dirk Foell, Claudia Garassino, Dan Kastner, Alberto Martini, Maria Pia Sormani, Nicolino Ruperto

Paediatrics Publications

BACKGROUND:
Different diagnostic and classification criteria are available for hereditary recurrent fevers (HRF)-familial Mediterranean fever (FMF), tumour necrosis factor receptor-associated periodic fever syndrome (TRAPS), mevalonate kinase deficiency (MKD) and cryopyrin-associated periodic syndromes (CAPS)-and for the non-hereditary, periodic fever, aphthosis, pharyngitis and adenitis (PFAPA). We aimed to develop and validate new evidence-based classification criteria for HRF/PFAPA.

METHODS:
Step 1: selection of clinical, laboratory and genetic candidate variables; step 2: classification of 360 random patients from the Eurofever Registry by a panel of 25 clinicians and 8 geneticists blinded to patients' diagnosis (consensus ≥80%); step 3: statistical analysis for the selection of …

Chromium: Rise And Shine In Peritoneal Dialysis Patients?, Guido Filler, Christopher Mcintyre

Paediatrics Publications

Some trace elements are altered with chronic kidney disease. Selenium, zinc, and manganese tend to be wasted, and there is growing evidence that selenium deficiency is associated with mortality on dialysis. Other trace elements accumulate, such as chromium, cobalt, lead, molybdenum, and vanadium. The highest chromium levels are found in dialysis patients. The dialysis modality may further affect these levels, especially in hemodialysis patients, where even small contaminations in the dialysis feed water may lead to a concentration gradient that increases the concentration of certain trace elements. Chromium levels in peritoneal dialysis (PD) patients have been understudied. A single cross-sectional …

Placental Micrornas In Pregnancies With Early Onset Intrauterine Growth Restriction And Preeclampsia: Potential Impact On Gene Expression And Pathophysiology., Zain Awamleh, Gregory B Gloor, Victor K M Han

Paediatrics Publications

BACKGROUND:
A normally developed placenta is integral to a successful pregnancy. Preeclampsia (PE) and intrauterine growth restriction (IUGR) are two common pregnancy related complications that maybe a result of abnormal placental development. Placental microRNAs (miRNAs) have been investigated as potential biomarkers for these complications, as they may play a role in placental development and pathophysiology by influencing gene expression. The purpose of this study is to utilize next-generation sequencing to determine miRNA and gene expression in human placental (chorionic villous) samples from three distinct patient groups with early-onset (EO) PE, IUGR, or PE + IUGR.

METHODS:
Placental tissues were collected …

The Stability Of Retrospective Pre-Injury Symptom Ratings Following Pediatric Concussion., Elizabeth F Teel, Roger L Zemek, Kenneth Tang, Gerard Gioia, Christopher Vaughan, Maegan Sady, Isabelle J Gagnon, Gurinder Sangha

Paediatrics Publications

Objective:
To determine the stability of children's retrospective ratings of pre-injury levels of symptoms over time following concussion.

Methods:
Children and adolescents (n = 3,063) between the ages of 5–17 diagnosed with a concussion by their treating pediatric emergency department (PED) physician within 48 h of injury completed the Post-Concussion Symptom Inventory (PCSI) at the PED and at 1, 2, 4, 8, and 12-weeks post-injury. At each time point, participants retrospectively recalled their pre-injury levels of post-injury symptoms. The PCSI has three age-appropriate versions for children aged 5–7 (PCSI-SR5), 8–12 (PCSI-SR8), and 13–18 (PCSI-SR13). Total scale, subscales (physical, cognitive, …

A National Survey Of Resources To Address Sepsis In Children In Tertiary Care Centers In Nigeria., Odiraa C Nwankwor, Brianna Mckelvie, Meg Frizzola, Krystal Hunter, Halima S Kabara, Abiola Oduwole, Tagbo Oguonu, Niranjan Kissoon

Paediatrics Publications

Background:
Infections leading to sepsis are major contributors to mortality and morbidity in children world-wide. Determining the capacity of pediatric hospitals in Nigeria to manage sepsis establishes an important baseline for quality-improvement interventions and resource allocations.

Objectives:
To assess the availability and functionality of resources and manpower for early detection and prompt management of sepsis in children at tertiary pediatric centers in Nigeria.

Methods:
This was an online survey of tertiary pediatric hospitals in Nigeria using a modified survey tool designed by the World Federation of Pediatric Intensive and Critical Care Societies (WFPICCS). The survey addressed all aspects of pediatric …

The Impact Of Pediatric Emergency Department Crowding On Patient And Health Care System Outcomes: A Multicentre Cohort Study., Quynh Doan, Hubert Wong, Garth Meckler, David Johnson, Antonia Stang, Andrew Dixon, Scott Sawyer, Tania Principi, April J Kam, Gary Joubert, Jocelyn Gravel, Mona Jabbour, Astrid Guttmann

Paediatrics Publications

BACKGROUND:
Emergency department overcrowding has been associated with increased odds of hospital admission and mortality after discharge from the emergency department in predominantly adult cohorts. The objective of this study was to evaluate the association between crowding and the odds of several adverse outcomes among children seen at a pediatric emergency department.

METHODS:
We conducted a retrospective cohort study involving all children visiting 8 Canadian pediatric emergency departments across 4 provinces between 2010 and 2014. We analyzed the association between mean departmental length of stay for each index visit and hospital admission within 7 days or death within 14 days …

Twelve Tips For Enhancing Student Engagement., Harm Peters, Marko Zdravkovic, Manuel João Costa, Antonio Celenza, Kulsoom Ghias, Debra Klamen, Liz Mossop, Michael Rieder, Vishna Devi Nadarajah, Danai Wangsaturaka, Martin Wohlin, Margot Weggemans

Paediatrics Publications

Student engagement refers to a broad range of activities where students participate in management, education, research, and community activities within their institutions. It is a mutually beneficial collaborative approach between students and their institutions. This article provides practical advice for the implementation or further development of student engagement at medical, dental, and veterinary schools. The tips provided are based on the experiences of a group of universities recently recognized for best practice in student engagement, and are supported by evidence from the literature. The tips cover overarching themes which include the creation of an institutional culture and formal framework for …

External Cold And Vibration For Pain Management Of Children Undergoing Needle-Related Procedures In The Emergency Department: A Randomised Controlled Non-Inferiority Trial Protocol., Ariane Ballard, Christelle Khadra, Samara Adler, Evelyne D Trottier, Benoit Bailey, Naveen Poonai, Jean Théroux, Sylvie Le May

Paediatrics Publications

INTRODUCTION: Needle-related procedures are considered as the most important source of pain and distress in children in hospital settings. Considering the physiological and psychological consequences that could result from these procedures, management of pain and distress through pharmacological and non-pharmacological methods is essential. Therefore, it is important to have interventions that are rapid, easy-to-use and likely to be translated into clinical practice for routine use. The aim of this study will be to determine whether a device combining cold and vibration (Buzzy) is non-inferior to a topical anaesthetic (liposomal lidocaine 4% cream) for pain management of children undergoing needle-related procedures …

Unanticipated Admissions To Paediatric Cardiac Critical Care After Cardiac Catheterisations., Erin Peebles, Michael R Miller, Lee N Benson, Tilman Humpl

Paediatrics Publications

OBJECTIVES: Cardiac catheterisation is commonly used for diagnosis and therapeutic interventions in paediatric cardiology. The inherent risk of the procedure can result in unanticipated admissions to critical care. Our goals were to provide a qualitative description of characteristics and evaluation of children admitted unexpectedly to the cardiac critical care unit (CCCU).

METHODS: A retrospective single centre review of cardiac catheterisation procedures was done between 1 January, 2003 and 30 April, 2013.

RESULTS: Of 9336 cardiac catheterisations performed, 146 (1.6%) were admitted from the catheterisation laboratory to the CCCU and met inclusion criteria. Of these 146 patients, 117 (1.3%) met criteria …

Use Of A Radial Artery ‘Slender’ Sheath For Facilitating Transfemoral Arterial Access For Neuroendovascular Embolization In A Very Young Infant, Timothy L. Miao, Enriqueta Lucar Figueroa, Khalid Bajunaid, Michael Mayich, Sandrine De Ribaupierre, Sachin K. Pandey

Paediatrics Publications

Pediatric neuroendovascular procedures are increasingly performed as several studies have shown the safety of these interventions. In the literature, an upper limit of 4 French catheter size is conventionally used for femoral access in neuroangiography of very young infants. However, this constraint in luminal size may not allow for more complex procedures. We present the previously unreported use of a radial 5 French slender catheter with ultrathin walls for femoral access for aneurysm embolization in a 3-month-old boy presenting with left M2 aneurysm rupture.

The Canadian Childhood Nephrotic Syndrome (Childneph) Study: Report On Mid-Study Feasibility, Recruitment And Main Measures., Susan M Samuel, Allison Dart, Guido Filler, Martin Bitzan, Maury Pinsk, Cherry Mammen, Alberto Nettel-Aguirre, Maneka A Perinpanayagam, Tomoko Takano, Rahul Chanchlani, Michael Zappitelli

Paediatrics Publications

BACKGROUND:
To assess reasons for continuing practice variation in the management of childhood nephrotic syndrome despite expert reviews and guidelines, we are conducting a longitudinal cohort study in children with glucocorticoid sensitive nephrotic syndrome. Objectives of this mid-study report are to describe patient and physician recruitment characteristics, glucocorticoid prescriptions, use of second line agents, biopsy practices, and adherence to study protocol.

METHODS:
Children with new onset nephrotic syndrome and providers are being recruited from all 12 pediatric nephrology centres across Canada with > 2½ years follow-up. Data collection points of observation are over a minimum 36 months. Details of prescribed glucocorticoids …

The Effects Of Tracheal Occlusion On Wnt Signaling In A Rabbit Model Of Congenital Diaphragmatic Hernia, Martina Mudri, Shane A. Smith, Christina Vanderboor, Jacob Davidson, Timothy R.H. Regnault, Andreana Bütter

Paediatrics Publications

Purpose: Tracheal occlusion (TO)reverses pulmonary hypoplasia (PH)in congenital diaphragmatic hernia (CDH), but its mechanism of action remains poorly understood. Wnt signaling plays a critical role in lung development, but few studies exist. The purpose of our study was to a)confirm that our CDH rabbit model produced PH which was reversed by TO and b)determine the effects of CDH +/− TO on Wnt signaling. Methods: CDH was created in fetal rabbits at 23 days, TO at 28 days, and lung collection at 31 days. Lung body weight ratio (LBWR)and mean terminal bronchiole density (MTBD)were determined. mRNA and miRNA expression was determined …

Gene Domain-Specific Dna Methylation Episignatures Highlight Distinct Molecular Entities Of Adnp Syndrome., Eric G Bend, Erfan Aref-Eshghi, David B Everman, R Curtis Rogers, Sara S Cathey, Eloise J Prijoles, Michael J Lyons, Heather Davis, Katie Clarkson, Karen W Gripp, Dong Li, Elizabeth Bhoj, Elaine Zackai, Paul Mark, Hakon Hakonarson, Laurie A Demmer, Michael A Levy, Jennifer Kerkhof, Alan Stuart, David Rodenhiser, Michael J Friez, Roger E Stevenson, Charles E Schwartz, Bekim Sadikovic

Paediatrics Publications

BACKGROUND:
ADNP syndrome is a rare Mendelian disorder characterized by global developmental delay, intellectual disability, and autism. It is caused by truncating mutations in ADNP, which is involved in chromatin regulation. We hypothesized that the disruption of chromatin regulation might result in specific DNA methylation patterns that could be used in the molecular diagnosis of ADNP syndrome.

RESULTS:
We identified two distinct and partially opposing genomic DNA methylation episignatures in the peripheral blood samples from 22 patients with ADNP syndrome. The "epi-ADNP-1" episignature included ~ 6000 mostly hypomethylated CpGs, and the "epi-ADNP-2" episignature included ~ 1000 predominantly hypermethylated CpGs. The …

Diagnostic Utility Of Genome-Wide Dna Methylation Testing In Genetically Unsolved Individuals With Suspected Hereditary Conditions., Erfan Aref-Eshghi, Eric G Bend, Samantha Colaiacovo, Michelle Caudle, Rana Chakrabarti, Melanie Napier, Lauren Brick, Lauren Brady, Deanna Alexis Carere, Michael A Levy, Jennifer Kerkhof, Alan Stuart, Maha Saleh, Arthur L Beaudet, Chumei Li, Maryia Kozenko, Natalya Karp, Chitra Prasad, Victoria Mok Siu, Mark A Tarnopolsky, Peter J Ainsworth, Hanxin Lin, David I Rodenhiser, Ian D Krantz, Matthew A Deardorff, Charles E Schwartz, Bekim Sadikovic

Paediatrics Publications

Conventional genetic testing of individuals with neurodevelopmental presentations and congenital anomalies (ND/CAs), i.e., the analysis of sequence and copy number variants, leaves a substantial proportion of them unexplained. Some of these cases have been shown to result from DNA methylation defects at a single locus (epi-variants), while others can exhibit syndrome-specific DNA methylation changes across multiple loci (epi-signatures). Here, we investigate the clinical diagnostic utility of genome-wide DNA methylation analysis of peripheral blood in unresolved ND/CAs. We generate a computational model enabling concurrent detection of 14 syndromes using DNA methylation data with full accuracy. We demonstrate the ability of this …

Poverty, Neighbourhood Antisocial Behaviour, And Children’S Mental Health Problems: Findings From The 2014 Ontario Child Health Study, Michael H. Boyle, Katholiki Georgiades, Laura Duncan, Laura Duncan, Li Wang, Jinette Comeau, Jinette Comeau, Tracie O. Afifi, William R. Avison, Graham Reid, Kathryn Bennett, Terry Bennett, Khrista Boylan, Michelle Butt, Charles Cunningham, Eric Duku, Jim Dunn, Katholiki Georgiades, Stelios Georgiades, Andrea Gonzalez, Geoffrey Hall, Magdalena Janus, Melissa Kimber, Ellen Lipman, Harriet Macmillan, Peter Rosenbaum, Roberto Sassi, Louis Schmidt, Noam Soreni

Paediatrics Publications

Objectives: To determine if levels of neighbourhood poverty and neighbourhood antisocial behaviour modify associations between household poverty and child and youth mental health problems. Methods: Data come from the 2014 Ontario Child Health Study—a provincially representative survey of 6537 families with 10,802 four- to 17-year-olds. Multivariate multilevel modelling was used to test if neighbourhood poverty and antisocial behaviour interact with household poverty to modify associations with children’s externalizing and internalizing problems based on parent assessments of children (4- to 17-year-olds) and self-assessments of youth (12- to 17-year-olds). Results: Based on parent assessments, neighbourhood poverty, and antisocial behaviour modified associations between …