Medical Specialties Commons^™

The 2014 Ontario Child Health Study—Methodology, Michael H. Boyle, Katholiki Georgiades, Laura Duncan, Laura Duncan, Jinette Comeau, Jinette Comeau, Li Wang, 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

Objective: To describe the methodology of the 2014 Ontario Child Health Study (OCHS): a province-wide, cross-sectional, epidemiologic study of child health and mental disorder among 4- to 17-year-olds living in household dwellings. Method: Implemented by Statistics Canada, the 2014 OCHS was led by academic researchers at the Offord Centre for Child Studies (McMaster University). Eligible households included families with children aged 4 to 17 years, who were listed on the 2014 Canadian Child Tax Benefit File. The survey design included area and household stratification by income and 3-stage cluster sampling of areas and households to yield a probability sample of …

Six-Month Prevalence Of Mental Disorders And Service Contacts Among Children And Youth In Ontario: Evidence From The 2014 Ontario Child Health Study, Katholiki Georgiades, Laura Duncan, Laura Duncan, Li Wang, Jinette Comeau, Jinette Comeau, Michael H. Boyle, Michael H. Boyle, Tracie O. Afifi, William R. Avison, Graham Reid, Kathryn Bennett, Terry Bennett, Khrista Boylan, Michelle Butt, Charles Cunningham, Eric Duku, Jim Dunn, 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 present the 6-month prevalence and sociodemographic correlates of mental disorders and mental health–related service contacts in a sample of children (4 to 11 years) and youth (12 to 17 years) in Ontario. Methods: The 2014 Ontario Child Health Study is a provincially representative survey of 6537 families with children aged 4 to 17 years in Ontario. DSM-IV-TR mental disorders were assessed using the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) and included mood (major depressive episode), anxiety (generalized anxiety, separation anxiety, social phobia, specific phobia), and behaviour disorders (attention-deficit/hyperactivity disorder, oppositional-defiant disorder, conduct disorder).The MINI-KID was …

Tracking Children’S Mental Health In The 21st Century: Lessons From The 2014 Ochs, Michael H. Boyle, Laura Duncan, Laura Duncan, Katholiki Georgiades, Jinette Comeau, Jinette Comeau, Graham J. Reid, Warren O’Briain, Robert Lampard, Charlotte Waddell, 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

No abstract provided.

Edwardsiella Tarda Infection Triggering Acute Relapse In Pediatric Crohn’S Disease, A K Li, M Barton, J A Delport, D Ashok

Paediatrics Publications

Crohn's disease exacerbations can often be associated with bacterial infections causing gastroenteritis. We report a child who experienced exacerbation of his Crohn's disease associated with a positive stool culture for

Pain Management Practices Surrounding Lumbar Punctures In Children: A Survey Of Canadian Emergency Physicians., Naveen Poonai, Victoria Brzozowski, Antonia S Stang, Amy L Drendel, Philippe Boisclair, Michael Miller, Stuart Harman, Samina Ali

Paediatrics Publications

OBJECTIVES:
Lumbar punctures (LPs) are painful for children, and analgesia is recommended by academic societies. However, less than one-third of pediatric emergency physicians (EPs) adhere to recommendations. We assessed the willingness to provide analgesia among pediatric and general EPs and explored patient and provider-specific barriers.

METHODS:
We surveyed physicians in the Pediatric Emergency Research Canada (PERC) or Canadian Association of Emergency Physicians (CAEP) databases from May 1 to August 1, 2016, regarding hypothetical scenarios for a 3-week-old infant, a 3-year-old child, and a 16-year-old child requiring an LP. The primary outcome was the willingness to provide analgesia. Secondary outcomes included …

Numb Regulates The Endocytosis And Activity Of The Anaplastic Lymphoma Kinase In An Isoform-Specific Manner, Ran Wei, Xuguang Liu, Courtney Voss, Wentao Qin, Lina Dagnino, Lei Li, Marc Vigny, Shawn Shun Cheng Li

Paediatrics Publications

NUMB is an evolutionarily conserved protein that plays an important role in cell adhesion, migration, polarity, and cell fate determination. It has also been shown to play a role in the pathogenesis of certain cancers, although it remains controversial whether NUMB functions as an oncoprotein or tumor suppressor. Here, we show that NUMB binds to anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase aberrantly activated in several forms of cancer, and this interaction regulates the endocytosis and activity of ALK. Intriguingly, the function of the NUMB-ALK interaction is isoform-dependent. While both p66-NUMB and p72-NUMB isoforms are capable of mediating the …

Multicentre, Randomised Clinical Trial Of Paediatric Concussion Assessment Of Rest And Exertion (Pedcare): A Study To Determine When To Resume Physical Activities Following Concussion In Children., Andrée-Anne Ledoux, Nicholas J Barrowman, Kathy Boutis, Adrienne Davis, Sarah Reid, Gurinder Sangha, Ken J Farion, Kevin Belanger, Mark S Tremblay, Keith Owen Yeates, Carol Dematteo, Nick Reed, Roger Zemek

Paediatrics Publications

INTRODUCTION:
Rest until symptom-free, followed by a progressive stepwise return to activities, is often prescribed in the management of paediatric concussions. Recent evidence suggests prolonged rest may hinder recovery, and early resumption of physical activity may be associated with more rapid recovery postconcussion. The primary objective is to determine whether the early reintroduction of non-contact physical activity beginning 72 hours postinjury reduces postconcussive symptoms at 2 weeks in children following an acute concussion as compared with a rest until asymptomatic protocol.

METHODS AND ANALYSIS:
This study is a randomised clinical trial across three Canadian academic paediatric emergency departments. A total …

Mechanistic Target Of Rapamycin Complex 1 Promotes The Expression Of Genes Encoding Electron Transport Chain Proteins And Stimulates Oxidative Phosphorylation In Primary Human Trophoblast Cells By Regulating Mitochondrial Biogenesis., Fredrick J Rosario, Madhulika B Gupta, Leslie Myatt, Theresa L Powell, Jeremy P Glenn, Laura Cox, Thomas Jansson

Paediatrics Publications

Trophoblast oxidative phosphorylation provides energy for active transport and protein synthesis, which are critical placental functions influencing fetal growth and long-term health. The molecular mechanisms regulating trophoblast mitochondrial oxidative phosphorylation are largely unknown. We hypothesized that mechanistic Target of Rapamycin Complex 1 (mTORC1) is a positive regulator of key genes encoding Electron Transport Chain (ETC) proteins and stimulates oxidative phosphorylation in trophoblast and that ETC protein expression is down-regulated in placentas of infants with intrauterine growth restriction (IUGR). We silenced raptor (mTORC1 inhibition), rictor (mTORC2 inhibition) or DEPTOR (mTORC1/2 activation) in cultured term primary human trophoblast (PHT) cells. mTORC1 inhibition …

Mutational Analysis Of Head And Neck Squamous Cell Carcinoma Stratified By Smoking Status., Farhad Ghasemi, Stephenie D Prokopec, Danielle Macneil, Neil Mundi, Steven F Gameiro, Christopher Howlett, William Stecho, Paul Plantinga, Nicole Pinto, Kara M Ruicci, Mohammed Imran Khan, John Yoo, Kevin Fung, Axel Sahovaler, David A Palma, Eric Winquist, Joe S Mymryk, John W Barrett, Paul C Boutros, Anthony C Nichols

Paediatrics Publications

Smoking has historically been recognized as a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). This study aimed to assess the mutational differences between heavy smokers (>20 pack years) and never smokers among the HNSCC patients within The Cancer Genome Atlas (TCGA). Single nucleotide variation and copy number aberration differences between heavy smokers and never smokers were compared within human papillomavirus-positive (HPV-positive) (n = 67) and HPV-negative (n = 431) TCGA cohorts with HNSCC, and the impact of these mutations on survival were assessed. No genes were differentially mutated between smoking and never-smoking patients with HPV-positive …

Cdk4 Inhibitors Thwart Immunity By Inhibiting Phospho-Rb-Nf-Kb Complexes, Seung J. Kim, Samuel Asfaha, Frederick A. Dick

Paediatrics Publications

PD-L1 plays a central role in immune recognition of cancer cells. In this issue of Molecular Cell, Jin et al. (2019) report that a phosphorylated retinoblastoma protein contacts the DNA-binding domain of p65 NF-kB, thereby blocking transcription of PD-L1.

Ctcf Governs The Identity And Migration Of Mge-Derived Cortical Interneurons., Adrienne Elbert, Daniel Vogt, Ashley Watson, Michael Levy, Yan Jiang, Emilie Brûlé, Megan E Rowland, John Rubenstein, Nathalie G Bérubé

Paediatrics Publications

The CCCTC-binding factor (CTCF) is a central regulator of chromatin topology recently linked to neurodevelopmental disorders such as intellectual disability, autism, and schizophrenia. The aim of this study was to identify novel roles of CTCF in the developing mouse brain. We provide evidence that CTCF is required for the expression of the LIM homeodomain factor LHX6 involved in fate determination of cortical interneurons (CINs) that originate in the medial ganglionic eminence (MGE). Conditional

Twinkle-Associated Mitochondrial Dna Depletion., Salma Remtulla, Cam-Tu Emilie Nguyen, Chitra Prasad, Craig Campbell

Paediatrics Publications

BACKGROUND: Autosomal recessive mutations in the nuclear Twinkle (C10orf2) gene cause a mitochondrial DNA depletion syndrome (MDS) characterized by early onset hepatoencephalopathy.

METHODS: We report a severe, early onset encephalopathy and multisystem failure case caused by novel recessive Twinkle gene mutations. Patient clinical, laboratory, and pathological features are reported and Twinkle-associated MDS literature reviewed.

RESULTS: Typical presentation includes symptom onset before age six months, failure to thrive, psychomotor regression, epileptic encephalopathy, sensory axonal neuropathy, cholestatic liver dysfunction, and occasionally, renal tubulopathy, movement disorders, and ophthalmoplegia. Death is typical before age four years.

CONCLUSIONS: In the differential diagnosis of early onset …

The Loss Of Atrx Increases Susceptibility To Pancreatic Injury And Oncogenic Kras In Female But Not Male Mice., Claire C Young, Ryan M Baker, Christopher J Howlett, Todd Hryciw, Joshua E Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L Pin

Paediatrics Publications

Background

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler ɑ-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS’s ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of Atrx …

Linked Mri Signatures Of The Brain's Acute And Persistent Response To Concussion In Female Varsity Rugby Players., Kathryn Y Manning, Alberto Llera, Gregory A Dekaban, Robert Bartha, Christy Barreira, Arthur Brown, Lisa Fischer, Tatiana Jevremovic, Kevin Blackney, Timothy J Doherty, Douglas D Fraser, Jeff Holmes, Christian F Beckmann, Ravi S Menon

Paediatrics Publications

Acute brain changes are expected after concussion, yet there is growing evidence of persistent abnormalities well beyond clinical recovery and clearance to return to play. Multiparametric MRI is a powerful approach to non-invasively study structure-function relationships in the brain, however it remains challenging to interpret the complex and heterogeneous cascade of brain changes that manifest after concussion. Emerging conjunctive, data-driven analysis approaches like linked independent component analysis can integrate structural and functional imaging data to produce linked components that describe the shared inter-subject variance across images. These linked components not only offer the potential of a more comprehensive understanding of …

Comprehensive Evaluation Of Right Heart Performance And Pulmonary Hemodynamics In Neonatal Pulmonary Hypertension: Evaluation Of Cardiopulmonary Performance In Neonatal Pulmonary Hypertension, Soume Bhattacharya, Shawn Sen, Philip T. Levy, Danielle R. Rios

Paediatrics Publications

Purpose of review: Pulmonary hypertension is characterized by an elevation of pulmonary artery pressures and prolonged exposure of the right ventricle to high afterload that collectively contribute to morbidity and mortality in both the term and preterm infants. This review summarizes the pathogenesis, etiologies, and hemodynamic profiles of the conditions that result in pulmonary hypertension in neonates. We explore the application of echocardiographic techniques for the assessment of right ventricular performance and pulmonary hemodynamics that enhance and guide the diagnosis and management strategies in neonates. Recent findings: Clinical assessments based on the determinants of mean pulmonary artery pressures (pulmonary vascular …

Surgical Technique For Developing A Rabbit Model Of Congenital Diaphragmatic Hernia And Tracheal Occlusion, M. Mudri, S. A. Smith, C. Vander Tuin, J. Davidson, T. R.H. Regnault, A. Bütter

Paediatrics Publications

The surgical model of congenital diaphragmatic hernia (CDH) has been utilized in exploring treatments and innovative therapies, such as tracheal occlusion (TO). The rabbit is an excellent surgical model compared to others due to lower cost, ease of care, short gestational period, and large litter size. This model is also ideal in studying lung hypoplasia of CDH because rabbit lung development is most similar to humans as alveolarization begins prior to birth and continues post-natally. However, the surgical technique in creating a rabbit model of CDH is quite difficult and information is lacking on how to establish this model. Therefore, …

Perceptions On Competence By Design In Urology, Peter Wang, Ernest Chan, Adam Forster, Jennifer Vergel De Dios, Alp Sener, Sumit Dave, Saad Chahine

Paediatrics Publications

Introduction: The Royal College of Physicians and Surgeons of Canada has begun implementing Competence by Design (CBD). However, it is unclear how much urology trainees and faculty know about CBD, their attitudes towards this change, and their willingness to embrace and participate in this new model of training. Methods: This cross-sectional study was conducted through an online survey, which was administered to all trainees and faculty at Canadian urology programs prior to the implementation of CBD. The final survey consisted of eight demographic questions, 17 five-point Likert items, one visual analog scale question, 11 multiple-choice questions, and two open-ended questions. …

Reply To: Calcium/Citrate Ratio And Risk Of Kidney Stone, Misan Lee, Carmen Inés Rodriguez Cuellar, Ravneet Nagra, Peter Zhan Tao Wang, Vipin Bhayana, Guido Filler

Paediatrics Publications

No abstract provided.

Does The Urinary Calcium/Citrate Ratio Add To The Diagnostic Workup Of Children At Risk Of Kidney Stones? A Cross-Sectional Study, Misan Lee, Carmen Inés Rodriguez Cuellar, Ravneet Nagra, Zhan Tao Peter Wang, Vipin Bhayana, Guido Filler

Paediatrics Publications

The purpose of the study was to evaluate urinary citrate/creatinine (U Ci /U Cr ) and urinary calcium/citrate (U Ca /U Ci ) ratios for distinguishing stone formers (SF) from non-stone formers (NSF) in an at-risk population. This was a retrospective study that included all pediatric patients who underwent urinary citrate testing from April 2017 to March 2018. The urinary levels of citrate, calcium, sodium, potassium, creatinine, oxalate, urate, pH, and specific gravity (SG) were measured in our clinical laboratory. Diagnosis of kidney stones was obtained through chart review. A total of 97 patients were included (46 NSF and 51 …

Maternal Undernourishment In Guinea Pigs Leads To Fetal Growth Restriction With Increased Hypoxic Cells And Oxidative Stress In The Brain., Yohei Maki, Karen Nygard, Robert R Hammond, Timothy Regnault, Bryan S Richardson

Paediatrics Publications

BACKGROUND: We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for brain hypoxia and oxidative stress.

METHODS: Guinea pigs were fed ad libitum (control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1) was injected into pregnant sows. Fetuses were then necropsied and brain tissues were processed for HP-1 (hypoxia marker) and 4HNE, 8-OHdG, and 3-nitrotyrosine (oxidative stress markers) immunoreactivity (IR).

RESULTS: FGR-MNR fetal and brain weights were decreased 38 and 12%, respectively, with brain/fetal weights thereby increased 45% as a measure …

"C.H.A.M.P. Families": Description And Theoretical Foundations Of A Paediatric Overweight And Obesity Intervention Targeting Parents-A Single-Centre Non-Randomised Feasibility Study., Kristen Reilly, Trish Tucker, Jennifer D. Irwin Phd, Andrew Johnson, Erin S Pearson, Dirk E Bock, Shauna M. Burke

Paediatrics Publications

Childhood obesity represents a significant global health challenge, and treatment interventions are needed. The purpose of this paper is to describe the components and theoretical model that was used in the development and implementation of a unique parent-focussed paediatric overweight/obesity intervention. C.H.A.M.P. Families was a single-centre, prospective intervention offered to parents of children aged between 6⁻14 years with a body mass index (BMI) ≥85th percentile for age and sex. The intervention included: (1) eight group-based (parent-only) education sessions over 13-weeks; (2) eight home-based activities; and (3) two group-based (family) follow-up support sessions. The first section of the manuscript contains a …

Effect Of Ultrafiltration During Hemodialysis On Hepatic And Total-Body Water: An Observational Study., Claire J Grant, Trevor P Wade, Charles A Mckenzie, Guido Filler, Christopher W Mcintyre, Huang S. Shih-Han

Paediatrics Publications

Background

The hepatic circulation is involved in adaptive systemic responses to circulatory stress. However, it is vulnerable to both chronic hypervolemia and cardiac dysfunction. The influence of hemodialysis (HD) and ultrafiltration (UF) upon liver water content has been understudied. We conducted a detailed pilot study to characterize the effects of HD upon liver water content and stiffness, referenced to peripheral fluid mobilization and total body water.

Methods

We studied 14 established HD patients without liver disease. Magnetic resonance imaging (MRI) together with ultrasound-based elastography and bioimpedance assessment were employed to measure hepatic water content and stiffness, body composition, and water …

Consensus-Based Care Recommendations For Adults With Myotonic Dystrophy Type 1., Tetsuo Ashizawa, Cynthia Gagnon, William J Groh, Laurie Gutmann, Nicholas E Johnson, Giovanni Meola, Richard Moxley, Shree Pandya, Mark T Rogers, Ericka Simpson, Nathalie Angeard, Guillaume Bassez, Kiera N Berggren, Deepak Bhakta, Marco Bozzali, Ann Broderick, Janice L B Byrne, Craig Campbell, Edith Cup, John W Day, Elisa De Mattia, Denis Duboc, Tina Duong, Katy Eichinger, Anne-Berit Ekstrom, Baziel Van Engelen, Belen Esparis, Bruno Eymard, Marla Ferschl, Shahinaz M Gadalla, Benjamin Gallais, Todd Goodglick, Chad Heatwole, James Hilbert, Venessa Holland, Marie Kierkegaard, Wilma J Koopman, Kari Lane, Daphne Maas, Ami Mankodi, Katherine D Mathews, Darren G Monckton, David Moser, Saman Nazarian, Linda Nguyen, Peg Nopoulos, Richard Petty, Janel Phetteplace, Jack Puymirat, Subha Raman, Louis Richer, Elisabetta Roma, Jacinda Sampson, Valeria Sansone, Benedikt Schoser, Laurie Sterling, Jeffrey Statland, S H Subramony, Cuixia Tian, Careniña Trujillo, Gordon Tomaselli, Chris Turner, Shannon Venance, Aparajitha Verma, Molly White, Stefan Winblad

Paediatrics Publications

Purpose of review: Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit.

Recent findings: The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page …

Phenytoin Activates Smad3 Phosphorylation And Periostin Expression In Drug-Induced Gingival Enlargement., Shawna S Kim, Georgia Nikoloudaki, Mark Darling, Michael J Rieder, Douglas W Hamilton

Paediatrics Publications

Drug-induced gingival enlargement (DIGE) is a fibrotic condition associated with systemic administration of the anti-epileptic drug, phenytoin. We have previously demonstrated that periostin, which is transforming growth factor-beta (TGF-β) inducible gene, is upregulated in various fibrotic conditions including gingival enlargement associated with nifedipine. The objective of this study was to assess periostin expression in phenytoin-induced gingival enlargement (PIGE) tissues and to investigate the mechanisms underlying periostin expression. Human PIGE tissues were assessed using Masson's trichrome, with cell infiltration and changes in extracellular matrix composition characterized through labeling with antibodies to periostin, phospho-SMAD 3, TGF-β, as well as the macrophage markers …

Dried Blood Spot Technique-Based Liquid Chromatography-Tandem Mass Spectrometry Method As A Simple Alternative For Benznidazole Pharmacokinetic Assessment, Danilo César Galindo Bedor, Noely Camila Tavares Cavalcanti Bedor, José Wellithom Viturino Da Silva, Giovana Damasceno Sousa, Davi Pereira De Santana, Facundo Garcia-Bournissen, Jaime Altcheh, Bethania Blum, Fabiana Alves, Isabela Ribeiro

Paediatrics Publications

Chagas disease (CD) is recognized as one of the major neglected global tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ have been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-pharmacodynamic relationships in CD. The purpose of this study was to develop and validate a bioanalytical method to quantify BNZ levels in small-volume whole-blood samples collected as dried blood spots (DBS). The analysis was performed using high-performance liquid chromatography-positive electrospray tandem mass spectrometry. PK evaluation in healthy male …

Multicenter Trial Of A Combination Probiotic For Children With Gastroenteritis., Stephen B Freedman, Sarah Williamson-Urquhart, Ken J Farion, Serge Gouin, Andrew R Willan, Naveen Poonai, Katrina Hurley, Philip M Sherman, Yaron Finkelstein, Bonita E Lee, Xiao-Li Pang, Linda Chui, David Schnadower, Jianling Xie, Marc Gorelick, Suzanne Schuh

Paediatrics Publications

Background

Gastroenteritis accounts for approximately 1.7 million visits to the emergency department (ED) by children in the United States every year. Data to determine whether the use of probiotics improves outcomes in these children are lacking.

Methods

We conducted a randomized, double-blind trial involving 886 children 3 to 48 months of age with gastroenteritis who presented to six pediatric EDs in Canada. Participants received a 5-day course of a combination probiotic product containing Lactobacillus rhamnosus R0011 and L. helveticus R0052, at a dose of 4.0×10

Results

Moderate-to-severe gastroenteritis within 14 days after enrollment occurred in 108 of 414 participants (26.1%) …

Bafopathies' Dna Methylation Epi-Signatures Demonstrate Diagnostic Utility And Functional Continuum Of Coffin-Siris And Nicolaides-Baraitser Syndromes., Erfan Aref-Eshghi, Eric G Bend, Rebecca L Hood, Laila C Schenkel, Deanna Alexis Carere, Rana Chakrabarti, Sandesh C S Nagamani, Sau Wai Cheung, Philippe M Campeau, Chitra Prasad, Victoria Mok Siu, Lauren Brady, Mark A Tarnopolsky, David J Callen, A Micheil Innes, Susan M White, Wendy S Meschino, Andrew Y Shuen, Guillaume Paré, Dennis E Bulman, Peter J Ainsworth, Hanxin Lin, David I Rodenhiser, Raoul C Hennekam, Kym M Boycott, Charles E Schwartz, Bekim Sadikovic

Paediatrics Publications

Coffin-Siris and Nicolaides-Baraitser syndromes (CSS and NCBRS) are Mendelian disorders caused by mutations in subunits of the BAF chromatin remodeling complex. We report overlapping peripheral blood DNA methylation epi-signatures in individuals with various subtypes of CSS (ARID1B, SMARCB1, and SMARCA4) and NCBRS (SMARCA2). We demonstrate that the degree of similarity in the epi-signatures of some CSS subtypes and NCBRS can be greater than that within CSS, indicating a link in the functional basis of the two syndromes. We show that chromosome 6q25 microdeletion syndrome, harboring ARID1B deletions, exhibits a similar CSS/NCBRS methylation profile. Specificity of this epi-signature was confirmed across …

Driver Mutations In Janus Kinases In A Mouse Model Of B-Cell Leukemia Induced By Deletion Of Pu.1 And Spi-B, Carolina R. Batista, Michelle Lim, Anne Sophie Laraḿee, Faisal Abu-Sardanah, Li S. Xu, Rajon Hossain, Gillian I. Bell, David A. Hess, Rodney P. Dekoter

Paediatrics Publications

Precursor B-cell acute lymphoblastic leukemia (B-ALL) is associated with recurrent mutations that occur in cancer-initiating cells. There is a need to understand how driver mutations influence clonal evolution of leukemia. The E26-Transformation-specific (ETS) transcription factors PU.1 and Spi-B (encoded by Spi1 and Spib) execute a critical role in B-cell development and serve as complementary tumor suppressors. Here, we used a mouse model to conditionally delete Spi1 and Spib genes in developing B cells. These mice developed B-ALL with a median time to euthanasia of 18 weeks. We performed RNA and whole-exome sequencing (WES) on leukemias isolated from Mb1-CreDPB mice and …

Tri-Ponderal Mass Index In Survivors Of Childhood Brain Tumors: A Cross-Sectional Study., E Danielle Sims, Kuan-Wen Wang, Adam Fleming, Donna L Johnston, Shayna M Zelcer, Shahrad Rod Rassekh, Sarah Burrow, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

Survivors of childhood brain tumors (SCBT) face a higher risk of cardiometabolic disorders and premature mortality compared to the general population. Excess adiposity is a known risk factor for these comorbidities. However, while SCBT have higher adiposity compared to healthy controls, measuring adiposity in clinical practice involves access to specialized equipment and may impact busy clinical services. Tri-ponderal Mass Index (TMI; kg/m

Sapropterin Treatment Prevents Congenital Heart Defects Induced By Pregestational Diabetes Mellitus In Mice., Anish Engineer, Tana Saiyin, Xiangru Lu, Andrew S Kucey, Brad L Urquhart, Thomas A Drysdale, Kambiz Norozi, Qingping Feng

Paediatrics Publications

Background Tetrahydrobiopterin is a cofactor of endothelial NO synthase ( eNOS ), which is critical to embryonic heart development. We aimed to study the effects of sapropterin (Kuvan), an orally active synthetic form of tetrahydrobiopterin on eNOS uncoupling and congenital heart defects ( CHD s) induced by pregestational diabetes mellitus in mice. Methods and Results Adult female mice were induced to pregestational diabetes mellitus by streptozotocin and bred with normal male mice to produce offspring. Pregnant mice were treated with sapropterin or vehicle during gestation. CHD s were identified by histological analysis. Cell proliferation, eNOS dimerization, and reactive oxygen species …