Medical Specialties Commons^™

Non-Pathological Bilious Vomiting Complicating Therapeutic Hypothermia For Hypoxic Ischaemic Encephalopathy In Neonates: A Retrospective Cohort Study, Julie Hukui, Sarah Jones, Kevin Coughlin, Simon Levin, Jennifer Ruth Foster

Paediatrics Publications

Objective Therapeutic hypothermia (TH) for moderate-to-severe neonatal hypoxic ischaemic encephalopathy (HIE) is generally described as safe. We performed this study to determine the incidence of bilious vomiting or bilious drainage (BVD) attributable to TH in this population. Design A single-centre, retrospective cohort study. Setting Neonatal and paediatric intensive care units (NICU and PICU) of a single tertiary care centre. Patients All newborns with HIE who met criteria for TH between 2009 and 2014. Interventions Cases were matched 1:1 for unit of care (NICU vs PICU), gestational age, gender, and Sarnat score with historic controls who did not receive TH. Groups …

Epigenetic Etiology Of Intellectual Disability., Shigeki Iwase, Nathalie G Bérubé, Zhaolan Zhou, Nael Nadif Kasri, Elena Battaglioli, Marilyn Scandaglia, Angel Barco

Paediatrics Publications

Intellectual disability (ID) is a prevailing neurodevelopmental condition associated with impaired cognitive and adaptive behaviors. Many chromatin-modifying enzymes and other epigenetic regulators have been genetically associated with ID disorders (IDDs). Here we review how alterations in the function of histone modifiers, chromatin remodelers, and methyl-DNA binding proteins contribute to neurodevelopmental defects and altered brain plasticity. We also discuss how progress in human genetics has led to the generation of mouse models that unveil the molecular etiology of ID, and outline the direction in which this field is moving to identify therapeutic strategies for IDDs. Importantly, because the chromatin regulators linked …

Canadian Guidelines For Controlled Pediatric Donation After Circulatory Determination Of Death-Summary Report, Matthew J Weiss, Laura Hornby, Bram Rochwerg, Michael Van Manen, Sonny Dhanani, V Ben Sivarajan, Amber Appleby, Mary Bennett, Daniel Buchman, Catherine Farrell, Aviva Goldberg, Rebecca Greenberg, Ram Singh, Thomas A Nakagawa, William Witteman, Jill Barter, Allon Beck, Kevin Coughlin, Alf Conradi, Cynthia Cupido, Rosanne Dawson, Anne Dipchand, Darren Freed, Karen Hornby, Valerie Langlois, Cheryl Mack, Meagan Mahoney, Deepak Manhas, Christopher Tomlinson, Samara Zavalkoff, Sam D Shemie

Paediatrics Publications

OBJECTIVES: Create trustworthy, rigorous, national clinical practice guidelines for the practice of pediatric donation after circulatory determination of death in Canada.

METHODS: We followed a process of clinical practice guideline development based on World Health Organization and Canadian Medical Association methods. This included application of Grading of Recommendations Assessment, Development, and Evaluation methodology. Questions requiring recommendations were generated based on 1) 2006 Canadian donation after circulatory determination of death guidelines (not pediatric specific), 2) a multidisciplinary symposium of national and international pediatric donation after circulatory determination of death leaders, and 3) a scoping review of the pediatric donation after circulatory …

Identification Of A Novel Synaptic Protein, Tmtc3, Involved In Periventricular Nodular Heterotopia With Intellectual Disability And Epilepsy, Sali M K Farhan, Kevin C J Nixon, Michelle Everest, Tara N Edwards, Shirley Long, Dmitri Segal, Maria J Knip, Heleen H Arts, Rana Chakrabarti, Jian Wang, John F Robinson, Donald Lee, Seyed M Mirsattari, C Anthony Rupar, Victoria M Siu, Forge Canada Consortium, Michael O Poulter, Robert A Hegele, Jamie M Kramer

Paediatrics Publications

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently …

Disparities In Rate, Triggers, And Management In Pediatric And Adult Cases Of Suspected Drug-Induced Anaphylaxis In Canada, Sofianne Gabrielli, Ann E Clarke, Harley Eisman, Judy Morris, Lawrence Joseph, Sebastien La Vieille, Peter Small, Rodrick Lim, Paul Enarson, Michal Zelcer, Edmond S Chan, Chris Mill, Moshe Ben-Shoshan

Paediatrics Publications

Introduction

Data is sparse on drug-induced anaphylaxis (DIA) and there have not been studies assessing the differences in clinical characteristics and management of DIA between adults and children.

Objective

We assessed the percentage, diagnosis, and management of DIA among all anaphylaxis visits in three pediatric and one adult emergency departments (ED) across Canada.

Methods

Children presenting to the Montreal Children's Hospital (MCH), British Columbia Children's Hospital (BCCH), and Children's Hospital at London Health Sciences Center and adults presenting to Hôpital du Sacré-Coeur with anaphylaxis were recruited as part of the Cross-Canada Anaphylaxis Registry. A standardized data form documenting the reaction …

Legionellosis Following Water Birth In A Hot Tub In A Canadian Neonate, Michelle Barton, Brianna Mckelvie, Aaron Campigotto, Tara Mullowney

Paediatrics Publications

No abstract provided.

Oral Morphine Versus Ibuprofen Administered At Home For Postoperative Orthopedic Pain In Children: A Randomized Controlled Trial, Naveen Poonai, Natasha Datoo, Samina Ali, Megan Cashin, Amy L Drendel, Rongbo Zhu, Natasha Lepore, Michael Greff, Michael Rieder, Debra Bartley

Paediatrics Publications

BACKGROUND: Oral morphine for postoperative pain after minor pediatric surgery, while increasingly popular, is not supported by evidence. We evaluated whether oral morphine was superior to ibuprofen for at-home management of children's postoperative pain.

METHODS: We conducted a randomized superiority trial comparing oral morphine (0.5 mg/kg) with ibuprofen (10 mg/kg) in children 5 to 17 years of age who had undergone minor outpatient orthopedic surgery (June 2013 to September 2016). Participants took up to 8 doses of the intervention drug every 6 hours as needed for pain at home. The primary outcome was pain, according to the Faces Pain Scale …

Targeting Cysteine Thiols For In Vitro Site-Specific Glycosylation Of Recombinant Proteins, Yoo Jung Choi, Jinhui Zhu, Steve Chung, Naveed Siddiqui, Qingping Feng, Peter B. Stathopulos

Paediatrics Publications

Stromal interaction molecule-1 (STIM1) is a type-I transmembrane protein located on the endoplasmic reticulum (ER) and plasma membranes (PM). ER-resident STIM1 regulates the activity of PM Orai1 channels in a process known as store operated calcium (Ca2+) entry which is the principal Ca2+ signaling process that drives the immune response. STIM1 undergoes post-translational N-glycosylation at two luminal Asn sites within the Ca2+ sensing domain of the molecule. However, the biochemical, biophysical, and structure biological effects of N-glycosylated STIM1 were poorly understood until recently due to an inability to readily obtain high levels of homogeneous N-glycosylated protein. Here, we describe the …

Scaffolding Proteins In The Development And Maintenance Of The Epidermal Permeability Barrier, Melissa Crawford, Lina Dagnino

Paediatrics Publications

The skin of mammals and other terrestrial vertebrates protects the organism against the external environment, preventing heat, water and electrolyte loss, as well as entry of chemicals and pathogens. Impairments in the epidermal permeability barrier function are associated with the genesis and/or progression of a variety of pathological conditions, including genetic inflammatory diseases, microbial and viral infections, and photodamage induced by UV radiation. In mammals, the outside-in epidermal permeability barrier is provided by the joint action of the outermost cornified layer, together with assembled tight junctions in granular keratinocytes found in the layers underneath. Tight junctions serve as both outside-in …

Mutations In Keops-Complex Genes Cause Nephrotic Syndrome With Primary Microcephaly, Daniela A Braun, Jia Rao, Geraldine Mollet, David Schapiro, Marie-Claire Daugeron, Weizhen Tan, Olivier Gribouval, Olivia Boyer, Patrick Revy, Tilman Jobst-Schwan, Johanna Magdalena Schmidt, Jennifer A Lawson, Denny Schanze, Shazia Ashraf, Jeremy F P Ullmann, Charlotte A Hoogstraten, Nathalie Boddaert, Bruno Collinet, Gaëlle Martin, Dominique Liger, Svjetlana Lovric, Monica Furlano, I Chiara Guerrera, Oraly Sanchez-Ferras, Jennifer F Hu, Anne-Claire Boschat, Sylvia Sanquer, Björn Menten, Sarah Vergult, Nina De Rocker, Merlin Airik, Tobias Hermle, Shirlee Shril, Eugen Widmeier, Heon Yung Gee, Won-Il Choi, Carolin E Sadowski, Werner L Pabst, Jillian K Warejko, Ankana Daga, Tamara Basta, Verena Matejas, Karin Scharmann, Sandra D Kienast, Babak Behnam, Brendan Beeson, Amber Begtrup, Malcolm Bruce, Gaik-Siew Ch'ng, Shuan-Pei Lin, Jui-Hsing Chang, Chao-Huei Chen, Megan T Cho, Patrick M Gaffney, Patrick E Gipson, Chyong-Hsin Hsu, Jameela A Kari, Yu-Yuan Ke, Cathy Kiraly-Borri, Wai-Ming Lai, Emmanuelle Lemyre, Rebecca Okashah Littlejohn, Amira Masri, Mastaneh Moghtaderi, Kazuyuki Nakamura, Fatih Ozaltin, Marleen Praet, Chitra Prasad, Agnieszka Prytula, Elizabeth R Roeder, Patrick Rump, Rhonda E Schnur, Takashi Shiihara, Manish D Sinha, Neveen A Soliman, Kenza Soulami, David A Sweetser, Wen-Hui Tsai, Jeng-Daw Tsai, Rezan Topaloglu, Udo Vester, David H Viskochil, Nithiwat Vatanavicharn, Jessica L Waxler, Klaas J Wierenga, Matthias T F Wolf, Sik-Nin Wong, Sebastian A Leidel, Gessica Truglio, Peter C Dedon, Annapurna Poduri, Shrikant Mane, Richard P Lifton, Maxime Bouchard, Peter Kannu, David Chitayat, Daniella Magen, Bert Callewaert, Herman Van Tilbeurgh, Martin Zenker, Corinne Antignac, Friedhelm Hildebrandt

Paediatrics Publications

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced …

Global, Regional, And National Comparative Risk Assessment Of 84 Behavioural, Environmental And Occupational, And Metabolic Risks Or Clusters Of Risks, 1990-2016: A Systematic Analysis For The Global Burden Of Disease Study 2016, Gbd 2016 Risk Factors Collaborators

Paediatrics Publications

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of risk factor exposure and attributable burden of disease. By providing estimates over a long time series, this study can monitor risk exposure trends critical to health surveillance and inform policy debates on the importance of addressing risks in context.

METHODS: We used the comparative risk assessment framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and …

Global, Regional, And National Incidence, Prevalence, And Years Lived With Disability For 328 Diseases And Injuries For 195 Countries, 1990-2016: A Systematic Analysis For The Global Burden Of Disease Study 2016, Gbd 2016 Disease And Injury Incidence And Prevalence Collaborators

Paediatrics Publications

BACKGROUND: As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016.

METHODS: We estimated prevalence and incidence for 328 diseases and injuries and 2982 sequelae, their non-fatal consequences. We used DisMod-MR 2.1, a Bayesian meta-regression tool, as the main method of estimation, ensuring consistency between …

Global, Regional, And National Disability-Adjusted Life-Years (Dalys) For 333 Diseases And Injuries And Healthy Life Expectancy (Hale) For 195 Countries And Territories, 1990-2016: A Systematic Analysis For The Global Burden Of Disease Study 2016, Gbd 2016 Dalys And Hale Collaborators

Paediatrics Publications

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI).

METHODS: We used results from the Global …

Insulin-Like Growth Factor Binding Protein-6 Alters Skeletal Muscle Differentiation Of Human Mesenchymal Stem Cells, Doaa Aboalola, Victor K. M. Han

Paediatrics Publications

Insulin-like growth factor binding protein-6 (IGFBP-6), the main regulator of insulin-like growth factor-2 (IGF-2), is a component of the stem cell niche in developing muscle cells. However, its role in muscle development has not been clearly defined. In this study, we investigated the role of IGFBP-6 in muscle commitment and differentiation of human mesenchymal stem cells derived from the placenta. We showed that placental mesenchymal stem cells (PMSCs) have the ability to differentiate into muscle cells when exposed to a specific culture medium by expressing muscle markers Pax3/7, MyoD, myogenin, and myosin heavy chain in a stage-dependent manner with the …

The Relationship Between Paediatric Practitioners And ‘Industry’, Susan Albersheim, Kevin Coughlin

Paediatrics Publications

Paediatric practitioners interact with industry representatives for many purposes but most often to receive information on new and existing products. While practitioners believe they are immune to the marketing influences exerted by these representatives, research has demonstrated otherwise. The literature suggests that the public is aware of such influences and that most people feel industry influence on practitioners is inappropriate. National guidelines go some way toward regulating practitioner–industry interactions, although they are not always clear or sufficient. The present practice point explores the context for these relationships, raises some ethical issues specific to paediatric practitioners and provides recommendations for maintaining …

Activating Transcription Factor 3 Promotes Loss Of The Acinar Cell Phenotype In Response To Cerulein-Induced Pancreatitis In Mice, Elena N Fazio, Claire C Young, Jelena Toma, Michael Levy, Kurt R Berger, Charis L Johnson, Rashid Mehmood, Patrick Swan, Alphonse Chu, Sean P Cregan, F Jeffrey Dilworth, Christopher J Howlett, Christopher L Pin

Paediatrics Publications

Pancreatitis is a debilitating disease of the exocrine pancreas that, under chronic conditions, is a major susceptibility factor for pancreatic ductal adenocarcinoma (PDAC). Although down-regulation of genes that promote the mature acinar cell fate is required to reduce injury associated with pancreatitis, the factors that promote this repression are unknown. Activating transcription factor 3 (ATF3) is a key mediator of the unfolded protein response, a pathway rapidly activated during pancreatic insult. Using chromatin immunoprecipitation followed by next-generation sequencing, we show that ATF3 is bound to the transcriptional regulatory regions of >30% of differentially expressed genes during the initiation of pancreatitis. …

Therapeutic And Prognostic Implications Of Braf V600e In Pediatric Low-Grade Gliomas., Alvaro Lassaletta, Michal Zapotocky, Matthew Mistry, Vijay Ramaswamy, Marion Honnorat, Rahul Krishnatry, Ana Guerreiro Stucklin, Nataliya Zhukova, Anthony Arnoldo, Scott Ryall, Catriona Ling, Tara Mckeown, Jim Loukides, Ofelia Cruz, Carmen De Torres, Cheng-Ying Ho, Roger J Packer, Ruth Tatevossian, Ibrahim Qaddoumi, Julie H Harreld, James D Dalton, Jean Mulcahy-Levy, Nicholas Foreman, Matthias A Karajannis, Shiyang Wang, Matija Snuderl, Amulya Nageswara Rao, Caterina Giannini, Mark Kieran, Keith L Ligon, Maria Luisa Garre, Paolo Nozza, Samantha Mascelli, Alessandro Raso, Sabine Mueller, Theodore Nicolaides, Karen Silva, Romain Perbet, Alexandre Vasiljevic, Cécile Faure Conter, Didier Frappaz, Sarah Leary, Courtney Crane, Aden Chan, Ho-Keung Ng, Zhi-Feng Shi, Ying Mao, Elizabeth Finch, David Eisenstat, Bev Wilson, Anne Sophie Carret, Peter Hauser, David Sumerauer, Lenka Krskova, Valerie Larouche, Adam Fleming, Shayna Zelcer, Nada Jabado, James T Rutka, Peter Dirks, Michael D Taylor, Shiyi Chen, Ute Bartels, Annie Huang, David W Ellison, Eric Bouffet, Cynthia Hawkins, Uri Tabori

Paediatrics Publications

Purpose BRAF V600E is a potentially highly targetable mutation detected in a subset of pediatric low-grade gliomas (PLGGs). Its biologic and clinical effect within this diverse group of tumors remains unknown.

Patients and Methods A combined clinical and genetic institutional study of patients with PLGGs with long-term follow-up was performed (N = 510). Clinical and treatment data of patients with BRAF V600E mutated PLGG (n = 99) were compared with a large international independent cohort of patients with BRAF V600E mutated-PLGG (n = 180).

Results BRAF V600E mutation was detected in 69 of 405 patients (17%) with PLGG across a …

Regulation Of Osteogenic Differentiation Of Placental-Derived Mesenchymal Stem Cells By Insulin-Like Growth Factors And Low Oxygen Tension, Amer Youssef, Victor K. M. Han

Paediatrics Publications

Placental mesenchymal stem cells (PMSCs) are multipotent cells that can differentiate in vitro to multiple lineages, including bone. Insulin-like growth factors (IGFs, IGF-1 and IGF-2) participate in maintaining growth, survival, and differentiation of many stem cells, including osteoprogenitors. Low oxygen tension (PO2) can maintain stem cell multipotency and impede osteogenic differentiation. In this study, we investigated whether PMSC osteogenic differentiation is influenced by low PO2 and by IGFs. Our results indicated that low PO2 decreased osteogenic markers RUNX2 and OPN; however, re-exposure to higher oxygen tension (room air) restored differentiation. IGFs, especially IGF-1, triggered an earlier expression of RUNX2 and …

Growth And Weight Gain In Children With Juvenile Idiopathic Arthritis: Results From The Reacch-Out Cohort., Jaime Guzman, Tristan Kerr, Leanne M Ward, Jinhui Ma, Kiem Oen, Alan M Rosenberg, Brian M Feldman, Gilles Boire, Kristin Houghton, Paul Dancey, Rosie Scuccimarri, Alessandra Bruns, Adam M Huber, Karen Watanabe Duffy, Natalie J Shiff, Roberta A Berard, Deborah M Levy, Elizabeth Stringer, Kimberly Morishita, Nicole Johnson, David A Cabral, Maggie Larché, Ross E Petty, Ronald M Laxer, Earl Silverman, Paivi Miettunen, Anne-Laure Chetaille, Elie Haddad, Lynn Spiegel, Stuart E Turvey, Heinrike Schmeling, Bianca Lang, Janet Ellsworth, Suzanne E Ramsey, Johannes Roth, Sarah Campillo, Susanne Benseler, Gaëlle Chédeville, Rayfel Schneider, Shirley M L Tse, Roxana Bolaria, Katherine Gross, Debbie Feldman, Bonnie Cameron, Roman Jurencak, Jean Dorval, Claire Leblanc, Claire St Cyr, Michele Gibbon, Rae S M Yeung, Ciarán M Duffy, Lori B Tucker

Paediatrics Publications

BACKGROUND: With modern treatments, the effect of juvenile idiopathic arthritis (JIA) on growth may be less than previously reported. Our objective was to describe height, weight and body mass index (BMI) development in a contemporary JIA inception cohort.

METHODS: Canadian children newly-diagnosed with JIA 2005-2010 had weight and height measurements every 6 months for 2 years, then yearly up to 5 years. These measurements were used to calculate mean age- and sex-standardized Z-scores, and estimate prevalence and cumulative incidence of growth impairments, and the impact of disease activity and corticosteroids on growth.

RESULTS: One thousand one hundred forty seven children …

Heterozygous De Novo Ubtf Gain-Of-Function Variant Is Associated With Neurodegeneration In Childhood., Simon Edvardson, Claudia M Nicolae, Pankaj B Agrawal, Cyril Mignot, Katelyn Payne, Asuri Narayan Prasad, Chitra Prasad, Laurie Sadler, Caroline Nava, Thomas E Mullen, Amber Begtrup, Berivan Baskin, Zöe Powis, Avraham Shaag, Boris Keren, George-Lucian Moldovan, Orly Elpeleg

Paediatrics Publications

Ribosomal RNA (rRNA) is transcribed from rDNA by RNA polymerase I (Pol I) to produce the 45S precursor of the 28S, 5.8S, and 18S rRNA components of the ribosome. Two transcription factors have been defined for Pol I in mammals, the selectivity factor SL1, and the upstream binding transcription factor (UBF), which interacts with the upstream control element to facilitate the assembly of the transcription initiation complex including SL1 and Pol I. In seven unrelated affected individuals, all suffering from developmental regression starting at 2.5-7 years, we identified a heterozygous variant, c.628G>A in UBTF, encoding p.Glu210Lys in UBF, which …

Choosing Wisely Canada: The Canadian College Of Medical Geneticists’ (Ccmg) List Of Five Items Physicians And Patients Should Question, Elaine Goh, Andrea Guerin, Joanna Lazier, Sharan Goobie, Tanya N. Nelson, Ron Agatep, Victoria Mok Siu, Yaren Y. Niederhoffer, Julie Richer

Paediatrics Publications

No abstract provided.

Brain Biomarkers And Pre-Injury Cognition Are Associated With Long-Term Cognitive Outcome In Children With Traumatic Brain Injury, Amy A Wilkinson, Maureen Dennis, Nevena Simic, Margot J Taylor, Benjamin R Morgan, Helena Frndova, Karen Choong, Craig Campbell, Douglas Fraser, Vicki Anderson, Anne-Marie Guerguerian, Russell Schachar, Jamie Hutchison

Paediatrics Publications

BACKGROUND: Children with traumatic brain injury (TBI) are frequently at risk of long-term impairments of attention and executive functioning but these problems are difficult to predict. Although deficits have been reported to vary with injury severity, age at injury and sex, prognostication of outcome remains imperfect at a patient-specific level. The objective of this proof of principle study was to evaluate a variety of patient variables, along with six brain-specific and inflammatory serum protein biomarkers, as predictors of long-term cognitive outcome following paediatric TBI.

METHOD: Outcome was assessed in 23 patients via parent-rated questionnaires related to attention deficit hyperactivity disorder …

Deviations From The Expected Relationship Between Serum Fgf23 And Other Markers In Children With Ckd: A Cross-Sectional Study., Daisy Liu, Ana Catalina Alvarez-Elías, Brooke Wile, Vladimir Belostotsky, Guido Filler

Paediatrics Publications

BACKGROUND: High levels of fibroblast growth factor-23 (FGF23) are associated with mortality. In chronic kidney disease (CKD), FGF23 levels rise as renal function declines. We analyzed the contribution of laboratory values to the variance of FGF23 levels in relationship to a curve of expected FGF23 levels for a given GFR.

METHODS: Following approval by the research ethics boards, we measured FGF23, CysC eGFR, creatinine, urea, albumin, calcium, phosphate, vitamin D metabolites, PTH, alkaline phosphatase, CRP, and venous gases in 141 pediatric CKD patients (45, 37, 32, 13 and 14 CKD stages I, II, III, IV, and V, respectively). Data were …

Eight-Year-Old Girl With Hepatomegaly, Becky Biqi Chen, Chitra Prasad, Joanna C Walsh, Dhandapani Ashok

Paediatrics Publications

CASE DESCRIPTION

An 8-year-old girl was referred for abdominal pain and elevated liver transaminases. She was previously healthy and was not on any medications. There was no prior history of blood transfusions, toxin exposures or parenteral nutrition. Her parents were nonconsanguineous, and of French and Irish descent. Her family has no history of liver diseases but maternal and paternal grandparents have elevated cholesterol. Her weight was 25.5 kg (27th percentile), height 127 cm (21st percentile) and body mass index (BMI) was 15.8 kg/m2 (42nd percentile). On abdominal examination, both liver and spleen were enlarged. There was no scleral icterus or …

Inhibition Of Mt1-Mmp Proteolytic Function And Erk1/2 Signalling Influences Cell Migration And Invasion Through Changes In Mmp-2 And Mmp-9 Levels, Mario A. Cepeda, Caitlin L. Evered, Jacob J.H. Pelling, Sashko Damjanovski

Paediatrics Publications

Membrane type-1 matrix metalloproteinase (MT1-MMP, MMP-14) is a unique protease that cleaves extracellular proteins, activates proMMPs, and initiates intracellular signalling. MCF-7 cells are non-invasive and deficient in MT1-MMP, MMP-2, and MMP-9 expression. We created an MCF-7 cell line (C2) that stably produces active MT1-MMP and demonstrated increased ERK1/2 phosphorylation. MAPK inhibition in this cell line showed an inverse relationship in MMP-2 and MMP-9 transcripts where levels of these genes increased and decreased, respectively. Using invasive MDA-MB 231 cells that endogenously produce MT1-MMP and have naturally high pERK levels, we demonstrated the identical inverse relationship between MMP-2 and -9 transcript and …

Psychometric Properties Of The Ndetei–Othieno–Kathuku (Nok) Scale: A Mental Health Assessment Tool For An African Setting, Christy A. Denckla, David M. Ndetei, Victoria N. Mutiso, Christine W. Musyimi, Abednego M. Musau, Eric S. Nandoya, Kelly K. Anderson, Snezana Milanovic, David Henderson, Kwame Mckenzie

Paediatrics Publications

Background: Research suggests that psychiatric conditions in children and adolescents are highly debilitating, with sparse resources for assessment and treatment in low- and middle-income countries (LMICs). Objectives: The primary aim of this study was to evaluate the reliability, validity, and latent factor structure of an ethnographically-grounded assessment instrument for detecting common mental health complaints among rural Kenyan children and adolescents. Methods: The Ndetei–Othieno–Kathuku Scale (NOK) was delivered to 2 282 children aged 10 to 18 years old. Exploratory factor analysis identified four latent factors. This structure was confirmed in subsequent confirmatory factor analyses. External validity was explored by investigating associations …

The Clinical Impact Of Copy Number Variants In Inherited Bone Marrow Failure Syndromes, Nicolas Waespe, Santhosh Dhanraj, Manju Wahala, Elena Tsangaris, Tom Enbar, Bozana Zlateska, Hongbing Li, Robert J Klaassen, Conrad V Fernandez, Geoff D E Cuvelier, John K Wu, Yves D Pastore, Mariana Silva, Jeffrey H Lipton, Joseé Brossard, Bruno Michon, Sharon Abish, Macgregor Steele, Roona Sinha, Mark J Belletrutti, Vicky R Breakey, Lawrence Jardine, Lisa Goodyear, Liat Kofler, Michaela Cada, Lillian Sung, Mary Shago, Stephen W Scherer, Yigal Dror

Paediatrics Publications

Inherited bone marrow failure syndromes (IBMFSs) comprise a genetically heterogeneous group of diseases with hematopoietic failure and a wide array of physical malformations. Copy number variants (CNVs) were reported in some IBMFSs. It is unclear what impact CNVs play in patients evaluated for a suspected diagnosis of IBMFS. Clinical and genetic data of 323 patients from the Canadian Inherited Marrow Failure Registry from 2001 to 2014, who had a documented genetic work-up, were analyzed. Cases with pathogenic CNVs (at least 1 kilobasepairs) were compared to cases with other mutations. Genotype-phenotype correlations were performed to assess the impact of CNVs. Pathogenic …

Association Of Suicidality And Depression With 5Α-Reductase Inhibitors, Blayne Welk, Eric Mcarthur, Michael Ordon, Kelly K. Anderson, Jade Hayward, Stephanie Dixon

Paediatrics Publications

IMPORTANCE There have been concerns raised by patients and regulatory agencies regarding serious psychiatric adverse effects associated with 5α-reductase inhibitors. OBJECTIVE To determine if there is an increased risk of suicide, self-harm, or depression among older men starting a 5α-reductase inhibitor for prostatic enlargement. DESIGN, SETTING, AND PARTICIPANTS A population-based, retrospective, matched cohort study using linked administrative data for 93 197 men ages 66 years or older (median [IQR] age, 75 [70-80] years) in Ontario, Canada, who initiated a new prescription for a 5α-reductase inhibitor during the study period (2003 through 2013). Participants were matched (using a propensity score that …

Allied Health Professional Support In Pediatric Inflammatory Bowel Disease: A Survey From The Canadian Children Inflammatory Bowel Disease Network—A Joint Partnership Of Cihr And The Ch.I.L.D. Foundation, Wael El-Matary, Eric I. Benchimol, David Mack, Hien Q. Huynh, Jeff Critch, Anthony Otley, Colette Deslandres, Kevan Jacobson, Jennifer Debruyn, Matthew W. Carroll, Eytan Wine, Johan Van Limbergen, Mary Sherlock, Kevin Bax, Sally Lawrence, Ernest Seidman, Robert Issenman, Thomas D. Walters, Peter Church, Anne M. Griffiths

Paediatrics Publications

Objectives. The current number of healthcare providers (HCP) caring for children with inflammatory bowel disease (IBD) across Canadian tertiary-care centres is underinvestigated. The aim of this survey was to assess the number of healthcare providers (HCP) in ambulatory pediatric IBD care across Canadian tertiary-care centres.

Methods. Using a self-administered questionnaire, we examined available resources in academic pediatric centres within the Canadian Children IBD Network. The survey evaluated the number of HCP providing ambulatory care for children with IBD.

Results. All 12 tertiary pediatric gastroenterology centres participating in the network responded. Median full-time equivalent (FTE) of allied health professionals providing IBD …

Pharmacogenomic Screening For Anthracycline-Induced Cardiotoxicity In Childhood Cancer, Folefac Aminkeng, Colin J D Ross, Shahrad R Rassekh, Michael J Rieder, Amit P Bhavsar, Shubhayan Sanatani, Daniel Bernstein, Michael R Hayden, Ursula Amstutz, Bruce C Carleton

Paediatrics Publications

No abstract provided.