Medicine and Health Sciences Commons^™

Cardiovascular Disease Risk Assessment In Patients With Familial Mediterranean Fever Related Renal Amyloidosis., Micol Romano, David Piskin, Roberta A Berard, Bradley C Jackson, Cengizhan Acikel, Juan J Carrero, Helen J Lachmann, Mahmut I Yilmaz, Erkan Demirkaya

Paediatrics Publications

Chronic inflammation and proteinuria is a risk factor for cardiovascular disease (CVD) in patients with chronic kidney diseases and rheumatologic disorders. Our aim was to investigate the CVD events (CVDEs) and survival between the patients with FMF-related AA amyloidosis and glomerulonephropathies (GN) to define possible predictors for CVDEs. A prospective follow-up study with FMF-amyloidosis and glomerulonephropathy (GN) was performed and patients were followed for CVDEs. Flow-mediated dilatation (FMD), FGF-23, serum lipid, hsCRP levels, BMI and HOMA were assessed. A Cox regression analysis was performed to evaluate the risk factors for CVDEs. There were 107 patients in the FMF-amyloidosis group and …

Screening And Treatment Outcomes In Adults And Children With Type 1 Diabetes And Asymptomatic Celiac Disease: The Cd-Diet Study., Farid H Mahmud, Antoine B M Clarke, Kariym C Joachim, Esther Assor, Charlotte Mcdonald, Fred Saibil, Heather A Lochnan, Zubin Punthakee, Amish Parikh, Andrew Advani, Baiju R Shah, Bruce A Perkins, Caroline S Zuijdwijk, David R Mack, Dror Koltin, Emilia N De Melo, Eugene Hsieh, Geetha Mukerji, Jeremy Gilbert, Kevin Bax, Margaret L Lawson, Maria Cino, Melanie D Beaton, Navaaz A Saloojee, Olivia Lou, Patricia H Gallego, Premysl Bercik, Robyn L Houlden, Ronnie Aronson, Susan E Kirsch, William G Paterson, Margaret A Marcon

Paediatrics Publications

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD.

RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA

RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%,

CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD.

Fri0547 The Effect Of Corrected Inflammation, Oxidative Stress And Endothelial Dysfunction On Fmd Levels In Patients With Selected Chronic Diseases: A Quasi-Experimental Study., Mahmut Ilker Yilmaz, Micol Romano, Mustafa Kemal Basarali, Abdelbaset Elzagallaai, Murat Karaman, Zeynep Demir, Muhammet Fatih Demir, Fatih Akcay, Melik Seyrek, Nuri Haksever, David Piskin, Rolando Cimaz, Michael Rieder, Erkan Demirkaya

Paediatrics Publications

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline …

The Effect Of Corrected Inflammation, Oxidative Stress And Endothelial Dysfunction On Fmd Levels In Patients With Selected Chronic Diseases: A Quasi-Experimental Study., Mahmut Ilker Yilmaz, Micol Romano, Mustafa Kemal Basarali, Abdelbaset Elzagallaai, Murat Karaman, Zeynep Demir, Muhammet Fatih Demir, Fatih Akcay, Melik Seyrek, Nuri Haksever, David Piskin, Rolando Cimaz, Michael Rieder, Erkan Demirkaya

Paediatrics Publications

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline …

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 …

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 …

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 …

Magnetic Resonance Imaging In The Diagnosis Of White Matter Signal Abnormalities., Ravi Datar, Asuri Narayan Prasad, Keng Yeow Tay, Charles Anthony Rupar, Pavlo Ohorodnyk, Michael Miller, Chitra Prasad

Paediatrics Publications

Background White matter abnormalities (WMAs) pose a diagnostic challenge when trying to establish etiologic diagnoses. During childhood and adult years, genetic disorders, metabolic disorders and acquired conditions are included in differential diagnoses. To assist clinicians and radiologists, a structured algorithm using cranial magnetic resonance imaging (MRI) has been recommended to aid in establishing working diagnoses that facilitate appropriate biochemical and genetic investigations. This retrospective pilot study investigated the validity and diagnostic utility of this algorithm when applied to white matter signal abnormalities (WMSAs) reported on imaging studies of patients seen in our clinics. Methods The MRI algorithm was applied to …

Peripheral Blood Epi-Signature Of Claes-Jensen Syndrome Enables Sensitive And Specific Identification Of Patients And Healthy Carriers With Pathogenic Mutations In Kdm5c, Laila C Schenkel, Erfan Aref-Eshghi, Cindy Skinner, Peter Ainsworth, Hanxin Lin, Guillaume Paré, David I Rodenhiser, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

Background

Claes-Jensen syndrome is an X-linked inherited intellectual disability caused by mutations in the

Results

Genome-wide DNA methylation analysis of 7 male patients affected with Claes-Jensen syndrome and 56 age- and sex-matched controls identified a specific DNA methylation defect (epi-signature) in the peripheral blood of these patients, including 1769 individual CpGs and 9 genomic regions. Six healthy female carriers showed less pronounced but distinctive changes in the same regions enabling their differentiation from both patients and controls. Highly specific computational model using the most significant methylation changes demonstrated 100% accuracy in differentiating patients, carriers, and controls in the training cohort, …

Birth Weight And Body Mass Index Z-Score In Childhood Brain Tumors: A Cross-Sectional Study, Kuan-Wen Wang, Russell J De Souza, Adam Fleming, Donna L Johnston, Shayna M Zelcer, Shahrad Rod Rassekh, Sarah Burrow, Lehana Thabane, M Constantine Samaan

Paediatrics Publications

Children with brain tumors (CBT) are at higher risk of cardiovascular disease and type 2 diabetes compared to the general population, in which birth weight is a risk factor for these diseases. However, this is not known in CBT. The primary aim of this study was to explore the association between birth weight and body mass measures in CBT, compared to non-cancer controls. This is a secondary data analysis using cross-sectional data from the CanDECIDE study (n = 78 CBT and n = 133 non-cancer controls). Age, sex, and birth weight (grams) were self-reported, and confirmed through examination of the …

Mental Disorder In Children With Physical Conditions: A Pilot Study, Alexandra Butler, Ryan J Van Lieshout, Ellen Louise Lipman, Harriet L Macmillan, Andrea Gonzalez, Jan Willem Gorter, Kathy Georgiades, Kathy N Speechley, Michael H Boyle, Mark A Ferro

Paediatrics Publications

Objectives

Methodologically, to assess the feasibility of participant recruitment and retention, as well as missing data in studying mental disorder among children newly diagnosed with chronic physical conditions (ie, multimorbidity). Substantively, to examine the prevalence of multimorbidity, identify sociodemographic correlates and model the influence of multimorbidity on changes in child quality of life and parental psychosocial outcomes over a 6-month follow-up.

Design

Prospective pilot study.

Setting

Two children's tertiary-care hospitals.

Participants

Children aged 6-16 years diagnosed in the past 6 months with one of the following: asthma, diabetes, epilepsy, food allergy or juvenile arthritis, and their parents.

Outcome Measures

Response, …

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 …

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 …

Identification Of Epigenetic Signature Associated With Alpha Thalassemia/Mental Retardation X-Linked Syndrome, Laila C Schenkel, Kristin D Kernohan, Arran Mcbride, Ditta Reina, Amanda Hodge, Peter J Ainsworth, David I Rodenhiser, Guillaume Pare, Nathalie G Bérubé, Cindy Skinner, Kym M Boycott, Charles Schwartz, Bekim Sadikovic

Paediatrics Publications

BACKGROUND: Alpha thalassemia/mental retardation X-linked syndrome (ATR-X) is caused by a mutation at the chromatin regulator gene

RESULTS: We performed genome-wide DNA methylation assessment of the peripheral blood samples from 18 patients with ATR-X and compared it to 210 controls. We demonstrated the evidence of a unique and highly specific DNA methylation "epi-signature" in the peripheral blood of ATRX patients, which was corroborated by targeted bisulfite sequencing experiments. Although genomically represented, differentially methylated regions showed evidence of preferential clustering in pericentromeric and telometric chromosomal regions, areas where ATRX has multiple functions related to maintenance of heterochromatin and genomic integrity.

CONCLUSION: …

Male Gender Promotes An Increased Inflammatory Response To Lipopolysaccharide In Umbilical Vein Blood., Shunaha Kim-Fine, Timothy Regnault, James S Lee, Sarah A Gimbel, Jill A Greenspoon, Jonathan Fairbairn, Kelly Summers, Barbra De Vrijer

Paediatrics Publications

OBJECTIVES: To establish gender-specific differences in maternal and fetal immune response in healthy human fetuses at term.

METHODS: Forty-five women with elective caesarean sections for uncomplicated singleton pregnancies were recruited for two studies. Using a multiplex biomarker immunoassay system, unstimulated maternal and fetal plasma concentrations of interleukin (IL)-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein (MIP)-1α, and tumor necrosis factor (TNF)-α were measured from one study population. Lipopolysaccharide (LPS)-stimulated cytokine response was measured in a second study.

RESULTS: There were no significant gender differences in either maternal or fetal unstimulated plasma cytokine concentrations, but concentrations of the proinflammatory cytokines IL-1β and …

The Long And Short Of It: The Role Of Telomeres In Fetal Origins Of Adult Disease., Stephanie E Hallows, Timothy Regnault, Dean H Betts

Paediatrics Publications

Placental insufficiency, maternal malnutrition, and other causes of intrauterine growth restriction (IUGR) can significantly affect short-term growth and long-term health. Following IUGR, there is an increased risk for cardiovascular disease and Type 2 Diabetes. The etiology of these diseases is beginning to be elucidated, and premature aging or cellular senescence through increased oxidative stress and DNA damage to telomeric ends may be initiators of these disease processes. This paper will explore the areas where telomere and telomerase biology can have significant effects on various tissues in the body in IUGR outcomes.