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Daymont C.,University of Manitoba | Daymont C.,Manitoba Institute of Child Health | Neal A.,Boston Childrens Hospital | Prosnitz A.,Yale New Haven Childrens Hospital | Cohen M.S.,University of Pennsylvania
Pediatrics | Year: 2013

OBJECTIVE: We sought to describe growth in young children with congenital heart disease (CHD) over time. METHODS: We performed a retrospective matched cohort study, identifying children with CHD in a large primary care network in Pennsylvania, New Jersey, and Delaware and matching them 10:1 with control subjects. The primary endpoint was the difference in mean World Health Organization z score for cases and controls for weight-forage (WFAZ), length-for-age (LFAZ), weight-for-length (WFLZ), and head circumference-for-age (HCFAZ) at traditional ages for preventive visits, stratified by CHD category. RESULTS: We evaluated 856 cases: 37 with single ventricle (SV) physiology, 52 requiring complex repair (CR), 159 requiring simple repair (SR), and 608 requiring no repair. For children in the SV, CR, and SR categories, large, simultaneous, and statistically significant (Student's t test P <05) decreases in WFAZ and LFAZ appeared within the first month of life, peaked near 4 months, and persisted through 24 or 36 months. There were fewer and smaller decreases in the no-repair group between 2 and 18 months. HC data were available between 1 week and 24 months; at those ages, decreases in mean HCFAZ generally paralleled decreases in WFAZ and LFAZ in the SV, CR, and SR groups. CONCLUSIONS: Children with CHD experience early, simultaneous decreases in growth trajectory across weight, length, and head circumference. The simultaneous decrease suggests a role for altered growth regulation in children with CHD. Copyright © 2013 by the American Academy of Pediatrics.

Coombs K.M.,University of Manitoba | Coombs K.M.,Manitoba Center for Proteomics and Systems Biology | Coombs K.M.,Manitoba Institute of Child Health
Expert Review of Proteomics | Year: 2011

Measurement of biologically important effector protein molecules has been a long-standing essential component of biological research. Advances in biotechnology, in the form of high-resolution mass spectrometers, and in bioinformatics, now allow the simultaneous quantitative analysis of thousands of proteins. While these techniques still do not allow definitive identification of the entire proteome of complex mixtures, such as cells, quantitative analyses of hundreds to thousands of proteins in such complex mixtures provides a means to elucidate molecular alterations that occur during perturbation of cellular systems. This article will outline considerations of reducing sample complexity, by strategies such as multidimensional separations (gel-based and chromatography-based, including multidimensional protein identification technology). In addition, some of the most common methods used to quantitatively measure proteins in complex mixtures (2D difference in-gel electrophoresis, isotope-coded affinity tags, isotope-coded protein labeling, tandem mass tags, isobaric tags for relative and absolute quantitation, stable isotope labeling of amino acids in cell culture and label-free), as well as recent examples of each strategy, are described. © 2011 Expert Reviews Ltd.

Comer B.S.,University of South Alabama | Camoretti-Mercado B.,University of South Florida | Kogut P.C.,University of Chicago | Halayko A.J.,University of Manitoba | And 3 more authors.
American Journal of Physiology - Lung Cellular and Molecular Physiology | Year: 2014

MicroRNA (miR)-146a and miR-146b are negative regulators of inflammatory gene expression in lung fibroblasts, epithelial cells, monocytes, and endothelial cells. The abundance of cyclooxygenase-2 (COX-2) and IL-1β is negatively regulated by the miR-146 family, suggesting miR-146a and/or miR-146b might modulate inflammatory mediator expression in airway smooth muscle thereby contributing to pathogenesis of asthma. To test this idea we compared miR-146a and miR-146b expression in human airway smooth muscle cells (hASMCs) from nonasthmatic and asthmatic subjects treated with cytomix (IL-1β, TNF-α, and IFNγ) and examined the miRNAs' effects on COX-2 and IL-1β expression. We found that cytomix treatment elevated miR-146a and miR-146b abundance. Induction with cytomix was greater than induction with individual cytokines, and asthmatic cells exhibited higher levels of miR-146a expression following cytomix treatment than nonasthmatic cells. Transfection of miR-146a or miR-146b mimics reduced COX-2 and IL-1β expression. A miR-146a inhibitor increased COX-2 and IL-1β expression, but a miR-146b inhibitor was ineffective. Repression of COX-2 and IL-1β expression by miR-146a correlated with reduced abundance of the RNA-binding protein human antigen R. These results demonstrate that miR-146a and miR-146b expression is inducible in hASMCs by proinflammatory cytokines and that miR-146a expression is greater in asthmatic cells. Both miR-146a and miR-146b can negatively regulate COX-2 and IL-1β expression at pharmacological levels, but loss-of-function studies showed that only miR-146a is an endogenous negative regulator in hASMCs. The results suggest miR-146 mimics may be an attractive candidate for further preclinical studies as an anti-inflammatory treatment of asthma. © 2014 the American Physiological Society.

El-Matary W.,Manitoba Institute of Child Health | Moroz S.P.,Manitoba Institute of Child Health | Bernstein C.N.,University of Manitoba
Journal of Pediatric Gastroenterology and Nutrition | Year: 2014

Objectives: The aim of this study was to describe the incidence and prevalence of inflammatory bowel disease (IBD) in children <17 years of age in 30 years from 1978 to 2007.Methods: From January 1, 1978, to December 31, 2007, the sex- and ageadjusted annual incidence and prevalence of pediatric IBD per 100,000 population were calculated based on the pediatric IBD database of the only pediatric tertiary center in the province. The annual health statistics records for the Province of Manitoba were used to calculate population estimates for the participants. To ensure validity of data, the University of Manitoba IBD Epidemiology Database was analyzed for patients <17 years of age from 1989 to 2000.Results: The sex- and age-adjusted incidence of pediatric Crohn disease has increased from 1.2/100,000 in 1978 to 4.68/100,000 in 2007 (P<0.001). For ulcerative colitis, the incidence has increased from 0.47/100,000 in 1978 to 1.64/100,000 in 2007 (P<0.001). During the same time period, the prevalence of Crohn disease has increased from 3.1 to 18.9/100,000 (P<0.001) and from 0.7 to 12.7/100,000 for ulcerative colitis (P<0.001). During the last 5 years of the study the average annual incidence of IBD in urban patients was 8.69/100,000 as compared with 4.75/100,000 for rural patients (P<0.001).Conclusions: The incidence and prevalence of pediatric IBD are increasing. The majority of patients were residents of urban Manitoba, confirming the important role of environmental factors in the etiopathogenesis of IBD. Copyright © 2014 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.

Armistead J.,University of Manitoba | Triggs-Raine B.,University of Manitoba | Triggs-Raine B.,Manitoba Institute of Child Health
FEBS Letters | Year: 2014

Collectively, the ribosomopathies are caused by defects in ribosome biogenesis. Although these disorders encompass deficiencies in a ubiquitous and fundamental process, the clinical manifestations are extremely variable and typically display tissue specificity. Research into this paradox has offered fascinating new insights into the role of the ribosome in the regulation of mRNA translation, cell cycle control, and signaling pathways involving TP53, MYC and mTOR. Several common features of ribosomopathies such as small stature, cancer predisposition, and hematological defects, point to how these diverse diseases may be related at a molecular level. © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

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