PubMed | University of British Columbia, Peter Gilgan Center for Research and Learning, Radboud University Nijmegen, Birmingham Childrens Hospital and Child & Family Research Institute
Type: Case Reports | Journal: Molecular genetics and metabolism | Year: 2016
We report a patient from a consanguineous family who presented with transient acute liver failure and biochemical patterns suggestive of disturbed urea cycle and mitochondrial function, for whom conventional genetic and metabolic investigations for acute liver failure failed to yield a diagnosis. Whole exome sequencing revealed a homozygous 12-bp deletion in PCK1 (MIM 614168) encoding cytosolic phosphoenolpyruvate carboxykinase (PEPCK); enzymatic studies subsequently confirmed its pathogenic nature. We propose that PEPCK deficiency should be considered in the young child with unexplained liver failure, especially where there are marked, accumulations of TCA cycle metabolites on urine organic acid analysis and/or an amino acid profile with hyperammonaemia suggestive of a proximal urea cycle defect during the acute episode. If suspected, intravenous administration of dextrose should be initiated. Long-term management comprising avoidance of fasting with the provision of a glucose polymer emergency regimen for illness management may be sufficient to prevent future episodes of liver failure. This case report provides further insights into the (patho-)physiology of energy metabolism, confirming the power of genomic analysis of unexplained biochemical phenotypes.
Maatta M.,University of British Columbia |
Maatta M.,Vancouver Coastal Health Research Institute |
Macdonald H.M.,University of British Columbia |
Macdonald H.M.,Vancouver Coastal Health Research Institute |
And 5 more authors.
Osteoporosis International | Year: 2015
Summary: Forearm fractures are common during growth. We studied bone strength in youth with a recent forearm fracture. In girls, suboptimal bone strength was associated with fractures. In boys, poor balance and physical inactivity may lead to fractures. Prospective studies will confirm these relationships and identify targets for prevention strategies.Introduction: The etiology of pediatric forearm fractures is unclear. Thus, we examined distal radius bone strength, microstructure, and density in children and adolescents with a recent low- or moderate-energy forearm fracture and those without forearm fractures.Methods: We assessed the non-dominant (controls) and non-fractured (cases) distal radius (7 % site) using high-resolution peripheral quantitative computed tomography (HR-pQCT) (Scanco Medical AG) in 270 participants (girls: cases n = 47, controls n = 61 and boys: cases n = 88, controls n = 74) aged 8–16 years. We assessed standard anthropometry, maturity, body composition (dual energy X-ray absorptiometry (DXA), Hologic QDR 4500 W) physical activity, and balance. We fit sex-specific logistic regression models for each bone outcome adjusting for maturity, ethnicity, height, and percent body fat.Results: In girls, impaired bone strength (failure load, ultimate stress) and a high load-to-strength ratio were associated with low-energy fractures (odds ratios (OR) 2.8–4.3). Low total bone mineral density (Tt.BMD), bone volume ratio, trabecular thickness, and cortical BMD and thickness were also associated with low-energy fractures (ORs 2.0–7.0). In boys, low Tt.BMD, but not bone strength, was associated with low-energy fractures (OR = 1.8). Boys with low-energy fractures had poor balance and higher percent body fat compared with controls (p < 0.05). Boys with fractures (both types) were less active than controls (p < 0.05).Conclusions: Forearm fracture etiology appears to be sex-specific. In girls, deficits in bone strength are associated with fractures. In boys, a combination of poor balance, excess body fat, and low physical activity may lead to fractures. Prospective studies are needed to confirm these relationships and clarify targets for prevention strategies. © 2014, International Osteoporosis Foundation and National Osteoporosis Foundation.
Pasalich D.S.,Simon Fraser University |
Pasalich D.S.,Child & Family Research Institute |
Witkiewitz K.,University of New Mexico |
McMahon R.J.,Simon Fraser University |
And 2 more authors.
Journal of Abnormal Child Psychology | Year: 2016
Little is known about intervening processes that explain how prevention programs improve particular youth antisocial outcomes. We examined whether parental harsh discipline and warmth in childhood differentially account for Fast Track intervention effects on conduct disorder (CD) symptoms and callous-unemotional (CU) traits in early adolescence. Participants included 891 high-risk kindergarteners (69 % male; 51 % African American) from urban and rural United States communities who were randomized into either the Fast Track intervention (n = 445) or non-intervention control (n = 446) groups. The 10-year intervention included parent management training and other services (e.g., social skills training, universal classroom curriculum) targeting various risk factors for the development of conduct problems. Harsh discipline (Grades 1 to 3) and warmth (Grades 1 and 2) were measured using parent responses to vignettes and direct observations of parent–child interaction, respectively. Parents reported on children’s CD symptoms in Grade 6 and CU traits in Grade 7. Results demonstrated indirect effects of the Fast Track intervention on reducing risk for youth antisocial outcomes. That is, Fast Track was associated with lower scores on harsh discipline, which in turn predicted decreased levels of CD symptoms. In addition, Fast Track was associated with higher scores on warmth, which in turn predicted reduced levels of CU traits. Our findings inform developmental and intervention models of youth antisocial behavior by providing evidence for the differential role of harsh discipline and warmth in accounting for indirect effects of Fast Track on CD symptoms versus CU traits, respectively. © 2015, Springer Science+Business Media New York.
Pasalich D.S.,Australian National University |
Fleming C.B.,University of Washington |
Oxford M.L.,University of Washington |
Zheng Y.,Simon Fraser University |
And 2 more authors.
Child Maltreatment | Year: 2016
Multiple placement changes disrupt continuity in caregiving and undermine well-being in children in child welfare. This study conducted secondary data analysis of a randomized controlled trial to examine whether a relationship-based intervention, Promoting First Relationships© (PFR), reduced risk for a maladaptive cascade from placement instability to less secure attachment to elevated externalizing problems. Participants included caregivers (birth or foster/kin) of toddlers (10–24 months) recently transitioned to their care because of child welfare placement decisions. Although main effects of PFR on security and externalizing problems were not previously observed, this study’s results revealed that PFR attenuated the association between multiple placement changes (baseline) and less security (postintervention) and that the indirect effect of placement instability on greater externalizing problems (6-month follow-up) via less security was evident only in toddlers in the comparison condition. These findings shed light on how a history of multiple caregiver changes may influence toddlers’ risk for poor adjustment in subsequent placements, and the promise of supporting caregivers through a parenting intervention to prevent such risk. © 2016, © The Author(s) 2016.
Fleming A.P.,University of Washington |
McMahon R.J.,Simon Fraser University |
McMahon R.J.,Child & Family Research Institute |
Moran L.R.,University of Washington |
And 2 more authors.
Journal of Attention Disorders | Year: 2015
Objective: ADHD affects between 2% and 8% of college students and is associated with broad functional impairment. No prior randomized controlled trials with this population have been published. The present study is a pilot randomized controlled trial evaluating dialectical behavior therapy (DBT) group skills training adapted for college students with ADHD. Method: Thirty-three undergraduates with ADHD between ages 18 and 24 were randomized to receive either DBT group skills training or skills handouts during an 8-week intervention phase. ADHD symptoms, executive functioning (EF), and related outcomes were assessed at baseline, post-treatment, and 3-month follow-up. Results: Participants receiving DBT group skills training showed greater treatment response rates (59-65% vs. 19-25%) and clinical recovery rates (53-59% vs. 6-13%) on ADHD symptoms and EF, and greater improvements in quality of life. Conclusion: DBT group skills training may be efficacious, acceptable, and feasible for treating ADHD among college students. A larger randomized trial is needed for further evaluation. © 2014 SAGE Publications
Kruse S.,Child & Family Research Institute |
Schneeberg A.,University of British Columbia |
Brussoni M.,University of British Columbia
Health and quality of life outcomes | Year: 2014
BACKGROUND: The purpose of this study was to determine the construct validity of the PedsQL™ health related quality of life (HRQoL) instrument for use among injured children and to examine the impact of using different modes of administration, including paper and pencil, online and telephone.METHODS: Two hundred thirty-three participants (aged 0 - 16) were recruited from hospital wards and the emergency department of a pediatric hospital in a large urban center in British Columbia, Canada. Data used to evaluate the construct validity of the PedsQL™ were collected from participants at the time of seeking injury treatment (baseline) to capture a retrospective measure of pre injury health, and one month post injury. Data used to compare different modes of administration (n = 44) were collected at baseline. To assess construct validity repeated measures analysis of variance (rANOVA) was used to determine whether the PedsQL™ tool was able to discriminate between patients pre and post injury while investigating possible interaction by category of length of stay in hospital. The impact of different modalities of administering the PedsQL™ on item responses was investigated using Bland-Altman plots.RESULTS: rANOVA showed significant differences in PedsQL™ total score between baseline and one month post injury (p < .001), and differences in mean total score at one month post injury by category of injury severity (p < .001). There was also significant interaction by category of injury severity for the change in PedsQL™ total score from baseline to one month (p < .001). Pearson's correlations were highly significant across three modalities of survey administration: paper and pencil, computer and telephone administration (range: .92 to .97, p < .001). Bland-Altman plots showed strong consistency.CONCLUSION: The PedsQL™ instrument is able to discriminate between pre and post injury HRQoL, as well as HRQoL post injury for injuries of varying severity. These findings are an indication that this instrument has good construct validity for the purpose of evaluating HRQoL of injured children. Data collected via paper-pencil, online and telephone administration were highly consistent. This is important as depending on the setting, clinical or research, different modalities of completing this instrument may be more appropriate.
George M.A.,University of British Columbia |
George M.A.,Child & Family Research Institute |
Bassani C.,Kwantlen Polytechnic University |
Bassani C.,Simon Fraser University
Ethnicity and Health | Year: 2016
ABSTRACT: Objectives. Our objective is to contribute to the literature regarding the association between immigrant children's health, their ethnicity and their living in neighbourhoods with a high ethnic concentration of one's own ethnicity. Using data from families from five ethnic groups who all immigrated to Vancouver metropolitan region in Canada, our research question asks: How ethnicity, ethnic concentration and living in a neighbourhood with others of the same ethnic background contribute to the health of immigrant children? Design. Two data sets are integrated in our study. The first is the New Canadian Children and Youth Study, which collected original data from five ethnic groups who immigrated to metropolitan Vancouver. The second data set, from which we derived neighbourhood data, is the Canadian census. The dependent variable is health status as reported by the parent. Independent variables are at both the individual and neighbourhood levels, including ethnicity, sex and the percentage of people living in the neighbourhood of the same ethnic background. Analysis was completed using hierarchical linear modelling. Results. Children (n = 759) from 24 neighbourhoods were included in the analyses. Health status varied by ethnicity and ethnic concentration, indicating the heterogeneity of immigrant populations. Conclusion. With the lack of research on the health of immigrant children and youth living in ethnic concentrations, our findings make an important contribution to understanding the influences on the well-being of immigrant populations. © 2015 Taylor & Francis.
PubMed | University of British Columbia, Microbiome Therapeutics and Child & Family Research Institute
Type: | Journal: Peptides | Year: 2015
Ghrelin is produced by the stomach, hypothalamus and pituitary. It circulates as acylated ghrelin (AG, which stimulates growth hormone (GH) secretion) and unacylated ghrelin (UAG). Acylation is mediated by the enzyme ghrelin O-acyltransferase (GOAT). In mice, pregnancy is associated with a marked increase in circulating pituitary GH. We investigated the role of AG and UAG in the surge of plasma GH concentrations in pregnant mice at the end of pregnancy.Using a mouse model generated on a C57BL/6 background (wild type, WT) in which the GOAT gene has been deleted (KO), we measured plasma AG, UAG and GH concentrations and tissue (stomach, pituitary and hypothalamus) preproghrelin and GOAT mRNA in non-pregnant (NP) and pregnant (P), WT and KO mice.GOAT deletion was associated with undetectable concentrations of AG. UAG concentrations were similar in all groups. In both WT and KO animals, mean GH concentrations increased 30 to 50 times during pregnancy. There was a tendency toward lower median GH concentrations in KO (301 ng/mL) compared to WT (428 ng/mL) mice (p=0.059). Preproghrelin expression was not affected by GOAT deletion or by pregnancy in the stomach. In contrast, pituitary and hypothalamic ghrelin gene expression were lower in KO-NP and KO-P mice compared to their WT counterparts.The complete absence of ghrelin acylation, which is associated with undetectable AG concentrations, does not prevent the marked increase in pituitary GH concentrations observed in pregnant mice, suggesting that AG is not the major mediator of GH secretion during pregnancy.
PubMed | University of British Columbia, University of Illinois at Chicago and Child & Family Research Institute
Type: | Journal: Molecular cytogenetics | Year: 2015
The presence of unique copy number variations (CNVs) in miscarriages suggests that their integral genes have a role in maintaining early pregnancy. In our previous work, we identified 19 unique CNVs in ~40% of studied euploid miscarriages, which were predominantly familial in origin. In our current work, we assessed their relevance to miscarriage by expression analysis of 14 genes integral to CNVs in available miscarriage chorionic villi. As familial CNVs could cause miscarriage due to imprinting effect, we investigated the allelic expression of one of the genes (TIMP2) previously suggested to be maternally expressed in placenta and involved in placental remodelling and embryo development.Six out of fourteen genes had detectable expression in villi and for three genes the RNA and protein expression was altered due to maternal CNVs. These genes were integral to duplication on Xp22.2 (TRAPPC2 and OFD1) or disrupted by a duplication mapping to 17q25.3 (TIMP2). RNA and protein expression was increased for TRAPPC2 and OFD1 and reduced for TIMP2 in carrier miscarriages. The three genes have roles in processes important for pregnancy development such as extracellular matrix homeostasis (TIMP2 and TRAPPC2) and cilia function (OFD1). TIMP2 allelic expression was not affected by the CNV in miscarriages in comparison to control elective terminations.We propose that functional studies of CNVs could help determine if and how the miscarriage CNVs affect the expression of integral genes. In case of parental CNVs, assessment of the function of their integral genes in parental reproductive tissues should be also considered in the future, especially if they affect processes relevant for pregnancy development and support.
PubMed | Child & Family Research Institute
Type: Journal Article | Journal: The Future of children | Year: 2012
Much public attention and many resources are focused on medical research to identify risk factors and mitigate symptoms of disability for individual children. But this focus will inevitably fail to prevent disabilities. Stephen Rauch and Bruce Lanphear argue for a broader focus on environmental influences that put entire populations at risk. They argue that identifying and eliminating or controlling environmental risk factors that incrementally increase the prevalence of disability is the key to preventing many disorders. Rauch and Lanphear examine emerging evidence that many disabilities of childhood have their roots in the environment--from toxins in air, water, and soil, to the stressors of poverty, to marketing practices that encourage unhealthy choices or discourage healthy ones. They review research on well-known environmental causes of disability, such as exposures to lead, cigarette smoke, and industrial air pollution. They point to new evidence suggesting that chemicals found in commonly used plastics may have subtle but serious effects on child development, and that many disabilities spring from the complex interplay of environmental risk factors and genetic susceptibility. Rauch and Lanphear make a case for turning our attention to societal or population-level interventions that would rely less on medical and genetic technology and more on policies and regulations that would reduce childrens exposure to ubiquitous environmental risks. Examples include required testing of new chemicals for developmental toxicity before they are put on the market; zoning regulations that separate residential communities from industrial areas; and restrictions on advertising of unhealthy products, such as tobacco, alcohol, and junk foods, to children. Rauch and Lanphear outline and assess the effectiveness of interventions that could be adopted, and suggest what a healthy modern community might look like. Such interventions, they acknowledge, are likely to be highly controversial, require both long-term investments and shifts in societal thinking, and produce less well-defined outcomes than individual medical treatments. But in the long run, the authors contend, such interventions could prevent many of the disabilities that now afflict millions of children and adults.