The Childrens Hospital Research Institute of Manitoba

Winnipeg, Canada

The Childrens Hospital Research Institute of Manitoba

Winnipeg, Canada
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McLean L.,University of Manitoba | McLean L.,The Childrens Hospital Research Institute of Manitoba | Russell K.,University of Manitoba | Russell K.,The Childrens Hospital Research Institute of Manitoba | And 6 more authors.
BMC Pediatrics | Year: 2017

Background: The study was designed to determine if youth <16 years are at a greater risk of serious injuries related to all-terrain vehicle (ATV) use compared to older adolescents and adults. Methods: We performed cross sectional study of children and adults presenting to pediatric and adult emergency departments between 1990 and 2009 in Canada. The primary exposure variable was age <16 years and the primary outcome measure was moderate to serious injury determined from physician report of type and severity of injury. Results: Among 5005 individuals with complete data, 58% were <16 years and 35% were admitted to hospital. The odds of a moderate to serious injury versus minor injury among ATV users <16 years of age was not different compared with those ≥16 years of age (OR: 0.94; 95% CI: 0.84, 1.06). After adjusting for era, helmet use, sex and driver status, youth <16 years were more likely to present with a head injury (aOR: 1.45; 95% CI: 1.19-1.77) or fractures (aOR: 1.60; 95% CI: 1.43-1.81), compared with those ≥16 years. Male participants (aOR: 1.21; 95% CI: 1.06-1.38) and drivers (aOR: 1.30, 95% CI: 1.12-1.51) were more likely to experience moderate or serious injuries than females and passengers. Helmet use was associated with significant protection from head injuries (aOR: 0.59; 95% CI: 0.44-0.78). Conclusions: Youth under 16 years are at an increased risk of head injuries and fractures. For youth and adults presenting to emergency departments with an ATV-related injury, moderate to serious injuries associated with ATV use are more common among drivers and males. Helmet use protected against head injuries, suggesting minimum age limits for ATV use and helmet use are warranted. © 2017 The Author(s).

Halipchuk J.,Health science Center Winnipeg | Temple B.,University of Manitoba | Dart A.,University of Manitoba | Dart A.,The Childrens Hospital Research Institute of Manitoba | And 3 more authors.
Canadian Journal of Diabetes | Year: 2017

Objective: To explore associations among prenatal, obstetric and perinatal factors and the development of childhood-onset type 2 diabetes. Methods: This retrospective, case-control study utilized administrative data housed at the Manitoba Centre for Health Policy. De-identified health records were examined from a sample of 270 children (aged 10 to 17 years at time of diagnosis) with type 2 diabetes and 1341 children without type 2 diabetes matched for age, sex and geographic location. Patients and control subjects were linked to their de-identified biological mothers' health records. Prenatal, obstetric and perinatal factors were investigated. Univariate and multivariable conditional regression analyses were conducted to identify key factors associated with the development of type 2 diabetes in children. Results: The mean age at diagnosis was 13.1 years, and 61% of patients were girls. The majority (71.1%) of children with type 2 diabetes resided in rural areas. Exposure to maternal pregestational diabetes increased the odds of childhood-onset type 2 diabetes nearly 6-fold, and exposure to gestational diabetes carried a 4-fold increased risk. Breastfeeding was found to be protective, decreasing the risk of childhood-onset type 2 diabetes (odds ratio = 0.52, 95% confidence interval = 0.36-0.74). Low maternal income was significantly associated with development of childhood-onset type 2 diabetes (odds ratio = 6.67, 95% confidence interval = 3.01-14.79). Conclusions: Health and social policies and programs are needed to provide financial, educational and clinical resources that target women whose pregnancies are affected by poverty, type 2 diabetes or gestational diabetes. Breastfeeding should be encouraged to aid in the prevention of childhood-onset type 2 diabetes. © 2017 Diabetes Canada.

Seshadri N.,University of Manitoba | Seshadri N.,The Childrens Hospital Research Institute of Manitoba | Jonasson M.E.,The Childrens Hospital Research Institute of Manitoba | Hunt K.L.,University of Manitoba | And 9 more authors.
Molecular Metabolism | Year: 2017

Objective Upregulation of uncoupling protein 2 (UCP2) is associated with impaired glucose-stimulated insulin secretion (GSIS), which is thought to be an important contributor to pathological β cell failure in obesity and type 2 diabetes (T2D); however, the physiological function of UCP2 in the β cell remains undefined. It has been suggested, but not yet tested, that UCP2 plays a physiological role in β cells by coordinating insulin secretion capacity with anticipated fluctuating nutrient supply, such that upregulation of UCP2 in the inactive/fasted state inhibits GSIS as a mechanism to prevent hypoglycemia. Therefore, we hypothesized that daily cycles of GSIS capacity are dependent on rhythmic and predictable patterns of Ucp2 gene expression such that low Ucp2 in the active/fed phase promotes maximal GSIS capacity, whereas elevated Ucp2 expression in the inactive/fasted phase supresses GSIS capacity. We further hypothesized that rhythmic Ucp2 expression is required for the maintenance of glucose tolerance over the 24 h cycle. Methods We used synchronized MIN6 clonal β cells and isolated mouse islets from wild type (C57BL6) and mice with β cell knockout of Ucp2 (Ucp2-βKO; and respective Ins2-cre controls) to determine the endogenous expression pattern of Ucp2 over 24 h and its impact on GSIS capacity and glucose tolerance over 24 h. Results A dynamic pattern of Ucp2 mRNA expression was observed in synchronized MIN6 cells, which showed a reciprocal relationship with GSIS capacity in a time-of-day-specific manner. GSIS capacity was suppressed in islets isolated from wild type and control mice during the light/inactive phase of the daily cycle; a suppression that was dependent on Ucp2 in the β cell and was lost in islets isolated from Ucp2-βKO mice or wild type islets treated with a UCP2 inhibitor. Finally, suppression of GSIS capacity by UCP2 in the light phase was required for the maintenance of normal patterns of glucose tolerance. Conclusions Our study suggests that Ucp2/UCP2 in the β cell is part of an important, endogenous, metabolic regulator that controls the temporal capacity of GSIS over the course of the day/night cycle, which, in turn, regulates time-of-day glucose tolerance. Targeting Ucp2/UCP2 as a therapeutic in type 2 diabetes or any other metabolic condition must take into account the rhythmic nature of its expression and its impact on glucose tolerance over 24 h, specifically during the inactive/fasted phase. © 2017 The Authors

Rabbi M.F.,University of Manitoba | Munyaka P.M.,University of Manitoba | Eissa N.,University of Manitoba | Metz-Boutigue M.-H.,French Institute of Health and Medical Research | And 4 more authors.
Frontiers in Microbiology | Year: 2017

The mammalian intestinal tract is heavily colonized with a dense, complex, and diversified microbial populations. In healthy individuals, an array of epithelial antimicrobial agents is secreted in the gut to aid intestinal homeostasis. Enterochromaffin cells (EC) in the intestinal epithelium are a major source of chromogranin A (CgA), which is a pro-hormone and can be cleaved into many bioactive peptides that include catestatin (CST). This study was carried out to evaluate the possible impact of CST on gut microbiota in vivo using a mouse model. The CST (Human CgA352-372) or normal saline was intrarectally administered in C57BL/6 male mice for 6 days and then sacrificed. Feces and colonic mucosa tissue samples were collected, DNA was extracted, the V4 region of bacterial 16S rRNA gene was amplified and subjected to MiSeq Illumina sequencing. The α-diversity was calculated using Chao 1 and β-diversity was determined using QIIME. Differences at the genus level were determined using partial least square discriminant analysis (PLS-DA). Phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) was used to predict functional capacity of bacterial community. CST treatment did not modify bacterial richness in fecal and colonic mucosa-associated microbiota; however, treatment significantly modified bacterial community composition between the groups. Also, CST-treated mice had a significantly lower relative abundance of Firmicutes and higher abundance of Bacteroidetes, observed only in fecal samples. However, at lower phylogenetic levels, PLS-DA analysis revealed that some bacterial taxa were significantly associated with the CST-treated mice in both fecal and colonic mucosa samples. In addition, differences in predicted microbial functional pathways in both fecal and colonic mucosa samples were detected. The results support the hypothesis that CST treatment modulates gut microbiota composition under non-pathophysiological conditions, however, the result of this study needs to be further validated in a larger experiment. The data may open new avenues for the development of a potential new line of antimicrobial peptides and their use as therapeutic agents to treat several inflammatory conditions of the gastrointestinal tract, such as inflammatory bowel disease (IBD), inflammatory bowel syndrome (IBS), or other health conditions. © 2017 Rabbi, Munyaka, Eissa, Metz-Boutigue, Khafipour and Ghia.

Vuong B.,University of Manitoba | Vuong B.,Kleysen Institute for Advanced Medicine | Odero G.,University of Manitoba | Odero G.,Kleysen Institute for Advanced Medicine | And 11 more authors.
Journal of Neuroinflammation | Year: 2017

Background: Birth cohort studies link gestational diabetes mellitus (GDM) with impaired cognitive performance in the offspring. However, the mechanisms involved are unknown. We tested the hypothesis that obesity-associated GDM induces chronic neuroinflammation and disturbs the development of neuronal circuitry resulting in impaired cognitive abilities in the offspring. Methods: In rats, GDM was induced by feeding dams a diet high in sucrose and fatty acids. Brains of neonatal (E20) and young adult (15-week-old) offspring of GDM and lean dams were analyzed by immunohistochemistry, cytokine assay, and western blotting. Young adult offspring of GDM and lean dams went also through cognitive assessment. Cultured microglial responses to elevated glucose and/or fatty acids levels were analyzed. Results: In rats, impaired recognition memory was observed in the offspring of GDM dams. GDM exposure combined with a postnatal high-fat and sucrose diet resulted in atypical inattentive behavior in the offspring. These cognitive changes correlated with reduced density and derangement of Cornu Ammonis 1 pyramidal neuronal layer, decreased hippocampal synaptic integrity, increased neuroinflammatory status, and reduced expression of CX3CR1, the microglial fractalkine receptor regulating microglial pro-inflammatory responses and synaptic pruning. Primary microglial cultures that were exposed to high concentrations of glucose and/or palmitate were transformed into an activated, amoeboid morphology with increased nitric oxide and superoxide production, and altered their cytokine release profile. Conclusions: These findings demonstrate that GDM stimulates microglial activation and chronic inflammatory responses in the brain of the offspring that persist into young adulthood. Reactive gliosis correlates positively with hippocampal synaptic decline and cognitive impairments. The elevated pro-inflammatory cytokine expression at the critical period of hippocampal synaptic maturation suggests that neuroinflammation might drive the synaptic and cognitive decline in the offspring of GDM dams. The importance of microglia in this process is supported by the reduced Cx3CR1 expression as an indication of the loss of microglial control of inflammatory responses and phagocytosis and synaptic pruning in GDM offspring.

Ameis D.,University of Manitoba | Ameis D.,The Childrens Hospital Research Institute of Manitoba | Khoshgoo N.,University of Manitoba | Khoshgoo N.,The Childrens Hospital Research Institute of Manitoba | And 2 more authors.
Seminars in Pediatric Surgery | Year: 2017

The outcomes of patients diagnosed with congenital diaphragmatic hernia (CDH) have recently improved. However, mortality and morbidity remain high, and this is primarily caused by the abnormal lung development resulting in pulmonary hypoplasia and persistent pulmonary hypertension. The pathogenesis of CDH is poorly understood, despite the identification of certain candidate genes disrupting normal diaphragm and lung morphogenesis in animal models of CDH. Defects within the lung mesenchyme and interstitium contribute to disturbed distal lung development. Frequently, a disturbance in the development of the pleuroperitoneal folds (PPFs) leads to the incomplete formation of the diaphragm and subsequent herniation. Most candidate genes identified in animal models have so far revealed relatively few strong associations in human CDH cases. CDH is likely a highly polygenic disease, and future studies will need to reconcile how disturbances in the expression of multiple genes cause the disease. Herein, we summarize the available literature on abnormal lung development associated with CDH. © 2017 Elsevier Inc.

PubMed | The Childrens Hospital Research Institute of Manitoba, University of New Brunswick, University of Manitoba, University of Edinburgh and University of British Columbia
Type: Journal Article | Journal: Canadian journal of diabetes | Year: 2015

The purpose of this study was to assess the feasibility and lived experiences of an intensive group-based lifestyle intervention for youth with type 2 diabetes (Beating Diabetes Together) (BDT).The study included 12 Indigenous youth with type 2 diabetes (mean age, 14 years; n=9 girls); they participated in a 16-week pilot study of an intensive, group-based lifestyle intervention. We conducted a mixed-methods investigation of the cardiometabolic responses and lived experiences in the intervention. Of the 12 youth with cardiometabolic risk data, 5 youth and 2 mothers participated in semistructured interviews. Interview participants were purposely selected based on the frequency of attendance and availability.The intervention was well attended (>75% retention), and youth perceived significant benefits from participation. Thematic analysis of the interviews revealed 3 major themes. First, youth and parents described living with type 2 diabetes as being emotionally challenging. They described this experience as being isolating and connected to feelings of guilt and defeat. Second, youth and parents discussed benefits of participating in BDT. They shared the significance of positive relationships and experiences and how those have helped to manage their illness. Third, youth described the aspects that they most enjoyed at BDT. Peer support was an important determinant of physical activity, but they considered dietary changes to be individual behaviours. Glycemic control, blood pressure and anthropometric measures were not different following the intervention.Our findings support the importance of maintaining an inclusive environment and relationship building when designing strategies to promote behaviour modification for Indigenous youth living with type 2 diabetes.

Wicklow B.,The Childrens Hospital Research Institute of Manitoba | Wicklow B.,University of Manitoba | Gallo S.,McGill University | Majnemer A.,Montreal Childrens Hospital | And 9 more authors.
Physical and Occupational Therapy in Pediatrics | Year: 2015

In addition to benefits for bone health, vitamin D is implicated in muscle function in children and adults. Aims: To determine if vitamin D dosage positively correlated with gross motor development at 3 and 6 months of age. We hypothesized that higher doses would be associated with higher scores for gross motor skills. Methods: A consecutive sample of 55 healthy, term, and breastfed infants from Montreal, Canada were recruited from a randomized trial of vitamin D supplementation between 2009 and 2012. Infants were randomized to 400 International Units (IU) (n = 19), 800 IU (n = 18) or 1,200 IU (n = 18) vitamin D3/day. Motor performance at 3 and 6 months was quantified by the Alberta Infant Motor Scale (AIMS). Plasma vitamin D3 metabolites were measured by tandem mass spectrometry. Results: AIMS scores did not differ at 3 months. However, total AIMS scores and sitting subscores were significantly higher at 6 months in infants receiving 400 IU/day compared to 800 IU/day and 1,200 IU/day groups (p < .05). There were weak negative correlations with length and C-3 epimer of 25(OH)D. Conclusions: In contrast to our hypothesis, gross motor achievements were significantly higher in infants receiving 400 IU/day vitamin D. Our findings also support longer infants being slightly delayed. © 2015 Taylor & Francis Group, LLC

West C.H.,University of Manitoba | Bell J.M.,The Childrens Hospital Research Institute Of Manitoba | Woodgate R.L.,University of Manitoba | Moules N.J.,University of Calgary
Journal of Family Nursing | Year: 2015

The illness suffering of families in childhood cancer is characterized in part by a loss of family normalcy. Hermeneutic phenomenology and family process research methods were used to analyze videotaped family intervention sessions and post-intervention family/clinician interviews. Within this article, some of the findings from the larger doctoral study that focused on the illness suffering of family members and relational, family systems intervention based on the Illness Beliefs Model are described. Although the larger study included findings of family interventions that addressed several aspects of the illness suffering experienced, this article details specific findings related to the theme of the loss of family normalcy and a longing to return home. Family systems intervention practices which facilitated a lessening of illness suffering included the following: offering new interpretations of suffering within a reflecting team, articulating family strength, sensitively acknowledging the illness suffering, and eliciting the experiences of family members in a shared therapeutic conversation. © The Author(s) 2015.

Davidson K.,University of Manitoba | Schroth R.J.,University of Manitoba | Schroth R.J.,The Childrens Hospital Research Institute of Manitoba | Schroth R.J.,Winnipeg Regional Health Authority | And 9 more authors.
BMC Pediatrics | Year: 2016

Background: Severe Early Childhood Caries (S-ECC) is an aggressive form of tooth decay in preschool children affecting quality of life and nutritional status. The purpose was to determine whether there is an association between Body Mass Index (BMI) and S-ECC. Methods: Children with S-ECC were recruited on the day of their slated dental surgery under general anesthesia. Age-matched, caries-free controls were recruited from the community. All children were participating in a larger study on nutrition and S-ECC. Analysis was restricted to children ≥ 24 months of age. Parents completed a questionnaire and heights and weights were recorded. BMI scores and age and gender adjusted BMI z-scores and percentiles were calculated. A p-value ≤ 0.05 was significant. Results: Two hundred thirty-five children were included (141 with S-ECC and 94 caries-free). The mean age was 43.3 ± 12.8 months and 50.2 % were male. Overall, 34.4 % of participants were overweight or obese. Significantly more children with S-ECC were classified as overweight or obese when compared to caries-free children (p = 0.038) and had significantly higher mean BMI z-scores than caries-free children (0.78 ± 1.26 vs. 0.22 ± 1.36, p = 0.002). Those with S-ECC also had significantly higher BMI percentiles (69.0 % ± 29.2 vs. 56.8 % ± 31.7, p = 0.003). Multiple linear regression analyses revealed that BMI z-scores were significantly and independently associated with S-ECC and annual household income as were BMI percentiles. Conclusions: Children with S-ECC in our sample had significantly higher BMI z-scores than caries-free peers. © 2016 Davidson et al.

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