A Positive Association Between Dietary Intake of Higher Cow's Milk-Fat Percentage and Non-High-Density Lipoprotein Cholesterol in Young Children.

OBJECTIVES: To determine the association between cow's milk-fat and non-high-density lipoprotein (non-HDL) cholesterol, a marker of cardiovascular disease (CVD) risk in young children, and whether this association is mediated by the typical volume of cow's milk consumed. STUDY DESIGN: A longitudinal study in 2- to 8-year-old children (n = 2890) was conducted through The Applied Research Group for Kids (TARGet Kids!), a practice-based research network in Toronto, Canada. Generalized estimating equations were used to examine the relationship between parent-reported cow's milk-fat percentage intake and serum non-HDL cholesterol concentrations as well as having high non-HDL cholesterol (≥3.75 mmol/L [145 mg/dL]), adjusting for covariates including age, sex, body mass index z score, breastfeeding duration, mother's ethnicity, and parental history of CVD. Bootstrap resampling (10 000 repetitions) was used to assess whether typical volume consumed mediated the association between cow's milk-fat percentage and non-HDL cholesterol. RESULTS: In total, 156 (5.4%) had high non-HDL cholesterol. Each percent increase in cow's milk-fat was associated with a 0.035 mmol/L (1.35 mg/dL) (P < .001) and 0.024 mmol/L (0.92 mg/dL) (P = .01) increase in non-HDL cholesterol, unadjusted and adjusted for covariates respectively. Cow's milk-fat percentage was not associated with greater odds of having high non-HDL cholesterol. Volume of cow's milk partially mediated the association between cow's milk-fat percentage and non-HDL cholesterol, accounting for 28% of the relationship (P < .001). CONCLUSIONS: Consumption of higher-fat cow's milk was associated with a small increase in non-HDL cholesterol but not greater odds of having high non-HDL cholesterol. Further research is needed to assess this relationship with other CVD risk factors in young children. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01869530.

Effect of Increasing the Dietary Protein Content of Breakfast on Subjective Appetite, Short-Term Food Intake and Diet-Induced Thermogenesis in Children.

Dietary protein affects energy balance by decreasing food intake (FI) and increasing energy expenditure through diet-induced thermogenesis (DIT) in adults. Our objective was to investigate the effects of increasing the dietary protein in an isocaloric breakfast on subjective appetite, FI, blood glucose, and DIT in 9-14 y children. Two randomized repeated measures designs were used. In experiment 1, 17 children (9 boys, 8 girls) consumed isocaloric meals (450 kcal) on four separate mornings containing: 7 g (control), 15 g (low protein, LP), 30 g (medium protein, MP) or 45 g (high protein, HP) of protein. Blood glucose and subjective appetite were measured at baseline and regular intervals for 4 h, and FI was measured at 4 h. In experiment 2, 9 children (6 boys, 3 girls) consumed the control or HP breakfast on two separate mornings, and both DIT and subjective appetite were determined over 5 h. In experiment 1, all dietary protein treatments suppressed subjective appetite compared to control (p < 0.001), and the HP breakfast suppressed FI compared with the LP breakfast and control (p < 0.05). In experiment 2, DIT was higher after HP than control (p < 0.05). In conclusion, increasing the dietary protein content of breakfast had favorable effects on satiety, FI, and DIT in children.

Effect of potatoes and other carbohydrate-containing foods on cognitive performance, glycemic response, and satiety in children.

Dietary carbohydrates have been shown to influence cognitive performance and satiety in children. However, it remains unclear whether the carbohydrate source is a primary determinant of cognitive performance and satiety. The objective was to compare the effects of white potatoes and other carbohydrate-containing foods on cognitive performance, glycemic response, and satiety in children. On 6 separate mornings, in random order, children (n = 22) consumed 50 g of available carbohydrates from microwaved mashed potatoes (prepared from fresh potatoes then frozen), deep-fried potato strips (French fries), hash browns, white rice, white beans, or skipped a meal. Cognitive performance, glycemic response, and satiety were measured over 180 min. Cognitive performance was measured using a battery of tests assessing verbal declarative memory, spatial memory, short-term memory, working memory, and information processing speed. Although cognitive performance after the treatment meals did not differ from meal skipping, children recalled more words after French fries (9.1 ± 0.4 words) compared with mashed potatoes (8.2 ± 0.3 words; p = 0.001) and white rice (8.4 ± 0.3 words; p = 0.04) on the verbal declarative memory test. Blood glucose concentrations were higher after white rice compared with white beans, mashed potatoes, and hash browns (p < 0.05). Change from baseline subjective average appetite (mm/kcal) was lower after mashed potatoes compared with all other treatment meals (p < 0.05). In conclusion, verbal declarative memory was higher after French fries and subjective average appetite was lower after mashed potatoes. Future longitudinal studies are needed to confirm these short-term findings and to elucidate the mechanism of action.

A prenatal case of split-hand malformation associated with 17p13.3 triplication - a dilemma in genetic counseling.

Copy number gain of 17p13.3 has been shown to be associated with developmental delay/autism and Split-Hand-Foot malformation. We report a case of fetus with bilateral split-hand malformation detected on prenatal ultrasound. Array comparative genomic hybridization detected 2 maternally inherited copy number gains in the 17p13.3 region with one of them involving the BHLHA9 gene and part of the YWHAE gene. The mother is normal in intelligence with mild right foot anomaly only. Although the BHLHA9 copy gain is known to be associated with split-hand-foot malformation, the penetrance and expressivity is highly variable. More challenging is the effect of partial YWHAE copy number gain on neurodevelopment is inconclusive based on current literature. This case highlights the difficulties of prenatal genetic counseling in array comparative genomic hybridization findings in clinical situation with incomplete understanding of genotype-phenotype correlation.

Telomerase inhibition as a novel therapy for pediatric ependymoma.

Ependymomas are the third most common pediatric brain tumor with an overall survival of approximately 50%. Recently, we showed that telomerase [human telomerase reverse transcriptase (hTERT)] expression is a predictor of poor outcome in pediatric ependymoma. Thus, we hypothesized that ependymomas with functional telomerase may behave more aggressively and that these patients may benefit from anti-telomerase therapy. To address our hypothesis, we investigated the effect of telomerase inhibition on primary ependymoma cells harvested at the time of surgery, as no animal models or established cell lines are readily available for this tumor. The cells were characterized for glial fibrillary acidic protein (GFAP) and hTERT expression, initial telomere length and telomerase activity. They were then subjected to telomerase inhibition (MST-312, 1 microM) and tested for effects on cell viability (MTT assay), proliferation (MIB-1), apoptosis (cleaved caspase 3) and DNA damage (gammaH2AX). After 72 h of telomerase inhibition, primary ependymoma cells showed a significant decrease in cell number (P < 0.001), accompanied by increased DNA damage (gammaH2AX expression) (P < 0.01) and decreased proliferative index (MIB-1) (P < 0.01). Half showed an increase in apoptosis (cleaved caspase 3). These data suggest that telomerase inhibition may be an effective adjuvant therapy in pediatric ependymoma, potentially inducing tumor growth arrest in the short term, independent of telomere shortening.

Telomerase inhibition induces acute ATM-dependent growth arrest in human astrocytomas.

The purpose of the study was to examine the degree of hTERT, the catalytic subunit of telomerase, expression in paediatric high-grade astrocytoma and to explore the potential of telomerase inhibition as a therapy for these tumours. hTERT was expressed at high levels in 36 of 44 paediatric astrocytomas. Telomerase inhibition induced acute DNA damage and ATM-pathway-dependent G2/M cell cycle arrest in astrocytomas in vitro, both occurring prior to telomere shortening itself. Our data suggest that telomerase inhibition could be a useful adjuvant therapy for high-grade astrocytomas, potentially inducing tumour growth arrest following short-term treatment.