Preventing symptomatic vitamin D deficiency and rickets among Indigenous infants and children in Canada.

Vitamin D deficiency (VitDD) rickets and other manifestations of severe VitDD, such as cardiomyopathy and hypocalcemic seizures, continue to be diagnosed in Canada. Breastfed Indigenous infants, particularly those living in northern communities, are disproportionately impacted, although formula-fed infants are not exempt in cases where the mother's vitamin D status is critically low. This statement deals with the prevention of rickets and hypocalcemia due to VitDD for Indigenous children, and revises an earlier document from the Canadian Paediatric Society. An assessment of the risk for VitDD is recommended for each maternal-infant dyad because of the link between maternal and infant VitDD. Along with supports for enhanced adherence, additional VitD supplementation is recommended for prenatal women and infants deemed at high risk and, in certain situations, intermittent higher dose supplementation may be required. Food insecurity can also contribute to rickets, so advocacy is required to prevent VitDD rickets in Indigenous children.

Perinatal and Early-Life Nutrition, Epigenetics, and Allergy.

Epidemiological studies have shown a dramatic increase in the incidence and the prevalence of allergic diseases over the last several decades. Environmental triggers including risk factors (e.g., pollution), the loss of rural living conditions (e.g., farming conditions), and nutritional status (e.g., maternal, breastfeeding) are considered major contributors to this increase. The influences of these environmental factors are thought to be mediated by epigenetic mechanisms which are heritable, reversible, and biologically relevant biochemical modifications of the chromatin carrying the genetic information without changing the nucleotide sequence of the genome. An important feature characterizing epigenetically-mediated processes is the existence of a time frame where the induced effects are the strongest and therefore most crucial. This period between conception, pregnancy, and the first years of life (e.g., first 1000 days) is considered the optimal time for environmental factors, such as nutrition, to exert their beneficial epigenetic effects. In the current review, we discussed the impact of the exposure to bacteria, viruses, parasites, fungal components, microbiome metabolites, and specific nutritional components (e.g., polyunsaturated fatty acids (PUFA), vitamins, plant- and animal-derived microRNAs, breast milk) on the epigenetic patterns related to allergic manifestations. We gave insight into the epigenetic signature of bioactive milk components and the effects of specific nutrition on neonatal T cell development. Several lines of evidence suggest that atypical metabolic reprogramming induced by extrinsic factors such as allergens, viruses, pollutants, diet, or microbiome might drive cellular metabolic dysfunctions and defective immune responses in allergic disease. Therefore, we described the current knowledge on the relationship between immunometabolism and allergy mediated by epigenetic mechanisms. The knowledge as presented will give insight into epigenetic changes and the potential of maternal and post-natal nutrition on the development of allergic disease.

The role of PKCζ in cord blood T-cell maturation towards Th1 cytokine profile and its epigenetic regulation by fish oil.

While immunodeficiency of immaturity of the neonate has been considered important as the basis for unusual susceptibility to infection, it has also been recognized that the ability to progress from an immature Th2 cytokine predominance to a Th1 profile has relevance in determining whether children will develop allergy, providing an opportunity for epigenetic regulation through environmental pressures. However, this notion remains relatively unexplored. Here, we present evidence that there are two major control points to explain the immunodeficiency in cord blood (CB) T-cells, a deficiency in interleukin (IL)-12 (IL-12) producing and IL-10 overproducing accessory cells, leading to a decreased interferon γ (IFNγ) synthesis and the other, an intrinsic defect in T-cell protein kinase C (PKC) ζ (PKCζ) expression. An important finding was that human CB T-cells rendered deficient in PKCζ, by shRNA knockdown, develop into low tumour necrosis factor α (TNFα) and IFNγ but increased IL-13 producing cells. Interestingly, we found that the increase in PKCζ levels in CB T-cells caused by prenatal supplementation with fish oil correlated with modifications of histone acetylation at the PKCζ gene (PRKCZ) promoter. The data demonstrate that PKCζ expression regulates the maturation of neonatal T-cells into specific functional phenotypes and that environmental influences may work via PKCζ to regulate these phenotypes and disease susceptibility.

Protein kinase Czeta: a novel protective neonatal T-cell marker that can be upregulated by allergy prevention strategies.

BACKGROUND: Variations in neonatal T-cell function have been associated with allergic disease. OBJECTIVES: To examine the relationship between neonatal T-cell protein kinase (PKC) expression and subsequent allergic disease. METHODS: T cells were purified from cord blood samples (n = 74) obtained from a cohort of mothers who received either 4 g/d fish oil or a placebo from 20 weeks of gestation. PKC expression was examined in relationship to supplementation, fatty acid levels, cytokine production, and allergic outcomes at 1 year and 2.5 years of age. RESULTS: Neonatal T-cell PKCzeta expression was lower in children who had evidence of allergic disease at 1 year (P = .001) and 2.5 years (P = .052) of age. It was also lower in children with sensitization (positive skin prick test) at each age (P = .02 and P = .072, respectively). PKCzeta expression was inversely correlated to PKCalpha (r = -0.28; P = .025), which was strongly related to IL-5 responses to allergens (ovalbumin, r = 0.59; P = .003; dust mite, r = 0.52; P = .011) at 1 year of age. Fish oil supplementation was associated with significantly higher PKCzeta expression (P = .014), whereas most other isozymes were reduced by fish oil supplementation. CONCLUSION: This is the first study to show that allergic disease is associated with altered expression of T-cell PKC isozymes in the neonatal period. It has also demonstrated that fish oil can modulate expression of PKC isozymes in a potentially favorable direction. CLINICAL IMPLICATIONS: Protein kinase Czeta should be explored further as an early marker and potential target for disease prevention.

Radionuclides and trace metals in Canadian moose near uranium mines: comparison of radiation doses and food chain transfer with cattle and caribou.

Tissues from 45 moose and 4 cattle were collected to assess the health of country foods near uranium mines in northern Saskatchewan. Bone, liver, kidney, muscle and rumen contents were analyzed for uranium, radium-226 (226Ra), lead-210 (210Pb), and polonium-210 (210Po). Cesium-137 (137Cs), potassium-40 (40K), and 27 trace metals were also measured in some tissues. Within the most active mining area, Po in liver and muscle declined significantly with distance from tailings, possibly influenced by nearby natural uranium outcrops. Moose from this area had significantly higher 226Ra, 210Pb, 210Po, and 137Cs in some edible soft tissues vs. one control area. However, soil type and diet may influence concentrations as much as uranium mining activities, given that a) liver levels of uranium, 226Ra, and 210Po were similar to a second positive control area with mineral-rich shale hills and b) 210Po was higher in cattle kidneys than in all moose. Enhanced food chain transfer from rumen contents to liver was found for selenium in the main mining area and for copper, molybdenum and cadmium in moose vs. cattle. Although radiological doses to moose in the main mining area were 2.6 times higher than doses to control moose or cattle, low moose intakes yielded low human doses (0.0068 mSv y(-1)), a mere 0.3% of the dose from intake of caribou (2.4 mSv y(-1)), the dietary staple in the area.