BackgroundAlthough discovery research has identified the importance of dozens of pro- and anti-inflammatory immune mediators in the pathogenesis, maintenance, exacerbation and resolution of inflammatory diseases, most human cohort studies have incorporated few or no immunological intermediate phenotypes in their analyses. Significant hindrances have been (1) the limited panel of biomarkers known to be readily detected in healthy human populations and (2) the stability, hence utility, of such biomarkers to repeated analysis.MethodsThe frequency and stability of 14 plasma biomarkers linked to in vivo immune regulation of allergic and autoimmune inflammatory disorders was determined in 140 healthy pediatric and adult participants. The impact of initial and multiple subsequent freeze/thaw cycles on pro-inflammatory (CCL2, CXCL10, IL-18, TNFα, IL-6), anti-inflammatory (IL-10, sTNF-RII, IL-1Ra), acute phase proteins (CRP, PTX3) and other biomarkers (sST2, IL-1RAcP) was subsequently quantified.ResultsMultiple biomarkers capable of providing an innate immune signature of inflammation were readily detected directly ex vivo in healthy individuals. These biomarker levels were unaffected when comparing paired data sets from freshly obtained, never frozen plasma or serum and matched aliquots despite extensive freeze/thaw cycles. Neither age nor sex affected stability. Similarly, no quantitative differences were found following repetitive analysis of inflammatory biomarkers in culture samples obtained following in vitro stimulation with TLR and RLR ligands.ConclusionsA broad panel of in vivo and ex vivo cytokine, chemokine and acute phase protein biomarkers that have been linked to human chronic inflammatory disorders are readily detected in vivo and remain stable for analysis despite multiple freeze thaw cycles. These data provide the foundation and confidence for large scale analyses of panels of inflammatory biomarkers to provide better understanding of immunological mechanisms underlying health versus disease.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-017-1154-3) contains supplementary material, which is available to authorized users.

Food allergies, and peanut allergy in particular, are leading causes of anaphylactic fatalities worldwide. The immune mechanisms that underlie food allergy remain ill-defined and controversial, in part because studies in humans typically focus on analysis of a limited number of prototypical Th1/Th2 cytokines. Here we determine the kinetics and prevalence of a broad panel of peanut-driven cytokine and chemokine responses in humans with current peanut allergy vs those with stable, naturally occurring clinical tolerance to peanut. Our primary focus is identification of novel indicators of immune dysregulation. Antigen-specific cytokine mRNA and protein responses were elicited in primary culture via peanut or irrelevant antigen (Leishmania extract, milk antigens) mediated stimulation of fresh peripheral blood cells from 40 individuals. Peanut extract exposure in vitro induced a broad panel of responses associated with Th2/Th9-like, Th1-like and Th17-like immunity. Peanut-dependent Type 2 cytokine responses were frequently found in both peanut allergic individuals and those who exhibit clinical tolerance to peanut ingestion. Among Th2/Th9-associated cytokines, IL-9 responses discriminated between allergic and clinically tolerant populations better than did commonly used IL-4, IL-5 or IL-13 responses. Comparison with responses evoked by unrelated control antigen-mediated stimulation showed that these differences are antigen-dependent and allergen-specific. Conversely, the intensity of IL-12, IL-17, IL-23 and IFN-γ production was indistinguishable in peanut allergic and peanut tolerant populations. In summary, the ability to generate and maintain cytokine responses to peanut is not inherently distinct between allergic and peanut tolerant humans. Quantitative differences in the intensity of cytokine production better reflects clinical phenotype, with optimally useful indicators being IL-9, IL-5, IL-13 and IL-4. Equivalent, and minimal, Ag-dependent pro-inflammatory cytokine levels in both healthy and peanut allergic volunteers argues against a key role for such cytokines in maintenance of clinical tolerance to food antigens in humans.

OBJECTIVES: The aim of this research is to examine the awareness and use of the Good Food Junction (GFJ), a not-for-profit full service cooperative grocery store in a former food desert in Saskatoon, Canada. METHODS:Through door-to-door sampling, 365 residents in their neighbourhoods surrounding the GFJ grocery store were recruited. Quantitative surveys examined awareness, use and primary use of GFJ, mode of transportation to and from GFJ and primary grocery stores, other food program use and demographic data. Differences between those who had or had not shopped at GFJ were characterized using descriptive statistics and Pearson's chi-square test. Univariate and multivariate logistic regression models were developed to predict shopping at GFJ and the use of GFJ as a primary grocery store. RESULTS:Of those surveyed, 69% had shopped at GFJ. A significant proportion of shoppers were Aboriginal, had an annual household income per person of less than $20,000, and participated in other food-based programs and initiatives. Aboriginal people (OR = 2.0, p = 0.03) and users of neighbourhood-based fruit and vegetable markets (OR = 2.7, p = 0.04) were significantly more likely, but new immigrants to Canada (OR = 0.3, p = 0.05) were significantly less likely to have ever shopped at GFJ. Aboriginal respondents (OR = 2.6, p = 0.04) were significantly more likely to use GFJ as their primary grocery store. CONCLUSION:Our results confirm both that GFJ is able to serve households where food insecurity is likely and, based on the prevalence of users, the importance and need for a full-service supermarket in Saskatoon's inner city.KEY WORDS: Food supply; food deprivation; intervention studies La traduction du résumé se trouve à la fin de l'article.

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Exclusive breastfeeding is recommended for the first six months of life, but many infants receive pumped milk, formula, donor human milk, or other nutritional sources during this critical period. Substantive evidence shows early nutrition influences development of the microbiome and immune system, affecting lifelong health. However, the underlying mechanisms are unclear and the nuances of human milk feeding are rarely considered. This review synthesizes evidence from human studies and model systems to discuss the impact of different nutritional sources on co-development of the gut microbiome, antigen tolerance, and immunity. We highlight two key mechanisms: epigenetics and the so-called “weaning reaction”. Collectively, this evidence highlights i) the fundamental role of parents’ own milk, fed directly at the breast, as a dynamic and personalized nutrition source that drives developmental programming, and ii) the deficiencies of alternative nutritional sources and priority research areas for improving these alternatives when direct breastfeeding is not possible.

There is little understanding of how the built environment shapes activity behaviours in children over different seasons. This study sought to establish how seasonal weather patterns, in a given year in a mid-western Canadian city, affect sedentary time (SED) in youth and how the relationship between season and SED are moderated by the built environment in their home neighbourhood. Families with children aged 9–14 years were recruited from the prairie city of Saskatoon, Canada. Location-specific, device-based SED was captured in children during three timeframes over a one-year period using GPS-paired accelerometers. Multilevel models are presented. Children accumulated significantly greater levels of SED in spring but significantly less SED in the fall months in comparison to the winter months. Children living in neighbourhoods with the highest density of destinations accumulated significantly less SED while in their home area in comparison to their counterparts, and this effect was more pronounced in the spring and summer months. On weekends, the rise in sedentariness within the home area was completely diminished in children living in neighbourhoods with the greatest number of destinations and highest activity friendliness. These results suggested that increasing neighbourhood amenities can lead to a reduced sedentariness of youth, though more so in the warmers months of the year.

BackgroundFood allergies are a major component of the burden of allergic disease. Accurate risk assessment for prediction of future clinical reactivity or clinical tolerance is limited by currently available techniques. Recent studies suggest that constitutively elevated global serum levels of IL-10, a cytokine that down-regulates both Th1 and Th2 cytokine production, may be useful in identifying human clinical tolerance to foods.ObjectiveDetermine the usefulness of constitutive IL-10 levels as a marker of clinical tolerance to peanut in children and adults.Methodology/Principal Findings107 subjects who were clinically tolerant to peanut and 94 subjects who were clinically allergic to peanut participated. Plasma was analyzed via ELISA to quantify the frequency of individuals with constitutive IL-10 levels and the intensity of those responses. The data were then stratified by age, gender and clinical status to assess the utility of this putative biomarker in specific at-risk groups. All 201 subjects had readily quantified plasma IL-10. Levels were no higher in subjects who were clinically tolerant to peanut than those in individuals clinically allergic to peanut. Stratification by age, gender or both did not improve the capacity of IL-10 levels to identify clinical tolerance to peanut.Conclusions/SignificancePlasma IL-10 levels are neither a useful biomarker of clinical tolerance to peanut nor a potential tool for identification of clinical tolerance to peanut in humans.

BackgroundThe COVID-19 pandemic is affecting all Canadian families, with some impacted differently than others. Our study aims to: 1) determine the prevalence and transmission of SARS-CoV-2 infection among Canadian families, 2) identify predictors of infection susceptibility and severity of SARS-CoV-2 and 3) identify health and psychosocial impacts of the COVID-19 pandemic.MethodsThis study builds upon the CHILD Cohort Study, an ongoing multi-ethnic general population prospective cohort consisting of 3454 Canadian families with children born in Vancouver, Edmonton, Manitoba, and Toronto between 2009-12. During the pandemic, 1462 CHILD households (5378 individuals) consented to participate in the CHILD COVID-19 Add-On Study involving: (1) brief biweekly surveys about COVID-19 symptoms and testing; (2) quarterly questionnaires assessing COVID-19 exposure, testing and vaccination status, physical and mental health, and pandemic-driven life changes; (3) in-home biological sampling kits to collect blood and stool. Mean ages were 9 years (range 0-17) for children and 43 years (range 18-85) for adults. Prevalence of SARS-CoV-2 infection will be estimated from survey data and confirmed through serology testing. We will combine these new data with a wealth of pre-pandemic CHILD data and use multivariate modelling and machine learning methods to identify risk and resilience factors for susceptibility and severity to the direct and indirect effects of the pandemic.InterpretationOur short-term findings will inform key stakeholders and knowledge users to shape current and future pandemic responses. Additionally, this study provides a unique resource to study the long-term impacts of the pandemic as the CHILD Cohort Study continues.