Community-based nutrition education and hands-on cooking intervention increases farmers' market use and vegetable servings.

OBJECTIVE: The objective of the current study was to evaluate the impact of the Market to MyPlate (M2MP) program on participants' reported farmers' market (FM) attitudes and shopping behaviours, frequency of serving vegetables to their families, food resource management behaviours and food security. A secondary objective was to identify facilitators and barriers to shopping at FM and food waste reduction techniques used by low-income families. DESIGN: The current study used a mixed methods evaluation embedded within a cluster randomised trial of the M2MP intervention. SETTING: The 7-week M2MP program was delivered at Extension offices and community centres in central Illinois. PARTICIPANTS: Participants included 120 adults and their families. Class cohorts were randomly assigned to one of three treatment groups: (1) nutrition education and cooking classes with produce allocations (PAE, n 39); (2) nutrition education and cooking classes only (EO, n 36) or (3) control group (n 45). RESULTS: Compared with control participants, PAE participants were significantly more likely to report shopping at FM (P = 0·029) and reported serving more vegetables to their families (P = 0·010) (EO participants did not differ from the control group on any outcomes). There were no differences between conditions in survey-based measures of food security or food resource management behaviours. Interview results describe facilitators and barriers to shopping at FM and a variety of food waste reduction techniques (including food placement and food resource management). CONCLUSIONS: These findings suggest that fresh produce provision coupled with nutrition and culinary education can positively impact shopping and dietary behaviours.

Community-based culinary and nutrition education intervention promotes fruit and vegetable consumption.

OBJECTIVE: The main objective of this study was to evaluate the impact of the Market to MyPlate (M2MP) program on fruit and vegetable consumption and cooking behaviours. Secondary objectives were to examine factors that affected participant retention and program completion, and analyse program feedback provided by participants. DESIGN: This study conducted a mixed methods evaluation embedded within a cluster randomised controlled trial of the M2MP intervention. Adult participants completed a pre- and post-program survey reporting on their fruit and vegetable consumption and cooking behaviours. A subsample participated in structured interviews, providing feedback about M2MP and the impact of the program. SETTING: Seven weekly classes took place in community centres and extension offices in central Illinois. PARTICIPANTS: 120 adults and their families participated. Class cohorts were randomly assigned to one of three treatment groups: (1) nutrition education and cooking classes with produce allocations (PAE, n 39); (2) nutrition education and cooking classes only (EO, n 36) or (3) control group (n 45). RESULTS: Compared to control, PAE participants reported larger increases from pre- to post-intervention in fruit (P = 0·001) and vegetable consumption (P = 0·002), with no differences in cooking frequency. Interview analyses identified key themes in behaviour changes due to M2MP, including reported increases in dietary variety, cooking self-efficacy and children's participation in cooking. CONCLUSIONS: PAE participants who received an intervention that directly increased their access to fresh produce (via produce allocations) increased their reported fruit and vegetable consumption. Though participants' cooking frequency did not change, interviewees reported increased variety, cooking confidence and family participation in cooking.

Lower Cord Blood IL-17 and IL-25, but Not Other Epithelial Cell-Derived Cytokines Are Associated with Atopic Dermatitis in Infancy.

BACKGROUND: There is a growing need for early biomarkers that may predict the development of atopic dermatitis (AD). As alterations in skin barrier may be a primary event in disease pathogenesis, epithelial cell (EC) cytokines expression patterns may be a potential biomarker in early life to target allergy preventive strategies towards "at-risk" infants. OBJECTIVES: The aim of this longitudinal investigation was to examine from birth over the course of infancy levels of the EC cytokines: thymic stromal lymphopoietin (TSLP), interleukin (IL)-33, IL-25, and IL-17 in infants at high-risk of AD due to maternal atopy. METHOD: We collected (n = 31) cord blood samples from atopic mothers and followed up their infants at 4-6 and 12 months of age for collection of peripheral venous blood samples and diagnosis of AD. TSLP concentration was measured by ELISA after acetone precipitation of the samples. IL-33, IL-25, and IL-17 levels were measured by Luminex. RESULTS: Seven infants who developed AD had lower levels of IL-25 and IL-17 at birth compared to the 24 infants who did not develop AD by 12 months of age. CONCLUSIONS: Lower cord blood levels of IL-17 and IL-25, but not other EC cytokines, were associated with the onset of AD during infancy. Our results highlight that the in-utero period appears critical, and potential maternal influences on cord blood EC-derived cytokine concentrations requires further exploration.

A role for early oral exposure to house dust mite allergens through breast milk in IgE-mediated food allergy susceptibility.

BACKGROUND: Successful prevention of food allergy requires the identification of the factors adversely affecting the capacity to develop oral tolerance to food antigen in early life. OBJECTIVES: This study sought to determine whether oral exposure to Dermatophagoides pteronyssinus through breast milk affects gut mucosal immunity with long-term effects on IgE-mediated food allergy susceptibility. METHODS: Gut immunity was explored in 2-week-old mice breast-fed by mothers exposed to D pteronyssinus, protease-inactivated D pteronyssinus, or to PBS during lactation. We further analyzed oral tolerance to a bystander food allergen, ovalbumin (OVA). In a proof-of-concept study, Der p 1 and OVA levels were determined in 100 human breast milk samples and the association with prevalence of IgE-mediated egg allergy at 1 year was assessed. RESULTS: Increased permeability, IL-33 levels, type 2 innate lymphoid cell activation, and Th2 cell differentiation were found in gut mucosa of mice nursed by mothers exposed to D pteronyssinus compared with PBS. This pro-Th2 gut mucosal environment inhibited the induction of antigen-specific FoxP3 regulatory T cells and the prevention of food allergy by OVA exposure through breast milk. In contrast, protease-inactivated D pteronyssinus had no effect on offspring gut mucosal immunity. Based on the presence of Der p 1 and/or OVA in human breast milk, we identified groups of lactating mothers, which mirror the ones found in mice to be responsible for different egg allergy risk. CONCLUSIONS: This study highlights an unpredicted potential risk factor for the development of food allergy, that is, D pteronyssinus allergens in breast milk, which disrupt gut immune homeostasis and prevents oral tolerance induction to bystander food antigen through their protease activity.

Children with nut allergies have impaired gene expression of Toll-like receptors pathway.

BACKGROUND: Trends in food allergies prompted investigation into the underlying mechanisms. Genetic and epigenetic factors are of high interest, and, in particular, the interplay between genes relating to immune factors directly and indirectly involved in food allergy pathogenesis. We sought to determine potential links between gene expression and epigenetic factors relating to Toll-like receptor (TLR) pathways and childhood food allergies. METHODS: In a cross-sectional study, samples from 80 children with and without food allergies were analysed for gene expression, DNA methylation and a range of immune factors relating to TLR pathways. TLR2, TLR4, CD14, IL5, IL13 and vitamin D were explored. RESULTS: The importance of these immune factors appeared to vary between the different types of food allergies. Expression of TLR2 (P < .001), TLR4 (P = .014) and CD14 (P = .028) varied significantly between children with no food allergy, allergy to nuts and peanuts, and allergy to eggs. DNA methylation in the promoter regions of these genes had a significant association with gene expression. These trends persisted when subjects were stratified by nut allergy vs no nut allergy. Furthermore, TLR2 (P = .001) and CD14 (P = .007) expressions were significantly lower in children with food allergies when compared to those without. CONCLUSION: Gene expression of TLR pathway genes was directly related to food allergy type, and DNA methylation had an indirect effect. TLR2 pathways are of significant interest in nut allergies.

A systematic review of school meal nudge interventions to improve youth food behaviors.

BACKGROUND: School meal programs have a large reach and thus are ideal environments in which to implement interventions targeting improved youth eating behaviors and reduced food waste. This systematic review summarizes the evidence on the effectiveness of school meal nudge interventions on influencing children's eating and waste behaviors. METHODS: Inclusion criteria required studies have participants in primary or secondary school (grades K-12) with interventions that occurred during school lunch or breakfast in the cafeteria and included at least one of the following outcomes: selection, consumption, waste, or school meal participation. Analyses of intervention outcomes were restricted to studies of strong and moderate quality. RESULTS: Twenty-nine studies were included in the quality assessment. Included interventions fell into three categories: 1) placement/convenience, 2) marketing/promotion, or 3) variety/portions. The 20 strong and moderate quality studies included in outcome analyses generally used strong data collection methods and study designs, but were limited by an overall lack of intervention fidelity checks. Multi-component interventions often did not use methods that allowed for separate analyses of outcomes for different intervention components. CONCLUSIONS: School meal nudge interventions were positively associated with food selection, and had an inconsistent relationship with food consumption. There were few studies evaluating the impact of nudge interventions on meal participation or food waste. The limited evidence available links nudges to improved meal participation, as well as undesirable increases in food waste. Future research in this area should use methods that incorporate implementation metrics, attend to systems factors, and allow the outcomes of individual intervention components to be isolated.

SmartStartAllergy: a novel tool for monitoring food allergen introduction in infants.

OBJECTIVES: To estimate the proportion of infants introduced to peanut and other common food allergens by 12 months of age; to collect information about parent-reported reactions to food. DESIGN, SETTING: Observational cohort study, applying the SmartStartAllergy SMS protocol and online questionnaire to parents of 12-month-old infants attending 69 Australian general practices between 21 September 2018 and 3 May 2019. PARTICIPANTS: 3374 parents recruited via the 69 participating general practices. MAIN OUTCOME MEASURES: Proportions of infants who had eaten peanut and other common food allergens; proportions with parent-reported reactions to food. RESULTS: 1940 of 3374 invited parents participated in the study (response rate, 57%), of whom 836 (46%) completed the online questionnaire. At 12 months of age, 1673 of 1940 infants had eaten peanut-including foods (86.2%; 95% confidence interval [CI], 84.6-87.7%); 235 of 1831 parents (12.8%; 95% CI, 11.3-14.5%) reported food-related reactions. Questionnaire responses indicated that dairy was the food type most frequently reported to cause a food-related reaction (72 of 835 exposed infants, 8.6%; 95% CI, 6.8-11%); peanut-related reactions were reported for 20 of 764 exposed children (2.6%; 95% CI, 1.6-4.0%). 97 of 250 parent-reported reactions to food (39%) did not include symptoms that suggested an IgE-mediated allergic reaction. CONCLUSION: Infant feeding practices in Australia have changed over the past decade; a large majority of infants are now fed peanut before 12 months of age. The SmartStartAllergy program allows monitoring of infant feeding practices in primary care, as well as of parent-reported reactions to food in infants.

Family food involvement is related to healthier dietary intake in preschool-aged children.

Children in the United States fall far short of meeting federal dietary recommendations. The unhealthy diets common amongst young children are of crucial public health concern, given that they can inhibit healthy development and are predictive of chronic diseases in adulthood. Research investigating behaviors that are related to dietary habits is crucial to allow a better understanding of the causes of unhealthy dietary practices. Involvement in food preparation is known to be associated with healthy dietary behaviors in school-aged children, but little is known about these behaviors and their correlates in younger children. The present study sought to examine the influences and correlates of involvement in family food preparation in children at ages three and four. Parents of preschool aged children (n = 497) completed surveys including information about demographic background, their children's family food involvement, dietary intake, mealtime routines, and problematic eating behaviors. Data were collected when children were three (wave one of the survey) and four years of age (wave two). Findings from this study indicate that family food involvement at age three is predictive of healthier dietary intake at age four (increased consumption of fruits and vegetables, decreased consumption of fast food). These findings indicate that family food involvement is predictive of healthier dietary behaviors in young children, and that outreach efforts focused on family food involvement in early childhood may improve children's dietary habits.

American mastodon extirpation in the Arctic and Subarctic predates human colonization and terminal Pleistocene climate change.

Existing radiocarbon ((14)C) dates on American mastodon (Mammut americanum) fossils from eastern Beringia (Alaska and Yukon) have been interpreted as evidence they inhabited the Arctic and Subarctic during Pleistocene full-glacial times (∼ 18,000 (14)C years B.P.). However, this chronology is inconsistent with inferred habitat preferences of mastodons and correlative paleoecological evidence. To establish a last appearance date (LAD) for M. americanum regionally, we obtained 53 new (14)C dates on 36 fossils, including specimens with previously published dates. Using collagen ultrafiltration and single amino acid (hydroxyproline) methods, these specimens consistently date to beyond or near the ∼ 50,000 y B.P. limit of (14)C dating. Some erroneously "young" (14)C dates are due to contamination by exogenous carbon from natural sources and conservation treatments used in museums. We suggest mastodons inhabited the high latitudes only during warm intervals, particularly the Last Interglacial [Marine Isotope Stage (MIS) 5] when boreal forests existed regionally. Our (14)C dataset suggests that mastodons were extirpated from eastern Beringia during the MIS 4 glacial interval (∼ 75,000 y ago), following the ecological shift from boreal forest to steppe tundra. Mastodons thereafter became restricted to areas south of the continental ice sheets, where they suffered complete extinction ∼ 10,000 (14)C years B.P. Mastodons were already absent from eastern Beringia several tens of millennia before the first humans crossed the Bering Isthmus or the onset of climate changes during the terminal Pleistocene. Local extirpations of mastodons and other megafaunal populations in eastern Beringia were asynchrononous and independent of their final extinction south of the continental ice sheets.

Levels of innate immune factors in preterm and term mothers' breast milk during the 1st month postpartum.

There is a paucity of data on the effect of preterm birth on the immunological composition of breast milk throughout the different stages of lactation. We aimed to characterise the effects of preterm birth on the levels of immune factors in milk during the 1st month postpartum, to determine whether preterm milk is deficient in antimicrobial factors. Colostrum (days 2-5 postpartum), transitional milk (days 8-12) and mature milk (days 26-30) were collected from mothers of extremely preterm (<28 weeks of gestation, n 15), very preterm (28-<32 weeks of gestation, n 15), moderately preterm (32-<37 weeks of gestation, n 15) and term infants (37-41 weeks of gestation, n 15). Total protein, lactoferrin, secretory IgA, soluble CD14 receptor (sCD14), transforming growth factor-ß2 (TGF-ß2), α defensin 5 (HD5), ß defensins 1 (HBD1) and 2, IL-6, IL-10, IL-13, interferon-γ, TNF-α and lysozyme (LZ) were quantified in milk. We examined the effects of lactation stage, gestational age, volume of milk expressed, mode of delivery, parity and maternal infection on milk immune factor concentrations using repeated-measures regression analysis. The concentrations of all factors except LZ and HD5 decreased over the 1st month postpartum. Extremely preterm mothers had significantly higher concentrations of HBD1 and TGF-ß2 in colostrum than term mothers did. After controlling for other variables in regression analyses, preterm birth was associated with higher concentrations of HBD1, LZ and sCD14 in milk samples. In conclusion, preterm breast milk contains significantly higher concentrations of some immune proteins than term breast milk.

Isotopic paleoecology of Clovis mammoths from Arizona.

The causes of megafaunal extinctions in North America have been widely debated but remain poorly understood. Mammoths (Mammuthus spp.) in the American Southwest were hunted by Clovis people during a period of rapid climate change, just before the regional onset of Younger Dryas cooling and mammoth extirpation. Thus, these mammoths may provide key insights into late Pleistocene extinction processes. Here we reconstruct the seasonal diet and climatic conditions experienced by mammoths in the San Pedro Valley of Arizona, using the carbon ((13)C/(12)C) and oxygen ((18)O/(16)O) isotope compositions of tooth enamel. These records suggest that Clovis mammoths experienced a warm, dry climate with sufficient summer rainfall to support seasonal C(4) plant growth. Monsoon intensity may have been reduced relative to the preceding time period, but there is no isotopic evidence for severe drought. However, it is possible that the "Clovis drought", inferred from stratigraphic evidence, occurred suddenly at the end of the animals' lives and thus was not recorded in the enamel isotopic compositions. Unlike mammoths that lived before the Last Glacial Maximum, Clovis mammoths regularly increased C(4) grass consumption during summer, probably seeking seasonally green grasslands farther from the river valley. This predictable seasonal behavior may have made mammoths easier to locate by Clovis hunters. Furthermore, Clovis mammoths probably had no previous experience of such sudden climatic change as is believed to have occurred at the time of their extinction.

Early regular egg exposure in infants with eczema: A randomized controlled trial.

BACKGROUND: Observational studies suggest that early regular ingestion of allergenic foods might reduce the risk of food allergy. OBJECTIVE: We sought to determine whether early regular oral egg exposure will reduce subsequent IgE-mediated egg allergy in infants with moderate-to-severe eczema. METHODS: In a double-blind, randomized controlled trial infants were allocated to 1 teaspoon of pasteurized raw whole egg powder (n = 49) or rice powder (n = 37) daily from 4 to 8 months of age. Cooked egg was introduced to both groups after an observed feed at 8 months. The primary outcome was IgE-mediated egg allergy at 12 months, as defined based on the results of an observed pasteurized raw egg challenge and skin prick tests. RESULTS: A high proportion (31% [15/49]) of infants randomized to receive egg had an allergic reaction to the egg powder and did not continue powder ingestion. At 4 months of age, before any known egg ingestion, 36% (24/67) of infants already had egg-specific IgE levels of greater than 0.35 kilounits of antibody (kUA)/L. At 12 months, a lower (but not significant) proportion of infants in the egg group (33%) were given a diagnosis of IgE-mediated egg allergy compared with the control group (51%; relative risk, 0.65; 95% CI, 0.38-1.11; P = .11). Egg-specific IgG4 levels were significantly (P < .001) greater in the egg group at both 8 and 12 months. CONCLUSION: Induction of immune tolerance pathways and reduction in egg allergy incidence can be achieved by early regular oral egg exposure in infants with eczema. Caution needs to be taken when these high-risk infants are first exposed to egg because many have sensitization already by 4 months of age.

Interaction Between Baseline Participant Factors and Treatment Effects Following Peanut Oral Immunotherapy.

BACKGROUND: The Probiotic Peanut Oral Immunotherapy-003 multicenter randomized trial found that both probiotic peanut oral immunotherapy (PPOIT) and peanut OIT alone (OIT) were effective compared with placebo in inducing clinical remission after 18 months of treatment, and improving health-related quality of life (HRQL) at 12 months after treatment. Understanding treatment effect modifiers can optimize outcomes through precision care. OBJECTIVES: This post hoc study examined baseline clinical and demographic participant factors that modified treatment effects. METHODS: The study sample included 201 children (aged 1-10 years) with challenge-confirmed peanut allergy. Exposure variables were baseline clinical and demographic factors. Outcomes were remission (double-blind, placebo-controlled food challenge, cumulative 4,950-mg peanut protein at 8 weeks after treatment) and HRQL (change in Food Allergy Quality of Life Questionnaire-Parent Form score). Interactions between baseline factors and treatment effects on remission and HRQL were explored with regression models. RESULTS: A higher degree of peanut sensitivity (large peanut skin prick test, high peanut specific IgE, and low reaction-eliciting dose at study entry challenge) and other concurrent allergic conditions (multiple food allergies, asthma, or wheeze) were associated with the decreased likelihood of attaining remission after both PPOIT and OIT treatment. History of anaphylaxis was associated with the reduced likelihood of remission after PPOIT compared with OIT. For the HRQL outcome, there was evidence that sex, history of anaphylaxis, and age modified treatment effects. CONCLUSIONS: Baseline participant factors modify PPOIT and OIT effects on remission and HRQL. Considering modifiers of treatment effect during participant selection may optimize treatment success and clinical trial design toward specific outcomes, such as the achievement of remission.

Early Peanut Immunotherapy in Children (EPIC) trial: protocol for a pragmatic randomised controlled trial of peanut oral immunotherapy in children under 5 years of age.

INTRODUCTION: Food allergy is a major public health challenge in Australia. Despite widespread uptake of infant feeding and allergy prevention guidelines the incidence of peanut allergy in infants has not fallen, and prevalence of peanut allergy in school-aged children continues to rise. Therefore, effective and accessible treatments for peanut allergy are required. There is high-quality evidence for efficacy of oral immunotherapy in children aged 4-17 years old; however, few randomised trials have investigated peanut oral immunotherapy (OIT) in young children. Furthermore, the use of food products for OIT with doses prepared and administered by parents without requiring pharmacy compounding has the potential to reduce costs associated with the OIT product. METHODS AND ANALYSIS: Early Peanut Immunotherapy in Children is an open-label randomised controlled trial of peanut OIT compared with standard care (avoidance) to induce desensitisation in children aged 1-4 years old with peanut allergy. n=50 participants will be randomised 1:1 to intervention (daily peanut OIT for 12 months) or control (peanut avoidance). The primary outcome is the proportion of children in each group with a peanut eliciting dose >600 mg peanut protein as assessed by open peanut challenge after 12 months, analysed by intention to treat. Secondary outcomes include safety as assessed by frequency and severity of treatment-related adverse events, quality of life measured using age-appropriate food allergy-specific questionnaires and immunological changes during OIT. ETHICS: The trial is approved by the Child and Adolescent Health Service Human Research Ethics Committee and prospectively registered with the Australia and New Zealand Clinical Trials Registry. DISSEMINATION: Trial outcomes will be published in a peer-review journal and presented and local and national scientific meetings. TRIAL REGISTRATION NUMBER: ACTRN12621001001886.

The Relationship between Fluid Milk, Water, and 100% Juice and Health Outcomes among Children and Adolescents.

Beverages can provide improved nutrient intake and hydration, but also pose concerns related to overnutrition or contamination for children and adolescents who are in a time of critical growth. This narrative review aims to understand the impact of milk, 100% juice, and water consumption on health-related outcomes in youth. The literature review conducted used PubMed, Web of Science, and CABI global. Forty-five research articles met the quality criteria and were included. Health organization and governmental resources were also reviewed to identify current intake and consumption recommendations. All beverages in this review were associated with a variety of desirable and undesirable findings that spanned over 40 different health outcomes. Most studies that assessed milk lacked clear distinction between milk type (flavored vs. unflavored) or fat percentage, making it difficult to understand the impact of milk consumption. The relationship between milk intake and anthropometric-related outcomes were mixed within and across studies. Water was consistently associated with better hydration, while 100% juice and flavored milk intake was associated with more desirable dietary patterns or nutrients that children are currently not consuming adequate amounts of. The implications of these findings were discussed in the context of the National School Lunch Program (NSLP), while considering the impact of issues such as contaminated water and lactose intolerance. This review suggests that water may be an optimal default beverage option in the NSLP to promote hydration and accommodate beverage preferences for those with lactose intolerance.

Nutrition Environment at Food Pantries Improves After Fresh Produce Donation Program.

OBJECTIVE: To evaluate the influence of the Growing Together Illinois fresh produce donation program and understand factors that affect produce distribution at participating food pantries. METHODS: In this intervention at 17 Illinois food pantries, Master Gardeners supported food donation gardens, and Supplemental Nutrition Assistance Program Education provided educational and environmental interventions to increase selection and use of fresh produce. This mixed-methods pre-post study assessed pantry characteristics and program impact via Nutrition Environment Food Pantry Assessment Tool evaluations, interview feedback from pantry staff, and structured pantry observations. RESULTS: Pantries experienced significant increases from preintervention to postintervention in providing various types of produce, marketing and nudging healthful products, providing additional resources, and total Nutrition Environment Food Pantry Assessment Tool scores. Participants had positive feedback about the program and educational interventions and reported the weekly timing of donations mitigated potential storage and spoilage issues. CONCLUSIONS AND IMPLICATIONS: Future research could focus on approaches to increase fresh produce in food pantries while supporting clients via nutrition and cooking education.

Identifying gene network patterns and associated cellular immune responses in children with or without nut allergy.

BACKGROUND: Although evidence suggests that the immune system plays a key role in the pathophysiology of nut allergy, the precise immunological mechanisms of nut allergy have not been systematically investigated. The aim of the present study was to identify gene network patterns and associated cellular immune responses in children with or without nut allergy. METHODS: Transcriptome profiling of whole blood cells was compared between children with and without nut allergy. Three genes were selected to be validated on a larger cohort of samples (n = 86) by reverse transcription-polymerase chain reactions (RT-qPCR). The composition of immune cells was inferred from the transcriptomic data using the CIBERSORTx algorithm. A co-expression network was constructed employing weighted gene co-expression network analysis (WGCNA) on the top 5000 most variable transcripts. The modules were interrogated with pathway analysis tools (InnateDB) and correlated with clinical phenotypes and cellular immune responses. RESULTS: Proportions of neutrophils were positively correlated and CD4+ T-cells and regulatory T-cells (Tregs) were negatively correlated with modules of nut allergy. We also identified 2 upregulated genes, namely Interferon Induced With Helicase C Domain 1 (IFIH1), DNA damage-regulated autophagy modulator 1 (DRAM1) and a downregulated gene Zinc Finger Protein 512B (ZNF512B) as hub genes for nut allergy. Further pathway analysis showed enrichment of type 1 interferon signalling in nut allergy. CONCLUSIONS: Our findings suggest that upregulation of type 1 interferon signalling and neutrophil responses and downregulation of CD4+ T-cells and Tregs are features of the pathogenesis of nut allergy.

Probiotic peanut oral immunotherapy versus oral immunotherapy and placebo in children with peanut allergy in Australia (PPOIT-003): a multicentre, randomised, phase 2b trial.

BACKGROUND: Oral immunotherapy is effective at inducing desensitisation to allergens and induces sustained unresponsiveness (ie, clinical remission) in a subset of patients, but causes frequent reactions. We aimed to investigate whether addition of a probiotic adjuvant improved the efficacy or safety of peanut oral immunotherapy. METHODS: PPOIT-003, a multicentre, randomised, phase 2b trial, was conducted in three tertiary hospitals in Australia (Adelaide [SA], Melbourne [VIC], and Perth [WA]) in children aged 1-10 years, weighing more than 7 kg, with peanut allergy confirmed by a double-blind placebo-controlled food challenge (cumulative 4950 mg dose of peanut protein) and positive peanut skin prick test (≥3 mm) or peanut-specific IgE (≥0·35 kU/L). Children were randomly assigned (2:2:1) to receive probiotic and peanut oral immunotherapy (PPOIT), placebo probiotic and peanut oral immunotherapy (OIT), or placebo probiotic and placebo OIT (placebo) for 18 months, and were followed up until 12 months after completion of treatment. Oral immunotherapy consisted of increasing doses of peanut protein (commercially available food-grade 12% defatted peanut flour [50% peanut protein]) until a 2000 mg daily maintenance dose was reached. The probiotic adjuvant was a daily dose of 2 × 1010 colony-forming units of the probiotic Lactobacillus rhamnosus ATCC 53103. Placebo immunotherapy comprised maltodextrin, brown food colouring, and peanut essence, and placebo probiotic was maltodextrin. Dual primary outcomes were 8-week sustained unresponsiveness, defined as no reaction to a cumulative dose of 4950 mg peanut protein at treatment completion and 8 weeks after treatment completion, in the PPOIT versus placebo groups and the PPOIT versus OIT groups, analysed by intention to treat. Safety endpoints were adverse events during the treatment phase, and peanut ingestion and reactions in the 12-month post-treatment period. This study is registered with the Australian New Zealand Clinical Trials Registry, 12616000322437. FINDINGS: Between July 4, 2016, and Sept 21, 2020, 201 participants were enrolled and included in the intention-to-treat analysis. 36 (46%) of 79 children in the PPOIT group and 42 (51%) of 83 children in the OIT group achieved sustained unresponsiveness compared with two (5%) of 39 children in the placebo group (risk difference 40·44% [95% CI 27·46 to 53·42] for PPOIT vs placebo, p<0·0001), with no difference between PPOIT and OIT (-5·03% [-20·40 to 10·34], p=0·52). Treatment-related adverse events were reported in 72 (91%) of 79 children in the PPOIT group, 73 (88%) of 83 children in the OIT group, and 28 (72%) of 39 children in the placebo group. Exposure-adjusted incidence of adverse events was 10·58 in the PPOIT group, 11·36 in the OIT, and 2·09 in the placebo group (ratio 0·92 [95% CI 0·85 to 0·99] for PPOIT vs OIT, p=0·042; 4·98 [4·11-6·03] for PPOIT vs placebo, p<0·0001; 5·42 [4·48-6·56] for OIT vs placebo, p<0·0001), with differences seen primarily in gastrointestinal symptoms and in children aged 1-5 years. During the 12-month post-treatment period, 60 (85%) of 71 participants in the PPOIT group, 60 (86%) of 70 participants in the OIT group, and six (18%) of 34 participants in the placebo group were eating peanut; rescue epinephrine use was infrequent (two [3%] of 71 in the PPOIT group, four [6%] of 70 in the OIT group, and none in the placebo group). INTERPRETATION: Both PPOIT and OIT were effective at inducing sustained unresponsiveness. Addition of a probiotic did not improve efficacy of OIT, but might offer a safety benefit compared with OIT alone, particularly in preschool children. FUNDING: National Health and Medical Research Council Australia and Prota Therapeutics.

C3 plant isotopic variability in a boreal mixed woodland: implications for bison and other herbivores.

Plant isotopic baselines are critical for accurately reconstructing ancient diets and environments and for using stable isotopes to monitor ecosystem conservation. This study examines the stable carbon and nitrogen isotope compositions (δ 13C, δ 15N) of terrestrial C3 plants in Elk Island National Park (EINP), Alberta, Canada, with a focus on plants consumed by grazers. EINP is located in a boreal mixed woodland ecozone close to the transition area between historic wood and plains bison habitats, and is currently home to separate herds of wood and plains bison. For this study, 165 C3 plant samples (grasses, sedges, forbs, shrubs, and horsetail) were collected from three habitat types (open, closed, and wet) during two seasons (summer and fall). There were no statistically significant differences in the δ 13C or δ 15N values of grasses, sedges, shrubs and forbs. On the other hand, plant δ 13C and δ 15N values varied among habitats and plant parts, and the values increased from summer to fall. These results have several implications for interpreting herbivore tissue isotopic compositions: (1) consuming different proportions of grasses, sedges, shrubs, and forbs might not result in isotopic niche partitioning, (2) feeding in different microhabitats or selecting different parts of the same types of plants could result in isotopic niche partitioning, and (3) seasonal isotopic changes in herbivore tissues could reflect seasonal isotopic changes in dietary plants rather than (or in addition to) changes in animal diet or physiology. In addition, the positively skewed plant δ 15N distributions highlight the need for researchers to carefully evaluate the characteristics of their distributions prior to reporting data (e.g., means, standard deviations) or applying statistical models (e.g., parametric tests that assume normality). Overall, this study reiterates the importance of accessing ecosystem-specific isotopic baselines for addressing research questions in archaeology, paleontology, and ecology.