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Background Health-promoting strategies targeting the food retail environment can influence consumer purchasing behaviour. Most strategies require the healthiness of available food and beverages to be determined. Healthiness classification systems exist; however, no system is linked to remote food retail point-of-sale systems. The objective of this study was to explore the feasibility and validity of a process to identify healthy food and beverages in food retail store point-of-sale systems, as applied in a discount card study in remote Aboriginal and Torres Strait Islander communities, Australia. Methods A convergent mixed methods study design was used. Feasibility was explored through semi-structured interviews with project and store team members involved in a process to identify healthy food and beverages in point-of-sale systems across five remote stores. Convergent validity was assessed by comparing alignment of classification of food and beverages via the expert-informed process used, with a technology-driven system underpinned by Australia’s Health Star Rating and discretionary classification, the Thumbs Rating system. Results All eight eligible project and store team members involved in the process were interviewed. The expert-informed process, while implemented successfully overall, was not entirely acceptable to participants. Challenges related to the manual classification of products, with participants recommending exploring automated processes to classify products. There was substantial alignment with technology-driven classification (86% of 6281 unique products). Misalignment was largely related to differences in criteria; the expert-informed process was underpinned by a food-based classification system, including selection of the healthier alternatives within food groups, and the Thumbs Rating system is underpinned by food-based classification with nutrient-profiling. Conclusion Alternative methods to the expert-informed process examined in this study should be considered to classify food and beverages in remote food retail point-of-sale systems. The Thumbs Rating provides a valid classification system and would provide an automated means of classification that could be linked to point-of-sale systems. A shift in classification for a small proportion of products, would need to be considered in applying the Thumbs Rating system to remote food retail interventions, or additional criteria overlaying the system could be implemented to meet specific criteria for targeted strategies.

The right to food security has been recognised internationally, and nationally in Australia by Aboriginal Community Controlled Health Organisations. This study aims to explore food (in)security and solutions for improvement of food security in remote Aboriginal and/or Torres Strait Islander communities in Australia, from the perspective of caregivers of children within the context of the family using photovoice. Participants took part in workshops discussing participant photographs of food (in)security, including solutions. Themes and sub-themes with associated solutions included traditional food use, sharing as a part of culture, the cost of healthy food, energy and transport, and housing and income. Community leaders used these data in setting priorities for advocacy to improve food security in their communities.

Background Maternal and early childhood nutrition is foundational in setting the course for lifetime metabolic and disease outcomes. Food security influences the achievement of optimal diets; however, little is known about how traditional food intake may influence this dynamic for Aboriginal and Torres Strait Islander people living in remote communities. This study describes diets and food security status of Aboriginal and Torres Strait Islander pregnant and breastfeeding women and children 6 months to 5 years in remote communities in Australia, and explores interactions between diet quality, food security and traditional food consumption. Methods Baseline data from a trial testing a discount on healthy foods and drinks were used. Participants from eight communities (four each in coastal Cape York, Queensland and desert Central Australia, Northern Territory) participated in June–September 2021. A validated food frequency questionnaire was used to assess usual intake and calculate a diet quality score. A modified version of the United States Department of Agriculture 18-item Household Food Security Scale Module measured food security status. A model was fitted to explore the interactions between diet quality, food security and traditional food consumption. Results Complete dietary data were available for 471 participants from 294 households. Average reported food group intakes of children were similar to recommended patterns, however except for adequate meat intakes those of women were not; mean diet quality scores were 23% higher in children than women ( p  < 0.001). Long-duration breastfeeding was described (36% of > 2–4 years breastfed). High rates of household food insecurity were reported (76%), although rates were lower in Cape York ( p  < 0.001). Reported traditional food intake was higher in Cape York than in Central Australia ( p  < 0.001). For diet quality, a significant three-way interaction between food security status, traditional food frequency and adult/child status was demonstrated ( p  = 0.005). Conclusions Remote community families carry out practices that protect and support the diet quality of children despite conditions that challenge food security and optimal diets. The role of traditional food consumption in reducing the impact of food insecurity on diet quality provides further evidence for Aboriginal and Torres Strait Islander food systems to be at the centre of comprehensive efforts to address food insecurity. Trial registration This work is part of a trial that has been registered with Australian New Zealand Clinical Trials Registry: ACTRN12621000640808. Trial registration date: 28/05/2021.

Background This study aimed to determine the relative validity of dietary quality index scores estimated using the updated version of the Menzies Remote Short-item Dietary Assessment Tool (MRSDAT), a food frequency questionnaire developed for use with remote Indigenous communities in Australia. Methods This validation study compares scores derived from the updated MRSDAT with those derived from 24-h recalls. Participants from nine remote communities across three discrete regions of Australia (Central Australia, North Northern Territory and Cape York) participated in June–September 2021, or May–July 2022. Participants were Indigenous children aged six months to five years, pregnant and/or breastfeeding Indigenous women, and overweight adult Indigenous males and females. The agreement between methods was explored using Lin’s concordance correlation coefficient (CCC), Bland–Altman plots, weighted Cohen’s kappa, paired samples t-tests and Wilcoxon signed-rank tests. Primary comparisons were completed for the whole sample, and primary and secondary comparisons for only participants with ≥ 2 × 24 h recalls. Results Ninety-nine participants were recruited. The MRSDAT estimated dietary quality index scores 0.31/100 points higher than 24-h recall estimates for participants with ≥ 2 × 24-h recalls, and 0.18/100 points higher for all participants, with consistent results for adults and children (CCC = Rc 0.58, 95% CI 0.39, 0.72). Conclusions Updates to the MRSDAT have resulted in dietary quality index scores highly comparable to those derived from 24-h recalls. The MRSDAT has the practical advantages of speed and convenience for research purposes, and the built-in instant dietary feedback feature has application to service delivery settings given the robust results demonstrated in this validation study.

Background The restrictions associated with the 2020 COVID-19 pandemic has resulted in changes to young children’s daily routines and habits. The impact on their participation in movement behaviours (physical activity, sedentary screen time and sleep) is unknown. This international longitudinal study compared young children’s movement behaviours before and during the COVID-19 pandemic. Methods Parents of children aged 3–5 years, from 14 countries (8 low- and middle-income countries, LMICs) completed surveys to assess changes in movement behaviours and how these changes were associated with the COVID-19 pandemic. Surveys were completed in the 12 months up to March 2020 and again between May and June 2020 (at the height of restrictions). Physical activity (PA), sedentary screen time (SST) and sleep were assessed via parent survey. At Time 2, COVID-19 factors including level of restriction, environmental conditions, and parental stress were measured. Compliance with the World Health Organizations (WHO) Global guidelines for PA (180 min/day [≥60 min moderate- vigorous PA]), SST (≤1 h/day) and sleep (10-13 h/day) for children under 5 years of age, was determined. Results Nine hundred- forty-eight parents completed the survey at both time points. Children from LMICs were more likely to meet the PA (Adjusted Odds Ratio [AdjOR] = 2.0, 95%Confidence Interval [CI] 1.0,3.8) and SST (AdjOR = 2.2, 95%CI 1.2,3.9) guidelines than their high-income country (HIC) counterparts. Children who could go outside during COVID-19 were more likely to meet all WHO Global guidelines (AdjOR = 3.3, 95%CI 1.1,9.8) than those who were not. Children of parents with higher compared to lower stress were less likely to meet all three guidelines (AdjOR = 0.5, 95%CI 0.3,0.9). Conclusion PA and SST levels of children from LMICs have been less impacted by COVID-19 than in HICs. Ensuring children can access an outdoor space, and supporting parents’ mental health are important prerequisites for enabling pre-schoolers to practice healthy movement behaviours and meet the Global guidelines.

Chemoimmunotherapy has recently failed to demonstrate significant clinical benefit in advanced bladder cancer patients; and the mechanism(s) underlying such suboptimal response remain elusive. To date, most studies have focused on tumor-intrinsic properties that render them “immune-excluded”. Here, we explore an alternative, drug-induced mechanism that impedes therapeutic response via disrupting the onset of immunogenic cell death. Using two immune-excluded syngeneic mouse models of muscle-invasive bladder cancer (MIBC), we show that platinum-based chemotherapy diminishes CD8+ T cell tumor infiltration and constraines their antitumoral activity, despite expression of activation markers IFNγ and granzyme B. Mechanistically, chemotherapy induces the release of prostaglandin E 2 (PGE 2 ) from dying cancer cells, which is an inhibitory damage-associated molecular pattern (iDAMP) that hinderes dendritic cell maturation. Upon pharmaceutical blockade of PGE 2 release, CD8+ T cells become tumoricidal and display an intraepithelial-infiltrating (or inflamed) pattern. This “iDAMP blockade” approach synergizes with chemotherapy and sensitizes bladder tumors towards anti-PD1 immune checkpoint inhibitor therapy. These findings provide a compelling rationale to evaluate this drug combination in future clinical trials. Chemoimmunotherapy recently failed to improve objective response for patients with advanced muscle-invasive bladder cancer (MIBC). Here using two murine models of immune-excluded MIBC, the authors show that resistance to chemoimmunotherapy can be overcome by blocking the COX-2/prostaglandin E2 axis, reinvigorating anti-tumor immune responses.

The development of the musculoskeletal system and its maintenance depends on the reciprocal relationship between muscle and bone. The size of skeletal muscles and the forces generated during muscle contraction are potent sources of mechanical stress on the developing skeleton, and they shape bone structure during growth. This is particularly evident in hypermuscular global myostatin (Mstn)‐null mice, where larger muscles during development increase bone mass and alter bone shape. However, whether muscle hypertrophy can similarly influence the shape of bones after the embryonic and prepubertal period is unknown. To address this issue, bone structure was assessed after inducing muscle hypertrophy in the lower hindlimbs of young‐adult C57BL/6J male mice by administering intramuscular injections of recombinant adeno‐associated viral vectors expressing follistatin (FST), a potent antagonist of Mstn. Two FST isoforms were used: the full‐length 315 amino acid isoform (FST‐315) and a truncated 288 amino acid isoform (FST‐288). In both FST‐treated cohorts, muscle hypertrophy was observed, and the anterior crest of the tibia, adjacent to the tibialis anterior muscle, was lengthened. Hypertrophy of the muscles surrounding the tibia caused the adjacent cortical shell to recede inward toward the central axis: an event driven by bone resorption adjacent to the hypertrophic muscle. The findings reveal that inducing muscle hypertrophy in mice can confer changes in bone shape in early adulthood. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

We sought to examine the regulatory effect of Meteorin-β (Metrnβ)/Meteorin like (Metrnl)/IL-41 on lung inflammation in allergic asthma. We found that Metrnβ was elevated significantly in asthmatic patients and in mice with allergic asthma induced by house dust mite (HDM) extract. Upon exposure to HDM, Metrnβ was secreted predominantly by airway epithelial cells and inflammatory cells, including macrophages and eosinophils. The increased Metrnβ effectively blocked the development of airway hyperreactivity (AHR) and decreased inflammatory cell airway infiltration and type 2 cytokine production, which was associated with downregulated DC-mediated adaptive immune responses. Moreover, Metrnβ impaired the maturation and function of bone marrow-derived dendritic cells in vitro. Asthmatic mice adoptively transferred with dendritic cells isolated from Metrnβ-treated allergic mice displayed decreased AHR, airway inflammation, and lung injury. Metrnβ also displayed anti-inflammatory properties in immunodeficient SCID mice with allergic asthma and in in vitro 3D ALI airway models. Moreover, blockade of Metrnβ by anti-Metrnβ antibody treatment promoted the development of allergic asthma. These results revealed the unappreciated protective roles of Metrnβ in alleviating DC-mediated Th2 inflammation in allergic asthma, providing the novel treatment strategy of therapeutic targeting of Metrnβ in allergic asthma.

Abstract Infertility is associated with the alteration of the seminal microbiome. However, the onset of dysbiosis remains controversial and the involvement of host factors remains elusive. This study investigates the alterations of the seminal microbiome in male infertility and examines the association and function of DEFB119, a reproductive-tract-specific host antimicrobial peptide, on the seminal microbiome and male fertility. While we observed comparable genera, diversity and evenness of bacterial communities, a marked decrease in the modularity of the metacommunities was observed in patients with abnormal spermiogram (n = 57) as compared to the control (n = 30). A marked elevation of DEFB119 was observed in a subpopulation of male infertile patients (n = 5). Elevated seminal DEFB119 was associated with a decrease in the observed genera, diversity and evenness of bacterial communities, and further distortion of the metacommunities. Mediation analysis suggests the involvement of elevated DEFB119 and dysbiosis of the seminal microbiome in mediating the abnormalities in the spermiogram. Functional experiments showed that recombinant DEFB119 significantly decrease the progressive motility of sperm in patients with abnormal spermiogram. Moreover, DEFB119 demonstrated species-specific antimicrobial activity against common seminal and nonseminal species. Our work identifies an important host factor that mediates the host–microbiome interaction and stratifies the seminal microbiome associated with male infertility. These results may lead to a new diagnostic method for male infertility and regimens for formulating the microbiome in the reproductive tract and other organ systems.