Neutrophil elastase selectively kills cancer cells and attenuates tumorigenesis.

Cancer cell genetic variability and similarity to host cells have stymied development of broad anti-cancer therapeutics. Our innate immune system evolved to clear genetically diverse pathogens and limit host toxicity; however, whether/how innate immunity can produce similar effects in cancer is unknown. Here, we show that human, but not murine, neutrophils release catalytically active neutrophil elastase (ELANE) to kill many cancer cell types while sparing non-cancer cells. ELANE proteolytically liberates the CD95 death domain, which interacts with histone H1 isoforms to selectively eradicate cancer cells. ELANE attenuates primary tumor growth and produces a CD8+T cell-mediated abscopal effect to attack distant metastases. Porcine pancreatic elastase (ELANE homolog) resists tumor-derived protease inhibitors and exhibits markedly improved therapeutic efficacy. Altogether, our studies suggest that ELANE kills genetically diverse cancer cells with minimal toxicity to non-cancer cells, raising the possibility of developing it as a broad anti-cancer therapy.

Lasofoxifene as a potential treatment for aromatase inhibitor-resistant ER-positive breast cancer.

BACKGROUND: Breast cancers treated with aromatase inhibitors (AIs) can develop AI resistance, which is often driven by estrogen receptor-alpha (ERα/ESR1) activating mutations, as well as by ER-independent signaling pathways. The breast ER antagonist lasofoxifene, alone or combined with palbociclib, elicited antitumor activities in a xenograft model of ER + metastatic breast cancer (mBC) harboring ESR1 mutations. The current study investigated the activity of LAS in a letrozole-resistant breast tumor model that does not have ESR1 mutations. METHODS: Letrozole-resistant, MCF7 LTLT cells tagged with luciferase-GFP were injected into the mammary duct inguinal glands of NSG mice (MIND model; 6 mice/group). Mice were randomized to vehicle, lasofoxifene ± palbociclib, fulvestrant ± palbociclib, or palbociclib alone 2-3 weeks after cell injections. Tumor growth and metastases were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis. The experiment was repeated with the same design and 8-9 mice in each treatment group. RESULTS: Western blot analysis showed that the MCF7 LTLT cells had lower ERα and higher HER2 expressions compared with normal MCF7 cells. Lasofoxifene ± palbociclib, but not fulvestrant, significantly reduced primary tumor growth versus vehicle as assessed by in vivo imaging of tumors at study ends. Percent tumor area in excised mammary glands was significantly lower for lasofoxifene plus palbociclib versus vehicle. Ki67 staining showed decreased overall tumor cell proliferation with lasofoxifene ± palbociclib. The lasofoxifene + palbociclib combination was also associated with significantly fewer bone metastases compared with vehicle. Similar results were observed in the repeat experiment. CONCLUSIONS: In a mouse model of letrozole-resistant breast cancer with no ESR1 mutations, reduced levels of ERα, and overexpression of HER2, lasofoxifene alone or combined with palbociclib inhibited primary tumor growth more effectively than fulvestrant. Lasofoxifene plus palbociclib also reduced bone metastases. These results suggest that lasofoxifene alone or combined with a CDK4/6 inhibitor may offer benefits to patients who have ER-low and HER2-positive, AI-resistant breast cancer, independent of ESR1 mutations.

Sex and race/ethnicity specific reference predictive equations for abdominal adiposity indices using anthropometry in US adults.

BACKGROUND AND AIMS: Abdominal adiposity indices have stronger associations with cardiometabolic risk factors compared to anthropometric measures but are rarely used in large scale studies due to the cost and efficiency. The aim of this study is to establish sex and race/ethnicity specific reference equations using anthropometric measures. METHODS AND RESULTS: A secondary data analysis (n = 6589) of healthy adults was conducted using data from National Health and Nutrition Examination Survey 2011-2018. Variables included in the analyses were anthropometric measures (height; weight; waist circumference, WC) and abdominal adiposity indices (android percent fat; android to gynoid ratio, A/G ratio; visceral adipose tissue area, VATA; visceral to subcutaneous adipose area ratio, VSR). Multivariable prediction models were developed using quantile regression. Bland-Altman was used for external validation of prediction models. Reference equations to estimate android percent fat, A/G ratio, VATA and VSR from anthropometric measurements were developed using a randomly selected subsample of 4613. These reference equations for four abdominal adiposity indices were then cross-validated in the remaining subsample of 1976. The measured and predicted android percent fat, A/G ratio, VATA and VSR were not statistically different (p > 0.05) except for the A/G ratio in Asian males and VSR in White females. The results of Bland-Altman further revealed that ≥93% of predicted abdominal adiposity indices fell within the limits of agreement (±1.96 standard deviation). CONCLUSION: The sex and race/ethnicity specific reference equations for abdominal adiposity indices established using anthropometrics in the present study have strong predictive ability in US healthy adults.

Labeling of a mutant estrogen receptor with an Affimer in a breast cancer cell line.

Mutations of the intracellular estrogen receptor alpha (ERα) is implicated in 70% of breast cancers. Therefore, it is of considerable interest to image various mutants (L536S, Y537S, D538G) in living cancer cell lines, particularly as a function of various anticancer drugs. We therefore developed a small (13 kDa) Affimer, which, after fluorescent labeling, is able to efficiently label ERα by traveling through temporary pores in the cell membrane, created by the toxin streptolysin O. The Affimer, selected by a phage display, predominantly labels the Y537S mutant and can tell the difference between L536S and D538G mutants. The vast majority of Affimer-ERαY537S is in the nucleus and is capable of an efficient, unrestricted navigation to its target DNA sequence, as visualized by single-molecule fluorescence. The Affimer can also differentiate the effect of selective estrogen receptor modulators. More generally, this is an example of a small binding reagent-an Affimer protein-that can be inserted into living cells with minimal perturbation and high efficiency, to image an endogenous protein.

Selective pressure of endocrine therapy activates the integrated stress response through NFκB signaling in a subpopulation of ER positive breast cancer cells.

BACKGROUND: While estrogen receptor (ER) positive breast tumors generally respond well to endocrine therapy (ET), up to 40% of patients will experience relapse, either while on endocrine therapy or after ET is completed. We previously demonstrated that the selective pressure of tamoxifen activates the NFκB pathway in ER + patient tumors, breast cancer cell lines, and breast cancer xenograft tumors, and that this activation allows for survival of a subpopulation of NFκB + cells that contribute to cell regrowth and tumor relapse after ET withdrawal. However, the mechanisms contributing to the expansion of an NFκB + cell population on ET are unknown. METHODS: Here, we utilized single-cell RNA sequencing and bioinformatics approaches to characterize the NFκB + cell population and its clinical relevance. Follow-up studies were conducted to validate our findings and assess the function of the integrated stress response pathway in breast cancer cell lines and patient-derived models. RESULTS: We found that the NFκB + population that arises in response to ET is a preexisting population is enriched under the selective pressure of ET. Based on the preexisting NFκB + cell population, we developed a gene signature and found that it is predictive of tumor relapse when expressed in primary ER + tumors and is retained in metastatic cell populations. Moreover, we identified that the integrated stress response (ISR), as indicated by increased phosphorylation of eIF2α, occurs in response to ET and contributes to clonogenic growth under the selective pressure of ET. CONCLUSIONS: Taken together, our findings suggest that a cell population with active NFκB and ISR signaling can survive and expand under the selective pressure of ET and that targeting this population may be a viable therapeutic strategy to improve patient outcome by eliminating cells that survive ET. Understanding the mechanisms by which breast cancer cells survive the selective pressure of ET may improve relapse rates and overall outcome for patients with ER + breast tumors.

Lasofoxifene as a potential treatment for therapy-resistant ER-positive metastatic breast cancer.

BACKGROUND: Endocrine therapy remains the mainstay of treatment for estrogen receptor-positive (ER+) breast cancer. Constitutively active mutations in the ligand binding domain of ERα render tumors resistant to endocrine agents. Breast cancers with the two most common ERα mutations, Y537S and D538G, have low sensitivity to fulvestrant inhibition, a typical second-line endocrine therapy. Lasofoxifene is a selective estrogen receptor modulator with benefits on bone health and breast cancer prevention potential. This study investigated the anti-tumor activity of lasofoxifene in breast cancer xenografts expressing Y537S and D538G ERα mutants. The combination of lasofoxifene with palbociclib, a CDK4/6 inhibitor, was also evaluated. METHODS: Luciferase-GFP tagged MCF7 cells bearing wild-type, Y537S, or D538G ERα were injected into the mammary ducts of NSG mice (MIND model), which were subsequently treated with lasofoxifene or fulvestrant as single agents or in combination with palbociclib. Tumor growth and metastasis were monitored with in vivo and ex vivo luminescence imaging, terminal tumor weight measurements, and histological analysis. RESULTS: As a monotherapy, lasofoxifene was more effective than fulvestrant at inhibiting primary tumor growth and reducing metastases. Adding palbociclib improved the effectiveness of both lasofoxifene and fulvestrant for tumor suppression and metastasis prevention at four distal sites (lung, liver, bone, and brain), with the combination of lasofoxifene/palbociclib being generally more potent than that of fulvestrant/palbociclib. X-ray crystallography of the ERα ligand binding domain (LBD) shows that lasofoxifene stabilizes an antagonist conformation of both wild-type and Y537S LBD. The ability of lasofoxifene to promote an antagonist conformation of Y537S, combined with its long half-life and bioavailability, likely contributes to the observed potent inhibition of primary tumor growth and metastasis of MCF7 Y537S cells. CONCLUSIONS: We report for the first time the anti-tumor activity of lasofoxifene in mouse models of endocrine therapy-resistant breast cancer. The results demonstrate the potential of using lasofoxifene as an effective therapy for women with advanced or metastatic ER+ breast cancers expressing the most common constitutively active ERα mutations.

The Structure-Function Relationship of Angular Estrogens and Estrogen Receptor Alpha to Initiate Estrogen-Induced Apoptosis in Breast Cancer Cells.

High-dose synthetic estrogen therapy was the standard treatment of advanced breast cancer for three decades until the discovery of tamoxifen. A range of substituted triphenylethylene synthetic estrogens and diethylstilbestrol were used. It is now known that low doses of estrogens can cause apoptosis in long-term estrogen deprived (LTED) breast cancer cells resistant to antiestrogens. This action of estrogen can explain the reduced breast cancer incidence in postmenopausal women over 60 who are taking conjugated equine estrogens and the beneficial effect of low-dose estrogen treatment of patients with acquired aromatase inhibitor resistance in clinical trials. To decipher the molecular mechanism of estrogens at the estrogen receptor (ER) complex by different types of estrogens-planar [17ß-estradiol (E2)] and angular triphenylethylene (TPE) derivatives-we have synthesized a small series of compounds with either no substitutions on the TPE phenyl ring containing the antiestrogenic side chain of endoxifen or a free hydroxyl. In the first week of treatment with E2 the LTED cells undergo apoptosis completely. By contrast, the test TPE derivatives act as antiestrogens with a free para-hydroxyl on the phenyl ring that contains an antiestrogenic side chain in endoxifen. This inhibits early E2-induced apoptosis if a free hydroxyl is present. No substitution at the site occupied by the antiestrogenic side chain of endoxifen results in early apoptosis similar to planar E2 The TPE compounds recruit coregulators to the ER differentially and predictably, leading to delayed apoptosis in these cells. SIGNIFICANCE STATEMENT: In this paper we investigate the role of the structure-function relationship of a panel of synthetic triphenylethylene (TPE) derivatives and a novel mechanism of estrogen-induced cell death in breast cancer, which is now clinically relevant. Our study indicates that these TPE derivatives, depending on the positioning of the hydroxyl groups, induce various conformations of the estrogen receptor's ligand-binding domain, which in turn produces differential recruitment of coregulators and subsequently different apoptotic effects on the antiestrogen-resistant breast cancer cells.

Versatile Peptide Macrocyclization with Diels-Alder Cycloadditions.

Macrocyclization can improve bioactive peptide ligands through preorganization of molecular topology, leading to improvement of pharmacologic properties like binding affinity, cell permeability, and metabolic stability. Here we demonstrate that Diels-Alder [4 + 2] cycloadditions can be harnessed for peptide macrocyclization and stabilization within a range of peptide scaffolds and chemical environments. Diels-Alder cyclization of diverse diene-dienophile reactive pairs proceeds rapidly, in high yield and with tunable stereochemical preferences on solid-phase or in aqueous solution. This reaction can be applied alone or in concert with other stabilization chemistries, such as ring-closing olefin metathesis, to stabilize loop, turn, and α-helical secondary structural motifs. NMR and molecular dynamics studies of model loop peptides confirmed preferential formation of endo cycloadduct stereochemistry, imparting significant structural rigidity to the peptide backbone that resulted in augmented protease resistance and increased biological activity of a Diels-Alder cyclized (DAC) RGD peptide. Separately, we demonstrated the stabilization of DAC α-helical peptides derived from the ERα-binding protein SRC2. We solved a 2.25 Å cocrystal structure of one DAC helical peptide bound to ERα, which unequivocally corroborated endo stereochemistry of the resulting Diels-Alder adduct, and confirmed that the unique architecture of stabilizing motifs formed with this chemistry can directly contribute to target binding. These data establish Diels-Alder cyclization as a versatile approach to stabilize diverse protein structural motifs under a range of chemical environments.

Prevalence and correlates of food insecurity among U.S. college students: a multi-institutional study.

BACKGROUND: College students may be vulnerable to food insecurity due to limited financial resources, decreased buying power of federal aid, and rising costs of tuition, housing, and food. This study assessed the prevalence of food insecurity and its sociodemographic, health, academic, and food pantry correlates among first-year college students in the United States. METHODS: A cross-sectional study was conducted among first-year students (n = 855) across eight U.S. universities. Food security status was assessed using the U.S. Department of Agriculture Adult Food Security Survey Module. Cohen's Perceived Stress Scale, Pittsburgh Sleep Quality Index, and Eating Attitudes Test-26 were used to assess perceived stress, sleep quality, and disordered eating behaviors, respectively. Participants self-reported their grade point average (GPA) and completed questions related to meal plan enrollment and utilization of on-campus food pantries. RESULTS: Of participating students, 19% were food-insecure, and an additional 25.3% were at risk of food insecurity. Students who identified as a racial minority, lived off-campus, received a Pell grant, reported a parental education of high school or less, and did not participate in a meal plan were more likely to be food-insecure. Multivariate logistic regression models adjusted for sociodemographic characteristics and meal plan enrollment indicated that food-insecure students had significantly higher odds of poor sleep quality (OR = 2.32, 95% CI: 1.43-3.76), high stress (OR = 4.65, 95% CI: 2.66-8.11), disordered eating behaviors (OR = 2.49, 95% CI: 1.20-4.90), and a GPA < 3.0 (OR = 1.91, 95% CI: 1.19-3.07) compared to food-secure students. Finally, while half of the students (56.4%) with an on-campus pantry were aware of its existence, only 22.2% of food-insecure students endorsed utilizing the pantry for food acquisition. CONCLUSIONS: Food insecurity among first-year college students is highly prevalent and has implications for academic performance and health outcomes. Higher education institutions should screen for food insecurity and implement policy and programmatic initiatives to promote a healthier college experience. Campus food pantries may be useful as short-term relief; however, its limited use by students suggest the need for additional solutions with a rights-based approach to food insecurity. TRIAL REGISTRATION: Retrospectively registered on ClinicalTrials.gov , NCT02941497.

Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer.

Estrogen therapy was used to treat advanced breast cancer in postmenopausal women for decades until the introduction of tamoxifen. Resistance to long-term estrogen deprivation (LTED) with tamoxifen and aromatase inhibitors used as a treatment of breast cancer inevitably occurs, but unexpectedly low-dose estrogen can cause regression of breast cancer and increase disease-free survival in some patients. This therapeutic effect is attributed to estrogen-induced apoptosis in LTED breast cancer. Here, we describe modulation of the estrogen receptor (ER) liganded with antiestrogens (endoxifen and 4-hydroxytamoxifen) and an estrogenic triphenylethylene (TPE), ethoxytriphenylethylene (EtOXTPE), on estrogen-induced apoptosis in LTED breast cancer cells. Our results show that the angular TPE estrogen (EtOXTPE) is able to induce the ER-mediated apoptosis only at a later time compared with planar estradiol in these cells. Using real-time polymerase chain reaction, chromatin immunoprecipitation, western blotting, molecular modeling, and X-ray crystallography techniques, we report novel conformations of the ER complex with an angular estrogen EtOXTPE and endoxifen. We propose that alteration of the conformation of the ER complexes, with changes in coactivator binding, governs estrogen-induced apoptosis through the protein kinase regulated by RNA-like endoplasmic reticulum kinase sensor system to trigger an unfolded protein response.

A "cross-stitched" peptide with improved helicity and proteolytic stability.

A new computational approach to obtain quantitative energy profiles for helix folding was used in the design of orthogonal hydrocarbon and lactam bicyclic peptides. The proteolytically stable, "cross-stitched" peptide SRC2-BCP1 shows nanomolar affinity for estrogen receptor α and X-ray crystallography confirms a helical binding pose.

Metabolism of megestrol acetate in vitro and the role of oxidative metabolites.

1. There is limited knowledge regarding the metabolism of megestrol acetate (MA), as it was approved by FDA in 1971, prior to the availability of modern tools for identifying specific drug-metabolizing enzymes. We determined the cytochrome P450s (P450s) and UDP-glucuronosyltransferases (UGTs) that metabolize MA, identified oxidative metabolites and determined pharmacologic activity at the progesterone, androgen and glucocorticoid receptors (PR, AR and GR, respectively). 2. Oxidative metabolites were produced using human liver microsomes (HLMs), and isolated for mass spectral (MS) and nuclear magnetic resonance (NMR) analyses. We screened recombinant P450s using MA at 62 µM (HLM Km for metabolite 1; M1) and 28 µM (HLM Km for metabolite 2; M2). UGT isoforms were simultaneously incubated with UDPGA, nicotinamide adenine dinucleotide phosphate (NADPH), CYP3A4 and MA. Metabolites were evaluated for pharmacologic activity on the PR, AR and GR. CYP3A4 and CYP3A5 are responsible for oxidative metabolism of 62 µM MA. 3. At 28 µM substrate concentration, CYP3A4 was the only contributing enzyme. Mass spectral and NMR data suggest metabolism of MA to two alcohols. After oxidation, MA is converted into two secondary glucuronides by UGT2B17 among other UGTs. MA, M1 and M2 had significant pharmacologic activity on the PR while only MA showed activity on the AR and GR.

Self-reported and observed feeding practices of Rhode Island Head Start teachers: Knowing what not to do.

PURPOSE: Through their feeding practices, adult caregivers play an important role in shaping children's eating behaviors. However, the feeding practices of child care teachers have received little attention. The purpose of this study was to compare child care teachers' self-reported feeding practices and observed feeding practices during a preschool meal. METHODS: Rhode Island Head Start teachers (n = 85) were observed during breakfast and lunch where feeding practices were coded using a tool adapted from the Environmental Policy Assessment and Observation (EPAO) tool. Teachers completed a questionnaire adapted from the EPAO Self-Report to capture self-reported feeding practices. Agreement between reported and observed was compared by percent agreement. RESULTS: Teachers were predominantly White (89%) and female (98%). There was a higher level of agreement among self-reported and observed controlling feeding practices (78.8-97.6% agreement) compared to healthful feeding practices (11.8-20.0% agreement). CONCLUSIONS: Although self-report measures are typically used to capture feeding practices, there are inconsistencies between self-report and observation measures. The inconsistencies found among healthful self-reported and observed feeding practices have implications for future research protocols, measurement refinement, and training of child care teachers.

Relationships of Sleep Duration With Weight-Related Behaviors of U.S. College Students.

This study describes sleep behaviors of U.S. college students (N = 1,252; 18-24 years old; 59% female) and examines associations of sleep duration with weight-related behaviors. More than one quarter of participants slept < 7 hr/night and had mean Pittsburgh Sleep Quality Index (PSQI) scores indicating poor sleep quality. There were significant differences for all PSQI scales among sleep duration categories, < 7 hr (n = 344), 7-8 hr (n = 449), ≥ 8 hr (n = 459) sleep/night. Compared to those who slept ≥ 8 hr, those who slept < 8 hr had significantly more negative eating attitudes (2% higher), poorer internal regulation of food (4% lower), and greater binge eating (4% higher) scores. Findings advocate for health care professionals to evaluate sleep behaviors of college students during office visits and promote good sleep behaviors.

Transtheoretical Model Constructs' Longitudinal Prediction of Sun Protection Over 24 Months.

PURPOSE: This research examined dynamic transtheoretical model (TTM) constructs for adopting sun protection practices. This secondary data analysis pooled four large population-based TTM-tailored intervention studies and examined use of constructs across three groups, organized by longitudinal progress: maintainers, relapsers, and stable non-changers. METHODS: A total of 3463 adults, in the USA, who met criteria for unsafe sun exposure at baseline received a TTM-tailored computerized intervention at baseline, 6 months, and 12 months. The final analytic sample consisted of 1894 participants; the majority were female, White, married, and middle-aged. The three groups were assessed with reliable and valid scales assessing use of TTM constructs at baseline, 6 months, 12 months, and 24 months. Analyses included a MANOVA followed by a series of ANOVAs, with Tukey follow-up tests assessing differences in use of TTM constructs across the three groups at each timepoint. RESULTS: Findings demonstrated that relapsers and maintainers were similar in their use of most TTM processes of change at baseline, with the exception of Consciousness Raising, Stimulus Control, Reinforcement Management, and Self-Liberation. CONCLUSIONS: These findings suggest that although relapsers reverted to unsafe sun practices, their overall greater use of processes of change indicates that their change efforts remain better than that of stable non-changers.

Fat Reduction Efforts: A 24-Month Longitudinal Comparison of a Large Sample of Maintainers, Relapsers, and Non-Changers.

This research examined dynamic transtheoretical model (TTM) constructs for dietary fat reduction. This secondary data analysis pooled three large population-based TTM-tailored school, worksite, medical, and home-based intervention studies and examined use of constructs across three groups organized by longitudinal progress (dynatypes): Maintainers, Relapsers, and Stable Non-Changers. The criteria for successful change, at the time, were that less than 30% of calories came from fat. A total of 2,718 adults met criteria for an unhealthy diet at baseline. The majority of participants were female, White, married, and middle-aged. Demographics, Stage of Change, Processes of Change, Decisional Balance, and Temptations were measured. Dynatype groups were assessed with reliable and valid scales assessing constructs at baseline and 6, 12, and 24 months. Analyses included a multivariate analysis of variance followed by a series of analyses of variance, with Tukey follow-up tests assessing differences in use of TTM constructs across the three groups at each time point. Relapsers and Maintainers were similar in their use of all TTM Processes of Change at baseline, with the exception of Self-Liberation (η(2) = 0.15, p < .001) and Reinforcement Management (η(2) = 0.01, p < .001). Although Relapsers reverted to an unhealthy diet, their overall greater use of Processes of Change suggests that their behaviors and strategy use remain better than that of the Stable Non-Changer group. Results suggest that specific cognitive and behavioral constructs may contribute differentially to intervention outcomes.

Stapled Peptides with γ-Methylated Hydrocarbon Chains for the Estrogen Receptor/Coactivator Interaction.

"Stapled" peptides are typically designed to replace two non-interacting residues with a constraining, olefinic staple. To mimic interacting leucine and isoleucine residues, we have created new amino acids that incorporate a methyl group in the γ-position of the stapling amino acid S5. We have incorporated them into a sequence derived from steroid receptor coactivator 2, which interacts with estrogen receptor α. The best peptide (IC50 =89 nm) replaces isoleucine 689 with an S-γ-methyl stapled amino acid, and has significantly higher affinity than unsubstituted peptides (390 and 760 nm). Through X-ray crystallography and molecular dynamics studies, we show that the conformation taken up by the S-γ-methyl peptide minimizes the syn-pentane interactions between the α- and γ-methyl groups.

The Green Eating Project: web-based intervention to promote environmentally conscious eating behaviours in US university students.

OBJECTIVE: To investigate the effectiveness of an online, interactive intervention, referred to as the Green Eating (GE) Project, to motivate university students to adopt GE behaviours. DESIGN: The study was quasi-experimental and integrated into courses for credit/extra credit. Courses were randomly stratified into experimental or non-treatment control. The 5-week intervention consisted of four modules based on different GE topics. Participants completed the GE survey at baseline (experimental, n 241; control, n 367) and post (experimental, n 187; control, n 304). The GE survey has been previously validated and consists of Transtheoretical Model constructs including stage of change (SOC), decisional balance (DB: Pros and Cons) and self-efficacy (SE: School and Home) as well as behaviours for GE. Modules contained basic information regarding each topic and knowledge items to assess content learning. SETTING: The GE Project took place at a public university in the north-eastern USA. SUBJECTS: Participants were full-time students between the ages of 18 and 24 years. RESULTS: The GE Project was effective in significantly increasing GE behaviours, DB Pros, SE School and knowledge in experimental compared with control, but did not reduce DB Cons or increase SE Home. Experimental participants were also more likely to be in later SOC for GE at post testing. CONCLUSIONS: The GE Project was effective in increasing GE behaviours in university students. Motivating consumers towards adopting GE could assist in potentially mitigating negative consequences of the food system on the environment. Future research could tailor the intervention to participant SOC to further increase the effects or design the modules for other participants.

Effect of a Technology-Integrated Curriculum on Sugary Drink and Snack Intake of Elementary-Aged Youth Experiencing Low Income.

OBJECTIVE: To describe the results of a technology-integrated intervention on sugar-sweetened beverage (SSB) and energy-dense snack intake with third graders experiencing low income. DESIGN: A 2 × 2 quasi-randomized cluster-block, parallel-group experimental research design. SETTING: Low-income schools in Rhode Island. PARTICIPANTS: Two-hundred seventeen intervention and 242 control third-grade students in low-income (89.6% and 88.2% free/reduced meals, respectively), ethnically and racially diverse (63% Hispanic/20% Black and 62% Hispanic/18% Black, respectively) schools. INTERVENTION(S): A 13-week in-school program held once per week for 1 hour. The hands-on, technology-integrated program used a modified version of the Body Quest: Food of the Warrior curriculum. MAIN OUTCOME MEASURE(S): Intake of SSB and energy-dense snacks, both salty and sweet snacks, using baseline (week 1) and postassessment (week 13) previous day self-recall. ANALYSIS: Generalized mixed modeling with nesting. RESULTS: Intervention students significantly reduced their SSB intake by 38% (0.5 times/d; F[1, 540] = 4.26; P = 0.04) and salty snack intake by 58% (0.8 times/d; F[1, 534] = 6.58, P < 0.01) from baseline to postassessment as compared with the control students. CONCLUSIONS AND IMPLICATIONS: Findings suggest a technology-integrated curriculum is effective in decreasing SSB and salty snacks in elementary-aged students of low-income, minoritized populations. Improved dietary habits can potentially influence other facets of students' lives.

The relationship between fat distribution and diabetes in US adults by race/ethnicity.

Introduction: This study examined the relationship between fat distribution and diabetes by sex-specific racial/ethnic groups. Methods: A secondary data analysis of National Health and Nutrition Examination Survey 2011-2018 data (n = 11,972) was completed. Key variables examined were visceral adipose tissue area (VATA), subcutaneous fat area (SFA), diabetes prevalence, and race/ethnicity. The association of VATA and SFA and diabetes prevalence was examined separately and simultaneously using multiple logistic regression. Bonferroni corrections were applied to all multiple comparisons between racial/ethnic groups. All analyses were adjusted for demographics and muscle mass. Results: VATA was positively associated with diabetes in both sexes (p < 0.001) and across all racial/ethnic groups (p < 0.05) except Black females. No statistically significant relationships were observed between SFA and diabetes while accounting for VATA with the exception of White females (p = 0.032). When comparing racial/ethnic groups, the relationship between VATA and diabetes was stronger in White and Hispanic females than in Black females (p < 0.005) while the relationship between SFA and diabetes did not differ between any racial/ethnic groups. Conclusion: This study found that VATA is associated with diabetes for both sexes across almost all racial/ethnic groups independent of SFA whereas the only significant relationship between SFA and diabetes, independent of VATA, was observed in White females. The findings indicated that visceral fat was more strongly associated with diabetes than subcutaneous. Additionally, there are health disparities in sex-specific racial/ethnic groups thus further study is warranted.