A low-glucose eating pattern is associated with improvements in glycemic variability among women at risk for postmenopausal breast cancer: an exploratory analysis.

Background: High glycemic variability (GV) is a biomarker of cancer risk, even in the absence of diabetes. The emerging concept of chrononutrition suggests that modifying meal timing can favorably impact metabolic risk factors linked to diet-related chronic disease, including breast cancer. Here, we examined the potential of eating when glucose levels are near personalized fasting thresholds (low-glucose eating, LGE), a novel form of timed-eating, to reduce GV in women without diabetes, who are at risk for postmenopausal breast cancer. Methods: In this exploratory analysis of our 16-week weight loss randomized controlled trial, we included 17 non-Hispanic, white, postmenopausal women (average age = 60.7 ± 5.8 years, BMI = 34.5 ± 6.1 kg/m2, HbA1c = 5.7 ± 0.3%). Participants were those who, as part of the parent study, provided 3-7 days of blinded, continuous glucose monitoring data and image-assisted, timestamped food records at weeks 0 and 16. Pearson's correlation and multivariate regression were used to assess associations between LGE and GV, controlling for concurrent weight changes. Results: Increases in LGE were associated with multiple unfavorable measures of GV including reductions in CGM glucose mean, CONGA, LI, J-Index, HBGI, ADDR, and time spent in a severe GV pattern (r = -0.81 to -0.49; ps < 0.044) and with increases in favorable measures of GV including M-value and LBGI (r = 0.59, 0.62; ps < 0.013). These associations remained significant after adjusting for weight changes. Conclusion: Low-glucose eating is associated with improvements in glycemic variability, independent of concurrent weight reductions, suggesting it may be beneficial for GV-related disease prevention. Further research in a larger, more diverse sample with poor metabolic health is warranted.Clinical trial registration: ClinicalTrials.gov, NCT03546972.

Dental caries and school readiness in 5-year-olds: A birth cohort data linkage study.

OBJECTIVE: To describe the association between dental caries and school readiness in 5-year-old children taking part in the Born in Bradford (BiB) birth cohort, UK. METHODS: The Early Years Foundation Stage Profile (EYFSP) assesses the school readiness of young children and is strongly predictive of future academic attainment. Children are recorded as 'emerging' (below expected), 'expected', or 'exceeding' in five key learning areas. The Oral Health Survey of 5-year-olds (OHS5) is undertaken biennially in England, assessing caries experience at a dentine threshold (d3mft). EYFSP and OHS5 were available for a proportion of children participating in BiB. Odds ratios and confidence intervals for caries experience were established, and odds ratios adjusted for significant sociodemographic variables. RESULTS: EYFSP and OHS5 data were available for 2.5% (n = 346) BiB participants. Nearly half (45.2%) had caries. A measure of socio-economic status, receiving free school meals, was the only demographic variable strongly related to caries experience (OR: 2.8, 95% CI: 1.6-4.9). After adjustment, children 'emerging' in EYFSP learning areas had 1.6- to 2.2-fold (95% CI: 1.0-3.8) higher odds of experiencing caries. Children 'exceeding' EYFSP learning areas had 2.3- to 4-fold (95% CI: 0.1-0.9) lower odds of caries experience. CONCLUSION: This is the first study to explore the association between caries experience and school readiness using a holistic assessment tool. The association was found across different learning areas and was comparable to and independent of socio-economic status. The findings indicate oral health-related absenteeism is not a causative factor. EYFSP shows potential to enhance the targeting of preventive interventions at a child, class or school level.

Metformin and Breast Cancer: Current Findings and Future Perspectives from Preclinical and Clinical Studies.

Over the last several decades, a growing body of research has investigated the potential to repurpose the anti-diabetic drug metformin for breast cancer prevention and/or treatment. Observational studies in the early 2000s demonstrated that patients with diabetes taking metformin had decreased cancer risk, providing the first evidence supporting the potential role of metformin as an anti-cancer agent. Despite substantial efforts, two decades later, the exact mechanisms and clinical efficacy of metformin for breast cancer remain ambiguous. Here, we have summarized key findings from studies examining the effect of metformin on breast cancer across the translational spectrum including in vitro, in vivo, and human studies. Importantly, we discuss critical factors that may help explain the significant heterogeneity in study outcomes, highlighting how metformin dose, underlying metabolic health, menopausal status, tumor subtype, membrane transporter expression, diet, and other factors may play a role in modulating metformin's anti-cancer effects. We hope that these insights will help with interpreting data from completed studies, improve the design of future studies, and aid in the identification of patient subsets with breast cancer or at high risk for the disease who are most likely to benefit from metformin treatment.

Trends in Diet and Cancer Research: A Bibliometric and Visualization Analysis.

Diet plays a critical role for patients across the cancer continuum. The World Cancer Research Fund International and the American Cancer Society have published evidence supporting the role of nutrition in cancer prevention. We conducted an analysis of the literature on dietary nutrients and cancer to uncover opportunities for future research. The objective of the bibliometric analysis was to describe trends in peer-reviewed publications on dietary components and cancer and to highlight research gaps. PubMed was queried for manuscripts with diet- and cancer-related keywords and Medical Subject Headings (MeSH) terms. Metadata covering 99,784 publications from 6469 journals were analyzed to identify trends since 1970 on diet topics across 19 tumor types. Publications focused largely on breast, colorectal, and liver cancer, with fewer papers linking diet with other cancers such as brain, gallbladder, or ovarian. With respect to "unhealthy" diets, many publications focused on high-fat diets and alcohol consumption. The largest numbers of publications related to "healthy" diets examined the Mediterranean diet and the consumption of fruits and vegetables. These findings highlight the need for additional research focused on under-investigated cancers and dietary components, as well as dietary studies during cancer therapy and post-therapy, which may help to prolong survivorship.

SIM2s directed Parkin-mediated mitophagy promotes mammary epithelial cell differentiation.

The functionally differentiated mammary gland adapts to extreme levels of stress from increased demand for energy by activating specific protective mechanisms to support neonatal health. Here, we identify the breast tumor suppressor gene, single-minded 2 s (SIM2s) as a novel regulator of mitophagy, a key component of this stress response. Using tissue-specific mouse models, we found that loss of Sim2 reduced lactation performance, whereas gain (overexpression) of Sim2s enhanced and extended lactation performance and survival of mammary epithelial cells (MECs). Using an in vitro model of MEC differentiation, we observed SIM2s is required for Parkin-mediated mitophagy, which we have previously shown as necessary for functional differentiation. Mechanistically, SIM2s localizes to mitochondria to directly mediate Parkin mitochondrial loading. Together, our data suggest that SIM2s regulates the rapid recycling of mitochondria via mitophagy, enhancing the function and survival of differentiated MECs.

HABIT: Health visitors delivering Advice in Britain on Infant Toothbrushing - an early-phase feasibility study of a complex oral health intervention.

OBJECTIVES: To conduct an early-phase feasibility study of an oral health intervention, Health visitors delivering Advice on Britain on Infant Toothbrushing (HABIT), delivered by Health Visitors to parents of children aged 9-12 months old. DESIGN: A mixed-methods, early-phase, non-controlled, feasibility study. PARTICIPANTS: Recruitment consisted of Group A-HABIT-trained Health Visitors (n=11) and Group B-parents of children aged 9-12 months old about to receive their universal health check (n=35). SETTING: Bradford, West Yorkshire, UK. INTERVENTION: A multidisciplinary team co-developed digital and paper-based training resources with health visitors and parents of young children. The intervention comprised of two components: (A) training for health visitors to deliver the HABIT intervention and (B) HABIT resources for parents, including a website, videos, toothbrushing demonstration and a paper-based leaflet with an oral health action plan. PRIMARY AND SECONDARY OUTCOME MEASURES: Recruitment, retention and intervention delivery were analysed as key process outcomes for Groups A and B. Group B demographics, self-reported toothbrushing behaviours, dietary habits and three objective measures of toothbrushing including plaque scores were collected at baseline, 2 weeks and 3 months post intervention. RESULTS: HABIT intervention delivery was feasible. Although the intended sample size was recruited (Group A=11 and Group B=35) it was more challenging than anticipated. Retention of Group B participants to final data collection was satisfactory (n=26). Total compliance with toothbrushing guidelines at baseline was low (30%), but significantly improved and was maintained 3 months after the intervention (68%). Plaque scores improved post intervention and participants found video recording of toothbrushing acceptable. Dietary habits remained largely unchanged. CONCLUSION: This feasibility study has demonstrated that HABIT is an appropriate oral health intervention. Adaptions to the study design are recommended to maximise recruitment and data collection in a definitive study. These quantitative findings have demonstrated an early signal of impact for improved oral health behaviours for young children at high risk of decay. TRIAL REGISTRATION NUMBER: ISRCTN55332414.

Co-design of an oral health intervention (HABIT) delivered by health visitors for parents of children aged 9-12 months.

BACKGROUND: Dental caries (tooth decay) in children is a national public health problem with impacts on the child, their family and wider society. Toothbrushing should commence from the eruption of the first primary tooth. Health visitors are a key provider of advice for parents in infancy and are ideally placed to support families to adopt optimal oral health habits. HABIT is a co-designed complex behaviour change intervention to support health visitors' oral health conversations with parents during the 9-12-month universal developmental home visit. METHODS: A seven stage co-design process was undertaken: (1) Preparatory meetings with healthcare professionals and collation of examples of good practice, (2) Co-design workshops with parents and health visitors, (3) Resource development and expert/peer review, (4) Development of an intervention protocol for health visitors, (5) Early-phase testing of the resources to explore acceptability, feasibility, impact and mechanism of action, (6) Engagement with wider stakeholders and refinement of the HABIT intervention for wider use, (7) Verification, Review and Reflection of Resources. RESULTS: Following preparatory meetings with stakeholders, interviews and co-design workshops with parents and health visitors, topic areas and messages were developed covering six key themes. The topic areas provided a structure for the oral health conversation and supportive resources in paper-based and digital formats. A five-step protocol was developed with health visitors to guide the oral health conversation during the 9-12 month visit. Following training of health visitors, an early-phase feasibility study was undertaken with preliminary results presented at a dissemination event where feedback for further refinement of the resources and training was gathered. The findings, feedback and verification have led to further refinements to optimise quality, accessibility, fidelity and behaviour change theory. CONCLUSION: The co-design methods ensured the oral health conversation and supporting resources used during the 9-12 month visit incorporated the opinions of families and Health Visitors as well as other key stakeholders throughout the development process. This paper provides key learning and a framework that can be applied to other healthcare settings. The structured pragmatic approach ensured that the intervention was evidence-based, acceptable and feasible for the required context. TRIAL REGISTRATION: ISRCTN55332414, Registration Date 11/11/2021.

Preventing ovariectomy-induced weight gain decreases tumor burden in rodent models of obesity and postmenopausal breast cancer.

BACKGROUND: Obesity and adult weight gain are linked to increased breast cancer risk and poorer clinical outcomes in postmenopausal women, particularly for hormone-dependent tumors. Menopause is a time when significant weight gain occurs in many women, and clinical and preclinical studies have identified menopause (or ovariectomy) as a period of vulnerability for breast cancer development and promotion. METHODS: We hypothesized that preventing weight gain after ovariectomy (OVX) may be sufficient to prevent the formation of new tumors and decrease growth of existing mammary tumors. We tested this hypothesis in a rat model of obesity and carcinogen-induced postmenopausal mammary cancer and validated our findings in a murine xenograft model with implanted human tumors. RESULTS: In both models, preventing weight gain after OVX significantly decreased obesity-associated tumor development and growth. Importantly, we did not induce weight loss in these animals, but simply prevented weight gain. In both lean and obese rats, preventing weight gain reduced visceral fat accumulation and associated insulin resistance. Similarly, the intervention decreased circulating tumor-promoting growth factors and inflammatory cytokines (i.e., BDNF, TNFα, FGF-2), with greater effects in obese compared to lean rats. In obese rats, preventing weight gain decreased adipocyte size, adipose tissue macrophage infiltration, reduced expression of the tumor-promoting growth factor FGF-1 in mammary adipose, and reduced phosphorylated FGFR indicating reduced FGF signaling in tumors. CONCLUSIONS: Together, these findings suggest that the underlying mechanisms associated with the anti-tumor effects of weight maintenance are multi-factorial, and that weight maintenance during the peri-/postmenopausal period may be a viable strategy for reducing obesity-associated breast cancer risk and progression in women.

Ghrelin and Cancer: Examining the Roles of the Ghrelin Axis in Tumor Growth and Progression.

Ghrelin, a hormone produced and secreted from the stomach, is prim arily known as an appetite stimulant. Recently, it has emerged as a potential regulator/biomarker of cancer progression. Inconsistent results on this subject make this body of literature difficult to interpret. Here, we attempt to identify commonalities in the relationships between ghrelin and various cancers, and summarize important considerations for future research. The main players in the ghrelin family axis are unacylated ghrelin (UAG), acylated ghrelin (AG), the enzyme ghrelin O-acyltransferase (GOAT), and the growth hormone secretagogue receptor (GHSR). GOAT is responsible for the acylation of ghrelin, after which ghrelin can bind to the functional ghrelin receptor GHSR-1a to initiate the activation cascade. Splice variants of ghrelin also exist, with the most prominent being In1-ghrelin. In this review, we focus primarily on the potential of In1-ghrelin as a biomarker for cancer progression, the unique characteristics of UAG and AG, the importance of the two known receptor variants GHSR-1a and 1b, as well as the possible mechanisms through which the ghrelin axis acts. Further understanding of the role of the ghrelin axis in tumor cell proliferation could lead to the development of novel therapeutic approaches for various cancers.

HABIT (Health visitors delivering Advice in Britain on Infant Toothbrushing): a qualitative exploration of the acceptability of a complex oral health intervention.

BACKGROUND: To explore the acceptability of the oral health intervention, HABIT (Health visitors delivering Advice in Britain on Infant Toothbrushing) to parents with young children aged 9-12 months and health visitors. METHODS: Following the delivery of the universal oral health intervention called HABIT, qualitative semi-structured interviews with parents and focus groups with health visitors were undertaken. Interviews were audio-recorded and transcribed. Health visitors completed self-reported diaries after delivering the HABIT intervention with parents. The qualitative data was analysed using framework analysis (guided by a theoretical framework of acceptability). RESULTS: Seventeen parents were interviewed, and five health visitors and three nursery nurses participated in two focus groups. Parents reported health visitors to be 'trusted' and valued the reassurance provided during the HABIT visit. Health visitors found the HABIT training and resources useful and valued the consistency and increased confidence in undertaking oral health conversations. There were, however, challenges in changing behaviour where families faced competing demands on time and resources. Both health visitors and parents described the importance of the intervention's timing and suggested that multiple visits may be needed to support optimal oral health habits. CONCLUSION: The HABIT intervention was acceptable to parents and health visitors. Health visitors would welcome a further refinement to enhance intervention delivery that specifically achieves a balance between using a guided script and retaining the flexibility to adapt the conversation to suit the needs of individual families. This, in turn, will maximise impact and enable parents of young children to adopt and maintain optimal home-based oral health behaviours for their child.

Noxious Stimulation Induces Acute Hemorrhage and Impairs Long-Term Recovery after Spinal Cord Injury (SCI) in Female Rats: Evidence Estrous Cycle May Have a Modulatory Effect.

Spinal cord injuries (SCIs) are often the result of traumatic accidents, which also produce multiple other injuries (polytrauma). Nociceptive input from associated injuries has been shown to significantly impair recovery post-SCI. Historically, work in our laboratory has focused exclusively on male animals; however, increasing incidence of SCI in females requires research to determine whether pain (nociceptive) input poses the same risk to their recovery. Some animal studies have shown that females demonstrate greater tissue preservation and better locomotor recovery post-SCI. Given this, we examined the effect of sex on SCI recovery in two pain models-intermittent electrical stimulation (shock) to the tail or capsaicin injection to the hindpaw. Female rats received a lower thoracic contusion injury and were exposed to noxious stimulation the next day. The acute effect of noxious input on cardiovascular function, locomotor performance, and hemorrhage were assessed. Treatment with capsaicin or noxious electrical stimulation disrupted locomotor performance, increased blood pressure, and disrupted stepping. Additional experiments examined the long-term consequences of noxious input, demonstrating that both noxious electrical stimulation and capsaicin impair long-term recovery in female rats. Interestingly, injury had a greater effect on behavioral performance when progesterone and estrogen were low (metestrus). Conversely, nociceptive input led to a greater disruption in locomotor performance and produced a greater rise in blood pressure in animals injured during estrus.

A Low-Glucose Eating Pattern Improves Biomarkers of Postmenopausal Breast Cancer Risk: An Exploratory Secondary Analysis of a Randomized Feasibility Trial.

Postmenopausal breast cancer is the most common obesity-related cancer death among women in the U.S. Insulin resistance, which worsens in the setting of obesity, is associated with higher breast cancer incidence and mortality. Maladaptive eating patterns driving insulin resistance represent a key modifiable risk factor for breast cancer. Emerging evidence suggests that time-restricted feeding paradigms (TRF) improve cancer-related metabolic risk factors; however, more flexible approaches could be more feasible and effective. In this exploratory, secondary analysis, we identified participants following a low-glucose eating pattern (LGEP), defined as consuming energy when glucose levels are at or below average fasting levels, as an alternative to TRF. Results show that following an LGEP regimen for at least 40% of reported eating events improves insulin resistance (HOMA-IR) and other cancer-related serum biomarkers. The magnitude of serum biomarkers changes observed here has previously been shown to favorably modulate benign breast tissue in women with overweight and obesity who are at risk for postmenopausal breast cancer. By comparison, the observed effects of LGEP were similar to results from previously published TRF studies in similar populations. These preliminary findings support further testing of LGEP as an alternative to TRF and a postmenopausal breast cancer prevention strategy. However, results should be interpreted with caution, given the exploratory nature of analyses.

Rapid Escalation of High-Volume Exercise during Caloric Restriction; Change in Visceral Adipose Tissue and Adipocytokines in Obese Sedentary Breast Cancer Survivors.

Aerobic exercise reduces risk for breast cancer and recurrence and promotes visceral adipose tissue (VAT) loss in obesity. However, few breast cancer survivors achieve recommended levels of moderate to vigorous physical activity (MVPA) without supervision. In a two-cohort study, feasibility of 12 weeks of partially supervised exercise was started concomitantly with caloric restriction and effects on body composition and systemic risk biomarkers were explored. In total, 22 obese postmenopausal sedentary women (including 18 breast cancer survivors) with median age of 60 and BMI of 37 kg/m2 were enrolled. Using personal trainers twice weekly at area YMCAs, MVPA was escalated to ≥200 min/week over 9 weeks. For cohort 2, maintenance of effect was assessed when study provided trainer services were stopped but monitoring, group counseling sessions, and access to the exercise facility were continued. Median post-escalation MVPA was 219 min/week with median 12-week mass and VAT loss of 8 and 19%. MVPA was associated with VAT loss which was associated with improved adiponectin:leptin ratio. In total, 9/11 of cohort-2 women continued the behavioral intervention for another 12 weeks without trainers. High MVPA continued with median 24-week mass and VAT loss of 12 and 29%. This intervention should be further studied in obese sedentary women.

Designing Relevant Preclinical Rodent Models for Studying Links Between Nutrition, Obesity, Metabolism, and Cancer.

Diet and nutrition are intricately related to cancer prevention, growth, and treatment response. Preclinical rodent models are a cornerstone to biomedical research and remain instrumental in our understanding of the relationship between cancer and diet and in the development of effective therapeutics. However, the success rate of translating promising findings from the bench to the bedside is suboptimal. Well-designed rodent models will be crucial to improving the impact basic science has on clinical treatment options. This review discusses essential experimental factors to consider when designing a preclinical cancer model with an emphasis on incorporatingthese models into studies interrogating diet, nutrition, and metabolism. The aims of this review are to (a) provide insight into relevant considerations when designing cancer models for obesity, nutrition, and metabolism research; (b) identify common pitfalls when selecting a rodent model; and (c) discuss strengths and limitations of available preclinical models.

Change in Blood and Benign Breast Biomarkers in Women Undergoing a Weight-Loss Intervention Randomized to High-Dose ω-3 Fatty Acids versus Placebo.

The inflammation-resolving and insulin-sensitizing properties of eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acids have potential to augment effects of weight loss on breast cancer risk. In a feasibility study, 46 peri/postmenopausal women at increased risk for breast cancer with a body mass index (BMI) of 28 kg/m2 or greater were randomized to 3.25 g/day combined EPA and DHA (ω-3-FA) or placebo concomitantly with initiation of a weight-loss intervention. Forty-five women started the intervention. Study discontinuation for women randomized to ω-3-FA and initiating the weight-loss intervention was 9% at 6 months and thus satisfied our main endpoint, which was feasibility. Between baseline and 6 months significant change (P < 0.05) was observed in 12 of 25 serum metabolic markers associated with breast cancer risk for women randomized to ω-3-FA, but only four for those randomized to placebo. Weight loss (median of 10% for trial initiators and 12% for the 42 completing 6 months) had a significant impact on biomarker modulation. Median loss was similar for placebo (-11%) and ω-3-FA (-13%). No significant change between ω-3-FA and placebo was observed for individual biomarkers, likely due to sample size and effect of weight loss. Women randomized to ω-3-FA exhibiting more than 10% weight loss at 6 months showed greatest biomarker improvement including 6- and 12-month serum adiponectin, insulin, omentin, and C-reactive protein (CRP), and 12-month tissue adiponectin. Given the importance of a favorable adipokine profile in countering the prooncogenic effects of obesity, further evaluation of high-dose ω-3-FA during a weight-loss intervention in obese high-risk women should be considered. PREVENTION RELEVANCE: This study examines biomarkers of response that may be modulated by omega-3 fatty acids when combined with a weight-loss intervention. While focused on obese, postmenopausal women at high risk for development of breast cancer, the findings are applicable to other cancers studied in clinical prevention trials.

"Strong Teeth": an early-phase study to assess the feasibility of an oral health intervention delivered by dental teams to parents of young children.

BACKGROUND: Tooth decay (caries) is a significant health burden in young children. There is strong evidence for the benefits of establishing appropriate home-based oral health behaviours in early childhood. Dental teams are well placed to provide this information and there is clear advice on what oral health information should be given to parents. However, research has shown that there is limited guidance, training and resources on how dental teams should deliver this advice. "Strong Teeth" is a complex oral health intervention, using evidence-based resources and training underpinned by behaviour change psychology, to support behaviour change conversations in dental practice. This early phase evaluation aims to assess the feasibility of this intervention, prior to a full-scale trial. METHODS: The study recruited 15 parents of children aged 0-2-years-old and 21 parents of children aged 3-5 years old, from five NHS dental practices across West Yorkshire. Participant demographics, self-reported brushing behaviours, dietary habits, a dental examination and three objective measures of toothbrushing were collected in a home-setting at baseline, then at 2-weeks and 2-months post-intervention. Recruitment, retention and intervention delivery were analysed as key process outcomes. Brushing habits were compared to national toothbrushing guidelines - the Delivering Better Oral Health toolkit (Public Health England). RESULTS: Strong Teeth was feasible to deliver in a General Dental Practice setting in 94% of cases. Feasibility of recruitment (37%) exceeded progression criterion, however retention of participants (75%) was below the progression criterion for the 0-2 age group. More than half of children recruited aged 3-5-years had caries experience (52%). Total compliance to toothbrushing guidance at baseline was low (28%) and increased after the intervention (52%), an improvement that was statistically significant. Dietary habits remained largely unchanged. Plaque scores significantly decreased in the 3-5-year-olds and toothbrushing duration increased in all age groups. CONCLUSION: "Strong Teeth" intervention delivery and data collection in the home setting was feasible. There was a positive indication of impact on reported toothbrushing behaviours. Some amendments to study design, particularly relating to the inclusion of the 0-2-year-old group, should be considered before progression to a full trial. Trial registration ISRCTN Register: ISRCTN10709150. Registered retrospectively 24/7/2019.

"Strong Teeth": the acceptability of an early-phase feasibility trial of an oral health intervention delivered by dental teams to parents of young children.

BACKGROUND: Dental caries (tooth decay) in children is a worldwide public health problem. The leading cause of caries is poor oral hygiene behaviours and the frequent consumption of sugary foods and drinks. Changing oral health habits requires effective behaviour change conversations. The dental practice provides an opportunity for dental teams to explore with parents the oral health behaviours they undertake for their young children (0-5 years old). However, evidence suggests that dental teams need further support, training and resources. Therefore, "Strong Teeth" (an oral health intervention) was co-developed to help dental teams undertake these behaviour change conversations. The current paper will explore the acceptability of the "Strong Teeth" intervention with dental teams and parents of children aged 0-5 years old using multiple datasets (interviews, focus groups and dental team member diaries) METHODS: Following the delivery of the "Strong Teeth" intervention, qualitative interviews with parents and focus groups with dental team members were undertaken. Interviews were audio-recorded, transcribed and analysed using a theoretical framework of acceptability. The self-reported dental team diaries supplemented the interviews and focus groups and were analysed using framework analysis. RESULTS: Four themes were developed: (1) integration within the dental practice; (2) incorporating the Oral-B electric toothbrush; (3) facilitating discussions and demonstrations; and (4) the practicality of the Disney Magic Timer app. Overall, the "Strong Teeth" intervention was acceptable to parents and dental teams. Parents felt the Oral-B electric toothbrush was a good motivator; however, the Disney Magic Timer app received mixed feedback on how well it could be used effectively in the home setting. Findings suggest that the intervention was more acceptable as a "whole team approach" when all members of the dental practice willingly participated. CONCLUSIONS: There are limited studies that use a robust process evaluation to measure the acceptability of an intervention. The use of the theoretical framework of acceptability helped identify aspects of the intervention that were positive and helped identify the interventions areas for enhancement moving forwards. Future modifications include enhanced whole team approach training to optimise acceptability to all those involved. TRIAL REGISTRATION: ISRCTN Register, (ISRCTN10709150).

Preclinical Models to Study Obesity and Breast Cancer in Females: Considerations, Caveats, and Tools.

Obesity increases the risk for breast cancer and is associated with poor outcomes for cancer patients. A variety of rodent models have been used to investigate these relationships; however, key differences in experimental approaches, as well as unique aspects of rodent physiology lead to variability in how these valuable models are implemented. We combine expertise in the development and implementation of preclinical models of obesity and breast cancer to disseminate effective practices for studies that integrate these fields. In this review, we share, based on our experience, key considerations for model selection, highlighting important technical nuances and tips for use of preclinical models in studies that integrate obesity with breast cancer risk and progression. We describe relevant mouse and rat paradigms, specifically highlighting differences in breast tumor subtypes, estrogen production, and strategies to manipulate hormone levels. We also outline options for diet composition and housing environments to promote obesity in female rodents. While we have applied our experience to understanding obesity-associated breast cancer, the experimental variables we incorporate have relevance to multiple fields that investigate women's health.

The In Vivo Net Energy Content of Resistant Starch and Its Effect on Macronutrient Oxidation in Healthy Adults.

The in vivo net energy content of resistant starch (RS) has not been measured in humans so it has not been possible to account for the contribution of RS to dietary energy intake. We aimed to determine the in vivo net energy content of RS and examine its effect on macronutrient oxidation. This was a randomized, double-blind cross-over study. Eighteen healthy adults spent 24 h in a whole room indirect calorimeter to measure total energy expenditure (TEE), substrate oxidation, and postprandial metabolites in response to three diets: 1) digestible starch (DS), 2) RS (33% dietary fiber; RS), or 3) RS with high fiber (RSF, 56% fiber). The in vivo net energy content of RS and RSF are 2.74 ± 0.41 and 3.16 ± 0.27 kcal/g, respectively. There was no difference in TEE or protein oxidation between DS, RS, and RSF. However, RS and RSF consumption caused a 32% increase in fat oxidation (p = 0.04) with a concomitant 18% decrease in carbohydrate oxidation (p = 0.03) versus DS. Insulin responses were unaltered after breakfast but lower in RS and RSF after lunch, at equivalent glucose concentrations, indicating improved insulin sensitivity. The average in vivo net energy content of RS is 2.95 kcal/g, regardless of dietary fiber content. RS and RSF consumption increase fat and decrease carbohydrate oxidation with postprandial insulin responses lowered after lunch, suggesting improved insulin sensitivity at subsequent meals.

Regular exercise potentiates energetically expensive hepatic de novo lipogenesis during early weight regain.

Exercise is a potent facilitator of long-term weight loss maintenance (WLM), whereby it decreases appetite and increases energy expenditure beyond the cost of the exercise bout. We have previously shown that exercise may amplify energy expenditure through energetically expensive nutrient deposition. Therefore, we investigated the effect of exercise on hepatic de novo lipogenesis (DNL) during WLM and relapse to obesity. Obese rats were calorically restricted with (EX) or without (SED) treadmill exercise (1 h/day, 6 days/wk, 15 m/min) to induce and maintain weight loss. After 6 wk of WLM, subsets of WLM-SED and WLM-EX rats were allowed ad libitum access to food for 1 day to promote relapse (REL). An energy gap-matched group of sedentary, relapsing rats (REL-GM) were provided a diet matched to the positive energy imbalance of the REL-EX rats. During relapse, exercise increased enrichment of hepatic DN-derived lipids and induced hepatic molecular adaptations favoring DNL compared with the gap-matched controls. In the liver, compared with both REL-SED and REL-GM rats, REL-EX rats had lower hepatic expression of genes required for cholesterol biosynthesis; greater hepatic expression of genes that mediate very low-density lipoprotein synthesis and secretion; and greater mRNA expression of Cyp27a1, which encodes an enzyme involved in the biosynthesis of bile acids. Altogether, these data provide compelling evidence that the liver has an active role in exercise-mediated potentiation of energy expenditure during early relapse.