Rationale, Design, and Baseline Characteristics of Participants in the Health@NUS mHealth Augmented Cohort Study Examining Student-to-Work Life Transition: Protocol for a Prospective Cohort Study.

BACKGROUND: Integration of mobile health data collection methods into cohort studies enables the collection of intensive longitudinal information, which gives deeper insights into individuals' health and lifestyle behavioral patterns over time, as compared to traditional cohort methods with less frequent data collection. These findings can then fill the gaps that remain in understanding how various lifestyle behaviors interact as students graduate from university and seek employment (student-to-work life transition), where the inability to adapt quickly to a changing environment greatly affects the mental well-being of young adults. OBJECTIVE: This paper aims to provide an overview of the study methodology and baseline characteristics of participants in Health@NUS, a longitudinal study leveraging mobile health to examine the trajectories of health behaviors, physical health, and well-being, and their diverse determinants, for young adults during the student-to-work life transition. METHODS: University students were recruited between August 2020 and June 2022 in Singapore. Participants would complete biometric assessments and questionnaires at 3 time points (baseline, 12-, and 24-month follow-up visits) and use a Fitbit smartwatch and smartphone app to continuously collect physical activity, sedentary behavior, sleep, and dietary data over the 2 years. Additionally, up to 12 two-week-long bursts of app-based ecological momentary surveys capturing lifestyle behaviors and well-being would be sent out among the 3 time points. RESULTS: Interested participants (n=1556) were screened for eligibility, and 776 participants were enrolled in the study between August 2020 and June 2022. Participants were mostly female (441/776, 56.8%), of Chinese ethnicity (741/776, 92%), undergraduate students (759/776, 97.8%), and had a mean BMI of 21.9 (SD 3.3) kg/m2, and a mean age of 22.7 (SD 1.7) years. A substantial proportion were overweight (202/776, 26.1%) or obese (42/776, 5.4%), had indicated poor mental well-being (World Health Organization-5 Well-Being Index ≤50; 291/776, 37.7%), or were at higher risk for psychological distress (Kessler Psychological Distress Scale ≥13; 109/776, 14.1%). CONCLUSIONS: The findings from this study will provide detailed insights into the determinants and trajectories of health behaviors, health, and well-being during the student-to-work life transition experienced by young adults. TRIAL REGISTRATION: ClinicalTrials.gov NCT05154227; https://clinicaltrials.gov/study/NCT05154227. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/56749.

Results from the Singapore 2022 report card on physical activity for children and adolescents.

Background: While it has been established that physical activity (PA) is key to promote overall health and well-being, insufficient physical activity among children and adolescents is a global problem, including Singapore. It is important to understand the local PA landscape among children and adolescents to decrease surveillance gaps and identify areas for improvement in promoting PA. The present article provides an overview of the development of the 2022 Active Healthy Kids Singapore Report Card and the results, as well as underscore limitations and gaps in the available evidence related to PA among children and adolescents in Singapore. Methods: Following the Global Matrix 4.0, the available data between July 2010 to July 2020 was synthesized for all 10 indicators by the work group and reviewed by a panel of experts. Data sources included published scientific articles, government and non-government reports, national surveys, and unpublished data from on-going research studies. Where possible, grades were informed by nationally representative surveys or large-scale longitudinal studies. Results: The grades assigned were: Overall Physical Activity (C-), Organized Sport and Physical Activity (B-), Active Play (C-), Active Transportation (C), Sedentary Behaviours (C-), Physical Fitness (Incomplete), Family and Peers (C-), School (Incomplete), Community and Environment (A+), Government (B). Conclusion: This is the first comprehensive evaluation of PA among children and adolescents in Singapore. It provides baseline grades valuable for future comparison. It also illustrates gaps in the existing evidence which can inform future surveillance, facilitate international comparisons and enable global efforts in promoting physical activity.

"You know what, I'm in the trend as well" - Understanding the inter-play between digital and real-life social influences on the food and activity choices of young adults.

OBJECTIVE: To understand young adults' perceptions of online and real-life social influences on their food and activity choices. DESIGN: A qualitative study involving seven focus groups. Thematic analyses using both deductive and inductive techniques were performed. SETTING: A polytechnic and a university in Singapore. PARTICIPANTS: A total of 46 full-time students, 19-24 years of age. RESULTS: Participants revealed that social media meets multiple needs, contributing to its ubiquitous use and facilitating content spread between social networks. Food-related content shared on social media were mostly commercial posts, marketing foods and eateries showcasing price-promotions, emphasizing sensory properties of foods, or creating narratives that activated trends. Subsequently, real-life social activities frequently revolve around marketed foods that were not necessarily healthy. In contrast, physical activity posts were rarely being followed up in real life. Portrayals describing a toxic gym culture could contribute to negative perceptions of peers' physical activity posts and a disinclination towards sharing such posts. Participants expressed that close, supportive social networks in real-life strongly influenced initiating and maintaining healthy lifestyles. However, in a society that highly values academic achievements, participants prioritized studying and socializing over healthy eating and physical activity. CONCLUSIONS: Overall, our findings reveal that virtual and real-life social influences have complex interactions affecting Asian young adults' behavioral choices and should be considered when designing interventions for this group. Regulations related to the digital marketing of unhealthy food, and improving the availability, accessibility, and affordability of healthier food options, particularly in the foodservice sector, would be of value to consider.

Identifying implementation gaps and priorities for the Singapore government to improve food environment policies: perspectives from a local expert panel.

OBJECTIVE: Singapore, an urbanised, developed nation, with a high reliance on food importation and a high prevalence of eating out is facing rising rates of obesity and diabetes. The objective of the current study was to characterise and evaluate the Singapore government's policies to improve the food environment and to identify and prioritise concrete actions. DESIGN: The Healthy Food Environment Policy Index tool and process were used. An expert panel rated the Singapore government's implementation of forty-seven indicators compared with international best practice in 2018. Indicators were prioritised, and specific recommendations were proposed by panel. SETTING: Singapore. PARTICIPANTS: Twenty experts primarily from academia. RESULTS: As compared with international benchmarks, the level of implementation of most indicators (thirty-three indicators, 70 %) by the Singapore government was evaluated as being at least moderate. Highly rated indicators included those related to provision of healthier meals at school, supporting the use of healthier ingredients by food vendors and governmental leadership. More policy indicators (6, 26 %) as compared with infrastructure support indicators (2, 8 %) received a 'very little or no implementation' rating. After rating, the experts prioritised eleven indicators and proposed thirty-one actions informed by several considerations including those of effectiveness, political acceptability, feasibility and unique characteristics of food retail in Singapore. CONCLUSIONS: Supported by documented evidence, an independent expert panel identified areas of strengths and provided specific recommendations to meaningfully improve the Singapore food environment to facilitate healthier eating. Fundamental recommendations including improving nutrition profiling and strengthening monitoring systems have the potential to positively influence environments across policy domains.

The effect of coffee consumption on insulin sensitivity and other biological risk factors for type 2 diabetes: a randomized placebo-controlled trial.

BACKGROUND: In observational studies, coffee consumption has been consistently associated with a lower risk of type 2 diabetes mellitus. Trials examining the effect of coffee consumption on glucose metabolism have been limited by the use of surrogate insulin sensitivity indices, small sample sizes, lack of blinding, and short follow-up duration. OBJECTIVES: We aimed to overcome limitations of previously conducted coffee trials in a randomized placebo-controlled trial of the effect of coffee consumption on insulin sensitivity. METHODS: We conducted a 24-wk randomized placebo-controlled trial in 126 overweight, non-insulin sensitive (HOMA-IR ≥1.30), Chinese, Malay, and Asian-Indian males and females aged 35-69 y. Participants were randomly assigned to receive 4 cups of instant regular coffee (n = 62) or 4 cups of a coffee-like placebo beverage (n = 64) per day. The primary outcome was the amount of glucose metabolized per kilogram of body weight per minute (Mbw) assessed during steady-state conditions with a hyperinsulinemic euglycemic clamp. Secondary outcomes included other clamp-based insulin sensitivity measures, biological mediators of insulin sensitivity, and measures of fasting glucose metabolism. RESULTS: Coffee consumption did not significantly change insulin sensitivity compared with placebo (percentage mean difference in Mbw = 4.0%; 95% CI: -8.3, 18.0%; P = 0.53). Furthermore, no significant differences in fasting plasma glucose (2.9%; 95% CI: -0.4, 6.3%; P = 0.09) or biological mediators of insulin resistance, such as plasma adiponectin (2.3%; 95% CI: -1.4, 6.2%; P = 0.22), were observed between coffee and placebo groups over 24 wk of intervention. Participants in the coffee arm experienced a loss of fat mass (FM) (-3.7%; 95% CI: -6.3, -1.1%; P = 0.006) and reduction in urinary creatinine concentrations (-21.2%; 95% CI: -31.4, -9.5%; P = 0.001) compared with participants in the placebo arm over 24 wk of intervention. CONCLUSIONS: Consuming 4 cups/d of caffeinated coffee for 24 wk had no significant effect on insulin sensitivity or biological mediators of insulin resistance but was associated with a modest loss of FM and reduction in urinary creatinine concentrations.This trial was registered at clinicaltrials.gov as NCT01738399. Registered on November 28, 2012. Trial sponsor: Nestlé Research, Lausanne, Switzerland. Trial site: National University of Singapore.

Young People's Attitudes and Motivations Toward Social Media and Mobile Apps for Weight Control: Mixed Methods Study.

BACKGROUND: Effective prevention at a young enough age is critical to halt the obesity epidemic. Mobile health (mHealth) apps would potentially reach large numbers at low-cost. While there is already a profusion of lifestyle apps, they are mostly non-evidence-based and evidently ineffective against rising obesity prevalence. OBJECTIVE: The aim of this study was to explore preferences and usage of lifestyle apps among young people in 6 countries. METHODS: A mixed methods study was conducted among young people aged 13 to 24 years residing in the United Kingdom, Belgium, Finland, Greece, Singapore, and New Zealand. Participants were recruited from Web advertisements on Facebook, asking for volunteers interested in mobile apps in general, not specific to lifestyle or health, to complete a short survey comprising 18 questions on demographics, weight gain, and mobile app preferences and then to join English-language online focus groups, which were held during 2017, in password-protected Web rooms, moderated by an experienced researcher. Descriptive statistics were carried out for the survey, and thematic analysis was applied to transcripts. RESULTS: A total of 2285 young people (610 adolescents aged 13-17 years and 1675 young adults aged 18-24 years) responded and completed the survey, with 72.0% (1645) reported being concerned about weight gain for themselves or friends. Later, 807 young people (376 adolescents and 431 young adults) were selected based on age and country to participate in 12 online focus groups, with 719 young people completing. Analysis revealed 4 main themes: (1) feelings toward personal weight; (2) perception of lifestyle apps and desired content for weight gain prevention; (3) social media apps, lifestyle apps, and motivation for downloading and retaining; and (4) data safety and data usage and confidentiality. Young people are interested in evidence-based advice in programs incorporating their preferences. CONCLUSIONS: Young people are commonly, and consistently across 6 countries, concerned about weight gain and obesity and would welcome evidence-based mHealth programs, provided the views of young people themselves are incorporated in the program content.

An 11-country study to benchmark the implementation of recommended nutrition policies by national governments using the Healthy Food Environment Policy Index, 2015-2018.

The Healthy Food Environment Policy Index (Food-EPI) aims to assess the extent of implementation of recommended food environment policies by governments compared with international best practices and prioritize actions to fill implementation gaps. The Food-EPI was applied in 11 countries across six regions (2015-2018). National public health nutrition panels (n = 11-101 experts) rated the extent of implementation of 47 policy and infrastructure support good practice indicators by their government(s) against best practices, using an evidence document verified by government officials. Experts identified and prioritized actions to address implementation gaps. The proportion of indicators at "very low if any," "low," "medium," and "high" implementation, overall Food-EPI scores, and priority action areas were compared across countries. Inter-rater reliability was good (GwetAC2 = 0.6-0.8). Chile had the highest proportion of policies (13%) rated at "high" implementation, while Guatemala had the highest proportion of policies (83%) rated at "very low if any" implementation. The overall Food-EPI score was "medium" for Australia, England, Chile, and Singapore, while "very low if any" for Guatemala. Policy areas most frequently prioritized included taxes on unhealthy foods, restricting unhealthy food promotion and front-of-pack labelling. The Food-EPI was found to be a robust tool and process to benchmark governments' progress to create healthy food environments.

Impact of tax and subsidy framed messages on high- and lower-sugar beverages sold in vending machines: a randomized crossover trial.

OBJECTIVE: Framing of fiscal incentives has been suggested to be important in influencing purchase decisions. We aimed to examine the effect of framing a modest price difference between high- and lower-sugar beverages as a tax or a subsidy respectively, using messages placed on vending machines to influence beverage purchases. DESIGN/SETTING: This is an 11-week randomized crossover trial conducted between August and November 2015, with a two-week run-in period before intervention, targeted at students, staff and faculty of a university campus in Singapore. Twenty-one beverage vending machines were used to implement the intervention involving 'tax message', 'subsidy message' and 'no message (control)'. The former two messages suggest 'a tax for high sugar beverages' or 'a subsidy for lower sugar beverages' respectively. Prices of the beverages offered were fixed at baseline and remained the same in all three experimental conditions: lower-sugar beverage options were priced ~ 10% lower than the corresponding high-sugar option. The machines were randomized to one of the 6 sequences of intervention. Each message intervention period was 3 weeks. The effect of messages was assessed by comparing average weekly units of beverages sold between interventions using mixed effects model. RESULTS: The average weekly units of high and lower-sugar beverages sold per vending machine were 115 and 98 respectively in the control condition. The percentage of high-sugar beverages sold was 54% in the control, 53% in the tax, and 54% in the subsidy message condition. There was no difference in the weekly units of high-sugar beverages sold for the tax message (- 2, 95% CI -8 to 5, p = 0.61) or the subsidy message (0, 95% CI -10 to 10, p = 0.96) conditions as compared with the control condition. Similarly, there was no difference in the weekly units of lower-sugar beverages sold for the tax message (4, 95% CI -4 to 13, p = 0.32) or the subsidy message (7, 95% CI -4 to 18, p = 0.18) conditions as compared with the control condition. CONCLUSIONS: The use of tax and subsidy messages to highlight modest price differences did not substantially reduce high-sugar beverage sales in vending machines on an Asian university campus.

Relative Validity and Reproducibility of a Food Frequency Questionnaire for Assessing Dietary Intakes in a Multi-Ethnic Asian Population Using 24-h Dietary Recalls and Biomarkers.

The assessment of diets in multi-ethnic cosmopolitan settings is challenging. A semi-quantitative 163-item food frequency questionnaire (FFQ) was developed for the adult Singapore population, and this study aimed to assess its reproducibility and relative validity against 24-h dietary recalls (24 h DR) and biomarkers. The FFQ was administered twice within a six-month interval in 161 adults (59 Chinese, 46 Malay, and 56 Indian). Fasting plasma, overnight urine, and 24 h DR were collected after one month and five months. Intra-class correlation coefficients between the two FFQ were above 0.70 for most foods and nutrients. The median correlation coefficient between energy-adjusted deattenuated FFQ and 24 h DR nutrient intakes was 0.40 for FFQ1 and 0.39 for FFQ2, highest for calcium and iron, and lowest for energy and carbohydrates. Significant associations were observed between urinary isoflavones and soy protein intake (r = 0.46), serum carotenoids and fruit and vegetable intake (r = 0.34), plasma eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and fish/seafood intake (r = 0.36), and plasma odd chain saturated fatty acids (SFA) and dairy fat intake (r = 0.25). Associations between plasma EPA + DHA and fish/seafood intake were consistent across ethnic groups (r = 0.28-0.49), while differences were observed for other associations. FFQ assessment of dietary intakes in modern cosmopolitan populations remains feasible for the purpose of ranking individuals' dietary exposures in epidemiological studies.

A randomized placebo-controlled trial of the effect of coffee consumption on insulin sensitivity: Design and baseline characteristics of the Coffee for METabolic Health (COMETH) study.

BACKGROUND: Coffee consumption has been consistently associated with a lower risk of type 2 diabetes mellitus in cohort studies. In addition, coffee components increased insulin sensitivity in animal models. However, data from intervention studies on the effect of coffee consumption on glucose metabolism have been limited by small sample sizes, lack of blinding, short follow-up duration and the use of surrogate indices of insulin sensitivity. We designed the Coffee for Metabolic Health (COMETH) study to evaluate the effect of coffee consumption on insulin sensitivity. METHODOLOGY: The COMETH study is a double-blind randomized placebo-controlled 24-week trial. Participants were overweight, male and female habitual coffee consumers who were of Chinese, Malay and Asian-Indian ethnicity. We excluded smokers, persons with diabetes, and persons with low insulin resistance (HOMA-IR < 1.30). Participants were randomly assigned to receive daily 4 cups of instant regular coffee or 4 cups of a coffee-like placebo beverage. The hyperinsulinemic euglycemic clamp was performed at baseline and at the end of 24 weeks to determine changes in the bodyweight standardized M-value. Secondary outcomes included changes in fasting glucose and insulin sensitivity mediators such as adiponectin, markers of inflammation, liver function, and oxidative stress.We enrolled 128 participants, 126 (57.1% males; aged 35-67 years) of whom completed baseline assessments. DISCUSSION: If improvement in insulin sensitivity in the coffee group is significantly greater than that of the placebo group, this would support the hypothesis that coffee consumption reduced risk of type 2 diabetes through biological pathways involving insulin sensitivity. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01738399. Registered on 28 November 2012. Trial Sponsor: Nestlé Research Center, Lausanne, Switzerland. Trial Site: National University of Singapore.

P-glycoprotein and vacuolar ATPase synergistically confer anthracycline resistance to fission yeast and human cells.

Drug resistance is a major hurdle to the success of chemotherapy. The permeability glycoprotein (P-gp) is an important factor dictating drug access to the cells, as it controls the efflux of chemotherapeutic agents against the concentration gradient. Pmd1, a P-gp-like protein, was recently isolated as a doxorubicin resistance gene in fission yeast. Although the null mutant of pmd1 (Δpmd1) exhibited sensitivity to doxorubicin, it showed an unexpectedly high resistance to the drug at relatively high concentrations. The data presented here suggest that this is due to the presence of cooperative processes that can complement and counteract drug cytotoxicity in the absence of Pmd1. One such factor, Rav1, is an essential factor in controlling the assembly of the pH-regulating transporter vacuolar-ATPase (V-ATPase) in fission yeast. The simultaneous disruption of Pmd1 and Rav1 resulted in a prominent accumulation of doxorubicin in the cytoplasm of cells, accompanied by a decline in cell viability. With concurrent treatment of pharmacological inhibitors in human cervical cancer cells, P-gp and V-ATPase were further shown to act synergistically to sensitize cells to doxorubicin also in the human cells. Furthermore, a novel Cornichon-like protein SPAC2C4.05 (herein named as Cor1) was demonstrated for the first time to be involved in the interaction with P-gp and V-ATPase to counteract doxorubicin-dependent cytotoxicity. Therefore this study identified a molecular cooperation between multiple membrane transporter proteins that confers chemoresistance to cells against the chemical insult of doxorubicin. Interestingly, this network exhibited differential effects to doxorubicin as compared with its close epimeric analog epirubicin, suggestive of the intricacy of the drug response regulated by this synergistic interaction. A model is discussed on how the versatility of this network can differentiate closely related chemical drug structures yet allow for the robustness to counteract a vast range of drugs.

Cellular robustness conferred by genetic crosstalk underlies resistance against chemotherapeutic drug doxorubicin in fission yeast.

Doxorubicin is an anthracycline antibiotic that is among one of the most commonly used chemotherapeutic agents in the clinical setting. The usage of doxorubicin is faced with many problems including severe side effects and chemoresistance. To overcome these challenges, it is important to gain an understanding of the underlying molecular mechanisms with regards to the mode of action of doxorubicin. To facilitate this aim, we identified the genes that are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe. We further demonstrated interplay between factors controlling various aspects of chromosome metabolism, mitochondrial respiration and membrane transport. In the nucleus we observed that the subunits of the Ino80, RSC, and SAGA complexes function in the similar epistatic group that shares significant overlap with the homologous recombination genes. However, these factors generally act in synergistic manner with the chromosome segregation regulator DASH complex proteins, possibly forming two major arms for regulating doxorubicin resistance in the nucleus. Simultaneous disruption of genes function in membrane efflux transport or the mitochondrial respiratory chain integrity in the mutants defective in either Ino80 or HR function resulted in cumulative upregulation of drug-specific growth defects, suggesting a rewiring of pathways that synergize only when the cells is exposed to the cytotoxic stress. Taken together, our work not only identified factors that are required for survival of the cells in the presence of doxorubicin but has further demonstrated that an extensive molecular crosstalk exists between these factors to robustly confer doxorubicin resistance.