Background Adolescence is characterised by changes in brain development, sleep and circadian biology. Sleep and circadian processes are important modulators of depression and anxiety, which can increase mental health difficulties, and often progress to chronic disorders in adulthood. This study aims to identify sleep and circadian-related mechanisms through which adolescents may either develop or demonstrate resilience to depression and anxiety. Methods SleepCHAMPzzz (Sleep and Circadian Health in Adolescents - a Mental-health Participation Study) is a longitudinal, multi-site study using complementary techniques to examine the pathway from sleep- and circadian-related changes to depression and anxiety during adolescence. To ensure the research findings are applicable across geographical, societal and cultural contexts, we will compare adolescent sleep and mental health trajectories in those living in lower, medium and higher income communities in the Global North (United Kingdom) and Global South (South Africa). We will work with lived-experience experts in the design, implementation, and dissemination phases to ensure relevant and context-sensitive research. Expected outcomes We hypothesise that circadian misalignment will drive poor sleep and night-time hyperarousal, which in turn will contribute to emotional dysregulation (characterised by over-active limbic circuits and under-active frontal circuits), a primary mechanism leading to depression and anxiety. Adolescents who experience less circadian misalignment and better sleep health will experience fewer symptoms or show recovery from symptoms of depression and anxiety. The strength and timing of specific biopsychosocial factors may moderate sleep/circadian and mental health associations. Conclusions By identifying how (mechanisms) and when (timing) sleep and mental health difficulties emerge, and what context-relevant factors influence the associations, data from this study may identify specific patterns of vulnerability. Such nuanced information can guide future interventions that both prevent and provide for early treatment of adolescent depression and anxiety, to reduce the future burden of care associated with chronic adult depression and anxiety.

People with HIV experience higher burden of cardiometabolic, mood, and cognitive disorders. Poor-quality and insufficient sleep are both associated with increased risk for these comorbidities and are more common in people with HIV. Although previous reviews have explored the prevalence and risk factors for sleep complaints in people with HIV, few have differentiated these complaints by potential underlying causes. Disordered sleep in people with HIV might arise from HIV-specific sleep disruptors, including direct effects of the virus, chronic inflammation, and antiretroviral treatment. There is also evidence that sleep is more fragile in people with HIV and some common sleep disorders, such as obstructive sleep apnoea, chronic insomnia, and circadian rhythm disorders, might be particularly problematic in people with HIV. Understanding how HIV uniquely disrupts sleep physiology could inform the development of tailored, mechanism-based management strategies to improve sleep health in people with HIV.

BACKGROUND:Sleep health is emerging as a public health priority due to its strong associations with several key domains of health. However, most of the existing literature are from studies located in high income settings and may not be representative of low-middle income settings. Leveraging the Modeling the Epidemiologic Transition Study, a study of cardiometabolic disease risk in five diverse African-origin populations, we explored differences in objectively measured sleep behavior across cohorts from Ghana, South Africa, Jamaica, Seychelles, and the United States. METHODS:Data from 809 participants (35-55 years old, 63% women) from the 5 Modeling the Epidemiologic Transition Study research sites were included. Objectively-measured sleep, using actigraphy, was scored according to the criteria of Patel and colleagues. For those with at least 5 nights of valid data, ecological mean sleep onset time, wake-up time, sleep duration, wake after sleep onset, and sleep efficiency were examined. FINDINGS:Adjusted models indicate that sleep onset was earlier in all sites when compared to US (p<.005). Sleep efficiency varied by locations, being lower in participants from Ghana, South Africa, and Jamaica when compared to United States (Ghana β: -3.7, South Africa: -5.8, Jamaica: -1.3, p<.05 for all) and higher in Seychelles when compared to United States (Seychelles β: 1.6; p=.02). Women presented with shorter sleep duration but with higher sleep efficiency. INTERPRETATION:Sleep duration, timing (wake time, midsleep time and sleep onset), and efficiency differ by country and sex, likely driven by socio-economic settings. Understanding sleep patterns in different contexts is needed to make informed and culturally appropriate health recommendations.

Temperatures across Africa are expected to rise at up to twice the rate of mean global temperatures, posing significant health threats to vulnerable communities. Prolonged exposure to high day- and night-time temperatures has been implicated in a myriad of adverse health outcomes. The built environment and inadequate housing can exacerbate these consequences, prompting the need to evaluate heat adaptation interventions as a sustainable adaptation strategy for low-income and informal settlement dwellers. The Heat Adaptation Benefits for Vulnerable groups In Africa (HABVIA) study aims to assess the impact of passive cooling interventions in homes on several key physiologic and mental health outcomes, as well as building internal thermal conditions. HABVIA is a 3-year prospective controlled study to identify, implement and assess heat adaptation solutions in four low-income communities in one urban and one rural site in Ghana and South Africa, respectively. In each site, N=240 participants (N=60 per site) will be assigned to intervention or control groups. The intervention is focused on lowering the nighttime temperature of the home environment. Health and biometric data will be collected through a combination of physiological measurements, questionnaires, and biochemical measures taken at 3 time points during the hot season. Clinical outcomes include objective sleep behaviour, core body temperature, physical activity, blood pressure, blood glucose, anthropometrics, and body composition. Indoor and outdoor environmental data will be collected continuously using fixed indoor sensors and automatic weather stations. Housing and community characteristics, and socio-economic information will be collected. Quantitative comparisons will be made between intervention and control conditions using generalised linear mixed models. Qualitative data from consultive workshops will be used to assess the acceptability and feasibility of the adaptations. Robust evaluation of the environmental and health outcomes of heat adaptations are limited for Africa, despite high climate vulnerability. HABVIA will address some of these gaps by assessing low-cost passive cooling interventions to promote heat resilience and improve health outcomes, providing real-world evidence for the feasibility of readily implementable and scalable adaptations in local contexts. Pan African Clinical Trials Registry (PACTR) PACTR202401521630856, version 1. Retrospectively registered on January 12, 2024.

Traditional obesity-related public health messaging often includes physical activity (PA) recommendations. However, at the population level, the data are conflicting, especially when comparing different self-reported vs measured techniques across different settings and populations. We measured the association between moderate-to-vigorous intensity PA (MVPA) and prospective weight change across five African-origin populations and the extent to which MVPA attenuated weight change over time. At baseline, 2,500 adults (median age: 37y) were recruited into the Modelling the Epidemiologic Transition Study (METS), from Ghana, South Africa, Jamaica, Seychelles, and US. 2000 participants were followed up 8 years later, with 851 participants having complete 7-day accelerometry to measure MVPA at both time points. Generalised estimating equations were used to explore the longitudinal association between weight and MVPA adjusted for several confounders. The obesity prevalence at baseline was 27.5% which increased to 38.0% at follow-up. Baseline MVPA varied from 7 (IQR: 4, 16) min/day in US women to 52 (IQR: 36, 78) min/day in South African men, and similarly at follow-up ranged from 8 min/day to 41 min/day among the same participant groups. While overall, engaging in higher MVPA levels was associated with a lower body weight, such that every additional 30 min of MVPA equalled a 600g lower body weight (p = 0.04), the interaction between time and MVPA was not statistically significant (p = 0.18). Therefore, regardless of the amount of MVPA at any time point, body weight increased over time. Despite the association between MVPA and weight, our results suggest that objectively measured longitudinal MVPA was not associated with the change in 8-year weight in African-origin adults. Our research confirms that while PA is a critical determinant of cardiovascular health, it alone may not be enough to stem the rising obesity burden.

Underlying mechanisms by which exposures to toxic metals/metalloids impact obesity and type 2 diabetes (T2DM) risk remain largely unknown. Gut microbiota have been strongly associated with cardiometabolic risk. To assess relationships between high metal exposures, gut dysbiosis, and metabolic dysregulation, we analyzed associations among gut microbiome taxa, dichotomized metal levels (arsenic, lead, mercury, cadmium), clinical measures (BMI, fasting blood glucose, blood pressure), and diagnoses (hypertension, obesity, diabetes) in 178 African-origin adults (52% female, mean age = 43.0 ± 6.4 years) from Ghana, South Africa, Jamaica, Seychelles, and USA. High vs. low lead and arsenic levels had a significant effect on beta diversity (p < 0.05). Seventy-one taxa were associated with high lead levels: 30 with elevated BMI, 22 with T2DM, and 23 with elevated fasting blood glucose (p < 0.05); 115 taxa were associated with high arsenic levels: 32 with elevated BMI, 33 with T2DM, and 26 with elevated blood glucose (p < 0.05). Porphyrin metabolism was the most enriched metabolic pathway in taxa associated with higher lead and arsenic exposure. These data provide the first findings from African-origin adults that demonstrate the association between the gut microbiome with lead and arsenic exposure and obesity and T2DM risk.

Sleep and mental health difficulties have been observed in response to COVID-19 pandemic-induced lockdowns, but few studies have described the impact of lockdown on individuals with self-reported insomnia. The purpose of this study was to compare the impact of lockdown on changes in symptoms of insomnia, depression and anxiety between persons with and without self-identified insomnia. In total, 1048 adult participants from the general South African population took part in this retrospective observational study during Alert Levels 4 and 3 in May and June 2020. They completed an online survey assessing current and past self-reported sleep disorders. Symptom profiles of insomnia (Insomnia Severity Index), depression (Patient Health Questionnaire-2) and anxiety (Generalised Anxiety Disorder 7-item scale) were assessed immediately before and during a 5-week lockdown (March–April 2020). Comparative analyses were conducted between participants who identified a current or previous diagnosis of insomnia (n = 135, Insomnia group, irrespective of whether they had current symptoms or not) and those reporting no sleep disorders (n = 700, No-Insomnia group). Participants who reported multiple sleep disorders were excluded from the analyses (n = 213). Symptoms of insomnia (p < 0.001), depression (p = 0.001) and anxiety (p = 0.001) worsened in all participants during lockdown compared to pre-lockdown measures. Time-by-group interaction effects were observed for all measures (p < 0.001) such that the Insomnia group reported larger increases in insomnia (p < 0.001), depression (p < 0.001) and anxiety (p < 0.001) scores compared to the No-Insomnia group during lockdown. Participants with self-reported insomnia, even if currently asymptomatic, were more vulnerable to worsening insomnia and depressive and anxiety-related symptoms during lockdown compared to those with no insomnia. This highlights vulnerability to mental-health-altering situations in individuals with self-identified insomnia, and thus the necessity to provide mental health support for this patient population.

Background: Non-communicable diseases (NCDs) such as obesity, hypertension (HPT), and type II diabetes (T2D) are of increasing concern in South Africa (SA), with women being more at risk. Authors conducted a scoping review to identify and map the evidence available about the barriers of access to obesity, HPT, and T2D care among women in SA. Methods: Arksey and O'Malley's framework for scoping review was used. The search of the literature was completed in the Scopus, Web of Science, and PubMed databases between April and May 2022. Only studies conducted among women in SA were eligible for inclusion. Identified barriers were mapped onto Levesque’s framework of access to health care to determine which points along the chain of accessing NCD health care among women are mostly impacted. Results: Seven articles were included in the review: qualitative (n=2), quantitative (n=2), mixed methods (n=2), and grey literature (n=1). The included studies reported barriers of access to HPT and T2D care only, and no study reported barriers to obesity care. Supply-side barriers included lack of knowledge about available services, physician heavy workloads, medicine stock-outs, limited availability of testing equipment, unaffordable transport costs, travelling longer distances, inefficiently longer waiting times, and delayed referral. Demand-side barriers included women having low self-awareness of NCD status, concerns about confidentiality, perceived discrimination, and poverty. Conclusions: Access to HPT and T2D services is impacted from perception of need to benefitting from care. Articles included identified barriers affecting the availability and accommodation dimension of access to care, suggesting that HPT and T2D care is often unavailable or that women are unable to reach health facilities or service providers. There is need for more and better-quality research about access to NCD health care in SA, especially among women having a disproportionately high burden of obesity, T2D, and HPT.

Objectives Given the increasing prevalence of obesity and need for effective interventions, there is a growing interest in understanding how an individual’s body image can inform obesity prevention and management. This study’s objective was to examine the use of silhouette showcards to measure body size perception compared with measured body mass index, and assess body size dissatisfaction, in three different African-origin populations spanning the epidemiological transition. An ancillary objective was to investigate associations between body size perception and dissatisfaction with diabetes and hypertension.Setting Research visits were completed in local research clinics in respective countries.Participants Seven hundred and fifty-one African-origin participants from the USA and the Republic of Seychelles (both high-income countries), and Ghana (low/middle-income country).Primary and secondary outcome measures Silhouette showcards were used to measure perceived body size and body size dissatisfaction. Objectively measured body size was measured using a scale and stadiometer. Diabetes was defined as fasting blood glucose ≥126 mg/dL and hypertension was defined as ≥130 mm Hg/80 mm Hg.Results Most women and men from the USA and Seychelles had ‘Perceived minus Actual weight status Discrepancy’ scores less than 0, meaning they underestimated their actual body size. Similarly, most overweight or obese men and women also underestimated their body size, while normal weight men and women were accurately able to estimate their body size. Finally, participants with diabetes were able to accurately estimate their body size and similarly desired a smaller body size.Conclusions This study highlights that overweight and obese women and men from countries spanning the epidemiological transition were unable to accurately perceive their actual body size. Understanding people’s perception of their body size is critical to implementing successful obesity prevention programmes across the epidemiological transition.

Abstract Disclosure: J. Jorgensen: None. C. Choo-Kang: None. L. Issa: None. J.A. Gilbert: None. G. Ecklu-Mensah: None. A. Luke: None. K. Bedu-Addo: None. T. Forrester: None. P. Bovet: None. E.V. Lambert: None. D. Rae: None. M. Argos: None. Y. Dai: None. R.M. Sargis: None. L.R. Dugas: None. B.T. Layden: None. Obesity is associated with an increased risk for cardiometabolic diseases, such as type 2 diabetes mellitus (T2D). Prior research has shown an association between toxic metals/metalloid (hereafter, “metals”) exposures, including arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd), and increased T2D risk. Importantly, metal exposure has been suggested to impact the gut microbiome. Gut microbiome composition and metabolism are key to the development and progression of obesity and diabetes, thus we propose a potential novel interaction via the gut microbiota between metals and T2D, although the exact pathway remains unclear. We studied a large African-origin cohort from Ghana, South Africa, Jamaica, Seychelles, and the US (n=188, 51% female, mean age=43.0±6.5 yr). Analyzing 16S rRNA Amplicon sequencing, anthropometrics, and creatinine-adjusted urinary metal levels, we observed metal levels were significantly associated with country of origin and in most countries were significantly associated with decreased microbial diversity. Metal levels were highest in Ghana and lowest in the US, and were significantly different between Ghana and the US for As and Pb (p-value < 2.2e-16). Individually, Pb levels were significantly associated with fasting blood glucose and BMI, As levels were associated with T2D diagnosis, and Hg levels were associated with obesity diagnosis. Pb levels were significantly associated with a lower proportion of potential acetate- and butyrate-producing microbial strains. Similarly, As levels were associated with decreased proportion of potential butyrate-producing genera. Microbial strains in individuals with high Pb levels showed significant association with obesity and T2D risk and strains in individuals with significant high As levels were associated with only T2D risk. Hg and Cd were not significantly associated with microbes and clinical status. These taxa are significantly associated with increased heme metabolism. With this study, we aimed to begin to describe the effect of metals and the risks for obesity and diabetes through its action within the gut microbiome. We demonstrate that toxic metal exposures were associated with differences in the gut microbiome and predicted metabolism that may also be associated with increased obesity and T2D risk. Presentation: 6/1/2024

OBJECTIVES:Corporate executive job demands may lead to poor sleep habits, increasing their risk for cardiometabolic disease. This study aimed to describe and explore associations between objectively measured habitual sleep characteristics and cardiometabolic disease risk of corporate executives, while accounting for occupational, psychological, and lifestyle factors. METHODS:Habitual sleep was measured using wrist-worn actigraphy and a sleep diary over seven consecutive days in 61 (68.3% men) corporate executives aged 46.4 ± 8.7years. A composite cardiometabolic disease risk score was determined using body mass index, waist circumference, blood pressure and fasting glucose and lipid concentrations. Prediction models were built using a backward stepwise selection approach to explore associations between sleep characteristics and cardiometabolic disease risk factors adjusting for occupational, psychological, and lifestyle covariates. RESULTS:Average total sleep time was 6.60 ± 0.75 hours, with 51.7% of participants reporting poor sleep quality and 26.2% extending their weekend sleep. Adjusted models showed that lower sleep efficiency (β = -0.25, 95%CI: -0.43; -0.08, P = .006), shorter weekday total sleep time (β = -1.37, 95% CI: -2.41, -0.32; P = .011) and catch-up sleep (β = 0.84, 95%CI: 0.08, 1.60, P = .002) were associated with higher cardiometabolic disease risk scores. Adjusted models also found that shorter average time-in-bed (ß=-2.00, 95%CI: -3.76; -0.18, P = .031), average total sleep time (ß=1.98, 95%CI: -3.70; -0.25, P = .025) and weekday total sleep time (β = -2.13, 95%CI: -3.56; -0.69, P = .025) as well as catch-up sleep (β = 1.67, 95% CI: 0.52; 2.83; P = .012) were all associated with a higher body mass index. CONCLUSION:Corporate executives who compromise sleep duration during the working week may increase their risk for obesity and future cardiometabolic disease.

South Africans living in low socioeconomic areas have self-reported unusually long sleep durations (approximately 9–10 h). One hypothesis is that these long durations may be a compensatory response to poor sleep quality as a result of stressful environments. This study aimed to investigate whether fear of not being safe during sleep is associated with markers of sleep quality or duration in men and women. South Africans (n = 411, 25–50 y, 57% women) of African-origin living in an urban township, characterised by high crime and poverty rates, participated in this study. Participants are part of a larger longitudinal cohort study: Modelling the Epidemiologic Transition Study (METS)–Microbiome. Customised questions were used to assess the presence or absence of fears related to feeling safe during sleep, and the Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index were used to assess daytime sleepiness, sleep quality and insomnia symptom severity respectively. Adjusted logistic regression models indicated that participants who reported fears related to safety during sleep were more likely to report poor sleep quality (PSQI > 5) compared to participants not reporting such fears and that this relationship was stronger among men than women. This is one of the first studies outside American or European populations to suggest that poor quality sleep is associated with fear of personal safety in low-SES South African adults.

Background Risk factors for cardiovascular disease (CVD) and sleep health are well-known to be sex- and race-specific. To build on the established relationship between sleep duration and CVD risk, this cross-sectional study aimed to describe sex-specific associations between CVD risk and other sleep characteristics (sleep quality, sleep timing and sleep onset latency) in low-income adults of African descent. Methods Self-reported sleep (Pittsburgh Sleep Quality Index [PSQI], Epworth Sleepiness Scale [ESS], Insomnia Severity Index [ISI]), demographic and lifestyle data were collected in 412 adults (56 % women, 35.0 ± 7.6y, 40 % employed) living in an informal settlement in South Africa. CVD risk was determined using the BMI-modified Framingham 10-year CVD risk formula. Results Logistic regression analyses, adjusted for employment, alcohol use and physical activity, indicated that men reporting poor sleep quality (OR: 1.95[95 %CI: 1.07–3.51], p=0.025) and earlier bedtimes (0.54[0.39–0.74], p<0.001) were more likely to belong to a higher 10-year CVD risk score quintile. Women reporting earlier bedtimes (0.72[0.55–0.95], p=0.020) and wake-up times (0.30[0.13–0.73], p=0.007), longer sleep-onset latency (1.47[1.43–1.88], p=0.003), shorter total sleep times (0.84[0.72–0.98], p=0.029), higher PSQI global scores (1.93[1.29–2.90], p=0.001) and more moderate to severe symptoms of insomnia (ISI≥15)(3.24[1.04–10.04], p=0.016) were more likely to belong to higher 10-year CVD risk score quintile. Conclusion In addition to sleep duration, we found that sleep quality, sleep timing and sleep onset latency are additional risk factors for CVD in adults of African descent. Sex-specific differences in the sleep-CVD-risk relationship observed suggests that future studies and recommendations about sleep health in relation to CVD should take sex into account.

Abstract Disclosure: J. Jorgensen: None. C. Choo-Kang: None. G. Ecklu-Mensah: None. J. Gilbert: None. A. Luke: None. K. Bedu-Addo: None. T.E. Forrester: None. P. Bovet: None. E.V. Lambert: None. D. Rae: None. L. Dugas: None. Y. Dai: None. B.T. Layden: None. Obesity is a global public health crisis, which since 1975 has tripled world-wide. Concomitantly, obesity-related conditions such as cardiovascular disease, stroke, and type 2 diabetes have also increased. An accepted common obesogenic factor has been a shift away from fiber-rich diets to ultra-processed foods. Fiber is digested by the gut microbiota, resulting in the production of short-chain fatty acids (SCFAs), and diets that are rich in fiber are associated with greater microbial diversity and increased serum and fecal SCFA levels. Yet, the mechanistic link between dietary fiber and improved metabolic outcomes, via SCFAs, is not clearly defined. We analyzed data from a large ongoing prospective study of African-origin adults from 5 countries (Ghana, South Africa, Jamaica, Seychelles & US), each with distinct dietary fiber intakes. Standard methods were used to assess taxonomy, Shannon alpha diversity and beta diversity, as well as taxonomic differences by fecal SCFA levels as a proxy for fiber intake. Thereafter, microbiota taxa were used to predict functional metabolite profiles, as well as the metabolic pathway abundances to identify differential metabolites correlated with SCFA levels. These profiles and pathways were correlated with SCFA levels within and between sites. As microbes interact and impact each other, we constructed differential microbial co-occurrence networks to identify hub species and differences in community configuration across sites comparing SCFA levels via Network Construction and comparison for Microbiome data (NetCoMi). The final sample included 1904 participants (age=42.57±8.04 yr). The mean BMI was lowest in Ghana (BMI=26.72±5.88 kg/m2), and highest in the US (BMI=34.42±9.06 kg/m2) with a p-value < 2.2e-16. Conversely, diets in Ghana had the highest fiber intake resulting in the highest fecal SCFA levels (8026.97±2605.38 µg/g) which was significantly greater than US SCFA levels (p-value < 2e-16). Not surprisingly, differences in microbial diversity were unique to each site as well as adiposity levels. Overall, non-obese individuals had a higher proportion of Prevotella, Allaprevotella compared to obese individuals who had higher proportions of Firmicutes. Prevotella and Allaprevotella are known SCFAs producers and previously shown to be anti-inflammatory in the gut, while Firmicutes are positively correlated with gut inflammation. We provide evidence that fiber-rich diets may act through the anti-inflammatory pathways associated with the gut microbiota in humans. Future research should elucidate the gut microbial mediated anti-inflammatory effects and the metabolic pathways to develop novel anti-inflammatory therapeutics. Presentation: Friday, June 16, 2023