Investigating light sensitivity in bipolar disorder (HELIOS-BD).

Many people with bipolar disorder have disrupted circadian rhythms. This means that the timing of sleep and wake activities becomes out-of-sync with the standard 24-hour cycle. Circadian rhythms are strongly influenced by light levels and previous research suggests that people with bipolar disorder might have a heightened sensitivity to light, causing more circadian rhythm disruption, increasing the potential for triggering a mood switch into mania or depression. Lithium has been in clinical use for over 70 years and is acknowledged to be the most effective long-term treatment for bipolar disorder. Lithium has many reported actions in the body but the precise mechanism of action in bipolar disorder remains an active area of research. Central to this project is recent evidence that lithium may work by stabilising circadian rhythms of mood, cognition and rest/activity. Our primary hypothesis is that people with bipolar disorder have some pathophysiological change at the level of the retina which makes them hypersensitive to the visual and non-visual effects of light, and therefore more susceptible to circadian rhythm dysfunction. We additionally hypothesise that the mood-stabilising medication lithium is effective in bipolar disorder because it reduces this hypersensitivity, making individuals less vulnerable to light-induced circadian disruption. We will recruit 180 participants into the HELIOS-BD study. Over an 18-month period, we will assess visual and non-visual responses to light, as well as retinal microstructure, in people with bipolar disorder compared to healthy controls. Further, we will assess whether individuals with bipolar disorder who are being treated with lithium have less pronounced light responses and attenuated retinal changes compared to individuals with bipolar disorder not being treated with lithium. This study represents a comprehensive investigation of visual and non-visual light responses in a large bipolar disorder population, with great translational potential for patient stratification and treatment innovation.

Gender differences in the relationship between sleep and age in a Brazilian cohort: the Baependi Heart Study.

Gender and age are well-established determinants of health and sleep health that influence overall health, which also often varies by gender and age. Sleep architecture is an important component of sleep health. The goal of this analysis was to examine whether associations between age and sleep stages differ by gender in the absence of moderate-severe obstructive sleep apnea (OSA) in a rural setting in Brazil. This study conducted polysomnography recordings in the Baependi Heart Study, a cohort of Brazilian adults. Our sample included 584 women and 309 men whose apnea-hypopnea index was ≤15 events/h. We used splines to distinguish non-linear associations between age, total sleep time, wake after sleep onset (WASO), N2, N3, and rapid-eye-movement sleep. The mean (standard deviation; range) age was 47 (14; 18-89) years. All sleep outcomes were associated with age. Compared to men, women had more N3 sleep and less WASO after adjusting for age. Model-based comparisons between genders at specific ages showed statistically higher mean WASO for men at ages 60 (+13.6 min) and 70 years (+19.5 min) and less N3 for men at ages 50 (-13.2 min), 60 (-19.0 min), and 70 years (-19.5 min) but no differences at 20, 30, 40 or 80 years. The other sleep measures did not differ by gender at any age. Thus, even in the absence of moderate-severe OSA, sleep architecture was associated with age across adulthood, and there were gender differences in WASO and N3 at older ages in this rural community.

Altered sleep architecture in diabetes and prediabetes: findings from the Baependi Heart Study.

STUDY OBJECTIVES: People with diabetes and prediabetes are more likely to have sleep-disordered breathing (SDB), but few studies examined sleep architecture in people with diabetes or prediabetes in the absence of moderate-severe SDB, which was the aim of our cross-sectional study. METHODS: This cross-sectional sample is from the Baependi Heart Study, a family-based cohort of adults in Brazil. About 1074 participants underwent at-home polysomnography (PSG). Diabetes was defined as fasting glucose >125 mg/dL or HbA1c > 6.4 mmol/mol or taking diabetic medication, and prediabetes was defined as HbA1c ≥ 5.7 & <6.5 mmol/mol or fasting glucose ≥ 100 & ≤125 mg/dl. We excluded participants with an apnea-hypopnea index (AHI) ≥ 30 in primary analyses and ≥ 15 in secondary analysis. We compared sleep stages among the 3 diabetes groups (prediabetes, diabetes, neither). RESULTS: Compared to those without diabetes, we found shorter REM duration for participants with diabetes (-6.7 min, 95%CI -13.2, -0.1) and prediabetes (-5.9 min, 95%CI -10.5, -1.3), even after adjusting for age, gender, BMI, and AHI. Diabetes was also associated with lower total sleep time (-13.7 min, 95%CI -26.8, -0.6), longer slow-wave sleep (N3) duration (+7.6 min, 95%CI 0.6, 14.6) and higher N3 percentage (+2.4%, 95%CI 0.6, 4.2), compared to those without diabetes. Results were similar when restricting to AHI < 15. CONCLUSIONS: People with diabetes and prediabetes had less REM sleep than people without either condition. People with diabetes also had more N3 sleep. These results suggest that diabetes and prediabetes are associated with differences in sleep architecture, even in the absence of moderate-severe sleep apnea.

Altered sleep architecture in diabetes and prediabetes: findings from the Baependi Heart Study.

Objective: People with diabetes are more likely to have obstructive sleep apnea, but there are few studies examining sleep architecture in people with diabetes, especially in the absence of moderate-severe sleep apnea. Therefore, we compared sleep architecture among people with diabetes, prediabetes or neither condition, whilst excluding people with moderate-severe sleep apnea. Research design and methods: This sample is from the Baependi Heart Study, a prospective, family-based cohort of adults in Brazil. 1,074 participants underwent at-home polysomnography (PSG). Diabetes was defined as 1) FBG>125 OR 2) HbA1c>6.4 OR 3) taking diabetic medication, and prediabetes was defined as 1) [(5.7≤HbA1c≤6.4) OR (100≤FBG≤125)] AND 2) not taking diabetic medication. We excluded participants that had an apnea-hypopnea index (AHI)>30 from these analyses to reduce confounding due to severe sleep apnea. We compared sleep stages among the 3 groups. Results: Compared to those without diabetes, we found shorter REM duration for participants with diabetes (-6.7min, 95%CI -13.2, -0.1) or prediabetes (-5.9min, 95%CI -10.5, -1.3), even after adjusting for age, gender, BMI, and AHI. Diabetes was also associated with lower total sleep time (-13.7min, 95%CI -26.8, -0.6), longer slow-wave sleep (N3) duration (+7.6min, 95%CI 0.6, 14.6) and higher N3 percentage (+2.4%, 95%CI 0.6, 4.2), compared to those without diabetes. Conclusions: People with diabetes and prediabetes had less REM sleep after taking into account potential confounders, including AHI. People with diabetes also had more N3 sleep. These results suggest that diabetes is associated with different sleep architecture, even in the absence of moderate-severe sleep apnea.

Predicting depressive symptoms in middle-aged and elderly adults using sleep data and clinical health markers: A machine learning approach.

OBJECTIVES: Comorbid depression is a highly prevalent and debilitating condition in middle-aged and elderly adults, particularly when associated with obesity, diabetes, and sleep disturbances. In this context, there is a growing need to develop efficient screening methods for cases based on clinical health markers for these comorbidities and sleep data. Thus, our objective was to detect depressive symptoms in these subjects, considering general biomarkers of obesity and diabetes and variables related to sleep and physical exercise through a machine learning approach. METHODS: We used the National Health and Nutrition Examination Survey (NHANES) 2015-2016 data. Eighteen variables on self-reported physical activity, self-reported sleep habits, sleep disturbance indicative, anthropometric measurements, sociodemographic characteristics and plasma biomarkers of obesity and diabetes were selected as predictors. A total of 2907 middle-aged and elderly subjects were eligible for the study. Supervised learning algorithms such as Lasso penalized Logistic Regression (LR), Random Forest (RF) and Extreme Gradient Boosting (XGBoost) were implemented. RESULTS: XGBoost provided greater accuracy and precision (87%), with a proportion of hits in cases with depressive symptoms above 80%. In addition, daytime sleepiness was the most significant predictor variable for predicting depressive symptoms. CONCLUSIONS: Sleep and physical activity variables, in addition to obesity and diabetes biomarkers, together assume significant importance to predict, with accuracy and precision of 87%, the occurrence of depressive symptoms in middle-aged and elderly individuals.

Delayed circadian rhythms in older Africans living with human immunodeficiency virus (HIV).

The increasing number of people living with human immunodeficiency virus, HIV, (PLWH) have an elevated incidence of risk for noncommunicable comorbidities, the aetiology of which remains incompletely understood. While sleep disturbances are often reported in PLWH, it is unknown to what extent they relate to changes in the circadian and/or sleep homeostatic processes. We studied the relationship between sleep characteristics, circadian phase, and HIV status in older adults from the HAALSI (Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa) subsample of the Agincourt Health and Demographic Surveillance System in South Africa (n = 187, 36 human immunodeficiency virus positive [HIV+], age: 66.7 ± 11.5 years, range 45-93 years), where HIV prevalence is high and (in contrast to the global north) does not associate significantly with potentially confounding behavioural differences. In participants with valid actigraphy data (n = 172), regression analyses adjusted for age and sex indicated that HIV+ participants had slightly later sleep onset (ß = .16, p = .039), earlier sleep offset times (ß = -.16, p = .049) and shorter total sleep times (ß = -.20, p = .009) compared to the HIV negative (HIV-) participants. In a subset of participants (n = 51, 11 HIV+), we observed a later dim light melatonin onset (DLMO) in HIV+ (21:16 ± 01:47) than in HIV- (20:06 ± 00:58) participants (p = .006). This substantial difference remained when adjusted for age and sex (ß = 1.21; p = .006). In 36 participants (6 HIV+) with DLMO and actigraphy data, median phase angle of entrainment was -6 min in the HIV+ group and +1 h 25 min in the HIV- group. DLMO time correlated with sleep offset (ρ = 0.47, p = .005) but not sleep onset (ρ = -0.086, p = .623). Collectively, our data suggest that the sleep phase occurred earlier than what would be biologically optimal among the HIV+ participants. This is the first report of a mistimed circadian phase in PLWH, which has important potential implications for their health and well-being, especially given the well-established relationships between circadian asynchrony and sleep deprivation with poorer health outcomes.

Sleep disturbances in HIV infection and their biological basis.

Antiretroviral therapy has significantly reduced morbidity and mortality in people living with HIV (PLWH). However, a direct consequence of higher survival is the development of ageing-related co-morbidities that have considerable potential to affect quality of life. Sleep disturbances in PLWH are a significant source of morbidity. A meta-analysis has estimated the prevalence of self-reported sleep disturbances in PLWH to be 58%, with commonly identified disturbances including insomnia, obstructive sleep apnoea and poor sleep quality. Not only do sleep disturbances impair daytime functioning, but chronic sleep disruption also associates with metabolic dysregulation and cardiometabolic disease. Therefore, an understanding of the pathogenesis of sleep disturbances in PLWH is important for reducing morbidity and improving quality of life. Several pathophysiological processes in HIV infection may cause sleep-wake dysregulation. In early infection stages, immunological changes such as expression of sleep-promoting cytokines could mediate sleep disturbances. Long term, chronic immune activation, in addition to side effects of antiretroviral therapy, may impact sleep homeostasis more severely, for example through increasing the risk of obstructive sleep apnoea. These sleep disturbances may further contribute to an inflammatory state, due to the bi-directional relationship between sleep and immunity. In summary, further elucidating the link between HIV, immune activation, and sleep is an underexplored avenue for minimising population morbidity and mortality.

Subjective sleep quality before and during the COVID-19 pandemic in a Brazilian rural population.

OBJECTIVES: Prior studies have examined sleep during the coronavirus disease 2019 (COVID-19) pandemic, but have few compared sleep measured both during and prior to COVID. We examined the impact of the COVID-19 pandemic on subjective sleep quality in general and separately by gender and age (<50 vs. ≥50 years). Further, we compared sleep quality between those who did and did not follow quarantine orders. METHODS: This sample is from the Baependi Heart Study, a family-based cohort of adults in South-eastern Brazil. Longitudinal data were from 417 individuals who completed the Pittsburgh Sleep Quality Index (PSQI) twice: between January 2010 and September 2014 (pre-COVID) and during the COVID-19 stay-at-home order March-June, 2020. Cross-sectional analysis included 800 participants. RESULTS: Mean (±SD) PSQI scores were significantly higher during than before COVID-19 (5.7 ± 3.8 vs. 5.0 ± 3.3, p < .01). This increase was significant among women and among adults ≥50 years but not in men or younger adults. The significant increase in PSQI was only observed in those who quarantined during COVID-19 (5.9 ±3.7 vs. 5.2 ±3.4, p < .01) and not those who did not quarantine (5.0 ± 3.7 vs. 4.5 ± 3, p = .12). In cross-sectional analyses, individuals who quarantined had higher PSQI scores than nonquarantined individuals (6.1 ± 3.9 vs. 5.0 ± 3.5, p < .01). The quarantine status-dependent differences were significant for women (6.4 ± 4 vs. 5.2 ± 3.7, p < .01) and older adults (6.6 ± 0.1 vs. 5.5 ± 3.3, p = .04). Differences by quarantine status were attenuated after adjusting for age and gender. CONCLUSIONS: Subjective sleep quality declined during the COVID-19 pandemic, particularly among women, older adults, and those compliant to quarantine orders.

Compared Heritability of Chronotype Instruments in a Single Population Sample.

It is well established that the oldest chronotype questionnaire, the morningness-eveningness questionnaire (MEQ), has significant heritability, and several associations have been reported between MEQ score and polymorphisms in candidate clock genes, a number of them reproducibly across populations. By contrast, there are no reports of heritability and genetic associations for the Munich chronotype questionnaire (MCTQ). Recent genome-wide association studies (GWAS) from large cohorts have reported multiple associations with chronotype as assessed by a single self-evaluation question. We have taken advantage of the availability of data from all these instruments from a single sample of 597 participants from the Brazilian Baependi Heart Study. The family-based design of the cohort allowed us to calculate the heritability (h2) for these measures. Heritability values for the best-fitted models were 0.37 for MEQ, 0.32 for MCTQ, and 0.28 for single-question chronotype (MEQ Question 19). We also calculated the heritability for the two major factors recently derived from MEQ, "Dissipation of sleep pressure" (0.32) and "Build-up of sleep pressure" (0.28). This first heritability comparison of the major chronotype instruments in current use provides the first quantification of the genetic component of MCTQ score, supporting its future use in genetic analysis. Our findings also suggest that the single chronotype question that has been used for large GWAS analyses captures a larger proportion of the dimensions of chronotype than previously thought.

Associations between sleep disturbances, diabetes and mortality in the UK Biobank cohort: A prospective population-based study.

Non-communicable diseases, including diabetes, are partly responsible for the deceleration of improvements of life expectancy in many countries. Diabetes is also associated with sleep disturbances. Our aim was to determine whether sleep disturbances, particularly in people with diabetes, were associated with increased mortality risk. Data from the UK Biobank were analysed (n = 487,728, mean follow-up time = 8.9 years). The primary exposure was sleep disturbances, assessed through the question: Do you have trouble falling asleep at night or do you wake up in the middle of the night? The primary outcome was mortality. We also dichotomized sleep disturbances into "never/sometimes" versus "usually" (frequently), and combined with the presence/absence of diabetes: 24.2% of participants reported "never/rarely" experiencing sleep disturbances, 47.8% "sometimes" and 28.0% "usually". In age- and sex-adjusted models, frequent sleep disturbances were associated with an increased risk of all-cause mortality (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.26-1.37), which remained significant in the fully adjusted model (HR 1.13, 95% CI 1.09-1.18). The presence of both diabetes and frequent sleep disturbances was associated with greater risk of all-cause mortality than either condition alone. In the fully adjusted model, the hazard ratio for all-cause mortality was 1.11 (95% CI, 1.07-1.15) for frequent sleep disturbances alone, 1.67 (95% CI, 1.57-1.76) for diabetes alone and 1.87 for both (95% CI, 1.75-2.01). Frequent sleep disturbances (experienced by more than one quarter of the sample) were associated with increased risk of all-cause mortality. Mortality risk was highest in those with both diabetes and frequent sleep disturbances. Complaints of difficulty falling or staying asleep merit attention by physicians.

Impact of obstructive sleep apnea on cardiometabolic health in a random sample of older adults in rural South Africa: building the case for the treatment of sleep disorders in underresourced settings.

STUDY OBJECTIVES: The association between obstructive sleep apnea (OSA) and increased cardiometabolic risk (CMR) has been well documented in higher-income countries. However, OSA and its association with CMR have not yet been investigated, based on objective measures, in southern Africa. We measured polysomnography-derived sleep characteristics, OSA prevalence, and its association with cardiometabolic diseases in a rural, low-income, African-ancestry sample of older adult participants in South Africa. METHODS: Seventy-five participants completed the study. Body mass index, hypertension, diabetes, dyslipidemia, and HIV status were determined. A continuous CMR score was calculated using waist circumference, random glucose, high-density-lipoprotein cholesterol, triglycerides, and mean arterial blood pressure. Sleep architecture, arousal index, and apnea-hypopnea index for detection of the OSA (apnea-hypopnea index ≥ 15 events/h) were assessed by home-based polysomnography. Associations between CMR score and age, sex, socioeconomic status, apnea-hypopnea index, and total sleep time were investigated by multivariable analysis. RESULTS: In our sample (53 women, age 66.1 ± 10.7 years, 12 HIV+), 60.7% of participants were overweight/obese, 61.3% were hypertensive, and 29.3% had undiagnosed OSA. Being older (P = .02) and having a higher body mass index (P = .02) and higher waist circumference (P < .01) were associated with OSA. Apnea-hypopnea index severity (ß = 0.011; P = .01) and being a woman (ß = 0.369; P = .01) were independently associated with a higher CMR score in socioeconomic status- and age-adjusted analyses. CONCLUSIONS: In this South African community with older adults with obesity and hypertension, OSA prevalence is alarming and associated with CMR. We show the feasibility of detecting OSA in a rural setting using polysomnography. Our results highlight the necessity for actively promoting health education and systematic screening and treatment of OSA in this population to prevent future cardiovascular morbidity, especially among women.

Genomic perspectives on the circadian clock hypothesis of psychiatric disorders.

Circadian rhythm disturbances are frequently described in psychiatric disorders such as major depressive disorder, bipolar disorder, and schizophrenia. Growing evidence suggests a biological connection between mental health and circadian rhythmicity, including the circadian influence on brain function and mood and the requirement for circadian entrainment by external factors, which is often impaired in mental illness. Mental (as well as physical) health is also adversely affected by circadian misalignment. The marked interindividual differences in this combined susceptibility, in addition to the phenotypic spectrum in traits related both to circadian rhythms and mental health, suggested the possibility of a shared genetic background and that circadian clock genes may also be candidate genes for psychiatric disorders. This hypothesis was further strengthened by observations in animal models where clock genes had been knocked out or mutated. The introduction of genome-wide association studies (GWAS) enabled hypothesis-free testing. GWAS analysis of chronotype confirmed the prominent role of circadian genes in these phenotypes and their extensive polygenicity. However, in GWAS on psychiatric traits, only one clock gene, ARNTL (BMAL1) was identified as one of the few loci differentiating bipolar disorder from schizophrenia, and macaque monkeys where the ARNTL gene has been knocked out display symptoms similar to schizophrenia. Another lesson from genomic analyses is that chronotype has an important genetic correlation with several psychiatric disorders and that this effect is unidirectional. We conclude that the effect of circadian disturbances on psychiatric disorders probably relates to modulation of rhythm parameters and extend beyond the core clock genes themselves.

What are we measuring with the morningness-eveningness questionnaire? Exploratory factor analysis across four samples from two countries.

Individual variability in diurnal preference or chronotype is commonly assessed with self-report scales such as the widely used morningness-eveningness questionnaire (MEQ). We sought to investigate the MEQ's internal consistency by applying exploratory factor analysis (EFA) to determine the number of underlying latent factors in four different adult samples, two each from the United Kingdom and Brazil (total N = 3,457). We focused on factors that were apparent in all samples, irrespective of particular sociocultural diversity and geographical characteristics, so as to show a common core reproducible structure across samples. Results showed a three-factor solution with acceptable to good model fit indexes in all studied populations. Twelve of the 19 MEQ items in the three-correlated factor solution loaded onto the same factors across the four samples. This shows that the scale measures three distinguishable, yet correlated constructs: (1) items related to how people feel in the morning, which we termed efficiency of dissipation of sleep pressure (recovery process) (items 1, 3, 4, 5, 7, 9, 13, and 19); (2) items related to how people feel before sleep, which we called sensitivity to buildup of sleep pressure (items 2, 10, and 12); and (3) peak time of cognitive arousal (item 11). Although the third factor was not regarded as consistent since only one item was common among all samples, it might represent subjective amplitude. These results suggested that the latent constructs of the MEQ reflect dissociable homeostatic processes in addition to a less consistent propensity for cognitive arousal at different times of the day. By analyzing answers to MEQ items that compose these latent factors, it may be possible to extract further knowledge of factors that affect morningness-eveningness.

Association between light exposure and metabolic syndrome in a rural Brazilian town.

CONTEXT: Metabolic syndrome (MetS) is a complex condition comprising a 'clustering' of components representing cardiometabolic risk factors for heart disease and diabetes; its prevalence rate is high and consequences serious. Evidence suggests that light exposure patterns and misalignment of circadian rhythms might contribute to MetS etiology by impacting energy metabolism and glucose regulation. OBJECTIVE: We hypothesised that individuals with MetS would show disrupted circadian and sleep parameters alongside differences in light exposure profiles. We investigated this using data from a cohort study in Brazil. METHODS: Data from 103 individuals from the Baependi Heart Cohort Study aged between 50 and 70 were analysed. Motor activity and light exposure were measured using wrist-worn actigraphy devices. Cardiometabolic data were used to calculate the number of MetS components present in each participant, and participants grouped as MetS/non-MetS according to standard guidelines. Between-group comparisons were made for the actigraphy measures; additionally, correlation analyses were conducted. RESULTS: Motor activity and circadian profiles showed no differences between groups. However, the MetS group presented lower light exposure during the day and higher light exposure at night. Correlation analyses, including all participants, showed that greater daytime light exposure and greater light exposure difference between day and night were associated with reduced MetS risk (a lower number of MetS components). Also, the light exposure difference between day and night correlated with body mass index across all participants. CONCLUSIONS: The observed results suggest a direct association between light exposure and MetS which appears to not be attributable to disruptions in circadian activity rhythm nor to sleep parameters. This link between light exposure patterns and MetS risk could inform possible prevention strategies.

Early chronotype with advanced activity rhythms and dim light melatonin onset in a rural population.

Studying communities at different stages of urbanisation and industrialisation can teach us how timing and intensity of light affect the circadian clock under real-life conditions. We have previously described a strong tendency towards morningness in the Baependi Heart Study, located in a small rural town in Brazil. Here, we tested the hypothesis that this morningness tendency is associated with early circadian phase based on objective measurements (as determined by dim light melatonin onset, DLMO, and activity) and light exposure. We also analysed how well the previously collected chronotype questionnaire data were able to predict these DLMO values. The average DLMO observed in 73 participants (40 female) was 20:03 ± 01:21, SD, with an earlier average onset in men (19:38 ± 01:16) than in women (20:24 ± 01:21; P ≤ .01). However, men presented larger phase angle between DLMO and sleep onset time as measured by actigraphy (4.11 hours vs 3.16 hours; P ≤ .01). Correlational analysis indicated associations between light exposure, activity rhythms and DLMO, such that early DLMO was observed in participants with higher exposure to light, higher activity and earlier light exposure. The strongest significant predictor of DLMO was morningness-eveningness questionnaire (MEQ) (beta=-0.35, P ≤ .05), followed by age (beta = -0.47, P ≤ .01). Sex, light exposure and variables derived from the Munich chronotype questionnaire were not significant predictors. Our observations demonstrate that both early sleep patterns and earlier circadian phase have been retained in this small rural town in spite of availability of electrification, in contrast to metropolitan postindustrial areas.

Poor sleep quality and lipid profile in a rural cohort (The Baependi Heart Study).

AIM: To test the association between cardiometabolic risk factors and subjective sleep quality assessed by the Pittsburgh sleep quality index (PSQI), independent of obstructive sleep apnea (OSA) and sleep duration. METHODS: A total of 573 participants from the Baependi Heart Study, a rural cohort from Brazil, completed sleep questionnaires and underwent polygraphy for OSA evaluation. Multivariable linear regression analysis tested the association between cardiovascular risk factors (outcome variables) and sleep quality measured by PSQI, adjusting for OSA and other potential confounders (age, sex, race, salary/wage, education, marital status, alcohol intake, obesity, smoking, hypertension, and sleep duration). RESULTS: The sample mean age was 43 ± 16 years, 66% were female, and mean body mass index (BMI) was 26 ± 5 kg/m2. Only 20% were classified as obese (BMI ≥30). Overall, 50% of participants reported poor sleep quality as defined by a PSQI score ≥5. A high PSQI score was significantly associated with higher very-low-density lipoprotein (VLDL) cholesterol levels (beta = 0.392, p = 0.012) and higher triglyceride levels (beta = 0.017, p = 0.006), even after adjustments, including the apnea-hypopnea index. Further adjustments accounting for marital status, alcohol intake, and medication use did not change these findings. No significant association was observed between PSQI scores and glucose or blood pressure. According to PSQI components, sleep disturbances (beta = 1.976, p = 0.027), sleep medication use (beta = 1.121, p = 0.019), and daytime dysfunction (beta = 1.290, p = 0.024) were significantly associated with higher VLDL serum levels. Only the daytime dysfunction domain of the PSQI components was significantly associated with higher triglyceride levels (beta = 0.066, p = 0.004). CONCLUSION: Poorer lipid profile was independently associated with poor sleep quality, assessed by the PSQI questionnaire, regardless of a normal sleep duration and accounting for OSA and socio-economic status.

Casein Kinase 1 Underlies Temperature Compensation of Circadian Rhythms in Human Red Blood Cells.

Temperature compensation and period determination by casein kinase 1 (CK1) are conserved features of eukaryotic circadian rhythms, whereas the clock gene transcription factors that facilitate daily gene expression rhythms differ between phylogenetic kingdoms. Human red blood cells (RBCs) exhibit temperature-compensated circadian rhythms, which, because RBCs lack nuclei, must occur in the absence of a circadian transcription-translation feedback loop. We tested whether period determination and temperature compensation are dependent on CKs in RBCs. As with nucleated cell types, broad-spectrum kinase inhibition with staurosporine lengthened the period of the RBC clock at 37°C, with more specific inhibition of CK1 and CK2 also eliciting robust changes in circadian period. Strikingly, inhibition of CK1 abolished temperature compensation and increased the Q10 for the period of oscillation in RBCs, similar to observations in nucleated cells. This indicates that CK1 activity is essential for circadian rhythms irrespective of the presence or absence of clock gene expression cycles.

Associations between sleep parameters, non-communicable diseases, HIV status and medications in older, rural South Africans.

As part of the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI), we investigated sleep habits and their interactions with HIV or non-communicable diseases (NCDs) in 5059 participants (median age: 61, interquartile range: 52-71, 54% females). Self-reported sleep duration was 8.2 ± 1.6h, and bed and rise times were 20:48 ± 1:15 and 05:31 ± 1:05 respectively. Ratings of insufficient sleep were associated with older age, lack of formal education, unemployment, and obesity (p < 0.05). Ratings of restless sleep were associated with being older, female, having more education, being unemployed, and single. Hypertension was associated with shorter self-reported sleep duration, poor sleep quality, restless sleep, and periods of stopping breathing during the night (p < 0.05). HIV positive individuals not on antiretroviral treatment (ART) reported more nocturnal awakenings than those on ART (p = 0.029) and HIV negative individuals (p = 0.024), suggesting a negative net effect of untreated infection, but not of ART, on sleep quality. In this cohort, shorter, poor-quality sleep was associated with hypertension, but average self-reported sleep duration was longer than reported in other regions globally. It remains to be determined whether this is particular to this cohort, South Africa in general, or low- to middle-income countries undergoing transition.