Recommendations for measuring and standardizing light for laboratory mammals to improve welfare and reproducibility in animal research.

Light enables vision and exerts widespread effects on physiology and behavior, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in an appropriate physiological and behavioral state. Furthermore, proper consideration of light during experimentation is important both when it is explicitly employed as an independent variable and as a general feature of the environment. This Consensus View discusses metrics to use for the quantification of light appropriate for nonhuman mammals and their application to improve animal welfare and the quality of animal research. It provides methods for measuring these metrics, practical guidance for their implementation in husbandry and experimentation, and quantitative guidance on appropriate light exposure for laboratory mammals. The guidance provided has the potential to improve data quality and contribute to reduction and refinement, helping to ensure more ethical animal use.

Associations between light exposure and sleep timing and sleepiness while awake in a sample of UK adults in everyday life.

Experimental and interventional studies show that light can regulate sleep timing and sleepiness while awake by setting the phase of circadian rhythms and supporting alertness. The extent to which differences in light exposure explain variations in sleep and sleepiness within and between individuals in everyday life remains less clear. Here, we establish a method to address this deficit, incorporating an open-source wearable wrist-worn light logger (SpectraWear) and smartphone-based online data collection. We use it to simultaneously record longitudinal light exposure (in melanopic equivalent daylight illuminance), sleep timing, and subjective alertness over seven days in a convenience sample of 59 UK adults without externally imposed circadian challenge (e.g., shift work or jetlag). Participants reliably had strong daily rhythms in light exposure but frequently were exposed to less light during the daytime and more light in pre-bedtime and sleep episodes than recommended [T. M. Brown et al., PLoS Biol. 20, e3001571 (2022)]. Prior light exposure over several hours was associated with lower subjective sleepiness with, in particular, brighter light in the late sleep episode and after wake linked to reduced early morning sleepiness (sleep inertia). Higher pre-bedtime light exposure was associated with longer sleep onset latency. Early sleep timing was correlated with more reproducible and robust daily patterns of light exposure and higher daytime/lower night-time light exposure. Our study establishes a method for collecting longitudinal sleep and health/performance data in everyday life and provides evidence of associations between light exposure and important determinants of sleep health and performance.

Assessment of the validity and reliability of edinburgh postpartum depression scale in Turkish men.

OBJECTIVES: Perinatal depression (PD) affects individuals during pregnancy and early parenthood, resembling major depression. Recent research highlights paternal perinatal depression (PPD) in fathers. PPD has adverse effects on fathers and their children. This study assesses the Turkish version of the Edinburgh Postnatal Depression Scale (EPDS) for Turkish fathers, aiming to provide a tool for PPD identification. METHODS: This methodological study validates the EPDS for Turkish fathers and explores associations with demographic and psychosocial factors. The study involved 295 fathers with infants aged 2 weeks to 12 months. The EPDS, originally designed for perinatal depression and validated in Turkish women, was used. Fathers completed a participant information questionnaire, the EPDS, and the Beck Depression Inventory (BDI) during clinic visits. Data on sociodemographic factors, paternal roles, and pregnancy and postpartum support were collected. Mothers also completed the EPDS. Descriptive statistics, exploratory factor analysis, confirmatory factor analysis, and correlation tests were used. RESULTS: The study included fathers with an average age of 30.5 years, mostly with a high school education or higher. The EPDS had a mean total score of 3.1. Factor analysis suggested a three-factor structure for the EPDS in Turkish fathers, including anhedonia, anxiety, and depression. Confirmatory factor analysis validated the three-factor structure, with acceptable model fit indices. Positive correlations were found between fathers' EPDS scores, maternal EPDS scores, and paternal BDI scores. The EPDS effectively discriminated between different levels of depression severity. Various factors, such as education level and lack of support during pregnancy and after childbirth, were associated with higher EPDS scores. CONCLUSIONS: These findings emphasize the significance of assessing and addressing PPD in fathers, supporting the use of the EPDS as a valid tool in the Turkish context. The three-factor structure aligns with international research, highlighting the importance of a multi-dimensional approach to PPD assessment. Early intervention can mitigate PPD's impact on fathers, mothers, and children, benefiting mental health and well-being.

Longitudinal sleep efficiency in the elderly and its association with health.

The relationships between older age and sleep efficiency have traditionally been assessed using cross-sectional studies that ignore changes within individuals as they age. This research examines the determinants of sleep efficiency, the heterogeneity in an individual's sleep efficiency trajectory across a period of up to 27 years in later life and its associations with health. The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age cohort (n = 6,375; age 42-94 years) was used in this study. Depression and health data were collected using self-report validated instruments (Cornell Medical Index, Beck Depression Inventory and Geriatric Depression Scale). Longitudinal sleep and sociodemographic data were collected using a study-specific self-report questionnaire. A mixed-effect model was performed for sleep efficiency with adjustments for time-invariant and time-variant predictors. Latent class analysis was used to demonstrate subgroups of sleep efficiency trajectories and associations between sleep efficiency clusters and health history of the participants were investigated. Older adults have decreased sleep efficiency over time, with 18.6% decline between 40 and 100 years of age. Three sleep efficiency trajectory clusters were identified: high (32%), medium (50%) and low sleep efficiency (18%). Belonging to the high sleep efficiency cluster was associated with having lower prevalence of hypertension, circulatory problems, general arthritis, breathing problems and recurrent episodes of depression compared to the low efficiency cluster. Overall, ageing decreases sleep efficiency. However, there are detectable subgroups of sleep efficiency that are related to prevalence of different diseases.

Seasonality and season of birth effect in the UK Biobank cohort.

OBJECTIVES: Humans live in environments that reduce the impact of seasonal cues. However, studies suggest that many aspects of human biology, such as birth, metabolism, health, and death are still annually rhythmic. METHODS: Using UK Biobank, a large (N = 502 536) population-based resource, we investigated the influence of seasonality on birth rate, basal metabolic rate, health, reaction speed, and sleep. We also investigated the association between season of birth and regional brain volumes, basal metabolic rate, health, reaction speed, and sleep. RESULTS: Our results showed that annual birth rate peaks in April and May. Individuals had the highest basal metabolic rate in December and January. Poorer subjective general health and slower reaction time were observed in May. Susceptibility to insomnia showed an opposite trend that peaked in autumn and winter. People reported shorter periods of sleep, easier waking, earlier chronotype, more daytime dozing, and napping in summer compared with winter. Our results suggest that season of birth may influence later-life characteristics. We also observed that the effect of season of birth is in the opposite direction of the seasonal rhythm for basal metabolic rate, reaction time, and insomnia. Moreover, our analysis showed that prevalence of allergy is higher among people born in spring compared to autumn. CONCLUSIONS: Overall, our findings indicate a significant effect of seasonality on a range of human traits and that early-life seasons appear to have an effect on health and behaviors in adulthood.

A Wrist-Worn Internet of Things Sensor Node for Wearable Equivalent Daylight Illuminance Monitoring.

Light exposure is a vital regulator of physiology and behavior in humans. However, monitoring of light exposure is not included in current wearable Internet of Things (IoT) devices, and only recently have international standards defined [Formula: see text] -optic equivalent daylight illuminance (EDI) measures for how the eye responds to light. This article reports a wearable light sensor node that can be incorporated into the IoT to provide monitoring of EDI exposure in real-world settings. We present the system design, electronic performance testing, and accuracy of EDI measurements when compared to a calibrated spectral source. This includes consideration of the directional response of the sensor, and a comparison of performance when placed on different parts of the body, and a demonstration of practical use over 7 days. Our device operates for 3.5 days between charges, with a sampling period of 30 s. It has 10 channels of measurement, over the range 415-910 nm, balancing accuracy and cost considerations. Measured [Formula: see text]-opic EDI results for 13 devices show a mean absolute error of less than 0.07 log lx, and a minimum between device correlation of 0.99. These findings demonstrate that accurate light sensing is feasible, including at wrist worn locations. We provide an experimental platform for use in future investigations in real-world light exposure monitoring and IoT-based lighting control.

Depression in older adults and its associations with sleep and synaptic density.

BACKGROUND: Depression among older adults is a global concern, contributing to disability and overall illness burden. Understanding its trajectory, associated risk factors, and implications for mortality is essential for effective intervention. Moreover, the relationship between depression, sleep disturbances, and synaptic density in the ageing brain remains complex and poorly understood. METHODS: Using data from the University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age cohort, comprising 6375 participants, we conducted comprehensive assessments of depression trajectories using generalized linear mixed models and mortality risks using Cox mixed-effects models. Generalized structural equation modelling was performed to explore longitudinal associations between sleep duration and depression. Lastly, associations between post-mortem synaptic density and depression were investigated. RESULTS: Our findings revealed that depression rates declined until age 80 before increasing again. Depression was associated with a 10 % increased risk of mortality in older adults. Reduced sleep was correlated with depression, and depression measured early in the study predicted future reduced sleep. Post-mortem analysis showed a global reduction in synaptic density associated with depression, particularly pronounced in the frontal lobe. LIMITATIONS: Limitations include recall bias, limiting generalizability due to dominantly including White British participants and difficulty in establishing causation between synaptic density and depression. CONCLUSION: Our study underscores the significance of addressing depression in older adults, not only for mental health but also for mortality risk and neurobiological health. Early detection and intervention strategies are crucial for improving outcomes in elderly populations, potentially mitigating adverse effects on sleep, synaptic density, cognitive health, and longevity.

Light-Dark and Activity Rhythm Therapy (L-DART) to Improve Sleep in People with Schizophrenia Spectrum Disorders: A Single-Group Mixed Methods Study of Feasibility, Acceptability and Adherence.

People with a diagnosis of schizophrenia often have poor sleep, even when their psychotic symptoms are relatively well managed. This includes insomnia, sleep apnoea, hypersomnia, and irregular or non-24 h sleep-wake timing. Improving sleep would better support recovery, yet few evidence-based sleep treatments are offered to this group. This paper presents a mixed methods feasibility and acceptability study of Light-Dark and Activity Rhythm Therapy (L-DART). L-DART is delivered by an occupational therapist over 12 weeks. It is highly personalisable to sleep phenotypes and circumstances. Ten participants with schizophrenia spectrum diagnoses and sleep problems received L-DART; their sleep problems and therapy goals were diverse. We measured recruitment, attrition, session attendance, and adverse effects, and qualitatively explored acceptability, engagement, component delivery, adherence, activity patterns, dynamic light exposure, self-reported sleep, wellbeing, and functioning. Recruitment was ahead of target, there was no attrition, and all participants received the minimum 'dose' of sessions. Acceptability assessed via qualitative reports and satisfaction ratings was good. Adherence to individual intervention components varied, despite high participant motivation. All made some potentially helpful behaviour changes. Positive sleep and functioning outcomes were reported qualitatively as well as in outcome measures. The findings above support testing the intervention in a larger randomised trial ISRCTN11998005.

Education mediating the associations between early life factors and frailty: a cross-sectional study of the UK Biobank.

OBJECTIVES: Exposures in utero and during infancy may impact the development of diseases later in life. They may be linked with development of frailty, although the mechanism is unclear. This study aims to determine the associations between early life risk factors and development of frailty among middle-aged and older adults as well as potential pathways via education, for any observed association. DESIGN: A cross-sectional study. SETTINGS: This study used data from UK Biobank, a large population-based cohort. PARTICIPANTS: 502 489 individuals aged 37-73 years were included in the analysis. PRIMARY AND SECONDARY OUTCOME MEASURES: Early life factors in this study included being breast fed as a baby, maternal smoking, birth weight, the presence of perinatal diseases, birth month and birth place (in or outside the UK). We developed a frailty index comprising 49 deficits. We used generalised structural equation modelling to examine the associations between early life factors and development of frailty and whether any observed association was mediated via educational attainment. RESULTS: A history of breast feeding and normal birth weight were associated with a lower frailty index while maternal smoking, the occurrence of perinatal diseases and birth month with a longer day length were associated with a higher frailty index. Educational level mediated the relationship between these early life factors and frailty index. CONCLUSIONS: This study highlights that biological and social risk occurring at different stages of life are related to the variations in frailty index in later life and suggests opportunities for prevention across the life course.

The effect of season of birth on brain epigenome-wide DNA methylation of older adults.

Perinatal light exposure predisposes towards health and behaviour in adulthood. Season of birth is associated with psychiatric, allergic, cardiovascular and metabolic problems. It has been proposed that early-life environmental light disrupts the development of biological rhythms which, in turn, influence later-life health. However, the mechanisms linking perinatal seasonal light to later-life biological rhythm and health in humans are unknown. In this study, we investigated the association between season of birth and epigenome-wide DNA methylation of two postmortem human brain regions (16 hypothalamus, 14 temporal cortex). We did not find statistically significant differences at the whole epigenome level, either because we lacked statistical power or that no association exists. However, when we examined 24 CpG sites that had the highest significance or differential methylation, we identified regions which may be associated with circadian rhythm entrainment, cholinergic neurotransmission and neural development. Amongst methylation of the core clock genes, we identified that hypothalamus Neuronal PAS Domain Protein 2 (NPAS2) gene has hypermethylated regions in long photoperiod-born individuals. In addition, we found nominal associations between season of birth and genes linked to chronotype and narcolepsy. Season of birth-related brain DNA methylation profile was different than a previously reported blood methylation profile, suggesting a tissue-specific mechanism of perinatal light programming. Overall, we are the first to analyse the relationship between season of birth and human brain DNA methylation. Further studies with larger sample sizes are required to confirm an imprinting effect of perinatal light on the circadian clock.

Associations between chronotype and employment status in a longitudinal study of an elderly population.

Individuals with an 'evening' chronotype tend to sleep and wake later than people described to be 'morning' type if given a free choice. Since early awakening times, due to school and occupation, may be more challenging for those with evening chronotype, they are expected to be at greater risk of adverse health, occupational and educational outcomes. Our objectives are to investigate associations between chronotype and occupational, educational and health outcomes in a longitudinal cohort. We use sleep, sociodemographic and health data from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age, 1982 through 2010. The relationship between employment and longitudinal midsleep trajectories were estimated using linear mixed models. Associations between employment status and Cornell Medical Index, Beck Depression Inventory scores, cortisol concentrations at different times of the day stratified by chronotype were estimated using regression. The relationship between chronotype, occupational success, education, and cognition were also examined using regression methods. In older adults, compared to non-employed participants, employed participants get up 0.45 hours earlier. Evening-type employed individuals had earlier midsleep time compared to their non-employed counterparts and had abnormal longitudinal trajectories with an increasing trend as they aged. Employed individuals with evening chronotype had a higher risk of depression than employed morning-types. Moreover, employed individuals with evening chronotype had a higher cortisol concentration at 14:00 h than non-employed individuals. In addition, memory score was lower in individuals with morning chronotype, however processing speed was higher in individuals with morning chronotype compared to evening. Morning-types had a higher age when they finished full time education. Relative to evening-types, those with morning chronotype were 6.5% more likely to be in a job classed as professional or intermediate. Our findings suggest that evening-types are at a disadvantage with regards to occupational, educational and health outcomes in older adults due to their vulnerability to circadian and sleep disruption.

Brighter Time: A Smartphone App Recording Cognitive Task Performance and Illuminance in Everyday Life.

Light is an influential regulator of behavioural and physiological state in mammals. Features of cognitive performance such as memory, vigilance and alertness can be altered by bright light exposure under laboratory and field conditions. However, the importance of light as a regulator of performance in everyday life is hard to assess and has so far remained largely unclear. We set out to address this uncertainty by developing a tool to capture measures of cognitive performance and light exposure, at scale, and during everyday life. To this end, we generated an app (Brighter Time) which incorporated a psychomotor vigilance (PVT), an N-back and a visual search task with questionnaire-based assessments of demographic characteristics, general health, chronotype and sleep. The app also measured illuminance during task completion using the smartphone's intrinsic light meter. We undertook a pilot feasibility study of Brighter Time based on 91-week-long acquisition phases within a convenience sample (recruited by local advertisements and word of mouth) running Brighter Time on their own smartphones over two study phases in winter and summer. Study compliance was suitable (median = 20/21 requested task completions per subject). Statistically significant associations were observed between subjective sleepiness and performance in all tasks. Significant daily variations in PVT and visual search performance were also observed. Higher illuminance was associated with reduced reaction time and lower inverse efficiency score in the visual search. Brighter Time thus represents a viable option for large-scale collection of cognitive task data in everyday life, and is able to reveal associations between task performance and sleepiness, time of day and current illuminance. Brighter Time's utility could be extended to exploring associations with longer-term patterns of light exposure and/or other light metrics by integrating with wearable light meters.

Early life factors and COVID-19 infection in England: A prospective analysis of UK Biobank participants.

This study aims to examine whether maternal smoking, birth weight, birth month and breastfeeding are associated with COVID-19 infection and hospitalisation. Maternal smoking was positively associated with COVID-19 infection. Breastfeeding was negatively associated with COVID-19 infection. The odds of being hospitalised due to COVID-19 were higher among those who had lower birthweight and mothers who were smoking during pregnancy.

Interactions between season of birth, chronological age and genetic polymorphisms in determining later-life chronotype.

Human chronotype, the temporal pattern of daily behaviors, is influenced by postnatal seasonal programming and ageing. The aim of this study was to investigate genetic variants that are associated with season of birth programming and longitudinal chronotype change. Longitudinal sleep timing and genotype data from 1449 participants were collected for up to 27 years. Gene-environment interaction analysis was performed for 445 candidate single nucleotide polymorphisms that have previously been associated with chronotype. Associations were tested using linear mixed model. We identified 67 suggestively significant genomic loci that have genotype-ageing interaction and 25 genomic loci that may have genotype-season of birth interaction in determining chronotype. We attempted to replicate the results using longitudinal data of the UK Biobank from approximately 30,000 participants. Biological functions of these genes suggest that epigenetic regulation of gene expression and neural development may have roles in these processes. The strongest associated gene for sleep trajectories was ALKBH5, which has functions of DNA repair and epigenetic regulation. A potential candidate gene for postnatal seasonal programming was SIRT1, which has previously been implicated in postnatal programming, ageing and longevity. Genetic diversity may explain the heterogeneity in ageing-related change of sleep timing and postnatal environmental programming of later-life chronotype.

Epigenetic Regulation of BMAL1 with Sleep Disturbances and Alzheimer's Disease.

BACKGROUND: An early symptom of Alzheimer's disease (AD) is a disturbance of the circadian rhythm that is associated with disrupted sleep/wake cycles. OBJECTIVE: To investigate if BMAL1, a key gene that drives the circadian cycle, is epigenetically regulated in brains in relation to longitudinal changes in cognition, sleep quality, and AD neuropathology. METHODS: Frontal cortex tissues were acquired from the Manchester Brain Bank (N = 96). DNA methylation at six CpG sites at the promoter of BMAL1, determined using bisulfite pyrosequencing, was tested for associations with Braak stage, CERAD score and Thal phase, longitudinal changes in cognition, sleep measurements and cross-section measures of depressive symptoms (BDI score). RESULTS: Methylation across all the CpGs strongly correlated with each other. We found increased CpG2 methylation with higher Braak (t(92), p = 0.015) and CERAD (t(94), p = 0.044) stages. No significance was found between longitudinal fluid intelligence, processing speed and memory tests, but methylation at CpG1 (r = 0.20, p = 0.05) and CpG4 (r = 0.20, p = 0.05) positively correlated with vocabulary. CpG2 positively correlated with cross-sectional fluid intelligence (r = 0.20 p = 0.05) and vocabulary (r = 0.22 p = 0.03). Though longitudinal analysis revealed no significance between sleep duration, midsleep and efficiency for any of the CpG sites, CpG3 (B = 0.03, 95% CI, p = 0.03) and CpG5 (B = 0.04, 95% CI, p = 0.01) significantly correlated with night wake. CpG4 correlated with depressive symptoms (B = -0.27, 95% CI, p = 0.02). CONCLUSION: Methylation of BMAL1 associated with tau pathology, changes in cognitive measures, a measure of sleep and depressive symptoms, suggesting an involvement of the circadian cycle.

Longitudinal change of sleep timing: association between chronotype and longevity in older adults.

Evening-oriented sleep timing preferences have been associated with risk of diabetes, cardiovascular diseases, obesity, psychiatric disorders, and increased mortality. This research aims to explore the relationship between diurnal preferences (chronotype), daily habits, metabolic health, and mortality, using longitudinal data from The University of Manchester Longitudinal Study of Cognition in Normal Healthy Old Age (6375 participants at inception, recruited in the North of England) with a long follow-up period (up to 35.5 years). Mixed models were used to investigate the influence of aging, socio-demographic, and seasonal factors on sleep timing. Results show that sleep timing shifted towards earlier time with aging. Test seasons influence chronotype of older adults but working schedules challenge seasonality of sleep timing. Moreover, the season of birth may set chronotype in adulthood. Individual chronotype trajectories were clustered using latent class analysis and analyzed against metabolic health and mortality. We observed a higher risk of hypertension in the evening-type cluster compared to morning-type individuals (Odds ratio = 1.88, 95%CI = 1.02/3.47, p = .04). Evening-type cluster was also associated with traits related to lower health such as reduced sport participation, increased risk of depression and psychoticism personality, late eating, and increased smoking and alcohol usage. Finally, Cox regression of proportional hazards was used to study the effects of chronotype on longevity after adjusting for sleep duration, age, gender, smoking, alcohol usage, general health, and social class. The survival analysis (82.6% censored by death) revealed that evening-type chronotype increased the likelihood of mortality (Hazard ratio = 1.15, 95%CI = 1.04/1.26, p = .005). Taken together, chronotype is influenced by aging and seasonal effects. Evening-type preference may have detrimental outcomes for human well-being and longevity.