Publications by authors named "Christian Cajochen"

166 Publications

Should We Re-think Regulations and Standards for Lighting at Workplaces? A Practice Review on Existing Lighting Recommendations.

Front Psychiatry 2021 13;12:652161. Epub 2021 May 13.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Nowadays lighting projects often include temporal variations of the light, both spectrally and in terms of intensity to consider non-visual effects of light on people. However, as of today there are no specific regulations. Compliance with common lighting standards that address visual aspects of light, often means that only little non-visually effective light reaches the eye. In this practice review we confront existing regulations and standards on visual lighting aspects with new recommendations on non-visual aspects and highlight conflicts among them. We conclude with lighting recommendations that address both aspects.
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http://dx.doi.org/10.3389/fpsyt.2021.652161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155670PMC
May 2021

Regular Caffeine Intake Delays REM Sleep Promotion and Attenuates Sleep Quality in Healthy Men.

J Biol Rhythms 2021 08 23;36(4):384-394. Epub 2021 May 23.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Acute caffeine intake can attenuate homeostatic sleep pressure and worsen sleep quality. Caffeine intake-particularly in high doses and close to bedtime-may also affect circadian-regulated rapid eye movement (REM) sleep promotion, an important determinant of subjective sleep quality. However, it is not known whether such changes persist under chronic caffeine consumption during daytime. Twenty male caffeine consumers (26.4 ± 4 years old, habitual caffeine intake 478.1 ± 102.8 mg/day) participated in a double-blind crossover study. Each volunteer completed a caffeine (3 × 150 mg caffeine daily for 10 days), a withdrawal (3 × 150 mg caffeine for 8 days then placebo), and a placebo condition. After 10 days of controlled intake and a fixed sleep-wake cycle, we recorded electroencephalography for 8 h starting 5 h after habitual bedtime (i.e., start on average at 04:22 h which is around the peak of circadian REM sleep promotion). A 60-min evening nap preceded each sleep episode and reduced high sleep pressure levels. While total sleep time and sleep architecture did not significantly differ between the three conditions, REM sleep latency was longer after daily caffeine intake compared with both placebo and withdrawal. Moreover, the accumulation of REM sleep proportion was delayed, and volunteers reported more difficulties with awakening after sleep and feeling more tired upon wake-up in the caffeine condition compared with placebo. Our data indicate that besides acute intake, also regular daytime caffeine intake affects REM sleep regulation in men, such that it delays circadian REM sleep promotion when compared with placebo. Moreover, the observed caffeine-induced deterioration in the quality of awakening may suggest a potential motive to reinstate caffeine intake after sleep.
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http://dx.doi.org/10.1177/07487304211013995DOI Listing
August 2021

Age-related neuroendocrine and alerting responses to light.

Geroscience 2021 Feb 26. Epub 2021 Feb 26.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland.

Aging is associated with sleep and circadian alterations, which can negatively affect quality of life and longevity. Importantly, the age-related reduction in light sensitivity, particularly in the short-wavelength range, may underlie sleep and circadian alterations in older people. While evidence suggests that non-image-forming (NIF) light responses may diminish in older individuals, most laboratory studies have low sample sizes, use non-ecological light settings (e.g., monochromatic light), and typically focus on melatonin suppression by light. Here, we investigated whether NIF light effects on endogenous melatonin levels and sleep frontal slow-wave activity (primary outcomes), and subjective sleepiness and sustained attention (secondary outcomes) attenuate with aging. We conducted a stringently controlled within-subject study with 3 laboratory protocols separated by ~ 1 week in 31 young (18-30 years; 15 women) and 16 older individuals (55-80 years; eight women). Each protocol included 2 h of evening exposure to commercially available blue-enriched polychromatic light (6500 K) or non-blue-enriched light (3000 K or 2500 K) at low levels (~ 40 lx, habitual in evening indoor settings). Aging significantly affected the influence of light on endogenous melatonin levels, subjective sleepiness, sustained attention, and frontal slow-wave activity (interaction: P < 0.001, P = 0.004, P = 0.007, P = 0.001, respectively). In young individuals, light exposure at 6500 K significantly attenuated the increase in endogenous melatonin levels, improved subjective sleepiness and sustained attention performance, and decreased frontal slow-wave activity in the beginning of sleep. Conversely, older individuals did not exhibit signficant differential light sensitivity effects. Our findings provide evidence for an association of aging and reduced light sensitivity, with ramifications to sleep, cognition, and circadian health in older people.
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http://dx.doi.org/10.1007/s11357-021-00333-1DOI Listing
February 2021

The impact of daily caffeine intake on nighttime sleep in young adult men.

Sci Rep 2021 Feb 25;11(1):4668. Epub 2021 Feb 25.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Acute caffeine intake can delay sleep initiation and reduce sleep intensity, particularly when consumed in the evening. However, it is not clear whether these sleep disturbances disappear when caffeine is continuously consumed during daytime, which is common for most coffee drinkers. To address this question, we investigated the sleep of twenty male young habitual caffeine consumers during a double-blind, randomized, crossover study including three 10-day conditions: caffeine (3 × 150 mg caffeine daily), withdrawal (3 × 150 mg caffeine for 8 days, then switch to placebo), and placebo (3 × placebo daily). After 9 days of continuous treatment, electroencephalographically (EEG)-derived sleep structure and intensity were recorded during a scheduled 8-h nighttime sleep episode starting 8 (caffeine condition) and 15 h (withdrawal condition) after the last caffeine intake. Upon scheduled wake-up time, subjective sleep quality and caffeine withdrawal symptoms were assessed. Unexpectedly, neither polysomnography-derived total sleep time, sleep latency, sleep architecture nor subjective sleep quality differed among placebo, caffeine, and withdrawal conditions. Nevertheless, EEG power density in the sigma frequencies (12-16 Hz) during non-rapid eye movement sleep was reduced in both caffeine and withdrawal conditions when compared to placebo. These results indicate that daily caffeine intake in the morning and afternoon hours does not strongly impair nighttime sleep structure nor subjective sleep quality in healthy good sleepers who regularly consume caffeine. The reduced EEG power density in the sigma range might represent early signs of overnight withdrawal from the continuous presence of the stimulant during the day.
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http://dx.doi.org/10.1038/s41598-021-84088-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907384PMC
February 2021

Daily Caffeine Intake Induces Concentration-Dependent Medial Temporal Plasticity in Humans: A Multimodal Double-Blind Randomized Controlled Trial.

Cereb Cortex 2021 May;31(6):3096-3106

Centre for Chronobiology, University Psychiatric Clinics, University of Basel, 4002 Basel, Switzerland.

Caffeine is commonly used to combat high sleep pressure on a daily basis. However, interference with sleep-wake regulation could disturb neural homeostasis and insufficient sleep could lead to alterations in human gray matter. Hence, in this double-blind, randomized, cross-over study, we examined the impact of 10-day caffeine (3 × 150 mg/day) on human gray matter volumes (GMVs) and cerebral blood flow (CBF) by fMRI MP-RAGE and arterial spin-labeling sequences in 20 habitual caffeine consumers, compared with 10-day placebo (3 × 150 mg/day). Sleep pressure was quantified by electroencephalographic slow-wave activity (SWA) in the previous nighttime sleep. Nonparametric voxel-based analyses revealed a significant reduction in GMV in the medial temporal lobe (mTL) after 10 days of caffeine intake compared with 10 days of placebo, voxel-wisely adjusted for CBF considering the decreased perfusion after caffeine intake compared with placebo. Larger GMV reductions were associated with higher individual concentrations of caffeine and paraxanthine. Sleep SWA was, however, neither different between conditions nor associated with caffeine-induced GMV reductions. Therefore, the data do not suggest a link between sleep depth during daily caffeine intake and changes in brain morphology. In conclusion, daily caffeine intake might induce neural plasticity in the mTL depending on individual metabolic processes.
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http://dx.doi.org/10.1093/cercor/bhab005DOI Listing
May 2021

Verification-phase tests show low reliability and add little value in determining [Formula: see text]O2max in young trained adults.

PLoS One 2021 11;16(1):e0245306. Epub 2021 Jan 11.

Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland.

Objective: This study compared the robustness of a [Formula: see text]-plateau definition and a verification-phase protocol to day-to-day and diurnal variations in determining the true [Formula: see text]. Further, the additional value of a verification-phase was investigated.

Methods: Eighteen adults performed six cardiorespiratory fitness tests at six different times of the day (diurnal variation) as well as a seventh test at the same time the sixth test took place (day-to-day variation). A verification-phase was performed immediately after each test, with a stepwise increase in intensity to 50%, 70%, and 105% of the peak power output.

Results: Participants mean [Formula: see text] was 56 ± 8 mL/kg/min. Gwet's AC1 values (95% confidence intervals) for the day-to-day and diurnal variations were 0.64 (0.22, 1.00) and 0.71 (0.42, 0.99) for [Formula: see text]-plateau and for the verification-phase 0.69 (0.31, 1.00) and 0.07 (-0.38, 0.52), respectively. In 66% of the tests, performing the verification-phase added no value, while, in 32% and 2%, it added uncertain value and certain value, respectively, in the determination of [Formula: see text].

Conclusion: Compared to [Formula: see text]-plateau the verification-phase shows lower reliability, increases costs and only adds certain value in 2% of cases.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245306PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7799856PMC
May 2021

Changing color and intensity of LED lighting across the day impacts on circadian melatonin rhythms and sleep in healthy men.

J Pineal Res 2021 Apr 18;70(3):e12714. Epub 2021 Jan 18.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

We examined whether dynamically changing light across a scheduled 16-h waking day influences sleepiness, cognitive performance, visual comfort, melatonin secretion, and sleep under controlled laboratory conditions in healthy men. Fourteen participants underwent a 49-h laboratory protocol in a repeated-measures study design. They spent the first 5 hours in the evening under standard lighting, followed by an 8-h nocturnal sleep episode at habitual bedtimes. Thereafter, volunteers either woke up to static light or to a dynamic light that changed spectrum and intensity across the scheduled 16-h waking day. Following an 8-h nocturnal sleep episode, the volunteers spent another 11 hours either under static or dynamic light. Static light attenuated the evening rise in melatonin levels more compared to dynamic light as indexed by a significant reduction in the melatonin AUC prior to bedtime during static light only. Participants felt less vigilant in the evening during dynamic light. After dynamic light, sleep latency was significantly shorter in both the baseline and treatment night while sleep structure, sleep quality, cognitive performance, and visual comfort did not significantly differ. The study shows that dynamic changes in spectrum and intensity of light promote melatonin secretion and sleep initiation in healthy men.
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http://dx.doi.org/10.1111/jpi.12714DOI Listing
April 2021

Evidence That Homeostatic Sleep Regulation Depends on Ambient Lighting Conditions during Wakefulness.

Clocks Sleep 2019 Dec 11;1(4):517-531. Epub 2019 Dec 11.

Department of Psychiatry and Behavioral Sciences, Stanford University, Palo Alto, CA 94305, USA;

We examined whether ambient lighting conditions during extended wakefulness modulate the homeostatic response to sleep loss as indexed by. slow wave sleep (SWS) and electroencephalographic (EEG) slow-wave activity (SWA) in healthy young and older volunteers. Thirty-eight young and older participants underwent 40 hours of extended wakefulness [i.e., sleep deprivation (SD)] once under dim light (DL: 8 lux, 2800 K), and once under either white light (WL: 250 lux, 2800 K) or blue-enriched white light (BL: 250 lux, 9000 K) exposure. Subjective sleepiness was assessed hourly and polysomnography was quantified during the baseline night prior to the 40-h SD and during the subsequent recovery night. Both the young and older participants responded with a higher homeostatic sleep response to 40-h SD after WL and BL than after DL. This was indexed by a significantly faster intra-night accumulation of SWS and a significantly higher response in relative EEG SWA during the recovery night after WL and BL than after DL for both age groups. No significant differences were observed between the WL and BL condition for these two particular SWS and SWA measures. Subjective sleepiness ratings during the 40-h SD were significantly reduced under both WL and BL compared to DL, but were not significantly associated with markers of sleep homeostasis in both age groups. Our data indicate that not only the duration of prior wakefulness, but also the experienced illuminance during wakefulness affects homeostatic sleep regulation in humans. Thus, working extended hours under low illuminance may negatively impact subsequent sleep intensity in humans.
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http://dx.doi.org/10.3390/clockssleep1040040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7445844PMC
December 2019

Validation of an Automatic Arousal Detection Algorithm for Whole-Night Sleep EEG Recordings.

Clocks Sleep 2020 Sep 16;2(3):258-272. Epub 2020 Jul 16.

GIGA-Cyclotron Research Centre-In Vivo Imaging, University of Liège, Allée du 6 Août 8 B30, B-4000 Sart-Tilman, 4000 Liège, Belgium.

Arousals during sleep are transient accelerations of the EEG signal, considered to reflect sleep perturbations associated with poorer sleep quality. They are typically detected by visual inspection, which is time consuming, subjective, and prevents good comparability across scorers, studies and research centres. We developed a fully automatic algorithm which aims at detecting artefact and arousal events in whole-night EEG recordings, based on time-frequency analysis with adapted thresholds derived from individual data. We ran an automated detection of arousals over 35 sleep EEG recordings in healthy young and older individuals and compared it against human visual detection from two research centres with the aim to evaluate the algorithm performance. Comparison across human scorers revealed a high variability in the number of detected arousals, which was always lower than the number detected automatically. Despite indexing more events, automatic detection showed high agreement with human detection as reflected by its correlation with human raters and very good Cohen's kappa values. Finally, the sex of participants and sleep stage did not influence performance, while age may impact automatic detection, depending on the human rater considered as gold standard. We propose our freely available algorithm as a reliable and time-sparing alternative to visual detection of arousals.
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http://dx.doi.org/10.3390/clockssleep2030020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115937PMC
September 2020

Incidence of depression in relation to transportation noise exposure and noise annoyance in the SAPALDIA study.

Environ Int 2020 11 4;144:106014. Epub 2020 Aug 4.

Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland.

Prospective evidence on the risk of depression in relation to transportation noise exposure and noise annoyance is limited and mixed. We aimed to investigate the associations of long-term exposure to source-specific transportation noise and noise annoyance with incidence of depression in the SAPALDIA (Swiss cohort study on air pollution and lung and heart diseases in adults) cohort. We investigated 4,581 SAPALDIA participants without depression in the year 2001/2002. Corresponding one-year mean road, railway and aircraft day-evening-night noise (Lden) was calculated at the most exposed façade of the participants' residential floors, and transportation noise annoyance was assessed on an 11-point scale. Incident cases of depression were identified in 2010/2011, and comprised participants reporting physician diagnosis, intake of antidepressant medication or having a short form-36 mental health score < 50. We used robust Poisson regressions to estimate the mutually adjusted relative risks (RR) and 95% confidence intervals (CI) of depression, independent of traffic-related air pollution and other potential confounders. Incidence of depression was 11 cases per 1,000 person-years. In single exposure models, we observed positive but in part, statistically non-significant associations (per 10 dB) of road traffic Lden [RR: 1.06 (0.93, 1.22)] and aircraft Lden [RR: 1.19 (0.93, 1.53)], and (per 1-point difference) of noise annoyance [RR: 1.05 (1.02, 1.08)] with depression risk. In multi-exposure model, noise annoyance effect remained unchanged, with weaker effects of road traffic Lden [(RR: 1.02 (0.89, 1.17)] and aircraft Lden [(RR: 1.17 (0.90, 1.50)]. However, there were statistically significant indirect effects of road traffic Lden [(β: 0.02 (0.01, 0.03)] and aircraft Lden [β: 0.01 (0.002, 0.02)] via noise annoyance. There were no associations with railway Lden in the single and multi-exposure models [(RR: 0.88 (0.75, 1.03)]. We made similar findings among 2,885 non-movers, where the effect modification and cumulative risks were more distinct. Noise annoyance effect in non-movers was stronger among the insufficiently active (RR: 1.09; 95%CI: 1.02, 1.17; p = 0.07) and those with daytime sleepiness [RR: 1.07 (1.02, 1.12); p = 0.008]. Cumulative risks of Lden in non-movers showed additive tendencies for the linear cumulative risk [(RR: 1.31 (0.90, 1.91)] and the categorical cumulative risk [(RR: 2.29 (1.02, 5.14)], and remained stable to noise annoyance. Transportation noise level and noise annoyance may jointly and independently influence the risk of depression. Combined long-term exposures to noise level seems to be most detrimental, largely acting via annoyance. The moderation of noise annoyance effect by daytime sleepiness and physical activity further contribute to clarifying the involved mechanisms. More evidence is needed to confirm these findings for effective public health control of depression and noise exposure burden.
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http://dx.doi.org/10.1016/j.envint.2020.106014DOI Listing
November 2020

Effects of the COVID-19 lockdown on human sleep and rest-activity rhythms.

Curr Biol 2020 07 10;30(14):R795-R797. Epub 2020 Jun 10.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Wilhelm-Klein-Str. 27, CH-4002 Basel, Switzerland; Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, CH-4055 Basel, Switzerland.

In modern societies, human rest-activity rhythms and sleep result from the tensions and dynamics between the conflicting poles of external social time (e.g., work hours and leisure activities) and an individual's internal biological time. A mismatch between the two has been suggested to induce 'social jetlag' [1] and 'social sleep restriction', that is, shifts in sleep timing and differences in sleep duration between work days and free days. Social jetlag [2,3] and sleep restrictions [4] have repeatedly been associated with negative consequences on health, mental wellbeing, and performance. In a large-scale quasi-experimental design, we investigated the effects of the phase with the most rigorous COVID-19 restrictions on the relationship between social and biological rhythms as well as sleep during a six-week period (mid-March until end of April 2020) in three European societies (Austria, Germany, Switzerland). We found that, on one hand, the restrictions reduced the mismatch between external (social) and internal (biological) sleep-wake timing, as indexed by significant reductions in social jetlag and social sleep restriction, with a concomitant increase in sleep duration. Sleep quality on the other hand was slightly reduced. The improved individual sleep-wake timing can presumably be attributed to an increased flexibility of social schedules, for instance due to more work being accomplished from home. However, this unprecedented situation also led to a significant increase in self-perceived burden, which was attendant to the decrease in sleep quality. These adverse effects may be alleviated by exposure to natural daylight as well as physical exercise.
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http://dx.doi.org/10.1016/j.cub.2020.06.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7284244PMC
July 2020

The independent association of source-specific transportation noise exposure, noise annoyance and noise sensitivity with health-related quality of life.

Environ Int 2020 10 15;143:105960. Epub 2020 Jul 15.

Swiss Tropical and Public Health Institute, Basel, Switzerland; University of Basel, Basel, Switzerland. Electronic address:

Noise exposure is affecting health-related quality of life (HRQoL). There are many modelling approaches linking specific noise sources with single health-related outcomes. However, an integrated approach is missing taking into account measured levels as well as noise annoyance and sensitivity and assessing their independent association with HRQoL domains. Therefore, we investigated the predictive association of most common transportation noise sources (aircraft, railway and road traffic) as well as transportation noise annoyance and noise sensitivity with HRQoL using data from SAPALDIA (Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults). We assessed 2035 subjects, who participated in the second and third wave of SAPALDIA (3&4) and had complete information on exposure, outcome and covariates. At SAPALDIA3, we calculated annual means (Lden) of source-specific transportation noise exposure at the most exposed facade of participant's dwelling floor height. Participants reported noise annoyance on the widely used 11-point ICBEN scale and answered to 10 questions assessing individual noise sensitivity. To assess the potentially predictive effect of these noise exposures, HRQoL was assessed about 8 years later (SAPALDIA4) using the SF-36. We performed predictive multiple quantile regression models to elucidate associations of noise parameters measured at SAPALDIA3 with median SF-36 scores at SAPALDIA4. Source-specific transportation noise exposures showed few yet not consistent associations with HRQoL scores. We observed statistically significant negative associations of transportation noise annoyance with HRQoL scores covering mental health components (adjusted difference in SF-36 mental health score between highest vs. lowest annoyance tertile: -2.54 (95%CI: -3.89; -1.20). Noise sensitivity showed strongest and most consistent associations with HRQoL scores covering both general and mental health components (adjusted difference in SF-36 scores between highest vs. lowest sensitivity tertile: Mental health -5.96 (-7.57; -4.36); general health -5.16 (-7.08; -3.24)). Within all noise parameters, we predominantly observed negative associations of noise sensitivity with HRQoL attaining a magnitude of potential clinical relevance. This implies that factors other than transportation noise exposure may be relevant for this exposure-outcome relation. Nonetheless, transportation noise annoyance showed relevant associations with mental health components, indicating a negative association of transportation noise with HRQoL.
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http://dx.doi.org/10.1016/j.envint.2020.105960DOI Listing
October 2020

Genome-Wide DNA Methylation in Peripheral Blood and Long-Term Exposure to Source-Specific Transportation Noise and Air Pollution: The SAPALDIA Study.

Environ Health Perspect 2020 06 1;128(6):67003. Epub 2020 Jun 1.

Swiss Tropical and Public Health Institute, Basel, Switzerland.

Background: Few epigenome-wide association studies (EWAS) on air pollutants exist, and none have been done on transportation noise exposures, which also contribute to environmental burden of disease.

Objective: We performed mutually independent EWAS on transportation noise and air pollution exposures.

Methods: We used data from two time points of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) from 1,389 participants contributing 2,542 observations. We applied multiexposure linear mixed-effects regressions with participant-level random intercept to identify significant Cytosine-phosphate-Guanine (CpG) sites and differentially methylated regions (DMRs) in relation to 1-y average aircraft, railway, and road traffic day-evening-night noise (Lden); nitrogen dioxide (); and particulate matter (PM) with aerodynamic diameter (). We performed candidate (CpG-based; cross-systemic phenotypes, combined into "allostatic load") and agnostic (DMR-based) pathway enrichment tests, and replicated previously reported air pollution EWAS signals.

Results: We found no statistically significant CpGs at false discovery rate . However, 14, 48, 183, 8, and 71 DMRs independently associated with aircraft, railway, and road traffic Lden; ; and , respectively, with minimally overlapping signals. Transportation Lden and air pollutants tendentially associated with decreased and increased methylation, respectively. We observed significant enrichment of candidate DNA methylation related to C-reactive protein and body mass index (aircraft, road traffic Lden, and ), renal function and "allostatic load" (all exposures). Agnostic functional networks related to cellular immunity, gene expression, cell growth/proliferation, cardiovascular, auditory, embryonic, and neurological systems development were enriched. We replicated increased methylation in cg08500171 () and decreased methylation in cg17629796 ().

Conclusions: Mutually independent DNA methylation was associated with source-specific transportation noise and air pollution exposures, with distinct and shared enrichments for pathways related to inflammation, cellular development, and immune responses. These findings contribute in clarifying the pathways linking these exposures and age-related diseases but need further confirmation in the context of mediation analyses. https://doi.org/10.1289/EHP6174.
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http://dx.doi.org/10.1289/EHP6174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7263738PMC
June 2020

Study protocol for a prospective randomised double-blind placebo-controlled clinical trial investigating a Better Outcome with Melatonin compared to Placebo Administered to normalize sleep-wake cycle and treat hypoactive ICU Delirium: the Basel BOMP-AID study.

BMJ Open 2020 04 30;10(4):e034873. Epub 2020 Apr 30.

Intensive Care Unit, University Hospital Basel, Basel, Switzerland.

Introduction: Delirium is frequently observed in the intensive care unit (ICU) population, in particular. Until today, there is no evidence for any reliable pharmacological intervention to treat delirium. The Basel BOMP-AID (etter utcome with elatonin compared to lacebo dministered to normalize sleep-wake cycle and treat hypoactive CU elirium) randomised trial targets improvement of hypoactive delirium therapy in critically ill patients and will be conducted as a counterpart to the Basel ProDex Study (Study Protocol, BMJ Open, July 2017) on hyperactive and mixed delirium. The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin administered at night restores a normal circadian rhythm, and that restoration of a normal circadian rhythm will cure delirium.

Methods And Analysis: The Basel BOMP-AID study is an investigator-initiated, single-centre, randomised controlled clinical trial for the treatment of hypoactive delirium with the once daily oral administration of melatonin 4 mg versus placebo in 190 critically ill patients. The primary outcome measure is delirium duration in 8-hour shifts. Secondary outcome measures include delirium-free days and death at 28 days after study inclusion, number of ventilator days, length of ICU and hospital stay, and sleep quality. Patients will be followed after 3 and 12 months for activities of daily living and mortality assessment. Sample size was calculated to demonstrate superiority of melatonin compared with placebo regarding the duration of delirium. Results will be presented using an intention-to-treat approach.

Ethics And Dissemination: This study has been approved by the Ethics Committee of Northwestern and Central Switzerland and will be conducted in compliance with the protocol, the current version of the Declaration of Helsinki, the International Conference on Harmonisation (ICH) of technical requirements for registration of pharmaceuticals for human use; Good Clinical Practice (GCP) or ISO EN 14155 (as far as applicable), as well as all national legal and regulatory requirements. Study results will be presented in international conferences and published in a peer-reviewed journal.

Trial Registration Number: NCT03438526.

Protocol Version: Clinical Study Protocol Version 3, 10.03.2019.
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http://dx.doi.org/10.1136/bmjopen-2019-034873DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7213885PMC
April 2020

Intraocular cataract lens replacement and light exposure potentially impact procedural learning in older adults.

J Sleep Res 2021 04 14;30(2):e13043. Epub 2020 Apr 14.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland.

Procedural learning declines with age and appropriately timed light exposure can improve cognitive performance in older individuals. Because cataract reduces light transmission and is associated with cognitive decline in older adults, we explored whether lens replacement (intraocular blue-blocking [BB] or UV-only blocking) in older patients with cataracts enhances the beneficial effects of light on procedural learning. Healthy older participants (n = 16) and older patients with post-cataract surgery (n = 13 with BB or UV lens replacement) underwent a randomized within-subject crossover laboratory design with three protocols. In each protocol, 3.5 hr dim-dark adaptation was followed by 2 hr evening blue-enriched (6,500K) or non-blue-enriched light exposure (3,000K or 2,500K), 30 min dim post-light, ~8 hr sleep and 2 hr morning dim light. Procedural learning was assessed by the alternating serial reaction time task (ASRT), as part of a larger test battery. Here, ASRT performance was indexed by type of trial (random or sequence) and sequence-specific (high or low probability) measures. During evening light exposure, we observed a significant effect of the interaction of "group" versus "light condition" on the type of trial (p = .04; p = .16; unadjusted and adjusted p-values, respectively) and sequence-specific learning (p = .04; p = .16; unadjusted and adjusted p-values, respectively), whereby patients with UV lens replacement performed better than patients with BB lens or non-cataract controls, during blue-enriched light exposure. Lens replacement in patients with cataracts may potentially be associated with beneficial effects of blue light on procedural learning. Thus, optimizing spectral lens transmission in patients with cataracts may help improve specific aspects of cognitive function, such as procedural learning.
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http://dx.doi.org/10.1111/jsr.13043DOI Listing
April 2021

Ultradian modulation of cortical arousals during sleep: effects of age and exposure to nighttime transportation noise.

Sleep 2020 07;43(7)

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

Study Objectives: The present study aimed at assessing the temporal non-rapid eye movement (NREM) EEG arousal distribution within and across sleep cycles and its modifications with aging and nighttime transportation noise exposure, factors that typically increase the incidence of EEG arousals.

Methods: Twenty-six young (19-33 years, 12 women) and 16 older (52-70 years, 8 women) healthy volunteers underwent a 6-day polysomnographic laboratory study. Participants spent two noise-free nights and four transportation noise exposure nights, two with continuous and two characterized by eventful noise (average sound levels of 45 dB, maximum sound levels between 50 and 62 dB for eventful noise). Generalized mixed models were used to model the time course of EEG arousal rates during NREM sleep and included cycle, age, and noise as independent variables.

Results: Arousal rate variation within NREM sleep cycles was best described by a u-shaped course with variations across cycles. Older participants had higher overall arousal rates than the younger individuals with differences for the first and the fourth cycle depending on the age group. During eventful noise nights, overall arousal rates were increased compared to noise-free nights. Additional analyses suggested that the arousal rate time course was partially mediated by slow wave sleep (SWS).

Conclusions: The characteristic u-shaped arousal rate time course indicates phases of reduced physiological sleep stability both at the beginning and end of NREM cycles. Small effects on the overall arousal rate by eventful noise exposure suggest a preserved physiological within- and across-cycle arousal evolution with noise exposure, while aging affected the shape depending on the cycle.
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http://dx.doi.org/10.1093/sleep/zsz324DOI Listing
July 2020

Transportation noise impairs cardiovascular function without altering sleep: The importance of autonomic arousals.

Environ Res 2020 03 30;182:109086. Epub 2019 Dec 30.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Switzerland; Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Switzerland. Electronic address:

Aims: Chronic exposure to nocturnal transportation noise has been linked to cardiovascular disorders with sleep impairment as the main mediator. Here we examined whether nocturnal transportation noise affects the main stress pathways, and whether it relates to changes in the macro and micro structure of sleep.

Methods And Results: Twenty-six young healthy participants (12 women, 24.6 ± 0.7 years, mean ± SE) spent five consecutive 24-h days and one last morning in the laboratory. The first (baseline) and last (recovery) nights comprised a quiet ambient scenario. In-between, four different noise scenarios (low/medium/high intermittent road or rail scenarios with an identical equivalent continuous sound level of 45 dB) were randomly presented during the 8-h nights. Participants felt more annoyed from the transportation noise scenarios compared to the quiet ambient scenario played back during the baseline and recovery nights (F = 10.2, p < 0.001). Nocturnal transportation noise did not significantly impact polysomnographically assessed sleep macrostructure, blood pressure, nocturnal catecholamine levels and morning cytokine levels. Evening cortisol levels increased after sleeping with highly intermittent road noise compared to baseline (p = 0.002, noise effect: F = 4.0, p = 0.005), a result related to increased cumulative duration of autonomic arousals during the noise nights (F = 3.4, p < 0.001; correlation: r = 0.64, p = 0.006).

Conclusion: Under controlled laboratory conditions, highly intermittent nocturnal road noise exposure at 45 dB increased the cumulative duration of autonomic arousals during sleep and next-day evening cortisol levels. Our results indicate that, without impairing sleep macrostructure, nocturnal transportation noise of 45 dB is a physiological stressor that affects the hypothalamic-pituitary-adrenal axis during the following day in healthy young good sleepers.
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http://dx.doi.org/10.1016/j.envres.2019.109086DOI Listing
March 2020

Polysomnographic features of pregnancy: A systematic review.

Sleep Med Rev 2020 04 5;50:101249. Epub 2019 Dec 5.

Sleep and Epilepsy Center, Neurocenter of Southern Switzerland, Civic Hospital of Lugano (EOC), Via Tesserete 46, Lugano, CH-6903, Switzerland.

Symptoms of sleep disturbances are common among pregnant women and generally worsen across gestation. Pregnancy-related sleep disorders are not only associated with a poor quality of life of the affected mothers, but also with adverse perinatal outcomes, including perinatal depression, gestational diabetes, preeclampsia, and preterm birth. The current knowledge about the impact of sleep disorders during pregnancy largely derives from the results of sleep surveys conducted in various populations. However, the number of studies examining changes in objective sleep variables during pregnancy via polysomnography has progressively increased in recent years. Here we systematically reviewed the polysomnographic studies available in the literature with the aim to describe the sleep pattern and to identify possible markers of sleep disruption in pregnant women. Based on our analysis, subjective worsening of sleep quality across gestation is related to objective changes in sleep macrostructure, which become particularly evident in the third trimester. Pregnancy per se does not represent an independent risk factor for developing major polysomnography-assessed sleep disorders in otherwise healthy women. However, in women presenting predisposing factors, such as obesity or hypertension, physiological changes occurring during pregnancy may contribute to the onset of pathological conditions, especially sleep-disordered breathing, which must be carefully considered.
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http://dx.doi.org/10.1016/j.smrv.2019.101249DOI Listing
April 2020

Caffeine-dependent changes of sleep-wake regulation: Evidence for adaptation after repeated intake.

Prog Neuropsychopharmacol Biol Psychiatry 2020 04 19;99:109851. Epub 2019 Dec 19.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland; Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland.

Background: Circadian and sleep-homeostatic mechanisms regulate timing and quality of wakefulness. To enhance wakefulness, daily consumption of caffeine in the morning and afternoon is highly common. However, the effects of such a regular intake pattern on circadian sleep-wake regulation are unknown. Thus, we investigated if daily daytime caffeine intake and caffeine withdrawal affect circadian rhythms and wake-promotion in habitual consumers.

Methods: Twenty male young volunteers participated in a randomised, double-blind, within-subject study with three conditions: i) caffeine (150 mg 3 x daily for 10 days), ii) placebo (3 x daily for 10 days) and iii) withdrawal (150 mg caffeine 3 x daily for eight days, followed by a switch to placebo for two days). Starting on day nine of treatment, salivary melatonin and cortisol, evening nap sleep as well as sleepiness and vigilance performance throughout day and night were quantified during 43 h in an in-laboratory, light and posture-controlled protocol.

Results: Neither the time course of melatonin (i.e. onset, amplitude or area under the curve) nor the time course of cortisol was significantly affected by caffeine or withdrawal. During withdrawal, however, volunteers reported increased sleepiness, showed more attentional lapses as well as polysomnography-derived markers of elevated sleep propensity in the late evening compared to both the placebo and caffeine condition.

Conclusions: The typical pattern of caffeine intake with consumption in both the morning and afternoon hours may not necessarily result in a circadian phase shift in the evening nor lead to clear-cut benefits in alertness. The time-of-day independent effects of caffeine withdrawal on evening nap sleep, sleepiness and performance suggest an adaptation to the substance, presumably in the homeostatic aspect of sleep-wake regulation.
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http://dx.doi.org/10.1016/j.pnpbp.2019.109851DOI Listing
April 2020

No evidence for an S cone contribution to acute neuroendocrine and alerting responses to light.

Curr Biol 2019 12;29(24):R1297-R1298

Centre for Chronobiology, Psychiatric Hospital of the University of Basel (UPK), 4002 Basel, Switzerland; Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, 4002 Basel, Switzerland.

Exposure to even moderately bright short-wavelength light in the evening can strongly suppress the production of melatonin and delay our circadian rhythm. These effects are mediated by the retinohypothalamic pathway, connecting a subset of retinal ganglion cells to the circadian pacemaker in the suprachiasmatic nucleus (SCN) in the brain. These retinal ganglion cells express the photosensitive protein melanopsin, rendering them intrinsically photosensitive (ipRGCs). But ipRGCs also receive input from the classical photoreceptors - the cones and rods. Here, in human participants, we examined whether the short-wavelength-sensitive (S) cones contribute to the neuroendocrine response to light by using stimuli which differed exclusively in the amount of S cone excitation by almost two orders of magnitude (ratio 1:83), but not in the excitation of long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cones, rods, and melanopsin. We specifically examined the S cones since the previously published action spectra for melatonin suppression [1,2] pointed to a possible role of S cones in addition to melanopsin. We find no evidence for a role of S cones in the acute alerting and melatonin-supressing response to evening light exposure.
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http://dx.doi.org/10.1016/j.cub.2019.11.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6926470PMC
December 2019

Visual and non-visual properties of filters manipulating short-wavelength light.

Ophthalmic Physiol Opt 2019 11;39(6):459-468

Centre for Chronobiology, Psychiatric Hospital of the University of Basel (UPK), Basel, Switzerland.

Purpose: Optical filters and tints manipulating short-wavelength light (sometimes called 'blue-blocking' or 'blue-attenuating' filters) are used in the management of a range of ocular, retinal, neurological and psychiatric disorders. In many cases, the only available quantification of the optical effects of a given optical filter is the spectral transmittance, which specifies the amount of light transmitted as a function of wavelength.

Methods: We propose a novel physiologically relevant and retinally referenced framework for quantifying the visual and non-visual effects of these filters, incorporating the attenuation of luminance (luminous transmittance), the attenuation of melanopsin activation (melanopsin transmittance), the colour shift, and the reduction of the colour gamut (gamut reduction). Using these criteria, we examined a novel database of spectral transmittance functions of optical filters (n = 121) which were digitally extracted from a variety of sources.

Results: We find a large diversity in the alteration of visual and non-visual properties. The spectral transmittance properties of the examined filters vary widely, in terms of shapes and cut-off wavelengths. All filters show relatively more melanopsin attenuation than luminance attenuation (lower melanopsin transmittance than luminous transmittance). Across the data set, we find that melanopsin transmittance and luminous transmittance are correlated.

Conclusions: We suggest that future studies and examinations of the physiological effects of optical filters quantify the visual and non-visual effects of the filters beyond the spectral transmittance, which will eventually aid in developing a mechanistic understanding of how different filters affect physiology. We strongly discourage comparing the downstream effects of different filters on, e.g. sleep or circadian responses, without considering their effects on the retinal stimulus.
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http://dx.doi.org/10.1111/opo.12648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887545PMC
November 2019

Self-Reported Sleep Disturbance from Road, Rail and Aircraft Noise: Exposure-Response Relationships and Effect Modifiers in the SiRENE Study.

Int J Environ Res Public Health 2019 10 29;16(21). Epub 2019 Oct 29.

Empa, Swiss Federal Laboratories for Materials Science and Technology, 8600 Dübendorf, Switzerland.

This survey investigates the cross-sectional association between nighttime road, rail and aircraft noise exposure and the probability to be highly sleep disturbed (%HSD), as measured by self-report in postal and online questionnaires. As part of the Swiss SiRENE study, a total of 5592 survey participants in the entire country were selected based on a stratified random sample of their dwelling. Self-reported sleep disturbance was measured using an ICBEN-style 5-point verbal scale. The survey was carried out in four waves at different times of the year. Source-specific noise exposure was calculated for several façade points for each dwelling. After adjustment for potential confounders, all three noise sources showed a statistically significant association between the nighttime noise level LNight at the most exposed façade point and the probability to report high sleep disturbance, as determined by logistic regression. The association was strongest for aircraft noise and weakest for road traffic noise. We a priori studied the role of a range of effect modifiers, including the "eventfulness" of noise exposure, expressed as the Intermittency Ratio (IR) metric, bedroom window position, bedroom orientation towards the closest street, access to a quiet side of the dwelling, degree of urbanization, sleep timing factors (bedtime and sleep duration), sleep medication intake, survey season and night air temperature. While bedroom orientation exhibited a strong moderating effect, with an Leq-equivalent of nearly 20 dB if the bedroom faces away from the nearest street, the LNight-%HSD associations were not affected by bedroom window position, sleep timing factors, survey season, or temperature.
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http://dx.doi.org/10.3390/ijerph16214186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861974PMC
October 2019

Associations of Various Nighttime Noise Exposure Indicators with Objective Sleep Efficiency and Self-Reported Sleep Quality: A Field Study.

Int J Environ Res Public Health 2019 10 9;16(20). Epub 2019 Oct 9.

Empa, Laboratory for Acoustics/Noise Control, Swiss Federal Laboratories for Materials Science and Technology, 8600 Dübendorf, Switzerland.

It is unclear which noise exposure time window and noise characteristics during nighttime are most detrimental for sleep quality in real-life settings. We conducted a field study with 105 volunteers wearing a wrist actimeter to record their sleep during seven days, together with concurrent outdoor noise measurements at their bedroom window. Actimetry-recorded sleep latency increased by 5.6 min (95% confidence interval (CI): 1.6 to 9.6 min) per 10 dB(A) increase in noise exposure during the first hour after bedtime. Actimetry-assessed sleep efficiency was significantly reduced by 2%-3% per 10 dB(A) increase in measured outdoor noise (L) for the last three hours of sleep. For self-reported sleepiness, noise exposure during the last hour prior to wake-up was most crucial, with an increase in the sleepiness score of 0.31 units (95% CI: 0.08 to 0.54) per 10 dB(A) L. Associations for estimated indoor noise were not more pronounced than for outdoor noise. Taking noise events into consideration in addition to equivalent sound pressure levels (L) only marginally improved the statistical models. Our study provides evidence that matching the nighttime noise exposure time window to the individual's diurnal sleep-wake pattern results in a better estimate of detrimental nighttime noise effects on sleep. We found that noise exposure at the beginning and the end of the sleep is most crucial for sleep quality.
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http://dx.doi.org/10.3390/ijerph16203790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6843841PMC
October 2019

Diurnal and day-to-day variations in isometric and isokinetic strength.

Chronobiol Int 2019 11 2;36(11):1537-1549. Epub 2019 Sep 2.

Department of Sport, Exercise and Health, Faculty of Medicine, University of Basel , Basel , Switzerland.

Time-of-day effects in strength performance have been extensively investigated due to their relevance in competitive sports. However, most studies use large measurement intervals making it difficult to monitor potential performance changes throughout the day. Furthermore, previous studies have exclusively focused on how the time of day affects strength on a group level and ignored the individual differences in the times of peak performance. Therefore, the main purpose of this study was to investigate the diurnal and day-to-day variations in isometric and isokinetic leg, arm and trunk strength over six different times of the day. Following a familiarization test, 19 trained males (age: 24.1 ± 2.5 years) performed isometric and isokinetic strength assessments at six different times of the day (7:00, 10:00, 13:00, 16:00, 19:00, and 21:00) with an isokinetic dynamometer. An eighth test session was performed at the same time of the day as the seventh test session to investigate the day-to-day variations and the difference between diurnal and day-to-day variations were compared. All tests were separated by at least 48 h. The start time for the first session was randomized. The mean maximum isometric leg strength was 5.85 ± 0.80 N.kg and 4.99 ± 0.78 N.kgat the peak and at the nadir of the day, respectively. The mean difference (95% CI) was 0.86 ± 0.47 N.kg (0.62; 1.10) for the diurnal variation and 0.30 ± 0.42 N.kg (0.09; 0.52) for the day-to-day variation. The mean maximum isometric arm strength was 1.68 ± 0.33 N.kg at the peak and 1.46 ± 0.19 N.kg at the nadir of the day, respectively. The mean difference (95% CI) was 0.21 ± 0.16 N.kg (0.14; 0.29) for the diurnal variation and 0.06 ± 0.05 N.kg (0.03; 0.08) for the day-to-day variation. The linear mixed-effects model showed little evidence for differences in isometric leg strength between the different times of the day (all -values >0.983). The present study demonstrated that diurnal variations in leg and arm strength are nearly three times higher than the day-to-day variations, but there was only little evidence for a time-of-day effect on a group level. The diurnal variations observed herein without time-of-day effects are suggestive that individuals achieve their peak performance at different times of the day. Therefore, performance tests should be carried out at the same time of the day to ensure comparability. Furthermore, depending on the difference between the time of competition and the time of peak performance, as well as the individual magnitude in diurnal variation, some athletes can have a clear disadvantage.: 95% CI, 95% confidence interval; SD, standard deviation; ICC, intraclass correlation coefficient.
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http://dx.doi.org/10.1080/07420528.2019.1658596DOI Listing
November 2019

Author Correction: Human brain patterns underlying vigilant attention: impact of sleep debt, circadian phase and attentional engagement.

Sci Rep 2019 Aug 22;9(1):12379. Epub 2019 Aug 22.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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http://dx.doi.org/10.1038/s41598-019-48856-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6704152PMC
August 2019

Binocular facilitation in light-mediated melatonin suppression?

J Pineal Res 2019 Nov 22;67(4):e12602. Epub 2019 Aug 22.

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Basel, Switzerland.

In humans, the production of melatonin is suppressed by light exposure. This effect is mediated by a retinal pathway involving the melanopsin-containing intrinsincally photosensitive retinal ganglion cells (ipRGCs), which exhibit maximum sensitivity to short-wavelength light. Here, based on extant and published data, we examine how signals from the two eyes are integrated in driving the suppression of melatonin by light. We find that melatonin suppression by light exposure to two eyes corresponds to a sensitivity shift by about 1.2 log units (factor ~17.4).
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http://dx.doi.org/10.1111/jpi.12602DOI Listing
November 2019

Social Jetlag and Chronotypes in the Chinese Population: Analysis of Data Recorded by Wearable Devices.

J Med Internet Res 2019 05 11;21(6):e13482. Epub 2019 May 11.

Center for Sleep Medicine, Sleep Research and Epileptology, Clinic Barmelweid AG, Barmelweid, Switzerland.

Background: Chronotype is the propensity for a person to sleep at a particular time during 24 hours. It is largely regulated by the circadian clock but constrained by work obligations to a specific sleep schedule. The discrepancy between biological and social time can be described as social jetlag (SJL), which is highly prevalent in modern society and associated with health problems. SJL and chronotypes have been widely studied in Western countries but have never been described in China.

Objective: We characterized the chronotypes and SJL in mainland China objectively by analyzing a database of Chinese sleep-wake pattern recorded by up-to-date wearable devices.

Methods: We analyzed 71,176 anonymous Chinese people who were continuously recorded by wearable devices for at least one week between April and July in 2017. Chronotypes were assessed (N=49,573) by the adjusted mid-point of sleep on free days (MSFsc). Early, intermediate, and late chronotypes were defined by arbitrary cut-offs of MSFsc <3 hours, between 3-5 hours, and >5 hours. In all subjects, SJL was calculated as the difference between mid-points of sleep on free days and work days. The correlations between SJL and age/body mass index/MSFsc were assessed by Pearson correlation. Random forest was used to characterize which factors (ie, age, body mass index, sex, nocturnal and daytime sleep durations, and exercise) mostly contribute to SJL and MSFsc.

Results: The mean total sleep duration of this Chinese sample is about 7 hours, with females sleeping on average 17 minutes longer than males. People taking longer naps sleep less during the night, but they have longer total 24-hour sleep durations. MSFsc follows a normal distribution, and the percentages of early, intermediate, and late chronotypes are approximately 26.76% (13,266/49,573), 58.59% (29,045/49,573), and 14.64% (7257/49,573). Adolescents are later types compared to adults. Age is the most important predictor of MSFsc suggested by our random forest model (relative feature importance: 0.772). No gender differences are found in chronotypes. We found that SJL follows a normal distribution and 17.07% (12,151/71,176) of Chinese have SJL longer than 1 hour. Nearly a third (22,442/71,176, 31.53%) of Chinese have SJL<0. The results showed that 53.72% (7127/13,266), 25.46% (7396/29,045), and 12.71% (922/7257) of the early, intermediate, and late chronotypes have SJL<0, respectively. SJL correlates with MSFsc (r=0.54, P<.001) but not with body mass index (r=0.004, P=.30). Random forest model suggests that age, nocturnal sleep, and daytime nap durations are the features contributing to SJL (their relative feature importance is 0.441, 0.349, and 0.204, respectively).

Conclusions: Our data suggest a higher proportion of early compared to late chronotypes in Chinese. Chinese have less SJL than the results reported in European populations, and more than half of the early chronotypes have negative SJL. In the Chinese population, SJL is not associated with body mass index. People of later chronotypes and long sleepers suffer more from SJL.
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http://dx.doi.org/10.2196/13482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595939PMC
May 2019

Characterization of the sleep disorder of anti-IgLON5 disease.

Sleep 2019 09;42(9)

Neurology Service, Hospital Clínic of Barcelona, Barcelona, Spain.

Study Objective: To characterize the sleep disorder of anti-IgLON5 disease.

Methods: We reviewed 27 video-polysomnographies (V-PSG), 6 multiple sleep latency tests (MSLT), 2 videsomnoscopies with dexmedetomidine, and 10 actigraphies recorded during the disease course of five patients. Due to severe sleep architecture abnormalities, we used a novel modified sleep scoring system combining conventional stages with a descriptive approach in which two additional stages were identified: undifferentiated-NREM (UN-NREM) and poorly structured N2 (P-SN2) sleep that were characterized by abnormal motor activation and absence or sparse elements of conventional NREM sleep.

Results: Sleep-related vocalizations, movements, behaviors, and respiratory abnormalities were reported by bed-partners. In all patients, NREM sleep onset and sleep reentering after an awakening occurred as UN-NREM (median: 29.8% of total sleep time [TST]) and P-SN2 sleep (14.5% TST) associated with vocalizations and simple and quasi-purposeful movements. Sleep initiation was normalized in one patient with a high dose of steroids, but NREM sleep abnormalities reappeared in subsequent V-PSG. In all patients, if sleep continued uninterrupted, there was a progressive normalization with normal N2 (11.7% TST) and N3 (22.3% TST) sleep but stridor and obstructive apnea emerged. REM sleep behavior disorder (RBD) occurred in four patients. Sleep initiation was also altered in MSLT and dexmedetomidine-induced sleep. Actigraphy showed a 10-fold increase of nocturnal activity compared with controls. Sleep abnormalities remained stable during the disease.

Conclusions: The sleep disorder of anti-IgLON5 disease presents as a complex sleep pattern characterized by abnormal sleep initiation with undifferentiated NREM sleep, RBD, periods of normal NREM sleep, stridor, and obstructive apnea.
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http://dx.doi.org/10.1093/sleep/zsz133DOI Listing
September 2019

Association of Intraocular Cataract Lens Replacement With Circadian Rhythms, Cognitive Function, and Sleep in Older Adults.

JAMA Ophthalmol 2019 Aug;137(8):878-885

Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland.

Importance: Cataract is associated with a progressive decline in light transmission due to the clouding and yellowing of the natural crystalline lens. While the downstream effects of aging lenses include long-term disruption of circadian rhythms, cognitive function, and sleep regulation, it remains unknown whether there is an association of intraocular cataract lens (IOLs) replacement with circadian rhythms, cognition, and sleep.

Objective: To test whether IOL replacement (blue blocking [BB] or ultraviolet [UV] only blocking) in older patients with previous cataract is associated with the beneficial light effects on the circadian system, cognition, and sleep regulation.

Design, Setting, And Participants: Cross-sectional study at the Centre for Chronobiology, University of Basel in Switzerland from February 2012 to April 2014, analyzed between June 2012 and September 2018. Sixteen healthy older controls and 13 patients with previous cataract and IOL replacement participated without medication and no medical and sleep comorbidities.

Exposures: Three and a half hours of prior light control (dim-dark adaptation), followed by 2 hours of evening blue-enriched (6500 K) or non-blue-enriched light exposure (3000 K and 2500 K), 30 minutes in dim post-light exposure, 8 hours of sleep opportunity, and 2 hours of morning dim light following sleep.

Main Outcomes And Measures: Salivary melatonin, cognitive tests, and sleep structure and electroencephalographic activity to test the association of IOLs with markers of circadian rhythmicity, cognitive performance, and sleep regulation, respectively.

Results: The participants included 16 healthy older controls with a mean (standard error of the mean [SEM]) of 63.6 (5.6) years; 8 women and 13 patients with previous cataract (mean [SEM] age, 69.9 [5.2] years; 10 women); 5 patients had UV IOLs and 8 had BB IOLs. Patients with previous cataract and IOLs had an attenuated increase in melatonin levels during light exposure (mean [SEM] increase in the BB group: 23.3% [2.6%] and in the UV lens group: 19.1% [2.1%]) than controls (mean [SEM] increase, 48.8% [5.2%]) (difference between means, 27.7; 95% CI, 15.4%-41.7%; P < .001). Cognitive function, indexed by sustained attention performance, was improved in patients with UV lens (mean [SEM], 276.9 [11.1] milliseconds) compared with patients with BB lens (mean [SEM], 348.3 [17.8] milliseconds) (difference between means, 71.4; 95% CI, 29.5%-113.1%; P = .002) during light exposure and in the morning after sleep. Patients with UV lens had increased slow-wave sleep (mean [SEM] increase, 13% [3.4%]) compared with controls (mean [SEM] increase, 5.2% [0.8%]) (percentage of total sleep time; difference between means, 7.9; 95% CI, 2.4%-13.4%; P = .02) and frontal non-rapid eye movement slow-wave activity (0.75-4.5 Hz) during the first sleep cycle (mean [SEM], 79.9 [13.6] μV2/Hz) compared with patients with BB lens (mean [SEM], 53.2 [10.7] μV2/Hz) (difference between means, 26.7; 95% CI, 9.2-48.9; P = .03).

Conclusions And Relevance: These in-laboratory empirical findings suggest that optimizing the spectral lens transmission in patients with previous cataract may minimize the adverse age-related effects on circadian rhythms, cognition, and sleep.
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http://dx.doi.org/10.1001/jamaophthalmol.2019.1406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547224PMC
August 2019

In Athletes, the Diurnal Variations in Maximum Oxygen Uptake Are More Than Twice as Large as the Day-to-Day Variations.

Front Physiol 2019 18;10:219. Epub 2019 Mar 18.

Department of Sport, Exercise and Health, Faculty of Medicine, University of Basel, Basel, Switzerland.

In competitive sports any substantial individual differences in diurnal variations in maximal performance are highly relevant. Previous studies have exclusively focused on how the time of day affects performance and disregarded the maximal individual diurnal variation of performance. Thus, the aims of this study were (1) to investigate the maximum diurnal variation in maximum oxygen uptake (VOmax), (2) to compare the diurnal variation of VOmax during the day to the day-to-day variation in VOmax, and (3) to investigate if there is a time-of-day effect on VOmax. Ten male and seven female athletes (mean VOmax: 58.2 ± 6.9 ml/kg/min) performed six maximal cardiopulmonary exercise tests including a verification-phase at six different times of the day (i.e., diurnal variation) and a seventh test at the same time the sixth test took place (i.e., day-to-day variation). The test times were 7:00, 10:00, 13:00, 16:00, 19:00, and 21:00. The order of exercise tests was the same for all participants to ensure sufficient recovery but the time of day of the first exercise test was randomized. We used paired -tests to compare the nadir and peak of diurnal variations, day-to-day variations and the difference between diurnal and day-to-day variations. The mean difference in VOmax was 5.0 ± 1.9 ml/kg/min (95% CI: 4.1, 6.0) for the diurnal variation and 2.0 ± 1.0 ml/kg/min (95% CI: 1.5, 2.5) for the day-to-day variation. The diurnal variation was significantly higher than the day-to-day variation with a mean difference of 3.0 ± 2.1 ml/kg/min (95% CI: 1.9, 4.1). The linear mixed effects model revealed no significant differences in VOmax for any pairwise comparison between the different times of the day (all > 0.11). This absence of a time-of-day effect is explained by the fact that peak VOmax was achieved at different times of the day by different athletes. The diurnal variations have meaningful implications for competitive sports and need to be considered by athletes. However, the results are also relevant to research. To increase signal-to-noise-ratio in intervention studies it is necessary to conduct cardiopulmonary exercise testing at the same time of the day for pre- and post-intervention exercise tests.
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http://dx.doi.org/10.3389/fphys.2019.00219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6431663PMC
March 2019
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