Background: Professional athletes navigate a multitude of unique challenges associated to sport-specific factors (e.g., training, travel and competition) and non-sport factors (e.g., performance... Show moreBackground: Professional athletes navigate a multitude of unique challenges associated to sport-specific factors (e.g., training, travel and competition) and non-sport factors (e.g., performance pressure, stress and anxiety) that can interfere with healthy sleep behaviors. Sleep plays a key role in proper biopsychosocial development as well as short- and long-term biological, physical, psychological, and cognitive health. As poor sleep quality is known to impair proper brain function, this study aimed to investigate the effect of sleep quality on a professional athlete's ability to train, recover, and perform, as well as their overall emotional and physical well-being. Methods: A cohort study was performed in 40 professional male cricket athletes from the Dutch national cricket team (mean age 26.5 ± 5.1 years). The athletes were monitored across a 22 weeks in-season training period. Sleep quality and overall emotional and physical well-being were assessed using daily sleep diaries and questionnaires which scored the readiness to train, stress levels, fatigue, muscle soreness and flu symptoms respectively. Quality of sleep and subsequent association with the consecutive elements of the well-being questionnaire were assessed through statistical using the student t-test and clinical differences with the methodology of Osoba and colleagues: 20% “very much change”. Results: The results demonstrated that the professional athletes assessed their sleep quality as average with a mean score of 3.4 out of 5. Lower perceived quality of sleep (<75th percentile) was correlated with a decreased readiness to train (mean score 3.2 [IQR: 3.0–4.0] vs. 3.5 [IQR: 3.0–5.0]; P < 0.001) and increased extent of muscle soreness (2.7 [IQR: 2.0–3.0] vs. 2.3 [IQR: 2–3]; P < 0.001), stress level (mean score 2.3 [IQR: 2.0–3.0] vs. 1.9 [IQR: 1.0–2.0]; P < 0.001) and perceived fatigue (mean score 2.9 [IQR: 2.0–3.0] vs. 2.3 [IQR: 2.0–3.0]; P < 0.001). Likewise, in patients with lower perceived quality of sleep, the proportion of players presenting with flu symptoms increased over 4-fold (4.1% vs. 17%; P < 0.001). Show less
Acute effects of exogenous melatonin have been widely reported to promote sleep or induce drowsiness in human. However, testing of the hypnotic effects of melatonin in nocturnal rodents has... Show moreAcute effects of exogenous melatonin have been widely reported to promote sleep or induce drowsiness in human. However, testing of the hypnotic effects of melatonin in nocturnal rodents has yielded contradictory results. The latter may be associated with differences in concentration, lighting conditions, time of administration of melatonin, and possibly the type of analysis. In this study, electroencephalogram (EEG) and electromyogram were recorded in pigmented male Brown Norway rats under both light-dark (LD) and constant dark (DD) conditions. Melatonin was administered intraperitoneally at a moderate dose of 3 mg/kg, at either 1 h after lights on under LD condition or 1 h after the activity offset under DD condition. The dosage is known to be able to entrain nocturnal rodents in DD conditions, but does not change sleep in rodents in LD. Only the rats under DD conditions showed a significant reduction in nonrapid eye movement (NREM) sleep latency, while the NREM sleep power spectrum remained unaffected. Under LD condition, melatonin did not alter NREM and rapid eye movement (REM) sleep latency, and had only minor effects on the NREM sleep EEG. Regardless of lighting conditions, melatonin administration resulted in less, but longer episodes for all vigilance states suggesting increased vigilance state consolidation. In the discussion, we compare our results with a summary of previously published data concerning the hypnotic effects of melatonin in polysomnographic/EEG-confirmed sleep in humans and nocturnal rodents. In conclusion, the hypnotic effect of exogenous melatonin in nocturnal rodents not only depends on the time of day, and concentration, but is also influenced by the lighting conditions. Regardless of inducing sleep or not, melatonin may consolidate sleep and through that enhance sleep quality. Show less
Wang, Y.M.; Melgers, M.; Meijer, J.H.; Deboer, T. 2023
Ketamine is known for its antidepressant effects, but the mechanism underlying this effect remains largely unclear. In contrast to most antidepressant drugs, the action of ketamine is rapid,... Show moreKetamine is known for its antidepressant effects, but the mechanism underlying this effect remains largely unclear. In contrast to most antidepressant drugs, the action of ketamine is rapid, suggesting a different mode of action. A rapid antidepressant effect is also observed following sleep deprivation (SD). In the present study, we aimed to evaluate the effect of a 6-h SD and acute ketamine treatment on vigilance states, locomotor activity, and electroencephalogram (EEG) power density spectra in Brown Norway rats under constant condition over 2 recording days. After SD and after the initial waking period induced by ketamine, both treatments induced a similar increase in non-rapid eye movement (NREM) sleep and EEG slow-wave activity (SWA) in NREM sleep. Rapid eye movement (REM) sleep was reduced immediately after both treatments but was recovered later only after the SD. The effects on the waking EEG differed between the treatments, with a faster theta peak during and after SD, and no change in the waking spectrum after ketamine. In conclusion, SD and ketamine both lead to an acute increment in NREM sleep SWA as well as in a reduction in REM sleep. The results suggest that selective suppression of REM sleep, combined with enhancement of SWA during NREM may be effective in the treatment of depression. Show less
Wolters, F.; Middendorp, H. van; Bergh, O. van den; Biermasz, N.R.; Meijer, O.C.; Evers, A.W.M. 2023
Background: The hormone cortisol plays important roles in human circadian and stress physiology and is an interesting target for interventions. Cortisol varies not only in response to stress but... Show moreBackground: The hormone cortisol plays important roles in human circadian and stress physiology and is an interesting target for interventions. Cortisol varies not only in response to stress but also as part of a diurnal rhythm. It shows a particularly sharp increase immediately after awakening, the cortisol awakening response (CAR). Cortisol can be affected by medication, but it is less clear whether it can also be affected by learning. Animal studies have consistently shown that cortisol can be affected by pharmacological conditioning, but the results in humans have been mixed. Other studies have suggested that conditioning is also possible during sleep and that the diurnal rhythm can be conditioned, but these findings have not yet been applied to cortisol conditioning. Objective: The objective of our study was to introduce a novel avenue for conditioning cortisol: by using the CAR as an unconditioned response and using scent conditioning while the participant is asleep. This study investigates an innovative way to study the effects of conditioning on cortisol and the diurnal rhythm, using a variety of devices and measures to make measurement possible at a distance and at unusual moments. Methods: The study protocol takes 2 weeks and is performed from the participant's home. Measures in week 1 are taken to reflect the CAR and waking under baseline conditions. For the first 3 nights of week 2, participants are exposed to a scent from 30 minutes before awakening until their normal time of awakening to allow the scent to become associated with the CAR. On the final night, participants are forced to wake 4 hours earlier, when cortisol levels are normally low, and either the same (conditioned group) or a different (control group) scent is presented half an hour before this new time. This allows us to test whether cortisol levels are higher after the same scent is presented. The primary outcome is the CAR, assessed by saliva cortisol levels, 0, 15, 30, and 45 minutes after awakening. The secondary outcomes are heart rate variability, actigraphy measures taken during sleep, and self-reported mood after awakening. To perform manipulations and measurements, this study uses wearable devices, 2 smartphone apps, web-based questionnaires, and a programmed scent device. Results: We completed data collection as of December 24, 2021. Conclusions: This study can provide new insights into learning effects on cortisol and the diurnal rhythm. If the procedure does affect the CAR and associated measures, it also has potential clinical implications in the treatment of sleep and stress disorders. Trial Registration: Netherlands Trial Register NL58792.058.16; https://trialsearch.who.int/Trial2.aspx?TrialID=NL7791 International Registered Report Identifier (IRRID): DERR1-10.2196/38087 Show less
Sleep/wake alterations are predominant in neurological and neuropsychiatric disorders involving dopamine dysfunction. Unfortunately, specific, mechanisms-based therapies for these debilitating... Show moreSleep/wake alterations are predominant in neurological and neuropsychiatric disorders involving dopamine dysfunction. Unfortunately, specific, mechanisms-based therapies for these debilitating sleep problems are currently lacking. The pathophysiological mechanisms of sleep/wake alterations within a hypodopaminergic MitoPark mouse model of Parkinson's disease (PD) are investigated. MitoPark mice replicate most PD-related sleep alterations, including sleep fragmentation, hypersomnia, and daytime sleepiness. Surprisingly, these alterations are not accounted for by a dysfunction in the circadian or homeostatic regulatory processes of sleep, nor by acute masking effects of light or darkness. Rather, the sleep phenotype is linked with the impairment of instrumental arousal and sleep modulation by behavioral valence. These alterations correlate with changes in high-theta (8-11.5 Hz) electroencephalogram power density during motivationally-charged wakefulness. These results demonstrate that sleep/wake alterations induced by dopamine dysfunction are mediated by impaired modulation of sleep by motivational valence and provide translational insights into sleep problems associated with disorders linked to dopamine dysfunction. Show less
Sleep/wake alterations are predominant in neurological and neuropsychiatric disorders involving dopamine dysfunction. Unfortunately, specific, mechanisms-based therapies for these debilitating... Show moreSleep/wake alterations are predominant in neurological and neuropsychiatric disorders involving dopamine dysfunction. Unfortunately, specific, mechanisms-based therapies for these debilitating sleep problems are currently lacking. The pathophysiological mechanisms of sleep/wake alterations within a hypodopaminergic MitoPark mouse model of Parkinson's disease (PD) are investigated. MitoPark mice replicate most PD-related sleep alterations, including sleep fragmentation, hypersomnia, and daytime sleepiness. Surprisingly, these alterations are not accounted for by a dysfunction in the circadian or homeostatic regulatory processes of sleep, nor by acute masking effects of light or darkness. Rather, the sleep phenotype is linked with the impairment of instrumental arousal and sleep modulation by behavioral valence. These alterations correlate with changes in high-theta (8–11.5 Hz) electroencephalogram power density during motivationally-charged wakefulness. These results demonstrate that sleep/wake alterations induced by dopamine dysfunction are mediated by impaired modulation of sleep by motivational valence and provide translational insights into sleep problems associated with disorders linked to dopamine dysfunction. Show less
Morwani Mangnani, J.; Giannos, P.; Belzer, C.; Beekman, M.; Slagboom, P.E.; Prokopidis, K. 2022
Major hallmarks of functional loss, loss of metabolic and musculoskeletal health and (multi)morbidity with aging are associated with sleep disturbances. With poor sleep shifts in gut microbial... Show moreMajor hallmarks of functional loss, loss of metabolic and musculoskeletal health and (multi)morbidity with aging are associated with sleep disturbances. With poor sleep shifts in gut microbial composition commonly manifest, which could mediate the pro-inflammatory state between sleep disturbances and sarcopenia. This systematic review presents the recent evidence on how sleep disturbances throughout the lifespan associate with and contribute to gut microbial composition changes, proposing a mechanism to understand the etiology of sarcopenia through sleep disturbances. The relationship between disturbed sleep and clinically relevant gut microbiota composition on health aspects of aging is discussed. A search was performed in PubMed, Cochrane Library, Scopus, Web of Science using keywords including (microbio* OR microflora) AND (sleep OR sleep disorder). Six cross-sectional population-based studies and five experimental clinical trials investigating healthy individuals with ages ranging from 4 to 71 were included. The cross-sectional studies reported similarities in associations with sleep disturbance and gut microbial diversity. In older adults, shorter sleep duration is associated with an increase in pro-inflammatory bacteria whereas increasing sleep quality is positively associated with an increase of beneficial Verrucomicrobia and Lentisphaerae phyla. In young adults, the effect of sleep disruption on gut microbiome composition, specifically the ratio of beneficial Firmicutes over Bacteroidetes phyla, remains contradictory and unclear. The findings of this review warrant further research in the modulation of the gut microbiome linking poor sleep with muscle-catabolic consequences throughout the lifespan. Show less
Wang, Y.M.; Zanden, S.Y. van der; Leerdam, S. van; Tersteeg, M.M.H.; Kastelein, A.; Michel, S.; ... ; Deboer, T. 2022
Simple Summary: Cancer-related fatigue (CRF) is a devastating side effect of cancer treatment, affecting the quality of life of many patients for years after treatment. This long-term side effect... Show moreSimple Summary: Cancer-related fatigue (CRF) is a devastating side effect of cancer treatment, affecting the quality of life of many patients for years after treatment. This long-term side effect often results in loss of social functioning and even job loss. The cause of CRF is unknown, and consequently, CRF is often considered a 'psychological problem', much to the frustration of the patients. Here, we show in an animal model that the severity of CRF depends on the working mechanism of the treatment. In addition, the data show that the CRF is probably caused by a dysfunctioning circadian clock and thus has a physiological basis, as this effect depends on the anticancer drug. Therefore, the findings may have implications for the selection of chemotherapy and thus strongly improve the quality of life of future cancer survivors. Cancer-related fatigue (CRF) is the most devastating long-term side effect of many cancer survivors that confounds the quality of life for months to years after treatment. However, the cause of CRF is poorly understood. As a result, cancer survivors, at best, receive psychological support. Chemotherapy has been shown to increase the risk of CRF. Here, we study therapy-induced fatigue in a non-tumor-bearing mouse model with three different topoisomerase II-poisoning cancer drugs. These drugs either induce DNA damage and/or chromatin damage. Shortly before and several weeks after treatment, running wheel activity and electroencephalographic sleep were recorded. We show that doxorubicin, combining DNA damage with chromatin damage, unlike aclarubicin or etoposide, induces sustained CRF in this model. Surprisingly, this was not related to changes in sleep. In contrast, our data indicate that the therapy-induced CRF is associated with a disrupted circadian clock. The data suggest that CRF is probably a circadian clock disorder that influences the quality of waking and that the development of CRF depends on the type of chemotherapy provided. These findings could have implications for selecting and improving chemotherapy for the treatment of cancer in order to prevent the development of CRF. Show less
Sleep deprivation reduces the response of neuronal activity in the suprachiasmatic nucleus (SCN) and the phase shift in circadian behaviour to phase shifting light pulses, and thus seems to impair... Show moreSleep deprivation reduces the response of neuronal activity in the suprachiasmatic nucleus (SCN) and the phase shift in circadian behaviour to phase shifting light pulses, and thus seems to impair the adaptation of the circadian clock to the external light-dark cycle. The question remains where in the pathway of light input to the SCN the response is reduced. We therefore investigated whether the electroretinogram (ERG) changes after sleep deprivation in wild-type mice and in Opn4(-/-)Gnat1(-/-) mutant mice. We found that the ERG is clearly affected by the Opn4(-/-)Gnat1(-/-) mutations, but that the ERG after sleep deprivation does not differ from the baseline response. The difference between wild-type and mutant is in accordance with the lack of functional rod and melanopsin in the retina of the mutant mice. We conclude that the decrease in light responsiveness of the SCN after sleep deprivation is probably not caused by changes at the retinal level, but rather at the postsynaptic site within the SCN, reflecting affected neurotransmitter signalling. Show less
Egmond, L.T. van; Meth, E.M.S.; Bukhari, S.; Engstrom, J.; Ilemosoglou, M.; Keller, J.A.; ... ; Benedict, C. 2022
Background: Acute sleep loss increases the brain's reactivity toward positive and negative affective stimuli. Thus, despite well-known reduced attention due to acute sleep loss, we hypothesized... Show moreBackground: Acute sleep loss increases the brain's reactivity toward positive and negative affective stimuli. Thus, despite well-known reduced attention due to acute sleep loss, we hypothesized that humans would gaze longer on happy, angry, and fearful faces than neutral faces when sleep-deprived. We also examined if facial expressions are differently perceived after acute sleep loss. Methods: In the present, within-subjects study, 45 young adults participated in one night of total sleep deprivation and one night with an 8-hour sleep opportunity. On the morning after each night, an eye tracker was used to measure participants time spent fixating images of happy, angry, fearful, and neutral faces. Participants also evaluated faces attractiveness, trustworthiness, and healthiness on a 100-mm visual analog scale. Results: Following sleep loss, participants struggled more fixating the faces than after sleep. The decrease in total fixation duration ranged from 6.3% to 10.6% after sleep loss (P<0.001). Contrary to our hypothesis, the reduction in total fixation duration occurred irrespective of the displayed emotion (P=0.235 for sleep*emotion interaction) and was also present for the upper (P<0.001) but not the lower part of the faces (except for the lower part of angry faces). Overall, faces were evaluated as less trustworthy (-2.6 mm) and attractive (???3.6 mm) after sleep loss (p<0.05). Discussion: Facial expressions are crucial for social interactions. Thus, spending less time fixating on faces after acute sleep loss may come along with several problems for social interactions, eg, inaccurate and delayed judgment of the emotional state of others. In addition, more negative social impressions of others may lead to social withdrawal in sleep-deprived humans. Show less
Basal ganglia (BG) are a set of subcortical nuclei that are involved in the control of a wide variety of motor, cognitive, and affective behaviors. Although many behavioral abnormalities associated... Show moreBasal ganglia (BG) are a set of subcortical nuclei that are involved in the control of a wide variety of motor, cognitive, and affective behaviors. Although many behavioral abnormalities associated with BG dysfunction overlap with the clinical picture precipitated by the lack of sleep, the impact of sleep alterations on neuronal activity in BG is unknown. Using wild-type C57BI mice, we investigated the circadian and sleep-related homeostatic modulation of neuronal activity in the three functional subdivisions of the striatum (i.e. sensorimotor, associative, and limbic striatum). We found no circadian modulation of activity in both ventral and dorsomedial striatum while the dorsolateral striatum displayed a significant circadian rhythm with increased firing rates during the subjective dark, active phase. By combining neuronal activity recordings with electroencephalogram (EEG) recordings, we found a strong modulation of neuronal activity by the nature of vigilance states with increased activity during wakefulness and rapid eye movement sleep relative to nonrapid eye movement sleep in all striatal subregions. Depriving animals of sleep for 6 h induced significant, but heterogenous alterations in the neuronal activity across striatal subregions. Notably, these alterations lasted for up to 48 h in the sensorimotor striatum and persisted even after the normalization of cortical EEG power densities. Our results show that vigilance and sleep states as well as their disturbances significantly affect neuronal activity within the striatum. We propose that these changes in neuronal activity underlie both the well-established links between sleep alterations and several disorders involving BG dysfunction as well as the maladaptive changes in behavior induced in healthy participants following sleep loss. Show less
Starreveld, D.E.J.; Daniels, L.A.; Kieffer, J.M.; Valdimarsdottir, H.B.; Geus, J. de; Lanfermeijer, M.; ... ; Bleiker, E.M.A. 2021
Simple SummaryCancer-related fatigue (CRF) is one of the most frequently reported symptoms with prevalence rates of 25 to 60 percent in (non-)Hodgkin lymphoma survivors. Several (pilot) studies... Show moreSimple SummaryCancer-related fatigue (CRF) is one of the most frequently reported symptoms with prevalence rates of 25 to 60 percent in (non-)Hodgkin lymphoma survivors. Several (pilot) studies showed promising effects of light therapy to reduce CRF. The aim of the current study is to evaluate the short- and long-term efficacy of light therapy on CRF and associated symptoms in chronically fatigued (non-)Hodgkin lymphoma survivors. Eighty-three survivors were exposed to bright white light (intervention) and another 83 survivors were exposed to dim white light (comparison). Results showed that all participants, irrespective of light condition, reported reduced levels of fatigue after the completion of light therapy. Similar results were found for depression, sleep quality, and some aspects of quality of life. No effect was found on circadian rhythms or objectively assessed sleep. Therefore, it is important to further investigate which aspects of intervention are associated with the improvements observed after light therapy.Purpose: To evaluate the short- and long-term effects of light therapy on fatigue (primary outcome) and sleep quality, depression, anxiety, quality of life, and circadian rhythms (secondary outcomes) in survivors of (non-)Hodgkin lymphoma presenting with chronic cancer-related fatigue. Methods: We randomly assigned 166 survivors (mean survival 13 years) to a bright white light intervention (BWL) or dim white light comparison (DWL) group. Measurements were completed at baseline (T0), post-intervention (T1), at three (T2), and nine (T3) months follow-up. A mixed-effect modeling approach was used to compare linear and non-linear effects of time between groups. Results: There were no significant differences between BWL and DWL in the reduction in fatigue over time. Both BWL and DWL significantly (p < 0.001) improved fatigue levels during the intervention followed by a slight reduction in this effect during follow-up (EST0-T1 = -0.71; EST1-T3 = 0.15). Similar results were found for depression, sleep quality, and some aspects of quality of life. Light therapy had no effect on circadian rhythms. Conclusions: BWL was not superior in reducing fatigue compared to DWL in HL and DLBCL survivors. Remarkably, the total sample showed clinically relevant and persistent improvements on fatigue not commonly seen in longitudinal observational studies in these survivors. Show less
Shift work, an essential part of our 24/7 society, inevitably leads to displacement of the habitual sleep period and thereby to misalignment of the internal circadian timing system with the rest... Show moreShift work, an essential part of our 24/7 society, inevitably leads to displacement of the habitual sleep period and thereby to misalignment of the internal circadian timing system with the rest-activity cycle and the environment. How interindividual differences in circadian organization affect sleep duration and timing during rotating shift work is not fully understood. The objective of this study was to assess the effect of chronotype, shift type, and their interaction on actigraphy-based sleep behavior in 74 police officers (20 women and 54 men; age [mean +/- SD]: 32.1 +/- 5.4 years) involved in rotating shift work throughout a 28- to 35-day work cycle consisting of morning, evening, and night shifts. Using linear mixed modeling, we found that chronotype was associated with sleep duration depending on the shift type: increasing morningness was correlated with longer sleep duration during series of consecutive morning shifts, while increasing eveningness was correlated with longer sleep duration during series of evening shifts. During series of night shifts, increasing eveningness was associated with a longer duration of the main sleep episode, but this relationship was attenuated and no longer significant when naps were taken into account due to increased napping in morning chronotypes during series of night shifts. Providing a detailed within-subject characterization of sleep behavior across a complete work cycle consisting of morning, evening, and night shifts, this study advances the understanding of the relationship between chronotype and sleep in rotating shift workers and supports the implementation of work schedules that take into account chronobiological principles. Show less
Cancer-related fatigue has been related to circadian disruptions and lower levels of sleep quality. However, it is unknown whether the circadian phase, which is associated with chronotype and... Show moreCancer-related fatigue has been related to circadian disruptions and lower levels of sleep quality. However, it is unknown whether the circadian phase, which is associated with chronotype and timing of sleep, is related to fatigue after cancer. The aims of this study were to investigate the associations between (1) chronotype and cancer-related fatigue and (2) sleep quality and cancer-related fatigue. In this cross-sectional questionnaire study, 458 (non-)Hodgkin lymphoma survivors (n = 231 female, mean age 49.7 years) completed a Visual Analogue Scale for fatigue (VAS-fatigue) from 0 (no fatigue) to 10 (worst imaginable fatigue), the Munich Chronotype Questionnaire (MCTQ), and the Pittsburgh Sleep Quality Index (PSQI) between October 2018 and July 2019. A hierarchical linear regression analysis was used to evaluate the associations between the dependent variable fatigue and chronotype (based on early, intermediate, or late average midsleep) in Model 1, and fatigue and sleep quality in Model 2. The results showed no indications for an association between chronotype and fatigue (all p values >= 0.50). There were associations between two (out of seven) aspects of sleep quality and fatigue: subjective sleep quality (p < 0.001) and daily dysfunctioning (p < 0.001). Therefore, it is more likely that fatigue is associated with self-reported sleep quality rather than with chronotype. However, experimental studies with objective, physiological data on circadian phase and sleep quality are necessary to confirm the conclusions of this cross-sectional study. Show less
Martens, L.G.; Luo, J.; Meulmeester, F.L.; Ashrafi, N.; Eekelen, E.W. van; Mutsert, R. de; ... ; Heemst, D. van 2020
The antioxidant vitamin E (alpha-tocopherol, alpha-TOH) protects lipids from oxidation by reactive oxygen species. We hypothesized that lifestyle factors associate with vitamin E metabolism marked... Show moreThe antioxidant vitamin E (alpha-tocopherol, alpha-TOH) protects lipids from oxidation by reactive oxygen species. We hypothesized that lifestyle factors associate with vitamin E metabolism marked by urinary alpha-tocopheronolactone hydroquinone (alpha-TLHQ) and alpha-carboxymethyl-hydroxychroman (alpha-CEHC levels), as potential reflection of lipid oxidation. We conducted a cross-sectional study in the Netherlands Epidemiology of Obesity Study. Serum alpha-TOH, and urinary alpha-TLHQ and alpha-CEHC were quantified by liquid chromatography coupled with tandem mass spectrometry. Information on the lifestyle factors (sleep, physical activity (PA), smoking and alcohol) were collected through questionnaires. Multivariable linear regression analyses were performed to assess the associations between the lifestyle factors and alpha-TOH measures. A total of 530 participants (46% men) were included with mean (SD) age of 56 (6) years. Of the examined lifestyle factors, only poor sleep was associated with a higher serum alpha-TOH (mean difference: 4% (95% CI: 1, 7%)). Current smoking was associated with higher urinary alpha-CEHC (32%: (14%, 53%)), with evidence of a dose-response relationship with smoking intensity (low pack years, 24% (2, 52%); high pack years, 55% (25, 93%)). Moderate physical activity was associated with a lower alpha-TLHQ relative to alpha-CEHC (-17%: (-26, -6%), compared with low PA). Only specific lifestyle factors associate with vitamin E metabolism. Examining serum alpha-TOH does not provide complete insight in vitamin E antioxidant capacity. Show less
Artificial light, despite its widespread and valuable use, has been associated with deterioration of health and well-being, including altered circadian timing and sleep disturbances, particularly... Show moreArtificial light, despite its widespread and valuable use, has been associated with deterioration of health and well-being, including altered circadian timing and sleep disturbances, particularly in nocturnal exposure. Recent findings from our lab reveal significant sleep and sleep electroencephalogram (EEG) changes owing to three months exposure to dim-light-at-night (DLAN). Aiming to further explore the detrimental effects of DLAN exposure, in the present study, we continuously recorded sleep EEG and the electromyogram for baseline 24-h and following 6-h sleep deprivation in a varied DLAN duration scheme. C57BL/6J mice were exposed to a 12:12 h light:DLAN cycle (75lux:5lux) vs. a 12:12 h light:dark cycle (75lux:0lux) for one day, one week, and one month. Our results show that sleep was already affected by a mere day of DLAN exposure with additional complications emerging with increasing DLAN exposure duration, such as the gradual delay of the daily 24-h vigilance state rhythms. We conducted detrended fluctuation analysis (DFA) on the locomotor activity data following 1-month and 3-month DLAN exposure, and a significantly less healthy rest-activity pattern, based on the decreased alpha values, was found in both conditions compared to the control light-dark. Taking into account the behavioral, sleep and the sleep EEG parameters, our data suggest that DLAN exposure, even in the shortest duration, induces deleterious effects; nevertheless, potential compensatory mechanisms render the organism partly adjustable and able to cope. We think that, for this reason, our data do not always depict linear divergence among groups, as compared with control conditions. Chronic DLAN exposure impacts the sleep regulatory system, but also brain integrity, diminishing its adaptability and reactivity, especially apparent in the sleep EEG alterations and particular low alpha values following DFA. Show less
Dim-light-at-night (DLAN) exposure is associated with health problems, such as metabolic disruptions, immunological modulations, oxidative stress, sleep problems, and altered circadian timing.... Show moreDim-light-at-night (DLAN) exposure is associated with health problems, such as metabolic disruptions, immunological modulations, oxidative stress, sleep problems, and altered circadian timing. Neurophysiological parameters, including sleep patterns, are altered in the course of aging in a similar way. Here, we investigated the effect of chronic (three months) DLAN exposure (12 L:12 Dim-light, 75:5 lux) on sleep and the sleep electroencephalogram (EEG), and rest-activity behavior in young (6-month-old, n = 9) and aged (18- n = 8, 24-month-old, n = 6) C57BL/6J mice and compared with age-matched controls (n = 11, n = 9 and n = 8, respectively). We recorded the EEG and electromyogram continuously for 48-h and conducted a 6-h sleep-deprivation. A delay in the phase angle of entrainment of locomotor activity and daily vigilance state rhythms was apparent in mice following DLAN exposure, throughout the whole age spectrum, rendering sleep characteristics similar among the three age DLAN groups and significantly different from the age-matched controls. Notably, slow-wave-activity in NREM sleep (SWA, EEG power density in 0.5-4.0 Hz) was differentially altered in young and aged DLAN mice. Particularly, SWA increased as a function of age, which was further accentuated following DLAN exposure. However, this was not found in the young DLAN animals, which were characterized by the lowest SWA levels. Concluding, long-term DLAN exposure induced more pronounced alterations in the sleep architecture of young mice, towards an aging phenotype, while it enhanced age-associated sleep changes in the older groups. Our data suggest that irrespective of age, chronic DLAN exposure deteriorates sleep behavior and may consequently impact general health. (C) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. Show less
Sleep in the ICU is poor and improving sleep proves to be challenging. However, clinical trials on the use of pharmacological and non-pharmacological interventions to improve sleep in the ICU are... Show moreSleep in the ICU is poor and improving sleep proves to be challenging. However, clinical trials on the use of pharmacological and non-pharmacological interventions to improve sleep in the ICU are scarce. The few clinical trials that have been performed are hampered by difficulty in obtaining reliable objective sleep measurements in the ICU environment. Therefore, firm evidence on the effect of all commonly used interventions is limited. Strategies to decrease noise and light exposure seem promising, since pilot studies and small clinical trials suggest that implementation is feasible and most interventions are low-cost. Standardisation of sleep-promoting protocols might lead to a possibility of performing multicentre trials that can provide much needed evidence on the efficacy of non-pharmacological interventions to improve sleep in the ICU. Although many different medications are used to improve sleep in the ICU, there is insufficient evidence in the literature to support the use of any of them to effectively improve sleep. The use of benzodiazepines is not recommended based on the lack of evidence for their efficacy and the association with increased risk of delirium. Emphasis on non-pharmacological sleep-promoting measures before prescribing medication is warranted, as it is currently not clear to what extent prescribing sleep-promoting medications is actually beneficial to ICU patients. Clinical trials on existing pharmacological options and expanding treatment options by considering sodium oxybate or suvorexant are logical future directions to improve the treatment of sleep problems in the ICU. Show less
Background Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the... Show moreBackground Actigraphy may provide a more valid assessment of sleep, circadian rhythm (CR), and physical activity (PA) than self-reported questionnaires, but has not been used widely to study the association with depression/anxiety and their clinical characteristics. Methods Fourteen-day actigraphy data of 359 participants with current (n = 93), remitted (n = 176), or no (n = 90) composite international diagnostic interview depression/anxiety diagnoses were obtained from the Netherlands Study of Depression and Anxiety. Objective estimates included sleep duration (SD), sleep efficiency, relative amplitude (RA) between day-time and night-time activity, mid sleep on free days (MSF), gross motor activity (GMA), and moderate-to-vigorous PA (MVPA). Self-reported measures included insomnia rating scale, SD, MSF, metabolic equivalent total, and MVPA. Results Compared to controls, individuals with current depression/anxiety had a significantly different objective, but not self-reported, PA and CR: lower GMA (23.83 vs. 27.4 milli-gravity/day, p = .022), lower MVPA (35.32 vs. 47.64 min/day, p = .023), lower RA (0.82 vs. 0.83, p = .033). In contrast, self-reported, but not objective, sleep differed between people with current depression/anxiety compared to those without current disorders; people with current depression/anxiety reported both shorter and longer SD and more insomnia. More depressive/anxiety symptoms and number of depressive/anxiety diagnoses were associated with larger disturbances of the actigraphy measures. Conclusion Actigraphy provides ecologically valid information on sleep, CR, and PA that enhances data from self-reported questionnaires. As those with more severe or comorbid forms showed the lowest PA and most CR disruptions, the potential for adjunctive behavioral and chronotherapy interventions should be explored, as well as the potential of actigraphy to monitor treatment response to such interventions. Show less
