Ocular Measures of Sleepiness Are Increased in Night Shift Workers Undergoing a Simulated Night Shift Near the Peak Time of the 6-Sulfatoxymelatonin Rhythm.

STUDY OBJECTIVE: The study examined the relationship between the circadian rhythm of 6-sulphatoxymelatonin (aMT6s) and ocular measures of sleepiness and neurobehavioral performance in shift workers undergoing a simulated night shift. METHODS: Twenty-two shift workers (mean age 33.4, SD 11.8 years) were tested at approximately the beginning (20:00) and the end (05:55) of a simulated night shift in the laboratory. At the time point corresponding to the end of the simulated shift, 14 participants were classified as being within range of 6-sulphatoxymelatonin (aMT6s) acrophase--defined as 3 hours before or after aMT6s peak--and 8 were classified as outside aMT6s acrophase range. Participants completed the Karolinska Sleepiness Scale (KSS) and the auditory psychomotor vigilance task (aPVT). Waking electroencephalography (EEG) was recorded and infrared reflectance oculography was used to collect ocular measures of sleepiness: positive and negative amplitude/velocity ratio (PosAVR, NegAVR), mean blink total duration (BTD), the percentage of eye closure (%TEC), and a composite score of sleepiness levels (Johns Drowsiness Scale; JDS). RESULTS: Participants who were tested within aMT6s acrophase range displayed higher levels of sleepiness on ocular measures (%TEC, BTD, PosAVR, JDS), objective sleepiness (EEG delta power frequency band), subjective ratings of sleepiness, and neurobehavioral performance, compared to those who were outside aMT6s acrophase range. CONCLUSIONS: The study demonstrated that objective ocular measures of sleepiness are sensitive to circadian rhythm misalignment in shift workers.

Caffeine does not entrain the circadian clock but improves daytime alertness in blind patients with non-24-hour rhythms.

OBJECTIVE/BACKGROUND: Totally blind individuals are highly likely to suffer from Non-24-Hour Sleep-Wake Disorder due to a failure of light to reset the circadian pacemaker in the suprachiasmatic nuclei. In this outpatient case series, we investigated whether daily caffeine administration could entrain the circadian pacemaker in non-entrained blind patients to alleviate symptoms of non-24-hour sleep-wake disorder. PATIENTS/METHODS: Three totally blind males (63.0 ± 7.5 years old) were studied at home over ~4 months. Urinary 6-sulphatoxymelatonin (aMT6s) rhythms were measured for 48 h every 1-2 weeks. Participants completed daily sleep-wake logs, and rated their alertness and mood using nine-point scales every ~2-4 h while awake on urine sampling days. Caffeine capsules (150 mg per os) were self-administered daily at 10 a.m. for approximately one circadian beat cycle based on each participant's endogenous circadian period τ and compared to placebo (n = 2) or no treatment (n = 1) in a single-masked manner. RESULTS: Non-24-h aMT6s rhythms were confirmed in all three participants (τ range = 24.32-24.57 h). Daily administration of 150 mg caffeine did not entrain the circadian clock. Caffeine treatment significantly improved daytime alertness at adverse circadian phases (p <0.0001) but did not decrease the occurrence of daytime naps compared with placebo. CONCLUSIONS: Although caffeine was able to improve daytime alertness acutely and may therefore provide temporary symptomatic relief, the inability of caffeine to correct the underlying circadian disorder means that an entraining agent is required to treat Non-24-Hour Sleep-Wake Disorder in the blind appropriately.

Circadian melatonin profiles during single 24-h shifts in anesthetists.

PURPOSE: It has been shown that shift work constitutes a great health hazard, particularly when chronodisruption is involved. Anesthetists are used to working for a certain number of 24-h shifts every month. The work-related lack of sleep in combination with light exposure is suspected to alter melatonin courses. The main aim of the present study was to analyze circadian melatonin profiles before, during, and after a 24-h shift in anesthetists and medical students (controls). Furthermore, we evaluated possible differences in melatonin profiles between the groups. Interactions between specific parameters were calculated. METHODS: Over three consecutive days, including a 24-h shift, urine samples were collected daily at five time points. 6-Sulfateoxymelatonin (aMT6-s) courses were assayed using a commercially available competitive immunoassay kit. RESULTS: Ten anesthetists aged between 29 and 35 years and ten medical students aged between 25 and 31 years were included in the study. aMT6-s fluctuated between nocturnal values of (mean [range]) 2.2 (1.4; 3.0) pg/ml and morning values of 25.5 (12.1; 39.0) pg/ml. A marked circadian rhythm of aMT6-s courses was observed in both groups. Analyses of variance showed an effect of the factor "time" on aMT6-s concentrations but not of the factor "anesthetists versus students". Correlations between aMT6-s, the amount of sleep, and the time since the last extended duration shift could be found. CONCLUSIONS: The results show no evidence for a single 24-h shift having a great impact on circadian disruption as evidenced by a similar melatonin profile for both groups over the study phase.

The correlation between urinary 5-hydroxyindoleacetic acid and sperm quality in infertile men and rotating shift workers.

BACKGROUND: Serotonin is a neurotransmitter that modulates a wide range of neuroendocrine functions. However, excessive circulating serotonin levels may induce harmful effects in the male reproductive system. The objective of this study was to evaluate whether the levels of urinary 5-hydroxyindoleacetic acid (5-HIIA), a major serotonin metabolite, correlate with different classical seminal parameters. METHODS: Human ejaculates were obtained from 40 men attending infertility counselling and rotating shift workers by masturbation after 4-5 days of abstinence. Urinary 5- HIIA concentration was quantified by using a commercial ELISA kit. Forward motility was assessed by a computer-aided semen analysis (CASA) system. Sperm concentration was determined using the haemocytometer method. Sperm morphology was evaluated after Diff-Quik staining, while sperm vitality was estimated after Eosin-Nigrosin vital staining. RESULTS: Our results show that urinary 5-HIIA levels obtained from a set of 20 volunteers negatively correlated with sperm concentration, forward motility, morphology normal range and sperm vitality. On the other hand, we checked the relationship between male infertility and urinary 5-HIIA levels in 20 night shift workers. Thus, urinary 5-HIIA levels obtained from 10 recently-proven fathers were significantly lower than those found in 10 infertile males. Additionally, samples from recent fathers exhibited higher sperm concentration, as well as better forward motility and normal morphology rate. CONCLUSIONS: In the light of our findings, we concluded that high serotonin levels, indirectly measured as urinary 5-HIIA levels, appear to play a role as an infertility determinant in male subjects.

Sleep length and quality, sleepiness and urinary melatonin among healthy Danish nurses with shift work during work and leisure time.

BACKGROUND: Sleep problems are common effects of shift work. The aim of the present study was to evaluate how different types of shift affect sleep and sleepiness, and to relate sleepiness to urinary 6-sulfatoxymelatonin. METHODS: A total of 166 volunteer healthy Danish nurses working day, evening, or night, respectively fixed and mixed schedules were included. Self-reports of sleep were assessed together with real-time sleepiness and spot urine samples analyzed for 6-sulfatoxymelatonin on a workday and a leisure day. RESULTS: On a day off the nurses slept longer, with a better quality and reported less sleepiness compared to a workday. Nurses on nightshift reported poorer sleep quality than nurses on other shifts. Sleepiness was highest for nurses on mixed schedules. Concentrations of urinary 6-sulfatoxymelatonin and sleepiness were generally correlated except for nurses working fixed nights. CONCLUSIONS: The poorest sleep quality was observed for nurses in mixed schedules working nights. The lack of correlation between sleepiness and 6-sulfatoxymelatonin on mixed night shift may indicate that the influence of endogenous melatonin is limited.

Changes in the concentration of urinary 6-sulphatoxymelatonin during a week of simulated night work.

The aim of the study was to examine the adaptation of participants to a common night work schedule using urinary 6-sulphatoxymelatonin (aMT6s) concentration as the circadian phase marker. Fifteen adults (7 male, 8 female, age = 21.9 yr) spent nine consecutive nights in the laboratory, including: (i) adaptation sleep, (ii) baseline sleep, and (iii) seven simulated night shifts (23:00-07:00 h) followed by daytime sleep. During the baseline and daytime sleeps, participants collected urine samples which were subsequently assayed for aMT6s. The concentration of aMT6s in urine for the first three day sleeps was significantly lower than for the baseline sleep, but there was no difference in aMT6s concentrations between any of the last three day sleeps and the baseline sleep. The data indicate that people may adapt to a pattern of work that includes seven consecutive night shifts if they adhere to a fixed sleep schedule, if their exposure to morning sunlight is minimised, and if they are provided with an ideal sleep environment.

Circadian abnormalities in older adults.

This study examined the circadian phase adjustment of symptomatic elders ages 60-79 years in comparison with that of young, healthy adults ages 20-40 years. Seventy-two elders with complaints of insomnia or depression, and 30 young, healthy adults were assessed for 5-7 days at home. Sleep and illumination were recorded with Actillume wrist monitors and sleep diaries. Urine was collected over two 24-hr periods and assayed for 6-sulphatoxymelatonin (6-smt). The volunteers were then observed continuously for 5 nights and 4 days in the laboratory. In the laboratory, sleep periods were fixed at 8 hr with polysomnographic assessment of sleep, apnea-hypopnea, and nocturnal myoclonus. Circadian dispersion, defined as the mean variation of 6-smt acrophase from the median age-specific acrophase, was significantly greater in the older vs. young adults. Likewise, circadian malsynchronization, defined as the absolute number of hours (advance or delay) between the 6-smt acrophase and the middle of the sleep period, was significantly greater in the older vs. young volunteers. For the older volunteers, multiple regressions were calculated associating sleep with potential correlates of sleep disturbance. Nocturnal myoclonus and circadian malsynchronization were more strongly associated with sleep impairment than other factors (e.g., sleep apnea, depression). These observations suggest that circadian malsynchronization might be a common and significant cause of disturbed sleep among adults over age 60.

Circadian rhythm of heart rate, urinary cortisol excretion, and sleep in civil air traffic controllers.

The examination of Air Traffic Controllers (ATCs) from the Warsaw Airport (Poland) included 24-hr ECG monitoring. The participants were 10 civil ATCs, 9 males and 1 woman. The study was carried out on a group of 19 ATCs during their duty periods, 14 of them working 12-hr shifts and 5 performing 24-hr duties. The participants collected urine every 4 hrs, and cortisol concentration was determined. Further, the survey included the quality and duration of sleep, and subjective fatigue in the 62 participants. In ATCs, shift work modifies natural rhythms of the circulatory system and decreases the ability for intensified mental work at night. In consequence ATCs experience frequent sleep disorders.