Further Assessments of the Relationship Between Jet Lag and Some of Its Symptoms

The disruption of circadian rhythms following time‐zone transitions gives rise to the syndrome of jet lag. The power of some of the symptoms of jet lag to predict the amount of jet lag measured at the same and at different times of the day has been investigated. Eleven healthy subjects were studied in an Isolation Unit for two days after a simulated flight from the UK to Beijing (8 time zones to the east). At six time‐points (08:30, 11:00, 14:00, 17:00, 20:00, and 23:00 h), the subjects recorded their jet lag, and the differences from “normal” (that is, from days in which there is no jet lag) of alertness, hunger, indigestion, concentration, motivation, and irritability. They recorded at 08:30 h the type of food they had eaten since rising at 08:00 h and, at the other times, the type of food eaten in the last three hours. Assessments were made by visual analogue scales or, in the case of type of food, by a nominal scale. Following the time‐zone transition, the adjustment of meals appeared to be complete almost immediately. Jet lag and its symptoms were present during both experimental days. Jet lag tended to rise during the course of the daytime, accompanied by falls in alertness, motivation, and concentration. Correlation matrices between jet lag and each of the other variables were produced, using lags between the variable (from up to 5 time‐points before the assessment of jet lag to 5 time‐points afterwards) and pooling the results from both days. These matrices indicated that significant correlations existed only between jet lag and alertness, concentration, and motivation, and then only when these other variables were assessed at the same time as jet lag or 1 or 2 time‐points earlier. Jet lag was then treated as the dependent variable and the symptoms as covariates in analysis of covariances (ANCOVAs), with the days treated as a random effect. This analysis enabled the significance of potential predictors of jet lag, together with their β‐coefficients (the relationship between a unit change of each significant predictor and the change in jet lag), to be calculated. Falls in alertness and motivation were significant predictors of increased jet lag, provided that they were measured at the same time, when they accounted for about 50% of the jet lag; when measured at other time‐points, they did not act as significant predictors. It is concluded that the amount of jet lag varies during the course of the day and that it can be predicted from contemporaneous assessments of alertness and motivation—but not from assessments made at other times of the day, nor from other variables that are symptoms of jet lag, even though these other variables are significantly increased. In considering the results of this and our previous study, we reiterate the view that the exact meaning of “jet lag” is complex and that the particular combination of factors that contribute to it might vary with the time of day that the assessment is made. Inferences about any decrements due to time‐zone transitions cannot be made reliably at times of the day that differ from the time when jet lag is assessed.     

The relationship between assessments of jet lag and some of its symptoms

The power of the symptoms of jet lag in predicting the amount of jet lag measured at the same and different times of the day has been investigated. A total of 85 subjects was studied for 6 days after a flight from the UK to Australia (10 time zones to the east). At 08:00, 12:00, 16:00, 20:00, and 24:00h, the subjects recorded their jet lag and fatigue. At 08:00h, they also assessed their sleep. At 12:00 and 16:00h, they assessed their attitude to a meal, as well as their motivation, commitment, and irritability. On retiring, they recorded bowel activity. Assessments were by visual analog scales. Jet lag was treated as the dependent variable and the symptoms as covariates in ANCOVAs. Fatigue was a powerful predictor of jet lag, provided it was measured at the same time, and some aspects of sleep predicted jet lag measured on retiring or rising. The other symptoms predicted jet lag less powerfully and/or at a wider range of times. It is concluded that, even though jet lag at any time of the day can be predicted from contemporaneous assessments of fatigue and that it can be predicted on retiring or rising from some aspects of changed sleep, jet lag is predicted less reliably from other symptoms, including aspects of mental performance. These findings question exactly what causes jet lag at a particular time of day, and so are relevant to studies which use this measurement to investigate the problems associated with time-zone transitions, and ways to ameliorate them.     

The Relationship Between Assessments of Jet Lag and Some of Its Symptoms

The power of the symptoms of jet lag in predicting the amount of jet lag measured at the same and different times of the day has been investigated. A total of 85 subjects was studied for 6 days after a flight from the UK to Australia (10 time zones to the east). At 08:00, 12:00, 16:00, 20:00, and 24:00h, the subjects recorded their jet lag and fatigue. At 08:00h, they also assessed their sleep. At 12:00 and 16:00h, they assessed their attitude to a meal, as well as their motivation, commitment, and irritability. On retiring, they recorded bowel activity. Assessments were by visual analog scales. Jet lag was treated as the dependent variable and the symptoms as covariates in ANCOVAs. Fatigue was a powerful predictor of jet lag, provided it was measured at the same time, and some aspects of sleep predicted jet lag measured on retiring or rising. The other symptoms predicted jet lag less powerfully and/or at a wider range of times. It is concluded that, even though jet lag at any time of the day can be predicted from contemporaneous assessments of fatigue and that it can be predicted on retiring or rising from some aspects of changed sleep, jet lag is predicted less reliably from other symptoms, including aspects of mental performance. These findings question exactly what causes jet lag at a particular time of day, and so are relevant to studies which use this measurement to investigate the problems associated with time‐zone transitions, and ways to ameliorate them.     

Transient changes in the pattern of food intake following a simulated time-zone transition to the east across eight time zones

Twelve healthy adults were studied, singly or in groups of up to four, in an Isolation Unit before (control days) and for 3 days after a simulated time-zone transition to the east across 8 time zones (the clock being changed from 15:00 to 23:00 h). Subjects were free to choose how to pass their waking hours (though naps were forbidden), and to eat what and when they wanted. A wide selection of food was provided, though the subjects had to prepare it. Subjects completed food intake questionnaire on waking and at 3 h intervals during the waking day. This questionnaire assessed the reasons for choosing not to eat a meal or, if a meal was eaten, the reasons for doing so, the type of meal chosen and the reasons for this choice, and subjective responses to the meal (hunger before, enjoyment during, and satiety afterwards). Subjects also recorded the incidence and degree of indigestion and jet lag at 3 h intervals after the time-zone transition. Following the time-zone transition, the subjects experienced significant amounts of jet lag and recorded a significant increase in the incidence of indigestion. They also showed significant changes in their pattern of food intake, but, whereas the patterns of food intake were no longer significantly different from control days by the third post-shift day, the symptoms of jet lag and indigestion were still present then. The distribution of daytime meals was significantly affected on the first post-shift day, with a redistribution of the times that the main, hot meals were eaten; these times indicated some influence of an unadjusted body clock. On this day also, the reasons for determining food intake continued to be dominated by hunger and appetite (hunger even increasing in the frequency with which it was cited), and the reason for not eating a meal, by a lack of hunger. On both control and post-shift days, there was a marked effect of meal type upon the responses to food intake, with cold food being rated least and large hot meals most when appetite before the meal, enjoyment during it, and satiety afterward were considered. However, evidence suggested that the degree to which larger hot meals were preferred to cold meals was significantly less marked after the time-zone transition. On control days, sleep was unbroken; whereas, after the time-zone transition, all subjects woke on at least one of the 3 nights studied. During the first post-shift night, about half of the subjects ate a meal, the reason given being that they were “hungry.” On those occasions when subjects woke but did not eat a meal, the reason cited was because they “could not be bothered” as frequently as because they were “not hungry.”. A simulated time-zone transition is associated with significant changes to the incidence of indigestion, pattern of food intake, and subjective responses to food. However, these changes are generally transient and are only weakly linked to the sensation of jet lag.     

First jet lag symptoms after travelling across multiple time zones

Jet lag is a consequence of desynchronisation of human endogenous circadian rhythm with respect to the immediate environment. The slower adaptation rate of the internal rhythm in contrast to rapid travel in commercial aircraft results in symptoms such as insomnia or daytime fatigue. A group of 53 travelling subjects answered the Charité Jet Lag Scale (CJLS) questionnaire, the first of its kind in German. The CJLS represents a holistic approach to the individual symptoms of jet lag. Study results indicate a possible enhancement by shortening the CJLS to a morning and evening report. Moreover, our study determined a decreasing exponential gradient for jet lag during the first days after travel. Physical and mental symptoms are identified as the primary predictors of jet lag. The CJLS and its future translations could lead to a consistent interviewing method – one key factor for development of future intervention methods to manage jet lag.     

Chronobiotic effects of the melatonin agonist LY 156735 following a simulated 9h time shift: results of a placebo-controlled trial

Introduction: The melatonin agonist LY 156735 (LY) is a new investigational drug under development to treat circadian rhythm disorders. The present study assessed the efficacy of LY to alleviate the symptoms of shift lag and to enhance readaptation of desynchronized circadian rhythms to a new time zone.

Subjects and methods: Eight healthy male volunteers of age 25-35 yr participated in three identical trials of 13d duration in a temporal isolation unit separated by washout intervals. A high dose (HD) of 5 mg and a low dose (LD) of 0.5 mg of LY and placebo (PL) were administered double-blinded in a three-period cross-over design. Each trial consisted of an adaptation period, a pre-shift period for baseline measurements, a simulated 9h phase-advance shift, and a post-shift period for follow-up. The time shift was performed at 23:00h of day 6 by advancing the laboratory time to 08:00h of day 7. Double-blind study medication was administered at 14:30h on day 6, and at 22:30h on days 7-10. Subjective ratings of jet lag, alertness, tenseness, and daytime fatigue were assessed using visual analog scales (VAS) and standardized questionnaires. The objective markers of readaptation included core body temperature, wrist actigraphy, cortisol and electrolyte excretion, and a battery of computerized performance tests.

Results: HD but not LD enhanced the readaptation speed of all physiological rhythms investigated, as demonstrated by a significantly faster movement of acrophases towards the post-shift target time. HD (p=0.05) significantly blunted the post-shift deterioration of performance in those tests that were sensitive to shift lag. Parameters of subjective well-being were not significantly affected by either dose.

Conclusion: This pilot study demonstrates the chronobiotic efficacy of LY when taken at a dose of 5 mg/d.     

Impact of hypobaric hypoxia in pressurized cabins of simulated long-distance flights on the 24 h patterns of biological variables, fatigue, and clinical status

Long-distance flights can cause a number of clinical problems in both passengers and crewmembers. Jet lag as well as mild hypoxia resulting from incomplete cabin pressurization could contribute to these problems. The objective of this study was to assess, using a chronobiological approach, the clinical impact of diurnal hypobaric, hypoxic exposure on fatigue and other common symptoms encountered during high-altitude exposure and to measure changes in blood chemistry (i.e., plasma creatinine, urea, uric acid, sodium, calcium, phosphorus, glycemia, and lipids). Fourteen healthy, diurnally active (from 07:00 to 23:00 h) male volunteers, aged 23 to 39 yrs, spent 8.5 h in a hypobaric chamber (08:00 to 16:30 h), at a simulated altitude of 8,000 ft (2,438 m). This was followed by an additional 8.5 h of study four weeks later at a simulated altitude of 12,000 ft (3,658 m). Clinical data were collected every 2 h between 08:00 and 18:00 h, and biological variables were assayed every 2 h over two (control and hypoxic-exposure) 24 h cycles. Clinical symptoms were more frequent with the 12,000 ft exposure. Wide interindividual variability was observed in the clinical tolerance to prolonged hypobaric hypoxia. The 24 h profiles of most biochemical variables were significantly altered at each altitude, with changes in mean plasma levels and a tendency toward phase delay, except for uric acid, which showed a phase advance. Changes in appetite mainly occurred with the simulated 12,000 ft exposure and may have been associated with changes in the postprandial glycemia profile. Finally, though the observed biochemical changes were significant, their clinical relevance must be clarified in studies involving actual long-distance flights.     

Diurnal variations in plasma ACTH, cortisol and beta-endorphin levels in cocaine addicts.

In order to establish possible alterations in the hypothalamic pituitary-adrenal axis and in ACTH-related opioids in cocaine addicts, plasma ACTH, cortisol and beta-endorphin levels were measured throughout the day in 9 cocaine addicts [age: 27 +/- 5 years (mean +/- SE); weight: 72 +/- 6.1 kg, duration of cocaine addiction: at least 2 years] on the day of their admission to a recovery community for drug abusers (first test) and after 15 days of abstinence (second test). Nine normal controls (age: 28 +/- 6 years; weight: 73 +/- 3.2 kg) were tested only once in a similar manner. Blood samples were taken at 06:00, 08:00, 10:00, 12:00, 18:00 and 20:00 h and served for hormonal assays. Urine samples were taken from cocaine addicts at 08:00 h on the experimental day and on the following day. Results of both urine assays were positive for cocaine catabolites, indicating cocaine administration during the day before the experimental test. From the day of their admission in the community (1st experimental day), the patients were forbidden to use cocaine. For 4 days after admission, they were treated with symptomatics to attenuate withdrawal symptoms. Thereafter, the patients underwent a washout period of pharmacological treatments for 10 days before being retested (second test). Urine samples taken at 08:00 h on this second experimental day and on the next day were negative for the presence of drug catabolites. During the first test, cocaine addicts showed higher plasma ACTH, cortisol and beta-endorphin levels than normal controls at all examined time points.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diurnal variations of serum GM-CSF levels

We aimed to investigate the daily variations of serum granulocyte-macrophage colony-stimulating factor (GM-CSF) levels and to correlate them with peripheral blood cells counts. Venous blood samples from eleven healthy volunteers were taken four times a day, being at 08:00, 14:00, 20:00 and 02:00h and serum GM-CSF levels measured by ELISA. We could not find a significant overall difference among GM-CSF levels at four different times of the day using the Friedman test. On the other hand, serum GM-CSF levels at night (20:00h) were found to be significantly increased when compared to the morning levels (08:00h) using the Wilcoxon test (P=0. 022). The levels of lymphocytes and white blood cells (WBCs) at 20:00h were also higher than the morning levels (08:00h) as expected. While there was a strong relationship between the morning levels of GM-CSF (08:00h) and all measurements of peripheral blood cells during the day, the levels of GM-CSF measured at 02:00, 14:00 and 20:00h were found to be significantly correlated with only the WBC levels. It was concluded that there may be a significant difference between morning and night levels of GM-CSF and morning levels of GM-CSF may be more important in the regulation of WBC counts during the day. These variations warrant further studies about diurnal rhythms of haematopoiesis chronotherapy with CSFs.     

Diurnal variation in temperature, mental and physical performance, and tasks specifically related to football (soccer)

Football (soccer) training and matches are scheduled at different times throughout the day. Association football involves a variety of fitness components as well as psychomotor and game-related cognitive skills. The purpose of the present research, consisting of two separate studies, was to determine whether game-related skills varied with time of day in phase with global markers of both performance and the body clock. In the first study, eight diurnally active male association football players (19.1+/-1.9 yrs of age; mean+/-SD) with 10.8+/-2.1 yrs playing experience participated. Measurements were made on different days at 08:00, 12:00, 16:00, and 20:00 h in a counterbalanced manner. Time-of-day changes in intra-aural temperature (used as a marker of the body clock), grip strength, reaction times, flexibility (markers of aspects of performance), juggling and dribbling tasks, and wall-volley test (football-specific skills) were compared. Significant (repeated measures analysis of variance, ANOVA) diurnal variations were found for body temperature (p<0.0005), choice reaction time (p<0.05), self-rated alertness (p<0.0005), fatigue (p<0.05), forward (sit-and-reach) flexibility (p<0.02), and right-hand grip strength (p<0.02), but not left-hand grip strength (p=0.40) nor whole-body (stand-and-reach) flexibility (p=0.07). Alertness was highest and fatigue lowest at 20:00 h. Football-specific skills of juggling performance showed significant diurnal variation (p<0.05, peak at 16:00 h), whereas performance on the wall-volley test tended to peak at 20:00 h and dribbling showed no time-of-day effect (p=0.55). In a second study, eight diurnally active subjects (23.0+/-0.7 yrs of age) completed five test sessions, at the same times as in the first study but with a second session at 08:00 h. Test-re-test comparisons at 08:00 h for all components indicated good reliability. Intra-aural temperature showed a significant time-of-day effect (p<0.001) with mean temperature at 16:00 h (36.4 degrees C) higher than at 08:00 h (35.4 degrees C). There was no significant effect of chronotype on the temperature acrophase (peak time) (p>0.05). Diurnal variation was found for performance tests, including sit-and-reach flexibility (p<0.01) and spinal hyper-extension (p<0.05). Peaks occurred between 16:00 and 20:00 h and the daytime changes paralleled the temperature rhythm. Diurnal variation was also found for football-specific tests, including dribbling time (p<0.001, peak at 20:00 h) and chip test performance (p<0.01), being more accurate at 16:00 h (mean error=0.75 m) than at 08:00 h (mean error=1.01 m). Results indicate football players perform at an optimum between 16:00 and 20:00 h when not only football-specific skills but also measures of physical performance are at their peak. Body temperature peaked at a similar time, but positive mood states seemed to peak slightly earlier. While causal links cannot be established in these experiments, the results indicate that the diurnal variation of some aspects of football performance is affected by factor(s) other than body temperature alone.     

Effect of melatonin on jet lag after long haul flights.

OBJECTIVE: To determine whether doses of the pineal hormone melatonin alleviate jet lag. DESIGN: Double blind, placebo controlled crossover trial. SETTING: Long haul return flights from Auckland, New Zealand, to London and back. SUBJECTS: Twenty volunteers with experience of transcontinental flights (eight women and 12 men aged 28 to 68). INTERVENTIONS: Melatonin (or placebo) 5 mg three days before flight, during flight, and once a day for three days after arrival. END POINT: Symptoms of jet lag. MEASUREMENTS AND MAIN RESULTS: Visual analogue scale for feelings of jet lag and tiredness; profile of moods states questionnaire for vigour-activity and fatigue-inertia; and retrospective ratings 10 days after arrival of sleep pattern, energy, and daytime tiredness. Feelings of jet lag were less for subjects taking melatonin (mean score 2.15 v 3.4); these subjects took fewer days than the placebo group to establish a normal sleep pattern (2.85 v 4.15), to not feel tired during the day (3.0 v 4.6), and to reach normal energy levels (3.25 v 4.7). Results for fatigue-inertia and vigour-activity were similar. For all subjects jet lag was more severe on the return (westward) than the outward (eastward) journey. CONCLUSIONS: Melatonin can alleviate jet lag and tiredness after long haul flights.     

A compromise phase position for permanent night shift workers: circadian phase after two night shifts with scheduled sleep and light/dark exposure

Night shift work is associated with a myriad of health and safety risks. Phase-shifting the circadian clock such that it is more aligned with night work and day sleep is one way to attenuate these risks. However, workers will not be satisfied with complete adaptation to night work if it leaves them misaligned during days off. Therefore, the goal of this set of studies is to produce a compromise phase position in which individuals working night shifts delay their circadian clocks to a position that is more compatible with nighttime work and daytime sleep yet is not incompatible with late nighttime sleep on days off. This is the first in the set of studies describing the magnitude of circadian phase delays that occurs on progressively later days within a series of night shifts interspersed with days off. The series will be ended on various days in order to take a "snapshot" of circadian phase. In this set of studies, subjects sleep from 23:00 to 7:00 h for three weeks. Following this baseline period, there is a series of night shifts (23:00 to 07:00 h) and days off. Experimental subjects receive five 15 min intermittent bright light pulses (approximately 3500 lux; approximately 1100 microW/cm2) once per hour during the night shifts, wear sunglasses that attenuate all visible wavelengths--especially short wavelengths ("blue-blockers")--while traveling home after the shifts, and sleep in the dark (08:30-15:30 h) after each night shift. Control subjects remain in typical dim room light (<50 lux) throughout the night shift, wear sunglasses that do not attenuate as much light, and sleep whenever they want after the night shifts. Circadian phase is determined from the circadian rhythm of melatonin collected during a dim light phase assessment at the beginning and end of each study. The sleepiest time of day, approximated by the body temperature minimum (Tmin), is estimated by adding 7 h to the dim light melatonin onset. In this first study, circadian phase was measured after two night shifts and day sleep periods. The Tmin of the experimental subjects (n=11) was 04:24+/-0.8 h (mean+/-SD) at baseline and 7:36+/-1.4 h after the night shifts. Thus, after two night shifts, the Tmin had not yet delayed into the daytime sleep period, which began at 08:30 h. The Tmin of the control subjects (n=12) was 04:00+/-1.2 h at baseline and drifted to 4:36+/-1.4 h after the night shifts. Thus, two night shifts with a practical pattern of intermittent bright light, the wearing of sunglasses on the way home from night shifts, and a regular sleep period early in the daytime, phase delayed the circadian clock toward the desired compromise phase position for permanent night shift workers. Additional night shifts with bright light pulses and daytime sleep in the dark are expected to displace the sleepiest time of day into the daytime sleep period, improving both nighttime alertness and daytime sleep but not precluding adequate sleep on days off.     

JET LAG IN ATHLETES AFTER EASTWARD AND WESTWARD TIME-ZONE TRANSITION

In healthy male top athletes several functions were measured after either a westbound flight over six time-zones (WEST: Frankfurt–Atlanta; n=13) or an eastbound flight over eight time-zones (EAST: Munich–Osaka; n=6). Under either condition the athletes performed two standardized exercise training units in the morning and in the afternoon within 24 h, investigations were done as controls in Germany and on day 1, 4, 6, and 11, after arrival. The primary aim of the study was to evaluate the effect of time-zone transitions on the 24h profiles of blood pressure (BP) and heart rate (HR) using an ambulatory BP device (SpaceLabs 90207), for up to 11 d after arrival at the destination. As additional parameters, we studied jet-lag symptoms, training performance, and training coordination by using visual analog scales. Finally, oral temperature and grip strength were measured, and saliva samples were analyzed for cortisol and melatonin. The study showed that all functions were disturbed on the first day after arrival at the destination, jet-lag symptoms remained until day 5–6 after WEST and day 7 after EAST, training performance was worst within the first 4 d after WEST. In accordance with earlier reports, cortisol, melatonin, body temperature, and grip strength were affected in their 24h profiles and additionally modified by the training units. Surprisingly, BP and HR were not only affected on the first day but also the time-zone transition led to an increase in BP after WEST and a decrease in BP after EAST. However, the training units seemed to influence the BP profile more than the time-zone transitions. HR rhythm was affected by both time-zone transitions and exercise. It is concluded that not only jet-lag symptoms but also alterations in physiological functions should be considered to occur in highly competitive athletes due to time-zone transition and, therefore, an appropriate time of reentrainment is recommended.     

Variations in diurnal and nocturnal waking state in air traffic controllers

Physiological variables of 22 air traffic controllers (ATCs), mean age 32, were continuously telemetrically recorded from 08:00 to 17:30 and on the following day from 19:00 to either 00:00 or 0.3:00. EEG (alpha and theta indices, slow delta waves), EOG (palpebral blinks), EMG (from the neck muscles) and EKG (HR) were recorded. Comparison between day and night shows an increase at night of HR and slow waves, particularly after midnight. These results were compared with similar ones obtained from two other populations of the same age having very different professional activities (university personnel and factory workers). The EEG indices and HR are higher in ATCs. The work load imposed by the need in air traffic control to maintain a high level of vigilance, especially difficult after midnight, is in great part responsible for the high values of physiological parameters observed in this study.     

Lack of exposure to natural light in the workspace is associated with physiological,sleep and depressive symptoms

The diurnal light cycle has a crucial influence on all life on earth. Unfortunately, modern society has modified this life-governing cycle by stressing maximum production and by giving insufficient attention to the ecological balance and homeostasis of the human metabolism. The aim of this study is to evaluate the effects of exposure or lack of exposure to natural light in a rest/activity rhythm on cortisol and melatonin levels, as well as on psychological variables in humans under natural conditions. This is a cross-sectional study. The subjects were allocated split into two groups according to their workspace (10 employees in the “with window” group and 10 in the “without window” group). All participants were women and wore anactigraph (Actiwatch 2, Philips Respironics), which measures activity and ambient light exposure, for seven days. Concentrations of melatonin and cortisol were measured from the saliva samples. Participants were instructed to collect saliva during the last day of use of the actigraph at 08:00 am, 4:00 pm and 10:00 pm. The subjects answered the Self-Reporting Questionnaire-20 (SRQ-20) to measure the presence of minor psychiatric disorders; the Montgomery-Asberg (MA) scale was used to measure depression symptoms, and the Pittsburgh Sleep Quality Index questionnaire (PSQI) was used to evaluate the quality of sleep. The Rayleigh analysis indicates that the two groups, “with window” an d “without window”, exhibited similar activities and light acrophases. In relation to light exposure, the mesor was significantly higher (t?=??2.651, p?=?0.023) in t he “with window” group (191.04?±?133.36) than in the “without window” group (73.8?±?42.05). Additionally, the “with window” group presented the highest amplitude of light exposure (298.07?±?222.97). Cortisol levels were significantly different between the groups at 10:00 pm (t?=?3.009, p?=?0.008; “without window” (4.01?±?0.91) “with window” (3.10?±?0.30)). In terms of the melatonin levels, the groups differed at two different times of day: 08:00 am (t?=?2.593, p?=?0.018) and 10:00 pm (t?=??2.939, p?=?0.009). The “with window” group had a lower melatonin level at 08:00 am (3.54?±?0.60) but a higher level at 10:00 pm (24.74?±?4.22) than the “without window” group. Higher cortisol levels were positively correlated with minor psychiatric disorders and depressive symptoms (MA) at 10:00 pm. Lower melatonin levels at 10:00 pm were correlated with depressive symptoms and poor quality of sleep (PSQI). Our study demonstrated that not only may light pollution affect human physiology but also lack of exposure to natural light is related to high levels of cortisol and lower levels of melatonin at night, and these, in turn, are related to depressive symptoms and poor quality of sleep.     

Timing Light Treatment for Eastward and Westward Travel Preparation

Jet lag degrades performance and operational readiness of recently deployed military personnel and other travelers. The objective of the studies reported here was to determine, using a narrow bandwidth light tower (500 nm), the optimum timing of light treatment to hasten adaptive circadian phase advance and delay. Three counterbalanced treatment order, repeated measures studies were conducted to compare melatonin suppression and phase shift across multiple light treatment timings. In Experiment 1, 14 normal healthy volunteers (8 men/6 women) aged 34.9±8.2 yrs (mean±SD) underwent light treatment at the following times: A) 06:00 to 07:00 h, B) 05:30 to 07:30 h, and C) 09:00 to 10:00 h (active control). In Experiment 2, 13 normal healthy subjects (7 men/6 women) aged 35.6±6.9 yrs, underwent light treatment at each of the following times: A) 06:00 to 07:00 h, B) 07:00 to 08:00 h, C) 08:00 to 09:00 h, and a no-light control session (D) from 07:00 to 08:00 h. In Experiment 3, 10 normal healthy subjects (6 men/4 women) aged 37.0±7.7 yrs underwent light treatment at the following times: A) 02:00 to 03:00 h, B) 02:30 to 03:30 h, and C) 03:00 to 04:00 h, with a no-light control (D) from 02:30 to 03:30 h. Dim light melatonin onset (DLMO) was established by two methods: when salivary melatonin levels exceeded a 1.0 pg/ml threshold, and when salivary melatonin levels exceeded three times the 0.9 pg/ml sensitivity of the radioimmunoasssy. Using the 1.0 pg/ml DLMO, significant phase advances were found in Experiment 1 for conditions A (p?<?.028) and B (p?<?0.004). Experiment 2 showed significant phase advances in conditions A (p?<?0.018) and B (p?<?0.003) but not C (p?<?0.23), relative to condition D. In Experiment 3, only condition B (p?<?0.035) provided a significant phase delay relative to condition D. Similar but generally smaller phase shifts were found with the 2.7 pg/ml DLMO method. This threshold was used to analyze phase shifts against circadian time of the start of light treatment for all three experiments. The best fit curve applied to these data (R²?=?0.94) provided a partial phase-response curve with maximum advance at approximately 9–11 h and maximum delay at approximately 5–6 h following DLMO. These data suggest largest phase advances will result when light treatment is started between 06:00 and 08:00 h, and greatest phase delays will result from light treatment started between 02:00 to 03:00 h in entrained subjects with a regular sleep wake cycle (23:00 to 07:00 h).     

Diurnal Variation in Temperature,Mental and Physical Performance,and Tasks Specifically Related to Football (Soccer)

Football (soccer) training and matches are scheduled at different times throughout the day. Association football involves a variety of fitness components as well as psychomotor and game‐related cognitive skills. The purpose of the present research, consisting of two separate studies, was to determine whether game‐related skills varied with time of day in phase with global markers of both performance and the body clock. In the first study, eight diurnally active male association football players (19.1±1.9 yrs of age; mean±SD) with 10.8±2.1 yrs playing experience participated. Measurements were made on different days at 08:00, 12:00, 16:00, and 20:00 h in a counterbalanced manner. Time‐of‐day changes in intra‐aural temperature (used as a marker of the body clock), grip strength, reaction times, flexibility (markers of aspects of performance), juggling and dribbling tasks, and wall‐volley test (football‐specific skills) were compared. Significant (repeated measures analysis of variance, ANOVA) diurnal variations were found for body temperature (p<0.0005), choice reaction time (p<0.05), self‐rated alertness (p<0.0005), fatigue (p<0.05), forward (sit‐and‐reach) flexibility (p<0.02), and right-hand grip strength (p<0.02), but not left-hand grip strength (p=0.40) nor whole‐body (stand‐and‐reach) flexibility (p=0.07). Alertness was highest and fatigue lowest at 20:00 h. Football‐specific skills of juggling performance showed significant diurnal variation (p<0.05, peak at 16:00 h), whereas performance on the wall‐volley test tended to peak at 20:00 h and dribbling showed no time‐of‐day effect (p=0.55). In a second study, eight diurnally active subjects (23.0±0.7 yrs of age) completed five test sessions, at the same times as in the first study but with a second session at 08:00 h. Test‐re‐test comparisons at 08:00 h for all components indicated good reliability. Intra‐aural temperature showed a significant time‐of‐day effect (p<0.001) with mean temperature at 16:00 h (36.4°C) higher than at 08:00 h (35.4°C). There was no significant effect of chronotype on the temperature acrophase (peak time) (p>0.05). Diurnal variation was found for performance tests, including sit‐and‐reach flexibility (p<0.01) and spinal hyper‐extension (p<0.05). Peaks occurred between 16:00 and 20:00 h and the daytime changes paralleled the temperature rhythm. Diurnal variation was also found for football‐specific tests, including dribbling time (p<0.001, peak at 20:00 h) and chip test performance (p<0.01), being more accurate at 16:00 h (mean error=0.75 m) than at 08:00 h (mean error=1.01 m). Results indicate football players perform at an optimum between 16:00 and 20:00 h when not only football‐specific skills but also measures of physical performance are at their peak. Body temperature peaked at a similar time, but positive mood states seemed to peak slightly earlier. While causal links cannot be established in these experiments, the results indicate that the diurnal variation of some aspects of football performance is affected by factor(s) other than body temperature alone.     

Delta5-3beta-hydroxysteroid dehydrogenase and estradiol-17beta-hydroxysteroid dehydrogenase activity in preimplantation hamster embryos

Preimplantation golden hamster (Mesocricetus auratus) embryos were recovered on days 1 (= day of finding spermatozoa in the vagina) through 4 of pregnancy. Postimplantation embryos were studied in sectioned gestation sacs excised on days 5 and 6. Δ⁵-3β-Hydroxysteroid dehydrogenase (3β-HSD) activity in embryos was determined histochemically. There was no enzyme activity on days 1 and 2. Weak activity was first observed at 08:00–09:00 hr on day 3, the activity then increased, peaked at 01:00–03:00 hr on day 4, considerably declined by 08:00–09:00 hr (day 4), and was absent on days 5 and 6. These results suggest that the preimplantation embryos synthesize steroid hormones. It was previously hypothesized (Dickmann and Dey, 1973, Dickmann and Dey, 1974) that, hormones synthesized by the preimplantation rat embryo participate in the regulation of morula to blastocyst transformation and implantation of the blastocyst. This hypothesis is applicable to the hamster.In addition to 3βHSD, estradiol-17β-hydroxysteroid dehydrogenase activity was observed in day 3 embryos, suggesting that the embryo synthesizes estrogen.     

Twenty-Four-Hour Variations in the Sensitivity of Rat Aorta to Vasoactive Agents

The presence of time-dependent variations in the in vitro sensitivity of aorta preparations to either vasoconstricting or relaxing agents was investigated in rats maintained in light from 08: 00 to 20: 00 and in darkness from 20: 00 to 08: 00. Rat thoracic aorta rings were obtained from animals sacrificed at four different times of the day. The rat aorta was found to be more sensitive to the constricting effect of phenylephrine at 15: 00, and of 5-hydroxytryptamine at 21: 00. On the other hand, both endothelium-dependent and -independent relaxations were more remarkable at 03: 00 than at other times of the day. These variations represented significant circadian rhythms when analyzed by analysis of variance. Different in vitro responsiveness to these agents might reflect changes in the sensitivity and/or number of related receptors in vascular preparations. In conclusion, the circadian time of animal sacrifice to obtain vascular preparations constitutes an important aspect of the research method and a key determinant of findings. (Chronobiology International, 13(6), 465-475, 1996)     

Optimal Schedules of Light Exposure for Rapidly Correcting Circadian Misalignment

Jet lag arises from a misalignment of circadian biological timing with the timing of human activity, and is caused by rapid transmeridian travel. Jet lag''s symptoms, such as depressed cognitive alertness, also arise from work and social schedules misaligned with the timing of the circadian clock. Using experimentally validated mathematical models, we develop a new methodology to find mathematically optimal schedules of light exposure and avoidance for rapidly re-entraining the human circadian system. In simulations, our schedules are found to significantly outperform other recently proposed schedules. Moreover, our schedules appear to be significantly more robust to both noise in light and to inter-individual variations in endogenous circadian period than other proposed schedules. By comparing the optimal schedules for thousands of different situations, and by using general mathematical arguments, we are also able to translate our findings into general principles of optimal circadian re-entrainment. These principles include: 1) a class of schedules where circadian amplitude is only slightly perturbed, optimal for dim light and for small shifts 2) another class of schedules where shifting occurs along the shortest path in phase-space, optimal for bright light and for large shifts 3) the determination that short light pulses are less effective than sustained light if the goal is to re-entrain quickly, and 4) the determination that length of daytime should be significantly shorter when delaying the clock than when advancing it.