Sleep Loss and Performance of Anaesthesia Trainees and Specialists

Fatigue risk associated with work schedules of hospital doctors is coming under increasing scrutiny, with much of the research and regulatory focus on trainees. However, provision of 24 h services involves both trainees and specialists, who have different but interdependent work patterns. This study examined work patterns, sleep (actigraphy, diaries) and performance (psychomotor vigilance task pre‐ and post‐duty) of 28 anaesthesia trainees and 20 specialists across a two‐week work cycle in two urban public hospitals. Trainees at one hospital worked back‐to‐back 12 h shifts, while the others usually worked 9 h day shifts but periodically worked a 14 h day (08:00–22:00 h) to maintain cover until arrival of the night shift (10 h). On 11% of day shifts and 23% of night shifts, trainees were working with ≥2 h of acute sleep loss. However, average sleep loss was not greater on night shifts, possibly because workload at night in one hospital often permitted some sleep. Post‐night shift performance was worse than post‐day shift performance for the median (t₍₁₃₁₎=3.57, p<0.001) and slowest 10% of reaction times (t₍₁₃₄₎=2.91, p<0.01). At the end of night shifts, poorer performance was associated with longer shift length, longer time since waking, greater acute sleep loss, and more total work in the past 24 h. Specialists at both hospitals had scheduled clinical duties during the day and were periodically scheduled on call to cover after‐hours services. On 8% of day shifts and 14% of day+call schedules, specialists were working with ≥2 h of acute sleep loss. They averaged 0.6 h less sleep when working day shifts (t_(23.5)=2.66, p=0.014) and 0.8 h less sleep when working day shifts+call schedules (t_(26.3)=2.65, p=0.013) than on days off. Post‐duty reaction times slowed linearly across consecutive duty days (median reaction time, t₍₁₃₁₎=?3.38, p<0.001; slowest 10%, t₍₁₆₀₎=?3.33, p<0.01; fastest 10%, t₍₁₃₈₎=?2.67, p<0.01). Poorer post‐duty performance was associated with greater acute sleep loss and longer time since waking, but better performance was associated with longer day shifts, consistent with circadian improvement in psychomotor performance across the waking day. This appears to be the first study to document sleep loss among specialist anaesthetists. Consistent with observations from experimental studies, the sleep loss of specialists across 12 consecutive working days was associated with a progressive decline in post‐duty PVT performance. However, this decline occurred with much less sleep restriction (< 1 h per day) than in laboratory studies, suggesting an exacerbating effect of extended wakefulness and/or cumulative fatigue associated with work demands. For both trainees and specialists, robust circadian variation in PVT performance was evident in this complex work setting, despite the potential confounds of variable shift durations and workloads. The relationship between PVT performance of an individual and the safe administration of anaesthesia in the operating theater is unknown. Nevertheless, the findings reinforce that any schedule changes to reduce work‐related fatigue need to consider circadian performance variation and the potential transfer of workload and fatigue risk between trainees and specialists.     

HIV Viremia and T-Cell Activation Differentially Affect the Performance of Glomerular Filtration Rate Equations Based on Creatinine and Cystatin C

Background

Serum creatinine and cystatin C are used as markers of glomerular filtration rate (GFR). The performance of these GFR markers relative to exogenously measured GFR (mGFR) in HIV-positive individuals is not well established.

Methods

We assessed the performance of the chronic kidney disease epidemiology collaboration equations based on serum concentrations of creatinine (eGFR_cr), cystatin C (eGFR_cys) and both biomarkers combined (eGFR_cr-cys) in 187 HIV-positive and 98 HIV-negative participants. Measured GFR was calculated by plasma iohexol clearance. Bias and accuracy were defined as the difference between eGFR and mGFR and the percentage of eGFR observations within 30% of mGFR, respectively. Activated CD4 and CD8 T-cells (CD38+ HLA-DR+) were measured by flow cytometry.

Results

The median mGFR was >100 ml/min/1.73 m² in both groups. All equations tended to be less accurate in HIV-positive than in HIV-negative subjects, with eGFR_cr-cys being the most accurate overall. In the HIV-positive group, eGFR_cys was significantly less accurate and more biased than eGFR_cr and eGFR_{cr_cys}. Additionally eGFR_cys bias and accuracy were strongly associated with use of antiretroviral therapy, HIV RNA suppression, and percentages of activated CD4 or CD8 T-cells. Hepatitis C seropositivity was associated with larger eGFR_cys bias in both HIV-positive and HIV-negative groups. In contrast, eGFR_cr accuracy and bias were not associated with HIV-related factors, T-cell activation, or hepatitis C.

Conclusions

The performance of eGFR_cys relative to mGFR was strongly correlated with HIV treatment factors and markers of T-cell activation, which may limit its usefulness as a GFR marker in this population.     

Comparison of Estimating Equations for the Prediction of Glomerular Filtration Rate in Kidney Donors before and after Kidney Donation

The aim of this study is to investigate the usefulness of the GFR-estimating equations to predict renal function in kidney donors before and after transplantation. We compared the performance of 24-hour-urine–based creatinine clearance (24 hr urine-CrCl), the Cockcroft-Gault formula (eGFR_CG), the Modification of Diet in Renal Disease equation (eGFR_MDRD), and the Chronic Kidney Disease Epidemiology Collaboration equation (eGFR_CKD-EPI) with technetium-diethylenetriaminepentaacetic acid (^99mTc-DTPA) clearance (mGFR) in 207 potential kidney donors and 108 uninephric donors. Before donation, eGFR_CKD-EPI showed minimal bias and did not show a significant difference from mGFR (P = 0.65, respectively) while 24 hr urine-CrCl and eGFR_MDRD significantly underestimated mGFR (P<0.001 for each). Precision and accuracy was highest in eGFR_CKD-EPI and this better performance was more dominant when renal function is higher than 90 mL·min⁻¹·1.73 m⁻². After kidney donation, eGFR_MDRD was superior to other equations in precision and accuracy in contrast to before donation. Within individual analysis, eGFR_MDRD showed better performance at post-donation compared to pre-donation, but eGFR_CKD-EPI and eGFR_CG showed inferior performance at post-donation. In conclusion, eGFR_CKD-EPI showed better performance compared to other equations before donation. In a uninephric donor, however, eGFR_MDRD is more appropriate for the estimation of renal function than eGFR_CKD-EPI.     

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 (～3500 lux; ～1100 µW/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 (T_min), 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 T_min 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 T_min had not yet delayed into the daytime sleep period, which began at 08:30 h. The T_min 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.     

Impact of Thyroid Function on Serum Cystatin C and Estimated Glomerular Filtration Rate: A Cross-Sectional Study

ObjectiveTo determine the relationship between thyroid-stimulating hormone (TSH) and cystatin C (CysC) and estimated glomerular filtration rate calculated by Cys^C (e^GFRCysC).MethodsWe conducted a cross-sectional study including 8,126 male participants. Serum creatinine (Cr), CysC, eGFR calculated by Cr (eGFR_Cr), and eGFR_CysC were determined and compared in euthyroid and subclinical thyroid dysfunction patients. Relationships between TSH and Cr, cystatin C, eGFR_Cr, and eGFR_CysC were assessed by linear and quadratic trend analyses. Odds ratios (ORs) of chronic kidney disease (CKD; eGFR<60 mL/min/1.73m²) were calculated according to categories of thyroid function using TSH values of 2.01-3.00 mIU/L as a reference.ResultsSerum CysC level was significantly elevated, and eGFR_CysC was significantly reduced in both sub-clinical hypothyroidism and subclinical hyperthyroidism. TSH was negatively and linearly associated with Cr and eGFR_Cr (P<.001). Quadratic trends were found between TSH and cystatin C or eGFR_CysC (P<.001). Compared with individuals with TSH of 2.01-3.00 mIU/L, the prevalence of CKD_CysC was significantly higher in subjects with TSH<0.40 mIU/L, 3.01-4.00 mIU/L, and 4.01-7.00 mIU/L, while the prevalence of CKD_Cr was only significantly higher in subjects with TSH>7.0 mIU/L.ConclusionDespite only studying male subjects and using eGFR rather than standard GFR, we conclude that thyroid function differentially affects serum CysC and Cr concentrations. Subclinical hypothyroidism and subclinical hyperthyroidism are both associated with elevated CysC, reduced eGFR_CysC, and higher prevalence of CKD_CysC. Assessment of renal function with CysC should be avoided in patients with thyroid dysfunction. (Endocr Pract. 2013;19:397-403)     

Sleep and Sleepiness of Fishermen on Rotating Schedules

Seafaring is a hazardous occupation with high death and injury rates, but the role of seafarer fatigue in these events is generally not well documented. The International Maritime Organization has identified seafarer fatigue as an important health and safety issue. Most research to date has focused on more regularly scheduled types of operations (e.g., merchant vessels, ferries), but there is relatively little information on commercial fishing, which often involves high day‐to‐day and seasonal variability in work patterns and workload. The present study was designed to monitor the sleep and sleepiness of commercial fishermen at home and during extended periods at sea during the peak of the hoki fishing season, with a view to developing better fatigue management strategies for this workforce. Sleep (wrist actigraphy and sleep diaries) and sleepiness (Karolinska Sleepiness Scale [KSS] before and after each sleep period) of 20 deckhands were monitored for 4–13 days at home and for 5–9 days at sea while working a nominal 12 h on/6 h off schedule. On the 12 h on/6 h off schedule, there was still a clear preference for sleep at night. Comparing the last three days at home and the first three days at sea showed that fishermen were more likely to have split sleep at sea (Wilcoxon signed ranks p<0.001), but the median sleep/24 h did not differ significantly by location (5.9 h at sea vs. 6.7 h at home). However, on 23% of days at sea, fishermen obtained<4 h total sleep/24 h, compared to 3% of days at home (p(χ²)<0.01). Sleep efficiency, mean activity counts/min sleep, and subjective ratings of sleep quality did not differ significantly between the last three days at home and the first three days at sea. However, sleepiness ratings remained higher after sleep at sea (Wilcoxon signed ranks p<0.05), with fishermen having post‐sleep KSS ratings ≥7 on 24% of days at sea vs. 9% of days at home (Wilcoxon signed ranks p<0.01). This work adds to the limited number of studies that objectively monitored the sleep of seafarers. It has the strength of operational fidelity but the weakness that large inter‐ and intra‐individual variability in sleep, combined with the small sample size, limited the power of the study to detect statistically significant differences between sleep at home and at sea. The clear preference for sleep at night during the 12 h on/6 h off schedule at sea is consistent with the expectation that this 18 h duty/rest cycle is outside the range of entrainment of the circadian pacemaker. High levels of acute sleep loss, and residual sleepiness after sleep, were much more common at sea than at home. The longer duration of trips during the peak of the fishing season increases the risk of performance impairment due to greater cumulative sleep loss than would be expected on typical three‐day trips. Key fatigue management strategies in this environment include that fishermen report to work as well rested as possible. Once at sea, the day‐to‐day variability in activities due to uncontrollable factors, such as fishing success, repairing gear, and weather conditions, mean that contingency planning is required for managing situations where the entire crew have experienced long periods of intensive work with minimum recovery opportunities.     

Sleep and Circadian Rhythms in Spousally Bereaved Seniors

A laboratory study of sleep and circadian rhythms was undertaken in 28 spousally bereaved seniors (≥60 yrs) at least four months after the loss event. Measures taken included two nights of polysomnography (second night used), ～36 h of continuous core body temperature monitoring, and four assessments of mood and alertness throughout a day. Preceding the laboratory study, two‐week diaries were completed, allowing the assessment of lifestyle regularity using the 17‐item Social Rhythm Metric (SRM) and the timing of sleep using the Pittsburgh Sleep Diary (PghSD). Also completed were questionnaires assessing level of grief (Texas Revised Inventory of Grief [TRIG] and Index of Complicated Grief [ICG]), subjective sleep quality (Pittsburgh Sleep Quality Index [PSQI]), morningness‐eveningness (Composite Scale of Morningness [CSM]), and clinical interview yielding a Hamilton Depression Rating Scale (HDRS) score. Grief was still present, as indicated by an average TRIG score of about 60. On average, the bereaved seniors habitually slept between ～23:00 and ～06:40 h, achieving ～6 h of sleep with a sleep efficiency of ～80%. They took about 30 min to fall asleep, and had their first REM episode after 75 min. About 20% of their sleep was in Stage REM, and about 3% in Stages 3 or 4 (slow wave sleep). Their mean PSQI score was 6.4. Their circadian temperature rhythms showed the usual classic shape with a trough at ～01:00 h, a fairly steep rise through the morning hours, and a more gradual rise to mid‐evening, with an amplitude of ～0.8°C. In terms of lifestyle regularity, the mean regularity (SRM) score was 3.65 (slightly lower than that usually seen in seniors). Mood and alertness showed time‐of‐day variation with peak alertness in the late morning and peak mood in the afternoon. Correlations between outcome sleep/circadian variables and level of grief (TRIG score) were calculated; there was a slight trend for higher grief to be associated with less time spent asleep (p=0.07) and reduced alertness at 20:00 h (p=0.05). Depression score was not correlated with TRIG score (p>0.20). When subjects were divided into groups by the nature of their late spouse's death (expected/after a long‐term chronic illness [n=18] versus unexpected [n=10]), no differences emerged in any of the variables. In conclusion, when studied at least four months after the loss event, there appears to be some sleep disruption in spousally bereaved seniors. However, this disruption does not appear to be due to bereavement‐related disruptions in the circadian system.     

Circadian clock component,LHY, tells a plant when to respond photosynthetically to light in nature

The circadian clock is known to increase plant growth and fitness, and is thought to prepare plants for photosynthesis at dawn and dusk; whether this happens in nature was unknown. We transformed the native tobacco, Nicotiana attenuata to silence two core clock components, NaLHY (irLHY) and NaTOC1 (irTOC1). We characterized growth and light‐ and dark‐adapted photosynthetic rates (A_c) throughout a 24 h day in empty vector‐transformed (EV), irLHY, and irTOC1 plants in the field, and in NaPhyA‐ and NaPhyB1‐silenced plants in the glasshouse. The growth rates of irLHY plants were lower than those of EV plants in the field. While irLHY plants reduced A_c earlier at dusk, no differences between irLHY and EV plants were observed at dawn in the field. irLHY, but not EV plants, responded to light in the night by rapidly increasing A_c. Under controlled conditions, EV plants rapidly increased A_c in the day compared to dark‐adapted plants at night; irLHY plants lost these time‐dependent responses. The role of NaLHY in gating photosynthesis is independent of the light‐dependent reactions and red light perceived by NaPhyA, but not NaPhyB1. In summary, the circadian clock allows plants not to respond photosynthetically to light at night by anticipating and gating red light‐mediated in native tobacco.     

Hypocretins: The Timing of Sleep and Waking

The appropriate time and place for sleep and waking are important factors for survival. Sleep and waking, rest and activity, flight and fight, feeding, and reproduction are all organized in relation to the day and night. A biological clock, the suprachiasmatic nucleus (SCN), synchronized by photic influences and other environmental cues, provides an endogenous timing signal that entrains circadian body rhythms and is complemented by a homeostatic sleep pressure factor. Cholinergic, catecholaminergic, serotonergic, and histaminergic nuclei control wakefulness and mutually interact with the SCN as well as sleep‐ and wake‐promoting neurons in the hypothalamus to form a bistable switch that controlls the timing of behavioral state transitions. Hypocretin neurons integrate circadian‐photic and nutritional‐metabolic influences and act as a conductor in the aminergic orchestra. Their loss causes narcolepsy, a disease conferring the inability to separate sleep and waking. Their role in appetitive behavior, stress, and memory functions is important to our understanding of addiction and compulsion.     

The internal circadian clock increases hunger and appetite in the evening independent of food intake and other behaviors

Objective:

Despite the extended overnight fast, paradoxically, people are typically not ravenous in the morning and breakfast is typically the smallest meal of the day. We assessed whether this paradox could be explained by an endogenous circadian influence on appetite with a morning trough, while controlling for sleep/wake and fasting/feeding effects.

Design and Methods:

Twelve healthy non‐obese adults (six males; age, 20‐42 years) were studied throughout a 13‐day laboratory protocol that balanced all behaviors, including eucaloric meals and sleep periods, evenly across the endogenous circadian cycle. Participants rated their appetite and food preferences by visual analog scales.

Results:

There was a large endogenous circadian rhythm in hunger, with the trough in the biological morning (8 AM) and peak in the biological evening (8 PM; peak‐to‐trough amplitude = 17%; P = 0.004). Similarly‐phased significant endogenous circadian rhythms were present in appetites for sweet, salty and starchy foods, fruits, meats/poultry, food overall, and for estimates of how much food participants could eat (amplitudes 14‐25%; all P < 0.05).

Conclusions:

In people who sleep at night, the intrinsic circadian evening peak in appetite may promote larger meals before the fasting period necessitated by sleep, whereas the circadian morning trough would theoretically facilitate the extended overnight fast. Furthermore, the circadian decline in hunger across the night would theoretically counteract the fasting‐induced hunger increase that could otherwise disrupt sleep.     

Efficient and Regular Patterns of Nighttime Sleep are Related to Increased Vulnerability to Microsleeps Following a Single Night of Sleep Restriction

Sleep-deprived people, or those performing extended monotonous tasks, can exhibit brief episodes in which they suspend performance and appear to fall asleep momentarily—behavioral microsleeps (“microsleeps”). In this study, microsleeps were identified using eye video and tracking response during a 20-min continuous tracking task undertaken by 16 healthy volunteers (mean age 24.9?yrs; 8 females, 8 males) in the early afternoon following a normally rested night and a night of restricted sleep (time-in-bed restricted to 4?h). Sessions were 1 wk apart and counterbalanced. Wrist actigraphy, self-reported sleepiness, and sleep quality were also recorded. We hypothesized that high microsleep rates when normally rested or after a night of sleep restriction would be related to poor sleep quality, sleep disturbance, circadian type, irregular sleep patterns, low daily sleep duration, or poor sleep efficiency. We also hypothesized that prior performance on a 10-min psychomotor vigilance task (PVT) (mean reaction time or number of PVT lapses) would be related to the number of microsleeps during the tracking task and that PVT performance could, therefore, be used as a fitness-for-duty indicator. The number of microsleeps during the tracking task increased following sleep restriction (mean 11.4 versus 27.9; p?=?0.03). There were no correlations between the number of microsleeps in the normally rested session and any of the actigraphically measured or self-reported sleep measures. However, the number of microsleeps following sleep restriction was correlated with sleep efficiency (r?=?0.73, p?=?0.001), sleep onset latency (r?=??0.57, p?=?0.02), and sleep onset time-of-day standard deviation (r?=??0.54, p?=?0.03) over 11 normally rested nights. There was no correlation between PVT performance and the subsequent number of microsleeps during the tracking task in either session. Attributes usually associated with beneficial nighttime sleep patterns—going to sleep at a similar time each night, falling asleep quickly, and infrequent arousals—were related to greater vulnerability to microsleeps following sleep restriction. There were intercorrelations between all the sleep measures associated with microsleep rate following sleep restriction, indicating that the measures form a pattern of behaviors and are not independently related to microsleep rate. Perhaps some people maintain a regular sleep pattern because they experience sleepiness the following day when their pattern is disrupted. Conversely, people with more variation in their sleep pattern may do so because this does not substantially increase sleepiness the following day. We conclude that people with consistent sleep patterns and efficient sleep may be more prone to microsleeps than other people when their usual regular pattern is disrupted by sleep restriction.     

Effects of Filtering Visual Short Wavelengths During Nocturnal Shiftwork on Sleep and Performance

Circadian phase resetting is sensitive to visual short wavelengths (450–480?nm). Selectively filtering this range of wavelengths may reduce circadian misalignment and sleep impairment during irregular light-dark schedules associated with shiftwork. We examined the effects of filtering short wavelengths (<480?nm) during night shifts on sleep and performance in nine nurses (five females and four males; mean age?±?SD: 31.3?±?4.6 yrs). Participants were randomized to receive filtered light (intervention) or standard indoor light (baseline) on night shifts. Nighttime sleep after two night shifts and daytime sleep in between two night shifts was assessed by polysomnography (PSG). In addition, salivary melatonin levels and alertness were assessed every 2?h on the first night shift of each study period and on the middle night of a run of three night shifts in each study period. Sleep and performance under baseline and intervention conditions were compared with daytime performance on the seventh day shift, and nighttime sleep following the seventh daytime shift (comparator). On the baseline night PSG, total sleep time (TST) (p?<?0.01) and sleep efficiency (p?=?0.01) were significantly decreased and intervening wake times (wake after sleep onset [WASO]) (p?=?0.04) were significantly increased in relation to the comparator night sleep. In contrast, under intervention, TST was increased by a mean of 40?min compared with baseline, WASO was reduced and sleep efficiency was increased to levels similar to the comparator night. Daytime sleep was significantly impaired under both baseline and intervention conditions. Salivary melatonin levels were significantly higher on the first (p?<?0.05) and middle (p?<?0.01) night shifts under intervention compared with baseline. Subjective sleepiness increased throughout the night under both conditions (p?<?0.01). However, reaction time and throughput on vigilance tests were similar to daytime performance under intervention but impaired under baseline on the first night shift. By the middle night shift, the difference in performance was no longer significant between day shift and either of the two night shift conditions, suggesting some adaptation to the night shift had occurred under baseline conditions. These results suggest that both daytime and nighttime sleep are adversely affected in rotating-shift workers and that filtering short wavelengths may be an approach to reduce sleep disruption and improve performance in rotating-shift workers. (Author correspondence: casper@lunenfeld.ca)     

Working Under Daylight Intensity Lamp: An Occupational Risk for Developing Circadian Rhythm Sleep Disorder?

A 47‐yr‐old male was admitted to the Institute for Fatigue and Sleep Medicine complaining of severe fatigue and daytime sleepiness. His medical history included diagnosis of depression and chronic fatigue syndrome. Antidepressant drugs failed to improve his condition. He described a gradual evolvement of an irregular sleep‐wake pattern within the past 20 yrs, causing marked distress and severe impairment of daily functioning. He had to change to a part‐time position 7 yrs ago, because he was unable to maintain a regular full‐time job schedule. A 10‐day actigraphic record revealed an irregular sleep-wake pattern with extensive day‐to‐day variability in sleep onset time and sleep duration, and a 36 h sampling of both melatonin level and oral temperature (12 samples, once every 3 h) showed abnormal patterns, with the melatonin peak around noon and oral temperature peak around dawn. Thus, the patient was diagnosed as suffering from irregular sleep‐wake pattern. Treatment with melatonin (5 mg, 2 h before bedtime) did not improve his condition. A further investigation of the patient's daily habits and environmental conditions revealed two important facts. First, his occupation required work under a daylight intensity lamp (professional diamond‐grading equipment of more than 8000 lux), and second, since the patient tended to work late, the exposure to bright light occurred mostly at night. To recover his circadian rhythmicity and stabilize his sleep‐wake pattern, we recommended combined treatment consisting of evening melatonin ingestion combined with morning (09:00 h) bright light therapy (0800 lux for 1 h) plus the avoidance of bright light in the evening. Another 10‐day actigraphic study done only 1 wk after initiating the combined treatment protocol revealed stabilization of the sleep‐wake pattern with advancement of sleep phase. In addition, the patient reported profound improvement in maintaining wakefulness during the day. This case study shows that chronic exposure to bright light at the wrong biological time, during the nighttime, may have serious effects on the circadian sleep‐wake patterns and circadian time structure. Therefore, night bright light exposure must be considered to be a risk factor of previously unrecognized occupational diseases of altered circadian time structure manifested as irregularity of the 24 h sleep‐wake cycle and melancholy.     

Assessment of serum beta-trace protein (BTP) measurement in the prediction of glomerular filtration rate. Comparison with serum cystatin C

Serum BTP measurement is sometimes believed to be an alternative marker of glomerular filtration rate (GFR) assessment. The aim of the present work was to investigate the correlation between creatinine, cystatin C, and BTP values in sera and to compare the diagnostic efficacy for serum BTP and cystatin C with the glomerular filtration rate estimate. 25 individuals were tested. GFR was estimated from creatinine clearance, serum cystatin C and BTP and urine alpha-1 microglobulin, albumin, GMT and creatinine were measured. BTP values correlated with cystatin C (r = 0.75; p < 0.01), creatinine (r = 0.73, p < 0.01), GFR (r = -0.46; p = 0.02), urine alpha-1-microglobulin (r = 0.66; p < 0.01). The diagnostic efficacy of BTP for reduced GFR was insufficient and the calculation of GFR with BTP was not included in the regression model.     

Gender Differences in Polysomnographic Sleep in Young Healthy Sleepers

Middle‐aged and elderly populations exhibit gender differences in polysomnographic (PSG) sleep; however, whether young men and women also show such differences remains unclear. Thirty‐one young healthy sleepers (16 men and 15 women, aged 18 to 30 yr, mean±SD, 20.5±2.4 yr) completed 3 consecutive overnight sessions in a sleep laboratory, after maintaining a stable sleep‐wake cycle for 1 wk before study entry. Standard PSG sleep and self‐rated sleepiness data were collected each night. Across nights, women showed better sleep quality than men: they fell asleep faster (shorter sleep onset latency) and had better sleep efficiency, with more time asleep and less time awake (all differences showed large effect sizes, d=0.98 to 1.12). By contrast, men were sleepier than women across nights. Both men and women demonstrated poorer overall sleep quality on the first night compared with the subsequent 2 nights of study. We conclude young adult healthy sleepers show robust gender differences in PSG sleep, like older populations, with better sleep quality in women than in men. These results highlight the importance of gender in sleep and circadian rhythm research studies employing young subjects and have broader implications for women's health issues relating to these topics.     

Young Women With Major Depression Live on Higher Homeostatic Sleep Pressure Than Healthy Controls

There is mounting evidence for the involvement of the sleep-wake cycle and the circadian system in the pathogenesis of major depression. However, only a few studies so far focused on sleep and circadian rhythms under controlled experimental conditions. Thus, it remains unclear whether homeostatic sleep pressure or circadian rhythms, or both, are altered in depression. Here, the authors aimed at quantifying homeostatic and circadian sleep-wake regulatory mechanisms in young women suffering from major depressive disorder and healthy controls during a multiple nap paradigm under constant routine conditions. After an 8-h baseline night, 9 depressed women, 8 healthy young women, and 8 healthy older women underwent a 40-h multiple nap protocol (10 short sleep-wake cycles) followed by an 8-h recovery night. Polysomnographic recordings were done continuously, and subjective sleepiness was assessed. In order to measure circadian output, salivary melatonin samples were collected during scheduled wakefulness, and the circadian modulation of sleep spindles was analyzed with reference to the timing of melatonin secretion. Sleep parameters as well as non-rapid eye movement (NREM) sleep electroencephalographic (EEG) spectra were determined for collapsed left, central, and right frontal, central, parietal, and occipital derivations for the night and nap-sleep episodes in the frequency range .75–25?Hz. Young depressed women showed higher frontal EEG delta activity, as a marker of homeostatic sleep pressure, compared to healthy young and older women across both night sleep episodes together with significantly higher subjective sleepiness. Higher delta sleep EEG activity in the naps during the biological day were observed in young depressed women along with reduced nighttime melatonin secretion as compared to healthy young volunteers. The circadian modulation of sleep spindles between the biological night and day was virtually absent in healthy older women and partially impaired in young depressed women. These data provide strong evidence for higher homeostatic sleep pressure in young moderately depressed women, along with some indications for impairment of the strength of the endogenous circadian output signal involved in sleep-wake regulation. This finding may have important repercussions on the treatment of the illness as such that a selective suppression of EEG slow-wave activity could promote acute mood improvement. (Author correspondence: Christian.cajochen@upkbs.ch)     

Mood,Alertness, and Performance in Response to Sleep Deprivation and Recovery Sleep in Experienced Shiftworkers Versus Non-Shiftworkers

Previous studies have shown increased sleepiness and mood changes in shiftworkers, which may be due to sleep deprivation or circadian disruption. Few studies, however, have compared responses of experienced shiftworkers and non-shiftworkers to sleep deprivation in an identical laboratory setting. The aim of this laboratory study, therefore, was to compare long-term shiftworkers and non-shiftworkers and to investigate the effects of one night of total sleep deprivation (30.5?h of continuous wakefulness) and recovery sleep on psychomotor vigilance, self-rated alertness, and mood. Eleven experienced male shiftworkers (shiftwork ≥5 yrs) were matched with 14 non-shiftworkers for age (mean?±?SD: 35.7?±?7.2 and 32.5?±?6.2 yrs, respectively) and body mass index (BMI) (28.7?±?3.8 and 26.6?±?3.4?kg/m², respectively). After keeping a 7-d self-selected sleep/wake cycle (7.5/8?h nocturnal sleep), both groups entered a laboratory session consisting of a night of adaptation sleep and a baseline sleep (each 7.5/8?h), a sleep deprivation night, and recovery sleep (4-h nap plus 7.5/8?h nighttime sleep). Subjective alertness and mood were assessed with the Karolinska Sleepiness Scale (KSS) and 9-digit rating scales, and vigilance was measured by the visual psychomotor vigilance test (PVT). A mixed-model regression analysis was carried out on data collected every hour during the sleep deprivation night and on all days (except for the adaptation day), at .25, 4.25, 5.25, 11.5, 12.5, and 13.5?h after habitual wake-up time. Despite similar circadian phase (melatonin onset), demographics, food intake, body posture, and environmental light, shiftworkers felt significantly more alert, more cheerful, more elated, and calmer than non-shiftworkers throughout the laboratory study. In addition, shiftworkers showed a faster median reaction time (RT) compared to non-shiftworkers, although four other PVT parameters did not differ between the groups. As expected, both groups showed a decrease in subjective alertness and PVT performance during and following the sleep deprivation night. Subjective sleepiness and most aspects of PVT performance returned to baseline levels after a nap and recovery sleep. The mechanisms underlying the observed differences between shiftworkers and non-shiftworkers require further study, but may be related to the absence of shiftwork the week prior to and during the laboratory study as well as selection into and out of shiftwork. (Author correspondence: sophie.wehrens@surrey.ac.uk)     

The Influence of Internal Time,Time Awake,and Sleep Duration on Cognitive Performance in Shiftworkers

To date, studies investigating the consequences of shiftwork have predominantly focused on external (local) time. Here, we report the daily variation in cognitive performance in rotating shiftworkers under real-life conditions using the psychomotor vigilance test (PVT) and show that this function depends both on external and internal (biological) time. In addition to this high sensitivity of PVT performance to time-of-day, it has also been extensively applied in sleep deprivation protocols. We, therefore, also investigated the impact of shift-specific sleep duration and time awake on performance. In two separate field studies, 44 young workers (17 females, 27 males; age range 20–36 yrs) performed a PVT test every 2?h during each shift. We assessed chronotype by the MCTQ^Shift (Munich ChronoType Questionnaire for shiftworkers). Daily sleep logs over the 4-wk study period allowed for the extraction of shift-specific sleep duration and time awake in a given shift, as well as average sleep duration (“sleep need”). Median reaction times (RTs) significantly varied across shifts, depending on both Local Time and Internal Time. Variability of reaction times around the 24 h mean (≈ ±5%) was best explained by a regression model comprising both factors, Local Time and Internal Time (p < .001). Short (15th percentile; RT_15%) and long (85th percentile; RT_85%) reaction times were differentially affected by Internal Time and Local Time. During night shifts, only median RT and RT_85% were impaired by the duration of time workers had been awake (p?<?.01, consistent with the highest sleep pressure), but not RT_15%. Proportion of sleep before a test day (relative to sleep need) significantly affected median RT and RT_85% during morning shifts (p?<?.01). RT_15% was worst in the beginning of the morning shift, but improved to levels above average with increasing time awake (p < .05), whereas RT_85% became worse (p < .05). Hierarchical mixed models confirmed the importance of chronotype and sleep duration on cognitive performance in shiftworkers, whereas the effect of time awake requires further research. Our finding that both Local Time and Internal Time, in conjunction with shift-specific sleep behavior, strongly influence performance extends predictions derived from laboratory studies. (Author correspondence: roenneberg@lmu.de)     

Regulation of root respiration in two species of Plantago that differ in relative growth rate: the effect of short- and long-term changes in temperature

This study investigates the effect of short‐ and long‐term changesin temperature on the regulation of root respiratory O₂ uptakeby substrate supply, adenylate restriction and/or the capacityof the respiratory system. The species investigated were the lowland Plantagolanceolata L. and alpine Plantago euryphylla Briggs, Carolin& Pulley, which are inherently fast‐ and slow‐growing, respectively. Theplants were grown hydroponically in a controlled environment (constant23 °C). The effect of long‐term exposure to lowtemperature on regulation of respiration was also assessed in P.lanceolata using plants transferred to 15/10 °C(day/night) for 7 d. Exogenous glucose and uncoupler (CCCP)were used to assess the extent to which respiration rates were limitedby substrate supply and adenylates. The results suggest that adenylatesand/or substrate supply exert the greatest control overrespiration at moderate temperatures (e.g. 15–30 °C)in both species. At low temperatures (5–15 °C),CCCP and glucose had little effect on respiration, suggesting thatrespiration was limited by enzyme capacity alone. The Q₁₀ (proportionalincrease of respiration per 10 °C) of respirationwas increased following the addition of CCCP and/or exogenousglucose. The degree of stimulation by CCCP was considerably lowerin P. euryphylla than P. lanceolata. This suggeststhat respiration rates operate much closer to the maximum capacity in P.euryphylla than P. lanceolata. When P. lanceolata wastransferred to 15 °C for 7 d, respirationacclimated to the lower growth temperature (as demonstrated by an increasein respiration rates measured at 25 °C). In addition,the Q₁₀ was higher, and the stimulatory effectof exogenous glucose and CCCP lower, in the cold‐acclimated rootsin comparison with their warm‐grown counterparts. Acclimation of P.lanceolata to different day/night‐time temperatureregimes was also investigated. The low night‐time temperature wasfound to be the most important factor influencing acclimation. The Q₁₀ valueswere also higher in plants exposed to the lowest night‐time temperature.The results demonstrate that short‐ and long‐term changes in temperaturealter the importance of substrate supply, adenylates and capacityof respiratory enzymes in regulating respiratory flux.     

RETRACTED ARTICLE: A mathematical model to study the relationship between the dietary profiles,core body temperature and sleep profile in the high school students

Body temperature (T_b), food intake and sleep cycle follows a circadian rhythm. Circadian variations of T_b may be influenced by changes in sleep time, late night consumption of high calorie diet and less physical activities. Deviations in any of these daily habits may alter the acrophase, mesor and amplitude of the cosinor curve of T_b. Changes in these confounding factors may also contribute to the body mass index (BMI) of the individual. This study was conducted on 29 high school going adolescents. We have employed an ideal cosinor model to study the changes in the 24 h cyclical changes in T_b (n = 12). Academic overload during examination days was seen in these high school going adults. Sleep duration and dietary habits were also studied in them to find out the relationship with BMI and circadian variations if any (n = 17). Higher BMI was observed in individuals having shorter sleep duration. BMI was high in students consuming high calorie diet at the time of the day when the body metabolism is normally low. A mathematical model exhibiting altered circadian rhythms is proposed that may be used to modify strategies to restore biorhythms for better health.