Perception versus Reality: The Relationship between Subjective and Objective Measures of Sleep When On-call under Simulated Laboratory Conditions.

BACKGROUND: On-call working arrangements have been shown to negatively impact sleep. However, workers may perceive their sleep to be worse than it actually is. The aim of this study was to compare participants' pre- and post-sleep estimates of sleep duration and sleep quality with objectively measured sleep when on-call under laboratory conditions. PARTICIPANTS: 72 healthy, adult males. METHODS: Analyses were performed on three interrelated studies, all of which consisted of four nights in a sleep laboratory. Following adaptation and baseline nights were two on-call nights (sleep opportunity 23:00 h - 07:00 h). Before and after each sleep opportunity, participants provided subjective estimates of sleep. Sleep was objectively measured using polysomnography. RESULTS: Estimated sleep duration (6.74 ± 1.13 h) and sleep onset latency (20.55 ± 14.85 min) were significantly poorer than objectively measured sleep outcomes (sleep duration 7.21 ± 1.25 h; sleep latency 13.20 ± 10.06 min). Of the variance in post-sleep estimated sleep duration, 14% was associated with objectively measured minutes of N3 (R2Δ = 0.55) and REM (R2Δ = 0.75). Additionally, 14% of post-sleep sleep quality estimation variance was associated with minutes of N2 (R2Δ = 0.60) and N3 (R2Δ = 0.79), measured by polysomnography. CONCLUSIONS: Some objective measures of sleep were associated with subjective estimates of sleep duration and sleep quality. However, individuals may overestimate sleep onset latency and underestimate sleep duration during on-call periods. It may be beneficial for on-call workers to actively reflect on feelings of fatigue/alertness for workplace fatigue management, rather than relying solely on estimates of sleep.

Population-based analysis of sociodemographic predictors, health-related quality of life and health service use associated with obstructive sleep apnoea and insomnia in Australia.

Although there is growing recognition of the effects of living with sleep disorders and the important role of primary care in their identification and management, studies indicate that the detection of sleep apnoea (OSA) and insomnia may still be low. This large representative community-based study (n=2977 adults) used logistic regression models to examine predictors of self-reported OSA and current insomnia and linear regression models to examine the association of these sleep conditions with both mental and physical components of health-related quality of life (HRQoL) and health service use. Overall, 5.6% (95% confidence interval (CI) 4.6-6.7) and 6.8% (95% CI 5.7-7.9) of subjects self-reported OSA (using a single-item question) and current insomnia (using two single-item questions) respectively. Many sociodemographic and lifestyle predictors for OSA and insomnia acted in different directions or showed different magnitudes of association. Both disorders had a similar adverse relationship with physical HRQoL, whereas mental HRQoL was more impaired among those with insomnia. Frequent consultations with a doctor were associated with a lower physical HRQoL across these sleep conditions; however, lower mental HRQoL among those frequently visiting a doctor was observed only among individuals with insomnia. The adverse relationship between sleep disorders and physical and mental HRQoL was substantial and should not be underestimated.

Community engagement in general practice: a qualitative study.

BACKGROUND Community engagement is believed to be an important component of quality primary health care. We aimed to capture specific examples of community engagement by general practices, and to understand the barriers that prevent engagement. METHODS We conducted 20 distinct interviews with 31 key informants from general practice and the wider community. The interviews were semi-structured around key relevant topics and were analysed thematically. RESULTS Key themes identified from the interview transcripts included an understanding of 'community', examples of community engagement and the perceived benefits and barriers to community-engaged general practice. We particularly explored aspects of community engagement with Maori. CONCLUSIONS General practices in the study do not think in terms of communities, and they do not have a systematic framework for engagement. Although local champions have generated some great initiatives, most practices seemed to lack a conceptual framework for engagement: who to engage with, how to engage with them, and how to evaluate the results of the engagement.

Waking qEEG to assess psychophysiological stress and alertness during simulated on-call conditions.

INTRODUCTION: On-call schedules are associated with stress and disrupted sleep. In a recent study, under non-sleep deprived conditions, low and high-stress on-call conditions did not significantly impact sleep quality but did impact next day performance. Our aim was to determine whether quantitative electroencephalography (qEEG) would reflect changes in cortical activity in on-call conditions, predicting that the high-stress condition would display faster qEEG frequencies compared with the control and low-stress condition. METHODS: Twenty-four healthy male participants (age: 26.5 ±â€¯4.0 yrs) spent four nights in a time-isolated sleep laboratory. The within-subjects, repeated measures experimental design assessed waking EEG, via the Karolinska Drowsiness Test (KDT) during four time-points across a control day and two experimental (on-call) days. Experimental days comprised a low-stress (LS - reading task) and high-stress (HS - speech task) condition and were counterbalanced. Mixed-models analysis was used to assess condition and time by EEG biomarkers: Alpha Attenuation Coefficient (AAC), Slowing Ratio (SR) and Scaling Exponent (SE). RESULTS: Main effects were found for all three biomarkers by condition, with pairwise analysis reported. There was a significant difference in AAC between the LS condition (M = 1.26 ±â€¯=1.24) and HS condition (M = 1.01 ±â€¯0.76 p = .02) indicating decreased alertness between LS and HS. A significant increase in SR between control (M = 7.1 ±â€¯4.3) and LS (M = 10.1 ±â€¯8.5 p = .0001), and a significant increase between the LS and HS (M = 7.8 ±â€¯6.8 p = .018) showing greatest EEG slowing in the LS condition, reflecting of a passive, sleepier brain state. The SE was significantly higher in the LS (M = 1.09, ±0.17) condition compared with control (M = 1.0, ±0.11 p = .001) indicating decreased alertness in the LS task. DISCUSSION: Using qEEG biomarkers, in contrast with our initial hypothesis, the current study found that compared with control, the LS condition resulted in greater EEG slowing. These findings have implications for on-call workers who engage in periods of passive attention and highlight a protective role task stress may play in maintaining alertness levels during on-call conditions.

Short-term studies of taurocholate uptake by ileal brush border membrane vesicles: anion effects.

Experiments allowing Na+-dependent short-term uptake measurements by ileal brush border vesicles were described. Glucose uptake was compared with taurocholate uptake in the presence of NaCl, NaSCN and Na2SO4. In contrast to the observation made with glucose, taurocholate transport was the same for the three electrolytes, indicating electroneutral taurocholate transport.

The effect of bile salts on the formation and hydrolysis of cholesterol esters by rat liver enzymes.

To determine the effects of different bile salts on the enzymic esterification of cholesterol and the hydrolysis of cholesterol esters rat liver homogenates and rat liver microsomes were incubated with varying amounts of different bile salts. Bile salts inhibited the formation of radioactive cholesterol esters in incubations of either rat liver homogenates or rat liver microsomes containing [14C]cholesterol. Chenodeoxycholate, glycochenodeoxycholate and taurochenodeoxycholate were more potent inhibitors than their comparable cholate analogues. Bile salts stimulated the hydrolysis of cholesterol esters when incubation were carried out with the liver homogenates. The dihydroxy bile salts were again more potent in this regard than the trihydroxylated bile salts. When the effects of bile salts on cholesterol ester hydrolysis were studied in in vitro incubations of hepatic microsomes a biphasic mode of acion was observed. In the absence of Na+ or K+ bile salts stimulated the hydrolysis of cholesterol oleate. However, following the addition of either Na+ or K+ to the microsomal incubations, bile salts caused an inhibition of cholesterol ester hydrolysis. Since cholesterol esterification was also inhibited under these conditions a direct inhibitory effect (not attributable to enhanced hydrolase activity) of the bile salts on the formation of cholesterol esters by the microsomes was established. Furthermore, this inhibition takes place at the transacylation step involving the fatty acyl-CoA ester and the sterol. These results suggest that bile salts can significantly alter the cholesterol-cholesterol ester profile in the liver, and furthermore, that these effects may be influenced by small changes in the intracellular environment in the region where these reactions occur.

The effect of evening bright light in delaying the circadian rhythms and lengthening the sleep of early morning awakening insomniacs.

Past studies have predicted that early morning awakening insomnia is associated with advanced or early circadian rhythms. Because bright light stimulation in the evening can delay the phase of circadian rhythms, we tested its effects on nine (4 females, 5 males) early morning awakening insomniacs. Their sleep was evaluated with wrist actigraphy and their temperature and melatonin circadian rhythms were measured in constant routine procedures. In the initial evaluation, the temperature rhythm phase positions of these insomniacs did appear to be earlier than normal. The subjects were then exposed to bright light stimulation (2,500 lux) from 2000 to 2400 hours on two consecutive evenings. Following the evening bright light treatment, temperature rhythm phase markers were delayed 2-4 hours and melatonin phase markers were delayed 1-2 hours. Sleep onset times were not changed but the mean final wake-up time was delayed from 0459 hours to 0611 hours, resulting in a mean increase of total sleep time of > 1 hour. This pilot study suggests that evening bright light stimulation may be an effective nondrug treatment for early morning awakening insomnia.

The sleep-evoked decrease of body temperature.

The circadian rhythm of deep body temperature consists of both an endogenous component and evoked components resulting from exogenous influences. Previous studies of the sleep-evoked effect have failed to control confounding influences, so that the effect of sleep per se has not been established. In the present study, eight good sleepers had their rectal temperatures recorded for 24 hours in each of two laboratory conditions employing a constant routine to control exogenous influences. Sleep was allowed at night in one condition. Following sleep onset, body temperature dropped more rapidly and remained lower than when wakefulness continued over the same time, resulting in a mean sleep-evoked decrease of 0.31 +/- 0.09 degree C. Fourier regression analysis showed a significant 24-hour (circadian) temperature rhythm, together with a 12-hour harmonic rhythm, in each condition. Circadian rhythm parameters were also altered by the sleep-evoked (or masking) effect, with the amplitude increased and the mean decreased when subjects slept at night in the constant routine. It was suggested that a constant routine methodology be used in studies of circadian rhythm differences and that Fourier regression be used in preference to simple cosine curve fitting to give a better approximation of the temperature rhythm.

Core body temperature is elevated during constant wakefulness in elderly poor sleepers.

STUDY OBJECTIVES: The aim of this study was to test for heightened physiological activity in elderly poor sleeepers compared to good sleepers under ad lib sleep and constant wakeful conditions. DESIGN AND SETTING: Subjects participated in a five-day protocol consisting of four nights of polysomnographic (PSG) and rectal temperature monitoring followed by 26 hours of continuous rectal temperature monitoring under controlled constant wakefulness. PARTICIPANTS: Participants were 16 self-reported sleep maintenance insomniacs and 16 self-reported good sleeping controls over 55 years of age. INTERVENTIONS: NA. MEASUREMENT AND RESULTS: Subjects were grouped according to (1) subjective sleep status and (2) into quartiles according to amount of PSG determined wake after sleep onset (WASO). Significant group differences in temperature were observed when subjects were classified according to PSG but not subjective criteria. In the former case, subjects with the lowest (bottom quartile) compared to the highest (top quartile) amount of PSG determined WASO showed lower sleep and nighttime constant wakeful core body temperatures. CONCLUSIONS: In the elderly, elevated core body temperature is associated with increased nocturnal wakefulness suggesting that physiological activation may underlie sleep maintenance insomnia. This was clearly significant when subjects were compared using objective criteria and temperature was collected under constant wakeful conditions.

The effect of sleep before or after learning on memory.

Early studies in which it was found that learning followed by sleep was better remembered than learning followed by wakefulness were interpreted as giving support for the Interference Theory of Forgetting. More recent studies have shown better retention over the first half of the night's sleep (slow-wave sleep) than over the second half (REM sleep), and conclusions have been drawn that a Decay Theory of Forgetting is more strongly supported. Those studies, however, confounded the type of sleep following learning with sleep prior to learning. When prior sleep was controlled in the present study, there was no support for a first half-night sleep benefit, and, contrary to Decay Theory, there was a second half-night benefit for high imagery material. The strong detrimental effect of sleep prior to learning was inconsistent with the Interference Theory of Forgetting and suggested, instead, the importance of the consolidation process for long-term memory.

Sleep-onset insomniacs have delayed temperature rhythms.

It was predicted from free running and ultradian cycle studies that sleep-onset insomniacs would have endogenous circadian rhythms that were phase delayed compared to good sleepers. Thirteen sleep-onset insomniacs and nine good sleepers were selected to differ only in their sleep-onset latencies as confirmed by polysomnography. their rectal temperatures were measured over a 26-h constant routine and analyzed with best-fit Fourier curves including 24-h fundamental and 12-h harmonic components. The temperature rhythm markers of the insomniacs' rhythms were approximately 2.5 h later than the respective phases of the good sleepers. The usual bedtimes of the insomniacs fell within the "wake maintenance zone" of their delayed temperature rhythm. The good sleepers had typical bedtimes several hours after their "wake maintenance zone" and closer to their body temperature minimum. It was suggested that manipulations to phase advance the insomniacs' rhythms would reduce their sleep-onset latencies. It was also predicted that early morning insomnia results from phase advanced circadian rhythms and that sleep maintenance insomnia results from an abnormal phase relationship between the 24-h temperature rhythm and 12-h sleep-alert rhythm.

The short-term benefits of brief and long naps following nocturnal sleep restriction.

STUDY OBJECTIVES: The purpose was to remedy the lack of experimental studies directly comparing the effects of brief and long daytime naps following nocturnal sleep restriction. DESIGN: Twelve young adult healthy sleepers participated in a repeated measures design comparing the effects of no nap, a 10-minute nap, and a 30-minute afternoon nap in each case following a night of 4.7 hours of total sleep time. Objective and subjective alertness measures and cognitive performance measures were taken before, then 5, 35, and 60 minutes after the termination of the nap. SETTING: N/A. PARTICIPANTS: N/A. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: In the no nap condition measures showed either no change or a decreases of alertness and performance across the testing period. Following the 10-minute nap there was an immediate improvement in subjective alertness and cognitive performance which was sustained for the hour of post nap testing. Immediately following the 30 minute nap most measures of alertness and performance declined but showed some recovery by the end of testing. CONCLUSIONS: Because the delayed benefits following the 30-minute nap may be due to sleep inertia, longer post-nap testing periods should be investigated. However, we conclude that the detrimental effects of sleep restriction were more rapidly and significantly ameliorated, at least within the hour following the nap, by a 10-minute afternoon nap.

Daytime melatonin administration in elderly good and poor sleepers: effects on core body temperature and sleep latency.

Melatonin has been shown to have hypnotic and hypothermic effects in young adults and has been proposed as treatment for insomnia. However, the hypnotic and thermoregulatory effects of melatonin remain to be simultaneously investigated for aged good and poor sleepers. The aim of this study was to explore the short-term effects of exogenous oral daytime melatonin on core body temperature, sleep latency, and subjective vigor and affect in aged women. Twelve sleep maintenance insomniacs and 10 good sleeping postmenopausal female subjects [mean (SD) age = 65.2 (7.4) years] participated in a double-blind, crossover study in which they received a capsule containing either melatonin (5 mg) or a placebo at 1400 hours. Continuous core body temperature and hourly multiple sleep latency tests (MSLT) were collected from 1100-2030 hours. Self-reported estimates of global vigor (sleepiness) and affect were collected prior to each MSLT using visual analog scales. Comparison of good and poor sleepers failed to reveal any significant differences in core body temperature, sleep latency, or subjective vigor and affect. However, for both groups combined, melatonin administration [absolute postadministration mean (SEM) = 36.9 (0.05) degrees C] significantly lowered core body temperature compared with placebo [37.1 (0.05) degrees C]. Similarly, melatonin administration significantly reduced latency to stage 1 (SOL1) and stage 2 (SOL2) [absolute postadministration mean SOL1 = 20.1 (1.7) and SOL2 = 20.7 (1.6) minutes] compared with placebo [SOL1 = 24.3 (1.2) and SOL2 = 25.2 (1.1) minutes]. Treatment had no significant effect on either vigor or affect. Overall, our results suggest that although short-term exogenous oral daytime melatonin has significant hypothermic and hypnotic effects in aged women, the size of the effects is modest.

Properties and biological significance of the ileal bile salt transport system.

The properties of a specific transport system for bile salts, which is located in the ileum of the small intestine are described. The system operates by a sodium ion cotransport mechanism, and it functions in maintaining a normal enterohepatic circulation of bile salts. Analysis of structure-activity data allows us to depict our hypothesis for the interaction of bile salt and Na with the membranal recognition site of this transport system. The sequellae of metabolic disorders which can arise following disease or surgical ablation of the ileal region of the intestine which result in an interrupted bile salt enterohepatic circulation are described. We suggest that these findings hold interest to toxicologists, since it is not beyond reason that toxic agents might exist which impair the function of this transport system specifically or which could poison the ileal mucosal cell. Such agents might be detected by the presence of some of the described metabolic disorders. Finally, we discuss the ileal transport of the sulfated esters of bile salts and the possibility that this might relate to that aspect of detoxification pertaining to their enhanced excretion.

Prostatic cancer. I. 6-Methylene-4-pregnen-3-ones as irreversible inhibitors of rat prostatic delta 4-3 ketosteroid 5 alpha-reductase.

Some derivatives of 6-methylene-4-pregnen-3-one were studied as inhibitors of delta 4-3-ketosteroid 5 alpha-reductase. Maximum inhibitory activity was shown by 17-acetoxy-6-methylene-4-pregnene-3,20-dione (AMPD). Irreversible inactivation was observed following preincubation of the enzyme with NADPH and AMPD. This inactivation was found to occur only in the presence of NADPH. As such enzyme inactivation was not due to the formation of a more inhibitory metabolic product, or to the formation of superoxide via a cytochrome P-450/NADPH pathway, it seemed likely that the observed inactivation was derived from an irreversible combination of the enzyme with AMPD. That this was probably the case was established by kinetic studies which revealed a pattern compatible with a kcat type of mechanism.

The synthesis of diazo, halo, and sulfoxy bile acid derivatives: potential affinity labels.

Bile acid derivatives, with and without C-3 sulfate groups, and having either the diazo- or halomethylketone moieties, have been synthesized in good yield and purity. The synthetic sequence, COOH leads to COC1 leads to COCHN2 leads to COCH2X, was used with deoxycholic and cholic acids, which requires carefully controlled quench, work-up, and purification procedures, especially for the 3-sulfate esters (made from deoxycholic acid derivatives only). The pure title compounds are anticipated to be useful chemical probes (affinity labels), especially the completely water soluble sulfates, toward our studies of ileal active transport of bile salts. A new use for Sephadex LH-20 as a sulfate ester protecting group is reported. Also developed were the use of acetamide hydrochloride complex as a mild hydrochlorination reagent and a neutral desalting method for sulfate esters of deoxycholic acid derivatives.

Phase resetting of the human circadian pacemaker with use of a single pulse of bright light.

Since the initial studies reporting that light can alter the phase position of the human circadian system, there has been increasing interest in the use of bright light as a tool for manipulating the phase position of the circadian pacemaker. Exposure protocols typically require subjects to receive 2-5 h of exposure over several circadian cycles. As a consequence, bright light treatment can involve a considerable time investment. However, recent studies indicate that a single pulse of bright light can produce significant phase shifts in the circadian pacemaker. If a single pulse of bright light can produce significant phase-shifting effects, multiple-pulse designs may be unnecessary. This study examined the phase-shifting effects of a single 4-h pulse of bright light (12,000 lux) in 14 male and one female subject aged between 19-45 years. With use of a "constant routine" to estimate circadian phase, a single 4-h pulse of light produced significant shifts in the phase of the core temperature rhythm. The timing of the exposure, relative to the core temperature rhythm, determined the degree and direction of the phase shift. Exposure immediately prior to habitual bedtime produced a mean phase delay in the core temperature of 2.39 h (SD = 1.37 h). In contrast, exposure immediately following habitual wake-up produced a mean phase advance of 1.49 h (SD = 2.06 h). In addition, the magnitude of the shift increased the closer the light pulse was to the individual's estimated endogenous core temperature minimum. There was, however, considerable interindividual variability in this relationship.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of light wavelength on suppression and phase delay of the melatonin rhythm.

Different wavelengths of light were compared for melatonin suppression and phase shifting of the salivary melatonin rhythm. The wavelengths compared were 660 nm (red), 595 nm (amber), 525 nm (green), 497 nm (blue/green), and 470 nm (blue). They were administered with light-emitting diodes equated for irradiance of 130 muW/cm2. Fifteen volunteers participated in all five wavelength conditions and a no light control condition, with each condition conducted over two consecutive evenings. Half-hourly saliva sam ples were collected from 19:00 to 02:00 on night 1 and until 01:00 on night 2. Light was administered for the experimental conditions on the first night only from midnight to 02:00. Percentage melatonin suppression on night 1 and dim light melatonin onset (DLMO) for each night were calculated. The shorter wavelengths of 470, 497, and 525 nm showed the greatest melatonin suppression, 65% to 81%. The shorter wavelengths also showed the greatest DLMO delay on night 2, ranging from 27 to 36 min. The results were consistent with the involvement of a scotopic mechanism in the regulation of circadian phase.

Urinary 6-sulfatoxymelatonin cycle-to-cycle variability.

For either clinical or research purposes, the timing of the nocturnal onset in production of the urinary melatonin metabolite 6-sulfatoxymelatonin (UaMT6s-onset), has been proposed as a reliable and robust marker of circadian phase. However, given that most circadian rhythms show cycle-to-cycle variability, the statistical reliability of phase estimates obtained from a single study using UaMT6s-onset remains to be determined. Following 2 weeks of sleep diary and wrist actigraphy, 15 young, healthy good sleepers participated in four UaMT6s sampling sessions spaced 1 day apart. During the sampling sessions subjects remained indoors under low light conditions and hourly urine samples were collected from 19:00 to 02:00 h. Samples were subsequently assayed for UaMT6s using standard radioimmunographic techniques. UaMT6s-onset was determined by the time at which melatonin production exceeded the average of three proceeding trials by 100%. Sleep onset times were derived from sleep diary and actigraphic measures taken before the melatonin collection nights. We found that there was no significant variation between nights in group mean UaMT6s-onset times, and intraindividual variability was small. In addition, UaMT6s-onset times were highly and significantly correlated between nights (grand mean r = 0.804). Our results suggest that within 95% confidence interval limits, individual UaMT6s-onset estimates obtained from a single night UaMT6s-onset study can be used to predict subsequent UaMT6s-onset times within +/- 97 min. A close temporal relationship was also found between the timing of UaMT6s-onset and sleep onset. Overall, our results suggest that under entrained conditions single-session UaMT6s-onset studies can provide reliable individual UaMT6s-onset phase estimates and that the protocol described in this study is a practical and noninvasive methodology.

The variability in circadian phase and amplitude estimates derived from sequential constant routines.

Both the constant routine (CR) and the dim light melatonin onset have been suggested as reliable methods to determine circadian phase from a single circadian cycle. However, both techniques lack published studies quantifying the intercycle variability in their phase resolution. To address this question eight healthy male subjects participated in two CRs, 7 days apart. Circadian phase was determined using 3-min samples of core body temperature and two hourly urinary sulphatoxy melatonin excretion rates. Phase and amplitude were estimated using simple (24 h) and complex (24 + 12 h) cosinor models of temperature data and the onset, offset, and a distance-weighted-least-squares (DWLS) fitted acrophase for the melatonin metabolite. The variability in phase estimates was measured using the mean absolute difference between successive CRs. Using the simple 24 h model of temperature data, the mean absolute phase difference was 51 min (SD = 35 min). Using the complex model, the mean absolute phase difference was 62 min (SD = 35 min). Using the DWLS fitted acrophase for the melatonin metabolite, the mean absolute phase difference between CR1 and CR2 was 40 min (SD = 26 min). The results indicate that for CRs a week apart, the mean absolute difference in an individual's phase estimate can vary by 40-60 min depending on the choice of dependent measure and analytic technique. In contrast to the intraindividual variability, the group results showed considerably less variability. The mean algebraic difference between CRs, using temperature- or melatonin-derived estimates, was less than 5 min, and well within the range of normal measurement error.