Regulation of wake-sleep states and state-dependent cardiovascular function in diet-induced obesity rats

Obesity often predisposes to coronary heart disease, heart failure, and sudden death. Also, several studies suggest a reciprocal enhancing interaction between obesity and sleep curtailment. Aim of the present study was to go deeper in the understanding of sleep and cardiovascular regulation in an animal model of diet-induced obesity (DIO). According to this, Wake-Sleep (W-S) regulation, and W-S dependent regulation of cardiovascular and metabolic/thermoregulatory function was studied in DIO rats, under normal laboratory conditions and during sleep deprivation and the following recovery period, enhancing either wake or sleep, respectively. After 8 weeks of the delivery of a hypercaloric (HC) diet, treated animals were heavier than those fed a normocaloric (NC) diet (NC: 441 ±17g; HC: 557±17g). HC rats slept more than NC ones during the activity period (Dark) of the normal 12h:12h light-dark (LD) cycle (Wake: 67.3±1.2% and 57.2 ±1.6%; NREM sleep (NREMS): 26.8±1.0% and 34.0±1.4%; REM sleep (REMS): 5.7±0. 6% and 8.6±0.7%; for NC and HC, respectively; p<0.05 for all). HC rats were hypertensive throughout the W-S states, as shown by the mean arterial blood pressure values across the 24-h period (Wake: 90.0±5.3 and 97.3±1.3; NREMS: 85.1±5.5 and 92.2±1.2; REMS: 87.2±4.5 and 96.5±1.1, mmHg for NC and HC, respectively; p<0.05 for all). Also, HC rats appeared to be slightly bradycardic compared to NC ones (Wake: 359.8±9.3 and 352.4±7.7; NREMS: 332.5±10.1 and 328.9±5.4; REMS: 338.5±9.3 and 334.4±5.8; bpm for NC and HC, respectively; p<0.05 for Wake). In HC animals, sleep regulation was not apparently altered during the sleep rebound observed in the recovery period following sleep deprivation, although REMS rebound appeared to be quicker in NC animals. In conclusion, these results indicate that in the rat obesity interfere with W-S and cardiovascular regulation and that DIO rats are suitable for further studies aimed at a better understanding of obesity comorbidities.

Benign neonatal sleep myoclonus: a review of the literature

OBJECTIVE: Neurologically normal term infants sometimes present with repetitive, rhythmic myoclonic jerks that occur during sleep. The condition, which is traditionally resolved by 3 months of age with no sequelae, is termed benign neonatal sleep myoclonus. The goal of this review was to synthesize the published literature on benign neonatal sleep myoclonus. METHODS: The US National Library of Medicine database and the Web-based search engine Google, through June 2009, were used as data sources. All articles published after the seminal description in 1982 as full-length articles or letters were collected. Reports that were published in languages other than English, French, German, Italian, Portuguese, or Spanish were not considered. RESULTS: We included 24 reports in which 164 term-born (96%) or near-term-born (4%) infants were described. Neonatal sleep myoclonus occurred in all sleep stages, disappeared after arousal, and was induced by rocking the infant or repetitive sound stimuli. Furthermore, in affected infants, jerks stopped or even worsened by holding the limbs or on medication with antiepileptic drugs. Finally, benign neonatal sleep myoclonus did not resolve by 3 months of age in one-third of the infants. CONCLUSIONS: This review provides new insights into the clinical features and natural course of benign neonatal sleep myoclonus. The most significant limitation of the review comes from the small number of reported cases.

Evidence of an association between sleep and levodopa-induced dyskinesia in an animal model of Parkinson's disease.

Levodopa-induced dyskinesia (LID) represents a major challenge for clinicians treating patients affected by Parkinson's disease (PD). Although levodopa is the most effective treatment for PD, the remodeling effects induced by disease progression and the pharmacologic treatment itself cause a narrowing of the therapeutic window because of the development of LID. Although animal models of PD provide strong evidence that striatal plasticity underlies the development of dyskinetic movements, the pathogenesis of LID is not entirely understood. In recent years, slow homeostatic adjustment of intrinsic excitability occurring during sleep has been considered fundamental for network stabilization by gradually modifying plasticity thresholds. So far, how sleep affects on LID has not been investigated. Therefore, we measured synaptic downscaling across sleep episodes in a parkinsonian animal model showing dyskinetic movements similar to LID. Our electrophysiological, molecular, and behavioral results are consistent with an impaired synaptic homeostasis during sleep in animals showing dyskinesia. Accordingly, sleep deprivation causes an anticipation and worsening of LID supporting a link between sleep and the development of LID.

Subjective perception of sleepiness in a driving simulator is different from that in the Maintenance of Wakefulness Test.

OBJECTIVE To test whether sleep-deprived, healthy subjects who do not always signal spontaneously perceived sleepiness (SPS) before falling asleep during the Maintenance of Wakefulness Test (MWT) would do so in a driving simulator. METHODS Twenty-four healthy subjects (20-26 years old) underwent a MWT for 40 min and a driving simulator test for 1 h, before and after one night of sleep deprivation. Standard electroencephalography, electrooculography, submental electromyography, and face videography were recorded simultaneously to score wakefulness and sleep. Subjects were instructed to signal SPS as soon as they subjectively felt sleepy and to try to stay awake for as long as possible in every test. They were rewarded for both "appropriate" perception of SPS and staying awake for as long as possible. RESULTS After sleep deprivation, seven subjects (29%) did not signal SPS before falling asleep in the MWT, but all subjects signalled SPS before falling asleep in the driving simulator (p <0.004). CONCLUSIONS The previous results of an "inaccurate" SPS in the MWT were confirmed, and a perfect SPS was shown in the driving simulator. It was hypothesised that SPS is more accurate for tasks involving continuous feedback of performance, such as driving, compared to the less active situation of the MWT. Spontaneously perceived sleepiness in the MWT cannot be used to judge sleepiness perception while driving. Further studies are needed to define the accuracy of SPS in working tasks or occupations with minimal or no performance feedback.

Identification of Sleep-Modulated Pathways Involved in Neuroprotection from Stroke.

STUDY OBJECTIVES Sleep deprivation (SDp) performed before stroke induces an ischemic tolerance state as observed in other forms of preconditioning. As the mechanisms underlying this effect are not well understood, we used DNA oligonucleotide microarray analysis to identify the genes and the gene-pathways underlying SDp preconditioning effects. DESIGN Gene expression was analyzed 3 days after stroke in 4 experimental groups: (i) SDp performed before focal cerebral ischemia (IS) induction; (ii) SDp performed before sham surgery; (iii) IS without SDp; and (iv) sham surgery without SDp. SDp was performed by gentle handling during the last 6 h of the light period, and ischemia was induced immediately after. SETTINGS Basic sleep research laboratory. MEASUREMENTS AND RESULTS Stroke induced a massive alteration in gene expression both in sleep deprived and non-sleep deprived animals. However, compared to animals that underwent ischemia alone, SDp induced a general reduction in transcriptional changes with a reduction in the upregulation of genes involved in cell cycle regulation and immune response. Moreover, an upregulation of a new neuroendocrine pathway which included melanin concentrating hormone, glycoprotein hormones-α-polypeptide and hypocretin was observed exclusively in rats sleep deprived before stroke. CONCLUSION Our data indicate that sleep deprivation before stroke reprogrammed the signaling response to injury. The inhibition of cell cycle regulation and inflammation are neuroprotective mechanisms reported also for other forms of preconditioning treatment, whereas the implication of the neuroendocrine function is novel and has never been described before. These results therefore provide new insights into neuroprotective mechanisms involved in ischemic tolerance mechanisms.

Role of sleep and sleep-related correlates in the development of delirium: A feasibility study

Purpose of the study. The purpose was to determine if sleep deprivation in hospitalized older adults predicts the development of delirium, and if sleep is predicted by nighttime light and sound levels. ^ Method. This observational feasibility study enrolled 54 adults ≥70 years of age (mean age 79, range 70–94) who were negative for delirium. The sample was monitored for sleep via wrist actigraphy, and light and sound levels were monitored from 2200 to 0700 the first night of hospitalization. The Richards Campbell Sleep Questionnaire (RCSQ) was administered to measure subjective sleep satisfaction. Subjects were assessed for delirium daily using the Confusion Assessment Method. ^ Conclusions. Of 50 subjects completing the study, two (4%) developed delirium. Mean nighttime sleep was 225 minutes (± 137) with frequent awakenings (13 ± 6) Light levels were elevated episodically (mean intense light = 64 lux, lasting 1¾ hours); median sound levels [49.65 dB(A)] exceeded WHO recommendations [35 dB(A)]. Neither median sound (r = -.63, p = 67) nor mean light levels (r = -.104, p = .47) significantly correlated with sleep. Mean RCSQ was 50.7 ± 24 and showed a moderate correlation with nighttime sleep minutes (r = .577, p .000). Power analysis determined that 294 subjects will be required to determine if nighttime sleep minutes predict delirium, and 182 subjects will be required to determine if sound and light levels predict nighttime sleep minutes.^

An evaluation of sleep hypnotic and stimulant effect on human performance using a computerized psychological test battery

This study evaluated the administration-time-dependent effects of a stimulant (Dexedrine 5-mg), a sleep-inducer (Halcion 0.25-mg) and placebo (control) on human performance. The investigation was conducted on 12 diurnally active (0700-2300) male adults (23-38 yrs) using a double-blind, randomized sixway-crossover three-treatment, two-timepoint (0830 vs 2030) design. Performance tests were conducted hourly during sleepless 13-hour studies using a computer generated, controlled and scored multi-task cognitive performance assessment battery (PAB) developed at the Walter Reed Army Institute of Research. Specific tests were Simple and Choice Reaction Time, Serial Addition/Subtraction, Spatial Orientation, Logical Reasoning, Time Estimation, Response Timing and the Stanford Sleepiness Scale. The major index of performance was "Throughput", a combined measure of speed and accuracy.^ For the Placebo condition, Single and Group Cosinor Analysis documented circadian rhythms in cognitive performance for the majority of tests, both for individuals and for the group. Performance was best around 1830-2030 and most variable around 0530-0700 when sleepiness was greatest (0300).^ Morning Dexedrine dosing marginally enhanced performance an average of 3% with reference to the corresponding in time control level. Dexedrine AM also increased alertness by 10% over the AM control. Dexedrine PM failed to improve performance with reference to the corresponding PM control baseline. With regard to AM and PM Dexedrine administrations, AM performance was 6% better with subjects 25% more alert.^ Morning Halcion administration caused a 7% performance decrement and 16% increase in sleepiness and a 13% decrement and 10% increase in sleepiness when administered in the evening compared to corresponding in time control data. Performance was 9% worse and sleepiness 24% greater after evening versus morning Halcion administration.^ These results suggest that for evening Halcion dosing, the overnight sleep deprivation occurring in coincidence with the nadir in performance due to circadian rhythmicity together with the CNS depressant effects combine to produce performance degradation. For Dexedrine, morning administration resulted in only marginal performance enhancement; Dexedrine in the evening was less effective, suggesting the 5-mg dose level may be too low to counteract the partial sleep deprivation and nocturnal nadir in performance. ^

Gender and age differences in the sleep habits : a cross-sectional study in adolescents

Objectives: Analyze gender and age differences in sleep habits in a sample of adolescents. Design: A cross-sectional study. Setting: Public schools of Viseu, Portugal. Participants: Sample consisted of 7534 students, aged 11-20 years (mean age: 14.96 ± 1.81 years; 53.6% girls). Measurements: Data was collected using a self-administered questionnaire, answered in class and consists of questions to assess insomnia (DSM-IV criteria), sleep patterns, socio-demographic and daily habit variables. Results: Mean sleep duration in this sample was 8.02 ± 1.13 h. Age interfered with sleep duration that decreased with the increasing of age, from 8.45 ± 1.14 h among 11/12 years old to 7.37 ± 1.04 h for ages ≥ 17 years old. Insomnia and symptoms of insomnia were associated with gender and with increasing of age. Nearly 80% of students reported daytime tiredness, 66.7% sleepiness during the day; 56.1% during classes and 47.6% reported waking up with headaches, all variables more prevalent among girls and older adolescents. Conclusions: The sleep problems and variables related to sleep have become more frequent among girls and with increasing age. We recommend that the promotion of sleep hygiene and prevention of the consequences should be encouraged in adolescents and their families, especially among the female gender and older adolescents.

Predicting driver's hypovigilance on monotonous roads: literature review.

Drivers' ability to react to unpredictable events deteriorates when exposed to highly predictable and uneventful driving tasks. Particularly, highway design reduces the driving task mainly to a lane-keeping one. It contributes to hypovigilance and road crashes as drivers are often not aware that their driving behaviour is impaired. Monotony increases fatigue, however, the fatigue community has mainly focused on endogenous factors leading to fatigue such as sleep deprivation. This paper focuses on the exogenous factor monotony which contributes to hypovigilance. Objective measurements of the effects of monotonous driving conditions on the driver and the vehicle's dynamics is systematically reviewed with the aim of justifying the relevance of the need for a mathematical framework that could predict hypovigilance in real-time. Although electroencephalography (EEG) is one of the most reliable measures of vigilance, it is obtrusive. This suggests to predict from observable variables the time when the driver is hypovigilant. Outlined is a vision for future research in the modelling of driver vigilance decrement due to monotonous driving conditions. A mathematical model for predicting drivers’ hypovigilance using information like lane positioning, steering wheel movements and eye blinks is provided. Such a modelling of driver vigilance should enable the future development of an in-vehicle device that detects driver hypovigilance in advance, thus offering the potential to enhance road safety and prevent road crashes.

Predicting effects of monotony on driver’s vigilance

Monotony has been identified as a contributing factor to road crashes. Drivers’ ability to react to unpredictable events deteriorates when exposed to highly predictable and uneventful driving tasks, such as driving on Australian rural roads, many of which are monotonous by nature. Highway design in particular attempts to reduce the driver’s task to a merely lane-keeping one. Such a task provides little stimulation and is monotonous, thus affecting the driver’s attention which is no longer directed towards the road. Inattention contributes to crashes, especially for professional drivers. Monotony has been studied mainly from the endogenous perspective (for instance through sleep deprivation) without taking into account the influence of the task itself (repetitiveness) or the surrounding environment. The aim and novelty of this thesis is to develop a methodology (mathematical framework) able to predict driver lapses of vigilance under monotonous environments in real time, using endogenous and exogenous data collected from the driver, the vehicle and the environment. Existing approaches have tended to neglect the specificity of task monotony, leaving the question of the existence of a “monotonous state” unanswered. Furthermore the issue of detecting vigilance decrement before it occurs (predictions) has not been investigated in the literature, let alone in real time. A multidisciplinary approach is necessary to explain how vigilance evolves in monotonous conditions. Such an approach needs to draw on psychology, physiology, road safety, computer science and mathematics. The systemic approach proposed in this study is unique with its predictive dimension and allows us to define, in real time, the impacts of monotony on the driver’s ability to drive. Such methodology is based on mathematical models integrating data available in vehicles to the vigilance state of the driver during a monotonous driving task in various environments. The model integrates different data measuring driver’s endogenous and exogenous factors (related to the driver, the vehicle and the surrounding environment). Electroencephalography (EEG) is used to measure driver vigilance since it has been shown to be the most reliable and real time methodology to assess vigilance level. There are a variety of mathematical models suitable to provide a framework for predictions however, to find the most accurate model, a collection of mathematical models were trained in this thesis and the most reliable was found. The methodology developed in this research is first applied to a theoretically sound measure of sustained attention called Sustained Attention Response to Task (SART) as adapted by Michael (2010), Michael and Meuter (2006, 2007). This experiment induced impairments due to monotony during a vigilance task. Analyses performed in this thesis confirm and extend findings from Michael (2010) that monotony leads to an important vigilance impairment independent of fatigue. This thesis is also the first to show that monotony changes the dynamics of vigilance evolution and tends to create a “monotonous state” characterised by reduced vigilance. Personality traits such as being a low sensation seeker can mitigate this vigilance decrement. It is also evident that lapses in vigilance can be predicted accurately with Bayesian modelling and Neural Networks. This framework was then applied to the driving task by designing a simulated monotonous driving task. The design of such task requires multidisciplinary knowledge and involved psychologist Rebecca Michael. Monotony was varied through both the road design and the road environment variables. This experiment demonstrated that road monotony can lead to driving impairment. Particularly monotonous road scenery was shown to have the most impact compared to monotonous road design. Next, this study identified a variety of surrogate measures that are correlated with vigilance levels obtained from the EEG. Such vigilance states can be predicted with these surrogate measures. This means that vigilance decrement can be detected in a car without the use of an EEG device. Amongst the different mathematical models tested in this thesis, only Neural Networks predicted the vigilance levels accurately. The results of both these experiments provide valuable information about the methodology to predict vigilance decrement. Such an issue is quite complex and requires modelling that can adapt to highly inter-individual differences. Only Neural Networks proved accurate in both studies, suggesting that these models are the most likely to be accurate when used on real roads or for further research on vigilance modelling. This research provides a better understanding of the driving task under monotonous conditions. Results demonstrate that mathematical modelling can be used to determine the driver’s vigilance state when driving using surrogate measures identified during this study. This research has opened up avenues for future research and could result in the development of an in-vehicle device predicting driver vigilance decrement. Such a device could contribute to a reduction in crashes and therefore improve road safety.

Diarrhoea risk factors in enterally tube fed critically ill patients : a retrospective audit

Objective: Diarrhoea in the enterally tube fed (ETF) intensive care unit (ICU) patient is a multifactorial problem. Diarrhoeal aetiologies in this patient cohort remain debatable; however, the consequences of diarrhoea have been well established and include electrolyte imbalance, dehydration, bacterial translocation, peri anal wound contamination and sleep deprivation. This study examined the incidence of diarrhoea and explored factors contributing to the development of diarrhoea in the ETF, critically ill, adult patient. ---------- Method: After institutional ethical review and approval, a single centre medical chart audit was undertaken to examine the incidence of diarrhoea in ETF, critically ill patients. Retrospective, non-probability sequential sampling was used of all emergency admission adult ICU patients who met the inclusion/exclusion criteria. ---------- Results: Fifty patients were audited. Faecal frequency, consistency and quantity were considered important criteria in defining ETF diarrhoea. The incidence of diarrhoea was 78%. Total patient diarrhoea days (r = 0.422; p = 0.02) and total diarrhoea frequency (r = 0.313; p = 0.027) increased when the patient was ETF for longer periods of time. Increased severity of illness, peripheral oxygen saturation (Sp02), glucose control, albumin and white cell count were found to be statistically significant factors for the development of diarrhoea. ---------- Conclusion: Diarrhoea in ETF critically ill patients is multi-factorial. The early identification of diarrhoea risk factors and the development of a diarrhoea risk management algorithm is recommended.

Stop and revive? : the effectiveness of nap and active rest breaks for reducing driver sleepiness

The incidence of sleep-related crashes has been estimated to account for approximately 20% of all fatal and severe crashes. The use of sleepiness countermeasures by drivers is an important component to reduce the incidence rates of sleep-related crashes. Taking a brief nap and stopping for a rest break are two highly publicised countermeasures for driver sleepiness and are also believed by drivers to be the most effective countermeasures. Despite this belief, there is scarce evidence to support the utility of these countermeasures for reducing driver sleepiness levels. Therefore, determining the effectiveness of these countermeasures is an important road safety concern. The current study utilised a young adult sample (N = 20) to investigate the effectiveness of a nap and an active rest break. The countermeasures effects were evaluated by physiological, behavioural (hazard perception skill), and subjective measures previously found sensitive to sleepiness. Participants initially completed two hours of a simulated driving task followed by a 15 minute nap opportunity or a 15 minute active rest break that included 10 minutes of brisk walking. After the break, participants completed one final hour of the simulated driving task. A within-subjects design was used so that each participant completed both the nap and the active rest break conditions on separate occasions. The analyses revealed that only the nap break provided any meaningful reduction in physiological sleepiness, reduced subjective sleepiness levels, and maintained hazard perception performance. In contrast, the active rest break had no effect for reducing physiological sleepiness and resulted in a decrement in hazard perception performance (i.e., an increase of reaction time latencies), with a transient reduction in subjective sleepiness levels. A number of theoretical, empirical and practical issues were identified by the current study.

Noise levels in a General Surgical Ward : a descriptive study

Aims and objectives.  This study was undertaken to measure and analyse levels of acoustic noise in a General Surgical Ward. Method.  Measurements were undertaken using the Norsonic 116 sound level meter (SLM) recording noise levels in the internationally agreed ‘A’ weighted scale. Noise level data and observational data as to the number of staff present were obtained and recorded at 5-min intervals over three consecutive days. Results.  Results of noise level analysis indicated that mean noise level within this clinical area was 42.28 dB with acute spikes reaching 70 dB(A). The lowest noise level attained was that of 36 dB(A) during the period midnight to 7 a.m. Non-parametric testing, using Spearman's Rho (two-tailed), found a positive relationship between the number of staff present and the level of noise recorded, indicating that the presence of hospital personnel strongly influences the level of noise within this area. Relevance to clinical practice.  Whilst the results of this may seem self-evident in many respects the problems of excessive noise production and the exposure to it for patients, hospital personnel and relatives alike continues unabated. What must be of concern is the psychophysiological effects excessive noise exposure has on individuals, for example, decreased wound healing, sleep deprivation and cardiovascular stimulation.

What knowledge do ICU nurses have with regard to the effects of noise exposure in the Intensive Care Unit?

This small-scale study was undertaken to assess what knowledge nursing staff from a General Intensive Care Unit held with regard to noise exposure. To assess knowledge a self-administered multiple-choice questionnaire was used. Rigorous peer-review insured content validity. This study produced poor results in terms of the knowledge nurses held with regard to noise related issues in particular the psychophysiological effects and current legislation concerning its safe exposure. Non-parametric testing, using Kruskal–Wallis found no significant difference between nursing grades, however, descriptive analysis demonstrated that the staff nurse grade (D and E) performed better overall. Whilst the results of this study may seem self-evident in some respects, it is the problems of exposure to excessive noise levels for both patients and hospital personnel, which are clearly not understood. The effects noise exposure has on individuals for example decreased wound healing; sleep deprivation and cardiovascular stimulation must be of concern especially in terms of patient care but more so for nursing staff especially the effects noise levels can have on cognitive task performance.

Hydration in non-suckling neonatal Brahman-cross calves

Objective To identify measures that most closely relate to hydration in healthy Brahman-cross neonatal calves that experience milk deprivation. Methods In a dry tropical environment, eight neonatal Brahman-cross calves were prevented from suckling for 2–3 days during which measurements were performed twice daily. Results Mean body water, as estimated by the mean urea space, was 74 ± 3% of body weight at full hydration. The mean decrease in hydration was 7.3 ± 1.1% per day. The rate of decrease was more than three-fold higher during the day than at night. At an ambient temperature of 39°C, the decrease in hydration averaged 1.1% hourly. Measures that were most useful in predicting the degree of hydration in both simple and multiple-regression prediction models were body weight, hindleg length, girth, ambient and oral temperatures, eyelid tenting, alertness score and plasma sodium. These parameters are different to those recommended for assessing calves with diarrhoea. Single-measure predictions had a standard error of at least 5%, which reduced to 3–4% if multiple measures were used. Conclusion We conclude that simple assessment of non-suckling Brahman-cross neonatal calves can estimate the severity of dehydration, but the estimates are imprecise. Dehydration in healthy neonatal calves that do not have access to milk can exceed 20% (>15% weight loss) in 1–3 days under tropical conditions and at this point some are unable to recover without clinical intervention.