Fighting by sleep-deprived rats as a possible manifestation of panic: effects of sodium lactate

Increased fighting is an effect of desynchronized sleep deprivation (DSD) in rats, and recently this behavior has been suggested to be spontaneous panic and equivalent to panic disorder. In the present study we tested this hypothesis by evaluating the effect of sodium lactate on this aggressiveness, because this substance is recognized to induce spontaneous panic attacks in patients. A total of 186 male albino Wistar rats, 250-350 g, 90-120 days of age, were submitted to DSD (multiple platform method) for 0, 4, or 5 days. At the end of the deprivation period the rats were divided into subgroups respectively injected intraperitoneally with 1.86, 2.98 and 3.72 g/kg of 1 M sodium lactate, or 1.86 and 3.72 g/kg of 2 M sodium lactate. The control animals were submitted to the same procedures but received equivalent injections of sodium chloride. Regardless of DSD time, sleep-deprived animals that received sodium lactate presented a significantly higher mean number of fights (0.13 ± 0.02 fights/min) and a longer mean time spent in confrontation (2.43 ± 0.66 s/min) than the controls (0.01 ± 0.006 fights/min and 0.12 ± 0.07 s/min, respectively; P<0.01, Student t-test). For the sodium lactate group, concentration of the solution and time of deprivation increased the number of fights, with the mean number of fights and mean duration of fighting episodes being greater with the 2.98 g/kg dose using 1 M lactate concentration. These results support the hypothesis that fighting induced by DSD is probably a spontaneous panic manifestation. However, additional investigations are necessary in order to accept this as a promising animal model for studies on panic disorder.

Association between sleep quality and quality of life in nursing professionals working rotating shifts

Objective: To analyze the association between sleep quality and quality of life of nursing professionals according to their work schedules. Methods: A prospective, cross-sectional, observational study was conducted between January and December 2010, with 264 nursing professionals, drawn from 989 subjects at Botucatu General Hospital and stratified by professional category. The Pittsburg Sleep Quality Index and the WHOQOL-bref were administered to evaluate sleep quality and quality of life, respectively. Self-reported demographic data were collected with a standard form. Continuous variables were reported as means and standard deviations, and categorical variables were expressed as proportions. Associations were evaluated using Spearman's correlation coefficient. The association of night-shift work and gender with sleep disturbance was evaluated by logistic regression analysis using a model adjusted for age and considering sleep disturbance the dependent variable. The level of significance was p < 0.05. Results: Night-shift work was associated with severe worsening of at least one component of sleep quality in the model adjusted for age (OR = 1.91; 95% CI 1.04; 3.50; p = 0.036). Female gender was associated with sleep disturbance (OR = 3.40; 95% CI 1.37; 8.40; p = 0.008). Quality of life and quality of sleep were closely correlated (R = -0.56; p < 0.001). Conclusions: Characteristics of the nursing profession affect sleep quality and quality of life, and these two variables are associated.

Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery

Pellegrino R, Sunaga DY, Guindalini C, Martins RC, Mazzotti DR, Wei Z, Daye ZJ, Andersen ML, Tufik S. Whole blood genome-wide gene expression profile in males after prolonged wakefulness and sleep recovery. Physiol Genomics 44: 1003-1012, 2012. First published September 4, 2012; doi: 10.1152/physiolgenomics.00058.2012.-Although the specific functions of sleep have not been completely elucidated, the literature has suggested that sleep is essential for proper homeostasis. Sleep loss is associated with changes in behavioral, neurochemical, cellular, and metabolic function as well as impaired immune response. Using high-resolution microarrays we evaluated the gene expression profiles of healthy male volunteers who underwent 60 h of prolonged wakefulness (PW) followed by 12 h of sleep recovery (SR). Peripheral whole blood was collected at 8 am in the morning before the initiation of PW (Baseline), after the second night of PW, and one night after SR. We identified over 500 genes that were differentially expressed. Notably, these genes were related to DNA damage and repair and stress response, as well as diverse immune system responses, such as natural killer pathways including killer cell lectin-like receptors family, as well as granzymes and T-cell receptors, which play important roles in host defense. These results support the idea that sleep loss can lead to alterations in molecular processes that result in perturbation of cellular immunity, induction of inflammatory responses, and homeostatic imbalance. Moreover, expression of multiple genes was downregulated following PW and upregulated after SR compared with PW, suggesting an attempt of the body to re-establish internal homeostasis. In silico validation of alterations in the expression of CETN3, DNAJC, and CEACAM genes confirmed previous findings related to the molecular effects of sleep deprivation. Thus, the present findings confirm that the effects of sleep loss are not restricted to the brain and can occur intensely in peripheral tissues.

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.

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.

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.

Sleep and academic performance of Portuguese teenagers

Abstract: Sleep has numerous important functions in the body, such as consolidation of memory, concentration and learning. Changes in sleep cycles in adolescents lead to sleep deprivation with consequences to academic performance. Our research question was What are the sleep habits that influence school performance (study environment, study planning, study method, reading skills, motivation to study, overall school performance) in adolescents? We aimed to identify sleep habits predictors of the quality of school performance in adolescents. Research Methods: Crosssectional analytical study. Data were collected through a self-administered questionnaire with socio-demographic questions, sleep habits and school performance scale. The sample consisted of 380 students between 7th and 9th grade, with an average age of 13.56 ± 1.23 years in the school year 2011/2012, from a 2nd and 3rd Cycle Basic School of the municipality of Viseu, Portugal. Findings: School performance in adolescents was associated with better subjective quality of sleep (p=0.000), with longer sleep duration (p=0.000), with watching tv/video before sleep (p=0.000), with the habit of studying before bedtime (p=0.012), with no computer use (p=0.013) and with reading habits before bed (p=0.000). School performance was also associated with adolescents who reported not feeling sleepy during class. The teenagers who sleep more and better, and who watch tv/video, study, do not use computers, and who read before going to bed, have a better school performance.

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.