Kimberly A. Honn

MicroRNA 132 alters sleep and varies with time in brain

MicroRNA (miRNA) levels in brain are altered by sleep deprivation; however, the direct effects of any miRNA on sleep have not heretofore been described. We report herein that intracerebroventricular application of a miRNA-132 mimetic (preMIR-132) decreased duration of non-rapid-eye-movement sleep (NREMS) while simultaneously increasing duration of rapid eye movement sleep (REMS) during the light phase. Further, preMIR-132 decreased electroencephalographic (EEG) slow-wave activity (SWA) during NREMS, an index of sleep intensity. In separate experiments unilateral supracortical application of preMIR-132 ipsilaterally decreased EEG SWA during NREMS but did not alter global sleep duration. In addition, after ventricular or supracortical injections of preMIR-132, the mimetic-induced effects were state specific, occurring only during NREMS. After local supracortical injections of the mimetic, cortical miRNA-132 levels were higher at the time sleep-related EEG effects were manifest. We also report that spontaneous cortical levels of miRNA-132 were lower at the end of the sleep-dominant light period compared with at the end of the dark period in rats. Results suggest that miRNAs play a regulatory role in sleep and provide a new tool for investigating sleep regulation.

Fatiguing effect of multiple take-offs and landings in regional airline operations

Fatigue is a risk factor for flight performance and safety in commercial aviation. In US commercial aviation, to help to curb fatigue, the maximum duration of flight duty periods is regulated based on the scheduled start time and the number of flight segments to be flown. There is scientific support for regulating maximum duty duration based on scheduled start time; fatigue is well established to be modulated by circadian rhythms. However, it has not been established scientifically whether the number of flight segments, per se, affects fatigue. To address this science gap, we conducted a randomized, counterbalanced, cross-over study with 24 active-duty regional airline pilots. Objective and subjective fatigue was compared between a 9-hour duty day with multiple take-offs and landings versus a duty day of equal duration with a single take-off and landing. To standardize experimental conditions and isolate the fatiguing effect of the number of segments flown, the entire duty schedules were carried out in a high-fidelity, moving-base, full-flight, regional jet flight simulator. Steps were taken to maintain operational realism, including simulated airplane inspections and acceptance checks, use of realistic dispatch releases and airport charts, real-world air traffic control interactions, etc. During each of the two duty days, 10 fatigue test bouts were administered, which included a 10-minute Psychomotor Vigilance Test (PVT) assessment of objective fatigue and Samn-Perelli (SP) and Karolinska Sleepiness Scale (KSS) assessments of subjective sleepiness/fatigue. Results showed a greater build-up of objective and subjective fatigue in the multi-segment duty day than in the single-segment duty day. With duty start time and duration and other variables that could impact fatigue levels held constant, the greater build-up of fatigue in the multi-segment duty day was attributable specifically to the difference in the number of flight segments flown. Compared to findings in previously published laboratory studies of simulated night shifts and nighttime sleep deprivation, the magnitude of the fatiguing effect of the multiple take-offs and landings was modest. Ratings of flight performance were not significantly reduced for the simulated multi-segment duty day. The US duty and flight time regulations for commercial aviation shorten the maximum duty duration in multi-segment operations by up to 25% depending on the duty start time. The present results represent an important first step in understanding fatigue in multi-segment operations, and provide support for the number of flight segments as a relevant factor in regulating maximum duty duration. Nonetheless, based on our fatigue results, a more moderate reduction in maximum duty duration as a function of the number of flight segments might be considered. However, further research is needed to include investigation of flight safety, and to extend our findings to nighttime operations.

Shift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being

Purpose of ReviewOur 24/7 society is dependent on shift work, despite mounting evidence for negative health outcomes from sleep displacement due to shift work. This paper reviews short- and long-term health consequences of sleep displacement and circadian misalignment due to shift work.Recent FindingsWe focus on four broad health domains: metabolic health, risk of cancer, cardiovascular health, and mental health. Circadian misalignment affects these domains by inducing sleep deficiency, sympathovagal and hormonal imbalance, inflammation, impaired glucose metabolism, and dysregulated cell cycles. This leads to a range of medical conditions, including obesity, metabolic syndrome, type II diabetes, gastrointestinal dysfunction, compromised immune function, cardiovascular disease, excessive sleepiness, mood and social disorders, and increased cancer risk.SummaryInteractions of biological disturbances with behavioral and societal factors shape the effects of shift work on health and well-being. Research is needed to better understand the underlying mechanisms and drive the development of countermeasures.

Validation of a portable, touch-screen psychomotor vigilance test

INTRODUCTION The Psychomotor Vigilance Test (PVT) measures effects of fatigue from sleep loss and circadian misalignment on sustained vigilance performance. To promote PVT use in field environments, a 5-min PVT version has been implemented on a personal digital assistant (PDA) with a touch screen. The present laboratory study was conducted to validate this PVT against a standard 10-min laptop PVT across 38 h of total sleep deprivation (TSD). METHODS Following a baseline sleep night, subjects underwent 38 h of TSD, during which they performed the PVT every hour, alternating between the two test platforms. The study concluded with a night of recovery sleep. RESULTS The primary outcome was the number of PVT lapses (reaction times > 500 ms). Both PVT platforms showed significant effects for the number of lapses across TSD test times involving an increase with time awake modulated by circadian rhythm. Laptop PVT lapses across test times exhibited a large effect size (f2 = 0.36), whereas PDA PVT lapses exhibited a medium effect size (f2 = 0.17). The laptop PVT showed a significant effect for the number of false starts during TSD similar to the temporal profile of lapses, while the PDA PVT had false starts throughout the TSD period. DISCUSSION The 5-min PDA PVT provided performance testing functionality and results comparable to the 10-min laptop PVT. The number of PDA PVT lapses tracked fatigue similarly to the laptop PVT lapses, albeit with smaller average ranges and effect sizes.

Sleep Deprivation Diminishes Attentional Control Effectiveness and Impairs Flexible Adaptation to Changing Conditions

Insufficient sleep is a global public health problem resulting in catastrophic accidents, increased mortality, and hundreds of billions of dollars in lost productivity. Yet the effect of sleep deprivation (SD) on decision making and performance is often underestimated by fatigued individuals and is only beginning to be understood by scientists. The deleterious impact of SD is frequently attributed to lapses in vigilant attention, but this account fails to explain many SD-related problems, such as loss of situational awareness and perseveration. Using a laboratory study protocol, we show that SD individuals can maintain information in the focus of attention and anticipate likely correct responses, but their use of such a top-down attentional strategy is less effective at preventing errors caused by competing responses. Moreover, when the task environment requires flexibility, performance under SD suffers dramatically. The impairment in flexible shifting of attentional control we observed is distinct from lapses in vigilant attention, as corroborated by the specificity of the influence of a genetic biomarker, the dopaminergic polymorphism DRD2 C957T. Reduced effectiveness of top-down attentional control under SD, especially when conditions require flexibility, helps to explain maladaptive performance that is not readily explained by lapses in vigilant attention.

P2X7 receptors in body temperature, locomotor activity, and brain mRNA and lncRNA responses to sleep deprivation

The ionotropic purine type 2X7 receptor (P2X7R) is a nonspecific cation channel implicated in sleep regulation and brain cytokine release. Many endogenous rhythms covary with sleep, including locomotor activity and core body temperature. Furthermore, brain-hypothalamic cytokines and purines play a role in the regulation of these physiological parameters as well as sleep. We hypothesized that these parameters are also affected by the absence of the P2X7 receptor. Herein, we determine spontaneous expression of body temperature and locomotor activity in wild-type (WT) and P2X7R knockout (KO) mice and how they are affected by sleep deprivation (SD). We also compare hypothalamic, hippocampal, and cortical cytokine- and purine-related receptor and enzyme mRNA expressions before and after SD in WT and P2X7RKO mice. Next, in a hypothesis-generating survey of hypothalamic long noncoding (lnc) RNAs, we compare lncRNA expression levels between strains and after SD. During baseline conditions, P2X7RKO mice had attenuated temperature rhythms compared with WT mice, although locomotor activity patterns were similar in both strains. After 6 h of SD, body temperature and locomotion were enhanced to a greater extent in P2X7RKO mice than in WT mice during the initial 2-3 h after SD. Baseline mRNA levels of cortical TNF-α and P2X4R were higher in the KO mice than WT mice. In response to SD, the KO mice failed to increase hypothalamic adenosine deaminase and P2X4R mRNAs. Further, hypothalamic lncRNA expressions varied by strain, and with SD. Current data are consistent with a role for the P2X7R in thermoregulation and lncRNA involvement in purinergic signaling.

Total sleep deprivation does not significantly degrade semantic encoding

ABSTRACT Sleep deprivation impairs performance on cognitive tasks, but it is unclear which cognitive processes it degrades. We administered a semantic matching task with variable stimulus onset asynchrony (SOA) and both speeded and self-paced trial blocks. The task was administered at the baseline and 24 hours later after 30.8 hours of total sleep deprivation (TSD) or matching well-rested control. After sleep deprivation, the 20% slowest response times (RTs) were significantly increased. However, the semantic encoding time component of the RTs remained at baseline level. Thus, the performance impairment induced by sleep deprivation on this task occurred in cognitive processes downstream of semantic encoding.

22nd International Symposium on Shiftwork and Working Time: Challenges and solutions for healthy working hours

This decade has brought unprecedented progress in the documentation and understanding of the associations between working time, sleep schedules and circadian rhythms on the one hand and performance, safety and health outcomes on the other. Big epidemiologic studies and large prospective cohort studies strengthen the evidence base regarding these complex associations. Impactful changes in hours of service regulations and work policies across the globe, and fatigue risk management efforts associated with these changes, yield new insights into the neurobiological, logistical, psychosocial, behavioural, legal and financial issues to be considered when evaluating and optimizing work schedules. Basic research discoveries regarding peripheral circadian rhythms, intricate cascades of metabolic processes and critical interactions with the microbiome shed new light on the vulnerability of shift workers to long-term adverse health outcomes such as gastrointestinal and cardiovascular disease and increased risk of cancer. In terms of making a difference, these are exciting times for working time research, which has become more multidisciplinary than ever. In June 2015, researchers from all around the world came together in Elsinore, Denmark, for the 22nd International Symposium on Shiftwork and Working Time. The overarching theme was “challenges and solutions for healthy working hours.” This special issue of Chronobiology International contains a collection of peer-reviewed papers stemming from the meeting, which together reflect the large diversity of disciplines and methods involved. Here, we give a brief overview of the articles that make up the special issue and provide some context for the main findings.

Effects of a 12-week physical activities programme on sleep in female university students

ABSTRACT Lack of sleep is known to negatively affect adolescent’s health and the links between regular physical activity and sleep are unclear.This pilot study investigated whether the regular practice of physical activities among sedentary female students would improve their sleep. Nineteen female students, identified as sedentary and having poor subjective sleep quality were assigned in two groups to a 12-week university physical activities programme in accordance with the recommendations of World Health Organisation (N = 10) or to a control condition (N = 9). Sleep was assessed with actigraphy before and after the study and with the Pittsburg Sleep Quality 15 Index (PSQI) at the beginning, middle, and end of the study. The intensity of physical activities was controlled by heart rate monitor. The analysis showed that sleep quality in the physical activities group improved, with the mean ± SD PSQI score decreasing from 9.1 ± 1.7 to 4.8 ± 2.0. Despite some limitations, these pilot data indicate that a physical activities programme is feasible to implement in students, and that participation in such a programme improves sleep in 18– 24 -year-old female adolescents. Further potential benefits remain to be investigated in follow-up research.