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79 records · Page 5

Circadian and sleep-dependent regulation of hormone release in humans

Daily oscillations characterize the release of nearly every hormone. The circadian pacemaker, located in the suprachiasmatic nucleus of the hypothalamus, generates circadian, approximately 24-hour rhythms in many physiologic functions. However, the observed hormonal oscillations do not simply reflect the output of this internal clock. Instead, daily hormonal profiles are the product of a complex interaction between the output of the circadian pacemaker, periodic changes in behavior, light exposure, neuroendocrine feedback mechanisms, gender, age, and the timing of sleep and wakefulness. The interaction of these factors can affect hormonal secretory pulse frequency and amplitude, with each endocrine system differentially affected by these factors. This chapter examines recent advances in understanding the effects on endocrine rhythms of a number of these factors. Sleep exerts a profound effect on endocrine secretion. Sleep is a dynamic process that is characterized by periodic changes in electrophysiologic activity. These electrophysiologic changes, which are used to mark the state and depth of sleep, are associated with periodic, short-term variations in hormonal levels. The secretion of hormones such as renin and human growth hormone are strongly influenced by sleep or wake state, while melatonin and cortisol levels are relatively unaffected by sleep or wake state. In addition, sleep is associated with changes in posture, behavior, and light exposure, each of which is known to affect endocrine secretion. Furthermore, the tight concordance of habitual sleep and wake times with certain circadian phases has made it difficult to distinguish sleep and circadian effects on these hormones. Specific protocols, designed to extract circadian and sleep information semi-independently, have been developed and have yielded important insights into the effects of these regulatory processes. These results may help to account for changes in endocrine rhythms observed in circadian rhythm sleep disorders, including the dyssomnia of shift work and visual impairment. Yet to be fully investigated are the interactions of these factors with age and gender. Characterization of the factors governing hormone secretion is critical to understanding the temporal regulation of endocrine systems and presents many exciting areas for future research.

Non-NASA Center↗

Stability, precision, and near-24-hour period of the human circadian pacemaker

Regulation of circadian period in humans was thought to differ from that of other species, with the period of the activity rhythm reported to range from 13 to 65 hours (median 25.2 hours) and the period of the body temperature rhythm reported to average 25 hours in adulthood, and to shorten with age. However, those observations were based on studies of humans exposed to light levels sufficient to confound circadian period estimation. Precise estimation of the periods of the endogenous circadian rhythms of melatonin, core body temperature, and cortisol in healthy young and older individuals living in carefully controlled lighting conditions has now revealed that the intrinsic period of the human circadian pacemaker averages 24.18 hours in both age groups, with a tight distribution consistent with other species. These findings have important implications for understanding the pathophysiology of disrupted sleep in older people.

NASA Discipline Regulatory Physiology↗

Stabilized NADH as a Countermeasure for Jet Lag

Current remedies for jet lag (phototherapy, melatonin, stimulant, and sedative medications) are limited in efficacy and practicality. The efficacy of a stabilized, sublingual form of reduced nicotin amide adenine dinucleotide (NADH, ENADAlert, Menuco Corp.) as a countermeasure for jet lag was examined. Because NADH increases cellular production of ATP and facilitates dopamine synthesis, it may counteract the effects of jet lag on cognitive functioning and sleepiness. Thirty-five healthy, employed subjects participated in this double-blind, placebo-controlled study. Training and baseline testing were conducted on the West Coast before subjects flew overnight to the East Coast, where they would experience a 3-hour time difference. Upon arrival, individuals were randomly assigned to receive either 20 mg of sublingual stabilized ADH (n=18) or identical placebo tablets (n=17). All participants completed computer-administered tests (including CogScreen7) to assess changes in cognitive functioning, mood, and sleepiness in the morning and afternoon. Jet lag resulted in increased sleepiness for over half the participants and deterioration of cognitive functioning for approximately one third. The morning following the flight, subjects experienced lapses of attention in addition to disruptions in working memory, divided attention, and visual perceptual speed. Individuals who received NADH performed significantly better on 5 of 8 cognitive and psychomotor test measures (P less than or equal to 0.5) and showed a trend for better performance on the other three measures (P less than or equal to .l0). Subjects also reported less sleepiness compared with those who received placebo. No adverse effects were observed with NADH treatment. Stabilized NADH significantly reduced jet lag-induced disruptions of cognitive functioning, was easily administered, and was found to have no adverse side effects.

Kay, Gary G.↗

Prescribed Travel Schedules for Fatigue Management

The NASA Fatigue Management Team is developing recommendations for managing fatigue during travel and for shift work operations, as Clinical Practice Guidelines for the Management of Circadian Desynchrony in ISS Operations. The Guidelines provide the International Space Station (ISS ) flight surgeons and other operational clinicians with evidence-based recommendations for mitigating fatigue and other factors related to sleep loss and circadian desynchronization. As much international travel is involved both before and after flight, the guidelines provide recommendations for: pre-flight training, in-flight operations, and post-flight rehabilitation. The objective of is to standardize the process by which care is provided to crewmembers, ground controllers, and other support personnel such as trainers, when overseas travel or schedule shifting is required. Proper scheduling of countermeasures - light, darkness, melatonin, diet, exercise, and medications - is the cornerstone for facilitating circadian adaptation, improving sleep, enhancing alertness, and optimizing performance. The Guidelines provide, among other things, prescribed travel schedules that outline the specific implementation of these mitigation strategies. Each travel schedule offers evidence based protocols for properly using the NASA identified countermeasures for fatigue. This presentation will describe the travel implementation schedules and how these can be used to alleviate the effects of jet lag and/or schedule shifts.

Whitmire, Alexandra↗

Validating and Verifying Biomathematical Models of Human Fatigue

Airline pilots experience acute and chronic sleep deprivation, sleep inertia, and circadian desynchrony due to the need to schedule flight operations around the clock. This sleep loss and circadian desynchrony gives rise to cognitive impairments, reduced vigilance and inconsistent performance. Several biomathematical models, based principally on patterns observed in circadian rhythms and homeostatic drive, have been developed to predict a pilots levels of fatigue or alertness. These models allow for the Federal Aviation Administration (FAA) and commercial airlines to make decisions about pilot capabilities and flight schedules. Although these models have been validated in a laboratory setting, they have not been thoroughly tested in operational environments where uncontrolled factors, such as environmental sleep disrupters, caffeine use and napping, may impact actual pilot alertness and performance. We will compare the predictions of three prominent biomathematical fatigue models (McCauley Model, Harvard Model, and the privately-sold SAFTE-FAST Model) to actual measures of alertness and performance. We collected sleep logs, movement and light recordings, psychomotor vigilance task (PVT), and urinary melatonin (a marker of circadian phase) from 44 pilots in a short-haul commercial airline over one month. We will statistically compare with the model predictions to lapses on the PVT and circadian phase. We will calculate the sensitivity and specificity of each model prediction under different scheduling conditions. Our findings will aid operational decision-makers in determining the reliability of each model under real-world scheduling situations.

fatigue↗

Fatigue Monitoring in Scheduled Airline Operations

Reporting and monitoring are important facets of a comprehensive Fatigue Risk Management System. As part of efforts to reduce fatigue risks, we partnered with an international airline to study 44 (4 Female) volunteer pilots over a 4 week period that included baseline earlymiddaylate flight days and rest days off. All study procedures were approved by an IRB and participants provided written informed consent prior to beginning the study. Reduced sleep duration was associated with both early and late duties. Performance was influenced by duty timing, time of day and time awake. TLX ratings were highest for mental and effort demands, while ATC and weather were the most identified hassle factors. Melatonin analysis revealed individual variations in circadian shift over the study period. The study results highlight the value of FRMS monitoring in airline operations. Ongoing crew education should emphasize individual variation and effective mitigation strategies. Further study could focus on workload and time of day scheduling factors.

sleep loss↗

Abstract: Orion Lighting Workaround for Maintaining Crew Circadian Entrainment

Introduction. Light is the major environmental time cue of our endogenous circadian pacemaker. Suboptimal crew circadian entrainment (CCE) is common and associated with acute and chronic medical symptoms. Additionally, fatigue from suboptimal CCE promotes problematic use of sleep medications. The Orion Cabin Lighting System (OCLS) consists of monochromatic light-emitting diode (LED) lamps. However, light is a powerful suppressor of melatonin and it is a disruptor of CCE if used at incorrect times. A commercial off the shelf (COTS) dynamic lighting system (COTS-DLS) is a potential workaround for maintaining CCE.

Matthew Lindsey↗