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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records

Molecular-Level Dysregulation of Insulin Pathways and Inflammatory Processes in Peripheral Blood Mononuclear Cells by Circadian Misalignment

Circadian misalignment due to night work has been associated with elevated risk for chronic diseases. Here, we investigated the effects of circadian misalignment using shotgun protein profiling of peripheral blood mononuclear cells taken from healthy humans during a constant routine protocol, which was conducted immediately after participants had been subjected to a 3-day simulated night shift schedule or a 3-day simulated day shift schedule. By comparing proteomic profiles between the simulated shift conditions, we identified proteins and pathways that are associated with the effects of circadian misalignment, and observed that insulin regulation pathways and inflammation-related proteins displayed markedly different temporal patterns after simulated night shift. Further, by integrating the proteomic profiles with previously assessed metabolomic profiles in a network-based approach, we found key associations between circadian dysregulation of protein-level pathways and metabolites of interest in the context of chronic metabolic diseases. Overall, our results suggest that circadian misalignment is associated with a tug of war between central clock mechanisms controlling insulin secretion and peripheral clock mechanisms regulating insulin sensitivity, which may lead to adverse long-term outcomes such as diabetes and obesity. Our study provides a molecular-level mechanism linking circadian misalignment and adverse long-term health consequences of night work.

59 BASIC BIOLOGICAL SCIENCES↗

Distinct Pattern of Oculomotor Impairment Associated with Acute Sleep Loss and Circadian Misalignment

Sleep loss and circadianmisalignment have long been known to impair human cognitive and motor performance with significant societal and health consequences. It is well known that human reaction time to a visual cue is impaired following sleep loss and circadian misalignment, but it has remained unclear how more complex visuomotor control behaviour is altered under these conditions. In this study, we measured 14 parameters of the voluntary ocular tracking response of 12 human participants (six females) to systematically examine the effects of sleep loss and circadianmisalignment using a constant routine 24 h acute sleep-deprivation paradigm. The combination of state-of-the-art oculometric and sleep-research methodologies allowed us to document, for the first time, large changes in many components of pursuit, saccades and visual motion processing as a function of time awake and circadian phase. Further, we observed a pattern of impairment across our set of oculometric measures that is qualitatively different from that observed previously with other mild neural impairments. We conclude that dynamic vision and visuomotor control exhibit a distinct pattern of impairment linked with time awake and circadian phase. Therefore, a sufficiently broad set of oculometric measures could provide a sensitive and specific behavioural biomarker of acute sleep loss and circadian misalignment. We foresee potential applications of such oculometric biomarkers assisting in the assessment of readiness-to-perform higher risk tasks and in the characterization of sub-clinical neural impairment in the face of a multiplicity of potential risk factors, including disrupted sleep and circadian rhythms.

Stone, Leland S.↗

Exploring the ARNTL and RORc Genes' Impact on Lipid Accumulation in the Liver via the Circadian Rhythm

The objective of our proposed experiment is to prove the significance of the upregulation of the ARNTL gene and down regulation of the RORc gene in space, highlighting their crucial roles in causing circadian rhythm misalignment during spaceflight, ultimately resulting in liver lipid accumulation. This experiment was created by thoroughly analyzing the genetic data (UseGalaxy) in OSD-245, Transcriptional analysis of liver from mice flown on the RR-6 mission (NASA GeneLab), and making a comparison between the Flight ISS Terminal and the Ground Control ISS Terminal groups. In our study, we intend to establish experimental groups of Mus musculus (lab mice), with 4 of these groups designated for space travel, while the remaining groups will serve as ground control samples on Earth. Both the space and ground conditions are categorized into four groups according to the genetic makeup of the mice. Within each condition, there will be a control group representing the wild type genes, and the experimental groups will involve knockout mice for ARNTL and RORc. We will then compare the lipid accumulation between the ground control mice and FLT mice to understand whether or not spaceflight causes lipid accumulation, due to a misaligned circadian rhythm. The experiment is anticipated to yield two main outcomes. Firstly, the upregulation of ARNTL is expected to rectify the circadian rhythm misalignment in space, consequently heightening lipid accumulation within the liver. Secondly, the downregulation of RORc is predicted to result in a diminished immune response in the liver, thereby facilitating lipid accumulation. Our space research is expected to aid in lipid buildup countermeasures, informing scientists regarding astronaut protection and providing insights into obesity and non-alcoholic fatty liver disease.

GL4HS↗

Identification of Cardiometabolic Vulnerabilities Caused by Effects of Synergistic Stressors that are Commonly Encountered During Space Missions

Microgravity is a physiologically challenging state even when at rest. Astronauts experience additional physical and mental stresses, such as prolonged exertion, sleep loss and circadian misalignment, that could impact cardiovascular function. The main goals of this four year NASA project are to characterize the independent and synergistic effects on cardiovascular and immune function of: (1) circadian misalignment; (2) sleep loss; and (3) varied physical and mental stressors, mimicking some of the synergistic stressors experienced by astronauts. Sixteen healthy volunteers, aged 35-55 years, will be studied with standardized behavioral stressors occurring across all circadian phases, both with and without accruing sleep loss, achieved via two 11-day "forced desynchrony" protocols performed in each subject (randomized, within-subject design), where wake periods are advanced 4-h each "day" (i.e. recurring 20-h "days"). One protocol permits 8.33 h sleep opportunity per 20-h "day" (=10 h sleep per 24-h), and the other permits 5 h sleep per 20-h "day" (=6 h sleep per 24-h; matching the reported sleep duration of astronauts). In both protocols, subjects will perform a standardized stress battery including a cognitively challenging task; bicycle exercise, and passive 60deg head up tilt. Outcome variables include blood pressure, heart rate, arrhythmia frequency, cardiac vagal tone (from heart rate variability), sympathetic activity (catecholamines), and endothelial function. Additional measures of cardiac function (echocardiography), responses to a passive 80deg head up tilt, maximal oxygen uptake, and immune function will be assessed at the beginning and at the end of each protocol (i.e., without and with sleep loss, and before and after circadian misalignment). We hope to identify the relative impact on cardiovascular risk markers of varied behavioural stressors while subjects experience circadian misalignment and sleep loss, mimicking some of the synergistic stressors experienced by astronauts. Supported by NASANNX1 OAR 1 OG.

Ruger, M.↗

Risk of Performance Decrements and Adverse Health Outcomes Resulting from Sleep Loss, Circadian Desynchronization, and Work Overload

Sleep loss, circadian desynchronization, and work overload occur to some extent for ground and flight crews, prior to and during spaceflight missions. Ground evidence indicates that such risk factors may lead to performance decrements and adverse health outcomes, which could potentially compromise mission objectives. Efforts are needed to identify the environmental and mission conditions that interfere with sleep and circadian alignment, as well as individual differences in vulnerability and resiliency to sleep loss and circadian desynchronization. Specifically, this report highlights a collection of new evidence to better characterize the risk and reveals new gaps in this risk as follows: Sleep loss is apparent during spaceflight. Astronauts consistently average less sleep during spaceflight relative to on the ground. The causes of this sleep loss remain unknown, however ground-based evidence suggests that the sleep duration of astronauts is likely to lead to performance impairment and short and long-term health consequences. Further research is needed in this area in order to develop screening tools to assess individual astronaut sleep need in order to quantify the magnitude of sleep loss during spaceflight; current and planned efforts in BHP's research portfolio address this need. In addition, it is still unclear whether the conditions of spaceflight environment lead to sleep loss or whether other factors, such as work overload lead to the reduced sleep duration. Future data mining efforts and continued data collection on the ISS will help to further characterize factors contributing to sleep loss. Sleep inertia has not been evaluated during spaceflight. Ground-based studies confirm that it takes two to four hours to achieve optimal performance after waking from a sleep episode. Sleep inertia has been associated with increased accidents and reduced performance in operational environments. Sleep inertia poses considerable risk during spaceflight when emergency situations necessitate that crewmembers wake from sleep and make quick decisions. A recently completed BHP investigation assesses the effects of sleep inertia upon abrupt awakening, with and without hypnotics currently used in spaceflight; results from this investigation will help to inform strategies relative to sleep inertia effects on performance. Circadian desynchrony has been observed during spaceflight. Circadian desynchrony during spaceflight develops due to schedule constraints requiring non-24 operations or 'slam-shifts' and due to insufficient or mis-timed light exposure. In addition, circadian misalignment has been associated with reduced sleep duration and increased medication use. In ground-based studies, circadian desynchrony has been associated with significant performance impairment and increased risk of accidents when operations coincide with the circadian nadir. There is a great deal of information available on how to manage circadian misalignment, however, there are currently no easily collected biomarkers that can be used during spaceflight to determine circadian phase. Current research efforts are addressing this gap. Work overload has been documented during current spaceflight operations. NASA has established work hour guidelines that limit shift duration, however, schedule creep, where duty requirements necessitate working beyond scheduled work hours, has been reported. This observation warrants the documentation of actual work hours in order to improve planning and in order to ensure that astronauts receive adequate down time. In addition to concerns about work overload, ground based evidence suggests that work underload may be a concern during deep space missions, where torpor may develop and physically demanding workload will be exchanged for monitoring of autonomous systems. Given that increased automation is anticipated for exploration vehicles, fatigue effects in the context of such systems needs to be further understood. Performance metrics are needed to evaluate fitness-for-duty during spaceflight. Although ground-based evidence supports the notion that sleep loss, circadian desynchronization and work overload lead to performance impairment, inconsistency in the measures used to evaluate performance during spaceflight make it difficult to evaluate the magnitude of performance impairment during spaceflight. Work is underway to standardize measures of performance evaluation during spaceflight. Once established, such performance indicators need to be correlated with operational performance. Individual differences in sleep need and circadian preference, phase shifting ability and period have been documented in ground-based studies. Individual differences in response to sleep loss and circadian misalignment have also been documented and are presumed to be associated with genetic polymorphisms. No studies have systematically reported individual differences in sleep or circadian-related outcomes during spaceflight. More work is needed in this area in order to identify genetic or phenotypic biomarkers that predict resilience or vulnerability to sleep loss in order to personalize countermeasure strategies and mitigate performance impairment during spaceflight. Two laboratory and field investigations specific to this topic are currently ongoing; additional efforts, including an effort to mine existing biological data from spaceflight relative to sleep and circadian outcomes, are planned. Sex differences in sleep need and circadian period and phase have been reported in ground-based studies. The impact of these sex differences on performance is unclear. Sex differences in sleep need and circadian rhythms have not been systematically studied during spaceflight, presumably due to the small number of women that have flown in space. More research is needed in this area to evaluate whether any of the observed sex differences in physiology lead to altered performance in spaceflight and on the ground.

Flynn-Evans, Erin↗

Introduction to Sleep and Circadian Physiology

The purpose of this talk is to provide an undergraduate student audience with basic information about the sleep and circadian challenges that astronauts and pilots face. Dr. Flynn-Evans will begin by highlighting how NASA works. She will next cover basic information about sleep, circadian rhythms, and performance, including how sleep works on earth. She will explain how people have circadian rhythms of different lengths and how the circadian clock has to be re-set each day. She will also describe how jet-lag works as an example of what happens during circadian misalignment. Dr. Flynn-Evans will describe how modest circadian misalignment affects airline pilots during short-haul flights. She will also describe how sleep is different in space and will highlight the challenges that astronauts face in low-earth orbit. She will discuss how astronauts have a shorter sleep duration in space relative to on the ground and how their schedules can shift due to operational constraints. She will also describe how these issues affect alertness and performance. She will then discuss how sleep and scheduling may be different on a long-duration mission to Mars. She will discuss the differences in light and day length on earth and mars and illustrate how those differences pose significant challenges to sleep and circadian rhythms.

Flynn-Evans, Erin↗

Space Transport and Fatigue

Space travel presents numerous challenges to fatigue management. Fatigue in space results from many of the same challenges that shiftworkers face on Earth, including inadequate sleep, circadian misalignment, and elevated workload. However, spaceflight also presents unique challenges including circadian misalignment due to non-24- hour light-dark cycles, erratic work schedules due to operational constraints, a microgravity sleep environment, constraints to habitat design, and an isolated and confined living environment. These challenges can be mitigated with fatigue management strategies and countermeasures specifically targeted for space travel. Those strategies can include light interventions, advanced scheduling tools, improved habitat design, and pharmacological countermeasures. What is needed is a future-facing approach to most effectively manage the challenges that may arise as advancements in space travel continue to develop at a rapid pace.

sleep deprivation and performance↗

Space Transport and Fatigue

Space travel presents numerous challenges to fatigue management. Fatigue in space results from many of the same challenges that shiftworkers face on Earth, including inadequate sleep, circadian misalignment, and elevated workload. However, spaceflight also presents unique challenges including circadian misalignment due to non-24- hour light-dark cycles, erratic work schedules due to operational constraints, a microgravity sleep environment, constraints to habitat design, and an isolated and confined living environment. These challenges can be mitigated with fatigue management strategies and countermeasures specifically targeted for space travel. Those strategies can include light interventions, advanced scheduling tools, improved habitat design, and pharmacological countermeasures. What is needed is a future-facing approach to most effectively manage the challenges that may arise as advancements in space travel continue to develop at a rapid pace.

sleep deprivation and performance↗

Sleep in High Stress Occupations

High stress occupations are associated with sleep restriction, circadian misalignment and demanding workload. This presentation will provide an overview of sleep duration, circadian misalignment and fatigue countermeasures and performance outcomes during spaceflight and commercial aviation.

spaceflight↗

Controlled Rest on the Flight Deck: Profile of Use, Challenges, and Best Practices

Managing fatigue in 24/7 operations is complex; fatigue and performance degradation can have health and safety consequences for the workers and can have economic and community consequences. We will present new findings on sleep, circadian misalignment, and performance in operational personnel. The presentations will shed light on how sleep and circadian misalignment affect workers' performance, safety, and health across multiple operations, and their application in fatigue risk management.As part of this symposium, I will discuss how pilots can use short naps (controlled rest) as a countermeasure to elevated sleepiness in-flight. My presentation will describe how and when controlled rest is used operationally and outline best practice guidelines for maximizing the benefits while managing the associated risks.

aviation↗

Evaluation of the Validity of Bio-Mathematical Models in Predicting Fatigue in an Operational Environment

During long-duration spaceflight missions, crewmembers and ground-support staff experience irregular sleep schedules, erratic natural light patterns, and high workload due to mission demands. Such conditions can cause circadian misalignment and sleep loss, which in turn cause deficits in cognitive performance. While bio-mathematical models have been implemented within workplace settings to predict fatigue profiles, the accuracy of sleep-wake models under conditions of non-traditional shiftwork is little known. Thus, the present study aims to evaluate the validity of four sleep-wake models (e.g., SAFTE-FAST, the Unified Model of Performance, the Adenosine-Circadian Model, and the State-Space Model) designed to predict human performance and fatigue levels against objective measures of performance in a spaceflight analog. To accomplish this aim, we will collect Psychomotor Vigilance Task (PVT) data from four crews (n=16) in the Human Exploration Research Analog (HERA) over 45 days. HERA is a closed, 3-story habitat at Johnson Space Center where inhabitants are exposed to extreme space exploration scenarios under varying sleep-wake conditions. The PVT is a simple reaction time test that involves minimal learning, making it sensitive to the effects of sleep loss and circadian misalignment. Findings from this study will help inform work scheduling and implementation of effective countermeasures (e.g., caffeine, lighting) to improve work efficiency and combat fatigue, as well as offer valuable insight into the applicability of bio-mathematical fatigue models in future space exploration missions.

fatigue↗

Night shift schedule causes circadian dysregulation of DNA repair genes and elevated DNA damage in humans

Circadian disruption has been identified as a risk factor for health disorders such as obesity, cardiovascular disease, and cancer. Although epidemiological studies suggest an increased risk of various cancers associated with circadian misalignment due to night shift work, the underlying mechanisms have yet to be elucidated. Here, we sought to investigate the potential mechanistic role that circadian disruption of cancer hallmark pathway genes may play in the increased cancer risk in shift workers. In a controlled laboratory study, we investigated the circadian transcriptome of cancer hallmark pathway genes and associated biological pathways in circulating leukocytes obtained from healthy young adults during a 24‐hour constant routine protocol following 3 days of simulated day shift or night shift. The simulated night shift schedule significantly altered the normal circadian rhythmicity of genes involved in cancer hallmark pathways. A DNA repair pathway showed significant enrichment of rhythmic genes following the simulated day shift schedule, but not following the simulated night shift schedule. In functional assessments, we demonstrated that there was an increased sensitivity to both endogenous and exogenous sources of DNA damage after exposure to simulated night shift. Our results suggest that circadian dysregulation of DNA repair may increase DNA damage and potentiate elevated cancer risk in night shift workers.

circadian misalignment↗

Sleep Issues in Aviation and Space

This article describes the factors that cause sleep issues in aviation and spaceflight. There are many causes of sleep disruption that are common to both domains, including, irregular schedules, circadian misalignment, and inadequate sleep environment. There are also factors that are unique to each type of operation that may lead to the manifestation of sleep disorders among these populations. Each of these factors, and their subsequent impact on sleep, are reviewed in this article.

Astronaut↗

Circadian regulation of human sleep and age-related changes in its timing, consolidation and EEG characteristics

The light-entrainable circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus regulates the timing and consolidation of sleep by generating a paradoxical rhythm of sleep propensity; the circadian drive for wakefulness peaks at the end of the day spent awake, ie close to the onset of melatonin secretion at 21.00-22.00 h and the circadian drive for sleep crests shortly before habitual waking-up time. With advancing age, ie after early adulthood, sleep consolidation declines, and time of awakening and the rhythms of body temperature, plasma melatonin and cortisol shift to an earlier clock hour. The variability of the phase relationship between the sleep-wake cycle and circadian rhythms increases, and in old age sleep is more susceptible to internal arousing stimuli associated with circadian misalignment. The propensity to awaken from sleep advances relative to the body temperature nadir in older people, a change that is opposite to the phase delay of awakening relative to internal circadian rhythms associated with morningness in young people. Age-related changes do not appear to be associated with a shortening of the circadian period or a reduction of the circadian drive for wake maintenance. These changes may be related to changes in the sleep process itself, such as reductions in slow-wave sleep and sleep spindles as well as a reduced strength of the circadian signal promoting sleep in the early morning hours. Putative mediators and modulators of circadian sleep regulation are discussed.

Review, Tutorial↗

NASA HRP Immunology Discipline - Use of Terrestrial Analogs

Due to the cost and operational constraints, as well as technical implementation limitations, it is desirous to perform relevant space physiology investigations first in terrestrial 'space analogs'. This is particularly true for initial investigations, which may then provide appropriate focus for subsequent flight investigations, or for mechanistic investigations that simply cannot be performed during spaceflight. Appropriate analog choice is extremely important. There are a wide variety of terrestrial space analogs, each relevant to a particular physiological discipline (or disciplines) and each with a particular fidelity (or lack thereof) to spaceflight, and each with unique operational constraints. The HRP Immunology Discipline is tasked with managing the HRP Risk concerning clinical risk for Astronaut crews related to spaceflight-associated immune dysregulation. Such dysregulation has been documented to occur during spaceflight, and found to persist for the duration of a 6-month ISS mission. Studies continue to characterize the onorbit phenomenon, but it generally consists of diminished immunocyte function, dysregulated cytokine profiles, and persistent herpesvirus reactivation. Causes are thought to synergistically include microgravity, psychological or physiological stress, radiation, and/or circadian misalignment. An appropriate terrestrial analog for immune dysregulation would replicate as many of these influences as possible. Such analogs may include clinostat or bioreactor cell culture (microgravity), hindlimb suspension (stress, fluid shifts, hypokinesis), or human deployment to remote or extreme environments (isolation, stress, circadian). Also, the laboratory setting may be used as an analog, or to augment analogs, such as sleep deprivation/misalignment or human centrifugation to replicate gravitational stress. As an appropriate example of a NASA Disciplines use of Terrestrial space analogs, this talk will discuss spaceflight associated immune dysregulation, terrestrial immune analogs, and recent analog investigations.

Crucian, Brian↗

A Summary Of: Collecting Sleep, Circadian, Fatigue, and Performance Data in Complex Operational Environments

Sleep loss and circadian misalignment contribute to a meaningful proportion of operational accidents and incidents. Countermeasures and work scheduling designs aimed at mitigating fatigue are typically evaluated in controlled laboratory environments, but the effectiveness of translating such strategies to operational environments can be challenging to assess. This manuscript summarizes an approach for collecting sleep, circadian, fatigue, and performance data in a complex operational environment. We studied 44 airline pilots over 34 days while they flew a fixed schedule, which included a baseline data collection with 5 days of mid-morning flights, four early flights, four high-workload mid-day flights, and four late flights that landed after midnight. Each work block was separated by 3-4 days of rest. To assess sleep, participants wore a wrist-worn research-validated activity monitor continuously and completed daily sleep diaries. To assess the circadian phase, pilots were asked to collect all urine produced in four or eight hourly bins during the 24 h after each duty block for the assessment of 6-sulfatoxymelatonin (aMT6s), which is a biomarker of the circadian rhythm. To assess subjective fatigue and objective performance, participants were provided with a touchscreen device used to complete the Samn-Perelli Fatigue Scale and Psychomotor Vigilance Task (PVT) during and after each flight, and at wake-time, mid-day, and bedtime. Using these methods, it was found that sleep duration was reduced during early starts and late finishes relative to baseline. Circadian phase shifted according to duty schedule, but there was a wide range in the aMT6s peak between individuals on each schedule. PVT performance was worse on the early, high-workload, and late schedules relative to baseline. Overall, the combination of these methods was practical and effective for assessing the influence of sleep loss and circadian phase on fatigue and performance in a complex operational environment.

Arsintescu, Lucica↗

Oculomotor Behavior Metrics Change According to Circadian Phase and Time Awake

There is a need for non-invasive, objective measures to forecast performance impairment arising from sleep loss and circadian misalignment, particularly in safety-sensitive occupations. Eye-tracking devices have been used in some operational scenarios, but such devices typically focus on eyelid closures and slow rolling eye movements and are susceptible to the intrusion of head movement artifacts. We hypothesized that an expanded suite of oculomotor behavior metrics, collected during a visual tracking task, would change according to circadian phase and time awake, and could be used as a marker of performance impairment.

sleep deprivation↗

Stress Induced Immune Dysregulation: A Continuum Spanning Antarctica Winterover, Spaceflight, and Terrestrial Patients

Spaceflight is a unique environment characterized by stress, microgravity, isolation, circadian misalignment, and radiation exposure and impacts immune health. Planned long duration missions to Mars are a top priority for NASA and mitigating the negative health consequences of spaceflight is particularly important. Terrestrial analogs are a vital aspect of spaceflight research since data from astronauts is limited and it is costly to receive samples from ISS. The most relevant ground analog would include station lifestyle, stress, disrupted circadian rhythms and isolation. This analysis compares various aspects of immune dysregulation in astronauts during long-duration orbital spaceflight to groundanalogs. Astronaut data were also compared to a clinical immunodeficiency population, shingles patients, to help interpret clinical risks during deep space missions. A comprehensive evaluation was performed across hypoxic interior Antarctica, normoxic coastal Antarctica, HERA, and astronauts which included plasma and mitogen stimulated cytokine profiles, T-cell function, and peripheral leukocyte distribution. A cross platform analysis was then performed to define in-flight immune alterations, determine analog appropriateness, and interpret clinical risk.

Krieger, Stephanie↗