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Astronaut behavioral and mental health are key factors for space mission success. NASA's Cognition test battery is often preceded by a brief 18-item Alertness and Mood Survey (AMS) adding subjective assessments to Cognition's 10 objective neuropsychological tests. Therefore, the main objective of this study was to generate a single AMS summary score for short (<6 months) and long (>6 months) space missions based on the relevance of individual items. With the paired comparison (PC) method, 19 subject matter experts (SMEs) were asked to rate the relevance of 14 AMS items for astronaut behavioral health. Boredom (22.1% of comparisons), monotony (23.1%), and sleepiness (35.6%) were considered the least relevant, and health (74.3%), depression (76.5%), and crew conflicts (77.9%) were considered the most relevant by SMEs. Six of the fourteen items differed statistically significantly between PCs for short- and long-duration missions: sleepiness, tiredness, energy level, and mental status were considered more relevant for short-duration missions, while monotony and loneliness were considered more relevant for long-duration missions (all adjusted p < 0.05). We also demonstrated systematic changes in AMS summary scores during a 60-day 6° head-down tilt bed rest (HDBR) study, with increased alertness and mood disturbance during and after the HDBR period relative to pre-HDBR levels. This analysis identified the AMS domains considered most relevant for space mission success by SMEs, and highlighted differences between long- and short-duration missions. The resulting AMS summary scores were based on item relevance and will be useful for monitoring astronaut behavioral health on short- and long-duration space missions. [ABSTRACT FROM AUTHOR]

Human movement is optimized to Earth's gravity and based on highly complex interactions between sensory and neuro-muscular systems. Yet, humans are able to adapt--at least partially--to extreme environments upon and beyond Earth's surface. With upcoming Lunar Gateway and Artemis missions, it is crucial to increase our understanding of the impact of hypogravity--i.e., reduced vertical loading--on physiological and sensory-motor performances to improve countermeasure programs, and define crewmember's readiness to perform mission critical tasks. Several methodologies designed to reduce vertical loading are used to simulate hypogravity on Earth, including body weight support (BWS) devices. Countering gravity and offloading the human body is also used in various rehabilitation scenarios to improve motor recovery in neurological and orthopedic impairments. Thus, BWS-devices have the potential of advancing theory and practice of both space exploration and terrestrial rehabilitation by improving our understanding of physiological and sensory-motor adaptations to reduced vertical loading and sensory input. However, lack of standardization of BWS-related research protocols and reporting hinders the exchange of key findings and new advancements in both areas. The aim of this introduction paper is to review the role of BWS in understanding human movement in simulated hypogravity and the use of BWS in terrestrial rehabilitation, and to identify relevant research areas contributing to the optimization of human spaceflight and terrestrial rehabilitation. One of the main aims of this research topic is to facilitate standardization of hypogravity-related research protocols and outcome reporting, aimed at optimizing knowledge transfer between space research and BWS-related rehabilitation sciences. [ABSTRACT FROM AUTHOR]

Efforts to understand the impact of spaceflight on the human body stem from growing interest in long-term space travel. Multiple organ systems are affected by microgravity and radiation, including the cardiovascular system. Previous transcriptomic studies have sought to reveal the changes in gene expression after spaceflight. However, little is known about the impact of long-term spaceflight on the mouse heart in vivo. This study focuses on the transcriptomic changes in the hearts of female C57BL/6J mice flown on the International Space Station (ISS) for 30 days. RNA was isolated from the hearts of three flight and three comparable ground control mice and RNA sequencing was performed. Our analyses showed that 1147 transcripts were significantly regulated after spaceflight. The MAPK, PI3K-Akt, and GPCR signaling pathways were predicted to be activated. Transcripts related to cytoskeleton breakdown and organization were upregulated, but no significant change in the expression of extracellular matrix (ECM) components or oxidative stress pathway-associated transcripts occurred. Our results indicate an absence of cellular senescence, and a significant upregulation of transcripts associated with the cell cycle. Transcripts related to cellular maintenance and survival were most affected by spaceflight, suggesting that cardiovascular transcriptome initiates an adaptive response to long-term spaceflight. [ABSTRACT FROM AUTHOR]

BACKGROUND: In spaceflight, acute urinary retention (AUR) could develop as a sequela of medication use, urinary tract infection, urolithiasis, or intentional urine holding. While AUR is generally treated with bladder decompression, urinary catheterization could be difficult operationally in terms of training and proficiency, supplies, and lack of space or privacy. This report discusses a case in which tamsulosin and lorazepam were used successfully on an offshore ship while awaiting medical evacuation, a situation that could arise in remote locations where aerospace operations are conducted. CASE REPORT: A 52-yr-old man with hypertension and obstructive sleep apnea but no formal diagnosis of benign prostatic hyperplasia was unable to urinate for over 16 h while on a deep-sea fishing vessel approximately 200 nmi offshore. By phone, the physician providing remote medical direction diagnosed AUR in the setting of possible infection and prescribed acetaminophen, ciprofloxacin, and a trial of tamsulosin as the ship did not have any medical personnel trained to perform urinary catheterization and there were no catheter supplies available. Lorazepam was later added for anxiolysis and potential smooth muscle relaxation. Within 1 h of initial medication administration, the patient successfully voided a large quantity of urine, which tested positive for infection by urine dipstick. The patient was continued on antibiotics and evacuated to a medical facility onshore for further management. DISCUSSION: P harmacological treatment could be considered as a temporizing measure where operational constraints limit the ability to perform urinary catheterization to relieve acute urinary retention. [ABSTRACT FROM AUTHOR]

Altered gravity affects hemodynamics and blood flow in the neck. At least one incidence of jugular venous thrombosis has been reported in an astronaut on the International Space Station. This investigation explores the impact of changes in the direction of the gravitational vector on the characteristics of the neck arteries and veins. Twelve subjects underwent graded tilt from 45° head-up to 45° head-down in 15° increments in both supine and prone positions. At each angle, the cross-sectional area of the left and right common carotid arteries (ACCA) and internal jugular veins (AIJV) were measured by ultrasound. Internal jugular venous pressure (IJVP) was also measured by compression sonography. Gravitational dose-response curves were generated from experimental data. ACCA did not show any gravitational dependence. Conversely, both AIJV and IJVP increased in a nonlinear fashion with head-down tilt. AIJV was significantly larger on the right side than the left side at all tilt angles. In addition, IJVP was significantly elevated in the prone position compared with the supine position, most likely because of raised intrathoracic pressure while prone. Dose-response curves were compared with existing experimental data from parabolic flight and spaceflight studies, showing good agreement on an acute timescale. The quantification of jugular hemodynamics as a function of changes in the gravitational vector presented here provides a terrestrial model to reference spaceflight-induced changes, contributes to the assessment of the pathogenesis of spaceflight venous thromboembolism events, and informs the development of countermeasures. [ABSTRACT FROM AUTHOR]

Magnetic force and gravity are two fundamental forces affecting all living organisms, including bacteria. On Earth, experimentally created magnetic force can be used to counterbalance gravity and place living organisms in conditions of magnetic levitation. Under conditions of microgravity, magnetic force becomes the only force that moves bacteria, providing an acceleration towards areas of the lowest magnetic field and locking cells in this area. In this review, we consider basic principles and experimental systems used to create a magnetic force strong enough to balance gravity. Further, we describe how magnetic levitation is applied in on-Earth microbiological studies. Next, we consider bacterial behavior under combined conditions of microgravity and magnetic force onboard a spacecraft. At last, we discuss restrictions on applications of magnetic force in microbiological studies and the impact of these restrictions on biotechnological applications under space and on-Earth conditions. [ABSTRACT FROM AUTHOR]

Although incidences of psychological crises occurring during space flight are reportedly rare, such events remain a distinct possibility and potential threat to future long-duration missions (e.g., a Mars mission). Extended residence in Antarctica offers an ideal setting for examining high-risk profiles for psychological crises. We therefore utilized data from a nine-month longitudinal study conducted at the McMurdo station to examine baseline and monthly reports of psychological and physical symptoms among four emergency evacuees compared to the remaining McMurdo sample (n = 84). Emergency evacuation occurred for medical reasons (n = 2) or for psychiatric reasons (n = 2). Evacuees were White, between 29 and 47 years of age, and mostly male (n = 1 female). There were few differences in evacuees' baseline scores compared to the full sample. Monthly assessments showed elevated anxiety symptoms to be most common among all evacuees. Elevated physical symptoms were also apparent among a psychiatric and a medical evacuee in the months prior to evacuation. For one psychiatric evacuee, declines in positive emotions preceded increased problems with self-regulation before evacuation. While preliminary, findings contribute to sparse information about the symptoms that precede emergency evacuations from extreme environments and underscore the importance of regular, structured self-report assessments. • Description of symptoms associated with emergency evacuation from Antarctica is limited. • We examined monthly changes in mental and physical health symptoms among four evacuees. • Anxiety was the most common and severe symptom reported by medical and psychiatric evacuees. • Increased physical complaints were endorsed by two evacuees during the month prior to evacuation. • Ongoing assessment of these domains is recommended in extreme environments. [ABSTRACT FROM AUTHOR]

Space operations in the United States has required the skills of aerospace medicine specialists since the before the inception of human spaceflight in 1958. The literature extensively covers physiology, clinical science, and conjectures on the nature and future of space medicine. The goals of this project were to examine the evolution of the operational spaceflight surgeon, define the role today, and explore the future of operational space medicine. The data gathered for this project were obtained from several sources including personal interviews with actively serving NASA personnel, a literature review identified by searches of MEDLINE, Current Contents, PubMed, Google Scholar, internal NASA records and databases, and references from relevant articles. Only articles published in English between 1961 and 2019 were included. Finally, to provide a primary account to compliment the findings from above eight oral histories were examined from leaders in this field. This paper reviews the evolution of operational spaceflight medicine from the NASA perspective, offers a modern definition by those who practice it on a daily basis and explores its future development as a profession. While this work is inherently limited as defined by the experiences of select individuals; the 336 combined years-of-service of the sources, personal interviews, and command perspectives of the authors attempt to lay a foundation for such a definition. Understanding and appreciating this history is key to the successful future development of operational spaceflight medicine as a specialty, and by extension to manned space exploration as a whole. • History of the operational flight surgeon from the NASA perspective. • Period - 1958 through the current time period. • The knowledge shared here has been collected from the historical record, first hand accounts. [ABSTRACT FROM AUTHOR]

Exposure to microgravity during spaceflight is known to be associated with rapid and drastic bone loss in humans, which can increase the risks of fragility fracture and renal stone formation. Furthermore, the recovery of bone loss may require a relatively long time after returning back to Earth. Therefore, bone loss has become a substantial obstacle to human exploration of outer space. Currently, the therapeutic effects of the countermeasures related to microgravity-induced bone loss, including exercise, pharmacological intervention and supplementation, are not sufficient. Moreover, each class of pharmacological drugs has potential side effects. Hence, it is urgent to find more safer and effective drugs to alleviate microgravity-induced bone loss. Melatonin is a tryptophan-derived methoxyindole synthetized and released principally from the pineal gland. The secondary source of melatonin are bone marrow, retina, gut and skin. The production of melatonin occurs almost exclusively during the night, so exposure to light at night can reduce its production. Through receptor-mediated and receptor-independent actions, melatonin functions pleiotropic physiological actions in vertebrate. Due to its production and secretion are closely related to the environmental light/dark cycle, the key function of melatonin is to regulate circadian rhythm. Moreover, there is credible evidence that melatonin possesses antioxidant, anti-aging, anti-inflammatory and anticancer properties. Interestingly, melatonin is capable of chelating metals, such as iron, aluminum, cadmium, copper, lead and zinc. It is worth noting that melatonin has high safety profile and positive effects on osteoporosis, including microgravity-induced bone loss. As an attractive multitasking molecule, in the present review we shed light on the potential benefits of melatonin in the prevention and treatment of microgravity-induced bone loss. • Circadian disruption, oxidative stress and elevated iron levels are main risk factors for microgravity-induced bone loss. • We discuss the potential utility of melatonin for microgravity-induced bone loss. • Melatonin may act as a circadian rhythm modulator against microgravity-induced bone loss. • Melatonin may act as a powerful antioxidant against microgravity-induced bone loss. • Melatonin may act as an iron-chelator against microgravity-induced bone loss. [ABSTRACT FROM AUTHOR]

This paper traces the early ideas of lunar architecture developed by the US and Soviet space programs. Starting with a historical overview of those achievements, highlighting specific engineering, architectural, and design elements; illustrated with images and drawings. Some of them will be described in more detail, showing the design and decision-making process from the first sketch to its implementation. One example of the great engineering and management capabilities is the development and inclusion of the deployable lunar roving vehicle (LRV). Other examples include the project DLB Zvezda by Barmin's Design Bureau of General Engineering that was under development between 1962 and 1974, and a US project Horizon – a study to set up a Lunar Military outpost conducted in 1959. The paper includes personal statements from astronauts and cosmonauts, as well as people involved along design and implementation processes. Based on a historical overview of achievements, this paper highlights particular architectural and design unique approaches that defined design strategies for creating space systems, spacecraft and habitats for decades to follow. • Lunar architecture developed by the US and Soviet space programs. • Specific engineering, architectural and design elements. • Lessons learned from earlier lunar base designs. • Space habitat designs. [ABSTRACT FROM AUTHOR]

INTRODUCTION: recently developed wearable monitoring devices can provide arterial oxygen saturation (Spo2) measurements, offering potential for use in aerospace operations. Pilots and passengers are already using these technologies, but their performance has not yet been established under conditions experienced in the flight environment such as environmental hypoxia and concurrent body motion. METHODS: an initial evaluation was conducted in 10 healthy subjects who were studied in a normobaric chamber during normoxia and at a simulated altitude of 15,000 ft (4572 m; 11.8% oxygen). Spo2 was measured simultaneously using a standard pulse oximeter and four wearable devices: apple Watch Series 6; Garmin Fēnix 6 watch; Cosinusso two in-ear sensor; and oxitone 1000m wrist-worn pulse oximeter. measurements were made while stationary at rest, during very slight body motion (induced by very low intensity cycling at 30 W on an ergometer), and during moderate body motion (induced by moderate intensity cycling at 150 W). RESULTS: missed readings, defined as failure to record an Spo2 value within 1 min, occurred commonly with all wearables. Even with only very slight body motion, most devices missed most readings (range of 12-82% missed readings) and the rate was higher with greater body motion (range 18-92%). one device tended to under-report Spo2, while the other devices tended to over-report Spo2. Performance decreased across the devices when oxygenation was reduced. DISCUSSION: in this preliminary evaluation, the wearable devices studied did not perform to the same standard as a traditional pulse oximeter. these limitations may restrict their utility in flight and require further investigation. [ABSTRACT FROM AUTHOR]

INTRODUCTION: ethyl acetate is a simple organic compound that occurs naturally and is used industrially as a solvent. it has been detected in the iSS atmosphere and is known to off-gas from building materials. As NASA astronauts have been and will be exposed to ethyl acetate during space missions, Spaceflight Maximum Allowable concentrations (SMAcs) were developed following an extensive review of the available literature. METHODS: toxicological data relevant to SMAc development was collected from electronic databases using principles of systematic review, and from previous assessments and reviews of ethyl acetate. RESULTS: From an initial pool of over 35,000 studies, 10 were identified as studies appropriate to support SMAc development. the toxicological properties of ethyl acetate are relatively straightforward. ethyl acetate is rapidly absorbed and converted by carboxyesterases to ethanol. At concentrations on the order of 400 ppm for 4-8 h, most volunteers experienced mild irritation but no lasting effects. in subchronic animal studies, mild sedative effects and changes in body weight and weight gain were observed at 750 ppm and above. DISCUSSION: Numerous studies were identified to support the development of both short- and long-duration SMAcs. No chronic studies were available, but the high quality of the subchronic studies and the short half-life of ethyl acetate support extrapolation to longer durations. [ABSTRACT FROM AUTHOR]

Although a number of studies have examined cognitive functions in space, the reasons behind the observed changes described by space research and anecdotal reports have not yet been elucidated. A potential source of cognitive changes is the cephalad fluid shift in the body caused by the lack of hydrostatic pressure under microgravity. These alterations can be modeled under terrestrial conditions using ground-based studies, such as head-down tilt bedrest (HDBR). In this review, we compare the results of the space and HDBR cognitive research. Results for baseline and in-flight/in-HDBR comparisons, and for baseline and post-flight/post-HDBR comparisons are detailed regarding sensorimotor skills, time estimation, attention, psychomotor speed, memory, executive functions, reasoning, mathematical processing, and cognitive processing of emotional stimuli. Beyond behavioral performance, results regarding brain electrical activity during simulated and real microgravity environments are also discussed. Finally, we highlight the research gaps and suggest future directions. [ABSTRACT FROM AUTHOR]

Microgravity as experienced during spaceflight affects a number of physiological processes in various organs. However, effects on the liver have yet been poorly documented. Nevertheless, the liver is a metabolically highly active organ involved in carbohydrate metabolism, lipid metabolism and xenobiotic biotransformation. The present paper provides an overview of the effects of microgravity on the liver observed in experimental animals during actual spaceflight and upon simulation of microgravity on Earth. These include (i) induction of liver injury and inflammation associated with apoptosis and oxidative stress, (ii) changes in liver carbohydrate metabolism resulting in the onset of a diabetogenic phenotype, (iii) modifications in hepatic lipid metabolism leading to early non‐alcoholic fatty liver disease and (iv) alterations of the hepatic xenobiotic biotransformation machinery. Although most of these observations remain to be fully validated in humans, appropriate measures to counteract liver pathogenesis should be considered, especially in view of long‐term space missions. [ABSTRACT FROM AUTHOR]

During future lunar missions, astronauts may be required to pilot vehicles while standing, and the associated kinematic and injury response is not well understood. In this study, we used human body modeling to predict unsuited astronaut kinematics and injury risk for piloted lunar launches and landings in the standing posture. Three pulses (2–5 g; 10–150 ms rise times) were applied in 10 directions (vertical; ± 10-degree offsets) for a total of 30 simulations. Across all simulations, motion envelopes were computed to quantify displacement of the astronaut's head (max 9.0 cm forward, 7.0 cm backward, 2.1 cm upward, 7.3 cm downward, 2.4 cm lateral) and arms (max 25 cm forward, 35 cm backward, 15 cm upward, 20 cm downward, 20 cm lateral). All head, neck, lumbar, and lower extremity injury metrics were within NASA's tolerance limits, except tibia compression forces (0–1543 N upper tibia; 0–1482 N lower tibia; tolerance—1350 N) and revised tibia index (0.04–0.58 upper tibia; 0.03–0.48 lower tibia; tolerance—0.43) for the 2.7 g/150 ms pulse. Pulse magnitude and duration contributed over 80% to the injury metric values, whereas loading direction contributed less than 3%. Overall, these simulations suggest piloting a lunar lander vehicle in the standing posture presents a tibia injury risk which is potentially outside NASA's acceptance limits and warrants further investigation. [ABSTRACT FROM AUTHOR]

Abstract Background As the interest in manned spaceflight increases, so does the requirement to understand the transcriptomic mechanisms that underlay the detrimental physiological adaptations of skeletal muscle to microgravity. While microgravity-induced differential gene expression (DGE) has been extensively investigated, the contribution of differential alternative splicing (DAS) to the plasticity and functional status of the skeletal muscle transcriptome has not been studied in an animal model. Therefore, by evaluating both DGE and DAS across spaceflight, we set out to provide the first comprehensive characterization of the transcriptomic landscape of skeletal muscle during exposure to microgravity. Methods RNA-sequencing, immunohistochemistry, and morphological analyses were conducted utilizing total RNA and tissue sections isolated from the gastrocnemius and quadriceps muscles of 30-week-old female BALB/c mice exposed to microgravity or ground control conditions for 9 weeks. Results In response to microgravity, the skeletal muscle transcriptome was remodeled via both DGE and DAS. Importantly, while DGE showed variable gene network enrichment, DAS was enriched in structural and functional gene networks of skeletal muscle, resulting in the expression of alternatively spliced transcript isoforms that have been associated with the physiological changes to skeletal muscle in microgravity, including muscle atrophy and altered fiber type function. Finally, RNA-binding proteins, which are required for regulation of pre-mRNA splicing, were themselves differentially spliced but not differentially expressed, an upstream event that is speculated to account for the downstream splicing changes identified in target skeletal muscle genes. Conclusions Our work serves as the first investigation of coordinate changes in DGE and DAS in large limb muscles across spaceflight. It opens up a new opportunity to understand (i) the molecular mechanisms by which splice variants of skeletal muscle genes regulate the physiological adaptations of skeletal muscle to microgravity and (ii) how small molecule splicing regulator therapies might thwart muscle atrophy and alterations to fiber type function during prolonged spaceflight.

In human cognitive neuroscience and neuropsychology studies, laboratory-based research tasks have been important to establish principles of brain function and its relationship to behaviour; however, they differ greatly from real-life experiences. Several elements of real-life situations that impact human performance, such as stressors, are difficult or impossible to replicate in the laboratory. Expeditions offer unique possibilities for studying human cognition in complex environments that can transfer to other situations with similar features. For example, as caves share several of the physical and psychological challenges of safety-critical environments such as spaceflight, underground expeditions have been developed as an analogue for astronaut training purposes, suggesting that they might also be suitable for studying aspects of behaviour and cognition that cannot be fully examined under laboratory conditions. While a large range of topics and tools have been proposed for application in such environments, few have been used in the field. Methods and procedures for maximizing the robustness and scientific value of expedition research designs must first be developed and validated. We tested the feasibility of collecting human physiological, cognitive, and subjective experience data concerning brain state, sleep, cognitive workload, and fatigue, during a speleological expedition in a remote region. We document our approaches and challenges experienced, and provide recommendations and suggestions to aid future work. The data support the idea that cave expeditions are relevant naturalistic paradigms that offer unique possibilities for cognitive neuroscience to complement laboratory work and help improve human performance and safety in operational environments. • Studying complex, naturalistic behaviours in humans complements laboratory work investigating brain function and behaviour. • The current work tested data collection techniques and tools, in the context of a speleological expedition. • Results support the feasibility of data collection in real expeditions and suggest practical steps for robust fieldwork. • We propose a framework categorizing experimental designs and addressing challenges in naturalistic settings. [ABSTRACT FROM AUTHOR]

Astronauts often face orientation challenges while on orbit, which can lead to operator errors in demanding spatial tasks. In this study, we investigated the impact of long-duration spaceflight on the neural processes supporting astronauts’ spatial orientation skills. Using functional magnetic resonance imaging (fMRI), we collected data from 16 astronauts six months before and two weeks after their International Space Station (ISS) missions while performing a spatial orientation task that requires generating a mental representation of one’s surroundings. During this task, astronauts exhibited a general reduction in neural activity evoked from spatial-processing brain regions after spaceflight. The neural activity evoked in the precuneus was most saliently reduced following spaceflight, along with less powerful effects observed in the angular gyrus and retrosplenial regions of the brain. Importantly, the reduction in precuneus activity we identified was not accounted for by changes in behavioral performance or changes in grey matter concentration. These findings overall show less engagement of explicitly spatial neurological processes at postflight, suggesting astronauts make use of complementary strategies to perform some spatial tasks as an adaptation to spaceflight. These preliminary findings highlight the need for developing countermeasures or procedures that minimize the detrimental effects of spaceflight on spatial cognition, especially in light of planned long-distance future missions.

A method was previously developed to identify participant-specific parameters in a model of trabecular bone adaptation from longitudinal computed tomography (CT) imaging. In this study, we use these numerical methods to estimate changes in astronaut bone health during the distinct phases of spaceflight and recovery on Earth. Astronauts (N = 16) received high-resolution peripheral quantitative CT (HR-pQCT) scans of their distal tibia prior to launch (L), upon their return from an approximately six-month stay on the international space station (R+0), and after six (R+6) and 12 (R+12) months of recovery. To model trabecular bone adaptation, we determined participant-specific parameters at each time interval and estimated their bone structure at R+0, R+6, and R+12. To assess the fit of our model to this population, we compared static and dynamic bone morphometry as well as the Dice coefficient and symmetric distance at each measurement. In general, modeled and observed static morphometry were highly correlated (R2> 0.94) and statistically different (p < 0.0001) but with errors close to HR-pQCT precision limits. Dynamic morphometry, which captures rates of bone adaptation, was poorly estimated by our model (p < 0.0001). The Dice coefficient and symmetric distance indicated a reasonable local fit between observed and predicted bone volumes. This work applies a general and versatile computational framework to test bone adaptation models. Future work can explore and test increasingly sophisticated models (e.g., those including load or physiological factors) on a participant-specific basis.

Background: Understanding and countering the well-established negative health consequences of spaceflight remains a primary challenge preventing safe deep space exploration. Targeted/personalized therapeutics are at the forefront of space medicine strategies, and cross-species molecular signatures now define the ‘typical’ spaceflight response. However, a lack of direct genotype–phenotype associations currently limits the robustness and, therefore, the therapeutic utility of putative mechanisms underpinning pathological changes in flight. Methods: We employed the worm Caenorhabditis elegans as a validated model of space biology, combined with ‘NemaFlex-S’ microfluidic devices for assessing animal strength production as one of the most reproducible physiological responses to spaceflight. Wild-type and dys-1 (BZ33) strains (a Duchenne muscular dystrophy (DMD) model for comparing predisposed muscle weak animals) were cultured on the International Space Station in chemically defined media before loading second-generation gravid adults into NemaFlex-S devices to assess individual animal strength. These same cultures were then frozen on orbit before returning to Earth for next-generation sequencing transcriptomic analysis. Results: Neuromuscular strength was lower in flight versus ground controls (16.6% decline, p < 0.05), with dys-1 significantly more (23% less strength, p < 0.01) affected than wild types. The transcriptional gene ontology signatures characterizing both strains of weaker animals in flight strongly corroborate previous results across species, enriched for upregulated stress response pathways and downregulated mitochondrial and cytoskeletal processes. Functional gene cluster analysis extended this to implicate decreased neuronal function, including abnormal calcium handling and acetylcholine signaling, in space-induced strength declines under the predicted control of UNC-89 and DAF-19 transcription factors. Finally, gene modules specifically altered in dys-1 animals in flight again cluster to neuronal/neuromuscular pathways, suggesting strength loss in DMD comprises a strong neuronal component that predisposes these animals to exacerbated strength loss in space. Conclusions: Highly reproducible gene signatures are strongly associated with space-induced neuromuscular strength loss across species and neuronal changes in calcium/acetylcholine signaling require further study. These results promote targeted medical efforts towards and provide an in vivo model for safely sending animals and people into deep space in the near future.

The human quest for sustainable habitation of extraterrestrial environments necessitates a robust understanding of life’s adaptability to the unique conditions of spaceflight. This study provides a comprehensive proteomic dissection of the Arabidopsis plant’s responses to the spaceflight environment through a meta-analysis of proteomics data from four separate spaceflight experiments conducted on the International Space Station (ISS) in different hardware configurations. Raw proteomics LC/MS spectra were analyzed for differential expression in MaxQuant and Perseus software. The analysis of dissimilarities among the datasets reveals the multidimensional nature of plant proteomic responses to spaceflight, impacted by variables such as spaceflight hardware, seedling age, lighting conditions, and proteomic quantification techniques. By contrasting datasets that varied in light exposure, we elucidated proteins involved in photomorphogenesis and skotomorphogenesis in plant spaceflight responses. Additionally, with data from an onboard 1 g control experiment, we isolated proteins that specifically respond to the microgravity environment and those that respond to other spaceflight conditions. This study identified proteins and associated metabolic pathways that are consistently impacted across the datasets. Notably, these shared proteins were associated with critical metabolic functions, including carbon metabolism, glycolysis, gluconeogenesis, and amino acid biosynthesis, underscoring their potential significance in Arabidopsis’ spaceflight adaptation mechanisms and informing strategies for successful space farming.

The demands of deep space pose a health risk to the central nervous system that has long been a concern when sending humans to space. While little is known about how spaceflight affects transcription spatially in the brain, a greater understanding of this process has the potential to aid strategies that mitigate the effects of spaceflight on the brain. Therefore, we performed GeoMx Digital Spatial Profiling of mouse brains subjected to either spaceflight or grounded controls. Four brain regions were selected: Cortex, Frontal Cortex, Corunu Ammonis I, and Dentate Gyrus. Antioxidants have emerged as a potential means of attenuating the effects of spaceflight, so we treated a subset of the mice with a superoxide dismutase mimic, MnTnBuOE-2-PyP 5+ (BuOE). Our analysis revealed hundreds of differentially expressed genes due to spaceflight in each of the four brain regions. Both common and region-specific transcriptomic responses were observed. Metabolic pathways and pathways sensitive to oxidative stress were enriched in the four brain regions due to spaceflight. These findings enhance our understanding of brain regional variation in susceptibility to spaceflight conditions. BuOE reduced the transcriptomic effects of spaceflight at a large number of genes, suggesting that this compound may attenuate oxidative stress-induced brain damage caused by the spaceflight environment.

Human movement is optimized to Earth's gravity and based on highly complex interactions between sensory and neuro-muscular systems. Yet, humans are able to adapt—at least partially—to extreme environments upon and beyond Earth's surface. With upcoming Lunar Gateway and Artemis missions, it is crucial to increase our understanding of the impact of hypogravity—i.e., reduced vertical loading—on physiological and sensory-motor performances to improve countermeasure programs, and define crewmember's readiness to perform mission critical tasks. Several methodologies designed to reduce vertical loading are used to simulate hypogravity on Earth, including body weight support (BWS) devices. Countering gravity and offloading the human body is also used in various rehabilitation scenarios to improve motor recovery in neurological and orthopedic impairments. Thus, BWS-devices have the potential of advancing theory and practice of both space exploration and terrestrial rehabilitation by improving our understanding of physiological and sensory-motor adaptations to reduced vertical loading and sensory input. However, lack of standardization of BWS-related research protocols and reporting hinders the exchange of key findings and new advancements in both areas. The aim of this introduction paper is to review the role of BWS in understanding human movement in simulated hypogravity and the use of BWS in terrestrial rehabilitation, and to identify relevant research areas contributing to the optimization of human spaceflight and terrestrial rehabilitation. One of the main aims of this research topic is to facilitate standardization of hypogravity-related research protocols and outcome reporting, aimed at optimizing knowledge transfer between space research and BWS-related rehabilitation sciences.

In preparation for lunar and Mars missions it is essential to consider the challenges to human health that are posed by long-duration deep space habitation via multiple stressors, including ionizing radiation, gravitational changes during flight and in orbit, other aspects of the space environment such as high level of carbon dioxide, and psychological stress from confined environment and social isolation. It remains unclear how these stressors individually or in combination impact the central nervous system (CNS), presenting potential obstacles for astronauts engaged in deep space travel. Although human spaceflight research only within the last decade has started to include the effects of radiation transmitted by galactic cosmic rays to the CNS, radiation is currently considered to be one of the main stressors for prolonged spaceflight and deep space exploration. Here we will review the current knowledge of CNS damage caused by simulated space radiation with an emphasis on neuronal and glial responses along with cognitive functions. Furthermore, we will present novel experimental approaches to integrate the knowledge into more comprehensive studies, including multiple stressors at once and potential translation to human functions. Finally, we will discuss the need for developing biomarkers as predictors for cognitive decline and therapeutic countermeasures to prevent CNS damage and the loss of cognitive abilities.

Background contextProlonged microgravity exposure is associated with localized low back pain and an elevated risk of post-flight disc herniation. Although the mechanisms by which microgravity impairs the spine are unclear, they should be foundational for developing in-flight countermeasures for maintaining astronaut spine health. Because human spine anatomy has adapted to upright posture on Earth, observations of how spaceflight affects the spine should also provide new and potentially important information on spine biomechanics that benefit the general population.PurposeThis study compares quantitative measures of lumbar spine anatomy, health, and biomechanics in astronauts before and after 6 months of microgravity exposure on board the International Space Station (ISS).Study designThis is a prospective longitudinal study.SampleSix astronaut crewmember volunteers from the National Aeronautics and Space Administration (NASA) with 6-month missions aboard the ISS comprised our study sample.Outcome measuresFor multifidus and erector spinae at L3-L4, measures include cross-sectional area (CSA), functional cross-sectional area (FCSA), and FCSA/CSA. Other measures include supine lumbar lordosis (L1-S1), active (standing) and passive (lying) flexion-extension range of motion (FE ROM) for each lumbar disc segment, disc water content from T2-weighted intensity, Pfirrmann grade, vertebral end plate pathology, and subject-reported incidence of chronic low back pain or disc injuries at 1-year follow-up.Methods3T magnetic resonance imaging and dynamic fluoroscopy of the lumbar spine were collected for each subject at two time points: approximately 30 days before launch (pre-flight) and 1 day following 6 months spaceflight on the ISS (post-flight). Outcome measures were compared between time points using paired t tests and regression analyses.ResultsSupine lumbar lordosis decreased (flattened) by an average of 11% (p=.019). Active FE ROM decreased for the middle three lumbar discs (L2-L3: -22.1%, p=.049; L3-L4: -17.3%, p=.016; L4-L5: -30.3%, p=.004). By contrast, no significant passive FE ROM changes in these discs were observed (p>.05). Disc water content did not differ systematically from pre- to post-flight. Multifidus and erector spinae changed variably between subjects, with five of six subjects experiencing an average decrease 20% for FCSA and 8%-9% for CSA in both muscles. For all subjects, changes in multifidus FCSA strongly correlated with changes in lordosis (r2=0.86, p=.008) and active FE ROM at L4-L5 (r2=0.94, p=.007). Additionally, changes in multifidus FCSA/CSA correlated with changes in lordosis (r2=0.69, p=.03). Although multifidus-associated changes in lordosis and ROM were present among all subjects, only those with severe, pre-flight end plate irregularities (two of six subjects) had post-flight lumbar symptoms (including chronic low back pain or disc herniation).ConclusionsWe observed that multifidus atrophy, rather than intervertebral disc swelling, associated strongly with lumbar flattening and increased stiffness. Because these changes have been previously linked with detrimental spine biomechanics and pain in terrestrial populations, when combined with evidence of pre-flight vertebral end plate insufficiency, they may elevate injury risk for astronauts upon return to gravity loading. Our results also have implications for deconditioned spines on Earth. We anticipate that our results will inform new astronaut countermeasures that target the multifidus muscles, and research on the role of muscular stability in relation to chronic low back pain and disc injury.

With manned missions to Mars on the horizon, understanding and preparing for the medical conditions these astronauts might face becomes vital. According to the literature, the most commonly reported medical events in space are dermatological in nature. Dermatologic conditions rarely threaten an astronaut's life or the mission. However, manifestations and management of dermatologic events become an important consideration in anticipation of spaceflights to Mars and beyond. Given the limited number of articles written about dermatological conditions in this specific population, this review summarizes current knowledge related to dermatology in space. Overall, common dermatologic conditions found during spaceflight include viral reactivations, contact dermatitis or eczematous patches, and skin infections. Diagnosis and treatment can be difficult given the lack of resources in space as well as the hazards and side effects of certain treatments. In this review article we aim to summarize common skin changes induced by spaceflight, describe previously reported skin conditions including current treatment options, explore the risk of skin cancer in this unique population, and address the challenge of remote diagnosis.

Although a number of studies have examined cognitive functions in space, the reasons behind the observed changes described by space research and anecdotal reports have not yet been elucidated. A potential source of cognitive changes is the cephalad fluid shift in the body caused by the lack of hydrostatic pressure under microgravity. These alterations can be modeled under terrestrial conditions using ground-based studies, such as head-down tilt bedrest (HDBR). In this review, we compare the results of the space and HDBR cognitive research. Results for baseline and in-flight/in-HDBR comparisons, and for baseline and post-flight/post-HDBR comparisons are detailed regarding sensorimotor skills, time estimation, attention, psychomotor speed, memory, executive functions, reasoning, mathematical processing, and cognitive processing of emotional stimuli. Beyond behavioral performance, results regarding brain electrical activity during simulated and real microgravity environments are also discussed. Finally, we highlight the research gaps and suggest future directions.

Space mutation causes genetic and phenotypic changes in biological materials. Transposon activation is an adaptive mechanism for organisms to cope with changes in the external environment, such as space mutation. Although transposon alterations have been widely reported in diverse plant species, few studies have assessed the global transposon alterations in plants exposed to the space environment. In this study, for the first time, the effects of transposon alterations in soybean caused by space mutation were considered. A new vegetable soybean variety, 'Zhexian 9' (Z9), derived from space mutation treatment of 'Taiwan 75' (T75), was genetically analyzed. Comparative analyses of these two soybean genomes uncovered surprising structural differences, especially with respect to translocation breakends, deletions, and inversions. In total, 12,028 structural variations (SVs) and 29,063 transposable elements (TEs) between T75 and Z9 were detected. In addition, 1336 potential genes were variable between T75 and Z9 in terms of SVs and TEs. These differential genes were enriched in functions such as defense response, cell wall-related processes, epigenetics, auxin metabolism and transport, signal transduction, and especially methylation, which implied that regulation of epigenetic mechanisms and TE activity are important in the space environment. These results are helpful for understanding the role of TEs in response to the space environment and provide a theoretical basis for the selection of wild plant materials suitable for space breeding. [ABSTRACT FROM AUTHOR]

Biological experiments performed in space crafts like space stations, space shuttles, and recoverable satellites has enabled extensive spaceflight life investigations (SLIs). In particular, SLIs have revealed distinguished space effects on microbial growth, survival, metabolite production, biofilm formation, virulence development and drug resistant mutations. These provide unique perspectives to ground-based microbiology and new opportunities for industrial pharmaceutical and metabolite productions. SLIs are with specialized experimental setups, analysis methods and research outcomes, which can be accessed by established databases National Aeronautics and Space Administration (NASA) Life Science Data Archive, Erasmus Experiment Archive, and NASA GeneLab. The increasing research across diverse fields may be better facilitated by databases of convenient search facilities and categorized presentation of comprehensive contents. We therefore developed the Space Life Investigation Database (SpaceLID) http://bidd.group/spacelid/, which collected SLIs from published academic papers. Currently, this database provides detailed menu search facilities and categorized contents about the studied phenomena, materials, experimental procedures, analysis methods, and research outcomes of 448 SLIs of 90 species (microbial, plant, animal, human), 81 foods and 106 pharmaceuticals, including 232 SLIs not covered by the established databases. The potential applications of SpaceLID are illustrated by the examples of published experimental design and bioinformatic analysis of spaceflight microbial phenomena. [ABSTRACT FROM AUTHOR]

Spaceflight exposes crewmembers to circadian misalignment and sleep loss, which impair cognition and increase the risk of errors and accidents. We compared the effects of an experimental dynamic lighting schedule (DLS) with a standard static lighting schedule (SLS) on circadian phase, self‐reported sleep and cognition during a 45‐day simulated space mission. Sixteen participants (mean age [±SD] 37.4 ± 6.7 years; 5 F; n = 8/lighting condition) were studied in four‐person teams at the NASA Human Exploration Research Analog. Participants were scheduled to sleep 8 h/night on two weekend nights, 5 h/night on five weekday nights, repeated for six 7‐day cycles, with scheduled waketime fixed at 7:00 a.m. Compared to the SLS where illuminance and spectrum remained constant during wake (~4000K), DLS increased the illuminance and short‐wavelength (blue) content of white light (~6000K) approximately threefold in the main workspace (Level 1), until 3 h before bedtime when illuminance was reduced by ~96% and the blue content also reduced throughout (~4000K × 2 h, ~3000K × 1 h) until bedtime. The average (±SE) urinary 6‐sulphatoxymelatonin (aMT6s) acrophase time was significantly later in the SLS (6.22 ± 0.34 h) compared to the DLS (4.76 ± 0.53 h) and more variable in SLS compared to DLS (37.2 ± 3.6 min vs. 28.2 ± 2.4 min, respectively, p =.04). Compared to DLS, self‐reported sleep was more frequently misaligned relative to circadian phase in SLS RR: 6.75, 95% CI 1.55–29.36, p =.01), but neither self‐reported sleep duration nor latency to sleep was different between lighting conditions. Accuracy in the abstract matching and matrix reasoning tests were significantly better in DLS compared to SLS (false discovery rate‐adjusted p ≤.04). Overall, DLS alleviated the drift in circadian phase typically observed in space analog studies and reduced the prevalence of self‐reported sleep episodes occurring at an adverse circadian phase. Our results support incorporating DLS in future missions, which may facilitate appropriate circadian alignment and reduce the risk of sleep disruption. [ABSTRACT FROM AUTHOR]

Introduction: Since Gagarin became the first human to travel into space and complete one orbit around the Earth, on 12 April 1961, the number of manned spaceflights has increased significantly. Spaceflight is still complex and has potential risk for incidents and accidents. The aim of this study was to analyze how safe it is for humans to travel in space. Objectives: This paper, therefore, summarizes incidents and accidents covering the six decades of manned spaceflight (1961–2020). Material and methods: Extensive PubMed, Cochrane, and Google Scholar searches were made with search strings of "incidents", "accident", "spaceflight", and "orbit", and including all vehicles so far. Search terms were combined by AND or OR in search strings. Of the results obtained, studies which evaluated manned spaceflight were included in the study. Data from the National Aeronautics Space Agency (NASA), the Russian Space Agency (ROSCOSMOS), the European Space Agency (ESA), and the Chinese Space Agency (CNSA), as well as from the Virgin Galactic and the SpaceX databases, were searched to complete data and to identify all the accomplished manned spaceflights, as well as all incidents and accidents that have occurred in the specific period. Search results were compared to findings on Wikipedia, Encyclopedia Astronautica, and other public webpages. Reference lists of included articles/homepages were also included for further potential data. Results: From 1961–2020, our data revealed an increasing number of manned space flights, n = 327. The number of times an astronaut has been sent to space, n = 1294, resulted in an accumulated n = 19,414 days spent in space. The number of days spent in orbit has constantly increased from 1961 until today. The number of incidents (altogether n = 36) and accidents (altogether n = 5) has constantly decreased. The number of astronauts who have died during spaceflight is represented by n = 19. The current statistical fatality rate is 5.8% (deaths per spaceflight) with the highest fatality rate in the 1960s (0.013 deaths/day spent in space), and the lowest rates in the 1990s and the period from 2010 until the present (no deaths). The most dangerous phases of spaceflight are launch, landing and staying in orbit. Altogether, n = 12 incidents (incident rate per spaceflight: 0.04) and one accident (accident rate: 0.003) during launch have been reported, n = 9 incidents (incident rate: 0.03) and two accidents (accident rate: 0.006) have been reported during landing and n = 10 incidents (incident rate: 0.03) have been reported in orbit. Discussion: Manned spaceflight over the last six decades has become significantly safer. Since 2003, no astronaut fatality has been reported. With greater international cooperation and maintaining of the International Space Station (ISS), the number of manned spaceflights and days spent in space has constantly increased, with constantly lower rates of incidents and accidents. [ABSTRACT FROM AUTHOR]

Background Iron metabolism imbalance could contribute to physical deconditioning experienced by astronauts due to its essential role in energy metabolism, cellular respiration, and oxygen transport. Objectives In this clinical exploratory study, we wanted to determine whether artificial gravity (AG) training modulated iron metabolism, RBC indices, and body lean mass in healthy male and female participants exposed to head-down tilt (HDT) bed rest, the reference ground-based model of microgravity. Methods We recruited 8 healthy female and 16 healthy male participants who were all exposed to HDT bed rest for 60 d. In addition, they were assigned to 3 experimental groups (n  = 8/each): controls, continuous AG training in a short-arm centrifuge (1 × 30 min/d), and intermittent AG training (6 × 5 min/d). Results The iron metabolism responses to simulated microgravity of the AG training groups did not differ significantly from the responses of controls. Independently from AG, we found that both serum iron concentrations (+31.3%, P  = 0.027) and transferrin saturation levels (+28.4%, P  = 0.009) increased in males after 6 d of HDT bed rest, as well as serum hepcidin concentrations (+36.9%, P  = 0.005). The increase of transferrin saturation levels persisted after 57 d of HDT bed rest (+13.5%, P  = 0.026), suggesting that long-term exposure to microgravity sustainably increases serum iron availability in males, and consequently the risk of iron excess or misdistribution. In females, 6 and 57 d of HDT bed rest did not significantly change serum iron, transferrin saturation, or hepcidin levels. Conclusions The data from this exploratory study suggest that 1) AG training does not influence the iron metabolism responses to microgravity; and 2) iron metabolism parameters, especially iron availability for cells, are significantly increased in males, but not in females, exposed to long-term simulated microgravity. Because of the small sample size of females, we nevertheless must be cautious before concluding that iron metabolism could differently respond to microgravity in females. This trial was registered at https://www.drks.de as DRKS00015677. [ABSTRACT FROM AUTHOR]

The identification of safe and easily-determined-inflight biomarkers to monitor the immune system of astronauts is mandatory to ensure their well-being and the success of the missions. In this report, we evaluated the relevance of two biomarkers whose determination could be easily implemented in a spacecraft in the near future by using bedridden volunteers as a groundbased model of the microgravity of spaceflight. Our data confirm the relevance of the neutrophil to lymphocyte ratio (NLR) and suggest platelet to lymphocyte ratio (PLR) monitoring to assess long-lasting immune diseases. We recommend coupling these ratios to other biomarkers, such as the quantification of cytokines and viral load measurements, to efficiently detect immune dysfunction, determine when countermeasures should be applied to promote immune recovery, prevent the development of disease, and track responses to treatment. [ABSTRACT FROM AUTHOR]

Understanding how plants respond and adapt to extraterrestrial conditions is essential for space exploration initiatives. Deleterious effects of the space environment on plant development have been reported, such as the unbalance of cell growth and proliferation in the root meristem, or gene expression reprogramming. However, plants are capable of surviving and completing the seed-to-seed life cycle under microgravity. A key research challenge is to identify environmental cues, such as light, which could compensate the negative effects of microgravity. Understanding the crosstalk between light and gravity sensing in space was the major objective of the NASA-ESA Seedling Growth series of spaceflight experiments (2013–2018). Different g-levels were used, with special attention to micro-g, Mars-g, and Earth-g. In spaceflight seedlings illuminated for 4 days with a white light photoperiod and then photostimulated with red light for 2 days, transcriptomic studies showed, first, that red light partially reverted the gene reprogramming induced by microgravity, and that the combination of microgravity and photoactivation was not recognized by seedlings as stressful. Two mutant lines of the nucleolar protein nucleolin exhibited differential requirements in response to red light photoactivation. This observation opens the way to directed-mutagenesis strategies in crop design to be used in space colonization. Further transcriptomic studies at different g-levels showed elevated plastid and mitochondrial genome expression in microgravity, associated with disturbed nucleus–organelle communication, and the upregulation of genes encoding auxin and cytokinin hormonal pathways. At the Mars g-level, genes of hormone pathways related to stress response were activated, together with some transcription factors specifically related to acclimation, suggesting that seedlings grown in partial-g are able to acclimate by modulating genome expression in routes related to space-environment-associated stress. [ABSTRACT FROM AUTHOR]

Current aerobic fitness testing during ISS flight does not assess either critical power (CP) or work capacity above CP (W′). Both CP and W′ have been demonstrated to be highly related to time of performance during ground analogues of lunar or planetary work tasks. This study was conducted to determine if CP measures differ between trials performed without (Control) and with (WMD) metabolic gas exchange data collection during 3-min supramaximal cycle ergometer tests. A secondary aim was to determine if peak oxygen consumption (VO 2peak) can be ascertained from a 3-min CP test. Subjects (n = 19: 11 M, 8 F) were young and healthy (VO 2peak 34.7 ± 7.7 ml/kg/min). Each completed four cycle trials: a ramp test to determine VO 2peak , a familiarization trial of the 3-min CP test, and two additional CP tests (control and WMD). Critical power (watts) was calculated as the mean power during the last 30 s of the CP tests. W′ was calculated as the power-time integral above CP. No differences (P = 0.11) were found for CP watts between the WMD trial and control conditions (172 ± 46 W, 169 ± 49 W, respectively). Similarly, no differences were found for W' (11.3 ± 5.4 WMD, 11.7 ± 4.4 kJ control, P = 0.61) and peak watts (627 ± 326 W WMD, 636 ± 335 W control, P = 0.84). No differences (P = 0.23) were observed between VO 2peak measured during the CP test (2517 ± 576 ml/min) and that of the initial ramp test (2564 ± 550 ml/min). CP, peak watts, and W' values were not influenced by gas exchange measurement performed during CP tests. It also appears that VO 2peak can be attained using the 3-min protocol. Consideration should be given towards CP testing on ISS and future missions. • The use of metabolic gas analysis does not interfere with critical power values. • It appears to be possible to obtain VO 2peak from a critical power test. • Critical power testing data can be used for exercise prescription. • NASA exercise testing/training protocols may benefit by incorporating critical power testing pre-, in-, and post-flight. [ABSTRACT FROM AUTHOR]

The present study investigated the stability of furosemide under space-flight conditions on board the International Space Station, as well as its pharmacokinetics and pharmacodynamics under conditions simulating exposure to some space-flight factors. Quantitative analysis of furosemide tablets by HPLC was performed before spaceflight (background), then after six months storage under normal ground conditions (control) and under spaceflight conditions (SF). The pharmacokinetics and pharmacodynamics of furosemide were studied in six healthy volunteers after a single oral dose of 40 mg under normal conditions (background) and under anti-orthostatic hypokinesia (ANOH). Quantitative content of furosemide in tablets before SF was 40.19 ± 0.28 mg (100.47 ± 0.71%), after 6 months storage: under normal conditions (control) – 39.9 ± 0.39 mg (99.73 ± 0.98%), under SF – 39.24 ± 0.72 mg (98.11 ± 1.80%), which was within the prescribed limits. Studying basic hemodynamic parameters showed that in ANOH conditions 6 h after furosemide administration there was a statistically significant increase of the stroke volume (SV) (+36.5 Δ%), a tendency for increasing of the stroke index (SI) (+36.5 Δ%) and decreasing of the total peripheral resistance (TPR) (−21.9 Δ%) compared to baseline study. It has been established that various factors of space flight (overloading, excessive vibration, microgravity, etc.) do not negatively influence the stability of furosemide in tablet form during storage for 6 months on board the International Space Station. [ABSTRACT FROM AUTHOR]

Weightlessness induces a cephalad shift of blood and cerebrospinal fluid that may increase intracranial pressure (ICP) during spaceflight, whereas lower body negative pressure (LBNP) may provide an opportunity to caudally redistribute fluids and lower ICP. To investigate the effects of spaceflight and LBNP on noninvasive indicators of ICP (nICP), we studied 13 crewmembers before and after spaceflight in seated, supine, and 15° head-down tilt postures, and at ~45 and ~150 days of spaceflight with and without 25 mmHg LBNP. We used four techniques to quantify nICP: cerebral and cochlear fluid pressure (CCFP), otoacoustic emissions (OAE), ultrasound measures of optic nerve sheath diameter (ONSD), and ultrasound-based internal jugular vein pressure (IJVp). On flight day 45, two nICP measures were lower than preflight supine posture [CCFP: mean difference -98.5 -nL (CI: -190.8 to -6.1 -nL), P = 0.037]; [OAE: -19.7° (CI: -10.4° to -29.1°), P < 0.001], but not significantly different from preflight seated measures. Conversely, ONSD was not different than any preflight posture, whereas IJVp was significantly greater than preflight seated measures [14.3 mmHg (CI: 10.1 to 18.5 mmHg), P < 0.001], but not significantly different than preflight supine measures. During spaceflight, acute LBNP application did not cause a significant change in nICP indicators. These data suggest that during spaceflight, nICP is not elevated above values observed in the seated posture on Earth. Invasive measures would be needed to provide absolute ICP values and more precise indications of ICP change during various phases of spaceflight. NEW & NOTEWORTHY The current study provides new evidence that intracranial pressure (ICP), as assessed with noninvasive measures, may not be elevated during long-duration spaceflight. In addition, the acute use of lower body negative pressure did not significantly reduce indicators of ICP during weightlessness. [ABSTRACT FROM AUTHOR]

As part of the risk management plan for human system risks at the US National Aeronautics and Space Administration (NASA), the NASA Human Systems Risk Board uses causal diagrams (in the form of directed, acyclic graphs, or DAGs) to communicate the complex web of events that leads from exposure to the spaceflight environment to performance and health outcomes. However, the use of DAGs in this way is relatively new at NASA, and thus far, no method has been articulated for testing their veracity using empirical data. In this paper, we demonstrate a set of procedures for doing so, using (a) a DAG related to the risk of bone fracture after exposure to spaceflight; and (b) four datasets originally generated to investigate this phenomenon in rodents. Tests of expected marginal correlation and conditional independencies derived from the DAG indicate that the rodent data largely agree with the structure of the diagram. Incongruencies between tests and the expected relationships in one of the datasets are likely explained by inadequate representation of a key DAG variable in the dataset. Future directions include greater tie-in with human data sources, including multiomics data, which may allow for more robust characterization and measurement of DAG variables. [ABSTRACT FROM AUTHOR]

Long-duration spaceflights beyond low-Earth orbit, including missions to the Moon and Mars, pose significant health risks. Although biomedical approaches commonly appear in the literature, considering psychological and social factors alongside physiologic health offers a more holistic approach to astronaut care. Integrating the biopsychosocial (BPS) framework into medical planning addresses complex spaceflight challenges and aids in developing mitigation strategies. This review examined health risks associated with long-duration spaceflight within a BPS framework. Sources included governmental space agencies, academic textbooks, and relevant publications from multiple databases. Considering the National Aeronautics and Space Administration's Human Research Program's 5 main hazards, a conceptual model was developed to highlight the multifactorial BPS effects of spaceflight. In space, astronauts face unique environments and biological adaptations, including fluid shift, plasma volume loss, bone density loss, and muscle atrophy. Noise and the absence of natural light disrupt circadian rhythms, causing sleep disturbances and fatigue, which affect physical and mental health. Studies on crews in isolated and confined extreme environments reveal psychosocial challenges, including impaired mood and cognition, interpersonal tension, and miscommunication. International collaboration in spaceflight introduces differences in communication, problem solving, and social customs due to diverse cultural backgrounds. Upcoming long-distance missions likely will amplify these challenges. This review emphasizes BPS health considerations in long-duration spaceflight. It highlights the interplay among psychological, social, and biological factors, advocating for multidisciplinary teams and a holistic approach to astronaut health and mission planning and the potential added value of BPS perspectives in considering countermeasures.

Various behavioral and mental health issues have been reported by space crews for decades, with the overall number of mental health complications expected to be higher than is publicly known. The broad range of mental health complications encountered in space is expected to grow as people venture deeper into space. Issues with privacy, dual relationships, and delayed communications make rendering effective psychological therapy difficult in a spaceflight environment and nearly impossible in deep space. Automated psychotherapy offers a way to provide psychotherapy to astronauts both in deep space and low Earth orbit. Although automated psychotherapy is growing in popularity on Earth, little is known about its efficacy in space. This viewpoint serves to highlight the knowns and unknowns regarding this treatment modality for future deep space missions, and places an emphasis on the need for further research into the applicability and practicality of automated psychotherapy for the spaceflight environment, especially as it relates to long-duration, deep space missions., (©Logan Smith. Originally published in the Interactive Journal of Medical Research (https://www.i-jmr.org/), 09.10.2024.)

Introduction: With increased access to commercial spaceflight and space tourism, plus a push for longer duration spaceflights, it is especially important to understand the impact of spaceflight on musculoskeletal health. Upper extremity injuries are the most common musculoskeletal injuries in spaceflight. It is, therefore, vital to determine the changes to the upper extremities during spaceflight. The purpose of this study was to examine the state of knowledge on the impact of spaceflight on upper extremity orthopedic health, and to identify knowledge gaps and future areas of research., Methods: A literature review was performed and studies and reports that amassed data on shoulder, elbow, wrist, and hand health were included., Results: Spaceflight decreases bone mineral density in the upper extremities and increases risk of fracture, especially upon return to gravitational environments. Spaceflight does not uniformly affect all muscles; in the shoulder, the various muscles crossing the joint appear to be variably affected: the deltoid experiences a greater degree of atrophy than the rotator cuff muscles. Spaceflight additionally affects the peripheral nervous system, with astronauts experiencing hand numbness and loss of manual dexterity but cause of these symptoms is undetermined. Spacesuits have also been implicated in causing upper extremity injury, especially while training for or performing extravehicular activities., Discussion: While upper extremity orthopedic health in spaceflight is incompletely understood, known adaptations increase risk for weakening and injury. Existing research provides valuable information for best practices, but there is still much to be discovered to optimize upper extremity health in spaceflight. Fiedler B, Jami M, Rakauskas T, Ahmed AS. Impact of spaceflight on upper extremity orthopedic health. Aerosp Med Hum Perform. 2024; 95(10):777-783.

Introduction: Acute calculous cholecystitis is a common surgical emergency and cholecystectomy is the gold-standard treatment. However, alternative drainage modalities such as percutaneous cholecystostomy tube (PCT) placement have been proposed for poor surgical candidates or in remote environments, such as space. We reviewed the literature to assess the theoretical utility of PCT to treat acute cholecystitis during long-duration spaceflight or on the Moon or Mars., Methods: A systematic review of 16 peer-reviewed articles published since 2018 was completed to describe the terrestrial efficacy of PCT placement for acute calculous cholecystitis., Results: The mean initial clinical success rate after PCT was 89.9% (range 82.2-100.0%). Duration of indwelling PCT ranged from median 6 to 58 d. Mean rate of recurrent cholecystitis was 15.8% (range 5.0-36.4%). A mean 35.6% of patients (range 18.0-61.0%) required interval cholecystectomy. Mean 30-d mortality was 9.6% (range 5.8-14.0%). A mean 18.6% of patients (range 7.2-30.0%) required repeat percutaneous intervention due to PCT placement complications., Discussion: While PCT achieves high rates of early resolution of cholecystitis, the long-term outcomes after PCT are relatively poor, with risk of recurrent cholecystitis, need for cholecystectomy, and frequent postprocedural complications requiring repeat procedural interventions. In cislunar space, the return to Earth for cholecystectomy following PCT may be achieved, eliminating some of these concerns. However, with long-duration space travel such as a mission to Mars, PCT is likely inadequate for the long-term treatment of cholecystitis. Prophylactic cholecystectomy, developing surgical capabilities in space, or preflight screening ultrasound for cholelithiasis should be seriously considered for long-duration spaceflight. Lazow SP, Siu M, Brown L, Kamine TH. Percutaneous cholecystostomy for acute cholecystitis during spaceflight. Aerosp Med Hum Perform. 2024; 95(10):771-776.

Background: Previous data in humans suggest that extreme physical inactivity (EPI) affects iron metabolism differently between sexes. Our objective was to deepen the underlying mechanisms by studying rats of both sexes exposed to hindlimb unloading (HU), the reference experimental model mimicking EPI., Methods: Eight-week-old male and female Wistar rats were assigned to control (CTL) or hindlimb unloading (HU) conditions (n = 12/group). After 7 days of HU, serum, liver, spleen, and soleus muscle were removed. Iron parameters were measured in serum samples, and ICP-MS was used to quantify iron in tissues. Iron metabolism genes and proteins were analysed by RT-qPCR and Western blot., Results: Compared with control males, control females exhibited higher iron concentrations in serum (+43.3%, p < 0.001), liver (LIC; +198%, P < 0.001), spleen (SIC; +76.1%, P < 0.001), and transferrin saturation (TS) in serum (+53.3%, P < 0.001), contrasting with previous observations in humans. HU rat males, but not females, exhibited an increase of LIC (+54% P < 0.001) and SIC (+30.1%, P = 0.023), along with a rise of H-ferritin protein levels (+60.9% and +134%, respectively, in liver and spleen; P < 0.05) and a decrease of TFRC protein levels (-36%; -50%, respectively, P < 0.05). HU males also exhibited an increase of splenic HO-1 and NRF2 mRNA levels, (p < 0.001), as well as HU females (P < 0.001). Concomitantly to muscle atrophy observed in HU animals, the iron concentration increased in soleus in females (+26.7, P = 0.004) while only a trend is observed in males (+17.5%, P = 0.088). In addition, the H-ferritin and myoglobin protein levels in soleus were increased in males (+748%, P < 0.001, +22%, P = 0.011, respectively) and in females (+369%, P < 0.001, +21.9%, P = 0.007, respectively), whereas TFRC and ferroportin (FPN) protein levels were reduced in males (-68.9%, P < 0.001, -76.8%, P < 0.001, respectively) and females (-75.9%, P < 0.001, -62.9%, P < 0.001, respectively). Interestingly, in both sexes, heme exporter FLVCR1 mRNA increased in soleus, while protein levels decreased (-39.9% for males P = 0.010 and -49.1% for females P < 0.001)., Conclusions: Taken together, these data support that, in rats (1) extreme physical inactivity differently impacts the distribution of iron in both sexes, (2) splenic erythrophagocytosis could play a role in this iron misdistribution. The higher iron concentrations in atrophied soleus from both sexes are associated with a decoupling between the increase in iron storage proteins (i.e., ferritin and myoglobin) and the decrease in levels of iron export proteins (i.e., FPN and FLVCR1), thus supporting an iron sequestration in skeletal muscle under extreme physical inactivity., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

SUMMARYUnderstanding the dynamic adaptive plasticity of microorganisms has been advanced by studying their responses to extreme environments. Spaceflight research platforms provide a unique opportunity to study microbial characteristics in new extreme adaptational modes, including sustained exposure to reduced forces of gravity and associated low fluid shear force conditions. Under these conditions, unexpected microbial responses occur, including alterations in virulence, antibiotic and stress resistance, biofilm formation, metabolism, motility, and gene expression, which are not observed using conventional experimental approaches. Here, we review biological and physical mechanisms that regulate microbial responses to spaceflight and spaceflight analog environments from both the microbe and host-microbe perspective that are relevant to human health and habitat sustainability. We highlight instrumentation and technology used in spaceflight microbiology experiments, their limitations, and advances necessary to enable next-generation research. As spaceflight experiments are relatively rare, we discuss ground-based analogs that mimic aspects of microbial responses to reduced gravity in spaceflight, including those that reduce mechanical forces of fluid flow over cell surfaces which also simulate conditions encountered by microorganisms during their terrestrial lifecycles. As spaceflight mission durations increase with traditional astronauts and commercial space programs send civilian crews with underlying health conditions, microorganisms will continue to play increasingly critical roles in health and habitat sustainability, thus defining a new dimension of occupational health. The ability of microorganisms to adapt, survive, and evolve in the spaceflight environment is important for future human space endeavors and provides opportunities for innovative biological and technological advances to benefit life on Earth., Competing Interests: The authors declare no conflict of interest.

SUMMARYThe human microbiota encompasses the diverse communities of microorganisms that reside in, on, and around various parts of the human body, such as the skin, nasal passages, and gastrointestinal tract. Although research is ongoing, it is well established that the microbiota exert a substantial influence on the body through the production and modification of metabolites and small molecules. Disruptions in the composition of the microbiota-dysbiosis-have also been linked to various negative health outcomes. As humans embark upon longer-duration space missions, it is important to understand how the conditions of space travel impact the microbiota and, consequently, astronaut health. This article will first characterize the main taxa of the human gut microbiota and their associated metabolites, before discussing potential dysbiosis and negative health consequences. It will also detail the microbial changes observed in astronauts during spaceflight, focusing on gut microbiota composition and pathogenic virulence and survival. Analysis will then turn to how astronaut health may be protected from adverse microbial changes via diet, exercise, and antibiotics before concluding with a discussion of the microbiota of spacecraft and microbial culturing methods in space. The implications of this review are critical, particularly with NASA's ongoing implementation of the Moon to Mars Architecture, which will include weeks or months of living in space and new habitats., Competing Interests: The authors declare no conflict of interest.