Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.

Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.

Human hypoxia models in aerospace medicine: Potential applications for human pharmacological research.

Aerospace medicine required controlled terrestrial models to investigate influences of altered atmosphere conditions, such as hypoxia, on human health and performance. These models could potentially be expanded to encompass disease conditions or treatment targets regulated through hypoxia or hypercapnia. Hypoxia, a condition in which the body is deprived of adequate oxygen supply, profoundly affects human physiology at multiple levels and contributes to the pathogenesis of various diseases. Experimental exposure to hypoxic conditions has gained recognition as a model for studying diseases such as pulmonary hypertension, chronic obstructive pulmonary disease, obstructive sleep apnoea, migraine and kidney disease. This approach may be particularly useful in mechanism-oriented early-stage clinical studies. This review discusses the ability of hypoxia models from space medicine research to mimic or induce these conditions in a controlled laboratory setting as a tool for testing the efficacy and safety of new pharmaceutical interventions.

Occupational physical demands and menstrual cycle irregularities in flight attendants and teachers.

OBJECTIVES: Flight attendants perform physically demanding work such as lifting baggage, pushing service carts and spending the workday on their feet. We examined if more frequent exposure to occupational physical demands could explain why previous studies have found that flight attendants have a higher reported prevalence of menstrual cycle irregularities than other workers. METHODS: We conducted a cross-sectional analysis of 694 flight attendants and 120 teachers aged 18-44 years from three US cities. Eligible participants were married, had not had a hysterectomy or tubal ligation, were not using hormonal contraception and were not recently pregnant. Participants reported menstrual cycle characteristics (cramps, pain, irregular cycles, flow, bleed length, cycle length) and occupational physical demands (standing, lifting, pushing/pulling, bending/twisting, overall effort). We used modified Poisson regression to examine associations between occupation (flight attendant, teacher) and menstrual irregularities; among flight attendants, we further examined associations between occupational physical demands and menstrual irregularities. RESULTS: All occupational physical demands were more commonly reported by flight attendants than teachers. Flight attendants reported more frequent menstrual cramps than teachers, and most occupational physical demands were associated with more frequent or painful menstrual cramps. Lifting heavy loads was also associated with irregular cycles. CONCLUSIONS: Occupational physical demands were associated with more frequent and worse menstrual pain among flight attendants. The physical demands experienced by these workers may contribute to the high burden of menstrual irregularities reported by flight attendants compared with other occupational groups, such as teachers.

How to modernize without compromising history: a case study of the Franzello Aeromedical Library's journey in updating collections, capabilities, and facilities.

Background: Academic libraries play a significant role in the student learning process. However, student needs and preferences as well as new paradigms of learning are driving libraries to transition from quiet book repositories to places of collaboration and open information. This descriptive, mixed methods case presentation explores the transition of one library, the United States Air Force School of Aerospace Medicine Franzello Aeromedical Library, in three key areas: collection, capability, and facility. Due to the niche subject matter and audience the library serves, this case also describes how the Franzello Aeromedical Library's distinct collection and capability remained intact throughout modernization. Case Presentation: The Franzello Aeromedical Library's modernization project aimed to augment the library as a cutting-edge resource supporting USAFSAM's education, consultation, and research mission to equip Aerospace Medicine Airmen with the skills and knowledge for healthcare delivery in austere environments. This project was approached using five phases: 1) best practices baseline, 2) baseline evaluation of library visitor needs, 3) collection weeding, 4) capability, and 5) space design and construction. Conclusion: As a result of this complex two-year project, several recommendations were gleaned. Use the effort as an opportunity to market library services to new audiences. Ensure all stakeholders are at the table from day one and in perpetuity to save time, and consider using purposeful decision-making models, such as Courses of Action, to make tough calls. Be prepared for delays by padding your timeline and compromise where necessary to keep the project alive. Finally, the authors recommend using in-project discovery and findings to plan for future need justification.

Crew Autonomy During Simulated Medical Event Management on Long Duration Space Exploration Missions.

OBJECTIVE: Our primary aim was to investigate crew performance during medical emergencies with and without ground-support from a flight surgeon located at mission control. BACKGROUND: There are gaps in knowledge regarding the potential for unanticipated in-flight medical events to affect crew health and capacity, and potentially compromise mission success. Additionally, ground support may be impaired or periodically absent during long duration missions. METHOD: We reviewed video recordings of 16 three-person flight crews each managing four unique medical events in a fully immersive spacecraft simulator. Crews were randomized to two conditions: with and without telemedical flight surgeon (FS) support. We assessed differences in technical performance, behavioral skills, and cognitive load between groups. RESULTS: Crews with FS support performed better clinically, were rated higher on technical skills, and completed more clinical tasks from the medical checklists than crews without FS support. Crews with FS support also had better behavioral/non-technical skills (information exchange) and reported significantly lower cognitive demand during the medical event scenarios on the NASA-TLX scale, particularly in mental demand and temporal demand. There was no significant difference between groups in time to treat or in objective measures of cognitive demand derived from heart rate variability and electroencephalography. CONCLUSION: Medical checklists are necessary but not sufficient to support high levels of autonomous crew performance in the absence of real-time flight surgeon support. APPLICATION: Potential applications of this research include developing ground-based and in-flight training countermeasures; informing policy regarding autonomous spaceflight, and design of autonomous clinical decision support systems.

Space flight and central nervous system: Friends or enemies? Challenges and opportunities for neuroscience and neuro-oncology.

Space environment provides many challenges to pilots, astronauts, and space scientists, which are constantly subjected to unique conditions, including microgravity, radiations, hypoxic condition, absence of the day and night cycle, etc. These stressful stimuli have the potential to affect many human physiological systems, triggering physical and biological adaptive changes to re-establish the homeostatic state. A particular concern regards the risks for the effects of spaceflight on the central nervous system (CNS), as several lines of evidence reported a great impact on neuroplasticity, cognitive functions, neurovestibular system, short-term memory, cephalic fluid shift, reduction in motor function, and psychological disturbances, especially during long-term missions. Aside these potential detrimental effects, the other side of the coin reflects the potential benefit of applicating space-related conditions on Earth-based life sciences, as cancer research. Here, we focused on examining the effect of real and simulated microgravity on CNS functions, both in humans and in cellular models, browsing the different techniques to experience or mime microgravity on-ground. Increasing evidence demonstrate that cancer cells, and brain cancer cells in particular, are negatively affected by microgravity, in terms of alteration in cell morphology, proliferation, invasion, migration, and apoptosis, representing an advancing novel side of space-based investigations. Overall, deeper understandings about the mechanisms by which space environment influences CNS and tumor biology may be promisingly translated into many clinical fields, ranging from aerospace medicine to neuroscience and oncology, representing an enormous pool of knowledge for the implementation of countermeasures and therapeutic applications.

Integrating the precision, sleep, and aerospace medicine fields: a systematic review of the genetic predisposition for obstructive sleep apnea in military aviation.

PURPOSE: Obstructive sleep apnea (OSA) is the most common pathologic sleep disorder with an estimated prevalence in the USA of up to 25% of adult males. With military aviation being heavily comprised of adult men, the impact of OSA on flying operations is concerning as OSA is disqualifying for all flying classes in the US Air Force. In order to minimize the impact of OSA on operations, early identification of at-risk patients is critical in disease management. Individuals could be identified for whom regular polysomnography testing may reveal OSA while mild or sub-clinical, at which point treatment may be initiated in order to promote continued medical qualification for duty and career retention. METHODS: We performed a keyword search of PubMed, EMBASE, and Google Scholar along with searches in the NHGRI/EBI GWAS Catalogue and the Atlas of GWAS Summary Statistics. We included primary research from candidate gene, GWAS, and meta-analyses. We also included other review articles in our search to confirm interpretations and implications of any genetic associations with OSA. Only studies related to OSA susceptibility or risk were included. RESULTS: We identified 134 publications reporting or reviewing genetic associations with OSA risk. These papers reported 301 variants, of which 195 were unique and 33 were replicated in at least two papers. With respect to the strength of association, 43 variants exhibited odds ratios greater than 2. Finally, there were 84 null results reported, 51 of which were in conflict with reported associations. CONCLUSION: There is ample evidence in the literature to confirm that genetics provide an important contribution to OSA development. The high number of strongly associated variants suggests that a polygenic risk model could be created with high predictive value for prognostic screening.

Cancer incidence and mortality in the USA Astronaut Corps, 1959-2017.

OBJECTIVES: Cancer incidence and mortality are important outcomes in the surveillance of long-term astronaut health. We compare cancer incidence rates, cancer-specific mortality rates, and cancer case-fatality ratios in US astronauts with those in the US general population. METHODS: We use standardised incidence ratios (SIRs) and standardised mortality ratios (SMRs) to index the incidence and mortality of various cancers against rates in the US general population, from the US astronaut cohort inception in April 1959 through 31 December 2017. We compare the lethality of these cancers using the relative case-fatality ratio. RESULTS: Overall cancer incidence and mortality were slightly lower than expected from national rates with SIR 82 (95% CI 63 to 104) and SMR 72 (95% CI 44 to 111) with a modest 14% reduction in case-fatality ratio. Prostate cancer and melanoma skin cancer had significant increases in incidence, with SIR of 162 (95% CI 109 to 232) and 252 (95% CI 126 to 452), respectively, though only melanoma had a significant increase in mortality, with SMR 508 (95% CI 105 to 1485). Lung cancer had a significant deficit of both cases and deaths, while colon cancer had sizeable (but not significant) reductions in incidence and mortality. CONCLUSIONS: The increase in incidence of melanoma is consistent with that observed in aircraft pilots, suggesting this may be associated with ultraviolet radiation or lifestyle factors rather than any astronaut-specific exposure. Reductions in lung cancer incidence and mortality, and trends towards such reductions in colon cancer, may be explained in part by healthy lifestyle, as well as differential screening among astronauts.

Factors associated with neck pain in fighter aircrew: a systematic review and meta-analysis.

Neck pain is a common complaint among fighter aircrew, impacting workforce health and operational capability. This systematic review aimed to identify, evaluate and synthesise the current evidence for factors associated with the occurrence of neck pain among fighter aircrew. Six electronic databases were searched in June 2019 and updated in June 2020 utilising the maximum date ranges. Included studies were appraised for methodological quality, ranked according to level of evidence and relevant data extracted. Where methods were homogeneous and data availability allowed, meta-analyses were performed. A total of 20 studies (16 cross sectional, one case-control, one retrospective cohort and two prospective cohort) were eligible for inclusion. Of the 44 factors investigated, consistent evidence was reported for greater occurrence of neck pain among aircrew operating more advanced aircraft and those exposed to more desk/computer work, while another 12 factors reported consistent evidence for no association. Of the 20 factors where meta-analyses could be performed, greater occurrence of neck pain was indicated for aircrew: flying more advanced aircraft, undertaking warm-up stretching and not placing their head against the seat under greater +Gz. Despite many studies investigating factors associated with neck pain among fighter aircrew, methodological limitations limited the ability to identify those factors that are most important to future preventive programmes. High-quality prospective studies with consistent use of definitions are required before we can implement efficient and effective programmes to reduce the prevalence and impact of neck pain in fighter aircrew. PROSPERO registration number: CRD42019128952.Neck pain is a common complaint among fighter aircrew, impacting workforce health and operational capability. This systematic review aimed to identify, evaluate and synthesise the current evidence for factors associated with the occurrence of neck pain among fighter aircrew.

The global incidence of in-flight medical emergencies: A systematic review and meta-analysis of approximately 1.5 billion airline passengers.

BACKGROUND: Medical emergencies during short- or long-haul commercial airline flights have become more commonplace due to the aviation industry's contemporary growth, the popularization of commercial flights, and an increased aging of air travelers with significant comorbidities. However, the precise incidence of onboard medical events on commercial airlines and the most common medical conditions is unclear. METHODS: In this systematic review and meta-analysis, we explored the incidence of in-flight medical emergencies among airline passengers and estimated the incidence rate by physiological body system, or organ class/syndrome for emergencies that may be associated with different body systems. We limited our search to cohort studies published between 1945 to October 31, 2020 in MEDLINE, Embase, Cochrane Library and official reports from the Federal Aviation Administration/International Air Transport Association, regardless of the language of publication. Only studies that evaluated the overall frequency of onboard medical events on commercial air carriers (in which they also presented the total number of annual revenue passengers) and the frequency of events by physiological body systems or organ class/syndrome were included. We excluded case reports and case series, systematic or narrative reviews, and studies addressing specific health-related conditions. Two independent investigators performed first- and second-phase study screening, abstracted data, and appraised risk of bias. We rated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Using a quality effect model, we meta-analyzed data associated with the incidence of in-flight medical emergencies, all-cause fatality, incidence of medical events by medical condition category, frequency of en-route diversion, presence of medical personnel on board, and the use of an automatic external defibrillator. We also extracted data regarding the cost of flight diversion. RESULTS: Of 18 individual studies with approximately 1.5 billion passengers, 11 reported the overall incidence of in-flight medical emergencies. Low certainty of evidence suggested that the global incidence of in-flight medical emergencies was 18.2 events per million passengers (95% CI 0.5 to 53.4 per million; I2 = 100%, P < 0.001, very low certainty), and an all-cause mortality rate was 0.21 per million passengers (95% CI 0 to 0.76 per million; I2 = 99%, P < 0.001, low certainty). The four most common categories of medical conditions or syndromes during flight were syncope, gastrointestinal events, respiratory and neurological diagnostic groups. The diversion rate was 11.1 per 100,000 flights (95% CI 5.9 to17.6 per 100,000 flights; I2 = 97%, P < 0.001), with an average cost ranging from $15,000 to $893,000 per unplanned emergency landing across studies which examined this outcome. CONCLUSIONS: In-flight medical events on commercial travels are extremely low with a corresponding very low in-flight mortality rate. Associated costs derived from en-route diversion might significantly influence airlines' budgetary equilibrium. Novel and modern standardized reporting systems or platforms should be internationally provided and enforced by health and aviation authorities to obtain higher quality patient-passengers datasets. Onboard volunteer medical providers must be aware of everyday life-threatening events during commercial flights and should consider the establishment of a connection between the aircraft and ground-based medical advisory services while assisting in-flight medical events.

Urological In-Flight Medical Events on Commercial Airlines.

PURPOSE: In-flight medical events are rare but may cause significant distress as access to care is limited. There is a paucity of data on in-flight urological medical events. We describe urological in-flight medical emergencies and report clinical and flight outcomes. MATERIALS AND METHODS: We reviewed all in-flight urological medical emergencies between 2015 and 2017 from MedAire®, a ground based medical support center that provides remote medical advisory services to approximately 35% of commercial airline passenger traffic worldwide. Our primary end point was the incidence rates of in-flight urological medical events. We also characterized the types of in-flight medical emergencies, in-flight management and their impact on flight status. Statistical analyses included Student's t-tests, chi-square analysis and analysis of variance. RESULTS: We identified 1,368 (1%) urological in-flight medical emergencies from a total of 138,612 in-flight medical emergencies, with an incidence of 0.5 per million passengers. The most common in-flight medical emergencies were lower urinary tract symptoms (35%), urinary retention (30%) and flank pain (21%). Among in-flight medical emergencies 883 (60%) resolved in flight, 273 (28%) required on-arrival medical evaluation and 21 (1.5%) resulted in flight diversions. Of the flight diversions the majority were due to urinary retention (12, 57%) and less commonly flank pain (6, 28%) and testicular/abdominal pain (3, 15%). CONCLUSIONS: The most common causes of urological in-flight medical emergencies are lower urinary tract symptoms, urinary retention and renal colic, the majority of which resolved in flight. These data are useful for informing flight personnel and emergency kit equipment needs to minimize the impact of these events when they occur.

Medicine in Extreme Environments: A New Medical Student Elective Class for Wilderness, Aerospace, Hyperbaric, Exercise, and Combat Medicine.

We developed an elective course titled Medicine in Extreme Environments (MEE) at the University of Texas Southwestern Medical Center for first- and second-year medical students. This course covered physiology, research, clinical practice, and career guidance regarding the fields of wilderness, space, hyperbaric, combat, and exercise medicine. The primary aim was to generate interest in and awareness of these seldom covered fields of medicine by exposing medical students to these disciplines during their preclinical years. A postcourse questionnaire was implemented to investigate whether the MEE course increased awareness of, interest in, and knowledge in the fields of medicine included in the curriculum. Through 2 iterations of the class, a total of 67 students enrolled in the course, and 38 students completed the questionnaire. After course completion, 95% felt they better understood the work and lifestyle of the fields covered, 100% learned more about concepts of each field, and 74% agreed that the elective influenced the direction of their future careers to include some part of the fields emphasized. Although only a limited number of students enrolled in this course, these initial findings suggest that the MEE curriculum may have some utility in promoting awareness of and interest in these medical disciplines among students who attend the course. With continued student and faculty support, this course will likely be continued annually at our institution. We believe that certain aspects of this course may be useful in helping develop similar courses at other medical schools.

Aeromedical Transfer of Patients with Viral Hemorrhagic Fever.

For >40 years, the British Royal Air Force has maintained an aeromedical evacuation facility, the Deployable Air Isolator Team (DAIT), to transport patients with possible or confirmed highly infectious diseases to the United Kingdom. Since 2012, the DAIT, a joint Department of Health and Ministry of Defence asset, has successfully transferred 1 case-patient with Crimean-Congo hemorrhagic fever, 5 case-patients with Ebola virus disease, and 5 case-patients with high-risk Ebola virus exposure. Currently, no UK-published guidelines exist on how to transfer such patients. Here we describe the DAIT procedures from collection at point of illness or exposure to delivery into a dedicated specialist center. We provide illustrations of the challenges faced and, where appropriate, the enhancements made to the process over time.

Pulmonary challenges of prolonged journeys to space: taking your lungs to the moon.

Space flight presents a set of physiological challenges to the space explorer which result from the absence of gravity (or in the case of planetary exploration, partial gravity), radiation exposure, isolation and a prolonged period in a confined environment, distance from Earth, the need to venture outside in the hostile environment of the destination, and numerous other factors. Gravity affects regional lung function, and the human lung shows considerable alteration in function in low gravity; however, this alteration does not result in deleterious changes that compromise lung function upon return to Earth. The decompression stress associated with extravehicular activity, or spacewalk, does not appear to compromise lung function, and future habitat (living quarter) designs can be engineered to minimise this stress. Dust exposure is a significant health hazard in occupational settings such as mining, and exposure to extraterrestrial dust is an almost inevitable consequence of planetary exploration. The combination of altered pulmonary deposition of extraterrestrial dust and the potential for the dust to be highly toxic likely makes dust exposure the greatest threat to the lung in planetary exploration.

Venous thromboembolism prophylaxis on flights.

Civil aviation has seen a steady increase in the number of scheduled flights over the last ten years and, as a result, more passengers are traveling by air. This has been associated with an increase in flight-related diseases, especially on long-haul flights. One of the most feared complications during flights is venous thromboembolism (VTE), but its true incidence is difficult to measure because of a lack of consensus on elements such as the definition of how long after landing a VTE can be considered to be related to a flight and even how long a flight must last to be considered of long duration. There has been much discussion of the pathophysiological mechanisms of flight-related VTE, of which passengers are at greatest risk, and of what prophylactic measures can be adopted safely and effectively. The purpose of this review is to clarify these points and describe current consensual conduct.

A novel flight surgeon training model at a joint military and civilian surgical residency program.

BACKGROUND: Graduating military preliminary interns are often required to fill flight surgeon billets. General surgery preliminary interns get experience evaluating surgical and trauma patients, but receive very little training in primary care and flight medicine. At a joint military and civilian training program, we developed a supplemental curriculum to help transition our interns into flight medicine. METHODS: From 2013 to 2016, we developed a lecture series focused on aerospace medicine, primary care, and specialty topics including dermatology, ophthalmology, orthopedics, pediatrics, psychiatry, and women's health. During the 2016 iteration attended by 10 interns, pre- and post-participation 10-item Likert scale surveys were administered. Questions focused on perceived preparedness for primary care role and overall enthusiasm for flight medicine. Open-ended surveys from 2013 to 2016 were also used to gauge the effect of the curriculum. RESULTS: The composite number of agreement responses (indicating increased comfort with presented material) increased 63% after course completion. Disagreement responses and neutral responses decreased 78% and 30%, respectively. Open-ended surveys from 14 participants showed an overall positive impression of the curriculum with all indicating it aided their transition to flight medicine. CONCLUSIONS: Survey responses indicate an overall perceived benefit from participation in the curriculum with more confidence in primary care topics and improved transition to a flight medicine tour. This model for supplemental aerospace medicine and primary care didactics should be integrated into any residency program responsible for training military preliminary interns who may serve as flight surgeons.

An overview of space medicine.

Space medicine is fundamental to the human exploration of space. It supports survival, function and performance in this challenging and potentially lethal environment. It is international, intercultural and interdisciplinary, operating at the boundaries of exploration, science, technology and medicine. Space medicine is also the latest UK specialty to be recognized by the Royal College of Physicians in the UK and the General Medical Council. This review introduces the field of space medicine and describes the different types of spaceflight, environmental challenges, associated medical and physiological effects, and operational medical considerations. It will describe the varied roles of the space medicine doctor, including the conduct of surgery and anaesthesia, and concludes with a vision of the future for space medicine in the UK.Space medicine doctors have a responsibility to space workers and spaceflight participants. These 'flight surgeons' are key in developing mitigation strategies to ensure the safety, health and performance of space travellers in what is an extreme and hazardous environment. This includes all phases from selection, training and spaceflight itself to post-flight rehabilitation and long-term health. The recent recognition of the speciality provides a pathway to train in this fascinating field of medicine and is a key enabler for the UK Government's commercial spaceflight ambition.

Aeromedical solutions for aerospace safety.

All facets of activity in the speciality of Aviation Medicine are essentially aimed at enhancing aerospace safety. This paper highlights some innovative changes brought about by Aerospace Medicine in the three major fields of the speciality namely, medical evaluation, aeromedical training and research. Based on lab and field studies, military aircrew are now permitted flying with Modifinil as 'Go' Pill and Zolpidem as 'No-Go' Pill during sustained operations. Several other drugs for disabilities like Hypertension and CAD are now permitted for aviators. Comprehensive revision of policy permitting early return to flying is an on-going process. OPRAM courses for all three streams of aircrew in IAF have contributed to reduce aircraft accident rates. Human Engineering Consultancy and expert advice is provided by specialists at IAM as well as those in the field. In future, the country needs to provide better post-service opportunities to aerospace medicine specialists. This, in turn, will attract bright young minds to the specialty. The ISRO Humanin-Space programme will be an exciting challenge for all in this unique field. Aerospace Medicine continues to provide aerospace safety solutions to the IAF and the aviation industry. The nation needs to continue to utilize and support this specialty.

Spaceflight Environment.

The safety and health of individuals who may be exposed to the spaceflight environment are first and foremost cared for through prevention. This environment, which encompasses microgravity, radiation, and alternobaric factors, can have physiologic impacts on every human system. Available medical care and resources in the spaceflight environment are currently limited by mass and volume constraints, with available medical resources thereby focusing on a patient's stabilization and evacuation. An understanding of the spaceflight environment and its possible effects is crucial for the treatment of individuals prior to, during, and after spaceflight.

Automated Psychotherapy in a Spaceflight Environment: Advantages, Drawbacks, and Unknowns.

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.