BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT: PART II - RADIATION CEREBRO/OPHTALMIC EFFECTS IN CHILDREN, PERSONS EXPOSED IN UTERO, ASTRONAUTS AND INTERVENTIONAL RADIOLOGISTS. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa: ChASTYNA II ­ RADIATsIINI TsEREBROOFTAL'MOLOGIChNI EFEKTY U DITEI, OSIB, EKSPONOVANYKh VNUTRIShN'O/UTROBNO, ASTRONAVTIV TA INTERVENTsIINYKh RADIOLOGIV.

BACKGROUND: Ionizing radiation (IR) can affect the brain and the visual organ even at low doses, while provoking cognitive, emotional, behavioral, and visual disorders. We proposed to consider the brain and the visual organ as potential targets for the influence of IR with the definition of cerebro-ophthalmic relationships as the «eye-brain axis¼. OBJECTIVE: The present work is a narrative review of current experimental, epidemiological and clinical data on radiation cerebro-ophthalmic effects in children, individuals exposed in utero, astronauts and interventional radiologists. MATERIALS AND METHODS: The review was performed according to PRISMA guidelines by searching the abstract and scientometric databases PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, Google Scholar, published from 1998 to 2021, as well as the results of manual search of peer-reviewed publications. RESULTS: Epidemiological data on the effects of low doses of IR on neurodevelopment are quite contradictory, while data on clinical, neuropsychological and neurophysiological on cognitive and cerebral disorders, especially in the left, dominant hemisphere of the brain, are nore consistent. Cataracts (congenital - after in utero irradiation) and retinal angiopathy are more common in prenatally-exposed people and children. Astronauts, who carry out longterm space missions outside the protection of the Earth's magnetosphere, will be exposed to galactic cosmic radiation (heavy ions, protons), which leads to cerebro-ophthalmic disorders, primarily cognitive and behavioral disorders and cataracts. Interventional radiologists are a special risk group for cerebro-ophthalmic pathology - cognitivedeficits, mainly due to dysfunction of the dominant and more radiosensitive left hemisphere of the brain, andcataracts, as well as early atherosclerosis and accelerated aging. CONCLUSIONS: Results of current studies indicate the high radiosensitivity of the brain and eye in different contingents of irradiated persons. Further research is needed to clarify the nature of cerebro-ophthalmic disorders in different exposure scenarios, to determine the molecular biological mechanisms of these disorders, reliable dosimetric support and taking into account the influence of non-radiation risk factors.

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.

Simulated Hypergravity Activates Hemostasis in Healthy Volunteers.

Background Hypergravity may promote human hemostasis thereby increasing thrombotic risk. Future touristic suborbital spaceflight will expose older individuals with chronic medical conditions, who are at much higher thromboembolic risk compared with professional astronauts, to hypergravity. Therefore, we tested the impact of hypergravity on hemostasis in healthy volunteers undergoing centrifugation. Methods and Results We studied 20 healthy seated men before and after 15 minutes under 3 Gz hypergravity on a long-arm centrifuge. We obtained blood samples for hemostasis testing before, immediately after, and 30 minutes after centrifugation. Tests included viscoelastic thromboelastometry, platelet impedance aggregometry, endothelial activation markers, blood rheology testing, microparticle analyses, and clotting factor analysis. Exposure to hypergravity reduced plasma volume by 12.5% (P=0.002) and increased the red blood cell aggregation index (P<0.05). With hypergravity, thrombelastographic clotting time of native blood shortened from 719±117 seconds to 628±89 seconds (P=0.038) and platetet reactivity increased (P=0.045). Hypergravity shortened partial thromboplastin time from 28 (26-29) seconds to 25 (24-28) seconds (P<0.001) and increased the activity of coagulation factors (eg, factor VIII 117 [93-134] versus 151 [133-175] %, P<0.001). Tissue factor concentration was 188±95 pg/mL before and 298±136 pg/mL after hypergravity exposure (P=0.023). Antithrombin (P=0.005), thrombin-antithrombin complex (P<0.001), plasmin-alpha2-antiplasmin complex (0.002), tissue-plasminogen activatior (P<0.001), and plasminogen activator inhibitor-1 (P=0.002) increased with centrifugation. Statistical adjustment for plasma volume attenuated changes in coagulation. Conclusions Hypergravity triggers low-level hemostasis activation through endothelial cell activation, increased viscoelasticity, and augmented platelet reactivity, albeit partly counteracted through endogenous coagulation inhibitors release. Hemoconcentration may contribute to the response.

Shifts in broadband power and alpha peak frequency observed during long-term isolation.

Prolonged periods of social isolation and spatial confinement do not only represent an issue that needs to be faced by a few astronauts during space missions, but can affect all of us as recently shown during pandemic situations. The fundamental question, how the brain adapts to periods of sensory deprivation and re-adapts to normality, has only received little attention. Here, we use eyes closed and eyes open resting-state electroencephalographic (EEG) recordings to investigate how neural activity is altered during 120 days of isolation in a spatially confined, space-analogue environment. After disentangling oscillatory patterns from 1/f activity, we show that isolation leads to a reduction in broadband power and a flattening of the 1/f spectral slope. Beyond that, we observed a reduction in alpha peak frequency during isolation, but did not find strong evidence for isolation-induced changes that are of oscillatory nature. Critically, all effects reversed upon release from isolation. These findings suggest that isolation and concomitant sensory deprivation lead to an enhanced cortical deactivation which might be explained by a reduction in the mean neuronal population firing rate.

CRaTER observations and permissible mission duration for human operations in deep space.

Prolonged exposure to the galactic cosmic ray (GCR) environment is a potentially limiting factor for manned missions in deep space. Evaluating the risk associated with the expected GCR environment is an essential step in planning a deep space mission. This requires an understanding of how the local interstellar spectrum is modulated by the heliospheric magnetic field (HMF) and how observed solar activity is manifested in the HMF over time. While current GCR models agree reasonably well with measured observations of GCR flux on the first matter, they must rely on imperfect or loose correlations to describe the latter. It is more accurate to use dose rates directly measured by instruments in deep space to quantify the GCR condition for a given period of time. In this work, dose rates observed by the Cosmic Ray Telescope for the Effects of Radiation (CRaTER) instrument are used to obtain the local GCR intensity and composition as a function of time. A response function is constructed that relates observed dose rates to solar modulation potential using a series of Monte Carlo radiation transport calculations. The record of observed solar modulation potential vs. time is then used to calculate a recent historical record of permissible mission duration (PMD) according to NASA's permissible exposure limits (PEL). Tables are provided for extreme values of PMD. Additional tables include risk of exposure-induced death (at upper 95% confidence interval) accrual rates and NASA effective dose rates as a function of solar modulation potential, astronaut age, sex, and shielding thickness. The significance of the PMD values reported in relation to likely transit duration requirements for future exploration missions is discussed. There is general agreement between CRaTER observations and the prescription of solar modulation vs. time given by the Badhwar-O'Neill 2014 GCR model. However, CRaTER observations do capture the effects of significant heliospheric transients, among other features, that are missing from the prescription of solar modulation potential vs. time.

A human mission to Mars: Predicting the bone mineral density loss of astronauts.

A round-trip human mission to Mars is anticipated to last roughly three years. Spaceflight conditions are known to cause loss of bone mineral density (BMD) in astronauts, increasing bone fracture risk. There is an urgent need to understand BMD progression as a function of spaceflight time to minimize associated health implications and ensure mission success. Here we introduce a nonlinear mathematical model of BMD loss for candidate human missions to Mars: (i) Opposition class trajectory (400-600 days), and (ii) Conjunction class trajectory (1000-1200 days). Using femoral neck BMD data (N = 69) from astronauts after 132-day and 228-day spaceflight and the World Health Organization's fracture risk recommendation, we predicted post-mission risk and associated osteopathology. Our model predicts 62% opposition class astronauts and 100% conjunction class astronauts will develop osteopenia, with 33% being at risk for osteoporosis. This model can help in implementing countermeasure strategies and inform space agencies' choice of crew candidates.

Assessment of Jugular Venous Blood Flow Stasis and Thrombosis During Spaceflight.

Importance: Exposure to a weightless environment during spaceflight results in a chronic headward blood and tissue fluid shift compared with the upright posture on Earth, with unknown consequences to cerebral venous outflow. Objectives: To assess internal jugular vein (IJV) flow and morphology during spaceflight and to investigate if lower body negative pressure is associated with reversing the headward fluid shift experienced during spaceflight. Design, Setting, and Participants: This prospective cohort study included 11 International Space Station crew members participating in long-duration spaceflight missions . Internal jugular vein measurements from before launch and approximately 40 days after landing were acquired in 3 positions: seated, supine, and 15° head-down tilt. In-flight IJV measurements were acquired at approximately 50 days and 150 days into spaceflight during normal spaceflight conditions as well as during use of lower body negative pressure. Data were analyzed in June 2019. Exposures: Posture changes on Earth, spaceflight, and lower body negative pressure. Main Outcomes and Measures: Ultrasonographic assessments of IJV cross-sectional area, pressure, blood flow, and thrombus formation. Results: The 11 healthy crew members included in the study (mean [SD] age, 46.9 [6.3] years, 9 [82%] men) spent a mean (SD) of 210 (76) days in space. Mean IJV area increased from 9.8 (95% CI, -1.2 to 20.7) mm2 in the preflight seated position to 70.3 (95% CI, 59.3-81.2) mm2 during spaceflight (P < .001). Mean IJV pressure increased from the preflight seated position measurement of 5.1 (95% CI, 2.5-7.8) mm Hg to 21.1 (95% CI, 18.5-23.7) mm Hg during spaceflight (P < .001). Furthermore, stagnant or reverse flow in the IJV was observed in 6 crew members (55%) on approximate flight day 50. Notably, 1 crew member was found to have an occlusive IJV thrombus, and a potential partial IJV thrombus was identified in another crew member retrospectively. Lower body negative pressure was associated with improved blood flow in 10 of 17 sessions (59%) during spaceflight. Conclusions and Relevance: This cohort study found stagnant and retrograde blood flow associated with spaceflight in the IJVs of astronauts and IJV thrombosis in at least 1 astronaut, a newly discovered risk associated with spaceflight. Lower body negative pressure may be a promising countermeasure to enhance venous blood flow in the upper body during spaceflight.

Mortality Among International Astronauts.

INTRODUCTION: Research on the mortality of space explorers has focused exclusively on U.S. astronauts and Soviet and Russian cosmonauts. However, other nations have organized space programs over the last 40 yr and the European Space Agency, the Canadian Space Agency, the China National Space Administration, and the Japan Aerospace Exploration Agency all offer an opportunity for further study of the mortality of space explorers.METHODS: We used biographical and vital data abstracted from public sources for European, Canadian, Chinese, and Japanese astronauts. Using general population mortality rates from the Human Mortality Database and mortality rates derived from the cohort of U.S. astronauts, we computed standardized mortality ratios.RESULTS: The groups displayed different preferences in selection of astronauts. As there were no deaths in any of the four groups, the point estimates for standardized mortality ratios were all 0. However, the European cohort experienced a statistically significant reduction in all-cause mortality risk in comparison to the European general population as well as in comparison to U.S. astronauts.DISCUSSION: The healthy worker effect predicts that all study cohorts should have lower all-cause mortality risk in comparison to their general populations. The general population of Japan has mortality rates low enough that any reduction in mortality risk may remain undetectable in the Japanese cohort. Continued surveillance of these populations in the coming decades will make them a useful addition to the evidence base for astronaut mortality.Reynolds RJ, Day SM. Mortality among international astronauts. Aerosp Med Hum Perform. 2019; 90(7):647-651.

Long-duration spaceflight adversely affects post-landing operator proficiency.

Performance of astronaut pilots during space shuttle landing was degraded after a few weeks of microgravity exposure, and longer-term exposure has the potential to impact operator proficiency during critical landing and post-landing operations for exploration-class missions. Full-motion simulations of operationally-relevant tasks were utilized to assess the impact of long-duration spaceflight on operator proficiency in a group of 8 astronauts assigned to the International Space Station, as well as a battery of cognitive/sensorimotor tests to determine the underlying cause of any post-flight performance decrements. A ground control group (N = 12) and a sleep restriction cohort (N = 9) were also tested to control for non-spaceflight factors such as lack of practice between pre- and post-flight testing and fatigue. On the day of return after 6 months aboard the space station, astronauts exhibited significant deficits in manual dexterity, dual-tasking and motion perception, and a striking degradation in the ability to operate a vehicle. These deficits were not primarily due to fatigue; performance on the same tasks was unaffected after a 30-h period of sleep restriction. Astronauts experienced a general post-flight malaise in motor function and motion perception, and a lack of cognitive reserve apparent only when faced with dual tasks, which had recovered to baseline by four days after landing.

Functional Task and Balance Performance in Bed Rest Subjects and Astronauts.

INTRODUCTION: The purpose of this study was to determine how short- and long-duration spaceflight affects astronauts' performance on functional tests that challenge the balance control system (Seated Egress and Walk; Object Translation; Recovery from Fall/Stand; and Jump Down) and on clinical tests of balance function (Computerized Dynamic Posturography and Tandem Walk). In addition, we examined how exercise affects functional performance after long-term axial body unloading during 70 d of bed rest at 6° head-down tilt. METHODS: Data were collected twice during the 2-mo period before spaceflight or during the 2-wk period before bed rest, and four times after flight or bed rest: on the day of landing or the day bed rest ended, 1 d and 6 d later, and a final session 12 d after bed rest or 30 d after spaceflight. RESULTS: For bed rest subjects, long-term axial unloading alone caused functional performance deficits immediately after bed rest. However, the addition of an exercise regimen did not significantly improve median functional performance immediately after this axial unloading. For spaceflight subjects, the length of the space mission was directly related to the severity of functional performance deficits within 1 d of landing and during the subsequent recovery period after flight. DISCUSSION: The performance data suggest that an additional sensorimotor-based countermeasure may be necessary to maintain functional performance at preflight levels immediately after spaceflight.Miller CA, Kofman IS, Brady RR, May-Phillips TR, Batson CD, Lawrence EL, Taylor LC, Peters BT, Mulavara AP, Feiveson AH, Reschke MF, Bloomberg JJ. Functional task and balance performance in bed rest subjects and astronauts. Aerosp Med Hum Perform. 2018; 89(9):805-815.

Ocular Counter Rolling in Astronauts After Short- and Long-Duration Spaceflight.

Ocular counter-rolling (OCR) is a reflex generated by the activation of the gravity sensors in the inner ear that stabilizes gaze and posture during head tilt. We compared the OCR measures that were obtained in 6 astronauts before, during, and after a spaceflight lasting 4-6 days with the OCR measures obtained from 6 astronauts before and after a spaceflight lasting 4-9 months. OCR in the short-duration fliers was measured using the afterimage method during head tilt at 15°, 30°, and 45°. OCR in the long-duration fliers was measured using video-oculography during whole body tilt at 25°. A control group of 7 subjects was used to compare OCR measures during head tilt and whole body tilt. No OCR occurred during head tilt in microgravity, and the response returned to normal within 2 hours of return from short-duration spaceflight. However, the amplitude of OCR was reduced for several days after return from long-duration spaceflight. This decrease in amplitude was not accompanied by changes in the asymmetry of OCR between right and left head tilt. These results indicate that the adaptation  of otolith-driven reflexes to microgravity is a long-duration process.

Occupational-Specific Strength Predicts Astronaut-Related Task Performance in a Weighted Suit.

BACKGROUND: Future space missions beyond low Earth orbit will require deconditioned astronauts to perform occupationally relevant tasks within a planetary spacesuit. The prediction of time-to-completion (TTC) of astronaut tasks will be critical for crew safety, autonomous operations, and mission success. This exploratory study determined if the addition of task-specific strength testing to current standard lower body testing would enhance the prediction of TTC in a 1-G test battery. METHODS: Eight healthy participants completed NASA lower body strength tests, occupationally specific strength tests, and performed six task simulations (hand drilling, construction wrenching, incline walking, collecting weighted samples, and dragging an unresponsive crewmember to safety) in a 48-kg weighted suit. The TTC for each task was recorded and summed to obtain a total TTC for the test battery. Linear regression was used to predict total TTC with two models: 1) NASA lower body strength tests; and 2) NASA lower body strength tests + occupationally specific strength tests. RESULTS: Total TTC of the test battery ranged from 20.2-44.5 min. The lower body strength test alone accounted for 61% of the variability in total TTC. The addition of hand drilling and wrenching strength tests accounted for 99% of the variability in total TTC. DISCUSSION: Adding occupationally specific strength tests (hand drilling and wrenching) to standard lower body strength tests successfully predicted total TTC in a performance test battery within a weighted suit. Future research should couple these strength tests with higher fidelity task simulations to determine the utility and efficacy of task performance prediction.Taylor A, Kotarsky CJ, Bond CW, Hackney KJ. Occupational-specific strength predicts astronaut-related task performance in a weighted suit. Aerosp Med Hum Perform. 2018; 89(1):58-62.

A Cohort Mortality Study Among Soviet and Russian Cosmonauts, 1961-2014.

INTRODUCTION: Over 500 people from different countries have been to space since the first manned spaceflight in 1961. Factors of space and spaceflights might cause functional and somatic disorders, leading to increased mortality. Our research goal was to assess cause-specific risk of death among Soviet and Russian cosmonauts who had at least one spaceflight. METHODS: The epidemiological cohort study included 115 male cosmonauts. The observation period was 54 yr (January 1, 1961-December 31, 2014) and 2707 person-years of follow-up were obtained. By the end of the period, 84 cosmonauts were still alive and 31 were deceased. The reference groups were the male population of Russia and of the Moscow Region, where Zvezdny City (Star City) is located. Mortality risk was assessed by standardized mortality ratio (SMR) with 95% confidence intervals (95% CI). RESULTS: Death risk in the cohort was significantly lower than that in both reference groups: for all causes (А00-Y98; SMR = 40), for diseases of the circulatory system (I00-I99; SMR = 37 and 35 compared to Russia and the Moscow Region, respectively), and for other causes, i.e., all causes except circulatory diseases, cancer, and accidents, (SMR = 8). Death risk for accidents (V01-Y98) in the cohort was 1.8-1.9 times lower than that in both reference groups: SMR = 52 (95% CI 19-139) and 56 (21-151), but was not statistically significant. SMR for cancer (C00-C97) was also below 100 (71 and 66), but insignificant. DISCUSSION: Our findings mainly characterize mortality among the first cosmonauts who have flown to space from 1961 through the 1970s, which indicates the necessity of continuing research.Ushakov IB, Voronkov YI, Bukhtiyarov IV, Tikhonova GI, Gorchakova TYu, Bryleva MS. A cohort mortality study among Soviet and Russian cosmonauts, 1961-2014. Aerosp Med Hum Perform. 2017; 88(12):1060-1065.

Mortality Due to Cardiovascular Disease Among Apollo Lunar Astronauts.

INTRODUCTION: Recent research has postulated increased cardiovascular mortality for astronauts who participated in the Apollo lunar missions. The conclusions, however, are based on small numbers of astronauts, are derived from methods with known weaknesses, and are not consistent with prior research. METHODS: Records for NASA astronauts and U.S. Air Force astronauts were analyzed to produce standardized mortality ratios. Lunar astronauts were compared to astronauts who have never flown in space (nonflight astronauts), those who have only flown missions in low Earth orbit (LEO astronauts), and the U.S. general population. RESULTS: Lunar astronauts were significantly older at cohort entry than other astronaut group and lunar astronauts alive as of the end of 2015 were significantly older than nonflight astronauts and LEO astronauts. No significant differences in cardiovascular disease (CVD) mortality rates between astronaut groups was observed, though lunar astronauts were noted to be at significantly lower risk of death by CVD than are members of the U.S. general population (SMR = 13, 95% CI = 3-39). DISCUSSION: The differences in age structure between lunar and nonlunar astronauts and the deaths of LEO astronauts from external causes at young ages lead to confounding in proportional mortality studies of astronauts. When age and follow-up time are properly taken into account using cohort-based methods, no significant difference in CVD mortality rates is observed. Care should be taken to select the correct study design, outcome definition, exposure classification, and analysis when answering questions involving rare occupational exposures.Reynolds RJ, Day SM. Mortality due to cardiovascular disease among Apollo lunar astronauts. Aerosp Med Hum Perform. 2017; 88(5):492-496.

No evidence for an increase in circulatory disease mortality in astronauts following space radiation exposures.

Previous analysis has shown that astronauts have a significantly lower standardized mortality ratio for circulatory disease mortality compared to the U.S. population, which is consistent with the rigorous selection process and healthy lifestyles of astronauts, and modest space radiation exposures from past space missions. However, a recent report by Delp et al. estimated the proportional mortality ratio for ages of 55-64 y of Apollo lunar mission astronauts to claim a high risk of cardiovascular disease due to space radiation compared to the U.S. population or to non-flight astronauts. In this Commentary we discuss important deficiencies in the methods and assumptions on radiation exposures used by Delp et al. that we judge cast serious doubt on their conclusions.

Statistical Evaluation of Causal Factors Associated with Astronaut Shoulder Injury in Space Suits.

INTRODUCTION: Shoulder injuries due to working inside the space suit are some of the most serious and debilitating injuries astronauts encounter. Space suit injuries occur primarily in the Neutral Buoyancy Laboratory (NBL) underwater training facility due to accumulated musculoskeletal stress. We quantitatively explored the underlying causal mechanisms of injury. METHODS: Logistic regression was used to identify relevant space suit components, training environment variables, and anthropometric dimensions related to an increased propensity for space-suited injury. Two groups of subjects were analyzed: those whose reported shoulder incident is attributable to the NBL or working in the space suit, and those whose shoulder incidence began in active duty, meaning working in the suit could be a contributing factor. RESULTS: For both groups, percent of training performed in the space suit planar hard upper torso (HUT) was the most important predictor variable for injury. Frequency of training and recovery between training were also significant metrics. The most relevant anthropometric dimensions were bideltoid breadth, expanded chest depth, and shoulder circumference. Finally, record of previous injury was found to be a relevant predictor for subsequent injury. The first statistical model correctly identifies 39% of injured subjects, while the second model correctly identifies 68% of injured subjects. DISCUSSION: A review of the literature suggests this is the first work to quantitatively evaluate the hypothesized causal mechanisms of all space-suited shoulder injuries. Although limited in predictive capability, each of the identified variables can be monitored and modified operationally to reduce future impacts on an astronaut's health.

Low Back Pain in Microgravity and Bed Rest Studies.

BACKGROUND: The prevalence of low back pain (LBP) for astronauts in space (68%) is higher than the 1-mo prevalence for the general population on Earth (39%). It is unclear whether differences occur between healthy subjects and astronauts with a history of LBP. Knowledge of this issue is important to assess whether a history of LBP could have an operational impact. METHODS: We evaluated LBP prospectively during short duration spaceflight (15 d; N=20) and compared this with similar data collected during two bed rest studies (N=40). Astronauts completed a questionnaire 5-10 d preflight, during each flight day, and 5-10 d postflight. RESULTS: All astronauts with a history of LBP also developed LBP in flight. These astronauts reported a significantly longer duration of LBP and a different pain location. LBP was most often experienced in the central area of the lower back during spaceflight with an incidence of 70% and a mean pain level of 3 (on a scale of 0-10). Pain resolved within 10 d of flight. No neurological signs were present. The most frequently reported countermeasure was assuming a "knees to chest (fetal tuck) position" combined with stretching. Greater LBP intensity was reported in spaceflight than bed rest with a trend indicating a greater number of days of pain during spaceflight. DISCUSSION: The current study represents a prospective study of LBP in spaceflight. The results indicate that LBP is self-limiting in spaceflight and should not pose an operational risk. Prior LBP on Earth appears to be a risk factor for LBP in spaceflight.

Effects of sex and gender on adaptation to space: cardiovascular alterations.

Sex and gender differences in the cardiovascular adaptation to spaceflight were examined with the goal of optimizing the health and safety of male and female astronauts at the forefront of space exploration. Female astronauts are more susceptible to orthostatic intolerance after space flight; the visual impairment intracranial pressure syndrome predominates slightly in males. Since spaceflight simulates vascular aging, sex-specific effects on vascular endothelium and thrombotic risk warrant examination as predisposing factors to atherosclerosis, important as the current cohort of astronauts ages. Currently, 20% of astronauts are women, and the recently selected astronaut recruits are 50% women. Thus there should be expectation that future research will reflect the composition of the overall population to determine potential benefits or risks. This should apply both to clinical studies and to basic science research.

Effects of sex and gender on adaptation to space: immune system.

This review is focused on sex and gender effects on immunological alterations occurring during space flight. Sex differences in immune function and the outcome of inflammatory, infectious, and autoimmune diseases are well documented. The work of the Immunology Workgroup identified numerous reasons why there could be sex and/or gender differences observed during and after spaceflight, but thus far, there has been very little investigation in this area of research. In most cases, this is due to either a low total number of subjects or the minimal number of female flight crew members available for these studies. Thus, the availability of a sufficient number of female subjects to enable statistical analysis of the data has been a limiting factor. As the inclusion of female crew members has increased in the recent past, such studies should be possible in the future. It is very difficult to obtain immunologic and infectious data in small animals that can be usefully extrapolated to humans undergoing spaceflight. Thus, it is recommended by the Immunology Workgroup that a greater emphasis be placed on studying astronauts themselves, with a focus on long-term evaluations of specific, known infectious risks.

Effects of sex and gender on adaptation to space: musculoskeletal health.

There is considerable variability among individuals in musculoskeletal response to long-duration spaceflight. The specific origin of the individual variability is unknown but is almost certainly influenced by the details of other mission conditions such as individual differences in exercise countermeasures, particularly intensity of exercise, dietary intake, medication use, stress, sleep, psychological profiles, and actual mission task demands. In addition to variations in mission conditions, genetic differences may account for some aspect of individual variability. Generally, this individual variability exceeds the variability between sexes that adds to the complexity of understanding sex differences alone. Research specifically related to sex differences of the musculoskeletal system during unloading is presented and discussed.