Abstract
With the development of human space technology, more and more astronauts fly into space. With the rapid development of commercial aerospace, more ordinary people will go to space for sightseeing. However, it should not be ignored that microgravity, space radiation, relative geometry, and orbit of space stations have various effects on the health of astronauts. In recent years, scholars in various countries have made considerable research progress in this field. This article analyzes the research history and current situation of this field, including the individual effects of space radiation, microgravity, orbit, and relative geometry, as well as their comprehensive effects. In addition, various nursing measures have been investigated.
1 Introduction
The known health battery hazards mediated by space flight jointly affect multiple biological systems, the impact source includes microgravity, space radiation, spacecraft orbit, and relative geometric relationship between space station and sun, etc. (Parazynski 2006; Jiang et al. 2017, Demontis et al. 2017, Moore et al. 2019, Jiang and Schmidt 2020, Willey et al. 2021). These hazards trigger recurrent astrobiological features, including DNA damage, oxidative stress, mitochondrial disorders, epigenetic/regulatory changes, telomere length dynamics, and changes in host–microbial interactions (Indo et al. 2016, Bisserier et al. 2021). The scope of health damage comes from a variety of physiological systems in the central nervous system, musculoskeletal system, cardiovascular system, liver, immunity, increased cancer/mutation risk, and circadian rhythm disorder (Myrrhe et al. 2020, Smith et al. 2020). The microgravity causes astronauts’ muscle atrophy, spacecraft orbit as well as the relative geometric relationship between space station and sun leads to astronauts’ inconsistent circadian rhythm, and space radiation leads to astronauts’ DNA damage. The adverse effects of space radiation are more significant during astronauts’ extravehicular activities (Figures 1 and 2). Many kinds of influences cannot be identified at present, which can be generally called the influence of the space environment on astronauts’ health. In addition, some, which are composed of many factors, may be the combined influence of space radiation and microgravity (Jiang et al. 2017, Jiang 2020) or the influence of inconsistent circadian rhythm caused by orbital geometry of space station and the Sun (Crucian et al. 2018, Jillings et al. 2020).
Astronauts leave the capsule in the Shenzhou 12 Mission.
The astronaut returned to the Tianhe core module after leaving the module in the Shenzhou 12 Mission.
Therefore, we first introduce the effects of various individual factors on the health of astronauts, especially those of space radiation and microgravity. There have been a large number of works of literatures on the effects of space radiation alone. Second, it introduces the comprehensive effects of various influences.
2 Typical effects on health
In this section, we investigate the research progress of typical effects on astronauts’ health, including space radiation, microgravity, as well as the spacecraft orbit and relative geometry to astronauts’ health.
2.1 Space radiation
Space radiation consists of three kinds of radiation: particles trapped in the Earth’s magnetic field (Chancellor et al. 2014, Cucinotta et al. 2014, Willey et al. 2021); particles launched into space during solar flares (solar particle events); and galactic cosmic rays are high-energy protons and heavy ions from outside the solar system (Figure 3). All these types of space radiation represent ionizing radiation. Space radiation also has very different effects on human DNA, cells, and tissues. This is largely due to increased ionization near the orbit of space radiating particles passing through the material. The energy of ionizing radiation is so great that it can knock electrons out of any atom it hits, thus ionizing the atom. This effect can destroy atoms in human cells, leading to future health problems, such as cataracts, cancer, and damage to the central nervous system. The energy lost when ionizing radiation passes through the material or living tissue is absorbed by the material or living tissue. The ionization of water and other cellular components will destroy the DNA molecules near the particle path, and its direct effect is the breakage of DNA chains, including the broken clusters near each other: a fracture of a cell that is not easily repaired. When cells are exposed to the type of radiation found on Earth, the frequency of such clusters of DNA breaks is much lower or does not occur at all. Because space radiation can destroy atoms, when it strikes spacecraft or astronauts in spacecraft, it can also produce more particles, including neutrons, which is called the secondary effect. The amount of space radiation that astronauts may receive while orbiting the Earth depends on several factors: (a) orbital altitude above the Earth – at higher altitudes, the Earth’s magnetic field is weak, so the protection against ionizing particles is low, and spacecraft pass through the captured radiation zone more often; (b) orbital inclination – the closer the spacecraft’s orbit is to the Earth’s poles, the higher the radiation level, because ionized particles are concentrated in the Earth’s magnetic field. In other words, when the inclination is near 90°C or the spacecraft is at the solar synchronous orbit or polar orbit, the radiation level is high; (c) solar cycle – the sun has an average 11-year cycle, and the number and intensity of solar flares increase dramatically, especially during the period when there are many sunspots; and (d) individual susceptibility – researchers are still trying to determine what makes one person more vulnerable to space radiation than another.
The two main radiation types are monitored by the radiation assessment detector and how the magnetic field around the Earth affects the radiation in near-Earth space. Figure courtesy of NASA/JPL-Caltech.
For the radiation dosage of astronauts, Sun et al. (2013) developed visual Chinese adult women (VCH-F) model and further modified it to generate a VCH-F astronaut (vch-fa) phantom to study the radiation protection of astronauts and related dose data. Based on the cryosection image, the original phantom was constructed by a non-uniform rational B-spline boundary surface to enhance the deformability, to fit the body parameters of Chinese female astronauts. The transport of radioactive particles of isotropic protons with an energy of 5,000–10,000 MeV is simulated in the Monte Carlo n particle expansion program. Sun et al. (2013) found that there are dose differences between the calculated results, especially the effective dose of the low-energy proton. The local skin thickness changes the breast dose curve toward the high energy direction but has little effect on the internal organs.
Space radiation can affect cardiovascular health, gene regulation, DNA damage, etc. (Rizzardi et al. 2013, Bezdan et al. 2020, Luxton et al. 2020, Bishawi et al. 2022, Deane et al. 2022). Bishawi et al. (2022) research found that the GCR5 ion in space radiation is related to the deterioration of heart structure and function, which may increase the incidence rate of cardiovascular health in astronauts. Rizzardi et al. (2013) investigate that the unique spaceflight stress environment during prolonged spaceflight has numerous effects on human health and physiology as well as on cells and molecules, including changes in bone density, cognitive performance, microbial changes, and gene regulation. Previous studies have collected inadequate data and have not integrated the simultaneous effects of multiple systems and data types on the same subject or on short missions. The same variables were monitored in an astronaut on a 340-day space mission and his non-participating twin for comparison of biological indicators of space flight impact factors. The results indicate significant changes in multiple data, and these influence pathways and mechanisms have important implications for future missions.
DNA damage also has significant impact on astronaut health. Using identical twins to study DNA damage is an effective method. Bezdan et al. (2020) compare the cfDNA characteristics of an astronaut with his identical twins and healthy donors on Earth, the astronaut performs his one-year mission at the international space station (ISS), and the cfDNA characteristics include fragment size, cell deconvolution, and nucleosome localization; they observed a significant increase in the precursor portion of cell-free mitochondrial DNA (CF mtDNA) during space flight. The analysis of post-flight exons in plasma showed that after a one-year flight mission, the circulating exons and patient-specific protein cargo (including brain-derived peptides) increased 30-fold. Luxton et al. (2020) investigated telomere length dynamics, and DNA damage responses in a relatively large astronaut cohort (n = 11) were assessed before, during, and after a one-year or shorter mission on the ISS, and found that astronauts’ telomeres were significantly shorter before and after space flight, and their telomerase activity was lower than that of the age- and sex-matched ground control group. Futhermore, they proposed a telomere adaptive response to chronic oxidative damage in extreme environments; that is, telomere-independent alternative lengthening of telomere pathway is activated instantaneously in normal somatic cells.
Peterson and Kovyrshina (2015) focused on correcting the effect of health workers of background (HWE) on the predicted lifetime risk estimates of radiation-induced cancer mortality and incidence rate for American astronauts and suggest that during the multiple Monte Carlo implementation of the life table, the typical life table method for predicting the mortality and incidence rate of radiation-induced cancer in astronauts and radiation workers can be improved by simulating the uncertainty of input rate, input excess risk coefficient, and deviation correction coefficient and adjusting HWE. The cardiovascular disease (CVD) mortality rate of Apollo astronauts (43%) was 4–5 times that of non-flight and lower Earth orbit astronauts (Delp et al. 2016).
To study the impact to astronaut health of space radiation, omics is a field that cannot be ignored. Chancellor et al. (2014) pointed out that ground research using model organisms to accurately simulate the biological effects of space radiation environment must be exposed to both proton and heavy ion sources, they suggest that “Omics” areas, including, genomics, proteomics, metabolomics, should also be used wisely and associated with phenotypic observations; they believed that this method would more accurately clarify the impact of space radiation on human physiology and help to formulate personalized radiation countermeasures for astronauts. Deane et al. (2022) investigated the number of ESA life science experiments conducted by each branch discipline each year from 1980 to 2020, identified and summarized the omics work led by European researchers, and highlighted the potential advantages of ESA member states in complex financing schemes. The special spaceflight environment can lead to changes in the body pathophysiology of astronauts during spaceflight, among which changes in the human microbiome play a very important role in the health of the body. Tesei et al. (2022) explored the various conditions that affect changes in the human body during spaceflight and discussed how the role of microorganisms can be used to improve these conditions, as well as the space environment conditions that affect the microbial composition. The main study analyzed microgravity, radiation, immunity, bone, cognitive function, sex differences, and pharmacomicrobiomics, and the importance of their interactions for spaceflight.
2.2 Microgravity
Space microgravity is also called zero gravity. Strictly speaking, it should be “zero weight.” Because the environment of space and the Earth’s surface is very different, the Earth’s surface is 1 g gravity environment, while space is in a vacuum state (Cox et al. 2002, Grimm et al. 2016, Tanaka et al. 2017, Winnard et al. 2019, Jiang et al. 2020, Willey et al. 2021). Astronauts living and working in space must adapt to this state of microgravity for a long time. In the microgravity environment, we will feel completely different from the ground. Due to the lack of gravity, the first thing astronauts feel is that their bodies are floating. Everything in the spaceship cabin, if not fixed with a belt, must float. If astronauts want to walk, they can only push and pull the bulkhead with both hands to help them move. If it is outside the module, it is necessary to use a special extravehicular activity device to help the astronauts “walk around.” In the absence of gravity, all the receptors related to gravity in the human body have changed. The limbs can no longer feel the weight, and the human body can no longer feel the movement of the head. This abnormal feeling causes astronauts to have an illusion of orientation. When they push and pull the bulkhead of the spacecraft by hand, they do not feel that they are moving forward and backward, but think that the spacecraft is moving forward and backward and that they are stationary. What is very interesting is that in the microgravity environment, astronauts’ strength has greatly increased, and they can easily do many actions that are difficult or impossible to complete on the ground, for example, use one finger to hold the top and do various tumbling movements at will. This microgravity environment will cause astronauts to suffer from dizziness, dizziness, nausea, sleepiness, and other symptoms, which will affect the internal organs. Once the astronaut enters the microgravity state, due to the lack of downward attraction of gravity, the body fluid will transfer to the upper body and head, resulting in swollen neck veins, puffy face, congestion of nasal cavity and sinuses, and stuffy nose. The transfer of body fluid will reduce the volume of plasma and blood concentration of astronauts, leading to anemia. Microgravity environment also has a certain impact on human muscles and bones.
Astronauts returning from space can experience abnormalities such as an increased heart rate, decreased blood pressure, and even fainting. Cox et al. (2002) investigated the hemodynamic changes induced by Valsalva scale operations in astronauts on Earth and space, as well as the changes in sympathetic and vagal pressure reflexes in microgravity. The results showed that muscular sympathetic nerve activity was much greater in space than on Earth. But the sympathetic pressure reflex gain is the same in space as it is on Earth, and the vagal pressure reflex gain is less in space than on Earth. This study shows that exposure to microgravity in space significantly increases arterial pressure and sympathetic reflex to Valsalva tension, decreases vagus reflex but does not significantly decrease sympathetic reflex gain. To study the microgravity influences the risk of long-term CVD, Ade et al. (2017) collected data from 310 NASA astronauts and 981 nonastronaut during the longitudinal study of astronaut health, non-astronauts and astronauts were matched on age, sex, and body mass index to assess acute and chronic incidence rate and mortality. The results show that 5.2% of astronauts had a clinical CVD endpoint and 2.9% of astronauts had a CAD endpoint, while the values for nonastronauts are 4.7 and 3.1%, respectively.
Microgravity leads to physiological disorders due to lack of gravity load, resulting in decreased bone mineral density, atrophy of skeletal muscle and postural muscle of lower limbs, and lengthening of the spine (Michalski et al. 2019). Experts proposed that the hip load capacity be included in the astronaut bone health standard. Scott et al. (2021) investigate that the loss of muscle mass is a major problem in long space flight, and ∼20% loss of muscle mass is observed before and after spaceflight. In a space flight with an average of 57 days, the panoramic ultrasound image of the muscle at the last 7 days on-orbit has no significant difference from the panoramic ultrasound image after landing.
2.3 Orbit and relative geometry
An orbit is a path. It is the way spacecraft goes around Earth or other celestial bodies in space. The orbit and relative geometry make the astronauts see the number of sunrises per day different from the Earth's surface. For instance, the Chinese space station can see 16 sunrises in a day. This is because the Chinese space station will orbit the Earth in 90 min, and each orbit will see a sunrise and sunset.
The causes of on-orbit sleep problems include cabin environmental factors, schedule adjustment, unreasonable work arrangement, impaired sleep balance regulation, circadian rhythm disorder, mental/physical discomfort, as well as light flashes from space radiation (Guo et al. 2014, Petersen et al. 2015, Peterse et al. 2016, Wu et al. 2018, Bevelacqua and Mortazavi 2018). Since astronaut Aldrin first reported in 1969, many astronauts have reported flash. These visually perceived flashes appear in different shapes, but they obviously move in the astronaut’s field of vision, which may lead to sleep problems at least to some extent. Using the fact that most of the galactic cosmic radiation (GCR) spectrum is composed of ions, a possible way to reduce the flash can be found, and these ions can be transferred from the spacecraft through electromagnetic fields (Bevelacqua and Mortazavi 2018). There are several kinds of countermeasures for sleep disturbance for astronauts on on-orbit flights, including pharmacological intervention, phototherapy, crew selection and training, traditional Chinese medicine, using electric and magnetic fields to deflect GCR, etc.
3 Synthetical effects on health
More chronic diseases are caused by the combined effects of space radiation, microgravity, as well as the spacecraft orbit and relative geometry. In addition, the cause of some health problem in spaceflight is not clear, such as astronauts’ immunity, eye structural changes, and gender difference.
During prolonged spaceflight, astronauts’ immunity is temporarily reduced due to a unique stressful environment, and varicella-zoster virus (VZV) is allowed to reactivate and proliferate to infect astronauts. The VZV causes chickenpox when it first infects the human body (Cohrs et al. 2008). After recovery, the virus is latent in the body’s ganglia and activates and proliferates at the right time to cause shingles. Studies have shown that the presence of the infectious VZV in the saliva of some astronauts has been confirmed by testing saliva samples from several astronauts who did not develop the disease. Mark et al. (2014) believe that gender causes physiological and psychological changes in space flight and will affect the health and best nursing care of astronauts; they investigate that more clinically significant cases of visual impairment caused by space flight have only been observed in male astronauts, but the sample size of long-term female astronauts is still relatively moderate.
Otsuka et al. (2017) studied the human cardiovascular dynamics in space flight and used five 24 h electrocardiographic (ECG) records from ten healthy astronauts with the data from before launch, 20.8 ± 2.9 (ISS01), 72.5 ± 3.9 (ISS02), and 152.8 ± 16.1 (ISS03) after launch, and after returning to Earth. They found that the amplitude of 90 min of ECG in space (ISS03) is about three times that of the Earth, especially in a group of seven astronauts who show different HRV curves before the flight. Baran et al. (2022) summarized all known CVDs related to human spaceflight, focusing on cardiovascular changes (in vivo) and cellular and molecular changes (in vitro) related to human spaceflight, as manned spaceflight is associated with a variety of cardiovascular risk factors; they proposed to study a variety of physiological changes and countermeasures for further orbit manned space missions through the use of microgravity platform.
Demontis et al. (2017) argue that microgravity and high radiation in space pose a threat to human health, but that the effects of space flight on the astronaut’s body are mostly reversible, which provides mechanistic insight into certain pathophysiological processes, and discusses the major stressors encountered in space and their effects on the human body, and will also discuss possible lessons for human health from space exploration that could be beneficial in protecting the health of space personnel as well as the health of the population on Earth.
Zhang and Hargens (2018) consider intracranial pressure (VIIP) syndrome to be a major unavoidable risk in skyflight, a condition NASA defines as spaceflight-induced symptoms from prolonged spaceflight-associated neuro-ocular syndrome (SANS). This increase in intracranial pressure is primarily due to loss of hydrostatic pressure and altered hemodynamics in the circulation of cerebrospinal fluid in the intracranial system. In space, chronic elevated intracranial pressure causes alterations in multiple structures and fluid systems in the eye resulting in VIIP syndrome. The results of this study will help to investigate the mechanisms and strategies for the adverse effects of prolonged spaceflight on the human body. During a long space flight, some astronauts experienced eye structural changes, including optic disc edema with symptoms similar to intracranial hypertension. Iwasaki et al. (2021) showed that in the nine astronauts without optic disc edema, the group average nipp estimates decreased significantly, indicating that cephalic fluid displacement during long space flight rarely increased post-flight intracranial pressure. Goodenow-Messman et al. (2018) used the flight values of 24 h urine chemistry of 1,517 astronauts, combined with the computational biochemical model, they studied the risk ratio of CaOx kidney stones during and after the flight, the analysis showed that protective intervention could reduce the risk of CaOx to the pre-flight level.
Hupfeld et al. (2022) investigated the impact of space manipulation on spaceflight on perivascular spaces (PVSs) and considered how the number and shape of PVS visible on magnetic resonance imaging (MRI) were affected by space flight, including previous space flight experience. The research includes 15 astronauts who performed two T1-weighted 3 T MRI scans before launch and four after returning to Earth after the ISS’s mission of about six months. The established automatic segmentation algorithm was used to calculate the number and morphology of PVS in white matter MRI. It indicates that experienced astronauts may show a detention effect compared with previous space battles. The greater the pre-flight PVS load, the more previous flight experience (r = 0.60–0.71), although these relationships were not statistically significant (p > 0.05). There was no significant correlation between the changes in ventricular volume before and after the flight and the changes in PVS characteristics. The existence of SANS is independent of PVS quantity or form. Previous space flight experience may be an important factor in determining the characteristics of PVS. Hupfeld et al. (2022) investigated the human brain structure and intracranial fluid changes in space due to prolonged exposure to extreme environments. There have been no studies of the PVS in the brain that contributes to fluid drainage and intracerebral homeostasis. We have studied the number and morphology of PVS by performing MRI of the brain in several astronauts and have shown that PVS can be identified in T1-weighted images from MRI scans.
4 Nursing measures
At present, many countries in the world have conducted a lot of research on the effects of space radiation and microgravity on the health of astronauts and taken certain protective measures. After many tests, some have achieved obvious results, but some diseases cannot be effectively solved at present, and further research is needed. The simplest nursing measure is to develop appropriate medical standards for astronaut selection. Johnston et al. (2014) discus the evolution of medical selection criteria in the space shuttle era and the most common reasons why applicants are disqualified; they used the data of astronaut candidates collected from the medical records and NASA archives from 1978–2004, and reviewed the medical disqualifications; they report that the most common nonconformities include visual, cardiovascular, mental, and behavioral disorders. During this period, three major expert panel reviews resulted in modifications and changes. The National Aeronautics and Space Administration (NASA) did not begin to compile astronaut medical policies until 1977. Policy development is based on NASA’s manned space flight efforts since 1958 to support the operational aspects of the upcoming space shuttle flight program and other future activities. For the past decade or so, people have been discussing this issue and planning to send humans back to the Moon, Mars, or an asteroid. Each mission requires unique medical capabilities, unique astronaut composition, and strong medical policies (Doarn 2011).
Furthermore, different scholars have carried out research on nursing measures for astronauts’ health risks in different ways, including the role of omics, space suits, and radiation health risk assessment (HRA). Schmidt and Goodwin (2013) investigate the role of “Omics” in improving the human ability, they proposed the concept of personalized medical care in human space flight in order to improve the safety and performance of astronauts. Stabler et al. (2017) introduce a lightweight compression suit called skinsuit, which is designed to provide head to foot (axial) load to offset the elongation of the spine during space flight. In order to study the possible negative effects of synthetic clothing on the skin microbiota, they identified the skin bacterial communities in the sebaceous glands and moist body parts of five healthy male volunteers who were assessed by the sebum kit. Each volunteer showed a different bacterial population in each skin area. Short time (8 h) dry superbuoyancy floating, whether wearing fitness kits or tight clothes, will cause changes in the composition of genus-level skin microbiota, but will have little or no impact on the community structure of the gate level or the richness and diversity of the bacterial population. Walsh et al. (2021) concluded that radiation-attributed decline in survival (RADS) amounts could be used for astronaut radiation HRA. For example, the doses of radiation exposure to astronauts on long-term missions to the Moon or Mars were statistically analyzed, and RADS dose responses were given for the incidence results of their body cancer, leukemia, lung cancer, and female breast cancer. The results can be used to analyze different RADS results with changes in age of exposure, age of attainment, and other factors. This alternative method has advantages over the example calculation method currently used for occupational HRA in European astronauts, and it can be applied in a long-term radiation protection approach for astronauts after mission exposure.
Some scholars have studied astronaut health countermeasures in catering. Tang et al. (2021) study found that adequate nutrition is needed during long-term space missions and that measures such as choosing the right type of food and adopting an effective diet have the potential to address nutritional deficiencies in the short term. However, a long-term sustainable space nutrition support system should consist primarily of fresh, natural food production and processing, as well as nutrient recovery and cultivation systems based on materials such as food scraps. The special stressful environment of space and the long-term missions faced in the future will increase the microgravity, radiation, and ROS production. In order to reduce the damage caused by ROS to the bodies of astronauts as well as future space colonists and tourists, Gómez et al. (2021) proposed to develop an antioxidant cocktail and explored the mechanisms of damage caused by ROS, the differences between the metabolism of antioxidant drugs in space and on the ground, and the characteristics and efficacy of antioxidants against ROS.
In addition, medical measures and medical skills of nonmedical staff are also the research directions that scholars pay attention to. Personalized medicine improves the health of patients through nursing treatment programs for different individuals to prevent and treat diseases, and individual responses to environmental factors can affect the effectiveness of disease treatment. Pavez Loriè et al. (2021) analysis found that under the special stressors of the space environment, human health research has significant individual differences in response to space simulation conditions, including differences in response to drugs and physiological changes caused by radiation. With the development of space technology, personalized medicine will become an inevitable requirement to maximize the therapeutic effect and minimize the side effects through precise treatment. Komorowski et al. (2018) found that future space exploration missions will require full autonomy and that anesthesia capabilities are essential, that the current empirical knowledge of anesthesia in space missions is inadequate, that the implementation of anesthesia in the unique space exploration environment is relatively difficult and limited by many factors, and that training in safe anesthesia in a limited environment, minimum safety, and monitoring can be expanded to space exploration missions. The acquisition of basic anesthesia skills is one of the very important factors that will enable not only medical personnel to achieve safe and effective anesthesia in future space exploration missions, but also non-physicians to practice anesthesia in crisis situations, such as simple general anesthesia. Cortés-Sánchez et al. (2022) found that the effect of microgravity had an effect on the carcinogenesis of normal cells and cancer cells. In addition, the harmful effect of radiation on cells seemed to be aggravated under microgravity. These new discoveries may help to find new and effective cancer treatments and provide health protection for human beings in the future long-term space flight and exploration of outer space.
5 Conclusions
In the process of space flight, due to space radiation, microgravity, spacecraft orbit, relative geometric relationship between space station and sun, etc., astronauts’ bodies will have a series of changes different from those on the ground. These difference includes telomere length dynamics and DNA damage, hemodynamic changes, changes in sympathetic and vagal pressure reflexes, loss of muscle mass, decreased bone mineral density, gender difference, sleep disturbance, change in immune system, increased cancer risk, etc. Some of them are caused by single factors, such as space radiation. Many other symptoms and diseases are caused by many factors. Till now, the number of astronauts is not very large. Therefore, the research results in astronaut medicine are not very fruitful. With the vigorous development of commercial aerospace and the development of human space travel, lunar base, Mars base and even planetary migration, the research on astronaut health will become more and more important in the future. The health problems of astronauts are closely related to the space environment, including space radiation and microgravity. Therefore, the research on the health of astronauts and nursing measures needs to be combined with the research on the space environment in order to deeply understand the mechanism of health problems.
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Funding information: The author acknowledges support from the National Natural Science Foundation of China (No. 11772356).
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Conflict of interest: The author declares no competing interests.
References
Ade CJ, Broxterman RM, Charvat JM, Barstow TJ. 2017. Incidence rate of cardiovascular disease end points in the national aeronautics and space administration astronaut corps. J Am Heart Assoc. 6(8):e005564.10.1161/JAHA.117.005564Search in Google Scholar PubMed PubMed Central
Baran R, Marchal S, Garcia Campos S, Rehnberg E, Tabury K, Baselet B, et al. 2022. The cardiovascular system in space: focus on in vivo and in vitro studies. Biomedicines. 10:59.10.3390/biomedicines10010059Search in Google Scholar PubMed PubMed Central
Bevelacqua JJ, Mortazavi SMJ. 2018. Commentary regarding “on-orbit sleep problems of astronauts and countermeasures”. Mil Med Res. 5(1):38.10.1186/s40779-018-0185-2Search in Google Scholar PubMed PubMed Central
Bezdan D, Grigorev K, Meydan C, Pelissier Vatter FA, Cioffi M, Rao V, et al. 2020. Cell-free DNA (cfDNA) and exosome profiling from a year-long human spaceflight reveals circulating biomarkers. iScience. 23:101844.10.1016/j.isci.2020.101844Search in Google Scholar PubMed PubMed Central
Bishawi M, Lee FH, Abraham DM, Glass C, Blocker SJ, Cox DJ, et al. 2022. Late onset cardiovascular dysfunction in adult mice resulting from galactic cosmic ray exposure. iScience. 25:104086.10.1016/j.isci.2022.104086Search in Google Scholar PubMed PubMed Central
Bisserier M, Shanmughapriya S, Rai AK, Gonzalez C, Brojakowska A, Garikipati V, et al. 2021. Cell-free mitochondrial DNA as a potential biomarker for astronauts’ health. J Am Heart Assoc. 10:e022055.10.1161/JAHA.121.022055Search in Google Scholar PubMed PubMed Central
Chancellor JC, Scott GBI, Sutton JP. 2014. Space radiation: the number one risk to astronaut health beyond low Earth orbit. Life. 4(3):491–510.10.3390/life4030491Search in Google Scholar PubMed PubMed Central
Cohrs RJ, Mehta SK, Schmid DS, Gilden DH, Pierson DL. 2008. Asymptomatic reactivation and shed of infectious varicella zoster virus in astronauts. J Med Virology. 80(6):1116–1122.10.1002/jmv.21173Search in Google Scholar PubMed PubMed Central
Cortés-Sánchez JL, Callant J, Krüger , Sahana J, Kraus A, Baselet B, et al. 2022. Cancer studies under space conditions: finding answers abroad. Biomedicines. 10:25.10.3390/biomedicines10010025Search in Google Scholar PubMed PubMed Central
Cox JF, Tahvanainen KU, Kuusela TA, Levine BD, Cooke WH, Mano T, et al. 2002. Influence of microgravity on astronauts’ sympathetic and vagal responses to Valsalva’s manoeuvre. J Physiol. 538(1):309–320.10.1113/jphysiol.2001.012574Search in Google Scholar PubMed PubMed Central
Crucian BE, Choukèr A, Simpson R, Mehta S, Marshall G, Smith SM, et al. 2018. Immune system dysregulation during spaceflight: potential countermeasures for deep space exploration missions. Front Immunol. 9:1437.10.3389/fimmu.2018.01437Search in Google Scholar PubMed PubMed Central
Cucinotta FA, Alp M, Sulzman F, Wang MM. 2014. Space radiation risks to the central nervous system. Life Sci Space Res. 2:54–69.10.1016/j.lssr.2014.06.003Search in Google Scholar
Deane CS, Space Omics Topical T, da Silveira WA, Herranz R. 2022. Space omics research in Europe: Contributions, geographical distribution and ESA member state funding schemes. iScience. 25:103920.10.1016/j.isci.2022.103920Search in Google Scholar PubMed PubMed Central
Delp MD, Charvat JM, Limoli CL, Globus RK, Ghosh P. 2016. Apollo Lunar astronauts show higher cardiovascular disease mortality: possible deep space radiation effects on the vascular endothelium. Sci Rep. 6:29901.10.1038/srep29901Search in Google Scholar PubMed PubMed Central
Demontis G, Germani MM, Caiani EG, Barravecchia I, Passino C, Angeloni D. 2017. Human pathophysiological adaptations to the space environment. Front Physiol. 8:547.10.3389/fphys.2017.00547Search in Google Scholar PubMed PubMed Central
Doarn CR. 2011. Medical policy development for human spaceflight at NASA: an evolution. Aviation Space Environ Med. 82(11):1073–1077.10.3357/ASEM.3103.2011Search in Google Scholar PubMed
Gómez X, Sanon S, Zambrano K, Asquel S, Bassantes M, Morales JE, et al. 2021. Key points for the development of antioxidant cocktails to prevent cellular stress and damage caused by reactive oxygen species (ROS) during manned space missions. npj Microgravity. 7:35.10.1038/s41526-021-00162-8Search in Google Scholar PubMed PubMed Central
Goodenow-Messman DA, Gokoglu SA, Kassemi M, Myers JG. 2018. Numerical characterization of astronaut CaOx renal stone incidence rates to quantify in-flight and post-flight relative risk. npj Microgravity. 8:2.10.1038/s41526-021-00187-zSearch in Google Scholar PubMed PubMed Central
Grimm D, Grosse J, Wehland M, Mann V, Reseland JE, Sundaresan A, et al. 2016. The impact of microgravity on bone in humans. Bone. 87:44–56.10.1016/j.bone.2015.12.057Search in Google Scholar PubMed
Guo JH, Qu WM, Chen SG, Chen XP, Lv K, Huang ZL, et al. 2014. Keeping the right time in space: importance of circadian clock and sleep for physiology and performance of astronauts. Military Med Res. 1:23.10.1186/2054-9369-1-23Search in Google Scholar PubMed PubMed Central
Hupfeld KE, Richmond SB, McGregor HR, Schwartz DL, Luther MN, Beltran NE, et al. 2022. Longitudinal MRI-visible perivascular space (PVS) changes with long-duration spacefight. Sci Rep. 12:7238.10.1038/s41598-022-11593-ySearch in Google Scholar PubMed PubMed Central
Indo HP, Majima HJ, Terada M, Suenaga S, Tomita K, Yamada S, et al. 2016. Changes in mitochondrial homeostasis and redox status in astronauts following long stays in space. Sci Rep. 6:39015.10.1038/srep39015Search in Google Scholar PubMed PubMed Central
Iwasaki KI, Ogawa Y, Kurazumi T, Imaduddin SM, Mukai C, Furukawa S, et al. 2021. Long-duration spaceflight alters estimated intracranial pressure and cerebral blood velocity. J Physiol. 599(4):1067–1081.10.1113/JP280318Search in Google Scholar PubMed PubMed Central
Jiang Y. 2020. Debris cloud of India anti-satellite test to Microsat-R satellite. Heliyon. 6(8):e04692.10.1016/j.heliyon.2020.e04692Search in Google Scholar PubMed PubMed Central
Jiang Y, Li H, Yang Y. 2020. Evolution of space debris for spacecraft in the Sun-synchronous orbit. Open Astron. 29(1):265–274.10.1515/astro-2020-0024Search in Google Scholar
Jiang Y, Schmidt J. 2020. Motion of dust ejected from the surface of asteroid (101955) Bennu. Heliyon. 6(10):e05275.10.1016/j.heliyon.2020.e05275Search in Google Scholar PubMed PubMed Central
Jiang Y, Schmidt J, Baoyin H. 2017. Hamiltonian formulation and perturbations for dust motion around cometary nuclei. Earth Moon Planets. 120:147–168.10.1007/s11038-017-9509-6Search in Google Scholar
Jillings S, Van Ombergen A, Tomilovskaya E, Rumshiskaya A, Litvinova L, Nosikova I, et al. 2020. Macro- and microstructural changes in cosmonauts’ brains after long-duration spaceflight. Sci Adv. 6(36):eaaz9488.10.1126/sciadv.aaz9488Search in Google Scholar PubMed PubMed Central
Johnston SL, Blue RS, Jennings RT, Tarver WJ, Gray GW. 2014. Astronaut medical selection during the shuttle era: 1981–2011. Aviation Space Environ Med. 85(8):823–827.10.3357/ASEM.3968.2014Search in Google Scholar PubMed
Komorowski M, Fleming S, Mawkin M, Hinkelbein J. 2018. Anaesthesia in austere environments: literature review and considerations for future space exploration missions. npj Microgravity. 4:5.10.1038/s41526-018-0039-ySearch in Google Scholar PubMed PubMed Central
Luxton JJ, McKenna MJ, Lewis A. 2020. Telomere length dynamics and DNA damage responses associated with long-duration spaceflight. Cell Rep. 33:108457.10.1016/j.celrep.2020.108457Search in Google Scholar PubMed
Mark S, Scott GB, Donoviel DB, Leveton LB, Mahoney E, Charles JB, et al. 2014. The impact of sex and gender on adaptation to space: executive summary. J Women’s Health. 23(11):941–947.10.1089/jwh.2014.4914Search in Google Scholar PubMed PubMed Central
Michalski AS, Amin S, Cheung AM, Cody DD, Keyak JH, Lang TF, et al. 2019. Hip load capacity cut-points for Astronaut Skeletal Health NASA finite element strength task group recommendations. npj Microgravity, 5:6.10.1038/s41526-019-0066-3Search in Google Scholar PubMed PubMed Central
Moore ST, Dilda V, Morris TR. 2019. Long-duration spaceflight adversely affects post-landing operator proficiency. Sci Rep. 9:2677.10.1038/s41598-019-39058-9Search in Google Scholar PubMed PubMed Central
Myrrhe J, Istasse E, Singh N, et al. 2020. Fundamental biological features of spaceflight: advancing the field to enable deep-space exploration. Cell 183:1162–1184.10.1016/j.cell.2020.10.050Search in Google Scholar PubMed PubMed Central
Otsuka K, Cornelissen G, Furukawa S, Kubo Y, Hayashi M, Shibata K, et al. 2017. Long-term exposure to space’s microgravity alters the time structure of heart rate variability of astronauts. Heliyon. 3:e00211.10.1016/j.heliyon.2016.e00211Search in Google Scholar PubMed PubMed Central
Parazynski SE. 2006. From model rockets to spacewalks: an astronaut physician’s journey and the science of the United States’ space program. Trans Am Clin Climatol Assoc. 117:273–281.Search in Google Scholar
Pavez Loriè E, Baatout S, Choukér A, Buchheim JI, Baselet B, Dello Russo C, et al. 2021. The future of personalized medicine in space: from observations to countermeasures. Front Bioeng Biotechnol. 9:739747.10.3389/fbioe.2021.739747Search in Google Scholar PubMed PubMed Central
Peterson LE, Kovyrshina T. 2015. Adjustment of lifetime risks of space radiation-induced cancer by the healthy worker effect and cancer misclassification. Heliyon. 1(4):e00048.10.1016/j.heliyon.2015.e00048Search in Google Scholar PubMed PubMed Central
Petersen N, Thieschäfer L, Ploutz-Snyder L, Damann V, Mester J. 2015. Reliability of a new test battery for fitness assessment of the European Astronaut corps. Extreme Physiol Med. 4:12.10.1186/s13728-015-0032-ySearch in Google Scholar PubMed PubMed Central
Petersen N, Jaekel P, Rosenberger A, Weber T, Scott J, Castrucci F, et al. 2016. Exercise in space: the European Space Agency approach to in-flight exercise countermeasures for long-duration missions on ISS. Extreme Physiol Med. 5:9.10.1186/s13728-016-0050-4Search in Google Scholar PubMed PubMed Central
Garrett-Bakelman FE, Darshi M, Green SJ, Gur RC, Lin L, Macias BR, et al. 2013. The NASA twins study: A multidimensional analysis of a year-long human spaceflight. Science. 364(6436):eaau8650.10.1126/science.aau8650Search in Google Scholar PubMed PubMed Central
Schmidt MA, Goodwin TJ. 2013. Personalized medicine in human space flight: using Omics based analyses to develop individualized countermeasures that enhance astronaut safety and performance. Metabolomics. 9(6):1134–1156.10.1007/s11306-013-0556-3Search in Google Scholar PubMed PubMed Central
Scott JM, Downs M, Martin DS, Hougland E, Sarmiento L, Arzeno N, et al. 2021. Teleguided self-ultrasound scanning for longitudinal monitoring of muscle mass during spaceflight. iScience. e24:102344.10.1016/j.isci.2021.102344Search in Google Scholar PubMed PubMed Central
Smith MG, Kelley M, Basner M. 2020. A brief history of spaceflight from 1961 to 2020: An analysis of missions and astronaut demographics. Acta Astronaut. 175:290–299.10.1016/j.actaastro.2020.06.004Search in Google Scholar PubMed PubMed Central
Stabler RA, Rosado H, Doyle R, Negus D, Carvil PA, Kristjánsson JG, et al. 2017. Impact of the Mk VI SkinSuit on skin microbiota of terrestrial volunteers and an International Space Station-bound astronaut. npj Microgravity. 23:23.10.1038/s41526-017-0029-5Search in Google Scholar PubMed PubMed Central
Sun W, Jia X, Xie T, Xu F, Liu Q. 2013. Construction of boundary-surface-based Chinese female astronaut computational phantom and proton dose estimation. J Radiat Res. 54:383–397.10.1093/jrr/rrs100Search in Google Scholar PubMed PubMed Central
Tanaka K, Nishimura N, Kawai Y. 2017. Adaptation to microgravity, deconditioning, and countermeasures. J Physiol Sci. 67:271–281.10.1007/s12576-016-0514-8Search in Google Scholar PubMed
Tang H, Rising HH, Majji M, Brown RD. 2021. Long-term space nutrition: a scoping review. Nutrients. 14(1):194.10.3390/nu14010194Search in Google Scholar PubMed PubMed Central
Tesei D, Jewczynko A, Lynch A, Urbaniak C. 2022. Understanding the complexities and changes of the astronaut microbiome for successful long-duration space missions. Life. 12:145.10.3390/life12040495Search in Google Scholar PubMed PubMed Central
Walsh L, Hafner L, Straube U, Ulanowski A, Fogtman A, Durante M, et al. 2021. A bespoke health risk assessment methodology for the radiation protection of astronauts. Radiat Environ Biophysics. 60(2):213–231.10.1007/s00411-021-00910-0Search in Google Scholar PubMed PubMed Central
Willey JS, Britten RA, Blaber E, Tahimic C, Chancellor J, Mortreux M, et al. 2021. The individual and combined effects of spaceflight radiation and microgravity on biologic systems and functional outcomes. J Env Sci Health C Toxicol Carcinog. 39(2):129–179.10.1080/26896583.2021.1885283Search in Google Scholar PubMed PubMed Central
Winnard A, Scott J, waters N, Vance M, Caplan N. 2019. Effect of time on human muscle outcomes during simulated microgravity exposure without countermeasures-systematic review. Front Physiol. 10:1046.10.3389/fphys.2019.01046Search in Google Scholar PubMed PubMed Central
Wu B, Wang Y, Wu X, Liu D, Xu D, Wang F. 2018. On-orbit sleep problems of astronauts and countermeasures. Military Med Res. 5:17.10.1186/s40779-018-0165-6Search in Google Scholar PubMed PubMed Central
Zhang LF, Hargens A. 2018. Spaceflight-induced intracranial hypertension and visual impairment: pathophysiology and countermeasures. Physiol Rev. 98(1):59–87.10.1152/physrev.00017.2016Search in Google Scholar PubMed
© 2022 Xinhua Cao, published by De Gruyter
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