Immune sensitization during 1 year in the Antarctic high-altitude Concordia Environment.

BACKGROUND: Antarctica is a challenging environment for humans. It serves as a spaceflight ground analog, reflecting some conditions of long-duration exploration class space missions. The French-Italian Concordia station in interior Antarctica is a high-fidelity analog, located 1000 km from the coast, at an altitude of 3232 m. The aim of this field study was to characterize the extent, dynamics, and key mechanisms of the immune adaptation in humans overwintering at Concordia for 1 year. METHODS: This study assessed immune functions in fourteen crewmembers. Quantitative and phenotypic analyses from human blood were performed using onsite flow cytometry together with specific tests on receptor-dependent and receptor-independent functional innate and adaptive immune responses. Transcriptome analyses and quantitative identification of key response genes were assessed. RESULTS: Dynamic immune activation and a two-step escalation/activation pattern were observed. The early phase was characterized by moderately sensitized global immune responses, while after 3-4 months, immune responses were highly upregulated. The cytokine responses to an ex vivo stimulation were markedly raised above baseline levels. These functional observations were reflected at the gene transcriptional level in particular through the modulation of hypoxia-driven pathways. CONCLUSIONS: This study revealed unique insights into the extent, dynamics, and genetics of immune dysfunctions in humans exposed for 1 year to the Antarctic environment at the Concordia station. The scale of immune function was imbalanced toward a sensitizing of inflammatory pathways.

Increased dietary iron and radiation in rats promote oxidative stress, induce localized and systemic immune system responses, and alter colon mucosal environment.

Astronauts are exposed to increased body iron stores and radiation, both of which can cause oxidative damage leading to negative health effects. The purpose of this study was to investigate combined effects of high dietary iron (650 mg/kg diet) and radiation exposure (0.375 Gy cesium-137 every other day for 16 d) on markers of oxidative stress, immune system function, and colon mucosal environment in male Sprague-Dawley rats (n=8/group). Control rats consumed adequate iron (45 mg/kg diet) and were not irradiated. Combined treatments increased liver glutathione peroxidase, serum catalase, and colon myeloperoxidase while decreasing total fecal short-chain fatty acid concentrations. The high-iron diet alone increased leukocyte count. Radiation decreased the T-cell CD4:CD8 ratio. Plasma iron was negatively correlated with cytokine production in activated monocytes. Genes involved in colon microbial signaling, immune response, and injury repair were altered by radiation. Genes involved with injury repair and pathogen recognition changed with dietary iron. These data demonstrate that dietary iron and radiation, alone and combined, contribute to oxidative stress that is related to immune system alterations in circulation and the colon. The model presented may help us better understand the changes to these systems that have been identified among astronauts.

Terrestrial stress analogs for spaceflight associated immune system dysregulation.

Recent data indicates that dysregulation of the immune system occurs and persists during spaceflight. Impairment of immunity, especially in conjunction with elevated radiation exposure and limited clinical care, may increase certain health risks during exploration-class deep space missions (i.e. to an asteroid or Mars). Research must thoroughly characterize immune dysregulation in astronauts to enable development of a monitoring strategy and validate any necessary countermeasures. Although the International Space Station affords an excellent platform for on-orbit research, access may be constrained by technical, logistical vehicle or funding limitations. Therefore, terrestrial spaceflight analogs will continue to serve as lower cost, easier access platforms to enable basic human physiology studies. Analog work can triage potential in-flight experiments and thus result in more focused on-orbit studies, enhancing overall research efficiency. Terrestrial space analogs generally replicate some of the physiological or psychological stress responses associated with spaceflight. These include the use of human test subjects in a laboratory setting (i.e. exercise, bed rest, confinement, circadian misalignment) and human remote deployment analogs (Antarctica winterover, undersea, etc.) that incorporate confinement, isolation, extreme environment, physiological mission stress and disrupted circadian rhythms. While bed rest has been used to examine the effects of physical deconditioning, radiation and microgravity may only be simulated in animal or microgravity cell culture (clinorotation) analogs. This article will characterize the array of terrestrial analogs for spaceflight immune dysregulation, the current evidence base for each, and interpret the analog catalog in the context of acute and chronic stress.

Integrating Cultural Humility into Medical Education Using a Structured and Interactive Workshop.

Background: Cultural humility is a lifelong commitment to self-evaluation, redressing power imbalances in patient-physician relationships and developing mutually trusting beneficial partnerships. Objective: The objective of this study was to determine the feasibility and efficacy of cultural humility training. Methods: From July 2020-March 2021, 90-minute educational workshops attended by 133 medical students, resident physicians and medical education faculty included 1) pre- and post- intervention surveys; 2) interactive presentation on equity and cultural humility principles; 3) participants explored sociocultural identities and power; and 4) reflective group discussions. Results: There were significant increases from pre to post intervention assessments for perception scores (3.89 [SEM= 0.04] versus 4.22 [0.08], p<0.001) and knowledge scores (0.52 [0.02] versus 0.67 [0.02], p<0.001). Commonest identities participants recognized as changing over time were personality = 40%, appearance = 36%, and age =35%. Commonest identities experienced as oppressed/subjugated were race/ethnicity = 54%, gender = 40% and religion = 28%; whilst commonest identities experienced as privileged were gender= 49%, race/ethnicity = 42% and appearance= 25%. Male participants assigned mean power score of 73% to gender identity compared to mean power score of -8% by female participants (P<0.001). Non-Hispanic Whites had mean power score for race identity of 62% compared to 13% for non-white participants (p<0.001). English as a second language was only acknowledged as an oppressed/subjugated identity by those born outside the United States (p<0.001). Conclusion: An interactive educational workshop can increase participants' knowledge and perceptions regarding cultural humility. Participants can self-reflect to recognize sociocultural identities that are oppressed/subjugated or privileged.

Immune system dysregulation occurs during short duration spaceflight on board the space shuttle.

BACKGROUND: Post-flight data suggests immunity is dysregulated immediately following spaceflight, however this data may be influenced by the stress effects of high-G entry and readaptation to terrestrial gravity. It is unknown if immunity is altered during spaceflight. METHODS: Blood samples were collected from 19 US Astronauts onboard the Space Shuttle ~24 h prior to landing and returned for terrestrial analysis. Assays consisted of leukocyte distribution, T cell blastogenesis and cytokine production profiles. RESULTS: Most bulk leukocyte subsets (WBC, differential, lymphocyte subsets) were unaltered during spaceflight, but were altered following landing. CD8+ T cell subsets, including cytotoxic, central memory and senescent were altered during spaceflight. T cell early blastogenesis varied by culture mitogen. Functional responses to staphylococcal enterotoxin were reduced during and following spaceflight, whereas response to anti-CD3/28 antibodies was elevated post-flight. The level of virus specific T cells were generally unaltered, however virus specific T cell function was depressed both during and following flight. Plasma levels of IFNα, IFNγ, IL-1ß, IL-4, IL-10, IL-12, and TNFα were significantly elevated in-flight, while IL-6 was significantly elevated at R + 0. Cytokine production profiles following mitogenic stimulation were significantly altered both during, and following spaceflight. Specifically, production of IFNγ, IL-17 and IL-10 were reduced, but production of TNFα and IL-8 were elevated during spaceflight. CONCLUSIONS: This study indicates that specific parameters among leukocyte distribution, T cell function and cytokine production profiles are altered during flight. These findings distinguish in-flight dysregulation from stress-related alterations observed immediately following landing.

Reduced fibrous capsule elastic fibers from biologic ECM-enveloped CIEDs in minipigs, supported with a novel compression mechanics model.

BACKGROUND: Fibrous capsules (Fb) in response to cardiovascular implantable electronic devices (CIEDs), including a pacemaker (P) system, can produce patient discomfort and difficulties in revision surgery due partially to their increased compressive strength, previously linked to elevated tissue fibers. OBJECTIVE: A preliminary study to quantify structural proteins, determine if biologic extracellular matrix-enveloped CIEDs (PECM) caused differential Fb properties, and to implement a realistic mechanical model. METHODS: Retrieved Fb (-P and -PECM) from minipigs were subjected to biomechanical (shear oscillation and uniaxial compression) and histological (collagen I and elastin) analyses. RESULTS: Fb-PECM showed significant decreases compared to Fb-P in: low strain-loss modulus (390 vs. 541 Pa) across angular frequencies, high strain-compressive elastic modulus (1043 vs. 2042 kPa), and elastic fiber content (1.92 vs. 3.15 µg/mg tissue). Decreases in elastin were particularly noted closer to the implant's surface (Fb-PECM = 71% vs. Fb-P = 143% relative to dermal elastin at mid-tangential sections) and verified with a solid mechanics hyperelasticity with direction-dependent fiber viscoelasticity compression simulation (r2 ≥ 98.9%). CONCLUSIONS: The biologic envelope composed of decellularized porcine small intestine submucosa ECM for CIEDs promoted fibrous tissues with less elastic fibers. Novel compression modeling analyses directly correlated this singular reduction to more desirable subcutaneous tissue mechanics.

Latent and lytic Epstein-Barr virus gene expression in the peripheral blood of astronauts.

Epstein-Barr virus (EBV) latent and replicative gene transcription was analyzed in peripheral blood B-lymphocytes from astronauts who flew on short-duration (∼11 days) Shuttle missions and long-duration (∼180 days) International Space Station (ISS) missions. Latent, immediate-early, and early gene replicative viral transcripts were detected in samples from six astronauts who flew on short-duration Shuttle missions, whereas viral gene transcription was mostly absent in samples from 24 healthy donors. Samples from six astronauts who flew on long-duration ISS missions were characterized by expanded expression of latent, immediate-early, and early gene transcripts and new onset expression of late replicative transcription upon return to Earth. These data indicate that EBV-infected cells are no longer expressing the restricted set of viral genes that characterize latency but are expressing latent and lytic gene transcripts. These data also suggest the possibility of EBV-related complications in future long-duration missions, in particular interplanetary travel.

Adrenocortical and immune responses following short- and long-duration spaceflight.

INTRODUCTION: Short-term spaceflight is associated with significant but reversible immunological alterations. However, little information exists on the effects of long-duration spaceflight on neuroimmune responses. METHODS: We collected multiple pre- and postflight samples from Shuttle and International Space Station (ISS) crewmembers in order to compare adrenocortical and immune responses between short- (approximately 11 d) and long-duration (approximately 180 d) spaceflight. RESULTS: In Shuttle crewmembers, increased stress hormone levels and altered leukocyte subsets were observed prior to launch and at landing. Additionally, typical stress-induced shifts in leukocyte and lymphocyte subsets, as well as the percentage of T-cells capable of producing intracellular IFN-gamma were also decreased just before launch and immediately after landing. Plasma IL-10 levels were increased before launch but not postflight. No preflight changes occurred in ISS crewmembers, but long-duration crewmembers exhibited significantly greater spikes in both plasma and urinary cortisol at landing as compared to Shuttle crewmembers. The percentage of T-cells capable of producing intracellular IFN-gamma was decreased in ISS crewmembers. Plasma IL-10 was increased postflight. Unexpectedly, stress-induced shifts in lymphocyte subpopulations were absent after long-duration flights despite significantly increased stress hormones at landing. CONCLUSION: Our results demonstrate significant differences in neuroimmune responses between astronauts flying on short-duration Shuttle missions versus long-duration ISS missions, and they agree with prior studies demonstrating the importance of mission duration in the magnitude of these changes.

Monocyte phenotype and cytokine production profiles are dysregulated by short-duration spaceflight.

INTRODUCTION: Immune system dysregulation has been demonstrated to occur during and immediately following spaceflight. As the initial bias and magnitude for an immune response is heavily influenced by monocyte/macrophage secreted cytokines, this study investigated monocyte phenotype and cytokine production patterns following short-duration spaceflight. METHODS: Secreted cytokine profiles were examined by cytometric bead array analysis of culture supernatants following whole blood culture activation with LPS or PMA+ionomycin. Nine short-duration Space Shuttle crewmembers participated in this study. RESULTS: Peripheral monocyte percentages were unaltered postflight. Constitutive monocyte expression of both CD62L and HLA-DR was reduced following spaceflight in a mission-specific fashion. Loss of either molecule indicates a functional disability of monocytes, either by inhibition of adhesion and tissue migration (CD62L) or by impaired antigen presentation (HLA-DR). Following LPS stimulation of monocytes, postflight expression of IL-6, TNFalpha, and IL-10 were significantly reduced (by 43%, 44%, and 41%, respectively) and expression of IL-1b was elevated (65%). IL-8 production was either elevated or reduced in a mission-specific fashion. Following PMA+ionomycin stimulation of all leukocyte populations, only expression of IL-6 was significantly reduced postflight. DISCUSSION: These data indicate that changes in monocyte constitutive phenotype and inflammatory cytokine production occur following short-duration spaceflight, which may impact overall crewmember immunocompetence. Also, monocyte/macrophage function may be highly sensitive to mission specific parameters.

The influence of spaceflight on the astronaut salivary microbiome and the search for a microbiome biomarker for viral reactivation.

BACKGROUND: Spaceflight impacts astronauts in many ways but little is known on how spaceflight affects the salivary microbiome and the consequences of these changes on astronaut health, such as viral reactivation. In order to understand this, the salivary microbiome was analyzed with 16S rRNA gene amplicon sequencing, and saliva viral titers were analyzed with quantitative polymerase chain reaction (qPCR) with primers specific for Epstein-Barr virus (EBV), herpes simplex virus (HSV), and varicella zoster virus (VZV) from 10 astronauts pre-flight, in-flight, and post-flight. RESULTS: Streptococcus was the most abundant organism in the saliva, making up 8% of the total organisms detected, and their diversity decreased during spaceflight. Other organisms that had statistically significant changes were Proteobacteria and Fusobacteria which increased during flight and Actinobacteria which decreased during flight. At the genus level, Catonella, Megasphera, and Actinobacillus were absent in more than half of saliva samples collected pre-flight but were then detected during flight. In those subjects that already had these genera pre-flight, their relative abundances increased during flight. Correlation analyses between the microbiome and viral titers revealed a positive correlation with Gracilibacteria, Absconditabacteria, and Abiotrophia and a negative correlation between Oribacterium, Veillonella, and Haemophilus. There was also a significant positive correlation between microbiome richness and EBV viral titers. CONCLUSIONS: This is the first study to look at how the salivary microbiome changes as a result of spaceflight and the search for bacterial biomarkers for viral reactivation. Further studies examining the role of specific organisms that were shown to be correlative and predictive in viral reactivation, a serious problem in astronauts during spaceflight, could lead to mitigation strategies to help prevent disease during both short and long duration space missions. Video abstract.

Countermeasures-based Improvements in Stress, Immune System Dysregulation and Latent Herpesvirus Reactivation onboard the International Space Station - Relevance for Deep Space Missions and Terrestrial Medicine.

The International Space Station (ISS) has continued to evolve from an operational perspective and multiple studies have monitored both stress and the immune system of ISS astronauts. Alterations were ascribed to a potentially synergistic array of factors, including microgravity, radiation, psychological stress, and circadian misalignment. Comparing similar data across 12 years of ISS construction and operations, we report that immunity, stress, and the reactivation of latent herpesviruses have all improved in ISS astronauts. Major physiological improvements seem to have initiated approximately 2012, a period coinciding with improvements onboard ISS including cargo delivery and resupply frequency, personal communication, exercise equipment and protocols, food quality and variety, nutritional supplementation, and schedule management. We conclude that spaceflight associated immune dysregulation has been positively influenced by operational improvements and biomedical countermeasures onboard ISS. Although an operational challenge, agencies should therefore incorporate, within vehicle design limitations, these dietary, operational, and stress-relieving countermeasures into deep space mission planning. Specific countermeasures that have benefited astronauts could serve as a therapy augment for terrestrial acquired immunodeficiency patients.

Effect of potassium citrate therapy on the risk of renal stone formation during spaceflight.

PURPOSE: Exposure to microgravity affects human physiology and results in changes in urinary chemical composition during and after spaceflight, favoring an increased risk of renal stones. We assessed the efficacy of potassium citrate to decrease the stone risk during and after spaceflight. MATERIALS AND METHODS: The study was done in 30 long duration spaceflight crew members to the space stations Mir and International Space Station. Before, during and after spaceflight 24-hour urine samples were collected to assess the renal stone risk. Potassium citrate (20 mEq) was ingested daily by International Space Station crew members in a double-blind, placebo controlled study. Mir crew members performed the identical protocol but did not ingest medication. RESULTS: Potassium citrate treated crew members had decreased urinary calcium excretion and maintained the calcium oxalate supersaturation risk at preflight levels compared to that in controls. Increased urinary pH in the treatment group decreased the risk of uric acid stones. CONCLUSIONS: Results from this investigation suggest that supplementation with potassium citrate may decrease the risk of renal stone formation during and immediately after spaceflight.

Immune status, latent viral reactivation, and stress during long-duration head-down bed rest.

INTRODUCTION: As logistical access for space research becomes more limited and NASA prepares for exploration-class missions, ground-based spaceflight analogs will increase in importance for biomedical countermeasures development. A monitoring of immune parameters was performed during the NASA Flight Analogs Project bed rest study (without countermeasure); to establish 'control' data against which future studies (with countermeasure) will be evaluated. Some of the countermeasures planned to be evaluated in future studies may impact immune function. METHODS: The immune assessment consisted of: leukocyte subset distribution, early T cell activation, intracellular cytokine profiles, latent viral reactivation, virus specific T cell levels and function, stress hormone levels, and a behavioral assessment using stress questionnaires. RESULTS: In general, subjects did not display altered peripheral leukocyte subsets, constitutive immune activation, altered T cell function, or significant latent viral reactivation (EBV, VZV). Levels of constitutively activated T cells (CD8+/CD69+) and virus-specific T cells (CMV and EBV) decreased during the study. Cortisol levels (plasma and saliva) did not vary significantly during 90-d bed rest. CONCLUSIONS: These data demonstrate the absence of significant immune system alteration and physiological stress during 90-d bed rest, and establish control data against which future studies (including countermeasures) may be compared.

Immune system dysregulation following short- vs long-duration spaceflight.

INTRODUCTION: Immune system dysregulation has been demonstrated to occur during and immediately following spaceflight. If found to persist during lengthy flights, this phenomenon could be a serious health risk to crewmembers participating in lunar or Mars missions. METHODS: A comprehensive postflight immune assessment was performed on 17 short-duration Space Shuttle crewmembers and 8 long-duration International Space Station (ISS) crewmembers. Testing consisted of peripheral leukocyte subset analysis, early T cell activation potential, and intracellular/secreted cytokine profiles. RESULTS: For Shuttle crewmembers, the distribution of the peripheral leukocyte subsets was found to be altered postflight. Early T cell activation was elevated postflight; however, the percentage of T cell subsets capable of being stimulated to produce IL-2 and IFN gamma was decreased. The ratio of secreted IFN gamma:IL-10 following T cell stimulation declined after landing, indicating a Th2 shift. For the ISS crewmembers, some alterations in peripheral leukocyte distribution were also detected after landing. In contrast to Shuttle crewmembers, the ISS crewmembers demonstrated a statistically significant reduction in early T cell activation potential immediately postflight. The percentage of T cells capable of producing IL-2 was reduced, but IFN gamma percentages were unchanged. A reduction in the secreted IFN gamma:IL-10 ratio (Th2 shift) was also observed postflight in the ISS crewmembers. CONCLUSION: These data indicate that consistent peripheral phenotype changes and altered cytokine production profiles occur following spaceflight of both short and long duration; however, functional immune dysregulation may vary related to mission duration. In addition, a detectable Th2 cytokine shift appears to be associated with spaceflight.

Neuroendocrine and immune responses to 16-day bed rest with realistic launch and landing G profiles.

BACKGROUND: Spaceflight is associated with increased glucocorticoids and catecholamines, both well-known for their immunosuppressive effects. The objective of this study was to develop a model of spaceflight by using a human centrifuge to reproduce launch and landing G forces along with bed rest to simulate microgravity. HYPOTHESIS: Acute changes in G forces are causal factors in neuroendocrine and immune changes. METHODS: Ten subjects underwent realistic launch G-force profiles followed by 16 d of 60 head-down tilt bed rest. At the end of the bed rest, subjects were subjected to realistic landing G-force profiles. Stress hormones and changes in leukocyte and lymphocyte subsets were measured in blood and urine samples over the course of the study. RESULTS: Similar to shorter Shuttle missions (i.e., < or = 9 d), plasma cortisol was significantly decreased at simulated landing while urinary epinephrine was significantly increased. Urinary cortisol was significantly increased after simulated launch. The pattern of leukocyte and lymphocyte changes also mirrored the changes found in shorter 9-d spaceflights. CONCLUSIONS: These data suggest a role for both catecholamines and glucocorticoids in mediating changes in leukocyte and lymphocyte subsets during simulated microgravity coupled with hypergravity. Our results were also strikingly similar to those from actual Shuttle missions and support our conclusion that we have developed a model of spaceflight.

Immune System Dysregulation During Spaceflight: Potential Countermeasures for Deep Space Exploration Missions.

Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered. Some crews experience persistent hypersensitivity reactions during flight. This phenomenon may, in synergy with extended duration and galactic radiation exposure, increase specific crew clinical risks during deep space exploration missions. The clinical challenge is based upon both the frequency of these phenomena in multiple crewmembers during low earth orbit missions and the inability to predict which specific individual crewmembers will experience these changes. Thus, a general countermeasure approach that offers the broadest possible coverage is needed. The vehicles, architecture, and mission profiles to enable such voyages are now under development. These include deployment and use of a cis-Lunar station (mid 2020s) with possible Moon surface operations, to be followed by multiple Mars flyby missions, and eventual human Mars surface exploration. Current ISS studies will continue to characterize physiological dysregulation associated with prolonged orbital spaceflight. However, sufficient information exists to begin consideration of both the need for, and nature of, specific immune countermeasures to ensure astronaut health. This article will review relevant in-place operational countermeasures onboard ISS and discuss a myriad of potential immune countermeasures for exploration missions. Discussion points include nutritional supplementation and functional foods, exercise and immunity, pharmacological options, the relationship between bone and immune countermeasures, and vaccination to mitigate herpes (and possibly other) virus risks. As the immune system has sentinel connectivity within every other physiological system, translational effects must be considered for all potential immune countermeasures. Finally, we shall discuss immune countermeasures in the context of their individualized implementation or precision medicine, based on crewmember specific immunological biases.

Immune system changes during simulated planetary exploration on Devon Island, high arctic.

BACKGROUND: Dysregulation of the immune system has been shown to occur during spaceflight, although the detailed nature of the phenomenon and the clinical risks for exploration class missions have yet to be established. Also, the growing clinical significance of immune system evaluation combined with epidemic infectious disease rates in third world countries provides a strong rationale for the development of field-compatible clinical immunology techniques and equipment. In July 2002 NASA performed a comprehensive immune assessment on field team members participating in the Haughton-Mars Project (HMP) on Devon Island in the high Canadian Arctic. The purpose of the study was to evaluate the effect of mission-associated stressors on the human immune system. To perform the study, the development of techniques for processing immune samples in remote field locations was required. Ten HMP-2002 participants volunteered for the study. A field protocol was developed at NASA-JSC for performing sample collection, blood staining/processing for immunophenotype analysis, whole-blood mitogenic culture for functional assessments and cell-sample preservation on-location at Devon Island. Specific assays included peripheral leukocyte distribution; constitutively activated T cells, intracellular cytokine profiles, plasma cortisol and EBV viral antibody levels. Study timepoints were 30 days prior to mission start, mid-mission and 60 days after mission completion. RESULTS: The protocol developed for immune sample processing in remote field locations functioned properly. Samples were processed on Devon Island, and stabilized for subsequent analysis at the Johnson Space Center in Houston. The data indicated that some phenotype, immune function and stress hormone changes occurred in the HMP field participants that were largely distinct from pre-mission baseline and post-mission recovery data. These immune changes appear similar to those observed in astronauts following spaceflight. CONCLUSION: The immune system changes described during the HMP field deployment validate the use of the HMP as a ground-based spaceflight/planetary exploration analog for some aspects of human physiology. The sample processing protocol developed for this study may have applications for immune studies in remote terrestrial field locations. Elements of this protocol could possibly be adapted for future in-flight immunology studies conducted during space missions.

Renal stone formation among astronauts.

INTRODUCTION: With the continued construction of the International Space Station, humans are living longer in the microgravity environment of space. However, many questions still exist as to the physiological effects of spaceflight on the human body. Bone loss, cardiovascular changes, and muscle atrophy are well-documented health risks to humans during spaceflight. Another potential serious health complication is the development of renal stones. The development of a renal stone may not only impact the health of the crewmember, but also the success of the mission. METHODS: A retrospective analysis of astronaut data from 24-h urine samples collected prior to launch and immediately after landing was performed. Urine characteristics associated with renal stone formation were analyzed and the relative injury supersaturations of stone-forming constituents calculated. RESULTS: In the current study, previously collected data to identify urinary factors associated with renal stone formation demonstrated an increased risk in astronauts who had actually formed a renal stone. Increased urinary supersaturation of the stone-forming salts was observed in those astronauts who formed renal stones. Similar changes in urinary supersaturation were noted among many astronauts after landing, indicating an increased postflight risk for stone formation. CONCLUSIONS: An assessment program should be undertaken to identify and evaluate astronauts with elevated risk factors prior to flight and immediately following landing. Individualized recommendations can be prescribed to astronauts and may include dietary changes, increased fluid intake, or medications to minimize the risk of stone formation.

Alterations in hematologic indices during long-duration spaceflight.

BACKGROUND: Although a state of anemia is perceived to be associated with spaceflight, to date a peripheral blood hematologic assessment of red blood cell (RBC) indices has not been performed during long-duration space missions. METHODS: This investigation collected whole blood samples from astronauts participating in up to 6-months orbital spaceflight, and returned those samples (ambient storage) to Earth for analysis. As samples were always collected near undock of a returning vehicle, the delay from collection to analysis never exceeded 48 h. As a subset of a larger immunologic investigation, a complete blood count was performed. A parallel stability study of the effect of a 48 h delay on these parameters assisted interpretation of the in-flight data. RESULTS: We report that the RBC and hemoglobin were significantly elevated during flight, both parameters deemed stable through the delay of sample return. Although the stability data showed hematocrit to be mildly elevated at +48 h, there was an in-flight increase in hematocrit that was ~3-fold higher in magnitude than the anticipated increase due to the delay in processing. CONCLUSIONS: While susceptible to the possible influence of dehydration or plasma volume alterations, these results suggest astronauts do not develop persistent anemia during spaceflight.

Latent virus reactivation in astronauts on the international space station.

Reactivation of latent herpes viruses was measured in 23 astronauts (18 male and 5 female) before, during, and after long-duration (up to 180 days) spaceflight onboard the international space station . Twenty age-matched and sex-matched healthy ground-based subjects were included as a control group. Blood, urine, and saliva samples were collected before, during, and after spaceflight. Saliva was analyzed for Epstein-Barr virus, varicella-zoster virus, and herpes simplex virus type 1. Urine was analyzed for cytomegalovirus. One astronaut did not shed any targeted virus in samples collected during the three mission phases. Shedding of Epstein-Barr virus, varicella-zoster virus, and cytomegalovirus was detected in 8 of the 23 astronauts. These viruses reactivated independently of each other. Reactivation of Epstein-Barr virus, varicella-zoster virus, and cytomegalovirus increased in frequency, duration, and amplitude (viral copy numbers) when compared to short duration (10 to 16 days) space shuttle missions. No evidence of reactivation of herpes simplex virus type 1, herpes simplex virus type 2, or human herpes virus 6 was found. The mean diurnal trajectory of salivary cortisol changed significantly during flight as compared to before flight (P = 0.010). There was no statistically significant difference in levels of plasma cortisol or dehydoepiandosterone concentrations among time points before, during, and after flight for these international space station crew members, although observed cortisol levels were lower at the mid and late-flight time points. The data confirm that astronauts undertaking long-duration spaceflight experience both increased latent viral reactivation and changes in diurnal trajectory of salivary cortisol concentrations.