Modern Magnetic Resonance Imaging Modalities to Advance Neuroimaging in Astronauts.

INTRODUCTION: The rapid development of the space industry requires a deeper understanding of spaceflight's impact on the brain. MRI research reports brain volume changes following spaceflight in astronauts, potentially affecting cognition. Recently, we have demonstrated that this evidence of volumetric changes, as measured by typical T1-weighted sequences (e.g., magnetization-prepared rapid gradient echo sequence; MPRAGE), is error-prone due to the microgravity-related redistribution of cerebrospinal fluid in the brain. More modern neuroimaging methods, particularly dual-echo MPRAGE (DEMPRAGE) and magnetization-prepared rapid gradient echo sequence utilizing two inversion pulses (MP2RAGE), have been suggested to be resilient to this error. Here, we tested if these imaging modalities offered consistent segmentation performance improvements in some commonly employed neuroimaging software packages.METHODS: We conducted manual gray matter tissue segmentation in traditional T1w MRI images to utilize for comparison. Automated tissue segmentation was performed for traditional T1w imaging, as well as on DEMPRAGE and MP2RAGE images from the same subjects. Statistical analysis involved a comparison of total gray matter volumes for each modality, and the extent of tissue segmentation agreement was assessed using a test of similarity (Dice coefficient).RESULTS: Neither DEMPRAGE nor MP2RAGE exhibited consistent segmentation performance across all toolboxes tested.DISCUSSION: This research indicates that customized data collection and processing methods are necessary for reliable and valid structural MRI segmentation in astronauts, as current methods provide erroneous classification and hence inaccurate claims of neuroplastic brain changes in the astronaut population.Berger L, Burles F, Jaswal T, Williams R, Iaria G. Modern magnetic resonance imaging modalities to advance neuroimaging in astronauts. Aerosp Med Hum Perform. 2024; 95(5):245-253.

Photorefractive Keratectomy and Laser-Assisted In Situ Keratomileusis on 6-Month Space Missions.

BACKGROUND: This article documents the stability of photorefractive keratectomy (PRK) and laser-assisted in situ keratomileusis (LASIK) in two astronauts during 6-mo missions to the International Space Station.CASE REPORTS: Ocular examinations including visual acuity, cycloplegic refraction, slit lamp examination, corneal topography, central corneal thickness, optical biometry (axial length/keratometry), applanation tonometry, and dilated fundus examination were performed on each astronaut before and after their missions, and in-flight visual acuity testing was done on flight day 30, 90, and R-30 (30 d before return). They were also questioned regarding visual changes during flight.DISCUSSION: We documented stable vision in both PRK and LASIK astronauts during liftoff, entry into microgravity, 6 mo on the International Space Station, descent, and landing. Our results suggest that both PRK and LASIK are stable and well tolerated during long-duration spaceflight.Gibson CR, Mader TH, Lipsky W, Schallhorn SC, Tarver WJ, Suresh R, Hauge TN, Brunstetter TJ. Photorefractive keratectomy and laser-assisted in situ keratomileusis on 6-month space missions. Aerosp Med Hum Perform. 2024; 95(5):278-281.

Intercropping on Mars: A promising system to optimise fresh food production in future martian colonies.

Future colonists on Mars will need to produce fresh food locally to acquire key nutrients lost in food dehydration, the primary technique for sending food to space. In this study we aimed to test the viability and prospect of applying an intercropping system as a method for soil-based food production in Martian colonies. This novel approach to Martian agriculture adds valuable insight into how we can optimise resource use and enhance colony self-sustainability, since Martian colonies will operate under very limited space, energy, and Earth supplies. A likely early Martian agricultural setting was simulated using small pots, a controlled greenhouse environment, and species compliant with space mission requirements. Pea (Pisum sativum), carrot (Daucus carota) and tomato (Solanum lycopersicum) were grown in three soil types ("MMS-1" Mars regolith simulant, potting soil and sand), planted either mixed (intercropping) or separate (monocropping). Rhizobia bacteria (Rhizobium leguminosarum) were added as the pea symbiont for Nitrogen-fixing. Plant performance was measured as above-ground biomass (g), yield (g), harvest index (%), and Nitrogen/Phosphorus/Potassium content in yield (g/kg). The overall intercropping system performance was calculated as total relative yield (RYT). Intercropping had clear effects on plant performance in Mars regolith, being beneficial for tomato but mostly detrimental for pea and carrot, ultimately giving an overall yield disadvantage compared to monocropping (RYT = 0.93). This effect likely resulted from the observed absence of Rhizobia nodulation in Mars regolith, negating Nitrogen-fixation and preventing intercropped plants from leveraging their complementarity. Adverse regolith conditions-high pH, elevated compactness and nutrient deficiencies-presumably restricted Rhizobia survival/nodulation. In sand, where more favourable soil conditions promoted effective nodulation, intercropping significantly outperformed monocropping (RYT = 1.32). Given this, we suggest that with simple regolith improvements, enhancing conditions for nodulation, intercropping shows promise as a method for optimising food production in Martian colonies. Specific regolith ameliorations are proposed for future research.

Microbial adaptation to spaceflight is correlated with bacteriophage-encoded functions.

Evidence from the International Space Station suggests microbial populations are rapidly adapting to the spacecraft environment; however, the mechanism of this adaptation is not understood. Bacteriophages are prolific mediators of bacterial adaptation on Earth. Here we survey 245 genomes sequenced from bacterial strains isolated on the International Space Station for dormant (lysogenic) bacteriophages. Our analysis indicates phage-associated genes are significantly different between spaceflight strains and their terrestrial counterparts. In addition, we identify 283 complete prophages, those that could initiate bacterial lysis and infect additional hosts, of which 21% are novel. These prophage regions encode functions that correlate with increased persistence in extreme environments, such as spaceflight, to include antimicrobial resistance and virulence, DNA damage repair, and dormancy. Our results correlate microbial adaptation in spaceflight to bacteriophage-encoded functions that may impact human health in spaceflight.

Chromosomal damage, gene expression and alternative transcription in human lymphocytes exposed to mixed ionizing radiation as encountered in space.

Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0-2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription.

Navigating the Challenges of 3D Printing Personalized Medicine in Space Explorations: A Comprehensive Review.

Space exploration has undergone a paradigm shift in recent years, with a growing emphasis on long-duration missions and human habitation on other celestial bodies. Private aerospace businesses are at the forefront of advancing the next iteration of spacecraft, encompassing a wide range of applications such as deep space exploration (e.g., SpaceX) and cost-effective satellite deployments (e.g., Rocketlab). One of the critical challenges associated with prolonged space missions is the provision of personalized medical care. 3D printing technology has emerged as a potential solution, enabling the on-demand production of personalized medical devices and medications. However, the unique conditions of space pose substantial challenges to the successful implementation of 3D printing for personalized medicine. Tremendous scope for research exists in terms of resource utilization and waste management in space ecosystem, robotic and artificial intelligence (AI) enabled tool utilization, remote operability, interplanetary travel, space education and training tools, digital twins, space tourism and in many other aspects of 3D printing for personalized medicine in space explorations.

Single-molecule long-read methylation profiling reveals regional DNA methylation regulated by Elongator Complex Subunit 2 in Arabidopsis roots experiencing spaceflight.

BACKGROUND: The Advanced Plant Experiment-04 - Epigenetic Expression (APEX-04-EpEx) experiment onboard the International Space Station examined the spaceflight-altered cytosine methylation in two genetic lines of Arabidopsis thaliana, wild-type Col-0 and the mutant elp2-5, which is deficient in an epigenetic regulator Elongator Complex Subunit 2 (ELP2). Whole-genome bisulfite sequencing (WGBS) revealed distinct spaceflight associated methylation differences, presenting the need to explore specific space-altered methylation at single-molecule resolution to associate specific changes over large regions of spaceflight related genes. To date, tools of multiplexed targeted DNA methylation sequencing remain limited for plant genomes. RESULTS: To provide methylation data at single-molecule resolution, Flap-enabled next-generation capture (FENGC), a novel targeted multiplexed DNA capture and enrichment technique allowing cleavage at any specified sites, was applied to survey spaceflight-altered DNA methylation in genic regions of interest. The FENGC capture panel contained 108 targets ranging from 509 to 704 nt within the promoter or gene body regions of gene targets derived from spaceflight whole-genome data sets. In addition to genes with significant changes in expression and average methylation levels between spaceflight and ground control, targets with space-altered distributions of the proportion of methylated cytosines per molecule were identified. Moreover, trends of co-methylation of different cytosine contexts were exhibited in the same DNA molecules. We further identified significant DNA methylation changes in three previously biological process-unknown genes, and loss-of-function mutants of two of these genes (named as EMO1 and EMO2 for ELP2-regulated Methylation in Orbit 1 and 2) showed enhanced root growth rate. CONCLUSIONS: FENGC simplifies and reduces the cost of multiplexed, targeted, single-molecule profiling of methylation in plants, providing additional resolution along each DNA molecule that is not seen in population-based short-read data such as WGBS. This case study has revealed spaceflight-altered regional modification of cytosine methylation occurring within single DNA molecules of cell subpopulations, which were not identified by WGBS. The single-molecule survey by FENGC can lead to identification of novel functional genes. The newly identified EMO1 and EMO2 are root growth regulators which may be epigenetically involved in plant adaptation to spaceflight.

Extraterrestrial agriculture: plant cultivation in space.

[Formula: see text] Researchers are using various techniques and technologies to study how plants grow in extraterrestrial conditions with the hopes of sustaining longer missions for exploring deep space as well as being able to one day cultivate crops on other planets.

The role of nuclear fragmentations in high energy transfers to a micro-object exposed to primary space radiation.

This paper describes events of anomalously high energy transfer to a micro-object by fragments of nuclei generated in nuclear interactions in the environment on board a spacecraft in flight in low-Earth orbit. An algorithm has been developed that allows for the calculation of the absorbed energy from one or more fragments - products of nuclear interaction. With this algorithm the energy distributions for a spherical micro-volume in an aqueous medium were calculated. And the resulting absorbed energy spectra from nuclear fragments and from primary cosmic rays were compared. The role of nuclear interactions in events of large energy transfers in micro-objects in the field of primary cosmic radiation has been evaluated. The calculations performed in this study showed that the energy in a micro-volume from nuclear events can be several times higher compared to the energy imparted by primary space radiation.

Cellular and Molecular Effects of Microgravity on the Immune System: A Focus on Bioactive Lipids.

Microgravity is one of the main stressors that astronauts are exposed to during space missions. This condition has been linked to many disorders, including those that feature dysfunctional immune homeostasis and inflammatory damage. Over the past 30 years, a significant body of work has been gathered connecting weightlessness-either authentic or simulated-to an inefficient reaction to pathogens, dysfunctional production of cytokines and impaired survival of immune cells. These processes are also orchestrated by a plethora of bioactive lipids, produced by virtually all cells involved in immune events, which control the induction, magnitude, outcome, compartmentalization and trafficking of immunocytes during the response to injury. Despite their crucial importance in inflammation and its modulation, however, data concerning the role of bioactive lipids in microgravity-induced immune dysfunctions are surprisingly scarce, both in quantity and in variety, and the vast majority of it focuses on two lipid classes, namely eicosanoids and endocannabinoids. The present review aims to outline the accumulated knowledge addressing the effects elicited by microgravity-both simulated and authentic-on the metabolism and signaling of these two prominent lipid groups in the context of immune and inflammatory homeostasis.

Space research to explore novel biochemical insights on Earth.

Travel to space has overcome unprecedent technological challenges and this has resulted in transfer of these technological results on Earth to better our lives. Health technology, medical devices, and research advancements in human biology are the first beneficiaries of this transfer. The real breakthrough came with the International Space Station, which endorsed multidisciplinary international scientific collaborations and boosted the research on pathophysiological adaptation of astronauts to life on space. These studies evidenced that life in space appeared to have exposed the astronauts to an accelerated aging-related pathophysiological dysregulation across multiple systems. In this review we emphasize the interaction between several biomarkers and their alteration in concentrations/expression/function by space stress factors. These altered interactions, suggest that different biochemical and hormonal factors, and cell signals, contribute to a complex network of pathophysiological mechanisms, orchestrating the homeostatic dysregulation of various organs/metabolic pathways. The main effects of space travel on altering cell organelles biology, ultrastructure, and cross-talk, have been observed in cell aging as well as in the disruption of metabolic pathways, which are also the causal factor of rare inherited metabolic disorders, one of the major pediatric health issue. The pathophysiologic breakthrough from space research could allow the development of precision health both on Earth and Space by promoting the validation of improved biomarker-based risk scores and the exploration of new pathophysiologic hypotheses and therapeutic targets. Nonstandard abbreviations: International Space Station (ISS), Artificial Intelligence (AI), European Space Agency (ESA), National Aeronautics and Space Agency (NASA), Low Earth Orbit (LEO), high sensitive troponin (hs-cTn), high sensitive troponin I (hs-cTn I), high sensitive troponin T, Brain Natriuretic Peptide (BNP), N terminal Brain Natriuretic Peptide (NT-BNP), cardiovascular disease (CVD), parathyroid hormone (PTH), urinary hydroxyproline (uHP), urinary C- and N-terminal telopeptides (uCTX and uNTX), pyridinoline (PYD), deoxypyridinoline (DPD), half-time (HF), serum Bone Alkaline Phosphatase (sBSAP), serum Alkaline Phosphatase (sAP), Carboxy-terminal Propeptide of Type 1 Procollagen (P1CP), serum Osteocalcin (sOC)), advanced glycation end products (AGEs), glycated hemoglobin A1c (HbA1c), Insulin-like growth factor 1 (IGF1), Growth Hormone (GH), amino acid (AA), ß-hydroxy-ß methyl butyrate (HMB), maple syrup urine disease (MSUD), non-communicable diseases (NCDs).

Bridging clinical radiotherapy and space radiation therapeutics through reactive oxygen species (ROS)-triggered delivery.

This review explores the convergence of clinical radiotherapy and space radiation therapeutics, focusing on ionizing radiation (IR)-generated reactive oxygen species (ROS). IR, with high-energy particles, induces precise cellular damage, particularly in cancer treatments. The paper discusses parallels between clinical and space IR, highlighting unique characteristics of high-charge and energy particles in space and potential health risks for astronauts. Emphasizing the parallel occurrence of ROS generation in both clinical and space contexts, the review identifies ROS as a crucial factor with dual roles in cellular responses and potential disease initiation. The analysis covers ROS generation mechanisms, variations, and similarities in terrestrial and extraterrestrial environments leading to innovative ROS-responsive delivery systems adaptable for both clinical and space applications. The paper concludes by discussing applications of personalized ROS-triggered therapeutic approaches and discussing the challenges and prospects of implementing these strategies in clinical radiotherapy and extraterrestrial missions. Overall, it underscores the potential of ROS-targeted delivery for advancing therapeutic strategies in terrestrial clinical settings and space exploration, contributing to human health improvement on Earth and beyond.

Space Ultrasound: A Proposal for Competency-based Ultrasound Training for In-flight Space Medicine.

Space travel has transformed in the past several years. Given the burgeoning market for space tourism, in-flight medical emergencies are likely to be expected. Ultrasound is one of the few diagnostic and therapeutic modalities available for astronauts in space. However, while point-of-care ultrasound (POCUS) is available, there is no current standard of training for astronaut preparation. We suggest an organized and structured methodology by which astronauts should best prepare for space with the medical equipment available on board. As technology continues to evolve, the assistance of other artificial intelligence and augmented reality systems are likely to facilitate training and dynamic real-time needs during space emergencies. Summary: As space tourism continues to evolve, an organized methodology for POCUS use is advised to best prepare astronauts for space.

"Spaceflight-to-Eye Clinic": Terrestrial advances in ophthalmic healthcare delivery from space-based innovations.

The phrase "Bench-to-Bedside" is a well-known phrase in medicine, highlighting scientific discoveries that directly translate to impacting patient care. Key examples of translational research include identification of key molecular targets in diseases and development of diagnostic laboratory tests for earlier disease detection. Bridging these scientific advances to the bedside/clinic has played a meaningful impact in numerous patient lives. The spaceflight environment poses a unique opportunity to also make this impact; the nature of harsh extraterrestrial conditions and medically austere and remote environments push for cutting-edge technology innovation. Many of these novel technologies built for the spaceflight environment also have numerous benefits for human health on Earth. In this manuscript, we focus on "Spaceflight-to-Eye Clinic" and discuss technologies built for the spaceflight environment that eventually helped to optimize ophthalmic health on Earth (e.g., LADAR for satellite docking now utilized in eye-tracking technology for LASIK). We also discuss current technology research for spaceflight associated neuro-ocular syndrome (SANS) that may also be applied to terrestrial ophthalmic health. Ultimately, various advances made to enable to the future of space exploration have also advanced the ophthalmic health of individuals on Earth.

Spaceflight impacts xyloglucan oligosaccharide abundance in Arabidopsis thaliana root cell walls.

Over the course of more than a decade, space biology investigations have consistently indicated that cell wall remodeling occurs in a variety of spaceflight-grown plants. Here, we describe a mass spectrometric method to study the fundamental composition of xyloglucan, the most abundant hemicellulose in dicot cell walls, in space-grown plants. Four representative Arabidopsis root samples, from a previously conducted spaceflight experiment - Advanced Plant EXperiment - 04 (APEX-04), were used to investigate changes in xyloglucan oligosaccharides abundances in spaceflight-grown plants compared to ground controls. In situ localized enzymatic digestions and surface sampling mass spectrometry analysis provided spatial resolution of the changes in xyloglucan oligosaccharides abundances. Overall, the results showed that oligosaccharide XXLG/XLXG and XXFG branching patterns were more abundant in the lateral roots of spaceflight-grown plants, while XXXG, XLFG, and XLFG/XLFG were more abundant in the lateral roots of ground control plants. In the primary roots, XXFG had a higher abundance in ground controls than in spaceflight plants. This methodology of analyzing the basic components of the cell wall in this paper highlights two important findings. First, that are differences in the composition of xyloglucan oligosaccharides in spaceflight root cell walls compared to ground controls and, second, most of these differences are observed in the lateral roots. Thus, the methodology described in this paper provides insights into spaceflight cell wall modifications for future investigations.

A no-fault risk compensation approach for radiation risks incurred in space travel.

In this paper we recommend an appropriate compensation approach should be established for fatality and disabilities that may occur due to space radiation exposures of government or industry workers. A brief review of compensation approaches for nuclear energy and nuclear weapons development workers in the United States and other countries is described. We then summarize issues in the application of probability of causation calculation and provide examples of probability of causation (PC) calculations for missions to the International Space Station and Earth's moon or for Mars exploration. The main focus of this paper follows with a recommendation of a no-fault approach to compensation with the creation of appropriate insurance policies funded by employers to cover all disabilities or fatality, without requiring proof of causation or restriction to conditions that imply causation. Importantly we propose that the compensation described should be managed by recourse to private insurers.