Safety protocols, precautions, and countermeasures aboard the International Space Station (ISS) to prevent ocular injury.

The International Space Station (ISS) is a $100 billion epicenter of human activity in the vacuum of space, displaying mankind's collective endeavor to explore the cosmic frontier. Even within the marvels of technological sophistication aboard the ISS, the human eye remains a highly vulnerable structure. In the absence of multiple layers of protection and risk assessments, crewmembers would face a substantial increase in vulnerability to ocular injury. Aside from stringent preflight screening criteria for astronauts, the ISS is equipped with ophthalmic medications, environmental control and life support systems (e.g., humidity regulation, carbon dioxide removal, pressurized device regulators), and radiation protection to reduce ocular injury. Moreover, additional countermeasures are currently being developed to mitigate the effects of spaceflight-associated neuro-ocular syndrome (SANS) and lunar dust toxicity for the Artemis Program missions. The success of future endeavors hinges not only on continued technological innovation, but also respecting the intricate interplay between human physiology and the extraterrestrial environments. Establishing habitations on the Moon and Mars, as well as NASA's Gateway Program (humanity's first space station around the Moon), will introduce a new set of challenges, underscoring the necessity for continuous insights into ocular health in space. We discuss the safety protocols, precautions, and countermeasures implemented on the ISS to prevent ocular injury - an aspect often overshadowed by the grandeur of space exploration.

Computational modeling of heart failure in microgravity transitions.

The space tourism industry is growing due to advances in rocket technology. Privatised space travel exposes non-professional astronauts with health profiles comprising underlying conditions to microgravity. Prior research has typically focused on the effects of microgravity on human physiology in healthy astronauts, and little is known how the effects of microgravity may play out in the pathophysiology of underlying medical conditions, such as heart failure. This study used an established, controlled lumped mathematical model of the cardiopulmonary system to simulate the effects of entry into microgravity in the setting of heart failure with both, reduced and preserved ejection fraction. We find that exposure to microgravity eventuates an increased cardiac output, and in patients with heart failure there is an unwanted increase in left atrial pressure, indicating an elevated risk for development of pulmonary oedema. This model gives insight into the risks of space flight for people with heart failure, and the impact this may have on mission success in space tourism.

Neurostimulation as a technology countermeasure for dry eye syndrome in astronauts.

Dry eye syndrome (DES) poses a significant challenge for astronauts during space missions, with reports indicating up to 30% of International Space Station (ISS) crew members. The microgravity environment of space alters fluid dynamics, affecting distribution of fluids on the surface of the eye as well as inducing cephalad fluid shifts that can alter tear drainage. Chronic and persistent DES not only impairs visual function, but also compromises the removal of debris, a heightened risk for corneal abrasions in the microgravity environment. Despite the availability of artificial tears on the ISS, the efficacy is challenged by altered fluid dynamics within the bottle and risks of contamination, thereby exacerbating the potential for corneal abrasions. In light of these challenges, there is a pressing need for innovative approaches to address DES in astronauts. Neurostimulation has emerged as a promising technology countermeasure for DES in spaceflight. By leveraging electrical signals to modulate neural function, neurostimulation offers a novel therapeutic avenue for managing DES symptoms. In this paper, we will explore the risk factors and current treatment modalities for DES, highlighting the limitations of existing approaches. Furthermore, we will delve into the novelty and potential of neurostimulation as a countermeasure for DES in future long-duration missions, including those to the Moon and Mars.

Biophysics of ophthalmic medications during spaceflight: Principles of ocular fluid dynamics and pharmacokinetics in microgravity.

As spaceflight becomes increasingly accessible and expansive to humanity, it is becoming ever more essential to consider the treatment of various eye diseases in these challenging environments. This paper delves into the increasing fascination with interplanetary travel and its implications for health management in varying environments. It specifically discusses the pharmacological management of ocular diseases, focusing on two key delivery methods: topical eye drops and intravitreal injections. The paper explores how microgravity impacts the administration of these treatments, a vital aspect in understanding drug delivery in space. An extensive analysis is presented on the pharmacokinetics of eye medications, examining the interaction between pharmaceuticals and ocular tissues in zero gravity. The goal of the paper is to bridge the understanding of fluid dynamics, microgravity and the human physiological systems to pave the way for innovative solutions faced by individuals in microgravity.

Impedance threshold device as a countermeasure for spaceflight associated neuro-ocular syndrome (SANS): Mitigating mechanisms in proposed pathophysiology.

Long-duration spaceflight (LDSF) is associated with unique hazards and linked with numerous human health risks including Spaceflight Associated Neuro-ocular Syndrome (SANS). The proposed mechanisms for SANS include microgravity induced cephalad fluid shift and increased Intracranial Pressure (ICP). SANS is a disorder seen only after LDSF and has no direct terrestrial pathologic counterpart as the zero G environment cannot be completely replicated on Earth. Head-down tilt, bed rest studies however have been used as a terrestrial analog and produce the cephalad fluid shift. Some proposed countermeasures for SANS include vasoconstrictive thigh cuffs and lower body negative pressure. Another potential researched countermeasure is the impedance threshold device (ITD) which can reduce ICP. We review the mechanisms of the ITD and its potential use as a countermeasure for SANS.

Coordinated lunar time (LTC): Implications of a lunar-centric time zone on astronaut health and space medicine.

Lunar exploration offers an exciting opportunity for humanity to advance scientific knowledge and future potential economic growth and possibly allow humans to become a multi-planetary species. On April 2, 2024 the US Office of Science and Technology Policy released a memorandum outlining the current Biden-Harris Administration's policy on the need to establish time standards at celestial bodies other than Earth. This memorandum also introduced the need for Coordinated Lunar Time (CLT), the concept of having a reference time for the moon. The establishment of CLT would provide a multitude of benefits for astronaut health, from expedition planning, to maintaining a sense of order in an austere environment. International agreements and collaboration will be required prior to the recognition of CLT.

Space surgery: a SAGES' white paper.

BACKGROUND: Space travel is experiencing a renaissance with expanding commercial and international efforts. Space surgery will have growing relevance as mission frequency and distances increase beyond low Earth orbit. METHODS: This white paper from the SAGES Space Surgery Task Force raises awareness among the SAGES membership regarding the challenges and opportunities surrounding this emerging field that anticipates surgical care in the most extreme, austere environments. RESULTS: Innovation in technology and preventive medicine principles will enhance the effectiveness of space surgical care when the need arises. The impact of advancements in space and terrestrial medicine to support space exploration indicates the need for a surgeon to oversee medical/surgical invasive treatment to ensure astronaut health and mission success. Advanced technology, including semi- and autonomous robotic systems, may be a preferred way to deliver this care in the foreseeable future. There is currently a need to develop training curricula and flight-compatible supplies and technology for physicians that deliver surgical care to this special patient population. The protocols and technology developed to address the unique challenges of space travel will provide value for care in space as well as in extreme, austere terrestrial environments on Earth. CONCLUSION: Space surgery will continue to evolve as commercial and government programs explore further into space. The SAGES Space Surgery Task Force is favorably positioned to significantly contribute to addressing some capability gaps in delivering surgical care in space.

Optimizing healthcare in space: the role of ultrasound imaging in medical conditions.

In the context of long-distance space travel, managing medical conditions presents unique challenges due to communication delays. Consequently, onboard physicians must possess proficiency in diagnostic tools such as ultrasound, which has demonstrated its efficacy in the Space. However, there is a notable lack of comprehensive discussion regarding its effectiveness in handling medical scenarios in the Space. This bibliometric and systematic review aims to provide an updated analysis of the evidence supporting the role of ultrasound imaging in diagnosing medical conditions within microgravity environments.

Special anatomy series. Imaging inner ear structures with high-frequency ultrasound: Application to physical rehabilitation space medicine.

Objective: The objective of this paper is to document the feasibility of image acquisition, image optimization, and sonographic appearance of the exposed anatomic windows of cadaveric inner ear dissection for purposes of potential future clinical evaluation as part of the developing area of physical and rehabilitation space medicine. Methods: Cadaveric dissection of the inner ear was conducted with the goal of exposing areas relevant to vestibular balance. Middle and inner ear structures of 3 human cadavers were imaged with multiple broadband transducers, including emphasis with higher frequency transducers. Results: The images were best optimized with 17 MHz and 22 MHz small footprint transducers. High-frequency ultrasound (US) images of the semicircular canals, vestibular and facial nerves, and utricles with reflected otoliths (otoconia) were obtained and reported in this article. Detailed visualization of both the vestibular nerve and facial nerve was accomplished, including identification of fascicular architecture. In addition, US reflection from the otoliths contained within the utricle was identified with sufficient clarity to provide surface measurements. Bony acoustic landmarks of the middle ear bones were identified by scanning externally from the tympanic membrane, including the dynamic movement of the bones with manual manipulation. Conclusion: US visualization has the potential to be an effective imaging modality to monitor potential changes to the otolith's size throughout extended space flight. To our knowledge, no prior study has reported US images of human inner ear structures.

Exploring the influence of microgravity on chemotherapeutic drug response in cancer: Unveiling new perspectives.

Microgravity, an altered gravity condition prevailing in space, has been reported to have a profound impact on human health. Researchers are very keen to comprehensively investigate the impact of microgravity and its intricate involvement in inducing physiological changes. Evidenced transformations were observed in the internal architecture including cytoskeletal organization and cell membrane morphology. These alterations can significantly influence cellular function, signalling pathways and overall cellular behaviour. Further, microgravity has been reported to alter in the expression profile of genes and metabolic pathways related to cellular processes, signalling cascades and structural proteins in cancer cells contributing to the overall changes in the cellular architecture. To investigate the effect of microgravity on cellular and molecular levels numerous ground-based simulation systems employing both in vitro and in vivo models are used. Recently, researchers have explored the possibility of leveraging microgravity to potentially modulate cancer cells against chemotherapy. These findings hold promise for both understanding fundamental processes and could potentially lead to the development of more effective, personalized and innovative approaches in therapeutic advancements against cancer.

FA4SANS-GAN: A Novel Machine Learning Generative Adversarial Network to Further Understand Ophthalmic Changes in Spaceflight Associated Neuro-Ocular Syndrome (SANS).

Purpose: To provide an automated system for synthesizing fluorescein angiography (FA) images from color fundus photographs for averting risks associated with fluorescein dye and extend its future application to spaceflight associated neuro-ocular syndrome (SANS) detection in spaceflight where resources are limited. Design: Development and validation of a novel conditional generative adversarial network (GAN) trained on limited amount of FA and color fundus images with diabetic retinopathy and control cases. Participants: Color fundus and FA paired images for unique patients were collected from a publicly available study. Methods: FA4SANS-GAN was trained to generate FA images from color fundus photographs using 2 multiscale generators coupled with 2 patch-GAN discriminators. Eight hundred fifty color fundus and FA images were utilized for training by augmenting images from 17 unique patients. The model was evaluated on 56 fluorescein images collected from 14 unique patients. In addition, it was compared with 3 other GAN architectures trained on the same data set. Furthermore, we test the robustness of the models against acquisition noise and retaining structural information when introduced to artificially created biological markers. Main Outcome Measures: For GAN synthesis, metric Fréchet Inception Distance (FID) and Kernel Inception Distance (KID). Also, two 1-sided tests (TOST) based on Welch's t test for measuring statistical significance. Results: On test FA images, mean FID for FA4SANS-GAN was 39.8 (standard deviation, 9.9), which is better than GANgio model's mean of 43.2 (standard deviation, 13.7), Pix2PixHD's mean of 57.3 (standard deviation, 11.5) and Pix2Pix's mean of 67.5 (standard deviation, 11.7). Similarly for KID, FA4SANS-GAN achieved mean of 0.00278 (standard deviation, 0.00167) which is better than other 3 model's mean KID of 0.00303 (standard deviation, 0.00216), 0.00609 (standard deviation, 0.00238), 0.00784 (standard deviation, 0.00218). For TOST measurement, FA4SANS-GAN was proven to be statistically significant versus GANgio (P = 0.006); versus Pix2PixHD (P < 0.00001); and versus Pix2Pix (P < 0.00001). Conclusions: Our study has shown FA4SANS-GAN to be statistically significant for 2 GAN synthesis metrics. Moreover, it is robust against acquisition noise, and can retain clear biological markers compared with the other 3 GAN architectures. This deployment of this model can be crucial in the International Space Station for detecting SANS. Financial Disclosures: The authors have no proprietary or commercial interest in any materials discussed in this article.

Ultrasound Biomicroscopy as a Novel, Potential Modality to Evaluate Anterior Segment Ophthalmic Structures during Spaceflight: An Analysis of Current Technology.

Ocular health is currently a major concern for astronauts on current and future long-duration spaceflight missions. Spaceflight-associated neuro-ocular syndrome (SANS) is a collection of ophthalmic and neurologic findings that is one potential physiologic barrier to interplanetary spaceflight. Since its initial report in 2011, our understanding of SANS has advanced considerably, with a primary focus on posterior ocular imaging including fundus photography and optical coherence tomography. However, there may be changes to the anterior segment that have not been identified. Additional concerns to ocular health in space include corneal damage and radiation-induced cataract formation. Given these concerns, precision anterior segment imaging of the eye would be a valuable addition to future long-duration spaceflights. The purpose of this paper is to review ultrasound biomicroscopy (UBM) and its potential as a noninvasive, efficient imaging modality for spaceflight. The analysis of UBM for spaceflight is not well defined in the literature, and such technology may help to provide further insights into the overall anatomical changes in the eye in microgravity.

Spaceflight-associated neuro-ocular syndrome: potential etiologies and connections to the glymphatic system.

The etiology of spaceflight-associated neuro-ocular syndrome (SANS) is a developing field of research, with many current hypotheses receiving varying degrees of support. This syndrome affects ∼70% of astronauts both during and after long-duration space missions, resulting in impaired near vision and visual scotomas (blind spots). In this article, three prominent risk factors for SANS including zero gravity conditions, extraterrestrial hypercapnic environments, and individual genetic predisposition are described. These risk factors are then compared and their pathophysiological pathways are divided into five current hypotheses for the development of SANS. Finally, glymphatic system impairment is explored as a potential mutual end point for these pathways in the development of SANS.

Prioritizing open science in space medicine: perspectives following the NASA "Transform to Open Science (TOPS)" Curriculum.

The National Aeronautics and Space Administration (NASA) has recently made a long-term commitment towards fostering open science. The NASA Transform to Open Science (TOPS) initiative provides recommendations, best practices, and tools related to open science. The principles of open science include the transparent sharing of data, findings, and methods and is designed to accelerate the pace of discovery and foster collaboration. The goal of open science is to allow data, publications, software, and physical samples to be accessible to all, regardless of being a professional or an amateur. In this paper, we summarize several key points open science that were presented as part of NASA's Open Science 101 Module 1 at an in-person training event in Washington, D.C., and include how open science can be beneficial for researchers and society as a whole.

Utility of ultrasound in managing acute medical conditions in space: a scoping review.

BACKGROUND: In long-distance spaceflight, the challenges of communication delays and the impracticality of rapid evacuation necessitate the management of medical emergencies by onboard physicians. Consequently, these physicians must be proficient in tools, such as ultrasound, which has proven itself a strong diagnostic imaging tool in space. Yet, there remains a notable gap in the discourse surrounding its efficacy in handling acute medical scenarios. This scoping review aims to present an updated analysis of the evidence supporting the role of ultrasound in diagnosing acute conditions within microgravity environments. METHODS: A systematic search was executed across three bibliographic databases: PubMed, EMBASE (Embase.com), and the Web of Science Core Collection. We considered articles published up to February 25, 2023, that highlighted the application of ultrasound in diagnosing acute medical conditions in either microgravity or microgravity-simulated settings. Exclusions were made for review papers, abstracts, and in-vitro studies. RESULTS: After removing duplicates, and filtering papers by pre-determined criteria, a total of 15 articles were identified that discuss the potential use of ultrasound in managing acute medical conditions in space. The publication date of these studies ranged from 1999 to 2020. A relatively similar proportion of these studies were conducted either on the International Space Station or in parabolic flight, with one performed in supine positioning to simulate weightlessness. The included studies discuss acute pathologies, such as abdominal emergencies, decompression sickness, deep venous thrombosis, acute lung pathologies, sinusitis, musculoskeletal trauma, genitourinary emergencies, and ocular emergencies. CONCLUSIONS: While ultrasound has shown promise in addressing various acute conditions, significant knowledge gaps remain, especially in gastrointestinal, cardiac, vascular, and reproductive emergencies. As we venture further into space, expanding our medical expertise becomes vital to ensure astronaut safety and mission success.

Radiation-induced ophthalmic risks of long duration spaceflight: Current investigations and interventions.

PURPOSE: As the average duration of space missions increases, astronauts will experience longer periods of exposure to risks of long duration space flight including microgravity and radiation. The risks from long-term exposure to space radiation remains ill-defined. We review the current literature on the possible and known risks of radiation on the eye (including radiation retinopathy) after long duration spaceflight. METHODS: A PubMed and Google Scholar search of the English language ophthalmic literature was performed from inception to July 11, 2022. The following search terms were utilized independently or in conjunction to build this manuscript: "Radiation Retinopathy", "Spaceflight", "Space Radiation", "Spaceflight Associated Neuro-Ocular Syndrome", "Microgravity", "Hypercapnia", "Radiation Shield", "Cataract", and "SANS". A concise and selective approach of references was conducted in including relevant original studies and reviews. RESULTS: A total of 65 papers were reviewed and 47 papers were included in our review. CONCLUSION: We discuss the potential and developing countermeasures to mitigate these radiation risks in preparation for future space exploration. Given the complex nature of space radiation, no single approach will fully reduce the risks of developing radiation maculopathy in long-duration spaceflight. Understanding and appropriately overcoming the risks of space radiation is key to becoming a multi-planetary species.

Gravity-efficient motor control is associated with contraction-dependent intracortical inhibition.

In humans, moving efficiently along the gravity axis requires shifts in muscular contraction modes. Raising the arm up involves shortening contractions of arm flexors, whereas the reverse movement can rely on lengthening contractions with the help of gravity. Although this control mode is universal, the neuromuscular mechanisms that drive gravity-oriented movements remain unknown. Here, we designed neurophysiological experiments that aimed to track the modulations of cortical, spinal, and muscular outputs of arm flexors during vertical movements with specific kinematics (i.e., optimal motor commands). We report a specific drop of corticospinal excitability during lengthening versus shortening contractions, with an increase of intracortical inhibition and no change in spinal motoneuron responsiveness. We discuss these contraction-dependent modulations of the supraspinal motor output in the light of feedforward mechanisms that may support gravity-tuned motor control. Generally, these results shed a new perspective on the neural policy that optimizes movement control along the gravity axis.

Simulated Microgravity-Induced Changes to Drug Response in Cancer Cells Quantified Using Fluorescence Morphometry.

Unlike plants that have special gravity-sensing cells, such special cells in animals are yet to be discovered. However, microgravity, the condition of apparent weightlessness, causes bone, muscular and immune system dysfunctions in astronauts following spaceflights. Decades of investigations show correlations between these organ and system-level dysfunctions with changes induced at the cellular level both by simulated microgravity as well as microgravity conditions in outer space. Changes in single bone, muscle and immune cells include morphological abnormalities, altered gene expression, protein expression, metabolic pathways and signaling pathways. These suggest that human cells mount some response to microgravity. However, the implications of such adjustments on many cellular functions and responses are not clear. Here, we addressed the question whether microgravity induces alterations to drug response in cancer cells. We used both adherent cancer cells (T98G) and cancer cells in suspension (K562) to confirm the known effects of simulated microgravity and then treated the K562 cells with common cancer drugs (hydroxyurea and paclitaxel) following 48 h of exposure to simulated microgravity via a NASA-developed rotary cell culture system. Through fluorescence-guided morphometry, we found that microgravity abolished a significant reduction (p < 0.01) in the nuclear-to-cytoplasm ratio of cancer cells treated with hydroxyurea. Our results call for more studies on the impact of microgravity on cellular drug response, in light of the growing need for space medicine, as space exploration grows.

Enhancing European capabilities for application of multi-omics studies in biology and biomedicine space research.

Following on from the NASA twins' study, there has been a tremendous interest in the use of omics techniques in spaceflight. Individual space agencies, NASA's GeneLab, JAXA's ibSLS, and the ESA-funded Space Omics Topical Team and the International Standards for Space Omics Processing (ISSOP) groups have established several initiatives to support this growth. Here, we present recommendations from the Space Omics Topical Team to promote standard application of space omics in Europe. We focus on four main themes: i) continued participation in and coordination with international omics endeavors, ii) strengthening of the European space omics infrastructure including workforce and facilities, iii) capitalizing on the emerging opportunities in the commercial space sector, and iv) capitalizing on the emerging opportunities in human subjects research.

Extended reality quantification of pupil reactivity as a non-invasive assessment for the pathogenesis of spaceflight associated neuro-ocular syndrome: A technology validation study for astronaut health.

The National Aeronautics and Space Administration (NASA) has rigorously documented a group of neuro-ophthalmic findings in astronauts during and after long-duration spaceflight known as spaceflight associated neuro-ocular syndrome (SANS). For astronaut safety and mission effectiveness, understanding SANS and countermeasure development are of utmost importance. Although the pathogenesis of SANS is not well defined, a leading hypothesis is that SANS might relate to a sub-clinical increased intracranial pressure (ICP) from cephalad fluid shifts in microgravity. However, no direct ICP measurements are available during spaceflight. To further understand the role of ICP in SANS, pupillometry can serve as a promising non-invasive biomarker for spaceflight environment as ICP is correlated with the pupil variables under illumination. Extended reality (XR) can help to address certain limitations in current methods for efficient pupil testing during spaceflight. We designed a protocol to quantify parameters of pupil reactivity in XR with an equivalent time duration of illumination on each eye compared to pre-existing, non-XR methods. Throughout the assessment, the pupil diameter data was collected using HTC Vive Pro-VR headset, thanks to its eye-tracking capabilities. Finally, the data was used to compute several pupil variables. We applied our methods to 36 control subjects. Pupil variables such as maximum and minimum pupil size, constriction amplitude, average constriction amplitude, maximum constriction velocity, latency and dilation velocity were computed for each control data. We compared our methods of calculation of pupil variables with the non-XR methods existing in the literature. Distributions of the pupil variables such as latency, constriction amplitude, and velocity of 36 control data displayed near-identical results from the non-XR literature for normal subjects. We propose a new method to evaluate pupil reactivity with XR technology to further understand ICP's role in SANS and provide further insight into SANS countermeasure development for future spaceflight.