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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Enabling Human Space Exploration Missions Through Progressively Earth Independent Medical Operations (EIMO).

Goal: Current Space Medicine operations depend on terrestrial support to manage medical events. As astronauts travel to destinations such as the Moon, Mars, and beyond, distance will substantially limit this support and require increasing medical autonomy from the crew. This paper defines Earth Independent Medical Operations (EIMO) and identifies key elements of a conceptual EIMO system. Methods: The NASA Human Research Program Exploration Medical Capability Element held a 2-day conference at Johnson Space Center in Houston, TX with NASA experts representing all aspects of Space Medicine. Results: EIMO will be a process enabling progressively resilient deep space exploration systems and crews to reduce risk and increase mission success. Terrestrial assets will continue to provide pre-mission screening, planning, health maintenance, and prevention, while onboard medical care will increasingly be the purview of the crew. Conclusions: This paper defines and describes the key components of EIMO.

Development of a Digital Platform: A Perspective to Advance Space Telepharmacy.

Goal: Lessons learned from decades of human spaceflight have helped advance the delivery of healthcare in rural and remote areas of the globe. Inclusion of the public in spaceflights is not yet accompanied by technology capable of monitoring their physical and mental health, managing clinical conditions, and rapidly identifying medical emergencies. Telepharmacy is a practice prioritizing pharmacotherapeutic guidance and monitoring to help improve patient quality of life, and can potentially expand the field of space medicine. We seek to advance pharmaceutical care through telepharmacy by developing a digital platform. Objective: This study focuses on the development of a digital platform for teleassistance and pharmaceutical teleconsulting services that builds on lessons learned in delivering space medicine. Methods: The platform contains evidence-based information on various drugs grouped by medical specialty, and also records and saves patient appointments. It has specific service protocols for service standardization, including artificial intelligence, to allow agility in services and escalation. All data is protected by privacy and professional ethics guidelines. Results: The telepharmacy platform is ready and currently undergoing testing for ground applications through validation studies in hospitals or medical clinics. Conclusions: Although developed for use on Earth, this telepharmacy platform provides a good example of how terrestrial healthcare knowledge and technology can be transferred to space missions.

Medicina humana espacial: Performance fisiológico y contramedidas para mejorar la salud del astronauta / Human Space Medicine: Physiological Performance And Countermeasures To Improve The Astronaut's Health

Se presenta este artículo de revisión con base en la evidencia científica actual sobre medicina espacial enfocada en fisiología humana y sus contramedidas. Por lo cual se realizó una búsqueda bibliográfica no sistemática de artículos científicos y libros de investigación en inglés-español de los últimos 7 años, que detallan su aplicación en seres humanos, modelos murinos y experimentos in vitro. Se tomaron en cuenta las condiciones del ambiente espacial como microgravedad y radiación que producen considerables cambios fisiológicos en el sistema cardiovascular (redistribución de líquidos, remodelación cardiovascular, arritmias); nervioso (sensitivomotores, neurosensoriales, neurovestibulares); respiratorio (cambios de volúmenes y capacidades); renal (litiasis); musculoesquelético (atrofia muscular, osteoporosis); hematológico (anemia); inmunológico (desregulación inmune) y digestivo (alteración de la microbiota intestinal). Además, existen procesos biológicos, moleculares y genéticos aún por explorar, para conocer y mitigar los mecanismos inciertos desencadenados en ambientes extremos y peligrosos. Por lo tanto, es una prioridad desarrollar e implementar contramedidas para reducir los efectos nocivos en la salud, con el objetivo de garantizar la adaptación, seguridad y performance del astronauta durante futuros viajes espaciales.

This Review Article is presented based on current scientific evidence on space medicine focused on human physiology and its countermeasures. Therefore, a non-systematic bibliographic search of scientific articles and research books in English-Spanish of the last 7 years was carried out, detailing their application in humans, murine models and in vitro experiments. The conditions of the space environment such as microgravity and radiation that produce considerable physiological changes in the cardiovascular system (redistribution of fluids, cardiovascular remodeling, arrhythmias) were taken into account; nervous (sensorimotor, neurosensory, neurovestibular); respiratory (volume and capacity changes); renal (lithiasis); musculoskeletal (muscular atrophy, osteoporosis); hematological (anemia); immunological (immune dysregulation) and digestive (intestinal microbiota disorder). In addition, there are biological, molecular and genetic processes still to be explored, in order to know and mitigate the uncertain mechanisms triggered in extreme and dangerous environments. Therefore, it is a priority to develop and implement countermeasures to reduce the harmful effects on health, with the aim of guaranteeing the astronaut's adaptation, safety and performance during future space flights.

Dynamic cerebral autoregulation after confinement in an isolated environment for 14 days

BACKGROUND@#To develop human space exploration, it is necessary to study the effects of an isolated and confined environment, as well as a microgravity environment, on cerebral circulation. However, no studies on cerebral circulation in an isolated and confined environment have been reported. Therefore, we investigated the effects of a 14-day period of confinement in an isolated environment on dynamic cerebral autoregulation.@*METHODS@#We participated in an isolation and confinement experiment conducted by the Japan Aerospace Exploration Agency in 2016. Eight healthy males were isolated and confined in a facility for 14 days. Data were collected on the days immediately before and after confinement. Arterial blood pressure waveforms were obtained using a finger blood pressure monitor, and cerebral blood flow velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography for 6 min during quiet rest in a supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between spontaneous variability of beat-to-beat mean arterial blood pressure and mean cerebral blood flow velocity.@*RESULTS@#Transfer function gain in the low- and high-frequency ranges increased significantly (0.54 ± 0.07 to 0.69 ± 0.09 cm/s/mmHg and 0.80 ± 0.05 to 0.92 ± 0.09 cm/s/mmHg, respectively) after the confinement.@*CONCLUSION@#The increases observed in transfer function gain may be interpreted as indicating less suppressive capability against transmission from arterial blood pressure oscillation to cerebral blood flow velocity fluctuation. These results suggest that confinement in an isolated environment for 14 days may impair dynamic cerebral autoregulation.@*TRIAL REGISTRATION@#UMIN000020703 , Registered 2016/01/22.

Tecnología espacial aplicada a la salud / The application of spatial technology in the health

Resumen La medicina espacial es la práctica de la medicina aplicada en el ser humano en el espacio exterior, incluyendo también el uso de la ciencia y tecnología para la prevención o el control de la exposición a los peligros que pueden causar problemas a la salud. El desarrollo de estas actividades repercute en la implementáción de nuevos instrumentos, tratamientos y aditamentos que propician un beneficio en la salud de to dos los que habitamos este planeta. En este artículo se verá como la inversión en ciencia y tecnología espacial repercute de manera directa e indirecta en beneficios para la salud en tierra. Todo lo que pasa o pasó en el universo impacta en la salud. La tecnología desarrollada para los vuelos espaciales ha traído grandes avances en esta materia, pero también en nuestro estilo de vida. Beneficios que propicia la inversión en esta rama, tanto en lo económico, lo social, y sobre todo en el tema de la salud humana.

Abstract Space medicine is the practice of Medicine applied to humans in outer space, including the use of science and technology for the prevention and control of hazards that could cause health problems. The development of these activities affects the implementation of new instruments, treatments and supplies that promote health benefits to all who inhabit this planet. This article reviews how the investment in space science and technology impacts on direct and indirect health benefits to Earth life. Everything that happens or has happened in the universe impacts our health. The technology developed for spaceflight has brought great advances in healthcare, but also in our lifestyle. These benefits bring investment in this area, both economically and socially, espedaily on human health.

Aerospace medicine

This paper presented briefly the different areas of discipline in aviation medicine and space medicine. The importance of having a basic knowledge in aviation medicine among the students, general medical practitioners and other personnel who have something to do with the equipment and aircraft design and manufacture is discussed. The presentation of the subject of space medicine touched only the well-known highlights of the present knowledge of the properties of space and the different problems that concern the human factor in manned space flights. (Summary)