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At least 235 records · Page 13

MicroRNA Based Countermeasure Rescue Health Risks Associated with Space Radiation and Microgravity

From our earlier work, we demonstrated a circulating microRNA (miRNA) signature that is present and involved with the general increased health risks during spaceflight. From this work we demonstrated that this miRNA signature impacted the overall biology and health with both the microgravity and space radiation components of the space environment. We showed that this miRNA signature can be an optimal biomarker for health risk and also has potential to be utilized as a countermeasure to mitigate the damage caused by the space environment by utilizing a human 3D microvascular tissue model. By applying a novel self-delivery system to target 3 miRNAs (i.e. antagomirs) from our spaceflight miRNA signature impacting cardiovascular health risks, we were able to completely mitigate damage caused by exposure to simulated Galactic Cosmic Ray (GCR) irradiation. Here we further expand on the countermeasure experiments to uncover the specific novel biology involved with this countermeasure and in vivo experiments that demonstrates that these antagomirs rescue damage caused to certain organs due to both microgravity and space radiation. Specifically, the miRNAs rescued damage to the heart and immune suppression that occurred in addition to other key biology. In addition, we have also observed with the 3D microvascular tissue model improved DNA double strand break repair machinery which can also contribute to improved recovery and protection against damage caused by space radiation. This work expands on our previous work and further uncovers how a potential minimally invasive countermeasure can be used to mitigate space environment effects.

Afshin Beheshti↗

Animal models and their importance to human physiological responses in microgravity

Two prominent theories to explain the physiological effects of microgravity relate to the cascade of changes associated with the cephalic shifts of fluids and the absence of tissue deformation forces. One-g experiments for humans used bed rest and the head-down tilt (HDT) method, while animal experiments have been conducted using the tail-suspended, head-down, and hindlimbs non-weightbearing model. Because of the success of the HDT approach with rats to simulate the gravitational effects on the musculoskeletal system exhibited by humans, the same model has been used to study the effects of gravity on the cardiopulmonary systems of humans and other vertebrates. Results to date indicate the model is effective in producing comparable changes associated with blood volume, erythropoiesis, cardiac mass, baroreceptor responsiveness, carbohydrate metabolism, post-flight VO2max, and post-flight cardiac output during exercise. Inherent with these results is the potential of the model to be useful in investigating responsible mechanisms. The suspension model has promise in understanding the capillary blood PO2 changes in space as well as the arterial PO2 changes in subjects participating in a HDT experiment. However, whether the model can provide insights on the up-or-down regulation of adrenoreceptors remains to be determined, and many investigators believe the HDT approach should not be followed to study gravitational influences on pulmonary function in either humans or animals. It was concluded that the tail-suspended animal model had sufficient merit to study in-flight and post-flight human physiological responses and mechanisms.

NASA Discipline Cardiopulmonary↗

Effects of Hind Limb Unloading on Pharmacokinetics of Procainamide in Mice

The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in space. It is prudent to expect that low gravity and free floating (and associated hemodynamic changes) could affect the absorption, distribution, metabolism and excretion of the drugs. Knowledge of these alterations is essential for adjusting the dosage and the regimen of drug administration. Among the medications of special interest are the cardiovascular drugs, especially the antiarrhythmic agents. In this study we used hind limb unloaded (HLU) mice as a model to investigate possible changes in the PK of a common antiarrhythmic drug procainamide (PA). Prior to drug administration the experimental animals were tail suspended for 24 hours and the control animals were kept free. PA (150-250 mg per kg) was given orally by a gavage procedure. After that the experimental mice were kept suspended for additional 1, 2, 3 and 6 hours. At these time points the serum concentration of PA and N-acetyl-procainamide (NAPA), an active metabolite which is formed by N-acetyltransferase in the liver, were measured by the fluorescence polarization immunoassay (FPIA) on the AxSYM autoanalyzer (Abbott Laboratories, Abbott Park, IL). The serum level of PA in HLU mice at 1 hour after administration was almost 40% lower than in controls. At 2-3 hours the difference still maintained, however, it was not statistically significant; at 6 hours no difference was detected. The level of NAPA in HLU mice was slightly lower at 1 and 2 hours but the difference did not reach statistical significance. The estimated PA half-life time in HLU mice was almost 55% longer than in control animals. These results confirm that hind limb unloading and related hemodynamic changes significantly alter the PK of PA. The effects are most likely primarily associated with a decrease in the drug absorption, especially within the first two hours after administration. At the same time prolongation of the PA half-life time in the HLU mice points towards slower drug elimination from the circulation.

Risin, Semyon A.↗

Spacelab Life Sciences flight experiments: an integrated approach to the study of cardiovascular deconditioning and orthostatic hypotension

The microgravity environment of spaceflight produces rapid cardiovascular changes which are adaptive and appropriate in that setting, but are associated with significant deconditioning and orthostatic hypotension on return to Earth's gravity. The rapidity with which these space flight induced changes appear and disappear provides an ideal model for studying the underlying pathophysiological mechanisms of deconditioning and orthostatic hypotension, regardless of etiology. Since significant deconditioning is seen after flights of very short duration, muscle atrophy due to inactivity plays, at most, a small role. These changes in circulatory control associated with cephalad fluid shifts, rather than inactivity per se, are probably more important factors. In order to test this hypothesis in a systematic way, a multidisciplinary approach which defines and integrates inputs and responses from a wide variety of circulatory sub-systems is required. The cardiovascular experiments selected for Spacelab Life Sciences flights 1 and 2 provide such an approach. Both human and animal models will be utilized. Pre- and post-flight characterization of the payload crew includes determination of maximal exercise capacity (bicycle ergometry), orthostatic tolerance (lower body negative pressure), alpha and beta adrenergic sensitivity (isoproterenol and phenylephrine infusions), baroreflex sensitivity (ECG-gated, stepwise changes in carotid artery transmural pressure with a pneumatic neck collar), and responses to a 24 h period of 5 deg head-down tilt. Measurements of cardiac output (CO2 and C2H2 rebreathing), cardiac chamber dimensions (phased-array 2-dimensional echocardiography), direct central venous pressure, leg volume (Thornton sock), limb blood flow and venous compliance (occlusion plethysmography), blood and plasma volumes, renal plasma flow and glomerular filtration rates, and various hormonal levels including catecholamines and atrial natriuretic factor will also be obtained. The central venous catheter will be inserted immediately pre-launch and monitored with heart rate and blood pressure in-flight until cardiac output, respiratory gas exchange and quantitative 2D echocardiography measurements can be performed. In-flight hemodynamic measurements will be repeated at rest and during submaximal exercise daily and also during maximal exercise midway through the flight to document the timecourse and extent of cardiovascular changes in the payload crew. Parallel studies are planned for the animals. In addition to measurements of right atrial and aortic pressures and cardiac output, a dorsal micro-circulatory chamber will allow determinations of changes in capillary and venular architecture and function in six of the rats. The techniques and findings from many of the SLS-1 and 2 supporting studies have already yielded significant information about circulatory regulation in patients with both hypo- and hypertension. The flight experiments themselves will provide new data to test the validity of both animal and human models currently used for simulating the fluid shifts of a micro-gravity environment. The development of effective countermeasures, not only for short and long duration space travellers, but also for Earth-bound medical patients can then be physiologically based on experimental data rather than anecdote.

Non-NASA Center↗

USSR Space Life Sciences Digest, issue 28

This is the twenty-eighth issue of NASA's Space Life Sciences Digest. It contains abstracts of 60 journal papers or book chapters published in Russian and of 3 Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. The abstracts in this issue have been identified as relevant to 20 areas of space biology and medicine. These areas include: adaptation, aviation medicine, botany, cardiovascular and respiratory systems, developmental biology, endocrinology, enzymology, equipment and instrumentation, hematology, human performance, immunology, life support systems, mathematical modeling, musculoskeletal system, neurophysiology, personnel selection, psychology, radiobiology, reproductive system, and space medicine.

Stone, Lydia Razran↗

Evaluation of Human Spaceflight-Related Tissue Weight Relief Using Whole Body Finite Element Model Simulations

Tissue Weight Relief (TWR) is a physiological condition observed in human spaceflight. It not only impacts the injury biomechanics of soft tissue but also the physiological responses of the cardiovascular system both due to fluid redistribution and the effect of tissue-related transmural pressure on the large venous blood vessels. Understanding the effects of tissue weight relief is especially important because of the role it may play in understanding the cause of Space Associated Neuro-Ocular Syndrome (SANS). SANS can be characterized by a number of ocular changes which reduce visual acuity and SANS related symptoms occur in up to 51% of astronauts. A prevailing theory for the causation of SANS is that of headward (cephalad) fluid shift and a prolonged increase of Intracranial Pressure (ICP) similar to intracranial hypertension, which is not fully supported by the experimental data or astronaut symptom reporting. However, it is still believed that SANS is caused by a pressure change in the eye and the surrounding tissues. It has been proposed that TWR plays a substantial role in affecting internal pressures and fluid shifts in microgravity. In this effort, two whole-body Finite Element (FE) models – Elemance and THUMS – are used to ascertain the microgravity-associated TWR of the musculature surrounding the lower body veins. Elemance and THUMS are physics-based computational models that have been validated and verified for several automotive and domestic applications, and as such, can simulate the relief of soft tissue weight due to changes in the gravitation vector. Specifically, the current effort modeled the transition of the gravitational vector from 1G to 0G, applied across the whole-body model in a supine position. For each 1G to 0G transition simulation, the lower body vein’s transmural pressure-time profile was extracted and averaged around the anterior portion of the thigh muscle. The ascertained transmural pressure changes from 1G to 0G transition are given in Figure 1 for the Elemance and the THUMS FE models. The transmural pressure changes of 10 mmHg and 21 mmHg are in the same order of magnitude as Lu’s value of 44 mmHg. It is to be noted that Lu implemented a 0D to 1D lumped parameter model and the Elemance and THUMS are 3D higher order computational models. This proof-of-concept approach demonstrates that TWR pressure can be adequately estimated with in silico techniques however, further in silico investigations need to be conducted to address the unique contributions to the transmural pressure from each of the computational models.

Finite element modeling↗

Impact of Climate Change on Heat-Related Mortality in Jiangsu Province, China

A warming climate is anticipated to increase the future heat-related total mortality in urban areas. However, little evidence has been reported for cause-specific mortality or nonurban areas. Here we assessed the impact of climate change on heat-related total and cause-specific mortality in both urban and rural counties of Jiangsu Province, China, in the next five decades. To address the potential uncertainty in projecting future heat-related mortality, we applied localized urban- and nonurban-specific exposure response functions, six population projections including a no population change scenario and five Shared Socioeconomic Pathways (SSPs), and 42 temperature projections from 21 global-scale general circulation models and two Representative Concentration Pathways (RCPs). Results showed that projected warmer temperatures in 2016-2040 and 2041-2065 will lead to higher heat-related mortality for total non-accidental, cardiovascular, respiratory, stroke, ischemic heart disease (IHD), and chronic obstructive pulmonary disease (COPD) causes occurring annually during May to September in Jiangsu Province, China. Nonurban residents in Jiangsu will suffer from more excess heat-related cause-specific mortality in 2016-2065 than urban residents. Variations across climate models and RCPs dominated the uncertainty of heat-related mortality estimation whereas population size change only had limited influence. Our findings suggest that targeted climate change mitigation and adaptation measures should be taken in both urban and nonurban areas of Jiangsu Province. Specific public health interventions should be focused on the leading causes of death (stroke, IHD, and COPD), whose health burden will be amplified by a warming climate.

projection↗

Acute wood smoke exposure is associated with cell-specific hippocampal transcriptomic responses in an accelerated ovarian failure mouse model

Background Wildfire events are increasing in frequency and intensity, and aging individuals demonstrate heightened biological susceptibility to air pollution exposures including increased risk of neurological sequelae. Declining ovarian hormones levels that occur with aging in females along with associated systemic physiological and inflammatory changes may contribute to increased cerebral vulnerability to air pollution, representing a potential but underexplored mechanism. Menopause and the menopausal transition represent a period of profound physiological change that affects cardiovascular, neurological, and immune health. Methods We tested whether peri-menopausal–like hormonal status amplifies hippocampal responses to acute wood smoke (WS) using an ovary-intact, 4-vinylcyclohexene diepoxide (VCD) model of moderate accelerated ovarian failure (AOF) in female C57BL/6 mice. Animals were exposed to HEPA-filtered air (FA) or WS for 4 h/day over 2 consecutive days (∼0.5 mg/m³). Exposure characterization confirmed a complex mixture of combustion products with significant levels of both trace metals and gas release during WS exposure. Results Spatial transcriptomics (10x Visium; n = 4 sections/group) with automated cell-type annotation identified astrocytes, GABAergic and glutamatergic neurons, oligodendrocytes, revealed cell type-specific transcriptional alterations following WS exposure. Distinct transcriptional patterns were observed across all identified neuronal and glial cell populations. Conclusion Together, these findings define a cell-type specific transcriptomic framework describing how WS exposure and ovarian hormone decline interact to influence hippocampal responses and identify potential cellular pathways relevant to hippocampal vulnerability.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Outcomes of a NASA Human Research Program’s (HRP) Space Radiation Element-sponsored Mini-Technical Interchange Meeting/workshop on Cardiovascular Disease Risk from Space Radiation

The NASA HRP’s Space Radiation Element funds research to characterize and mitigate adverse health outcomes from space radiation including cardiovascular risks to astronauts to enable deep space exploration and sustained human presence in space. Non-cancer effects such as damage to the cardiovascular system have been observed at clinically relevant high doses of ionizing radiation. However, an association between lower doses and risk of cardiovascular disease (CVD) remains somewhat controversial, especially in relation to the existence of low dose thresholds, radiation quality, and dose-rate effects, as well as gaps in characterizing the mechanisms and major pathways of disease. To facilitate, accelerate, and incubate new ideas to characterize and mitigate this risk, the Element is planning to organize a series of miniature technical interchange meetings (Tiny-TIMs) to provide a venue for HRP-funded investigators and thought leaders to present ongoing work and engage in open discussion on presented results, limitations of current approaches, incorporating better experimental strategies, model systems, etc. The initial Tiny-TIM held during the NASA HRP Investigators’ Workshop earlier this year – Upping the ante on characterizing and mitigating cardiovascular disease risk from space radiation exposure – aimed to stimulate discussion on the current state of scientific knowledge of CVD risk from space-like radiation exposure. The Tiny-TIM consisted of two 90-minute sessions; the first session concentrated on current knowledge of CVD risk from space radiation and the second session focused on innovative ideas, newer approaches, and techniques to accelerate research. The second session was followed by an open spirited discussion amongst peers on the current issues impeding the characterization of CVD risk from space radiation. The Element facilitated the discussion using a set of pressing open questions/gaps in knowledge that need to be addressed by the scientific community. The outcomes of the Tiny-TIM will be presented along with a plan of proposed future workshops and other initiatives of the Space Radiation Element.

Janapriya Saha↗

Study report on interfacing major physiological subsystem models: An approach for developing a whole-body algorithm

Using a whole body algorithm simulation model, a wide variety and large number of stresses as well as different stress levels were simulated including environmental disturbances, metabolic changes, and special experimental situations. Simulation of short term stresses resulted in simultaneous and integrated responses from the cardiovascular, respiratory, and thermoregulatory subsystems and the accuracy of a large number of responding variables was verified. The capability of simulating significantly longer responses was demonstrated by validating a four week bed rest study. In this case, the long term subsystem model was found to reproduce many experimentally observed changes in circulatory dynamics, body fluid-electrolyte regulation, and renal function. The value of systems analysis and the selected design approach for developing a whole body algorithm was demonstrated.

Fitzjerrell, D. G.↗

Somatic Mutation Analysis in Spaceflight: NASA Twins Genome Study

The NASA Twins Genome Study investigates the effects of spaceflight on somatic mutation accumulation by comparing genome-wide sequence data from a spaceflight astronaut and his Earth-bound twin. Utilizing advanced computational software on high performance computers, this study identifies and maps somatic mutations, with implications for understanding spaceflight-associated health risks, including cancer, neurodegeneration, and cardiovascular disease. The findings aim to bridge rodent and human space research, offering insights into tissue-specific pathophysiology, risk models, and potential therapeutic interventions.

somatic mutation↗

Simulated Microgravity Alters Gene Regulation Linked to Immunity and Cardiovascular Disease

Microgravity exposure induces a cephalad fluid shift and an overall reduction in physical activity levels which can lead to cardiovascular deconditioning in the absence of countermeasures. Future spaceflight missions will expose crew to extended periods of microgravity among other stressors, the effects of which on cardiovascular health are not fully known. In this study, we determined cardiac responses to extended microgravity exposure using the rat hindlimb unloading (HU) model. We hypothesized that exposure to prolonged simulated microgravity and subsequent recovery would lead to increased oxidative damage and altered expression of genes involved in the oxidative response. To test this hypothesis, we examined hearts of male (three and nine months of age) and female (3 months of age) Long–Evans rats that underwent HU for various durations up to 90 days and reambulated up to 90 days post-HU. Results indicate sex-dependent changes in oxidative damage marker 8-hydroxydeoxyguanosine (8-OHdG) and antioxidant gene expression in left ventricular tissue. Three-month-old females displayed elevated 8-OHdG levels after 14 days of HU while age-matched males did not. In nine-month-old males, there were no differences in 8-OHdG levels between HU and normally loaded control males at any of the timepoints tested following HU. RNAseq analysis of left ventricular tissue from nine-month-old males after 14 days of HU revealed upregulation of pathways involved in pro-inflammatory signaling, immune cell activation and differential expression of genes associated with cardiovascular disease progression. Taken together, these findings provide a rationale for targeting antioxidant and immune pathways and that sex differences should be taken into account in the development of countermeasures to maintain cardiovascular health in space.

Genetics & Heredity↗

Radiation Transport Models in Space: from Supernovae to Cells

Humans embarking on deep space exploration missions will encounter persistent exposure to galactic cosmic rays (GCR) - an energetic and highly complex radiation field that is unlike anything found on Earth. Exposure to such radiation fields is attributed to various adverse health effects, including cancer, cardiovascular disease, and cognitive impairment and is identified by NASA as one of the five main hazards of human spaceflight. It is therefore critical to be able to fully characterize the exposure received by humans behind shielding in space and project consequent health risks. A wide variety of computational models have been developed over the years to help meet this requirement. In this talk, an overview of the GCR environment in deep space is provided. Methods of propagating GCR fields through the shielding that protects humans in space are described along with simulation tools used to assess biological damage at the cellular scale. Finally, the NASA cancer risk model is briefly described, and risk projections are provided for various mission scenarios. Radiation transport models and solution methods pervade many aspects of this talk. For example, the GCR spectrum impinging on spacecraft is determined by solving the Fokker-Planck transport equation to propagate cosmic rays (believed to originate from supernovae) from the edge of the heliosphere to the vicinity of Earth. The Boltzmann transport equation is solved to transport this GCR spectrum through shielding and human tissue. Monte Carlo methods are used to simulate the transport of low energy electrons that dominate biological damage at the cellular scale. Progress and challenges in each of these areas will be highlighted.

Tony C. Slaba↗

USSR Space Life Sciences Digest, issue 7

This is the seventh issue of NASA's USSR Space Life Sciences Digest. It contains abstracts of 29 papers recently published in Russian language periodicals and bound collections and of 8 new Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. Additional features include two interviews with the Soviet Union's cosmonaut physicians and others knowledgable of the Soviet space program. The topics discussed at a Soviet conference on problems in space psychology are summarized. Information about English translations of Soviet materials available to readers is provided. The topics covered in this issue have been identified as relevant to 29 areas of aerospace medicine and space biology. These areas are adaptation, biospherics, body fluids, botany, cardiovascular and respiratory systems, developmental biology, endocrinology, enzymology, exobiology, genetics, habitability and environment effects, hematology, human performance, immunology, life support systems, mathematical modeling, metabolism, microbiology, morphology and cytology, musculoskeletal system, neurophysiology, nutrition, perception, personnel selection, psychology, radiobiology, and space medicine.

Hooke, L. R.↗

USSR Space Life Sciences Digest, Issue 10

The USSR Space Life Sciences Digest contains abstracts of 37 papers recently published in Russian language periodicals and bound collections and of five new Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. Additional features include the translation of a book chapter concerning use of biological rhythms as a basis for cosmonaut selection, excerpts from the diary of a participant in a long-term isolation experiment, and a picture and description of the Mir space station. The abstracts included in this issue were identified as relevant to 25 areas of aerospace medicine and space biology. These areas are adaptation, biological rhythms, biospherics, body fluids, botany, cardiovascular and respiratory systems, developmental biology, endocrinology, enzymology, group dynamics, habitability and environmental effects, hematology, human performance, immunology, life support systems, mathematical modeling, metabolism, microbiology, morphology and cytology, musculosketal system, neurophysiology, nutrition, personnel selection, psychology, and radiobiology.

Hooke, Lydia Razran↗

USSR Space Life Sciences Digest, issue 15

This is the 15th issue of NASA's USSR Space Life Sciences Digest. It contains abstracts of 59 papers published in Russian language periodicals or presented at conferences and of two new Soviet monographs. Selected abstracts are illustrated with figures and tables from the original. An additional feature is a review of a conference devoted to the physiology of extreme states. The abstracts included in this issue have been identified as relevant to 29 areas of space biology and medicine. These areas are adaptation, biological rhythms, biospherics, body fluids, botany, cardiovascular and respiratory systems, endocrinology, enzymology, equipment and instrumentation, exobiology, genetics, habitability and environment effects, human performance, immunology, life support systems, mathematical modeling, metabolism, microbiology, musculoskeletal system, neurophysiology, nutrition, operational medicine, perception. personnel selection, psychology, radiobiology, reproductive biology, and space biology and medicine.

Hooke, Lydia Razran↗

USSR Space Life Sciences Digest, issue 4

The fourth issue of NASA's USSR Space Life Science Digest includes abstracts for 42 Soviet periodical articles in 20 areas of aerospace medicine and space biology and published in Russian during the last third of 1985. Selected articles are illustrated with figures and tables from the original. In addition, translated introductions and tables of contents for 17 Russian books on 12 topics related to NASA's life science concerns are presented. Areas covered are: adaptation, biological rhythms, biospherics, body fluids, botany, cardiovascular and respiratory systems, cytology, developmental biology, endocrinology, exobiology, habitability and environmental effects, health and medical treatment, hematology, histology, human performance, immunology, mathematical modeling, metabolism, microbiology, musculoskeletal system, neurophysiology, nutrition, perception, personnel selection, psychology, and radiobiology. Two book reviews translated from the Russian are included and lists of additional relevant titles available in English with pertinent ordering information are given.

Hooke, L. R.↗

Translational Cellular Research on the International Space Station

The emerging field of Translational Research aims to coalesce interdisciplinary findings from basic science for biomedical applications. To complement spaceflight research using human subjects, translational studies can be designed to address aspects of space-related human health risks and help develop countermeasures to prevent or mitigate them, with therapeutical benefits for analogous conditions experienced on Earth. Translational research with cells and model organisms is being conducted onboard the International Space Station (ISS) in connection with various human systems impacted by spaceflight, such as the cardiovascular, musculoskeletal, and immune systems. Examples of recent cell-based translational investigations on the ISS include the following. The JAXA investigation Cell Mechanosensing seeks to identify gravity sensors in skeletal muscle cells to develop muscle atrophy countermeasures by analyzing tension fluctuations in the plasma membrane, which changes the expression of key proteins and genes. Earth applications of this study include therapeutic approaches for some forms of muscular dystrophy, which appear to parallel aspects of muscle wasting in space. Spheroids is an ESA investigation examining the system of endothelial cells lining the inner surface of all blood vessels in terms of vessel formation, cellular proliferation, and programmed cell death, because injury to the endothelium has been implicated as underpinning various cardiovascular and musculoskeletal problems arising during spaceflight. Since endothelial cells are involved in the functional integrity of the vascular wall, this research has applications to Earth diseases such as atherosclerosis, diabetes, and hypertension. The goal of the T-Cell Activation in Aging NASA investigation is to understand human immune system depression in microgravity by identifying gene expression patterns of candidate molecular regulators, which will provide further insight into factors that may play a critical role in immune function loss during aging. In addition, Omics investigations with cells have synergistic applications ranging from the evaluation of pharmacological countermeasures to drug discovery. Thus, cell-based translational research onboard the ISS is bidirectionally bridging cutting-edge cellular and molecular approaches with space bioastronautics and human health methodologies on Earth.

Love, John↗