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At least 145 records · Page 8

Digital Microfluidics Sample Analyzer

Three innovations address the needs of the medical world with regard to microfluidic manipulation and testing of physiological samples in ways that can benefit point-of-care needs for patients such as premature infants, for which drawing of blood for continuous tests can be life-threatening in their own right, and for expedited results. A chip with sample injection elements, reservoirs (and waste), droplet formation structures, fluidic pathways, mixing areas, and optical detection sites, was fabricated to test the various components of the microfluidic platform, both individually and in integrated fashion. The droplet control system permits a user to control droplet microactuator system functions, such as droplet operations and detector operations. Also, the programming system allows a user to develop software routines for controlling droplet microactuator system functions, such as droplet operations and detector operations. A chip is incorporated into the system with a controller, a detector, input and output devices, and software. A novel filler fluid formulation is used for the transport of droplets with high protein concentrations. Novel assemblies for detection of photons from an on-chip droplet are present, as well as novel systems for conducting various assays, such as immunoassays and PCR (polymerase chain reaction). The lab-on-a-chip (a.k.a., lab-on-a-printed-circuit board) processes physiological samples and comprises a system for automated, multi-analyte measurements using sub-microliter samples of human serum. The invention also relates to a diagnostic chip and system including the chip that performs many of the routine operations of a central labbased chemistry analyzer, integrating, for example, colorimetric assays (e.g., for proteins), chemiluminescence/fluorescence assays (e.g., for enzymes, electrolytes, and gases), and/or conductometric assays (e.g., for hematocrit on plasma and whole blood) on a single chip platform.

Pollack, Michael G.↗

Evaluation of Treadmill Exercise in a Lower Body Negative Pressure Chamber as a Countermeasure for Weightlessness-Induced Bone Loss: a Bed Rest Study with Identical Twins

Counteracting bone loss is required for future space exploration. We evaluated the ability of treadmill exercise in a LBNP chamber to counteract bone loss in a 30-day bed rest study. Eight pairs of identical twins were randomly assigned to sedentary control or exercise groups. Exercise within LBNP decreased the bone resorption caused by bed rest and may provide a countermeasure for spaceflight. INTRODUCTION: Bone loss is one of the greatest physiological challenges for extended-duration space missions. The ability of exercise to counteract weightlessness-induced bone loss has been studied extensively, but to date, it has proven ineffective. We evaluated the effectiveness of a combination of two countermeasures-treadmill exercise while inside a lower body negative pressure (LBNP) chamber-on bone loss during a 30-day bed rest study. MATERIALS AND METHODS: Eight pairs of identical twins were randomized into sedentary (SED) or exercise/LBNP (EX/LBNP) groups. Blood and urine samples were collected before, several times during, and after the 30-day bed rest period. These samples were analyzed for markers of bone and calcium metabolism. Repeated measures ANOVA was used to determine statistical significance. Because identical twins were used, both time and group were treated as repeated variables. RESULTS: Markers of bone resorption were increased during bed rest in samples from sedentary subjects, including the collagen cross-links and serum and urinary calcium concentrations. For N-telopeptide and deoxypyridinoline, there were significant (p < 0.05) interactions between group (SED versus EX/LBNP) and phase of the study (sample collection point). Pyridinium cross-links were increased above pre-bed rest levels in both groups, but the EX/LBNP group had a smaller increase than the SED group. Markers of bone formation were unchanged by bed rest in both groups. CONCLUSIONS: These data show that this weight-bearing exercise combined with LBNP ameliorates some of the negative effects of simulated weightlessness on bone metabolism. This protocol may pave the way to counteracting bone loss during spaceflight and may provide valuable information about normal and abnormal bone physiology here on Earth.

Twin Study↗

Early and Late Damages in Chromosome 3 of Human Lymphocytes After Radiation Exposure

Tumor formation in humans or animals is a multi-step process. An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. GI is defined as elevated or persistent genetic damages occurring many generations after the cells are exposed. While early studies have demonstrated radiation-induced GI in several cell types as detected in endpoints such as mutation, apoptosis and damages in chromosomes, the dependence of GI on the quality of radiation remains uncertain. To investigate GI in human lymphocytes induced by both low- and high-LET radiation, we initially exposed white blood cells collected from healthy subjects to gamma rays in vitro, and cultured the cells for multiple generations. Chromosome aberrations were analyzed in cells collected at first mitosis post irradiation and at several intervals during the culture period. Among a number of biological endpoints planned for the project, the multi-color banding fluorescent in situ hybridization (mBAND) allows identification of inversions that were expected to be stable. We present here early and late chromosome aberrations detected with mBAND in chromosome 3 after gamma exposure. Comparison of chromosome damages in between human lymphocytes and human epithelial cells is also discussed

Sunagawa, Mayumi↗

Detection and quantification of Epstein-Barr virus EBER1 in EBV-infected cells by fluorescent in situ hybridization and flow cytometry

A rapid and highly sensitive fluorescent in situ hybridization (FISH) assay was developed to detect Epstein Barr virus (EBV)-infected cells in peripheral blood. Multiple fluorescein-labeled antisense oligonucleotide probes were designed to hybridize to the EBER1 transcript, which is highly expressed in latently infected cells. After a rapid (30 min) hybridization, the cells were analyzed by flow cytometry. EBER1 was detected in several positive control cell lines that have variable numbers of EBV genome copies. No EBER1 was detected in two known EBV-negative cell lines. Northern blot analyses confirmed the presence and quantity of EBER1 transcripts in each cell line. This method was used to quantify the number of EBV-infected cells in peripheral blood from a patient with chronic mononucleosis. These results indicate that EBV-infected cells can be detected at the single cell level, and that this assay can be used to quantify the number of EBV-infected cells in clinical samples.

NASA Discipline Regulatory Physiology↗

First results from Spacelab 2

Preliminary results of physical experiments carried out during the Spacelab 2 Shuttle mission are summarized. Attention is given to experiments in the fields of plasma dynamics; solar physics; high-energy astrophysics; and astronomy. Plasma experiments included an ejectable plasma diagnosics package and measurements of the passive charging of the Shuttle vehicle in the surrounding space plasma. The solar physics instrument package consisted of a solar spectral irradiance monitor; a solar optical universal polarimeter (SOUP); and a solar helium abundance high-resolution telescope and spectrograph (HRTS). Astronomical observations were performed using a scanning infrared telescope (IRT) which consisted of a highly baffled herschelian telescope and 10 detectors covering wavelengths from 2 to 120 microns. Cosmic-ray nuclei were detected and analyzed using gas Cerenkov counters and a transition radiation detector. Addition experiments included a thin film fluid dynamics payload and analysis of blood samples taken from the mission specialists. Complete data records from the experiments have now been distributed for an analysis period which will take at least a year. A table listing the Spacelab 2 experiments and their principal investigators is provided.

Urban, E. W.↗

DNA Damage Response to Low and High-LET in a Large Cohort of Mice and Humans and Latest Advancement in NASA Space Omics

This presentation will first focus on a thorough evaluation of the DNA damage response to both low and high-LET in a cohort of 76 mice primary skin fibroblast derived from 15 different strains or in human blood mononuclear cells derived from 550 healthy donors. In both the human and mice work, we have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Results on humans are still preliminary as we are still in the process of collecting and isolating primary blood mononuclear cells from 500 to 800 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. The second part of the talk will focus on describing GeneLab: The NASA Systems Biology Platform for Space Omics Repository, Analysis and Visualization. NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). Started as a repository designed to archive precious omics from space experiments, GeneLab has expanded its scope to maximize the intelligibility of the raw data (e.g. RNAseq, microarray, WGBS, metagenome), particularly for users with limited bioinformatics knowledge. As such GeneLab is now providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome), to help users explore important questions: Which genes or proteins are expressed differently in space for various living organisms? What are the consequences arising from these changes? What specifics DNA mutations or epigenetic changes happen in space? What species or genetic features lead to better adaption to such a unique environment? In this presentation, we will report on the current and future objectives for GeneLab, and review recent published studies relating molecular changes observed in various animal models and tissue with microgravity, radiation, circadian rhythm, hydration and carbon dioxide conditions.

DNA repair kinetics↗

To develop a spectral analyzer for physiological and medical use

Scientific requirements necessary to develop a spectral analyzer for monitoring mammalian subjects, are discussed. The analyzer measures dynamic or time dependent data as a measure of the subjects operating status. Measurable data include metabolic rate, body temperature, and blood constituents like glucose, oxygen, and carbon dioxide, and lactic acid. Metabolic cycles were found with periodicities in the range of minutes and hours; longer cycles in body weight (3 1/2 days and 60 days), indicative of metabolic processes, were also found.

Iberall, A.↗

Specialized physiological studies in support of manned space flight

The effects of a diuretic (Lasix) induced dehydration on the cardiovascular and hematological responses to lower body negative pressure (LBNP) were analyzed and compared to previous observations on dehydration following exercise in the heat. During LBNP runs the subjects were monitored for changes in blood volume, heart rate, blood pressure, and variations in the volume of the left calf. It was concluded that Lasix dehydration produced a depletion of the body electrolytes at the expense of both the plasma and extravascular compartments. Striking differences were found between those subjects who were physically active (Runners: R) and those who did not engage in any regular physical activity (Non-runners: NR). Tolerance to LBNP (Torr x min) was significantly lower in the R's than the NR's before and after dehydration, however the R's lost more of their tolerance after dehydration with Lasix than after exercise in the heat for about the same fluid loss. The opposite was true for the NR's. Two factors appear to be responsible for the lower LBNP tolerance in R's: parasympathetic inhibition of cardiac activity during LBNP and a greater propensity to pool blood in the lower extremities.

Luft, U. C.↗

Radiation-Induced Leukemia at Doses Relevant to Radiation Therapy: Modeling Mechanisms and Estimating Risks

Because many cancer patients are diagnosed earlier and live longer than in the past, second cancers induced by radiation therapy have become a clinically significant issue. An earlier biologically based model that was designed to estimate risks of high-dose radiation induced solid cancers included initiation of stem cells to a premalignant state, inactivation of stem cells at high radiation doses, and proliferation of stem cells during cellular repopulation after inactivation. This earlier model predicted the risks of solid tumors induced by radiation therapy but overestimated the corresponding leukemia risks. Methods: To extend the model to radiation-induced leukemias, we analyzed in addition to cellular initiation, inactivation, and proliferation a repopulation mechanism specific to the hematopoietic system: long-range migration through the blood stream of hematopoietic stem cells (HSCs) from distant locations. Parameters for the model were derived from HSC biologic data in the literature and from leukemia risks among atomic bomb survivors v^ ho were subjected to much lower radiation doses. Results: Proliferating HSCs that migrate from sites distant from the high-dose region include few preleukemic HSCs, thus decreasing the high-dose leukemia risk. The extended model for leukemia provides risk estimates that are consistent with epidemiologic data for leukemia risk associated with radiation therapy over a wide dose range. For example, when applied to an earlier case-control study of 110000 women undergoing radiotherapy for uterine cancer, the model predicted an excess relative risk (ERR) of 1.9 for leukemia among women who received a large inhomogeneous fractionated external beam dose to the bone marrow (mean = 14.9 Gy), consistent with the measured ERR (2.0, 95% confidence interval [CI] = 0.2 to 6.4; from 3.6 cases expected and 11 cases observed). As a corresponding example for brachytherapy, the predicted ERR of 0.80 among women who received an inhomogeneous low-dose-rate dose to the bone marrow (mean = 2.5 Gy) was consistent with the measured ERR (0.62, 95% Cl =-0.2 to 1.9). Conclusions: An extended, biologically based model for leukemia that includes HSC initiation, inactivation, proliferation, and, uniquely for leukemia, long-range HSC migration predicts, %Kith reasonable accuracy, risks for radiationinduced leukemia associated with exposure to therapeutic doses of radiation.

Shuryak, Igor↗

Wintertime Brine Discharge at the Surface of a Cold Polar Glacier and the Unexpected Absence of Associated Seismicity

A subglacial groundwater system beneath Taylor Glacier, Antarctica, discharges hypersaline, iron-rich brine episodically at the glacier surface to create Blood Falls. However, the triggering mechanism for these brine release events is not yet understood. Identifying which fracture processes are observed seismically can help us better characterize the hydrological system at Taylor Glacier, and more generally, provide us with a broader understanding of englacial hydrologic activity in cold glaciers. We document wintertime brine discharge using time-lapse photography. Subfreezing air temperatures during the brine discharge indicate that surface melt-induced hydrofracture is an unlikely trigger for brine release. Further, we analyze local seismic data to test a hypothesis that fracturing generates elevated surface wave energy preceding and/or coinciding with brine release events. Our results show no discernible elevated Rayleigh wave activity prior to or during Blood Falls brine release. Instead, we find a pattern of seismic events dominated by a seasonal signal, with more Rayleigh events occurring in the summer than the winter from the Blood Falls source area. We calculate that the volumetric opening of cracks that would generate Rayleigh waves at our detection limits are of similar size to myriad cracks in glacier ice, lake ice, and frozen sediment in the terminus area. We therefore propose that any fracturing coincident with brine release activity likely consists of a series of smaller opening events that are masked by other seismicity in the local environment.

58 GEOSCIENCES↗

Excessive Aurantiochytrium acetophilum docosahexaenoic acid supplementation decreases growth performance and breast muscle mass of broiler chickens

We report Docosahexaenoic acid (DHA) is an n-3 polyunsaturated fatty acid with health-promoting potential. This study was to investigate effects of supplemental DHA from Aurantiochytrium acetophilum on growth performance, health status, meat quality, and protein synthesis signaling of broiler chickens. Day-old male chicks were housed in an environmental control room (6 cages/treatment, 8 chicks/cage), and fed a corn-soybean meal basal diet supplemented with the DHA-rich A. acetophilum biomass (Heliae, Gilbert, AZ) at 0, 1, 2, and 4% (0, 1.7, 3.4 and 6.8 g DHA/kg diet) for 6 weeks. Growth performance was measured weekly. Blood samples were collected at weeks 3 and 6 (2 chicks/cage). Four tissues were sampled (2 chicks/cage) for biochemical and meat quality analyses. Data were analyzed by one-way ANOVA and regression. Compared with the control, the 4% A. acetophilum diet decreased (p < 0.05) body weight gain (19%) and gain to feed ratio (19%) during weeks 4–6. The A. acetophilum supplementation dose-dependently decreased (p < 0.05, R 2 = 0.21–0.54) plasma alanine amino transferase activity and glucose concentrations, but had little effect on plasma activity of alkaline phosphatase or concentrations of inorganic phosphorus and uric acid at weeks 3 and 6. Compared with the control, the 4% A. acetophilum diet decreased (p < 0.05) breast muscle weight by 21%, and down-regulated (p < 0.05) mRNA levels of mammalian target of rapamycin and ribosomal s6 protein (S6), and protein levels of phosphorylated S6 to S6 and phosphorylated S6 kinase beta 1 to S6 kinase beta 1. The A. acetophilum supplementation linearly increased (p < 0.01) lipid peroxidation (R 2 = 0.62–0.90) and hardness and chewiness (R 2 = 0.34–0.44) of breast and thigh muscles. In conclusion, supplemental 4% (6.8 g DHA/kg), but not 1 or 2%, of A. acetophilum impaired growth performance, breast muscle mass accumulation, and(or) protein synthesis signaling of broilers.

59 BASIC BIOLOGICAL SCIENCES↗

Radiation and the Immune System

Radiation has profound effects on the immune system. This makes it particularly important to study in order to protect astronauts venturing into deep space and cancer patients considering radiotherapy treatments. Beyond the Earth's magentic field lies galactic cosmic radiation, which contains heavy ion based rays. Immune alterations in response to radiation depends on factors such as the type and amount of radiation, and potentially even the genes of the individual being exposed. In order to study the effects of cosmic radiation on the immune system, we are exposing primary human immune cells to various types and amounts of radiation. To measure sensitivity to radiation, we are quantifying the DNA damage within the cells before irradiation, 4 hours after irradiation, and 24 hours after irradiation. DNA damage is visualized by fluorescently staining for known DNA repair proteins, which get recruited to the site of damage within a cell. These results will be analyzed to search for correlations between immune cell responses and the type of radiation, amount of radiation, or any genetic markers present in the human blood donors. We will also be attempting to determine which specific immune cells are most suspectible to radiation damage. These correlations and discoveries will contribute to making long duration human deep space exploration a possibility, and can even be used to design more personalized and effective radiation treatments for cancer patients.

Malkani, Sherina S.↗

Decreased NK-Cell Cytotoxicity after Short Flights on the Space Shuttle

Cytotoxic activity of natural killer (NK) cells and cell surface marker expression of peripheral blood mononuclear cells (PBMCs) isolated from 11 U.S. astronauts on two different missions were determined before and after 9 or 10 days of spaceflight aboard the space shuttle. Blood samples were collected 10 and 3 days before launch, within 3 hours after landing, and 3 days after landing. All PBMC preparations were cryopreserved and analyzed simultaneously in a 4-hour cytotoxicity "Cr-release assay using NK-sensitive K-562 target cells. Compared to preflight values, NK-cell cytotoxicity (corrected for lymphopenia observed on landing day) was significantly decreased at landing (P < 0.0125). It then apparently began to recover and approached preflight values by 3 days after landing. Consistent with decreased NK-cell cytotoxicity, significant increases from preflight values were found in plasma adrenocorticotropic hormone at landing. Plasma and urinary cortisol levels did not change significantly from preflight values. Expression of major lymphocyte surface markers (CD3, CD4, CD8, CD14, CD16, CD56), determined by flow cytometric analysis, revealed no consistent phenotypic changes in relative percent of NK or other lymphoid cells after 10 days of spaceflight.

Mehta, Satish K.↗

Angiogenesis and osteogenesis in an orthopedically expanded suture

The purpose of this study was to examine the angiogenic and the subsequent osteogenic responses during a 96-hour time-course after sutural expansion. Fifty rats were divided into: (1) a control group that received only angiogenic induction through injection of 5 ng/gm recombinant human endothelial cell growth factor (rhECGF); (2) an experimental group that received orthopedic expansion and rhECGF; (3) a sham group that received expansion and sodium chloride (NaCl) injection; and (4) a baseline group that received no expansion or injection. All rats were injected with 3H-thymidine (1.0 microCi/gm) 1 hour before death to label the DNA of S-phase cells. Demineralized sections (4 microm thick) were stained with hematoxylin and eosin. Angiogenesis and cell migration were analyzed with a previously established cell kinetics model. Analysis of variance was used to test the hypothesis that enhancement of angiogenesis stimulates reestablishment of osteogenic capability. Blood vessel number, area, and endothelial cell-labeled index significantly increased in experimental groups, but no difference was found between control and baseline groups. Labeled-pericyte index and activated pericyte numbers in the experimental group were also higher than in the sham groups. These results show that supplemental rhECGF enhances angiogenesis in expanded sutures but not in nonexpanded sutures. Data also suggest that pericytes are the source of osteoblasts in an orthopedically expanded suture.

NASA Discipline Musculoskeletal↗

Pharmacokinetics of Acetaminophen in Hind Limbs Unloaded Mice: A Model System Simulating the Effects of Low Gravity on Astronauts in Space

The pharmacokinetics (PK) of medications administered to astronauts could be altered by the conditions in Space. 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 in astronauts. Acquiring of such knowledge has inherent difficulties due to limited opportunities for experimenting in Space. One of the approaches is to use model systems that simulate some of the Space conditions on Earth. In this study we used hind limbs unloaded mice (HLU) to investigate the possible changes in PK of acetaminophen, a widely used analgesic with high probability of use by astronauts. The HLU is recognized as an appropriate model for simulating the effects of low gravity on hemodynamic parameters. Mice were tail suspended (n = 24) for 24-96 hours prior to introduction of acetaminophen (150 - 300 mg/kg). The drug (in aqueous solution containing 10% ethyl alcohol by volume) was given orally by a gavage procedure and after the administration of acetaminophen mice were additionally suspended for 30 min, 1 and 2 hours. Control mice (n = 24) received the same dose of acetaminophen and were kept freely all the time. Blood specimens were obtained either from retroorbital venous sinuses or from heart. Acetaminophen concentration was measured in plasma by the fluorescent polarization immunoassay and the AxSYM analyzer (Abbott Laboratories). In control mice peak acetaminophen concentration was achieved at 30 min. By 1 hour the concentration decreased to less than 50% of the peak level and at 2 hours the drug was almost undetectable in the serum. HLU for 24 hours significantly altered the acetaminophen pharmacokinetic: at 30 min the acetaminophen concentrations were significantly (both statistically and medically significant) lower than in control mice. The concentrations also reduced less significantly after 1 and 2 hours. At 2 hours approximately 20% of the drug still remained in the circulation. After 96 hrs of HLU the changes in acetaminophen PK were less prominent. These data indicate that short term HLU causes significant changes in acetaminophen PK most likely associated with HUL-related hemodynamic changes. However, after 96 hour these changes diminished. This suggests hemodynamic adaptation to the HUL conditions that possibly occurs also in real space conditions.

Peterson, Amanda↗

ISS Technology Demonstrations for Future Spaceflight Medical Systems

Throughout the history of human spaceflight, crewmembers have experienced various in-flight medical conditions including illness and injury. Planned missions to the Moon and Mars will require capabilities to maintain the health of future space travelers. Mass, power, and volume available in the vehicles and habitats for these missions will be severely constrained; resupply of resources will be limited or non-existent, as will opportunities for evacuation to Earth. Furthermore, ground-based support will be hampered by communication latencies and blackouts. These vehicle and mission constraints will necessitate a medical system that has been efficiently planned, providing on-board procedural guidance in addition to a variety of medical devices and consumable resources. Medical capabilities required for the diagnosis and treatment of potential medical conditions during future spaceflight missions may include real-time health monitoring, medical imaging, and biomarker analyses ( e.g., blood or urine). Terrestrial medicine shares these needs, thus many of these medical capabilities could likely be satisfied by Commercial-Off-The-Shelf (COTS) devices and methodologies; however, in some cases the unique space environment and increased mission duration will drive the need to modify technologies and the way care is provided. NASA’s Human Research Program (HRP) Exploration Medical Capability (ExMC) Element and Mars Campaign Office’s Exploration Medical Integrated Product Team (XMIPT) are working together to decrease medical risk during exploration missions. Flight-tested medical diagnostic and treatment technologies are necessary to effectively manage medical conditions relevant to exploration missions while meeting vehicle constraints, integrating with medical decision-support tools, and enabling increasingly Earth-independent operations. Several projects have leveraged the ISS as a testbed for exploration, including 1) i n- situ blood analysis, 2) medical inventory, 3) intravenous fluid generation, and 4) autonomous medical procedure guidance. Management of several in-flight medical conditions, such as bacterial and viral infections and acute radiation syndrome, is dramatically improved with ability to assess blood cell populations, electrolytes, and metabolites. I n December 2020 and January 2021 ExMC performed an ISS technology demonstration (Tech Demo) of the HemoCue® WBC DIFF analyzer (HemoCue, Brea, CA), a COTS device that was modified to enable functionality in a spaceflight environment. This Tech Demo marked the first time that hematology measurements were successfully performed real-time in microgravity. Also modified and demonstrated was the reusable Handheld Electrolytes and Lab Technology for Humans (rHEALTH) ONE analyzer (rHEALTH, Bedford, MA), which uses flow cytometry and sheath-based hydrodynamic focusing methodologies. The rHEALTH ONE ISS Tech Demo in May 2022 demonstrated test results obtained in-flight matched those on the ground. NASA currently relies on crew self-reporting to manage and maintain medical inventory on ISS.The ability to maintain an accurate inventory becomes more critical during long duration missions since the crew will need to be increasingly autonomous in finding and utilizing medical items, including those scenarios when alternative treatments need to be considered due to limited or no resupply. HRP’s Medical Consumables Tracking (MCT) project was developed by ZIN Technologies, Inc. (Cleveland, OH), and demonstrated real-time tracking of medical supplies aboard the ISS between December 2016 and July 2018. The MCT system design utilized Radio Frequency Identification Device (RFID) technology to perform automated inventory and was installed in the Crew Health Care System (CHeCS) Resupply Stowage Rack (RSR). The challenge of limited shelf life, exacerbated by the lack of resupply opportunities, affects a plethora of medical system components including consumables, pharmaceuticals, and intravenous (IV) fluid. In 2010, ExMC funded ZIN Technologies, Inc. (Cleveland, OH), to develop the Intravenous Fluid Generation (IVGEN) system. IV fluids were successfully generated with IVGEN using the potable water supply on ISS during ISS Expedition 23. The XMIPT is in the process of developing a miniaturized version of the original IVGEN hardware for a future Tech Demo aboard the ISS. Current ISS medical operations rely heavily on preflight training and real-time remote guidance, both of which become impractical or impossible for exploration missions. The primary goal of the Autonomous Medical Officer Support (AMOS) Software Tech Demos on ISS was to confirm telemedical proof-of-concept for autonomous medical imaging in an operational setting. This novel software tool shifts emphasis from preflight training and real-time remote guidance to in-flight just-in-time instruction, a new and necessary paradigm for crew medical autonomy. AMOS introduces a novel, streamlined skill management concept for exploration missions featuring comprehensive training and guidance modules for ultrasound examinations using the ISS Ultrasound 2 (a modified GE Vivid-q™; General Electric HealthCare, Chicago, IL). With no prior crew training or remote guidance, two Tech Demos on the ISS (April 2020 and June 2022) resulted in high quality, clinically useful image sets. We will provide a review of historical, current, and planned medical devices and technologies considered for inclusion within future spaceflight medical systems and summarize hardware development activities and medical device tech demos conducted on the ISS.

Astronaut health and performance↗

A dual-input nonlinear system analysis of autonomic modulation of heart rate

Linear analyses of fluctuations in heart rate and other hemodynamic variables have been used to elucidate cardiovascular regulatory mechanisms. The role of nonlinear contributions to fluctuations in hemodynamic variables has not been fully explored. This paper presents a nonlinear system analysis of the effect of fluctuations in instantaneous lung volume (ILV) and arterial blood pressure (ABP) on heart rate (HR) fluctuations. To successfully employ a nonlinear analysis based on the Laguerre expansion technique (LET), we introduce an efficient procedure for broadening the spectral content of the ILV and ABP inputs to the model by adding white noise. Results from computer simulations demonstrate the effectiveness of broadening the spectral band of input signals to obtain consistent and stable kernel estimates with the use of the LET. Without broadening the band of the ILV and ABP inputs, the LET did not provide stable kernel estimates. Moreover, we extend the LET to the case of multiple inputs in order to accommodate the analysis of the combined effect of ILV and ABP effect on heart rate. Analyzes of data based on the second-order Volterra-Wiener model reveal an important contribution of the second-order kernels to the description of the effect of lung volume and arterial blood pressure on heart rate. Furthermore, physiological effects of the autonomic blocking agents propranolol and atropine on changes in the first- and second-order kernels are also discussed.

NASA Discipline Regulatory Physiology↗

Structural Characterization of Toxicologically Relevant Cd 2+ -L-Cysteine Complexes

The exposure of humans to Cd exerts adverse human health effects at low chronic exposure doses, but the underlying biomolecular mechanisms are incompletely understood. To gain insight into the toxicologically relevant chemistry of Cd 2+ in the bloodstream, we employed an anion-exchange HPLC coupled to a flame atomic absorption spectrometer (FAAS) using a mobile phase of 100 mM NaCl with 5 mM Tris-buffer (pH 7.4) to resemble protein-free blood plasma. The injection of Cd 2+ onto this HPLC-FAAS system was associated with the elution of a Cd peak that corresponded to [CdCl 3 ] - /[CdCl 4 ] 2- complexes. The addition of 0.1–10 mM L-cysteine (Cys) to the mobile phase significantly affected the retention behavior of Cd 2+ , which was rationalized by the on-column formation of mixed CdCysxCly complexes. From a toxicological point of view, the results obtained with 0.1 and 0.2 mM Cys were the most relevant because they resembled plasma concentrations. The corresponding Cd-containing (~30 μM) fractions were analyzed by X-ray absorption spectroscopy and revealed an increased sulfur coordination to Cd 2+ when the Cys concentration was increased from 0.1 to 0.2 mM. The putative formation of these toxicologically relevant Cd species in blood plasma was implicated in the Cd uptake into target organs and underscores the notion that a better understanding of the metabolism of Cd in the bloodstream is critical to causally link human exposure with organ-based toxicological effects.

59 BASIC BIOLOGICAL SCIENCES↗