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At least 199 records · Page 11

Incidence of Latent Virus Shedding during Space Flight

Measurements of immune parameters of both cellular and innate immunity indicate alterations in immune function in astronauts. Immune changes are due to stress and perhaps other factors associated with launch, flight, and landing phases. Medical relevance of observed changes is not known. The reactivation of latent viruses has been identified as an important in vivo indicator of clinically relevant immune changes. The polymerase chain reaction (PCR) was used to detect the presence of specific viral DNA in body fluids. Initial studies demonstrated Epstein-Barr virus (EBV) reactivation during all 3 mission phases. EBV is shed in saliva following reactivation from B-cells. Incidence of EBV in saliva was higher than control subjects during all 3 mission phases. However, quantitative PCR revealed 10-fold higher levels of EBV DNA present in saliva collected during flight than found in pre- and post flight specimens. To determine if other latent viruses showed similar effects, cytomegalovirus (CMV), another herpes virus, shed in urine following reactivation was studied. A very low incidence (less than 2%) of CMV in urine is found in healthy, lowstressed individuals. However, 25-50% of astronauts shed CMV in their urine before, during, or after flight. Our studies are now focused on varicella-zoster virus (VZV), the etiological agent of chicken-pox during childhood and shingles later in life. We demonstrated reactivation of VZV and shedding of the virus during and after spaceflight in saliva of astronauts with no sign of active infection or symptoms. The maximum shedding of VZV occurred during the flight phase and diminishes rapidly during the first five days after landing. We have utilized the same PCR assay for VZV in a clinical study of shingles patients. Generally, shingles patients shed much more VZV in saliva than astronauts. However, the VZV levels in astronauts overlap with the lower range of VZV numbers in shingles patients. Saliva from shingles patients and astronauts were cultured and infectious VZV was recovered from both groups. We have concluded that multiple latent viruses do reactivate before, during, and after spaceflight and serve as very sensitive indicators for diminished cellular immunity. Future plans will be focused on the clinical risks posed by the reactivation of these viruses. Initial efforts will determine the effect of longer missions on the International Space Station on the reactivation patterns of these viruses.

Mehta, Satish K.↗

Latent Virus Reactivation: From Space to Earth

Reactivation of latent viruses is a recognized consequence of decreased immunity. More recently viral reactivation has been identified as an important in vivo indicator of clinically relevant immune changes. Viral reactivation can be determined quickly and easily by the presence of virus in saliva and other body fluids. Real-time polymerase chain reaction (PCR) is a highly sensitive and specific molecular method to detect the presence of specific viral DNA. Studies in astronauts demonstrated that herpes simplex virus type 1(HSV-1), Epstein-Barr Virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate at rates above normal during and after spaceflight in response to moderately decreased T-cell immunity. This technology was expanded to patients on Earth beginning with human immune deficiency virus (HIV) immuno-compromised patients. The HIV patients shed EBV in saliva at rates 9-fold higher than observed in astronauts demonstrating that the level of EBV shedding reflects the severity of impaired immunity. Whereas EBV reactivation is not expected to produce serious effects in astronauts on missions of 6 months or less, VZV reactivation in astronauts could produce shingles. Reactivation of live, infectious VZV in astronauts with no symptoms was demonstrated in astronauts during and after spaceflight. We applied our technology to study VZV-induced shingles in patients. In a study of 54 shingles patients, we showed salivary VZV was present in every patient on the day antiviral (acyclovir) treatment was initiated. Pain and skin lesions decreased with antiviral treatment. Corresponding decreases in levels of VZV were also observed and accompanied recovery. Although the level of VZV in shingles patients before the treatment was generally higher than those found in astronauts, lower range of VZV numbers in shingles patients overlapped with astronaut s levels. This suggests a potential risk of shingles to astronauts resulting from reactivation of VZV. In another clinical study of 25 shingles patients, PCR technology detected VZV in the serum and peripheral blood mononuclear cells of all 25 patients demonstrating for the first time that viremia is a common manifestation of herpes shingles.

Mehta, Satish K.↗

NASA Tech Briefs, September 2004

Topics covered include: Brazing SiC/SiC Composites to Metals; Composite-Material Tanks with Chemically Resistant Liners; Thermally Conductive Metal-Tube/Carbon-Composite Joints; Improved BN Coatings on SiC Fibers in SiC Matrices; Iterative Demodulation and Decoding of Non-Square QAM; Measuring Radiation Patterns of Reconfigurable Patch Antennas on Wafers; Low-Cutoff, High-Pass Digital Filtering of Neural Signals; Further Improvement in 3DGRAPE; Ground Support Software for Spaceborne Instrumentation; MER SPICE Interface; Simulating Operation of a Planetary Rover; Analyzing Contents of a Computer Cache; Discrepancy Reporting Management System; Silicone-Rubber Microvalves Actuated by Paraffin; Hydraulic Apparatus for Mechanical Testing of Nuts; Heat Control via Torque Control in Friction Stir Welding; Manufacturing High-Quality Carbon Nanotubes at Lower Cost; Setup for Visual Observation of Carbon-Nanotube Arc Process; Solution Preserves Nucleic Acids in Body-Fluid Specimens; Oligodeoxynucleotide Probes for Detecting Intact Cells; Microwave-Spectral Signatures Would Reveal Concealed Objects; Digital Averaging Phasemeter for Heterodyne Interferometry; Optoelectronic Instrument Monitors pH in a Culture Medium; Imaging of gamma-Irradiated Regions of a Crystal; Photodiode-Based, Passive Ultraviolet Dosimeters; Discrete Wavelength-Locked External Cavity Laser; Flexible Shields for Protecting Spacecraft Against Debris; Part 2 of a Computational Study of a Drop-Laden Mixing Layer; Controllable Curved Mirrors Made from Single-Layer EAP Films; and Demonstration of a Pyrotechnic Bolt-Retractor System.

Source record↗

Saliva Preservative for Diagnostic Purposes

Saliva is an important body fluid for diagnostic purposes. Glycoproteins, glucose, steroids, DNA, and other molecules of diagnostic value are found in saliva. It is easier to collect as compared to blood or urine. Unfortunately, saliva also contains large numbers of bacteria that can release enzymes, which can degrade proteins and nucleic acids. These degradative enzymes destroy or reduce saliva s diagnostic value. This innovation describes the formulation of a chemical preservative that prevents microbial growth and inactivates the degradative enzymes. This extends the time that saliva can be stored or transported without losing its diagnostic value. Multiple samples of saliva can be collected if needed without causing discomfort to the subject and it does not require any special facilities to handle after it is collected.

Pierson, Duane L.↗

Psychophysiology of Spaceflight and Aviation

In space, the absence of gravity alone causes unique physiological stress. Significant biomedical changes, across multiple organ systems, such as body fluid redistribution, diminished musculoskeletal strength, changes in cardiac function and sensorimotor control have been reported. The time course of development of these disorders and severity of symptoms experienced by individuals varies widely. Space motion sickness (SMS) is an example of maladaptation to microgravity, which occurs early in the mission and can have profound effects on physical health and crew performance. Disturbances in sleep quality, perception, emotional equilibrium and mood have also been reported, with impact to health and performance varying widely across individuals. And lastly, post-flight orthostatic intolerance, low blood pressure experienced after returning to Earth, is also of serious concern. Both the Russian and American space programs have a varied list of human errors and mistakes, which adversely impacted mission goals. Continued probability of human exposure to microgravity for extended time periods provides a rationale for the study of the effects of stress. The primary focus of this research group is directed toward examining individual differences in: (a) prediction of susceptibility to these disorders, (b) assessment of symptom severity, (c) evaluation of the effectiveness of countermeasures, and (d) developing and testing a physiological training method, Autogenic-Feedback Training Exercise (AFTE) as a countermeasure with multiple applications. The present paper reports on the results of a series of human flight experiments with AFTE aboard the Space Shuttle and Mir Space Station, and during emergency flight scenarios on Earth.

Cowings, Patricia↗

FRET-Aptamer Assays for Bone Marker Assessment, C-Telopeptide, Creatinine, and Vitamin D

Astronauts lose 1.0 to 1.5% of their bone mass per month on long-duration spaceflights. NASA wishes to monitor the bone loss onboard spacecraft to develop nutritional and exercise countermeasures, and make adjustments during long space missions. On Earth, the same technology could be used to monitor osteoporosis and its therapy. Aptamers bind to targets against which they are developed, much like antibodies. However, aptamers do not require animal hosts or cell culture and are therefore easier, faster, and less expensive to produce. In addition, aptamers sometimes exhibit greater affinity and specificity vs. comparable antibodies. In this work, fluorescent dyes and quenchers were added to the aptamers to enable pushbutton, one-step, bind-and-detect fluorescence resonance energy transfer (FRET) assays or tests that can be freeze-dried, rehydrated with body fluids, and used to quantitate bone loss of vitamin D levels with a handheld fluorometer in the spacecraft environment. This work generated specific, rapid, one-step FRET assays for the bone loss marker C-telopeptide (CTx) when extracted from urine, creatinine from urine, and vitamin D congeners in diluted serum. The assays were quantified in nanograms/mL using a handheld fluorometer connected to a laptop computer to convert the raw fluorescence values into concentrations of each analyte according to linear standard curves. DNA aptamers were selected and amplified for several rounds against a 26- amino acid form of CTx, creatinine, and vitamin D. The commonalities between loop structures were studied, and several common loop structures were converted into aptamer beacons with a fluorophore and quencher on each end. In theory, when the aptamer beacon binds its cognate target (CTx bone peptide, creatinine, or vitamin D), it is forced open and no longer quenched, so it gives off fluorescent light (when excited) in proportion to the amount of target present in a sample. This proportional increase in fluorescence is called a "lights on" FRET response. The vitamin D aptamer beacon gives a "lights off" or inversely proportional fluorescence response to the amount of vitamin D present in diluted serum. These FRET-aptamer assays are rapid (<30 minutes), sensitive (low ng/mL detection limits), and quite easy to carry out (add sample, mix, and detect in the handheld reader). Benefits include the speed of the assays as well as the small amount of space taken up by the handheld reader and cuvette assays. The aptamer DNA sequences represent novel additional features of the existing (patent-pending) FRET-aptamer assay platform.

Bruno, John G.↗

Determination of Roles of Microgravity and Ionizing Radiation on the Reactivation of Epstein-Barr Virus In Vitro

Astronauts experience symptomatic and asymptomatic herpes virus reactivation during spaceflight. We have shown increases in reactivation of Epstein-Barr virus (EBV), cytomegalovirus (CMV) and varicella zoster virus (VZV) and shedding in body fluids (saliva and urine) in astronauts during space travel. Alterations in immunity, increased stress hormone levels, microgravity, increased radiation, and other conditions unique to spaceflight may promote reactivation of latent herpes viruses. Unique mechanico-physico forces associated with spaceflight can have profound effects on cellular function, especially immune cells. In space flight analog studies such as Antarctica, bed rest studies, and NASA's undersea habitat (Aquarius), reactivation of these viruses occurred, but to a lesser extent than spaceflight. Spaceflight analogs model some spaceflight factors, but none of the analogs recreates all factors experienced in space. Most notably, microgravity and radiation are not included in many analogs. Stress, processed through the HPA axis and SAM systems, induces viral reactivation. However, the respective roles of microgravity and increased space radiation levels or if any synergy exists are not known. Therefore, we studied the effect of modeled space radiation and/or microgravity, independent of the immune system on the changes in cellular gene expression that results in viral (EBV) reactivation. The effects of modeled microgravity and low shear on EBV replication and cellular and EBV gene expression were studied in human B-lymphocyte cell cultures. Latently infected B-lymphocytes were propagated in the rotating wall bioreactor and irradiated with the various dosages of gamma irradiation. At specific time intervals following exposure to modeled microgravity, the cells and supernatant were harvested and reactivation of EBV were assessed by measuring EBV and gene expression, DNA methylation, and infectious virus production.

Mehta, Satish K↗

Handheld Fluorescence Resonance Energy Transfer (FRET)-Aptamer Sensor for Bone Markers

Astronauts lose significant bone mass during lengthy space flights. NASA wishes to monitor this bone loss in order to develop nutritional and exercise countermeasures. Operational Technologies Corporation (OpTech) has developed a handheld device that quantifies bone loss in a spacecraft environment. The innovation works by adding fluorescent dyes and quenchers to aptamers to enable pushbutton, one-step bind-and-detect FRET assays that can be freeze-dried, rehydrated with body fluids, and used to quantify bone loss.

Bruno, John G.↗

Herpesviruses in Saliva and Their Clinical Significance

Saliva has been used as a source of biological markers for a wide spectrum of normal and disease states for a long time. It is a non-invasive, easily accessible, and self-collected body fluid that contains a variety of measurable biological substances. While mostly water, saliva also contains ions, carbohydrates, proteins and peptides, exfoliated cells, nucleic acids, and microorganisms. Saliva can reflect tissue levels of some natural substances and a large variety of molecules introduced for therapeutic use, emotional status; hormonal status, immunological status, neurological effects, and nutritional and metabolic status. It can also be used to monitor a variety of drugs including marijuana, cocaine, and alcohol. It is the most cost-effective approach for screening large population in community mass screening programs and for longitudinal sampling of hospitalized individuals aimed at monitoring viral load dynamics and treatment response. During the COVID-19 pandemic, scientific evidence emerged indicating that molecular tests performed on saliva have diagnostic sensitivity and specificity comparable to those observed with nasopharyngeal swabs for SARS-CoV-2 RNA detection. The presence of IgA and IgG antibodies at the mucosal level has been demonstrated to influence the progression of viral infection and the severity of clinical manifestation. As saliva contains both respiratory secretions and immunological components, it has wide applications, ranging from clinical diagnostics to post-vaccine disease burden and immunity surveillance.

Douglass Diak↗

Transcapillary fluid responses to lower body negative pressure

The effect of lower body negative pressure (LBNP) on transcapillary fluid balance, with and without saline ingestion, was investigated in normally hydrated human subjects by measuring leg interstitial fluid pressure, leg circumference, plasma volume, and net whole body transcapillary fluid transport during and after supine LBNP in human subjects. The results indicate that prolonged LBNP, especially with saline ingestion, promotes fluid filtration into lower body tissues.

Aratow, Michael↗

Numerical solution for low-velocity penetration of rigid body into still fluid

A modified marker-and-cell computational method is developed which can be used to study problems related to impact and penetration of a rigid body into a viscous medium. The method has been applied to solving (in two dimensions) the problem of low-velocity penetration of a rigid block into still water. The solution gives the complete pressure and velocity of the flow field so that the force and displacement time histories of the rigid body during the impact and entry phase are evaluated from the boundary stresses imposed by the fluid on the rigid body. Some limited experimental comparisons are also given to demonstrate the feasibility of the computational method.

Cheng, R. Y.-K.↗

Computer simulation of preflight blood volume reduction as a countermeasure to fluid shifts in space flight

Fluid shifts in weightlessness may cause a central volume expansion, activating reflexes to reduce the blood volume. Computer simulation was used to test the hypothesis that preadaptation of the blood volume prior to exposure to weightlessness could counteract the central volume expansion due to fluid shifts and thereby attenuate the circulatory and renal responses resulting in large losses of fluid from body water compartments. The Guyton Model of Fluid, Electrolyte, and Circulatory Regulation was modified to simulate the six degree head down tilt that is frequently use as an experimental analog of weightlessness in bedrest studies. Simulation results show that preadaptation of the blood volume by a procedure resembling a blood donation immediately before head down bedrest is beneficial in damping the physiologic responses to fluid shifts and reducing body fluid losses. After ten hours of head down tilt, blood volume after preadaptation is higher than control for 20 to 30 days of bedrest. Preadaptation also produces potentially beneficial higher extracellular volume and total body water for 20 to 30 days of bedrest.

Simanonok, K. E.↗

Creeping flow of a conducting fluid past axisymmetric bodies in the presence of an aligned magnetic field

The use of strong magnetic fields for the control of particle settling in metallic systems is investigated by altering the fluid mechanics in the melt. The fluid mechanism of particle settling is analyzed for the motion around single, axisymmetric particles in the limit of creeping flow for a fluid with a large electrical conductivity. The drag is found to increase proportionately to the intensity of the magnetic field or the Hartmann number Ha. The flowfield forms boundary layers, which thin out with increasing Ha, along the surfaces parallel to the flow. For axisymmetric bodies, the boundary layer separates as the poles of the surface are approached and encloses regions of almost stagnant fluid. These regions spread upstream and downstream along the body with increasing Ha, thereby trapping the particle in a column of stagnant fluid.

Kyrlidis, A.↗

Distribution of fluids in the body of the centrifuged rat

The effects of exposure to an elevated g-level throughout the period of rapid growth is investigated in a comparison of a group of female Sprague-Dawley rats centrifuged as adults with other groups centrifuged for prolonged intervals starting shortly after weaning. The fluid-solid composition of total body, heart, liver, gut, skin, and muscle for both study groups is compared with that of a control group. None of the changes as a result of centrifugation were truly persistent. The only increases in mass associated with centrifugation and the only responses to centrifugation per se were observed in the skin values.

Pitts, G. C.↗

Heating Analysis of the Lockheed Lifting Body

Computational fluid dynamic (CFD) analysis is performed on the Lockheed Lifting Body Single-Stage-to-Orbit vehicle to determine the heat transfer to the vehicle during its descent trajectory. Seven species, chemical nonequilibriurn computations using the GASP code will be completed at several trajectory points to assess the thermal protection requirements of the vehicle. Sophisticated surface boundary conditions including in-depth conduction, catalycity, and a variable temperature wall have been incorporated into the flow solver.

Palmer, Grant↗