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NASA NTRS2010

Filovirus Research: The Need for an Integrated Approach in Time and Space

The episodic appearance of Ebola virus (EBOV) and Marburg virus (MARV) across central Africa over the last 15 years not only underscores the importance of filoviruses as uniquely virulent agents to both human and wildlife communities but also implies a very complex transmission scenario that must be understood if we are to prevent or mitigate filovirus outbreaks in the future. Efforts of a global network of scientists and healthcare workers have expanded our knowledge of filoviruses to meet the growing threat of Ebola and Marburg hemorrhagic fevers in Africa. In recent decades, several newly emerging diseases have resulted in major threats to both affected communities and global public health. Viruses from wildlife hosts in particular, have exhibited a capability for cross-species transmission (CST), and have caused high-impact diseases in humans Such as Ebola and Marburg hemorrhagic fevers, Nipah and severe acute respiratory syndrome (SAILS). It has been estimated that about 60.3% (Jones et al. 2008) of human infectious diseases are of animal origin (zoonoses) and even some important viral diseases that are traditionally considered of human origin, for example measles and smallpox, may very well have their prehistoric origins in wildlife (Wolfe et al 2007). It maybe logical and prudent therefore, to anticipate that there are other, new filoviruses out there that will cross into humans at some point in time. If we anticipate that these will happen and wish to be prepared for and mitigate this potential, then an understanding of filoviruses as a biologic system in the environment will be essential to that process. We will need to know how the ecological dynamic of CST interacts with a 'new' viruse's evolutionary factors to overcome environmental, demographic and host-specific barriers to transmission and infectivity to humans.

Pinzon, Jorge E.↗
NASA NTRS2013

Emerging and Reemeriging Human Bunyavirus Infections and Climate Change

The Bunyaviridae family includes a growing number of viruses that have contributed to the burden of emerging and reemerging infectious diseases around the globe. Many of these viruses cause severe clinical outcomes in human and animal populations, the results of which can be detrimental to public health and the economies of affected communities. The threat to endemic and non-native regions is particularly high, and national and international public health agencies are often on alert. Many of the bunyaviruses cause severe clinical disease including hemorrhage, organ failure, and death leading to their high-risk classification. Hantaviruses and Rift Valley fever virus (RVFV) (genus Phlebovirus) are National Institute of Allergy and Infectious Diseases Category A priority pathogens in the United States. Viral hemorrhagic fevers, a classification that includes many bunyaviruses, are immediately notifiable in the European Union. The emergence of new and reemerging bunyaviruses has resulted in numerous human and animal fatalities. Outbreaks of Rift Valley fever (RVF) in East Africa (1997/1998, 2006/2007), Sudan (2007), Southern Africa (2008-2010), Kenya (1997/1998, 2006/2007) (Anyamba et al., 2009, 2010; Breiman et al., 2010; Grobbelaar et al., 2011; Woods et al., 2002) and Saudi Arabia & Yemen (2000, 2010) (Food and Agriculture Organization, 2000; Hjelle and Glass, 2000; Madani et al., 2003) and the emergence of Sin Nombre virus (1993) (Hjelle and Glass, 2000) and most recently Schmallenberg virus (2011) (DEFRA, 2012) are prime examples of the devastating and worldwide toll bunyaviruses have on health and economies. Climate variability (precipitation and temperature in particular) greatly influence the ecological conditions that drive arboviral disease outbreaks across the globe. Several human and animal disease outbreaks have been influenced by changes in climate associated with the El Niño Southern Oscillation (ENSO) phenomenon including the bunyaviruses RVFV and Sin Nombre (an etiologic agent of hantavirus pulmonary syndrome (HPS)), as well as Murray Valley encephalitis, chikungunya, and malaria to name but a few (Anyamba et al., 2009; Bouma and Dye, 1997; Chretien et al., 2007; Engelthaler et al., 1999; Kovats et al., 2003; Linthicum et al., 1999; Nicholls, 1986). Most bunyaviruses exhibit episodic outbreak patterns with seasonal or annual trends dependent upon climate conditions, vector abundance, and the proximity of a susceptible population. The implications for continued climate change are dire, especially with regard to vector-borne diseases, many of which can cause severe morbidity, sequelae, and death. Increased rainfall and widening endemicity as a result of climate change, compounded by the emergence of new viruses, poses a serious threat to a greater geographic range beyond the regions of endemicity.

Bunyavirus↗
NASA NTRSDate not supplied

Comparison of Multispectral Imaging and Traditional Fundoscopy in the Detection of Terrestrial Retinal and Optic Nerve Pathologies like those Encountered During and/or Immediately Following Long-Duration Spaceflight

INTRODUCTION: The purpose of this investigation was to evaluate if MultiColor Imaging (MCI) can replace color fundus photography (CFP) as a diagnostic screening tool during spaceflight. MCI significantly reduces crew time (approx. 115 minutes/session, 36 hours/year) by eliminating nominal on-orbit fundoscopy sessions, while also providing the option to capture a larger field of view (55 vs. 35). METHODS: A comprehensive PubMed literature search was conducted using the following key words: multicolor, multispectral, imaging, retina, choroid, optic nerve, optic disc, and papilledema. Publications were filtered based on optic nerve and chorioretinal pathologies matching those seen during or immediately after spaceflight: optic disc edema (ODE), cotton wool spots (CWS), retinal hemorrhage, pigment epithelial detachment (PED), and serous chorioretinopathy (SCR). In a separate effort, 44 multicolor images (30 abnormal) of terrestrial patients were graded and compared to corresponding color fundus images acquired at the Doheny Eye Centers and UCLA. RESULTS: The search identified 340 articles; 9 describing MCI in relevant pathologies, 6 comparing MCI to CFP. MCI is superior in detecting CWS (1 paper), PED (2 papers), retinal hemorrhages (2 papers), and choroidal folds (1 paper), and can better delineate extent or boundaries of subretinal fluid and identify areas of RPE damage in SCR (2 papers). On MCI, ODE was described as a hyperreflective ring with a green shift and indistinct disc margins, with equaldetectability as using CFP (3 papers). Grading at Doheny Eye Institute confirmed these findings. DISCUSSION: MCI can effectively detect all retinal and optic nerve findings detectable by CFP during and immediately post-spaceflight and represents a suitable replacement as an on-orbit diagnostic screening tool. Additionally, by eliminating the nominal on-orbit fundoscopy sessions, dozens of crew hours are spared per year by utilizing MCI.

Jorge Nagel↗
NASA NTRS1966

Histopathology of the Chimpanzee Ear

Four female and two male chimpanzees were secured in various positions on a Daisy Decelerator and subjected to forces ranging from 54 to 180 G. It was found that forces in excess of 54 G may rupture the tympanic membranes and cause subepithelial hemorrhages in the middle ear. The majority of cases showed proteinaceous material, with or without cells in the petrous air spaces. When exposed to forces above 119 G, there was engorgement and often rupture of the pericarotid venous plexus. When supine, distortion of both superior and posterior semicircular canals was found. With forces in excess of 54 G, the cupulae of the cristae ampullaris were either elevated or destroyed. The hair processes were also often broken off. The otolithic membranes, especially of the maculae utriculi were also elevated or otherwise distorted and the saccule was often partially collapsed. In several instances, there was an overabundance of a proteinaceous substance in the lumina of the vestibular apparatus and in the cochlear ducts with their associated scalae. In half the cases, the cochlear duct was narrowed by the depression of the vestibular membrane. Although there seems to be considerable individual variation in ability to withstand these forces, neither age, sex nor weight appear to directly influence the results. The possible sources for the materials found both in the air cells and labyrinth are discussed.

ACCELERATION TOLERANCE↗
NASA NTRS1972

Studies of effects of closed microbial ecology. Report of 180-day test period

Experiments were performed to determine the influence closed microbial ecologies have on modification or simplification of natural intestinal flora of ferrets in a closed environmental system. On the basis of previous tests in which certain species (Salmonella and Bacteroides) were decreased at 90 days of enclosure, a second trial was constructed for 180-day tests. In this trial there was little difference in the 8 major classes of intestinal flora between animals in the Open and Closed environmental groups except for the level of Lactobacillus. It is of extreme importance to note that when both Open and Closed groups contracted hemorrhagic gastritis, the interrelationship of this agent with other intestinal flora produced a more profound effect on animals from the Closed Group, particularly with reference to Lactobacillus levels.

Kenyon, A. J.↗
NASA NTRS1974

Aeromonas proteolyrica bacteria in aerospace environments

Preflight studies on Aeromonas proteolytica are reported to investigate the possibility of genetic alterations resulting in increased proteolysis in spacecraft environments. This organism may be present on human tissue and could pose medical problems if its endopeptidase and a hemolysin were to be produced in ususually high quantities or altered in such a way as to be more effective in their activities. Considered are: (1) Development of a nutrative holding medium for suspension of organisms; (2) the establishment of baseline information for the standardization of the assay for endopeptidase levels and hemolytic titers; (3) formulation of a method by which intracutaneous hemorrhage could be quantitated in guinea pig tissue; and (4) the responses of these organisms to parameters of spaceflight and experimentation.

Foster, B. G.↗
NASA NTRS1975

Toxicologic evaluation of the migration of a plasticizer, DI (2-ethylhexyl) phthalate (DEHP) from vinyl plastics

The intravenous administration of DEHP solubilized by means of a number of different detergents leads to respiratory distress and death in rats. At autopsy the lungs are grossly enlarged, edamatous, and hemorrhagic. Light and electron microscopic evaluation of the lungs indicate engorgement of the interalveolar septa with edema fluid and polymorphonuclear leucocytes, degranulation of the leukocytes, and progessive destruction of the endothelial and epithelial cells. Consistent with the conclusion that solubilized DEHP results in a syndrome of "shock lung" is the associated massive fall in arterial blood pressure and the prevention of the lung pathology by pretreatment with pharmacologic doses of an antiinflammatory steroid, methylprednisolone. Evidence is also presented that suggests that the DEHP inadvertently administered to humans during transfusions is also in a solubilized state in the plasma.

Rubin, R. J.↗
NASA NTRS1975

Acute pulmonary pathology and sudden death in rats following the intravenous administration of the plasticizer, DI (2-ethylhexyl) phthalate, solubilized with Tween surfactants

Intravenous administration of 200-300 mg/kg of di(2-ethylhexyl)phthalate (DEHP) solubilized in aqueous solutions of several Tween surfactants caused respiratory distress in rats. There was a dose-dependent lethality with death generally occurring within 90 minutes after injection. The lungs from DEHP:Tween treated animals were enlarged, generally darkened, and in some cases showed hemorrhagic congestion. Neither the overt symptoms nor the morphologic alterations resulting from DEHP:Tween administration could be reproduced by intravenous administration of aqueous Tween solutions alone. The absence of pulmonary abnormalities following the intravenous administration of DEHP as an aqueous emulsion given either alone or even as soon as 2 minutes after pretreatment with Tween 80, suggests that the specific in vivo interaction between DEHP and Tween surfactants depends on the prior formation of water-soluble micelles of DEHP.

Schulz, C. O.↗
NASA NTRS1975

Launch, flight, and recovery

The final phase to fly five pocket mice in the Apollo XVII command module was carried out at the NASA Kennedy Space Center. Upon completion of the 13-d space flight, the package was removed from the spacecraft and, after having been purged with an oxygen-helium gas mixture, was flown to American Samoa. Four of the five mice were recovered alive from the package. Analysis of the mouse that died during the flight revealed several factors that could have contributed to its death, the chief of which was massive hemorrhage in its middle ear cavities.

Look, B. C.↗
NASA NTRS1975

Results of ear examination

In the five pocket mice flown on Apollo XVII, no evidence was found that the inner ear had been damaged, though poor fixation precluded detailed study. On the other hand, the middle ear cavity was involved in all the mice, hemorrhage having occurred in response to excursions in pressure within the canister that housed the mice during their flight. The same occurred in flight control mice which had been subjected to pressure excursions of much the same magnitude. A greater degree of exudation into air cells and greater leukotaxis were noted in the flight animals than in the control animals. There was no increase in leukocyte population along the paths of the 23 cosmic-ray particles registered in the subscalp dosimeters that traversed the middle ear cavities of the flight mice. The increased exudation and the greater response by leukocytes in the flight mice may have been causally related to the lesions found in their olfactory mucosa but there were no data in support of this possibility.

Haymaker, W.↗
NASA NTRS1974

The Acute Inhalation Toxicity in Rats from the Pyrolysis Products of Four Fluoropolymers

Male Sprague-Dawley rats (225?250 g) were exposed to the thermal degradation products from four fluoropolymers. The three polymers containing vinylidene fluoride and hexafluoropropene (VF2/HFP) were pyrolyzed at 550? and 800?C, whereas polytetrafluoroethylene (PTFE) was pyrolyzed at 625 and 800?C. At the lower temperatures, the pyrolysate from the copolymer of vinylidene fluoride and hexafluoropropene (VF2/HFP) was less toxic than the pyrolysates from either the terpolymer of vinyidene fluoride, hexafluoropropene, and tetrafluoroethylene (VF2/HFP/TFE) or the copolymer of vinylidene fluoride and hexafluoropropene with ?additives? (VF2/HFP-A). However, the pyrolysates from the VF2/HFP-containing materials produced less toxic products than the pyrolysate from PTFE at 625?C. When the pyrolysis temperature was increased to 800?C, very little difference was noted between the pyrolysis toxicity for any of the VF2/HFP-containing polymers with the most toxic pyrolysate again produced by PTFE. Carbon monoxide levels were all sublethal. No correlation could be established between hydrolyzable fluoride levels and the lethality of the pyrolysates. Death following exposure occurred within 48 hr due to acute pulmonary edema and hemorrhage. Survival of this acute phase was followed by alveolar lymphocytic infiltration and peribronchial tissue proliferation.

Carter, V. L., Jr.↗
NASA NTRS1976

Cardiovascular function during sustained +G/z/ stress

The development of aerospace systems capable of very high levels of positive vertical accelerators stress has created a need for a better understanding of the cardiovascular responses to acceleration. Using a canine model, the heart and cardiovascular system were instrumented to continuously measure coronary blood flow, cardiac output, left ventricular and aortic root pressure, and oxygen saturation in the aorta, coronary sinus, and right ventricle. The animals were exposed to acceleration profiles up to +6 G, 120 s at peak G; a seatback angle of 45 deg was simulated in some experiments. Radiopaque contrast medium was injected to visualize the left ventricular chamber, coronary vasculature, aorta, and branches of the aorta. The results suggest mechanisms responsible for arrhythmias which may occur, and subendocardial hemorrhage which has been reported in other animals.

Erickson, H. H.↗
NASA NTRS1975

Study report on combining diagnostic and therapeutic considerations with subsystem and whole-body simulation

Current applications of simulation models for clinical research described included tilt model simulation of orthostatic intolerance with hemorrhage, and modeling long term circulatory circulation. Current capabilities include: (1) simulation of analogous pathological states and effects of abnormal environmental stressors by the manipulation of system variables and changing inputs in various sequences; (2) simulation of time courses of responses of controlled variables by the altered inputs and their relationships; (3) simulation of physiological responses of treatment such as isotonic saline transfusion; (4) simulation of the effectiveness of a treatment as well as the effects of complication superimposed on an existing pathological state; and (5) comparison of the effectiveness of various treatments/countermeasures for a given pathological state. The feasibility of applying simulation models to diagnostic and therapeutic research problems is assessed.

Furukawa, S.↗
NASA NTRS1980

Emergency medicine and the airline passenger

Problems related to immediate medical care in case of in-flight emergencies are discussed with reference to such critical types of medical emergencies as obstructed airway, cardiac dysfunction, trauma, hemorrhage, hypoxia, and pain. It is shown that training flight attendants to deal with in-flight medical emergencies and to use first-aid support equipment and essential and useful drugs may later help with stabilization of a victim and allow continuing the flight to the scheduled destination without the need for a diverted landing. Among the steps suggested in order to upgrade inflight welfare and safety of passengers are the development of an advisory circular by the FAA covering standardized training for flight attendants, regulatory action requiring upgrading of the present rudimentary first-aid kit, and the enactment of Good Samaritan legislation by the U.S. Government.

Mohler, S. R.↗
NASA NTRS1983

Avian embryonic development in hyperdynamic environments

Embryos which developed for 24 hours in the oviduct of hens maintained at 2 G and which were subsequently incubated at Earth gravity had a 14% reduction in hatchability. Increased mortality during the first 4 days, and an increase in embryonic abnormalities were of the types usually found during the first mortality peak (2-3 days). Embryos in eggs that were produced at Earth gravity and continued their development on the centrifuge at fields of 2 G or less did not appear to be greatly affected by the treatment. At 4 G, 91% of the embryos died, mostly on the first and second days of incubation. Abnormalities prominent in the centrifuged eggs include: (a) a failure of the primitive streak to develop; (b) interference with the development of the axial skeleton; (c) multiple hemorrhages, mostly petechial which is consistent with capillary fragility; and (d) retardation of embryo growth, possibly caused by an interference with gaseous diffusion, the result of an acceleration-induced increase in gas density in the centrifuging incubator.

Abbott, U. K.↗
NASA NTRS1991

Microgravity and the lung

Results are presented from studies of the effect of microgravity on the lungs of rats flown on the Cosmos 2044 mission, and from relevant laboratory experiments. The effects of microgravity fall into five categories: topographical structure and function, the lung volumes and mechanics, the intrathoracic blood pressures and volumes, the pulmonary deposition of aerosol, and denitrogenaton during EVA. The ultrastructure of the left lungs of rats flown for 14 days on the Cosmos 2044 spacecraft and that of some tail-suspended rats disclosed presence of red blood cells in the alveolar spaces, indicating that pulmonary hemorrhage and pulmonary edema occurred in these rats. Possible causes for this phenomenon are discussed.

West, John B.↗