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At least 307 records · Page 17

Comparison of Routes of Administration, Frequency, and Duration of Favipiravir Treatment in Mouse and Guinea Pig Models of Ebola Virus Disease

Favipiravir is a ribonucleoside analogue that has been explored as a therapeutic for the treatment of Ebola Virus Disease (EVD). Promising data from rodent models has informed nonhuman primate trials, as well as evaluation in patients during the 2013–2016 West African EVD outbreak of favipiravir treatment. However, mixed results from these studies hindered regulatory approval of favipiravir for the indication of EVD. This study examined the influence of route of administration, duration of treatment, and treatment schedule of favipiravir in immune competent mouse and guinea pig models using rodent-adapted Zaire ebolavirus (EBOV). A dose of 300 mg/kg/day of favipiravir with an 8-day treatment was found to be fully effective at preventing lethal EVD-like disease in BALB/c mice regardless of route of administration (oral, intraperitoneal, or subcutaneous) or whether it was provided as a once-daily dose or a twice-daily split dose. Preclinical data generated in guinea pigs demonstrates that an 8-day treatment of 300 mg/kg/day of favipiravir reduces mortality following EBOV challenge regardless of route of treatment or duration of treatments for 8, 11, or 15 days. This work supports the future translational development of favipiravir as an EVD therapeutic.

60 APPLIED LIFE SCIENCES↗

Towards prevention and prediction of infectious diseases with virus sterilization using ultraviolet light and low-temperature plasma and bio-sensing devices for health and hygiene care

Inspired by the ideas of many authors, we provide insight on state-of-the-art potential technologies for the prevention and prediction of infectious diseases before they spread. This review also surveys virus sterilization with ultraviolet light and low temperature plasma technologies. Researchers in the various fields of medicine, materials, electronics, and plasma sciences have addressed increasingly challenging demands and the discussion encompasses the major challenges in societies that are faced with the threat of infectious diseases. In addition, technologies that use nanomaterials are evaluated for infection prevention and hygiene purposes. Advances in biomedical diagnostics for health care in terms of complementary metal-oxide-semiconductor transistors-based devices and telemetry for health monitoring are also reviewed.

60 APPLIED LIFE SCIENCES↗

A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes

Abstract Complement evasion is a hallmark of extracellular microbial pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease. Lyme disease spirochetes express nearly a dozen outer surface lipoproteins that bind complement components and interfere with their native activities. Among these, BBK32 is unique in its selective inhibition of the classical pathway. BBK32 blocks activation of this pathway by selectively binding and inhibiting the C1r serine protease of the first component of complement, C1. To understand the structural basis for BBK32-mediated C1r inhibition, we performed crystallography and size-exclusion chromatography–coupled small angle X-ray scattering experiments, which revealed a molecular model of BBK32-C in complex with activated human C1r. Structure-guided site-directed mutagenesis was combined with surface plasmon resonance binding experiments and assays of complement function to validate the predicted molecular interface. Analysis of the structures shows that BBK32 inhibits activated forms of C1r by occluding substrate interaction subsites (i.e., S1 and S1’) and reveals a surprising role for C1r B loop–interacting residues for full inhibitory activity of BBK32. The studies reported in this article provide for the first time (to our knowledge) a structural basis for classical pathway–specific inhibition by a human pathogen.

Garrigues, Ryan J. (ORCID:0000000259233250)↗

Potentiality for obtaining poria disease signatures in the Oregon Cascades from orbital altitudes

A prime photographic signature indicator of an important forest disease was identified in valuable Douglas-fir stands of the Pacific Northwest. The disease signature was verified by a multidisciplinary team of scientists to be the direct result of the Poria weirii root-rot syndrome in the Douglas-fir and hemlock stands of the high Cascades in Oregon. It is readily discernible on small-scale suborbital photography and has good potential for detection from earth-orbiting satellites or remote sensing platforms.

Wear, J. F.↗

Psychosocial factors in coronary heart disease

The relationship between job satisfaction and coronary heart disease is explored for blue and white collar groups, different personalities and physiological risk factors. Differences found among administrators, engineers and scientists with regard to variables associated with heart disease are in terms of physiology, personality, reported job stress, and smoking.

French, J. R. P., Jr.↗

Studies on disease transmission in spacecraft environments

The effects of the Skylab gas mixtures on general health and immunocompetence of mice and ferrets subjected to the Skylab space cabin environment (SCE) were initially studied in a stainless steel low pressure facility which was maintained at gas ratios of 30% nitrogen and 70% oxygen under 5 psia, and which consisted of two subchambers, that permitted mutual isolation of experimental groups and/or selective removal of animals without return of the entire cabin to ambient pressure was developed. The studies demonstrated that ferrets immunized with Brucella Strain 19 prior to being housed in SCE had decreased synthesis of IgG compared to their respective controls. The possibility of latent infections being responsible for stress-induced upper respiratory diseases of astronauts required that the role of neutralizing antibody as a function of antibody affinity/avidity be investigated. The model consisted of Aleutian disease virus (ADV) which infects ferrets and mink resulting in nonneutralized immune complexes. These studies demonstrated that early antibody to ADV had lower affinity/avidity than late antibody with respect to chronicity. These studies culminated in a description of antibody affinity, first isolation of ADV and its cultivation in vitro.

Kenyon, A. J.↗

Investigations of remote sensing techniques for early detection of Dutch elm disease

Several forms of aerial photography were pursued in quest of a technique which could provide early detection of Dutch elm disease. The two most promising techniques tested were multispectral photography with object enhancement and biband ratioing coupled with scanning microdensitometry. For practical purposes the multispectral system has the advantage of providing a readily interpretable image in a relatively short time. Laboratory studies indicated that less emphasis should be placed on the use of a red filter or the near infrared beyond 750 mm for early detection of stress within a single plant species. Color infrared film would be optimal when used for a long term detection of loss of plant vigor which results in a physical change in a plant canopy, but should find minimal practicality for early detection of specific sources of plant stress such as Dutch elm disease. Considerable discretion should be used when interpreting imagery on copy film because of loss of resolution and color definition.

Hammerschlag, R. S.↗

Evaluation of thallium-201 scanning for detection of latent coronary artery disease

The use of thallium imaging as a noninvasive method to accurately screen shuttle passengers for latent coronary artery disease was investigated. All radionuclide procedures were performed using an Anger type camera with a high resolution collimator. A minimum of 200,000 counts were collected for each image using a 20% window centered on the 69-83 keV X-rays. For the images obtained following injection with the patient at rest, the testing was begun 10 minutes after injection. Injections of TT during exercise were made at a point near the termination of the treadmill procedure as determined by either the appearance of ST segment changes on the electrocardiogram consistant with subendocardial ischemia, the appearance of angina-like chest pain in the patient or fatigue in the patient which required cessation of the test. The severity of heart disease was based on the medical history, physical exam, exercise electrocardiograms, chest X-rays and the coronary arteriogram.

Johnson, P. C.↗

Assessment of oxygen and carbogen therapy effect in Meniere's disease according to clinical and electroencephalographic data

The method of constructing fields on the basis of EEG data gives a quantitative characterization of bioelectrical activity. Fields of average rates of the change of potentials in healthy people have a well defined configuration, where the greatest rates are found in the occipital zones, lower in the frontal and parietal, and least in the temporal zones. In response to functional loads the form of the field remains the same because of a synchronous change in the average rates in both hemispheres of the cerebrum to the same extent. The configuration of the fields of background bioelectric activity of the cerebrum in people with Meniere's disease is not uniform. On the basis of this investigation, a clear correlation was found between the subjective sensations of patients during oxygen and carbogen therapy and the changes in the spatial characteristics of the field of potentials of the cerebrum. This correlation makes it possible to objectively identify the nature of the vascular disturbances in Meniere's disease, develop a pathogenetic treatment plan, and evaluate its effectiveness.

Boronoyev, A. B.↗

Meniere's disease: A surgeon's tactics

Surgical procedures for treating Meniere's disease are discussed. Based on the results of 250 operations, it is concluded that interventions are sufficiently effective not only with vestibular dysfunction, but also with hearing disorders. In surgical treatment of Meniere's disease, it is expedient to adhere to by-stage tactics: to start with the simplest and least traumatic interventions - operations on the nerves of the tympanic cavity, and if these are ineffective to use more complex methods, including drainage or shunting of the endolymphatic sac.

Soldatov, I.↗

Modelling Rift Valley fever (RVF) disease vector habitats using active and passive remote sensing systems

The NASA Ames Ecosystem Science and Technology Branch and the U.S. Army Medical Research Institute of Infectious Diseases are conducting research to detect Rift Valley fever (RVF) vector habitats in eastern Africa using active and passive remote-sensing. The normalized difference vegetation index (NDVI) calculated from Landsat TM and SPOT data is used to characterize the vegetation common to the Aedes mosquito. Relationships have been found between the highest NDVI and the 'dambo' habitat areas near Riuru, Kenya on both wet and dry data. High NDVI values, when combined with the vegetation classifications, are clearly related to the areas of vector habitats. SAR data have been proposed for use during the rainy season when optical systems are of minimal use and the short frequency and duration of the optimum RVF mosquito habitat conditions necessitate rapid evaluation of the vegetation/moisture conditions; only then can disease potential be stemmed and eradication efforts initiated.

Ambrosia, Vincent G.↗

Use of T7 RNA polymerase to direct expression of outer Surface Protein A (OspA) from the Lyme disease Spirochete, Borrelia burgdorferi

The OspA gene from a North American strain of the Lyme disease Spirochete, Borrelia burgdorferi, was cloned under the control of transciption and translation signals from bacteriophage T7. Full-length OspA protein, a 273 amino acid (31kD) lipoprotein, is expressed poorly in Escherichia coli and is associated with the insoluble membrane fraction. In contrast, a truncated form of OspA lacking the amino-terminal signal sequence which normally would direct localization of the protein to the outer membrane is expressed at very high levels (less than or equal to 100 mg/liter) and is soluble. The truncated protein was purified to homogeneity and is being tested to see if it will be useful as an immunogen in a vaccine against Lyme disease. Circular dichroism and fluorescence spectroscopy was used to characterize the secondary structure and study conformational changes in the protein. Studies underway with other surface proteins from B burgdorferi and a related spirochete, B. hermsii, which causes relapsing fever, leads us to conclude that a strategy similar to that used to express the truncated OspA can provide a facile method for producing variations of Borrelia lipoproteins which are highly expressed in E. coli and soluble without exposure to detergents.

Dunn, John J.↗

CLIPS: A tool for corn disease diagnostic system and an aid to neural network for automated knowledge acquisition

This paper describes the building of a corn disease diagnostic expert system using CLIPS, and the development of a neural expert system using the fact representation method of CLIPS for automated knowledge acquisition. The CLIPS corn expert system diagnoses 21 diseases from 52 symptoms and signs with certainty factors. CLIPS has several unique features. It allows the facts in rules to be broken down to object-attribute-value (OAV) triples, allows rule-grouping, and fires rules based on pattern-matching. These features combined with the chained inference engine result to a natural user query system and speedy execution. In order to develop a method for automated knowledge acquisition, an Artificial Neural Expert System (ANES) is developed by a direct mapping from the CLIPS system. The ANES corn expert system uses the same OAV triples in the CLIPS system for its facts. The LHS and RHS facts of the CLIPS rules are mapped into the input and output layers of the ANES, respectively; and the inference engine of the rules is imbedded in the hidden layer. The fact representation by OAC triples gives a natural grouping of the rules. These features allow the ANES system to automate rule-generation, and make it efficient to execute and easy to expand for a large and complex domain.

Wu, Cathy↗

Neocytolysis Contributes to the Anemia of Renal Disease

Neocytolysis is a recently described physiologic process effecting selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin depression appears to initiate the process, providing rationale to investigate its contributions to the anemia of renal disease. When erythropoietin therapy was withheld, four of five stable hemodialysis patients demonstrated Cr-51 red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these patients received oral (13)C-glycine and (15)N-glycine and showed pathologic enrichment of stool porphyrins by the most recently ingested isotope when EPO therapy was held. This confirms selective hemolysis of newly-released red cells. (One patient had chronic hemolysis by isotope studies of blood and stool.) Thus, neocytolysis can contribute to the anemia of renal disease and explains some unresolved issues about such anemia. One implication is the prediction that intravenous bolus erythropoietin therapy is metabolically and economically inefficient compared to lower doses given more frequently subcutaneously.

Rice, Lawrence↗

Communicable Disease Research

The COSMIC program FITLOS is used regularly by the Centers for Disease Control (CDC), for analyzing data from radioimmunoassays, which involve testing human body substances to provide information on how deficits or excesses of those substances affect a body's ability to ward off disease. A liquid scintillation counter's data is analyzed by the FITLOS program. FITLOS data, then aids in establishing reference methods for hospitals and other health laboratories in their radioimmunoassays. CDC's use of this program enabled them to avoid the cost of designing and developing a new program.

Source record↗

Myonuclear domains in muscle adaptation and disease

Adult skeletal muscle fibers are among the few cell types that are truly multinucleated. Recently, evidence has accumulated supporting a role for the modulation of myonuclear number during muscle remodeling in response to injury, adaptation, and disease. These studies have demonstrated that muscle hypertrophy is associated with, and is dependent on, the addition of newly formed myonuclei via the fusion of myogenic cells to the adult myofiber, whereas muscle atrophy and disease appear to be associated with the loss of myonuclei, possibly through apoptotic-like mechanisms. Moreover, these studies also have demonstrated that myonuclear domain size, i. e., the amount of cytoplasm per myonucleus, is unchanged following the acute phase of hypertrophy but is reduced following atrophy. Together these data demonstrate that modulation of myonuclear number or myonuclear domain size (or both) is a mechanism contributing to the remodeling of adult skeletal muscle in response to alterations in the level of normal neuromuscular activity. Copyright 1999 John Wiley & Sons, Inc.

Review, Tutorial↗

Neocytolysis contributes to the anemia of renal disease

Neocytolysis is a recently described physiological process affecting the selective hemolysis of young red blood cells in circumstances of plethora. Erythropoietin (EPO) depression appears to initiate the process, providing the rationale to investigate its contributions to the anemia of renal disease. When EPO therapy was withheld, four of five stable hemodialysis patients showed chromium 51 (51Cr)-red cell survival patterns indicative of neocytolysis; red cell survival was short in the first 9 days, then normalized. Two of these four patients received oral 13C-glycine and 15N-glycine, and there was a suggestion of pathological isotope enrichment of stool porphyrins when EPO therapy was held, again supporting selective hemolysis of newly released red cells that take up the isotope (one patient had chronic hemolysis indicated by isotope studies of blood and stool). Thus, neocytolysis can contribute to the anemia of renal disease and explain some unresolved issues about such anemia. One implication is the prediction that intravenous bolus EPO therapy is metabolically and economically inefficient compared with lower doses administered more frequently subcutaneously.

Non-NASA Center↗

Milk and other dietary influences on coronary heart disease

While dietary links to ischemic heart disease (IHD) and coronary heart disease (CHD) mortality have been studied for many years, the correlation has not clearly been resolved, especially for older populations. In this paper, a multi-country statistical approach involving 32 countries is used to find dietary links to IHD and CHD for various age groups aged 35+. For IHD, milk carbohydrates were found to have the highest statistical association for males aged 35+ and females aged 65+, while for females aged 35-64, sugar was found to have the highest association. In the case of CHD, non-fat milk was found to have the highest association for males aged 45+ and females aged 75+, while for females 65-74, milk carbohydrates and sugar had the highest associations, and for females aged 45-64, sugar had the highest association. A number of mechanisms have been proposed in the literature that might explain the milk carbohydrate or non-fat milk association. One of the most prominent theories is that animal proteins contribute to homocysteine (Hcy) production; however, milk more than meat lacks adequate B vitamins to convert Hcy to useful products. Lactose and calcium in conjunction with Hcy from consumption of non-fat milk may also contribute to calcification of the arteries.

Coronary Disease/etiology↗