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At least 109 records · Page 6

A Primary Care Approach to the Diagnosis and Management of Peripheral Arterial Disease

The objectives of this work are: (1) Be able to recognize characteristic symptoms of intermittent claudication (2) Diagnose PAD on the basis of history, physical exam, and simple limb blood pressure measurements (3) Recognize the significance of peripheral artery disease as a marker for coronary or cerebrovascular atherosclerosis (4) Provide appropriate medical management of atherosclerosis risk factors-- including use of antiplatelet therapy to reduce risk of myocardial infarction, stroke and death (5) Manage symptoms of intermittent claudication with program of smoking cessation, exercise, and medication The diagnosis of intermittent claudication secondary to peripheral artery disease (PAD) can often be made on the basis of history and physical examination. Additional evaluation of PAD is multi-modal and the techniques used will vary depending on the nature and severity of the patient's presenting problem. Most patients can be appropriately managed without referral for specialized diagnostic services or interventions.

Dawson, David L.↗

Growth Control and Disease Mechanisms in Computational Embryogeny

This paper presents novel approach to applying growth control and diseases mechanisms in computational embryogeny. Our method, which mimics fundamental processes from biology, enables individuals to reach maturity in a controlled process through a stochastic environment. Three different mechanisms were implemented; disease mechanisms, gene suppression, and thermodynamic balancing. This approach was integrated as part of a structural evolutionary model. The model evolved continuum 3-D structures which support an external load. By using these mechanisms we were able to evolve individuals that reached a fixed size limit through the growth process. The growth process was an integral part of the complete development process. The size of the individuals was determined purely by the evolutionary process where different individuals matured to different sizes. Individuals which evolved with these characteristics have been found to be very robust for supporting a wide range of external loads.

Genetic algorithm↗

Reducing Tick-Borne Disease in Alabama: Linking Health Risk Perception with Spatial Analysis Using the NASA Earth Observing System

Lyme disease (LD) accounts for most vector-borne disease reports in the U.S., and although its existence in Alabama remains controversial, other tick-borne illnesses (TBI) such as Southern Tick-Associated Rash Illness (STARI) pose a health concern in the state. Phase One of the Marshall Space Flight Center-UAB DEVELOP study of TBI identified the presence of the chain of infection for LD (Ixodes scapularis ticks carrying Borrelia burgdorferi bacteria) and STARI (Amblyomma americanum ticks and an as-yet-unconfirmed agent) in Alabama. Both LD and STARI are associated with the development of erythema migrans rashes around an infected tick bite, and while treatable with oral antibiotics, a review of educational resources available to state residents revealed low levels of prevention information. To improve prevention, recognition, and treatment of TBI in Alabama, Phase Two builds a health communication campaign based on vector habitat mapping and risk perception assessment. NASA Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) satellite imagery identified likely tick habitats using remotely sensed measurements of vegetation vigor (Normalized Difference Vegetation Index) and soil moisture. Likely tick habitats, identified as those containing both high vegetation density and soil moisture, included Oak Mountain State Park, Bankhead National Forest, and Talladega National Forest. To target a high-risk group -- outdoor recreation program participants at Alabama universities -- the study developed a behavior survey instrument based on existing studies of LD risk factors and theoretical constructs from the Social Ecological Model and Health Belief Model. The survey instrument was amended to include geographic variables in the assessment of TBI knowledge, attitudes, and prevention behaviors, and the vector habitat model will be expanded to incorporate additional environmental variables and in situ data. Remotely sensed environmental data combined with risk perception assessments inform an ongoing outreach campaign consisting of stakeholder meetings and educational seminars.

Hemmings, S.↗

Using Earth Observations to Understand and Predict Infectious Diseases

This presentation discusses the processes from data collection and processing to analysis involved in unraveling patterns between disease outbreaks and the surrounding environment and meteorological conditions. We used these patterns to estimate when and where disease outbreaks will occur. As a case study, we will present our work on assessing the relationship between meteorological conditions and influenza in Central America. Our work represents the discovery, prescriptive and predictive aspects of data analytics.

public health↗

Radiation Exposure and Mortality from Cardiovascular Disease and Cancer in Early NASA Astronauts: Space for Exploration

Of the many possible health challenges posed during extended exploratory missions to space, the effects of space radiation on cardiovascular disease and cancer are of particular concern. There are unique challenges to estimating those radiation risks; care and appropriate and rigorous methodology should be applied when considering small cohorts such as the NASA astronaut population. The objective of this work was to establish whether there is evidence for excess cardiovascular disease or cancer mortality in an early NASA astronaut cohort and determine if a correlation exists between space radiation exposure and mortality.

Elgart, S. R.↗

Microbial Monitoring and the Risk of Infectious Disease Aboard the International Space Station

The International Space Station (ISS) is a semi-closed habitat in low Earth orbit with environmental conditions provided by an advanced life support system that controls temperature and recycles air and most of the potable water. The crew's activities, such as eating, sleeping, hygiene, and laboratory research, are performed in relatively close proximity. Research in the laboratory includes a myriad of experiments, including those with rodents, plants, and pathogenic microorganisms. Despite these conditions, in-flight monitoring of ISS indicates that the microbial diversity is similar to homes on earth. Accordingly, the crew is generally very healthy, however infectious disease does occur and potential routes of infection by obligate and opportunistic pathogens cannot be completely prevented. Determining the extent of this risk is further complicated, as microorganisms can alter their characteristics in response to spaceflight culture, as exemplified by the increase in virulence of the enteric pathogen Salmonella enterica Typhimurium during spaceflight compared to otherwise identical cultures grown on Earth. Taken together, these factors suggest a need for continued microbiological monitoring and research to understand and mitigate the risk of infectious disease during long duration missions.

Ott, C. Mark↗

Simulated Weightlessness Alters Cardiomyocyte Structure and Transcriptional Regulation of Mediators Related to Immunity and Cardiovascular Disease

Spaceflight and the ensuing fluid shifts, together with an overall reduction in physical activity, lead to acute and latent effects on the cardiovascular system. This current study makes use of the rodent hindlimb unloading (HU) model to determine how factors such as sex, age, and duration of exposure impact cardiac responses to weightlessness. We hypothesize that extended exposure to simulated weightlessness and the ensuing recovery alters cardiac structure and expression of select genes, including those involved in redox signaling which together, negatively impact long-term cardiac tissue health. To begin to test this hypothesis, male and female rats underwent HU at various durations up to 90 days, with a subset reambulated after 90 days of HU. Physiological stress or contractility changes lead to alterations in ventricular cardiomyocyte size and ventricular wall thickness to adapt to greater functional demand and mitigate mechanical stress to ventricular tissue; under certain conditions, these changes also may mark progression to cardiac failure. Hence, left ventricular cardiomyocyte size (cardiomyocyte cross sectional area, CSA) was quantified to determine if HU leads to structural adaptation responses in cardiac tissue and if age and sex had any impact on this outcome. Cardiomyocyte CSA of older males (9 months) were altered by HU in a time-dependent manner, where HU led to decreases in CSA at 14 days and increases at 90 days. In contrast, younger males (3 months) did not show any changes at day 14 of HU. CSA of females (3 months) was increased in response to short-term HU (14 days) suggesting sex-dependence of structural changes. In older HU males, cardiomyocyte CSA was comparable to controls after 90 days of re-ambulation. Levels of the DNA oxidative damage marker, 8-hydroxydeoxyguanosine (8-OHdG) were greater in left ventricular tissue of females that underwent HU compared to sex-matched controls, while there were no such differences in older or younger males. To gain insight into the signals that drive cardiac adaptations to HU, global transcriptomic analysis (RNAseq) was performed on left ventricular tissue of older males that underwent 14 days of HU. Short-term simulated weightlessness led to differential expression of genes involved in immune and pro-inflammatory signaling. A subset of these genes play a role in autoimmune and cardiovascular disease and are targets of current drugs used to treat bradycardia, hypertension, atherosclerosis and rheumatoid arthritis, amongst others. Oxidative damage/redox signaling pathways were not enriched at the timepoint tested in older males. Since young females displayed greater oxidative damage to DNA, activation of oxidative stress responses at earlier or later time points cannot be ruled out. In summary, simulated weightlessness in adult rats caused changes in cardiomyocyte structure in a sex and age-dependent manner, and the transcriptional regulation of key mediators of immunity and cardiovascular disease, meriting further study to define cardiac risks for interplanetary travel of human crew. Our findings also confirm the value of the rat HU model for cardiac health and countermeasure research.

Tahimic, Candice↗

An Adverse Outcome Pathway for Potential Space Radiation Induced Neurological Diseases

Astronauts have begun to spend increasingly longer periods in space, putting themselves in foreign environments in order to explore the unknown. Space radiation is one of the largest health risks faced by astronauts on their missions. The space radiation environment has the ability to cause high levels of irreversible damage. Multiple sources of charged particle radiation exist in the space environment that may increase risk of carcinogenesis, degeneration of bodily tissue (e.g. gastrointestinal, cardiovascular, or pulmonary), acute radiation syndromes, and acute and late central nervous system (CNS) disorders. In order to help inform an understanding of the risk of degenerative CNS disease due to radiation exposure, an initial step is presented here to develop an adverse outcome pathway from radiation exposure focused on Alzheimer’s disease.

Mi, Kaitlyn↗

Utility of Terrestrial Cardiovascular Disease Data in Astronaut Radiation Risk Assessment – A Case Study Showing Increased Risk with Clonal Hematopoiesis of Indeterminate Potential

Cardiovascular disease (CVD) is associated with high doses of radiation and is are cognized health risk for astronauts on multiple or long duration exploration missions to the Moon or Mars. Currently, radiation risk assessment is based on background population disease rates and does not consider individual risk factors that may modify analysis, especially at lower radiation doses.

Zarana S Patel↗

Cardiovascular Disease Spaceflight Equivalent Stressor Risk Modeling Project

The risk of cardiovascular disease (CVD) may be exacerbated by spaceflight hazards including radiation, isolation, distance from the Earth, gravity fields, and closed or confined environments. This project aims to use epidemiologic, scientific research evidence of surrogate spaceflight stressors on analog populations in terrestrial cohorts to model CVD risk for spaceflight conditions. To date, Dr. Butler and the multi-disciplinary CVD Spaceflight Equivalent Stressors (SES) team have conducted a formal systematic literature review on the risk of sleep loss as it relates to cardiovascular disease outcomes and are currently working on a meta-analysis for the data gathered from nearly 100 studies and their various CVD outcomes. The research will continue to examine other surrogate stressors in depth, such as altered gravity, radiation exposure, noise, etc. with cardiovascular outcomes to determine an overall combined spaceflight risk for long term future missions such as Artemis Lunar and Mars missions.

Jennifer Butler↗

Outcomes of a Mini Technical Interchange Meeting Concerning the Risk of Cardiovascular Disease from Exposure to Space Radiation

The NASA Human Research Program’s (HRP) Space Radiation Element (SRE) funds research to characterize and mitigate adverse health outcomes from exposure to space radiation to enable deep space exploration and sustained human presence in space. Damage to the cardiovascular system has been observed after exposure to clinically relevant doses of ionizing radiation. However, an association between lower radiation doses and cardiovascular disease (CVD) remains controversial, and questions pertaining to dose thresholds, radiation quality and dose-rate effects, and gaps in characterizing the mechanisms and major pathways of CVD remain. To solicit new ideas for characterizing and mitigating this risk, the SRE is organizing a series of miniature technical interchange meeting (Tiny-TIM) that provide a venue for HRP-funded investigators and thought leaders to present ongoing work and engage in open discussion on relevant topics. The initial Tiny-TIM: Upping the Ante on Characterizing and Mitigating Cardiovascular Disease Risk from Space Radiation Exposure, held at the NASA HRP Investigators’ Workshop (IWS) earlier this year, consisted of two 90-minute sessions; the first focused on current knowledge of CVD risk from space radiation exposure, and the second focused on innovative ideas, and newer approaches and techniques to accelerate research. The second session was followed by an open, spirited discussion amongst peers on the current issues impeding the characterization of CVD risk. SRE leadership facilitated the discussion using a set of pressing questions and gaps in knowledge that need to be addressed by the scientific community. This poster presents the outcomes of the Tiny-TIM, along with proposed future workshops and the SRE’s other initiatives.

Janapriya Saha↗

Climate-disease connections: Rift Valley Fever in Kenya

All known Rift Valley fever(RVF) outbreaks in Kenya from 1950 to 1998 followed periods of abnormally high rainfall. On an interannual scale, periods of above normal rainfall in East Africa are associated with the warm phase of the El Nino/Southern Oscillation (ENSO) phenomenon. Anomalous rainfall floods mosquito-breeding habitats called dambos, which contain transovarially infected mosquito eggs. The eggs hatch Aedes mosquitoes that transmit the RVF virus preferentially to livestock and to humans as well. Analysis of historical data on RVF outbreaks and indicators of ENSO (including Pacific and Indian Ocean sea surface temperatures and the Southern Oscillation Index) indicates that more than three quarters of the RVF outbreaks have occurred during warm ENSO event periods. Mapping of ecological conditions using satellite normalized difference vegetation index (NDVI) data show that areas where outbreaks have occurred during the satellite recording period (1981-1998) show anomalous positive departures in vegetation greenness, an indicator of above-normal precipitation. This is particularly observed in arid areas of East Africa, which are predominantly impacted by this disease. These results indicate a close association between interannual climate variability and RVF outbreaks in Kenya.

Rift Valley Fever/epidemiology/transmission↗

Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

Non-NASA Center↗

Cell and molecular biology of simian virus 40: implications for human infections and disease

Simian virus 40 (SV40), a polyomavirus of rhesus macaque origin, was discovered in 1960 as a contaminant of polio vaccines that were distributed to millions of people from 1955 through early 1963. SV40 is a potent DNA tumor virus that induces tumors in rodents and transforms many types of cells in culture, including those of human origin. This virus has been a favored laboratory model for mechanistic studies of molecular processes in eukaryotic cells and of cellular transformation. The viral replication protein, named large T antigen (T-ag), is also the viral oncoprotein. There is a single serotype of SV40, but multiple strains of virus exist that are distinguishable by nucleotide differences in the regulatory region of the viral genome and in the part of the T-ag gene that encodes the protein's carboxyl terminus. Natural infections in monkeys by SV40 are usually benign but may become pathogenic in immunocompromised animals, and multiple tissues can be infected. SV40 can replicate in certain types of simian and human cells. SV40-neutralizing antibodies have been detected in individuals not exposed to contaminated polio vaccines. SV40 DNA has been identified in some normal human tissues, and there are accumulating reports of detection of SV40 DNA and/or T-ag in a variety of human tumors. This review presents aspects of replication and cell transformation by SV40 and considers their implications for human infections and disease pathogenesis by the virus. Critical assessment of virologic and epidemiologic data suggests a probable causative role for SV40 in certain human cancers, but additional studies are necessary to prove etiology.

Review↗