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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records

The Management of Chronic Disease: a Study of Employee Morbidity and Mortality at the NASA, Goddard Space Flight Center, 1966 - 1971

Several approaches to studying chronic disease patterns in the employee population at Goddard Space Flight Center from 1966 to 1970 are presented. Attempts were made to summarize preliminary data for 1971 and relate this data to specific programs and events which may have had some causative influence. Investigative data for the study cover records of periodic and return to work examinations, injury and illness visit reports, mortality data, and health trends with and without external influences.

Villafana, C.↗

Health Care Usage During the COVID-19 Pandemic and the Adoption of Telemedicine: Retrospective Study of Chronic Disease Cohorts

Background: The COVID-19 pandemic accelerated telehealth adoption across disease cohorts of patients. For many patients, routine medical care was no longer an option, and others chose not to visit medical offices in order to minimize COVID-19 exposure. In this study, we take a comprehensive multidisease approach in studying the impact of the COVID-19 pandemic on health care usage and the adoption of telemedicine through the first 12 months of the COVID-19 pandemic. Objective: We studied the impact of the COVID-19 pandemic on in-person health care usage and telehealth adoption across chronic diseases to understand differences in telehealth adoption across disease cohorts and patient demographics (such as the Social Vulnerability Index [SVI]). Methods: We conducted a retrospective cohort study of 6 different disease cohorts (anxiety: n=67,578; depression: n=45,570; diabetes: n=81,885; kidney failure: n=29,284; heart failure: n=21,152; and cancer: n=35,460). We used summary statistics to characterize changes in usage and regression analysis to study how patient characteristics relate to in-person health care and telehealth adoption and usage during the first 12 months of the pandemic. Results: We observed a reduction in in-person health care usage across disease cohorts (ranging from 10% to 24%). For most diseases we study, telehealth appointments offset the reduction in in-person visits. Furthermore, for anxiety and depression, the increase in telehealth usage exceeds the reduction in in-person visits (by up to 5%). We observed that younger patients and men have higher telehealth usage after accounting for other covariates. Patients from higher SVI areas are less likely to use telehealth; however, if they do, they have a higher number of telehealth visits, after accounting for other covariates. Conclusions: The COVID-19 pandemic affected health care usage across diseases, and the role of telehealth in replacing in-person visits varies by disease cohort. Understanding these differences can inform current practices and provides opportunities to further guide modalities of in-person and telehealth visits. Critically, further study is needed to understand barriers to telehealth service usage for patients in higher SVI areas. A better understanding of the role of social determinants of health may lead to more support for patients and help individual health care providers improve access to care for patients with chronic conditions.

60 APPLIED LIFE SCIENCES↗

A Simplified Model of Adenine-Induced Chronic Kidney Disease Using SKH1 Mice

Commonly used adenine-induced chronic kidney disease (CKD) murine models often employ C57BL/6 mice; however, this strain has inherent limitations due to its natural resistance to developing key pathological features of CKD, such as tubulointerstitial fibrosis and inflammation. There have been attempts to overcome these barriers by using multiple concentrations of adenine-supplemented diets or by performing prolonged experiments up to 20 weeks. Here, we demonstrate that SKH1 Elite mice develop clinically relevant CKD phenotypes (e.g., polyuria, proteinuria, inflammation, and renal fibrosis) over the course of only 6 weeks of low-dose (0.15%) adenine supplementation. As a docile, immunocompetent, and hairless strain, SKH1 Elite mice offer several logistical advantages over C57BL/6 mice, including ease of handling and the ability to study dermal conditions, which are often secondary to CKD.

60 APPLIED LIFE SCIENCES↗

Blood Volume: Importance and Adaptations to Exercise Training, Environmental Stresses and Trauma/Sickness

This paper reviews the influence of several perturbations (physical exercise, heat stress, terrestrial altitude, microgravity, and trauma/sickness) on adaptations of blood volume (BV), erythrocyte volume (EV), and plasma volume (PV). Exercise training can induced BV expansion; PV expansion usually occurs immediately, but EV expansion takes weeks. EV and PV expansion contribute to aerobic power improvements associated with exercise training. Repeated heat exposure induces PV expansion but does not alter EV. PV expansion does not improve thermoregulation, but EV expansion improves thermoregulation during exercise in the heat. Dehydration decreases PV (and increases plasma tonicity) which elevates heat strain and reduces exercise performance. High altitude exposure causes rapid (hours) plasma loss. During initial weeks at altitude, EV is unaffected, but a gradual expansion occurs with extended acclimatization. BV adjustments contribute, but are not key, to altitude acclimatization. Microgravity decreases PV and EV which contribute to orthostatic intolerance and decreased exercise capacity in astronauts. PV decreases may result from lower set points for total body water and central venous pressure, which EV decrease bay result form increased erythrocyte destruction. Trauma, renal disease, and chronic diseases cause anemia from hemorrhage and immune activation, which suppressions erythropoiesis. The re-establishment of EV is associated with healing, improved life quality, and exercise capabilities for these injured/sick persons.

Sawka, Michael N.↗

Protein turnover in atrophying muscle: from nutritional intervention to microarray expression analysis

PURPOSE OF REVIEW: In response to decreased usage, skeletal muscle undergoes adaptive reductive remodeling due to the decrease in tension on the weight bearing components of the musculo-skeletal system. This response occurs with uncomplicated disuse (e.g. bed rest, space flight), as a secondary consequence of several widely prevalent chronic diseases for which activity is reduced (e.g. chronic obstructive pulmonary disease and chronic heart failure) and is part of the aging process. The problem is therefore one of considerable clinical importance. RECENT FINDINGS: The impaired function and exercise intolerance is related more to the associated muscle wasting rather than to the specific organ system primarily impacted by the disease. Progress has continued in describing the use of anabolic drugs and dietary manipulation. The major advance in the field has been: (i) the discovery of the atrogin-1 gene and (ii) the application of microarray expression analysis and proteomics with the objectives of obtaining comprehensive understanding of the pathways changed with disuse atrophy. SUMMARY: Disuse atrophy is a common clinical problem. There is a need for therapeutic interventions that do not involve exercise. A better understanding of the changes, particularly at the molecular level, could indicate hitherto unsuspected sites for nutritional and pharmacological intervention.

Non-NASA Center↗

Longitudinal Surveillance for Chronic Health Conditions in Former United States Department of Energy Site Workers

The aim of the study was to determine (1) the rate at which rescreening former Department of Energy site workers identifies noncommunicable chronic diseases and (2) the development of comorbid conditions. Incidence and prevalence of hypertension, diabetes, reduced kidney function, and peripheral neuropathy at both initial and return screenings were calculated. Risk ratio of chronic disease development at return screening based on the presence of other conditions at initial screening were estimated with generalized linear regression. Prevalence of reduced kidney function was 19% at initial examination and 30% at return examination. The screening program was responsible for identifying 81% of reduced kidney function cases. Similar findings were present for the other chronic conditions examined. As a result, former worker health surveillance programs help identify significant health conditions among DOE workers, subcontractors, and visitors. Longitudinal screening of participants detects additional chronic conditions.

59 BASIC BIOLOGICAL SCIENCES↗

Gene Expression of Pathogens in Simulated Microgravity

Extended exposure to radiation and microgravity in space has been linked to astronauts developing chronic diseases upon returning to Earth. The Gram-negative pathogen Serratia marcescens has been shown to potentially cause significant infections in humans and in insect models on Earth. Our recent findings also showed that S. marcescens shows an increase in virulence after a short period of growth in the spaceflight environment, which raises initiatives to find the correlation between space environment and the increased virulence. Because we know that the health of astronauts is immunocompromised in space, it is possible that the combination of increased bacterial virulence and the weakened immune system will cause astronauts to be more susceptible to chronic diseases in extended spaceflight. With 75% of human disease genes being conserved in the fruit fly Drosophila melanogaster, these insects act as an ideal model organism to study the human immune system. The high accessibility, low cost, high rate of reproductivity, and short lifespans of D. melanogaster facilitate efficient, high-quality research that seeks to understand altered virulence of this opportunistic pathogen. In this ground-based study, we will use a rotating wall vessel apparatus to simulate microgravity and determine how pathogenicity changes by evaluating differences in gene expression for S. marcescens between bacteria grown in simulated microgravity conditions and controls. We will compare the results of our findings to gene expression patterns in actual spaceflight samples of S. marcescens grown on the ISS (International Space Station) during a recent validation mission, to see if there are common mechanisms across our simulated microgravity and actual spaceflight microgravity samples that both show increased virulence in the fruit fly. With extended space travel in the foreseeable future, understanding how human physiology will be affected by these different factors will help mitigate risks and deaths.

spaceflight analogue↗

A Preliminary Analysis of Calcifying Particles in the Serum and Prostates of Patients with Prostatic Inflammation

Chronic diseases of the prostate such as benign prostatic hyperplasia (BPH) & chronic pelvic pain syndrome (CPPS) have associated findings of chronic inflammation, despite a lack of causal relationship. Numerous attempts to define an infectious agent responsible for the clinical findings have been inconsistent. The possibility of an infectious agent, that has not been uncovered with routine culturing methods, forms the basis for this study. Serum from 940 healthy Finnish men were compared with serum from 40 Crohn's, 40 path dx prostatitis, & 40 with path dx carcinoma, using an enzyme-linked immunosorbant assay (ELISA), to detect antigens specific to Nanobacteria(NB) utilizing monoclonal antibodies (Ab) 5/3 and 8D10. This ELISA has not been validated for detecting NB-associated with clinical prostatic disease, yet cross-reactivity with other bacterial species is low. Immunohistochemistry was performed on de-paraffinized prostatic tissue slides, de-calcified with EDTA and stained with the DAKO Catalyzed Signal Amplification kit, employing 8D10 as the primary (target/antigen-detecting) Ab. The mean (plus or minus SD) & median concentrations of NB antigen (U/50 L) were 379.59 (plus or minus 219.28) & 640.00 for patients with prostatitis (BPH) vs 3.31 (plus or minus 3.55) & 2.94 for prostate adenocarcinoma, 1.88 (plus or minus 2.94) & 0.80 for Crohn's disease, & 7.43 (plus or minus 25.57) & 0.00 for patients with no clinical prostatic disease. Unpaired t-tests revealed statistically significant differences between the prostatitis (BPH) sera & each of the other groups with p less than 0.005, but no differences between the other groups themselves. Preliminary studies with immunohistochemistry & 3-D confocal microscopy reveal 16/24 tissue sections + for NB Ag in BPH vs. only 2/22 tissue sections with prostate cancer. The preliminary findings of this serum screening study suggest that NB antigen may be commonly found in the serum of patients with the pathological diagnosis of prostatitis. Preliminary immunohistologic studies, suggest that NB may be found within the gland itself at a higher rate in patients with BPH relative to patients with adenocarcinoma, however confirmatory studies with a more specific ELISA technique, primary cultures, & with larger numbers of patients in a prospective design are required to determine if 1) NB are a causative organism for clinical hyperplastic and inflammatory disease, & if 2) serological testing can be used to discriminate patients with nanobacterial-associated prostatic disease.

Jones, Jeffrey A.↗

Evidence Report: Risk of Cardiovascular Disease and Other Degenerative Tissue Effects from Radiation Exposure

Occupational radiation exposure from the space environment may result in non-cancer or non-CNS degenerative tissue diseases, such as cardiovascular disease, cataracts, and respiratory or digestive diseases. However, the magnitude of influence and mechanisms of action of radiation leading to these diseases are not well characterized. Radiation and synergistic effects of radiation cause DNA damage, persistent oxidative stress, chronic inflammation, and accelerated tissue aging and degeneration, which may lead to acute or chronic disease of susceptible organ tissues. In particular, cardiovascular pathologies such as atherosclerosis are of major concern following gamma-ray exposure. This provides evidence for possible degenerative tissue effects following exposures to ionizing radiation in the form of the GCR or SPEs expected during long-duration spaceflight. However, the existence of low dose thresholds and dose-rate and radiation quality effects, as well as mechanisms and major risk pathways, are not well-characterized. Degenerative disease risks are difficult to assess because multiple factors, including radiation, are believed to play a role in the etiology of the diseases. As additional evidence is pointing to lower, space-relevant thresholds for these degenerative effects, particularly for cardiovascular disease, additional research with cell and animal studies is required to quantify the magnitude of this risk, understand mechanisms, and determine if additional protection strategies are required.The NASA PEL (Permissive Exposure Limit)s for cataract and cardiovascular risks are based on existing human epidemiology data. Although animal and clinical astronaut data show a significant increase in cataracts following exposure and a reassessment of atomic bomb (A-bomb) data suggests an increase in cardiovascular disease from radiation exposure, additional research is required to fully understand and quantify these adverse outcomes at lower doses (less than 0.5 gray (SI unit for ionizing radiation dosage, i.e. one joule of radiation energy per one kilogram of matter)) to facilitate risk prediction. This risk has considerable uncertainty associated with it, and no acceptable model for projecting degenerative tissue risk is currently available. In particular, risk factors such as obesity, alcohol, and tobacco use can act as confounding factors that contribute to the large uncertainties. The PELs could be violated under certain scenarios, including following a large SPE (solar proton event) or long-term GCR (galactic cosmic ray) exposure. Specifically, for a Mars mission, the accumulated dose is sufficiently high that epidemiology data and preliminary risk estimates suggest a significant risk for cardiovascular disease. Ongoing research in this area is intended to provide the evidence base for accurate risk quantification to determine criticality for extended duration missions. Data specific to the space radiation environment must be compiled to quantify the magnitude of this risk to decrease the uncertainty in current PELs and to determine if additional protection strategies are required. New research results could lead to estimates of cumulative radiation risk from CNS and degenerative tissue diseases that, when combined with the cancer risk, may have major negative impacts on mission design, costs, schedule, and crew selection. The current report amends an earlier report (Human Research Program Requirements Document, HRP-47052, Rev. C, dated Jan 2009) in order to provide an update of evidence since 2009.

Patel, Zarana↗

Chronic obstructive pulmonary disease among former United States Department of Energy workers: comorbidities and lung function changes

Chronic Obstructive Pulmonary Disease (COPD) is a major cause of morbidity and mortality in the United States and is frequently associated with multiple comorbidities which lead to poor COPD outcomes in the general population. However, little is known regarding COPD comorbidities in occupational cohorts whose exposure experiences could result in differences in comorbidities compared to the general population. These differences may also be important for assessing COPD outcomes such as lung function changes or decline. Therefore, the objectives of this study were to: (1) identify and describe clusters of COPD comorbidities among Department of Energy (DOE) former workers; (2) assess if the attributes of the identified clusters differ from those identified among the general population based on the published literature, and (3) identify predictors of lung function changes and decline among DOE former workers.

60 APPLIED LIFE SCIENCES↗

Potential Health Impacts, Treatments, and Countermeasures of Martian Dust on Future Human Space Exploration

The challenges of human space exploration produce some of humanity’s greatest technological and scientific advances, not excluding innovations in medicine. The microgravity environment causes a whole host of physiological changes, and exposure to dust on the Moon caused considerable pulmonary distress to astronauts during the Apollo missions. As the National Aeronautics and Space Administration (NASA)and other space organizations prepare for long duration exploration missions to Mars, the hazards and consequences of the Martian surface need to be accounted for. This review investigates how substances analogous to the hazardous components of Martian dust have caused disease in people on Earth. Because of the small grain size of Martian dust, dust on Mars is more likely to cause lung irritation, absorb into the bloodstream, and lead to diseases in astronauts. Toxic components of Martian dust to astronaut health include perchlorates, silica, nanophase iron oxides, and gypsum in addition to trace amounts of toxic metals whose abundances are debated: chromium, beryllium, arsenic, and cadmium. Predicted effects of dust exposure ranges from asymptomatic to life threatening, with many substances being carcinogenic and most damage impacting the pulmonary system. The longer transit time for astronauts to return home makes the operations of performing emergency medical treatment more difficult and increases both the likelihood and consequences of developing chronic disease. Exposure mitigation needs to be prioritized; however, supplements may be taken to prevent disease from breakthrough exposures and treatment regimens could lessen morbidity and mortality. Treatments and equipment need to be carefully thought out and transported with the astronauts to be prepared for all possible scenarios.

Justin L Wang↗

bmdrc: Python package for quantifying phenotypes from chemical exposures with benchmark dose modeling

Though chemical exposures are known to potentially have negative impacts on health, including contributing to chronic diseases such as cancer, the quantitative contribution of risk is not fully understood for every chemical. A commonly used approach to quantify levels of risk is to measure the proportion of organisms (such as a total number of zebrafish on a plate or mice in a cage) with abnormal behavioral responses or morphology at increasing concentrations of chemical exposure. A particular challenge with processing the proportional data from these assays is the appropriate estimation of chemical concentration levels that result in malformations or acute toxicity, as these values typically vary between experimental measurements. The recommended approach by the Environmental Protection Agency (EPA) is to fit benchmark dose curves with specific filters and model fitting steps, which are crucial to properly processing the proportional data. Several tools exist for the fitting of benchmark dose response curves, but none are standalone Python libraries built to process both morphological and behavioral data as proportions with all the EPA recommended filters, filter parameters, models, and model parameters. Thus, here we present the benchmark dose response curve (bmdrc) Python library, which was built to closely follow these EPA guidelines with helpful visualizations of filters and fitted model curves, and reports for reproducibility purposes. bmdrc is open-source and has demonstrated utility as a support package to an existing web portal for information on chemicals (https://srp.pnnl.gov). Our package will support any toxicology analysis where the response is a proportional value at increasing levels of a concentration of a chemical or chemical mixture.

Superfund↗

NASA occupational medicine programs: Our obligation to management

Factors to be considered in forming policies for managing NASA's health maintenance program to provide optimum arrangement for quality medical care are discussed. Topics include scheduling routine physical examinations, job related stress, prevalence of chronic diseases, additions to the PROM data system, and disease trends among personnel.

Arnoldt, L. B.↗

Molecular Signaling in Muscle Plasticity

Extended spaceflight under microgravity conditions leads to significant atrophy of weight-bearing muscles. Atrophy and hypertrophy are the extreme outcomes of the high degree of plasticity exhibited by skeletal muscle. Stimuli which control muscle plasticity include neuronal, hormonal, nutritional, and mechanical inputs. The mechanical stimulus for muscle is directly related to the work or exercise against a load performed. Little or no work is performed by weight-bearing muscles under microgravity conditions. A major hypothesis is that focal adhesion kinase (FAK) which is associated with integrin at the adherens junctions and costa meres of all skeletal muscles is an integral part of the major mechanism for molecular signaling upon mechanical stimulation in all muscle fibers. Additionally, we propose that myotonic protein kinase (DMPK) and dystrophin (DYSTR) also participate in distinct mechanically stimulated molecular signaling pathways that are most critical in type I and type II muscle fibers, respectively. To test these hypotheses, we will use the paradigms of hindlimb unloading and overloading in mice as models for microgravity conditions and a potential exercise countermeasure, respectively, in mice. We expect that FAK loss-of-function will impair hypertrophy and enhance atrophy in all skeletal muscle fibers whereas DYSTR and DMPK loss-of-function will have similar but more selective effects on Type IT and Type I fibers, respectively. Gene expression will be monitored by muscle-specific creatine kinase M promoter-reporter construct activity and specific MRNA and protein accumulation in the soleus (type I primarily) and plantaris (type 11 primarily) muscles. With these paradigms and assays, the following Specific Project Aims will be tested in genetically altered mice: 1) identify the roles of DYSTR and its pathway; 2) evaluate the roles of the DMPK and its pathway; 3) characterize the roles of FAK and its pathway and 4) genetically analyze the mechanisms and interactions between the FAK, DYSTR, and DMPK-associated pathways in single and specific combinations of mutants. The identification of potential signaling mechanisms may permit future development of pharmacological countermeasures for amelioration and prevention of the microgravity-induced atrophy in extended spaceflight, and the analysis of both overloading and unloading paradigms may provide further support for development of exercise-based countermeasures. Understanding the basic mechanisms of molecular signaling in muscle plasticity may aid our understanding and treatment of skeletal muscle atrophy not only in spaceflight but in similar problems of the aging population, in prolonged bed rest, and in cachexia associated with chronic disease.

Epstein, Henry F.↗