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At least 55 records · Page 3

Effects of 2-deoxy-D-glucose administration on immune parameters in mice

Physical exercise and diet alterations have been shown to affect immune parameters. Similar effects are also induced by the administration of the non-metabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The current study was designed to characterize the effects of glucoprivation induced by 2-DG administration on leukocyte subset distribution and function. BDF1 mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, 1000 or 1500 mg/kg of 2-DG. Two hours after the last injection of 2-DG, immunological parameters were analyzed. A dose-dependent increase in plasma glucose concentrations of mice injected once with up to 1500 mg/kg of 2-DG was observed (p < 0.001). After either one or three injections of up to 1500 mg/kg of 2-DG, corticosterone levels, leukocyte counts in the spleen, and CD3+ cells in the thymus increased. In vitro proliferation of partially purified lymphocytes from the spleen in the presence of both concanavalin-A and lipopolysaccharide decreased in a dose dependent manner (p < 0.05). In addition, after three injections, the proportion of both thymocytes and splenocytes bearing alphabeta-TCR increased as the concentration of 2-DG increased (p < 0.01). These results demonstrate that 2-DG administration induced dose-dependent changes in both thymus and spleen cell distribution and function.

NASA Discipline Regulatory Physiology↗

Programmed administration of parathyroid hormone increases bone formation and reduces bone loss in hindlimb-unloaded ovariectomized rats

Gonadal insufficiency and reduced mechanical usage are two important risk factors for osteoporosis. The beneficial effects of PTH therapy to reverse the estrogen deficiency-induced bone loss in the laboratory rat are well known, but the influence of mechanical usage in this response has not been established. In this study, the effects of programed administration of PTH on cancellous bone volume and turnover at the proximal tibial metaphysis were determined in hindlimb-unloaded, ovariectomized (OVX), 3-month-old Sprague-Dawley rats. PTH was administered to weight-bearing and hindlimb-unloaded OVX rats with osmotic pumps programed to deliver 20 microg human PTH (approximately 80 microg/kg x day) during a daily 1-h infusion for 7 days. Compared with sham-operated rats, OVX increased longitudinal and radial bone growth, increased indexes of cancellous bone turnover, and resulted in net resorption of cancellous bone. Hindlimb unloading of OVX rats decreased longitudinal and radial bone growth, decreased osteoblast number, increased osteoclast number, and resulted in a further decrease in cancellous bone volume compared with those in weight-bearing OVX rats. Programed administration of PTH had no effect on either radial or longitudinal bone growth in weight-bearing and hindlimb-unloaded OVX rats. PTH treatment had dramatic effects on selected cancellous bone measurements; PTH maintained cancellous bone volume in OVX weight-bearing rats and greatly reduced cancellous bone loss in OVX hindlimb-unloaded rats. In the latter animals, PTH treatment prevented the hindlimb unloading-induced reduction in trabecular thickness, but the hormone was ineffective in preventing either the increase in osteoclast number or the loss of trabecular plates. Importantly, PTH treatment increased the retention of a baseline flurochrome label, osteoblast number, and bone formation in the proximal tibial metaphysis regardless of the level of mechanical usage. These findings demonstrate that programed administration of PTH is effective in increasing osteoblast number and bone formation and has beneficial effects on bone volume in the absence of weight-bearing and gonadal hormones. We conclude that the actions of PTH on cancellous bone are independent of the level of mechanical usage.

NASA Discipline Musculoskeletal↗

Immune alterations in male and female mice after 2-deoxy-D-glucose administration

Administration of 2-deoxy-D-glucose (2-DG) induces acute cellular glucoprivation. In the current study, we examined differences in immune parameters after 2-DG administration in both sexes. Male and female BDF1 mice were injected three times, 48 h apart, either with a saline solution (control group) or with 2-DG in saline (500 mg/kg). Two hours after the last injection, blood and spleens were collected. Plasma levels of interleukin-1beta, and interferon-gamma levels were measured. Additionally, the levels of the specific leukocyte antigens CD3, CD4, CD8, T cell receptor (TCR) alpha/beta, I-Ad, and H-2Ld/H-2Db were evaluated by flow cytometry on both blood and spleen cells. The blastogenic response of leukocytes from both tissues to mitogens was assessed. Levels of glucose, corticosterone, testosterone, progesterone, 17beta-estradiol, follicle-stimulating hormone, and luteinizing hormone were also determined. Increases in the percentage of cells bearing TCR alpha/beta and I-Ad in the blood and H-2Ld/H-2Db in the spleen were observed in the 2-DG-treated group for both sexes. In contrast, higher corticosterone and IL-1beta plasma concentrations, as well as higher percentages of splenocytes bearing TCR alpha/beta and I-Ad, and lower mitogen-induced proliferation of mature T splenocytes (79%) were observed in female but not in male mice injected with 2-DG compared with those injected with saline (p < 0.05). Taken together, these results suggest that female mice are more sensitive than male mice to immune alterations induced by 2-DG administration.

Non-NASA Center↗

An Examination of the Indiana State University Aerospace Administration Program

Declining enrollments in the Indiana State University (ISU) aerospace administration program prompted this case study. which evaluates the program in comparison with parallel programs at other universities, industry standards, and an independent audit. Survey instruments were administered to graduates, faculty, and employers for their views on competencies of an excellent aerospace administration program Results show the deficiency of the ISU program. Graduates, faculty, and employers rated all competencies-from moderate to considerable importance-similarly for an excellent program. Recommendations for program improvement were made, and suggestions for further research include studies to evaluate the effectiveness of a revised aerospace administration program.

Schwab, Gregory L.↗

Tropospheric Airborne Meteorological Data Reporting (TAMDAR) Sensor Validation and Verification on National Oceanographic and Atmospheric Administration (NOAA) Lockheed WP-3D Aircraft

As part of the National Aeronautics and Space Administration's Aviation Safety and Security Program, the Tropospheric Airborne Meteorological Data Reporting project (TAMDAR) developed a low-cost sensor for aircraft flying in the lower troposphere. This activity was a joint effort with support from Federal Aviation Administration, National Oceanic and Atmospheric Administration, and industry. This paper reports the TAMDAR sensor performance validation and verification, as flown on board NOAA Lockheed WP-3D aircraft. These flight tests were conducted to assess the performance of the TAMDAR sensor for measurements of temperature, relative humidity, and wind parameters. The ultimate goal was to develop a small low-cost sensor, collect useful meteorological data, downlink the data in near real time, and use the data to improve weather forecasts. The envisioned system will initially be used on regional and package carrier aircraft. The ultimate users of the data are National Centers for Environmental Prediction forecast modelers. Other users include air traffic controllers, flight service stations, and airline weather centers. NASA worked with an industry partner to develop the sensor. Prototype sensors were subjected to numerous tests in ground and flight facilities. As a result of these earlier tests, many design improvements were made to the sensor. The results of tests on a final version of the sensor are the subject of this report. The sensor is capable of measuring temperature, relative humidity, pressure, and icing. It can compute pressure altitude, indicated air speed, true air speed, ice presence, wind speed and direction, and eddy dissipation rate. Summary results from the flight test are presented along with corroborative data from aircraft instruments.

Tsoucalas, George↗

Evidence of thyroxine formation following iodine administration in Sprague-Dawley rats

Iodine (I2) has been proposed to be used as a water disinfectant on the manned space station. Previous work has shown that subchronic administration of I2 to Sprague-Dawley rats in drinking water significantly increases plasma thyroxine/triiodothyronine (T4/T3) levels. This is not observed with iodide (I-) treatment. The present study addresses the possibility that I2 reacts with deiodinated T4 metabolites in the gastrointestinal tract to resynthesize T4. Incubation of diiodothyronine (T2), T3, or reverse T3 with I2 in phosphate-buffered saline resulted in the formation of T4 as measured by radioimmunoassay. Washes from the initial segments of the small intestine of the rat show that substrates are present that react with I2 to produce T4. Single oral doses of I2 to rats produced significant dose-related increases in serum T4 and decreases in T3 concentrations after 2 h. Administration of an equivalent dose of I- did not alter significantly plasma T4 concentrations. Higher concentrations of a radioactive substance that bound a T4-specific antibody are present in plasma of animals treated with 125I2 compared to 125I-. These data support the hypothesis that I2 reacts with metabolites of thyroid hormone in the gastrointestinal tract to resynthesize T4 and elevate its levels in blood.

NASA Discipline Environmental Health↗

Protective effects of intravitreal administration of mesenchymal stem cell-derived exosomes in an experimental model of optic nerve injury

Traumatic optic neuropathy results in the loss of retinal ganglion cells (RGCs), leading to unavoidable visual impairment. However, there is no effective therapy by far. Accumulated studies support the perception that mesenchymal stem cells (MSCs) secrete exosomes that serve as a protective paracrine factor. The study aimed to explore and evaluate the potential therapeutic effects of intravitreal transplantation of MSC-derived exosomes (MSC-exos) in an experimental model of optic nerve crush (ONC). Exosomes were isolated from rat MSCs and characterized by transmission electron microscope and western blotting. At the onset of ONC, a single intravitreal injection of exosomes or PBS was administered to the rats. At day 30, hematoxylin and eosin staining, immunohistochemistry, and βIII-tubulin staining were performed to evaluate the survival of RGCs. Moreover, TUNEL assay was used to examine the apoptosis of RGCs. Inflammation-relevant factors were identified via quantitative polymerase chain reaction. The expression levels of cell apoptosis-related molecules and key members of the PI3K/AKT signaling pathway were determined via western blot analysis. We found that MSC-exos exhibited typical characteristic morphologies (cup-shaped) and sizes (peak size of 93 nm). Furthermore, they exhibited substantial expression of the exosome markers CD63 and TSG101, but lacked the expression of the cellular marker GM130. Treatment with intravitreal MSC-exos notably promoted the survival of RGCs in ONC rats. The level of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8, and MCP-1, were reduced, whereas those of the anti-inflammatory factor IL-10 were increased. Moreover, the apoptosis induced by ONC was decreased by the administration of MSC-exos via upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 activity. Furthermore, MSC-exos significantly stimulated AKT phosphorylation, whereas LY294002 restored the apoptosis-preventing effects of MSC-exos. The results of our results demonstrated that intravitreal administration of MSC-exos ameliorates ONC-induced injury in a rat model. These findings might aid in the development of effective exosome-based therapeutic strategies for the treatment of optic nerve degeneration.

60 APPLIED LIFE SCIENCES↗

Machine learning prediction of incidence of Alzheimer’s disease using large-scale administrative health data

Nationwide population-based cohort provides a new opportunity to build an automated risk prediction model based on individuals’ history of health and healthcare beyond existing risk prediction models. We tested the possibility of machine learning models to predict future incidence of Alzheimer’s disease (AD) using large-scale administrative health data. From the Korean National Health Insurance Service database between 2002 and 2010, we obtained de-identified health data in elders above 65 years (N = 40,736) containing 4,894 unique clinical features including ICD-10 codes, medication codes, laboratory values, history of personal and family illness and socio-demographics. To define incident AD we considered two operational definitions: “definite AD” with diagnostic codes and dementia medication (n = 614) and “probable AD” with only diagnosis (n = 2026). We trained and validated random forest, support vector machine and logistic regression to predict incident AD in 1, 2, 3, and 4 subsequent years. For predicting future incidence of AD in balanced samples (bootstrapping), the machine learning models showed reasonable performance in 1-year prediction with AUC of 0.775 and 0.759, based on “definite AD” and “probable AD” outcomes, respectively; in 2-year, 0.730 and 0.693; in 3-year, 0.677 and 0.644; in 4-year, 0.725 and 0.683. The results were similar when the entire (unbalanced) samples were used. Important clinical features selected in logistic regression included hemoglobin level, age and urine protein level. This study may shed a light on the utility of the data-driven machine learning model based on large-scale administrative health data in AD risk prediction, which may enable better selection of individuals at risk for AD in clinical trials or early detection in clinical settings.

97 MATHEMATICS AND COMPUTING↗

URINARY EXCRETION OF PLUTONIUM IN MAYAK WORKERS DURING AND AFTER CA-DTPA ADMINISTRATION

Chelation therapy is sometimes used after potential exposures to plutonium to increase urinary excretion of the radionuclide to improve the accuracy of bioassay measurements. The purpose of this report is to describe the enhancement of urinary excretion of plutonium during and after the administration of the trisodium salt of calcium diethylenetriaminepentaacetate (Ca-DTPA) daily for 3 d to a group of male and female plutonium workers from the Mayak Production Association in Ozyorsk, Russia. One-hundred and two cases (18 females and 84 males) were selected where urinary contents of plutonium, prior to chelation, exceeded the detection threshold. Daily urine collections were obtained during the 3 d of Ca-DTPA treatments. In addition, 58 of these cases had urine bioassays at 1–45 d after chelation. The daily enhancement over baseline values excretion of plutonium was found to be 50.4×/1.4 (geometric mean and geometric standard deviation); 58.9×/1.2; 72.9×/1.4 in the first, second and third days of Ca-DTPA administration. The mean enhancement for the 3-d period was 60.1×/1.7. The rate of plutonium excretion from 1 to 45 d after chelation decreased with a half-period of 3.9 d and the chelation enhancement factor (Кenh-i) is described by the function Кenh-i = (0.79 ± 0.24) + (42.9 ± 1.2) × e-(0.18 ± 0.01) × day.

Environmental Sciences & Ecology↗

Effect of dehydroepiandrosterone administration before in vitro fertilization on the live birth rate in poor ovarian responders according to the Bologna criteria: A randomised controlled trial

Abstract Objective To evaluate the effect of dehydroepiandrosterone (DHEA) pre‐treatment before in vitro fertilization and embryo transfer (IVF‐ET) on the live birth rate in infertile women with poor ovarian response (POR) defined according to the Bologna criteria. Design A randomized, double‐blind, placebo‐controlled trial. Setting Nine reproductive medical centers in China. Population A total of 821 participants with POR defined according to the Bologna criteria were enrolled in the study between April 2016 and December 2018. Methods Eligible participants were randomly assigned to receive either DHEA ( n = 410) or placebo ( n = 411) treatments for 4–12 weeks prior to IVF‐ET, in a 1:1 ratio. Main outcome measures Live birth rate after the first embryo transfer. Results Thirty‐six (8.8%) of 410 women in the DHEA group and 37 (9.0%) of 411 women in the placebo group had a live birth, with no significant difference observed between groups (relative risk, 0.98, 95% CI, 0.63–1.51; p = 0.911). There were no significant differences in the number of retrieved oocytes, and the rates of clinical pregnancy, pregnancy loss, and cumulative live births between the two groups. Conclusions DHEA administration prior to IVF‐ET had no beneficial effect on the live birth rate relative to placebo in women with POR defined according to the Bologna criteria. Tweetable Abstract No benefit was found in poor ovarian responders who received DHEA administration prior to IVF.

Wang, Ze↗

Effects of exogenous GnRH administration on lambing performance of oestrus‐synchronized Kazak ewes during the breeding season

Abstract The objective of this study was to investigate the effects of GnRH at insemination on lambing performance of Kazak ewes. Oestrus was synchronized in 774 adult Kazak ewes using an intravaginal sponge impregnated with flurogestone acetate. The sponge was left in the vagina for 12 days followed with an injection of 330 IU of eCG at sponge removal. Each ewe was inseminated twice at 48 h and 60 h after sponge removal. The treatment group ( n = 387) was intramuscularly injected at the first insemination with a dose of 25 μg GnRH and the control group ( n = 387) with saline solution. The results showed that GnRH administration significantly decreased the fertility rate. In addition, significant differences were observed between the two groups in terms of the twin birth rate, the abortion rate and the litter size. In conclusion, GnRH administration at insemination was not recommended in Kazak ewes undergoing the fixed time artificial insemination during the breeding season. The breed may be a critical determinant of the potential for the exploitation of GnRH application in sheep breeding programmes.

Zhang, Jing↗

Characteristics of Veterans With Depression Who Use the Veterans Choice Program of the Veterans Health Administration

Objective: The Veterans Choice Program (VCP) of the Veterans Health Administration (VHA) allowed eligible veterans to use their benefits with participating providers outside the VHA. The authors aimed to identify characteristics of veterans with depression who used or did not use mental health care through the VCP. Methods: In this cross-sectional study, the authors analyzed secondary data from the national VHA Corporate Data Warehouse. VHA administrative data were linked with VCP claims to examine characteristics of VCP-eligible veterans with depression. Further, the study sample included 595,943 unique veterans who were enrolled in the VHA before 2013, were eligible for the VCP in 2016, were alive in 2018, and had an assessed Patient Health Questionnaire–9 (PHQ-9) score or depressive disorder diagnosis documented in the VHA between 2016 and 2018. Results: Veterans who used the VCP had lower medical comorbidity scores and lived in less socioeconomically disadvantaged counties, compared with veterans who received only VHA care. VCP veterans were also more likely to have a PHQ-9 score assessment and to have higher mean depression scores. Mean counts of annual mental health visits per 1,000 veterans were markedly higher for direct VHA care than for care provided via the VCP. As a percentage of the total counts of visits per 1,000 veterans across the VCP and VHA, residential programs and outpatient procedures were the services that were most frequently delivered through the VCP. Conclusions: Between 2016 and 2018, the VCP was used primarily to augment mental health care provided by the VHA, rather than to fill a gap in care.

60 APPLIED LIFE SCIENCES↗

UTrain Manual for Training Administrators

This Institutional Training Administrative Procedure provides the business rules that must be followed when working in UTrain. As commercial off-the-shelf software with customizations, UTrain cannot address all the implementation business requirements, and thus, administrative business rules and processes were defined and documented. Many business rules were incorporated into the UTrain training materials. UTrain is the Laboratory’s official learning management system. UTrain is the system of record for all Laboratory training, qualification, certification, and worker authorization. All training at LANL must be documented in UTrain. The detailed steps of how to operate UTrain are contained in the UTrain courses and training manuals and in the UTrain job aids, not in this document.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗

Evaluation of Building 23-117, Administration Building, Nevada National Security Site, Nye County, Nevada

The U.S. Department of Energy (DOE) National Nuclear Security Administration Nevada Field Office (NNSA/NFO) plans to update the façade of Building 23-117, Administration Building (Nevada State Historic Preservation Office [SHPO] Resource No. B15256), at the Nevada National Security Site (NNSS) in Nye County, Nevada. The NNSA/NFO is implementing a long-term project to modernize the town of Mercury for future mission needs. The project is considered an undertaking subject to review under Title 54 of United States Code (USC) § 306108, commonly known as Section 106 of the National Historic Preservation Act, Title 54 USC § 300101, et seq., and its implementing regulations, Title 36 of the Code of Federal Regulations (36 CFR) Part 800.

54 ENVIRONMENTAL SCIENCES↗

Watchmen 3.1.0 System Administrator Guide

This document is a system administrator guide for the Watchmen tool. It describes how system administrator should install the application components and configure the host system.

97 MATHEMATICS AND COMPUTING↗

Watchmen 3.3.0 System Administrators Guide

This document is a system administrator guide for the Watchmen tool. It describes how system administrator should install the application components and configure the host system.

97 MATHEMATICS AND COMPUTING↗

Watchmen 3.0.0 System Administrators Guide

This document is a system administrator guide for the Watchmen tool. It describes how system administrator should install the application components and configure the host system.

97 MATHEMATICS AND COMPUTING↗

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↗