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At least 577 records · Page 32

Lipid A’s Structure Mediates Neisseria gonorrhoeae Fitness during Experimental Infection of Mice and Men

Phosphoethanolamine (PEA) on Neisseria gonorrhoeae lipid A influences gonococcal inflammatory signaling and susceptibility to innate host defenses in in vitro models. Here, we evaluated the role of PEA-decorated gonococcal lipid A in competitive infections in female mice and in male volunteers. We inoculated mice and men with mixtures of wild-type N. gonorrhoeae and an isogenic mutant that lacks the PEA transferase, LptA. LptA production conferred a marked survival advantage for wild-type gonococci in the murine female genital tract and in the human male urethra. Our studies translate results from test tube to animal model and into the human host and demonstrate the utility of the mouse model for studies of virulence factors of the human-specific pathogen N. gonorrhoeae that interact with non-host-restricted elements of innate immunity. These results validate the use of gonococcal LptA as a potential target for development of novel immunoprophylactic strategies or antimicrobial treatments.

59 BASIC BIOLOGICAL SCIENCES↗

Organochlorine pesticides and risk of papillary thyroid cancer in U.S. military personnel: a nested case-control study

Background: The effects of organochlorine pesticide (OCP) exposure on the development of human papillary thyroid cancer (PTC) are not well understood. A nested case-control study was conducted with data from the U.S. Department of Defense Serum Repository (DoDSR) cohort between 2000 and 2013 to assess associations of individual OCPs serum concentrations with PTC risk. Methods: This study included 742 histologically confirmed PTC cases (341 females, 401 males) and 742 individually-matched controls with pre-diagnostic serum samples selected from the DoDSR. Associations between categories of lipid-corrected serum concentrations of seven OCPs and PTC risk were evaluated for classical PTC and follicular PTC using conditional logistic regression, adjusted for body mass index category and military branch to compute odds ratios (OR) and 95% confidence intervals (CIs). Effect modification by sex, birth cohort, and race was examined. Results: There was no evidence of associations between most of the OCPs and PTC, overall or stratified by histological subtype. Overall, there was no evidence of an association between hexachlorobenzene (HCB) and PTC, but stratified by histological subtype HCB was associated with significantly increased risk of classical PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 1.61, 95% CI, 1.09, 2.38; p for trend = 0.05) and significantly decreased risk of follicular variant PTC (third tertile above the limit of detection (LOD) vs. <LOD, OR = 0.38, 95% CI, 0.16, 0.91; p for trend = 0.04). Further stratified by sex, risk of classical PTC was higher for females (third tertile above LOD vs. <LOD, OR = 2.23, 95% CI: 1.23, 4.06; p-trend = 0.02) than for males (OR = 1.22, 95%CI: 0.72–2.08; p-trend = 0.56), though the test for interaction by sex was not statistically significant (p-interaction = 0.30). Similarly, β-hexachlorocyclohexane (β-HCCH) was associated with a higher risk for classical PTC for women with concentrations ≥LOD versus <LOD (OR = 1.76, 95% CI: 1.07, 2.89), while the effects were null for men. There were no consistent trends when stratified by race or birth year. Conclusions: The U.S. Environmental Protection Agency has classified HCB and other OCPs we studied here as probable human carcinogens. Our findings of increased risks for classical PTC associated with increased concentrations of HCB and β-HCCH, which were stronger among females, should be replicated in future studies of other populations.

60 APPLIED LIFE SCIENCES↗

Engineering a modular 44 Ti/ 44 Sc generator: eluate evaluation in preclinical models and estimation of human radiation dosimetry

Background: 44 Sc/ 47 Sc is an attractive theranostic pair for targeted in vivo positron emission tomographic (PET) imaging and beta-particle treatment of cancer. The 44 Ti/ 44 Sc generator allows daily onsite production of this diagnostic isotope, which may provide an attractive alternative for PET facilities that lack in-house irradiation capabilities. Early animal and patient studies have demonstrated the utility of 44 Sc. In our current study, we built and evaluated a novel clinical-scale 44 Ti/ 44 Sc generator, explored the pharmacokinetic profiles of 44 ScCl 3 , [ 44 Sc]-citrate and [ 44 Sc]-NODAGA (1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid) in naïve mice, and estimated the radiation burden of 44 ScCl 3 in humans. Methods: 44 Ti/ 44 Sc (101.2 MBq) in 6 M HCl solution was utilized to assemble a modular ZR resin containing generator. After assembly, 44 Sc was eluted with 0.05 M HCl for further PET imaging and biodistribution studies in female Swiss Webster mice. Based on the biodistribution data, absorbed doses of 44 / 47 ScCl 3 in human adults were calculated for 18 organs and tissues using the IDAC-Dose software. Results: 44 Ti in 6 M HCl was loaded onto the organic resin generator with a yield of 99.97%. After loading and initial stabilization, 44 ScCl 3 was eluted with 0.05 M HCl in typical yields of 82.9 ± 5.3% (N = 16), which was normalized to the estimated generator capacity. Estimated generator capacity was computed based on elution time interval and the total amount of 44 Ti loaded on the generator. Run in forward and reverse directions, the 44 Sc/ 44 Ti ratio from a primary column was significantly improved from 1038 ± 440 to 3557 ± 680 (Bq/Bq) when a secondary, replaceable, ZR resin cartridge was employed at the flow outlet. In vivo imaging and ex vivo distribution studies of the reversible modular generator for 44 ScCl 3 , [ 44 Sc]-citrate and [ 44 Sc]-NODAGA show that free 44 Sc remained in the circulation significantly longer than the chelated 44 Sc. The dose estimation of 44 ScCl 3 reveals that the radiation burden is 0.146 mSv/MBq for a 70 kg adult male and 0.179 mSv/MBq for a 57 kg adult female. Liver, spleen and heart wall will receive the highest absorbed dose: 0.524, 0.502, and 0.303 mGy/MBq, respectively, for the adult male. Conclusions: A clinical-scale 44 Ti/ 44 Sc generator system with a modular design was developed to supply 44 ScCl 3 in 0.05 M HCl, which is suitable for further radiolabeling and in vivo use. Our data demonstrated that free 44 ScCl 3 remained in the circulation for extended periods, which resulted in approximately 10 times greater radiation burden than stably chelated 44 Sc. Stable 44 Sc/ 47 Sc-complexation will be more favorable for in vivo use and for clinical utility.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Intrahepatic Cholangiocarcinoma: Socioeconomic Discrepancies, Contemporary Treatment Approaches and Survival Trends from the National Cancer Database

Objective: The aim of this study was to evaluate socioeconomic discrepancies in current treatment approaches and survival trends among patients with intrahepatic cholangiocarcinoma (ICC). Methods: The 2004–2015 National Cancer Database was retrospectively analyzed for histopathologically proven ICC. Treatment predictors were evaluated using multinomial logistic regression and overall survival via multivariable Cox models. Results: Overall, 12,837 ICC patients were included. Multiple factors influenced treatment allocation, including age, education, comorbidities, cancer stage, grade, treatment center, and US state region (multivariable p < 0.05). The highest surgery rates were observed in the Middle Atlantic (28.7%) and lowest rates were observed in the Mountain States (18.4%). Decreased ICC treatment likelihood was observed for male African Americans with Medicaid insurance and those with low income (multivariable p < 0.05). Socioeconomic treatment discrepancies translated into decreased overall survival for patients of male sex (vs. female; hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.16–1.26, p < 0.001), with low income (< $37,999 vs. ≥ $63,000 annually; HR 1.07, 95% CI 1.01–1.14, p = 0.032), and with Medicaid insurance (vs. private insurance; HR 1.13, 95% CI 1.04–1.23, p = 0.006). Both surgical and non-surgical ICC management showed increased survival compared with no treatment, with the longest survival for surgery (5-year overall survival for surgery, 33.5%; interventional oncology, 11.8%; radiation oncology/chemotherapy, 4.4%; no treatment, 3.3%). Among non-surgically treated patients, interventional oncology yielded the longest survival versus radiation oncology/chemotherapy (HR 0.73, 95% CI 0.65–0.82, p < 0.001). Conclusions: ICC treatment allocation and outcome demonstrated a marked variation depending on socioeconomic status, demography, cancer factors, and US geography. Healthcare providers should address these discrepancies by providing surgery and interventional oncology as first-line treatment to all eligible patients, with special attention to the vulnerable populations identified in this study.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

Preconception paternal bisphenol A exposure induces sex-specific anxiety and depression behaviors in adult rats

Bisphenol A (BPA), an environmental endocrine-disrupting compound, has drawn a great attention for its adverse effect on behavioral development. Maternal exposure to this compound has been reported to induce anxiety and depression in offspring, but the effect of its paternal exposure is rarely discussed. This study investigated whether preconception paternal BPA exposure can affect the emotions of male rats and their offspring. Eighteen adult male rats (F0) received either a vehicle or 50 μg/kg/day BPA diet for 21 weeks and were then mated with non-exposed females to produce offspring (F1). The affective behaviors of F0 and F1 rats were evaluated in the open-field test, the elevated-plus maze and the forced swimming test, and their serum corticosterone were then examined. BPA exposure induced increased anxiety behaviors along with increased serum corticosterone in F0 rats. This paternal exposure also led to increased anxiety behaviors in F1 females and aggravated depression behaviors in both sexes of F1 rats. Furthermore, only F1 females exhibited increased serum corticosterone. Overall, these data indicate that preconception paternal exposure to a low dose of BPA may induce transgenerational sex-specific impairments in the affection of adult rats.

59 BASIC BIOLOGICAL SCIENCES↗

Stochastic parametric skeletal dosimetry model for humans: Pediatric and adult computational skeleton phantoms for internal bone marrow dosimetry

Currently, computational phantoms that simulate skeletal tissues are used in active red bone marrow (AM) internal dosimetry. Up-to-date reference computational phantoms recommended by the ICRP are based on the analysis of CT-images of cadavers. Such phantoms have significant disadvantages. One disadvantage is that the assessment of uncertainty due to the population variability of skeleton dimensions and microstructure results from the limited availability of autopsy material. Another disadvantage is the simplified modelling of cortical layer and bone microarchitecture. A method of stochastic parametric skeletal dosimetry modelling of the bone structures – SPSD modelling – has been developed as an alternative to the ICRP reference phantoms. In the framework of this approach, skeletal phantom parameters are evaluated based on extensively reviewed results of published measurements of real bones. The SPSD approach allows for the assessment of both population-average values and their variability. SPSD-phantoms of the skeleton are modelled in voxel representation. They consist of smaller phantoms of the bone sites – segments – described by simple geometric shapes with uniform microarchitecture parameters. Such segmentation makes it possible to account for non-homogeneous skeletal microarchitecture and to model the bone structure with the required voxel resolution to elaborate suitable skeletal phantoms. The current study presents the parameters of the SPSD skeletal phantoms for the following age-groups: newborn, 1-year-old, 5-year-old, 10-year-old, 15-year-old (male and female), and adult (male and female). This skeletal phantom can be used for dosimetry as an alternative to available reference phantoms for bone-seeking radionuclides. The above-mentioned age- and sex-specific skeletal phantoms are comprised of 289 unique segments. The characteristics of the SPSD phantoms do not contradict published data and are in good agreement with the measurement results of real bones.

Science & Technology - Other Topics↗

Lung Cancer in the Mayak Workers Cohort: Risk Estimation and Uncertainty Analysis

The workers at the Mayak nuclear facility near Ozyorsk, Russia are a primary source of information about exposure to radiation at low-dose rates, since they were subject to protracted exposures to external gamma rays and to internal exposures from plutonium inhalation. Here we re-examine lung cancer mortality rates and assess the effects of external gamma and internal plutonium exposures using recently developed Monte Carlo dosimetry systems. Using individual lagged mean annual lung doses computed from the dose realizations, we fit excess relative risk (ERR) models to the lung cancer mortality data for the Mayak Workers Cohort using risk-modeling software. We then used the corrected information matrix (CIM) approach to widen the confidence intervals of ERR by taking into account the uncertainty in doses represented by multiple realizations from the Monte Carlo dosimetry systems. Findings of this work revealed that there were 930 lung cancer deaths during follow-up. Plutonium lung doses (but not gamma doses) were generally higher in the new dosimetry systems than those used in the previous analysis. This led to a reduction in the risk per unit dose compared to prior estimates. The estimated ERR/Gy for external gamma-ray exposure was 0.19 (95% CI: 0.07 to 0.31) for both sexes combined, while the ERR/Gy for internal exposures based on mean plutonium doses were 3.5 (95% CI: 2.3 to 4.6) and 8.9 (95% CI: 3.4 to 14) for males and females at attained age 60. Accounting for uncertainty in dose had little effect on the confidence intervals for the ERR associated with gamma-ray exposure, but had a marked impact on confidence intervals, particularly the upper bounds, for the effect of plutonium exposure [adjusted 95% CIs: 1.5 to 8.9 for males and 2.7 to 28 for females]. In conclusion, lung cancer rates increased significantly with both external gamma-ray and internal plutonium exposures. Accounting for the effects of dose uncertainty markedly increased the width of the confidence intervals for the plutonium dose response but had little impact on the external gamma dose effect estimate. Adjusting risk estimate confidence intervals using CIM provides a solution to the important problem of dose uncertainty. This work demonstrates, for the first time, that it is possible and practical to use our recently developed CIM method to make such adjustments in a large cohort study.

uncertainty, radiation risk estimation, Mayak Prod↗

Morphological and molecular characterization of Paratylenchus beltsvillensis n. sp. (Tylenchida: Paratylenchidae) from the rhizosphere of pine tree ( Pinus virginiana Mill) in Maryland, USA

The pin nematode, Paratylechus beltsvillensis sp. collected from rhizosphere soil of a Virginia pine tree (Pinus virginiana Mill) growing in Little Paint Branch Park, Beltsville, Prince George’s County, Maryland, USA, is described and illustrated along with light and scanning electron photomicrographs. Females, males, and juveniles of this new species were recovered from soil samples using the sugar centrifugal flotation and Baermann funnel extraction methods. Morphologically, females are short, body length ranging from 245 to 267 μm, stylet from 70 to 75 μm long with anchor shaped knobs, vulva located at 70–73% and small vulval flap, spermatheca large, and ovoid filled with sperms. Lateral field with three incisures, of which the outer two are prominent. Tail slender, having a rounded tail terminus. Males without stylet and have a degenerated pharynx, spicules = 17–20 µm and gubernaculum = 5.0–5.5 µm. Both morphological observations and molecular analysis of ITS and partial 28S ribosomal RNA gene sequences indicated that the specimens collected from the soil at Beltsville Park from rhizosphere soil samples from Virginia pine represents a new pin nematode species.

59 BASIC BIOLOGICAL SCIENCES↗

Ecological Monitoring and Compliance Program 2014 Report

The Ecological Monitoring and Compliance Program (EMAC), funded through the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office (NNSA/NFO, formerly Nevada Site Office), monitors the ecosystem of the Nevada National Security Site (NNSS) and ensures compliance with laws and regulations pertaining to NNSS biota. This report summarizes the program’s activities conducted by National Security Technologies, LLC (NSTec), during calendar year 2014. Program activities included (a) biological surveys at proposed activity sites, (b) desert tortoise compliance, (c) ecosystem monitoring, (d) sensitive plant species monitoring, (e) sensitive and protected/regulated animal monitoring, and (f) habitat restoration monitoring. During 2014, all applicable laws, regulations, and permit requirements were met, enabling EMAC to achieve its intended goals and objectives. Sensitive and protected/regulated species of the NNSS include 42 plants, 1 mollusk, 2 reptiles, 236 birds, and 27 mammals. These species are protected, regulated, or considered sensitive according to state or federal regulations and natural resource agencies and organizations. The desert tortoise (Gopherus agassizii) and the western yellow-billed cuckoo (Coccyzus americanus) are the only species on the NNSS protected under the Endangered Species Act, both listed as threatened. However, only one record of the cuckoo has ever been documented on the NNSS, and there is no good habitat for this species on the NNSS. It is considered a rare migrant. Biological surveys for the presence of sensitive and protected/regulated species and important biological resources on which they depend were conducted for 18 projects. A total of 199.18 hectares (ha) was surveyed for these projects. Sensitive and protected/regulated species and important biological resources found during these surveys included a predator burrow, one sidewinder rattlesnake (Crotalus cerastes), two mating speckled rattlesnakes (Crotalus mitchellii), and several species of cacti. NSTec provided to project managers a written summary report of all survey findings and mitigation recommendations, where applicable. Of the 18 projects on the NNSS, 15 occurred within the range of the threatened desert tortoise. Approximately 2.19 ha of desert tortoise habitat were disturbed. No desert tortoises were accidentally injured or killed by project activities, and no tortoises were killed by vehicles. On 13 occasions, tortoises were moved off the road and out of harm’s way. Six tortoises were found and transmitters attached as part of an approved study to assess impacts of vehicles on tortoises on the NNSS. NSTec biologists continued to monitor 37 juvenile desert tortoises as part of a collaborative effort to study survival and temperament of translocated animals. From 1978 until 2013, there has been an average of 11.2 wildland fires per year on the NNSS with an average of about 83.7 ha burned per fire. There were no wildland fires documented on the NNSS during 2014. Results from the wildland fuel surveys showed a very low risk of wildland fire due to reduced fuel loads caused by limited natural precipitation. Limited reptile trapping and reptile roadkill surveys were conducted to better define species distribution on the NNSS. Sixteen reptiles were trapped representing five species. Combined with data from 2013, 183 road kills were detected, representing 11 snake and 8 lizard species. Selected natural water sources were monitored to assess trends in physical and biological parameters, and one new water source was found. Wildlife use at five water troughs and four radiologically contaminated sumps was documented using motion-activated cameras. As part of the statewide effort to disseminate information throughout the botanical community, NSTec prepared a shape file with site-specific data for all 17 sensitive plants on the NNSS and provided it to the Nevada Natural Heritage Program for inclusion in their statewide database. No field surveys were conducted this year for sensitive plants on the NNSS due to poor growing conditions. Surveys of sensitive and protected/regulated animals during 2014 focused on winter raptors, bats, wild horses (Equus caballus), mule deer (Odocoileus hemionus), desert bighorn sheep (Ovis Canadensis nelsoni), and mountain lions (Puma concolor). Two permanent, long-term winter raptor survey routes were established and sampled in January and February. A total of 27 raptors representing 4 species were observed. The wild horse population increased from 30 to 41, with several yearlings recruiting into the population, possibly due to the death of a mountain lion known to prey on horse foals. Mule deer abundance and density measured with standardized deer surveys was similar to 2013 and appears to be stable. Desert bighorn sheep, including rams, ewes, and lambs, were detected using motion-activated cameras at four water sources. There are plans to conduct helicopter surveys to census the population during September 2015 and then capture and radio-collar up to 20 sheep during November 2015. Over 150 sheep scat samples have been collected for genetic analysis to try to determine how sheep on the NNSS are related to surrounding sheep populations. Information is presented about bird mortalities, Migratory Bird Treaty Act compliance, and a summary of nuisance animals and their control on the NNSS. A total of 93 mountain lion images (i.e., photographs or video clips) were taken during 220,379 camera hours at 16 of 32 sites sampled and another 11,946 images of at least 29 species other than mountain lions were taken as well. A mountain lion telemetry study continued in 2014. NNSS7 was tracked from January 1 to November 15 using a global positioning system satellite transmitter. He consumed 21 mule deer, 17 desert bighorn sheep, 1 juvenile bobcat, and 3 coyotes. Mule deer were primarily taken in the summer and fall. No new mountain lions were captured. A minimum of four adult lions (two males, two females), a subadult male, and three kittens were known to inhabit the NNSS during 2014. Two previously revegetated sites on the NNSS and one on the Tonopah Test Range (TTR) were monitored in 2014. The cover cap on the U-3ax/bl disposal unit, revegetated in 2000, and the 92-Acre Site at the Area 5 Radioactive Waste Management Complex, revegetated in 2011, were the restoration sites monitored on the NNSS. The Corrective Action Unit 407 Rollercoaster RADSAFE site, revegetated in 2000, was the restoration site monitored on the TTR. Plant cover and density were recorded at all sites except U-3ax/bl (qualitative monitoring), and reclamation success standards were evaluated, where applicable.

54 ENVIRONMENTAL SCIENCES↗

A Spatially Explicit Individual-Based Modeling Approach to Evaluate the Cumulative Effects of Wind Energy Development on the Greater Sage-Grouse: Sensitivity Analysis and Validation of Key Parameters

To address the need for an approach to evaluate cumulative ecological impacts of wind energy development, particularly those on critical wildlife habitats and species, the authors developed a proof-of-concept, landscape-based, spatially explicit individual-based modeling (IBM) framework for populations of the greater sage-grouse (Centrocercus urophasianus) in Albany County, Wyoming, based on published and other available information on the life history of the species. This sage-grouse IBM estimates the spatial and temporal movements of sage-grouse based on modeled effects of habitat characteristics and developments on sage-grouse condition, survivorship, and reproduction. After completing the initial version of the model, we conducted a series of sensitivity analyses of key model parameters and validation of lek occurrences and spatial distributions to better understand performance of the model relative to observed values of important life history characteristics. The parameter sensitivity analysis was conducted as a series of one-factor-at-a-time tests in which the values of selected parameters were individually varied to evaluate the corresponding effects on model output. We examined the model’s response to changes in parameter values to gain insight into the overall robustness of the model, identify key driver parameters, and initiate qualitative validation. Five functions selected for sensitivity analyses were (1) the rate of change in body condition in relationship to habitat suitability index (HSI) of occupied habitat (condition change rate), (2) the effect of competition between individuals with overlapping home ranges expressed as a percentage reduction in HSI (competition factor), (3) value of condition at which survivorship probability is equal to zero (zero survivorship condition), (4) the relationship between female body condition and clutch size, and (5) the relationship between female body condition and nest success. We varied the parameter values to be tested for the sensitivity analysis around the original value used in the model (i.e., tested values were higher and lower than the model’s original value) to examine the effect of this variation on the predicted output of the model. Model outputs evaluated in the sensitivity analysis included (1) predicted age-class distribution (as measured by the percentage of immature individuals within the population); (2) predicted sex ratio; (3) predicted age-sex class distribution (percent of population in each of six age-sex classes, i.e., male and female juveniles, yearlings, and adults); (4) lifespan; (5) population size; and (6) spatial distribution. Of the five parameters analyzed, condition change rate, survivorship, clutch size, and nest success did not substantially affect any of the evaluated model outputs. For the predicted age-class distribution, the percentage of immature individuals predicted by the model for these four parameters ranged from 61.9% to 65.0%, which was reasonable with respect to the reference values of 51.4 to 57.8% in published studies. The ratio of females to males ranged from 1.09 to 1.14, which was comparable to the reference values of 1.2 to 3.0 presented in an existing study. The predicted mean lifespan ranged from 1.62 to 1.74 years, which appears to be reasonable with respect to the reference values of 0.9 to 1.1 years for sharp-tail grouse and greater prairie chickens presented by published studies. The predicted population size ranged from 1,877 to 3,140. This prediction would be reasonable with respect to our estimate of 5,000 yearlings and adults, which was based on the USFWS estimate for the state of Wyoming scaled to the number of leks in the county. The predicted spatial distribution was not substantially affected by the parameter values examined. In our sensitivity analyses, the only tested parameter that had a noticeable effect on model output was competition factor. Over the range of values tested for this parameter, predicted population size exhibited the largest range (from 1,833 to 4,737) of all parameters tested. As the competition factor increased, the predicted population size decreased. This reflects the effect competition had on the number of individuals that could co occur in high-quality habitat patches. Despite this apparently significant effect, the range of values appears to be reasonable with respect to our estimate of 5,000 yearlings and adults, which was based on the USFWS estimate for the state of Wyoming scaled to the number of leks in the county.

17 WIND ENERGY↗

Species Extrapolation of Propyl Acetate Dose Metrics

We demonstrate the ability of the propyl PBPK model to predict dose metrics of propyl acetate, propanol, and propionic acid from a standard 90-day subchronic inhalation study of propyl acetate in male and female rats. The model was used to predict the same dose metrics in “reference” male and female humans using the same exposure conditions. Finally, we used reverse dosimetry with the model to predict what exposure conditions would lead to the same dose metrics measured in rats. These extrapolations of internal dose metrics based on known species differences in physiology and measured differences in metabolism offer a more scientific species extrapolation than conventional uncertainty approaches, potentially of interest for risk assessment.

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTAN↗

Mule Deer Monitoring Report For Fiscal Year 2013

Population characteristics of mule deer (Odocoileus hemionus) on the Hanford Site have been monitored since 1994. Roadside surveys have been conducted during the post-hunting period from November to January to assess age and sex ratios, and the frequency of testicular atrophy in males. Because the mule deer have been largely protected from hunting on the Hanford Site for 50 years, the herd has developed unique population characteristics, including a large proportion of older males (Tiller et al. 1997).

54 ENVIRONMENTAL SCIENCES↗

Molecular and morphological characterization of Tylenchus zeae n. sp. (Nematoda: Tylenchida) from Corn ( Zea mays ) in South Carolina

Specimens of a tylenchid nematode were recovered in 2019 from soil samples collected from a corn field, located in Pickens County, South Carolina, USA. A moderate number of Tylenchus sp. adults (females and males) were recovered. Extracted nematodes were examined morphologically and molecularly for species identification, which indicated that the specimens of the tylenchid adults were a new species, described herein as Tylenchus zeae n. sp. Morphological examination and the morphometric details of the specimens were very close to the original descriptions of Tylenchus sherianus and T. rex. However, females of the new species can be differentiated from these species by body shape and length, shape of excretory duct, distance between anterior end and esophageal intestinal valve, and a few other characteristics given in the diagnosis. Males of the new species can be differentiated from the two closely related species by tail, spicules, and gubernaculum length. Cryo-scanning electron microscopy confirmed head bearing five or six annules; four to six cephalic sensilla represented by small pits at the rounded corners of the labial plate; a small, round oral plate; and a large, pit-like amphidial opening confined to the labial plate and extending three to four annules beyond it. Phylogenetic analysis of 18S rRNA gene sequences placed Tylenchus zeae n. sp. in a clade with Tylenchus arcuatus and several Filenchus spp., and the mitochondrial cytochrome oxidase c subunit 1 (COI) gene region separated the new species from T. arcuatus and other tylenchid species. In the 28S tree, T. zeae n. sp. showed a high level of sequence divergence and was positioned outside of the main Tylenchus-Filenchus clade.

18S↗

Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with ¹¹C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: ¹¹C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, including brain and torso or pelvis scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned following pretreatment with a clinical dose of the aromatase inhibitor letrozole (“blocking” studies). Time activity curves were obtained and standard uptake values (SUV) calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole body radiation exposures were calculated using Olinda software. Results: Liver uptake was higher than all other organs, but was not blocked by pretreatment with letrozole. Mean SUVs in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (ranging from 0.48±0.05 in lungs to 1.5±0.13 in kidneys). Mean ovarian SUVs (3.08±0.7) were comparable to brain levels and higher than all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced ¹¹C-vorozole uptake. Conclusions: PET with ¹¹C-vorozole is useful for assessing physiological changes in estrogen synthesis capacity in the human body. Baseline levels in breasts, lungs and bones are low, supporting further investigation of this tracer as a new tool for detection of aromatase-overexpressing primary tumors or metastases in these organs and optimization of treatment in cancer and other disorders in which aromatase inhibitors are useful.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗

Effect of in utero and lactational exposure to antiretroviral therapy on the gut microbial composition and metabolic function in aged rat offspring

Despite the highly effective impact of antiretroviral therapy (ART) in reducing mother-to-child transmission of human immunodeficiency virus (HIV), there are concerns of long-term impacts of ART on the health of the offspring. The implications of perinatal exposure to antiviral drugs on the gut bacterial population and metabolic function in the offspring is unclear but may influence health outcomes given the various reported effects of the microbiome in human health. This study aims to gain insight into the potential effect ofin uteroand lactational exposure to ART on gut microbiota populations and short‐chain fatty acids (SCFAs) production in aged rat offspring. Pregnant rats were administered a combination of antiretroviral drugs (abacavir/dolutegravir/lamivudine) at two different dose levels during gestation and throughout lactation, and the fecal bacterial abundance and SCFA levels of the offspring were analyzed when they reached 12 months of age. Our results showed dose-dependent and sex-based differences in fecal microbial abundance at various taxonomic levels. Specifically, we found a decline inFirmicutesin males, and an increase inActinobacteriaamong males and females. Furthermore, a sex-specific distribution reorganization ofLactobacillus,Bifidobacterium, andAkkermansiawas identified. No significant difference in the concentration of prominent SCFAs and IgA levels were identified. These findings provide preliminary information indicating the need to evaluate perinatal effects of ART more comprehensively on the gut bacterial and metabolic function in future studies, and their potential role in offspring health outcomes.

Research & Experimental Medicine↗

Probiotic Lactobacillus acidophilus Strain INMIA 9602 Er 317/402 Administration Reduces the Numbers of Candida albicans and Abundance of Enterobacteria in the Gut Microbiota of Familial Mediterranean Fever Patients

Intestinal microorganisms play a crucial role in health and disease. The disruption of host–microbiota homeostasis has been reported to occur not only during disease development but also as a result of medication. Familial Mediterranean fever (FMF) is an inflammatory genetic disease characterized by elevated systemic reactivity against the commensal gut microbiota and high levels of Candida albicans in the gut. This study’s major objective was to investigate the effects of commercial probiotic Narine on the relative abundance of gut bacteria (specifically, enterobacteria, lactobacilli, Staphylococcus aureus, and enterococci) of C. albicans carrier and non-carrier FMF patients in remission. Our main finding indicates that the probiotic reduces numbers of C. albicans and abundance of enterobacteria in male and female patients of C. albicans carriers and non-carriers. It has pivotal effect on Enterococcus faecalis: increase in male non-carriers and decrease in female ones regardless of C. albicans status. No effect was seen for Lactobacillus and S. aureus. Our data suggest that M694V/V726A pyrin inflammasome mutations leading to FMF disease may contribute to gender-specific differences in microbial community structure in FMF patients. The study’s secondary objective was to elucidate the gender-specific differences in the gut’s microbial community of FMF patients. The tendency was detected for higher counts of enterobacteria in female FMF subjects. However, the small number of patients of these groups preclude from conclusive statements, pointing at the need for additional investigations with appropriate for statistical analysis groups of subjects involved in the study.

59 BASIC BIOLOGICAL SCIENCES↗

Host genetics and gut microbiota composition: Baseline gut microbiota composition as a possible prognostic factor for the severity of COVID-19 in patients with familial Mediterranean fever disease

It is known that the gut microbiome of a healthy person affects the process of COVID-19 after getting infected with SARS-CoV-2 virus. It is also believed that colchicine can alleviate the severity of COVID-19. Current investigations aimed to evaluate the associations between the baseline gut microbiota composition of healthy and Familial Mediterranean fever (FMF) - carrier Armenian men populations, and the severity of the COVID-19 disease after their infection with the SARS-CoV-2. The study has a purpose of answering three core questions: i. Do the characteristics of gut microbiome of Armenians affect the course of COVID-19 severity? ii. How does the COVID-19 disease course on go for FMF patients who have been taking colchicine as a medication over the years after getting infected with SARS-CoV-2? iii. Is there an initial gut micribiota structure pattern for non-FMF and FMF patients in the cases when COVID-19 appears in mild form? The gut microbiota composition in non-FMF and FMF patients before the first infection (mild and moderate course of COVID-19) was considered. COVID-19 was diagnosed by SARS-CoV-2 nucleic acid RT-PCR in nasopharyngeal swab and/or sputum. The number of patients with male FMF with mild COVID-19 was approximately two times higher than that of non-FMF male subjects with COVID-19. In addition, an association of COVID-19 disease severity with the baseline gut Prevotella, Clostridium hiranonis, Eubacterium biforme, Veillonellaceae, Coprococcus, and Blautia diversities in the non-FMF and FMF populations were revealed by us, which can be used as risk/prognostic factor for the severity of COVID-19.

60 APPLIED LIFE SCIENCES↗

Developmental exposure to corn grown on Lake Erie dredged material: a preliminary analysis

While corn is considered to be a healthy food option, common agricultural practices, such as the application of soil amendments, might be introducing contaminants of concern (COC) into corn plants. The use of dredged material, which contain contaminants such as heavy metals, polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs), as a soil amendment is increasing. Contaminants from these amendments can accumulate in corn kernels harvested from plants grown on these sediments and potentially biomagnify in organisms that consume them. The extent to which secondary exposure to such contaminants in corn affect the mammalian central nervous system has been virtually unexplored. In this preliminary study, we examine the effects of exposure to corn grown in dredge amended soil or a commercially available feed corn on behavior and hippocampal volume in male and female rats. Perinatal exposure to dredge-amended corn altered behavior in the open-field and object recognition tasks in adulthood. Additionally, dredge-amended corn led to a reduction in hippocampal volume in male but not female adult rats. These results suggest the need for future studies examining how dredge-amended crops and/or commercially available feed corn may be exposing animals to COC that can alter neurodevelopment in a sex-specific manner. This future work will provide insight into the potential long-term consequences of soil amendment practices on the brain and behavior.

59 BASIC BIOLOGICAL SCIENCES↗