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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 361 records · Page 20
All sourcesNASA NTRSDOE OSTI
DOE OSTI2014

Inhibition of HAS2 induction enhances the radiosensitivity of cancer cells via persistent DNA damage

Highlights: •HAS2 may be a promising target for the radiosensitization of human cancer. •HAS2 is elevated (up to ∼10-fold) in irradiated radioresistant and -sensitive cancer cells. •HAS2 knockdown sensitizes cancer cells to radiation. •HAS2 knockdown potentiates irradiation-induced DNA damage and apoptotic death. •Thus, the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. -- Abstract: Hyaluronan synthase 2 (HAS2), a synthetic enzyme for hyaluronan, regulates various aspects of cancer progression, including migration, invasion and angiogenesis. However, the possible association of HAS2 with the response of cancer cells to anticancer radiotherapy, has not yet been elucidated. Here, we show that HAS2 knockdown potentiates irradiation-induced DNA damage and apoptosis in cancer cells. Upon exposure to radiation, all of the tested human cancer cell lines exhibited marked (up to 10-fold) up-regulation of HAS2 within 24 h. Inhibition of HAS2 induction significantly reduced the survival of irradiated radioresistant and -sensitive cells. Interestingly, HAS2 depletion rendered the cells to sustain irradiation-induced DNA damage, thereby leading to an increase of apoptotic death. These findings indicate that HAS2 knockdown sensitizes cancer cells to radiation via persistent DNA damage, further suggesting that the irradiation-induced up-regulation of HAS2 contributes to the radioresistance of cancer cells. Thus, HAS2 could potentially be targeted for therapeutic interventions aimed at radiosensitizing cancer cells.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

Nanoparticle-mediated antagonism of sustained endosomal signaling of the calcitonin receptor-like receptor provides enhanced and persistent relief of oral cancer pain

By improving the delivery and tumor retention of chemotherapeutics, nanomedicines hold potential for cancer treatment. The usefulness of nanoparticle (NP)-encapsulated analgesics for the cancer pain treatment is comparatively unexplored. We investigated whether NPs encapsulating olcegepant (OCP), an antagonist of the calcitonin receptor-like receptor (CLR) for the calcitonin gene-related peptide (CGRP), effectively relieved oral cancer pain in mice. Because persistent endosomal CLR signaling in Schwann cells mediates craniofacial pain, we reasoned that the predisposition of NPs to accumulate in endosomes could be leveraged to effectively relieve oral cancer pain. By expressing biosensors for activated CLR, Gα proteins and β-arrestins in HEK293T and Schwann cells, we found that CGRP activates CLR signaling first at the plasma membrane and then in early, late and recycling endosomes and the cis- and trans-Golgi apparatus. We synthesized biocompatible NPs encapsulating OCP and fluorophores by integrating hydrophobic ion pairing nanoformulation with Flash NanoPrecipitation. NPs slowly released OCP and accumulated in early endosomes, leading to sustained inhibition of endosomal CLR signaling in HEK293T and Schwann cells. Oral cancers were established in mice, which led to heightened pain-like responses. After intra-tumoral injection, NPs were retained in tumors for at least one week. OCP-loaded NPs almost completely reversed allodynia and hyperalgesia for a prolonged period, whereas unencapsulated OCP had small and transient effects. The NP accumulation in endosomal sites of pain signaling, the sustained release of antagonist, and the retention of NPs in tumors explain their beneficial actions. Thus, NP-encapsulation holds promise for the relief of painful cancers that are inadequately treated by opioids.

Calcitonin gene-related peptide↗
DOE OSTI2023

Antiretroviral therapy reveals triphasic decay of intact SIV genomes and persistence of ancestral variants

The decay kinetics of HIV-1-infected cells are critical to understand virus persistence. We evaluated the frequency of simian immunodeficiency virus (SIV)-infected cells for 4 years of antiretroviral therapy (ART). The intact proviral DNA assay (IPDA) and an assay for hypermutated proviruses revealed short- and long-term infected cell dynamics in macaques starting ART ~1 year after infection. Intact SIV genomes in circulating CD4+T cells showed triphasic decay with an initial phase slower than the decay of the plasma virus, a second phase faster than the second phase decay of intact HIV-1, and a stable third phase reached after 1.6–2.9 years. Hypermutated proviruses showed bi- or mono-phasic decay, reflecting different selective pressures. Viruses replicating at ART initiation had mutations conferring antibody escape. With time on ART, viruses with fewer mutations became more prominent, reflecting decay of variants replicating at ART initiation. Collectively, these findings confirm ART efficacy and indicate that cells enter the reservoir throughout untreated infection.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Formation of environmentally persistent free radicals (EPFRs) on ZnO at room temperature: Implications for the fundamental model of EPFR generation

Environmentally persistent free radicals (EPFRs) have significant environmental and public health impacts. Here, we demonstrate that EPFRs formed on ZnO nanoparticles provide two significant surprises. First, EPR spectroscopy shows that phenoxy radicals form readily on ZnO nanoparticles at room temperature, yielding EPR signals similar to those previously measured after 250°C exposures. Vibrational spectroscopy supports the conclusion that phenoxy-derived species chemisorb to ZnO nanoparticles under both exposure temperatures. Second, DFT calculations indicate that electrons are transferred from ZnO to the adsorbed organic (oxidizing the Zn), the opposite direction proposed by previous descriptions of EPFR formation on metal oxides.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

A Specific Mutational Signature Associated with DNA 8-Oxoguanine Persistence in MUTYH-defective Colorectal Cancer

8-Oxoguanine, a common mutagenic DNA lesion, generates G:C > T:A transversions via mispairing with adenine during DNA replication. When operating normally, the MUTYH DNA glycosylase prevents 8-oxoguanine-related mutagenesis by excising the incorporated adenine. Biallelic MUTYH mutations impair this enzymatic function and are associated with colorectal cancer (CRC) in MUTYH-Associated Polyposis (MAP) syndrome. Here in this paper, we perform whole-exome sequencing that reveals a modest mutator phenotype in MAP CRCs compared to sporadic CRC stem cell lines or bulk tumours. The excess G:C > T:A transversion mutations in MAP CRCs exhibits a novel mutational signature, termed Signature 36, with a strong sequence dependence. The MUTYH mutational signature reflecting persistent 8-oxoG:A mismatches occurs frequently in the APC, KRAS, PIK3CA, FAT4, TP53, FAT1, AMER1, KDM6A, SMAD4 and SMAD2 genes that are associated with CRC. In conclusion, the occurrence of Signature 36 in other types of human cancer indicates that DNA 8-oxoguanine-related mutations might contribute to the development of cancer in other organs.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2016

Implementation of data citations and persistent identifiers at the ORNL DAAC

A requirement of data archives is that data holdings can be easily discovered, accessed, and used. One approach to improving data discovery and access is through data citations coupled with Digital Object Identifiers (DOI). The Oak Ridge National Laboratory Distributed Active Archive Center (ORNL DAAC) since 1998 has issued data citations that have been accepted and used in peer-reviewed journals. Citation elements established by the ORNL DAAC are similar to those used for journal articles (authors, year, product title, and information to locate), and beginning in 2007 included a DOI that is persistent, actionable, specific, and complete. The approach used at the ORNL DAAC also allows for referring to subsets of the data, by including within the citation the temporal and spatial extent, and parameters used. Data citations allow readers to find data and reproduce the results of the research article, and also use those data to test new hypotheses, design new sample collections, or construct or evaluate models. The ORNL DAAC uses a manual method to compile data citations and has developed a database that links research articles and their use of specific ORNL DAAC data products. Automation of the data citation compilation process, as is the case for articles, will enable data citations to become a more common practice. In addition to enhancing discovery and access of the data used in a research article, the citation gives credit to data generators, data centers and their funders, and, through citation indices, determine the scientific impact of a data set.

96 KNOWLEDGE MANAGEMENT AND PRESERVATION↗
DOE OSTI2016

Persistence of the herbicides florasulam and halauxifen-methyl in alluvial and saline alluvial soils, and their effects on microbial indicators of soil quality

In this study, the persistence of florasulam and halauxifen-methyl in combination was investigated in an alluvial (AL) and saline alluvial (SAL) soils under laboratory condition at field recommended (FR) dose (i.e. 12.76 g a.i. ha -1 ), 10 FR and 0FR (control) throughout the experiment. Effect of these herbicides on soil microbial biomass carbon (MBC), basal soil respiration (BSR), substrate induced soil respiration (SIR), hydrolysis of fluorescein diacetate (FDHA) and β-glucosidase activities was also measured under same conditions. The residues of florasulam and haluaxifen-methyl were extracted with acetonitrile using modified QuChERS method, followed by quantification using liquid chromatography-mass spectrometry (LC-MS/MS). Half-lives of florasulam and halauxifen-methyl were in the range of 12.65-16.82 days and 7.13-10.24 days in AL respectively and the same for SAL was 15.28-17.60 days and 7.25-8.88 days. Herbicide treatment inhibited MBC, BSR, SIR, and microbial metabolic quotient (qCO 2 ) up to 30 days of incubation at the applied doses in both the soils. At the end of incubation, FR treated soils became statistically at par with control. However, the FDHA and β-glucosidase activities were affected in both the soils at the applied doses of the herbicide up to 15 days. Thereafter, the FR treated soils were statistically at par with control. Finally, data revealed that, recommended dose of this herbicide formulation did not ultimately impair microbial components of the studied soils.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2014

Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals—Depot differences and dysmetabolism implications

Background: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (R{sub S}=0.310, p<0.01) and duration of obesity (R{sub S}=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (R{sub S}=0.277, p<0.01), with relevance for vAT (R{sub S}=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens. - Highlights: • POPs are pervasive in this sample of obese patients undergoing bariatric surgery. • Distinct adipose tissues have dissimilar POPs storage capability. • Despite the presence of obesity, POPs are important for metabolic dysregulation.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Self-rated health and chronic conditions are associated with blood concentrations of persistent organic pollutants in the general population of Catalonia, Spain

Background: Self-rated health (SRH) is a powerful predictor of mortality, morbidity, and need for health services. SRH generally increases with educational level, and decreases with age, number of chronic conditions, and body mass index (BMI). Because human concentrations of most persistent organic pollutants (POPs) also vary by age, education, and BMI, and because of the physiological and clinical effects of POPs, we hypothesized that body concentrations of POPs are inversely associated with SRH. Objectives: To analyze the relation between serum concentrations of POPs and SRH in the general population of Catalonia, Spain, taking into account sociodemographic factors and BMI, as well as chronic health conditions and mental disorders, measured by the General Health Questionnaire-12 (GHQ-12). Methods: POP serum concentrations were measured by gas chromatography with electron-capture detection in 919 participants of the Catalan Health Interview Survey. Results: Individuals with higher concentrations of POPs had significantly poorer SRH; e.g., the median concentration of HCB in subjects with poor SRH was twice as high as in subjects with excellent SRH (366 ng/g vs. 169 ng/g, respectively; p-value<0.001). In crude models and in models adjusted for sex and BMI, the POPs-SRH association was often dose-dependent, and the likelihood of poor or regular SRH was 2 to 4-times higher in subjects with POP concentrations in the top quartile. In models adjusted for age or for chronic conditions virtually all ORs were near unity. No associations were found between POP levels and GHQ-12. Conclusions: Individuals with higher concentrations of POPs had significantly poorer SRH, an association likely due to age and chronic conditions, but not to sex, education, social class, BMI, or mental disorders. - Highlights: • The relation between POPs and self-rated and mental health has seldom been studied. • Subjects with higher POP levels had poorer self-rated health (SRH) (dose-dependent). • The number of chronic conditions was positively related to POP levels. • The POPs-SRH association was likely due to age (or birth cohort), and to chronic conditions. • Causal or not, the fact is that people with poorer SRH often have higher levels of POPs.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Contrasted accumulation patterns of persistent organic pollutants and mercury in sympatric tropical dolphins from the south-western Indian Ocean

Due to their high trophic position and long life span, small cetaceans are considered as suitable bioindicators to monitor the presence of contaminants in marine ecosystems. Here, we document the contamination with persistent organic pollutants (POPs) and total mercury (T-Hg) of spinner (Stenella longirostris, n =21) and Indo-Pacific bottlenose dolphins (Tursiops aduncus, n=32) sampled from the coastal waters of La Réunion (south-western Indian Ocean). In addition, seven co-occurring teleost fish species were sampled and analyzed as well. Blubber samples from living dolphins and muscle from teleosts were analyzed for polychlorinated biphenyls (PCBs), DDT and metabolites (DDTs), chlordanes (CHLs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), and polybrominated diphenyl ethers (PBDEs). Methoxylated PBDEs (MeO-PBDEs), reported as having a natural origin, were also analyzed. T-Hg levels were measured in blubber and skin biopsies of the two dolphin species. Stable isotopes δ{sup 13}C and δ{sup 15}N values were determined in skin of the dolphins and in the muscle of teleosts. For PCBs, HCHs and T-Hg, concentrations were significantly higher in T. aduncus than in S. longirostris. For other POP levels, intra-species variability was high. MeO-PBDEs were the dominant compounds (55% of the total POPs) in S. longirostris, while PCBs dominated (50% contribution) in T. aduncus. Other contaminants showed similar profiles between the two species. Given the different patterns of POPs and T-Hg contamination and the δ{sup 15}N values observed among analyzed teleosts, dietary and foraging habitat preferences most likely explain the contrasted contaminant profiles observed in the two dolphin species. Levels of each class of contaminants were significantly higher in males than females. Despite their spatial and temporal overlap in the waters of La Réunion, S. longirostris and T. aduncus are differently exposed to contaminant accumulation. - Highlights: • POPs and total Hg were measured in spinner and bottlenose dolphins from La Réunion. • Levels of PCBs, PBDEs and T-Hg were lower in spinner than in bottlenose dolphins. • Contrasted contaminant profiles were observed between the two dolphin species. • Profiles are most likely explained by dietary and foraging habitat preferences.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Monthly variation in faeces:blood concentration ratio of persistent organic pollutants over the first year of life: a case study of one infant

Previous studies have found that the concentrations of a range of persistent organic pollutants (POPs) in faeces is linearly proportional to the POP concentrations in blood of human adults irrespective of age and gender. In order to investigate the correlation between POP concentrations in faeces and blood in infants, the monthly variation of POP concentrations in faeces over the first year of life of one infant was investigated in this study and compared to modelled blood concentrations. Faecal samples were collected from one male infant daily. The samples were pooled by month and analysed for three selected POPs (2,2{sup ′},4,4{sup ′},5,5{sup ′}-Hexachlorobiphenyl (PCB153), p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) and 2,2{sup ′},4,4′-tetrabromodiphenyl ether (BDE47)). The POP concentrations in faecal samples increased for the first four months by a factor of 2.9, 4.9 and 1.4 for PCB153, BDE47, and p,p′-DDE, respectively. The faecal concentrations of all POPs decreased rapidly following the introduction of formula and solid food to the diet and subsequent weaning of the infant. Further, a one-compartment model was developed to estimate the daily POP concentrations in the blood of the infant. The POP concentrations in blood were predicted to vary much less over the first year than those observed in faeces. The faeces:blood concentration ratio of selected POPs (K{sub fb}) differed significantly (P<0.0001) between the period before and after weaning, and observed changes in K{sub fb} are far greater than the uncertainty in the estimated K{sub fb}. A more stable K{sub fb} after weaning indicates the possibility of applying the stable K{sub fb} values for non-invasive assessment of internal exposure in infants after weaning. The intra-individual variation in K{sub fb} in infants is worthy of further investigation. - Highlights: • Measured POPs concentrations in faecal samples decreased rapidly following weaning. • Ratio of faecal:blood concentrations (K{sub fb}) changed over the first year of life. • The change in K{sub fb} was not governed by the change in chemical intake with the diet. • The K{sub fb} might be affected primarily by the partitioning properties of faeces.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Lower levels of Persistent Organic Pollutants, metals and the marine omega 3-fatty acid DHA in farmed compared to wild Atlantic salmon (Salmo salar)

Contaminants and fatty acid levels in farmed- versus wild Atlantic salmon have been a hot topic of debate in terms of food safety. The present study determined dioxins (polychlorinated dibenzo-p-dioxin and dibenzofuran), polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides (OCPs), metals and fatty acids in wild and farmed Atlantic salmon. Contaminant levels of dioxins, PCBs, OCPs (DDT, dieldrin, lindane, chlordane, Mirex, and toxaphene), and mercury were higher in wild salmon than in farmed salmon, as were the concentrations of the essential elements selenium, copper, zinc and iron, and the marine omega-3 fatty acid docosahexaenoic acid (DHA). PBDE, endosulfan, pentachlorobenzene, hexachlorobenzene, cadmium and lead levels were low and comparable in both wild and farmed fish, and there was no significant difference in the marine omega-3 fatty acid eicosapentaenoic acid (EPA) concentration. The total fat content was significantly higher in farmed than wild salmon due to a higher content of both saturated and monounsaturated fatty acids, as well as a higher content of omega-6 fatty acids. The omega-3 to omega-6 fatty acid ratio was considerably lower in farmed than wild salmon due to the high level of omega-6 fatty acids. Contaminant concentrations in Atlantic salmon were well below maximum levels applicable in the European Union. Atlantic salmon, both farmed and wild, is a good source of EPA and DHA with a 200 g portion per week contributing 3.2 g or 2.8 g respectively, being almost twice the intake considered adequate for adults by the European Food Safety Authority (i.e. 250 mg/day or 1.75 g/week). - Highlights: • A comprehensive study of contaminants and nutrients in farmed- and wild Atlantic salmon. • Wild salmon had higher levels of persistent organic pollutants and mercury than farmed salmon. • Farmed salmon had higher levels of omega-6 fatty acids than wild salmon. • Farmed- and wild salmon had comparable levels of EPA, whereas farmed salmon had lower levels of DHA.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Assumed non-persistent environmental chemicals in human adipose tissue; matrix stability and correlation with levels measured in urine and serum

The aim of this study was to (1) optimize a method for the measurement of parabens and phenols in adipose tissue, (2) evaluate the stability of chemical residues in adipose tissue samples, and (3) study correlations of these compounds in urine, serum, and adipose tissue. Samples were obtained from adults undergoing trauma surgery. Nine phenols and seven parabens were determined by isotope diluted TurboFlow-LC-MS/MS. The analytical method showed good accuracy and precision. Limits of detection (LOD) for parabens and phenols ranged from 0.05 to 1.83 ng/g tissue. Good recovery rates were found, even when biological samples remained defrosted up to 24 h. Benzophenone-3 (BP-3; range of values: 70% of adipose tissue samples, while bisphenol-A (BPA; 40% of adipose tissue samples. In general, levels were similar between adipose tissue and serum, while a correlation between adipose tissue and urine was only found for BP-3. In conclusion, adipose tissue samples in this study were found to contain environmental chemicals considered to be non-persistent, whose levels were weakly or not at all correlated with the urine burden. Therefore, adipose tissue may potentially provide additional information to that obtained from other biological matrices. Further investigations are warranted to explore whether adipose tissue might be a suitable matrix for assessment of the consequences for human health of mid/long-term exposure to these chemicals. - Highlights: • We analyzed levels of endocrine disruptors in adipose tissue, serum and urine. • We found BPA, TCS, BP-3, 2-PP and MeP in >40% of the adipose tissue samples. • Adipose tissue levels of npEDCs did not correlate with those in urine or serum. • Adipose tissue levels may have a different biological meaning.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2017

Integrated assessment of infant exposure to persistent organic pollutants and mercury via dietary intake in a central western Mediterranean site (Menorca Island)

In this research the levels of organochlorine compounds (OCs) and mercury (Hg) in several food items from Menorca Island were presented. The dietary exposure assessment was performed in children population from the island. Finally, body burden of OCs and Hg in these infants were associated with their dietary intakes of the selected food items. The dietary exposure to persistent pollutants by children population from Menorca Island was assessed. The concentrations of 11 organochlorine pesticides, 6 polychlorinated biphenils (PCBs) and 1 inorganic toxic element, Hg, were determined in 46 food samples that included fish, shellfish, meat, fruit, vegetables, cheese and eggs, which were acquired in local markets and department stores in the Menorca Island. The most contaminated food items were fish and shellfish, followed by meat and cheese products. OC levels were similar or lower than in other previous studies. However, 66% of the analysed fish and shellfish species for Hg exceeded the human consumption safety limits according to the European Union Legislation. Pollutant data from food was combined with the pattern of consumption of these foodstuffs in order to calculate the estimated daily intake (EDI) of these contaminants. According to our results, fish and fruit were the main sources of OCs to the EDIs (contributing to 37% and 29%, respectively) while fish and shellfish were the main sources of Hg (76% and 17%). The estimated EDIs of OCs were well below to the reported FAO/WHO Tolerable Intakes. However, estimated weekly intake of Hg would exceed the Provisional Tolerable Weekly Intake indicated by EFSA in the case that the only fish and seafood source would be from the central western Mediterranean. Direct associations between fish/shellfish consumption and hair concentrations of Hg and fish and meat consumption and 4,4’-DDT concentrations in venous serum in the Menorcan children were observed. - Highlights: • The levels of the organochlorine compounds in the Menorcan food items were low. • Mercury was above the EU recommendations in 66% of the analysed seafood samples. • Fish/shellfish consumption was related with the Hg levels in hair of children. • 4,4’-DDT in serum of children was related to fish and meat consumption. • The Hg weekly intake of Menorcan children exceeded more than twice the EFSA limits.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Maternal and paternal serum concentrations of persistent organic pollutants and the secondary sex ratio: A population-based preconception cohort study

Highlights: • Recent declines in the SSR in some countries may be attributed to exposure to POPs. • Maternal PCB 128 and paternal HCB were associated with a female excess. • Maternal mirex and paternal PCB 128 and p,p′-DDE were associated with a male excess. • These findings await corroboration given the exploratory design of this study. Recent declines in the secondary sex ratio (SSR), defined as the ratio of males to females at birth, in some industrialized countries may be attributed to exposure to environmental toxicants such as persistent organic pollutants (POPs). This study aimed to evaluate the association of couples’ preconception exposure to POPs with the SSR. The study cohort comprised 235 couples who were enrolled in the Longitudinal Investigation of Fertility and the Environment (LIFE) Study between 2005 and 2009 prior to conception and prospectively followed through delivery of a singleton birth. Upon enrollment, couples’ serum concentrations (ng/g) were measured for 9 organochlorine pesticides, 1 polybrominated biphenyl, 10 polybrominated diphenyl ethers, and 36 polychlorinated biphenyls (PCBs). Birth outcome data including infant sex were collected upon delivery. Modified Poisson regression models were used to estimate the relative risks (RRs) and 95% confidence intervals (CIs) of a male birth for each chemical. Of the 56 POPs examined, maternal PCB 128 and paternal hexachlorobenzene were significantly associated with a female excess (RRs, 0.75 [95% CI, 0.60–0.94] and 0.81 [95% CI, 0.68–0.97] per 1 SD increase in log-transformed serum chemical concentrations, respectively), whereas maternal mirex and paternal PCB 128 and p,p′-dichlorodiphenyldichloroethylene were significantly associated with a male excess (RR range, 1.10–1.22 per 1 SD increase in log-transformed serum chemical concentrations). After adjusting for multiple comparisons, only maternal mirex remained significantly associated with the SSR. This exploratory study on multiple classes of POPs demonstrated no conclusive evidence on the association between parental preconception exposure to POPs and the SSR.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Persistent organic pollutants, skull size and bone density of polar bears (Ursus maritimus) from East Greenland 1892–2015 and Svalbard 1964–2004

Highlights: • Density in East Greenland males decreased over time. • Size in East Greenland females tented to decrease over time. • Size was highest in Svalbard polar bears. • Density was positive correlated to POPs. • Environmental changes and POPs may affect bone density and size. We investigated skull size (condylobasal length; CBL) and bone mineral density (BMD) in polar bears (Ursus maritimus) from East Greenland (n = 307) and Svalbard (n = 173) sampled during the period 1892–2015 in East Greenland and 1964–2004 at Svalbard. Adult males from East Greenland showed a continuous decrease in BMD from 1892 to 2015 (linear regression: p < 0.01) indicating that adult male skulls collected in the early pre-pollution period had the highest BMD. A similar decrease in BMD over time was not found for the East Greenland adult females. However, there was a non-significant trend that the skull size of adult East Greenland females was negatively correlated with collection year 1892–2015 (linear regression: p = 0.06). No temporal change was found for BMD or skull size in Svalbard polar bears (ANOVA: all p > 0.05) nor was there any significant difference in BMD between Svalbard and East Greenland subpopulations. Skull size was larger in polar bears from Svalbard than from East Greenland (two-way ANOVA: p = 0.003). T-scores reflecting risk of osteoporosis showed that adult males from both East Greenland and Svalbard are at risk of developing osteopenia. Finally, when correcting for age and sex, BMD in East Greenland polar bears increased with increasing concentrations of persistent organic pollutants (POPs) i.e. ΣPCB (polychlorinated biphenyls), ΣHCH (hexachlorohexane), HCB (hexachlorobenzene) and ΣPBDE (polybrominated diphenyl ethers) while skull size increased with ΣHCH concentrations all in the period 1999–2014 (multiple linear regression: all p < 0.05, n = 175). The results suggest that environmental changes over time, including exposure to POPs, may affect bone density and size of polar bears.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women

Highlights: • The 5 year longitudinal trend in POP levels in an elderly cohort was evaluated. • Significant decreases in plasma levels of 18 POPs was observed. • A larger decline in plasma levels observed in elderly men versus elderly women. • Those who lost more weight showed a smaller decline in POP plasma concentrations. • Those with larger increases in plasma lipids showed a smaller decline in POP levels. Prospective cohort studies evaluating the temporal trends of background-level persistent organic pollutants (POPs) and their potential negative health effects in humans are needed.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2018

Effects of biometrics, location and persistent organic pollutants on blood clinical-chemical parameters in polar bears (Ursus maritimus) from Svalbard, Norway

Highlights: • BCCPs in polar bears may be affected by sex, age, biometrics, lipids and location. • POPs were correlated with HCT and HDL in females, and HCT, GGT, ASAT and CHOL in males. • POPs related biological effects on liver and kidney BCCP values were suggested. • HCT may be used as a simple cost-efficient biomarker of POP exposure in polar bears. • POPs effects on HDL and CHOL may indicate increased risk of cardiovascular disease in polar bears. In the present study, blood clinical-chemical parameters (BCCPs) were analysed in 20 female and 18 male Svalbard polar bears (Ursus maritimus) captured in spring 2007. The aim was to study how age, body condition (BC), biometrics, plasma lipid content and geographical location may confound the relationship between persistent organic pollutants (POPs) including PCBs, HCB, chlordanes, DDTs, HCHs, mirex and OH-PCBs and the concentrations of 12 specific BCCPs (hematocrit [HCT], hemoglobin [HB], aspartate aminotransferase [ASAT], alanine aminotransferase [ALAT], γ-glutamyltransferase [GGT], creatine kinase [CK], triglycerides [TG], cholesterol [CHOL], high-density lipoprotein [HDL], creatinine (CREA], urea, potassium (K]), and to investigate if any of these BCCPs may be applied as potential biomarkers for POP exposure in polar bears. Initial PCA and O-PLS modelling showed that age, lipids, BC and geographical location (longitude and latitude) were important parameters explaining BCCPs in females. Following subsequent partial correlation analyses correcting for age and lipids, multiple POPs in females were still significantly correlated with HCT and HDL (all p < 0.05). In males, age, BM, BC and longitude were important parameters explaining BCCPs. Following partial correlation analyses correcting for age, biometrics, lipids and longitude in males, multiple POPs were significantly correlated with HCT, ASAT, GGT and CHOL (all p < 0.05). In conclusion, several confounding parameters has to be taken into account when studying the relations between BCCPs and POPs in polar bears. When correcting for these, in particular HCT may be used as a simple cost-efficient biomarker of POP exposure in polar bears. Furthermore, decreasing HDL concentrations and increasing CHOL concentration with increasing POP concentrations may indicate responses related to increased risk of cardiovascular disease. We therefore suggest to further study POP exposure and lipidome response to increase knowledge of the risk of cardiometabolic syndrome in polar bears.

54 ENVIRONMENTAL SCIENCES↗