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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 901 records · Page 50
All sourcesNASA NTRSDOE OSTI
DOE OSTI2018

Apolipoprotein E plays crucial roles in maintaining bone mass by promoting osteoblast differentiation via ERK1/2 pathway and by suppressing osteoclast differentiation via c-Fos, NFATc1, and NF-κB pathway

Highlights: • Aged ApoE-KO mice exhibit severe osteoporosis compared to WT mice. • ApoE promotes osteoblastogenesis via ERK1/2 pathway. • ApoE inhibits osteoclastogenesis via c-Fos, NFATc1 and NF-κB pathways. Apolipoprotein E (ApoE) plays crucial roles not only in lipid metabolism but also in bone metabolism. Specifically ApoE4, one of major ApoE isoforms, has been demonstrated to be associated with increased risk of developing osteoporosis compared to another major isoform ApoE3. However, the detailed mechanism of how the different ApoE isoforms affect bone metabolism remains unclear. Micro-CT analyses of distal femora demonstrated severely decreased bone mass in 48-week-old female homozygous ApoE-knockout (ApoE-KO) mice compared to age- and gender-matched wild type C57BL/6 J (WT) mice. Physiological levels of either ApoE3 or ApoE4 protein (1–20 μg/ml) significantly increased the expression of osteoblast-related genes and alkaline phosphatase (ALP) activity of primary calvarial osteoblasts by inhibiting extracellular signal-regulated kinase 1/2 (ERK1/2) pathway in a dose-dependent manner, and ApoE3 showed greater osteoblastic induction compared to ApoE4. Furthermore, both ApoE3 and ApoE4 protein inhibited osteoclastogenesis and the expression of osteoclast-related genes of mouse bone marrow derived macrophages (BMDM) via down regulation of c-Fos, nuclear factor of activated T-cells 1 (NFATc1) and nuclear factor-kappa B (NF-κB) pathway. Moreover, ApoE3 showed greater inhibition of c-Fos, dendritic cell-specific transmembrane protein (DC-STAMP), and Cathepsin K gene expression compared to ApoE4. Collectively, ApoE plays crucial roles in preserving bone mass, suggesting that targeting ApoE and its isoforms as a promising treatment candidate of both osteoporosis and hyperlipidemia.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Dietary omega-3 and -6 fatty acids affect the expression of prostaglandin E2 synthesis enzymes and receptors in mice uteri during the window of pre-implantation

Highlights: • Dietary omega-3 and -6 could affect uterine expression of PGE pathway especially mPGES and EP2 during pre-implantation period. • Uterine expression of mPGES and EP2 on the day of implantation has a positive correlation with implantation rate. • One of the important mechanisms of PUFA in affecting female pregnancy is through mPGES and EP2. Considering possible effects of poly-unsaturated fatty acids (PUFA) on embryo implantation more likely through PGs, we investigated effects of dietary omega-3 and -6 PUFA on prostaglandin E2 (PGE2) signaling in mice uterus during pre-implantation period. The mRNA expressions of microsomal- and cytosolic- PGE synthase (mPGES and cPGES) and protein expressions of PGE receptor 2 and 4 (EP2 and EP4) were evaluated in uterus tissues of control as well as omega 3 and omega 6 received mice at days 1–5 of pregnancy. Expression of cPGES gene was not significantly different between groups but the mPGES expression on days 4 and 5 of pregnancy in supplemented groups was higher than controls. Omega-3 significantly decreased EP2 levels on days 3 and 4, while omega-6 caused an increase on days 3–5 of pregnancy. The levels of EP4 were significantly higher in the omega-6 group than other groups on days 4 and 5 of pregnancy. Also the implantation rate was higher in omega -6 compared to omega-3 group (p = 0.006). Moreover, there were significant correlations between implantation rate with expression levels of mPGES and EP2. Our results showed negative and positive effects of respectively dietary omega-3 and -6 PUFA on PGE2 signaling and implantation rate.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

4-Hydroxybenzoic acid (4-HBA) enhances the sensitivity of human breast cancer cells to adriamycin as a specific HDAC6 inhibitor by promoting HIPK2/p53 pathway

Highlights: • 4-Hydroxybenzoic acid enhances the sensitivity of MCF-7/ADM to ADM-induced apoptosis. • 4-Hydroxybenzoic acid induces apoptosis in breast cancer cell lines. • 4-Hydroxybenzoic acid induces cell cycle arrest in G2/M phase. Breast cancer is reported a very complex disease along with heterogeneous morphological characteristics and unrelated clinical behavior, and is a leading cancer among female. Nevertheless, chemo-resistance is frequently observed. Adriamycin (ADM) is a always employed drug to treat clinical breast cancer. However, strong resistance to ADM limited its clinical efficacy. Deregulation of HDAC6 activity is linked to various diseases including cancer resulting in accumulating interest for developing HDAC6 inhibitors. In the present study, for the first time, we found that 4-Hydroxybenzoic acid (4-HBA), as histone deacetylase 6 (HDAC6) inhibitor, could successfully reverse ADM resistance in human breast cancer cells. 4-HBA significantly promoted the anticancer effect of ADM on apoptosis induction, as evidenced by the increased expressions of Caspase-3 and PARP cleavage, which was associated with the promotion p53 and homeodomain interacting protein kinase-2 (HIPK2) expressions in ADM-resistant breast cancer cells. Furthermore, the suppressive effect of ADM on drug-resistant breast cancer cells was accelerated by 4-HBA through increasing the number of cells distributed in G2/M phase of cell cycle arrest. Inhibiting HIPK2/p53 pathway could abolish 4-HBA/ADM co-treatment-induced apoptosis and G2/M cell cycle arrest. Importantly, HDAC6 expressions were also significantly down-regulated in ADM-resistance breast cancer cells co-treated with ADM and 4-HBA. Additionally, 4-HBA clearly potentiated the anticancer role of ADM in the MCF-7 breast cancer animal model with low toxicity. Therefore, 4-HBA could be applied as an effective HDAC6 inhibitor to reverse human breast cancer resistance. Herein, the 4-HBA and ADM combination might represent as a useful therapeutic strategy to prevent human breast cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Assessment of the subcutaneous degradation process of insoluble hyaluronic acid in rats

Highlights: • Assessment of the subcutaneous degradation process of insoluble hyaluronic acid. • The speed of degradation of in vivo insoluble hyaluronic acid membranes varies depending on their swelling rate. • The process of degradation of insoluble hyaluronic acid in the subcutaneous over time was elucidated. Insoluble hyaluronic acid (IHA) may prevent adhesions by forming a physical barrier during the period when postoperative adhesions form. This study was performed to verify the changes that a solid IHA membrane undergoes as it is degraded in vivo, and to ascertain the swelling rate of IHA required for it to function as a physical barrier during the postoperative adhesion formation period. Nine female WI rats weighing 300–400 g were used. Discs 8 mm in diameter were cut out of dry IHA membranes made of IHA with a swelling rate (wet weight/dry weight) of either 2.47 (high-swelling IHA) or 1.94 (low-swelling IHA). They were placed in saline to swell and then washed with saline before subcutaneous implantation in four pockets in each rat. The high-swelling IHA started to degrade more rapidly than the low-swelling IHA. There was no evidence of degradation of the low-swelling IHA until day 7, but once it had started, the speed of degradation tended to be similar to that of the high-swelling IHA. The present results showed that, when IHA is implanted subcutaneously in rats, it is degraded over time in a phased process. The swelling rate required for the use of IHA as a postoperative adhesion barrier was also suggested.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Correlation of spatio-temporal characteristics of intestinal inflammation with IL-17 in a rat model of hypoganglionosis

Highlights: • Concomitant expression of C-RP, TNF-, and IL-17 in HD-like animal model induced by benzalkonium chloride. • Their expression maintained the highest level at Day 21. • IL-17 may be involved in spatio-temporal inflammation. Interleukin 17 expression is increased in children with Hirschsprung disease, which is characterized by intestinal inflammation. This study designed to exploit the characteristics of intestinal inflammation and examine the correlation of interleukin 17 in this process of hypoganglionosis model established by benzalkonium chloride treatment. Colon sections from female rats were treated with benzalkonium chloride to induce hypoganglionosis or with saline alone as a sham control. C-reactive protein and tumor necrosis factor- were used as markers of inflammation. Expression of C-reactive protein, tumor necrosis factor-, and interleukin 17 was assessed in colon tissue and blood serum on days 7, 14 and 21 after treatment. The correlation between C-reactive protein, tumor necrosis factor-, and interleukin 17 expression was estimated using the Spearman's rank-correlation coefficient. C-reactive protein, tumor necrosis factor-, and interleukin 17 were strongly expressed in submucosa and mucosa layers and serum from treated animals. The expression of C-reactive protein, tumor necrosis factor-, and interleukin 17 maintained the highest level at Day 21. Only C-reactive protein and tumor necrosis factor- expression was increased in control animals and only on day 7. Spearman's rank correlation coefficient was significant in C-reactive protein, tumor necrosis factor-, and interleukin 17 at Day 7, 14 and 21. Concomitant upregulation of C-reactive protein, tumor necrosis factor-, and interleukin 17 and significant positive correlations between C-reactive protein, tumor necrosis factor-, and interleukin 17 may imply that interleukin 17 is involved in spatio-temporal inflammation induced by benzalkonium chloride.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

MFAP5 suppression inhibits migration/invasion, regulates cell cycle and induces apoptosis via promoting ROS production in cervical cancer

Highlights: • Suppression of MFAP5 reduces migration/invasion, regulates cell cycle and induces apoptosis in cervical cancer cells. • Inhibition of MFAP5 promotes ROS generation to prevent cervical cancer progression in vitro. • MFAP5 down-regulation inhibits cervical cancer growth in vivo. Cervical cancer is one of the most lethal types of cancer among female. Microfibrillar-associated protein 5 (MFAP5) is an extracellular matrix (ECM) glycoprotein, and is confirmed to be involved in cell signaling during microfibril assembly, elastinogenesis and cell survival. However, the role of MFAP5 in cervical cancer development and progression remains poorly understood. In the study, MFAP5 was over-expressed in human cervical cancers, and in different cervical cancer cell lines. Patients suffering from cervical cancer with low MFAP5 expression exhibited better survival rate. Suppressing MFAP5 in cervical cancer cells markedly reduced the cell proliferation, migration and invasion by modulating epithelial-mesenchymal transition (EMT)-related signaling pathway. In addition, MFAP5 knockdown induced large number of cells distributed in G2/M phase, along with reduced Cyclin B1, Cyclin D1 and cyclin-dependent kinase 4 (CDK4) expressions, and enhanced p21 and p53 levels. Moreover, apoptosis was highly induced by MFAP5 silence through reducing Bcl-xl and Bcl-2 expressions, and promoting Bax, cleaved Caspase-3 and poly (ADP-Ribose) polymerase (PARP) expressions in cervical cancer cells. Reactive oxygen species (ROS) production levels were also higher in MFAP5-knockdown cells, along with Jun-N-terminal kinase (JNK) activation. Importantly, we found that MFAP5 knockdown-inhibited cervical cancer cell growth was dependent on ROS production. Finally, the depletion of MFAP5 prevented cervical cancer progression in vivo. In summary, our study identified a critical role played by MFAP5 in the progression of cervical cancer and the potential mechanisms by which exerted its effects, indicating that targeting MFAP5-related pathways could be conducive to the therapies for cervical cancer.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Osteocytic oxygen sensing: Distinct impacts of VHL and HIF-2alpha on bone integrity

Skeletal fracture resistance emerges from multiple components of bone structure like microarchitecture, matrix mineralization, and organization. These characteristics are engendered via mechanisms like the hypoxia-inducible factors (HIF) pathway, involving two paralogs, HIF-1α and HIF-2α. Under normoxia, HIF-α is targeted for degradation via von-Hippel Lindau (VHL); hypoxia enables HIF-α stabilization and induction of target genes. We previously showed that osteocytic Vhl deletion or expression of degradation-resistant HIF-2α cDR female mice each produced high bone mass, whereas degradation-resistant osteocytic HIF-1α produced no overt phenotype. We report within that Vhl cKO increased bone strength, while HIF-2α cDR displayed markedly reduced bone strength below Cre-negative controls. This suggests that VHL and HIF-2α drive distinct responses that promote disparate effects on bone strength. Both Vhl deletion or HIF-2α accumulation generated two discrete bone morphologies: an outer lamellar cortex and a woven, poorly mineralized endocortex that imparted dramatically different functional outcomes. Our studies reveal novel influence of osteocytic HIF-2α signaling on collagen matrix organization, mineralization, and bone strength.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Effect of bisphosphonate treatment on the oim mouse middle ear ossicles' structure, composition and hearing

Hearing loss is common in people with osteogenesis imperfecta (OI or brittle bone disease). Bisphosphonates are commonly used to treat long bone fragility in children with OI. However, its impact on the bone quality of the middle ear ossicles and hearing remains unknown. This study determines whether bisphosphonates treatment itself may contribute to hearing loss in OI by evaluating its effects in the oim/oim mouse model of severe OI having normal auditory function. Specifically, this study reports the effects of alendronate (ALN), a nitrogen-containing bisphosphonate, on ossicle morphology, porosity, and elemental composition in 14-week-old oim/oim mice treated weekly, starting at 2 weeks of age. The ossicles were examined using synchrotron microtomography and X-ray fluorescence microscopy (XFM). Hearing was assessed longitudinally until 26 weeks of age by determining auditory brainstem response (ABR) thresholds in another group of mice also treated weekly starting at 2 weeks of age. ALN treatment further reduces in size the already small oim/oim ossicles, specifically in female mice. Porosity, bone composition, and hearing function, however, were generally not affected by the ALN treatment. Furthermore, ALN does not prevent joint fusions, excessive bone formations, or enlarged joint spaces in WT or oim/oim experimental groups. One ALN-treated oim/oim mouse with a bone formation in the interior of the footplate, and one ALN-treated WT mouse with a fixed footplate had frequency-specific hearing loss. Since footplate abnormalities are not observed in PBS-treated mice in this study, it remains unclear whether ALN fails to prevent these changes or contributes to their development. Future studies should investigate the mechanisms of ossicular abnormalities and bisphosphonates modulatory role in the ossicles.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Intersecting heuristic adaptive strategies, building design and energy saving intentions when facing discomfort environment: A cross-country analysis

Occupants' adaptive strategies play an important role in the energy consumption of office buildings. Previous research has mostly focused on the adaptive strategies triggered by occupants' indoor discomfort; however, it is crucial to understand if specific adaptive strategies are linked to occupants' energy-saving intentions. This study explores the relationships among employees’ heuristic decision-making in their first choice of adaptive strategies (technological solutions or personal adjustments) when facing extreme discomfort conditions, and their energy-saving intentions, then links these patterns with building design, workplace contextual factors, and demographics. A cross-sectional survey was collected among university employees from China, Brazil, Italy, Poland, Switzerland, and the US. Our results demonstrated that the accessibility to indoor environmental controls (IECs) and office type are the significant factors for adaptive strategies. There was a positive relationship between the number of IEC features and the percentage of employees choosing a technological solution. When feeling too hot, occupants in private offices are more likely to adopt a technological solution, whereas occupants in cubicles are more likely to choose a personal adjustment. Occupants with energy-saving intentions are less likely to choose thermostat adjustments or use portable devices as adaptive strategies than their counterparts. Lastly, the cluster analysis suggests females were more likely to use adaptive strategies for energy-saving purposes than males. The majority of occupants would turn on/off lighting to save energy. The study provides the contributions in the connection between the heuristic decision-making process and energy-saving intentions and recommendations on design strategies for building architects, engineers, and managers.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2024

Visual feedback and guided balance training in an immersive virtual reality environment for lower extremity rehabilitation

Balance training is essential for physical rehabilitation procedures, as it can improve functional mobility and enhance cognitive coordination. However, conventional balance training methods may have limitations in terms of motivation, real-time objective feedback, and personalization, which a virtual reality (VR) setup may provide a better alternative. In this work, we present an immersive VR training environment for lower extremity balance rehabilitation with real-time guidance and feedback. The VR training environment immerses the user in a 3D ice rink model where a virtual coach (agent) leads them through a series of balance poses, and the user controls a trainee avatar with their own movements. Here we developed two coaching styles: positive-reinforcement and autonomous-supportive, and two viewpoints of the trainee avatar: first-person and third-person. The proposed environment was evaluated in a user study with healthy, non-clinical participants (n = 16, 24.4 ± 5.7 years old, 9 females). Our results show that participants showed stronger performance in the positive-reinforcement style compared to the autonomous-supportive style. Additionally, in the third-person viewpoint, the participants exhibited more stability in the positive-reinforcement style compared to the autonomous-supportive style. For viewpoint, participants exhibited stronger performance in the first-person viewpoint compared to third-person in the autonomous-supportive style, while they were comparable in the positive-reinforcement style. We observed no significant effects on the foot height and number of mistakes. Furthermore, we report the analysis of user performance with balance training poses and subjective measures based on questionnaires to assess the user experience, usability, and task load. The proposed VR balance training could offer an interactive, adaptive, and engaging environment and open new potential research directions for lower extremity rehabilitation.

97 MATHEMATICS AND COMPUTING↗
DOE OSTI2022

Tea consumption and risk of bladder cancer in the Bladder Cancer Epidemiology and Nutritional Determinants (BLEND) Study: Pooled analysis of 12 international cohort studies

Tea has been shown to be associated with reduced risk of several diseases including cardiovascular diseases, stroke, metabolic syndrome, and obesity. However, the results on the relationship between tea consumption and bladder cancer are conflicting. This research aimed to assess the association between tea consumption and risk of bladder cancer using a pooled analysis of prospective cohort data. Individual data from 532,949 participants in 12 cohort studies, were pooled for analyses. Cox regression models stratified by study centre was used to estimate hazard ratios (HR) and corresponding 95% CIs. Fractional polynomial regression models were used to examine the dose–response relationship. A higher level of tea consumption was associated with lower risk of bladder cancer incidence (compared with no tea consumption: HR = 0.87, 95% C.I. = 0.77–0.98 for low consumption; HR = 0.86, 95% C.I. = 0.77–0.96 for moderate consumption; HR = 0.84, 95% C.I. = 0.75–0.95 for high consumption). When stratified by sex and smoking status, this reduced risk was statistically significant among men and current and former smokers. In addition, dose–response analyses showed a lower bladder cancer risk with increment of 100 ml of tea consumption per day (HR-increment = 0.97; 95% CI = 0.96–0.98). A similar inverse association was found among males, current and former smokers while never smokers and females showed non-significant results, suggesting potential sex-dependent effect. Higher consumption of tea is associated with reduced risk of bladder cancer with potential interaction with sex and smoking status. Further studies are needed to clarify the mechanisms for a protective effect of tea (e.g. inhibition of the survival and proliferation of cancer cells and anti-inflammatory mechanisms) and its interaction with smoking and sex.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2019

Estimation of cerebral blood flow velocity during breath-hold challenge using artificial neural networks

The effect of untreated Obstructive Sleep Apnoea (OSA) on cerebral haemodynamics and CA impairment is an active field of research interest. A breath-hold challenge is usually used in clinical and research settings to simulate cardiovascular and cerebrovascular changes that mimic OSA events. This work utilises temporal arterial oxygen saturation (SpO 2 ) and photoplethysmography (PPG) signals to estimate the temporal cerebral blood flow velocity (CBFv) waveform. Measurements of CBFv, SpO 2 , and PPG, were acquired concurrently from volunteers performing two different protocols of breath-hold challenge in the supine position. Past values of the SpO 2 and PPG signals were used to estimate the current values of CBFv using different permutations and topologies of supervised learning with shallow artificial neural networks (ANNs). Measurements from one protocol were used to train the ANNs and find the optimum topologies, which in turn were tested using the other protocol. Data collected from 10 normotensive, healthy subjects (four females, age 28.5 ± 6.1 years, Body Mass Index (BMI) 24.0 ± 4.7 kg/m 2 ) were used in this study. The results show that different subjects have different optimum topologies for ANNs, thus indicating the effects of inter-subject variability on ANNs. Successfully reconstructed blind waveforms for the same subject group in the second protocol showed a reasonable accuracy of 60–80% estimation compared to the measured waveforms.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Prenatal exposure to mixtures of persistent endocrine disrupting chemicals and postnatal body size in British girls

Endocrine disrupting chemical (EDC) exposure is ubiquitous. EDC exposure during critical windows of development may interfere with the body's endocrine system, affecting growth. Previous human studies have examined one EDC at a time in relation to infant growth. By studying mixtures, the human experience can be better approximated. We investigated the association of prenatal exposure to persistent EDCs (per- and polyfluoroalkyl substances (PFAS), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs)) as mixtures with postnatal body size among female offspring. We used a sub-sample of the Avon Longitudinal Study of Parents and Children (N = 425), based in the United Kingdom. We quantified 52 EDCs in maternal serum collected during pregnancy. We used Bayesian kernel machine regression with a random intercept to examine the association of prenatal concentrations of EDC mixtures with longitudinal postnatal body size measures for each EDC class separately (PFAS, PCBs, and OCPs) and for all three classes combined. Weight and height measures at 0, 2, 9, and 19 months were obtained by health professionals as part of routine child health surveillance. The mixture representing all three classes combined (31 chemicals) (n = 301) was inversely associated with postnatal body size. Holding all EDCs in the 31-chemical mixture at the 75th percentile compared to the 50th percentile was associated with 0.15 lower weight-for-age z-score (95% credible interval –0.26, –0.03). Weak inverse associations were also seen for height-for-age and body mass index-for-age scores. Furthermore, these results suggest that prenatal exposure to mixtures of persistent EDCs may affect postnatal body size.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Genetic variations and their interaction with thirdhand smoke exposure on anxiety and memory in Collaborative Cross mice

Thirdhand smoke (THS) is linked to adverse health effects, but the effect of genetic variations on behavioral outcomes is poorly understood. To investigate this, we assessed anxiety- and memory-related behaviors in 820 mice from 21 strains of the genetically diverse Collaborative Cross (CC) mouse that were exposed to THS from 4 through 10 weeks of age. Anxiety was evaluated with a light/dark box assay with a previously established risk score system. Females were generally more sensitive: THS reduced anxiety risk in strains CC013, CC019, and CC051, but increased risk in CC036 and CC061, while males showed no significant effects. Memory was tested using passive avoidance: impairments were observed in both sexes in CC016 and CC019, with sex-dependent effects in CC002 and CC051. A genome-wide association study identified 2,347 SNPs associated with anxiety and 1,568 SNPs with memory, with 32 and 85 SNPs, respectively, interacting with THS exposure. Enrichment analyses revealed distinct biological processes underlying susceptibility, including axonogenesis, synapse organization, cognition, and learning and memory. KEGG pathway analysis identified distinct genetic pathways, including GTPase binding and GTPase regulatory activity, that act as critical molecular switches in the brain that regulate synaptic plasticity, dendritic spine structure, and neuronal signaling, directly influencing anxiety-like behaviors and memory formation. These findings show that THS exposure affects neurobehavioral outcomes in a sex- and genotype-dependent manner, highlighting critical gene-environment interactions and providing a foundation for mechanistic insights into THS neurotoxicity

Anxiety↗
DOE OSTI2020

The direct and indirect effects of copper on vector-borne disease dynamics

Metal pollution is a growing concern that affects the health of humans and animals globally. Copper is an essential insect micronutrient required for respiration, pigmentation and oxidative stress protection but can also act as a potentially toxic trace element. While several studies have focused on the negative fitness effects of copper on the aquatic larvae of mosquitoes, the effects of larval copper exposure on adult mosquito fitness (i.e., survival and fecundity) and their ability to transmit parasites (i.e., vector competence) remains unclear. Here, using a well-studied model vector-parasite system, the mosquito Aedes aegypti and parasite Dirofilaria immitis, we show that sublethal copper exposure in larval mosquitoes alters adult female fecundity and vector competence. Specifically, mosquitoes exposed to copper had a hormetic fecundity response and mosquitoes exposed to 600 μg/L of copper had significantly fewer infective parasite larvae than control mosquitoes not exposed to copper. Therefore, exposure of mosquito larvae to copper levels far below EPA-mandated safe drinking water limits (1300 μg/L) can impact vector-borne disease dynamics not only by reducing mosquito abundance (through increased larval mortality), but also by reducing parasite transmission risk. Our results also demonstrated that larval copper is retained through metamorphosis to adulthood in mosquitoes, indicating that these insects could transfer copper from aquatic to terrestrial foodwebs, especially in urban areas where they are abundant. To our knowledge this is the first study to directly link metal exposure with vector competence (i.e., ability to transmit parasites) in any vector-parasite system. Additionally, it also demonstrates unequivocally that mosquitoes can transfer contaminants from aquatic to terrestrial ecosystems. These results have broad implications for public health because they directly linking contaminants and vector-borne disease dynamics, as well as linking mosquitoes and contaminant dynamics.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2013

Exposure to pyrethroids insecticides and serum levels of thyroid-related measures in pregnant women

Possible association between environmental exposure to pyrethroid insecticides and serum thyroid-related measures was explored in 231 pregnant women of 10–12 gestational weeks recruited at a university hospital in Tokyo during 2009–2011. Serum levels of free thyroxine (fT4), thyroid stimulating hormone (TSH) and thyroid biding globulin (TBG) and urinary pyrethroid insecticide metabolite (3-phenoxybenzoic acid, 3-PBA) were measured. Obstetrical information was obtained from medical records and dietary and lifestyle information was collected by self-administered questionnaire. Geometric mean concentration of creatinine-adjusted urinary 3-PBA was 0.363 (geometric standard deviation: 3.06) μg/g cre, which was consistent with the previously reported levels for non-exposed Japanese adult females. The range of serum fT4, TSH and TBG level was 0.83–3.41 ng/dL, 0.01–27.4 μIU/mL and 16.4–54.4 μg/mL, respectively. Multiple regression analysis was carried out by using either one of serum levels of thyroid-related measures as a dependent variable and urinary 3-PBA as well as other potential covariates (age, pre-pregnancy BMI, parity, urinary iodine, smoking and drinking status) as independent variables: 3-PBA was not found as a significant predictor of serum level of thyroid-related measures. Lack of association may be due to lower pyrethroid insecticide exposure level of the present subjects. Taking the ability of pyrethroid insecticides and their metabolite to bind to nuclear thyroid hormone (TH) receptor, as well as their ability of placental transfer, into consideration, it is warranted to investigate if pyrethroid pesticides do not have any effect on TH actions in fetus brain even though maternal circulating TH level is not affected. -- Highlights: • Pyrethroid exposure and thyroid hormone status was examined in pregnant women. • Urinary 3-phenoxybenzoic acid was used as a biomarker of exposure. • Iodine nutrition, age and other covariates were included in statistical models. • No association was found between levels of thyroid hormone and pyrethroid exposure. • The result may be ascribed to lower exposure level.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Passive exposures of children to volatile trihalomethanes during domestic cleaning activities of their parents

Domestic cleaning has been proposed as a determinant of trihalomethanes (THMs) exposure in adult females. We hypothesized that parental housekeeping activities could influence children's passive exposures to THMs from their mere physical presence during domestic cleaning. In a recent cross-sectional study (n=382) in Cyprus [41 children (<18y) and 341 adults (≥18y)], we identified 29 children who met the study's inclusion criteria. Linear regression models were applied to understand the association between children sociodemographic variables, their individual practices influencing ingestion and noningestion exposures to ΣTHMs, and their urinary THMs levels. Among the children-specific variables, age alone showed a statistically significant inverse association with their creatinine-adjusted urinary ΣTHMs (r{sub S}=−0.59, p<0.001). A positive correlation was observed between urinary ΣTHMs (ng g{sup −1}) of children and matched-mothers (r{sub S}=0.52, p=0.014), but this was not the case for their matched-fathers (r{sub S}=0.39, p=0.112). Time spent daily by the matched-mothers for domestic mopping, toilet and other cleaning activities using chlorine-based cleaning products was associated with their children's urinary THMs levels (r{sub S}=0.56, p=0.007). This trend was not observed between children and their matched-fathers urinary ΣTHMs levels, because of minimum amount of time spent by the latter in performing domestic cleaning. The proportion of variance of creatinine-unadjusted and adjusted urinary ΣTHMs levels in children that was explained by the matched-mothers covariates was 76% and 74% (p<0.001), respectively. A physiologically-based pharmacokinetic model adequately predicted urinary chloroform excretion estimates, being consistent with the corresponding measured levels. Our findings highlighted the influence of mothers' domestic cleaning activities towards enhancing passive THMs exposures of their children. The duration of such activities could be further tested as a valid indicator of children's THMs body burden. - Highlights: • First report on THMs exposure assessment in matched parents and children. • Duration of domestic cleaning by mothers influenced passive exposure to THMs in children. • Matched-fathers did little cleaning and thereby no contribution to passive exposure to THMs in children. • Reverse dosimetry showed a good agreement between predicted and observed urinary chloroform. • Passive exposures to THMs require new attention in survey questionnaires and epidemiology.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2015

Human exposure to trace elements through the skin by direct contact with clothing: Risk assessment

Metals in textile products and clothing are used for many purposes, such as metal complex dyes, pigments, mordant, catalyst in synthetic fabrics manufacture, synergists of flame retardants, antimicrobials, or as water repellents and odour-preventive agents. When present in textile materials, heavy metals may mean a potential danger to human health. In the present study, the concentrations of a number of elements (Al, As, B, Ba, Be, Bi, Cd, Co, Cr, Cu, Fe, Hg, Mg, Mn, Mo, Ni, Pb, Sb, Sc, Se, Sm, Sn, Sr, Tl, V, and Zn) were determined in skin-contact clothes. Analysed clothes were made of different materials, colours, and brands. Interestingly, we found high levels of Cr in polyamide dark clothes (605 mg/kg), high Sb concentrations in polyester clothes (141 mg/kg), and great Cu levels in some green cotton fabrics (around 280 mg/kg). Dermal contact exposure and human health risks for adult males, adult females, and for <1-year-old children were assessed. Non-carcinogenic and carcinogenic risks were below safe (HQ<1) and acceptable (<10{sup −6}) limits, respectively, according to international standards. However, for Sb, non-carcinogenic risk was above 10% of the safety limit (HQ>0.1) for dermal contact with clothes. - Highlights: • We determined in skin-contact clothes the concentrations of a number of metals. • Dermal contact exposure and health risks for adults and for 1-year-old children were assessed. • Carcinogenic risks were considered as acceptable (<10{sup −6}). • For non-carcinogenic risks, only Sb exceeded a 10% of the HQ for dermal contact with clothes.

54 ENVIRONMENTAL SCIENCES↗