Customized Corneal Cross-Linking-A Mathematical Model.

PubMed

Caruso, Ciro; Epstein, Robert L; Ostacolo, Carmine; Pacente, Luigi; Troisi, Salvatore; Barbaro, Gaetano

2017-05-01

To improve the safety, reproducibility, and depth of effect of corneal cross-linking with the ultraviolet A (UV-A) exposure time and fluence customized according to the corneal thickness. Twelve human corneas were used for the experimental protocol. They were soaked using a transepithelial (EPI-ON) technique using riboflavin with the permeation enhancer vitamin E-tocopheryl polyethylene glycol succinate. The corneas were then placed on microscope slides and irradiated at 3 mW/cm for 30 minutes. The UV-A output parameters were measured to build a new equation describing the time-dependent loss of endothelial protection induced by riboflavin during cross-linking, as well as a pachymetry-dependent and exposure time-dependent prescription for input UV-A fluence. The proposed equation was used to establish graphs prescribing the maximum UV-A fluence input versus exposure time that always maintains corneal endothelium exposure below toxicity limits. Analysis modifying the Lambert-Beer law for riboflavin oxidation leads to graphs of the maximum safe level of UV-A radiation fluence versus the time applied and thickness of the treated cornea. These graphs prescribe UV-A fluence levels below 1.8 mW/cm for corneas of thickness 540 μm down to 1.2 mW/cm for corneas of thickness 350 μm. Irradiation times are typically below 15 minutes. The experimental and mathematical analyses establish the basis for graphs that prescribe maximum safe fluence and UV-A exposure time for corneas of different thicknesses. Because this clinically tested protocol specifies a corneal surface clear of shielding riboflavin on the corneal surface during UV-A irradiation, it allows for shorter UV-A irradiation time and lower fluence than in the Dresden protocol.

Electrical Field Dependence of Protein Conformation and Channel Function in Lipid Membranes of Different Compositions

DTIC Science & Technology

1989-07-01

surface because of the previous potential sweeps ). c- Cyclic voltamograms after different exposure times of the Hg drop electrode to a solution of lpg/ml...Cd + and 10-M NaCl. b - Cyclic voltamograms under similar conditions. Exposure time indicated, sweep rate O.2V/sec. specific capacitance < 4pf/cm 2...alamethicin. Cyclic voltametry shows (Fig. 3b) that it is the reduction current depending on the transport of TI+ ions across the monolayer to the electrode

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. Inmore » all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.« less

An Assessment of Potential Exposure and Risk from Estrogens in Drinking Water

PubMed Central

Caldwell, Daniel J.; Mastrocco, Frank; Nowak, Edward; Johnston, James; Yekel, Harry; Pfeiffer, Danielle; Hoyt, Marilyn; DuPlessie, Beth M.; Anderson, Paul D.

2010-01-01

Background Detection of estrogens in the environment has raised concerns in recent years because of their potential to affect both wildlife and humans. Objectives We compared exposures to prescribed and naturally occurring estrogens in drinking water to exposures to naturally occurring background levels of estrogens in the diet of children and adults and to four independently derived acceptable daily intakes (ADIs) to determine whether drinking water intakes are larger or smaller than dietary intake or ADIs. Methods We used the Pharmaceutical Assessment and Transport Evaluation (PhATE) model to predict concentrations of estrogens potentially present in drinking water. Predicted drinking water concentrations were combined with default water intake rates to estimate drinking water exposures. Predicted drinking water intakes were compared to dietary intakes and also to ADIs. We present comparisons for individual estrogens as well as combined estrogens. Results In the analysis we estimated that a child’s exposures to individual prescribed estrogens in drinking water are 730–480,000 times lower (depending upon estrogen type) than exposure to background levels of naturally occurring estrogens in milk. A child’s exposure to total estrogens in drinking water (prescribed and naturally occurring) is about 150 times lower than exposure from milk. Adult margins of exposure (MOEs) based on total dietary exposure are about 2 times smaller than those for children. Margins of safety (MOSs) for an adult’s exposure to total prescribed estrogens in drinking water vary from about 135 to > 17,000, depending on ADI. MOSs for exposure to total estrogens in drinking water are about 2 times lower than MOSs for prescribed estrogens. Depending on the ADI that is used, MOSs for young children range from 28 to 5,120 for total estrogens (including both prescribed and naturally occurring sources) in drinking water. Conclusions The consistently large MOEs and MOSs strongly suggest that prescribed and total estrogens that may potentially be present in drinking water in the United States are not causing adverse effects in U.S. residents, including sensitive subpopulations. PMID:20194073

Time dependency of strainrange partitioning life relationships

NASA Technical Reports Server (NTRS)

Kalluri, S.; Manson, S. S.

1984-01-01

The effect of exposure time (or creep rate) on the CP life relationship is established by conducting isothermal CP tests at varying exposure times on 316 Ss at 1300 and 1500 F. A reduction in the CP cycle life is observed with an increase in the exposure time of the CP test at a given inelastic strain-range. This phenomenon is characterized by modifying the Manson-Coffin type of CP relationship. Two new life relationships: (1) the Steady State Creep Rate (SSRC) Modified CP life relationship, and (2) the Failure Time (FT) Modified CP life relationship, are developed in this report. They account for the effect of creep rate and exposure time within the CP type of waveform. The reduction in CP cyclic life in the long exposure time tests is attributed to oxidation and the precipitation of carbides along the grain boundaries.

Parental Smoking Exposure and Adolescent Smoking Trajectories

PubMed Central

Gilman, Stephen E.; Rende, Richard; Luta, George; Tercyak, Kenneth P.; Niaura, Raymond S.

2014-01-01

OBJECTIVE: In a multigenerational study of smoking risk, the objective was to investigate the intergenerational transmission of smoking by examining if exposure to parental smoking and nicotine dependence predicts prospective smoking trajectories among adolescent offspring. METHODS: Adolescents (n = 406) ages 12 to 17 and a parent completed baseline interviews (2001–2004), and adolescents completed up to 2 follow-up interviews 1 and 5 years later. Baseline interviews gathered detailed information on parental smoking history, including timing and duration, current smoking, and nicotine dependence. Adolescent smoking and nicotine dependence were assessed at each time point. Latent Class Growth Analysis identified prospective smoking trajectory classes from adolescence into young adulthood. Logistic regression was used to examine relationships between parental smoking and adolescent smoking trajectories. RESULTS: Four adolescent smoking trajectory classes were identified: early regular smokers (6%), early experimenters (23%), late experimenters (41%), and nonsmokers (30%). Adolescents with parents who were nicotine-dependent smokers at baseline were more likely to be early regular smokers (odds ratio 1.18, 95% confidence interval 1.05–1.33) and early experimenters (odds ratio 1.04, 95% confidence interval 1.04–1.25) with each additional year of previous exposure to parental smoking. Parents’ current non-nicotine–dependent and former smoking were not associated with adolescent smoking trajectories. CONCLUSIONS: Exposure to parental nicotine dependence is a critical factor influencing intergenerational transmission of smoking. Adolescents with nicotine-dependent parents are susceptible to more intense smoking patterns and this risk increases with longer duration of exposure. Research is needed to optimize interventions to help nicotine-dependent parents quit smoking early in their children’s lifetime to reduce these risks. PMID:24819567

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence.

PubMed

Flynn, Padrig B; Busetti, Alessandro; Wielogorska, Ewa; Chevallier, Olivier P; Elliott, Christopher T; Laverty, Garry; Gorman, Sean P; Graham, William G; Gilmore, Brendan F

2016-05-31

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30-60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa.

Non-thermal Plasma Exposure Rapidly Attenuates Bacterial AHL-Dependent Quorum Sensing and Virulence

PubMed Central

Flynn, Padrig B.; Busetti, Alessandro; Wielogorska, Ewa; Chevallier, Olivier P.; Elliott, Christopher T.; Laverty, Garry; Gorman, Sean P.; Graham, William G.; Gilmore, Brendan F.

2016-01-01

The antimicrobial activity of atmospheric pressure non-thermal plasma has been exhaustively characterised, however elucidation of the interactions between biomolecules produced and utilised by bacteria and short plasma exposures are required for optimisation and clinical translation of cold plasma technology. This study characterizes the effects of non-thermal plasma exposure on acyl homoserine lactone (AHL)-dependent quorum sensing (QS). Plasma exposure of AHLs reduced the ability of such molecules to elicit a QS response in bacterial reporter strains in a dose-dependent manner. Short exposures (30–60 s) produce of a series of secondary compounds capable of eliciting a QS response, followed by the complete loss of AHL-dependent signalling following longer exposures. UPLC-MS analysis confirmed the time-dependent degradation of AHL molecules and their conversion into a series of by-products. FT-IR analysis of plasma-exposed AHLs highlighted the appearance of an OH group. In vivo assessment of the exposure of AHLs to plasma was examined using a standard in vivo model. Lettuce leaves injected with the rhlI/lasI mutant PAO-MW1 alongside plasma treated N-butyryl-homoserine lactone and n-(3-oxo-dodecanoyl)-homoserine lactone, exhibited marked attenuation of virulence. This study highlights the capacity of atmospheric pressure non-thermal plasma to modify and degrade AHL autoinducers thereby attenuating QS-dependent virulence in P. aeruginosa. PMID:27242335

Duration and Timing of Exposure to Neighborhood Poverty and the Risk of Adolescent Parenthood

PubMed Central

Wodtke, Geoffrey T.

2013-01-01

Theory suggests that the impact of neighborhood poverty depends on both the duration and timing of exposure. Previous research, however, does not properly analyze the sequence of neighborhoods to which children are exposed throughout the early life course. This study investigates the effects of different longitudinal patterns of exposure to disadvantaged neighborhoods on the risk of adolescent parenthood. It follows a cohort of children in the PSID from age 4 to 19 and uses novel methods for time-varying exposures that overcome critical limitations of conventional regression when selection processes are dynamic. Results indicate that sustained exposure to poor neighborhoods substantially increases the risk of becoming a teen parent and that exposure to neighborhood poverty during adolescence may be more consequential than exposure earlier during childhood. PMID:23720166

Stress response in rat brain after different durations of noise exposure.

PubMed

Samson, James; Sheeladevi, Rathinasamy; Ravindran, Rajan; Senthilvelan, Manohar

2007-01-01

The alteration in the levels of plasma corticosterone, brain norepinephrine (NE), and expression of brain heat shock proteins (Hsp70) after different durations of noise exposure (acute, 1 day; sub-acute, 15 days; chronic, 30 days) has been studied to analyze their role in combating time-dependent stress effects of noise. Broadband white noise (100dB) exposure to male Wistar albino rats significantly increased the levels of plasma corticosterone and NE in all three durations of noise exposure. The sustained increase observed in their levels in the chronic group suggests that animals are not getting adapted to noise even after 30 days of exposure. The important role of Hsp70 in combating noise induced stress is evident from the significant increase in its expression after chronic exposure, while there was a reciprocal decrease in the NE and corticosterone when compared with their levels after acute and sub-acute noise exposure. This clearly indicates that the time-dependent stress response to noise exposure is a complex mechanism involving highly interconnected systems such as hypothalamo-pituitary-adrenal (HPA) axis, heat shock proteins and may have serious implications in vital organs, particularly in the brain when there is a prolonged noise exposure.

Timing and Frequency of Sublethal Exposure Modifies the Induction and Retention of Increased Insecticide Tolerance in Wood Frogs (Lithobates sylvaticus).

PubMed

Jones, Devin K; Yates, Erika K; Mattes, Brian M; Hintz, William D; Schuler, Matthew S; Relyea, Rick A

2018-05-22

While the paradigm for increased tolerance to pesticides has been by selection on constitutive (naïve) traits, recent research has shown it can also occur through phenotypic plasticity. However, the time period in which induction can occur, the duration of induced tolerance, and the influence of multiple induction events remain unknown. We hypothesized that the induction of increased pesticide tolerance is limited to early sensitive periods, the magnitude of induced tolerance depends on the number of exposures, and the retention of induced tolerance depends on the time elapsed after an exposure and the number of exposures. To test these hypotheses, we exposed wood frog tadpoles to either a no-carbaryl control (water) or 0.5 mg/L carbaryl at four time periods, and later tested their tolerance to carbaryl using time-to-death assays. We discovered that tadpoles induced increased tolerance early and midway, but not late, in our experiment and their constitutive tolerance increased with age. We found no difference in the magnitude of induced tolerance following one or two exposures. Lastly, induced pesticide tolerance was reversed within 6 d, but was retained only when tadpoles experienced all four consecutive exposures. Phenotypic plasticity provides an immediate response for sensitive amphibian larvae to early pesticide exposures and reduces phenotypic mismatches in aquatic environments contaminated by agrochemicals. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Daytime Effect of Monochromatic Blue Light on EEG Activity Depends on Duration and Timing of Exposure in Young Men

PubMed Central

Iskra-Golec, Irena; Golonka, Krystyna; Wyczesany, Miroslaw; Smith, Lawrence; Siemiginowska, Patrycja; Wątroba, Joanna

2017-01-01

Growing evidence suggests an alerting effect of monochromatic blue light on brain activity. Little is known about the moderation of those effects by timing and duration of exposure. The present electroencephalography (EEG ) study examined such moderations on delta, theta, alpha1, alpha2, and beta EEG bands. A counterbalanced repeated-measures design was applied. The 16-hr daytime period was divided into three sessions: 07:00-12:20, 12:20-17:40, and 17:40-23:00 (timing of exposure). Two light conditions comparable in luminance but differing in wavelength were applied, namely polychromatic white light and monochromatic blue light (460 nm). There were two durations of exposure—the shorter one lasting 30 min and the longer one lasting 4 hrs. Thirty male students participated in the study. Four factors analyses of variance (ANOV As, for light conditions, timing of exposure, duration of exposure, and brain area) were performed on each EEG band. Results indicated an alerting effect of short exposure to monochromatic blue light at midday and in the evening, which was demonstrated by a decrease in lower frequency bands (alpha1, delta, and theta, respectively). Long exposure to blue light may have a reverse effect, especially in the morning and at midday, when increases in lower frequency bands (theta in the morning and theta and alpha1 at midday) were observed. It can be concluded that the daytime effect of monochromatic blue light on EEG activity depends on timing and duration of exposure. PMID:29062437

Balance between early life tolerance and sensitization in allergy: dependence on the timing and intensity of prenatal and postnatal allergen exposure of the mother.

PubMed

Fusaro, Ana Elisa; de Brito, Cyro Alves; Taniguchi, Eliana Futata; Muniz, Bruno Pacola; Victor, Jefferson Russo; Orii, Noemia Mie; Duarte, Alberto José da Silva; Sato, Maria Notomi

2009-09-01

Allergens can be maternally transferred to the fetus or neonate, though it is uncertain how this initial allergen exposure may impact the development of allergy responses. To evaluate the roles of timing and level of maternal allergen exposure in the early life sensitization of progeny, female BALB/c mice were given ovalbumin (OVA) orally during pregnancy, lactation or weekly at each stage to investigate the immunoglobulin E (IgE) antibody production and cellular responsiveness of their offspring. Exposure to OVA during pregnancy was also evaluated in OVA-specific T-cell receptor (TCR) transgenic (DO11.10) mice. The effect of prenatal antigen exposure on offspring sensitization was dependent on antigen intake, with low-dose OVA inducing tolerance followed by neonatal immunization that was sustained even when pups were immunized when 3 weeks old. These offspring received high levels of transforming growth factor-beta via breastfeeding. High-dose exposure during the first week of pregnancy or perinatal period induced transient inhibition of IgE production following neonatal immunization; although for later immunization IgE production was enhanced in these offspring. Postnatal maternal antigen exposure provided OVA transference via breastfeeding, which consequently induced increased offspring susceptibility to IgE antibody production according to week post-birth. The effect of low-dose maternal exposure during pregnancy was further evaluated using OVA transgenic TCR dams as a model. These progeny presented pronounced entry of CD4(+) T cells into the S phase of the cell cycle with a skewed T helper type 2 response early in life, revealing the occurrence of allergen priming in utero. The balance between tolerance and sensitization depended on the amount and timing of maternal allergen intake during pregnancy.

Oxidative stress mediated toxicity of TiO2 nanoparticles after a concentration and time dependent exposure of the aquatic macrophyte Hydrilla verticillata.

PubMed

Spengler, Annette; Wanninger, Lena; Pflugmacher, Stephan

2017-09-01

The present study focused on oxidative stress effects in the aquatic macrophyte Hydrilla verticillata after exposure to titanium dioxide nanoparticles (TiO 2 -NPs). Experiments were conducted with different TiO 2 -NPs and concentrations (0.1 mg/L and 10 mg/L) in a time-dependent manner (0 h, 24 h, 48 h, 96 h, 168 h). To assess various levels of the oxidative stress response in H. verticillata, the level of hydrogen peroxide (H 2 O 2 ), the ratio of reduced to oxidized glutathione (GSH/GSSG), and activities of the antioxidative enzymes catalase (CAT) and glutathione reductase (GR) were evaluated. Study results imply oxidative stress effects after TiO 2 -NP exposure as adaptations in plant metabolism became apparent to counteract increased ROS formation. All TiO 2 -NPs caused elevated activities of the enzymes CAT and GR. Moreover, decreased ratios of GSH/GSSG indicated an activation of GSH-dependent pathways counteracting ROS formation. Plants exposed to a bulk-sized control revealed a size-dependent influence on the antioxidative stress response. As H 2 O 2 level increases were solely detected after exposure to 10 mg/L TiO 2 -NPs and nano-exposed plants showed normalization in its antioxidative stress response after 168h of exposure, it can be suggested that macrophytes are able to cope with currently predicted low-level exposures to TiO 2 -NPs. Copyright © 2017 Elsevier B.V. All rights reserved.

High shear induces platelet dysfunction leading to enhanced thrombotic propensity and diminished hemostatic capacity.

PubMed

Chen, Zengsheng; Mondal, Nandan K; Zheng, Shirong; Koenig, Steven C; Slaughter, Mark S; Griffith, Bartley P; Wu, Zhongjun J

2017-11-28

Thrombosis and bleeding are devastating adverse events in patients supported with blood-contacting medical devices (BCMDs). In this study, we delineated that high non-physiological shear stress (NPSS) caused platelet dysfunction that may contribute to both thrombosis and bleeding. Human blood was subjected to NPSS with short exposure time. Levels of platelet surface GPIbα and GPVI receptors as well as activation level of GPIIb/IIIa in NPSS-sheared blood were examined with flow cytometry. Adhesion of sheared platelets on fibrinogen, von Willibrand factor (VWF), and collagen was quantified with fluorescent microscopy. Ristocetin- and collagen-induced platelet aggregation was characterized by aggregometry. NPSS activated platelets in a shear and exposure time-dependent manner. The number of activated platelets increased with increasing levels of NPSS and exposure time, which corresponded well with increased adhesion of sheared platelets on fibrinogen. Concurrently, NPSS caused shedding of GPIbα and GPVI in a manner dependent on shear and exposure time. The loss of intact GPIbα and GPVI increased with increasing levels of NPSS and exposure time. The number of platelets adhered on VWF and collagen decreased with increasing levels of NPSS and exposure time, respectively. The decrease in the number of platelets adhered on VWF and collagen corresponded well with the loss in GPIbα and GPVI on platelet surface. Both ristocetin- and collagen-induced platelet aggregation in sheared blood decreased with increasing levels of NPSS and exposure time. The study clearly demonstrated that high NPSS causes simultaneous platelet activation and receptor shedding, resulting in a paradoxical effect on platelet function via two distinct mechanisms. The results from the study suggested that the NPSS could induce the concurrent propensity for both thrombosis and bleeding in patients.

A study on quantitative analysis of exposure dose caused by patient depending on time and distance in nuclear medicine examination

NASA Astrophysics Data System (ADS)

Kim, H. S.; Cho, J. H.; Shin, S. G.; Dong, K. R.; Chung, W. K.; Chung, J. E.

2013-01-01

This study evaluated possible actions that can help protect against and reduce radiation exposure by measuring the exposure dose for each type of isotope that is used frequently in nuclear medicine before performing numerical analysis of the effective half-life based on the measurement results. From July to August in 2010, the study targeted 10, 6 and 5 people who underwent an 18F-FDG (fludeoxyglucose) positron emission tomography (PET) scan, 99mTc-HDP bone scan, and 201Tl myocardial single-photon emission computed tomography (SPECT) scan, respectively, in the nuclear medicine department. After injecting the required medicine into the subjects, a survey meter was used to measure the dose depending on the distance from the heart and time elapsed. For the 18F-FDG PET scan, the dose decreased by approximately 66% at 90 min compared to that immediately after the injection and by 78% at a distance of 1 m compared to that at 0.3 m. In the 99mTc-HDP bone scan, the dose decreased by approximately 71% in 200 min compared to that immediately after the injection and by approximately 78% at a distance of 1 m compared to that at 0.3 m. In the 201Tl myocardial SPECT scan, the dose decreased by approximately 30% in 250 min compared to that immediately after the injection and by approximately 55% at a distance of 1 m compared to that at 0.3 m. In conclusion, the dose decreases by a large margin depending on the distance and time. In conclusion, this study measured the exposure doses by isotopes, distance from the heart and exposure time, and found that the doses were reduced significantly according the distance and the time.

Micronucleus formation induced by dielectric barrier discharge plasma exposure in brain cancer cells

NASA Astrophysics Data System (ADS)

Kaushik, Nagendra K.; Uhm, Hansup; Ha Choi, Eun

2012-02-01

Induction of micronucleus formation (cytogenetic damage) in brain cancer cells upon exposure of dielectric barrier discharge plasma has been investigated. We have investigated the influence of exposure and incubation times on T98G brain cancer cells by using growth kinetic, clonogenic, and micronucleus formation assay. We found that micronucleus formation rate directly depends on the plasma exposure time. It is also shown that colony formation capacity of cells has been inhibited by the treatment of plasma at all doses. Cell death and micronucleus formation are shown to be significantly elevated by 120 and 240 s exposure of dielectric barrier discharge plasma.

Severe and Moderate Asthma Exacerbations in Asthmatic Children and Exposure to Ambient Air Pollutants

PubMed Central

Tétreault, Louis-Francois; Doucet, Marieve; Gamache, Philippe; Fournier, Michel; Brand, Allan; Kosatsky, Tom; Smargiassi, Audrey

2016-01-01

Background: It is well established that short-term exposure to ambient air pollutants can exacerbate asthma, the role of early life or long-term exposure is less clear. We assessed the association between severe asthma exacerbations with both birth and annual exposure to outdoor air pollutants with a population-based cohort of asthmatic children in the province of Quebec (Canada). Method: Exacerbations of asthma occurring between 1 April 1996 and 31 March 2011 were defined as one hospitalization or emergency room visit with a diagnosis of asthma for children (<13 years old) already diagnosed with asthma. Annual daily average concentrations of ozone (O3) and nitrogen dioxide (NO2) were estimated at the child’s residential postal code. Satellite based levels of fine particulate (PM2.5) estimated for a grid of 10 km by 10 km were also assigned to postal codes of residence for the whole province. Hazard ratios (HRs) were estimated from Cox models with a gap time approach for both birth and time-dependant exposure. Results: Of the 162,752 asthmatic children followed (1,020,280 person-years), 35,229 had at least one asthma exacerbation. The HRs stratified by age groups and adjusted for the year of birth, the ordinal number of exacerbations, sex, as well as material and social deprivation, showed an interquartile range increase in the time-dependant exposure to NO2 (4.95 ppb), O3 (3.85 ppb), and PM2.5 (1.82 μg/m3) of 1.095 (95% CI 1.058–1.131), 1.052 (95% CI 1.037–1.066) and 1.025 (95% CI 1.017–1.031), respectively. While a positive association was found to PM2.5, no associations were found between exposure at birth to NO2 or O3. Conclusions: Our results support the conclusion, within the limitation of this study, that asthma exacerbations in asthmatic children are mainly associated with time dependent residential exposures less with exposure at birth. PMID:27490556

Nonlinear time dependence of dark current in charge-coupled devices

NASA Astrophysics Data System (ADS)

Dunlap, Justin C.; Bodegom, Erik; Widenhorn, Ralf

2011-03-01

It is generally assumed that charge-coupled device (CCD) imagers produce a linear response of dark current versus exposure time except near saturation. We found a large number of pixels with nonlinear dark current response to exposure time to be present in two scientific CCD imagers. These pixels are found to exhibit distinguishable behavior with other analogous pixels and therefore can be characterized in groupings. Data from two Kodak CCD sensors are presented for exposure times from a few seconds up to two hours. Linear behavior is traditionally taken for granted when carrying out dark current correction and as a result, pixels with nonlinear behavior will be corrected inaccurately.

Surface microhardness of a resin composite exposed to a "first-generation" LED curing lamp, in vitro.

PubMed

Keogh, Pauraic; Ray, Noel J; Lynch, Christopher D; Burke, Francis M; Hannigan, Ailish

2004-12-01

This investigation determined the minimum exposure times consistent with optimised surface microhardness parameters for a commercial resin composite cured using a "first-generation" light-emitting diode activation lamp. Disk specimens were exposed and surface microhardness numbers measured at the top and bottom surfaces for elapsed times of 1 hour and 24 hours. Bottom/top microhardness number ratios were also calculated. Most microhardness data increased significantly over the elapsed time interval but microhardness ratios (bottom/top) were dependent on exposure time only. A minimum exposure of 40 secs is appropriate to optimise microhardness parameters for the combination of resin composite and lamp investigated.

Successive Onset of Molecular, Cellular and Tissue-Specific Responses in Midgut Gland of Littorina littorea Exposed to Sub-Lethal Cadmium Concentrations

PubMed Central

Benito, Denis; Izagirre, Urtzi; Dallinger, Reinhard; Soto, Manu

2017-01-01

Cadmium (Cd) is one of the most harmful metals, being toxic to most animal species, including marine invertebrates. Among marine gastropods, the periwinkle (Littorina littorea) in particular can accumulate high amounts of Cd in its midgut gland. In this organ, the metal can elicit extensive cytological and tissue-specific alterations that may reach, depending on the intensity of Cd exposure, from reversible lesions to pathological cellular disruptions. At the same time, Littorina littorea expresses a Cd-specific metallothionein (MT) that, due to its molecular features, expectedly exerts a protective function against the adverse intracellular effects of this metal. The aim of the present study was, therefore, to assess the time course of MT induction in the periwinkle’s midgut gland on the one hand, and cellular and tissue-specific alterations in the digestive organ complex (midgut gland and digestive tract) on the other, upon exposure to sub-lethal Cd concentrations (0.25 and 1 mg Cd/L) over 21 days. Depending on the Cd concentrations applied, the beginning of alterations of the assessed parameters followed distinct concentration-dependent and time-dependent patterns, where the timeframe for the onset of the different response reactions became narrower at higher Cd concentrations compared to lower exposure concentrations. PMID:28829377

Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay

PubMed Central

Gülsoy, Nagihan; Yavas, Cüneyd; Mutlu, Özal

2015-01-01

The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P < 0,05) on both concentrations and exposure times were observed in experimental groups. DNA damage was highest at 96 h and 24 h for all BX and BA concentrations, respectively in peripheral blood of D. rerio. For the first time, our study demonstrates the effect of waterborne BA and BX exposure on genotoxicity at the molecular level, which may contribute to understanding the mechanism of boric acid and borax-induced genotoxicity in fish. PMID:26862320

Genotoxic effects of boric acid and borax in zebrafish, Danio rerio using alkaline comet assay.

PubMed

Gülsoy, Nagihan; Yavas, Cüneyd; Mutlu, Özal

2015-01-01

The present study is conducted to determine the potential mechanisms of Boron compounds, boric acid (BA) and borax (BX), on genotoxicity of zebrafish Danio rerio for 24, 48, 72 and 96-hours acute exposure (level:1, 4, 16, 64 mg/l BA and BX) in semi-static bioassay experiment. For that purpose, peripheral erythrocytes were drawn from caudal vein and Comet assay was applied to assess genotoxicity. Acute (96 hours) exposure and high concentrations of boric acid and borax increases % tail DNA and Olive tail moment. Genotoxicity was found for BA as concentration-dependent and BX as concentration and time dependent manner. In general, significant effects (P < 0,05) on both concentrations and exposure times were observed in experimental groups. DNA damage was highest at 96 h and 24 h for all BX and BA concentrations, respectively in peripheral blood of D. rerio. For the first time, our study demonstrates the effect of waterborne BA and BX exposure on genotoxicity at the molecular level, which may contribute to understanding the mechanism of boric acid and borax-induced genotoxicity in fish.

Hippocampal neurogenesis enhancers promote forgetting of remote fear memory after hippocampal reactivation by retrieval

PubMed Central

Ishikawa, Rie; Fukushima, Hotaka; Frankland, Paul W; Kida, Satoshi

2016-01-01

Forgetting of recent fear memory is promoted by treatment with memantine (MEM), which increases hippocampal neurogenesis. The approaches for treatment of post-traumatic stress disorder (PTSD) using rodent models have focused on the extinction and reconsolidation of recent, but not remote, memories. Here we show that, following prolonged re-exposure to the conditioning context, enhancers of hippocampal neurogenesis, including MEM, promote forgetting of remote contextual fear memory. However, these interventions are ineffective following shorter re-exposures. Importantly, we find that long, but not short re-exposures activate gene expression in the hippocampus and induce hippocampus-dependent reconsolidation of remote contextual fear memory. Furthermore, remote memory retrieval becomes hippocampus-dependent after the long-time recall, suggesting that remote fear memory returns to a hippocampus dependent state after the long-time recall, thereby allowing enhanced forgetting by increased hippocampal neurogenesis. Forgetting of traumatic memory may contribute to the development of PTSD treatment. DOI: http://dx.doi.org/10.7554/eLife.17464.001 PMID:27669409

Experimental phytophotodermatitis.

PubMed

Gonçalves, N E L; de Almeida, H L; Hallal, E C; Amado, M

2005-12-01

Phytophotodermatitis (PPD) is defined as a phototoxic reaction of the skin after contact with substances derived from plants and subsequent exposure to sunlight. It is a frequent disease in our outpatient clinics during summer because of contact with Tahitian lemon. Our objectives were to experimentally reproduce PPD in rats, to identify whether PPD is induced by minimal exposure periods to sunlight, to find what kinds of lemons and which parts of the lemon (the fruit juice or the peel juice) may trigger the disease; to know whether the use of sunblock prevents the reaction; and to perform light microscopy of the lesions to describe their histology. Adult rats (Rattus norwegicus), three in each experiment, were used. After painting the rats with the fruit juice or the peel juice they were exposed to sunlight for 2.5, 5, 7.5, and 10 min. Tahitian and Sicilian lemons were used in the experiments. Biopsies with 3-mm punches of different times of exposure were performed. The peel juice of both lemons reproduced PPD, which was clinically evident after 48 h. When the peel juice was alone applied there was no reaction; moreover, exposure to sunlight alone triggered no reaction. Two and a half minutes of exposure time was sufficient to induce phototoxic reaction, which was time dependent (the longer the exposure the more intense the reaction). Histopathological studies showed epithelial time-dependent vacuolar degeneration. The use of sunblock diminished the intensity of the reaction but did not prevent it. PPD can be reproduced in an animal model. It may be caused by the peel juice of Tahitian and Sicilian lemon. Because of an extremely short time of exposure (2.5 min) is sufficient to induce PPD it is necessary to alert the population, of the need for caution when handling lemons, especially outdoors despite using sunblock.

Wavelength dependent recovery of UV-mediated damage: Tying up the loose ends of optical based powdery mildew management.

PubMed

Suthaparan, Aruppillai; Pathak, Ranjana; Solhaug, Knut Asbjørn; Gislerød, Hans Ragnar

2018-01-01

Controlled environment chamber experiments at Petri dish level were conducted to examine the wavelength and dose dependent efficacy of ultraviolet (UV) radiation, the recovery action potential of optical radiation applied concomitantly/subsequently to effective UV treatment, and the lapse time between UV treatment and subsequent exposure to recovery wavelength on germination efficiency of Oidium neolycopersici conidia. Conidia of eight- to nine-day-old colonies were dusted on water agar surface in Petri dishes and exposed to UV treatments (without lid). Immediately after UV treatments, Petri dishes were sealed and incubated in darkness or differing optical environments generated using seven different radiation sources (range 290nm to 780nm). Twenty-four hours after UV treatment, fifty conidia from each sample were assessed for germination. Compared to non-UV controls, <10% of the conidia germinated after 30s of exposure to 254nm or 283nm UV and subsequent dark incubation. Conidia germination was almost negligible if the exposure duration increased to 4min. Germination was about 60% with broad spectrum UV after 1min of exposure, and about 35% after 2 to 4min of exposure. There was no reduction of conidia germination with the exposure of ≤4min with 310nm. With the tested wavelength and dose ranges, germination recovery was effective in the 350nm to 500nm range. Germination efficiency of conidia treated with effective UV was significantly higher (>73%) if incubated subsequently in the 350nm to 500nm range (germination recovery). Furthermore, germination recovery depends on the characteristics of UV treatment (wavelength, and duration of exposure) and the lapse time between UV treatment and subsequent exposure to optical radiation in the recovery range. The findings of this study provide key criteria for wavelength selection, combination and application time in the optical radiation range, enabling improved design of optical based management strategies against powdery mildews. Copyright © 2017 Elsevier B.V. All rights reserved.

PM2.5-induced alterations of cell cycle associated gene expression in lung cancer cells and rat lung tissues.

PubMed

Zhao, Hui; Yang, Biao; Xu, Jia; Chen, Dong-Mei; Xiao, Chun-Ling

2017-06-01

The aim of the current study was to investigate the expression of cell cycle-associated genes induced by fine particulate matter (PM 2.5 ) in lung cancer cell line and tissues. The pulmonary lymph node metastasis cells (H292) were treated with PM 2.5 in vitro. Wistar rats were used to perform an in vivo study. Rats were randomly assigned to experiment and control groups and those in the experiment group were exposed to PM 2.5 once every 15 d, while those in the control group were exposed to normal saline. The cell cycle-associated genes expression was analyzed by real-time PCR. Trachea and lung tissues of rats were processed for scanning electron microscopic (SEM) examinations. Exposure of H292 cells to PM 2.5 dramatically increased the expressions of p53 and cyclin-dependent kinase 2 (CDK2) after 24h of exposure (p<0.01) and markedly increased the expressions of the cell division cycle 2 (Cdc2) and cyclin B after 48h of exposure (p<0.01), while those genes expressions were significantly reduced after 72h of exposure, at which time the expression of p21 was predominant (p<0.01). In vivo studies further demonstrated these results. The results of SEM suggested that both of the trachea and lung tissues were damaged and the degree of damage was time-dependent. In conclusion, PM 2.5 can induce significantly alterations of p53 and CDK2 in the early phase, Cdc2 and cyclin B in mid-term and p21 in long-term exposure. The degree of PM 2.5 -induced damage to the trachea and lung tissue was time-dependent. Copyright © 2017. Published by Elsevier B.V.

Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny.

PubMed

Ling, Binbing; Aziz, Caroline; Wojnarowicz, Chris; Olkowski, Andrew; Alcorn, Jane

2010-10-14

Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine) on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg) twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20). Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn) mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age.

Timing and Duration of Drug Exposure Affects Outcomes of a Drug-Nutrient Interaction During Ontogeny

PubMed Central

Ling, Binbing; Aziz, Caroline; Wojnarowicz, Chris; Olkowski, Andrew; Alcorn, Jane

2010-01-01

Significant drug-nutrient interactions are possible when drugs and nutrients share the same absorption and disposition mechanisms. During postnatal development, the outcomes of drug-nutrient interactions may change with postnatal age since these processes undergo ontogenesis through the postnatal period. Our study investigated the dependence of a significant drug-nutrient interaction (cefepime-carnitine) on the timing and duration of drug exposure relative to postnatal age. Rat pups were administered cefepime (5 mg/kg) twice daily subcutaneously according to different dosing schedules (postnatal day 1-4, 1-8, 8-11, 8-20, or 1-20). Cefepime significantly reduced serum and heart L-carnitine levels in postnatal day 1-4, 1-8 and 8-11 groups and caused severe degenerative changes in ventricular myocardium in these groups. Cefepime also altered the ontogeny of several key L-carnitine homeostasis pathways. The qualitative and quantitative changes in levels of hepatic γ-butyrobetaine hydroxylase mRNA and activity, hepatic trimethyllysine hydroxlase mRNA, intestinal organic cation/carnitine transporter (Octn) mRNA, and renal Octn2 mRNA depended on when during postnatal development the cefepime exposure occurred and duration of exposure. Despite lower levels of heart L-carnitine in earlier postnatal groups, levels of carnitine palmitoyltransferase mRNA and activity, heart Octn2 mRNA and ATP levels in all treatment groups remained unchanged with cefepime exposure. However, changes in other high energy phosphate substrates were noted and reductions in the phosphocreatine/ATP ratio were found in rat pups with normal serum L-carnitine levels. In summary, our data suggest a significant drug-nutrient transport interaction in developing neonates, the nature of which depends on the timing and duration of exposure relative to postnatal age. PMID:27721360

Short and long-term exposure of CNS cell lines to BPA-f a radiosensitizer for boron neutron capture therapy: safety dose evaluation by a battery of cytotoxicity tests.

PubMed

De Simone, U; Manzo, L; Ferrari, C; Bakeine, J; Locatelli, C; Coccini, T

2013-03-01

Despite the current clinical use of boronophenylalanine-fructose (BPA-f), as radiosensitizer, in BNCT application for brain tumors, still remains to be determined the safety dose of this agent. We evaluated the potential risk of primary BPA-f toxicity before neutronic irradiation at different concentrations (0-100μgBeq/ml) after short- and long-term exposure (4-48h and 7-10 days), using a battery of tests (i.e. MTT assay, calcein-AM/Propidium Iodide staining, clonogenic test) in CNS cell models (D384 and SH-SY5Y), and non-neuronal primary human fibroblasts (F26). MTT data showed: (i) no cytotoxic effects after short-term exposure (4h) to any of BPA-f concentrations tested in all cell models; (ii) dose- and time-dependent mitochondrial activity impairment in D384 and SH-SY5Y cells only (with 60% and 40% cell death in D384 and SH-SY5Y, respectively, after 48h exposure to BPA-f 100μgBeq/ml). By Calcein-AM/PI staining, BPA-f treatment was specific toward SH-SY5Y cells only: a dose-dependent cell density reduction was observed, with a more pronounced effect after 48h exposure (15-40% at doses ranging 20-100μgBeq/ml). Clonogenic data revealed dose-dependent decrease of cell proliferative capacity in all cell lines, still the SH-SY5Y cells were the most sensitive ones: the lowest dose (20μgBeq/ml) produced 90% cell decrease. These results indicate dose- and time-dependent cytotoxic effects of BPA-f, with CNS cells showing a lower tolerance compared to fibroblasts. Long-term exposure to BPA-f compromised the proliferative capacity regardless of cell model type (cell sensitivity being SH-SY5Y>D384>F26). In short-time exposure, BPA-f exhibits a safe dosage up to 40μgBeq/ml for the viability of CNS cell lines. Copyright © 2012 Elsevier Inc. All rights reserved.

Dose- and time-dependent expression of aryl hydrocarbon receptor (AhR) and aryl hydrocarbon receptor nuclear translocator (ARNT) in PCB-, B[a]P-, and TBT-exposed intertidal copepod Tigriopus japonicus.

PubMed

Kim, Bo-Mi; Rhee, Jae-Sung; Hwang, Un-Ki; Seo, Jung Soo; Shin, Kyung-Hoon; Lee, Jae-Seong

2015-02-01

The aryl hydrocarbon receptor (AhR) and aryl hydrocarbon nuclear translocator (ARNT) genes from the copepod Tigriopus japonicus (Tj) were cloned to examine their potential functions in the invertebrate putative AhR-CYP signaling pathway. The amino acid sequences encoded by the Tj-AhR and Tj-ARNT genes showed high similarity to homologs of Daphnia and Drosophila, ranging from 68% and 70% similarity for the AhR genes to 56% for the ARNT genes. To determine whether Tj-AhR and Tj-ARNT are modulated by environmental pollutants, transcriptional expression of Tj-AhR and Tj-ARNT was analyzed in response to exposure to five concentrations of polychlorinated biphenyl (PCB 126) (control, 10, 50, 100, 500 μg L(-1)), benzo[a]pyrene (B[a]P) (control, 5, 10, 50, 100 μg L(-1)), and tributyltin (TBT) (control, 1, 5, 10, 20 μg L(-1)) 24h after exposure. A time-course experiment (0, 3, 6, 12, 24h) was performed to analyze mRNA expression patterns after exposure to PCB, B[a]P, and TBT. T. japonicus exhibited dose-dependent and time-dependent upregulation of Tj-AhR and Tj-ARNT in response to pollutant exposure, and the degree of expression was dependent on the pollutant, suggesting that pollutants such as PCB, B[a]P, and TBT modulate expression of Tj-AhR and Tj-ARNT genes in the putative AhR-CYP signaling pathway. Copyright © 2014 Elsevier Ltd. All rights reserved.

Comparison of laser Doppler and laser speckle contrast imaging using a concurrent processing system

NASA Astrophysics Data System (ADS)

Sun, Shen; Hayes-Gill, Barrie R.; He, Diwei; Zhu, Yiqun; Huynh, Nam T.; Morgan, Stephen P.

2016-08-01

Full field laser Doppler imaging (LDI) and single exposure laser speckle contrast imaging (LSCI) are directly compared using a novel instrument which can concurrently image blood flow using both LDI and LSCI signal processing. Incorporating a commercial CMOS camera chip and a field programmable gate array (FPGA) the flow images of LDI and the contrast maps of LSCI are simultaneously processed by utilizing the same detected optical signals. The comparison was carried out by imaging a rotating diffuser. LDI has a linear response to the velocity. In contrast, LSCI is exposure time dependent and does not provide a linear response in the presence of static speckle. It is also demonstrated that the relationship between LDI and LSCI can be related through a power law which depends on the exposure time of LSCI.

UVA Irradiation of Dysplastic Keratinocytes: Oxidative Damage versus Antioxidant Defense

PubMed Central

Nechifor, Marina T.; Niculiţe, Cristina M.; Urs, Andreea O.; Regalia, Teodor; Mocanu, Mihaela; Popescu, Alexandra; Manda, Gina; Dinu, Diana; Leabu, Mircea

2012-01-01

UVA affects epidermal cell physiology in a complex manner, but the harmful effects have been studied mainly in terms of DNA damage, mutagenesis and carcinogenesis. We investigated UVA effects on membrane integrity and antioxidant defense of dysplastic keratinocytes after one and two hours of irradiation, both immediately after exposure, and 24 h post-irradiation. To determine the UVA oxidative stress on cell membrane, lipid peroxidation was correlated with changes in fatty acid levels. Membrane permeability and integrity were assessed by propidium iodide staining and lactate dehydrogenase release. The effects on keratinocyte antioxidant protection were investigated in terms of catalase activity and expression. Lipid peroxidation increased in an exposure time-dependent manner. UVA exposure decreased the level of polyunsaturated fatty acids, which gradually returned to its initial value. Lactate dehydrogenase release showed a dramatic loss in membrane integrity after 2 h minimum of exposure. The cell ability to restore membrane permeability was noted at 24 h post-irradiation (for one hour exposure). Catalase activity decreased in an exposure time-dependent manner. UVA-irradiated dysplastic keratinocytes developed mechanisms leading to cell protection and survival, following a non-lethal exposure. The surviving cells gained an increased resistance to apoptosis, suggesting that their pre-malignant status harbors an abnormal ability to control their fate. PMID:23222638

Testing the time-scale dependence of delayed interactions: A heat wave during the egg stage shapes how a pesticide interacts with a successive heat wave in the larval stage.

PubMed

Janssens, Lizanne; Tüzün, Nedim; Stoks, Robby

2017-11-01

Under global change organisms are exposed to multiple, potentially interacting stressors. Especially interactions between successive stressors are poorly understood and recently suggested to depend on their timing of exposure. We particularly need studies assessing the impact of exposure to relevant stressors at various life stages and how these interact. We investigated the single and combined impacts of a heat wave (mild [25 °C] and extreme [30 °C]) during the egg stage, followed by successive exposure to esfenvalerate (ESF) and a heat wave during the larval stage in damselflies. Each stressor caused mortality. The egg heat wave and larval ESF exposure had delayed effects on survival, growth and lipid peroxidation (MDA). This resulted in deviations from the prediction that stressors separated by a long time interval would not interact: the egg heat wave modulated the interaction between the stressors in the larval stage. Firstly, ESF caused delayed mortality only in larvae that had been exposed to the extreme egg heat wave and this strongly depended upon the larval heat wave treatment. Secondly, ESF only increased MDA in larvae not exposed to the egg heat wave. We found little support for the prediction that when there is limited time between stressors, synergistic interactions should occur. The intermediate ESF concentration only caused delayed mortality when combined with the larval heat wave, and the lowest ESF concentrations only increased oxidative damage when followed by the mild larval heat wave. Survival selection mitigated the interaction patterns between successive stressors that are individually lethal, and therefore should be included in a predictive framework for the time-scale dependence of the outcome of multistressor studies with pollutants. The egg heat wave shaping the interaction pattern between successive pesticide exposure and a larval heat wave highlights the connectivity between the concepts of 'heat-induced pesticide sensitivity' and 'pesticide-induced heat sensitivity'. Copyright © 2017 Elsevier Ltd. All rights reserved.

Skin permeability enhancement by Bacillus subtilis alkaline protease: Application to transdermal drug delivery.

PubMed

Nounou, Mohamed I; Zaghloul, Taha I; Ahmed, Nehal A; Eid, Amira A; El-Khordagui, Labiba K

2017-08-30

Enzymes may offer great potentials in topical pharmaceutical applications provided that treatment conditions are controlled for efficacy and safety. In this study, the effect of alkaline protease produced by recombinant Bacillus subtilis cells on the ex-vivo permeability of rabbit ear skin was investigated under different conditions of enzyme activity (5-60 units) and exposure time (15-60min). Data for transepidermal water loss (TEWL) and permeation of a hydrophilic dye, rhodamine B (Rb), indicated biphasic activity-dependent and exposure time-dependent skin permeability. Maximum effects were obtained at 20 proteolytic units and 30min exposure. Findings proved consistent with histopathological changes indicating progressive stratum corneum (SC) loss and disruption of the dermo-epidermal junction at 20 units and up to 30min exposure time followed by dermal hyalinization at longer exposure. This was associated with progressive loss of skin hair. Applying the identified pretreatment conditions to transdermal delivery of vardenafil in a gel base across dorsal rat skin indicated a significant increase in plasma levels at 30 and 60min with minimal histopathological changes 5days post enzyme treatment. Accordingly, the recombinant B. subtilis alkaline protease offers promise as a pharmaceutical enzyme for transdermal drug delivery bioenhancement and dermatological applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Stress indicator gene expression profiles, colony dynamics and tissue development of honey bees exposed to sub-lethal doses of imidacloprid in laboratory and field experiments.

PubMed

De Smet, Lina; Hatjina, Fani; Ioannidis, Pavlos; Hamamtzoglou, Anna; Schoonvaere, Karel; Francis, Frédéric; Meeus, Ivan; Smagghe, Guy; de Graaf, Dirk C

2017-01-01

In this study, different context-dependent effects of imidacloprid exposure on the honey bee response were studied. Honey bees were exposed to different concentrations of imidacloprid during a time period of 40 days. Next to these variables, a laboratory-field comparison was conducted. The influence of the chronic exposure on gene expression levels was determined using an in-house developed microarray targeting different immunity-related and detoxification genes to determine stress-related gene expression changes. Increased levels of the detoxification genes encoding, CYP9Q3 and CYT P450, were detected in imidacloprid-exposed honey bees. The different context-dependent effects of imidacloprid exposure on honey bees were confirmed physiologically by decreased hypopharyngeal gland sizes. Honey bees exposed to imidacloprid in laboratory cages showed a general immunosuppression and no detoxification mechanisms were triggered significantly, while honey bees in-field showed a resilient response with an immune stimulation at later time points. However, the treated colonies had a brood and population decline tendency after the first brood cycle in the field. In conclusion, this study highlighted the different context-dependent effects of imidacloprid exposure on the honey bee response. These findings warn for possible pitfalls concerning the generalization of results based on specific experiments with short exposure times. The increased levels of CYT P450 and CYP9Q3 combined with an immune response reaction can be used as markers for bees which are exposed to pesticides in the field.

Stress indicator gene expression profiles, colony dynamics and tissue development of honey bees exposed to sub-lethal doses of imidacloprid in laboratory and field experiments

PubMed Central

Ioannidis, Pavlos; Hamamtzoglou, Anna; Schoonvaere, Karel; Francis, Frédéric; Meeus, Ivan; Smagghe, Guy; de Graaf, Dirk C.

2017-01-01

In this study, different context-dependent effects of imidacloprid exposure on the honey bee response were studied. Honey bees were exposed to different concentrations of imidacloprid during a time period of 40 days. Next to these variables, a laboratory-field comparison was conducted. The influence of the chronic exposure on gene expression levels was determined using an in-house developed microarray targeting different immunity-related and detoxification genes to determine stress-related gene expression changes. Increased levels of the detoxification genes encoding, CYP9Q3 and CYT P450, were detected in imidacloprid-exposed honey bees. The different context-dependent effects of imidacloprid exposure on honey bees were confirmed physiologically by decreased hypopharyngeal gland sizes. Honey bees exposed to imidacloprid in laboratory cages showed a general immunosuppression and no detoxification mechanisms were triggered significantly, while honey bees in-field showed a resilient response with an immune stimulation at later time points. However, the treated colonies had a brood and population decline tendency after the first brood cycle in the field. In conclusion, this study highlighted the different context-dependent effects of imidacloprid exposure on the honey bee response. These findings warn for possible pitfalls concerning the generalization of results based on specific experiments with short exposure times. The increased levels of CYT P450 and CYP9Q3 combined with an immune response reaction can be used as markers for bees which are exposed to pesticides in the field. PMID:28182641

Information-sharing tendency on Twitter and time evolution of tweeting

NASA Astrophysics Data System (ADS)

Kwon, H. W.; Kim, H. S.; Lee, K.; Choi, M. Y.

2013-03-01

While topics on Twitter may be categorized according to their predictability and sustainability, some topics have characteristics depending on the time scale. Here we propose a good measure for the transition of sustainability, which we call the information-sharing tendency, and find that the unpredictability on Twitter is provoked by the exposure of Twitter users to external environments, e.g., mass media and other social network services. In addition, it is demonstrated that the numbers of articles and comments on on-line newspapers serve as plausible measures of exposure. From such measures of exposure, the time evolution of tweeting can be described, when the information-sharing tendency is known.

Matrix Population Model for Estimating Effects from Time-Varying Aquatic Exposures: Technical Documentation

EPA Science Inventory

The Office of Pesticide Programs models daily aquatic pesticide exposure values for 30 years in its risk assessments. However, only a fraction of that information is typically used in these assessments. The population model employed herein is a deterministic, density-dependent pe...

Utilising shade to optimize UV exposure for vitamin D

NASA Astrophysics Data System (ADS)

Turnbull, D. J.; Parisi, A. V.

2008-01-01

Numerous studies have stated that humans need to utilise full sun radiation, at certain times of the day, to assist the body in synthesising the required levels of vitamin D3. The time needed to be spent in the full sun depends on a number of factors, for example, age, skin type, latitude, solar zenith angle. Current Australian guidelines suggest exposure to approximately 1/6 to 1/3 of a minimum erythemal dose (MED), depending on age, would be appropriate to provide adequate vitamin D3 levels. The aim of the study was to determine the exposure times to diffuse solar UV to receive exposures of 1/6 and 1/3 MED for a changing solar zenith angle in order to assess the possible role that diffuse UV (scattered radiation) may play in vitamin D3 effective UV exposures (UVD3). Diffuse and global erythemal UV measurements were conducted at five minute intervals over a twelve month period for a solar zenith angle range of 4° to 80° at a latitude of 27.6° S. For diffuse UV exposures of 1/6 and 1/3 MED, solar zenith angles smaller than 60° and 50° respectively can be utilised for exposure times of less than 10 min. Spectral measurements showed that, for a solar zenith angle of 40°, the UVA (315-400 nm) in the diffuse component of the solar UV is reduced by approximately 62% compared to the UVA in the global UV, whereas UVD3 wavelengths are only reduced by approximately 43%. At certain latitudes, diffuse UV under shade may play an important role in providing the human body with adequate levels of UVD3 (290-330 nm) radiation without experiencing the high levels of damaging UVA observed in full sun.

Utilising shade to optimize UV exposure for vitamin D

NASA Astrophysics Data System (ADS)

Turnbull, D. J.; Parisi, A. V.

2008-06-01

Numerous studies have stated that humans need to utilise full sun radiation, at certain times of the day, to assist the body in synthesising the required levels of vitamin D3. The time needed to be spent in the full sun depends on a number of factors, for example, age, skin type, latitude, solar zenith angle. Current Australian guidelines suggest exposure to approximately 1/6 to 1/3 of a minimum erythemal dose (MED), depending on age, would be appropriate to provide adequate vitamin D3 levels. The aim of the study was to determine the exposure times to diffuse solar UV to receive exposures of 1/6 and 1/3 MED for a changing solar zenith angle in order to assess the possible role that diffuse UV (scattered radiation) may play in vitamin D3 effective UV exposures (UVD3). Diffuse and global erythemal UV measurements were conducted at five minute intervals over a twelve month period for a solar zenith angle range of 4° to 80° at a latitude of 27.6° S. For a diffuse UV exposure of 1/3 MED, solar zenith angles smaller than approximately 50° can be utilised for exposure times of less than 10 min. Spectral measurements showed that, for a solar zenith angle of 40°, the UVA (315-400 nm) in the diffuse component of the solar UV is reduced by approximately 62% compared to the UVA in the global UV, whereas UVD3 wavelengths are only reduced by approximately 43%. At certain latitudes, diffuse UV under shade may play an important role in providing the human body with adequate levels of UVD3 (290-315 nm) radiation without experiencing the high levels of UVA observed in full sun.

Laser absorption waves in metallic capillaries

NASA Astrophysics Data System (ADS)

Anisimov, V. N.; Arutiunian, R. V.; Bol'Shov, L. A.; Kanevskii, M. F.; Kondrashov, V. V.

1987-07-01

The propagation of laser absorption waves in metallic capillaries was studied experimentally and numerically during pulsed exposure to CO2 laser radiation. The dependence of the plasma front propagation rate on the initial air pressure in the capillary is determined. In a broad range of parameters, the formation time of the optically opaque plasma layer is governed by the total laser pulse energy from the beginning of the exposure to the instant screening appears, and is weakly dependent on the pulse shape and gas pressure.

Extinction of Contextual Fear with Timed Exposure to Enriched Environment: A Differential Effect

PubMed Central

Hegde, Preethi; O'Mara, Shane; Laxmi, Thenkanidiyoor Rao

2017-01-01

Background Extinction of fear memory depends on the environmental and emotional cues. Furthermore, consolidation of extinction is also dependent on the environmental exposure. But, the relationship of the time of the exposure to a variety of environmental cues is not well known. The important region involved in facilitation of extinction of fear memory is through diversion of the flow of information leaving the lateral nucleus of amygdala. Purpose The study aimed to address a question to explain how these brain regions react to environmental stimulation during the retention and extinction of fear memory. Methods An enriched environment (EE) is assumed to mediate extinction of fear memory, we examined the apparent discrepancy between the effects of defensive response, the freezing behavior induced by Pavlovian classical fear conditioning by subjecting them to variance in the timing to EE. The different timing of EE exposure was 10 days of EE either before fear conditioning and/or after extinction training to the rats. The local field potentials was recorded from CA1 hippocampus, lateral nucleus of amygdala and infralimbic region of medial prefrontal cortex (mPFC) during the fear learning and extinction from the control rats and rats exposed to EE before and after fear conditioning. Results Exposure to EE before the fear conditioning and after extinction training was more effective in the extinction fear memory. In addition, we also found switching from exploratory locomotion to freezing during retention of contextual fear memory which was associated with decreased theta power and reduced synchronized theta oscillations in CA1-hippocampus, lateral nucleus of amygdala, and infralimbic region of mPFC. Conclusion Thus, we propose that the timing of exposure to EE play a key role in the extinction of fear memory. PMID:28588364

Modelling survival: exposure pattern, species sensitivity and uncertainty.

PubMed

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B; Van den Brink, Paul J; Veltman, Karin; Vogel, Sören; Zimmer, Elke I; Preuss, Thomas G

2016-07-06

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

Modelling survival: exposure pattern, species sensitivity and uncertainty

NASA Astrophysics Data System (ADS)

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I.; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B.; van den Brink, Paul J.; Veltman, Karin; Vogel, Sören; Zimmer, Elke I.; Preuss, Thomas G.

2016-07-01

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans.

Cerebral Asymmetries in Sleep-Dependent Processes of Memory Consolidation

ERIC Educational Resources Information Center

Peigneux, Philippe; Schmitz, Remy; Willems, Sylvie

2007-01-01

Preference for previously seen, unfamiliar objects reflects a memory bias on affective judgment, known as the "mere exposure effect" (MEE). Here, we investigated the effect of time, post-exposure sleep, and the brain hemisphere solicited on preference generalization toward objects viewed in different perspectives. When presented in the right…

Indoor Residence Times of Semivolatile Organic Compounds: Model Estimation and Field Evaluation

EPA Science Inventory

Indoor residence times of semivolatile organic compounds (SVOCs) are a major and mostly unavailable input for residential exposure assessment. We calculated residence times for a suite of SVOCs using a fugacity model applied to residential environments. Residence times depend on...

Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?

PubMed

Spear, Linda Patia

2015-09-01

There are two key alcohol use patterns among human adolescents that confer increased vulnerability for later alcohol abuse/dependence, along with neurocognitive alterations: (a) early initiation of use during adolescence, and (b) high rates of binge drinking that are particularly prevalent late in adolescence. The central thesis of this review is that lasting neurobehavioral outcomes of these two adolescent exposure patterns may differ. Although it is difficult to disentangle consequences of early use from later binge drinking in human studies given the substantial overlap between groups, these two types of problematic adolescent use are differentially heritable and hence separable to some extent. Although few studies using animal models have manipulated alcohol exposure age, those studies that have have typically observed timing-specific exposure effects, with more marked (or at least different patterns of) lasting consequences evident after exposures during early-mid adolescence than late-adolescence/emerging adulthood, and effects often restricted to male rats in those few instances where sex differences have been explored. As one example, adult male rats exposed to ethanol during early-mid adolescence (postnatal days [P] 25-45) were found to be socially anxious and to retain adolescent-typical ethanol-induced social facilitation into adulthood, effects that were not evident after exposure during late-adolescence/emerging adulthood (P45-65); exposure at the later interval, however, induced lasting tolerance to ethanol's social inhibitory effects that was not evident after exposure early in adolescence. Females, in contrast, were little influenced by ethanol exposure at either interval. Exposure timing effects have likewise been reported following social isolation as well as after repeated exposure to other drugs such as nicotine (and cannabinoids), with effects often, although not always, more pronounced in males where studied. Consistent with these timing-specific exposure effects, notable maturational changes in brain have been observed from early to late adolescence that could provide differential neural substrates for exposure timing-related consequences, with for instance exposure during early adolescence perhaps more likely to impact later self-administration and social/affective behaviors, whereas exposures later in adolescence may be more likely to influence cognitive tasks whose neural substrates (such as the prefrontal cortex [PFC]) are still undergoing maturation at that time. More work is needed, however to characterize timing-specific effects of adolescent ethanol exposures and their sex dependency, determine their neural substrates, and assess their comparability to and interactions with adolescent exposure to other drugs and stressors. Such information could prove critical for informing intervention/prevention strategies regarding the potential efficacy of efforts directed toward delaying onset of alcohol use versus toward reducing high levels of use and risks associated with that use later in adolescence. Copyright © 2015 Elsevier Inc. All rights reserved.

ADOLESCENT ALCOHOL EXPOSURE: ARE THERE SEPARABLE VULNERABLE PERIODS WITHIN ADOLESCENCE?

PubMed Central

Spear, Linda Patia

2015-01-01

There are two key alcohol use patterns among human adolescents that confer increased vulnerability for later alcohol abuse/dependence, along with neurocognitive alterations: (a) early initiation of use during adolescence, and (b) high rates of binge drinking that are particularly prevalent late in adolescence. The central thesis of this review is that lasting neurobehavioral outcomes of these two adolescent exposure patterns may differ. Although it is difficult to disentangle consequences of early use from later binge drinking in human studies given the substantial overlap between groups, these two types of problematic adolescent use are differentially heritable and hence separable to some extent. Although few studies using animal models have manipulated alcohol exposure age, those studies that have have typically observed timing-specific exposure effects, with more marked (or at least different patterns of) lasting consequences evident after exposures during early-mid adolescence than late-adolescence/emerging adulthood, and effects often restricted to male rats in those few instances where sex differences have been explored. As one example, adult male rats exposed to ethanol during early-mid adolescence (postnatal days [P] 25-45) were found to be socially anxious and to retain adolescent-typical ethanol-induced social facilitation into adulthood, effects that were not evident after exposure during late-adolescence/emerging adulthood (P45-65); exposure at the later interval, however, induced lasting tolerance to ethanol's social inhibitory effects that was not evident after exposure early in adolescence. Females, in contrast, were little influenced by ethanol exposure at either interval. Exposure timing effects have likewise been reported following social isolation as well as after repeated exposure to other drugs such as nicotine (and cannabinoids), with effects often, although not always, more pronounced in males where studied. Consistent with these timing-specific exposure effects, notable maturational changes in brain have been observed from early to late adolescence that could provide differential neural substrates for exposure timing-related consequences, with for instance exposure during early adolescence perhaps more likely to impact later self-administration and social/affective behaviors, whereas exposures later in adolescence may be more likely to influence cognitive tasks whose neural substrates (such as the prefrontal cortex [PFC]) are still undergoing maturation at that time. Substantial more work is needed, however to characterize timing-specific effects of adolescent ethanol exposures and their sex dependency, determine their neural substrates, and assess their comparability to and interactions with adolescent exposure to other drugs and stressors. Such information could prove critical for informing intervention/prevention strategies regarding the potential efficacy of efforts directed toward delaying onset of alcohol use versus toward reducing high levels of use and risks associated with that use later in adolescence. PMID:25624108

Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies

PubMed Central

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Tremlett, Helen

2016-01-01

In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time. Both assessments revealed that the PTDM approach did not adequately address immortal time bias. Based on our simulation results, another recently proposed observational data analysis technique, the sequential Cox approach, was found to be more useful than the PTDM approach (Cox: bias = −0.002, mean squared error = 0.025; PTDM: bias = −1.411, mean squared error = 2.011). We applied these approaches to investigate the association of β-interferon treatment with delaying disability progression in a multiple sclerosis cohort in British Columbia, Canada (Long-Term Benefits and Adverse Effects of Beta-Interferon for Multiple Sclerosis (BeAMS) Study, 1995–2008). PMID:27455963

The impact of intratracheally instilled carbon black on the cardiovascular system of rats: elevation of blood homocysteine and hyperactivity of platelets.

PubMed

Kim, Hwa; Oh, Seok-Jeong; Kwak, Hui-Chan; Kim, Jong-Kyu; Lim, Cheol-Hong; Yang, Jeong-Sun; Park, Kwangsik; Kim, Sang-Kyum; Lee, Moo-Yeol

2012-01-01

Carbon black (CB) is an industrial chemical with high potential for human exposure. Although the relationship between exposure to particulate matter (PM) and cardiovascular disease is well documented, the risk of adverse cardiovascular effects attributed to CB particles has not been clearly characterized. This study was performed to (1) investigate the effects of CB on cardiovascular system and (2) identify the target tissue or potential biomarkers. Carbon black with a distinct particle size, N330 (ultrafine particle) and N990 (fine particle), was intratracheally instilled into rats at a doses of 1, 3, or 10 mg/kg. Measurements of thrombotic activity and determination of plasma homocysteine levels, cardiac functionality, and inflammatory responses were conducted at 24-h and 1-wk time points. Exposure to N330 accelerated platelet-dependent blood clotting at 10 mg/kg, the highest exposure tested. Unexpectedly, both N330 and N990 led to prolongation of activated partial thromboplastin time (aPTT), whereas these CB particles failed to affect prothrombin time (PT). N990 produced a significant elevation in the level of plasma homocysteine, a well-established etiological factor in cardiovascular diseases. Both N330 and N990 induced apparent inflammation in the lungs; however, both particles failed to initiate systemic inflammation. Neither CB particle produced observable cardiac symptoms as detected by electrocardiography. Taken together, data show CB exposure enhanced the cardiovascular risk by inducing hyperhomocysteinemia and platelet hyperactivity, although these effects may be variable depending on particle size and exposure duration. Homocysteine may be a potential biomarker for cardiovascular toxicity following CB exposure.

Transcription patterns of genes encoding four metallothionein homologs in Daphnia pulex exposed to copper and cadmium are time- and homolog- dependent

PubMed Central

Asselman, Jana; Shaw, Joseph R.; Glaholt, Stephen P.; Colbourne, John K.; De Schamphelaere, Karel AC.

2013-01-01

Metallothioneins are proteins that play an essential role in metal homeostasis and detoxification in nearly all organisms studied to date. Yet discrepancies between outcomes of chronic and acute exposure experiments hamper the understanding of the regulatory mechanisms of their isoforms following metal exposure. Here, we investigated transcriptional differences among four identified homologs (mt1–mt4) in Daphnia pulex exposed across time to copper and cadmium relative to a control. Transcriptional upregulation of mt1 and mt3 was detected on day four following exposure to cadmium, whereas that of mt2 and mt4 was detected on day two and day eight following exposure to copper. These results confirm temporal and metal-specific differences in the transcriptional induction of genes encoding metallothionein homologs upon metal exposure which should be considered in ecotoxicological monitoring programs of metal-contaminated water bodies. Indeed, the mRNA expression patterns observed here illustrate the complex regulatory system associated with metallothioneins, as these patterns are not only dependent on the metal, but also on exposure time and the homolog studied. Further phylogenetic analysis and analysis of regulatory elements in upstream promoter regions revealed a high degree of similarity between metallothionein genes of Daphnia pulex and Daphnia magna, a species belonging to the same genus. These findings, combined with a limited amount of available expression data for D. magna metallothionein genes, tentatively suggest a potential generalization of the metallothionein response system between these Daphnia species. PMID:24113165

Sporicidal effects of iodine-oxide thermite reaction products

NASA Astrophysics Data System (ADS)

Russell, Rod; Bless, Stephan; Blinkova, Alexandra; Chen, Tiffany

2012-03-01

Iodine pentoxide-aluminum thermite reactions have been driven by impacts at 1000 m/s on steel plates 3 mm or thicker. This reaction releases iodine gas that is known to be a sporicide. To test the impact reactions for sporicidal effects, reactions took place in closed chambers containing dried Bacillus subtilis spores. The reduction in colony-forming units was dependent on the exposure time; long exposure times resulted in a 105 decrease in germination rate. This was shown to be due to the gas exposure rather than the heat or turbulence. Sporicidal effectiveness was increased by adding neodymium and saran resin.

A long term study of pulmonary function among US refractory ceramic fibre workers

PubMed Central

LeMasters, Grace K; Hilbert, Timothy J; Levin, Linda S; Rice, Carol H; Borton, Eric K; Lockey, James E

2010-01-01

Background Cross-sectional studies have shown declines in lung function among refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study followed current and former workers (n=1396) for up to 17 years and collected 5243 pulmonary function tests. Methods Cumulative fibre exposure and production years were categorised into exposure levels at five manufacturing locations. Conventional longitudinal models did not adequately partition age-related changes from other time-dependent variables. Therefore, a restricted cubic spline model was developed to account for the non-linear decline with age. Results Cumulative fibre >60 fibre-months/cc showed a significant loss in lung function at the first test. When results were examined longitudinally, cumulative exposure was confounded with age as workers with the highest cumulative exposure were generally older. A longitudinal model adjusted by age groups was implemented to control for this confounding. No consistent longitudinal loss in lung function was observed with RCF exposure. Smoking, initial weight and weight increase were significant factors. Conclusion No consistent decline was observed longitudinally with exposure to RCF, although cross-sectional and longitudinal findings were discordant. Confounding and accelerated lung function declines with ageing and the correlation of multiple time-dependent variables should be considered in order to minimise error and maximise precision. An innovative statistical methodology for these types of data is described. PMID:20798015

Nicotine Dependence and Alcohol Problems from Adolescence to Young Adulthood.

PubMed

Dierker, Lisa; Selya, Arielle; Rose, Jennifer; Hedeker, Donald; Mermelstein, Robin

Despite the highly replicated relationship between symptoms associated with both alcohol and nicotine, little is known about this association across time and exposure to both drinking and smoking. In the present study, we evaluate if problems associated with alcohol use are related to emerging nicotine dependence symptoms and whether this relationship varies from adolescence to young adulthood, after accounting for both alcohol and nicotine exposure. The sample was drawn from the Social and Emotional Contexts of Adolescent Smoking Patterns Study which measured smoking, nicotine dependence, alcohol use and alcohol related problems over 6 assessment waves spanning 6 years. Analyses were based on repeated assessment of 864 participants reporting some smoking and drinking 30 days prior to individual assessment waves. Mixed-effects regression models were estimated to examine potential time, smoking and/or alcohol varying effects in the association between alcohol problems and nicotine dependence. Inter-individual differences in mean levels of alcohol problems and within subject changes in alcohol problems from adolescence to young adulthood were each significantly associated with nicotine dependence symptoms over and above levels of smoking and drinking behaviour. This association was consistent across both time and increasing levels of smoking and drinking. Alcohol related problems are a consistent risk factor for nicotine dependence over and above measures of drinking and smoking and this association can be demonstrated from the earliest experiences with smoking in adolescents, through the establishment of more regular smoking patterns across the transition to young adulthood. These findings add to accumulating evidence suggesting that smoking and drinking may be related through a mechanism that cannot be wholly accounted for by exposure to either substance.

Dose-time-response association between occupational asbestos exposure and pleural mesothelioma.

PubMed

Lacourt, Aude; Lévêque, Emilie; Guichard, Elie; Gilg Soit Ilg, Anabelle; Sylvestre, Marie-Pierre; Leffondré, Karen

2017-09-01

Early occupational exposure to asbestos has been shown to be associated with an increased risk of pleural mesothelioma (PM), which suggests that the timing of exposure might play a role in the dose-response relationship. However, none studies has evaluated the relative impact of increasing the annual intensity of occupational exposure to asbestos at each time of the whole exposure history. Yet such evaluation would allow the comparison of the risks of PM associated with different longitudinal profiles of occupational exposure to asbestos. Our objective was to estimate the time-dependent relative impact of asbestos exposure intensity over the whole occupational history and to compare the resulting estimated risks of PM associated with different profiles of exposure, using data from a large French case-control study. This study included 1196 male cases recruited in 1987-2006 and 2369 matched controls on birth year. Occupational exposure to asbestos was assessed using a job exposure matrix and represented in logistic regression models using a flexible weighted cumulative index of exposure. Due to much stronger weights of early doses of asbestos exposure, subjects who accumulated 20 fibres/mL over their entire job history with high doses during the first years and low doses thereafter were at higher risk of PM than those who accumulated most of the doses later (OR=2.37 (95% CI 2.01 to 2.87)). This study provides new insights on the dose-time-response relationship between occupational asbestos and PM and illustrates the importance of considering timing of exposure in its association with cancer risk. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Soil mineral alters the effect of Cd on the alkaline phosphatase activity.

PubMed

Tan, Xiangping; He, Yike; Wang, Ziquan; Li, Chenghui; Kong, Long; Tian, Haixia; Shen, Weijun; Megharaj, Mallavarapu; He, Wenxiang

2018-05-30

The toxicity of heavy metals (HMs) to soil enzymes is directly influenced by the status of the enzyme (free vs. immobilized on minerals) and the duration of exposure. However, little information is available on the interaction effect of HMs, mineral, and exposure time on soil enzyme activities. We investigated the interaction mechanism of alkaline phosphatase (ALP) with minerals (montmorillonite and goethite) and the response of free and immobilized ALP to cadmium (Cd) toxicity under different exposure times. The adsorption isotherms of ALP on both minerals were L-type. The maximum adsorption capacity of goethite for ALP was 3.96 times than montmorillonite, although both had similar adsorption constant (K). Goethite showed a greater inhibitory effect on ALP activity than montmorillonite. The toxicity of Cd to free- and goethite-ALP was enhanced with increasing exposure time, indicating a time-dependent inhibition. However, Cd toxicity to montmorillonite-ALP was not affected by the exposure time. The inhibition of Cd to soil enzyme activity is influenced by the properties of mineral complexes and the duration of exposure. A further understanding of the time pattern of HMs toxicity is helpful for accurately assessing the hazards of HMs to soil enzyme activity. Copyright © 2018 Elsevier Inc. All rights reserved.

Consequences of ethanol exposure on cued and contextual fear conditioning and extinction in adulthood differ depending on timing of exposure

PubMed Central

Broadwater, Margaret; Spear, Linda P.

2013-01-01

Some evidence suggests that adolescents are more sensitive than adults to ethanol-induced cognitive deficits and that these effects may be long-lasting. The purpose of Exp 1 was to determine if early-mid adolescent [Postnatal day (P) 28-48] intermittent ethanol exposure would affect later learning and memory in a Pavlovian fear conditioning paradigm differently than comparable exposures in adulthood (P70-90). In Exp 2 animals were exposed to ethanol during mid-late adolescence (P35-55) to assess whether age of initiation within the adolescent period would influence learning and memory differentially. Male Sprague-Dawley rats were given 4 g/kg i.g. ethanol (25%) or water every 48 hours for a total of 11 exposures. After a 22 day non-ethanol period, animals were fear conditioned to a context (relatively hippocampal-dependent task) or tone (amygdala-dependent task), followed by retention tests and extinction (mPFC-dependent) of this conditioning. Despite similar acquisition, a deficit in context fear retention was evident in animals exposed to ethanol in early adolescence, an effect not observed after a comparable ethanol exposure in mid-late adolescence or adulthood. In contrast, animals that were exposed to ethanol in mid-late adolescence or adulthood showed enhanced resistance to context extinction. Together these findings suggest that repeated ethanol imparts long-lasting consequences on learning and memory, with outcomes that differ depending on age of exposure. These results may reflect differential influence of ethanol on the brain as it changes throughout ontogeny and may have implications for alcohol use not only throughout the developmental period of adolescence, but also in adulthood. PMID:23938333

Clove oil as an anaesthetic for adult sockeye salmon: Field trials

USGS Publications Warehouse

Woody, C.A.; Nelson, Jack L.; Ramstad, K.

2002-01-01

Wild migrating sockeye salmon Oncorhynchus nerka exposed to 20, 50 and 80 mg 1-1 of clove oil could be handled within 3 min, recovered within 10 min, and survived 15 min exposure trials. Fish tested at 110 mg 1-1 did not recover from 15 min exposure trials. Response curves developed for induction and recovery time considered the following predictors: clove oil concentration, sex, fish length and depth. A significant positive dependence was observed between induction time and fish length for 20, 50 and 80 mg 1-1 test concentrations; no dependence was observed between induction time and length at 110 and 140 mg 1-1. Recovery time differed as a function of clove oil concentration, but not fish size. A concentration of 50 mg 1-1 is recommended for anaesthetizing sockeye salmon ranging in length from 400 to 550 mm at water temperatures averaging 9-10??C.

SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

EPA Science Inventory

The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

Inhibition of cancer cell growth by exposure to a specific time-varying electromagnetic field involves T-type calcium channels.

PubMed

Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

2015-01-01

Electromagnetic field (EMF) exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca(2+) influx which could be blocked by inhibitors of voltage-gated T-type Ca(2+) channels. Blocking Ca(2+) uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca(2+) influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy.

Inhibition of Cancer Cell Growth by Exposure to a Specific Time-Varying Electromagnetic Field Involves T-Type Calcium Channels

PubMed Central

Buckner, Carly A.; Buckner, Alison L.; Koren, Stan A.; Persinger, Michael A.; Lafrenie, Robert M.

2015-01-01

Electromagnetic field (EMF) exposures affect many biological systems. The reproducibility of these effects is related to the intensity, duration, frequency, and pattern of the EMF. We have shown that exposure to a specific time-varying EMF can inhibit the growth of malignant cells. Thomas-EMF is a low-intensity, frequency-modulated (25-6 Hz) EMF pattern. Daily, 1 h, exposures to Thomas-EMF inhibited the growth of malignant cell lines including B16-BL6, MDA-MB-231, MCF-7, and HeLa cells but did not affect the growth of non-malignant cells. Thomas-EMF also inhibited B16-BL6 cell proliferation in vivo. B16-BL6 cells implanted in syngeneic C57b mice and exposed daily to Thomas-EMF produced smaller tumours than in sham-treated controls. In vitro studies showed that exposure of malignant cells to Thomas-EMF for > 15 min promoted Ca2+ influx which could be blocked by inhibitors of voltage-gated T-type Ca2+ channels. Blocking Ca2+ uptake also blocked Thomas-EMF-dependent inhibition of cell proliferation. Exposure to Thomas-EMF delayed cell cycle progression and altered cyclin expression consistent with the decrease in cell proliferation. Non-malignant cells did not show any EMF-dependent changes in Ca2+ influx or cell growth. These data confirm that exposure to a specific EMF pattern can affect cellular processes and that exposure to Thomas-EMF may provide a potential anti-cancer therapy. PMID:25875081

Personal carbon monoxide exposure in five European cities and its determinants

NASA Astrophysics Data System (ADS)

Georgoulis, L. B.; Hänninen, O.; Samoli, E.; Katsouyanni, K.; Künzli, N.; Polanska, L.; Bruinen de Bruin, Y.; Alm, S.; Jantunen, M.

Studies involving carbon monoxide (CO) exposure assessment are mainly based on measurements at outdoor fixed sites or in various indoor micro-environments. Few studies have been based on personal exposure measurements. In this paper, we report results on personal measurements of CO in five European cities and we investigate determinants which may influence this personal exposure. Within the multi-centre European EXPOLIS study, personal exposure to CO, measured every minute for 48 h, of 401 randomly selected study participants (mainly non-smokers) was monitored in Athens, Basle, Helsinki, Milan and Prague. Each participant also completed a time-microenvironment-activity diary and an extended questionnaire. In addition, for the same time period, ambient levels of CO from fixed site stations were collected. There are significant differences in both personal exposure and ambient levels within the five cities, ranging from high values in Milan and Athens to low in Helsinki. Ambient levels are a significant correlate and determinant of CO 48-h personal exposure in all cities. From the other determinants studied (time spent in street traffic, time of exposure to ETS and time of exposure to gas burning devices) none was consistently significant for all cities. Change of the ambient CO levels from the 25th to the 75th percentile of its distribution resulted in a 1.5-2 fold increase of 48-h personal exposure. Short time personal exposure was also studied in order to assess the influence of specific sources. Exposure levels were significantly higher when participants were in street traffic and in indoor locations in the presence of smokers. Personal 48-h exposure of non-smokers to CO varies among urban populations depending primarily on the ambient levels. For a CO source to be a significant determinant of the personal 48-h CO exposure, it has to affect the levels of CO in the person's proximity for an adequate length of time. Activities of individuals affect shorter term personal exposure.

Prenatal Cocaine Disrupts Serotonin Signaling-Dependent Behaviors: Implications for Sex Differences, Early Stress and Prenatal SSRI Exposure

PubMed Central

Williams, Sarah K; Lauder, Jean M; Johns, Josephine M

2011-01-01

Prenatal cocaine (PC) exposure negatively impacts the developing nervous system, including numerous changes in serotonergic signaling. Cocaine, a competitive antagonist of the serotonin transporter, similar to selective serotonin reuptake inhibitors (SSRIs), also blocks dopamine and norepinephrine transporters, leaving the direct mechanism through which cocaine disrupts the developing serotonin system unclear. In order to understand the role of the serotonin transporter in cocaine’s effect on the serotonergic system, we compare reports concerning PC and prenatal antidepressant exposure and conclude that PC exposure affects many facets of serotonergic signaling (serotonin levels, receptors, transporters) and that these effects differ significantly from what is observed following prenatal SSRI exposure. Alterations in serotonergic signaling are dependent on timing of exposure, test regimens, and sex. Following PC exposure, behavioral disturbances are observed in attention, emotional behavior and stress response, aggression, social behavior, communication, and like changes in serotonergic signaling, these effects depend on sex, age and developmental exposure. Vulnerability to the effects of PC exposure can be mediated by several factors, including allelic variance in serotonergic signaling genes, being male (although fewer studies have investigated female offspring), and experiencing the adverse early environments that are commonly coincident with maternal drug use. Early environmental stress results in disruptions in serotonergic signaling analogous to those observed with PC exposure and these may interact to produce greater behavioral effects observed in children of drug-abusing mothers. We conclude that based on past evidence, future studies should put a greater emphasis on including females and monitoring environmental factors when studying the impact of PC exposure. PMID:22379462

Reliability, resilience and vulnerability criteria for the evaluation of time-dependent health risks: A hypothetical case study of wellhead protection

NASA Astrophysics Data System (ADS)

Rodak, C. M.; Silliman, S. E.; Bolster, D.

2012-12-01

A hypothetical case study of groundwater contaminant protection was carried out using time-dependent health risk calculations. The case study focuses on a hypothetical zoning project for parcels of land around a well field in northern Indiana, where the control of cancer risk relative to a mandated cancer risk threshold is of concern in the management strategy. Within our analysis, we include both uncertainty in the subsurface transport and variability in population behavior in the calculation of time-dependent health risks. From these results we introduce risk maps, a visual representation of the probability of an unacceptable health risk as a function of population behavior and the time at which exposure to the contaminant begins. We also evaluate the time-dependent risks with three criteria from water resource literature: reliability, resilience, and vulnerability (RRV). With respect to health risk from a groundwater well, the three criteria determine: the probability that a well produces safe water (reliability), the probability that a contaminated well returns to an uncontaminated state within a specified time interval (resilience), and the overall severity in terms of health impact of the contamination at a well head (vulnerability). The results demonstrate that the distributions of RRV values for each parcel of land are linked to the time-dependent concentration profile of the contaminant at the well, and the toxicological characteristics of the contaminant. The proposed time-dependent risk calculation expands on current techniques to include a continuous exposure start time, capable of reproducing the maximum risk while providing information on the severity and duration of health risks. Overall this study suggests that, especially in light of the inherent complexity of health-groundwater systems, RRV are viable criteria for relatively simple and effective evaluation of time-dependent health risk. It is argued that the RRV approach, as applied to consideration of potential health impact, allows for more informed, health-based decisions regarding zoning for wellhead protection.

Understanding the exposure-time effect on speckle contrast measurements for laser displays

NASA Astrophysics Data System (ADS)

Suzuki, Koji; Kubota, Shigeo

2018-02-01

To evaluate the influence of exposure time on speckle noise for laser displays, speckle contrast measurement method was developed observable at a human eye response time using a high-sensitivity camera which has a signal multiplying function. The nonlinearity of camera light sensitivity was calibrated to measure accurate speckle contrasts, and the measuring lower limit noise of speckle contrast was improved by applying spatial-frequency low pass filter to the captured images. Three commercially available laser displays were measured over a wide range of exposure times from tens of milliseconds to several seconds without adjusting the brightness of laser displays. The speckle contrast of raster-scanned mobile projector without any speckle-reduction device was nearly constant over various exposure times. On the contrary to this, in full-frame projection type laser displays equipped with a temporally-averaging speckle-reduction device, some of their speckle contrasts close to the lower limits noise were slightly increased at the shorter exposure time due to the noise. As a result, the exposure-time effect of speckle contrast could not be observed in our measurements, although it is more reasonable to think that the speckle contrasts of laser displays, which are equipped with the temporally-averaging speckle-reduction device, are dependent on the exposure time. This discrepancy may be attributed to the underestimation of temporal averaging factor. We expected that this method is useful for evaluating various laser displays and clarify the relationship between the speckle noise and the exposure time for a further verification of speckle reduction.

Exposure matrix development for the Libby cohort.

PubMed

Noonan, C W

2006-11-01

The Libby, MT, cohort includes current and former residents with potential historical exposure to asbestos-contaminated vermiculite. This cohort includes individuals with a broad range of exposure experiences and work histories. While both occupational and nonoccupational exposure pathways were found to be relevant in recent investigations of health effects among this cohort, there has not been a comprehensive approach to characterizing these varied exposure pathways. Any approach toward assessing historical exposures among this population must account for three general categories: (1) occupational exposures, (2) residential exposures, and (3) exposures related to a variety of nonoccupational activities thought to be associated with vermiculite/asbestos exposure in this community. First, a job exposure matrix is commonly used in occupational epidemiology to assess historical worker exposures, allowing for the incorporation of numerous occupational categories and weighting factors applied to specific jobs for different time periods. Second, residential exposures can best be quantified by integrating individuals' residential histories with data on environmental asbestos contamination in the community. Previous soil or sediment sampling as well as air modeling could inform estimates of time- and spatial-dependent exposure concentrations for a residential exposure matrix. Finally, exposure opportunities due to nonoccupational activities could be weighted by factors such as time, geography, environmental sampling, and an assessment of the relative importance for each pathway. These three matrices for occupational, residential, and activity exposure pathways could be combined or used separately to provide a more comprehensive and quantitative, or semiquantitative, assessment of individual exposure in future epidemiological studies of this cohort.

Organ doses from radionuclides on the ground. Part I. Simple time dependences

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jacob, P.; Paretzke, H.G.; Rosenbaum, H.

1988-06-01

Organ dose equivalents of mathematical, anthropomorphical phantoms ADAM and EVA for photon exposures from plane sources on the ground have been calculated by Monte Carlo photon transport codes and tabulated in this article. The calculation takes into account the air-ground interface and a typical surface roughness, the energy and angular dependence of the photon fluence impinging on the phantom and the time dependence of the contributions from daughter nuclides. Results are up to 35% higher than data reported in the literature for important radionuclides. This manuscript deals with radionuclides, for which the time dependence of dose equivalent rates and dosemore » equivalents may be approximated by a simple exponential. A companion manuscript treats radionuclides with non-trivial time dependences.« less

Translation of Toxicity Data into CW Agent Toxicity Estimates

DTIC Science & Technology

2003-07-01

UNLIMITED UNCLASSIFIED/UNLIMITEDPrepared by Douglas R. Sommerville, PE US Army ECBC, APG, MD Dependence of Toxic Effect on Exposure Time Inhalation (IH...to longer exposure durations. Toxicity estimates for exposure durations ranging from 2 to 360 minutes have been derived for six agents (GA, GB, GD...individuals having effects greater in severity than the defining effect of the ECTYY Cn T = k Toxic load equation 5 6 Edgewood Chemical Biological Center

Early-Life Phthalate Exposure and Adiposity at 8 Years of Age.

PubMed

Shoaff, Jessica; Papandonatos, George D; Calafat, Antonia M; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P; Yolton, Kimberly; Braun, Joseph M

2017-09-11

Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. In 219 mother-child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1-8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate-adiposity associations at each visit, test differences in phthalate-adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): -4.8, -0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022.

Early-Life Phthalate Exposure and Adiposity at 8 Years of Age

PubMed Central

Papandonatos, George D.; Calafat, Antonia M.; Ye, Xiaoyun; Chen, Aimin; Lanphear, Bruce P.; Yolton, Kimberly; Braun, Joseph M.

2017-01-01

Background: Early-life phthalate exposure may influence child adiposity, but prior studies have not determined if there are periods of enhanced vulnerability to phthalates. Objective: To examine the relationship between child adiposity at 8 y of age and repeated urinary biomarkers of phthalate exposure from gestation through childhood to determine if there are distinct periods of vulnerability. Methods: In 219 mother–child pairs from Cincinnati, Ohio, we quantified nine urinary phthalate metabolites up to two times prenatally and six times from 1–8 y of age. We measured child body mass index (BMI), waist circumference, and percent body fat at 8 y of age. To identify periods of vulnerability, we used two statistical methods to estimate phthalate–adiposity associations at each visit, test differences in phthalate–adiposity associations across visits, and model trajectories of phthalate concentrations for children at different levels of adiposity. Results: Prenatal phthalate concentrations were not associated with excess child adiposity. Monobenzyl phthalate (MBzP) concentrations during pregnancy and childhood were inversely associated with adiposity. The associations of di(2-ethylhexyl) phthalate (∑DEHP) metabolites and monoethyl phthalate (MEP) with child adiposity depended on the timing of exposure. A 10-fold increase in ∑DEHP at 1 and 5 y was associated with a 2.7% decrease [95% confidence interval (CI): −4.8, −0.5] and 2.9% increase (95% CI: 0.3, 5.5) in body fat, respectively. MEP concentrations at 5 and 8 y of age were associated with higher child adiposity, but earlier childhood concentrations were not. Conclusion: In this cohort, we did not find evidence of an obesogenic effect of prenatal phthalate exposure. Positive associations between postnatal MEP and ∑DEHP concentrations depended on the timing of exposure. https://doi.org/10.1289/EHP1022 PMID:28935615

The Transient Dermal Exposure II: Post-Exposure Absorption and Evaporation of Volatile Compounds

PubMed Central

FRASCH, H. FREDERICK; BUNGE, ANNETTE L.

2016-01-01

The transient dermal exposure is one where the skin is exposed to chemical for a finite duration, after which the chemical is removed and no residue remains on the skin’s surface. Chemical within the skin at the end of the exposure period can still enter the systemic circulation. If it has some volatility, a portion of it will evaporate from the surface before it has a chance to be absorbed by the body. The fate of this post-exposure “skin depot” is the focus of this theoretical study. Laplace domain solutions for concentration distribution, flux, and cumulative mass absorption and evaporation are presented, and time domain results are obtained through numerical inversion. The Final Value Theorem is applied to obtain the analytical solutions for the total fractional absorption by the body and evaporation from skin at infinite time following a transient exposure. The solutions depend on two dimensionless variables: χ, the ratio of evaporation rate to steady-state dermal permeation rate; and the ratio of exposure time to membrane lag time. Simple closed form algebraic equations are presented that closely approximate the complete analytical solutions. Applications of the theory to the dermal risk assessment of pharmaceutical, occupational, and environmental exposures are presented for four example chemicals. PMID:25611182

Modelling survival: exposure pattern, species sensitivity and uncertainty

PubMed Central

Ashauer, Roman; Albert, Carlo; Augustine, Starrlight; Cedergreen, Nina; Charles, Sandrine; Ducrot, Virginie; Focks, Andreas; Gabsi, Faten; Gergs, André; Goussen, Benoit; Jager, Tjalling; Kramer, Nynke I.; Nyman, Anna-Maija; Poulsen, Veronique; Reichenberger, Stefan; Schäfer, Ralf B.; Van den Brink, Paul J.; Veltman, Karin; Vogel, Sören; Zimmer, Elke I.; Preuss, Thomas G.

2016-01-01

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans. PMID:27381500

Elevated Radiation Exposure Associated With Above Surface Flat Detector Mini C-Arm Use.

PubMed

Martin, Dennis P; Chapman, Talia; Williamson, Christopher; Tinsley, Brian; Ilyas, Asif M; Wang, Mark L

2017-11-01

This study aims to test the hypothesis that: (1) radiation exposure is increased with the intended use of Flat Surface Image Intensifier (FSII) units above the operative surface compared with the traditional below-table configuration; (2) this differential increases in a dose-dependent manner; and (3) radiation exposure varies with body part and proximity to the radiation source. A surgeon mannequin was seated at a radiolucent hand table, positioned for volar distal radius plating. Thermoluminescent dosimeters measured exposure to the eyes, thyroid, chest, hand, and groin, for 1- and 15-minute trials from a mini C-arm FSII unit positioned above and below the operating surface. Background radiation was measured by control dosimeters placed within the operating theater. At 1-minute of exposure, hand and eye dosages were significantly greater with the flat detector positioned above the table. At 15-minutes of exposure, hand radiation dosage exceeded that of all other anatomic sites with the FSII in both positions. Hand exposure was increased in a dose-dependent manner with the flat detector in either position, whereas groin exposure saw a dose-dependent only with the flat detector beneath the operating table. These findings suggest that the surgeon's hands and eyes may incur greater radiation exposure compared with other body parts, during routine mini C-arm FSII utilization in its intended position above the operating table. The clinical impact of these findings remains unclear, and future long-term radiation safety investigation is warranted. Surgeons should take precautions to protect critical body parts, particularly when using FSII technology above the operating with prolonged exposure time.

Time allocation shifts and pollutant exposure due to traffic congestion: an analysis using the national human activity pattern survey.

PubMed

Zhang, Kai; Batterman, Stuart A

2009-10-15

Traffic congestion increases air pollutant exposures of commuters and urban populations due to the increased time spent in traffic and the increased vehicular emissions that occur in congestion, especially "stop-and-go" traffic. Increased time in traffic also decreases time in other microenvironments, a trade-off that has not been considered in previous time activity pattern (TAP) analyses conducted for exposure assessment purposes. This research investigates changes in time allocations and exposures that result from traffic congestion. Time shifts were derived using data from the National Human Activity Pattern Survey (NHAPS), which was aggregated to nine microenvironments (six indoor locations, two outdoor locations and one transport location). After imputing missing values, handling outliers, and conducting other quality checks, these data were stratified by respondent age, employment status and period (weekday/weekend). Trade-offs or time-shift coefficients between time spent in vehicles and the eight other microenvironments were then estimated using robust regression. For children and retirees, congestion primarily reduced the time spent at home; for older children and working adults, congestion shifted the time spent at home as well as time in schools, public buildings, and other indoor environments. Changes in benzene and PM(2.5) exposure were estimated for the current average travel delay in the U.S. (9 min day(-1)) and other scenarios using the estimated time shifts coefficients, concentrations in key microenvironments derived from the literature, and a probabilistic analysis. Changes in exposures depended on the duration of the congestion and the pollutant. For example, a 30 min day(-1) travel delay was determined to account for 21+/-12% of current exposure to benzene and 14+/-8% of PM(2.5) exposure. The time allocation shifts and the dynamic approach to TAPs improve estimates of exposure impacts from congestion and other recurring events.

Contribution to volatile organic compound exposures from time spent in stores and restaurants and bars.

PubMed

Loh, Miranda M; Houseman, E Andres; Levy, Jonathan I; Spengler, John D; Bennett, Deborah H

2009-11-01

Many people spend time in stores and restaurants, yet there has been little investigation of the influence of these microenvironments on personal exposure. Relative to the outdoors, transportation, and the home, these microenvironments have high concentrations of several volatile organic compounds (VOCs). We developed a stochastic model to examine the effect of VOC concentrations in these microenvironments on total personal exposure for (1) non-smoking adults working in offices who spend time in stores and restaurants or bars and (2) non-smoking adults who work in these establishments. We also compared the effect of working in a smoking versus non-smoking restaurant or bar. Input concentrations for each microenvironment were developed from the literature whereas time activity inputs were taken from the National Human Activity Patterns Survey. Time-averaged exposures were simulated for 5000 individuals over a weeklong period for each analysis. Mean contributions to personal exposure from non-working time spent in stores and restaurants or bars range from <5% to 20%, depending on the VOC and time-activity patterns. At the 95th percentile of the distribution of the proportion of personal exposure attributable to time spent in stores and restaurants or bars, these microenvironments can be responsible for over half of a person's total exposure to certain VOCs. People working in restaurants or bars where smoking is allowed had the highest fraction of exposure attributable to their workplace. At the median, people who worked in stores or restaurants tended to have 20-60% of their total exposures from time spent at work. These results indicate that stores and restaurants can be large contributors to personal exposure to VOCs for both workers in those establishments and for a subset of people who visit these places, and that incorporation of these non-residential microenvironments can improve models of personal exposure distributions.

Reversal of prenatal morphine exposure-induced memory deficit in male but not female rats.

PubMed

Nasiraei-Moghadam, Shiva; Sherafat, Mohammad Amin; Safari, Mir-Shahram; Moradi, Fatemeh; Ahmadiani, Abolhassan; Dargahi, Leila

2013-05-01

Impaired memory performance in offspring is one of the long-lasting neurobehavioral consequences of prenatal opiate exposure. Here, we studied the effects of prenatal morphine exposure on inhibitory avoidance memory performance in male and female offspring and also investigated whether these deficits are reversible during the postnatal development. Pregnant Wistar rats received morphine sulfate through drinking water, from the first day of gestation up to the day 13, M₁₋₁₃, or to the time of delivery, M₁₋₂₁. Four- and ten-week-old (adolescent and adult, respectively) male and female offspring were subjected to behavioral assays and then analysis of proteins involved in apoptosis or in synaptic plasticity. Results revealed that adolescent and adult female rats failed in passive avoidance retention task in both M₁₋₁₃ and M₁₋₂₁ groups. Adolescent and adult male offspring were similar to control animals in M₁₋₁₃ group. However M₁₋₂₁ impaired retention task in prepubertal male offspring, and this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2 ratio and cleaved caspase-3 were significantly increased in both M₁₋₁₃ and M₁₋₂₁ adolescent and adult female rats, but only in M₁₋₂₁ adolescent male rats. Furthermore, prenatal morphine exposure reduced the expression of brain-derived neurotrophic factor precursor protein in adolescent and adult female offspring and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin-dependent kinase II ratio in adolescent male and female rats. Altogether, the results show that prenatal morphine exposure, depending on the time or duration of exposure, has distinct effects on male and female rats, and postnatal development may reverse these deficits more likely in males.

Light at night acutely impairs glucose tolerance in a time-, intensity- and wavelength-dependent manner in rats.

PubMed

Opperhuizen, Anne-Loes; Stenvers, Dirk J; Jansen, Remi D; Foppen, Ewout; Fliers, Eric; Kalsbeek, Andries

2017-07-01

Exposure to light at night (LAN) has increased dramatically in recent decades. Animal studies have shown that chronic dim LAN induced obesity and glucose intolerance. Furthermore, several studies in humans have demonstrated that chronic exposure to artificial LAN may have adverse health effects with an increased risk of metabolic disorders, including type 2 diabetes. It is well-known that acute exposure to LAN affects biological clock function, hormone secretion and the activity of the autonomic nervous system, but data on the effects of LAN on glucose homeostasis are lacking. This study aimed to investigate the acute effects of LAN on glucose metabolism. Male Wistar rats were subjected to i.v. glucose or insulin tolerance tests while exposed to 2 h of LAN in the early or late dark phase. In subsequent experiments, different light intensities and wavelengths were used. LAN exposure early in the dark phase at ZT15 caused increased glucose responses during the first 20 min after glucose infusion (p < 0.001), whereas LAN exposure at the end of the dark phase, at ZT21, caused increased insulin responses during the first 10 min (p < 0.01), indicating that LAN immediately induces glucose intolerance in rats. Subsequent experiments demonstrated that the effect of LAN was both intensity- and wavelength-dependent. White light of 50 and 150 lx induced greater glucose responses than 5 and 20 lx, whereas all intensities other than 5 lx reduced locomotor activity. Green light induced glucose intolerance, but red and blue light did not, suggesting the involvement of a specific retina-brain pathway. Together, these data show that exposure to LAN has acute adverse effects on glucose metabolism in a time-, intensity- and wavelength-dependent manner.

Human responses to bright light of different durations.

PubMed

Chang, Anne-Marie; Santhi, Nayantara; St Hilaire, Melissa; Gronfier, Claude; Bradstreet, Dayna S; Duffy, Jeanne F; Lockley, Steven W; Kronauer, Richard E; Czeisler, Charles A

2012-07-01

Light exposure in the early night induces phase delays of the circadian rhythm in melatonin in humans. Previous studies have investigated the effect of timing, intensity, wavelength, history and pattern of light stimuli on the human circadian timing system. We present results from a study of the duration–response relationship to phase-delaying bright light. Thirty-nine young healthy participants (16 female; 22.18±3.62 years) completed a 9-day inpatient study. Following three baseline days, participants underwent an initial circadian phase assessment procedure in dim light (<3 lux), and were then randomized for exposure to a bright light pulse (∼10,000 lux) of 0.2 h, 1.0 h, 2.5 h or 4.0 h duration during a 4.5 h controlled-posture episode centred in a 16 h wake episode. After another 8 h sleep episode, participants completed a second circadian phase assessment. Phase shifts were calculated from the difference in the clock time of the dim light melatonin onset (DLMO) between the initial and final phase assessments. Exposure to varying durations of bright light reset the circadian pacemaker in a dose-dependent, non-linear manner. Per minute of exposure, the 0.2 h duration was over 5 times more effective at phase delaying the circadian pacemaker (1.07±0.36 h) as compared with the 4.0 h duration (2.65±0.24 h). Acute melatonin suppression and subjective sleepiness also had a dose-dependent response to light exposure duration. These results provide strong evidence for a non-linear resetting response of the human circadian pacemaker to light duration.

Acute inhalative exposure assessment: derivation of guideline levels with special regard to sensitive subpopulations and time scaling.

PubMed

Mielke, Hans; Gundert, Anna; Abraham, Klaus; Gundert-Remy, Ursula

2005-10-30

Risk assessment for acute airborne exposure to volatile organic compounds (VOCs), including exposure to chemical warfare agents, requires consideration of local and systemic effects at high concentrations. The operating procedure developed by the US Acute Exposure Guideline Level (AEGL) committee has gained special attention, in part because of the international collaboration in the project. The procedure defines three levels (AEGL-1: discomfort; AEGL-2: irreversible or other serious, long-lasting adverse effects; AEGL-3: life-threatening effects or death) for different exposure times (10 and 30 min, and 1, 4 and 8 h). In this article, the methodology for deriving AEGL values is reported. Extending the areas covered by the existing AEGL methodology, sensitive subpopulations are dealt with in more detail. Sensitive persons are expected to suffer from stronger effects when exposed to a given external concentration. Using a kinetic model with the sample substance dichloromethane (DCM), the higher internal exposure of children is quantified and compared to a healthy, young adult. The difference is shown to depend on age, on dose, and on duration of exposure. Furthermore, several ways are presented to derive AEGL values for exposure times which differ from the exposure duration in animal studies ('time scaling'). In comparison to the conventional procedure, the alternative approaches are based on mechanistic models of the toxicodynamic effect. Use of these models results in AEGL values which are biologically justified.

Cognitive effects of radiation emitted by cellular phones: the influence of exposure side and time.

PubMed

Luria, Roy; Eliyahu, Ilan; Hareuveny, Ronen; Margaliot, Menachem; Meiran, Nachshon

2009-04-01

This study examined the time dependence effects of exposure to radiofrequency radiation (RFR) emitted by standard GSM cellular phones on the cognitive functions of humans. A total of 48 healthy right-handed male subjects performed a spatial working memory task (that required either a left-hand or a right-hand response) while being exposed to one of two GSM phones placed at both sides of the head. The subjects were randomly divided into three groups. Each group was exposed to one of three exposure conditions: left-side of the head, right-side, or sham-exposure. The experiment consisted of 12 blocks of trials. Response times (RTs) and accuracy of the responses were recorded. It was found that the average RT of the right-hand responses under left-side exposure condition was significantly longer than those of the right-side and sham-exposure groups averaged together during the first two time blocks. These results confirmed the existence of an effect of exposure on RT, as well as the fact that exposure duration (together with the responding hand and the side of exposure) may play an important role in producing detectable RFR effects on performance. Differences in these parameters might be the reason for the failure of certain studies to detect or replicate RFR effects. (c) 2008 Wiley-Liss, Inc.

Chronic intermittent ethanol exposure and withdrawal alters (3α,5α)-3-hydroxy-pregnan-20-one immunostaining in cortical and limbic brain regions of C57BL/6J mice.

PubMed

Maldonado-Devincci, Antoniette M; Cook, Jason B; O'Buckley, Todd K; Morrow, Danielle H; McKinley, Raechel E; Lopez, Marcelo F; Becker, Howard C; Morrow, A Leslie

2014-10-01

The GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) has been studied during withdrawal from ethanol (EtOH) in humans, rats, and mice. Serum 3α,5α-THP levels decreased, and brain levels were not altered following acute EtOH administration (2 g/kg) in male C57BL/6J mice; however, the effects of chronic intermittent ethanol (CIE) exposure on 3α,5α-THP levels have not been examined. Given that CIE exposure changes subsequent voluntary EtOH drinking in a time-dependent fashion following repeated cycles of EtOH exposure, we conducted a time-course analysis of CIE effects on 3α,5α-THP levels in specific brain regions known to influence drinking behavior. Adult male C57BL/6J mice were exposed to 4 cycles of CIE to induce EtOH dependence. All mice were sacrificed and perfused at 1 of 2 time points, 8 or 72 hours following the final exposure cycle. Free-floating brain sections (40 μm; 3 to 5 sections/region/animal) were immunostained and analyzed to determine relative levels of cellular 3α,5α-THP. Withdrawal from CIE exposure produced time-dependent and region-specific effects on immunohistochemical detection of 3α,5α-THP levels across cortical and limbic brain regions. A transient reduction in 3α,5α-THP immunoreactivity was observed in the central nucleus of the amygdala 8 hours after withdrawal from CIE (-31.4 ± 9.3%). Decreases in 3α,5α-THP immunoreactivity were observed 72 hours following withdrawal in the medial prefrontal cortex (-25.0 ± 9.3%), nucleus accumbens core (-29.9 ± 6.6%), and dorsolateral striatum (-18.5 ± 6.0%), while an increase was observed in the CA3 pyramidal cell layer of the hippocampus (+42.8 ± 19.5%). Sustained reductions in 3α,5α-THP immunoreactivity were observed at both time points in the lateral amygdala (8 hours -28.3 ± 12.8%; 72 hours -27.5 ± 12.4%) and in the ventral tegmental area (8 hours -26.5 ± 9.9%; 72 hours -31.6 ± 13.8%). These data suggest that specific neuroadaptations in 3α,5α-THP levels may be present in regions of brain that mediate anxiety, stress, and reinforcement relevant to EtOH dependence. The changes that occur at different time points likely modulate neurocircuitry involved in EtOH withdrawal as well as the elevated drinking observed after CIE exposure. Copyright © 2014 by the Research Society on Alcoholism.

Thermoregulation is impaired in an environment without circadian time cues

NASA Technical Reports Server (NTRS)

Fuller, C. A.; Sulzman, F. M.; Moore-Ede, M. C.

1978-01-01

Thirteen adult male squirrel monkeys were restrained to a metabolism chair for periods of two or more weeks within an isolation chamber having controlled environmental lighting and ambient temperature. The monkeys were subjected to mild 6-hour cold exposures at all circadian phases of the day. It was found that a prominent circadian rhythm in body temperature, regulated against mild cold exposure, was present in those monkeys synchronized in a 24-hour light-dark cycle. Cold exposures were found to produce decreased core body temperatures when the circadian rhythms were free running or when environmental time indicators were not present. It is concluded that the thermoregulating system depends on the internal synchronization of the circadian time-keeping system.

Oxidative damage mediated iNOS and UCP-2 upregulation in rat brain after sub-acute cyanide exposure: dose and time-dependent effects.

PubMed

Bhattacharya, Rahul; Singh, Poonam; John, Jebin Jacob; Gujar, Niranjan L

2018-04-03

Cyanide-induced chemical hypoxia is responsible for pronounced oxidative damage in the central nervous system. The disruption of mitochondrial oxidative metabolism has been associated with upregulation of uncoupling proteins (UCPs). The present study addresses the dose- and time-dependent effect of sub-acute cyanide exposure on various non-enzymatic and enzymatic oxidative stress markers and their correlation with inducible-nitric oxide synthase (iNOS) and uncoupling protein-2 (UCP-2) expression. Animals received (oral) triple distilled water (vehicle control), 0.25 LD50 potassium cyanide (KCN) or 0.50 LD50 KCN daily for 21 d. Animals were sacrificed on 7, 14 and 21 d post-exposure to measure serum cyanide and nitrite, and brain malondialdehyde (MDA), reduced glutathione (GSH), glutathione disulfide (GSSG), cytochrome c oxidase (CCO), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CA) levels, together with iNOS and UCP-2 expression, and DNA damage. The study revealed that a dose- and time-dependent increase in cyanide concentration was accompanied by corresponding CCO inhibition and elevated MDA levels. Decrease in GSH levels was not followed by reciprocal change in GSSG levels. Diminution of SOD, GPx, GR and CA activity was congruent with elevated nitrite levels and upregulation of iNOS and UCP-2 expression, without any DNA damage. It was concluded that long-term cyanide exposure caused oxidative stress, accompanied by upregulation of iNOS. The upregulation of UCP-2 further sensitized the cells to cyanide and accentuated the oxidative stress, which was independent of DNA damage.

Duration and timing of daily light exposure influence the rapid shifting of BALB/cJ mouse circadian locomotor rhythms.

PubMed

Vajtay, Thomas J; St Thomas, Jeremy J; Takacs, Tyrus E; McGann, Eric G; Weber, E Todd

2017-10-01

Photic entrainment of the murine circadian system can typically be explained with a discrete model in which light exposures near dusk and dawn can either advance or delay free-running rhythms to match the external light cycle period. In most mouse strains, the magnitude of those phase shifts is limited to several hours per day; however, the BALB/cJ mouse can re-entrain to large (6-8hour) phase advances of the light/dark cycle. In this study, we demonstrate that the circadian responses of BALB/cJ mice are dependent on duration as well as timing of light exposure, with significantly larger phase shifts resulting from >6-hour light exposures, yet loss of entrainment to photoperiods of <2-3hours per day or to skeleton photoperiods. Intermittent light exposures of the same total duration but distributed differentially over the same period of time as that of a 6-hour phase advance of the light cycle yielded phase shifts of different magnitudes depending on the pattern of exposure. Both negative and positive masking responses to light and darkness, respectively, were exaggerated in BALB/cJ mice under a T7 light cycle, but were not responsible for their rapid re-entrainment to chronic phase shifting of the light dark cycle. These results collectively suggest that the innately jetlag-resistant BALB/cJ mouse circadian system provides an alternative murine model in which to elucidate the limitations of photic entrainment observed in other commonly used strains of mice. Copyright © 2017 Elsevier Inc. All rights reserved.

A generic multi-hazard and multi-risk framework and its application illustrated in a virtual city

NASA Astrophysics Data System (ADS)

Mignan, Arnaud; Euchner, Fabian; Wiemer, Stefan

2013-04-01

We present a generic framework to implement hazard correlations in multi-risk assessment strategies. We consider hazard interactions (process I), time-dependent vulnerability (process II) and time-dependent exposure (process III). Our approach is based on the Monte Carlo method to simulate a complex system, which is defined from assets exposed to a hazardous region. We generate 1-year time series, sampling from a stochastic set of events. Each time series corresponds to one risk scenario and the analysis of multiple time series allows for the probabilistic assessment of losses and for the recognition of more or less probable risk paths. Each sampled event is associated to a time of occurrence, a damage footprint and a loss footprint. The occurrence of an event depends on its rate, which is conditional on the occurrence of past events (process I, concept of correlation matrix). Damage depends on the hazard intensity and on the vulnerability of the asset, which is conditional on previous damage on that asset (process II). Losses are the product of damage and exposure value, this value being the original exposure minus previous losses (process III, no reconstruction considered). The Monte Carlo method allows for a straightforward implementation of uncertainties and for implementation of numerous interactions, which is otherwise challenging in an analytical multi-risk approach. We apply our framework to a synthetic data set, defined by a virtual city within a virtual region. This approach gives the opportunity to perform multi-risk analyses in a controlled environment while not requiring real data, which may be difficultly accessible or simply unavailable to the public. Based on the heuristic approach, we define a 100 by 100 km region where earthquakes, volcanic eruptions, fluvial floods, hurricanes and coastal floods can occur. All hazards are harmonized to a common format. We define a 20 by 20 km city, composed of 50,000 identical buildings with a fixed economic value. Vulnerability curves are defined in terms of mean damage ratio as a function of hazard intensity. All data are based on simple equations found in the literature and on other simplifications. We show the impact of earthquake-earthquake interaction and hurricane-storm surge coupling, as well as of time-dependent vulnerability and exposure, on aggregated loss curves. One main result is the emergence of low probability-high consequences (extreme) events when correlations are implemented. While the concept of virtual city can suggest the theoretical benefits of multi-risk assessment for decision support, identifying their real-world practicality will require the study of real test sites.

Multi-exposure speckle imaging of cerebral blood flow: a pilot clinical study (Conference Presentation)

NASA Astrophysics Data System (ADS)

Richards, Lisa M.; Kazmi, S. M. S.; Olin, Katherine E.; Waldron, James S.; Fox, Douglas J.; Dunn, Andrew K.

2017-03-01

Monitoring cerebral blood flow (CBF) during neurosurgery is essential for detecting ischemia in a timely manner for a wide range of procedures. Multiple clinical studies have demonstrated that laser speckle contrast imaging (LSCI) has high potential to be a valuable, label-free CBF monitoring technique during neurosurgery. LSCI is an optical imaging method that provides blood flow maps with high spatiotemporal resolution requiring only a coherent light source, a lens system, and a camera. However, the quantitative accuracy and sensitivity of LSCI is limited and highly dependent on the exposure time. An extension to LSCI called multi-exposure speckle imaging (MESI) overcomes these limitations, and was evaluated intraoperatively in patients undergoing brain tumor resection. This clinical study (n = 7) recorded multiple exposure times from the same cortical tissue area, and demonstrates that shorter exposure times (≤1 ms) provide the highest dynamic range and sensitivity for sampling flow rates in human neurovasculature. This study also combined exposure times using the MESI model, demonstrating high correlation with proper image calibration and acquisition. The physiological accuracy of speckle-estimated flow was validated using conservation of flow analysis on vascular bifurcations. Flow estimates were highly conserved in MESI and 1 ms exposure LSCI, with percent errors at 6.4% ± 5.3% and 7.2% ± 7.2%, respectively, while 5 ms exposure LSCI had higher errors at 21% ± 10% (n = 14 bifurcations). Results from this study demonstrate the importance of exposure time selection for LSCI, and that intraoperative MESI can be performed with high quantitative accuracy.

The Canadian Human Activity Pattern Survey: report of methods and population surveyed.

PubMed

Leech, J A; Wilby, K; McMullen, E; Laporte, K

1996-01-01

The assessment of health risk due to environmental contaminants depends upon accurate estimates of the distribution of population exposures. Exposure assessment, in turn, requires information on the time people spend in micro-environments and their activities during periods of exposure. This paper describes preliminary results including study methodology and population sampled in a large Canadian survey of time-activity patterns. A 24-hour diary recall survey was performed in 2381 households (representing a 65% response rate) to describe in detail the timing, location and activity pattern of one household member (the adult or child with the next birthday). Four cities (Toronto, Vancouver, Edmonton and Saint John, NB) and their suburbs were sampled by random-digit dialling over a nine-month period in 1994/1995. Supplemental questionnaires inquiring about sociodemographic information, house and household characteristics and potential exposure to toxins in the air and water were also administered. In general, the results show that respondents spend the majority of their time indoors (88.6%) with smaller proportions of time outdoors (6.1%) and in vehicles (5.3%). Children under the age of 12 spend more time both indoors and outdoors and less time in transit than do adults. The data from this study will be used to define more accurately the exposure of Canadians to a variety of toxins in exposure assessment models and to improve upon the accuracy of risk assessment for a variety of acute and chronic health effects known or suspected to be related to environmental exposures.

Dose-dependent fluoxetine effects on boldness in male Siamese fighting fish.

PubMed

Dzieweczynski, Teresa L; Campbell, Brennah A; Kane, Jessica L

2016-03-01

As the use of pharmaceuticals and personal care products (PPCPs) continues to rise, these compounds enter the environment in increasing frequency. One such PPCP, fluoxetine, has been found in detectable amounts in aquatic ecosystems worldwide, where it may interfere with the behavior of exposed organisms. Fluoxetine exposure has been found to influence boldness and exploration in a range of fish species; however, how it might alter behavior in multiple contexts or over time is rarely examined. To this end, the effects of fluoxetine on boldness over time were studied in male Siamese fighting fish. Three different groups of males (0, 0.5 and 5 µg l(-1) fluoxetine) were tested in multiple boldness assays (empty tank, novel environment and shoal) once a week for 3 weeks to collect baseline measures and then at three different time points post-exposure. The effects of these varying exposure amounts on behavior were then examined for overall response, consistency and across-context correlations. Unexposed males were bolder in all contexts, were more consistent within a context, and had stronger between-context correlations than exposed males. Fluoxetine had dose-dependent effects on behavior, as males that received the higher dose exhibited greater behavioral effects. This study stresses the potential fitness consequences of fluoxetine exposure and suggests that examining behavioral effects of PPCPs under different dosing regimens and in multiple contexts is important to gain an increased understanding of how exposure affects behavior. © 2016. Published by The Company of Biologists Ltd.

Concerted application of LC-MS and ligand binding assays to better understand exposure of a large molecule drug.

PubMed

Xu, Weifeng; Jiang, Hao; Titsch, Craig; Gadkari, Snaehal; Batog, Alicja; Wang, Bonnie; Hippeli, Lauren; Yamamoto, Brent; Chadwick, Kristina; Wheeler, Jennifer; Thompson, Chris; Stahl, James; Willett, Scott; DeSilva, Binodh S; Myler, Heather; Dodge, Robert W; Pillutla, Renuka C

2018-06-20

A ligand-binding assay (LBA) was used to measure exposure of PRM-151, the recombinant form of human pentraxin-2 (PTX-2), a complex pentamer with multiple binding partners. However, the assay showed a lack of dose-dependent exposure in select preclinical species and it could not differentiate the infused PRM-151 from the endogenous PTX-2 in nonhuman primates. Instead of assessing interference from its multiple binding partners, which could be time consuming and laborious, a LC-MS assay avoid of these interference was implemented to measure 'total' drug without the use of immunoaffinity capture reagents. The resultant LC-MS data confirmed the original data and the lack of dose-dependent exposure is now understood to be due to the multiple and diverse targets and functions and resultant complex biodistribution rather than an assay artifact.

Moisture effects in heat transfer through clothing systems for wildland firefighters.

PubMed

Lawson, Lelia K; Crown, Elizabeth M; Ackerman, Mark Y; Dale, J Douglas

2004-01-01

Wildland firefighters work in unfavourable environments involving both heat and moisture. Moisture in clothing systems worn by wildland firefighters may increase or decrease heat transfer, depending on its source and location in the clothing system, location on the body, timing of application and degree of sorption. In this experiment, 4 outerwear/underwear combinations were exposed to 1 of 5 different conditions varying on amount and location of moisture. The fabric systems were then exposed to either a high-heat-flux flame exposure (83 kW/m(2)) or a low-heat-flux radiant exposure (10 kW/m(2)). Under high-heat-flux flame exposures, external moisture tended to decrease heat transfer through the fabric systems, while internal moisture tended to increase heat transfer. Under low-heat-flux radiant exposures, internal moisture decreased heat transfer through the fabric systems. The nature and extent of such differences was fabric dependent. Implications for test protocol development are discussed.

Investigating Intergenerational Differences in Human PCB Exposure due to Variable Emissions and Reproductive Behaviors

PubMed Central

Quinn, Cristina L.; Wania, Frank; Czub, Gertje; Breivik, Knut

2011-01-01

Background Reproductive behaviors—such as age of childbearing, parity, and breast-feeding prevalence—have changed over the same historical time period as emissions of polychlorinated biphenyls (PCB) and may produce intergenerational differences in human PCB exposure. Objectives Our goal in this study was to estimate prenatal, postnatal, and lifetime PCB exposures for women at different ages according to year of birth, and to evaluate the impact of reproductive characteristics on intergenerational differences in exposure. Methods We used the time-variant mechanistic model CoZMoMAN to calculate human bioaccumulation of PCBs, assuming both hypothetical constant and realistic time-variant emissions. Results Although exposure primarily depends on when an individual was born relative to the emission history of PCBs, reproductive behaviors can have a significant impact. Our model suggests that a mother’s reproductive history has a greater influence on the prenatal and postnatal exposures of her children than it does on her own cumulative lifetime exposure. In particular, a child’s birth order appears to have a strong influence on their prenatal exposure, whereas postnatal exposure is determined by the type of milk (formula or breast milk) fed to the infant. Conclusions Prenatal PCB exposure appears to be delayed relative to the time of PCB emissions, particularly among those born after the PCB production phaseout. Consequently, the health repercussions of environmental PCBs can be expected to persist for several decades, despite bans on their production for > 40 years. PMID:21156396

Exposure of welders and other metal workers to ELF magnetic fields.

PubMed

Skotte, J H; Hjøllund, H I

1997-01-01

This study assessed exposure to extremely low frequency (ELF) magnetic fields of welders and other metal workers and compared exposure from different welding processes. Exposure to ELF magnetic fields was measured for 50 workers selected from a nationwide cohort of metal workers and 15 nonrandomly selected full-time welders in a shipyard. The measurements were carried out with personal exposure meters during 3 days of work for the metal workers and I day of work for the shipyard welders. To record a large dynamic range of ELF magnetic field values, the measurements were carried out with "high/low" pairs of personal exposure meters. Additional measurements of static magnetic fields at fixed positions close to welding installations were done with a Hall-effect fluxmeter. The total time of measurement was 1273 hours. The metal workers reported welding activity for 5.8% of the time, and the median of the work-period mean exposure to ELF magnetic fields was 0.18 microT. DC metal inert or active gas welding (MIG/MAG) was used 80% of the time for welding, and AC manual metal arc welding (MMA) was used 10% of the time. The shipyard welders reported welding activity for 56% of the time, and the median and maximum of the workday mean exposure to ELF magnetic fields was 4.70 and 27.5 microT, respectively. For full-shift welders the average workday mean was 21.2 microT for MMA welders and 2.3 microT for MIG/MAG welders. The average exposure during the effective time of welding was estimated to be 65 microT for the MMA welding process and 7 microT for the MIG/MAG welding process. The time of exposure above 1 microT was found to be a useful measure of the effective time of welding. Large differences in exposure to ELF magnetic fields were found between different groups of welders, depending on the welding process and effective time of welding. MMA (AC) welding caused roughly 10 times higher exposure to ELF magnetic fields compared with MIG/MAG (DC) welding. The measurements of static fields suggest that the combined exposure to static and ELF fields of MIG/MAG (DC) welders and the exposure to ELF fields of MMA (AC) welders are roughly of the same level.

Recent progresses in outcome-dependent sampling with failure time data.

PubMed

Ding, Jieli; Lu, Tsui-Shan; Cai, Jianwen; Zhou, Haibo

2017-01-01

An outcome-dependent sampling (ODS) design is a retrospective sampling scheme where one observes the primary exposure variables with a probability that depends on the observed value of the outcome variable. When the outcome of interest is failure time, the observed data are often censored. By allowing the selection of the supplemental samples depends on whether the event of interest happens or not and oversampling subjects from the most informative regions, ODS design for the time-to-event data can reduce the cost of the study and improve the efficiency. We review recent progresses and advances in research on ODS designs with failure time data. This includes researches on ODS related designs like case-cohort design, generalized case-cohort design, stratified case-cohort design, general failure-time ODS design, length-biased sampling design and interval sampling design.

Recent progresses in outcome-dependent sampling with failure time data

PubMed Central

Ding, Jieli; Lu, Tsui-Shan; Cai, Jianwen; Zhou, Haibo

2016-01-01

An outcome-dependent sampling (ODS) design is a retrospective sampling scheme where one observes the primary exposure variables with a probability that depends on the observed value of the outcome variable. When the outcome of interest is failure time, the observed data are often censored. By allowing the selection of the supplemental samples depends on whether the event of interest happens or not and oversampling subjects from the most informative regions, ODS design for the time-to-event data can reduce the cost of the study and improve the efficiency. We review recent progresses and advances in research on ODS designs with failure time data. This includes researches on ODS related designs like case–cohort design, generalized case–cohort design, stratified case–cohort design, general failure-time ODS design, length-biased sampling design and interval sampling design. PMID:26759313

Tissue-specific changes in OGG1 and SOD mRNA expression caused by NaOCl exposure in black seabream ( Acanthopagrus schlegelii)

NASA Astrophysics Data System (ADS)

Park, Ho-Ra; Kim, Yong; Yeo, Won-Jun; Kim, Ji-Hye; Han, Kyung-Nam

2017-09-01

The DNA-damage defense mechanism was studied in black seabreams after oxidative stress caused by exposure to sodium hypochlorite (NaOCl). Liver, muscle, and brain tissues were obtained after different NaOCl-exposure times (0, 24, 48, 72, and 96 h) and concentrations (0.5, 1, 1.5, 2, and 3 mg/L), after which oxoguanine glycosylase (OGG1) and superoxide dismutase (SOD) mRNA-expression levels were analyzed. At all NaOCl concentrations tested, liver OGG1 expression increased to a maximum in a time-dependent manner after NaOCl exposure and then decreased. In muscles, OGG1 expression increased over time following exposure to a low concentration of NaOCl (0.5, 1, and 1.5 mg/L), whereas it showed a mixed pattern (both increases and decreases observed) in the high-concentration groups (2 and 3 mg/L). SOD mRNA expression increased over time, both in the liver and muscles. In the brain, both OGG1 and SOD mRNA expression levels were highest after exposure to the lowest NaOCl concentration (0.5 mg/L), whereas basal levels were maintained over time at higher concentrations. These results indicate that OGG1 and SOD provide resistance to oxidative stress in black seabreams. In addition, continuous exposure to oxidative stress can suppress enzyme expression, suggesting a risk for long-term exposure to NaOCl.

Age-dependent inhibition of pentobarbital sleeping time by ozone in mice and rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Canada, A.T.; Calabrese, E.J.; Leonard, D.

1986-09-01

The effect of age on the metabolism of pentobarbital in mice and rats was investigated following exposure to 0.3 ppm of ozone for 3.75 hr. Young animals were 2.5 months of age and the mature were 18 months. The pentobarbital sleeping time was significantly prolonged following the ozone exposure in both the mice and rats when compared with an air control. No ozone effect on sleeping time was found in the young animals. The results indicate that there may be an age-related sensitivity to the occurrence of ozone-related inhibition of pentobarbital metabolism.

Modeling exposure–lag–response associations with distributed lag non-linear models

PubMed Central

Gasparrini, Antonio

2014-01-01

In biomedical research, a health effect is frequently associated with protracted exposures of varying intensity sustained in the past. The main complexity of modeling and interpreting such phenomena lies in the additional temporal dimension needed to express the association, as the risk depends on both intensity and timing of past exposures. This type of dependency is defined here as exposure–lag–response association. In this contribution, I illustrate a general statistical framework for such associations, established through the extension of distributed lag non-linear models, originally developed in time series analysis. This modeling class is based on the definition of a cross-basis, obtained by the combination of two functions to flexibly model linear or nonlinear exposure-responses and the lag structure of the relationship, respectively. The methodology is illustrated with an example application to cohort data and validated through a simulation study. This modeling framework generalizes to various study designs and regression models, and can be applied to study the health effects of protracted exposures to environmental factors, drugs or carcinogenic agents, among others. © 2013 The Authors. Statistics in Medicine published by John Wiley & Sons, Ltd. PMID:24027094

Mass casualty chemical exposure and implications for respiratory failure.

PubMed

Muskat, Peter C

2008-01-01

Exposure to chemical agents, both deliberate and accidental, over the past 100 years has resulted in the deaths of thousands and a significant number of casualties requiring hospitalization. The respiratory system is an important portal of entry into the human body for many of these agents, and pulmonary symptoms are a hallmark of many chemical exposures. The 4 major chemical warfare agents are: lung-damaging, blood, blister, and nerve compounds. The review will cover historical exposures, signs and symptoms, treatment, and long-term consequences. There are numerous examples of deliberate (as well as accidental) exposure to harmful chemicals, and each incident requires the provider to understand the signs and symptoms of the particular chemical so that the correct treatment is provided. The respiratory implications of these agents appear to be dose and timing dependent, with full recovery often seen if supportive measures and appropriate antidotes are administered in a timely fashion.

Wood Products Thermal Degradation and Fire

Treesearch

Mark Dietenberger; Laura Hasburgh

2016-01-01

As wood reaches elevated temperatures, the different chemical components undergo thermal degradation that affect the performance of wood. The extent of these changes depends on the temperature level and length of time under exposure conditions. Permanent reductions in strength and modulus of elasticity can occur at temperatures >65 °C, with the amount depending...

D-cycloserine combined with cue exposure therapy fails to attenuate subjective and physiological craving in cocaine dependence.

PubMed

Santa Ana, Elizabeth J; Prisciandaro, James J; Saladin, Michael E; McRae-Clark, Aimee L; Shaftman, Stephanie R; Nietert, Paul J; Brady, Kathleen T

2015-04-01

Based on preclinical studies showing that the partial N-methyl-D-aspartate (NMDA) agonist D-cycloserine (DCS) facilitates extinction of cocaine self-administration and cocaine-induced conditioned place preference, we evaluated whether 50 mg of DCS would reduce craving to cocaine cues when combined with cue exposure (CE) in cocaine dependent humans. In this double-blind placebo-controlled pilot study, 47 cocaine dependent participants were randomized to DCS or placebo (PBO), plus CE. Participants received DCS or PBO 30 minutes prior to two CE sessions, conducted one day apart. Craving and heart rate was assessed prior to CE sessions, during CE trials, and after CE trials. These measures were assessed again at a 1-week follow-up (session 3) after the second CE session. DCS failed to significantly attenuate cocaine cue reactivity based on subjective craving and physiological reactivity (heart rate) compared to PBO. The CE protocol, consisting of repeated exposure to drug cues combined with skills training, resulted in extinction to cocaine cues as suggested by decreased craving within and between sessions in both treatment conditions. All participants exhibited elevated heart rate with repeated exposures, demonstrating a potentiation in heart rate between sessions. 50 mg of DCS may not be effective for extinguishing reactivity to drug cues for individuals with cocaine dependence. Future studies examining the effect of DCS on facilitating extinction to drug cues should examine variations in cue exposure length, number of CE presentations, and timing of DCS dose administration prior to cue exposures, which may differentially impact drug cue reactivity. © American Academy of Addiction Psychiatry.

The effects of some hydrophobic gases on the pulmonary surfactant system.

PubMed Central

Daniels, S; Paton, W D; Smith, E B

1979-01-01

1. Decompression from exposures to raised ambient pressure of sulphur hexafluoride, carbon tetrafluoride, hexafluoro-ethane and nitrous oxide results in the formation of dense foam and pulmonary oedema. 2. The degree of pulmonary oedema produced is dependent on the exposure pressure, although the exposure time required is short in comparison to tissue saturation times. 3. The effect is not prevented by atropine, ephedrine or hydrocortisone. 4. The effect is also produced in vitro by saturated solutions of halothane, chloroform and ether. 5. It is suggested that the mechanism of action is physical with physico-chemical factor involved being a differential partition of these gases within the surfactant: membrane complex. PMID:581651

Environmental degradation of 316 stainless steel in high temperature low cycle fatigue

NASA Technical Reports Server (NTRS)

Kalluri, Sreeramesh; Manson, S. Stanford; Halford, Gary R.

1987-01-01

Procedures based on modification of the conventional Strainrange Partitioning method are proposed to characterize the time-dependent degradation of engineering alloys in high-temperature, low-cycle fatigue. Creep-fatigue experiments were conducted in air using different waveforms of loading on 316 stainless steel at 816 C (1500 F) to determine the effect of exposure time on cyclic life. Reductions in the partitioned cyclic lives were observed with an increase in the time of exposure (or with the corresponding decrease in the steady-state creep rate) for all the waveforms involving creep strain. Excellent correlations of the experimental data were obtained by modifying the Conventional Strainrange Partitioning life relationships involving creep strain using a power-law term of either: (1) time of exposure, or (2) steady-state creep rate of the creep-fatigue test. Environmental degradation due to oxidation, material degradation due to the precipitation of carbides along the grain boundaries and detrimental deformation modes associated with the prolonged periods of creep were observed to be the main mechanisms responsible for life reductions at long exposure times.

Effects of Cadmium on Lipid Storage and Metabolism in the Freshwater Crab Sinopotamon henanense

PubMed Central

Yang, Jian; Liu, Dongmei; Jing, Weixin; Dahms, Hans-Uwe; Wang, Lan

2013-01-01

Since environmental effects of molecular traits are often questioned we analyze here the molecular effects of cadmium (Cd) on lipid pathways and their effects on tissues development. Lipids are an important energy source for the developing embryo, and accumulate in the ovary and hepatopancreas of decapod crustaceans. The extend of Cd affecting lipid storage and metabolism, is studied here with the freshwater crabs Sinopotamon henanense. Crabs were exposed to water-born Cd at 1.45, 2.9, 5.8 mg/l for 10, 15, and 20 days. With significantly increased Cd accumulation in exposed crabs, lipid content in hepatopancreas and ovary showed a time-dependent and concentration-dependent reduction, being at least one of the reasons for a lower ovarian index (OI) and hepatopancreatic index (HI). After 10-day exposure increased triglyceride (TG) level in hemolymph and up-regulation of pancreatic lipase (PL) activity in the hepatopancreas suggested an increased nutritional lipid uptake. However, two processes led to lower lipid levels upon Cd exposure: an increased utilization of lipids and a down-regulated lipoprotein lipase (LPL) led to insufficient lipid transport. 10-day Cd exposure also triggered the production of β-nicotinamide adenine dinucleotide 2'-phosphate reduced tetrasodium salt hydrate (NADPH), as well as to the synthesis of adenosine triphosphate (ATP) and fatty acids. With increasing exposure time, the crabs at 15 and 20-day exposure contained less lipid and TG, suggesting that more energy was consumed during the exposure time. Meanwhile, the level of NADPH, ATP and the activity of PL, LPL, fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC) activity was down-regulated suggesting an impairment of the crab metabolism by Cd in addition to causing a lower lipid level. PMID:24130894

Exposure to nature gardens has time-dependent associations with mood improvements for people with mid- and late-stage dementia: Innovative practice.

PubMed

White, Piran Cl; Wyatt, Jonathan; Chalfont, Garuth; Bland, J Martin; Neale, Christopher; Trepel, Dominic; Graham, Hilary

2017-01-01

Exposure to green space and nature has a potential role to play in the care of people with dementia, with possible benefits including improved mood and slower disease progression. In this observational study at a dementia care facility in the UK, we used carer-assessed measures to evaluate change in mood of residents with mid- to late-stage dementia following exposure to a nature garden. We found that exposure to nature was associated with a beneficial change in patient mood. There was a non-linear relationship between time spent outdoors and mood outcome. Improvements in patient mood were associated with relatively short duration exposures to nature, and no additional measureable increases in mood were found with exposures beyond 80-90 minutes duration. Whilst further investigation is required before causality can be determined, these results raise important questions for policy about the integration of outdoor space into the design of dementia care facilities and programmes.

Photothermal damage is correlated to the delivery rate of time-integrated temperature

NASA Astrophysics Data System (ADS)

Denton, Michael L.; Noojin, Gary D.; Gamboa, B. Giovanna; Ahmed, Elharith M.; Rockwell, Benjamin A.

2016-03-01

Photothermal damage rate processes in biological tissues are usually characterized by a kinetics approach. This stems from experimental data that show how the transformation of a specified biological property of cells or biomolecule (plating efficiency for viability, change in birefringence, tensile strength, etc.) is dependent upon both time and temperature. However, kinetic methods require determination of kinetic rate constants and knowledge of substrate or product concentrations during the reaction. To better understand photothermal damage processes we have identified temperature histories of cultured retinal cells receiving minimum lethal thermal doses for a variety of laser and culture parameters. These "threshold" temperature histories are of interest because they inherently contain information regarding the fundamental thermal dose requirements for damage in individual cells. We introduce the notion of time-integrated temperature (Tint) as an accumulated thermal dose (ATD) with units of °C s. Damaging photothermal exposure raises the rate of ATD accumulation from that of the ambient (e.g. 37 °C) to one that correlates with cell death (e.g. 52 °C). The degree of rapid increase in ATD (ΔATD) during photothermal exposure depends strongly on the laser exposure duration and the ambient temperature.

High environmental ammonia exposure has developmental-stage specific and long-term consequences on the cortisol stress response in zebrafish.

PubMed

Williams, Tegan A; Bonham, Luke A; Bernier, Nicholas J

2017-12-01

The capacity for early life environmental stressors to induce programming effects on the endocrine stress response in fish is largely unknown. In this study we determined the effects of high environmental ammonia (HEA) exposure on the stress response in larval zebrafish, assessed the tolerance of embryonic and larval stages to HEA, and evaluated whether early life HEA exposure has long-term consequences on the cortisol response to a novel stressor. Exposure to 500-2000μM NH 4 Cl for 16h did not affect the gene expression of corticotropin-releasing factor (CRF) system components in 1day post-fertilization (dpf) embryos, but differentially increased crfa, crfb and CRF binding protein (crfbp) expression and stimulated both dose- and time-dependent increases in the whole body cortisol of 5dpf larvae. Pre-acclimation to HEA at 1dpf did not affect the cortisol response to a subsequent NH 4 Cl exposure at 5dpf. In contrast, pre-acclimation to HEA at 5dpf caused a small but significant reduction in the cortisol response to a second NH 4 Cl exposure at 10dpf. While continuous exposure to 500-2000μM NH 4 Cl between 0 and 5dpf had a modest effect on mean survival time, exposure to 400-1000μM NH 4 Cl between 10 and 14dpf decreased mean survival time in a dose-dependent manner. Moreover, pre-acclimation to HEA at 5dpf significantly decreased the risk of mortality to continuous NH 4 Cl exposure between 10 and 14dpf. Finally, while HEA at 1dpf did not affect the cortisol stress response to a novel vortex stressor at 5dpf, the same HEA treatment at 5dpf abolished vortex stressor-induced increases in whole body cortisol at 10 and 60dpf. Together these results show that the impact of HEA on the cortisol stress response during development is life-stage specific and closely linked to ammonia tolerance. Further, we demonstrate that HEA exposure at the larval stage can have persistent effects on the capacity to respond to stressors in later life. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of Statistical Approaches for Dealing With Immortal Time Bias in Drug Effectiveness Studies.

PubMed

Karim, Mohammad Ehsanul; Gustafson, Paul; Petkau, John; Tremlett, Helen

2016-08-15

In time-to-event analyses of observational studies of drug effectiveness, incorrect handling of the period between cohort entry and first treatment exposure during follow-up may result in immortal time bias. This bias can be eliminated by acknowledging a change in treatment exposure status with time-dependent analyses, such as fitting a time-dependent Cox model. The prescription time-distribution matching (PTDM) method has been proposed as a simpler approach for controlling immortal time bias. Using simulation studies and theoretical quantification of bias, we compared the performance of the PTDM approach with that of the time-dependent Cox model in the presence of immortal time. Both assessments revealed that the PTDM approach did not adequately address immortal time bias. Based on our simulation results, another recently proposed observational data analysis technique, the sequential Cox approach, was found to be more useful than the PTDM approach (Cox: bias = -0.002, mean squared error = 0.025; PTDM: bias = -1.411, mean squared error = 2.011). We applied these approaches to investigate the association of β-interferon treatment with delaying disability progression in a multiple sclerosis cohort in British Columbia, Canada (Long-Term Benefits and Adverse Effects of Beta-Interferon for Multiple Sclerosis (BeAMS) Study, 1995-2008). © The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stringari, James; Nunes, Adriana K.C.; Franco, Jeferson L.

2008-02-15

During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/l, diluted in drinkingmore » water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PND) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F{sub 2}-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F{sub 2}-isoprostanes levels at all time points. Significant negative correlations were found between F{sub 2}-isoprostanes and GSH, as well as between F{sub 2}-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at birth. Even though the cerebral mercury concentration decreased to nearly basal levels at postnatal day 21, GSH levels, GPx and GR activities remained decreased in MeHg-exposed mice, indicating that prenatal exposure to MeHg affects the cerebral GSH antioxidant systems by inducing biochemical alterations that endure even when mercury tissue levels decrease and become indistinguishable from those noted in pups born to control dams. This study is the first to show that prenatal exposure to MeHg disrupts the postnatal development of the glutathione antioxidant system in the mouse brain, pointing to an additional molecular mechanism by which MeHg induces pro-oxidative damage in the developing CNS. Moreover, our experimental observation corroborates previous reports on the permanent functional deficits observed after prenatal MeHg exposure.« less

Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

PubMed Central

Stringari, James; Nunes, Adriana KC; Franco, Jeferson L; Bohrer, Denise; Garcia, Solange C; Dafre, Alcir L; Milatovic, Dejan; Souza, Diogo O; Rocha, João BT; Aschner, Michael; Farina, Marcelo

2010-01-01

During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/L, diluted in drinking water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PNDs) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F2-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F2-isoprostanes levels at all time points. Significant negative correlations were found between F2-isoprostanes and GSH, as well as between F2-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at birth. Even though the cerebral mercury concentration decreased to nearly basal levels at postnatal day 21, GSH levels, GPx and GR activities remained decreased in MeHg-exposed mice, indicating that prenatal exposure to MeHg affects the cerebral GSH antioxidant systems by inducing biochemical alterations that endure even when mercury tissue levels decrease and become indistinguishable from those noted in pups born to control dams. This study is the first to show that prenatal exposure to MeHg disrupts the postnatal development of the glutathione antioxidant system in the mouse brain, pointing to an additional molecular mechanism by which MeHg induces pro-oxidative damage in the developing CNS. Moreover, our experimental observation corroborates previous reports on the permanent functional deficits observed after prenatal MeHg exposure. PMID:18023834

Exposure of luminous marine bacteria to low-dose gamma-radiation.

PubMed

Kudryasheva, N S; Petrova, A S; Dementyev, D V; Bondar, A A

2017-04-01

The study addresses biological effects of low-dose gamma-radiation. Radioactive 137 Cs-containing particles were used as model sources of gamma-radiation. Luminous marine bacterium Photobacterium phosphoreum was used as a bioassay with the bioluminescent intensity as the physiological parameter tested. To investigate the sensitivity of the bacteria to the low-dose gamma-radiation exposure (≤250 mGy), the irradiation conditions were varied as follows: bioluminescence intensity was measured at 5, 10, and 20°С for 175, 100, and 47 h, respectively, at different dose rates (up to 4100 μGy/h). There was no noticeable effect of gamma-radiation at 5 and 10°С, while the 20°С exposure revealed authentic bioluminescence inhibition. The 20°С results of gamma-radiation exposure were compared to those for low-dose alpha- and beta-radiation exposures studied previously under comparable experimental conditions. In contrast to ionizing radiation of alpha and beta types, gamma-emission did not initiate bacterial bioluminescence activation (adaptive response). As with alpha- and beta-radiation, gamma-emission did not demonstrate monotonic dose-effect dependencies; the bioluminescence inhibition efficiency was found to be related to the exposure time, while no dose rate dependence was found. The sequence analysis of 16S ribosomal RNA gene did not reveal a mutagenic effect of low-dose gamma radiation. The exposure time that caused 50% bioluminescence inhibition was suggested as a test parameter for radiotoxicity evaluation under conditions of chronic low-dose gamma irradiation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Do environmental dynamics matter in fate models? Exploring scenario dynamics for a terrestrial and an aquatic system.

PubMed

Morselli, Melissa; Terzaghi, Elisa; Di Guardo, Antonio

2018-01-24

Nowadays, there is growing interest in inserting more ecological realism into risk assessment of chemicals. On the exposure evaluation side, this can be done by studying the complexity of exposure in the ecosystem, niche partitioning, e.g. variation of the exposure scenario. Current regulatory predictive approaches, to ensure simplicity and predictive ability, generally keep the scenario as static as possible. This could lead to under or overprediction of chemical exposure depending on the chemical and scenario simulated. To account for more realistic exposure conditions, varying temporally and spatially, additional scenario complexity should be included in currently used models to improve their predictive ability. This study presents two case studies (a terrestrial and an aquatic one) in which some polychlorinated biphenyls (PCBs) were simulated with the SoilPlusVeg and ChimERA models to show the importance of scenario variation in time (biotic and abiotic compartments). The results outlined the importance of accounting for planetary boundary layer variation and vegetation dynamics to accurately predict air concentration changes and the timing of chemical dispersion from the source in terrestrial systems. For the aquatic exercise, the results indicated the need to account for organic carbon forms (particulate and dissolved organic carbon) and vegetation biomass dynamics. In both cases the range of variation was up to two orders of magnitude depending on the congener and scenario, reinforcing the need for incorporating such knowledge into exposure assessment.

Disaggregation of nation-wide dynamic population exposure estimates in The Netherlands: Applications of activity-based transport models

NASA Astrophysics Data System (ADS)

Beckx, Carolien; Int Panis, Luc; Uljee, Inge; Arentze, Theo; Janssens, Davy; Wets, Geert

Traditional exposure studies that link concentrations with population data do not always take into account the temporal and spatial variations in both concentrations and population density. In this paper we present an integrated model chain for the determination of nation-wide exposure estimates that incorporates temporally and spatially resolved information about people's location and activities (obtained from an activity-based transport model) and about ambient pollutant concentrations (obtained from a dispersion model). To the best of our knowledge, it is the first time that such an integrated exercise was successfully carried out in a fully operational modus for all models under consideration. The evaluation of population level exposure in The Netherlands to NO 2 at different time-periods, locations, for different subpopulations (gender, socio-economic status) and during different activities (residential, work, transport, shopping) is chosen as a case-study to point out the new features of this methodology. Results demonstrate that, by neglecting people's travel behaviour, total average exposure to NO 2 will be underestimated by 4% and hourly exposure results can be underestimated by more than 30%. A more detailed exposure analysis reveals the intra-day variations in exposure estimates and the presence of large exposure differences between different activities (traffic > work > shopping > home) and between subpopulations (men > women, low socio-economic class > high socio-economic class). This kind of exposure analysis, disaggregated by activities or by subpopulations, per time of day, provides useful insight and information for scientific and policy purposes. It demonstrates that policy measures, aimed at reducing the overall (average) exposure concentration of the population may impact in a different way depending on the time of day or the subgroup considered. From a scientific point of view, this new approach can be used to reduce exposure misclassification.

The protective effect of autophagy on mouse spermatocyte derived cells exposure to 1800MHz radiofrequency electromagnetic radiation.

PubMed

Liu, Kaijun; Zhang, Guowei; Wang, Zhi; Liu, Yong; Dong, Jianyun; Dong, Xiaomei; Liu, Jinyi; Cao, Jia; Ao, Lin; Zhang, Shaoxiang

2014-08-04

The increasing exposure to radiofrequency (RF) radiation emitted from mobile phone use has raised public concern regarding the biological effects of RF exposure on the male reproductive system. Autophagy contributes to maintaining intracellular homeostasis under environmental stress. To clarify whether RF exposure could induce autophagy in the spermatocyte, mouse spermatocyte-derived cells (GC-2) were exposed to 1800MHz Global System for Mobile Communication (GSM) signals in GSM-Talk mode at specific absorption rate (SAR) values of 1w/kg, 2w/kg or 4w/kg for 24h, respectively. The results indicated that the expression of LC3-II increased in a dose- and time-dependent manner with RF exposure, and showed a significant change at the SAR value of 4w/kg. The autophagosome formation and the occurrence of autophagy were further confirmed by GFP-LC3 transient transfection assay and transmission electron microscopy (TEM) analysis. Furthermore, the conversion of LC3-I to LC3-II was enhanced by co-treatment with Chloroquine (CQ), indicating autophagic flux could be enhanced by RF exposure. Intracellular ROS levels significantly increased in a dose- and time-dependent manner after cells were exposed to RF. Pretreatment with anti-oxidative NAC obviously decreased the conversion of LC3-I to LC3-II and attenuated the degradation of p62 induced by RF exposure. Meanwhile, phosphorylated extracellular-signal-regulated kinase (ERK) significantly increased after RF exposure at the SAR value of 2w/kg and 4w/kg. Moreover, we observed that RF exposure did not increase the percentage of apoptotic cells, but inhibition of autophagy could increase the percentage of apoptotic cells. These findings suggested that autophagy flux could be enhanced by 1800MHz GSM exposure (4w/kg), which is mediated by ROS generation. Autophagy may play an important role in preventing cells from apoptotic cell death under RF exposure stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

NEIGHBORHOOD EFFECT HETEROGENEITY BY FAMILY INCOME AND DEVELOPMENTAL PERIOD: EVIDENCE FROM A COUNTERFACTUAL MODEL OF HIGH SCHOOL GRADUATION

PubMed Central

Wodtke, Geoffrey T.; Elwert, Felix; Harding, David J.

2016-01-01

Effects of disadvantaged neighborhoods on child educational outcomes likely depend on a family's economic resources and the timing of neighborhood exposures during the course of child development. This study investigates how timing of exposure to disadvantaged neighborhoods during childhood versus adolescence affects high school graduation and whether these effects vary across families with different income levels. It follows 6,137 children in the PSID from childhood through adolescence and overcomes methodological problems associated with the joint endogeneity of neighborhood context and family income by adapting novel counterfactual methods—a structural nested mean model estimated via two-stage regression-with-residuals—for time-varying treatments and time-varying effect moderators. Results indicate that exposure to disadvantaged neighborhoods, particularly during adolescence, has a strong negative effect on high school graduation, and that this negative effect is more severe for children from poor families. PMID:27017709

Outcome-Dependent Sampling with Interval-Censored Failure Time Data

PubMed Central

Zhou, Qingning; Cai, Jianwen; Zhou, Haibo

2017-01-01

Summary Epidemiologic studies and disease prevention trials often seek to relate an exposure variable to a failure time that suffers from interval-censoring. When the failure rate is low and the time intervals are wide, a large cohort is often required so as to yield reliable precision on the exposure-failure-time relationship. However, large cohort studies with simple random sampling could be prohibitive for investigators with a limited budget, especially when the exposure variables are expensive to obtain. Alternative cost-effective sampling designs and inference procedures are therefore desirable. We propose an outcome-dependent sampling (ODS) design with interval-censored failure time data, where we enrich the observed sample by selectively including certain more informative failure subjects. We develop a novel sieve semiparametric maximum empirical likelihood approach for fitting the proportional hazards model to data from the proposed interval-censoring ODS design. This approach employs the empirical likelihood and sieve methods to deal with the infinite-dimensional nuisance parameters, which greatly reduces the dimensionality of the estimation problem and eases the computation difficulty. The consistency and asymptotic normality of the resulting regression parameter estimator are established. The results from our extensive simulation study show that the proposed design and method works well for practical situations and is more efficient than the alternative designs and competing approaches. An example from the Atherosclerosis Risk in Communities (ARIC) study is provided for illustration. PMID:28771664

Investigation of terahertz radiation influence on rat glial cells

PubMed Central

Borovkova, Mariia; Serebriakova, Maria; Fedorov, Viacheslav; Sedykh, Egor; Vaks, Vladimir; Lichutin, Alexander; Salnikova, Alina; Khodzitsky, Mikhail

2016-01-01

We studied an influence of continuous terahertz (THz) radiation (0.12 – 0.18 THz, average power density of 3.2 mW/cm2) on a rat glial cell line. A dose-dependent cytotoxic effect of THz radiation is demonstrated. After 1 minute of THz radiation exposure a relative number of apoptotic cells increased in 1.5 times, after 3 minutes it doubled. This result confirms the concept of biological hazard of intense THz radiation. Diagnostic applications of THz radiation can be restricted by the radiation power density and exposure time. PMID:28101417

Oxidation characteristics of 440 C CRES in gaseous oxygen (GOX) environments. [Corrosion Resistant Steel

NASA Technical Reports Server (NTRS)

Dennies, Daniel P.; Parsons, Terry D.

1986-01-01

The oxidation characteristics of 440 C corrosion-resistant steel are evaluated. The dependence of oxide color, type, and thickness, material hardness, and microstructure on temperature is examined. The effects of exposure time, passivation layer, and oxygen pressure on the oxide formation are investigated. A direct relationship between temperature and oxide color, formation, and thickness is detected. It is observed that the exposure time does not affect the microstructure or oxide color, type, or thickness; however, the passivation layer does affect oxide color and type.

Biochemical changes to fibroblast cells subjected to ionizing radiation.

PubMed

Jones, Pamala; Benghuzzi, Hamed; Tucci, Michelle; Richards, Latoya; Harrison, George; Patel, Ramesh

2008-01-01

High energy X-rays are capable of interacting with biological membranes to cause both functional and structural modifications. The goal of the present study was to investigate the effects human fibroblast cells exposed multiple times to 10 Gy over time. Following exposures of 2, 3, or 4 times to 10 Gy/10min the cells were evaluated for cell number changes, membrane damage, and intracellular glutathione content after 24, 48 and 72 hours. Twenty-four hours following exposure the cell numbers were reduced and increased levels of cellular membrane damage was evident. This trend was observed for the duration of the study. Interestingly, there was not an exposure dependent increase in cell damage or cell loss with time. Intracellular antioxidant systems were activated as indicated by anincrease in total cellular glutathione content. Additional studies are needed to determine if the cellular reduction is caused by a direct effect of the X-rays targeting the DNA or an indirect effect of the X-ray targeting the cellular membrane, which then generates radicals that target cell cycle checkpoints or DNA damage. In conclusion, fibroblast cells can be used to determine early and late events of cellular function following exposure to harmful levels of radiation exposure and results of exposure can be seen within twenty four hours.

Effects of tributyltin (TBT) on in vitro hormonal and biotransformation responses in Atlantic salmon (Salmo salar).

PubMed

Mortensen, Anne S; Arukwe, Augustine

2009-01-01

The mechanisms by which the biocide tributyltin (TBT) and its metabolites affect the hormonal and xenobiotic biotransformation pathways in aquatic species are not well understood. In this study hepatocytes isolated from salmon were used to evaluate the mechanistical effects of TBT on fish hormonal and xenobiotic biotransformation pathways. Cells were exposed to 0.01, 0.1, 1, or 5 microM TBT and samples were collected at 0, 12, 24, or 48 h following exposure. Gene expression patterns were evaluated using quantitative polymerase chain reaction (PCR), and cytochrome P-450 (CYP)-mediated enzyme activities were evaluated by ethoxyresorufin, benzyloxyresorufin, and pentoxyresorufin O-deethylase (EROD, BROD, and PROD, respectively) activity assays. Generally, exposure of hepatocytes to 1 microM (at 48 h) and 5 microM TBT (at 12, 24, and 48 h) consistently produced reductions in all mRNA species investigated. TBT produced significant decreases of vitellogen (Vtg) expression at 48 h and modified the expression patterns of estrogen receptors (ERalpha and ERbeta) and androgen receptor-beta (ARbeta) that were dependent on time and TBT concentration. In the xenobiotic biotransformation pathway, TBT produced differential expression patterns that were dependent on exposure time and concentration for all salmonid AhR2 isoforms (AhR2alpha, AhR2beta, AhR2delta, and AhR2gamma). For CYP1A1, CYP3A, AhRR, and Arnt mRNA, TBT produced exposure- and time-specific modulations. Catalytic CYP activities showed that BROD activity increased in an apparent concentration-specific manner in cells exposed to TBT for 12 h. Interestingly, EROD activity showed a TBT concentration-dependent increase at 24 h and PROD at 12 and 48 h of exposure. In general our data show that TBT differentially modulated hormonal and biotransformation responses in the salmon in vitro system. The apparent and consistent decrease of the studied responses with time in 1 and 5 microM exposed hepatocytes suggest a possible transcription inhibitory effect of TBT.

Automatic mechanisms for measuring subjective unit of discomfort.

PubMed

Hartanto, D W I; Kang, Ni; Brinkman, Willem-Paul; Kampmann, Isabel L; Morina, Nexhmedin; Emmelkamp, Paul G M; Neerincx, Mark A

2012-01-01

Current practice in Virtual Reality Exposure Therapy (VRET) is that therapists ask patients about their anxiety level by means of the Subjective Unit of Discomfort (SUD) scale. With an aim of developing a home-based VRET system, this measurement ideally should be done using speech technology. In a VRET system for social phobia with scripted avatar-patient dialogues, the timing of asking patients to give their SUD score becomes relevant. This study examined three timing mechanisms: (1) dialogue dependent (i.e. naturally in the flow of the dialogue); (2) speech dependent (i.e. when both patient and avatar are silent); and (3) context independent (i.e. randomly). Results of an experiment with non-patients (n = 24) showed a significant effect for the timing mechanisms on the perceived dialogue flow, user preference, reported presence and user dialog replies. Overall, dialogue dependent timing mechanism seems superior followed by the speech dependent and context independent timing mechanism.

Cytotoxicity, permeability, and inflammation of metal oxide nanoparticles in human cardiac microvascular endothelial cells: cytotoxicity, permeability, and inflammation of metal oxide nanoparticles.

PubMed

Sun, Jing; Wang, Shaochuang; Zhao, Dong; Hun, Fei Han; Weng, Lei; Liu, Hui

2011-10-01

Wide applications and extreme potential of metal oxide nanoparticles (NPs) increase occupational and public exposure and may yield extraordinary hazards for human health. Exposure to NPs has a risk for dysfunction of the vascular endothelial cells. The objective of this study was to assess the cytotoxicity of six metal oxide NPs to human cardiac microvascular endothelial cells (HCMECs) in vitro. Metal oxide NPs used in this study included zinc oxide (ZnO), iron(III) oxide (Fe(2)O(3)), iron(II,III) oxide (Fe(3)O(4)), magnesium oxide (MgO), aluminum oxide (Al(2)O(3)), and copper(II) oxide (CuO). The cell viability, membrane leakage of lactate dehydrogenase, intracellular reactive oxygen species, permeability of plasma membrane, and expression of inflammatory markers vascular cell adhesion molecule-1, intercellular adhesion molecule-1, macrophage cationic peptide-1, and interleukin-8 in HCMECs were assessed under controlled and exposed conditions (12-24 h and 0.001-100 μg/ml of exposure). The results indicated that Fe(2)O(3), Fe(3)O(4), and Al(2)O(3) NPs did not have significant effects on cytotoxicity, permeability, and inflammation response in HCMECs at any of the concentrations tested. ZnO, CuO, and MgO NPs produced the cytotoxicity at the concentration-dependent and time-dependent manner, and elicited the permeability and inflammation response in HCMECs. These results demonstrated that cytotoxicity, permeability, and inflammation in vascular endothelial cells following exposure to metal oxide nanoparticles depended on particle composition, concentration, and exposure time. © Springer Science+Business Media B.V. 2011

The impacts of repeated cold exposure on insects.

PubMed

Marshall, Katie E; Sinclair, Brent J

2012-05-15

Insects experience repeated cold exposure (RCE) on multiple time scales in natural environments, yet the majority of studies of the effects of cold on insects involve only a single exposure. Three broad groups of experimental designs have been employed to examine the effects of RCE on insect physiology and fitness, defined by the control treatments: 'RCE vs cold', which compares RCE with constant cold conditions; 'RCE vs warm', which compares RCE with constant warm conditions; and 'RCE vs matched cold' which compares RCE with a prolonged period of cold matched by time to the RCE condition. RCE are generally beneficial to immediate survival, and increase cold hardiness relative to insects receiving a single prolonged cold exposure. However, the effects of RCE depend on the study design, and RCE vs warm studies cannot differentiate between the effects of cold exposure in general vs RCE in particular. Recent studies of gene transcription, immune function, feeding and reproductive output show that the responses of insects to RCE are distinct from the responses to single cold exposures. We suggest that future research should attempt to elucidate the mechanistic link between physiological responses and fitness parameters. We also recommend that future RCE experiments match the time spent at the stressful low temperature in all experimental groups, include age controls where appropriate, incorporate a pilot study to determine time and intensity of exposure, and measure sub-lethal impacts on fitness.

Measurement of the timing behaviour of off-the-shelf cameras

NASA Astrophysics Data System (ADS)

Schatz, Volker

2017-04-01

This paper presents a measurement method suitable for investigating the timing properties of cameras. A single light source illuminates the camera detector starting with a varying defined delay after the camera trigger. Pixels from the recorded camera frames are summed up and normalised, and the resulting function is indicative of the overlap between illumination and exposure. This allows one to infer the trigger delay and the exposure time with sub-microsecond accuracy. The method is therefore of interest when off-the-shelf cameras are used in reactive systems or synchronised with other cameras. It can supplement radiometric and geometric calibration methods for cameras in scientific use. A closer look at the measurement results reveals deviations from the ideal camera behaviour of constant sensitivity limited to the exposure interval. One of the industrial cameras investigated retains a small sensitivity long after the end of the nominal exposure interval. All three investigated cameras show non-linear variations of sensitivity at O≤ft({{10}-3}\\right) to O≤ft({{10}-2}\\right) during exposure. Due to its sign, the latter effect cannot be described by a sensitivity function depending on the time after triggering, but represents non-linear pixel characteristics.

Effect of fetal alcohol exposure on adult symptoms of nicotine, alcohol, and drug dependence.

PubMed

Yates, W R; Cadoret, R J; Troughton, E P; Stewart, M; Giunta, T S

1998-06-01

The objective of this study is to examine the effect of fetal alcohol exposure on later substance dependence using an adoption study method. One hundred ninety-seven adoptees were interviewed for substance abuse disorders, including nicotine, alcohol, and drug dependence. Twenty-one adoptees had mothers who drank during pregnancy. Adoptees with fetal alcohol exposure were compared with those without fetal alcohol exposure for symptoms of adult nicotine, alcohol, and drug dependence. Adoptee symptom counts for alcohol, drug, and nicotine dependence were higher for those exposed to alcohol in utero. The effect of fetal alcohol exposure remained after controlling for gender, biological parent alcohol dependence diagnosis, birth weight, gestational age and other environmental variables. Fetal alcohol exposure may produce increased risk for later nicotine, alcohol, and drug dependence. Possible effects of fetal alcohol exposure on development of adult substance use patterns needs attention in genetic studies of substance abuse.

Comparison of the effectiveness of virtual cue exposure therapy and cognitive behavioral therapy for nicotine dependence.

PubMed

Park, Chan-Bin; Choi, Jung-Seok; Park, Su Mi; Lee, Jun-Young; Jung, Hee Yeon; Seol, Jin-Mi; Hwang, Jae Yeon; Gwak, Ah Reum; Kwon, Jun Soo

2014-04-01

Previous studies have reported promising results regarding the effect of repeated virtual cue exposure therapy on nicotine dependence. This study aimed to compare the effectiveness of virtual cue exposure therapy (CET) and cognitive behavioral therapy (CBT) for nicotine dependence. Thirty subjects with nicotine dependence participated in 4 weeks of treatment with either virtual CET (n=15) or CBT (n=15). All patients were male, and none received nicotine replacement treatment during the study period. The main setting of the CET used in this study was a virtual bar. The primary foci of the CBT offered were (a) smoking cessation education, (b) withdrawal symptoms, (c) coping with high-risk situations, (d) cognitive reconstruction, and (e) stress management. Daily smoking count, level of expiratory carbon monoxide (CO), level of nicotine dependence, withdrawal symptoms, and subjective craving were examined on three occasions: week 0 (baseline), week 4 (end of treatment), and week 12 (follow-up assessment). After treatment, the daily smoking count, the expiratory CO, and nicotine dependence levels had significantly decreased. These effects continued during the entire study period. Similar changes were observed in both virtual CET and CBT groups. We found no interaction between type of therapy and time of measurement. Although the current findings are preliminary, the present study provided evidence that virtual CET is effective for the treatment of nicotine dependence at a level comparable to CBT.

Generalized semiparametric varying-coefficient models for longitudinal data

NASA Astrophysics Data System (ADS)

Qi, Li

In this dissertation, we investigate the generalized semiparametric varying-coefficient models for longitudinal data that can flexibly model three types of covariate effects: time-constant effects, time-varying effects, and covariate-varying effects, i.e., the covariate effects that depend on other possibly time-dependent exposure variables. First, we consider the model that assumes the time-varying effects are unspecified functions of time while the covariate-varying effects are parametric functions of an exposure variable specified up to a finite number of unknown parameters. The estimation procedures are developed using multivariate local linear smoothing and generalized weighted least squares estimation techniques. The asymptotic properties of the proposed estimators are established. The simulation studies show that the proposed methods have satisfactory finite sample performance. ACTG 244 clinical trial of HIV infected patients are applied to examine the effects of antiretroviral treatment switching before and after HIV developing the 215-mutation. Our analysis shows benefit of treatment switching before developing the 215-mutation. The proposed methods are also applied to the STEP study with MITT cases showing that they have broad applications in medical research.

Modeling methylene chloride exposure-reduction options for home paint-stripper users.

PubMed

Riley, D M; Small, M J; Fischhoff, B

2000-01-01

Home improvement is a popular activity, but one that can also involve exposure to hazardous substances. Paint stripping is of particular concern because of the high potential exposures to methylene chloride, a solvent that is a potential human carcinogen and neurotoxicant. This article presents a general methodology for evaluating the effectiveness of behavioral interventions for reducing these risks. It doubles as a model that assesses exposure patterns, incorporating user time-activity patterns and risk-mitigation strategies. The model draws upon recent innovations in indoor air-quality modeling to estimate exposure through inhalation and dermal pathways to paint-stripper users. It is designed to use data gathered from home paint-stripper users about room characteristics, amount of stripper used, time-activity patterns and exposure-reduction strategies (e.g., increased ventilation and modification in the timing of stripper application, scraping, and breaks). Results indicate that the effectiveness of behavioral interventions depends strongly on characteristics of the room (e.g., size, number and size of doors and windows, base air-exchange rates). The greatest simple reduction in exposure is achieved by using an exhaust fan in addition to opening windows and doors. These results can help identify the most important information for product labels and other risk-communication materials.

Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition.

PubMed

Falgreen, Steffen; Laursen, Maria Bach; Bødker, Julie Støve; Kjeldsen, Malene Krag; Schmitz, Alexander; Nyegaard, Mette; Johnsen, Hans Erik; Dybkær, Karen; Bøgsted, Martin

2014-06-05

In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves' dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological interpretations. Time independent summary statistics may aid the understanding of drugs' action mechanism on tumour cells and potentially renew previous drug sensitivity evaluation studies.

Exposure time independent summary statistics for assessment of drug dependent cell line growth inhibition

PubMed Central

2014-01-01

Background In vitro generated dose-response curves of human cancer cell lines are widely used to develop new therapeutics. The curves are summarised by simplified statistics that ignore the conventionally used dose-response curves’ dependency on drug exposure time and growth kinetics. This may lead to suboptimal exploitation of data and biased conclusions on the potential of the drug in question. Therefore we set out to improve the dose-response assessments by eliminating the impact of time dependency. Results First, a mathematical model for drug induced cell growth inhibition was formulated and used to derive novel dose-response curves and improved summary statistics that are independent of time under the proposed model. Next, a statistical analysis workflow for estimating the improved statistics was suggested consisting of 1) nonlinear regression models for estimation of cell counts and doubling times, 2) isotonic regression for modelling the suggested dose-response curves, and 3) resampling based method for assessing variation of the novel summary statistics. We document that conventionally used summary statistics for dose-response experiments depend on time so that fast growing cell lines compared to slowly growing ones are considered overly sensitive. The adequacy of the mathematical model is tested for doxorubicin and found to fit real data to an acceptable degree. Dose-response data from the NCI60 drug screen were used to illustrate the time dependency and demonstrate an adjustment correcting for it. The applicability of the workflow was illustrated by simulation and application on a doxorubicin growth inhibition screen. The simulations show that under the proposed mathematical model the suggested statistical workflow results in unbiased estimates of the time independent summary statistics. Variance estimates of the novel summary statistics are used to conclude that the doxorubicin screen covers a significant diverse range of responses ensuring it is useful for biological interpretations. Conclusion Time independent summary statistics may aid the understanding of drugs’ action mechanism on tumour cells and potentially renew previous drug sensitivity evaluation studies. PMID:24902483

[Eye lens radiation exposure during ureteroscopy with and without a face protection shield: Investigations on a phantom model].

PubMed

Zöller, G; Figel, M; Denk, J; Schulz, K; Sabo, A

2016-03-01

Eye lens radiation exposure during radiologically-guided endoscopic procedures may result in radiation-induced cataracts; therefore, we investigated the ocular radiation exposure during ureteroscopy on a phantom model. Using an Alderson phantom model and eye lens dosimeters, we measured the ocular radiation exposure depending on the number of X-ray images and on the duration of fluoroscopic imaging. The measurements were done with and without using a face protection shield. We could demonstrate that a significant ocular radiation exposure can occur, depending on the number of X-ray images and on the duration time of fluoroscopy. Eye lens doses up to 0.025 mSv were recorded even using modern digital X-ray systems. Using face protection shields this ocular radiation exposure can be reduced to a minimum. The International Commission on Radiological Protection (ICRP) recommendations of a mean eye lens dosage of 20 mSv/year may be exceeded during repeated ureteroscopy by a high volume surgeon. Using a face protection shield, the eye lens dose during ureteroscopy could be reduced to a minimum in a phantom model. Further investigations will show whether these results can be transferred to real life ureteroscopic procedures.

Stimulation of the brain with radiofrequency electromagnetic field pulses affects sleep-dependent performance improvement.

PubMed

Lustenberger, Caroline; Murbach, Manuel; Dürr, Roland; Schmid, Marc Ralph; Kuster, Niels; Achermann, Peter; Huber, Reto

2013-09-01

Sleep-dependent performance improvements seem to be closely related to sleep spindles (12-15 Hz) and sleep slow-wave activity (SWA, 0.75-4.5 Hz). Pulse-modulated radiofrequency electromagnetic fields (RF EMF, carrier frequency 900 MHz) are capable to modulate these electroencephalographic (EEG) characteristics of sleep. The aim of our study was to explore possible mechanisms how RF EMF affect cortical activity during sleep and to test whether such effects on cortical activity during sleep interact with sleep-dependent performance changes. Sixteen male subjects underwent 2 experimental nights, one of them with all-night 0.25-0.8 Hz pulsed RF EMF exposure. All-night EEG was recorded. To investigate RF EMF induced changes in overnight performance improvement, subjects were trained for both nights on a motor task in the evening and the morning. We obtained good sleep quality in all subjects under both conditions (mean sleep efficiency > 90%). After pulsed RF EMF we found increased SWA during exposure to pulse-modulated RF EMF compared to sham exposure (P < 0.05) toward the end of the sleep period. Spindle activity was not affected. Moreover, subjects showed an increased RF EMF burst-related response in the SWA range, indicated by an increase in event-related EEG spectral power and phase changes in the SWA range. Notably, during exposure, sleep-dependent performance improvement in the motor sequence task was reduced compared to the sham condition (-20.1%, P = 0.03). The changes in the time course of SWA during the exposure night may reflect an interaction of RF EMF with the renormalization of cortical excitability during sleep, with a negative impact on sleep-dependent performance improvement. Copyright © 2013 Elsevier Inc. All rights reserved.

Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol

PubMed Central

Nimitvilai, Sudarat; Lopez, Marcelo F; Mulholland, Patrick J; Woodward, John J

2016-01-01

Alcoholism is associated with changes in brain reward and control systems, including the prefrontal cortex. In prefrontal areas, the orbitofrontal cortex (OFC) has been suggested to have an important role in the development of alcohol-abuse disorders and studies from this laboratory demonstrate that OFC-mediated behaviors are impaired in alcohol-dependent animals. However, it is not known whether chronic alcohol (ethanol) exposure alters the fundamental properties of OFC neurons. In this study, mice were exposed to repeated cycles of chronic intermittent ethanol (CIE) exposure to induce dependence and whole-cell patch-clamp electrophysiology was used to examine the effects of CIE treatment on lateral OFC (lOFC) neuron excitability, synaptic transmission, and plasticity. Repeated cycles of CIE exposure and withdrawal enhanced current-evoked action potential (AP) spiking and this was accompanied by a reduction in the after-hyperpolarization and a decrease in the functional activity of SK channels. CIE mice also showed an increase in the AMPA/NMDA ratio, and this was associated with an increase in GluA1/GluA2 AMPA receptor expression and a decrease in GluN2B NMDA receptor subunits. Following CIE treatment, lOFC neurons displayed a persistent long-term potentiation of glutamatergic synaptic transmission following a spike-timing-dependent protocol. Lastly, CIE treatment diminished the inhibitory effect of acute ethanol on AP spiking of lOFC neurons and reduced expression of the GlyT1 transporter. Taken together, these results suggest that chronic exposure to ethanol leads to enhanced intrinsic excitability and glutamatergic synaptic signaling of lOFC neurons. These alterations may contribute to the impairment of OFC-dependent behaviors in alcohol-dependent individuals. PMID:26286839

Pulmonary toxicity following exposure to a tile coating product containing alkylsiloxanes. A clinical and toxicological evaluation

PubMed Central

Nørgaard, A. W.; Hansen, J. S.; Sørli, J. B.; Jacobsen, P.; Lynggard, F.; Levin, M.; Nielsen, G. D.; Wolkoff, P.; Ebbehøj, N. E.; Larsen, S. T.

2014-01-01

Context Coating products are widely used for making surfaces water and dirt repellent. However, on several occasions the use of these products has been associated with lung toxicity. Objective In the present study, we evaluated the toxic effects of an aerosolized tile-coating product. Methods Thirty-nine persons, who reported respiratory and systemic symptoms following exposure to the tile-coating product, were clinically examined. The product was analysed chemically and furthermore, the exposure scenario was reconstructed using a climate chamber and the toxicological properties of the product were studied using in vivo and by in vitro surfactometry. Results The symptoms developed within few hours and included coughing, tachypnoea, chest pain, general malaise and fever. The physical examination revealed perihilar lung infiltrates on chest radiograph and reduced blood oxygen saturation. The acute symptoms resolved gradually within 1–3 days and no delayed symptoms were observed. By means of mass spectrometry and X-ray spectroscopy, it was shown that the product contained non-fluorinated alkylsiloxanes. The exposure conditions in the supermarket were reconstructed under controlled conditions in a climate chamber and particle and gas exposure levels were monitored over time allowing estimation of human exposure levels. Mice exposed to the product developed symptoms of acute pulmonary toxicity in a concentration-and time-dependent manner. The symptoms of acute pulmonary toxicity likely resulted from inhibition of the pulmonary surfactant function as demonstrated by in vitro surfactometry. Among these patients only a partial association between the level of exposure and the degree of respiratory symptoms was observed, which could be because of a high inter-individual difference in sensitivity and time-dependent changes in the chemical composition of the aerosol. Conclusion Workers need to cautiously apply surface coating products because the contents can be highly toxic through inhalation, and the aerosols can disperse to locations remote from the worksite and affect bystanders. PMID:24815546

Impact of Early Postnatal Androgen Exposure on Voice Development

PubMed Central

Grisa, Leila; Leonel, Maria L.; Gonçalves, Maria I. R.; Pletsch, Francisco; Sade, Elis R.; Custódio, Gislaine; Zagonel, Ivete P. S.; Longui, Carlos A.; Figueiredo, Bonald C.

2012-01-01

Background The impact of early postnatal androgen exposure on female laryngeal tissue may depend on certain characteristics of this exposure. We assessed the impact of the dose, duration, and timing of early androgen exposure on the vocal development of female subjects who had been treated for adrenocortical tumor (ACT) in childhood. Methods The long-term effects of androgen exposure on the fundamental vocal frequency (F0), vocal pitch, and final height and the presence of virilizing signs were examined in 9 adult (age, 18.4 to 33.5 years) and 10 adolescent (13.6 to 17.8 years) female ACT patients. We also compared the current values with values obtained 0.9 years to 7.4 years after these subjects had undergone ACT surgery, a period during which they had shown normal androgen levels. Results Of the 19 subjects, 17 (89%) had been diagnosed with ACT before 4 years of age, 1 (5%) at 8.16 years, and 1 (5%) at 10.75 years. Androgen exposure (2 to 30 months) was sufficiently strong to cause pubic hair growth in all subjects and clitoromegaly in 74% (14/19) of the subjects, but did not reduce their height from the target value. Although androgen exposure induced a remarkable reduction in F0 (132 Hz) and moderate pitch virilization in 1 subject and partial F0 virilization, resulting in F0 of 165 and 169 Hz, in 2 subjects, the majority had normal F0 ranging from 189 to 245 Hz. Conclusions Female laryngeal tissue is less sensitive to androgen exposure between birth and adrenarche than during other periods. Differential larynx sensitivity to androgen exposure in childhood and F0 irreversibility in adulthood are age-, concentration-, duration-, and timing-dependent events that may also be affected by exposure to inhibitory or stimulatory hormones. Further studies are required to better characterize each of these factors. PMID:23284635

[Evaluation of the risk on hearing loss at soldiers].

PubMed

Konopka, Wiesław; Olszewski, Jurek; Straszyński, Piotr

2006-01-01

Noise produced by weapons may be harmful to soldiers during military service. Exposure to impulse noise during compulsory military service depends on the number of shots, explosion impulses, distance of injured ear from causal firearm as well as on the use of hearing protectors. Weapons produce impulse noises, which are characterized by peak pressure level and frequency. The purpose of this work was to calculate and estimate risk on hearing at soldiers during one year of the military service. The study comparised three groups of soldiers with different kind of exposure to noise divided according total noise exposure. In order to evaluate the amount of the exposure to impulse noise the total level of noise and the spectrum analysis were performed for all types of weapons, which were used during military service. The equivalent continuous A-weighted sound pressure level, L A eq, Te [dB], maximum A-weighted sound pressure level, L A max [dB] and C weighted peak sound pressure level, L C peak [dB] were measured. The highest total exposure to noise concerned group I (2222,9 kPa(2)/s for right ear and 22212,8 kPa(2)/s for left one) with total exposure time 248,3 minutes. In the II group estimated total exposure to noise was 611,8 kPa(2)/s for right ear and 743,6 kPa(2)/s for left one. In the III group least exposed to noise, estimated total exposure to noise was 103 kPa(2)/s for right ear and 109 kPa(2)/s for left one with total time exposure 17,8 minutes. Difference between groups is dependent on kind of military service. Estimated exposure to weapons noise may prevent soldiers before hearing loss. We did not notice differences between sites of ears.

Precise fabrication of a 5 nm graphene nanopore with a helium ion microscope for biomolecule detection

NASA Astrophysics Data System (ADS)

Deng, Yunsheng; Huang, Qimeng; Zhao, Yue; Zhou, Daming; Ying, Cuifeng; Wang, Deqiang

2017-01-01

We report a scalable method to fabricate high-quality graphene nanopores for biomolecule detection using a helium ion microscope (HIM). HIM milling shows promising capabilities for precisely controlling the size and shape, and may allow for the potential production of nanopores at wafer scale. Nanopores could be fabricated at different sizes ranging from 5 to 30 nm in diameter in few minutes. Compared with the current solid-state nanopore fabrication techniques, e.g. transmission electron microscopy, HIM is fast. Furthermore, we investigated the exposure-time dependence of graphene nanopore formation: the rate of pore expansion did not follow a simple linear relationship with exposure time, but a fast expansion rate at short exposure time and a slow rate at long exposure time. In addition, we performed biomolecule detection with our patterned graphene nanopore. The ionic current signals induced by 20-base single-stranded DNA homopolymers could be used as a basis for homopolymer differentiation. However, the charge interaction of homopolymer chains with graphene nanopores, and the conformations of homopolymer chains need to be further considered to improve the accuracy of discrimination.

Wettability of naturally aged silicone and EPDM composite insulators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gubanski, S.M.; Vlastos, A.E.

1990-07-01

This paper reports the wettability of aged surfaces and of the bulk of naturally aged silicone and EPDM insulator housings and of silicone elastomer insulator coatings studied. The samples were taken either directly from the insulators or treated by exposing them to corona discharges and/or to saline pollution. The results show that the contact angles of the silicone rubber insulator surfaces are larger than the contact angles of the RTV silicone rubber coating and of the EPDM rubber insulator surfaces, especially when the surfaces are aged. When the insulators were exposed to corona discharges, the contact angles of the siliconemore » rubber insulators are reduced but after the exposure they recover with time. The contact angles of the EPDM rubber insulators, however, after the exposure, continue to reduce. When exposed to artificial saline pollution, the silicone rubber insulators show a limited recovery of their contact angles with time, while, when exposed to corona discharge, they show a recovery of the contact angle after the exposure. The time for recovery is dependent on the exposure time to the corona discharges.« less

Accounting for Berkson and Classical Measurement Error in Radon Exposure Using a Bayesian Structural Approach in the Analysis of Lung Cancer Mortality in the French Cohort of Uranium Miners.

PubMed

Hoffmann, Sabine; Rage, Estelle; Laurier, Dominique; Laroche, Pierre; Guihenneuc, Chantal; Ancelet, Sophie

2017-02-01

Many occupational cohort studies on underground miners have demonstrated that radon exposure is associated with an increased risk of lung cancer mortality. However, despite the deleterious consequences of exposure measurement error on statistical inference, these analyses traditionally do not account for exposure uncertainty. This might be due to the challenging nature of measurement error resulting from imperfect surrogate measures of radon exposure. Indeed, we are typically faced with exposure uncertainty in a time-varying exposure variable where both the type and the magnitude of error may depend on period of exposure. To address the challenge of accounting for multiplicative and heteroscedastic measurement error that may be of Berkson or classical nature, depending on the year of exposure, we opted for a Bayesian structural approach, which is arguably the most flexible method to account for uncertainty in exposure assessment. We assessed the association between occupational radon exposure and lung cancer mortality in the French cohort of uranium miners and found the impact of uncorrelated multiplicative measurement error to be of marginal importance. However, our findings indicate that the retrospective nature of exposure assessment that occurred in the earliest years of mining of this cohort as well as many other cohorts of underground miners might lead to an attenuation of the exposure-risk relationship. More research is needed to address further uncertainties in the calculation of lung dose, since this step will likely introduce important sources of shared uncertainty.

Toxicity of o,p′-DDE to medaka d-rR strain after a one-time embryonic exposure by in ovo nanoinjection: An early through juvenile life cycle assessment

USGS Publications Warehouse

Villalobos, Sergio A.; Papoulias, Diana M.; Pastva, Stephanie D.; Blankenship, Alan L.; Meadows, John C.; Tillitt, Donald E.; Giesy, John P.

2003-01-01

The toxicity of o,p′-DDE (1,1-dichloro-2-(p-chlorophenyl)-2-(o-chlorophenyl) ethylene) was evaluated in embryos of medaka (Oryzias latipes) following a one time exposure via nanoinjection. Medaka eggs (early gastrula) were injected with 0.5 nl of triolein (vehicle control) or 0.5 nl of 4 graded doses (0.0005-0.5 ng/egg) of o,p′-DDE in triolein. Embryos were allowed to develop, and fry were reared. Embryonic survival was monitored daily during the first 10 d until hatching and thereafter, on a weekly basis until day 59, at which time the fish were monitored for sexual maturity until day 107. In general, o,p′-DDE caused a dose- and time-dependent mortality. No changes in mortality were observed between the last two time points (day 38 and 59, respectively), and hence a 59 day-LD50 of 346 ng o,p′-DDE/egg was derived from the linear dose-response relationship. Prior to late stage death, only isolated cases of cardiovascular lesions and spinal deformities were observed, but were not dose-dependent. The lowest observable adverse effect level (LOAEL), based on upper 95% CI for regression line=0.0018 mg/kg, and the LOAEL based on exposure doses=0.5 mg/kg. Likewise, the no observable adverse effect level (NOAEL) based on linear extrapolation to 100% survival=0.0000388 mg/kg, while the NOAEL based on exposure doses=0.05 mg/kg. The nanoinjection medaka model has potential in the study of hormonally active compounds in the environment.

Effects of electromagnetic radiation exposure on stress-related behaviors and stress hormones in male wistar rats.

PubMed

Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

2014-11-01

Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure.

Effects of Electromagnetic Radiation Exposure on Stress-Related Behaviors and Stress Hormones in Male Wistar Rats

PubMed Central

Mahdavi, Seyed Mohammad; Sahraei, Hedayat; Yaghmaei, Parichehreh; Tavakoli, Hassan

2014-01-01

Studies have demonstrated that electromagnetic waves, as the one of the most important physical factors, may alter cognitive and non-cognitive behaviors, depending on the frequency and energy. Moreover, non-ionizing radiation of low energy waves e.g. very low frequency waves could alter this phenomenon via alterations in neurotransmitters and neurohormones. In this study, short, medium, and long-term exposure to the extremely low frequency electromagnetic field (ELF-EMF) (1 and 5 Hz radiation) on behavioral, hormonal, and metabolic changes in male Wistar rats (250 g) were studied. In addition, changes in plasma concentrations for two main stress hormones, noradrenaline and adrenocorticotropic hormone (ACTH) were evaluated. ELF-EMF exposure did not alter body weight, and food and water intake. Plasma glucose level was increased and decreased in the groups which exposed to the 5 and 1Hz wave, respectively. Plasma ACTH concentration increased in both using frequencies, whereas nor-adrenaline concentration showed overall reduction. At last, numbers of rearing, sniffing, locomotor activity was increased in group receiving 5 Hz wave over the time. In conclusions, these data showed that the effects of 1 and 5 Hz on the hormonal, metabolic and stress-like behaviors may be different. Moreover, the influence of waves on stress system is depending on time of exposure. PMID:25489427

[Dependence of anti-inflammatory effects of high peak-power pulsed electromagnetic radiation of extremely high frequency on exposure parameters].

PubMed

Gapeev, A B; Mikhaĭlik, E N; Rubanik, A V; Cheremis, N K

2007-01-01

A pronounced anti-inflammatory effect of high peak-power pulsed electromagnetic radiation of extremely high frequency was shown for the first time in a model of zymosan-induced footpad edema in mice. Exposure to radiation of specific parameters (35, 27 GHz, peak power 20 kW, pulse widths 400-600 ns, pulse repetition frequency 5-500 Hz) decreased the exudative edema and local hyperthermia by 20% compared to the control. The kinetics and the magnitude of the anti-inflammatory effect were comparable with those induced by sodium diclofenac at a dose of 3 mg/kg. It was found that the anti-inflammatory effect linearly increased with increasing pulse width at a fixed pulse repetition frequency and had threshold dependence on the average incident power density of the radiation at a fixed pulse width. When animals were whole-body exposed in the far-field zone of radiator, the optimal exposure duration was 20 min. Increasing the average incident power density upon local exposure of the inflamed paw accelerated both the development of the anti-inflammatory effect and the reactivation time. The results obtained will undoubtedly be of great importance in the hygienic standardization of pulsed electromagnetic radiation and in further studies of the mechanisms of its biological action.

Neovascularization and Angiogenic Gene Expression Following Chronic Arsenic Exposure in Mice

PubMed Central

Soucy, Nicole V.; Mayka, Debra; Klei, Linda R.; Nemec, Antonia A.; Bauer, John A.; Barchowsky, Aaron

2015-01-01

Exposure to arsenic in drinking water increases incidence of cardiovascular diseases. However, the basic mechanisms and genetic changes that promote these diseases are unknown. This study investigated the effects of chronic arsenic exposure on vessel growth and expression of angiogenic and tissue remodeling genes in cardiac tissues. Male mice were exposed to low to moderately high levels of arsenite (AsIII) for 5, 10, or 20 wk in their drinking water. Vessel growth in Matrigel implants was tested during the last 2 wk of each exposure period. Implant vascularization increased in mice exposed to 5–500 ppb AsIII for 5 wk. Similar increases were seen following exposure to 50–250 ppb of AsIII over 20 wk, but the response to 500 ppb decreased with time. RT-PCR analysis of cardiac mRNA revealed differential expression of angiogenic or tissue remodeling genes, such as vascular endothelial cell growth factor (VEGF), VEGF receptors, plasminogen activator inhibitor-1, endothelin-1, and matrix metalloproteinase-9, which varied with time or amount of exposure. VEGF receptor mRNA and cardiac microvessel density were reduced by exposure to 500 ppb AsIII for 20 wk. These data demonstrate differential concentration and time-dependent effects of chronic arsenic exposure on cardiovascular phenotype and vascular remodeling that may explain the etiology for AsIII-induced disease. PMID:15738583

Impact of climate change on occupational exposure to solar radiation.

PubMed

Grandi, Carlo; Borra, Massimo; Militello, Andrea; Polichetti, Alessandro

2016-01-01

Occupational exposure to solar radiation may induce both acute and long-term effects on skin and eyes. Personal exposure is very difficult to assess accurately, as it depends on environmental, organisational and individual factors. The ongoing climate change interacting with stratospheric ozone dynamics may affect occupational exposure to solar radiation. In addition, tropospheric levels of environmental pollutants interacting with solar radiation may be altered by climate dynamics, so introducing another variable affecting the overall exposure to solar radiation. Given the uncertainties regarding the direction of changes in exposure to solar radiation due to climate change, compliance of outdoor workers with protective measures and a proper health surveillance are crucial. At the same time, education and training, along with the promotion of healthier lifestyles, are of paramount importance.

Nanosilica induced dose-dependent cytotoxicity and cell type-dependent multinucleation in HepG2 and L-02 cells

NASA Astrophysics Data System (ADS)

Yu, Yongbo; Duan, Junchao; Li, Yang; Yu, Yang; Hu, Hejing; Wu, Jing; Zhang, Yannan; Li, Yanbo; CaixiaGuo; Zhou, Xianqing; Sun, Zhiwei

2016-11-01

The prevalent exposure to nanosilica gained concerns about health effects of these particles on human beings. Although nanosilica-induced multinucleation has been confirmed previously, the underlying mechanism was still not clear; this study was to investigate the origination of multinucleated cells caused by nanosilica (62 nm) in both HepG2 and L-02 cells. Cell viability and cellular uptake was determined by MTT assay and transmission electron microscope (TEM), respectively. Giemsa staining was applied to detect multinucleation. To clarify the origination of multinucleated cells, fluorescent probes, PKH26 and PKH67, time-lapse observation were further conducted by confocal microscopy. Results indicated that nanosilica particles were internalized into cells and induced cytotoxicity in a dose-dependent manner. Quantification analysis showed that nanosilica significantly increased the rates of binucleated and multinucleated cells, which suggested mitotic catastrophe induction. Moreover, dynamic visualization verified that multinucleation resulted from cell fusion in HepG2 cells not in L-02 cells after nanosilica exposure, suggesting cell type-dependent multinucleation formation. Both multinucleation and cell fusion were involved in genetic instability, which emphasized the significance to explore the multinucleation induced by nanosilica via environmental, occupational and consumer product exposure.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Batal, Mohamed; Département de Toxicologie et Risques Chimiques, Unité de Brûlure Chimique, Institut de Recherche Biomédicale des Armées, Antenne de La Tronche; Boudry, Isabelle

Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM–DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6 h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNAmore » adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM–DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker. - Highlights: • Sulfur mustard adducts are formed in DNA after skin exposure. • DNA damage formation is an early event in the pathological process of skin burn. • The amount of SM–DNA adducts is maximal at the earliest time point investigated. • Adducts are still detected 3 weeks after exposure. • Sulfur mustard diffuses in skin especially when large doses are applied.« less

The effect of UV-Vis to near-infrared light on the biological response of human dental pulp cells

NASA Astrophysics Data System (ADS)

Hadis, Mohammed A.; Cooper, Paul R.; Milward, Michael R.; Gorecki, Patricia; Tarte, Edward; Churm, James; Palin, William M.

2015-03-01

Human dental pulp cells (DPCs) were isolated and cultured in phenol-red-free α-MEM/10%-FCS at 37ºC in 5% CO2. DPCs at passages 2-4 were seeded (150μL; 25,000 cell/ml) in black 96-microwell plates with transparent bases. 24h post-seeding, cultures were irradiated using a bespoke LED array consisting of 60 LEDs (3.5mW/cm2) of wavelengths from 400-900nm (10 wavelengths, n=6) for time intervals of up to 120s. Metabolic and mitochondrial activity was assessed via a modified MTT assay. Statistical differences were identified using multi-factorial analysis of variance and post-hoc Tukey tests (P=0.05). The biological responses were significantly dependent upon post-irradiation incubation period, wavelength and exposure time (P<0.05). At shorter wavelength irradiances (400nm), a reduction in mitochondrial activity was detected although not significant, whereas longer wavelength irradiances (at 633, 656, 781 and 799nm) significantly increased mitochondrial activity (P<0.05) in DPCs. At these wavelengths, mitochondrial activity was generally increased for exposures less than 90s with 30s exposures being most effective with 24h incubation. Increasing the post-irradiation incubation period increased the measured response and identified further significance (P<0.05). The biological responses of human DPCs were wavelength, exposure-time and incubation period dependent. The optimisation of irradiation parameters will be key to the successful application of LLLT in dentistry.

Sex Differences in Early Postnatal Microglial Colonization of the Developing Rat Hippocampus Following a Single-Day Alcohol Exposure.

PubMed

Ruggiero, M J; Boschen, K E; Roth, T L; Klintsova, A Y

2018-06-01

Microglia are involved in various homeostatic processes in the brain, including phagocytosis, apoptosis, and synaptic pruning. Sex differences in microglia colonization of the developing brain have been reported, but have not been established following alcohol insult. Developmental alcohol exposure represents a neuroimmune challenge that may contribute to cognitive dysfunction prevalent in humans with Fetal Alcohol Spectrum Disorders (FASD) and in rodent models of FASD. Most studies have investigated neuroimmune activation following adult alcohol exposure or following multiple exposures. The current study uses a single day binge alcohol exposure model (postnatal day [PD] 4) to examine sex differences in the neuroimmune response in the developing rat hippocampus on PD5 and 8. The neuroimmune response was evaluated through measurement of microglial number and cytokine gene expression at both time points. Male pups had higher microglial number compared to females in many hippocampal subregions on PD5, but this difference disappeared by PD8, unless exposed to alcohol. Expression of pro-inflammatory marker CD11b was higher on PD5 in alcohol-exposed (AE) females compared to AE males. After alcohol exposure, C-C motif chemokine ligand 4 (CCL4) was significantly increased in female AE pups on PD5 and PD8. Tumor necrosis factor-α (TNF-α) levels were also upregulated by AE in males on PD8. The results demonstrate a clear difference between the male and female neuroimmune response to an AE challenge, which also occurs in a time-dependent manner. These findings are significant as they add to our knowledge of specific sex-dependent effects of alcohol exposure on microglia within the developing brain.

Arsenic is Cytotoxic and Genotoxic to Primary Human Lung Cells

PubMed Central

Xie, Hong; Huang, ShouPing; Martin, Sarah; Wise, John P.

2014-01-01

Arsenic originates from both geochemical and numerous anthropogenic activities. Exposure of the general public to significant levels of arsenic is widespread. Arsenic is a well-documented human carcinogen. Long-term exposure to high levels of arsenic in drinking water have been linked to bladder, lung, kidney, liver, prostate, and skin cancer. Among them, lung cancer is of great public concern. However, little is known about how arsenic causes lung cancer and few studies have considered effects in normal human lung cells. The purpose of this study was to determine the cytotoxicity and genotoxicity of arsenic in human primary bronchial fibroblast and epithelial cells. Our data show that arsenic induces a concentration-dependent decrease in cell survival after short (24 h) or long (120 h) exposures. Arsenic induces concentration-dependent but not time-dependent increases in chromosome damage in fibroblasts. No chromosome damage is induced after either 24 h or 120 h arsenic exposure in epithelial cells. Using neutral comet assay and gamma-H2A.X foci forming assay, we found that 24 h or 120 h exposure to arsenic induces increases in DNA double strand breaks in both cell lines. These data indicate that arsenic is cytotoxic and genotoxic to human lung primary cells but lung fibroblasts are more sensitive to arsenic than epithelial cells. Further research is needed to understand the specific mechanisms involved in arsenic-induced genotoxicity in human lung cells. PMID:24291234

Absorption, distribution and excretion of inhaled hydrogen fluoride in the rat

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morris, J.B.

1979-01-01

Rats were subjected to whole body HF exposure for 6 hrs or to nose-only HF exposure for 1 hr. Total and/or ionic fluoride concentrations in selected tissues were determined at various times following exposure. In rats sacrificed 6 hrs after whole body exposure, dose-dependent increases in lung, plasma, and kidney total and ionic fluoride concentration occurred. Rats excreted more fluoride in the urine after whole body exposure than could be explained by the amount of HF inhaled. Considerable evidence suggests that airborne HF deposits on fur and is then ingested due to preening activity. Urinary fluoride excretion was increased bymore » nose-only exposure. The urinary fluoride excretion accounted for approximately twice the fluoride estimated to be inhaled during exposure. Tissue fluoride concentrations were elevated immediately after nose-only exposure. Fluoride concentrations in lung and kidney returned to control levels within 12 hrs. Plasma fluoride concentration was slightly elevated 24 hrs after the start of the 1 hr exposure but was at control levels at 96 hrs. Immediately following nose-only exposure, lung ionic fluoride concentrations were less than plasma ionic fluoride concentrations suggesting that the fluoride in the lung had reached that site via plasma transport rather than by inhalation. A dose-dependent increase in plasma ionic fluoride concentration occurred after upper respiratory tract HF exposure providing strong evidence that fluoride is absorbed systemically from that site. The plasma ionic fluoride concentration after upper respiratory tract exposure was of sufficient magnitude to account for the plasma fluoride concentrations observed in intact nose-only exposed rats. (ERB)« less

Biotransformation in the zebrafish embryo -temporal gene transcription changes of cytochrome P450 enzymes and internal exposure dynamics of the AhR binding xenobiotic benz[a]anthracene.

PubMed

Kühnert, Agnes; Vogs, Carolina; Seiwert, Bettina; Aulhorn, Silke; Altenburger, Rolf; Hollert, Henner; Küster, Eberhard; Busch, Wibke

2017-11-01

Not much is known about the biotransformation capability of zebrafish (Danio rerio) embryos. For understanding possible toxicity differences to adult fish, it might be crucial to understand the biotransformation of chemicals in zebrafish embryos i.e. as part of toxicokinetics. The biotransformation capabilities were analysed for two different stages of zebrafish embryos in conjunction with the internal concentrations of a xenobiotic. Zebrafish embryos of the late cleavage/early blastula period (2-26 hpf) and the early pharyngula period (26-50 hpf) were exposed for 24 h to the AhR binding compound benz[a]anthracene (BaA). Time dependent changes in cyp transcription (cyp1a, cyp1b1, cyp1c1 and cyp1c2) as well as concentration & time-dependent courses of BaA in the fish embryo and the exposure medium were analysed. Additionally, the CYP mediated formation of biotransformation products was investigated. We found correlations between transcriptional responses and the internal concentration for both exposure types. These correlations were depending on the start of the exposure i.e. the age of the exposed embryo. While no significant induction of the examined gene transcripts was observed in the first 12 h of exposure beginning in the blastula period a correlation was apparent when exposure started later i.e. in the pharyngula period. A significant induction of cyp1a was detected already after 1.5 h of BaA exposure. Gene transcripts for cyp1b1, cyp1c1 and cyp1c2 showed expressions distinctly different from cyp1a and were, in general, less inducible by BaA in both exposure windows. The toxicokinetic analysis showed that the biotransformation capability was fivefold higher in the older fish embryos. Biotransformation products of phase I reactions were found between 32 hpf and 50 hpf and were tentatively identified as benz[a]anthracene-phenol and benz[a]anthracene-dihydrodiol-epoxide. In conclusion, not only duration but also onset of exposure in relation to the developmental stage of zebrafish embryos is important in the analysis and interpretation of effects due to different biotransformation capabilities. Copyright © 2017 Elsevier Ltd. All rights reserved.

Deviations from Haber’s Law for Multiple Measures of Acute Lung Injury in Chlorine-Exposed Mice

PubMed Central

Hoyle, Gary W.; Chang, Weiyuan; Chen, Jing; Schlueter, Connie F.; Rando, Roy J.

2010-01-01

Chlorine gas is considered a chemical threat agent that can cause acute lung injury. Studies in the early 20th century on war gases led Haber to postulate that the dose of an inhaled chemical expressed as the product of gas concentration and exposure time leads to a constant toxicological effect (Haber’s Law). In the present work, mice were exposed to a constant dose of chlorine (100 ppm-h) delivered using different combinations of concentration and time (800 ppm/7.5 min, 400 ppm/15 min, 200 ppm/30 min, and 100 ppm/60 min). Significant effects of exposure protocol on survival evaluated 6 h after exposure were observed, ranging from 0% for the 7.5-min exposure to 100% for the 30- and 60-min exposures. Multiple parameters indicative of lung injury were examined to determine if any aspects of lung injury were differentially affected by the exposure protocols. Most parameters (pulmonary edema, neutrophil influx, and levels of protein, immunoglobulin M, and the chemokine KC [Cxcl1] in lavage fluid) indicated that lung injury was most pronounced for the 15-min exposure and least for the 60-min exposure. In contrast, changes in pulmonary function at baseline and in response to inhaled methacholine were similar following the three exposure regimens. The results indicate that the extent of lung injury following chlorine inhalation depends not only on total dose but also on the specifics of exposure concentration and time, and they suggest that evaluation of countermeasures against chlorine-induced lung injury should be performed using multiple types of exposure scenarios. PMID:20819911

Antiorthostatic test as a model to study antigravity mechanisms of the cardiovascular system.

PubMed

Yarullin, K K; Vasilyeva, T D; Alekseev, D A

1976-01-01

The paper presents rheographic investigations of regional haemodynamics (brain, lungs, liver and limbs) during antiorthostatic exposures of varying intensity (-15, -30, -45 degrees, times of exposure 20, 40 and 60 min). Our findings show that the pattern and time of the function of compensatory mechanisms preventing excessive vascular compliance [correction of complicance] under the influence of the hydrostatic blood column depend on the value and length of antiorthostasis, because prolonged venous congestion results not only in congestive circulatory hypoxia but also in arterial hypoxia due to compensatory limitation of arterial inflow.

Rapid fibrin plug formation within cutaneous ablative fractional CO2 laser lesions.

PubMed

Kositratna, Garuna; Evers, Michael; Sajjadi, Amir; Manstein, Dieter

2016-02-01

Ablative fractional laser procedures have been shown to facilitate topical drug delivery into the skin. Past studies have mainly used ex vivo models to demonstrate enhanced drug delivery and in vivo studies have investigated laser created channels over a time course of days and weeks rather than within the first few minutes and hours after exposures. We have noticed rapid in vivo fibrin plug formation within ablative fractional laser lesions impairing passage through the laser created channels. In vivo laser exposures were performed in a porcine model. A fractional CO2 laser (AcuPulse™ system, AcuScan 120™ handpiece, Lumenis, Inc., Yokneam, Israel) was programmed in quasi-continuous wave (QCW) mode, at 40W, 50 mJ per pulse, 5% coverage, nominal 120 µm spot size, 8 × 8 mm square pattern, 169 MTZs per scan. Six millimeters punch biopsies were procured at 0, 2, 5, 10, 15, 30, 60, 90 minutes after completion of each scan, then fixed in 10% formalin. 12 repeats were performed of each time point. Skin samples were processed for serial vertically cut paraffin sections (5 μm collected every 25 μm) then H&E and special immunohistochemistry staining for fibrin and platelet. Dimensions of Microscopic Treatment Zones (MTZs) and extent of fibrin plug were assessed and quantified histologically. Ex vivo laser exposures of the identical laser parameter were performed on porcine and human skin at different storage conditions. Histology procured at various predetermined time intervals after in vivo fractional CO2 laser exposures revealed a rapidly forming fibrin plug initiating at the bottom of the MTZ lesions. At longer time intervals, the fibrin plug was extending towards the superficial sections. Within the first 5 minutes, more than 25% length of the entire laser-ablated channel was filled with a fibrin plug. With increased time intervals, the cavity was progressively filled with a fibrin plug. At 90 minutes, more than 90% length of the entire laser-ablated channel was occluded. Ex vivo exposures failed to produce any significant fibrin plug formation. The current study has demonstrated rapid fibrin plug formation after ablative fractional laser procedures. It was shown that the passage through laser created pathways is critically time dependent for in vivo exposures. In contrast, ex vivo exposures do not exhibit such time dependent passage capacity. In particular, drug, substance, and cell delivery studies for ablative fractional laser treatments should take early fibrin plug formation into consideration and further investigate the impact on transdermal delivery. © 2015 Wiley Periodicals, Inc.

Photon Counting Imaging with an Electron-Bombarded Pixel Image Sensor

PubMed Central

Hirvonen, Liisa M.; Suhling, Klaus

2016-01-01

Electron-bombarded pixel image sensors, where a single photoelectron is accelerated directly into a CCD or CMOS sensor, allow wide-field imaging at extremely low light levels as they are sensitive enough to detect single photons. This technology allows the detection of up to hundreds or thousands of photon events per frame, depending on the sensor size, and photon event centroiding can be employed to recover resolution lost in the detection process. Unlike photon events from electron-multiplying sensors, the photon events from electron-bombarded sensors have a narrow, acceleration-voltage-dependent pulse height distribution. Thus a gain voltage sweep during exposure in an electron-bombarded sensor could allow photon arrival time determination from the pulse height with sub-frame exposure time resolution. We give a brief overview of our work with electron-bombarded pixel image sensor technology and recent developments in this field for single photon counting imaging, and examples of some applications. PMID:27136556

Time-dependent clustering analysis of the second BATSE gamma-ray burst catalog

NASA Technical Reports Server (NTRS)

Brainerd, J. J.; Meegan, C. A.; Briggs, Michael S.; Pendleton, G. N.; Brock, M. N.

1995-01-01

A time-dependent two-point correlation-function analysis of the Burst and Transient Source Experiment (BATSE) 2B catalog finds no evidence of burst repetition. As part of this analysis, we discuss the effects of sky exposure on the observability of burst repetition and present the equation describing the signature of burst repetition in the data. For a model of all burst repetition from a source occurring in less than five days we derive upper limits on the number of bursts in the catalog from repeaters and model-dependent upper limits on the fraction of burst sources that produce multiple outbursts.

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure.

PubMed

Rautava, Samuli; Walker, W Allan; Lu, Lei

2016-06-01

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment. Copyright © 2016 the American Physiological Society.

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure

PubMed Central

Rautava, Samuli; Lu, Lei

2016-01-01

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1β and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1β-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1β-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment. PMID:27056727

Evaluation of cognitive behaviors in young offspring of C57BL/6J mice after gestational nicotine exposure during different time-windows.

PubMed

Alkam, Tursun; Kim, Hyoung-Chun; Mamiya, Takayoshi; Yamada, Kiyofumi; Hiramatsu, Masayuki; Nabeshima, Toshitaka

2013-12-01

Gestational nicotine exposure is associated with cognitive abnormalities in young offspring. However, practical strategies for prevention or treatment of impaired cognitive behaviors of offspring are not available due to the lack of systematic investigation of underlying mechanism. Therefore, this study aimed at examining the effects of gestational and/or perinatal nicotine exposure (GPNE) on cognitive behaviors in offspring of C57BL/6J mice to provide systematic behavioral data. Pregnant mice were exposed to nicotine via sweetened drinking water during six time-windows, including gestational day 0 to day 13 (G0-G13), G14-postnatal day 0 (P0), G0-P0, G14-P7, G0-P7, and P0-P7. During P42-P56 days, both male and female offspring were given a battery of behavioral tests. Depending on the time of exposure, GPNE impaired working memory, object-based attention, and prepulse inhibition in male and female offspring to different extents. Nicotine exposure during G14-P0 also decreased norepinephrine turnover in the prefrontal cortex on P28 and P56. Overall results indicate that nicotine exposure during any time-windows of development impairs cognitive behaviors in offspring, and suggest that certain time-windows, e.g., G14-P0, should be selected for further studies on the underlying neurochemical or molecular mechanisms.

[Natural history of occupational hearing loss induced by noise].

PubMed

de Almeida, S I; Albernaz, P L; Zaia, P A; Xavier, O G; Karazawa, E H

2000-01-01

To evaluate the clinical and audiometric characteristics of occupational hearing loss induced by noise, according to age and time of exposition in years. 222 patients with occupational sensorineural hearing loss induced by noise were studied retrospectively, correlating the auditive clinical claims, alterations of audiometric thresholds at frequencies of 250 Hz to 8000 Hz, speech discrimination indicator with age and time of exposure. As a control group were used the audiometric threshold of a population of same medium age, without morbid antecedents of hearing illness, as preconized by ISO 1999 (1990). The group were divided into subgroups and three decades of exposure were analyzed. It was verified that the clinical claims of hipoacusia increases according to the age and time of exposure. The frequency of tinnitus is constant. The audiometric thresholds in the second decade of exposure present variations that depend on the age. The several audiometric curves are parallel, but they are not horizontal. The worst thresholds were found in the high frequencies from 3000 Hz to 8000 Hz, as a clinical and physiopathological consequences of the commitment of basal areas of cochlea. The speech discrimination showed to be worst according to the increase of age and time of exposure. Patients with hearing loss disacusia induced by occupational noise present characteristic audiometric thresholds that vary according to age and time of exposure to noise. These characteristics defined and resumed in audiometric curves can constitute a standard of comparison, evaluation and control for exposed populations.

The effect of moisture content within multilayer protective clothing on protection from radiation and steam.

PubMed

Su, Yun; Li, Jun; Song, Guowen

2018-06-01

The moisture from skin sweat and atmospheric water affects the thermal protective performance provided by multilayer protective clothing. Four levels of moisture content were selected to evaluate the impact of moisture on thermal protection under dry (thermal radiation) and wet (thermal radiation and low-pressure steam) heat exposure. Also, the role of moisture and its relationship with exposure time were analyzed based on skin heat flux and Henriques integral value. The addition of moisture to a fabric system was found to result in differences in second-degree and third-degree skin burn times. When moisture is added to a fabric system, it both acts as a thermal conductor to present a negative effect and provides a positive effect owing to thermal storage of water and evaporative heat loss. The positive or negative effects of moisture are mainly dependent on the thermal exposure time, the moisture content and the presence of hot steam.

A land-use regression model for estimating microenvironmental diesel exposure given multiple addresses from birth through childhood.

PubMed

Ryan, Patrick H; Lemasters, Grace K; Levin, Linda; Burkle, Jeff; Biswas, Pratim; Hu, Shaohua; Grinshpun, Sergey; Reponen, Tiina

2008-10-01

The Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) is a prospective birth cohort whose purpose is to determine if exposure to high levels of diesel exhaust particles (DEP) during early childhood increases the risk for developing allergic diseases. In order to estimate exposure to DEP, a land-use regression (LUR) model was developed using geographic data as independent variables and sampled levels of a marker of DEP as the dependent variable. A continuous wind direction variable was also created. The LUR model predicted 74% of the variability in sampled values with four variables: wind direction, length of bus routes within 300 m of the sample site, a measure of truck intensity within 300 m of the sampling site, and elevation. The LUR model was subsequently applied to all locations where the child had spent more than eight hours per week from through age three. A time-weighted average (TWA) microenvironmental exposure estimate was derived for four time periods: 0-6 months, 7-12 months, 13-24 months, 25-36 months. By age two, one third of the children were spending significant time at locations other than home and by 36 months, 39% of the children had changed their residential addresses. The mean cumulative DEP exposure estimate increased from age 6 to 36 months from 70 to 414 microg/m3-days. Findings indicate that using birth addresses to estimate a child's exposure may result in exposure misclassification for some children who spend a significant amount of time at a location with high exposure to DEP.

Possible relationship between endocrine disrupting chemicals and hormone dependent gynecologic cancers.

PubMed

Dogan, Selen; Simsek, Tayup

2016-07-01

The effects of the natural and synthetic estrogens have been studied for a long time but the data regarding estrogen related chemicals (endocrine disrupting chemicals, EDCs) and their effects on reproductive system are scarce. EDCs are hormone like agents that are readily present in the environment, which may alter the endocrine system of humans and animals. Approximately 800 chemicals are known or suspected to have the potential to function as EDC. Potential role of EDCs on reproductive disease has gained attention in medical literature in recent years. We hypothesize that exposure to low doses of EDCs in a chronic manner could cause hormone dependent genital cancers including ovarian and endometrial cancer. Long term exposure to low concentrations of EDCs may exert potentiation effect with each other and even with endogenous estrogens and could inhibit enzymes responsible for estrogen metabolism. Exposure time to these EDCs is essential as we have seen from Diethylstilbestrol experience. Dose-response curves of EDCs are also unpredictable. Hence mode of action of EDCs are more complex than previously thought. In the light of these controversies lower doses of EDCs in long term exposure is not harmless. Possibility of this relationship and this hypothesis merit further investigation especially through in vivo studies that could better show the realistic environmental exposure. With the confirmation of our hypothesis, possible EDCs could be identified and eliminated from general use as a public health measure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Exposure to peer delinquency as a mediator between self-report pubertal timing and delinquency: A longitudinal study of mediation

PubMed Central

Negriff, Sonya; Ji, Juye; Trickett, Penelope K.

2013-01-01

This study examined exposure to peer delinquency as a mediator between pubertal timing and self-reported delinquency longitudinally and whether this mediational model was moderated by either gender or maltreatment experience. Data were obtained from Time 1, 2, and 3 of a longitudinal study of maltreatment and development. At Time 1 the sample comprised 454 children aged 9–13 years. Analyses via structural equation modeling supported full mediation. Gender did not moderate this mediational relationship, but maltreatment experience did. The results show that early maturing males and females are both at risk for being exposed to peers that may draw them into delinquent behavior. Additionally, the mechanism linking early pubertal timing to delinquency differs depending on maltreatment experience. PMID:21262055

Arab Americans' acculturation and tobacco smoking.

PubMed

Al-Omari, Hasan; Scheibmeir, Monica

2009-04-01

Limited information is available about Arab Americans' smoking behaviors. The aim of this study was to describe Arab Americans' smoking behaviors and any relationship between tobacco dependence and acculturation. This was a cross-sectional study. Arab American smokers and ex-smokers (N = 96) participated in the study. Nicotine dependence, acculturation, and tobacco use questionnaires were used to measure the major variables. Analyses revealed a significant positive correlation between acculturation and tobacco dependence and between tobacco exposure and tobacco dependence. Arab Americans who behaved most like their ethnic peers and spent more time with Arab Americans were more dependent on nicotine.

Toxic industrial chemicals and chemical weapons: exposure, identification, and management by syndrome.

PubMed

Tomassoni, Anthony J; French, Robert N E; Walter, Frank G

2015-02-01

Toxidromes aid emergency care providers in the context of the patient presenting with suspected poisoning, unexplained altered mental status, unknown hazardous materials or chemical weapons exposure, or the unknown overdose. The ability to capture an adequate chemical exposure history and to recognize toxidromes may reduce dependence on laboratory tests, speed time to delivery of specific antidote therapy, and improve selection of supportive care practices tailored to the etiologic agent. This article highlights elements of the exposure history and presents selected toxidromes that may be caused by toxic industrial chemicals and chemical weapons. Specific antidotes for toxidromes and points regarding their use, and special supportive measures, are presented. Copyright © 2015 Elsevier Inc. All rights reserved.

High-speed imaging using CMOS image sensor with quasi pixel-wise exposure

NASA Astrophysics Data System (ADS)

Sonoda, T.; Nagahara, H.; Endo, K.; Sugiyama, Y.; Taniguchi, R.

2017-02-01

Several recent studies in compressive video sensing have realized scene capture beyond the fundamental trade-off limit between spatial resolution and temporal resolution using random space-time sampling. However, most of these studies showed results for higher frame rate video that were produced by simulation experiments or using an optically simulated random sampling camera, because there are currently no commercially available image sensors with random exposure or sampling capabilities. We fabricated a prototype complementary metal oxide semiconductor (CMOS) image sensor with quasi pixel-wise exposure timing that can realize nonuniform space-time sampling. The prototype sensor can reset exposures independently by columns and fix these amount of exposure by rows for each 8x8 pixel block. This CMOS sensor is not fully controllable via the pixels, and has line-dependent controls, but it offers flexibility when compared with regular CMOS or charge-coupled device sensors with global or rolling shutters. We propose a method to realize pseudo-random sampling for high-speed video acquisition that uses the flexibility of the CMOS sensor. We reconstruct the high-speed video sequence from the images produced by pseudo-random sampling using an over-complete dictionary.

Short-term memory for pictures seen once or twice.

PubMed

Martini, Paolo; Maljkovic, Vera

2009-06-01

The present study is concerned with the effects of exposure time, repetition, spacing and lag on old/new recognition memory for generic visual scenes presented in a RSVP paradigm. Early memory studies with verbal material found that knowledge of total exposure time at study is sufficient to accurately predict memory performance at test (the Total Time Hypothesis), irrespective of number of repetitions, spacing or lag. However, other studies have disputed such simple dependence of memory strength on total study time, demonstrating super-additive facilitatory effects of spacing and lag, as well as inhibitory effects, such as the Ranschburg effect, Repetition Blindness and the Attentional Blink. In the experimental conditions of the present study we find no evidence of either facilitatory or inhibitory effects: recognition memory for pictures in RSVP supports the Total Time Hypothesis. The data are consistent with an Unequal-Variance Signal Detection Theory model of memory that assumes the average strength and the variance of the familiarity of pictures both increase with total study time. The main conclusion is that the growth of visual scene familiarity with temporal exposure and repetition is a stochastically independent process.

Repeated Exposure to Ketamine-Xylazine during Early Development Impairs Motor Learning-dependent Dendritic Spine Plasticity in Adulthood

PubMed Central

Huang, Lianyan; Yang, Guang

2014-01-01

Background Recent studies in rodents suggest that repeated and prolonged anesthetic exposure at early stages of development leads to cognitive and behavioral impairments later in life. However, the underlying mechanism remains unknown. In this study, we tested whether exposure to general anesthesia during early development will disrupt the maturation of synaptic circuits and compromise learning-related synaptic plasticity later in life. Methods Mice received ketamine/xylazine (20/3 mg/kg) anesthesia for one or three times, starting at either early [postnatal day 14 (P14)] or late (P21) stages of development (n=105). Control mice received saline injections (n=34). At P30, mice were subjected to rotarod motor training and fear conditioning. Motor learning-induced synaptic remodeling was examined in vivo by repeatedly imaging fluorescently-labeled postsynaptic dendritic spines in the primary motor cortex before and after training using two-photon microscopy. Results Three exposures to ketamine/xylazine anesthesia between P14–18 impair the animals’ motor learning and learning-dependent dendritic spine plasticity [new spine formation, 8.4 ± 1.3% (mean ± SD) versus 13.4 ± 1.8%, P = 0.002] without affecting fear memory and cell apoptosis. One exposure at P14 or three exposures between P21–25 has no effects on the animals’ motor learning or spine plasticity. Finally, enriched motor experience ameliorates anesthesia-induced motor learning impairment and synaptic deficits. Conclusion Our study demonstrates that repeated exposures to ketamine/xylazine during early development impair motor learning and learning-dependent dendritic spine plasticity later in life. The reduction in synaptic structural plasticity may underlie anesthesia-induced behavioral impairment. PMID:25575163

Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature

PubMed Central

Honavar, Jaideep; Bradley, Eddie; Bradley, Kelley; Oh, Joo Yeun; Vallejo, Matthew O.; Kelley, Eric E.; Cantu-Medellin, Nadiezhda; Doran, Stephen; Dell’italia, Louis J.; Matalon, Sadis; Patel, Rakesh P.

2014-01-01

Exposure to chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400ppm, 30min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex-vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24–48 hours post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ~2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E+) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (~4mmHg) lower in rats that had been exposed to Cl2 gas 24 hours earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity. PMID:24769334

Effects of Ionizing Radiation on Human Adipose Derived Mesenchymal Stem Cells and their Differentiation towards the Osteoblastic Lineage

NASA Astrophysics Data System (ADS)

Konda, Bikash; Baumstark-Khan, Christa; Hellweg, Christine; Reitz, Guenther; Lau, Patrick

Radiation exposure and musculoskeletal disuse are among the major challenges during space missions. Astronauts face the problem to lose bone calcium due to uncoupling of bone formation and resorption. Bone forming osteoblasts can be derived from the undifferentiated mesenchymal stem cell compartment (MSC). In this study, the ability of human adipose tissue derived stem cells (ATSC) to differentiate into the osteoblastic lineage was examined after radiation exposure in presence of medium supplementation with osteogenic additives (ß-glycerophosphate, ascorbic acid and dexamethasone). The SAOS-2 cell line (human osteosarcoma cell line) was used as control for osteoblastic differentiation. Changes in cellular morphology, cell cycle progression, as well as cellular radiation sensitivity were characterized after ionizing radiation exposure with X-rays and heavy ions (Ti). Rapidly proliferating SAOS-2 cells are less radiation-sensitive than slowly proliferating ATSC cells after X-ray (CFA: dose effect curves show D0 values of 1 Gy and 0.75 Gy for SAOS-2 and ATSC, respectively) exposure. Heavy ion (Ti) exposure resulted in a greater extent of cells accumulating in the G2/M phase of the cell cycle in a dose-dependent manner when compared to X-ray exposure. Differentiation of cells towards the osteoblastic lineage was quantified by hydroxyapatite (HA) deposition using Lonza OsteoImageTM mineralization assay. The deposition of HA after X- and Ti-irradiation for highly proliferating SAOS-2 cells showed a dose-dependent time delay while slowly proliferating ATSC showed no effect from radiation exposure. More detailed investigation is required to reveal the radiation dependent mechanism of bone loss in astronauts.

A new form of the calibration curve in radiochromic dosimetry. Properties and results

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamponi, Matteo, E-mail: mtamponi@aslsassari.it; B

Purpose: This work describes a new form of the calibration curve for radiochromic dosimetry that depends on one fit parameter. Some results are reported to show that the new curve performs as well as those previously used and, more importantly, significantly reduces the dependence on the lot of films, the film orientation on the scanner, and the time after exposure. Methods: The form of the response curve makes use of the net optical densities ratio against the dose and has been studied by means of the Beer–Lambert law and a simple modeling of the film. The new calibration curve hasmore » been applied to EBT3 films exposed at 6 and 15 MV energy beams of linear accelerators and read-out in transmission mode by means of a flatbed color scanner. Its performance has been compared to that of two established forms of the calibration curve, which use the optical density and the net optical density against the dose. Four series of measurements with four lots of EBT3 films were used to evaluate the precision, accuracy, and dependence on the time after exposure, orientation on the scanner and lot of films. Results: The new calibration curve is roughly subject to the same dose uncertainty, about 2% (1 standard deviation), and has the same accuracy, about 1.5% (dose values between 50 and 450 cGy), as the other calibration curves when films of the same lot are used. Moreover, the new calibration curve, albeit obtained from only one lot of film, shows a good agreement with experimental data from all other lots of EBT3 films used, with an accuracy of about 2% and a relative dose precision of 2.4% (1 standard deviation). The agreement also holds for changes of the film orientation and of the time after exposure. Conclusions: The dose accuracy of this new form of the calibration curve is always equal to or better than those obtained from the two types of curves previously used. The use of the net optical densities ratio considerably reduces the dependence on the lot of films, the landscape/portrait orientation, and the time after exposure. This form of the calibration curve could become even more useful with new optical digital devices using monochromatic light.« less

A new form of the calibration curve in radiochromic dosimetry. Properties and results.

PubMed

Tamponi, Matteo; Bona, Rossana; Poggiu, Angela; Marini, Piergiorgio

2016-07-01

This work describes a new form of the calibration curve for radiochromic dosimetry that depends on one fit parameter. Some results are reported to show that the new curve performs as well as those previously used and, more importantly, significantly reduces the dependence on the lot of films, the film orientation on the scanner, and the time after exposure. The form of the response curve makes use of the net optical densities ratio against the dose and has been studied by means of the Beer-Lambert law and a simple modeling of the film. The new calibration curve has been applied to EBT3 films exposed at 6 and 15 MV energy beams of linear accelerators and read-out in transmission mode by means of a flatbed color scanner. Its performance has been compared to that of two established forms of the calibration curve, which use the optical density and the net optical density against the dose. Four series of measurements with four lots of EBT3 films were used to evaluate the precision, accuracy, and dependence on the time after exposure, orientation on the scanner and lot of films. The new calibration curve is roughly subject to the same dose uncertainty, about 2% (1 standard deviation), and has the same accuracy, about 1.5% (dose values between 50 and 450 cGy), as the other calibration curves when films of the same lot are used. Moreover, the new calibration curve, albeit obtained from only one lot of film, shows a good agreement with experimental data from all other lots of EBT3 films used, with an accuracy of about 2% and a relative dose precision of 2.4% (1 standard deviation). The agreement also holds for changes of the film orientation and of the time after exposure. The dose accuracy of this new form of the calibration curve is always equal to or better than those obtained from the two types of curves previously used. The use of the net optical densities ratio considerably reduces the dependence on the lot of films, the landscape/portrait orientation, and the time after exposure. This form of the calibration curve could become even more useful with new optical digital devices using monochromatic light.

Cytotoxic Effects of Nonionic Iodinated Contrast Agent on Human Adipose-derived Mesenchymal Stem Cells.

PubMed

Wu, Tao; Nie, Hai; Dietz, Allan B; Salek, David R; Smith, Jay; van Wijnen, Andre J; Qu, Wenchun

2018-05-31

Transplantation of mesenchymal stem cells (MSCs) is a promising therapy for degenerative spine conditions. However, cell therapy for painful spine degeneration presently requires use of contrast agents during fluoroscopy-guided injections and the effects of these agents on MSCs represents a gap in knowledge. To investigate the biological effects of contrast media that are co-injected with MSCs. Prospective observational study. Academic medical center. Patient-derived clinical-grade culture expanded MSCs. Iohexol(Omnipaque300) was reduced to 12.5%, 25%, 50% and 100% of the stock solution and incubated with MSCs for 30 minutes, 4 hours and 48 hours. We also used complete media and 12.5%, 25%, 50%, 100% of phosphate buffered saline (PBS) as control group. We examined cytotoxicity of Iohexol at different concentrations and exposure duration, as well as the potential for recovery over time. Cell counts, mitochondrial activity, and quantitative real time reverse-transcriptase polymerase chain reaction (qRT-PCR) of related genes were analyzed immediately after exposure (day 0) and after two days of exposure (day 2). Human MSCs exhibit a time- and concentration-dependent cytotoxic response to iodinated CM. A brief 30min exposure did not affect MSCs function and viability. However, extended treatment with iohexol for 4 hours at 50% or higher concentration had a significant impact on both viability and gene expression in MSCs. CM (Omnipaque300) is cytotoxic to MSCs in a time-and concentration-dependent manner. Hence, the concentration of CM that accompanies MSC injections should be carefully considered during mesenchymal stem cell therapy for disc degenerative diseases. Copyright © 2018 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

Comparison of high MRI T1 signals with manganese concentration in brains of cynomolgus monkeys after 8 months of stainless steel welding-fume exposure.

PubMed

Park, Jung Duck; Chung, Yong Hyun; Kim, Choong Yong; Ha, Chang Soo; Yang, Seoung Oh; Khang, Hyun Soo; Yu, In Kyu; Cheong, Hae Kwan; Lee, Jong Seong; Song, Chang-Woo; Kwon, Il Hoon; Han, Jeong Hee; Sung, Jae Hyuck; Heo, Jeong Doo; Choi, Byung Sun; Im, Ruth; Jeong, Jayoung; Yu, Il Je

2007-09-01

Several pharmacokinetic studies on inhalation exposure to manganese (Mn) have already demonstrated that Mn readily accumulates in the olfactory and brain regions. However, a shortening of the magnetic resonance imaging (MRI) T1 relaxation time or high T1 signal intensity in specific sites of the brain, including the globus pallidus and subcortical frontal white matter, as indicative of tissue manganese accumulation has not yet been clearly established for certain durations of known doses of welding-fume exposure in experimental animals. Accordingly, to investigate the movement of manganese after welding-fume exposure, six cynomolgus monkeys were acclimated and assigned to three dose groups: unexposed, low dose (31 mg/m(3) total suspended particulate [TSP], 0.9 mg/m(3) of Mn), and high dose (62 mg/m(3) TSP, 1.95 mg/m(3) of Mn) of total suspended particulate. The primates were exposed to manual metal arc stainless steel (MMA-SS) welding fumes for 2 h per day in an inhalation chamber system equipped with an automatic fume generator. Magnetic resonance imaging (MRI) studies were conducted before the initiation of exposure and thereafter every month. The tissue Mn concentrations were then measured after a plateau was reached regarding the shortening of the MRI T1 relaxation time. A dose-dependent increase in the Mn concentration was found in the lungs, while noticeable increases in the Mn concentrations were found in certain tissues, such as the liver, kidneys, and testes. Slight increases in the Mn concentrations were found in the caudate, putamen, frontal lobe, and substantia nigra, while a dose-dependent noticeable increase was only found in the globus pallidus. Therefore, the present results indicated that a shortening of the MRI T1 relaxation time corresponded well with the Mn concentration in the globus pallidus after prolonged welding-fume exposure.

Predictors, Indicators, and Validated Measures of Dependence in Menthol Smokers

PubMed Central

Muhammad-Kah, Raheema; Rimmer, Lonnie; Liang, Qiwei

2014-01-01

This article presents a comprehensive review of the menthol cigarette dependence-related literature and results from an original analysis of the Total Exposure Study (TES), which included 1,100 menthol and 2,400 nonmenthol adult smokers. The substantial scientific evidence available related to age of first cigarette, age of regular use, single-item dependence indicators (smoking frequency, cigarettes per day, time to first cigarette, night waking to smoke), smoking duration, numerous validated and widely accepted measures of nicotine/cigarette dependence, and our analysis of the TES do not support that menthol smokers are more dependent than nonmenthol smokers or that menthol increases dependence. PMID:24738914

Compatibility of Automatic Exposure Control with New Screen Phosphors in Diagnostic Roentgenography.

NASA Astrophysics Data System (ADS)

Mulvaney, James Arthur

1982-03-01

Automatic exposure control systems are used in diagnostic roentgenography to obtain proper film density for a variety of patient examinations and roentgenographic techniques. Most automatic exposure control systems have been designed for use with par speed, calcium tungstate intensifying screens. The use of screens with faster speeds and new phosphor materials has put extreme demands on present systems. The performance of a representative automatic exposure control system is investigated to determine its ability to maintain constant film density over a wide range of x-ray tube voltages and acrylic phantom thicknesses with four different intensifying screen phosphors. The effects of x-ray energy dependence, generator switching time and stored change are investigated. The system is able to maintain film density to within plus or minus 0.2 optical density units for techniques representing adult patients. A single nonadjustable tube voltage compensation circuit is adequate for the four different screen phosphors for x-ray tube voltages above sixty peak kilovolts. For techniques representing pediatric patients at high x-ray tube voltages, excess film density occurs due to stored charge in the transformer and high-voltage cables. An anticipation circuit in the automatic exposure control circuit can be modified to correct for stored charge effects. In a separate experiment the energy dependence of three different ionization chamber detectors used in automatic exposure control systems is compared directly with the energy dependence of three different screen phosphors. The data on detector sensitivity and screen speed are combined to predict the best tube voltage compensation for each combination of screen and detector.

Social factors associated with nitrogen dioxide (NO2) exposure during pregnancy: the INMA-Valencia project in Spain.

PubMed

Llop, Sabrina; Ballester, Ferran; Estarlich, Marisa; Iñiguez, Carmen; Ramón, Rosa; Gonzalez, Ma Carmen; Murcia, Mario; Esplugues, Ana; Rebagliato, Marisa

2011-03-01

Numerous studies have focused on the effects of exposure to air pollution on health; however, certain subsets of the population tend to be more exposed to such pollutants depending on their social or demographic characteristics. In addition, exposure to toxicants during pregnancy may play a deleterious role in fetal development as fetuses are especially vulnerable to external insults. The present study was carried out within the framework of the INMA (Infancia y Medio Ambiente or Childhood and the Environment) multicenter cohort study with the objective of identifying the social, demographic, and life-style factors associated with nitrogen dioxide (NO(2)) exposure in the subjects in the cohort. The study comprised 785 pregnant women who formed part of the INMA cohort in Valencia, Spain. Outdoor levels of NO(2) were measured at 93 sampling sites spread over the study area during four different sampling periods lasting 7 days each. Multiple regression models were used for mapping outdoor NO(2) throughout the area. Individual exposure was assigned as: 1) the estimated outdoor NO(2) levels at home, and 2) the average of estimated outdoor NO(2) levels at home and work, weighted according to the time spent in each environment. The subjects' socio-demographic and life-style information was obtained through a questionnaire. In the multiple linear analyses, the outdoor NO(2) levels assigned to each home were taken to be the dependent variable. Other variables included in the model were: age, country of origin, smoking during pregnancy, parity, season of the year, and social class. These same variables remained in the model when the dependent variable was changed to the NO(2) levels adjusted for the subjects' time-activity patterns. We found that younger women, those coming from Latin American countries, and those belonging to the lower social strata were exposed to higher NO(2) levels, both as measured outside their homes as well as when time-activity patterns were taken into account. These subgroups also have a higher probability of being exposed to NO(2) levels over 40 μg/m(3), which is the annual limit for maximum safe exposure, as established by European Directive 2008/50/EC. Copyright © 2011 Elsevier Ltd. All rights reserved.

Size-Dependent Deposition, Translocation, and Microglial Activation of Inhaled Silver Nanoparticles in the Rodent Nose and Brain

PubMed Central

Patchin, Esther Shin; Anderson, Donald S.; Silva, Rona M.; Uyeminami, Dale L.; Scott, Grace M.; Guo, Ting; Van Winkle, Laura S.; Pinkerton, Kent E.

2016-01-01

Background: Silver nanoparticles (AgNP) are present in personal, commercial, and industrial products, which are often aerosolized. Current understanding of the deposition, translocation, and health-related impacts of AgNP inhalation is limited. Objectives: We determined a) the deposition and retention of inhaled Ag in the nasal cavity from nose-only exposure; b) the timing for Ag translocation to and retention/clearance in the olfactory bulb (OB); and c) whether the presence of Ag in the OB affects microglial activity. Methods: Male Sprague-Dawley rats were exposed nose-only to citrate-buffered 20- or 110-nm AgNP (C20 or C110, respectively) or citrate buffer alone for 6 hr. The nasal cavity and OB were examined for the presence of Ag and for biological responses up to 56 days post-exposure (8 weeks). Results: The highest nasal Ag deposition was observed on Day 0 for both AgNP sizes. Inhalation of aerosolized C20 resulted in rapid translocation of Ag to the OB and in microglial activation at Days 0, 1, and 7. In contrast, inhalation of C110 resulted in a gradual but progressive transport of Ag to and retention in the OB, with a trend for microglial activation to variably be above control. Conclusions: The results of this study show that after rats experienced a 6-hr inhalation exposure to 20- and 110-nm AgNP at a single point in time, Ag deposition in the nose, the rate of translocation to the brain, and subsequent microglial activation in the OB differed depending on AgNP size and time since exposure. Citation: Patchin ES, Anderson DS, Silva RM, Uyeminami DL, Scott GM, Guo T, Van Winkle LS, Pinkerton KE. 2016. Size-dependent deposition, translocation, and microglial activation of inhaled silver nanoparticles in the rodent nose and brain. Environ Health Perspect 124:1870–1875; http://dx.doi.org/10.1289/EHP234 PMID:27152509

The use of chlorine dioxide for the inactivation of copepod zooplankton in drinking water treatment.

PubMed

Lin, Tao; Chen, Wei; Cai, Bo

2014-01-01

The presence of zooplankton in drinking water treatment system may cause a negative effect on the aesthetic value of drinking water and may also increase the threat to human health due to they being the carriers of bacteria. Very little research has been done on the effects of copepod inactivation and the mechanisms involved in this process. In a series of bench-scale experiments we used a response surface method to assess the sensitivity of copepod to inactivation when chlorine dioxide (ClO₂) was used as a disinfectant. We also assessed the effects of the ClO₂dosage, exposure time, organic matter concentration and temperature. Results indicated that the inactivation rate improved with increasing dosage, exposure time and temperature, whereas it decreased with increasing organic matter concentration. Copepod inactivation was more sensitive to the ClO₂dose than that to the exposure time, while being maintained at the same Ct-value conditions. The activation energy at different temperatures revealed that the inactivation of copepods with ClO₂was temperature-dependent. The presence of organic matter resulted in a lower available dose as well as a shorter available exposure time, which resulted in a decrease in inactivation efficiency.

Neuritin reverses deficits in murine novel object associative recognition memory caused by exposure to extremely low-frequency (50 Hz) electromagnetic fields

PubMed Central

Zhao, Qian-Ru; Lu, Jun-Mei; Yao, Jin-Jing; Zhang, Zheng-Yu; Ling, Chen; Mei, Yan-Ai

2015-01-01

Animal studies have shown that electromagnetic field exposure may interfere with the activity of brain cells, thereby generating behavioral and cognitive disturbances. However, the underlying mechanisms and possible preventions are still unknown. In this study, we used a mouse model to examine the effects of exposure to extremely low-frequency (50 Hz) electromagnetic fields (ELF MFs) on a recognition memory task and morphological changes of hippocampal neurons. The data showed that ELF MFs exposure (1 mT, 12 h/day) induced a time-dependent deficit in novel object associative recognition memory and also decreased hippocampal dendritic spine density. This effect was observed without corresponding changes in spontaneous locomotor activity and was transient, which has only been seen after exposing mice to ELF MFs for 7-10 days. The over-expression of hippocampal neuritin, an activity-dependent neurotrophic factor, using an adeno-associated virus (AAV) vector significantly increased the neuritin level and dendritic spine density. This increase was paralleled with ELF MFs exposure-induced deficits in recognition memory and reductions of dendritic spine density. Collectively, our study provides evidence for the association between ELF MFs exposure, impairment of recognition memory, and resulting changes in hippocampal dendritic spine density. Neuritin prevented this ELF MFs-exposure-induced effect by increasing the hippocampal spine density. PMID:26138388

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

NASA Astrophysics Data System (ADS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning.

Neuritin reverses deficits in murine novel object associative recognition memory caused by exposure to extremely low-frequency (50 Hz) electromagnetic fields.

PubMed

Zhao, Qian-Ru; Lu, Jun-Mei; Yao, Jin-Jing; Zhang, Zheng-Yu; Ling, Chen; Mei, Yan-Ai

2015-07-03

Animal studies have shown that electromagnetic field exposure may interfere with the activity of brain cells, thereby generating behavioral and cognitive disturbances. However, the underlying mechanisms and possible preventions are still unknown. In this study, we used a mouse model to examine the effects of exposure to extremely low-frequency (50 Hz) electromagnetic fields (ELF MFs) on a recognition memory task and morphological changes of hippocampal neurons. The data showed that ELF MFs exposure (1 mT, 12 h/day) induced a time-dependent deficit in novel object associative recognition memory and also decreased hippocampal dendritic spine density. This effect was observed without corresponding changes in spontaneous locomotor activity and was transient, which has only been seen after exposing mice to ELF MFs for 7-10 days. The over-expression of hippocampal neuritin, an activity-dependent neurotrophic factor, using an adeno-associated virus (AAV) vector significantly increased the neuritin level and dendritic spine density. This increase was paralleled with ELF MFs exposure-induced deficits in recognition memory and reductions of dendritic spine density. Collectively, our study provides evidence for the association between ELF MFs exposure, impairment of recognition memory, and resulting changes in hippocampal dendritic spine density. Neuritin prevented this ELF MFs-exposure-induced effect by increasing the hippocampal spine density.

Cocaine Promotes Coincidence Detection and Lowers Induction Threshold during Hebbian Associative Synaptic Potentiation in Prefrontal Cortex.

PubMed

Ruan, Hongyu; Yao, Wei-Dong

2017-01-25

Addictive drugs usurp neural plasticity mechanisms that normally serve reward-related learning and memory, primarily by evoking changes in glutamatergic synaptic strength in the mesocorticolimbic dopamine circuitry. Here, we show that repeated cocaine exposure in vivo does not alter synaptic strength in the mouse prefrontal cortex during an early period of withdrawal, but instead modifies a Hebbian quantitative synaptic learning rule by broadening the temporal window and lowers the induction threshold for spike-timing-dependent LTP (t-LTP). After repeated, but not single, daily cocaine injections, t-LTP in layer V pyramidal neurons is induced at +30 ms, a normally ineffective timing interval for t-LTP induction in saline-exposed mice. This cocaine-induced, extended-timing t-LTP lasts for ∼1 week after terminating cocaine and is accompanied by an increased susceptibility to potentiation by fewer pre-post spike pairs, indicating a reduced t-LTP induction threshold. Basal synaptic strength and the maximal attainable t-LTP magnitude remain unchanged after cocaine exposure. We further show that the cocaine facilitation of t-LTP induction is caused by sensitized D1-cAMP/protein kinase A dopamine signaling in pyramidal neurons, which then pathologically recruits voltage-gated l-type Ca 2+ channels that synergize with GluN2A-containing NMDA receptors to drive t-LTP at extended timing. Our results illustrate a mechanism by which cocaine, acting on a key neuromodulation pathway, modifies the coincidence detection window during Hebbian plasticity to facilitate associative synaptic potentiation in prefrontal excitatory circuits. By modifying rules that govern activity-dependent synaptic plasticity, addictive drugs can derail the experience-driven neural circuit remodeling process important for executive control of reward and addiction. It is believed that addictive drugs often render an addict's brain reward system hypersensitive, leaving the individual more susceptible to relapse. We found that repeated cocaine exposure alters a Hebbian associative synaptic learning rule that governs activity-dependent synaptic plasticity in the mouse prefrontal cortex, characterized by a broader temporal window and a lower threshold for spike-timing-dependent LTP (t-LTP), a cellular form of learning and memory. This rule change is caused by cocaine-exacerbated D1-cAMP/protein kinase A dopamine signaling in pyramidal neurons that in turn pathologically recruits l-type Ca 2+ channels to facilitate coincidence detection during t-LTP induction. Our study provides novel insights on how cocaine, even with only brief exposure, may prime neural circuits for subsequent experience-dependent remodeling that may underlie certain addictive behavior. Copyright © 2017 the authors 0270-6474/17/370986-12$15.00/0.

Time-dependent inhibitory effects of Tris(1, 3-dichloro-2-propyl) phosphate on growth and transcription of genes involved in the GH/IGF axis, but not the HPT axis, in female zebrafish.

PubMed

Zhu, Ya; Su, Guanyong; Yang, Dandong; Zhang, Yongkang; Yu, Liqin; Li, Yufei; Giesy, John P; Letcher, Robert J; Liu, Chunsheng

2017-10-01

Growth curves were used to determine sensitive exposure windows for evaluation of developmental toxicity of chemicals to zebrafish. Dose- and time-dependent effects on body mass, body length and expression of genes involved in the growth hormone/insulin-like growth factor (GH/IGF) axis and the hypothalamic-pituitary-thyroid (HPT) axis were examined after exposure to environmentally relevant concentrations of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP). Based on growth curves, zebrafish grew most rapidly between 60 and 90 days post fertilization (dpf). Exposure to environmentally relevant concentrations of TDCIPP significantly decreased body mass and body length and down-regulated expression of several genes involved in the GH/IGF axis of female zebrafish, but no such effects were observed in male zebrafish. Exposure to TDCIPP did not change concentrations of thyroid hormones or expression of genes along the HPT axis in female and male zebrafish. These results suggest that growth stages of zebrafish between 60 and 90 dpf might be most appropriate for evaluation of developmental toxicity of chemicals, and down-regulation of genes involved in the GH/IGF axis, but not the HPT axis, might be responsible for the observed growth inhibition in females exposed to TDCIPP. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Evaluation of radiation exposure of personnel in an orthopaedic and trauma operation theatre using the new real-time dosimetry system "dose aware"].

PubMed

Müller, M C; Strauss, A; Pflugmacher, R; Nähle, C P; Pennekamp, P H; Burger, C; Wirtz, D C

2014-08-01

There is a positive correlation between operation time and staff exposure to radiation during intraoperative use of C-arm fluoroscopy. Due to harmful effects of exposure to long-term low-dose radiation for both the patient and the operating team it should be kept to a minimum. AIM of this study was to evaluate a novel dosimeter system called Dose Aware® (DA) enabling radiation exposure feedback of the personal in an orthopaedic and trauma operation theatre in real-time. Within a prospective study over a period of four month, DA was applied by the operation team during 104 orthopaedic and trauma operations in which the C-arm fluoroscope was used in 2D-mode. During ten operation techniques, radiation exposure of the surgeon, the first assistant, the theatre nurse and the anaesthesiologist was evaluated. Seventy-three operations were analysed. The surgeon achieved the highest radiation exposure during dorsolumbar spinal osteosynthesis, kyphoplasty and screw fixation of sacral fractures. The first assistant received a higher radiation exposure compared to the surgeon during plate osteosynthesis of distal radius fractures (157 %), intramedullary nailing of pertrochanteric fractures (143 %) and dorsolumbar spinal osteosynthesis (240 %). During external fixation of ankle fractures (68 %) and screw fixation of sacral fractures (66 %) radiation exposure of the theatre nurse exceeded 50 % of the surgeon's radiation exposure. During plate osteosynthesis of distal radius fractures (157 %) and intramedullary splinting of clavicular fractures (115 %), the anaesthesiologist received a higher radiation exposure than the surgeon. The novel dosimeter system DA provides real-time radiation exposure feedback of the personnel in an orthopaedic and trauma operation theatre for the first time. Data of this study demonstrate that radiation exposure of the personnel depends on the operation type. The first assistant, the theatre nurse and the anaesthesiologist might be exposed to higher radiation doses than the surgeon. DA might help to increase awareness concerning irradiation in an orthopaedic and trauma operation theatre and might enhance staff compliance in using radiation protection techniques. Georg Thieme Verlag KG Stuttgart · New York.

Microplastic Size-Dependent Toxicity, Oxidative Stress Induction, and p-JNK and p-p38 Activation in the Monogonont Rotifer (Brachionus koreanus).

PubMed

Jeong, Chang-Bum; Won, Eun-Ji; Kang, Hye-Min; Lee, Min-Chul; Hwang, Dae-Sik; Hwang, Un-Ki; Zhou, Bingsheng; Souissi, Sami; Lee, Su-Jae; Lee, Jae-Seong

2016-08-16

In this study, we evaluated accumulation and adverse effects of ingestion of microplastics in the monogonont rotifer (Brachionus koreanus). The dependence of microplastic toxicity on particle size was investigated by measuring several in vivo end points and studying the ingestion and egestion using 0.05-, 0.5-, and 6-μm nonfunctionalized polystyrene microbeads. To identify the defense mechanisms activated in response to microplastic exposure, the activities of several antioxidant-related enzymes and the phosphorylation status of mitogen-activated protein kinases (MAPKs) were determined. Exposure to polystyrene microbeads of all sizes led to significant size-dependent effects, including reduced growth rate, reduced fecundity, decreased lifespan and longer reproduction time. Rotifers exposed to 6-μm fluorescently labeled microbeads exhibited almost no fluorescence after 24 h, while rotifers exposed to 0.05- and 0.5-μm fluorescently labeled microbeads displayed fluorescence until 48 h, suggesting that 6-μm microbeads are more effectively egested from B. koreanus than 0.05- or 0.5-μm microbeads. This observation provides a potential explanation for our findings that microbead toxicity was size-dependent and smaller microbeads were more toxic. In vitro tests revealed that antioxidant-related enzymes and MAPK signaling pathways were significantly activated in response to microplastic exposure in a size-dependent manner.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhondt, Stijn, E-mail: stijn.dhondt@vub.ac.be; Beckx, Carolien, E-mail: Carolien.Beckx@vito.be; Degraeuwe, Bart, E-mail: Bart.Degraeuwe@vito.be

In both ambient air pollution epidemiology and health impact assessment an accurate assessment of the population exposure is crucial. Although considerable advances have been made in assessing human exposure outdoors, the assessments often do not consider the impact of individual travel behavior on such exposures. Population-based exposures to NO{sub 2} and O{sub 3} using only home addresses were compared with models that integrate all time-activity patterns-including time in commute-for Flanders and Brussels. The exposure estimates were used to estimate the air pollution impact on years of life lost due to respiratory mortality. Health impact of NO{sub 2} using an exposuremore » that integrates time-activity information was on average 1.2% higher than when assuming that people are always at their home address. For ozone the overall estimated health impact was 0.8% lower. Local differences could be much larger, with estimates that differ up to 12% from the exposure using residential addresses only. Depending on age and gender, deviations from the population average were seen. Our results showed modest differences on a regional level. At the local level, however, time-activity patterns indicated larger differences in exposure and health impact estimates, mainly for people living in more rural areas. These results suggest that for local analyses the dynamic approach can contribute to an improved assessment of the health impact of various types of pollution and to the understanding of exposure differences between population groups. - Highlights: Black-Right-Pointing-Pointer Exposure to ambient air pollution was assessed integrating population mobility. Black-Right-Pointing-Pointer This dynamic exposure was integrated into a health impact assessment. Black-Right-Pointing-Pointer Differences between the dynamic and residential exposure were quantified. Black-Right-Pointing-Pointer Modest differences in health impact were found at a regional level. Black-Right-Pointing-Pointer At municipal level larger differences were found, influenced by gender and age.« less

Chronic intermittent ethanol exposure leads to alterations in brain-derived neurotrophic factor within the frontal cortex and impaired behavioral flexibility in both adolescent and adult rats

PubMed Central

Fernandez, Gina M.; Lew, Brandon J.; Vedder, Lindsey C.; Savage, Lisa M

2017-01-01

Chronic intermittent exposure to ethanol (EtOH; CIE) that produces binge-like levels of intoxication has been associated with age-dependent deficits in cognitive functioning. Male Sprague-Dawley rats were exposed to CIE (5 g/kg, 25% EtOH, 13 intragastric gavages) beginning at three ages: early adolescence (postnatal day [PD] 28), mid-adolescence (PD35) and adulthood (PD72). In experiment 1, rats were behaviorally tested following CIE. Spatial memory was not affected by CIE, but adult CIE rats were impaired at acquiring a non-spatial discrimination task and subsequent reversal tasks. Rats exposed to CIE during early or mid-adolescence were impaired on the first reversal, demonstrating transient impairment in behavioral flexibility. Blood EtOH concentrations negatively correlated with performance on reversal tasks. Experiment 2 examined changes in brain derived neurotrophic factor (BNDF) levels within the frontal cortex (FC) and hippocampus (HPC) at four time points: during intoxication, 24-hrs after the final EtOH exposure (acute abstinence), 3-weeks following abstinence (recovery) and after behavioral testing. HPC BDNF levels were not affected by CIE at any time point. During intoxication, BDNF was suppressed in the FC, regardless of the age of exposure. However, during acute abstinence, reduced FC BDNF levels persisted in early adolescent CIE rats, whereas adult CIE rats displayed an increase in BDNF levels. Following recovery, neurotrophin levels in all CIE rats recovered. Our results indicate that intermittent binge-like EtOH exposure leads to acute disruptions in FC BDNF levels and long-lasting behavioral deficits. However, the type of cognitive impairment and its duration differ depending on the age of exposure. PMID:28257889

Uptake of silver nanoparticles by monocytic THP-1 cells depends on particle size and presence of serum proteins

NASA Astrophysics Data System (ADS)

Kettler, Katja; Giannakou, Christina; de Jong, Wim H.; Hendriks, A. Jan; Krystek, Petra

2016-09-01

Human health risks by silver nanoparticle (AgNP) exposure are likely to increase due to the increasing number of NP-containing products and demonstrated adverse effects in various cell lines. Unfortunately, results from (toxicity) studies are often based on exposure dose and are often measured only at a fixed time point. NP uptake kinetics and the time-dependent internal cellular concentration are often not considered. Macrophages are the first line of defense against invading foreign agents including NPs. How macrophages deal with the particles is essential for potential toxicity of the NPs. However, there is a considerable lack of uptake studies of particles in the nanometer range and macrophage-like cells. Therefore, uptake rates were determined over 24 h for three different AgNPs sizes (20, 50 and 75 nm) in medium with and without fetal calf serum. Non-toxic concentrations of 10 ng Ag/mL for monocytic THP-1 cells, representing realistic exposure concentration for short-term exposures, were chosen. The uptake of Ag was higher in medium without fetal calf serum and showed increasing uptake for decreasing NP sizes, both on NP mass and on number basis. Internal cellular concentrations reached roughly 32/10 %, 25/18 % and 21/15 % of the nominal concentration in the absence of fetal calf serum/with fetal calf serum for 20-, 50- and 75-nm NPs, respectively. Our research shows that uptake kinetics in macrophages differ for various NP sizes. To increase the understanding of the mechanism of NP toxicity in cells, the process of uptake (timing) should be considered.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure.

PubMed

Tucker, Deirdre K; Macon, Madisa B; Strynar, Mark J; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E

2015-07-01

Perfluorooctanoic acid (PFOA) is a developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1mg/kg) has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. Also an evaluation of female serum hormone levels and pubertal timing onset revealed no effects of PFOA compared to controls in either strain. These data suggest that the mammary gland is more sensitive to early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. Published by Elsevier Inc.

The mammary gland is a sensitive pubertal target in CD-1 and C57Bl/6 mice following perinatal perfluorooctanoic acid (PFOA) exposure

PubMed Central

Tucker, Deirdre K.; Macon, Madisa B.; Strynar, Mark J.; Dagnino, Sonia; Andersen, Erik; Fenton, Suzanne E.

2015-01-01

Perfluorooctanoic acid (PFOA) is a known developmental toxicant in mice, with varied strain outcomes depending on dose and period of exposure. The impact of PFOA on female mouse pubertal development at low doses (≤1 mg/kg), however, has yet to be determined. Therefore, female offspring from CD-1 and C57Bl/6 dams exposed to PFOA, creating serum concentrations similar to humans, were examined for pubertal onset, including mammary gland development. Mouse pups demonstrated a shorter PFOA elimination half-life than that reported for adult mice. Prenatal exposure to PFOA caused significant mammary developmental delays in exposed female offspring in both strains. Delays started during puberty and persisted into young adulthood; severity was dose-dependent. In contrast, an evaluation of serum hormone levels and pubertal timing onset in the same offspring revealed no effects of PFOA compared to controls in either strain. Therefore, our data suggest that the mammary gland is more sensitive to the effects of early low level PFOA exposures compared to other pubertal endpoints, regardless of strain. PMID:25499722

Brain region-specific gene expression changes after chronic intermittent ethanol exposure and early withdrawal in C57BL/6J mice

PubMed Central

Melendez, Roberto I.; McGinty, Jacqueline F.; Kalivas, Peter W.; Becker, Howard C.

2014-01-01

Neuroadaptations that participate in the ontogeny of alcohol dependence are likely a result of altered gene expression in various brain regions. The present study investigated brain region-specific changes in the pattern and magnitude of gene expression immediately following chronic intermittent ethanol (CIE) exposure and 8 hours following final ethanol exposure [i.e. early withdrawal (EWD)]. High-density oligonucleotide microarrays (Affymetrix 430A 2.0, Affymetrix, Santa Clara, CA, USA) and bioinformatics analysis were used to characterize gene expression and function in the prefrontal cortex (PFC), hippocampus (HPC) and nucleus accumbens (NAc) of C57BL/6J mice (Jackson Laboratories, Bar Harbor, ME, USA). Gene expression levels were determined using gene chip robust multi-array average followed by statistical analysis of microarrays and validated by quantitative real-time reverse transcription polymerase chain reaction and Western blot analysis. Results indicated that immediately following CIE exposure, changes in gene expression were strikingly greater in the PFC (284 genes) compared with the HPC (16 genes) and NAc (32 genes). Bioinformatics analysis revealed that most of the transcriptionally responsive genes in the PFC were involved in Ras/MAPK signaling, notch signaling or ubiquitination. In contrast, during EWD, changes in gene expression were greatest in the HPC (139 genes) compared with the PFC (four genes) and NAc (eight genes). The most transcriptionally responsive genes in the HPC were involved in mRNA processing or actin dynamics. Of the few genes detected in the NAc, the most representatives were involved in circadian rhythms. Overall, these findings indicate that brain region-specific and time-dependent neuroadaptive alterations in gene expression play an integral role in the development of alcohol dependence and withdrawal. PMID:21812870

Hexavalent Chromium Cr(VI) Up-Regulates COX-2 Expression through an NFκB/c-Jun/AP-1–Dependent Pathway

PubMed Central

Zuo, Zhenghong; Cai, Tongjian; Li, Jingxia; Zhang, Dongyun; Yu, Yonghui

2012-01-01

Background: Hexavalent chromium [Cr(VI)] is recognized as a human carcinogen via inhalation. However, the molecular mechanisms by which Cr(VI) causes cancers are not well understood. Objectives: We evaluated cyclooxygenase-2 (COX-2) expression and the signaling pathway leading to this induction due to Cr(VI) exposure in cultured cells. Methods: We used the luciferase reporter assay and Western blotting to determine COX-2 induction by Cr(VI). We used dominant negative mutant, genetic knockout, gene knockdown, and chromatin immunoprecipitation approaches to elucidate the signaling pathway leading to COX-2 induction. Results: We found that Cr(VI) exposure induced COX-2 expression in both normal human bronchial epithelial cells and mouse embryonic fibroblasts in a concentration- and time-dependent manner. Deletion of IKKβ [inhibitor of transcription factor NFκB (IκB) kinase β; an upstream kinase responsible for nuclear factor κB (NFκB) activation] or overexpression of TAM67 (a dominant-negative mutant of c-Jun) dramatically inhibited the COX-2 induction due to Cr(VI), suggesting that both NFκB and c-Jun/AP-1 pathways were required for Cr(VI)-induced COX-2 expression. Our results show that p65 and c-Jun are two major components involved in NFκB and AP-1 activation, respectively. Moreover, our studies suggest crosstalk between NFκB and c-Jun/AP-1 pathways in cellular response to Cr(VI) exposure for COX-2 induction. Conclusion: We demonstrate for the first time that Cr(VI) is able to induce COX-2 expression via an NFκB/c-Jun/AP-1–dependent pathway. Our results provide novel insight into the molecular mechanisms linking Cr(VI) exposure to lung inflammation and carcinogenesis. PMID:22472290

Recovery from welding-fume-exposure-induced MRI T1 signal intensities after cessation of welding-fume exposure in brains of cynomolgus monkeys.

PubMed

Han, Jeong Hee; Chung, Yong Hyun; Park, Jung Duck; Kim, Choong Yong; Yang, Seoung Oh; Khang, Hyun Soo; Cheong, Hae Kwan; Lee, Jong Seong; Ha, Chang Soo; Song, Chang-Woo; Kwon, Il Hoon; Sung, Jae Hyuck; Heo, Jeong Doo; Kim, Na-Young; Huang, Mingai; Cho, Myung Haing; Yu, Il Je

2008-09-01

The shortening of the MRI T1 relaxation time, indicative of a high signal intensity in a T1-weighted MRI, is known as a useful biomarker for Mn exposure after short-term welding-fume exposure. A previous monkey experimental study found that the T1 relaxation times decreased time-dependently after exposure, and a visually detectable high signal intensity appeared after 150 days of exposure. The nadir for the shortening of the T1 relaxation time was also previously found to correspond well with the blood Mn concentration in welders, suggesting a correlation between a prolonged high blood Mn concentration and shortened T1 relaxation time. Accordingly, to clarify the clearance of the brain Mn concentration after the cessation of welding-fume exposure, cynomolgus monkeys were assigned to 3 groups-unexposed, low dose (31 mg/m(3) total suspended particulate (TSP), 0.9 mg Mn/m(3)), and high dose (62 mg/m(3) TSP, 1.95 mg Mn/m(3))-and exposed to manual metal-arc stainless steel (MMA-SS) welding fumes for 2 h per day for 8 mo in an inhalation chamber system equipped with an automatic fume generator. After reaching the peak MRI T1 signal intensity (shortest T1 relaxation time), the monkeys were allowed to recover by ceasing the welding-fume exposure. Within 2 mo, the MRI T1 signal intensities for the exposed monkeys returned to nearly the same level as those for the unexposed monkeys, indicating the potential for recovery from a high MRI T1 signal intensity induced by welding-fume exposure, even after prolonged exposure. Clearance of the Mn tissue concentration was also demonstrated in the globus pallidus, plus other tissues from the brain, liver, spleen, and blood. In contrast, there was no clearance of the lung concentrations of Mn, indicating that a soluble form of Mn was transported to the blood and brain. Therefore, the solubility of Mn in welding fumes would appear to be an important determinant as regards the retention of blood Mn levels and brain tissue Mn concentrations in welders.

Concentration-and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to twelve weeks

EPA Science Inventory

Inorganic arsenic (AsD is a known human bladder carcinogen. The objective of this study was to examine the concentration dependence of the genomic response to ASi in the urinary bladders of mice. C57BL/6J mice were exposed for 1 or 12 weeks to arsenate in drinking water at concen...

Near infrared radiation damage mechanism in the lens

NASA Astrophysics Data System (ADS)

Söderberg, Per G.; Talebizadeh, Nooshin; Galichanin, Konstantin; Kronschläger, Martin; Schulmeister, Karl; Yu, Zhaohua

2015-03-01

The current data strongly indicates that there is no photochemical effect of in vivo exposure to 1090 nm near IRR radiation within the pupil. Four groups of 20 Sprague-Dawley rats were unilaterally exposed in vivo to 96 W·cm-2 centered inside the pupil for 10, 18, 33 and 60 min, respectively depending on group belonging. This resulted in radiant exposure doses of 57, 103, 198 and 344 kJ·cm-2. Temperature evolution at the limbus during the exposure and difference of intensity of forward light scattering between the exposed and the contralateral not exposed eye was measured at 1 week after exposure. The temperature at the limbus was found to increase exponentially towards an asymptote with an asymptote temperature of around 7 °C and a time constant (1/k) of around 15 s. No increase of light scattering was found despite that the cumulated radiant exposure dose was [80;250] times the threshold for photochemically induced cataract suggested by previous empirical data. It is concluded that at 1090 nm near IRR there is no photochemical effect.

Biologic Monitoring of Exposure to Environmental Chemicals throughout the Life Stages: Requirements and Issues for Consideration for the National Children’s Study

PubMed Central

Barr, Dana B.; Wang, Richard Y.; Needham, Larry L.

2005-01-01

Biomonitoring of exposure is a useful tool for assessing environmental exposures. The matrices available for analyses include blood, urine, breast milk, adipose tissue, and saliva, among others. The sampling can be staged to represent the particular time period of concern: preconceptionally from both parents, from a pregnant woman during each of the three trimesters, during and immediately after childbirth, from the mother postnatally, and from the child as it develops to 21 years of age. The appropriate sample for biomonitoring will depend upon matrix availability, the time period of concern for a particular exposure or health effect, and the different classes of environmental chemicals to be monitored. This article describes the matrices available for biomonitoring during the life stages being evaluated in the National Children’s Study; the best biologic matrices for exposure assessment for each individual chemical class, including consideration of alternative matrices; the analytical methods used for analysis, including quality control procedures and less costly alternatives; the costs of analysis; optimal storage conditions; and chemical and matrix stability during long-term storage. PMID:16079083

Noise exposure of immature rats can induce different age-dependent extra-auditory alterations that can be partially restored by rearing animals in an enriched environment.

PubMed

Molina, S J; Capani, F; Guelman, L R

2016-04-01

It has been previously shown that different extra-auditory alterations can be induced in animals exposed to noise at 15 days. However, data regarding exposure of younger animals, that do not have a functional auditory system, have not been obtained yet. Besides, the possibility to find a helpful strategy to restore these changes has not been explored so far. Therefore, the aims of the present work were to test age-related differences in diverse hippocampal-dependent behavioral measurements that might be affected in noise-exposed rats, as well as to evaluate the effectiveness of a potential neuroprotective strategy, the enriched environment (EE), on noise-induced behavioral alterations. Male Wistar rats of 7 and 15 days were exposed to moderate levels of noise for two hours. At weaning, animals were separated and reared either in standard or in EE cages for one week. At 28 days of age, different hippocampal-dependent behavioral assessments were performed. Results show that rats exposed to noise at 7 and 15 days were differentially affected. Moreover, EE was effective in restoring all altered variables when animals were exposed at 7 days, while a few were restored in rats exposed at 15 days. The present findings suggest that noise exposure was capable to trigger significant hippocampal-related behavioral alterations that were differentially affected, depending on the age of exposure. In addition, it could be proposed that hearing structures did not seem to be necessarily involved in the generation of noise-induced hippocampal-related behaviors, as they were observed even in animals with an immature auditory pathway. Finally, it could be hypothesized that the differential restoration achieved by EE rearing might also depend on the degree of maturation at the time of exposure and the variable evaluated, being younger animals more susceptible to environmental manipulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Detecting changes in dynamic and complex acoustic environments

PubMed Central

Boubenec, Yves; Lawlor, Jennifer; Górska, Urszula; Shamma, Shihab; Englitz, Bernhard

2017-01-01

Natural sounds such as wind or rain, are characterized by the statistical occurrence of their constituents. Despite their complexity, listeners readily detect changes in these contexts. We here address the neural basis of statistical decision-making using a combination of psychophysics, EEG and modelling. In a texture-based, change-detection paradigm, human performance and reaction times improved with longer pre-change exposure, consistent with improved estimation of baseline statistics. Change-locked and decision-related EEG responses were found in a centro-parietal scalp location, whose slope depended on change size, consistent with sensory evidence accumulation. The potential's amplitude scaled with the duration of pre-change exposure, suggesting a time-dependent decision threshold. Auditory cortex-related potentials showed no response to the change. A dual timescale, statistical estimation model accounted for subjects' performance. Furthermore, a decision-augmented auditory cortex model accounted for performance and reaction times, suggesting that the primary cortical representation requires little post-processing to enable change-detection in complex acoustic environments. DOI: http://dx.doi.org/10.7554/eLife.24910.001 PMID:28262095

Toward risk reduction: predicting the future burden of occupational cancer.

PubMed

Hutchings, Sally; Rushton, Lesley

2011-05-01

Interventions to reduce cancers related to certain occupations should be evidence-based. The authors have developed a method for forecasting the future burden of occupational cancer to inform strategies for risk reduction. They project risk exposure periods, accounting for cancer latencies of up to 50 years, forward in time to estimate attributable fractions for a series of forecast target years given past and projected exposure trends and under targeted reduction scenarios. Adjustment factors for changes in exposed numbers and levels are applied in estimation intervals within the risk-exposure periods. The authors illustrate the methods by using a range of scenarios for reducing lung cancer due to occupational exposure to respirable crystalline silica. Attributable fractions for lung cancer due to respirable crystalline silica could be potentially reduced from 2.07% in 2010 to nearly 0% by 2060, depending on the timing and success of interventions. Focusing on achieving compliance with current exposure standards in small industries can be more effective than setting standards at a lower level. The method can be used to highlight high-risk carcinogens, industries, and occupations. It is adaptable for other countries and other exposure situations in the general environment and can be extended to include socioeconomic impact assessment.

The Epigenetic Link between Prenatal Adverse Environments and Neurodevelopmental Disorders

PubMed Central

Kundakovic, Marija; Jaric, Ivana

2017-01-01

Prenatal adverse environments, such as maternal stress, toxicological exposures, and viral infections, can disrupt normal brain development and contribute to neurodevelopmental disorders, including schizophrenia, depression, and autism. Increasing evidence shows that these short- and long-term effects of prenatal exposures on brain structure and function are mediated by epigenetic mechanisms. Animal studies demonstrate that prenatal exposure to stress, toxins, viral mimetics, and drugs induces lasting epigenetic changes in the brain, including genes encoding glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf). These epigenetic changes have been linked to changes in brain gene expression, stress reactivity, and behavior, and often times, these effects are shown to be dependent on the gestational window of exposure, sex, and exposure level. Although evidence from human studies is more limited, gestational exposure to environmental risks in humans is associated with epigenetic changes in peripheral tissues, and future studies are required to understand whether we can use peripheral biomarkers to predict neurobehavioral outcomes. An extensive research effort combining well-designed human and animal studies, with comprehensive epigenomic analyses of peripheral and brain tissues over time, will be necessary to improve our understanding of the epigenetic basis of neurodevelopmental disorders. PMID:28335457

Emergency Dose Estimation Using Optically Stimulated Luminescence from Human Tooth Enamel.

PubMed

Sholom, S; Dewitt, R; Simon, S L; Bouville, A; McKeever, S W S

2011-09-01

Human teeth were studied for potential use as emergency Optically Stimulated Luminescence (OSL) dosimeters. By using multiple-teeth samples in combination with a custom-built sensitive OSL reader, (60)Co-equivalent doses below 0.64 Gy were measured immediately after exposure with the lowest value being 27 mGy for the most sensitive sample. The variability of OSL sensitivity, from individual to individual using multiple-teeth samples, was determined to be 53%. X-ray and beta exposure were found to produce OSL curves with the same shape that differed from those due to ultraviolet (UV) exposure; as a result, correlation was observed between OSL signals after X-ray and beta exposure and was absent if compared to OSL signals after UV exposure. Fading of the OSL signal was "typical" for most teeth with just a few of incisors showing atypical behavior. Typical fading dependences were described by a bi-exponential decay function with "fast" (decay time around of 12 min) and "slow" (decay time about 14 h) components. OSL detection limits, based on the techniques developed to-date, were found to be satisfactory from the point-of-view of medical triage requirements if conducted within 24 hours of the exposure.

Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells.

PubMed

Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

2018-04-01

Exposure to specific electromagnetic field (EMF) patterns can affect a variety of biological systems. We have shown that exposure to Thomas-EMF, a low-intensity, frequency-modulated (25-6 Hz) EMF pattern, inhibited growth and altered cell signaling in malignant cells. Exposure to Thomas-EMF for 1 h/day inhibited the growth of malignant cells including B16-BL6 mouse melanoma cells, MDA-MB-231, MDA-MB-468, BT-20, and MCF-7 human breast cancer and HeLa cervical cancer cells but did not affect non-malignant cells. The Thomas-EMF-dependent changes in cell proliferation were mediated by adenosine 3',5'-cyclic monophosphate (cAMP) and extracellular-signal-regulated kinase (ERK) signaling pathways. Exposure of malignant cells to Thomas-EMF transiently changed the level of cellular cAMP and promoted ERK phosphorylation. Pharmacologic inhibitors (SQ22536) and activators (forskolin) of cAMP production both blocked the ability of Thomas-EMF to inhibit cell proliferation, and an inhibitor of the MAP kinase pathway (PD98059) was able to partially block Thomas-EMF-dependent inhibition of cell proliferation. Genetic modulation of protein kinase A (PKA) in B16-BL6 cells also altered the effect of Thomas-EMF on cell proliferation. Cells transfected with the constitutively active form of PKA (PKA-CA), which interfered with ERK phosphorylation, also interfered with the Thomas-EMF effect on cell proliferation. The non-malignant cells did not show any EMF-dependent changes in cAMP levels, ERK phosphorylation, or cell growth. These data indicate that exposure to the specific Thomas-EMF pattern can inhibit the growth of malignant cells in a manner dependent on contributions from the cAMP and MAP kinase pathways. Bioelectromagnetics. 39;217-230, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Evaluation of human exposure to single electromagnetic pulses of arbitrary shape.

PubMed

Jelínek, Lukás; Pekárek, Ludĕk

2006-03-01

Transient current density J(t) induced in the body of a person exposed to a single magnetic pulse of arbitrary shape or to a magnetic jump is filtered by a convolution integral containing in its kernel the frequency and phase dependence of the basic limit value adopted in a way similar to that used for reference values in the International Commission on Non-lonising Radiation Protection statement. From the obtained time-dependent dimensionless impact function W(J)(t) can immediately be determined whether the exposure to the analysed single event complies with the basic limit. For very slowly varying field, the integral kernel is extended to include the softened ICNIRP basic limit for frequencies lower than 4 Hz.

Space-Based Solar Power System Architecture

DTIC Science & Technology

2012-12-01

alternatives to fossil fuels: nuclear fission reactors, hydroelectric power, wind turbines and solar power to name just a few. Each has advantages...powered laser could give people or wildlife serious burns or cause blindness and possibly even death depending on exposure proximity and time. 11

Characterizing the weathering induced changes in optical performance and properties of poly(ethylene-terephthalate) via MaPd:RTS spectroscopy

NASA Astrophysics Data System (ADS)

Gordon, Devin A.; DeNoyer, Lin; Meyer, Corey W.; Sweet, Noah W.; Burns, David M.; Bruckman, Laura S.; French, Roger H.

2017-08-01

Poly(ethylene-terephthalate) (PET) film is widely used in photovoltaic module backsheets for its dielectric break- down strength, and in applications requiring high optical clarity for its high transmission in the visible region. However, PET degrades and loses optical clarity under exposure to ultraviolet (UV) irradiance, heat, and moisture. Stabilizers are often included in PET formulation to increase its longevity; however, even these are subject to degradation and further reduce optical clarity. To study the weathering induced changes in the optical properties in PET films, samples of a UV-stabilized grade of PET were exposed to heat, moisture, and UV irradiance as prescribed by ASTM-G154 Cycle 4 for 168 hour time intervals. UV-Vis reflection and transmission spectra were collected via Multi-Angle, Polarization-Dependent, Reflection, Transmission, and Scattering (MaPd:RTS) spectroscopy after each exposure interval. The resulting spectra were used to calculate the complex index of refraction throughout the UV-Vis spectral region via an iterative optimization process based upon the Fresnel equations. The index of refraction and extinction coefficient were found to vary throughout the UV-Vis region with time under exposure. The spectra were also used to investigate changes in light scattering behavior with increasing exposure time. The intensity of scattered light was found to increase at higher angles with time under exposure.

The influence of hydrocarbon composition and exposure conditions on jet fuel-induced immunotoxicity.

PubMed

Hilgaertner, Jianhua W; He, Xianghui; Camacho, Daniel; Badowski, Michael; Witten, Mark; Harris, David T

2011-11-01

Chronic jet fuel exposure could be detrimental to the health and well-being of exposed personnel, adversely affect their work performance and predispose these individuals to increased incidences of infectious disease, cancer and autoimmune disorders. Short-term (7 day) JP-8 jet fuel exposure has been shown to cause lung injury and immune dysfunction. Physiological alterations can be influenced not only by jet fuel exposure concentration (absolute amount), but also are dependent on the type of exposure (aerosol versus vapor) and the composition of the jet fuel (hydrocarbon composition). In the current study, these variables were examined with relation to effects of jet fuel exposure on immune function. It was discovered that real-time, in-line monitoring of jet fuel exposure resulted in aerosol exposure concentrations that were approximately one-eighth the concentration of previously reported exposure systems. Further, the effects of a synthetic jet fuel designed to eliminate polycyclic aromatic hydrocarbons were also examined. Both of these changes in exposure reduced but did not eliminate the deleterious effects on the immune system of exposed mice.

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats

PubMed Central

Bruijnzeel, Adriaan W.; Qi, Xiaoli; Guzhva, Lidia V.; Wall, Shannon; Deng, Jie V.; Gold, Mark S.; Febo, Marcelo; Setlow, Barry

2016-01-01

Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has a biphasic effect on locomotor activity. PMID:27065006

Behavioral Characterization of the Effects of Cannabis Smoke and Anandamide in Rats.

PubMed

Bruijnzeel, Adriaan W; Qi, Xiaoli; Guzhva, Lidia V; Wall, Shannon; Deng, Jie V; Gold, Mark S; Febo, Marcelo; Setlow, Barry

2016-01-01

Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has a biphasic effect on locomotor activity.

Visual Inspection of Surfaces

NASA Technical Reports Server (NTRS)

Hughes, David; Perez, Xavier

2007-01-01

This presentation evaluates the parameters that affect visual inspection of cleanliness. Factors tested include surface reflectance, surface roughness, size of the largest particle, exposure time, inspector and distance from sample surface. It is concluded that distance predictions were not great, particularly because the distance at which contamination is seen may depend on more variables than those tested. Most parameters estimates had confidence of 95% or better, except for exposure and reflectance. Additionally, the distance at which surface is visibly contaminated decreases with increasing reflectance, roughness, and exposure. The distance at which the surface is visually contaminated increased with the largest particle size. These variables were only slightly affected the observer.

Terrestrial Microcosm Evaluation of Two Army Smoke-Producing Compounds.

DTIC Science & Technology

1988-01-29

a greenhouse under natural or controlled photoperiods (depending on the time of year) with rainfall input simulated. Parameters monitored S ’a. ’ ’a...Sixty intact soil-core microcosms that had been extracted from an undisturbed (for m. iy years) field site were set up in a greenhouse under strict...tests. The 60 cures were divided equally between two greenhouse bays, 30 cores for exposure to RP/BR and 30 cores for exposure to WP. Within each group

Brief hyperopic defocus or form deprivation have varying effects on eye growth and ocular rhythms depending on the time-of-day of exposure.

PubMed

Nickla, Debora L; Jordan, Kelsey; Yang, Jane; Totonelly, Kristen

2017-08-01

It is generally accepted that myopic defocus is a more potent signal to the emmetropization system than hyperopic defocus: one hour per day of myopic defocus cancels out 11 h of hyperopic defocus. However, we have recently shown that the potency of brief episodes of myopic defocus at inhibiting eye growth depends on the time of day of exposure. We here ask if this will also be true of the responses to brief periods of hyperopic defocus: may integration of the signal depend on time of day? If so, are the rhythms in axial length and choroidal thickness altered? Hyperopic defocus: Birds had one eye exposed to hyperopic defocus by the wearing of -10D lenses for 2 or 6 h at one of 3 times of day for 5 days: Morning (7 am - 9 am: n = 13; 7 am - 1 pm: n = 6), Mid-day (12 pm - 2 pm: n = 20; 10 am - 4 pm: n = 8), or Evening (7 pm - 9 pm: n = 12; 2 pm - 8 pm: n = 11). A separate group wore monocular lenses continually as a control (n = 12). Form deprivation: Birds wore a diffuser over one eye for 2 h at one of 3 times of day for 5 days: Morning (n = 12); Mid-day (n = 19) or Evening (n = 6). For all groups, ocular dimensions were measured using high-frequency A-scan ultrasonography at noon on the first day, under inhalation anesthesia. On day 5, eye dimensions were re-measured at 12 pm, and refractive errors were measured using a Hartinger's refractometer. A subset of birds in the 2-h lens group (morning, n = 8; mid-day, n = 8; evening, n = 6), and the deprivation group (n = 6 per time point), were also measured at 6 pm, 12 am, 6 am and 12 pm on the last day of exposure, to obtain the parameters of the diurnal rhythms in axial length and choroidal thickness. The effects of 2 h of defocus depended on time of day of exposure: it stimulated eye growth when exposure was in the morning and inhibited it when it was at mid-day (change in vitreous chamber, X-C; ANOVA p < 0.0005; 120 μm vs -77 μm/5d, respectively; t-tests: p = 0.001; p = 0.01; post-hoc tests: p = 0.002). For mid-day, experimental eyes were more hyperopic (1.4 D; p < 0.0001). Similar to 2 h defocus, 6 h exposures at mid-day inhibited growth and produced hyperopia (X-C: -167 μm; t-test p = 0.005; RE: 1.8 D; p = 0.03). The effects of 2 h of FD were similar to those of hyperopic defocus in inhibiting growth for mid-day exposures, but FD inhibited growth for the morning exposures as well (Axial length: X-C: Morning: -122 μm; mid-day: -92 μm; ttests p = 0.006 and p = 0.016 respectively). Experimental eyes were more hyperopic (1.8 D; 1.0 D; p < 0.05). The rhythms in axial length were altered for the morning exposures in both conditions. Form deprivation in the morning, which caused inhibition, caused the phases of the two rhythms to shift toward one another (peaks at 6:00 am and 10:45 am for choroid and axial length respectively). Our findings imply that the retinal "integrator", and/or scleral growth regulator exhibit diurnal rhythms. Furthermore, they suggest that reading activities early in the day may be contraindicated in school children at risk of becoming myopic. Copyright © 2017 Elsevier Ltd. All rights reserved.

Atmospheric Ionizing Radiation and Human Exposure

NASA Technical Reports Server (NTRS)

Wilson, John W.; Mertens, Christopher J.; Goldhagen, Paul; Friedberg, W.; DeAngelis, G.; Clem, J. M.; Copeland, K.; Bidasaria, H. B.

2005-01-01

Atmospheric ionizing radiation is of interest, apart from its main concern of aircraft exposures, because it is a principal source of human exposure to radiations with high linear energy transfer (LET). The ionizing radiations of the lower atmosphere near the Earth s surface tend to be dominated by the terrestrial radioisotopes. especially along the coastal plain and interior low lands, and have only minor contributions from neutrons (11 percent). The world average is substantially larger but the high altitude cities especially have substantial contributions from neutrons (25 to 45 percent). Understanding the world distribution of neutron exposures requires an improved understanding of the latitudinal, longitudinal, altitude and spectral distribution that depends on local terrain and time. These issues are being investigated in a combined experimental and theoretical program. This paper will give an overview of human exposures and describe the development of improved environmental models.

Atmospheric Ionizing Radiation and Human Exposure

NASA Technical Reports Server (NTRS)

Wilson, J. W.; Goldhagen, P.; Friedberg, W.; DeAngelis, G.; Clem, J. M.; Copeland, K.; Bidasaria, H. B.

2004-01-01

Atmospheric ionizing radiation is of interest, apart from its main concern of aircraft exposures, because it is a principal source of human exposure to radiations with high linear energy transfer (LET). The ionizing radiations of the lower atmosphere near the Earth s surface tend to be dominated by the terrestrial radioisotopes especially along the coastal plain and interior low lands and have only minor contributions from neutrons (11 percent). The world average is substantially larger but the high altitude cities especially have substantial contributions from neutrons (25 to 45 percent). Understanding the world distribution of neutron exposures requires an improved understanding of the latitudinal, longitudinal, altitude and spectral distribution that depends on local terrain and time. These issues are being investigated in a combined experimental and theoretical program. This paper will give an overview of human exposures and describe the development of improved environmental models.

Breast cancer risk from low-dose exposures to ionizing radiation: results of parallel analysis of three exposed populations of women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Land, C.E.; Boice, J.D. Jr.; Shore, R.E.

1980-08-01

Breast cancer incidence data were analyzed from three populations of women exposed to ionizing radiation: survivors of the Hiroshima and Nagasaki atomic bombs, patients in Massachusetts tuberculosis sanitoria who were exposed to multiple chest fluoroscopies, and patients treated by X-rays for acute postpartum mastitis in Rochester, New York. Parallel analyses by radiation dose, age at exposure, and time after exposure suggested that risk of radiation-induced cancer increased approximately linearly with increasing dose and was heavily dependent on age at exposure; however, the risk was otherwise remarkably similar among the three populations, at least for ages 10 to 40 years atmore » exposure, and followed the same temporal pattern of occurrence as did breast cancer incidence in nonexposed women of similar ages.« less

Studying DDT Susceptibility at Discriminating Time Intervals Focusing on Maximum Limit of Exposure Time Survived by DDT Resistant Phlebotomus argentipes (Diptera: Psychodidae): an Investigative Report.

PubMed

Rama, Aarti; Kesari, Shreekant; Das, Pradeep; Kumar, Vijay

2017-07-24

Extensive application of routine insecticide i.e., dichlorodiphenyltrichloroethane (DDT) to control Phlebotomus argentipes (Diptera: Psychodidae), the proven vector of visceral leishmaniasis in India, had evoked the problem of resistance/tolerance against DDT, eventually nullifying the DDT dependent strategies to control this vector. Because tolerating an hour-long exposure to DDT is not challenging enough for the resistant P. argentipes, estimating susceptibility by exposing sand flies to insecticide for just an hour becomes a trivial and futile task.Therefore, this bioassay study was carried out to investigate the maximum limit of exposure time to which DDT resistant P. argentipes can endure the effect of DDT for their survival. The mortality rate of laboratory-reared DDT resistant strain P. argentipes exposed to DDT was studied at discriminating time intervals of 60 min and it was concluded that highly resistant sand flies could withstand up to 420 min of exposure to this insecticide. Additionally, the lethal time for female P. argentipes was observed to be higher than for males suggesting that they are highly resistant to DDT's toxicity. Our results support the monitoring of tolerance limit with respect to time and hence points towards an urgent need to change the World Health Organization's protocol for susceptibility identification in resistant P. argentipes.

Genotoxicity and cytotoxicity response to environmentally relevant complex metal mixture (Zn, Cu, Ni, Cr, Pb, Cd) accumulated in Atlantic salmon (Salmo salar). Part I: importance of exposure time and tissue dependence.

PubMed

Stankevičiūtė, Milda; Sauliutė, Gintarė; Svecevičius, Gintaras; Kazlauskienė, Nijolė; Baršienė, Janina

2017-10-01

Health impact of metal mixture at environment realistic concentrations are difficult to predict especially for long-term effects where cause-and-effect relationships may not be directly obvious. This study was aimed to evaluate metal mixture (Zn-0.1, Cu-0.01, Ni-0.01, Cr-0.01, Pb-0.005 and Cd-0.005 mg/L, respectively for 1, 2, 4, 7, 14 and 28 days at concentrations accepted for the inland waters in EU) genotoxicity (micronuclei, nuclear buds, nuclear buds on filament), cytotoxicity (8-shaped nuclei, fragmented-apoptotic erythrocytes), bioaccumulation, steady-state and the reference level of geno-cytotoxicity in hatchery-reared Atlantic salmon tissues. Metals accumulated mostly in gills and kidneys, to the lesser extent in the muscle. Uptake of metals from an entire mixture in the fish for 14 days is sufficient to reach steady-state Cr, Pb concentrations in all tissues; Zn, Cu-in kidneys and muscle, Ni-in liver, kidneys, muscle and Cd-in muscle. Treatment with metal mixture significantly increased summed genotoxicity levels at 7 days of exposure in peripheral blood and liver erythrocytes, at 14 days of exposure in gills and kidney erythrocytes. Significant elevation of cytotoxicity was detected after 2 and 14 days of exposure in gills erythrocytes and after 28 days-in peripheral blood erythrocytes. The amount of Cu, Cr, Pb and Cd accumulated in tissues was dependent upon duration of exposure; nuclear buds, 8-shaped nuclei frequencies also were dependent upon duration of exposure. This study indicates that metals at low levels when existing in mixture causes significant geno-cytotoxicity responses and metals bioaccumulation in salmon.

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at differentmore » developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner. • The nicotine-induced secondary motoneuron axonal pathfinding errors can occur independent of any muscle fiber alterations. • Nicotine exposure primarily affects dorsal projecting secondary motoneurons axons. • Nicotine-induced primary motoneuron axon pathfinding errors can influence secondary motoneuron axon morphology.« less

Revealing Behavioral Learning Deficit Phenotypes Subsequent to In Utero Exposure to Benzo(a)pyrene

PubMed Central

McCallister, Monique M.; Li, Zhu; Zhang, Tongwen; Ramesh, Aramandla; Clark, Ryan S.; Maguire, Mark; Hutsell, Blake; Newland, M. Christopher; Hood, Darryl B.

2016-01-01

To characterize behavioral deficits in pre-adolescent offspring exposed in utero to Benzo(a)pyrene [B(a)P], timed-pregnant Long Evans Hooded rats were treated with B(a)P (150, 300, 600, and 1200 µg/kg BW) or peanut oil (vehicle) on E14, 15, 16, and 17. Following birth, during the pre-weaning period, B(a)P metabolites were examined in plasma and whole brain or cerebral cortex from exposed and control offspring. Tissue concentrations of B(a)P metabolites were (1) dose-dependent and (2) followed a time-dependence for elimination with ∼60% reduction by PND5 in the 1200 µg/kg BW experimental group. Spatial discrimination-reversal learning was utilized to evaluate potential behavioral neurotoxicity in P40–P60 offspring. Late-adolescent offspring exposed in utero to 600 and 1200 µg/kg BW were indistinguishable from their control counterparts for ability to acquire an original discrimination (OD) and reach criterion. However, a dose-dependent effect of in utero B(a)P-exposure was evident upon a discrimination reversal as exposed offspring perseverated on the previously correct response. This newly characterized behavioral deficit phenotype for the first reversal was not apparent in either the (1) OD or (2) subsequent reversal sessions relative to the respective control offspring. Furthermore, the expression of activity related-cytoskeletal-associated protein (Arc), an experience-dependent cortical protein marker known to be up-regulated in response to acquisition of a novel behavior, was greater in B(a)P-exposed offspring included in the spatial discrimination cohort versus home cage controls. Collectively, these findings support the hypothesis that in utero exposure to B(a)P during critical windows of development representing peak periods of neurogenesis results in behavioral deficits in later life. PMID:26420751

Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats.

PubMed

Lindquist, Derick H; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E

2013-09-01

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink-conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4-9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 ms) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 ms) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus. Published by Elsevier Inc.

Neonatal ethanol exposure results in dose-dependent impairments in the acquisition and timing of the conditioned eyeblink response and altered cerebellar interpositus nucleus and hippocampal CA1 unit activity in adult rats

PubMed Central

Lindquist, Derick H.; Sokoloff, Greta; Milner, Eric; Steinmetz, Joseph E.

2013-01-01

Exposure to ethanol in neonatal rats results in reduced neuronal numbers in the cerebellar cortex and deep nuclei of juvenile and adult animals. This reduction in cell numbers is correlated with impaired delay eyeblink conditioning (EBC), a simple motor learning task in which a neutral conditioned stimulus (CS; tone) is repeatedly paired with a co-terminating unconditioned stimulus (US; periorbital shock). Across training, cell populations in the interpositus (IP) nucleus model the temporal form of the eyeblink conditioned response (CR). The hippocampus, though not required for delay EBC, also shows learning-dependent increases in CA1 and CA3 unit activity. In the present study, rat pups were exposed to 0, 3, 4, or 5 mg/kg/day of ethanol during postnatal days (PD) 4–9. As adults, CR acquisition and timing were assessed during 6 training sessions of delay EBC with a short (280 msec) interstimulus interval (ISI; time from CS onset to US onset) followed by another 6 sessions with a long (880 msec) ISI. Neuronal activity was recorded in the IP and area CA1 during all 12 sessions. The high-dose rats learned the most slowly and, with the moderate-dose rats, produced the longest CR peak latencies over training to the short ISI. The low dose of alcohol impaired CR performance to the long ISI only. The 3E (3 mg/kg/day of ethanol) and 5E (5 mg/kg/day of ethanol) rats also showed slower-than-normal increases in learning-dependent excitatory unit activity in the IP and CA1. The 4E (4 mg/kg/day of ethanol) rats showed a higher rate of CR production to the long ISI and enhanced IP and CA1 activation when compared to the 3E and 5E rats. The results indicate that binge-like ethanol exposure in neonatal rats induces long-lasting, dose-dependent deficits in CR acquisition and timing and diminishes conditioning-related neuronal excitation in both the cerebellum and hippocampus. PMID:23871534

Effects of spatial coherence in diffraction phase microscopy.

PubMed

Edwards, Chris; Bhaduri, Basanta; Nguyen, Tan; Griffin, Benjamin G; Pham, Hoa; Kim, Taewoo; Popescu, Gabriel; Goddard, Lynford L

2014-03-10

Quantitative phase imaging systems using white light illumination can exhibit lower noise figures than laser-based systems. However, they can also suffer from object-dependent artifacts, such as halos, which prevent accurate reconstruction of the surface topography. In this work, we show that white light diffraction phase microscopy using a standard halogen lamp can produce accurate height maps of even the most challenging structures provided that there is proper spatial filtering at: 1) the condenser to ensure adequate spatial coherence and 2) the output Fourier plane to produce a uniform reference beam. We explain that these object-dependent artifacts are a high-pass filtering phenomenon, establish design guidelines to reduce the artifacts, and then apply these guidelines to eliminate the halo effect. Since a spatially incoherent source requires significant spatial filtering, the irradiance is lower and proportionally longer exposure times are needed. To circumvent this tradeoff, we demonstrate that a supercontinuum laser, due to its high radiance, can provide accurate measurements with reduced exposure times, allowing for fast dynamic measurements.

On the extinction probability in models of within-host infection: the role of latency and immunity.

PubMed

Yan, Ada W C; Cao, Pengxing; McCaw, James M

2016-10-01

Not every exposure to virus establishes infection in the host; instead, the small amount of initial virus could become extinct due to stochastic events. Different diseases and routes of transmission have a different average number of exposures required to establish an infection. Furthermore, the host immune response and antiviral treatment affect not only the time course of the viral load provided infection occurs, but can prevent infection altogether by increasing the extinction probability. We show that the extinction probability when there is a time-dependent immune response depends on the chosen form of the model-specifically, on the presence or absence of a delay between infection of a cell and production of virus, and the distribution of latent and infectious periods of an infected cell. We hypothesise that experimentally measuring the extinction probability when the virus is introduced at different stages of the immune response, alongside the viral load which is usually measured, will improve parameter estimates and determine the most suitable mathematical form of the model.

Product Deformulation to Inform High-throughput Exposure ...

EPA Pesticide Factsheets

The health risks posed by the thousands of chemicals in our environment depends on both chemical hazard and exposure. However, relatively few chemicals have estimates of exposure intake, limiting the understanding of risks. We have previously developed a heuristics-based exposure estimation method that depends on simple factors such as the presence or absence of chemicals in consumer products to estimate exposure for thousands of chemicals. Although this method was predictive when compared with human biomonitoring data, limited data are available on the chemical constituents within most articles of commerce. We aim to broaden the number of products with constituent chemical information and refine exposure models by quantifying constituent concentration. A selection of five samples each from 20 diverse consumer product categories (e.g., lotion, clothing, carpet) were analyzed using solvent extraction followed by gas chromatograph (GC) x GC Time of Flight Mass Spectrometry (GCxGC-TOF/MS), which is suited for forensic investigation of complex matrices. In an examination of five plastic children’s toys, a total of 306 unique compounds were identified across all toys, including 102 Tox21 chemicals such as diethyl phthalate and bisphenol AF. As many as 114 and as few as 56 chemicals were identified in each toy. Across the five toys, a range of 0 to 40 unique peaks remain unidentified. Interestingly, bisphenol A (BPA) was identified in a children’s toy marked

Adenylyl cylases 1 and 8 mediate select striatal-dependent behaviors and sensitivity to ethanol stimulation in the adolescent period following acute neonatal ethanol exposure.

PubMed

Susick, Laura L; Lowing, Jennifer L; Bosse, Kelly E; Hildebrandt, Clara C; Chrumka, Alexandria C; Conti, Alana C

2014-08-01

Neonatal alcohol exposure in rodents causes dramatic neurodegenerative effects throughout the developing nervous system, particularly in the striatum, acutely after exposure. These acute neurodegenerative effects are augmented in mice lacking adenylyl cyclases 1 and 8 (AC1/8) as neonatal mice with a genetic deletion of both AC isoforms (DKO) have increased vulnerability to ethanol-induced striatal neurotoxicity compared to wild type (WT) controls. While neonatal ethanol exposure is known to negatively impact cognitive behaviors, such as executive functioning and working memory in adolescent and adult animals, the threshold of ethanol exposure required to impinge upon developmental behaviors in mice has not been extensively examined. Therefore, the purpose of this study was to determine the behavioral effects of neonatal ethanol exposure using various striatal-dependent developmental benchmarks and to assess the impact of AC1/8 deletion on this developmental progression. WT and DKO mice were treated with 2.5 g/kg ethanol or saline on postnatal day (P)6 and later subjected to the wire suspension, negative geotaxis, postural reflex, grid hang, tail suspension and accelerating rotarod tests at various time points. At P30, mice were evaluated for their hypnotic responses to 4.0 g/kg ethanol by using the loss of righting reflex assay and ethanol-induced stimulation of locomotor activity after 2.0 g/kg ethanol. Ethanol exposure significantly impaired DKO performance in the negative geotaxis test while genetic deletion of AC1/8 alone increased grid hang time and decreased immobility time in the tail suspension test with a concomitant increase in hindlimb clasping behavior. Locomotor stimulation was significantly increased in animals that received ethanol as neonates, peaking significantly in ethanol-treated DKO mice compared to ethanol-treated WT controls, while sedation duration following high-dose ethanol challenge was unaffected. These data indicate that the maturational parameters examined in the current study may not be sensitive enough to detect effects of a single ethanol exposure during the brain growth spurt period. Genetic deletion of AC1/8 reveals a role for these cylases in attenuating ethanol-induced behavioral effects in the neonatally-exposed adolescent. Published by Elsevier B.V.

Long-term changes in amphetamine-induced reinforcement and aversion in rats following exposure to 56Fe particle

NASA Technical Reports Server (NTRS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.

2003-01-01

Exposing rats to heavy particles produces alterations in the functioning of dopaminergic neurons and in the behaviors that depend upon the integrity of the dopaminergic system. Two of these dopamine-dependent behaviors include amphetamine-induced reinforcement, measure using the conditioned place preference procedure, and amphetamine-induced reinforcement, measured using the conditioned place preference procedure, and amphetamine-induced aversion, measured using the conditioned taste aversion. Previous research has shown that exposing rats to 1.0 Gy of 1GeV/n 56Fe particles produced a disruption of an amphetamine-induced taste aversion 3 days following exposure, but produced an apparent enhancement of the aversion 112 days following exposure. The present experiments were designed to provide a further evaluation of these results by examining taste aversion learning 154 days following exposure to 1.0 Gy 56Fe particles and to establish the convergent validity of the taste aversion results by looking at the effects of exposure on the establishment of an amphetamine-induced conditioned place preference 3, 7, and 16 weeks following irradiation. The taste aversion results failed to confirm the apparent enhancement of the amphetamine-induced CTA observed in the prior experiment. However, exposure to 56Fe particles prevented the acquisition of amphetamine-induced place preference at all three-time intervals. The results are interpreted as indicating that exposure to heavy particles can produce long-term changes in behavioral functioning. c2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved.

Neuromast hair cells retain the capacity of regeneration during heavy metal exposure.

PubMed

Montalbano, G; Capillo, G; Laurà, R; Abbate, F; Levanti, M; Guerrera, M C; Ciriaco, E; Germanà, A

2018-07-01

The neuromast is the morphological unit of the lateral line of fishes and is composed of a cluster of central sensory cells (hair cells) surrounded by support and mantle cells. Heavy metals exposure leads to disruption of hair cells within the neuromast. It is well known that the zebrafish has the ability to regenerate the hair cells after damage caused by toxicants. The process of regeneration depends on proliferation, differentiation and cellular migration of sensory and non-sensory progenitor cells. Therefore, our study was made in order to identify which cellular types are involved in the complex process of regeneration during heavy metals exposure. For this purpose, adult zebrafish were exposed to various heavy metals (Arsenic, cadmium and zinc) for 72h. After acute (24h) exposure, immunohistochemical localization of S100 (a specific marker for hair cells) in the neuromasts highlighted the hair cells loss. The immunoreaction for Sox2 (a specific marker for stem cells), at the same time, was observed in the support and mantle cells, after exposure to arsenic and cadmium, while only in the support cells after exposure to zinc. After chronic (72h) exposure the hair cells were regenerated, showing an immunoreaction for S100 protein. At the same exposure time to the three metals, a Sox2 immunoreaction was expressed in support and mantle cells. Our results showed for the first time the regenerative capacity of hair cells, not only after, but also during exposure to heavy metals, demonstrated by the presence of different stem cells that can diversify in hair cells. Copyright © 2018 Elsevier GmbH. All rights reserved.

[Evaluation of an Experimental Production Wireless Dose Monitoring System for Radiation Exposure Management of Medical Staff].

PubMed

Fujibuchi, Toshioh; Murazaki, Hiroo; Kuramoto, Taku; Umedzu, Yoshiyuki; Ishigaki, Yung

2015-08-01

Because of the more advanced and more complex procedures in interventional radiology, longer treatment times have become necessary. Therefore, it is important to determine the exposure doses received by operators and patients. The aim of our study was to evaluate an experimental production wireless dose monitoring system for pulse radiation in diagnostic X-ray. The energy, dose rate, and pulse fluoroscopy dependence were evaluated as the basic characteristics of this system for diagnostic X-ray using a fully digital fluoroscopy system. The error of 1 cm dose equivalent rate was less than 15% from 35.1 keV to 43.2 keV with energy correction using metal filter. It was possible to accurately measure the dose rate dependence of this system, which was highly linear until 100 μSv/h. This system showed a constant response to the pulse fluoroscopy. This system will become useful wireless dosimeter for the individual exposure management by improving the high dose rate and the energy characteristics.

Impact of Microplastic Beads and Fibers on Waterflea (Ceriodaphnia dubia) Survival, Growth, and Reproduction: Implications of Single and Mixture Exposures.

PubMed

Ziajahromi, Shima; Kumar, Anupama; Neale, Peta A; Leusch, Frederic D L

2017-11-21

There is limited knowledge regarding the adverse effects of wastewater-derived microplastics, particularly fibers, on aquatic biota. In this study, we examined the acute (48 h) and chronic (8 d) effects of microplastic polyester fibers and polyethylene (PE) beads on freshwater zooplankton Ceriodaphnia dubia. We also assessed the acute response of C. dubia to a binary mixture of microplastic beads and fibers for the first time. Acute exposure to fibers and PE beads both showed a dose-dependent effect on survival. An equitoxic binary mixture of beads and fibers resulted in a toxic unit of 1.85 indicating less than additive effects. Chronic exposure to lower concentrations did not significantly affect survival of C. dubia, but a dose-dependent effect on growth and reproduction was observed. Fibers showed greater adverse effects than PE beads. While ingestion of fibers was not observed, scanning electron microscopy showed carapace and antenna deformities after exposure to fibers, with no deformities observed after exposure to PE beads. While much of the current research has focused on microplastic beads, our study shows that microplastic fibers pose a greater risk to C. dubia, with reduced reproductive output observed at concentrations within an order of magnitude of reported environmental levels.

Membrane-aerated biofilm proton and oxygen flux during chemical toxin exposure.

PubMed

McLamore, E S; Zhang, W; Porterfield, D M; Banks, M K

2010-09-15

Bioreactors containing sessile bacteria (biofilms) grown on hollow fiber membranes have been used for treatment of many wastestreams. Real time operational control of bioreactor performance requires detailed knowledge of the relationship between bulk liquid water quality and physiological transport at the biofilm-liquid interface. Although large data sets exist describing membrane-aerated bioreactor effluent quality, very little real time data is available characterizing boundary layer transport under physiological conditions. A noninvasive, microsensor technique was used to quantify real time (≈1.5 s) changes in oxygen and proton flux for mature Nitrosomonas europaea and Pseudomonas aeruginosa biofilms in membrane-aerated bioreactors following exposure to environmental toxins. Stress response was characterized during exposure to toxins with known mode of action (chlorocarbonyl cyanide phenyl-hydrazone and potassium cyanide), and four environmental toxins (rotenone, 2,4-dinitrophenol, cadmium chloride, and pentachlorophenol). Exposure to sublethal concentrations of all environmental toxins caused significant increases in O(2) and/or H(+) flux (depending on the mode of action). These real time microscale signatures (i.e., fingerprints) of O(2) and H(+) flux can be coupled with bulk liquid analysis to improve our understanding of physiology in counter-diffusion biofilms found within membrane aerated bioreactors; leading to enhanced monitoring/modeling strategies for bioreactor control.

Survival protein anoctamin-6 controls multiple platelet responses including phospholipid scrambling, swelling, and protein cleavage.

PubMed

Mattheij, Nadine J A; Braun, Attila; van Kruchten, Roger; Castoldi, Elisabetta; Pircher, Joachim; Baaten, Constance C F M J; Wülling, Manuela; Kuijpers, Marijke J E; Köhler, Ralf; Poole, Alastair W; Schreiber, Rainer; Vortkamp, Andrea; Collins, Peter W; Nieswandt, Bernhard; Kunzelmann, Karl; Cosemans, Judith M E M; Heemskerk, Johan W M

2016-02-01

Scott syndrome is a rare bleeding disorder, characterized by altered Ca(2+)-dependent platelet signaling with defective phosphatidylserine (PS) exposure and microparticle formation, and is linked to mutations in the ANO6 gene, encoding anoctamin (Ano)6. We investigated how the complex platelet phenotype of this syndrome is linked to defective expression of Anos or other ion channels. Mice were generated with heterozygous of homozygous deficiency in Ano6, Ano1, or Ca(2+)-dependent KCa3.1 Gardos channel. Platelets from these mice were extensively analyzed on molecular functions and compared with platelets from a patient with Scott syndrome. Deficiency in Ano1 or Gardos channel did not reduce platelet responses compared with control mice (P > 0.1). In 2 mouse strains, deficiency in Ano6 resulted in reduced viability with increased bleeding time to 28.6 min (control 6.4 min, P < 0.05). Platelets from the surviving Ano6-deficient mice resembled platelets from patients with Scott syndrome in: 1) normal collagen-induced aggregate formation (P > 0.05) with reduced PS exposure (-65 to 90%); 2) lowered Ca(2+)-dependent swelling (-80%) and membrane blebbing (-90%); 3) reduced calpain-dependent protein cleavage (-60%); and 4) moderately affected apoptosis-dependent PS exposure. In conclusion, mouse deficiency of Ano6 but not of other channels affects viability and phenocopies the complex changes in platelets from hemostatically impaired patients with Scott syndrome. © FASEB.

Integrating genetic and toxicogenomic information for determining underlying susceptibility to developmental disorders.

PubMed

Robinson, Joshua F; Port, Jesse A; Yu, Xiaozhong; Faustman, Elaine M

2010-10-01

To understand the complex etiology of developmental disorders, an understanding of both genetic and environmental risk factors is needed. Human and rodent genetic studies have identified a multitude of gene candidates for specific developmental disorders such as neural tube defects (NTDs). With the emergence of toxicogenomic-based assessments, scientists now also have the ability to compare and understand the expression of thousands of genes simultaneously across strain, time, and exposure in developmental models. Using a systems-based approach in which we are able to evaluate information from various parts and levels of the developing organism, we propose a framework for integrating genetic information with toxicogenomic-based studies to better understand gene-environmental interactions critical for developmental disorders. This approach has allowed us to characterize candidate genes in the context of variables critical for determining susceptibility such as strain, time, and exposure. Using a combination of toxicogenomic studies and complementary bioinformatic tools, we characterize NTD candidate genes during normal development by function (gene ontology), linked phenotype (disease outcome), location, and expression (temporally and strain-dependent). In addition, we show how environmental exposures (cadmium, methylmercury) can influence expression of these genes in a strain-dependent manner. Using NTDs as an example of developmental disorder, we show how simple integration of genetic information from previous studies into the standard microarray design can enhance analysis of gene-environment interactions to better define environmental exposure-disease pathways in sensitive and resistant mouse strains. © Wiley-Liss, Inc.

Time-dependence of lung injury in mice acutely exposed to cylindrospermopsin.

PubMed

Oliveira, V R; Carvalho, G M C; Avila, M B; Soares, R M; Azevedo, S M F O; Ferreira, T S; Valença, S S; Faffe, D S; Zin, Walter Araujo

2012-10-01

Cylindrospermopsin is a cyanobacterial toxin of increasing environmental importance, as it can lead to disease if orally or intravenously absorbed. However, its in vivo lung impairment has not been documented. Thus, we aimed at verifying whether cylindrospermopsin can induce lung injury and establish its putative dependence on the time elapsed since exposure. BALB/c mice were intratracheally injected with either saline (NaCl 0.9%, 50 μL, SAL group, n = 12) or a sublethal dose (70 μg/kg) of semi-purified extract of cylindrospermopsin (CYN groups, n = 52). Lung mechanics, histological and biochemical analyses, and cylindrospermopsin presence in lungs and liver were determined in independent groups at 2, 8, 24, 48, and 96 h after cylindrospermopsin instillation. There was a significant increase in static elastance at 24 and 48 h after exposure to cylindrospermopsin, while viscoelastic component of elastance and viscoelastic pressure rose at 48 h. Alveolar collapse augmented in CYN groups at 8 h. A significant increase in polymorphonuclear influx into lung parenchyma, as well as a higher myeloperoxidase activity started off at 24 h. Exposure to cylindrospermopsin increased lipid peroxidation and superoxide dismutase activity and reduced catalase activity in CYN groups. The toxin was detected in lungs and liver of all CYN mice. In conclusion, cylindrospermopsin exposure impaired lung mechanics, which was preceded by lung parenchyma inflammation and oxidative stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

Analysis of the hologram recording on the novel chloride photo-thermo-refractive glass

NASA Astrophysics Data System (ADS)

Ivanov, S. A.; Nikonorov, N. V.; Dubrovin, V. D.; Krykova, V. A.

2017-05-01

In this research, we present new holographic material based on fluoride photo-thermo-refractive glass(PTR) - chloride PTR glass. One of the benefit of this type of PTR glass is positive refractive index change. During this work, for the first-time volume Bragg gratings were recorded in this kind of material. The first experiments revealed that such gratings are mixed i.e. possess both absorption and phase components. Complex analysis shows that both refractive index and absorption coefficient are modulated inside the grating structure. We found out that at first there is no strict dependence of the refractive index change from dosage, but as we continue the process of thermal treatment - dependence is appear. Exposure influence on the refractive index change for this glass differs from fluoride one and shows some sort of saturation after the exposure of 4-6 J/cm2 . We distinguished refractive index change and absorption coefficient change and observed both behavior with increasing thermal treatment time. We found out that the increase of thermal treatment time results in the significant refractive index change. At the same time the absorption does `not practically change. It was found that maximum modulation of refractive index is comparable with fluoride PTR glass and achieves value of 1600 ppm. The modulation of absorption is equal to induced absorption caused by silver nanoparticles and depends from reading wavelength. Our study shows that almost all absorption is modulated inside the grating.

Developmental toxicity and risk assessment of nonylphenol to the South American toad, Rhinella arenarum.

PubMed

Mariel, Aronzon Carolina; Alejandra, Babay Paola; Silvia, Pérez Coll Cristina

2014-09-01

The toxicity of Nonylphenol, an emerging pollutant, on the common South American toad Rhinella arenarum was stage and time dependent, thus Median Lethal Concentrations (LC50) for acute (96h), short-term chronic (168h) and chronic exposure (336h) were 1.06; 0.96 and 0.17mgNP/L from embryonic period (S.4), whereas for exposure from larvae (S.25), LC50 remained constant at 0.37mgNP/L from 96h to 168h, decreasing to 0.11mgNP/L at 336h. NOEC-168h for exposure from embryos was 0.025mgNP/L. The Teratogenic Potential (NOEC-lethality/NOEC-sublethal effects) was 23 times higher than the threshold value, indicating a high risk for embryos to be malformed in absence of significant lethality and representing a threat for the species conservation. By comparing with other amphibians, the early development of R. arenarum was very sensitive to NP. The results highlight the relevance of extending the exposure time and look for the most sensitive stage in order to perform the bioassays for conservation purposes. Copyright © 2014 Elsevier B.V. All rights reserved.

Time course of skin features and inflammatory biomarkers after liquid sulfur mustard exposure in SKH-1 hairless mice.

PubMed

Mouret, Stéphane; Wartelle, Julien; Batal, Mohamed; Emorine, Sandy; Bertoni, Marine; Poyot, Thomas; Cléry-Barraud, Cécile; Bakdouri, Nacera El; Peinnequin, André; Douki, Thierry; Boudry, Isabelle

2015-01-05

Sulfur mustard (SM) is a strong bifunctional alkylating agent that produces severe tissue injuries characterized by erythema, edema, subepidermal blisters and a delayed inflammatory response after cutaneous exposure. However, despite its long history, SM remains a threat because of the lack of effective medical countermeasures as the molecular mechanisms of these events remain unclear. This limited number of therapeutic options results in part of an absence of appropriate animal models. We propose here to use SKH-1 hairless mouse as the appropriate model for the design of therapeutic strategies against SM-induced skin toxicity. In the present study particular emphasis was placed on histopathological changes associated with inflammatory responses after topical exposure of dorsal skin to three different doses of SM (0.6, 6 and 60mg/kg) corresponding to a superficial, a second-degree and a third-degree burn. Firstly, clinical evaluation of SM-induced skin lesions using non invasive bioengineering methods showed that erythema and impairment of skin barrier increased in a dose-dependent manner. Histological evaluation of skin sections exposed to SM revealed that the time to onset and the severity of symptoms including disorganization of epidermal basal cells, number of pyknotic nuclei, activation of mast cells and neutrophils dermal invasion were dose-dependent. These histopathological changes were associated with a dose- and time-dependent increase in expression of specific mRNA for inflammatory mediators such as interleukins (IL1β and IL6), tumor necrosis factor (TNF)-α, cycloxygenase-2 (COX-2), macrophage inflammatory proteins (MIP-1α, MIP-2 and MIP-1αR) and keratinocyte chemoattractant (KC also called CXCL1) as well as adhesion molecules (L-selectin and vascular cell adhesion molecule (VCAM)) and growth factor (granulocyte colony-stimulating factor (Csf3)). A dose-dependent increase was also noted after SM exposure for mRNA of matrix metalloproteinases (MMP9) and laminin-γ2 which are associated with SM-induced blisters formation. Taken together, our results show that SM-induced skin histopathological changes related to inflammation is similar in SKH-1 hairless mice and humans. SKH-1 mouse is thus a reliable animal model for investigating the SM-induced skin toxicity and to develop efficient treatment against SM-induced inflammatory skin lesions. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Improving the relevance and efficiency of human exposure assessments within the process of regulatory risk assessment.

PubMed

Money, Chris

2018-01-24

The process for undertaking exposure assessments varies dependent on its purpose. But for exposure assessments to be relevant and accurate, they are reliant on access to reliable information on key exposure determinants. Acquiring such information is seldom straightforward and can take significant time and resources. This articles examines how the application of tiered and targeted approaches to information acquisition, within the context of European human health risk assessments, can not only lead to improvements in the efficiency and effectiveness of the process but also in the confidence of stakeholders in its outputs. The article explores how the benefits might be further improved through the coordination of such activities, as well as those areas that represent barriers to wider international harmonisation.

Phase-shifting human circadian rhythms: influence of sleep timing, social contact and light exposure

NASA Technical Reports Server (NTRS)

Duffy, J. F.; Kronauer, R. E.; Czeisler, C. A.

1996-01-01

1. Both the timing of behavioural events (activity, sleep and social interactions) and the environmental light-dark cycle have been reported to contribute to entrainment of human circadian rhythms to the 24 h day. Yet, the relative contribution of those putative behavioural synchronizers to that of light exposure remains unclear. 2. To investigate this, we inverted the schedule of rest, sedentary activity and social contact of thirty-two young men either with or without exposure to bright light. 3. On this inverted schedule, the endogenous component of the core temperature rhythm of subjects who were exposed to bright light showed a significant phase shift, demonstrating that they were adapting to the new schedule. In contrast, the core temperature rhythm of subjects who were not exposed to bright light moved on average 0.2 h later per day and after 10 days had not significantly adapted to the new schedule. 4. The direction of phase shift in the groups exposed to bright light was dependent on the time of bright light exposure, while control subjects drifted to a later hour regardless of the timing of their schedule of sleep timing, social contact and meals. 5. These results support the concept that the light-dark cycle is the most important synchronizer of the human circadian system. They suggest that inversion of the sleep-wake, rest-activity and social contact cycles provides relatively minimal drive for resetting the human circadian pacemaker. 6. These data indicate that interventions designed to phase shift human circadian rhythms for adjustment to time zone changes or altered work schedules should focus on properly timed light exposure.

The effects of ropivacaine hydrochloride on the expression of CaMK II mRNA in the dorsal root ganglion neurons.

PubMed

Wen, Xianjie; Lai, Xiaohong; Li, Xiaohong; Zhang, Tao; Liang, Hua

2016-12-01

In this study, we identified the subtype of Calcium/calmodulin-dependent protein kinase II (CaMK II) mRNA in dorsal root ganglion neurons and observed the effects of ropivacaine hydrochloride in different concentration and different exposure time on the mRNA expression. Dorsal root ganglion neurons were isolated from the SD rats and cultured in vitro. The mRNA of the CaMK II subtype in dorsal root ganglion neurons were detected by real-time PCR. As well as, the dorsal root ganglion neurons were treated with ropivacaine hydrochloride in different concentration (1mM,2mM, 3mM and 4mM) for the same exposure time of 4h, or different exposure time (0h,2h,3h,4h and 6h) at the same concentration(3mM). The changes of the mRNA expression of the CaMK II subtype were observed with real-time PCR. All subtype mRNA of the CaMK II, CaMK II α , CaMK II β , CaMK II δ , CaMK II γ , can be detected in dorsal root ganglion neurons. With the increased of the concentration and exposure time of the ropivacaine hydrochloride, all the subtype mRNA expression increased. Ropivacaine hydrochloride up-regulate the CaMK II β , CaMK II δ , CaMK II g mRNA expression with the concentration and exposure time increasing. The nerve blocking or the neurotoxicity of the ropivacaine hydrochloride maybe involved with CaMK II. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Relative importance of school bus-related microenvironments to children's pollutant exposure.

PubMed

Behrentz, Eduardo; Sabin, Lisa D; Winer, Arthur M; Fitz, Dennis R; Pankratz, David V; Colome, Steven D; Fruin, Scott A

2005-10-01

Real-time concentrations of black carbon, particle-bound polycyclic aromatic hydrocarbons, nitrogen dioxide, and fine particulate counts, as well as integrated and real-time fine particulate matter (PM2.5) mass concentrations were measured inside school buses during long commutes on Los Angeles Unified School District bus routes, at bus stops along the routes, at the bus loading/unloading zone in front of the selected school, and at nearby urban "background" sites. Across all of the pollutants, mean concentrations during bus commutes were higher than in any other microenvironment. Mean exposures (mean concentration times time spent in a particular microenvironment) in bus commutes were between 50 and 200 times greater than those for the loading/unloading microenvironment, and 20-40 times higher than those for the bus stops, depending on the pollutant. Although the analyzed school bus commutes represented only 10% of a child's day, on average they contributed one-third of a child's 24-hr overall black carbon exposure during a school day. For species closely related to vehicle exhaust, the within- cabin exposures were generally dominated by the effect of surrounding traffic when windows were open and by the bus's own exhaust when windows were closed. Low-emitting buses generally exhibited high concentrations only when traveling behind a diesel vehicle, whereas high-emitting buses exhibited high concentrations both when following other diesel vehicles and when idling without another diesel vehicle in front of the bus. To reduce school bus commute exposures, we recommend minimizing commute times, avoiding caravanning with other school buses, using the cleanest buses for the longest bus routes, maintaining conventional diesel buses to eliminate visible emissions, and transitioning to cleaner fuels and advanced particulate control technologies as soon as possible.

Mercury in Children: Current State on Exposure through Human Biomonitoring Studies

PubMed Central

Ruggieri, Flavia; Majorani, Costanza; Domanico, Francesco; Alimonti, Alessandro

2017-01-01

Mercury (Hg) in children has multiple exposure sources and the toxicity of Hg compounds depends on exposure routes, dose, timing of exposure, and developmental stage (be it prenatal or postnatal). Over the last decades, Hg was widely recognized as a threat to the children’s health and there have been acknowledgements at the international level of the need of a global policy intervention—like the Minamata treaty—aimed at reducing or preventing Hg exposure and protecting the child health. National human biomonitoring (HBM) data has demonstrated that low levels of exposure of Hg are still an important health concern for children, which no one country can solve alone. Although independent HBM surveys have provided the basis for the achievements of exposure mitigation in specific contexts, a new paradigm for a coordinated global monitoring of children’s exposure, aimed at a reliable decision-making tool at global level is yet a great challenge for the next future. The objective of the present review is to describe current HBM studies on Hg exposure in children, taking into account the potential pathways of Hg exposure and the actual Hg exposure levels assessed by different biomarkers. PMID:28498344

Adenosine Amine Congener as a Cochlear Rescue Agent

PubMed Central

Vlajkovic, Srdjan M.; Chang, Hao; Paek, Song Yee; Chi, Howard H.-T.; Sreebhavan, Sreevalsan; Telang, Ravindra S.; Tingle, Malcolm; Housley, Gary D.; Thorne, Peter R.

2014-01-01

We have previously shown that adenosine amine congener (ADAC), a selective A1 adenosine receptor agonist, can ameliorate noise- and cisplatin-induced cochlear injury. Here we demonstrate the dose-dependent rescue effects of ADAC on noise-induced cochlear injury in a rat model and establish the time window for treatment. Methods. ADAC (25–300 μg/kg) was administered intraperitoneally to Wistar rats (8–10 weeks old) at intervals (6–72 hours) after exposure to traumatic noise (8–16 kHz, 110 dB sound pressure level, 2 hours). Hearing sensitivity was assessed using auditory brainstem responses (ABR) before and 12 days after noise exposure. Pharmacokinetic studies investigated ADAC concentrations in plasma after systemic (intravenous) administration. Results. ADAC was most effective in the first 24 hours after noise exposure at doses >50 μg/kg, providing up to 21 dB protection (averaged across 8–28 kHz). Pharmacokinetic studies demonstrated a short (5 min) half-life of ADAC in plasma after intravenous administration without detection of degradation products. Conclusion. Our data show that ADAC mitigates noise-induced hearing loss in a dose- and time-dependent manner, but further studies are required to establish its translation as a clinical otological treatment. PMID:25243188

Parental alcohol dependence and the transmission of adolescent behavioral disinhibition: a study of adoptive and non-adoptive families.

PubMed

King, Serena M; Keyes, Margaret; Malone, Stephen M; Elkins, Irene; Legrand, Lisa N; Iacono, William G; McGue, Matt

2009-04-01

To examine the genetic and environmental influences of parental alcoholism on offspring disinhibited behavior. We compared the effect of parental alcoholism history on offspring in adoptive and non-adoptive families. In families with a history of parental alcohol dependence, we examined the effect of exposure to parental alcoholism symptoms during the life-time of the adolescent. Setting Assessments occurred at the University of Minnesota from 1998 to 2004. Adolescents adopted in infancy were ascertained systematically from records of three private Minnesota adoption agencies; non-adopted adolescents were ascertained from Minnesota birth records. Adolescents and their rearing parents participated in in-person assessments. For adolescents, measures included self- reports of delinquency, deviant peers, substance use, antisocial attitudes and personality. For parents, we conducted DSM-IV clinical assessments of alcohol abuse and dependence. A history of parental alcohol dependence was associated with higher levels of disinhibition only when adolescents were related biologically to their rearing parents. Within families with a history of parental alcoholism, exposure to parental alcohol misuse during the life-time of the adolescent was associated with increased odds of using alcohol in adopted adolescents only. These findings suggest that the association between a history of parental alcohol dependence and adolescent offspring behavioral disinhibition is attributable largely to genetic rather than environmental transmission. We also obtained some evidence for parental alcohol misuse as a shared environmental risk factor in adoptive families.

Detection on emamectin benzoate-induced apoptosis and DNA damage in Spodoptera frugiperda Sf-9 cell line.

PubMed

Wu, Xiwei; Zhang, Lei; Yang, Chao; Zong, Mimi; Huang, Qingchun; Tao, Liming

2016-01-01

Emamectin benzoate (EMB), an important macrocyclic lactone insecticide that belongs to the avermectin family and possesses excellent potency in controlling pests, is non-carcinogenic and non-mutagenic conducted in rats and mice, but EMB-induced cytotoxicity and genotoxicity in arthropod insect have been seldom reported yet. In the present paper, we quantified the cytotoxicity of EMB through the detections on cell viability, DNA damage, and cell apoptosis in Spodoptera frugiperda Sf-9 cells in vitro. The results showed that EMB caused a concentration- and time-dependent reduction on the viability of Sf-9 cells, and the median inhibitory concentrations (IC50) were 3.34μM at 72h of exposure. The dual acridine orange/ethidium bromide staining showed that exposure to EMB induced a significant time- and concentration-dependent increase on cell apoptosis. The alkaline comet assay revealed that EMB induced significant increases on single-strand DNA breaks, and the percentage of γH2AX-positive cells represented a time- and concentration-dependent formation of DNA double-strand breaks in Sf-9 cells. Interestingly, the similar cytotoxic actions of EMB also went for the human cancerous HeLa cells as a control cell group. Data demonstrated the potential cytotoxic effect of EMB on Sf-9 cells that was significantly greater than the effect of hydrogen peroxide at the same concentrations. Copyright © 2015 Elsevier Inc. All rights reserved.

Time and dose-response effects of honokiol on UVB-induced skin cancer development.

PubMed

Guillermo, Ruth F; Chilampalli, Chandeshwari; Zhang, Xiaoying; Zeman, David; Fahmy, Hesham; Dwivedi, Chandradhar

2012-06-01

Honokiol has shown chemopreventive effects in chemically-induced and UVB-induced skin cancer in mice. In this investigation, we assessed the time-effects of a topical low dose of honokiol (30 μg), and then the effects of different honokiol doses (30, 45, and 60 μg) on a UVB-induced skin cancer model to find an optimal dose and time for desirable chemopreventive effects. UVB radiation (30 mJ/cm(2), 5 days/week for 25 or 27 weeks) was used to induce skin carcinogenesis in SKH-1 mice. For the time-response experiment 30 μg honokiol in acetone was applied topically to the animals before the UVB exposure (30 min, 1 h, and 2 h) and after the UVB exposure (immediately, 30 min, and 1 h). Control groups were treated with acetone. For the dose-response study, animals were treated topically with acetone or honokiol (30, 45, and 60 μg) one hour before the UVB exposure. In the time-response experiment, honokiol inhibited skin tumor multiplicity by 49-58% while reducing tumor volumes by 70-89%. In the dose-response study, honokiol (30, 45, and 60 μg) significantly decreased skin tumor multiplicity by 36-78% in a dose-dependent manner, while tumor area was reduced by 76-94%. Honokiol (60 μg) significantly reduced tumor incidence by 40% as compared to control group. Honokiol applied in very low doses (30 μg) either before or after UVB radiation shows chemopreventive effects. Honokiol (30, 45, and 60 μg) prevents UVB-induced skin cancer in a dose-dependent manner. Honokiol can be an effective chemopreventive agent against skin cancer.

Influence of gravity on the circadian timing system

NASA Technical Reports Server (NTRS)

Fuller, C. A.; Hoban-Higgins, T. M.; Griffin, D. W.; Murakami, D. M.

1994-01-01

The circadian timing system (CTS) is responsible for daily temporal coordination of physiological and behavioral functions both internally and with the external environment. Experiments in altered gravitational environments have revealed changes in circadian rhythms of species ranging from fungi to primates. The altered gravitational environments examined included both the microgravity environment of spaceflight and hyperdynamic environments produced by centrifugation. Acute exposure to altered gravitational environments changed homeostatic parameters such as body temperature. These changes were time of day dependent. Exposure to gravitational alterations of relatively short duration produced changes in both the homeostatic level and the amplitude of circadian rhythms. Chronic exposure to a non-earth level of gravity resulted in changes in the period of the expressed rhythms as well as in the phase relationships between the rhythms and between the rhythms and the external environment. In addition, alterations in gravity appeared to act as a time cue for the CTS. Altered gravity also affected the sensitivity of the pacemaker to other aspects of the environment (i.e., light) and to shifts of time cues. Taken together, these studies lead to the conclusion that the CTS is indeed sensitive to gravity and its alterations. This finding has implications for both basic biology and space medicine.

Risk assessments using the Strain Index and the TLV for HAL, Part I: Task and multi-task job exposure classifications.

PubMed

Kapellusch, Jay M; Bao, Stephen S; Silverstein, Barbara A; Merryweather, Andrew S; Thiese, Mathew S; Hegmann, Kurt T; Garg, Arun

2017-12-01

The Strain Index (SI) and the American Conference of Governmental Industrial Hygienists (ACGIH) Threshold Limit Value for Hand Activity Level (TLV for HAL) use different constituent variables to quantify task physical exposures. Similarly, time-weighted-average (TWA), Peak, and Typical exposure techniques to quantify physical exposure from multi-task jobs make different assumptions about each task's contribution to the whole job exposure. Thus, task and job physical exposure classifications differ depending upon which model and technique are used for quantification. This study examines exposure classification agreement, disagreement, correlation, and magnitude of classification differences between these models and techniques. Data from 710 multi-task job workers performing 3,647 tasks were analyzed using the SI and TLV for HAL models, as well as with the TWA, Typical and Peak job exposure techniques. Physical exposures were classified as low, medium, and high using each model's recommended, or a priori limits. Exposure classification agreement and disagreement between models (SI, TLV for HAL) and between job exposure techniques (TWA, Typical, Peak) were described and analyzed. Regardless of technique, the SI classified more tasks as high exposure than the TLV for HAL, and the TLV for HAL classified more tasks as low exposure. The models agreed on 48.5% of task classifications (kappa = 0.28) with 15.5% of disagreement between low and high exposure categories. Between-technique (i.e., TWA, Typical, Peak) agreement ranged from 61-93% (kappa: 0.16-0.92) depending on whether the SI or TLV for HAL was used. There was disagreement between the SI and TLV for HAL and between the TWA, Typical and Peak techniques. Disagreement creates uncertainty for job design, job analysis, risk assessments, and developing interventions. Task exposure classifications from the SI and TLV for HAL might complement each other. However, TWA, Typical, and Peak job exposure techniques all have limitations. Part II of this article examines whether the observed differences between these models and techniques produce different exposure-response relationships for predicting prevalence of carpal tunnel syndrome.

Assessing the Effectiveness of Ramp-Up During Sonar Operations Using Exposure Models.

PubMed

von Benda-Beckmann, Alexander M; Wensveen, Paul J; Kvadsheim, Petter H; Lam, Frans-Peter A; Miller, Patrick J O; Tyack, Peter L; Ainslie, Michael A

2016-01-01

Ramp-up procedures are used to mitigate the impact of sound on marine mammals. Sound exposure models combined with observations of marine mammals responding to sound can be used to assess the effectiveness of ramp-up procedures. We found that ramp-up procedures before full-level sonar operations can reduce the risk of hearing threshold shifts with marine mammals, but their effectiveness depends strongly on the responsiveness of the animals. In this paper, we investigated the effect of sonar parameters (source level, pulse-repetition time, ship speed) on sound exposure by using a simple analytical model and highlight the mechanisms that limit the effectiveness of ramp-up procedures.

Brief Exposure to Secondhand Smoke Reversibly Impairs Endothelial Vasodilatory Function

PubMed Central

2014-01-01

Introduction: We sought to determine the effects of brief exposures to low concentrations of tobacco secondhand smoke (SHS) on arterial flow-mediated dilation (FMD, a nitric oxide-dependent measure of vascular endothelial function), in a controlled animal model never before exposed to smoke. In humans, SHS exposure for 30min impairs FMD. It is important to gain a better understanding of the acute effects of exposure to SHS at low concentrations and for brief periods of time. Methods: We measured changes in FMD in rats exposed to a range of real-world levels of SHS for durations of 30min, 10min, 1min, and 4 breaths (roughly 15 s). Results: We observed a dose-response relationship between SHS particle concentration over 30min and post-exposure impairment of FMD, which was linear through the range typically encountered in smoky restaurants and then saturated at higher concentrations. One min of exposure to SHS at moderate concentrations was sufficient to impair FMD. Conclusions: Brief SHS exposure at real-world levels reversibly impairs FMD. Even 1min of SHS exposure can cause reduction of endothelial function. PMID:24302638

Effects of elevated dissolved carbon dioxide and perfluorooctane sulfonic acid, given singly and in combination, on steroidogenic and biotransformation pathways of Atlantic cod.

PubMed

Preus-Olsen, Gunnhild; Olufsen, Marianne O; Pedersen, Sindre Andre; Letcher, Robert J; Arukwe, Augustine

2014-10-01

In the aquatic environments, the predicted changes in water temperature, pO2 and pCO2 could result in hypercapnic and hypoxic conditions for aquatic animals. These conditions are thought to affect several basic cellular and physiological mechanisms. Yet, possible adverse effects of elevated CO2 (hypercapnia) on teleost fish, as well as combined effects with emerging and legacy environmental contaminants are poorly investigated. In this study, juvenile Atlantic cod (Gadus morhua) were divided into groups and exposed to three different water bath PFOS exposure regimes (0 (control), 100 and 200 μg L(-1)) for 5 days at 1h/day, followed by three different CO2-levels (normocapnia, moderate (0.3%) and high (0.9%)). The moderate CO2 level is the predicted near future (within year 2300) level, while 0.9% represent severe hypercapnia. Tissue samples were collected at 3, 6 and 9 days after initiated CO2 exposure. Effects on the endocrine and biotransformation systems were examined by analyzing levels of sex steroid hormones (E2, T, 11-KT) and transcript expression of estrogen responsive genes (ERα, Vtg-α, Vtg-β, ZP2 and ZP3). In addition, transcripts for genes encoding xenobiotic metabolizing enzymes (cyp1a and cyp3a) and hypoxia-inducible factor (HIF-1α) were analyzed. Hypercapnia alone produced increased levels of sex steroid hormones (E2, T, 11-KT) with concomitant mRNA level increase of estrogen responsive genes, while PFOS produced weak and time-dependent effects on E2-inducible gene transcription. Combined PFOS and hypercapnia exposure produced increased effects on sex steroid levels as compared to hypercapnia alone, with transcript expression patterns that are indicative of time-dependent interactive effects. Exposure to hypercapnia singly or in combination with PFOS produced modulations of the biotransformation and hypoxic responses that were apparently concentration- and time-dependent. Loading plots of principal component analysis (PCA) produced a significant grouping of individual scores according to the exposure scenarios at day 6 and 9. Overall, the PCA analysis produced a unique clustering of variables that signifies a positive correlation between exposure to high PFOS concentration and mRNA expression of E2 responsive genes. Notably, this pattern was not evident for individuals exposed to PFOS concentrations in combination with elevated CO2 scenarios. To our knowledge, the present study is the first of its kind, to evaluate such effects using combined exposure to a perfluoroalkyl sulfonate and elevated levels of CO2 saturation, representative of future oceanic climate change, in any fish species or lower vertebrate. Copyright © 2014 Elsevier B.V. All rights reserved.

Investigations into the Reusability of Amidoxime-Based Polymeric Adsorbents for Seawater Uranium Extraction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kuo, Li-Jung; Pan, Horng-Bin; Wai, Chien M.

The ability to re-use amidoxime-based polymeric adsorbents is a critical component in reducing the overall cost of the technology to extract uranium from seawater. This report describes an evaluation of adsorbent reusability in multiple re-use (adsorption/stripping) cycles in real seawater exposures with potassium bicarbonate (KHCO3) elution using several amidoxime-based polymeric adsorbents. The KHCO3 elution technique achieved ~100% recovery of uranium adsorption capacity in the first re-use. Subsequent re-uses showed significant drops in adsorption capacity. After the 4th re-use with the ORNL AI8 adsorbent, the 56-day adsorption capacity dropped to 28% of its original capacity. FTIR spectra revealed that there wasmore » a conversion of the amidoxime ligands to carboxylate groups during extended seawater exposure, becoming more significant with longer the exposure time. Ca and Mg adsorption capacities also increased with each re-use cycle supporting the hypothesis that long term exposure resulted in converting amidoxime to carboxylate, enhancing the adsorption of Ca and Mg. Shorter seawater exposure (adsorption/stripping) cycles (28 vs. 42 days) had higher adsorption capacities after re-use, but the shorter exposure cycle time did not produce an overall better performance in terms of cumulative exposure time. Recovery of uranium capacity in re-uses may also vary across different adsorbent formulations. Through multiple re-use the adsorbent AI8 can harvest 10 g uranium/kg adsorbent in ~140 days, using a 28-day adsorption/stripping cycle, a performance much better than would be achieved with a single use of the adsorbent through very long-term exposure (saturation capacity = 7.4 g U/kg adsorbent). A time dependent seawater exposure model to evaluate the cost associated with reusing amidoxime-based adsorbents in real seawater exposures was developed. The cost to extract uranium from seawater ranged from $610-830/kg U was predicted. Model simulation suggests that a short seawater exposure cycle (< 15 days) is the optimal deployment period for lower uranium production cost in seawater uranium mining.« less

Contribution of radon and radon daughters to respiratory cancer.

PubMed Central

Harley, N; Samet, J M; Cross, F T; Hess, T; Muller, J; Thomas, D

1986-01-01

This article reviews studies on the contribution of radon and radon daughters to respiratory cancer and proposes recommendations for further research, particularly a national radon survey. The steady-state outdoor radon concentration averages 200 pCi/m3, and indoor levels are about 4 times higher. The primary source of radon in homes is the underlying soil; entry depends on multiple variables and reduced ventilation for energy conservation increases indoor radon levels. Occupational exposures are expressed in units of radon daughter potential energy concentration or working level (WL). Cumulative exposure is the product of the working level and the time exposed. The unit for cumulative exposure is the working level month (WLM). The occupational standard for radon exposure is 4 WLM/year, and 2 WLM/year has been suggested as a guideline for remedial action in homes. Epidemiologic studies show that miners with cumulative radon daughter exposures somewhat below 100 WLM have excess lung cancer mortality. Some 3% to 8% of miners studied have developed lung cancer attributable to radon daughters. All of the underground mining studies show an increased risk of lung cancer with radon daughter exposure. All cell types of lung cancer increased with radon exposure. If radon and smoking act in a multiplicative manner, then the risk for smokers could be 10 times that for nonsmokers. The potential risk of lung cancer appears to be between 1 and 2 per 10,000/WLM, which yields a significant number of lung cancers as some 220 million persons in the United States are exposed on average to 10 to 20 WLM/lifetime. PMID:3830103

Effects of genistein in the maternal diet on reproductive development and spatial learning in male rats.

PubMed

Ball, Evan R; Caniglia, Mary Kay; Wilcox, Jenna L; Overton, Karla A; Burr, Marra J; Wolfe, Brady D; Sanders, Brian J; Wisniewski, Amy B; Wrenn, Craige C

2010-03-01

Endocrine disruptors, chemicals that disturb the actions of endogenous hormones, have been implicated in birth defects associated with hormone-dependent development. Phytoestrogens are a class of endocrine disruptors found in plants. In the current study we examined the effects of exposure at various perinatal time periods to genistein, a soy phytoestrogen, on reproductive development and learning in male rats. Dams were fed genistein-containing (5 mg/kg feed) food during both gestation and lactation, during gestation only, during lactation only, or during neither period. Measures of reproductive development and body mass were taken in the male offspring during postnatal development, and learning and memory performance was assessed in adulthood. Genistein exposure via the maternal diet decreased body mass in the male offspring of dams fed genistein during both gestation and lactation, during lactation only, but not during gestation only. Genistein decreased anogenital distance when exposure was during both gestation and lactation, but there was no effect when exposure was limited to one of these time periods. Similarly, spatial learning in the Morris water maze was impaired in male rats exposed to genistein during both gestation and lactation, but not in rats exposed during only one of these time periods. There was no effect of genistein on cued or contextual fear conditioning. In summary, the data indicate that exposure to genistein through the maternal diet significantly impacts growth in male offspring if exposure is during lactation. The effects of genistein on reproductive development and spatial learning required exposure throughout the pre- and postnatal periods. Copyright 2009 Elsevier Inc. All rights reserved.

The effect of a low iron diet and early life methylmercury exposure in Daphnia pulex

PubMed Central

Hudson, Sherri L.; Doke, Dzigbodi A.; Gohlke, Julia M.

2016-01-01

Iron (Fe) deficiency increases risk for adverse health outcomes in humans; however little is known about the potential interaction with methylmercury (MeHg) exposure. Studies testing multiple stressor hypotheses are expensive and time consuming in mammalian model systems; therefore, determining relevance of alternative models is important. Daphnia pulex were fed standard or low-Fe diets of freshwater algae, Ankistrodesmus falcatus. MeHgCl (1600 ng/L) or vehicle was added to culture media for 24 h during early life, and the combinatorial effects of a low-Fe diet and MeHg exposure on lifespan, maturation time, and reproduction were evaluated. Lipid storage effects were measured using image analysis of Oil Red O staining and triacylglyceride quantification. Our results show a dose-dependent reduction in lifespan in D. pulex fed low Fe diets. Lipid analysis suggests an interactive effect of diet and MeHg exposure, with MeHg exposure increasing lipid storage in D. pulex fed a low-Fe diet. These findings suggest the effects of dietary iron intake and early life MeHg exposure in D. pulex may be mediated by changes in energetics that result in differential lipid storage. Therefore, lipid storage in D. pulex may be a useful screen for detecting long-term effects of multiple stressors early in life. PMID:26806633

Emergency Dose Estimation Using Optically Stimulated Luminescence from Human Tooth Enamel

PubMed Central

Sholom, S.; DeWitt, R.; Simon, S.L.; Bouville, A.; McKeever, S.W.S.

2011-01-01

Human teeth were studied for potential use as emergency Optically Stimulated Luminescence (OSL) dosimeters. By using multiple-teeth samples in combination with a custom-built sensitive OSL reader, 60Co-equivalent doses below 0.64 Gy were measured immediately after exposure with the lowest value being 27 mGy for the most sensitive sample. The variability of OSL sensitivity, from individual to individual using multiple-teeth samples, was determined to be 53%. X-ray and beta exposure were found to produce OSL curves with the same shape that differed from those due to ultraviolet (UV) exposure; as a result, correlation was observed between OSL signals after X-ray and beta exposure and was absent if compared to OSL signals after UV exposure. Fading of the OSL signal was “typical” for most teeth with just a few of incisors showing atypical behavior. Typical fading dependences were described by a bi-exponential decay function with “fast” (decay time around of 12 min) and “slow” (decay time about 14 h) components. OSL detection limits, based on the techniques developed to-date, were found to be satisfactory from the point-of-view of medical triage requirements if conducted within 24 hours of the exposure. PMID:21949479

Environmental exposure effects on composite materials for commercial aircraft

NASA Technical Reports Server (NTRS)

Hoffman, Daniel J.; Bielawski, William J.

1991-01-01

A study was conducted to determine the effects of long term flight and ground exposure on three commercially available graphite-epoxy material systems: T300/5208, T300/5209, and T300/934. Sets of specimens were exposed on commercial aircraft and ground racks for 1, 2, 3, 5, and 10 years. Inflight specimen sites included both the interior and exterior of aircraft based in Hawaii, Texas, and New Zealand. Ground racks were located at NASA-Dryden and the above mentioned states. Similar specimens were exposed to controlled lab conditions for up to 2 years. After each exposure, specimens were tested for residual strength and a dryout procedure was used to measure moisture content. Both room and high temperature residual strengths were measured and expressed as a pct. of the unexposed strength. Lab exposures included the effects of time alone, moisture, time on moist specimens, weatherometer, and simulated ground-air-ground cycling. Residual strengths of the long term specimens were compared with residual strengths of the lab specimens. Strength retention depended on the exposure condition and the material system. Results showed that composite materials can be successfully used on commercial aircraft if environmental effects are considered.

The effect of exposure duration on the subjective discomfort of aircraft cabin noise.

PubMed

Huang, Yu; Jiang, Weikang

2017-01-01

The time dependency for subjective responses to noise has been a controversial question over many years. For durations of up to 10 min, the discomfort produced by three levels of noise (ie 60, 70 and 80 dBA) was investigated in this experimental study to determine the relation of discomfort to the time duration of noise. The rate of increase in discomfort with increasing duration was 1.5 dB per doubling of exposure duration, whereas it is currently assumed to be 3 dB per doubling of exposure duration. The sound dose level (SDL) was proposed to predict the discomfort caused by noise of long duration. The combination of SDL and vibration dose value (VDV) provided more consistent estimates of the equivalent comfort contours between noise and vibration over durations from 2 to 32 s than the combination of sound exposure level and VDV or that of sound pressure level and r.m.s. acceleration. Practitioner Summary: The discomfort produced by noise of long duration can be well predicted from a new definition of sound dose level, where the discomfort increases at 1.5 dB per doubling of exposure duration.

Learning complex temporal patterns with resource-dependent spike timing-dependent plasticity.

PubMed

Hunzinger, Jason F; Chan, Victor H; Froemke, Robert C

2012-07-01

Studies of spike timing-dependent plasticity (STDP) have revealed that long-term changes in the strength of a synapse may be modulated substantially by temporal relationships between multiple presynaptic and postsynaptic spikes. Whereas long-term potentiation (LTP) and long-term depression (LTD) of synaptic strength have been modeled as distinct or separate functional mechanisms, here, we propose a new shared resource model. A functional consequence of our model is fast, stable, and diverse unsupervised learning of temporal multispike patterns with a biologically consistent spiking neural network. Due to interdependencies between LTP and LTD, dendritic delays, and proactive homeostatic aspects of the model, neurons are equipped to learn to decode temporally coded information within spike bursts. Moreover, neurons learn spike timing with few exposures in substantial noise and jitter. Surprisingly, despite having only one parameter, the model also accurately predicts in vitro observations of STDP in more complex multispike trains, as well as rate-dependent effects. We discuss candidate commonalities in natural long-term plasticity mechanisms.

Recurrence quantification analysis to characterize cyclical components of environmental elemental exposures during fetal and postnatal development

PubMed Central

Austin, Christine; Gennings, Chris; Tammimies, Kristiina; Bölte, Sven; Arora, Manish

2017-01-01

Environmental exposures to essential and toxic elements may alter health trajectories, depending on the timing, intensity, and mixture of exposures. In epidemiologic studies, these factors are typically analyzed as a function of elemental concentrations in biological matrices measured at one or more points in time. Such an approach, however, fails to account for the temporal cyclicity in the metabolism of environmental chemicals, which if perturbed may lead to adverse health outcomes. Here, we conceptualize and apply a non-linear method–recurrence quantification analysis (RQA)–to quantify cyclical components of prenatal and early postnatal exposure profiles for elements essential to normal development, including Zn, Mn, Mg, and Ca, and elements associated with deleterious health effects or narrow tolerance ranges, including Pb, As, and Cr. We found robust evidence of cyclical patterns in the metabolic profiles of nutrient elements, which we validated against randomized twin-surrogate time-series, and further found that nutrient dynamical properties differ from those of Cr, As, and Pb. Furthermore, we extended this approach to provide a novel method of quantifying dynamic interactions between two environmental exposures. To achieve this, we used cross-recurrence quantification analysis (CRQA), and found that elemental nutrient-nutrient interactions differed from those involving toxicants. These rhythmic regulatory interactions, which we characterize in two geographically distinct cohorts, have not previously been uncovered using traditional regression-based approaches, and may provide a critical unit of analysis for environmental and dietary exposures in epidemiological studies. PMID:29112980

Time-Course of the Ethanol-like Discriminative Stimulus Effects of Abused Inhalants in Mice

PubMed Central

Bowen, Scott E.

2009-01-01

Abused solvents have effects similar to those of abused depressant drugs. This experiment evaluated the time course of the discriminative stimulus effects of toluene and 1,1,1-trichloroethane (TRI). Mice were trained to discriminate between i.p. injections of ethanol (EtOH;1.25 g/kg) and saline in a two-lever operant task in which responding was under the control of a fixed-ratio 20 schedule. After 20-min inhalation exposures to toluene (500–6000 ppm) or TRI (1,000–12,000 ppm), stimulus generalization was examined at 0, 5, 10, 20, and 40 min post-exposure. Ethanol doses ≥ 0.25 g/kg produced increases in EtOH-lever responding with full substitution occurring immediately after testing for doses between 1.25 and 2.5 g/kg. Toluene and TRI produced increased EtOH-lever responding at 0–10 min post exposure with some EtOH-lever responding occurring up to 20-min post exposure. Response rates were not decreased for any concentration of toluene or TRI immediately following inhalant exposure but several concentrations elevated rates from 5–40 min post exposure. These results confirm and extend previous studies and show these solvents produce similar effects in EtOH-lever responding but with potency differences. The time-dependent differences in EtOH-lever responding suggest that as solvents are cleared from the body, the EtOH-like subjective effects also fade. PMID:18722399

Leukemia risk associated with chronic external exposure to ionizing radiation in a French cohort of nuclear workers.

PubMed

Metz-Flamant, C; Samson, E; Caër-Lorho, S; Acker, A; Laurier, D

2012-11-01

Leukemia is one of the earliest cancer effects observed after acute exposure to relatively high doses of ionizing radiation. Leukemia mortality after external exposure at low doses and low-dose rates has been investigated at the French Atomic Energy Commission (CEA) and Nuclear Fuel Company (AREVA NC) after an additional follow-up of 10 years. The cohort included radiation-monitored workers employed for at least one year during 1950-1994 at CEA or AREVA NC and followed during 1968-2004. Association between external exposure and leukemia mortality was estimated with excess relative risk (ERR) models and time-dependent modifying factors were investigated with time windows. The cohort included 36,769 workers, followed for an average of 28 years, among whom 73 leukemia deaths occurred. Among the workers with a positive recorded dose, the mean cumulative external dose was 21.7 mSv. Results under a 2-year lag assumption suggested that the risk of leukemia (except chronic lymphatic leukemia) increased significantly by 8% per 10 mSv. The magnitude of the association for myeloid leukemia was larger. The higher ERR/Sv for doses received 2-14 years earlier suggest that time since exposure modifies the effect. The ERR/Sv also appeared higher for doses received at exposure rates ≥20 mSv per year. These results are consistent with those found in other studies of nuclear workers. However, confidence intervals are still wide. Further analyses should be conducted in pooled cohorts of nuclear workers.

Children's exposure assessment of radiofrequency fields: Comparison between spot and personal measurements.

PubMed

Gallastegi, Mara; Huss, Anke; Santa-Marina, Loreto; Aurrekoetxea, Juan J; Guxens, Mònica; Birks, Laura Ellen; Ibarluzea, Jesús; Guerra, David; Röösli, Martin; Jiménez-Zabala, Ana

2018-05-24

Radiofrequency (RF) fields are widely used and, while it is still unknown whether children are more vulnerable to this type of exposure, it is essential to explore their level of exposure in order to conduct adequate epidemiological studies. Personal measurements provide individualized information, but they are costly in terms of time and resources, especially in large epidemiological studies. Other approaches, such as estimation of time-weighted averages (TWAs) based on spot measurements could simplify the work. The aims of this study were to assess RF exposure in the Spanish INMA birth cohort by spot measurements and by personal measurements in the settings where children tend to spend most of their time, i.e., homes, schools and parks; to identify the settings and sources that contribute most to that exposure; and to explore if exposure assessment based on spot measurements is a valid proxy for personal exposure. When children were 8 years old, spot measurements were conducted in the principal settings of 104 participants: homes (104), schools and their playgrounds (26) and parks (79). At the same time, personal measurements were taken for a subsample of 50 children during 3 days. Exposure assessment based on personal and on spot measurements were compared both in terms of mean exposures and in exposure-dependent categories by means of Bland-Altman plots, Cohen's kappa and McNemar test. Median exposure levels ranged from 29.73 (in children's bedrooms) to 200.10 μW/m 2 (in school playgrounds) for spot measurements and were higher outdoors than indoors. Median personal exposure was 52.13 μW/m 2 and median levels of assessments based on spot measurements ranged from 25.46 to 123.21 μW/m 2 . Based on spot measurements, the sources that contributed most to the exposure were FM radio, mobile phone downlink and Digital Video Broadcasting-Terrestrial, while indoor and personal sources contributed very little (altogether <20%). Similar distribution was observed with personal measurements. There was a bias proportional to power density between personal measurements and estimates based on spot measurements, with the latter providing higher exposure estimates. Nevertheless, there were no systematic differences between those methodologies when classifying subjects into exposure categories. Personal measurements of total RF exposure showed low to moderate agreement with home and bedroom spot measurements and agreed better, though moderately, with TWA based on spot measurements in the main settings where children spend time (homes, schools and parks; Kappa = 0.46). Exposure assessment based on spot measurements could be a feasible proxy to rank personal RF exposure in children population, providing that all relevant locations are being measured. Copyright © 2018. Published by Elsevier Ltd.

Treadmill stress test after diesel exhaust particulate exposure reveals a time-dependent shift from parasympathetic to sympathetic dominance

EPA Science Inventory

Epidemiological studies suggest that particulate matter (PM) air pollution is a major trigger of acute cardiac events-including arrhythmia-especially in those with preexisting cardiac disease. Diesel exhaust (DE) contributes the majority of urban fine and ultrafine PM, and is thu...

Temporal Variability of Daily Personal Magnetic Field Exposure Metrics in Pregnant Women

PubMed Central

Lewis, Ryan C.; Evenson, Kelly R.; Savitz, David A.; Meeker, John D.

2015-01-01

Recent epidemiology studies of power-frequency magnetic fields and reproductive health have characterized exposures using data collected from personal exposure monitors over a single day, possibly resulting in exposure misclassification due to temporal variability in daily personal magnetic field exposure metrics, but relevant data in adults are limited. We assessed the temporal variability of daily central tendency (time-weighted average, median) and peak (upper percentiles, maximum) personal magnetic field exposure metrics over seven consecutive days in 100 pregnant women. When exposure was modeled as a continuous variable, central tendency metrics had substantial reliability, whereas peak metrics had fair (maximum) to moderate (upper percentiles) reliability. The predictive ability of a single day metric to accurately classify participants into exposure categories based on a weeklong metric depended on the selected exposure threshold, with sensitivity decreasing with increasing exposure threshold. Consistent with the continuous measures analysis, sensitivity was higher for central tendency metrics than for peak metrics. If there is interest in peak metrics, more than one day of measurement is needed over the window of disease susceptibility to minimize measurement error, but one day may be sufficient for central tendency metrics. PMID:24691007

Chemical mixtures: Evaluation of risk for child-specific exposures in a multi-stressor environment

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pohl, H.R.; Abadin, H.G.

Evaluating the health impact from exposure to chemical mixtures is multifaceted. One component is exposure. Exposure, and consequently risk assessment for mixtures and chemicals in general, are often viewed in terms of a given exposure to a given population at a given location over a given time period. However, environmental exposures are present throughout human lifetime. As a result, an evaluation of risk must include the distinctive characteristics related to chemical exposures which will impact risk depending upon the particular life stage where exposure occurs. Risks to offspring may be associated with unique exposures in utero, during infancy, childhood, ormore » adolescent periods. For example, exposure of infants to anthropogenic chemicals via breast milk may be of concern. The Agency for Toxic Substances and Disease Registry's (ATSDR's) approach to evaluating risks associated with exposure to mixtures of chemicals is presented. In addition to the breast milk issues, indoor exposure to combined air pollutants, drinking water contaminants, and soil and dust contaminants are discussed. The difference between a mixture's risk evaluation for children and adults is in the distinct exposure scenarios resulting from variations in behavior, physiology, and/or pharmacokinetics between adults and children rather than in the method for the specific mixtures evaluation per se.« less

Natural and Induced Environment in Low Earth Orbit

NASA Technical Reports Server (NTRS)

Wilson, John W.; Badavi, Francis F.; Kim, Myung-Hee Y.; Clowdsley, Martha S.; Heinbockel, John H.; Cucinotta, Francis A.; Badhwar, Gautam D.; Atwell, William; Huston, Stuart L.

2002-01-01

The long-term exposure of astronauts on the developing International Space Station (ISS) requires an accurate knowledge of the internal exposure environment for human risk assessment and other onboard processes. The natural environment is moderated by the solar wind which varies over the solar cycle. The neutron environment within the Shuttle in low Earth orbit has two sources. A time dependent model for the ambient environment is used to evaluate the natural and induced environment. The induced neutron environment is evaluated using measurements on STS-31 and STS-36 near the 1990 solar maximum.

Transcriptomic profile of host response in mouse brain after exposure to plant toxin abrin.

PubMed

Bhaskar, A S Bala; Gupta, Nimesh; Rao, P V Lakshmana

2012-09-04

Abrin toxin is a plant glycoprotein, which is similar in structure and properties to ricin and is obtained from the seeds of Abrus precatorius (jequirity bean). Abrin is highly toxic, with an estimated human fatal dose of 0.1-1 μg/kg, and has caused death after accidental and intentional poisoning. Abrin is a potent biological toxin warfare agent. There are no chemical antidotes available against the toxin. Neurological symptoms like delirium, hallucinations, reduced consciousness and generalized seizures were reported in human poisoning cases. Death of a patient with symptoms of acute demyelinating encephalopathy with gastrointestinal bleeding due to ingestion of abrin seeds was reported in India. The aim of this study was to examine both dose and time-dependent transcriptional responses induced by abrin in the adult mouse brain. Mice (n=6) were exposed to 1 and 2 LD50 (2.83 and 5.66 μg/kg respectively) dose of abrin by intraperitoneal route and observed over 3 days. A subset of animals (n=3) were sacrificed at 1 and 2 day intervals for microarray and histopathology analysis. None of the 2 LD50 exposed animals survived till 3 days. The histopathological analysis showed the severe damage in brain and the infiltration of inflammatory cells in a dose and time dependent manner. The abrin exposure resulted in the induction of rapid immune and inflammatory response in brain. Clinical biochemistry parameters like lactate dehydrogenase, aspartate aminotransferase, urea and creatinine showed significant increase at 2-day 2 LD50 exposure. The whole genome microarray data revealed the significant regulation of various pathways like MAPK pathway, cytokine-cytokine receptor interaction, calcium signaling pathway, Jak-STAT signaling pathway and natural killer cell mediated toxicity. The comparison of differential gene expression at both the doses showed dose dependent effects of abrin toxicity. The real-time qRT-PCR analysis of selected genes supported the microarray data. This is the first report on host-gene response using whole genome microarray in an animal model after abrin exposure. The data generated provides leads for developing suitable medical counter measures against abrin poisoning. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The mere exposure effect depends on an odor's initial pleasantness.

PubMed

Delplanque, Sylvain; Coppin, Géraldine; Bloesch, Laurène; Cayeux, Isabelle; Sander, David

2015-01-01

The mere exposure phenomenon refers to improvement of one's attitude toward an a priori neutral stimulus after its repeated exposure. The extent to which such a phenomenon influences evaluation of a priori emotional stimuli remains under-investigated. Here we investigated this question by presenting participants with different odors varying in a priori pleasantness during different sessions spaced over time. Participants were requested to report each odor's pleasantness, intensity, and familiarity. As expected, participants became more familiar with all stimuli after the repetition procedure. However, while neutral and mildly pleasant odors showed an increase in pleasantness ratings, unpleasant and very pleasant odors remained unaffected. Correlational analyses revealed an inverse U-shape between the magnitude of the mere exposure effect and the initial pleasantness of the odor. Consequently, the initial pleasantness of the stimuli appears to modulate the impact of repeated exposures on an individual's attitude. These data underline the limits of mere exposure effect and are discussed in light of the biological relevance of odors for individual survival.

Infrared skin damage thresholds from 1319-nm continuous-wave laser exposures

NASA Astrophysics Data System (ADS)

Oliver, Jeffrey W.; Vincelette, Rebecca; Noojin, Gary D.; Clark, Clifton D.; Harbert, Corey A.; Schuster, Kurt J.; Shingledecker, Aurora D.; Kumru, Semih S.; Maughan, Justin; Kitzis, Naomi; Buffington, Gavin D.; Stolarski, David J.; Thomas, Robert J.

2013-12-01

A series of experiments were conducted in vivo using Yucatan miniature pigs (Sus scrofa domestica) to determine thermal damage thresholds to the skin from 1319-nm continuous-wave Nd:YAG laser irradiation. Experiments employed exposure durations of 0.25, 1.0, 2.5, and 10 s and beam diameters of ˜0.6 and 1 cm. Thermal imagery data provided a time-dependent surface temperature response from the laser. A damage endpoint of fifty percent probability of a minimally visible effect was used to determine threshold for damage at 1 and 24 h postexposure. Predicted thermal response and damage thresholds are compared with a numerical model of optical-thermal interaction. Resultant trends with respect to exposure duration and beam diameter are compared with current standardized exposure limits for laser safety. Mathematical modeling agreed well with experimental data, predicting that though laser safety standards are sufficient for exposures <10 s, they may become less safe for very long exposures.

Fluoxetine exposure impacts boldness in female Siamese fighting fish, Betta splendens.

PubMed

Dzieweczynski, Teresa L; Kane, Jessica L; Campbell, Brennah A; Lavin, Lindsey E

2016-01-01

The present study examined the effects of the selective serotonin reuptake inhibitor, fluoxetine, on the behavior of female Siamese fighting fish, Betta splendens, in three different boldness assays (Empty Tank, Novel Environment, Social Tendency). When females were unexposed to fluoxetine, boldness was consistent within a context and correlated across assays. Fluoxetine exposure affected behavior within and among individuals on multiple levels. Exposure reduced overall boldness levels, made females behave in a less consistent manner, and significantly reduced correlations over time and across contexts. Fluoxetine exerted its effects on female Betta splendens behavior in a dose-dependent fashion and these effects persisted even after females were housed in clean water. If fluoxetine exposure impacts behaviors such as exploration that are necessary to an individual’s success, this may yield evolutionary consequences. In conclusion, the results show that fluoxetine exposure alters behavior beyond the level of overall response and highlights the importance of studying the behavioral effects of inadvertent pharmaceutical exposure in multiple contexts and with different dosing regimes.

The mere exposure effect depends on an odor’s initial pleasantness

PubMed Central

Delplanque, Sylvain; Coppin, Géraldine; Bloesch, Laurène; Cayeux, Isabelle; Sander, David

2015-01-01

The mere exposure phenomenon refers to improvement of one’s attitude toward an a priori neutral stimulus after its repeated exposure. The extent to which such a phenomenon influences evaluation of a priori emotional stimuli remains under-investigated. Here we investigated this question by presenting participants with different odors varying in a priori pleasantness during different sessions spaced over time. Participants were requested to report each odor’s pleasantness, intensity, and familiarity. As expected, participants became more familiar with all stimuli after the repetition procedure. However, while neutral and mildly pleasant odors showed an increase in pleasantness ratings, unpleasant and very pleasant odors remained unaffected. Correlational analyses revealed an inverse U-shape between the magnitude of the mere exposure effect and the initial pleasantness of the odor. Consequently, the initial pleasantness of the stimuli appears to modulate the impact of repeated exposures on an individual’s attitude. These data underline the limits of mere exposure effect and are discussed in light of the biological relevance of odors for individual survival. PMID:26191021

Laboratory evaluation of three strains of the entomopathogenic fungus Metarhizium anisopliae for controlling Dermanyssus gallinae.

PubMed

Tavassoli, M; Ownag, A; Pourseyed, S H; Mardani, K

2008-06-01

The pathogenicity of three strains of the entomopathogenic fungus Metarhizium anisopliae on different life stages of Dermanyssus gallinae was evaluated in the laboratory. All the strains tested were virulent to D. gallinae but pathogenicity varied among the strains. Strain V245 induced a higher mortality rate using different concentrations than other two strains. The estimated median lethal concentration of different strains of M. anisopliae against D. gallinae varied depending on the exposure time of D. gallinae to M. anisopliae. It was concluded that the pathogenicity of the entomopathogenic fungus M. anisopliae on different life stages of D. gallinae was concentration and time dependent.

A fast double shutter for CCD-based metrology

NASA Astrophysics Data System (ADS)

Geisler, R.

2017-02-01

Image based metrology such as Particle Image Velocimetry (PIV) depends on the comparison of two images of an object taken in fast succession. Cameras for these applications provide the so-called `double shutter' mode: One frame is captured with a short exposure time and in direct succession a second frame with a long exposure time can be recorded. The difference in the exposure times is typically no problem since illumination is provided by a pulsed light source such as a laser and the measurements are performed in a darkened environment to prevent ambient light from accumulating in the long second exposure time. However, measurements of self-luminous processes (e.g. plasma, combustion ...) as well as experiments in ambient light are difficult to perform and require special equipment (external shutters, highspeed image sensors, multi-sensor systems ...). Unfortunately, all these methods incorporate different drawbacks such as reduced resolution, degraded image quality, decreased light sensitivity or increased susceptibility to decalibration. In the solution presented here, off-the-shelf CCD sensors are used with a special timing to combine neighbouring pixels in a binning-like way. As a result, two frames of short exposure time can be captured in fast succession. They are stored in the on-chip vertical register in a line-interleaved pattern, read out in the common way and separated again by software. The two resultant frames are completely congruent; they expose no insensitive lines or line shifts and thus enable sub-pixel accurate measurements. A third frame can be captured at the full resolution analogue to the double shutter technique. Image based measurement techniques such as PIV can benefit from this mode when applied in bright environments. The third frame is useful e.g. for acceleration measurements or for particle tracking applications.

Speckle-field propagation in 'frozen' turbulence: brightness function approach

NASA Astrophysics Data System (ADS)

Dudorov, Vadim V.; Vorontsov, Mikhail A.; Kolosov, Valeriy V.

2006-08-01

Speckle-field long- and short-exposure spatial correlation characteristics for target-in-the-loop (TIL) laser beam propagation and scattering in atmospheric turbulence are analyzed through the use of two different approaches: the conventional Monte Carlo (MC) technique and the recently developed brightness function (BF) method. Both the MC and the BF methods are applied to analysis of speckle-field characteristics averaged over target surface roughness realizations under conditions of 'frozen' turbulence. This corresponds to TIL applications where speckle-field fluctuations associated with target surface roughness realization updates occur within a time scale that can be significantly shorter than the characteristic atmospheric turbulence time. Computational efficiency and accuracy of both methods are compared on the basis of a known analytical solution for the long-exposure mutual correlation function. It is shown that in the TIL propagation scenarios considered the BF method provides improved accuracy and requires significantly less computational time than the conventional MC technique. For TIL geometry with a Gaussian outgoing beam and Lambertian target surface, both analytical and numerical estimations for the speckle-field long-exposure correlation length are obtained. Short-exposure speckle-field correlation characteristics corresponding to propagation in 'frozen' turbulence are estimated using the BF method. It is shown that atmospheric turbulence-induced static refractive index inhomogeneities do not significantly affect the characteristic correlation length of the speckle field, whereas long-exposure spatial correlation characteristics are strongly dependent on turbulence strength.

Speckle-field propagation in 'frozen' turbulence: brightness function approach.

PubMed

Dudorov, Vadim V; Vorontsov, Mikhail A; Kolosov, Valeriy V

2006-08-01

Speckle-field long- and short-exposure spatial correlation characteristics for target-in-the-loop (TIL) laser beam propagation and scattering in atmospheric turbulence are analyzed through the use of two different approaches: the conventional Monte Carlo (MC) technique and the recently developed brightness function (BF) method. Both the MC and the BF methods are applied to analysis of speckle-field characteristics averaged over target surface roughness realizations under conditions of 'frozen' turbulence. This corresponds to TIL applications where speckle-field fluctuations associated with target surface roughness realization updates occur within a time scale that can be significantly shorter than the characteristic atmospheric turbulence time. Computational efficiency and accuracy of both methods are compared on the basis of a known analytical solution for the long-exposure mutual correlation function. It is shown that in the TIL propagation scenarios considered the BF method provides improved accuracy and requires significantly less computational time than the conventional MC technique. For TIL geometry with a Gaussian outgoing beam and Lambertian target surface, both analytical and numerical estimations for the speckle-field long-exposure correlation length are obtained. Short-exposure speckle-field correlation characteristics corresponding to propagation in 'frozen' turbulence are estimated using the BF method. It is shown that atmospheric turbulence-induced static refractive index inhomogeneities do not significantly affect the characteristic correlation length of the speckle field, whereas long-exposure spatial correlation characteristics are strongly dependent on turbulence strength.

Fractography of the high temperature hydrogen attack of a medium carbon steel

NASA Technical Reports Server (NTRS)

Melson, H. G.; Moorhead, R. D.

1975-01-01

Microscopic fracture processes were studied which are associated with hydrogen attack of a medium carbon steel in a well-controlled, high-temperature, high-purity hydrogen environment. Exposure to a hydrogen pressure and temperature of 3.5 MN/m2 and 575 C was found to degrade room temperature tensile properties with increasing exposure time. After 408 hr, yield and ultimate strengths were reduced by more than 40 percent and elongation was reduced to less than 2 percent. Initial fissure formation was found to be associated with manganese rich particles, most probably manganese oxide, aligned in the microstructure during the rolling operation. Fissure growth was found to be associated with a reduction in carbide content of the microstructure and was inhibited by the depletion of carbon. The interior surfaces of sectioned fissures or bubbles exhibit both primary and secondary cracking by intergranular separation. The grain surfaces were rough and rounded, suggesting a diffusion-associated separation process. Specimens that failed at room temperature after exposure to hydrogen were found to exhibit mixed mode fracture having varying amounts of intergranular separation, dimple formation, and cleavage, depending on exposure time.

Long-term behaviour of solid oxide fuel cell interconnect materials in contact with Ni-mesh during exposure in simulated anode gas at 700 and 800 °C

NASA Astrophysics Data System (ADS)

Garcia-Fresnillo, L.; Shemet, V.; Chyrkin, A.; de Haart, L. G. J.; Quadakkers, W. J.

2014-12-01

In the present study the long-term behaviour of two ferritic steels, Crofer 22 APU and Crofer 22H, in contact with a Ni-mesh during exposure in simulated anode gas, Ar-4%H2-2%H2O, at 700 and 800 °C for exposure times up to 3000 h was investigated. Ni diffusion from the Ni-mesh into the steel resulted in the formation of an austenitic zone whereas diffusion of iron and chromium from the steel into the Ni-mesh resulted in the formation of chromia base oxides in the Ni-mesh. Depending on the chemical composition of the steel, the temperature and the exposure time, interdiffusion processes between ferritic steel and Ni-mesh also resulted in σ-phase formation at the austenite-ferrite interface and in Laves-phase dissolution in the austenitic zone. The extent and morphology of the σ-phase formation are discussed on the basis of thermodynamic considerations, including reaction paths in the ternary alloy system Fe-Ni-Cr.

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

PubMed Central

2010-01-01

Background Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level. Methods Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. Results Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and MMP9. Conclusions Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume. PMID:20525249

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice.

PubMed

Zeidler-Erdely, Patti C; Kashon, Michael L; Li, Shengqiao; Antonini, James M

2010-06-03

Debate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level. Mice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done. Overall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and MMP9. Collectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.

Vanadium Induces Dopaminergic Neurotoxicity Via Protein Kinase C-Delta Dependent Oxidative Signaling Mechanisms: Relevance to Etiopathogenesis of Parkinson's Disease

PubMed Central

Afeseh Ngwa, Hilary; Kanthasamy, Arthi; Anantharam, Vellareddy; Song, Chunjuan; Witte, Travis; Houk, R. S.; Kanthasamy, Anumantha G.

2009-01-01

Environmental exposure to neurotoxic metals through various sources including exposure to welding fumes has been linked to an increased incidence of Parkinson's disease (PD). Welding fumes contain many different metals including vanadium typically present as particulates containing vanadium pentoxide (V2O5). However, possible neurotoxic effects of this metal oxide on dopaminergic neuronal cells are not well studied. In the present study, we characterized vanadium-induced oxidative stress-dependent cellular events in cell culture models of PD. V2O5 was neurotoxic to dopaminergic neuronal cells including primary nigral dopaminergic neurons and the EC50 was determined to be 37 μM in N27 dopaminergic neuronal cell model. The neurotoxic effect was accompanied by a time-dependent uptake of vanadium and upregulation of metal transporter proteins Tf and DMT1 in N27 cells. Additionally, vanadium resulted in a threefold increase in reactive oxygen species generation, followed by release of mitochondrial cytochrome c into cytoplasm and subsequent activation of caspase-9 (>fourfold) and caspase-3 (>ninefold). Interestingly, vanadium exposure induced proteolytic cleavage of native protein kinase Cdelta (PKCδ, 72-74 kDa) to yield a 41 kDa catalytically active fragment resulting in a persistent increase in PKCδ kinase activity. Co-treatment with pan-caspase inhibitor ZVAD-FMK significantly blocked vanadium-induced PKCδ proteolytic activation, indicating that caspases mediate PKCδ cleavage. Also, co-treatment with Z-VAD-FMK almost completely inhibited V2O5-induced DNA fragmentation. Furthermore, PKCδ knockdown using siRNA protected N27 cells from V2O5-induced apoptotic cell death. Collectively, these results demonstrate vanadium can exert neurotoxic effects in dopaminergic neuronal cells via caspase-3-dependent PKCδ cleavage, suggesting that metal exposure may promote nigral dopaminergic degeneration. PMID:19646462

Stress before extinction learning enhances and generalizes extinction memory in a predictive learning task.

PubMed

Meir Drexler, Shira; Hamacher-Dang, Tanja C; Wolf, Oliver T

2017-05-01

In extinction learning, the individual learns that a previously acquired association (e.g. between a threat and its predictor) is no longer valid. This learning is the principle underlying many cognitive-behavioral psychotherapeutic treatments, e.g. 'exposure therapy'. However, extinction is often highly-context dependent, leading to renewal (relapse of extinguished conditioned response following context change). We have previously shown that post-extinction stress leads to a more context-dependent extinction memory in a predictive learning task. Yet as stress prior to learning can impair the integration of contextual cues, here we aim to create a more generalized extinction memory by inducing stress prior to extinction. Forty-nine men and women learned the associations between stimuli and outcomes in a predictive learning task (day 1), extinguished them shortly after an exposure to a stress/control condition (day 2), and were tested for renewal (day 3). No group differences were seen in acquisition and extinction learning, and a renewal effect was present in both groups. However, the groups differed in the strength and context-dependency of the extinction memory. Compared to the control group, the stress group showed an overall reduced recovery of responding to the extinguished stimuli, in particular in the acquisition context. These results, together with our previous findings, demonstrate that the effects of stress exposure on extinction memory depend on its timing. While post-extinction stress makes the memory more context-bound, pre-extinction stress strengthens its consolidation for the acquisition context as well, making it potentially more resistant to relapse. These results have implications for the use of glucocorticoids as extinction-enhancers in exposure therapy. Copyright © 2017 Elsevier Inc. All rights reserved.

Bayesian effect estimation accounting for adjustment uncertainty.

PubMed

Wang, Chi; Parmigiani, Giovanni; Dominici, Francesca

2012-09-01

Model-based estimation of the effect of an exposure on an outcome is generally sensitive to the choice of which confounding factors are included in the model. We propose a new approach, which we call Bayesian adjustment for confounding (BAC), to estimate the effect of an exposure of interest on the outcome, while accounting for the uncertainty in the choice of confounders. Our approach is based on specifying two models: (1) the outcome as a function of the exposure and the potential confounders (the outcome model); and (2) the exposure as a function of the potential confounders (the exposure model). We consider Bayesian variable selection on both models and link the two by introducing a dependence parameter, ω, denoting the prior odds of including a predictor in the outcome model, given that the same predictor is in the exposure model. In the absence of dependence (ω= 1), BAC reduces to traditional Bayesian model averaging (BMA). In simulation studies, we show that BAC, with ω > 1, estimates the exposure effect with smaller bias than traditional BMA, and improved coverage. We, then, compare BAC, a recent approach of Crainiceanu, Dominici, and Parmigiani (2008, Biometrika 95, 635-651), and traditional BMA in a time series data set of hospital admissions, air pollution levels, and weather variables in Nassau, NY for the period 1999-2005. Using each approach, we estimate the short-term effects of on emergency admissions for cardiovascular diseases, accounting for confounding. This application illustrates the potentially significant pitfalls of misusing variable selection methods in the context of adjustment uncertainty. © 2012, The International Biometric Society.

Exposure enriched outcome dependent designs for longitudinal studies of gene-environment interaction.

PubMed

Sun, Zhichao; Mukherjee, Bhramar; Estes, Jason P; Vokonas, Pantel S; Park, Sung Kyun

2017-08-15

Joint effects of genetic and environmental factors have been increasingly recognized in the development of many complex human diseases. Despite the popularity of case-control and case-only designs, longitudinal cohort studies that can capture time-varying outcome and exposure information have long been recommended for gene-environment (G × E) interactions. To date, literature on sampling designs for longitudinal studies of G × E interaction is quite limited. We therefore consider designs that can prioritize a subsample of the existing cohort for retrospective genotyping on the basis of currently available outcome, exposure, and covariate data. In this work, we propose stratified sampling based on summaries of individual exposures and outcome trajectories and develop a full conditional likelihood approach for estimation that adjusts for the biased sample. We compare the performance of our proposed design and analysis with combinations of different sampling designs and estimation approaches via simulation. We observe that the full conditional likelihood provides improved estimates for the G × E interaction and joint exposure effects over uncorrected complete-case analysis, and the exposure enriched outcome trajectory dependent design outperforms other designs in terms of estimation efficiency and power for detection of the G × E interaction. We also illustrate our design and analysis using data from the Normative Aging Study, an ongoing longitudinal cohort study initiated by the Veterans Administration in 1963. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Validation of methods to control for immortal time bias in a pharmacoepidemiologic analysis of renin-angiotensin system inhibitors in type 2 diabetes.

PubMed

Yang, Xilin; Kong, Alice Ps; Luk, Andrea Oy; Ozaki, Risa; Ko, Gary Tc; Ma, Ronald Cw; Chan, Juliana Cn; So, Wing Yee

2014-01-01

Pharmacoepidemiologic analysis can confirm whether drug efficacy in a randomized controlled trial (RCT) translates to effectiveness in real settings. We examined methods used to control for immortal time bias in an analysis of renin-angiotensin system (RAS) inhibitors as the reference cardioprotective drug. We analyzed data from 3928 patients with type 2 diabetes who were recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs) for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs. During a median follow-up period of 5.45 years, 7.23% (n = 284) patients developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of immortal time among the users. In multivariable analysis, time-dependent drug-exposure Cox models and Cox models that moved immortal time from users to nonusers both severely inflated the HR, and time-fixed models that included immortal time deflated the HR. Use of time-fixed Cox models that excluded immortal time resulted in a HR of only 0.89 (95% CI, 0.68-1.17) for CVD associated with RAS inhibitors, which is closer to the values reported in RCTs. In pharmacoepidemiologic analysis, time-dependent drug exposure models and models that move immortal time from users to nonusers may introduce substantial bias in investigations of the effects of RAS inhibitors on CVD in type 2 diabetes.

Tensile properties of latex paint films with TiO2 pigment

NASA Astrophysics Data System (ADS)

Hagan, Eric W. S.; Charalambides, Maria N.; Young, Christina T.; Learner, Thomas J. S.; Hackney, Stephen

2009-05-01

The tensile properties of latex paint films containing TiO2 pigment were studied with respect to temperature, strain-rate and moisture content. The purpose of performing these experiments was to assist museums in defining safe conditions for modern paintings held in collections. The glass transition temperature of latex paint binders is in close proximity to ambient temperature, resulting in high strain-rate dependence in typical exposure environments. Time dependence of modulus and failure strain is discussed in the context of time-temperature superposition, which was used to extend the experimental time scale. Nonlinear viscoelastic material models are also presented, which incorporate a Prony series with the Ogden or Neo-Hookean hyperelastic function for different TiO2 concentrations.

LUNG INJURY AFTER OZONE EXPOSURE IS IRON-DEPENDENT

EPA Science Inventory

We tested the hypothesis that oxidative stress and biological effect after ozone (O3) exposure are dependent on changes in iron homeostasis. After O3 exposure, healthy volunteers demonstrated increased lavage concentrations of iron, transferrin, lactoferrin, and ferritin. In norm...

Sustainability of radiologically contaminated territories.

PubMed

Mück, Konrad

2003-01-01

Decisions on appropriate countermeasures in the case of a contamination of large areas due to fallout from a weapon's detonations or a serious reactor or reprocessing plant accident depend on fallout level and the time period required for the exposure levels to fall below a given intervention limit. This is particularly relevant for countermeasures with high costs and substantial consequences to the population involved, such as relocation or soil perturbation. Natural processes which result in a decrease in activity concentrations in foodstuffs and external exposure with time, are least detrimental to the soil among all countermeasures proposed for rehabilitation of contaminated areas. The impact of these natural self-healing effects (soil sustainability) on the temporal activity reduction in foodstuffs, as well as their effect on the time period required for exposure levels to decrease to sufficiently low levels to allow unrestricted re-utilization and re-settlement of the land, are discussed. Depending on the type of foodstuff, in Central Europe this temporal decrease follows an effective half life of about 0.25-1.3 y from first to second year after fallout, followed by a decrease in milk with an effective half-life of 1-2 y in the next 7 y and about 5 y thereafter, while in cereals and vegetables in Austria a decrease by 2.3 y and in fruit by 1.3 y over a period of more than a decade is observed. In contrast, the decrease in foodstuffs derived from semi-natural environs is much slower by an effective half-life of roughly 8 y. The time-span for adequate recovery of a contaminated territory, therefore, depends on the fallout level and the radionuclides involved and the contribution of natural and semi-natural derived foodstuffs to the diet. It is shown that for 137Cs and a typical Central European diet the time span amounts to about 1 y for a deposition of 300 kBq m(-2) and to about 10 y for a deposition of 10,000 kBq m(-2). Thus it is demonstrated that natural restoration effects may contribute significantly to the environmentally safe and sustainable resettlement of an area substantially contaminated with fission products.

Sex-dependent alteration of cardiac cytochrome P450 gene expression by doxorubicin in C57Bl/6 mice.

PubMed

Grant, Marianne K O; Seelig, Davis M; Sharkey, Leslie C; Zordoky, Beshay N

2017-01-01

There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known. Therefore, in the present study, we determined the effect of acute DOX exposure on the expression of CYP genes in the hearts of both male and female C57Bl/6 mice. Acute DOX cardiotoxicity was induced by a single intraperitoneal injection of 20 mg/kg DOX in male and female adult C57Bl/6 mice. Cardiac function was assessed 5 days after DOX exposure by trans-thoracic echocardiography. Mice were euthanized 1 day or 6 days after DOX or saline injection. Thereafter, the hearts were harvested and weighed. Heart sections were evaluated for pathological lesions. Total RNA was extracted and expression of natriuretic peptides, inflammatory and apoptotic markers, and CYP genes was measured by real-time PCR. Adult female C57Bl/6 mice were protected from acute DOX-induced cardiotoxicity as they show milder pathological lesions, less inflammation, and faster recovery from DOX-induced apoptosis and DOX-mediated inhibition of beta-type natriuretic peptide. Acute DOX exposure altered the gene expression of multiple CYP genes in a sex-dependent manner. In 24 h, DOX exposure caused male-specific induction of Cyp1b1 and female-specific induction of Cyp2c29 and Cyp2e1. Acute DOX exposure causes sex-dependent alteration of cardiac CYP gene expression. Since cardiac CYP enzymes metabolize several endogenous compounds to biologically active metabolites, sex-dependent alteration of CYP genes may play a role in the sexual dimorphism of acute DOX-induced cardiotoxicity.

Photovoltaic studies of Dye Sensitized Solar cells Fabricated from Microwave Exposed Photo anodes

NASA Astrophysics Data System (ADS)

Ramachandran, Anju; Sreekala, C. O.; Sreelatha, K. S.; Jinchu, I.

2018-02-01

The configuration of Dye Sensitized solar cells (DSSC), consists of sintered nanoparticle titanium dioxide film, dyes, electrolyte and counter electrodes. Upon the absorption of photons by the dye molecules, excitons are generated, subsequently electrons are injected into the TiO2 photoanode. Afterward the electrons injected into the TiO2 photoanode, to produce photocurrent, scavenged by redox couple, and the hole transport to the photo cathode. The power conversion efficiency of the device depends on the amount of dye adsorbed by the photoanode. This paper explores in enhancing the efficiency of the device by controlled microwave exposure. With same exposure time, the photoanode is exposed at three different frequencies. SEM analysis is carried out to find the porosity of the photoanode on exposure. Current density is found to have an effect on microwave exposure.

Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

PubMed Central

Menelaou, Evdokia; Paul, Latoya T.; Perera, Surangi N.; Svoboda, Kurt R.

2015-01-01

Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMN). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30µM). Previous work showed that the paralytic mutant zebrafish known as sofa potato, exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. PMID:25668718

Changes in cue reactivity and attentional bias following experimental cue exposure and response prevention: a laboratory study of the effects of D-cycloserine in heavy drinkers.

PubMed

Kamboj, Sunjeev K; Massey-Chase, Rachel; Rodney, Lydia; Das, Ravi; Almahdi, Basil; Curran, H Valerie; Morgan, Celia J A

2011-09-01

The effects of D-cycloserine (DCS) in animal models of anxiety disorders and addiction indicate a role for N-methyl D-aspartate (NMDA) receptors in extinction learning. Exposure/response prevention treatments for anxiety disorders in humans are enhanced by DCS, suggesting a promising co-therapy regime, mediated by NMDA receptors. Exposure/response prevention may also be effective in problematic drinkers, and DCS might enhance habituation to cues in these individuals. Since heavy drinkers show ostensible conditioned responses to alcohol cues, habituation following exposure/response prevention should be evident in these drinkers, with DCS enhancing this effect. The objective of this study is to investigate the effect of DCS on exposure/response prevention in heavy drinkers. In a randomised, double-blind, placebo-controlled study, heavy social drinkers recruited from the community received either DCS (125 mg; n = 19) or placebo (n = 17) 1 h prior to each of two sessions of exposure/response prevention. Cue reactivity and attentional bias were assessed during these two sessions and at a third follow-up session. Between-session drinking behaviour was recorded. Robust cue reactivity and attentional bias to alcohol cues was evident, as expected of heavy drinkers. Within- and between-session habituation of cue reactivity, as well as a reduction in attentional bias to alcohol cues over time was found. However, there was no evidence of greater habituation in the DCS group. Subtle stimulant effects (increased subjective contentedness and euphoria) which were unrelated to exposure/response prevention were found following DCS. DCS does not appear to enhance habituation of alcohol cue reactivity in heavy non-dependent drinkers. Its utility in enhancing treatments based on exposure/response prevention in dependent drinkers or drug users remains open.

Dependence for food-related activities in the elderly.

PubMed

Bierhals, Isabel Oliveira; Meller, Fernanda de Oliveira; Assunção, Maria Cecília Formoso

2016-04-01

The objective of this study was to describe dependence for the activities of food shopping, preparing meals and eating in elderly residents from the city of Pelotas, Rio Grande do Sul. Bivariate analysis and ordinal logistic regression were employed to assess the three dependencies and exposure variables studied. Of the 1,451 older adults assessed, 21.1% required assistance for some activities where this care was given predominantly by son/daughter and partners. The highest prevalence of dependence was for food shopping (20.7%), followed by preparing meals (11.5%) and eating (2.0%). Elderly aged 80 years or older were more likely to be in a greater dependence category than individuals aged 60-69 years, with odds ratios of 5.0 for men and 7.1 for women. The odds ratio in individuals who self-rated their health as regular, poor or very poor was approximately 2.3 times greater, proving similar for both genders. Women with no partner had a 1.7 times greater chance of dependence whilst individuals with greater educational level exhibited 70.0% protection for their reference category; men with lower socioeconomic level had a 5.3 times greater chance of dependence than individuals with higher socioeconomic level. These results highlight the most vulnerable subgroups for dependencies and the importance of a family caregiver.

Rheological behavior of rat mesangial cells during swelling in vitro.

PubMed

Craelius, W; Huang, C J; Guber, H; Palant, C E

1997-01-01

The response of cells to mechanical forces depends on the rheological properties of their membranes and cytoplasm. To characterize those properties, mechanical and electrical responses to swelling were measured in rat mesangial cells (MC) using electrophysiologic and video microscopic techniques. Ion transport rates during hyposmotic exposures were measured with whole-cell recording electrodes. Results showed that cell swelling varied nonlinearly with positive internal pressure, consistent with a viscoelastic cytoplasm. The extrapolated area expansivity modulus for small deformations was estimated to be 450 dyne/cm. Cell swelling, caused either by positive pipet pressure or hyposmotic exposure (40-60 mOsm Kg-1), rapidly induced an outwardly rectifying membrane conductance with an outward magnitude 4-5 times the baseline conductance of 0.9 +/- 0.5 nS (p < .01). Swelling-induced (SI) current was weakly selective for K+ over Na+, partially reversed upon return to isotonicity, and was antagonized by 0.5 mM GdCl3 (p < 0.02; n = 6). Isolated cells treated with GdCl3 rapidly lysed after hypotonic exposure, in contrast to untreated cells that exhibited regulatory volume decrease (RVD). Our results indicate that volume regulation by MC depends upon a large swelling-induced K+ efflux, and suggest that swelling in MC is a viscoelastic process, with a viscosity dependent on the degree of swelling.

Roles of platelet STIM1 and Orai1 in glycoprotein VI- and thrombin-dependent procoagulant activity and thrombus formation.

PubMed

Gilio, Karen; van Kruchten, Roger; Braun, Attila; Berna-Erro, Alejandro; Feijge, Marion A H; Stegner, David; van der Meijden, Paola E J; Kuijpers, Marijke J E; Varga-Szabo, David; Heemskerk, Johan W M; Nieswandt, Bernhard

2010-07-30

In platelets, STIM1 has been recognized as the key regulatory protein in store-operated Ca(2+) entry (SOCE) with Orai1 as principal Ca(2+) entry channel. Both proteins contribute to collagen-dependent arterial thrombosis in mice in vivo. It is unclear whether STIM2 is involved. A key platelet response relying on Ca(2+) entry is the surface exposure of phosphatidylserine (PS), which accomplishes platelet procoagulant activity. We studied this response in mouse platelets deficient in STIM1, STIM2, or Orai1. Upon high shear flow of blood over collagen, Stim1(-/-) and Orai1(-/-) platelets had greatly impaired glycoprotein (GP) VI-dependent Ca(2+) signals, and they were deficient in PS exposure and thrombus formation. In contrast, Stim2(-/-) platelets reacted normally. Upon blood flow in the presence of thrombin generation and coagulation, Ca(2+) signals of Stim1(-/-) and Orai1(-/-) platelets were partly reduced, whereas the PS exposure and formation of fibrin-rich thrombi were normalized. Washed Stim1(-/-) and Orai1(-/-) platelets were deficient in GPVI-induced PS exposure and prothrombinase activity, but not when thrombin was present as co-agonist. Markedly, SKF96365, a blocker of (receptor-operated) Ca(2+) entry, inhibited Ca(2+) and procoagulant responses even in Stim1(-/-) and Orai1(-/-) platelets. These data show for the first time that: (i) STIM1 and Orai1 jointly contribute to GPVI-induced SOCE, procoagulant activity, and thrombus formation; (ii) a compensating Ca(2+) entry pathway is effective in the additional presence of thrombin; (iii) platelets contain two mechanisms of Ca(2+) entry and PS exposure, only one relying on STIM1-Orai1 interaction.

ADHD Symptoms in Middle Adolescence Predict Exposure to Person-Related Life Stressors in Late Adolescence in 5-HTTLPR S-allele Homozygotes.

PubMed

Brinksma, Djûke M; Hoekstra, Pieter J; de Bildt, Annelies; Buitelaar, Jan K; van den Hoofdakker, Barbara J; Hartman, Catharina A; Dietrich, Andrea

2017-12-19

Literature suggests that life stressors predict attention-deficit/hyperactivity disorder (ADHD) symptoms and that this relationship is moderated by the serotonin transporter polymorphism (5-HTTLPR). It is less clear whether, on reverse, ADHD symptoms may influence the risk of exposure to life stressors. Furthermore, the role of life stressors may vary across development depending on the type of life stressor. We used threewave longitudinal data of 1,306 adolescents from the general population and clinicreferred cohort of the TRacking Adolescents' Individual Lives Survey. The 5-HTTLPR genotype (SS, LS, LL), parent-reported ADHD symptoms at three time points (T1: Mage = 11.2; T2: Mage = 13.5; T3: Mage = 16.2 years), and the number of personrelated ('dependent') and environment-related ('independent') life stressors occurring between measurements (T1-T2, T2-T3) were assessed. Using path analyses, we examined bidirectional relations between exposure to these life stressors and ADHD symptoms between the separate waves moderated by 5-HTTLPR status. Exposure to life stressors did not predict ADHD symptoms. Rather, we found that in 5-HTTLPR Sallele homozygotes, ADHD symptoms in middle adolescence (T2) predicted exposure to the number of person-related life stressors later in adolescence (T2-T3, p = 0.001). There was no relation with environment-related life stressors. Our study suggests that S-allele homozygotes with higher levels of ADHD symptoms in middle adolescence are more vulnerable to becoming exposed to person-related ('dependent') life stressors in late adolescence. Findings emphasize the need to be aware of social-emotional adversities that may occur in genetically vulnerable adolescents with ADHD symptoms in the transition into adulthood.

Effects of Thermal Exposure on Properties of Al-Li Alloys

NASA Technical Reports Server (NTRS)

Shah, Sandeep; Wells, Douglas; Stanton, William; Lawless, Kirby; Russell, Carolyn; Wagner, John; Domack, Marcia; Babel, Henry; Farahmand, Bahram; Schwab, David;

Exposure time-dependent thermal effects of radiofrequency electromagnetic field exposure on the whole body of rats.

PubMed

Ohtani, Shin; Ushiyama, Akira; Maeda, Machiko; Hattori, Kenji; Kunugita, Naoki; Wang, Jianqing; Ishii, Kazuyuki

2016-01-01

We investigated the thermal effects of radiofrequency electromagnetic fields (RF-EMFs) on the variation in core temperature and gene expression of some stress markers in rats. Sprague-Dawley rats were exposed to 2.14 GHz wideband code division multiple access (W-CDMA) RF signals at a whole-body averaged specific absorption rate (WBA-SAR) of 4 W/kg, which causes behavioral disruption in laboratory animals, and 0.4 W/kg, which is the limit for the occupational exposure set by the International Commission on Non-Ionizing Radiation Protection guideline. It is important to understand the possible in vivo effects derived from RF-EMF exposures at these intensities. Because of inadequate data on real-time core temperature analyses using free-moving animal and the association between stress and thermal effects of RF-EMF exposure, we analyzed the core body temperature under nonanesthetic condition during RF-EMF exposure. The results revealed that the core temperature increased by approximately 1.5°C compared with the baseline and reached a plateau till the end of RF-EMF exposure. Furthermore, we analyzed the gene expression of heat-shock proteins (Hsp) and heat-shock transcription factors (Hsf) family after RF-EMF exposure. At WBA-SAR of 4 W/kg, some Hsp and Hsf gene expression levels were significantly upregulated in the cerebral cortex and cerebellum following exposure for 6 hr/day but were not upregulated after exposure for 3 hr/day. On the other hand, there was no significant change in the core temperature and gene expression at WBA-SAR of 0.4 W/kg. Thus, 2.14-GHz RF-EMF exposure at WBA-SAR of 4 W/kg induced increases in the core temperature and upregulation of some stress markers, particularly in the cerebellum.

Time-dependent effect of intensity of smoking and of occupational exposure to asbestos on the risk of lung cancer: results from the ICARE case-control study.

PubMed

Lévêque, Emilie; Lacourt, Aude; Luce, Danièle; Sylvestre, Marie-Pierre; Guénel, Pascal; Stücker, Isabelle; Leffondré, Karen

2018-05-18

To estimate the impact of intensity of both smoking and occupational exposure to asbestos on the risk of lung cancer throughout the whole exposure history. Data on 2026 male cases and 2610 male controls came from the French ICARE (Investigation of occupational and environmental causes of respiratory cancers) population-based, case-control study. Lifetime smoking history and occupational history were collected from standardised questionnaires and face-to-face interviews. Occupational exposure to asbestos was assessed using a job exposure matrix. The effects of annual average daily intensity of smoking (reported average number of cigarettes smoked per day) and asbestos exposure (estimated average daily air concentration of asbestos fibres at work) were estimated using a flexible weighted cumulative index of exposure in logistic regression models. Intensity of smoking in the 10 years preceding diagnosis had a much stronger association with the risk of lung cancer than more distant intensity. By contrast, intensity of asbestos exposure that occurred more than 40 years before diagnosis had a stronger association with the risk of lung cancer than more recent intensity, even if intensity in the 10 years preceding diagnosis also had a significant effect. Our results illustrate the dynamic of the effect of intensity of both smoking and occupational exposure to asbestos on the risk of lung cancer. They confirm that the timing of exposure plays an important role, and suggest that standard analytical methods assuming equal weights of intensity over the whole exposure history may be questionable. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Shorter Exposures to Harder X-Rays Trigger Early Apoptotic Events in Xenopus laevis Embryos

PubMed Central

Dong, JiaJia; Mury, Sean P.; Drahos, Karen E.; Moscovitch, Marko

2010-01-01

Background A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. Methodology/Principal Findings We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. Conclusions/Significance Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes. PMID:20126466

Inhibition of cardiac sodium currents by toluene exposure

PubMed Central

Cruz, Silvia L; Orta-Salazar, Gerardo; Gauthereau, Marcia Y; Millan-Perez Peña, Lourdes; Salinas-Stefanón, Eduardo M

2003-01-01

Toluene is an industrial solvent widely used as a drug of abuse, which can produce sudden sniffing death due to cardiac arrhythmias. In this paper, we tested the hypothesis that toluene inhibits cardiac sodium channels in Xenopus laevis oocytes transfected with Nav1.5 cDNA and in isolated rat ventricular myocytes. In oocytes, toluene inhibited sodium currents (INa+) in a concentration-dependent manner, with an IC50 of 274 μM (confidence limits: 141–407μM). The inhibition was complete, voltage-independent, and slowly reversible. Toluene had no effect on: (i) the shape of the I–V curves; (ii) the reversal potential of Na+; and (iii) the steady-state inactivation. The slow recovery time constant from inactivation of INa+ decreased with toluene exposure, while the fast recovery time constant remained unchanged. Block of INa+ by toluene was use- and frequency-dependent. In rat cardiac myocytes, 300 μM toluene inhibited the sodium current (INa+) by 62%; this inhibition was voltage independent. These results suggest that toluene binds to cardiac Na+ channels in the open state and unbinds either when channels move between inactivated states or from an inactivated to a closed state. The use- and frequency-dependent block of INa+ by toluene might be responsible, at least in part, for its arrhythmogenic effect. PMID:14534149

Emergent Auditory Feature Tuning in a Real-Time Neuromorphic VLSI System.

PubMed

Sheik, Sadique; Coath, Martin; Indiveri, Giacomo; Denham, Susan L; Wennekers, Thomas; Chicca, Elisabetta

2012-01-01

Many sounds of ecological importance, such as communication calls, are characterized by time-varying spectra. However, most neuromorphic auditory models to date have focused on distinguishing mainly static patterns, under the assumption that dynamic patterns can be learned as sequences of static ones. In contrast, the emergence of dynamic feature sensitivity through exposure to formative stimuli has been recently modeled in a network of spiking neurons based on the thalamo-cortical architecture. The proposed network models the effect of lateral and recurrent connections between cortical layers, distance-dependent axonal transmission delays, and learning in the form of Spike Timing Dependent Plasticity (STDP), which effects stimulus-driven changes in the pattern of network connectivity. In this paper we demonstrate how these principles can be efficiently implemented in neuromorphic hardware. In doing so we address two principle problems in the design of neuromorphic systems: real-time event-based asynchronous communication in multi-chip systems, and the realization in hybrid analog/digital VLSI technology of neural computational principles that we propose underlie plasticity in neural processing of dynamic stimuli. The result is a hardware neural network that learns in real-time and shows preferential responses, after exposure, to stimuli exhibiting particular spectro-temporal patterns. The availability of hardware on which the model can be implemented, makes this a significant step toward the development of adaptive, neurobiologically plausible, spike-based, artificial sensory systems.

Emergent Auditory Feature Tuning in a Real-Time Neuromorphic VLSI System

PubMed Central

Sheik, Sadique; Coath, Martin; Indiveri, Giacomo; Denham, Susan L.; Wennekers, Thomas; Chicca, Elisabetta

2011-01-01

Many sounds of ecological importance, such as communication calls, are characterized by time-varying spectra. However, most neuromorphic auditory models to date have focused on distinguishing mainly static patterns, under the assumption that dynamic patterns can be learned as sequences of static ones. In contrast, the emergence of dynamic feature sensitivity through exposure to formative stimuli has been recently modeled in a network of spiking neurons based on the thalamo-cortical architecture. The proposed network models the effect of lateral and recurrent connections between cortical layers, distance-dependent axonal transmission delays, and learning in the form of Spike Timing Dependent Plasticity (STDP), which effects stimulus-driven changes in the pattern of network connectivity. In this paper we demonstrate how these principles can be efficiently implemented in neuromorphic hardware. In doing so we address two principle problems in the design of neuromorphic systems: real-time event-based asynchronous communication in multi-chip systems, and the realization in hybrid analog/digital VLSI technology of neural computational principles that we propose underlie plasticity in neural processing of dynamic stimuli. The result is a hardware neural network that learns in real-time and shows preferential responses, after exposure, to stimuli exhibiting particular spectro-temporal patterns. The availability of hardware on which the model can be implemented, makes this a significant step toward the development of adaptive, neurobiologically plausible, spike-based, artificial sensory systems. PMID:22347163

Comparative study of time-dependent effects of 4 and 8 Hz mechanical vibration at infrasound frequency on E. coli K-12 cells proliferation.

PubMed

Martirosyan, Varsik; Ayrapetyan, Sinerik

2015-01-01

The aim of the present work is to study the time-dependent effects of mechanical vibration (MV) at infrasound (IS) frequency at 4 and 8 Hz on E. coli K-12 growth by investigating the cell proliferation, using radioactive [(3)H]-thymidine assay. In our previous work it was suggested that the aqua medium can serve as a target through which the biological effect of MV on microbes could be realized. At the same time it was shown that microbes have mechanosensors on the surface of the cells and can sense small changes of the external environment. The obtained results were shown that the time-dependent effects of MV at 4 and 8 Hz frequency could either stimulate or inhibit the growth of microbes depending from exposure time. It more particularly, the invention relates to a method for controlling biological functions through the application of mechanical vibration, thus making it possible to artificially control the functions of bacterial cells, which will allow us to develop method that can be used in agriculture, industry, medicine, biotechnology to control microbial growth.

Time-dependent effect of graphene on the structure, abundance, and function of the soil bacterial community.

PubMed

Ren, Wenjie; Ren, Gaidi; Teng, Ying; Li, Zhengao; Li, Lina

2015-10-30

The increased application of graphene raises concerns about its environmental impact, but little information is available on the effect of graphene on the soil microbial community. This study evaluated the impact of graphene on the structure, abundance and function of the soil bacterial community based on quantitative real-time polymerase chain reaction (qPCR), pyrosequencing and soil enzyme activities. The results show that the enzyme activities of dehydrogenase and fluorescein diacetate (FDA) esterase and the biomass of the bacterial populations were transiently promoted by the presence of graphene after 4 days of exposure, but these parameters recovered completely after 21 days. Pyrosequencing analysis suggested a significant shift in some bacterial populations after 4 days, and the shift became weaker or disappeared as the exposure time increased to 60 days. During the entire exposure process, the majority of bacterial phylotypes remained unaffected. Some bacterial populations involved in nitrogen biogeochemical cycles and the degradation of organic compounds can be affected by the presence of graphene. Copyright © 2015 Elsevier B.V. All rights reserved.

Correlation of tissue concentrations of the pyrethroid bifenthrin with neurotoxicity in the rat.

PubMed

Scollon, Edward J; Starr, James M; Crofton, Kevin M; Wolansky, Marcelo J; DeVito, Michael J; Hughes, Michael F

2011-11-28

The potential for human exposure to pyrethroid pesticides has prompted pharmacodynamic and pharmacokinetic research to better characterize risk. This work tested the hypothesis that blood and brain concentrations of the pyrethroid bifenthrin are predictive of neurotoxic effects. Adult male Long Evans rats received a single oral dose of bifenthrin dissolved in corn oil. Using figure-eight mazes, motor activity was measured for 1h at 4- and 7-h following exposure to bifenthrin (0-16mg/kg or 0-9mg/kg, respectively; n=4-8/group). Whole blood and brains were collected immediately following motor activity assays. Bifenthrin concentrations in blood and brain were quantified using HPLC/MS/MS. Bifenthrin exposure decreased motor activity from 20% to 70% in a dose-dependent manner at both time points. The relationship between motor activity data and administered dose, and blood and brain bifenthrin concentrations were described using a sigmoidal E(max) model. The relationships between motor activity and administered dose or blood concentrations were different between the 4- and 7-h time points. The relationship between motor activity and brain concentration was not significantly different between the two time points. These data suggest that momentary brain concentration of bifenthrin may be a more precise dose metric for predicting behavioral effects because the relationship between brain concentration and locomotor activity is independent of the time of exposure. Published by Elsevier Ireland Ltd.

Plasma discharge and time-dependence of its effect to bacteria.

PubMed

Justan, I; Cernohorska, L; Dvorak, Z; Slavicek, P

2014-07-01

Several types of plasma discharge have been proven to have a capacity for sterilization. Our goal is to introduce new nonthermal plasma pencil. We used it to sterilize different microbial populations with differing ages. We used a plasma discharge of the following characteristics: radio frequency barrier discharger at atmospheric pressure with a working frequency of 13.56 MHz, and the working gas used was argon. We performed 110 tests with the following microbial populations: Pseudomonas aeruginosa, Staphylococcus aureus, Proteus species, and Klebsiella pneumoniae. All populations were inoculated on the previous day and also on the day of our experiment. We made our evaluations the following day and also after 5 days, with all our microbial populations. Eradication of microbial populations is dependent on the plasma discharge exposure time in all cases. With regard to freshly inoculated microbes, we were able to sterilize agar with intensive exposure lasting for 10 s of colonies Pseudomonas, Proteus, and Klebsiella. The most resistant microbe seems to be S. aureus, which survives 5 s of coherent exposure in half of the cases. Using the lightest plasma discharge exposure, we achieved a maximum of 10(4)-10(5) CFU/mL (colony-forming unit - CFU). Regarding older microbial populations inoculated the day before the experiment, we can only decrease population growth to 10(5) CFU/mL approximately, but never completely sterilize. The plasma discharge with our characteristics could be used for the sterilization of the aforementioned superficially growing microbes, but does not sufficiently affect deeper layers and thus seems to be a limitation for eradication of the already erupted colonies.

Magnetic resonance microscopy-based analyses of the neuroanatomical effects of gestational day 9 ethanol exposure in mice

PubMed Central

Parnell, Scott E.; Holloway, Hunter T.; O’Leary-Moore, Shonagh K.; Dehart, Deborah B.; Paniaqua, Beatriz; Oguz, Ipek; Budin, Francois; Styner, Martin A.; Johnson, G. Allan; Sulik, Kathleen K.

2013-01-01

Animal model-based studies have shown that ethanol exposure during early gestation induces developmental stage-specific abnormalities of the face and brain. The exposure time-dependent variability in ethanol’s teratogenic outcomes is expected to contribute significantly to the wide spectrum of effects observed in humans with fetal alcohol spectrum disorder (FASD). The work presented here employs a mouse FASD model and magnetic resonance microscopy (MRM; high resolution magnetic resonance imaging) in studies designed to further our understanding of the developmental stage-specific defects of the brain that are induced by ethanol. At neurulation stages, i.e. at the beginning of gestational day (GD) 9 and again 4 hours later, time-mated C57Bl/6J dams were intraperitoneally administered 2.9 g/kg ethanol or vehicle. Ethanol-exposed fetuses were collected on GD 17, processed for MRM analysis, and results compared to comparably staged controls. Linear and volume measurements as well as shape changes for numerous individual brain regions were determined. GD 9 ethanol exposure resulted in significantly increased septal region width, reduction of cerebellar volume, and enlargement of all of the ventricles. Additionally, the results of shape analyses showed that many areas of the ethanol-exposed brains including the cerebral cortex, hippocampus and right striatum were significantly misshapen. These data demonstrate that ethanol can induce dysmorphology that may not be obvious based on volumetric analyses alone, highlight the asymmetric aspects of ethanol-induced defects, and add to our understanding of ethanol’s developmental stage-dependent neuroteratogenesis. PMID:23911654

Time-dependent enhancement of lymphocyte activation by mitogens after exposure to isolation or water scheduling.

PubMed

Jessop, J J; Gale, K; Bayer, B M

1988-01-01

The effects of isolation and water scheduling on mitogen induced lymphocyte proliferation were investigated. Isolated rats were animals which had been raised in group-housed conditions and then transferred to individual cages with ad lib access to water for a 1 or 2 week period. Water scheduled rats were maintained in group housing (5 rats per cage) with ad lib access to food but with access to water for a single 30 minute session each day. Responses of these groups were compared to those of animals which had been continuously group-housed with ad lib access to food and water. No differences in lymphocyte responses to phytohemagglutinin (PHA) were found 1 week after exposure to isolation. However, after 2 weeks, splenic and blood T lymphocytes from isolated animals demonstrated an increased proliferative response to suboptimum and maximum concentrations of PHA. Splenic B lymphocyte responses to lipopolysaccharide (LPS) from isolated animals were also increased by 2- to 3-fold compared to group-housed controls. Two weeks of exposure of animals to daily water scheduling similarly increased the splenic lymphocyte proliferation. This increased responsiveness to PHA was not accompanied by a significant change in the sensitivity of the lymphocytes to PHA, in the total number of white blood cells, or the proportion of splenic T or T helper lymphocytes. Our results show that the increase in lymphocyte proliferation is time-dependent, requires greater than 1 week of exposure to isolation and is due to factors other than changes in sensitivity to mitogen or T lymphocyte number.

Effects of Phonation Time and Magnitude Dose on Vocal Fold Epithelial Genes, Barrier Integrity, and Function

PubMed Central

Kojima, Tsuyoshi; Valenzuela, Carla V.; Novaleski, Carolyn K.; Van Deusen, Mark; Mitchell, Joshua R.; Garrett, C. Gaelyn; Sivasankar, M. Preeti; Rousseau, Bernard

2014-01-01

Objective To investigate the effects of increasing time and magnitude doses of vibration exposure on transcription of the vocal fold's junctional proteins, structural alterations, and functional tissue outcomes. Study Design Animal study. Methods 100 New Zealand White breeder rabbits were studied. Dependent variables were measured in response to increasing time doses (30, 60, or 120 minutes) and magnitude doses (control, modal intensity, and raised intensity) of vibration exposure. Messenger RNA expression of occludin, zonula occluden-1 (ZO-1), E-cadherin, β-catenin, interleukin 1β (IL-1β), cyclooxygenase-2 (COX-2), transforming growth factor β-1 (TGFβ1), and fibronectin were measured. Tissue structural alterations were assessed using transmission electron microscopy (TEM). Transepithelial resistance was used to measure functional tissue outcomes. Results Occludin gene expression was downregulated in vocal folds exposed to 120 minute time doses of raised intensity phonation, relative to control, and modal intensity phonation. ZO-1 gene expression was upregulated following a 120 minute time dose of modal intensity phonation, compared to control, and downregulated after a 120 minute time dose of raised intensity phonation, compared to modal intensity phonation. E-cadherin gene expression was downregulated after a120 minute time dose of raised intensity phonation, compared to control and modal intensity phonation. TEM revealed extensive desquamation of the stratified squamous epithelial cells with increasing time and magnitude doses of vibration exposure. A general observation of lower transepithelial resistance measures was made in tissues exposed to raised intensity phonation, compared to all other groups. Conclusions This study provides evidence of vocal fold tissue responses to varying time and magnitude doses of vibration exposure. Level of Evidence N/A PMID:25073715

Cytotoxicity of copper (II) oxide nanoparticles in rat intestinal cells: effect of simulated gastrointestinal fluids and generation of oxidative stress

EPA Science Inventory

Metallic oxide nanoparticles (NPs) have a variety of applications in industry, medicine and commercial products. Exposure to NPs can occur by inhalation, dermal contact and oral ingestion. We have previously reported on the dose- and time-dependent cytotoxicity of CuO NPs (size...

Influence of Image Interactivity on Approach Responses towards an Online Retailer.

ERIC Educational Resources Information Center

Fiore, Ann Marie; Jin, Hyun-Jeong

2003-01-01

Measured the effect of exposure to an image interactivity function from an apparel retailer's Web site on approach responses towards the retailer. Dependent variables included attitude towards the online store, willingness to purchase, probability of spending more time than planned shopping, and likelihood of patronizing the online retailer's…

Less-toxic corrosion inhibitors

NASA Technical Reports Server (NTRS)

Humphries, T. S.

1981-01-01

Combinations of borates, nitrates, phosphates, silicates, and sodium MBT protect aluminum from corrosion in fresh water. Most effective combinations contained sodium phosphate and were alkaline. These inhibitors replace toxic chromates which are subject to governmental restrictions, but must be used in larger quantities. Experimental exposure times varied from 1 to 14 months depending upon nature of submersion solution.

Radiation exposure of patient and surgeon in minimally invasive kidney stone surgery.

PubMed

Demirci, A; Raif Karabacak, O; Yalçınkaya, F; Yiğitbaşı, O; Aktaş, C

2016-05-01

Percutaneous nephrolithotomy (PNL) and retrograde intrarenal surgery (RIRS) are the standard treatments used in the endoscopic treatment of kidney stones depending on the location and the size of the stone. The purpose of the study was to show the radiation exposure difference between the minimally invasive techniques by synchronously measuring the amount of radiation the patients and the surgeon received in each session, which makes our study unique. This is a prospective study which included 20 patients who underwent PNL, and 45 patients who underwent RIRS in our clinic between June 2014 and October 2014. The surgeries were assessed by dividing them into three steps: step 1: the access sheath or ureter catheter placement, step 2: lithotripsy and collection of fragments, and step 3: DJ catheter or re-entry tube insertion. For the PNL and RIRS groups, mean stone sizes were 30mm (range 16-60), and 12mm (range 7-35); mean fluoroscopy times were 337s (range 200-679), and 37s (range 7-351); and total radiation exposures were 142mBq (44.7 to 221), and 4.4mBq (0.2 to 30) respectively. Fluoroscopy times and radiation exposures at each step were found to be higher in the PNL group compared to the RIRS group. When assessed in itself, the fluoroscopy time and radiation exposure were stable in RIRS, and the radiation exposure was the highest in step 1 and the lowest in step 3 in PNL. When assessed for the 19 PNL patients and the 12 RIRS patients who had stone sizes≥2cm, the fluoroscopy time in step 1, and the radiation exposure in steps 1 and 2 were found to be higher in the PNL group than the RIRS group (P<0.001). Although there is need for more prospective randomized studies, RIRS appears to be a viable alternate for PNL because it has short fluoroscopy time and the radiation exposure is low in every step. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Scene Context Dependency of Pattern Constancy of Time Series Imagery

NASA Technical Reports Server (NTRS)

Woodell, Glenn A.; Jobson, Daniel J.; Rahman, Zia-ur

2008-01-01

A fundamental element of future generic pattern recognition technology is the ability to extract similar patterns for the same scene despite wide ranging extraneous variables, including lighting, turbidity, sensor exposure variations, and signal noise. In the process of demonstrating pattern constancy of this kind for retinex/visual servo (RVS) image enhancement processing, we found that the pattern constancy performance depended somewhat on scene content. Most notably, the scene topography and, in particular, the scale and extent of the topography in an image, affects the pattern constancy the most. This paper will explore these effects in more depth and present experimental data from several time series tests. These results further quantify the impact of topography on pattern constancy. Despite this residual inconstancy, the results of overall pattern constancy testing support the idea that RVS image processing can be a universal front-end for generic visual pattern recognition. While the effects on pattern constancy were significant, the RVS processing still does achieve a high degree of pattern constancy over a wide spectrum of scene content diversity, and wide ranging extraneousness variations in lighting, turbidity, and sensor exposure.

Corrosion of Alloy 690 process pot by sulfate containing high level radioactive waste at feed stage

NASA Astrophysics Data System (ADS)

Sengupta, P.; Soudamini, N.; Kaushik, C. P.; Jagannath; Mishra, R. K.; Kale, G. B.; Raj, K.; Das, D.; Sharma, B. P.

2008-02-01

Prolonged exposure of Alloy 690 process pot to sulfate containing high level radioactive waste leads to (a) depletion of Cr from the alloy, (b) intergranular attack and (c) building up of Cr 2O 3-Ni 2O 3-Fe 2O 3 mixed oxide surface layer containing Na and Cs sulfate precipitates. Time dependence of material loss from Alloy 690 is found to follow a linear relationship of the type Δ w (material loss) = -7.05 + 0.05 t. Corrosion rate calculated for 2400 h exposure is 3.66 mpy. Cr and Ni leach rates obtained for the same sample are 1.61 g m -2 d -1 and 2.52 g m -2 d -1, respectively. Ni leach rates followed a linear time dependence relationship of the type dNL Ni/d t (leach rate) = -0.09 + 0.027 t, whereas Cr leach rates obeyed a non-linear relationship of the type dNL Cr/d t (leach rate) = 0.241 + 0.027 t - 1.33 × 10 -4t1/2.

The toxic effects of silver nanoparticles on blood mononuclear cells.

PubMed

Barkhordari, A; Barzegar, S; Hekmatimoghaddam, H; Jebali, A; Rahimi Moghadam, S; Khanjani, N

2014-07-01

Nanoparticles have become one of the leading technologies over the past two years. The extensive use of nanoparticles has raised great concern about their occupational fate and biological effects. With an increase in the production and use of nanomaterial, it is more likely to get exposed to them occupationally and environmentally. To assess the toxicity of silver nanoparticles on human mononuclear cells. In this in vitro experimental study, suspensions of blood mononuclear cells from 10 young healthy men were incubated with 10-nm silver nanoparticles in different concentrations (range: 1-500 μg/mL) for 6 and 24 hours by MTT assay. Positive and negative controls were used for comparison. After 6 hours of exposure, 10.9% to 48.4% of the cells died. After 24 hours of exposure, the rate ranged from 56.8% to 86.3%. Regardless of the exposure time, the maximum cytotoxicity was observed at the concentration of 500 μg/mL of silver nanoparticles. By increasing the exposure time to 24 hours, the cytotoxicity of nanoparticles substantially increased at all concentrations. Cell death was significantly higher when compared to the controls (p<0.01). Silver nanoparticles possess both time- and dose-dependent cytotoxicity and can thus be considered as very toxic for mononuclear cells.

Viability of fungal and actinomycetal spores after microwave radiation of building materials.

PubMed

Górny, Rafał L; Mainelis, Gediminas; Wlazło, Agnieszka; Niesler, Anna; Lis, Danuta O; Marzec, Stanisław; Siwińska, Ewa; Łudzeń-Izbińska, Beata; Harkawy, Aleksander; Kasznia-Kocot, Joanna

2007-01-01

The effects of microwave radiation on viability of fungal and actinomycetal spores growing on agar (medium optimal for growth) as well as on wooden panel and drywall (common building construction/finishing materials) were studied. All materials were incubated at high (97-99%) and low (32-33%) relative humidity to mimic "wet" and "dry" environmental conditions. Two microwave power densities (10 and 60 mW/cm2) and three times of exposure (5, 30, and 60 min) were tested to find the most effective parameters of radiation which could be applied to non-invasive reduction or cleaning of building materials from microbial contaminants. Additionally, a control of the surface temperature during the experiments allowed differentiation between thermal and microwave effect of such radiation. The results showed that the viability of studied microorganisms differed depending on their strains, growth conditions, power density of microwave radiation, time of exposure, and varied according to the applied combination of the two latter elements. The effect of radiation resulting in a decrease of spore viability on "wet" wooden panel and drywall was generally observed at 60 min exposure. Shorter exposure times decreased the viability of fungal spores only, while in actinomycetes colonizing the studied building materials, such radiation caused an opposite (supporting growth) effect.

Acute, low-dose methamphetamine administration improves attention/information processing speed and working memory in methamphetamine-dependent individuals displaying poorer cognitive performance at baseline

PubMed Central

Mahoney, James J.; Jackson, Brian J.; Kalechstein, Ari D.; De La Garza, Richard; Newton, Thomas F.

2012-01-01

Abstinent methamphetamine (Meth) dependent individuals demonstrate poorer performance on tests sensitive to attention/information processing speed, learning and memory, and working memory when compared to non-Meth dependent individuals. The poorer performance on these tests may contribute to the morbidity associated with Meth-dependence. In light of this, we sought to determine the effects of acute, low-dose Meth administration on attention, working memory, and verbal learning and memory in 19 non-treatment seeking, Meth-dependent individuals. Participants were predominantly male (89%), Caucasian (63%), and cigarette smokers (63%). Following a four day, drug-free washout period, participants were given a single-blind intravenous infusion of saline, followed the next day by 30 mg of Meth. A battery of neurocognitive tasks was administered before and after each infusion, and performance on measures of accuracy and reaction time were compared between conditions. While acute Meth exposure did not affect test performance for the entire sample, participants who demonstrated relatively poor performance on these tests at baseline, identified using a median split on each test, showed significant improvement on measures of attention/information processing speed and working memory when administered Meth. Improved performance was seen on the following measures of working memory: choice reaction time task (p≤0.04), a 1-back task (p≤0.01), and a 2-back task (p≤0.04). In addition, those participants demonstrating high neurocognitive performance at baseline experienced similar or decreased performance following Meth exposure. These findings suggest that acute administration of Meth may temporarily improve Meth-associated neurocognitive performance in those individuals experiencing lower cognitive performance at baseline. As a result, stimulants may serve as a successful treatment for improving cognitive functioning in those Meth-dependent individuals experiencing neurocognitive impairment. PMID:21122811

Shared and unshared exposure measurement error in occupational cohort studies and their effects on statistical inference in proportional hazards models.

PubMed

Hoffmann, Sabine; Laurier, Dominique; Rage, Estelle; Guihenneuc, Chantal; Ancelet, Sophie

2018-01-01

Exposure measurement error represents one of the most important sources of uncertainty in epidemiology. When exposure uncertainty is not or only poorly accounted for, it can lead to biased risk estimates and a distortion of the shape of the exposure-response relationship. In occupational cohort studies, the time-dependent nature of exposure and changes in the method of exposure assessment may create complex error structures. When a method of group-level exposure assessment is used, individual worker practices and the imprecision of the instrument used to measure the average exposure for a group of workers may give rise to errors that are shared between workers, within workers or both. In contrast to unshared measurement error, the effects of shared errors remain largely unknown. Moreover, exposure uncertainty and magnitude of exposure are typically highest for the earliest years of exposure. We conduct a simulation study based on exposure data of the French cohort of uranium miners to compare the effects of shared and unshared exposure uncertainty on risk estimation and on the shape of the exposure-response curve in proportional hazards models. Our results indicate that uncertainty components shared within workers cause more bias in risk estimation and a more severe attenuation of the exposure-response relationship than unshared exposure uncertainty or exposure uncertainty shared between individuals. These findings underline the importance of careful characterisation and modeling of exposure uncertainty in observational studies.

Shared and unshared exposure measurement error in occupational cohort studies and their effects on statistical inference in proportional hazards models

PubMed Central

Laurier, Dominique; Rage, Estelle

2018-01-01

Exposure measurement error represents one of the most important sources of uncertainty in epidemiology. When exposure uncertainty is not or only poorly accounted for, it can lead to biased risk estimates and a distortion of the shape of the exposure-response relationship. In occupational cohort studies, the time-dependent nature of exposure and changes in the method of exposure assessment may create complex error structures. When a method of group-level exposure assessment is used, individual worker practices and the imprecision of the instrument used to measure the average exposure for a group of workers may give rise to errors that are shared between workers, within workers or both. In contrast to unshared measurement error, the effects of shared errors remain largely unknown. Moreover, exposure uncertainty and magnitude of exposure are typically highest for the earliest years of exposure. We conduct a simulation study based on exposure data of the French cohort of uranium miners to compare the effects of shared and unshared exposure uncertainty on risk estimation and on the shape of the exposure-response curve in proportional hazards models. Our results indicate that uncertainty components shared within workers cause more bias in risk estimation and a more severe attenuation of the exposure-response relationship than unshared exposure uncertainty or exposure uncertainty shared between individuals. These findings underline the importance of careful characterisation and modeling of exposure uncertainty in observational studies. PMID:29408862

Statins and Risk of Lower Limb Revision Surgery: The Influence of Differences in Study Design Using Electronic Health Records From the United Kingdom and Denmark

PubMed Central

Lalmohamed, Arief; van Staa, Tjeerd P.; Vestergaard, Peter; Leufkens, Hubertus G. M.; de Boer, Anthonius; Emans, Pieter; Cooper, Cyrus; de Vries, Frank

2016-01-01

Abstract Previous observational studies on statins have shown variable results based on the methodology used. Our objective was to study the association between statins and orthopedic implant failure and to explore the influence of methodological differences in study design. Our study base consisted of patients with a primary total joint replacement in Denmark and the United Kingdom (n = 189,286; 1987–2012). We used 4 study designs: 1) case-control (each patient with revision surgery matched to 4 controls), 2) time-dependent cohort (postoperative statin use as a time-varying exposure variable), 3) immortal time cohort (misclassifying the time postoperatively before statin use), and 4) time-exclusion cohort (excluding the time postoperatively before statin use). Cox proportional hazards models and logistic regression were used to estimate incidence rate ratios. In the time-dependent cohort design, statin use was associated with a decreased risk of revision surgery (adjusted incidence rate ratio (IRR) = 0.90, 95% confidence interval (CI): 0.85, 0.96), which was similar to our case-control results (IRR = 0.87, 95% CI: 0.81, 0.93). In contrast, both time-fixed cohort designs yielded substantially lower risk estimates (IRR = 0.36 (95% CI: 0.34, 0.38) and IRR = 0.65 (95% CI: 0.63, 0.68), respectively). We discourage the use of time-fixed cohort studies, which may falsely suggest protective effects. The simple choice of how to classify exposure can substantially change results from biologically plausible to implausible. PMID:27317693

Maternal depression and intimate partner violence exposure: Longitudinal analyses of the development of aggressive behavior in an at-risk sample.

PubMed

Holmes, Megan R; Yoon, Susan; Berg, Kristen A

2017-07-01

A substantial body of literature has documented the negative effects of intimate partner violence (IPV) on a wide range of children's developmental outcomes. However, whether a child's exposure to IPV leads to increased adjustment difficulties is likely to depend on a variety of factors, including the caregiver's mental health and the developmental time period when IPV exposure occurs. The present study seeks to improve our understanding of the long-term effects of IPV exposure and maternal depression on the development of children's overt aggressive behavior. Longitudinal analyses (i.e., latent growth curve modeling) examining three time points (toddler: age 2-3 years, preschool/kindergarten: age 4-5 years, and elementary school: age 6-8 years) were conducted using 1,399 at-risk children drawn from the National Survey of Child and Adolescent Well-Being (NSCAW-I). IPV exposure during age 2-3 years was significantly related to concurrent aggressive behavior and aggressive behavior during age 4-5 years. At all three time points, IPV was significantly associated with maternal depression, which in turn, was significantly related to higher levels of aggressive behavior. There was also a significant indirect lagged effect of IPV exposure at age 2-3 years through maternal depression on aggressive behavior at age 4-5 years. Results indicated that maternal depression was a strong predictor of increased reports of overt aggressive behavior, suggesting that interventions to buffer the effects of IPV exposure should focus on relieving maternal depression and fostering productive social behavior in children. Aggr. Behav. 43:375-385, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Assimilation of elements and digestion in grass shrimp pre-exposed to dietary mercury.

PubMed

Seebaugh, David R; Wallace, William G; L'amoreaux, William J; Stewart, Gillian M

2012-08-01

Grass shrimp Palaemonetes pugio were fed mercury (Hg)-contaminated oligochaetes for 15 days and analyzed for Hg, cadmium (Cd), and carbon assimilation efficiencies (AE) as well as toxicological end points related to digestion. Disproportionate increases in stable Hg concentrations in shrimp did not appear to be related to partitioning to trophically available Hg in worms. Hg AE by pre-exposed shrimp reached a plateau (approximately 53 %), whereas Cd AE varied (approximately 40-60 %) in a manner that was not dose-dependent. Carbon AE did not differ among treatments (approximately 69 %). Gut residence time was not impacted significantly by Hg pre-exposure (grand median approximately 465 min), however, there was a trend between curves showing percentages of individuals with markers in feces over time versus treatment. Feces-elimination rate did not vary with dietary pre-exposure. Extracellular protease activity varied approximately 1.9-fold but did not exhibit dose-dependency. pH increased over the range of Hg pre-exposures within the anterior (pH approximately 5.33-6.51) and posterior (pH approximately 5.29-6.25) regions of the cardiac proventriculus and Hg assimilation exhibited a negative relationship to hydrogen ion concentrations. The results of this study indicate that previous Hg ingestion can elicit post-assimilatory impacts on grass shrimp digestive physiology, which may, in turn, influence Hg assimilation during subsequent digestive cycles.

An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival

DOE PAGES

Snijders, Antoine M.; Langley, Sasha; Mao, Jian-Hua; ...

2014-06-30

The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels. We identified an estrous-variable and hormone-dependent genemore » cluster enriched for Type-1 interferon genes. Cox regression identified a 117-gene signature of interferon-associated genes, which correlated with lower frequencies of metastasis in breast cancer patients. LDIR (10cGy) exposure had no detectable effect on mammary transcripts. However, peripheral WBC counts varied across the estrous cycle and LDIR exposure reduced lymphocyte counts and cytokine levels in tumor-susceptible mice. Our finding of variations in mammary Type-1 interferon and immune functions across the estrous cycle provides a mechanism by which timing of breast tumor surgery during the menstrual cycle may have clinical relevance to a patient's risk for distant metastases.« less

An interferon signature identified by RNA-sequencing of mammary tissues varies across the estrous cycle and is predictive of metastasis-free survival

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snijders, Antoine M.; Langley, Sasha; Mao, Jian-Hua

The concept that a breast cancer patient's menstrual stage at the time of tumor surgery influences risk of metastases remains controversial. The scarcity of comprehensive molecular studies of menstrual stage-dependent fluctuations in the breast provides little insight. To gain a deeper understanding of the biological changes in mammary tissue and blood during the menstrual cycle and to determine the influence of environmental exposures, such as low-dose ionizing radiation (LDIR), we used the mouse to characterize estrous-cycle variations in mammary gene transcripts by RNA-sequencing, peripheral white blood cell (WBC) counts and plasma cytokine levels. We identified an estrous-variable and hormone-dependent genemore » cluster enriched for Type-1 interferon genes. Cox regression identified a 117-gene signature of interferon-associated genes, which correlated with lower frequencies of metastasis in breast cancer patients. LDIR (10cGy) exposure had no detectable effect on mammary transcripts. However, peripheral WBC counts varied across the estrous cycle and LDIR exposure reduced lymphocyte counts and cytokine levels in tumor-susceptible mice. Our finding of variations in mammary Type-1 interferon and immune functions across the estrous cycle provides a mechanism by which timing of breast tumor surgery during the menstrual cycle may have clinical relevance to a patient's risk for distant metastases.« less

SATB2 participates in regulation of menadione-induced apoptotic insults to osteoblasts.

PubMed

Wei, Jyh-Ding; Lin, Yi-Ling; Tsai, Cheng-Hsiu; Shieh, Hui-Shan; Lin, Pei-I; Ho, Wei-Pin; Chen, Ruei-Ming

2012-07-01

Special AT-rich sequence binding protein 2 (SATB2), a nuclear matrix attachment region-binding protein, can regulate embryonic development, cell differentiation, and cell survival. Previous studies showed that SATB2 is involved in osteoblast differentiation and skeletal development. In this study, we evaluated the role of SATB2 in oxidative stress-induced apoptotic insults to human osteoblast-like MG63 cells and mouse MC3T3-E1 cells. Exposure of MG63 cells to menadione increased intracellular reactive oxygen species levels in a concentration- and time-dependent manner. Simultaneously, menadione-induced oxidative stress triggered cell shrinkage and decreased cell viability. In addition, treatment of MG63 cells with menadione time-dependently decreased the mitochondrial membrane potential but enhanced caspase-3 activity. As a result, menadione-induced DNA fragmentation and cell apoptosis. As to the mechanism, exposure of MG63 cells to menadione amplified SATB2 messenger (m)RNA and protein expression in a time-dependent manner. Knockdown of translation of SATB2 mRNA using RNA interference led to chromatin disruption and nuclear damage. When MG63 cells and MC3T3-E1 cells were treated with SATB2 small interfering RNA, menadione-induced cell apoptosis was increased. We conclude that menadione causes oxidative stress in human osteoblasts and induces cellular apoptosis via a mitochondrion-caspase protease pathway. In addition, SATB2 may play a crucial role in protecting against oxidative stress-induced osteoblast apoptosis. Copyright © 2012 Orthopaedic Research Society.

Dose- and time-dependent pharmacokinetics of apigenin trimethyl ether.

PubMed

Elhennawy, Mai Gamal; Lin, Hai-Shu

2018-06-15

Apigenin trimethyl ether (5,7,4'-trimethoxyflavone, ATE), one of the key polymethoxyflavones present in black ginger (rhizome of Kaempferia parviflora) possesses various health-promoting activities. To optimize its medicinal application, the pharmacokinetics of ATE was assessed in Sprague-Dawley rats with emphases to identify the impacts from dose and repeated dosing on its major pharmacokinetic parameters. Plasma ATE levels were monitored by liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. Upon single intravenous administration (2 mg/kg), plasma levels of ATE declined through an apparent first-order process while dose-escalation to 4 and 8 mg/kg led to its non-linear disposition, which could be described by the Michaelis-Menten model. Similarly, dose-dependent oral pharmacokinetics was confirmed and when the dose was escalated from 5 to 15 and 45 mg/kg, much longer mean residence time (MRT 0→last ), higher dose-normalized maximal plasma concentration (C max /Dose) and exposure (AUC/Dose) were observed at 15 and/or 45 mg/kg. One-week daily oral administration of ATE at 15 mg/kg caused its accelerated elimination and the plasma exposure (AUC) after intravenous (2 mg/kg) and oral administration (15 mg/kg) dropped ~40 and 60%, respectively. As ATE displayed both dose- and time-dependent pharmacokinetics, caution is needed in the medicinal applications of ATE and/or black ginger. Copyright © 2018 Elsevier B.V. All rights reserved.

A new ultrasonic transducer sample cell for in situ small-angle scattering experiments

NASA Astrophysics Data System (ADS)

Gupta, Sudipta; Bleuel, Markus; Schneider, Gerald J.

2018-01-01

Ultrasound irradiation is a commonly used technique for nondestructive diagnostics or targeted destruction. We report on a new versatile sonication device that fits in a variety of standard sample environments for neutron and X-ray scattering instruments. A piezoelectric transducer permits measuring of the time-dependent response of the sample in situ during or after sonication. We use small-angle neutron scattering (SANS) to demonstrate the effect of a time-dependent perturbation on the structure factor of micelles formed from sodium dodecyl sulfate surfactant molecules. We observe a substantial change in the micellar structure during and after exposure to ultrasonic irradiation. We also observe a time-dependent relaxation to the equilibrium values of the unperturbed system. The strength of the perturbation of the structure factor depends systematically on the duration of sonication. The relaxation behavior can be well reproduced after multiple times of sonication. Accumulation of the recorded intensities of the different sonication cycles improves the signal-to-noise ratio and permits reaching very short relaxation times. In addition, we present SANS data for the micellar form factor on alkyl-poly (ethylene oxide) surfactant molecules irradiated by ultrasound. Due to the flexibility of our new in situ sonication device, different experiments can be performed, e.g., to explore molecular potentials in more detail by introducing a systematic time-dependent perturbation.

Temporal Dependence of Chromosomal Aberration on Radiation Quality and Cellular Genetic Background

NASA Technical Reports Server (NTRS)

Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

2017-01-01

Radiation induced cancer risks are driven by genetic instability. It is not well understood how different radiation sources induce genetic instability in cells with different genetic background. Here we report our studies on genetic instability, particularly chromosome instability using fluorescence in situ hybridization (FISH), in human primary lymphocytes, normal human fibroblasts, and transformed human mammary epithelial cells in a temporal manner after exposure to high energy protons and Fe ions. The chromosome spread was prepared 48 hours, 1 week, 2 week, and 1 month after radiation exposure. Chromosome aberrations were analyzed with whole chromosome specific probes (chr. 3 and chr. 6). After exposure to protons and Fe ions of similar cumulative energy (??), Fe ions induced more chromosomal aberrations at early time point (48 hours) in all three types of cells. Over time (after 1 month), more chromosome aberrations were observed in cells exposed to Fe ions than in the same type of cells exposed to protons. While the mammary epithelial cells have higher intrinsic genetic instability and higher rate of initial chromosome aberrations than the fibroblasts, the fibroblasts retained more chromosomal aberration after long term cell culture (1 month) in comparison to their initial frequency of chromosome aberration. In lymphocytes, the chromosome aberration frequency at 1 month after exposure to Fe ions was close to unexposed background, and the chromosome aberration frequency at 1 month after exposure to proton was much higher. In addition to human cells, mouse bone marrow cells isolated from strains CBA/CaH and C57BL/6 were irradiated with proton or Fe ions and were analyzed for chromosome aberration at different time points. Cells from CBA mice showed similar frequency of chromosome aberration at early and late time points, while cells from C57 mice showed very different chromosome aberration rate at early and late time points. Our results suggest that relative biological effectiveness (RBE) of radiation are different for different radiation sources, for different cell types, and for the same cell type with different genetic background at different times after radiation exposure. Caution must be taken in using RBE value to estimate biological effects from radiation exposure.

Persistence of Space Radiation Induced Cytogenetic Damage in the Blood Lymphocytes of Astronauts

NASA Technical Reports Server (NTRS)

George, Kerry; Cucinotta, Francis A.

2008-01-01

Cytogenetic damage in astronaut's peripheral blood lymphocytes is a useful in vivo marker of space radiation induced damage. Moreover, if radiation induced chromosome translocations persist in peripheral blood lymphocytes for many years, as has been assumed, they could potentially be used to measure retrospective doses or prolonged low dose rate exposures. However, as more data becomes available, evidence suggests that the yield of translocations may decline with time after exposure, at least in the case of space radiation exposures. We present our latest follow-up measurements of chromosome aberrations in astronauts blood lymphocytes assessed by FISH painting and collected a various times beginning directly after return from space to several years after flight. For most individuals the analysis of individual time-courses for translocations revealed a temporal decline of yields with different half-lives. Since the level of stable aberrations depends on the interplay between natural loss of circulating T-lymphocytes and replenishment from the stem or progenitor cells, the differences in the rates of decay could be explained by inter-individual variation in lymphocyte turn over. Biodosimetry estimates derived from cytogenetic analysis of samples collected a few days after return to earth lie within the range expected from physical dosimetry. However, a temporal decline in yields may indicate complications with the use of stable aberrations for retrospective dose reconstruction, and the differences in the decay time may reflect individual variability in risk from space radiation exposure. In addition, limited data on multiple flights show a lack of correlation between time in space and translocation yields. Data from one crewmember who has participated in two separate long-duration space missions and has been followed up for over 10 years provides limited information on the effect of repeat flights and show a possible adaptive response to space radiation exposure.

Persistence of DNA on clothes after exposure to water for different time periods-a study on bathtub, pond, and river.

PubMed

Helmus, Janine; Zorell, Sarah; Bajanowski, Thomas; Poetsch, Micaela

2018-01-01

DNA traces on clothes of drowned bodies can provide important evidence for police investigations, especially in cases of suspected suicides or homicides. However, it is generally assumed that the water "erodes" a large part of the DNA depending especially on the exposure time. In forensic casework, DNA of suspects could be found frequently on clothes of drowned bodies after hours, sometimes days of exposure to water. This study was conducted to attempt a general statement about the conditions under which sufficient DNA remains can be expected for molecular genetic analysis. For this purpose, different scenarios were designed including DNA from three to five people, different types of waters (tap, pond, bathtub and river) for various time periods, with higher water pressure, different temperature, and soapy water (bathtub). Epithelial cells and blood cells were mounted on cotton cloths, and the DNA left after exposure was analyzed using the Powerplex® ESX17fast kit. In the indoor experiments, complete profiles could be seen even after 10 min rinsing of clothes under the tap and after 1 week in the bathtub. Outdoors, the results differed considerably between summer and winter as well as between pond and river. The longest exposure time still resulting in a complete profile was 2 weeks for a sample with skin cells in the pond during winter. In summer, the time period for erasing the bulk of DNA was 4 hours regarding epithelial samples and more than 1 day for blood samples in pond and river environments. All in all, the results demonstrate that DNA could still be recovered from clothes exposed to water for more than 1 week.

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.

PubMed

Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

2017-03-01

Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437-446; http://dx.doi.org/10.1289/EHP360.

Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice

PubMed Central

Ba, Qian; Li, Mian; Chen, Peizhan; Huang, Chao; Duan, Xiaohua; Lu, Lijun; Li, Jingquan; Chu, Ruiai; Xie, Dong; Song, Haiyun; Wu, Yongning; Ying, Hao; Jia, Xudong; Wang, Hui

2016-01-01

Background: Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear. Objectives: We investigated the effects of early exposure to cadmium, at an environmentally relevant dosage, on adult metabolism and the mechanism of action. Methods: We established mouse models with low-dose cadmium (LDC) exposure in early life to examine the long-term metabolic consequences. Intestinal flora measurement by 16S rDNA sequencing, microbial ecological analyses, and fecal microbiota transplant was conducted to explore the potential underlying mechanisms. Results: Early LDC exposure (100 nM) led to fat accumulation in adult male mice. Hepatic genes profiling revealed that fatty acid and lipid metabolic processes were elevated. Gut microbiota were perturbed by LDC to cause diversity reduction and compositional alteration. Time-series studies indicated that the gut flora at early-life stages, especially at 8 weeks, were vulnerable to LDC and that an alteration during this period could contribute to the adult adiposity, even if the microbiota recovered later. The importance of intestinal bacteria in LDC-induced fat accumulation was further confirmed through microbiota transplantation and removal experiments. Moreover, the metabolic effects of LDC were observed only in male, but not female, mice. Conclusions: An environmental dose of cadmium at early stages of life causes gut microbiota alterations, accelerates hepatic lipid metabolism, and leads to life-long metabolic consequences in a sex-dependent manner. These findings provide a better understanding of the health risk of cadmium in the environment. Citation: Ba Q, Li M, Chen P, Huang C, Duan X, Lu L, Li J, Chu R, Xie D, Song H, Wu Y, Ying H, Jia X, Wang H. 2017. Sex-dependent effects of cadmium exposure in early life on gut microbiota and fat accumulation in mice. Environ Health Perspect 125:437–446; http://dx.doi.org/10.1289/EHP360 PMID:27634282

Prenatal and postnatal mothering by diesel exhaust PM2.5-exposed dams differentially program mouse energy metabolism.

PubMed

Chen, Minjie; Liang, Shuai; Zhou, Huifen; Xu, Yanyi; Qin, Xiaobo; Hu, Ziying; Wang, Xiaoke; Qiu, Lianglin; Wang, Wanjun; Zhang, Yuhao; Ying, Zhekang

2017-01-18

Obesity is one of the leading threats to global public health. It is consequent to abnormal energy metabolism. Currently, it has been well established that maternal exposure to environmental stressors that cause inappropriate fetal development may have long-term adverse effects on offspring energy metabolism in an exposure timing-dependent manner, known as developmental programming of health and diseases paradigm. Rapidly increasing evidence has indicated that maternal exposure to ambient fine particles (PM 2.5 ) correlates to abnormal fetal development. In the present study, we therefore assessed whether maternal exposure to diesel exhaust PM 2.5 (DEP), the major component of ambient PM 2.5 in urban areas, programs offspring energy metabolism, and further examined how the timing of exposure impacts this programming. The growth trajectory of offspring shows that although prenatal maternal exposure to DEP did not impact the birth weight of offspring, it significantly decreased offspring body weight from postnatal week 2 until the end of observation. This weight loss effect of prenatal maternal exposure to DEP coincided with decreased food intake but not alteration in brown adipose tissue (BAT) morphology. The hypophagic effect of prenatal maternal exposure to DEP was in concord with decreased hypothalamic expression of an orexigenic peptide NPY, suggesting that the prenatal maternal exposure to DEP impacts offspring energy balance primarily through programming of food intake. Paradoxically, the reduced body weight resulted from prenatal maternal exposure to DEP was accompanied by increased mass of epididymal adipose tissue, which was due to hyperplasia as morphological analysis did not observe any hypertrophy. In direct contrast, the postnatal mothering by DEP-exposed dams increased offspring body weight during lactation and adulthood, paralleled by markedly increased fat accumulation and decreased UCP1 expression in BAT but not alteration in food intake. The weight gain induced by postnatal mothering by DEP-exposed dams was also expressed as an increased adiposity. But it concurred with a marked hypertrophy of adipocytes. Prenatal and postnatal mothering by DEP-exposed dams differentially program offspring energy metabolism, underscoring consideration of the exposure timing when examining the adverse effects of maternal exposure to ambient PM 2.5 .

Radiation dose effect of DNA repair-related gene expression in mouse white blood cells.

PubMed

Li, Ming-juan; Wang, Wei-wei; Chen, Shi-wei; Shen, Qian; Min, Rui

2011-10-01

The aim of this study was to screen molecular biomarkers for biodosimetry from DNA repair-related gene expression profiles. Mice were subjected to whole-body exposure with 60Co gamma rays with a dose range of 0-8 Gy at a dose rate of 0.80 Gy/min. RNA was extracted from the peripheral blood of irradiated mice at 4, 8, 12, 24 and 48hrs post-irradiation. The mRNA transcriptional changes of 11 genes related to DNA damage and repair were detected using real-time quantitative polymerase chain reaction (RT-PCR). Of the 11 genes examined, CDKN1A (cyclin-dependent kinase inhibitor 1A or p21, Cip1) and ATM (ataxia telangiectasia mutated) expression levels were found to be heavily up- and down-regulated, respectively, with exposure dose increasing at different post-irradiation times. RAD50 (RAD50 homolog), PLK3 (polo-like kinase 3), GADD45A (growth arrest and DNA damage-inducible, alpha), DDB2 (damage-specific DNA-binding protein 2), BBC3 (BCL2-binding component 3) and IER5 (immediate early response 5) gene expression levels were found to undergo significant oscillating changes over a broad dose range of 2-8 Gy at post-exposure time points observed. Three of the genes were found not to change within the observed exposure dose and post-radiation time ranges. The results of this study add to the biodosimetry with biomarker data pool and will be helpful for constructing appropriate gene expression biomarker systems to evaluate radiation exposure doses.

Effects of Dim Light at Night on Food Intake and Body Mass in Developing Mice.

PubMed

Cissé, Yasmine M; Peng, Juan; Nelson, Randy J

2017-01-01

Appropriately timed light is critical for circadian organization; exposure to dim light at night (dLAN) disrupts temporal organization of endogenous biological timing. Exposure to dLAN in adult mice is associated with elevated body mass and changes in metabolism putatively driven by voluntary changes in the time of food intake. We predicted that exposure of young mice to LAN could affect adult metabolic function. At 3 weeks (Experiment 1) or 5 weeks (Experiment 2) of age, mice were either maintained in standard light-dark (DARK) cycles or exposed to nightly dLAN (5 lux). In the first two experiments, food intake and locomotor activity were assessed after 4 weeks and a glucose tolerance test was administered after 6 weeks in experimental lighting conditions. In Experiment 3, tissues were collected around the clock at 6 h intervals to investigate rhythmic hepatic clock gene expression in mice exposed to dLAN from 3 or 5 weeks of age. Male and female mice exposed to dLAN beginning at 3 weeks of age displayed similar growth rates and body mass to DARK-reared offspring, despite increasing day-time food intake. Exposure to dLAN beginning at 5 weeks of age increased body mass and daytime food intake in male, but not female, mice. Consistent with the body mass phenotype, clock gene expression was unaltered in the liver. In contrast to adults, dLAN exposure during the development of the peripheral circadian system has sex- and development-dependent effects on body mass gain.

Flame exposure time on Langmuir probe degradation, ion density, and thermionic emission for flame temperature.

PubMed

Doyle, S J; Salvador, P R; Xu, K G

2017-11-01

The paper examines the effect of exposure time of Langmuir probes in an atmospheric premixed methane-air flame. The effects of probe size and material composition on current measurements were investigated, with molybdenum and tungsten probe tips ranging in diameter from 0.0508 to 0.1651 mm. Repeated prolonged exposures to the flame, with five runs of 60 s, resulted in gradual probe degradations (-6% to -62% area loss) which affected the measurements. Due to long flame exposures, two ion saturation currents were observed, resulting in significantly different ion densities ranging from 1.16 × 10 16 to 2.71 × 10 19 m -3 . The difference between the saturation currents is caused by thermionic emissions from the probe tip. As thermionic emission is temperature dependent, the flame temperature could thus be estimated from the change in current. The flame temperatures calculated from the difference in saturation currents (1734-1887 K) were compared to those from a conventional thermocouple (1580-1908 K). Temperature measurements obtained from tungsten probes placed in rich flames yielded the highest percent error (9.66%-18.70%) due to smaller emission current densities at lower temperatures. The molybdenum probe yielded an accurate temperature value with only 1.29% error. Molybdenum also demonstrated very low probe degradation in comparison to the tungsten probe tips (area reductions of 6% vs. 58%, respectively). The results also show that very little exposure time (<5 s) is needed to obtain a valid ion density measurement and that prolonged flame exposures can yield the flame temperature but also risks damage to the Langmuir probe tip.

Diesel exhaust and lung cancer in the trucking industry: exposure-response analyses and risk assessment.

PubMed

Steenland, K; Deddens, J; Stayner, L

1998-09-01

Diesel exhaust is considered a probable human carcinogen by the International Agency for Research on Cancer (IARC). The epidemiologic evidence rests on studies of lung cancer among truck drivers, bus drivers, shipyard workers, and railroad workers. The general public is exposed to diesel exhaust in ambient air. Two regulatory agencies are now considering regulating levels of diesel exhaust: the California EPA (ambient levels) and the Mine Safety Health Administration (MSHA) (occupational levels). To date, there have been few quantitative exposure-response analyses of diesel and lung cancer based on human data. We conducted exposure-response analyses among workers in the trucking industry, adjusted for smoking. Diesel exhaust exposure was estimated based on a 1990 industrial hygiene survey. Past exposures were estimated assuming that they were a function of 1) the number of heavy duty trucks on the road, 2) the particulate emissions (grams/mile) of diesel engines over time, and 3) leaks from trucks' exhaust systems for long-haul drivers. Regardless of assumptions about past exposure, all analyses resulted in significant positive trends in lung cancer risk with increasing cumulative exposure. A male truck driver exposed to 5 micrograms/m3 of elemental carbon (a typical exposure in 1990, approximately five times urban background levels) would have a lifetime excess risk of lung cancer of 1-2% above a background risk of 5%. We found a lifetime excess risk ten times higher than the 1 per 1,000 excess risk allowed by OSHA in setting regulations. There are about 2.8 million truck drivers in the U.S. Our results depend on estimates about unknown past exposures, and should be viewed as exploratory. They conform reasonably well to recent estimates for diesel-exposed railroad workers done by the California EPA, although those results themselves have been disputed.

Vitamin D response of older people in residential aged care to sunlight-derived ultraviolet radiation.

PubMed

Durvasula, Seeta; Gies, Peter; Mason, Rebecca S; Chen, Jian Sheng; Henderson, Stuart; Seibel, Markus J; Sambrook, Philip N; March, Lynette M; Lord, Stephen R; Kok, Cindy; Macara, Monique; Parmenter, Trevor R; Cameron, Ian D

2014-01-01

The aim of this study was to determine the vitamin D response to sunlight ultraviolet radiation in older people. Increases in vitamin D depended on the season of exposure, but the changes were small. Natural sun exposure is not a practical intervention for vitamin D deficiency in this population. The purpose of this study is to measure the ultraviolet radiation (UVR) exposure of those in residential aged care in an earlier trial of sunlight exposure and to determine its effect on their vitamin D response. Attendance data, demographic, clinical and biochemical variables for 248 participants were used for a secondary analysis of a previous cluster randomized trial of sunlight exposure and falls. The ambient solar UV Index data were used to calculate the participants' UVR dose. Multiple linear regression was used to test if UVR exposure over 6 months, as measured by the standard erythemal dose (SED), was a predictor of vitamin D response, controlling for age, gender, BMI, calcium intake, baseline vitamin D and season of exposure. The median 25-hydroxyvitamin D (25OHD) was 32.4 nmol/L at baseline and 34.6 nmol/L at 6 months (p = 0.35). The significant predictors of 25OHD at 6 months were UVR exposures in spring-summer (coefficient = 0.105, 95 % confidence interval (CI) 0.001-0.209, p = 0.05) and autumn-winter (coefficient = 0.056, 95 % CI 0.005-0.107, p = 0.03) and baseline vitamin D (adjusted coefficient = 0.594, 95 % CI 0.465-0.724, p = 0.00). In those starting sunlight sessions in spring, an increase of 1 unit in log SED was associated with 11 % increase in 25OHD. Natural UVR exposure can increase 25OHD levels in older people in residential care, but depends on the season of exposure. However, due to inadequate sun exposure, 25OHD did not reach optimal levels. Nevertheless, where sun exposure is encouraged in this group, the focus for the start of exposure should be in the months of spring or autumn, as this timing was associated with a vitamin D response.

Ultraviolet B exposure activates Stat3 signaling via phosphorylation at tyrosine705 in skin of SKH1 hairless mouse: a target for the management of skin cancer?

PubMed

Ahsan, Haseeb; Aziz, Moammir Hasan; Ahmad, Nihal

2005-07-22

Understanding the molecular determinants of ultraviolet (UV) response may lead to the development of novel targets; and therefore, better approaches for the management of cancers, which mainly arise due to the exposure of skin to UV (particularly its UVB spectrum). Signal transducer and activator of transcription (Stat) proteins have been shown to activate multiple signaling pathways to contribute to oncogenesis. Here, we studied the regulation of Stat3 during UVB exposure-mediated responses in the skin of SKH-1 hairless mouse, a model regarded to possess relevance to human situations. Our data demonstrated that a single UVB (180 mJ/cm(2)) exposure to the skin of SKH-1 hairless mice resulted in significant upregulation in (i) protein levels of Stat3 and (ii) phosphorylation of Stat3 at tyrosine(705). Further, the activation of Stat3 was found to be associated with a decrease in apoptotic response of UVB and a gradual time-dependent increase in leukocyte infiltration and hyperplasia. In conclusion, we have demonstrated, for the first time, that UVB exposure to skin resulted in an activation of pro-survival protein Stat3. Based on our observation, we suggest that Stat3 could serve as a target for the management of UVB exposure-mediated damages including skin cancer.

Effect of bright light at night on core temperature, subjective alertness and performance as a function of exposure time.

PubMed

Foret, J; Daurat, A; Tirilly, G

1998-01-01

This simulated night shift study measured the effects of moderate bright light (a 4-hour pulse starting at 2000 or 0400) during the exposure night and subsequent night (dim light). Eight young males remained confined with little physical activity to a laboratory in groups of 4. After a night of reference, they were active for 24 hours; then after a morning recovery sleep, they were active again for 16 hours. Continuously measured rectal temperature proved to be immediately sensitive to 4 hours of bright light, particularly when given at the end of the night. Self-assessed alertness and also performance on a task with a high requirement for short-term memory were improved by the exposure to bright light. During the subsequent night the subjects were exposed only to dim light. Core temperature, subjective alertness and performance continued to show a time course depending on the preceding bright light exposure. Probably because evening exposure to bright light and morning sleep both had a phase-delaying effect, the effects on the circadian pacemaker were more pronounced. Thus, for practical applications in long night shifts, bright light can be considered to improve mood and alertness immediately but the possibility of modifying the circadian "clock" during subsequent nights should be taken into consideration, in particular after exposure to bright light in the evening.

The human circulating miRNome reflects multiple organ disease risks in association with short-term exposure to traffic-related air pollution.

PubMed

Krauskopf, Julian; Caiment, Florian; van Veldhoven, Karin; Chadeau-Hyam, Marc; Sinharay, Rudy; Chung, Kian Fan; Cullinan, Paul; Collins, Peter; Barratt, Benjamin; Kelly, Frank J; Vermeulen, Roel; Vineis, Paolo; de Kok, Theo M; Kleinjans, Jos C

2018-04-01

Traffic-related air pollution is a complex mixture of particulate matter (PM) and gaseous pollutants, such as nitrogen dioxide (NO2). PM exposure contributes to the pathogenesis of many diseases including several types of cancer, as well as pulmonary, cardiovascular and neurodegenerative diseases. Also exposure to NO2 has been related to increased cardiovascular mortality. In search of an early diagnostic biomarker for improved air pollution-associated health risk assessment, recent human studies have shown that certain circulating miRNAs are altered upon exposure to traffic-related air pollutants. Here, we present for the first time a global analysis of the circulating miRNA genome in an experimental cross-over study of a human population exposed to traffic-related air pollution. By utilizing next-generation sequencing technology and detailed real-time exposure measurements we identified 54 circulating miRNAs to be dose- and pollutant species-dependently associated with PM10, PM2.5, black carbon, ultrafine particles and NO2 already after 2 h of exposure. Bioinformatics analysis suggests that these circulating miRNAs actually reflect the adverse consequences of traffic pollution-induced toxicity in target tissues including the lung, heart, kidney and brain. This study shows the strong potential of circulating miRNAs as novel biomarkers for environmental health risk assessment. Copyright © 2018 Elsevier Ltd. All rights reserved.

The impact of life stress on adult depression and anxiety is dependent on gender and timing of exposure.

PubMed

Herbison, Carly E; Allen, Karina; Robinson, Monique; Newnham, John; Pennell, Craig

2017-10-01

There is debate about the relative importance of timing of stressful events prenatally and over the life course and risk for subsequent depressive/anxious illness. The aim of this study was to examine the relative roles of prenatal stress and postnatal stress trajectories in predicting depression and anxiety in early adulthood in males and females. Exposure to life stress events was examined in the Western Australian Pregnancy Cohort (Raine) Study during pregnancy and ages 1, 2, 3, 5, 8, 10, 14, and 17 years. At age 20, offspring completed the Depression Anxiety Stress Scale. Prenatal stress and trajectories of stress events from age 1 to 17 were analyzed in linear regression analyses. Five postnatal stress trajectories were identified. In females, medium to high chronic stress exposure or exposure during puberty/adolescence predicted depression and anxiety symptoms while low or reduced stress exposure over the life course did not, after adjustment for relevant confounders. High stress early in pregnancy contributed to male depression/anxiety symptoms independent of postnatal stress trajectory. In females, postnatal stress trajectory was more important than prenatal stress in predicting depression/anxiety symptoms. Interventions focused on reducing and managing stress events around conception/pregnancy and exposure to chronic stress are likely to have beneficial outcomes on rates of depression and anxiety in adults.

Enhanced UV exposure on a ski-field compared with exposures at sea level.

PubMed

Allen, Martin; McKenzie, Richard

2005-05-01

Personal erythemal UV monitoring badges, which were developed to monitor the UV exposure of school children, were used to measure UV exposures received by one of the authors (MA) at the Mt Hutt ski-field, in New Zealand. These were then compared with measurements taken at the same times from a nearby sea level site in Christchurch city. The badges were designed to give instantaneous readings of erythemally-weighted (i.e., "sun burning") UV radiation and were cross-calibrated against meteorological grade UV instruments maintained by the National Institute of Water & Atmospheric Research (NIWA). All skiing and calibration days were clear and almost exclusively cloud free. It was found that the UV maxima for horizontal surfaces at the ski-field (altitude approximately 2 km) were 20-30% greater than at the low altitude site. Larger differences between the sites were observed when the sensor was oriented perpendicular to the sun. The personal doses of UV received by a sensor on the skier's lapel during two days of skiing activity were less than those received by a stationary detector on a horizontal surface near sea level. The exposures depended strongly on the time of year, and in mid-October the maximum UV intensity on the ski-field was 60% greater than in mid-September. The UV exposure levels experienced during skiing were smaller than the summer maxima at low altitudes.

[Testicular germ cell tumours and early exposures to pesticides: The TESTEPERA pilot study].

PubMed

Béranger, Rémi; Blain, Jeffrey; Baudinet, Cédric; Faure, Elodie; Fléchon, Aude; Boyle, Helen; Chasles, Virginie; Charbotel, Barbara; Schüz, Joachim; Fervers, Béatrice

2014-03-01

Testicular germ cell tumors (TGCT) represent the most frequent cancer in men aged between 15 and 45 years. Current hypotheses are focusing on environmental exposures occurring during prenatal periods. However, very few studies have explored intra-uterine environmental exposure related to TGCT. TESTEPERA is a pilot case-control study aiming to determine the effectiveness of different recruitment approaches in the French context and to verify our ability to collect relevant data on their prenatal periods. Between 2011 and 2012, 150 male subjects were contacted in the Rhône-Alpes region (58 cases from a cancer center and 92 controls from a regional maternity). Participation rate varied from 33% for cases diagnosed in 2008 vs 68% for cases diagnosed in 2010. Participation rate of controls varied depending on modalities of contact (13% for face-to-face recruitment; 0% for contact by phone only; 50% for face-to-face contact with phone reminder). Data collection allowed precise job identification and geolocation of subjects' addresses. Precision of geolocation was dependent upon the level of urbanization (p < 0.001) but not on the time period (p = 0.52). Our results support the feasibility of a case-control study focusing on the relation between TGCT and environmental pesticide exposures during early and later life.

Potential for adult-based epidemiological studies to characterize overall cancer risks associated with a lifetime of CT scans.

PubMed

Shuryak, Igor; Lubin, Jay H; Brenner, David J

2014-06-01

Recent epidemiological studies have suggested that radiation exposure from pediatric CT scanning is associated with small excess cancer risks. However, the majority of CT scans are performed on adults, and most radiation-induced cancers appear during middle or old age, in the same age range as background cancers. Consequently, a logical next step is to investigate the effects of CT scanning in adulthood on lifetime cancer risks by conducting adult-based, appropriately designed epidemiological studies. Here we estimate the sample size required for such studies to detect CT-associated risks. This was achieved by incorporating different age-, sex-, time- and cancer type-dependent models of radiation carcinogenesis into an in silico simulation of a population-based cohort study. This approach simulated individual histories of chest and abdominal CT exposures, deaths and cancer diagnoses. The resultant sample sizes suggest that epidemiological studies of realistically sized cohorts can detect excess lifetime cancer risks from adult CT exposures. For example, retrospective analysis of CT exposure and cancer incidence data from a population-based cohort of 0.4 to 1.3 million (depending on the carcinogenic model) CT-exposed UK adults, aged 25-65 in 1980 and followed until 2015, provides 80% power for detecting cancer risks from chest and abdominal CT scans.

Nitroxides are more efficient inhibitors of oxidative damage to calf skin collagen than antioxidant vitamins.

PubMed

Venditti, Elisabetta; Scirè, Andrea; Tanfani, Fabio; Greci, Lucedio; Damiani, Elisabetta

2008-01-01

Reactive oxygen species generated upon UV-A exposure appear to play a major role in dermal connective tissue transformations including degradation of skin collagen. Here we investigate on oxidative damage to collagen achieved by exposure to (i) UV-A irradiation and to (ii) AAPH-derived radicals and on its possible prevention using synthetic and natural antioxidants. Oxidative damage was identified through SDS-PAGE, circular dichroism spectroscopy and quantification of protein carbonyl residues. Collagen (2 mg/ml) exposed to UV-A and to AAPH-derived radicals was degraded in a time- and dose-dependent manner. Upon UV-A exposure, maximum damage was observable at 730 kJ/m2 UV-A, found to be equivalent to roughly 2 h of sunshine, while exposure to 5 mM AAPH for 2 h at 50 degrees C lead to maximum collagen degradation. In both cases, dose-dependent protection was achieved by incubation with muM concentrations of nitroxide radicals, where the extent of protection was shown to be dictated by their structural differences whereas the vitamins E and C proved less efficient inhibitors of collagen damage. These results suggest that nitroxide radicals may be able to prevent oxidative injury to dermal tissues in vivo alternatively to commonly used natural antioxidants.

High-level dietary cadmium exposure is associated with global DNA hypermethylation in the gastropod hepatopancreas

PubMed Central

Popescu, Cristina; Draghici, George A.; Andrica, Florina-Maria; Privistirescu, Ionela A.; Gergen, Iosif I.; Stöger, Reinhard

2017-01-01

5-methylcytosine (5mC) is a key epigenetic mark which influences gene expression and phenotype. In vertebrates, this epigenetic mark is sensitive to Cd exposure, but there is no information linking such an event with changes in global 5mC levels in terrestrial gastropods despite their importance as excellentecotoxicological bioindicators of metal contamination. Therefore, we first evaluated total 5mC content in DNA of the hepatopancreas of adult Cantareus aspersus with the aim to determine whether this epigenetic mark is responsive to Cd exposure. The experiment was conducted under laboratory conditions and involved a continuous exposure, multiple dose- and time-point (14, 28, and 56 days) study design. Hepatopancreas cadmium levels were measured using Flame Atomic Absorption Spectrometry and the percentage of 5-mC in samples using an ELISA-based colorimetric assay. Snail death rates were also assessed. Our results, for the first time, reveal the presence of 5mC in C. aspersus and provide evidence for Cd-induced changes in global 5mC levels in DNA of gastropods and mollusks. Although less sensitive than tissue accumulation, DNA methylation levels responded in a dose- and time-dependent manner to dietary cadmium, with exposure dose having a much stronger effect than exposure duration. An obvious trend of increasing 5mC levels was observed starting at 28 days of exposure to the second highest dose and this trend persisted at the two highest treatments for close to one month, when the experiment was terminated after 56 days. Moreover, a strong association was identified between Cd concentrations in the hepatopancreas and DNA methylation levels in this organ. These data indicate an overall trend towards DNA hypermethylation with elevated Cd exposure. No consistent lethal effect was observed, irrespective of time point and Cd-dosage. Overall, our findings suggest that the total 5mC content in DNA of the hepatopancreas of land snails is responsive to sublethal Cd exposure and give new insights into invertebrate environmental epigenetics. PMID:28877233

Optical absorption coefficient, time of thermal relaxation, time of surface threshold, and time of heat incubation for PMMA samples at the CO2 laser-beam wavelength of 10.6 microm.

PubMed

Canestri, Franco

2006-10-01

This paper discusses in detail the mathematical identification of the optical absorption alpha (cm(1)) of Beer's law, a crucial parameter to study the development of laser beam craters into dry poly(methyl methacrylate) (PMMA) samples exposed to steady CO(2) laser beams emitting radiation at lambda = 10.6 microm in continuous- wave (CW) mode. Three additional time-dependent coefficients have been determined as well. In clinical applications, these results are important in order to precisely quantify and forecast the ablation capabilities of the CO(2) laser beam, to optimize its usage in the operating room, and to address the safety issues related to surgical interventions on human tissue. Currently, the data available in the literature do not allow the identification of the numerical value of alpha (cm(1)) for PMMA at lambda = 10.6 microm with enough, and therefore satisfactory, accuracy. Additionally, the correct identification of the optical absorption of PMMA would allow the isolation, with better accuracy, of other key time-dependent coefficients, such as relaxation time, surface threshold time, and heat incubation time, which are all described in the literature in a qualitative rather than quantitative fashion. Correct bone cement preparation depends on the value of alpha (cm(1)) of the PMMA in order to avoid unwanted complications in patients during cement removal via laser techniques. The laser in use was configured in different combinations with the following parameters: transverse electromagnetic modes (TEMnm), output power (I0), exposure times (te), and focal lengths (fk). Several PMMA blocks (1 cm x 4 cm x 4 cm) were exposed to CW radiation of three commercially available CO(2) medical laser devices showing a TEM11 mode. Each block was exposed to the beam on a horizontal and well-polished surface of each sample. Four focal lengths (2.5", 5", 7.5", and 15.75" [400 mm]) were used to focus the beam on the well-polished and dry surface of the PMMA samples. The resulting dimensions of the craters were measured after each exposure, which has been kept at a 10-Watt CW beam. Exposure time ranged from 0.5 to 2 sec. The value of alpha = 502 (cm(1)) for PMMAat 10.6 microm was identified, matching other results reported in the literature for similar compact media in the absence of water content, such as PMMA. The time of thermal relaxation was 9.358 x 10(4) sec, the time of surface threshold was 9.365 x 10(4) sec, and the time of heat incubation was 3.6 x 10(7) sec (all three for PMMAat 10.6 microm for any exposure). Using the calculated value of alpha, one of the practical clinical recommendations would be, for instance, to reduce or to abolish the utilization of colorant dopants in the preparation of the bone cement mixture and therefore reduce the danger of bone damage possible during the removal of bone cement via laser techniques. Other examples refer to other clinical bone and dental treatments.

Flux threshold determination for tungsten nano-fuzz formation using an 80 eV He-ion beam

NASA Astrophysics Data System (ADS)

Meyer, Fred W.; Bannister, Mark E.; Parish, Chad M.

2017-10-01

At the ORNL Multicharged Ion Research Facility (MIRF), we have extended our investigation of flux thresholds for He-ion induced nano-fuzz formation on hot tungsten surfaces down to plasma-edge-relevant energies of 80 eV. We measured the size of the incident ion beam by accurate flux-profile measurements, and the size of the region where tungsten nano-fuzz was formed by post-exposure SEM surface analysis and real-time monitoring of the hot W surface-emissivity change throughout the beam exposure. If tungsten nano-fuzz formation had a fluence threshold, the size of the observed nano-fuzz region would be expected to increase with exposure time, eventually filling the entire ion beam spot. Instead, we found that the region of nano-fuzz formation (1) was always smaller than the beam spot itself and (2) did not increase in size with time, i.e. with accumulated He ion fluence. By comparison of the flux profile and the spatial extent of the fuzz region we determined a flux threshold of 9.5 +-3×1019/m2s at 80 eV He ion impact energy. We show that the observed flux-threshold energy dependence for nano-fuzz formation, which we have now mapped out from 80 eV to 8.5 keV, is well reproduced by the combined energy dependences of He-ion reflection, He-ion range and target-damage creation, determined using SRIM. Research sponsored by the LDRD program at ORNL, managed by UT-Battelle for the USDOE, and by the DOE OFES.

Characterization of exposures to nanoscale particles and fibers during solid core drilling of hybrid carbon nanotube advanced composites.

PubMed

Bello, Dhimiter; Wardle, Brian L; Zhang, Jie; Yamamoto, Namiko; Santeufemio, Christopher; Hallock, Marilyn; Virji, M Abbas

2010-01-01

This work investigated exposures to nanoparticles and nanofibers during solid core drilling of two types of advanced carbon nanotube (CNT)-hybrid composites: (1) reinforced plastic hybrid laminates (alumina fibers and CNT); and (2) graphite-epoxy composites (carbon fibers and CNT). Multiple real-time instruments were used to characterize the size distribution (5.6 nm to 20 microm), number and mass concentration, particle-bound polyaromatic hydrocarbons (b-PAHs), and surface area of airborne particles at the source and breathing zone. Time-integrated samples included grids for electron microscopy characterization of particle morphology and size resolved (2 nm to 20 microm) samples for the quantification of metals. Several new important findings herein include generation of airborne clusters of CNTs not seen during saw-cutting of similar composites, fewer nanofibers and respirable fibers released, similarly high exposures to nanoparticles with less dependence on the composite thickness, and ultrafine (< 5 nm) aerosol originating from thermal degradation of the composite material.

The role of temporal delay and repeated prospective memory cue exposure on the deactivation of completed intentions.

PubMed

Walser, Moritz; Plessow, Franziska; Goschke, Thomas; Fischer, Rico

2014-07-01

Previous studies have shown that completed prospective memory (PM) intentions entail aftereffects in terms of ongoing-task-performance decrements in trials containing repeated PM cues which previously served as PM cues triggering the intended action. Previous research reported that PM aftereffects decrease over time, thus revealing a specific time course of PM aftereffects. In the present study, we tested two accounts for this pattern, assuming either that the decline of aftereffects is related to the temporal distance to PM task completion or may be a result of the repeated exposure of repeated PM cues in the ongoing task. In three experiments, we manipulated both the temporal distance to PM task completion and the frequency of repeated PM cues and demonstrated that aftereffects of completed intentions declined with repeated exposure of formerly relevant PM cues. In addition, effects of repeated exposure were not only limited to the repetition of specific PM-cue exemplars but also generalized to other semantically related PM cues within the PM-cue category. Together, findings show that decreased aftereffects of completed intentions are not related to the temporal duration of the subsequent test block, but crucially depend on the repeated exposure of the previously relevant PM cues.

Moringa oleifera Leaf Extract: Beneficial Effects on Cadmium Induced Toxicities - A Review

PubMed Central

Mallya, Roopashree; Vinodini, NA; Chatterjee, Poulomi; Mithra, Prasanna

2017-01-01

Environment has been contaminated by heavy metals ever since the original magma of earth has solidified. One such toxin is cadmium. Cadmium that has been around since the industrial age, is considered hazardous both to us and to the environment. From time immemorial man is dependent on plants available in nature for several health benefits. Moringa oleifera, has nutritional, pharmacological and antioxidant properties, thus having several medicinal applications. In the present article, we discuss the dose and time dependent damage due to exposure to cadmium on kidneys, liver, testis, lipid profile and haematological parameters in adult Wistar rats and the protective effects of Moringa oleifera (pre-treatment) on cadmium induced damage. PMID:28571135

Time- and dose-dependent changes in neuronal activity produced by X radiation in brain slices.

PubMed

Pellmar, T C; Schauer, D A; Zeman, G H

1990-05-01

A new method of exposing tissues to X rays in a lead Faraday cage has made it possible to examine directly radiation damage to isolated neuronal tissue. Thin slices of hippocampus from brains of euthanized guinea pigs were exposed to 17.4 ke V X radiation. Electrophysiological recordings were made before, during, and after exposure to doses between 5 and 65 Gy at a dose rate of 1.54 Gy/min. Following exposure to doses of 40 Gy and greater, the synaptic potential was enhanced, reaching a steady level soon after exposure. The ability of the synaptic potential to generate a spike was reduced and damage progressed after termination of the radiation exposure. Recovery was not observed following termination of exposure. These results demonstrate that an isolated neuronal network can show complex changes in electrophysiological properties following moderate doses of ionizing radiation. An investigation of radiation damage directly to neurons in vitro will contribute to the understanding of the underlying mechanisms of radiation-induced nervous system dysfunction.

Exposure Assessment at 30 000 Feet: Challenges and Future Directions

PubMed Central

Grajewski, Barbara; Pinkerton, Lynne E.

2015-01-01

Few studies of cancer mortality and incidence among flight crew have included a detailed assessment of both occupational exposures and lifestyle factors that may influence the risk of cancer. In this issue, Kojo et al. (Risk factors for skin cancer among Finnish airline cabin crew. Ann. Occup. Hyg 2013; 57: 695–704) evaluated the relative contributions of ultraviolet and cosmic radiation to the incidence of skin cancer in Finnish flight attendants. This is a useful contribution, yet the reason flight crew members have an increased risk of skin cancer compared with the general population remains unclear. Good policy decisions for flight crew will depend on continued and emerging effective collaborations to increase study power and improve exposure assessment in future flight crew health studies. Improving the assessment of occupational exposures and non-occupational factors will cost additional time and effort, which are well spent if the role of exposures can be clarified in larger studies. PMID:23818455

Oxidative stress and DNA damage induced by imidacloprid in zebrafish (Danio rerio).

PubMed

Ge, Weili; Yan, Saihong; Wang, Jinhua; Zhu, Lusheng; Chen, Aimei; Wang, Jun

2015-02-18

Imidacloprid is a neonicotinoid insecticide that can have negative effects on nontarget animals. The present study was conducted to assess the toxicity of various imidacloprid doses (0.3, 1.25, and 5 mg/mL) on zebrafish sampled after 7, 14, 21, and 28 days of exposure. The levels of catalase (CAT), superoxide dismutase (SOD), reactive oxygen species (ROS), glutathione-S-transferase (GST), and malondialdehyde (MDA) and the extent of DNA damage were measured to evaluate the toxicity of imidacloprid on zebrafish. SOD and GST activities were noticeably increased during early exposure but were inhibited toward the end of the exposure period. In addition, the CAT levels decreased to the control level following their elevation during early exposure. High concentrations of imidacloprid (1.25 and 5 mg/L) induced excessive ROS production and markedly increased MDA content on the 21st day of exposure. DNA damage was dose- and time-dependent. In conclusion, the present study showed that imidacloprid can induce oxidative stress and DNA damage in zebrafish.

Trimethoprim use in early pregnancy and the risk of miscarriage: a register-based nationwide cohort study.

PubMed

Andersen, J T; Petersen, M; Jimenez-Solem, E; Broedbaek, K; Andersen, E W; Andersen, N L; Afzal, S; Torp-Pedersen, C; Keiding, N; Poulsen, H E

2013-08-01

The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2∙04 (95% confidence interval 1∙43-2∙91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.

Evaluation of pesticide toxicities with differing mechanisms using Caenorhabditis elegans.

PubMed

Ruan, Qin-Li; Ju, Jing-Juan; Li, Yun-Hui; Liu, Ran; Pu, Yue-Pu; Yin, Li-Hong; Wang, Da-Yong

2009-01-01

The aim of this study was to (1) determine whether model organism Caenorhabditis elegans was sensitive to pesticides at the maximum concentration limits regulated by national agency standards, and (2) examine the multi-biological toxicities occurring as a result of exposure to pesticides. Five pesticides, namely, chlorpyrifos, imibacloprid, buprofezin, cyhalothrin, and glyphosate, with four different mechanisms of action were selected for the investigation. In accordance with national agency requirements, 4 exposed groups were used for each tested pesticide with the concentration scales ranging from 1.0 x 10(-3) to 1 mg/L. L4 larvae were exposed for 24 and 72 h, respectively. Endpoints of locomotion, propagation, and development were selected for the assay as parameters of toxicity. After exposure for 24 h, both the body bend frequency and head thrash frequency of nematodes exposed to chlorpyrifos, imibacloprid, and cyhalothrin decreased in a concentration-dependent manner, and there were significant differences between exposed groups at maximum concentration level (MCL) compared to control. The generation time of nematodes exposed to buprofezin 24 h significantly increased in a concentration-dependent manner in the highest exposed group. When exposed for 72 h, the body bend frequency and head thrash frequency of nematodes exposed to cyhalothrin markedly decreased at MCL. The generation time and brood size of nematodes exposed to buprofezin were reduced in a concentration-dependent manner. The behavior of nematodes was sensitive to pesticides with neurotoxic properties, while pesticides affecting insect growth modified the reproductive system. The effects of pesticides on nematodes exposed for 24 h appeared more sensitive than with exposure for 72 h. Caenorhabditis elegans may thus be used for assessing the adverse effects of pesticide residues in aquatic environment.

Ethanol Dose- and Time-dependently Increases α and β Subunits of Mitochondrial ATP Synthase of Cultured Neonatal Rat Cardiomyocytes.

PubMed

Mashimo, Keiko; Arthur, Peter G; Ohno, Youkichi

2015-01-01

Mitochondria are target subcellular organelles of ethanol. In this study, the effects of ethanol on protein composition was examined with 2-dimensional electrophoresis of protein extracts from cultured neonatal rat cardiomyocytes exposed to 100 mM ethanol for 24 hours. A putative β subunit of mitochondrial ATP synthase was increased, which was confirmed by Western blot. The cellular protein abundances in the α and β subunits of ATP synthase increased in dose (0, 10, 50, and 100 mM) - and time (0.5 hour and 24 hours) -dependent manners. The DNA microarray analysis of total RNA extract demonstrated that gene expression of the corresponding messenger RNAs of these subunit proteins did not significantly alter due to 24-hour ethanol exposure. Therefore, protein expression of these nuclear-encoded mitochondrial proteins may be regulated at the translational, rather than the transcriptional, level. Alternatively, degradation of these subunit proteins might be decreased. Additionally, cellular ATP content of cardiomyocytes scarcely decreased following 24-hour exposure to any examined concentrations of ethanol. Previous studies, together with this study, have demonstrated that protein abundance of the α subunit or β subunit or both subunits of ATP synthase after ethanol exposure or dysfunctional conditions might differ according to tissue: significant increases in heart but decreases in liver and brain. Thus, it is suggested that the abundance of subunit proteins of mitochondrial ATP synthase in the ethanol-exposed heart, being different from that in the liver and brain, should increase dose-dependently through either translational upregulation or decreased degradation or both to maintain ATP production, as the heart requires much more energy than other tissues for continuing sustained contractions.

Environmental Immunology: Lessons learned from exposure to a select panel of immunotoxicants

PubMed Central

Kreitinger, Joanna M.; Beamer, Celine A.; Shepherd, David M.

2016-01-01

Exposure to environmental contaminants can produce profound effects on the immune system. Many different classes of xenobiotics can significantly suppress or enhance immune responsiveness depending on the levels (i.e. dose) and context (i.e. timing, route) of exposure. While defining the effects that toxicants can have on the immune system is a valuable component to improving public health, environmental immunology has greatly enhanced our understanding of how the immune system functions and explore new immunotherapies. This Brief Review focuses on three different examples of how immunotoxicology has benefitted the field of immunology, presenting information on (A) the aryl hydrocarbon receptor (AhR) signaling pathway, (B) the immunomodulatory effects of nanomaterials, and (C) the impact of xenobiotic exposure on the developing immune system. Collectively, contributions from immunotoxicology have significantly enhanced public health and spurred seminal advances in both basic and applied immunology. PMID:27044635

Light qualities and dose influence ascorbate pool size in detached oat leaves.

PubMed

Mastropasqua, Linda; Borraccino, Giuseppe; Bianco, Laura; Paciolla, Costantino

2012-02-01

In this work, we studied the mechanism of light influence on AsA pool size in Avena sativa L. under the effects of low intensity light at different wavelengths. Exposure to low intensity light of oat leaf segments incubated in water or in l-galactono-1,4-lactone (GL), resulted in an increase in AsA content compared with the dark control. This increase was due to modulation of l-galactono-1,4-lactone dehydrogenase (GLDH; EC 1.3.2.3) light-dependent activity and was dependent on the size of the endogenous GL pool. Both blue and red light were effective in increasing AsA, and this increase depended on both exposure time and light intensity. Protein biosynthesis, photosynthesis and calcium were involved in controlling the level of light-dependent AsA. We suggest that multiple checkpoints correlated to the presence of light underlie the ascorbate pool size. The presence of a light-activated switch for the maintenance of an adequate AsA level seems to be necessary for the various tasks of scavenging reactive oxygen species, in response to the dark-light cycle which plants experience under natural conditions. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Musician earplugs: Appreciation and protection

PubMed Central

Bockstael, Annelies; Keppler, Hannah; Botteldooren, Dick

2015-01-01

Recreational music exposure is a potential risk factor for noise-induced hearing loss (NIHL). Augmented hearing protectors have been designed with modified attenuation characteristics to combine hearing protection and listening comfort. However, to date, only a few independent studies have assessed the performance of those augmented protectors in realistic exposure conditions. This study compares the listening experience and temporary effects on cochlear status with different types of earplugs after exposure to contemporary club music. Five different types of commercially available hearing protectors were worn, all commonly used during leisure-time music exposure. Four of them were augmented premolded earplugs and the fifth type was an inexpensive, standard earplug frequently distributed for free at music events. During five different test sessions of 30 min each, participants not professionally involved in music wore one particular type of protector. Contemporary club music was played at sound pressure levels (SPLs) representative of concerts and bars. After each listening session, a questionnaire on sound quality and general appreciation was completed. In addition, otoacoustic emissions (OAEs) were measured directly before and after music exposure. The reported appreciation clearly differed depending on the addressed characteristics and the specific earplug type. In this test group, the reported appreciation mainly depended on comfort and looks, while differences in sound quality were less noticeable. The changes in OAE amplitude before and after noise exposure were small in terms of clinical standards. Nevertheless, the observed temporary shifts differed systematically for the different types of hearing protectors, with two types of musician earplug showing a more systematic decline than the others. Further research with respect to actual use and achieved protection for real, unsupervised music exposure is warranted. PMID:26168950

Exposure of rats to environmental tobacco smoke during cerebellar development alters behavior and perturbs mitochondrial energetics.

PubMed

Fuller, Brian F; Cortes, Diego F; Landis, Miranda K; Yohannes, Hiyab; Griffin, Hailey E; Stafflinger, Jillian E; Bowers, M Scott; Lewis, Mark H; Fox, Michael A; Ottens, Andrew K

2012-12-01

Environmental tobacco smoke (ETS) exposure is linked to developmental deficits and disorders with known cerebellar involvement. However, direct biological effects and underlying neurochemical mechanisms remain unclear. We sought to identify and evaluate underlying neurochemical change in the rat cerebellum with ETS exposure during critical period development. We exposed rats to daily ETS (300, 100, and 0 µg/m3 total suspended particulate) from postnatal day 8 (PD8) to PD23 and then assayed the response at the behavioral, neuroproteomic, and cellular levels. Postnatal ETS exposure induced heightened locomotor response in a novel environment on par initially with amphetamine stimulation. The cerebellar mitochondrial subproteome was significantly perturbed in the ETS-exposed rats. Findings revealed a dose-dependent up-regulation of aerobic processes through the modification and increased translocation of Hk1 to the mitochondrion with corresponding heightened ATP synthase expression. ETS exposure also induced a dose-dependent increase in total Dnm1l mitochondrial fission factor; although more active membrane-bound Dnm1l was found at the lower dose. Dnm1l activation was associated with greater mitochondrial staining, particularly in the molecular layer, which was independent of stress-induced Bcl-2 family dynamics. Further, electron microscopy associated Dnm1l-mediated mitochondrial fission with increased biogenesis, rather than fragmentation. The critical postnatal period of cerebellar development is vulnerable to the effects of ETS exposure, resulting in altered behavior. The biological effect of ETS is underlain in part by a Dnm1l-mediated mitochondrial energetic response at a time of normally tight control. These findings represent a novel mechanism by which environmental exposure can impact neurodevelopment and function.

Musician earplugs: Appreciation and protection.

PubMed

Bockstael, Annelies; Keppler, Hannah; Botteldooren, Dick

2015-01-01

Recreational music exposure is a potential risk factor for noise-induced hearing loss (NIHL). Augmented hearing protectors have been designed with modified attenuation characteristics to combine hearing protection and listening comfort. However, to date, only a few independent studies have assessed the performance of those augmented protectors in realistic exposure conditions. This study compares the listening experience and temporary effects on cochlear status with different types of earplugs after exposure to contemporary club music. Five different types of commercially available hearing protectors were worn, all commonly used during leisure-time music exposure. Four of them were augmented premolded earplugs and the fifth type was an inexpensive, standard earplug frequently distributed for free at music events. During five different test sessions of 30 min each, participants not professionally involved in music wore one particular type of protector. Contemporary club music was played at sound pressure levels (SPLs) representative of concerts and bars. After each listening session, a questionnaire on sound quality and general appreciation was completed. In addition, otoacoustic emissions (OAEs) were measured directly before and after music exposure. The reported appreciation clearly differed depending on the addressed characteristics and the specific earplug type. In this test group, the reported appreciation mainly depended on comfort and looks, while differences in sound quality were less noticeable. The changes in OAE amplitude before and after noise exposure were small in terms of clinical standards. Nevertheless, the observed temporary shifts differed systematically for the different types of hearing protectors, with two types of musician earplug showing a more systematic decline than the others. Further research with respect to actual use and achieved protection for real, unsupervised music exposure is warranted.

Physiological response of cardiac tissue to bisphenol a: alterations in ventricular pressure and contractility

PubMed Central

Brooks, Daina; Chandra, Akhil; Jaimes, Rafael; Sarvazyan, Narine; Kay, Matthew

2015-01-01

Biomonitoring studies have indicated that humans are routinely exposed to bisphenol A (BPA), a chemical that is commonly used in the production of polycarbonate plastics and epoxy resins. Epidemiological studies have shown that BPA exposure in humans is associated with cardiovascular disease; however, the direct effects of BPA on cardiac physiology are largely unknown. Previously, we have shown that BPA exposure slows atrioventricular electrical conduction, decreases epicardial conduction velocity, and prolongs action potential duration in excised rat hearts. In the present study, we tested if BPA exposure also adversely affects cardiac contractile performance. We examined the impact of BPA exposure level, sex, and pacing rate on cardiac contractile function in excised rat hearts. Hearts were retrogradely perfused at constant pressure and exposed to 10−9-10−4 M BPA. Left ventricular developed pressure and contractility were measured during sinus rhythm and during pacing (5, 6.5, and 9 Hz). Ca2+ transients were imaged from whole hearts and from neonatal rat cardiomyocyte layers. During sinus rhythm in female hearts, BPA exposure decreased left ventricular developed pressure and inotropy in a dose-dependent manner. The reduced contractile performance was exacerbated at higher pacing rates. BPA-induced effects on contractile performance were also observed in male hearts, albeit to a lesser extent. Exposure to BPA altered Ca2+ handling within whole hearts (reduced diastolic and systolic Ca2+ transient potentiation) and neonatal cardiomyocytes (reduced Ca2+ transient amplitude and prolonged Ca2+ transient release time). In conclusion, BPA exposure significantly impaired cardiac performance in a dose-dependent manner, having a major negative impact upon electrical conduction, intracellular Ca2+ handing, and ventricular contractility. PMID:25980024

Acute toxicity, biochemical and histopathological responses of endosulfan in Chanos chanos.

PubMed

Kumar, Neeraj; Ambasankar, K; Krishnani, K K; Gupta, S K; Bhushan, Shashi; Minhas, P S

2016-09-01

This study investigated 96h median lethal concentration of endosulfan (99%, pure α: β ratio of 7:3) by conducting static non-renewable acute toxicity bio-assay in Chanos chanos juvenile with average weight (110±5.65g). Further, the effect of different definitive doses (18.5, 19.5, 20.5, 21.5 and 22.5µg/L) of endosulfan on metabolic, heamato-immunoligcal and histopathological response were probed. Anti-oxidative enzymes CAT, SOD and GST showed significant (p<0.01) increase of activity in the liver, gill and brain during exposure to endosulfan in a dose and time dependent manner. The brain AChE activity showed significant (p<0.01) inhibition from 18.5 to 22.5µg/L exposure of endosulfan than the control group. LDH and MDH activity gradually increased with consequent increasing dose of endosulfan exposure in the liver, gill and brain. Similarly, ALT, AST and G6PDH activities in both liver and gill increased with consequent increases in the dose of endosulfan exposure. Immunological profile such as blood glucose and serum cortisol level significantly enhanced while respiratory burst activity declined with consequent increasing doses of endosulfan exposure. Histopathological alteration in the gill demonstrated curling of secondary lamellae, thickening of primary epithelium, shorting of secondary lamellae, epithelial hyperplasia, fusion of secondary lamellae, aneurism, and collapsed secondary lamellae due to dose dependent exposure of endosulfan. Liver histology illustrated cloudy swelling and necrosis with pyknotic nuclei to the moderate dose of endosulfan, whereas higher dose of endosulfan (21.5µg/L) displayed severe necrosis of hepatic cells. Overall results clearly indicate that acute exposure of endosulfan led to pronounced deleterious alterations on biochemical, heamato-immunological, and histopathological responses of C. chanos juvenile. Copyright © 2016 Elsevier Inc. All rights reserved.

Use Behaviors, Dependence, and Nicotine Exposure Associated with Ad Libitum Cigar Smoking

PubMed Central

Claus, Eric D.; Moeller, Benjamin C.; Harbour, Darlene; Kuehl, Philip J.; McGuire, Michael; Vivar, Juan C.; Schroeder, Megan J.

2018-01-01

Objectives To examine factors important to cigar smoking and subsequent nicotine exposure, we evaluated the impact of cigar type, cigarette smoking history, and inhalation behaviors on nicotine dependence, smoking topography, and biomarkers of exposure in current exclusive cigar smokers. Methods Adult, exclusive cigar smokers (N = 77) were recruited based on cigar type, cigarette smoking history, and self-reported inhalation behaviors. Participants smoked their own brand product ad libitum for up to one hour; dependence symptoms, smoking topography, and biomarkers of exposure were assessed. Results Cigar smokers showed low levels of dependence. Cigar smoking alleviated withdrawal and craving symptoms, increased plasma nicotine concentration, and increased exhaled CO. Multiple regression analyses indicate that inhalation behaviors were associated with increased dependence and greater reductions in withdrawal symptoms upon cigar smoking. Large cigar smokers smoked longer and smoked more tobacco than small cigar and cigarillo smokers. Furthermore, large cigar smokers and self-reported inhalers were exposed to more nicotine than small cigar smokers and non-inhalers. Conclusions Our study suggests that cigar type and smoking behaviors affect dependence and nicotine exposure upon cigar smoking. These findings provide additional insight into the substantial risks associated with cigar smoking. PMID:29516029

Estimated UV doses to psoriasis patients during climate therapy at Gran Canaria in March 2006

NASA Astrophysics Data System (ADS)

Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.

2008-01-01

Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.

Associations between air emissions from sour gas processing plants and indices of cow retainment and survival in dairy herds in Alberta

PubMed Central

Scott, H. Morgan; Soskolne, Colin L.; Lissemore, Kerry D.; Martin, S. Wayne; Shoukri, Mohamed M.; Coppock, Robert W.; Guidotti, Tee L.

2003-01-01

This paper describes the results of an investigation into the effects of air emissions from sour gas processing plants on indices of retainment or survival of adult female dairy cattle on farms in Alberta; namely, the productive lifespan of individual animals, and annual herd-level risks for culling and mortality. Using a geographical information system, 2 dispersion models — 1 simple and 1 complex — were used to assess historical exposures to sour gas emissions at 1382 dairy farm sites from 1985 through to 1994. Multivariable survival models, adjusting for the dependence of survival responses within a herd over time, as well as potential confounding variables, were utilized to determine associations between sour gas exposure estimates and the time from the first calving date to either death or culling of 150 210 dairy cows. Generalized linear models were used to model the relationship between herd-level risks for culling and mortality and levels of sour gas exposure. No significant (P < 0.05) associations were found with the time to culling (n = 70 052). However, both dispersion model exposure estimates were significantly associated (P < 0.05) with a decreased hazard for mortality; that is, in cases where cattle had died on-farm (n = 8743). There were no significant associations (P > 0.05) between herd culling risks and the 2 dispersion model exposure estimates. There was no measurable impact of plant emissions on the annual herd risk of mortality. PMID:12528823

Development of photo-modified starch/kefiran/TiO2 bio-nanocomposite as an environmentally-friendly food packaging material.

PubMed

Goudarzi, Vahid; Shahabi-Ghahfarrokhi, Iman

2018-05-21

This paper reports on an experiment in which starch/kefiran/TiO 2 (SKT)-based bio-nanocomposite films were developed and modified by photo-chemical reaction. In so doing, film-forming solutions were exposed to ultraviolet A (UV-A) for different times (1, 6, and 12 h). The obtained results indicated that increasing UV-A exposure time brought about an increase (≈14.9%) in the tensile strength of bio-nanocomposites. However, elongation at break and Young's modulus of irradiated film specimen decreased (≈32%, ≈12%, respectively) by increasing UV-A exposure time, and the moisture-sensitive parameters of specimen decreased using UV-A irradiation. According to the results, the functional properties of irradiated bio-nanocomposite are depended on the ratio of cross-linkages between polymer chains and the potentially produced mono and disaccharide by UV-A. Copyright © 2018. Published by Elsevier B.V.

Inactivation of Clostridium difficile spores by microwave irradiation.

PubMed

Ojha, Suvash Chandra; Chankhamhaengdecha, Surang; Singhakaew, Sombat; Ounjai, Puey; Janvilisri, Tavan

2016-04-01

Spores are a potent agent for Clostridium difficile transmission. Therefore, factors inhibiting spores have been of continued interest. In the present study, we investigated the influence of microwave irradiation in addition to conductive heating for C. difficile spore inactivation in aqueous suspension. The spores of 15 C. difficile isolates from different host origins were exposed to conductive heating and microwave irradiation. The complete inhibition of spore viability at 10(7) CFU/ml was encountered following microwave treatment at 800 W for 60 s, but was not observed in the conductive-heated spores at the same time-temperature exposure. The distinct patterns of ultrastructural alterations following microwave and conductive heat treatment were observed and the degree of damages by microwave was in the exposure time-dependent manner. Microwave would therefore be a simple and time-efficient tool to inactivate C. difficile spores, thus reducing the risk of C. difficile transmission. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thermal Exposure Effects on Properties of Al-Li Alloy Plate Products

NASA Technical Reports Server (NTRS)

Shah, Sandeep; Wells, Douglas; Wagner, John; Babel, Henry

2002-01-01

Aluminum-Lithium (AL-Li) alloys offer significant performance benefits for aerospace structural applications due to their higher specific properties compared with conventional aluminum alloys. For example, the application of an Al-Li alloy to the space shuttle external cryogenic fuel tank contributed to the weight savings that enabled successful deployment of International Space Station components. The composition and heat treatment of this alloy were optimized specifically for strength-toughness considerations for an expendable cryogenic tank. Time dependent properties related to reliability, such as thermal stability, fatigue, and corrosion, will be of significant interest when materials are evaluated for a reusable cryotank structure. As most aerospace structural hardware is weight sensitive, a reusable cryotank will be designed to the limits of the materials mechanical properties. Therefore, this effort was designed to establish the effects of thermal exposure on the mechanical properties and microstructure of one relatively production mature alloy and two developmental alloys C458 and L277. Tensile and fracture toughness behavior was evaluated after exposure to temperatures as high as 3oooF for up to IO00 hrs. Microstructural changes were also evaluated to correlate with the observed data trends. The ambient temperature parent metal data showed an increase in strength and reduction in elongation after exposure at lower temperatures. Strength reached a peak with intermediate temperature exposure followed by a decrease at highest exposure temperature. Characterizing the effect of thermal exposure on the properties of Al-Li alloys is important to defining a service limiting temperature, exposure time, and end-of-life properties.

Chronic methamphetamine exposure induces cardiac fas-dependent and mitochondria-dependent apoptosis.

PubMed

Liou, Cher-Ming; Tsai, Shiow-Chwen; Kuo, Chia-Hua; Williams, Timothy; Ting, Hua; Lee, Shin-Da

2014-06-01

Very limited information regarding the influence of chronic methamphetamine exposure on cardiac apoptosis is available. In this study, we evaluate whether chronic methamphetamine exposure will increase cardiac Fas-dependent (type I) and mitochondria-dependent (type II) apoptotic pathways. Thirty-two male Wistar rats at 3-4 months of age were randomly divided into a vehicle-treated group [phosphate-buffered saline (PBS) 0.5 ml SQ per day] and a methamphetamine-treated group (MA 10 mg/kg SQ per day) for 3 months. We report that after 3 months of exposure, abnormal myocardial architecture, more minor cardiac fibrosis and cardiac TUNEL-positive apoptotic cells were observed at greater frequency in the MA group than in the PBS group. Protein levels of TNF-α, Fas ligand, Fas receptor, Fas-associated death domain, activated caspase-8, and activated caspase-3 (Fas-dependent apoptosis) extracted from excised hearts were significantly increased in the MA group, compared to the PBS group. Protein levels of cardiac Bak, t-Bid, Bak to Bcl-xL ratio, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptosis) were significantly increased in the MA group, compared with the PBS group. The results from this study reveal that chronic methamphetamine exposure will activate cardiac Fas-dependent and mitochondria-dependent apoptotic pathways, which may indicate a possible mechanism for developing cardiac abnormalities in humans with chronic methamphetamine abuse.

Western diets induce blood-brain barrier leakage and alter spatial strategies in rats.

PubMed

Hargrave, Sara L; Davidson, Terry L; Zheng, Wei; Kinzig, Kimberly P

2016-02-01

Western diet (WD) intake induces obesity and metabolic dysfunction. The present study examined the effects of WD on hippocampal-dependent cognitive functioning and blood-brain barrier (BBB) permeability as a function of exposure duration, obesity phenotype, and peripheral markers of energy regulation. The use of hippocampal-dependent "place" or hippocampal-independent "response" strategies in a Y maze was assessed in male rats following 10, 40, and 90 days of WD exposure in diet-induced obese (DIO) rats, in diet resistant (DR) rats that are relatively insensitive to the obesogenic properties of WD, and in chow-fed controls. Insulin, glucose, and BBB permeability throughout several loci in the hippocampus, striatum, and cerebellum were evaluated in relation to duration of WD exposure, obesity phenotype, and type of strategy used. DIO rats had increased body weight and adiposity throughout the study, and elevated 10-day glucose and 90-day insulin levels. Throughout the study, chow-fed and DR rats reliably relied on a place strategy. DIO rats, in contrast, favored a response strategy at the 10- and 90-day time points. BBB leakage was observed in the dorsal striatum and multiple subregions of the hippocampus of DIO, but not DR or chow-fed rats. Increased ventral hippocampal BBB permeability and blood glucose levels were associated with reduced place strategy use. These data indicate that WD-induced BBB leakage is dependent on duration of diet exposure as well as obesity phenotype, and implicates BBB leakage and impaired glucoregulation in behavioral strategy and cognitive performance. (c) 2016 APA, all rights reserved).

Validation of Methods to Control for Immortal Time Bias in a Pharmacoepidemiologic Analysis of Renin–Angiotensin System Inhibitors in Type 2 Diabetes

PubMed Central

Yang, Xilin; Kong, Alice PS; Luk, Andrea OY; Ozaki, Risa; Ko, Gary TC; Ma, Ronald CW; Chan, Juliana CN; So, Wing Yee

2014-01-01

Background Pharmacoepidemiologic analysis can confirm whether drug efficacy in a randomized controlled trial (RCT) translates to effectiveness in real settings. We examined methods used to control for immortal time bias in an analysis of renin–angiotensin system (RAS) inhibitors as the reference cardioprotective drug. Methods We analyzed data from 3928 patients with type 2 diabetes who were recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs) for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs. Results During a median follow-up period of 5.45 years, 7.23% (n = 284) patients developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of immortal time among the users. In multivariable analysis, time-dependent drug-exposure Cox models and Cox models that moved immortal time from users to nonusers both severely inflated the HR, and time-fixed models that included immortal time deflated the HR. Use of time-fixed Cox models that excluded immortal time resulted in a HR of only 0.89 (95% CI, 0.68–1.17) for CVD associated with RAS inhibitors, which is closer to the values reported in RCTs. Conclusions In pharmacoepidemiologic analysis, time-dependent drug exposure models and models that move immortal time from users to nonusers may introduce substantial bias in investigations of the effects of RAS inhibitors on CVD in type 2 diabetes. PMID:24747198

The mare reproductive loss syndrome and the eastern tent caterpillar: a toxicokinetic/statistical analysis with clinical, epidemiologic, and mechanistic implications.

PubMed

Sebastian, Manu; Gantz, Marie G; Tobin, Thomas; Harkins, J Daniel; Bosken, Jeffrey M; Hughes, Charlie; Harrison, Lenn R; Bernard, William V; Richter, Dana L; Fitzgerald, Terrence D

2003-01-01

During 2001, central Kentucky experienced acute transient epidemics of early and late fetal losses, pericarditis, and unilateral endophthalmitis, collectively referred to as mare reproductive loss syndrome (MRLS). A toxicokinetic/statistical analysis of experimental and field MRLS data was conducted using accelerated failure time (AFT) analysis of abortions following administration of Eastern tent caterpillars (ETCs; 100 or 50 g/day or 100 g of irradiated caterpillars/day) to late-term pregnant mares. In addition, 2001 late-term fetal loss field data were used in the analysis. Experimental data were fitted by AFT analysis at a high (P <.0001) significance. Times to first abortion ("lag time") and abortion rates were dose dependent. Lag times decreased and abortion rates increased exponentially with dose. Calculated dose x response data curves allow interpretation of abortion data in terms of "intubated ETC equivalents." Analysis suggested that field exposure to ETCs in 2001 in central Kentucky commenced on approximately April 27, was initially equivalent to approximately 5 g of intubated ETCs/day, and increased to approximately 30 g/day at the outbreak peak. This analysis accounts for many aspects of the epidemiology, clinical presentations, and manifestations of MRLS. It allows quantitative interpretation of experimental and field MRLS data and has implications for the basic mechanisms underlying MRLS. The results support suggestions that MRLS is caused by exposure to or ingestion of ETCs. The results also show that high levels of ETC exposure produce intense, focused outbreaks of MRLS, closely linked in time and place to dispersing ETCs, as occurred in central Kentucky in 2001. With less intense exposure, lag time is longer and abortions tend to spread out over time and may occur out of phase with ETC exposure, obscuring both diagnosis of this syndrome and the role of the caterpillars.

Induction of pulmonary fibrosis by cerium oxide nanoparticles

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, Jane Y., E-mail: jym1@cdc.gov; Mercer, Robert R.; Barger, Mark

2012-08-01

Cerium compounds have been used as a diesel engine catalyst to lower the mass of diesel exhaust particles, but are emitted as cerium oxide (CeO{sub 2}) nanoparticles in the diesel exhaust. In a previous study, we have demonstrated a wide range of CeO{sub 2}-induced lung responses including sustained pulmonary inflammation and cellular signaling that could lead to pulmonary fibrosis. In this study, we investigated the fibrogenic responses induced by CeO{sub 2} in a rat model at various time points up to 84 days post-exposure. Male Sprague Dawley rats were exposed to CeO{sub 2} by a single intratracheal instillation. Alveolar macrophagesmore » (AM) were isolated by bronchial alveolar lavage (BAL). AM-mediated cellular responses, osteopontin (OPN) and transform growth factor (TGF)-β1 in the fibrotic process were investigated. The results showed that CeO{sub 2} exposure significantly increased fibrotic cytokine TGF-β1 and OPN production by AM above controls. The collagen degradation enzymes, matrix metalloproteinase (MMP)-2 and -9 and the tissue inhibitor of MMP were markedly increased in the BAL fluid at 1 day- and subsequently declined at 28 days after exposure, but remained much higher than the controls. CeO{sub 2} induced elevated phospholipids in BAL fluid and increased hydroxyproline content in lung tissue in a dose- and time-dependent manner. Immunohistochemical analysis showed MMP-2, MMP-9 and MMP-10 expressions in fibrotic regions. Morphological analysis noted increased collagen fibers in the lungs exposed to a single dose of 3.5 mg/kg CeO{sub 2} and euthanized at 28 days post-exposure. Collectively, our studies show that CeO{sub 2} induced fibrotic lung injury in rats, suggesting it may cause potential health effects. -- Highlights: ► Cerium oxide exposure significantly affected the following parameters in the lung. ► Induced fibrotic cytokine OPN and TGF-β1 production and phospholipidosis. ► Caused imbalance of the MMP-9/ TIMP-1 ratio that favors fibrosis. ► Cerium oxide particles were detected in lung tissue and AM. ► Cerium oxide caused lung fibrosis in a dose- and time-dependent manner.« less

Modeling cumulative dose and exposure duration provided insights regarding the associations between benzodiazepines and injuries.

PubMed

Abrahamowicz, Michal; Bartlett, Gillian; Tamblyn, Robyn; du Berger, Roxane

2006-04-01

Accurate assessment of medication impact requires modeling cumulative effects of exposure duration and dose; however, postmarketing studies usually represent medication exposure by baseline or current use only. We propose new methods for modeling various aspects of medication use history and employment of them to assess the adverse effects of selected benzodiazepines. Time-dependent measures of cumulative dose or duration of use, with weighting of past exposures by recency, were proposed. These measures were then included in alternative versions of the multivariable Cox model to analyze the risk of fall related injuries among the elderly new users of three benzodiazepines (nitrazepam, temazepam, and flurazepam) in Quebec. Akaike's information criterion (AIC) was used to select the most predictive model for a given benzodiazepine. The best-fitting model included a combination of cumulative duration and current dose for temazepam, and cumulative dose for flurazepam and nitrazepam, with different weighting functions. The window of clinically relevant exposure was shorter for flurazepam than for the two other products. Careful modeling of the medication exposure history may enhance our understanding of the mechanisms underlying their adverse effects.

Joint Toxicity of Arsenic, Copper and Glyphosate on Behavior, Reproduction and Heat Shock Protein Response in Caenorhabditis elegans.

PubMed

Wang, Yunbiao; Ezemaduka, Anastasia N; Li, Zhuheng; Chen, Zhanyan; Song, Chuantao

2017-04-01

The soil nematode Caenorhabditis elegans was used in 24-h acute exposures to arsenic (As), copper (Cu) and glyphosate (GPS) and to mixtures of As/Cu and As/GPS to investigate the effects of mixture exposures in the worms. A synergistic type of interaction was observed for acute toxicity with the As/Cu and As/GPS mixtures. Sublethal 24-h exposures of 1/1000, 1/100 and 1/10 of the LC50 concentrations for As, Cu and GPS individually and for As/Cu and As/GPS mixtures were conducted to observe responses in locomotory behavior (head thrashing), reproduction, and heat shock protein expression. Head thrash frequency and reproduction exhibited concentration dependent decreases in both individual and combined exposures to the tested chemical stressors, and showed synergistic interactions even at micromolar concentrations. Furthermore, the HSP70 protein level was significantly increased following exposure to individual and combined chemical stressors in wild-type C. elegans. Our findings establish for the first time the effects of exposure to As/GPS and As/Cu mixtures in C. elegans.

Secondhand smoke exposure levels in outdoor hospitality venues: a qualitative and quantitative review of the research literature.

PubMed

Licht, Andrea S; Hyland, Andrew; Travers, Mark J; Chapman, Simon

2013-05-01

This paper considers the evidence on whether outdoor secondhand smoke (SHS) is present in hospitality venues at high levels enough to potentially pose health risks, particularly among employees. Searches in PubMed and Web of Science included combinations of environmental tobacco smoke, secondhand smoke, or passive smoke AND outdoor, yielding 217 and 5,199 results, respectively through June, 2012. Sixteen studies were selected that reported measuring any outdoor SHS exposures (particulate matter (PM) or other SHS indicators). The SHS measurement methods were assessed for inclusion of extraneous variables that may affect levels or the corroboration of measurements with known standards. The magnitude of SHS exposure (PM2.5) depends on the number of smokers present, measurement proximity, outdoor enclosures, and wind. Annual excess PM2.5 exposure of full-time waitstaff at outdoor smoking environments could average 4.0 to 12.2 μg/m3 under variable smoking conditions. Although highly transitory, outdoor SHS exposures could occasionally exceed annual ambient air quality exposure guidelines. Personal monitoring studies of waitstaff are warranted to corroborate these modeled estimates.

4-Nonylphenol induced DNA damage and repair in fish, Channa punctatus after subchronic exposure.

PubMed

Sharma, Madhu; Chadha, Pooja

2017-07-01

The detection of a possible DNA damaging effect of 4-nonylphenol (NP) after subchronic exposure and repair after cessation of exposure to Channa punctatus is the aim of the present study. Channa punctatus was exposed to different concentrations (0.15 mg/l, 0.10 mg/l, and 0.07 mg/l) of NP along with positive control (ethanol) and negative control (water) for 90 d and after that allowed to recover for 30 d. Comet assay and micronucleus assay were used for the determination of DNA damage and repair by using blood cells. The effect was seen after 30, 60, and 90 d of exposure. Time- and dose-dependent increase in DNA damage was found as revealed by both the end points studied. Evident recovery was observed after 30 d of cessation of exposure. Blood cells were successfully appeared to achieve the restoration of DNA integrity. Hence, the study aimed to improve the knowledge of the genetic hazard to fish associated with NP exposure and provide a wide scope to discover the efficiency of DNA repair system in C. punctatus.

Pesticide risk assessment in free-ranging bees is weather and landscape dependent.

PubMed

Henry, Mickaël; Bertrand, Colette; Le Féon, Violette; Requier, Fabrice; Odoux, Jean-François; Aupinel, Pierrick; Bretagnolle, Vincent; Decourtye, Axel

2014-07-10

The risk assessment of plant protection products on pollinators is currently based on the evaluation of lethal doses through repeatable lethal toxicity laboratory trials. Recent advances in honeybee toxicology have, however, raised interest on assessing sublethal effects in free-ranging individuals. Here, we show that the sublethal effects of a neonicotinoid pesticide are modified in magnitude by environmental interactions specific to the landscape and time of exposure events. Field sublethal assessment is therefore context dependent and should be addressed in a temporally and spatially explicit way, especially regarding weather and landscape physiognomy. We further develop an analytical Effective Dose (ED) framework to help disentangle context-induced from treatment-induced effects and thus to alleviate uncertainty in field studies. Although the ED framework involves trials at concentrations above the expected field exposure levels, it allows to explicitly delineating the climatic and landscape contexts that should be targeted for in-depth higher tier risk assessment.

Volatile compounds and phenolic composition of virgin olive oil: optimization of temperature and time of exposure of olive pastes to air contact during the mechanical extraction process.

PubMed

Servili, Maurizio; Selvaggini, Roberto; Taticchi, Agnese; Esposto, Sonia; Montedoro, GianFrancesco

2003-12-31

The operative conditions of malaxation such as temperature and time of exposure of olive pastes to air contact (TEOPAC) affect volatile and phenolic composition of virgin olive oil (VOO) and, as a consequence, its sensory and healthy qualities. In this paper, optimal temperature and TEOPAC during malaxation were studied, in lab scale, in two Italian cultivars using phenolic compounds, volatile composition, and sensory analysis of VOO as markers. The optimal temperature and TEOPAC, selected by response surface modeling,were cultivar-dependent being 30 min of TEOPAC at the lowest temperature investigated (22 degrees C) and 0 min of TEOPAC at 26 degrees C for Frantoio and Moraiolo cultivars, respectively.

VizieR Online Data Catalog: Galaxy And Mass Assembly (GAMA) DR1 (Driver+, 2011)

NASA Astrophysics Data System (ADS)

Driver, S. P.; Hill, D. T.; Kelvin, L. S.; Robotham, A. S. G.; Liske, J.; Norberg, P.; Baldry, I. K.; Bamford, S. P.; Hopkins, A. M.; Loveday, J.; Peacock, J. A.; Andrae, E.; Bland-Hawthorn, J.; Brough, S.; Brown, M. J. I.; Cameron, E.; Ching, J. H. Y.; Colless, M.; Conselice, C. J.; Croom, S. M.; Cross, N. J. G.; de Propris, R.; Dye, S.; Drinkwater, M. J.; Ellis, S.; Graham, A. W.; Grootes, M. W.; Gunawardhana, M.; Jones, D. H.; van Kampen, E.; Maraston, C.; Nichol, R. C.; Parkinson, H. R.; Phillipps, S.; Pimbblet, K.; Popescu, C. C.; Prescott, M.; Roseboom, I. G.; Sadler, E. M.; Sansom, A. E.; Sharp, R. G.; Smith, D. J. B.; Taylor, E.; Thomas, D.; Tuffs, R. J.; Wijesinghe, D.; Dunne, L.; Frenk, C. S.; Jarvis, M. J.; Madore, B. F.; Meyer, M. J.; Seibert, M.; Staveley-Smith, L.; Sutherland, W. J.; Warren, S. J.

2012-09-01

All GAMA 2dF pointings (tiles) were observed during dark or grey time with exposure times mostly ranging from 3000 to 5000s (in three to five exposures) depending on seeing and sky brightness. Observations were generally conducted at an hour angle of less than 2h (the median zenith distance of the observations is 35°) and with the Atmospheric Dispersion Corrector engaged. We used the 580V and 385R gratings with central wavelengths of 4800 and 7250Å in the blue and red arms, respectively, separated by a 5700Å dichroic. This set-up yielded a continuous wavelength coverage of 3720-8850Å at a resolution of ~3.5Å (in the blue channel) and ~5.5Å (in the red channel). (2 data files).

The influence of propofol anesthesia exposure on nonaversive memory retrieval and expression of molecules involved in memory process in the dorsal hippocampus in peripubertal rats.

PubMed

Pavković, Željko; Milanović, Desanka; Ruždijić, Sabera; Kanazir, Selma; Pešić, Vesna

2018-06-01

The effects of anesthetic drugs on postoperative cognitive function in children are not well defined and have not been experimentally addressed. The present study aimed to examine the influence of propofol anesthesia exposure on nonaversive hippocampus-dependent learning and biochemical changes involved in memory process in the dorsal hippocampus, in peripubertal rats as the rodent model of periadolescence. The intersession spatial habituation and the novel object recognition tasks were used to assess spatial and nonspatial, nonaversive hippocampus-dependent learning. The exposure to anesthesia was performed after comparably long acquisition phases in both tasks. Behavioral testing lasted for 2 consecutive days (24-hour retention period). Changes in the expression of molecules involved in memory retrieval/reconsolidation were examined in the dorsal hippocampus by Western blot and immunohistochemistry, at the time of behavioral testing. Exposure to propofol anesthesia resulted in inappropriate assessment of spatial novelty at the beginning of the test session and affected continuation of acquisition in the spatial habituation test. The treatment did not affect recognition of the novel object at the beginning of the test session but it attenuated overall preference to novelty, reflecting retrieval of a weak memory. The expression of phosphorylated extracellular signal-regulated kinase 2 (involved in memory retrieval) was decreased while the level of phosphorylated Ca 2+ /calmodulin-dependent protein kinase IIα and early growth response protein 1 (involved in memory reconsolidation) was increased in the dorsal hippocampus. The level of Finkel-Biskis-Jinkins murine osteosarcoma viral oncogene homolog B (neuronal activity indicator) was increased in the dorsal dentate gyrus. Enhanced exploratory activity was still evident in the propofol anesthesia exposure (PAE) group 48 hour after the treatment in both tasks. In peripubertal rats, propofol anesthesia exposure affects memory retrieval and acquisition of new learning in the spatial and nonspatial, nonaversive learning tasks 24 hour after the treatment, along with the expression of molecules that participate in memory retrieval/reconsolidation in the dorsal hippocampus. These results may have clinical implications, favoring control of basic cognitive functions in older children after the propofol exposure. © 2018 John Wiley & Sons Ltd.

Instrumental variables analysis using multiple databases: an example of antidepressant use and risk of hip fracture.

PubMed

Uddin, Md Jamal; Groenwold, Rolf H H; de Boer, Anthonius; Gardarsdottir, Helga; Martin, Elisa; Candore, Gianmario; Belitser, Svetlana V; Hoes, Arno W; Roes, Kit C B; Klungel, Olaf H

2016-03-01

Instrumental variable (IV) analysis can control for unmeasured confounding, yet it has not been widely used in pharmacoepidemiology. We aimed to assess the performance of IV analysis using different IVs in multiple databases in a study of antidepressant use and hip fracture. Information on adults with at least one prescription of a selective serotonin reuptake inhibitor (SSRI) or tricyclic antidepressant (TCA) during 2001-2009 was extracted from the THIN (UK), BIFAP (Spain), and Mondriaan (Netherlands) databases. IVs were created using the proportion of SSRI prescriptions per practice or using the one, five, or ten previous prescriptions by a physician. Data were analysed using conventional Cox regression and two-stage IV models. In the conventional analysis, SSRI (vs. TCA) was associated with an increased risk of hip fracture, which was consistently found across databases: the adjusted hazard ratio (HR) was approximately 1.35 for time-fixed and 1.50 to 2.49 for time-varying SSRI use, while the IV analysis based on the IVs that appeared to satisfy the IV assumptions showed conflicting results, e.g. the adjusted HRs ranged from 0.55 to 2.75 for time-fixed exposure. IVs for time-varying exposure violated at least one IV assumption and were therefore invalid. This multiple database study shows that the performance of IV analysis varied across the databases for time-fixed and time-varying exposures and strongly depends on the definition of IVs. It remains challenging to obtain valid IVs in pharmacoepidemiological studies, particularly for time-varying exposure, and IV analysis should therefore be interpreted cautiously. Copyright © 2016 John Wiley & Sons, Ltd.

Effects of prolonged ethanol vapor exposure on forced swim behavior, and neuropeptide Y and corticotropin-releasing factor levels in rat brains.

PubMed

Walker, Brendan M; Drimmer, David A; Walker, Jennifer L; Liu, Tianmin; Mathé, Aleksander A; Ehlers, Cindy L

2010-09-01

Depressive symptoms in alcohol-dependent individuals are well-recognized and clinically relevant phenomena. The etiology has not been elucidated although it is clear that the depressive symptoms may be alcohol independent or alcohol induced. To contribute to the understanding of the neurobiology of chronic ethanol use, we investigated the effects of chronic intermittent ethanol vapor exposure on behaviors in the forced swim test (FST) and neuropeptide Y (NPY) and corticotropin-releasing factor (CRF) levels in specific brain regions. Adult male Wistar rats were subjected to intermittent ethanol vapor (14 h on/10 h off) or air exposure for 2 weeks and were then tested at three time points corresponding to acute withdrawal (8-12 h into withdrawal) and protracted withdrawal (30 and 60 days of withdrawal) in the FST. The behaviors that were measured in the five-min FST consisted of latency to immobility, swim time, immobility time, and climbing time. The FST results showed that the vapor-exposed animals displayed depressive-like behaviors; for instance, decreased latency to immobility in acute withdrawal and decreased latency to immobility, decreased swim time and increased immobility time in protracted withdrawal, with differences between air- and vapor-exposed animals becoming more pronounced over the 60-day withdrawal period. NPY levels in the frontal cortex of the vapor-exposed animals were decreased compared with the control animals, and CRF levels in the amygdala were correlated with increased immobility time. Thus, extended ethanol vapor exposure produced long-lasting changes in FST behavior and NPY levels in the brain. Copyright © 2010 Elsevier Inc. All rights reserved.

Association of screen time with self-perceived attention problems and hyperactivity levels in French students: a cross-sectional study

PubMed Central

Guichard, Elie; Kurth, Tobias

2016-01-01

Objective To investigate whether high levels of screen time exposure are associated with self-perceived levels of attention problems and hyperactivity in higher education students. Design Cross-sectional study among participants of the i-Share cohort. Setting French-speaking students of universities and higher education institutions. Participants 4816 graduate students who were at least 18 years old. Exposure Screen time was assessed by self-report of the average time spent on five different screen activities on smartphone, television, computer and tablet and categorised into quartiles. Main outcome measure We used the Attention Deficit Hyperactivity Disorder Self-Report Scale (ASRS-v1.1) concerning students’ behaviour over the past 6 months to measure self-perceived levels of attention problems and hyperactivity. Responses were summarised into a global score as well as scores for attention problems and hyperactivity. Results The 4816 participants of this study had a mean age of 20.8 years and 75.5% were female. Multivariable ordinary regression models showed significant associations of screen time exposure with quintiles of the total score of self-perceived attention problems and hyperactivity levels as well as the individual domains. Compared to the lowest screen time exposure category, the ORs (95% CI) were 1.58 (1.37 to 1.82) for each increasing level of quintiles of the global score, 1.57 (1.36 to 1.81) for increasing quintiles of attention levels and 1.25 (1.09 to 1.44) for increasing quartiles of hyperactivity. Conclusions Results of this large cross-sectional study among French university and higher education students show dose-dependent associations between screen time and self-perceived levels of attention problems and hyperactivity. Further studies are warranted to evaluate whether interventions could positively influence these associations. PMID:26920440

The toxic effects of ammonia exposure on antioxidant and immune responses in Rockfish, Sebastes schlegelii during thermal stress.

PubMed

Kim, Shin-Hu; Kim, Jun-Hwan; Park, Myoung-Ae; Hwang, Seong Don; Kang, Ju-Chan

2015-11-01

Rockfish, Sebastes schlegelii (mean weight 14.53 ± 1.14 cm, and mean weight 38.36 ± 3.45 g) were exposed for 4 weeks (2 weeks and 4 weeks) with the different levels of ammonia in the concentrations of 0, 0.1, 0.5, 1.0mg/L at 19 and 24°C. The ammonia exposure induced significant alterations in antioxidant responses. The activities of SOD, CAT, and GST were considerably increased by the ammonia exposure depending on water temperature, whereas the GSH level was notably decreased after 2 and 4 weeks. In the stress indicators, the cortisol and HSP 70 were significantly elevated by the exposure to ammonia depending on water temperature. In innate immune responses, the phagocytosis and lysozyme activity were notably decreased by ammonia exposure depending on water temperature after 2 and 4 weeks. The results suggest that ammonia exposure depending on water temperature can induce the considerable alterations in antioxidant responses, stress, and immune inhibition. Copyright © 2015 Elsevier B.V. All rights reserved.

Impact of Exposure to Childhood Maltreatment on Transitions to Alcohol Dependence in Women and Men.

PubMed

Oberleitner, Lindsay M S; Smith, Philip H; Weinberger, Andrea H; Mazure, Carolyn M; McKee, Sherry A

2015-11-01

Childhood maltreatment decreases age of first use and speeds the transition from first use to dependence (i.e., telescoping) for alcohol use, however, it is currently unknown whether this influence is the same for men and women. Analyses were conducted with the National Epidemiologic Survey on Alcohol and Related Conditions (n = 34,653). Outcome variables included age of alcohol initiation and time to onset of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol dependence. Predictor variables included gender and childhood maltreatment. Linear and Poisson regression analyses were conducted. Results demonstrated that in regard to age of drinking initiation, individuals who experienced childhood maltreatment initiated 1 year earlier than those without maltreatment, however, there was no interaction of this relationship with gender. Regarding the time to dependence, it was found that women who experienced childhood maltreatment demonstrated telescoping (shorter time between onset and dependence) compared to women without maltreatment and men (both with and without maltreatment). Women with a history of childhood maltreatment are particularly vulnerable to an accelerated time from initiation of alcohol use until dependence, a pattern indicative of increased negative alcohol-related outcomes. Findings highlight the need for development of gender-specific prevention efforts and behavioral treatments to aid in early intervention of problematic alcohol use in women. © The Author(s) 2015.

Diurnal changes in CN metabolism and response of rice seedlings to UV-B radiation.

PubMed

Yun, Hyejin; Lim, Sunhyung; Kim, Yangmin X; Lee, Yejin; Lee, Seulbi; Lee, Deogbae; Park, Keewoong; Sung, Jwakyung

2018-03-13

Plants regulate a number of primary metabolites, including carbohydrates, organic acids, and amino acids, in response to UV-B radiation. Therefore, it is essential to understand the time-dependent response of rice plants to UV-B stress. This study focused on the response of plants to UV-B at different leaf developmental phases (emerging, growing, and maturing) in an attempt to fully comprehend the metabolic shift. We analyzed the expression levels of genes related to starch/sucrose metabolism in the leaf blades of rice seedlings (Oryza sativa L. "Saechuchenog") exposed to UV-B irradiation for short (1 day) and long terms (5 days) using quantitative real-time polymerase chain reaction. We also examined the diurnal variations in the contents of primary metabolites using an established GCTOF-MS (gas chromatography time of flight-mass spectrometry) method. The results showed that the levels of primary metabolites were largely dependent upon the diurnal rhythm and leaf developmental phase. The young leaves (sink) produced and accumulated starch rather than sucrose. The short-term (4 h, 1 day) UV-B exposure inhibited sucrose synthesis, which could be the first target of UV-B radiation. Following short- and long-term (5 days) exposure to UV-B radiation, the dynamic response of primary metabolites was evaluated. It was found that the content of carbohydrates decreased throughout the period of exposure to UV-B stress, especially in terms of sucrose concentration. However, the content of the majority of amino acids increased after an early decrease. Our data revealed that the metabolic response, as well as the gene expression, differed with the period (intensity) of exposure to UV-B radiation and with the phase of leaf development. These findings provide new insights for a better understanding of the metabolic response of a variety of plant species exposed to a wide range of UV-B radiation. Copyright © 2018. Published by Elsevier GmbH.

Effect of nickel chloride on cell proliferation.

PubMed

D'Antò, Vincenzo; Valletta, Rosa; Amato, Massimo; Schweikl, Helmut; Simeone, Michele; Paduano, Sergio; Rengo, Sandro; Spagnuolo, Gianrico

2012-01-01

Metal alloys used in dentistry and in other biomedical fields may release nickel ions in the oral environment. The release of nickel might influence the normal biological and physiological processes, including tissue wound healing, cell growth and proliferation. The aim of this study was to evaluate in vitro the effects of nickel ions on cell cycle, viability and proliferation. Human osteosarcoma cells (U2OS) and human keratinocytes (HaCat) were exposed to different nickel chloride (NiCl(2)) concentrations (0 - 5mM) for various periods exposure. The viability of cultured cells was estimated by flow cytometry using Annexin V-FITC and Propidium Iodide (PI). Cell proliferation was evaluated by using carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) and flow cytometry. Finally, the effects of NiCl(2) on cell cycle were assessed and quantified by flow cytometry. Statistical analysis was performed by means of ANOVA followed by Tukey's test. NiCl(2) induced a dose and time dependent decrease in cell viability. After 24h, 1mM NiCl(2) caused a similar and significant reduction of viability in U2OS and HaCat cells, while higher NiCl(2) concentrations and longer exposure times showed a reduced cytotoxic effect in HaCat as compared to U2OS cells. Exposure to NiCl(2) caused a dose- and time-dependent inhibition of cell proliferation in both cell lines tested, with a prominent effect on U2OS cells. Furthermore, both cell lines exposed to NiCl(2) exhibited significant changes in cell cycle distribution after 24h exposure 2mM NiCl2, as compared to untreated cells (p<0.05). Our results indicate that release of nickel ions may affect cell proliferation. The inhibition of cell growth by NiCl2 is mediated by both cell cycle arrest and by induction of cell death.

Effect of Nickel Chloride on Cell Proliferation

PubMed Central

D’Antò, Vincenzo; Valletta, Rosa; Amato, Massimo; Schweikl, Helmut; Simeone, Michele; Paduano, Sergio; Rengo, Sandro; Spagnuolo, Gianrico

2012-01-01

Objective: Metal alloys used in dentistry and in other biomedical fields may release nickel ions in the oral environment. The release of nickel might influence the normal biological and physiological processes, including tissue wound healing, cell growth and proliferation. The aim of this study was to evaluate in vitro the effects of nickel ions on cell cycle, viability and proliferation. Materials and Methods: Human osteosarcoma cells (U2OS) and human keratinocytes (HaCat) were exposed to different nickel chloride (NiCl2) concentrations (0 - 5mM) for various periods exposure. The viability of cultured cells was estimated by flow cytometry using Annexin V-FITC and Propidium Iodide (PI). Cell proliferation was evaluated by using carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) and flow cytometry. Finally, the effects of NiCl2 on cell cycle were assessed and quantified by flow cytometry. Statistical analysis was performed by means of ANOVA followed by Tukey’s test. Results: NiCl2 induced a dose and time dependent decrease in cell viability. After 24h, 1mM NiCl2 caused a similar and significant reduction of viability in U2OS and HaCat cells, while higher NiCl2 concentrations and longer exposure times showed a reduced cytotoxic effect in HaCat as compared to U2OS cells. Exposure to NiCl2 caused a dose- and time-dependent inhibition of cell proliferation in both cell lines tested, with a prominent effect on U2OS cells. Furthermore, both cell lines exposed to NiCl2 exhibited significant changes in cell cycle distribution after 24h exposure 2mM NiCl2, as compared to untreated cells (p<0.05). Conclusion: Our results indicate that release of nickel ions may affect cell proliferation. The inhibition of cell growth by NiCl2 is mediated by both cell cycle arrest and by induction of cell death. PMID:23198004

Longitudinal study of parasite-induced mortality of a long-lived host: the importance of exposure to non-parasitic stressors.

PubMed

Chin, Hilary M-H; Luong, Lien T; Shostak, Allen W

2017-12-01

Hosts face mortality from parasitic and environmental stressors, but interactions of parasitism with other stressors are not well understood, particularly for long-lived hosts. We monitored survival of flour beetles (Tribolium confusum) in a longitudinal design incorporating cestode (Hymenolepis diminuta) infection, starvation and exposure to the pesticide diatomaceous earth (DE). We found that cestode cysticercoids exhibit increasing morphological damage and decreasing ability to excyst over time, but were never eliminated from the host. In the presence of even mild environmental stressors, host lifespan was reduced sufficiently that extensive degradation of cysticercoids was never realized. Median host lifespan was 200 days in the absence of stressors, and 3-197 days with parasitism, starvation and/or DE. Early survival of parasitized hosts was higher relative to controls in the presence of intermediate concentrations of DE, but reduced under all other conditions tested. Parasitism increased host mortality in the presence of other stressors at times when parasitism alone did not cause mortality, consistent with an interpretation of synergy. Environmental stressors modified the parasite numbers needed to reveal intensity-dependent host mortality, but only rarely masked intensity dependence. The longitudinal approach produced observations that would have been overlooked or misinterpreted if survival had only been monitored at a single time point.

Predictive models of poly(ethylene-terephthalate) film degradation under multi-factor accelerated weathering exposures

PubMed Central

Ngendahimana, David K.; Fagerholm, Cara L.; Sun, Jiayang; Bruckman, Laura S.

2017-01-01

Accelerated weathering exposures were performed on poly(ethylene-terephthalate) (PET) films. Longitudinal multi-level predictive models as a function of PET grades and exposure types were developed for the change in yellowness index (YI) and haze (%). Exposures with similar change in YI were modeled using a linear fixed-effects modeling approach. Due to the complex nature of haze formation, measurement uncertainty, and the differences in the samples’ responses, the change in haze (%) depended on individual samples’ responses and a linear mixed-effects modeling approach was used. When compared to fixed-effects models, the addition of random effects in the haze formation models significantly increased the variance explained. For both modeling approaches, diagnostic plots confirmed independence and homogeneity with normally distributed residual errors. Predictive R2 values for true prediction error and predictive power of the models demonstrated that the models were not subject to over-fitting. These models enable prediction under pre-defined exposure conditions for a given exposure time (or photo-dosage in case of UV light exposure). PET degradation under cyclic exposures combining UV light and condensing humidity is caused by photolytic and hydrolytic mechanisms causing yellowing and haze formation. Quantitative knowledge of these degradation pathways enable cross-correlation of these lab-based exposures with real-world conditions for service life prediction. PMID:28498875

Comparative study of neurologic effects of nano-TiO2 versus SiO2 after direct intracerebral exposure in mice

NASA Astrophysics Data System (ADS)

Balvay, A.; Thieriet, N.; Lakhdar, L.; Bencsik, A.

2013-04-01

Titanium and silicon dioxide nanoparticles (TiO2 and SiO2 NPs) are now in daily use in many commercial products of which food, sunscreens, toothpastes or cosmetics. However, their effects on human body, especially on the central nervous system, are still unclear. The aim of this study was to determine whether direct exposition of the brain to TiO2 and SiO2 NPs results in alternations in nervous system function. C57Bl6 mice were exposed to 5 and 10 μg doses of TiO2 and SiO2 NPs through intracerebroventricular administration using a stereotaxic approach. Then the neurologic effects were investigated using motor performance parameters, measured on a rotarod at 20 rpm or at an accelerating rod (from 4 to 40 rpm). Before and after injection, motor activity is registered individually for each mouse exposed, once a week, for 8 weeks. Besides, a group of 3 mice is culled at 1, 2, 3, 4 and 8 weeks after exposure in order to study the time dependant effect on the histopathology of the brain (gliosis, inflammatory process...). Both rotarod tests (accelerating and at 20 rpm) showed that TiO2 and SiO2 NPs exposure could significantly impair the motor performances, even several weeks after initial acute exposure. The first examination of the brain histopathology revealed microglial activation. As it appeared to grow throughout the brain in a time dependant manner this suggests the induction of a long lasting neuroinflammation. These primary findings indicated that exposure to TiO2 and SiO2 NPs could possibly impair the locomotor ability and this deficit may be possibly attributed at least to an inflammatory process maintained till 8 weeks after exposure in the mouse brain. To fully investigate the neurotoxicological consequences of TiO2 and SiO2 NPs exposure, brain contents in these NPs will be also investigated as well as other alterations like neurotransmitter levels. These preliminary data already underline the necessity of more in vivo studies to better characterize TiO2 and SiO2 NPs exposure effects especially on human brain for long-term and low-dose treatment.

Effects of long-time elevated temperature exposures on hot-isostatically-pressed power-metallurgy Udimet 700 alloys with reduced cobalt contents

NASA Technical Reports Server (NTRS)

Hart, F. H.

1984-01-01

Because almost the entire U.S. consumption of cobalt depends on imports, this metal has been designated "strategic'. The role and effectiveness of cobalt is being evaluated in commercial nickel-base superalloys. Udiment 700 type alloys in which the cobalt content was reduced from the normal 17% down to 12.7%, 8.5%, 4.3%, and 0% were prepared by standard powder metallurgy techniques and hot isostatically pressed into billets. Mechanical testing and microstructural investigations were performed. The mechanical properties of alloys with reduced cobalt contents which were heat-treated identically were equal or better than those of the standard alloy, except that creep rates tended to increase as cobalt was reduced. The effects of long time exposures at 760 C on mechanical properties and at 760 C and 845 C on microstructures were determined. Decreased tensile properties and shorter rupture lives with increased creep rates were observed in alloy modifications. The exposures caused gamma prime particle coarsening and formation of sigma phase in the alloys with higher cobalt contents. Exposure at 845 C also reduced the amount of MC carbides.

The effects of repeated exposure to graphic fear appeals on cigarette packages: A field experiment.

PubMed

Dijkstra, Arie; Bos, Colin

2015-03-01

Experimental studies on the effects of graphic fear appeals on cigarette packages typically expose smokers in a single session to a fear appeal, although in practice the exposure is always repeated. The present study applied an improved study design with repeated exposure to fear appeals on cigarette packages. In this field-experiment, 118 smokers were assigned to 1 of 2 conditions with either graphic fear appeals or textual warnings on their cigarette packages. During 3 weeks, fear and disgust were assessed 6 times. The intention to quit smoking after 3 weeks and quitting activity during the 3 weeks were the dependent measures. The effects of 3 pretest individual difference moderators were tested: disengagement beliefs, number of cigarettes smoked a day, and readiness to quit. Three weeks of exposure to the graphic fear appeals led to a stronger intention to quit, but only when smokers scored low on disengagement beliefs, or were heavier smokers. In addition, smokers low in disengagement more often reported to have cut down on smoking in the graphic condition. There were no indications of habituation of fear and disgust over the 3 weeks. The effects of graphic fear appeals depended on smokers' characteristics: The moderators may explain the mixed findings in the literature. The lack of habituation may be caused by the renewal of the graphics every few days. The used field-experimental design with natural repeated exposure to graphics is promising. (c) 2015 APA, all rights reserved).

Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy

PubMed Central

Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose; Breazeale, Kathryn G.; Price, Matthew; Davis, Michael; Duncan, Erica; Ressler, Kerry J.; Bradley, Bekh; Rizzo, Albert; Tuerk, Peter W.; Rothbaum, Barbara O.

2017-01-01

Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either D-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients’ level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). PMID:27183343

Pulmonary Cerium Dioxide Nanoparticles Exposure Differentially Impairs Coronary and Mesenteric Arteriolar Reactivity

PubMed Central

Minarchick, Valerie C; Stapleton, Phoebe A; Porter, Dale W; Wolfarth, Michael G; Çiftyürek, Engin; Barger, Mark; Sabolsky, Edward M.; Nurkiewicz, Timothy R

2013-01-01

Cerium dioxide nanoparticles (CeO2 NPs) are an engineered nanomaterial that possesses unique catalytic, oxidative and reductive properties. Currently, CeO2 NPs are being used as a fuel catalyst but these properties are also utilized in the development of potential drug treatments for radiation and stroke protection. These uses of CeO2 NPs present a risk for human exposure; however, to date no studies have investigated the effects of CeO2 NPs on the microcirculation following pulmonary exposure. Previous studies in our laboratory with other nanomaterials have shown impairments in normal microvascular function after pulmonary exposures. Therefore, we predicted that CeO2 NP exposure would cause microvascular dysfunction that is dependent on the tissue bed and dose. Twenty-four hour post exposure to CeO2 NPs (0–400 μg), mesenteric and coronary arterioles were isolated and microvascular function was assessed. Our results provided evidence that pulmonary CeO2 NP exposure impairs endothelium-dependent and -independent arteriolar dilation in a dose-dependent manner. The CeO2 NP exposure dose which causes a 50% impairment in arteriolar function (EC50) was calculated and ranged from 15 – 100 μg depending on the chemical agonist and microvascular bed. Microvascular assessments with acetylcholine revealed a 33–75% reduction in function following exposure. Additionally, there was a greater sensitivity to CeO2 NP exposure in the mesenteric microvasculature due to the 40% decrease in the calculated EC50 compared to the coronary microvasculature EC50. CeO2 NP exposure increased mean arterial pressure in some groups. Taken together these observed microvascular changes may likely have detrimental effects on local blood flow regulation and contribute to cardiovascular dysfunction associated with particle exposure. PMID:23645470

Images and Spectra of Time Dependent Two Component Advective Flow in Presence of Outflows

NASA Astrophysics Data System (ADS)

Chatterjee, Arka; Chakrabarti, Sandip K.; Ghosh, Himadri; Garain, Sudip K.

2018-05-01

Two Component Advective Flow (TCAF) successfully explains the spectral and temporal properties of outbursting or persistent sources. Images of static TCAF with Compton cloud or CENtrifugal pressure supported Boundary Layer (CENBOL) due to gravitational bending of photons have been studied before. In this paper, we study time dependent images of advective flows around a Schwarzschild black hole which include cooling effects due to Comptonization of soft photons from a Keplerian disks well as the self-consistently produced jets and outflows. We show the overall image of the disk-jet system after convolving with a typical beamwidth. A long exposure image with time dependent system need not show the black hole horizon conspicuously, unless one is looking at a soft state with no jet or the system along the jet axis. Assuming these disk-jet configurations are relevant to radio emitting systems also, our results would be useful to look for event horizons in high accretion rate Supermassive Black Holes in Seyfert galaxies, RL Quasars.

Structurally distinct polycyclic aromatic hydrocarbons induce differential transcriptional responses in developing zebrafish

PubMed Central

Goodale, Britton C.; Tilton, Susan C.; Wilson, Glenn; Corvi, Margaret M.; Janszen, Derek B.; Anderson, Kim A.; Waters, Katrina M.; Tanguay, Robert L.

2014-01-01

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous in the environment as components of fossil fuels and by-products of combustion. These multi-ring chemicals differentially activate the Aryl Hydrocarbon Receptor (AHR) in a structurally dependent manner, and induce toxicity via both AHR-dependent and-independent mechanisms. PAH exposure is known to induce developmental malformations in zebrafish embryos, and recent studies have shown cardiac toxicity induced by compounds with low AHR affinity. Unraveling the potentially diverse molecular mechanisms of PAH toxicity is essential for understanding the hazard posed by complex PAH mixtures present in the environment. We analyzed transcriptional responses to PAH exposure in zebrafish embryos exposed to benz(a)anthracene (BAA), dibenzothiophene (DBT) and pyrene (PYR) at concentrations that induced developmental malformations by 120 hours post-fertilization (hpf). Whole genome microarray analysis of mRNA expression at 24 and 48 hpf identified genes that were differentially regulated over time and in response to the three PAH structures. PAH body burdens were analyzed at both time points using GC-MS, and demonstrated differences in PAH uptake into the embryos. This was important for discerning dose-related differences from those that represented unique molecular mechanisms. While BAA misregulated the least number of transcripts, it caused strong induction of cyp1a and other genes known to be downstream of the AHR, which were not induced by the other two PAHs. Analysis of functional roles of misregulated genes and their predicted regulatory transcription factors also distinguished the BAA response from regulatory networks disrupted by DBT and PYR exposure. These results indicate that systems approaches can be used to classify the toxicity of PAHs based on the networks perturbed following exposure, and may provide a path for unraveling the toxicity of complex PAH mixtures. PMID:23656968

L-Ascorbate Protects Against Methamphetamine-Induced Neurotoxicity of Cortical Cells via Inhibiting Oxidative Stress, Autophagy, and Apoptosis.

PubMed

Huang, Ya-Ni; Yang, Ling-Yu; Wang, Jing-Ya; Lai, Chien-Cheng; Chiu, Chien-Tsai; Wang, Jia-Yi

2017-01-01

Methamphetamine (METH)-induced cell death contributes to the pathogenesis of neurotoxicity; however, the relative roles of oxidative stress, apoptosis, and autophagy remain unclear. L-Ascorbate, also called vitamin (Vit.) C, confers partial protection against METH neurotoxicity via induction of heme oxygenase-1. We further investigated the role of Vit. C in METH-induced oxidative stress, apoptosis, and autophagy in cortical cells. Exposure to lower concentrations (0.1, 0.5, 1 mM) of METH had insignificant effects on ROS production, whereas cells exposed to 5 mM METH exhibited ROS production in a time-dependent manner. We confirmed METH-induced apoptosis (by nuclear morphology revealed by Hoechst 33258 staining and Western blot showing the protein levels of pro-caspase 3 and cleaved caspase 3) and autophagy (by Western blot showing the protein levels of Belin-1 and conversion of microtubule-associated light chain (LC)3-I to LC3-II and autophagosome staining by monodansylcadaverine). The apoptosis as revealed by cleaved caspase-3 expression marked an increase at 18 h after METH exposure while both autophagic markers, Beclin 1 and LC3-II, marked an increase in cells exposed to METH for 6 and 24 h, respectively. Treating cells with Vit. C 30 min before METH exposure time-dependently attenuated the production of ROS. Vitamin C also attenuated METH-induced Beclin 1 and LC3-II expression and METH toxicity. Treatment of cells with Vit. C before METH exposure attenuated the expression of cleaved caspase-3 and reduced the number of METH-induced apoptotic cells. We suggest that the protective effect of Vit. C against METH toxicity might be through attenuation of ROS production, autophagy, and apoptosis.

Effects of extremely low frequency magnetic field on oxidative balance in brain of rats.

PubMed

Ciejka, Elzbieta; Kleniewska, P; Skibska, B; Goraca, A

2011-12-01

Extremely low frequency magnetic field (ELF-MF) may result in oxidative DNA damage and lipid peroxidation with an ultimate effect on a number of systemic disturbances and cell death. The aim of the study is to assess the effect of ELF-MF parameters most frequently used in magnetotherapy on reactive oxygen species generation (ROS) in brain tissue of experimental animals depending on the time of exposure to this field. The research material included adult male Sprague-Dawley rats, aged 3-4 months. The animals were divided into 3 groups: I - control (shame) group; II - exposed to the following parameters of the magnetic field: 7 mT, 40 Hz, 30 min/day, 10 days; III - exposed to the ELF-MF parameters of 7 mT, 40 Hz, 60 min/day, 10 days. The selected parameters of oxidative stress: thiobarbituric acid reactive substances (TBARS), hydrogen peroxide (H(2)O(2)), total free sulphydryl groups (-SH groups) and protein in brain homogenates were measured after the exposure of rats to the magnetic field. ELF-MF parameters of 7 mT, 40 Hz, 30 min/day for 10 days caused a significant increase in lipid peroxidation and insignificant increase in H(2)O(2) and free -SH groups. The same ELF-MF parameters but applied for 60 min/day caused a significant increase in free -SH groups and protein concentration in the brain homogenates indicating the adaptive mechanism. The study has shown that ELF-MF applied for 30 min/day for 10 days can affect free radical generation in the brain. Prolongation of the exposure to ELF-MF (60/min/day) caused adaptation to this field. The effect of ELF-MF irradiation on oxidative stress parameters depends on the time of animal exposure to magnetic field.

Effects of prenatal alcohol and cigarette exposure on offspring substance use in multiplex, alcohol-dependent families.

PubMed

O'Brien, Jessica W; Hill, Shirley Y

2014-12-01

Prenatal exposures to alcohol, cigarettes, and other drugs of abuse are associated with numerous adverse consequences for affected offspring, including increased risk for substance use and abuse. However, maternal substance use during pregnancy appears to occur more often in those with a family history of alcohol dependence. Utilizing a sample that is enriched for familial alcohol dependence and includes controls selected for virtual absence of familial alcohol dependence could provide important information on the relative contribution of familial risk and prenatal exposures to offspring substance use. A sample of multigenerational families specifically ascertained to be at either high or low risk for developing alcohol dependence (AD) provided biological offspring for a longitudinal prospective study. High-risk families were selected based on the presence of 2 alcohol-dependent sisters. Low-risk families were selected on the basis of minimal first and second-degree relatives with AD. High-risk (HR = 99) and Low-risk offspring (LR = 110) were assessed annually during childhood and biennially in young adulthood regarding their alcohol, drug, and cigarette use. At the first childhood visit, mothers were interviewed concerning their prenatal use of substances. High-risk mothers were more likely to use alcohol, cigarettes, and other drugs during pregnancy than low-risk control mothers, and to consume these substances in greater quantities. Across the sample, prenatal exposure to alcohol was associated with increased risk for both offspring cigarette use and substance use disorders (SUD), and prenatal cigarette exposure was associated with increased risk for offspring cigarette use. Controlling for risk status by examining patterns within the HR sample, prenatal cigarette exposure remained a specific predictor of offspring cigarette use, and prenatal alcohol exposure was specifically associated with increased risk for offspring SUD. Women with a family history of SUD are at increased risk for substance use during pregnancy. Both familial loading for alcohol dependence and prenatal exposure to alcohol or cigarettes are important risk factors in the development of offspring substance use. An inadequate assessment of family history may obscure important interactions between familial risk and prenatal exposures on offspring outcomes. Copyright © 2015 by the Research Society on Alcoholism.

The effect of differences in time to detection of circulating microbubbles on the risk of decompression sickness

NASA Technical Reports Server (NTRS)

Kumar, K. V.; Gilbert, J. H.; Powell, M. R.; Waligora, J. M.

1992-01-01

Circulating microbubbles (CMB) are frequently detected prior to the appearance of symptoms of Decompression Sickness (DCS). It is difficult to analyze the effect of CMB on symptoms due to differences in the time to detection of CMB. This paper uses survival analysis models to evaluate the risk of symptoms in the presence of CMB. Methods: Information on 81 exposures to an altitude of 6,400 m (6.5 psi) for a period of three hours, with simulated extravehicular activities, was examined. The presence or absence of CMB was included as a time dependent covariate of the Cox proportional hazards regression model. Using this technique, the subgroup of exposures with CMB was analyzed further. Mean (S.D.) time in minutes to onset of CMB and symptoms were 125 (63) and 165 (33) respectively, following the three hours exposure. The risk of symptoms (17/81) increased 14 times in the presence of CMB, after controlling for variations in time to detection of CMB. Further, the risk was lower when time to detection of CMB was greater than 60 minutes (risk ratio = 0.96; 95 percent confidence intervals = 0.94 - 0.99 0.99 P less than 0.01) compared to CMB before 60 minutes at altitude. Conclusions: Survival analysis showed that individual risk of DCS changes significantly due to variations in time to detection of CMB. This information is important in evaluating the risk of DCS in the presence of CMB.

In Vitro Activity of Manuka Honey and Polyhexamethylene Biguanide on Filamentous Fungi and Toxicity to Human Cell Lines

PubMed Central

Yabes, Joseph M.; White, Brian K.; Murray, Clinton K.; Sanchez, Carlos J.; Mende, Katrin; Beckius, Miriam L.; Zera, Wendy C.; Wenke, Joseph C.; Akers, Kevin S.

2016-01-01

Soft-tissue invasive fungal infections are increasingly recognized as significant entities directly contributing to morbidity and mortality. They complicate clinical care, requiring aggressive surgical debridement and systemic antifungal therapy. To evaluate new topical approaches to therapy, we examined the antifungal activity and cytotoxicity of Manuka Honey (MH) and polyhexamethylene biguanide (PHMB). The activities of multiple concentrations of MH (40%, 60%, 80%) and PHMB (0.01%, 0.04%, 0.1%) against 13 clinical mold isolates were evaluated using a time-kill assay between 5 min and 24 h. Concentrations were selected to represent current clinical use. Cell viability was examined in parallel for human epidermal keratinocytes, dermal fibroblasts and osteoblasts, allowing determination of the 50% viability (LD50) concentration. Antifungal activity of both agents correlated more closely with exposure time than concentration. Exophiala and Fusarium growth was completely suppressed at 5 min for all PHMB concentrations, and at 12 and 6 h, respectively, for all MH concentrations. Only Lichtheimia had persistent growth to both agents at 24 h. Viability assays displayed concentration-and time-dependent toxicity for PHMB. For MH, exposure time predicted cytotoxicity only when all cell types were analyzed in aggregate. This study demonstrates that MH and PHMB possess primarily time-dependent antifungal activity, but also exert in vitro toxicity on human cells which may limit clinical use. Further research is needed to determine ideal treatment strategies to optimize antifungal activity against molds while limiting cytotoxicity against host tissues in vivo. PMID:27601610

Congenital Dandy Walker malformation associated with first trimester warfarin: a case report and literature review.

PubMed

Kaplan, L C

1985-12-01

While the warfarin embryopathy is well defined, central nervous system abnormalities associated with gestational warfarin exposure require further definition. Based on the timing of warfarin exposure in humans, it has been proposed that second- and third-trimester exposure predisposes to CNS abnormalities while first-trimester exposure more typically is associated with the warfarin embryopathy. A case is presented of a liveborn male with Dandy Walker malformation, agenesis of the corpus callosum, and Peter anomaly of the right eye who was exposed to warfarin between the 8th and 12th weeks of gestation who had none of the stigmata of the warfarin embryopathy. His is the first known case of exposure confined to the first trimester, and the fifth case of Dandy Walker malformation among a total of 15 CNS cases associated with this drug. This case offers evidence that Dandy Walker malformation may represent a distinct complication of in utero first-trimester exposure, and consideration of these particular abnormalities with exposure limited to a period prior to the known appearance of vitamin K-dependent clotting factors suggests that warfarin has a direct teratogenic effect on central nervous system morphogenesis.

Pre-exposure to cocaine or morphine attenuates taste avoidance conditioning in adolescent rats: Drug specificity in the US pre-exposure effect.

PubMed

Clasen, Matthew M; Hempel, Briana J; Riley, Anthony L

2017-05-01

Although the attenuating effects of drug history on conditioned taste avoidance (CTA) learning have been widely investigated in adults, such effects in adolescents have not been well characterized. Recent research has suggested that the display of the drug pre-exposure effect during adolescence may be drug dependent given that pre-exposure to ethanol attenuates subsequent conditioning, whereas pre-exposure to the classic emetic lithium chloride (LiCl) fails to do so. The present study began investigating the possible drug-dependent nature of the effects of drug pre-exposure by pre-exposing and conditioning adolescent male Sprague-Dawley rats to drugs from two additional classes, specifically psychostimulants (cocaine; Experiment 1) and opioids (morphine; Experiment 2). Consistent with prior work with ethanol (but not LiCl), prior exposure to both cocaine and morphine attenuated taste avoidance induced by these compounds. Although this work supports the view of drug-dependent pre-exposure effects on taste avoidance learning during adolescence, research is needed to assess its mechanisms. © 2017 Wiley Periodicals, Inc.

Vitamin D Synthesis by UV Radiation: the Importance of Ozone Monitoring

NASA Astrophysics Data System (ADS)

Olds, W. J.; Moore, M. R.; Kimlin, M. G.

2006-12-01

The majority of humans rely on incidental sun exposure to maintain vitamin D sufficiency. Depending on where thresholds of vitamin D "sufficiency" are defined, it was recently stated that up to one billion people worldwide have suboptimal vitamin D levels (Bouillon, R., University of Leuven). Even in sunny southeast Queensland, the world's skin cancer capital, a 2006 study uncovered deficiency rates of up to 78% (at a threshold of 75 nmol/L of circulating 25-hydroxyvitamin D). Vitamin D regulates calcium absorption and inadequate levels are proven to result in osteomalacia, osteoporosis, rickets, bone pain and general skeletal weakness. Recent evidence also suggests vitamin D plays a preventative role in autoimmune diseases including numerous cancers, diabetes, schizophrenia, coronary heart disease, depression and other disorders. The most promising means of alleviating the worldwide burden of vitamin D deficiency seems to be by increased UV exposure. However, a much more mature understanding of UV exposures encountered in everyday life is required. This understanding is fundamentally founded in geophysics. UV exposures are strongly influenced by season/time of year, time of day, climate, location, pollution, aerosols and, importantly, ozone. In this work, we use computer simulations to obtain daily totals of vitamin D producing UV at numerous latitudes during one year. The ozone concentration is varied from 260 DU to 360 DU to determine the role of ozone variability on the ambient levels of vitamin D UV. Vitamin D synthesis is highly dependent on UVB. In our results, we demonstrate that this has important implications. Namely, vitamin D is strongly affected by ozone variability, since ozone filters UVB more strongly than UVA. Moreover, since erythema (sunburn) can occur at UVA wavelengths, ozone variation will more strongly affect vitamin D synthesis than erythema. Our results highlight that ozone monitoring is essential for understanding appropriate UV exposures for vitamin D health. We finally discuss implications for population health and how geophysics continues to play a vital role in addressing the widespread dilemma of vitamin D deficiency.

Prediction of Drug-Drug Interactions with Crizotinib as the CYP3A Substrate Using a Physiologically Based Pharmacokinetic Model.

PubMed

Yamazaki, Shinji; Johnson, Theodore R; Smith, Bill J

2015-10-01

An orally available multiple tyrosine kinase inhibitor, crizotinib (Xalkori), is a CYP3A substrate, moderate time-dependent inhibitor, and weak inducer. The main objectives of the present study were to: 1) develop and refine a physiologically based pharmacokinetic (PBPK) model of crizotinib on the basis of clinical single- and multiple-dose results, 2) verify the crizotinib PBPK model from crizotinib single-dose drug-drug interaction (DDI) results with multiple-dose coadministration of ketoconazole or rifampin, and 3) apply the crizotinib PBPK model to predict crizotinib multiple-dose DDI outcomes. We also focused on gaining insights into the underlying mechanisms mediating crizotinib DDIs using a dynamic PBPK model, the Simcyp population-based simulator. First, PBPK model-predicted crizotinib exposures adequately matched clinically observed results in the single- and multiple-dose studies. Second, the model-predicted crizotinib exposures sufficiently matched clinically observed results in the crizotinib single-dose DDI studies with ketoconazole or rifampin, resulting in the reasonably predicted fold-increases in crizotinib exposures. Finally, the predicted fold-increases in crizotinib exposures in the multiple-dose DDI studies were roughly comparable to those in the single-dose DDI studies, suggesting that the effects of crizotinib CYP3A time-dependent inhibition (net inhibition) on the multiple-dose DDI outcomes would be negligible. Therefore, crizotinib dose-adjustment in the multiple-dose DDI studies could be made on the basis of currently available single-dose results. Overall, we believe that the crizotinib PBPK model developed, refined, and verified in the present study would adequately predict crizotinib oral exposures in other clinical studies, such as DDIs with weak/moderate CYP3A inhibitors/inducers and drug-disease interactions in patients with hepatic or renal impairment. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

The dynamics of categorization: Unraveling rapid categorization.

PubMed

Mack, Michael L; Palmeri, Thomas J

2015-06-01

We explore a puzzle of visual object categorization: Under normal viewing conditions, you spot something as a dog fastest, but at a glance, you spot it faster as an animal. During speeded category verification, a classic basic-level advantage is commonly observed (Rosch, Mervis, Gray, Johnson, & Boyes-Braem, 1976), with categorization as a dog faster than as an animal (superordinate) or Golden Retriever (subordinate). A different story emerges during ultra-rapid categorization with limited exposure duration (<30 ms), with superordinate categorization faster than basic or subordinate categorization (Thorpe, Fize, & Marlot, 1996). These two widely cited findings paint contrary theoretical pictures about the time course of categorization, yet no previous study has investigated them together. We systematically examined two experimental factors that could explain the qualitative difference in categorization across the two paradigms: exposure duration and category trial context. Mapping out the time course of object categorization by manipulating exposure duration and the timing of a post-stimulus mask revealed that brief exposure durations favor superordinate-level categorization, but with more time a basic-level advantage emerges. However, these advantages were modulated by category trial context. With randomized target categories, the superordinate advantage was eliminated; and with only four repetitions of superordinate categorization within an otherwise randomized context, the basic-level advantage was eliminated. Contrary to theoretical accounts that dictate a fixed priority for certain levels of abstraction in visual processing and access to semantic knowledge, the dynamics of object categorization are flexible, depending jointly on the level of abstraction, time for perceptual encoding, and category context. (c) 2015 APA, all rights reserved).

THE DYNAMICS OF CATEGORIZATION: UNRAVELING RAPID CATEGORIZATION

PubMed Central

Mack, Michael L.; Palmeri, Thomas J.

2015-01-01

We explore a puzzle of visual object categorization: Under normal viewing conditions, you spot something as a dog fastest, but at a glance, you spot it faster as an animal. During speeded category verification, a classic basic-level advantage is commonly observed (Rosch, Mervis, Gray, Johnson, & Boyes-Braem, 1976), with categorization as a dog faster than as an animal (superordinate) or Golden Retriever (subordinate). A different story emerges during ultra-rapid categorization with limited exposure duration (<30ms), with superordinate categorization faster than basic or subordinate categorization (Thorpe, Fize, & Marlot, 1996). These two widely cited findings paint contrary theoretical pictures about the time course of object categorization, yet no study has previously investigated them together. Over five experiments, we systematically examined two experimental factors that could explain the qualitative difference in categorization across the two paradigms: exposure duration and category trial context. Mapping out the time course of object categorization by manipulating exposure duration and the timing of a post-stimulus mask revealed that brief exposure durations favor superordinate-level categorization, but with more time a basic-level advantage emerges. But this superordinate advantage was modulated significantly by target category trial context. With randomized target categories, the superordinate advantage was eliminated; and with “blocks” of only four repetitions of superordinate categorization within an otherwise randomized context, the advantage for the basic-level was eliminated. Contrary to some theoretical accounts that dictate a fixed priority for certain levels of abstraction in visual processing and access to semantic knowledge, the dynamics of object categorization are flexible, depending jointly on the level of abstraction, time for perceptual encoding, and category context. PMID:25938178

Investigating the American Time Use Survey from an exposure modeling perspective.

PubMed

George, Barbara Jane; McCurdy, Thomas

2011-01-01

This paper describes an evaluation of the US Bureau of Labor Statistics' American Time Use Survey (ATUS) for potential use in modeling human exposures to environmental pollutants. The ATUS is a large, on-going, cross-sectional survey of where Americans spend time and what activities they undertake in those locations. The data are reported as a series of sequential activities over a 24-h time period--a "diary day"--starting at 0400 hours. Between 12,000 and 13,000 surveys are obtained each year and the Bureau has plans to continue ATUS for the foreseeable future. The ATUS already has about 73,000 diary days of data, more than twice as many as that which currently exists in the US Environmental Protection Agency's (EPA) "Consolidated Human Activity Database" (CHAD) that the Agency uses for exposure modeling purposes. There are limitations for using ATUS in modeling human exposures to environmental pollutants. The ATUS does not report the location for a number of activities regarded as "personal." For 2006, personal activities with missing location information totaled 572 min/day, on average, for survey participants: about 40% of their day. Another limitation is that ATUS does not distinguish between indoor and outdoor activities at home, two of the traditional locational demarcations used in human exposure modeling. This lack of information affects exposure estimates to both indoor and outdoor air pollutants and potentially affects non-dietary ingestion estimates for children, which can vary widely depending on whether or not a child is indoors. Finally, a detailed analysis of the work travel activity in a subsample from ATUS 2006 indicates that the coding scheme is not fully consistent with a CHAD-based exposure modeling approach. For ATUS respondents in this subsample who reported work as an activity, roughly 48% of their days were missing work travel at one or both ends of the work shift or reported within work-shift travel inconsistently. An extensive effort would be needed to recode work travel data from ATUS for EPA's exposure modeling purposes.

Temporal aspects of tumorigenic response to individual and mixed carcinogens. Comprehensive progress report, June 1, 1975--May 31, 1978. [Mouse skin, rats, hamsters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Albert, R.E.; Burns, F.J.; Altshuler, B.

1978-02-01

The research proposed here is designed to obtain a better understanding of the temporal kinetics of tumor induction when one or more carcinogens are present simultaneously or sequentially for prolonged periods of time. Studies done to date under this contract have shown that carcinogenesis in mouse skin by polycyclic aromatic hydrocarbon carcinogens is consistent with the induction of dependent and autonomous cell transformations by the carcinogen followed by the conversion of autonomous tumor cells into malignancies at a rate which is determined by the level of carcinogen exposure. Dependent cell transformations remain latent in the skin unless expressed by amore » promoting agent. Dependent neoplasia appears to follow one-hit kinetics while malignancy is a multihit endpoint. Dose-related and time-related aspects of tumor induction are separable in the initiation-promotion system of mouse skin which along with rat skin and hamster lung is being used as a model for testing hypotheses. Results to date provide the basis for a new interpretation of the linear non-threshold extrapolation model. The broad aim of the study is to provide a basis or rationale for estimating risks associated with prolonged exposures to carcinogens found in the environment and to predict how different tissues and species respond to the same carcinogens.« less

Transcriptional up-regulation of the human androgen receptor by androgen in bone cells.

PubMed

Wiren, K M; Zhang, X; Chang, C; Keenan, E; Orwoll, E S

1997-06-01

Androgen regulation of androgen receptor (AR) expression has been observed in a variety of tissues, generally as inhibition, and is thought to attenuate cellular responses to androgen. AR is expressed in osteoblasts, the bone-forming cell, suggesting direct actions of androgens on bone. Here we characterized the effect of androgen exposure on AR gene expression in human osteoblastic SaOS-2 and U-2 OS cells. Treatment of osteoblastic cells with the nonaromatizable androgen 5alpha-dihydrotestosterone increased AR steady state messenger RNA levels in a time- and dose-dependent fashion. Reporter assays with 2.3 kilobases of the proximal 5'-flanking region of the human AR promoter linked to the chloramphenicol acetyltransferase gene in transfected cultures showed that up-regulation of AR promoter activity by androgen was time and dose dependent. Treatment with other steroid hormones, including progesterone, 17beta-estradiol, and dexamethasone, was without effect. The antiandrogen hydroxyflutamide completely antagonized androgen up-regulation. Thus, in contrast to many other androgen target tissues, androgen exposure increases steady state AR messenger RNA levels in osteoblasts. This regulation occurs at least partially at the level of transcription, is mediated by the 5'-promoter region of the AR gene, and is dependent on functional AR. These results suggest that physiological concentrations of androgens have significant effects on AR expression in skeletal tissue.

A threatened beluga (Delphinapterus leucas) population in the traffic lane: vessel-generated noise characteristics of the Saguenay-St. Lawrence Marine Park, Canada.

PubMed

McQuinn, Ian H; Lesage, Véronique; Carrier, Dominic; Larrivée, Geneviève; Samson, Yves; Chartrand, Sylvain; Michaud, Robert; Theriault, James

2011-12-01

The threatened resident beluga population of the St. Lawrence Estuary shares the Saguenay-St. Lawrence Marine Park with significant anthropogenic noise sources, including marine commercial traffic and a well-established, vessel-based whale-watching industry. Frequency-dependent (FD) weighting was used to approximate beluga hearing sensitivity to determine how noise exposure varied in time and space at six sites of high beluga summer residency. The relative contribution of each source to acoustic habitat degradation was estimated by measuring noise levels throughout the summer and noise signatures of typical vessel classes with respect to traffic volume and sound propagation characteristics. Rigid-hulled inflatable boats were the dominant noise source with respect to estimated beluga hearing sensitivity in the studied habitats due to their high occurrence and proximity, high correlation with site-specific FD-weighted sound levels, and the dominance of mid-frequencies (0.3-23 kHz) in their noise signatures. Median C-weighted sound pressure level (SPL(RMS)) had a range of 19 dB re 1 μPa between the noisiest and quietest sites. Broadband SPL(RMS) exceeded 120 dB re 1 μPa 8-32% of the time depending on the site. Impacts of these noise levels on St. Lawrence beluga will depend on exposure recurrence and individual responsiveness. © 2011 Acoustical Society of America

Mechanism of low-level laser therapy (LLLT) effects on rat mast cells

NASA Astrophysics Data System (ADS)

Popov, Gennady K.; Solovyova, Ludmila I.; Kosel, Arnold I.

2000-11-01

The low power laser radiation is widely applied for treatment of various diseases. In our research we investigated the influence of low power laser radiation on the mast cells degranulation process. The object of the research were the mesentery mast cells of the rat thin intestine. A loop of thin intestine was irradiated by the therapeutic diode laser device Uley - 2K (lambda - 890 nm, pulse). The process of mast cells degranulation served as a criterion for their functional activity estimation. The estimation was fulfilled with the help of light microscope (toluidine blue staining, pH02,0; degranulating mast cells counting on 100 cells; immersion technique; X 980). To study the dependence of degranulation process of mast cells irradiated with lasre from intracellular calcium (Ca2+) concentration we applied 0,000015 M solution of verapamil, which was applied to the mesentery for 2 minutes. Laser radiation (890 nm) stimulates mesentery mast cells degranulation. This effect is dose-dependent. Maximal degranulation was registered after laser irradiation wiht power 25 mW, exposure time 15-30 s (energy density 7.5 x 103 J/m2 to 6 x 104 j/m2). Further increasing of exposure time caused the effect decreasing. The results of our experiments with verpamil let us suppose light interaction with the voltage-dependent subunit of calcium channel, changing intracellular Ca2+ and leading to stimulatory effects.

Beyond crosswalks: reliability of exposure assessment following automated coding of free-text job descriptions for occupational epidemiology.

PubMed

Burstyn, Igor; Slutsky, Anton; Lee, Derrick G; Singer, Alison B; An, Yuan; Michael, Yvonne L

2014-05-01

Epidemiologists typically collect narrative descriptions of occupational histories because these are less prone than self-reported exposures to recall bias of exposure to a specific hazard. However, the task of coding these narratives can be daunting and prohibitively time-consuming in some settings. The aim of this manuscript is to evaluate the performance of a computer algorithm to translate the narrative description of occupational codes into standard classification of jobs (2010 Standard Occupational Classification) in an epidemiological context. The fundamental question we address is whether exposure assignment resulting from manual (presumed gold standard) coding of the narratives is materially different from that arising from the application of automated coding. We pursued our work through three motivating examples: assessment of physical demands in Women's Health Initiative observational study, evaluation of predictors of exposure to coal tar pitch volatiles in the US Occupational Safety and Health Administration's (OSHA) Integrated Management Information System, and assessment of exposure to agents known to cause occupational asthma in a pregnancy cohort. In these diverse settings, we demonstrate that automated coding of occupations results in assignment of exposures that are in reasonable agreement with results that can be obtained through manual coding. The correlation between physical demand scores based on manual and automated job classification schemes was reasonable (r = 0.5). The agreement between predictive probability of exceeding the OSHA's permissible exposure level for polycyclic aromatic hydrocarbons, using coal tar pitch volatiles as a surrogate, based on manual and automated coding of jobs was modest (Kendall rank correlation = 0.29). In the case of binary assignment of exposure to asthmagens, we observed that fair to excellent agreement in classifications can be reached, depending on presence of ambiguity in assigned job classification (κ = 0.5-0.8). Thus, the success of automated coding appears to depend on the setting and type of exposure that is being assessed. Our overall recommendation is that automated translation of short narrative descriptions of jobs for exposure assessment is feasible in some settings and essential for large cohorts, especially if combined with manual coding to both assess reliability of coding and to further refine the coding algorithm.

Exposure to Ambient Particulate Matter during Specific Gestational Periods Produces Adverse Obstetric Consequences in Mice

PubMed Central

Blum, Jason L.; Chen, Lung-Chi

2017-01-01

Background: Epidemiological studies associate inhalation of fine-sized particulate matter (PM2.5) during pregnancy with preterm birth (PTB) and low birth weight (LBW) but disagree over which time frames are most sensitive, or if effects are cumulative. Objectives: Our objective was to provide experimental plausibility for epidemiological observations by testing the hypothesis that exposure to PM2.5 during discrete periods of pregnancy results in PTB and LBW. Methods: For the first study, timed-pregnant B6C3F1 mice were exposed to concentrated ambient PM2.5 (CAPs) or filtered air (FA) throughout pregnancy [6 h/d from gestational day (GD) 0.5 through GD16.5]. A follow-up study examined the effects of CAPs exposure during discrete gestational periods (1: GD0.5–5.5; 2: GD6.5–14.5; 3: GD14.5–16.5; 4: GD0.5–16.5) aligning to milestones during human development. Results: In the first experiment, exposure to 160 μg CAPs/m3 throughout pregnancy decreased gestational term by 0.5 d (∼1.1  wk decrease for humans) and birth weight by 11.4% compared with FA. The follow-up experiment investigated timing of CAPs exposure (mean concentrations at 178, 193, 171, and 173 μg/m3 for periods 1–4, respectively). Pregnancy was significantly shortened (vs. FA) by ∼0.4d when exposure occurred during gestational periods 2 and 4, and by ∼0.5d if exposure occurred during period 3. Exposure during periods 1, 2, and 4 reduced birth weight by ∼10% compared with FA, and placental weight was reduced (∼8%) on GD17.5 if exposure occurred only during period 3. Conclusions: Adverse PM2.5-induced outcomes such as PTB and LBW are dependent upon the periods of maternal exposure. The results of these experimental studies could contribute significantly to air pollution policy decisions in the future. https://doi.org/10.1289/EHP1029 PMID:28893721

Preconception Brief: Occupational/Environmental Exposures

PubMed Central

Gehle, Kim

2006-01-01

In the last decade, more than half of U.S. children were born to working mothers and 65% of working men and women were of reproductive age. In 2004 more than 28 million women age 18–44 were employed full time. This implies the need for clinicians to possess an awareness about the impact of work on the health of their patients and their future offspring. Most chemicals in the workplace have not been evaluated for reproductive toxicity, and where exposure limits do exist, they were generally not designed to mitigate reproductive risk. Therefore, many toxicants with unambiguous reproductive and developmental effects are still in regular commercial or therapeutic use and thus present exposure potential to workers. Examples of these include heavy metals, (lead, cadmium), organic solvents (glycol ethers, percholoroethylene), pesticides and herbicides (ethylene dibromide) and sterilants, anesthetic gases and anti-cancer drugs used in healthcare. Surprisingly, many of these reproductive toxicants are well represented in traditional employment sectors of women, such as healthcare and cosmetology. Environmental exposures also figure prominently in evaluating a woman’s health risk and that to a pregnancy. Food and water quality and pesticide and solvent usage are increasingly topics raised by women and men contemplating pregnancy. The microenvironment of a woman, such as her choices of hobbies and leisure time activities also come into play. Caregivers must be aware of their patients’ potential environmental and workplace exposures and weigh any risk of exposure in the context of the time-dependent window of reproductive susceptibility. This will allow informed decision-making about the need for changes in behavior, diet, hobbies or the need for added protections on the job or alternative duty assignment. Examples of such environmental and occupational history elements will be presented together with counseling strategies for the clinician. PMID:16897370

DNA adducts and liver DNA replication in rats during chronic exposure to N-nitrosodimethylamine (NDMA) and their relationships to the dose-dependence of NDMA hepatocarcinogenesis.

PubMed

Souliotis, Vassilis L; Henneman, John R; Reed, Carl D; Chhabra, Saranjit K; Diwan, Bhalchandra A; Anderson, Lucy M; Kyrtopoulos, Soterios A

2002-03-20

Exposure of rats to the hepatocarcinogen N-nitrosodimethylamine (NDMA) (0.2-2.64 ppm in the drinking water) for up to 180 days resulted in rapid accumulation of N7- and O6-methylguanine in liver and white blood cell DNA, maximum adduct levels being reached within 1-7 days, depending on the dose. The levels of both adducts remained constant up to treatment day 28, subsequently declining slowly to about 40% of maximal levels for the liver and 60% for white blood cells by day 180. In order to elucidate the role of DNA replication in NDMA hepatocarcinogenesis, changes in liver cell labeling index (LI) were also measured on treatment days 21, 120 and 180. Although the time- and dose-dependence of the observed effects were complex, a clear trend towards increased rates of hepatocyte LI, as indicated by BrdU incorporation, with increasing NDMA doses was evident, particularly above 1 ppm, a concentration above which NDMA hepatocarcinogenicity is known to increase sharply. In contrast, no increase in Kupffer cell DNA replication was found at any of the doses employed, in accordance with the low susceptibility of these cells to NDMA-induced carcinogenesis. No significant increase in the occurrence of necrotic or apoptotic cells was noted under the treatment conditions employed. These results suggest that, in addition to the accumulation of DNA damage, alterations in hepatocyte DNA replication during the chronic NDMA exposure may influence the dose-dependence of its carcinogenic efficacy.

Time Averaged Transmitter Power and Exposure to Electromagnetic Fields from Mobile Phone Base Stations

PubMed Central

Bürgi, Alfred; Scanferla, Damiano; Lehmann, Hugo

2014-01-01

Models for exposure assessment of high frequency electromagnetic fields from mobile phone base stations need the technical data of the base stations as input. One of these parameters, the Equivalent Radiated Power (ERP), is a time-varying quantity, depending on communication traffic. In order to determine temporal averages of the exposure, corresponding averages of the ERP have to be available. These can be determined as duty factors, the ratios of the time-averaged power to the maximum output power according to the transmitter setting. We determine duty factors for UMTS from the data of 37 base stations in the Swisscom network. The UMTS base stations sample contains sites from different regions of Switzerland and also different site types (rural/suburban/urban/hotspot). Averaged over all regions and site types, a UMTS duty factor F ≈ 0.32 ± 0.08 for the 24 h-average is obtained, i.e., the average output power corresponds to about a third of the maximum power. We also give duty factors for GSM based on simple approximations and a lower limit for LTE estimated from the base load on the signalling channels. PMID:25105551

Ozone disinfection of home nebulizers effectively kills common cystic fibrosis bacterial pathogens.

PubMed

Towle, Dana; Baker, Vanisha; Schramm, Craig; O'Brien, Matthew; Collins, Melanie S; Feinn, Richard; Murray, Thomas S

2018-05-01

The Cystic Fibrosis Foundation (CFF) recommends routine nebulizer disinfection for patients but compliance is challenging due to the heavy burden of home care. SoClean® is a user friendly ozone based home disinfection device currently for home respiratory equipment. The objective of this study was to determine whether SoClean® has potential as a disinfection device for families with CF by killing CF associated bacteria without altering nebulizer output. Ozone based disinfection effectively kills bacterial pathogens inoculated to home nebulizer equipment without gross changes in nebulizer function. Common bacterial pathogens associated with CF were inoculated onto the PariLC® jet nebulizer and bacterial recovery compared with or without varied ozone exposure. In separate experiments, nebulizer output was estimated after repeated ozone exposure by weighing the nebulizer. Ozone disinfection was time dependent with a 5 min infusion time and 120 min dwell time effectively killing >99.99% bacteria tested including Pseudomonas aeruginosa and Staphylococcus aureus. Over 250 h of repeat ozone exposure did not alter nebulizer output. This suggests SoClean® has potential as a user-friendly disinfection technique for home respiratory equipment. © 2018 Wiley Periodicals, Inc.

Wavelength dependence of laser-induced retinal injury

NASA Astrophysics Data System (ADS)

Lund, David J.; Edsall, Peter; Stuck, Bruce E.

2005-04-01

The threshold for laser-induced retinal damage is dependent primarily upon the laser wavelength and the exposure duration. The study of the wavelength dependence of the retinal damage threshold has been greatly enhanced by the availability of tunable lasers. The Optical Parametric Oscillator (OPO), capable of providing useful pulse energy throughout a tuning range from 400 nm to 2200 nm, made it possible to determine the wavelength dependence of laser-induced retinal damage thresholds for q-switched pulses throughout the visible and NIR spectrum. Studies using the a tunable TI:Saph laser and several fixed-wavelength lasers yielded threshold values for 0.1 s exposures from 440 nm to 1060 nm. Laser-induced retinal damage for these exposure durations results from thermal conversion of the incident laser irradiation and an action spectrum for thermal retinal damage was developed based on the wavelength dependent transmission and absorption of ocular tissue and chromatic aberration of the eye optics. Long (1-1000s) duration exposures to visible laser demonstrated the existence of non-thermal laser-induced retinal damage mechanisms having a different action spectrum. This paper will present the available data for the wavelength dependence of laser-induced thermal retinal damage and compare this data to the maximum permissible exposure levels (MPEs) provided by the current guidelines for the safe use of lasers.

Comparative MicroRNA Expression Patterns in Fibroblasts after Low and High Doses of Low-LET Radiation Exposure

NASA Technical Reports Server (NTRS)

Maes, Olivier C.; Xu, Suying; Hada, Megumi; Wu, Honglu; Wang, Eugenia

2007-01-01

Exposure to ionizing radiation causes DNA damage to cells, and provokes a plethora of cellular responses controlled by unique gene-directed signaling pathways. MicroRNAs (miRNAs) are small (22-nucleotide), non-coding RNAs which functionally silence gene expression by either degrading the messages or inhibiting translation. Here we investigate radiation-dependent changes in these negative regulators by comparing the expression patterns of all 462 known human miRNAs in fibroblasts, after exposure to low (0.1 Gy) or high (2 Gy) doses of X-rays at 30 min, 2, 6 and 24 hrs post-treatment. The expression patterns of microRNAs after low and high doses of radiation show a similar qualitative down-regulation trend at early (0.5 hr) and late (24 hr) time points, with a quantitatively steeper slope following the 2 Gy exposures. Interestingly, an interruption of this downward trend is observed after the 2 Gy exposure, i.e. a significant up-regulation of microRNAs at 2 hrs, then reverting to the downward trend by 6 hrs; this interruption at the intermediate time point was not observed with the 0.1 Gy exposure. At the early time point (0.5 hr), candidate gene targets of selected down-regulated microRNAs, common to both 0.1 and 2 Gy exposures, were those functioning in chromatin remodeling. Candidate target genes of unique up-regulated microRNAs seen at a 2 hr intermediate time point, after the 2 Gy exposure only, are those involved in cell death signaling. Finally, putative target genes of down-regulated microRNAs seen at the late (24 hr) time point after either doses of radiation are those involved in the up-regulation of DNA repair, cell signaling and homeostasis. Thus we hypothesize that after radiation exposure, microRNAs acting as hub negative regulators for unique signaling pathways needed to be down-regulated so as to de-repress their target genes for the proper cellular responses, including DNA repair and cell maintenance. The unique microRNAs up-regulated at 2 hr after 2 Gy suggest the cellular response to functionally suppress the apoptotic death signaling reflex after exposure to high dose radiation. Further analyses with transcriptome and global proteomic profiling will validate the reciprocal expression of signature microRNAs selected in our radiation-exposed cells, and their candidate target gene families, and test our hypothesis that unique radiation-specific microRNAs are keys in governing signaling responses for damage control of this environmental hazard.

Basic Characteristics of Laser Heating in Thermoluminescence and of Laser-Stimulated Luminescence

DTIC Science & Technology

1990-07-15

as examples. These include LiF:Mg,Ti ( TLD -100, Harshaw Chemical Corporation) in form of chips, which are widely used in the dosimetry of ionizing...take dosimetry ( TLD ) of ionizing radiation because it holds pro- the form of discrete circular spots whose diameter is smaller mise as a solution to...function of typical phosphor, we choose the most widely used dosimetry time after onset of the laser exposure, the time-dependent material LiF:Mg,Ti ( TLD

The role of cadmium in obesity and diabetes.

PubMed

Tinkov, Alexey A; Filippini, Tommaso; Ajsuvakova, Olga P; Aaseth, Jan; Gluhcheva, Yordanka G; Ivanova, Juliana M; Bjørklund, Geir; Skalnaya, Margarita G; Gatiatulina, Eugenia R; Popova, Elizaveta V; Nemereshina, Olga N; Vinceti, Marco; Skalny, Anatoly V

2017-12-01

Multiple studies have shown an association between environmental exposure to hazardous chemicals including toxic metals and obesity, diabetes, and metabolic syndrome. At the same time, the existing data on the impact of cadmium exposure on obesity and diabetes are contradictory. Therefore, the aim of the present work was to review the impact of cadmium exposure and status on the risk and potential etiologic mechanisms of obesity and diabetes. In addition, since an effect of cadmium exposure on incidence of diabetes mellitus and insulin resistance was suggested by several epidemiologic studies, we carried out a meta-analysis of all studies assessing risk of prevalence and incidence of diabetes. By comparing the highest versus the lowest cadmium exposure category, we found a high risk of diabetes incidence (odds ratio=1.38, 95% confidence interval 1.12-1.71), which was higher for studies using urine as exposure assessment. On the converse, results of epidemiologic studies linking cadmium exposure and overweight or obesity are far less consistent and even conflicting, also depending on differences in exposure levels and the specific marker of exposure (blood, urine, hair, nails). In turn, laboratory studies demonstrated that cadmium adversely affects adipose tissue physiopathology through several mechanisms, thus contributing to increased insulin resistance and enhancing diabetes. However, intimate biological mechanisms linking Cd exposure with obesity and diabetes are still to be adequately investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

Environmental factors associated with a spectrum of neurodevelopmental deficits.

PubMed

Mendola, Pauline; Selevan, Sherry G; Gutter, Suzanne; Rice, Deborah

2002-01-01

A number of environmental agents have been shown to demonstrate neurotoxic effects either in human or laboratory animal studies. Critical windows of vulnerability to the effects of these agents occur both pre- and postnatally. The nervous system is relatively unique in that different parts are responsible for different functional domains, and these develop at different times (e.g., motor control, sensory, intelligence and attention). In addition, the many cell types in the brain have different windows of vulnerability with varying sensitivities to environmental agents. This review focuses on two environmental agents, lead and methylmercury, to illustrate the neurobehavioral and cognitive effects that can result from early life exposures. Special attention is paid to distinguishing between the effects detected following episodes of poisoning and those detected following lower dose exposures. Perinatal and childhood exposure to high doses of lead results in encephalopathy and convulsions. Lower-dose lead exposures have been associated with impairment in intellectual function and attention. At high levels of prenatal exposure, methylmercury produces mental retardation, cerebral palsy and visual and auditory deficits in children of exposed mothers. At lower levels of methylmercury exposure, the effects in children have been more subtle. Other environmental neurotoxicants that have been shown to produce developmental neurotoxicity include polychlorinated biphenyls (PCBs), dioxins, pesticides, ionizing radiation, environmental tobacco smoke, and maternal use of alcohol, tobacco, marijuana and cocaine. Exposure to environmental agents with neurotoxic effects can result in a spectrum of adverse outcomes from severe mental retardation and disability to more subtle changes in function depending on the timing and dose of the chemical agent. Copyright 2002 Wiley-Liss, Inc.

Time dependent uptake, bioaccumulation and biotransformation of cell free crude extract microcystins from Lake Amatitlán, Guatemala by Ceratophyllum demersum, Egeria densa and Hydrilla verticillata.

PubMed

Romero-Oliva, Claudia Suseth; Contardo-Jara, Valeska; Pflugmacher, Stephan

2015-10-01

Recent studies evidence that macrophytes can uptake and bioaccumulate microcystins (MC) from contaminated environments, suggesting their use in phytoremediation. In the present study Ceratophyllum demersum, Egeria densa and Hydrilla verticillata were exposed to cell free crude extracts (CE) containing three MC congeners MC-LR, MC-RR and MC-YR at a total MC concentration of 104.4 ± 7.6 μg/L from Lake Amatitlán, Guatemala. Time dependent total glutathione (tGSH), glutathione disulfide (GSSG), disappearance of MC from exposure medium and macrophyte uptake as well as calculated uptake and biotransformation rates and bioconcentration factors (BCF) were monitored after 1, 4, 8 hours (h) and 1, 3, 7 and 14 days (d). Results showed that tGSH concentrations in all exposed macrophytes were enhanced by CE. Disappearance of 62.1 ± 13, 40.8 ± 3.1 and 37.8 ± 3.5 μg/L total MCs from exposure mediums with E. densa, H. verticillata and C. demersum were observed after 1 h. Followed by the total elimination of MCs in exposure medium from H. verticillata after 14 d. Highest MC bioaccumulation capacity (BCF), was observed in E. densa followed by C. demersum and H. verticillata. The here presented results imply the strong MC phytoremediation potential of the evaluated macrophytes. Copyright © 2015 Elsevier Ltd. All rights reserved.

In Vitro Toxicity and Epigenotoxicity of Different Types of Ambient Particulate Matter

PubMed Central

Miousse, Isabelle R.; Chalbot, Marie-Cecile G.; Pathak, Rupak; Lu, Xiaoyan; Nzabarushimana, Etienne; Krager, Kimberly; Aykin-Burns, Nukhet; Hauer-Jensen, Martin; Demokritou, Philip; Kavouras, Ilias G.; Koturbash, Igor

2015-01-01

Exposure to ambient particulate matter (PM) has been associated with adverse health effects, including pulmonary and cardiovascular disease. Studies indicate that ambient PM originated from different sources may cause distinct biological effects. In this study, we sought to investigate the potential of various types of PM to cause epigenetic alterations in the in vitro system. RAW264.7 murine macrophages were exposed for 24 and 72 h to 5- and 50-μg/ml doses of the water soluble extract of 6 types of PM: soil dust, road dust, agricultural dust, traffic exhausts, biomass burning, and pollen, collected in January–April of 2014 in the area of Little Rock, Arkansas. Cytotoxicity, oxidative potential, epigenetic endpoints, and chromosomal aberrations were addressed. Exposure to 6 types of PM resulted in induction of cytotoxicity and oxidative stress in a type-, time-, and dose-dependent manner. Epigenetic alterations were characterized by type-, time-, and dose-dependent decreases of DNA methylation/demethylation machinery, increased DNA methyltransferases enzymatic activity and protein levels, and transcriptional activation and subsequent silencing of transposable elements LINE-1, SINE B1/B2. The most pronounced changes were observed after exposure to soil dust that were also characterized by hypomethylation and reactivation of satellite DNA and structural chromosomal aberrations in the exposed cells. The results of our study indicate that the water-soluble fractions of the various types of PM have differential potential to target the cellular epigenome. PMID:26342214

Dose- and time-dependent gene expression alterations in prostate and colon cancer cells after in vitro exposure to carbon ion and X-irradiation

PubMed Central

Suetens, Annelies; Moreels, Marjan; Quintens, Roel; Soors, Els; Buset, Jasmine; Chiriotti, Sabina; Tabury, Kevin; Gregoire, Vincent; Baatout, Sarah

2015-01-01

Hadrontherapy is an advanced form of radiotherapy that uses beams of charged particles (such as protons and carbon ions). Compared with conventional radiotherapy, the main advantages of carbon ion therapy are the precise absorbed dose localization, along with an increased relative biological effectiveness (RBE). This high ballistic accuracy of particle beams deposits the maximal dose to the tumor, while damage to the surrounding healthy tissue is limited. Currently, hadrontherapy is being used for the treatment of specific types of cancer. Previous in vitro studies have shown that, under certain circumstances, exposure to charged particles may inhibit cell motility and migration. In the present study, we investigated the expression of four motility-related genes in prostate (PC3) and colon (Caco-2) cancer cell lines after exposure to different radiation types. Cells were irradiated with various absorbed doses (0, 0.5 and 2 Gy) of accelerated 13C-ions at the GANIL facility (Caen, France) or with X-rays. Clonogenic assays were performed to determine the RBE. RT-qPCR analysis showed dose- and time-dependent changes in the expression of CCDC88A, FN1, MYH9 and ROCK1 in both cell lines. However, whereas in PC3 cells the response to carbon ion irradiation was enhanced compared with X-irradiation, the effect was the opposite in Caco-2 cells, indicating cell-type–specific responses to the different radiation types. PMID:25190155

Chronic exposure to trichloroethylene increases DNA methylation of the Ifng promoter in CD4+ T cells.

PubMed

Gilbert, Kathleen M; Blossom, Sarah J; Erickson, Stephen W; Broadfoot, Brannon; West, Kirk; Bai, Shasha; Li, Jingyun; Cooney, Craig A

2016-10-17

CD4 + T cells in female MRL+/+ mice exposed to solvent and water pollutant trichloroethylene (TCE) skew toward effector/memory CD4 + T cells, and demonstrate seemingly non-monotonic alterations in IFN-γ production. In the current study we examined the mechanism for this immunotoxicity using effector/memory and naïve CD4 + T cells isolated every 6 weeks during a 40 week exposure to TCE (0.5mg/ml in drinking water). A time-dependent effect of TCE exposure on both Ifng gene expression and IFN-γ protein production was observed in effector/memory CD4 + T cells, with an increase after 22 weeks of exposure and a decrease after 40 weeks of exposure. No such effect of TCE was observed in naïve CD4 + T cells. A cumulative increase in DNA methylation in the CpG sites of the promoter of the Ifng gene was observed in effector/memory, but not naïve, CD4 + T cells over time. Also unique to the Ifng promoter was an increase in methylation variance in effector/memory compared to naïve CD4 + T cells. Taken together, the CpG sites of the Ifng promoter in effector/memory CD4 + T cells were especially sensitive to the effects of TCE exposure, which may help explain the regulatory effect of the chemical on this gene. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Human phase response curve to a 1 h pulse of bright white light

PubMed Central

St Hilaire, Melissa A; Gooley, Joshua J; Khalsa, Sat Bir S; Kronauer, Richard E; Czeisler, Charles A; Lockley, Steven W

2012-01-01

The phase resetting response of the human circadian pacemaker to light depends on the timing of exposure and is described by a phase response curve (PRC). The current study aimed to construct a PRC for a 1 h exposure to bright white light (∼8000 lux) and to compare this PRC to a <3 lux dim background light PRC. These data were also compared to a previously completed 6.7 h bright white light PRC and a <15 lux dim background light PRC constructed under similar conditions. Participants were randomized for exposure to 1 h of either bright white light (n= 18) or <3 lux dim background light (n= 18) scheduled at 1 of 18 circadian phases. Participants completed constant routine (CR) procedures in dim light (<3 lux) before and after the light exposure to assess circadian phase. Phase shifts were calculated as the difference in timing of dim light melatonin onset (DLMO) during pre- and post-stimulus CRs. Exposure to 1 h of bright white light induced a Type 1 PRC with a fitted peak-to-trough amplitude of 2.20 h. No discernible PRC was observed in the <3 lux dim background light PRC. The fitted peak-to-trough amplitude of the 1 h bright light PRC was ∼40% of that for the 6.7 h PRC despite representing only 15% of the light exposure duration, consistent with previous studies showing a non-linear duration–response function for the effects of light on circadian resetting. PMID:22547633

Human phase response curve to a 1 h pulse of bright white light.

PubMed

St Hilaire, Melissa A; Gooley, Joshua J; Khalsa, Sat Bir S; Kronauer, Richard E; Czeisler, Charles A; Lockley, Steven W

2012-07-01

The phase resetting response of the human circadian pacemaker to light depends on the timing of exposure and is described by a phase response curve (PRC). The current study aimed to construct a PRC for a 1 h exposure to bright white light (∼8000 lux) and to compare this PRC to a <3 lux dim background light PRC. These data were also compared to a previously completed 6.7 h bright white light PRC and a <15 lux dim background light PRC constructed under similar conditions. Participants were randomized for exposure to 1 h of either bright white light (n=18) or <3 lux dim background light (n=18) scheduled at 1 of 18 circadian phases. Participants completed constant routine (CR) procedures in dim light (<3 lux) before and after the light exposure to assess circadian phase. Phase shifts were calculated as the difference in timing of dim light melatonin onset (DLMO) during pre- and post-stimulus CRs. Exposure to 1 h of bright white light induced a Type 1 PRC with a fitted peak-to-trough amplitude of 2.20 h. No discernible PRC was observed in the <3 lux dim background light PRC. The fitted peak-to-trough amplitude of the 1 h bright light PRC was ∼40% of that for the 6.7 h PRC despite representing only 15% of the light exposure duration, consistent with previous studies showing a non-linear duration–response function for the effects of light on circadian resetting.

Estimating individual-level exposure to airborne polycyclic aromatic hydrocarbons throughout the gestational period based on personal, indoor, and outdoor monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, H.; Perera, F.; Pac, A.

2008-11-15

Current understanding on health effects of long-term polycyclic aromatic hydrocarbon (PAH) exposure is limited by lack of data on time-varying nature of the pollutants at an individual level. In a cohort of pregnant women in Krakow, Poland, we examined the contribution of temporal, spatial, and behavioral factors to prenatal exposure to airborne PAHs within each trimester and developed a predictive model of PAH exposure over the entire gestational period. The observed personal, indoor, and outdoor B(a)P levels we observed in Krakow far exceed the recommended Swedish guideline value for B(a)P of 0.1 ng/m{sup 3}. Based on simultaneously monitored levels, themore » outdoor PAH level alone accounts for 93% of total variability in personal exposure during the heating season. Living near the Krakow bus depot, a crossroad, and the city, center and time spent outdoors or commuting were not associated with higher personal exposure. During the nonheating season only, a 1-hr increase in environmental tobacco smoke (ETS) exposure was associated with a 10-16% increase in personal exposure to the nine measured PAHs. A 1{degree}C decrease in ambient temperature was associated with a 3-5% increase in exposure to benz(a)anthracene, benzo(k)fluoranthene, and dibenz(a,h)anthracene, after accounting for the outdoor concentration. A random effects model demonstrated that mean personal exposure at a given gestational period depends on the season, residence location, and ETS. Considering that most women reported spending < 3 hr/day outdoors, most women in the study were exposed to outdoor-originating PAHs within the indoor setting. Cross-sectional, longitudinal monitoring supplemented with questionnaire data allowed development of a gestation-length model of individual-level exposure with high precision and validity.« less

Perinatal Bisphenol A Exposure and Adult Glucose Homeostasis: Identifying Critical Windows of Exposure

PubMed Central

Liu, Jingli; Yu, Pan; Qian, Wenyi; Li, Yan; Zhao, Jingjing; Huan, Fei; Wang, Jun; Xiao, Hang

2013-01-01

Bisphenol A (BPA) is a widespread endocrine-disrupting chemical used as the building block for polycarbonate plastics. Epidemiological evidence has correlated BPA exposure with higher risk of heart disease and type 2 diabetes. However, it remains unknown whether there are critical windows of susceptibility to BPA exposure on the development of dysglycemia. This study was an attempt to investigate the critical windows and the long-term consequences of perinatal exposure to BPA on glucose homeostasis. Pregnant mice were given either vehicle or BPA (100 µg/kg/day) at different time of perinatal stage: 1) on days 1–6 of pregnancy (P1–P6, preimplantation exposure); 2) from day 6 of pregnancy until postnatal day (PND) 0 (P6–PND0, fetal exposure); 3) from lactation until weaning (PND0–PND21, neonatal exposure); and 4) from day 6 of gestation until weaning (P6–PND21, fetal and neonatal exposure). At 3, 6 and 8 months of age, offspring in each group were challenged with glucose and insulin tolerance tests. Then islet morphometry and β-cell function were measured. The glucose homeostasis was impaired in P6-PND0 mice from 3 to 6 months of age, and this continued to 8 months in males, but not females. While in PND0-PND21 and P6-PND21 BPA-treated groups, only the 3-month-old male offspring developed glucose intolerance. Moreover, at the age of 3 months, perinatal exposure to BPA resulted in the increase of β-cell mass mainly due to the coordinate changes in cell replication, neogenesis, and apoptosis. The alterations of insulin secretion and insulin sensitivity, rather than β-cell mass, were consistent with the development of glucose intolerance. Our findings suggest that BPA may contribute to metabolic disorders relevant to glucose homeostasis and the effects of BPA were dose, sex, and time-dependent. Fetal development stage may be the critical window of susceptibility to BPA exposure. PMID:23675523

Long-term effects of the rain exposure shortly after the atomic bombings in Hiroshima and Nagasaki.

PubMed

Sakata, Ritsu; Grant, Eric J; Furukawa, Kyoji; Misumi, Munechika; Cullings, Harry; Ozasa, Kotaro; Shore, Roy E

2014-12-01

The "black rain" that fell after the atomic bombings of Hiroshima and Nagasaki has been generally believed to contain radioactive materials. During 1949-1961 the Atomic Bomb Casualty Commission conducted surveys that included a query about exposure to the rain that fell a short time after the bombings. This article presents the first report of those data in relation to possible adverse health outcomes. This study looked at Life Span Study subjects who were in either city at the time of bombing and had an estimated direct radiation dose from the bombs (n = 86,609). The mortality data from 1950-2005 and cancer incidence data from 1958-2005 were used. Excess relative risks (ERRs) of subjects who were exposed to rain compared to those who reported no rain exposure were calculated using a Poisson regression model. In Hiroshima 11,661 subjects (20%) reported that they were exposed to rain, while in Nagasaki only 733 subjects (2.6%) reported rain exposure. To avoid outcome dependent biases (i.e., recall of exposure after a health outcome has already occurred), the primary analyses were based on events that occurred during 1962-2005. No significant risks due to rain exposure were observed for death due to all causes, all solid cancer or leukemia in Hiroshima. In Nagasaki there was no significantly elevated rain exposure-associated risks for 1962-2005, however, for 1950-2005 there was a weak association for all-cause mortality (ERR = 0.08; 95% confidence interval 0.00006, 0.17; P = 0.05). For incidence of solid cancer and leukemia, no significantly elevated rain exposure risks were observed in either city. These results failed to show deleterious health effects from rain exposure. While these data represent the most extensive set of systematically collected data on rain exposure of the atomic bomb survivors, they are limited by substantial uncertainties regarding exposures and missing individual data, so cautious interpretation is advised.

Time dependent decreases in central α7 nicotinic acetylcholine receptors associated with haloperidol and risperidone treatment in rats

PubMed Central

Terry, Alvin V.; Gearhart, Debra A.

2007-01-01

α7 nicotinic acetylcholine receptor deficits may contribute to cognitive dysfunction in schizophrenia; however, the contribution of antipsychotic drug exposure to these deficits is unknown. In this study, rats were treated orally with haloperidol (2.0 mg/kg/day) or risperidone (2.5 mg/kg/day) for 15 or 90 days. Subsequent immunoassays indicated that both antipsychotics were associated with α7 nicotinic receptor decreases in the basal forebrain and prefrontal cortex when administered for 90 (but not 15) days, a result that was confirmed in autoradiographic experiments. These data suggest that haloperidol and risperidone may be associated with time dependent decreases in an important neurobiological substrate of memory. PMID:17601556

In utero and postnatal exposure to arsenic alters pulmonary structure and function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lantz, R. Clark; Southwest Environmental Health Science Center, University of Arizona, Tucson, AZ 85721; BIO5 Institute, University of Arizona, Tucson, AZ 85721

2009-02-15

In addition to cancer endpoints, arsenic exposures can also lead to non-cancerous chronic lung disease. Exposures during sensitive developmental time points can contribute to the adult disease. Using a mouse model, in utero and early postnatal exposures to arsenic (100 ppb or less in drinking water) were found to alter airway reactivity to methacholine challenge in 28 day old pups. Removal of mice from arsenic exposure 28 days after birth did not reverse the alterations in sensitivity to methacholine. In addition, adult mice exposed to similar levels of arsenic in drinking water did not show alterations. Therefore, alterations in airwaymore » reactivity were irreversible and specific to exposures during lung development. These functional changes correlated with protein and gene expression changes as well as morphological structural changes around the airways. Arsenic increased the whole lung levels of smooth muscle actin in a dose dependent manner. The level of smooth muscle mass around airways was increased with arsenic exposure, especially around airways smaller than 100 {mu}m in diameter. This increase in smooth muscle was associated with alterations in extracellular matrix (collagen, elastin) expression. This model system demonstrates that in utero and postnatal exposure to environmentally relevant levels of arsenic can irreversibly alter pulmonary structure and function in the adults.« less

Body size-dependent Cd accumulation in the zebra mussel Dreissena polymorpha from different routes.

PubMed

Tang, Wen-Li; Evans, Douglas; Kraemer, Lisa; Zhong, Huan

2017-02-01

Understanding body size-dependent metal accumulation in aquatic organisms (i.e., metal allometry) is critical in interpreting biomonitoring data. While growth has received the most attention, little is known about controls of metal exposure routes on metal allometry. Here, size-dependent Cd accumulation in zebra mussels (Dreissena polymorpha) from different routes were investigated by exposing mussels to A.( 111 Cd spiked algae+ 113 Cd spiked river water) or B.( 111 Cd spiked sediments+ 113 Cd spiked river water). After exposure, 111 Cd or 113 Cd levels in mussel tissue were found to be negatively correlated with tissue weight, while Cd allometry coefficients (b values) were dependent on Cd exposure routes: -0.664 for algae, -0.241 for sediments and -0.379 for river water, compared to -0.582 in un-exposed mussels. By comparing different Cd exposure routes, we found that size-dependent Cd bioaccumulation from algae or river water could be more responsible for the overall size-dependent Cd accumulation in mussels, and the relative importance of the two sources was dependent on mussel size ranges: Cadmium obtained from algae (algae-Cd) was more important in size-dependent Cd accumulation in smaller mussels (tissue dry weight < 5 mg), while river water-Cd became more important in larger individuals (tissue dry weight > 5 mg). In contrast, sediment-Cd contributed only a small amount to Cd accumulation in zebra mussels and may have little effect on size-dependent Cd bioaccumulation. Our results suggest that size-dependent Cd accumulation in mussels could be largely affected by exposure routes, which should be considered when trying to interpret Cd biomonitoring data of zebra mussels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Human Dose-Response Data for Francisella tularensis and a Dose- and Time-Dependent Mathematical Model of Early-Phase Fever Associated with Tularemia After Inhalation Exposure.

PubMed

McClellan, Gene; Coleman, Margaret; Crary, David; Thurman, Alec; Thran, Brandolyn

2018-04-25

Military health risk assessors, medical planners, operational planners, and defense system developers require knowledge of human responses to doses of biothreat agents to support force health protection and chemical, biological, radiological, nuclear (CBRN) defense missions. This article reviews extensive data from 118 human volunteers administered aerosols of the bacterial agent Francisella tularensis, strain Schu S4, which causes tularemia. The data set includes incidence of early-phase febrile illness following administration of well-characterized inhaled doses of F. tularensis. Supplemental data on human body temperature profiles over time available from de-identified case reports is also presented. A unified, logically consistent model of early-phase febrile illness is described as a lognormal dose-response function for febrile illness linked with a stochastic time profile of fever. Three parameters are estimated from the human data to describe the time profile: incubation period or onset time for fever; rise time of fever; and near-maximum body temperature. Inhaled dose-dependence and variability are characterized for each of the three parameters. These parameters enable a stochastic model for the response of an exposed population through incorporation of individual-by-individual variability by drawing random samples from the statistical distributions of these three parameters for each individual. This model provides risk assessors and medical decisionmakers reliable representations of the predicted health impacts of early-phase febrile illness for as long as one week after aerosol exposures of human populations to F. tularensis. © 2018 Society for Risk Analysis.

Comparison of gestational dating methods and implications for exposure-outcome associations: an example with PM2.5 and preterm birth.

PubMed

Rappazzo, Kristen M; Lobdell, Danelle T; Messer, Lynne C; Poole, Charles; Daniels, Julie L

2017-02-01

Estimating gestational age is usually based on date of last menstrual period (LMP) or clinical estimation (CE); both approaches introduce potential bias. Differences in methods of estimation may lead to misclassification and inconsistencies in risk estimates, particularly if exposure assignment is also gestation-dependent. This paper examines a 'what-if' scenario in which alternative methods are used and attempts to elucidate how method choice affects observed results. We constructed two 20-week gestational age cohorts of pregnancies between 2000 and 2005 (New Jersey, Pennsylvania, Ohio, USA) using live birth certificates: one defined preterm birth (PTB) status using CE and one using LMP. Within these, we estimated risk for 4 categories of preterm birth (PTBs per 10 6 pregnancies) and risk differences (RD (95% CIs)) associated with exposure to particulate matter (PM 2.5 ). More births were classified preterm using LMP (16%) compared with CE (8%). RD divergences increased between cohorts as exposure period approached delivery. Among births between 28 and 31 weeks, week 7 PM 2.5 exposure conveyed RDs of 44 (21 to 67) for CE and 50 (18 to 82) for LMP populations, while week 24 exposure conveyed RDs of 33 (11 to 56) and -20 (-50 to 10), respectively. Different results from analyses restricted to births with both CE and LMP are most likely due to differences in dating methods rather than selection issues. Results are sensitive to choice of gestational age estimation, though degree of sensitivity can vary by exposure timing. When both outcome and exposure depend on estimate of gestational age, awareness of nuances in the method used for estimation is critical. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Membranotropic effects of electromagnetic radiation of extremely high frequency on Escherichia coli].

PubMed

Trchunian, A; Ogandzhanian, E; Sarkisian, E; Gonian, S; Oganesian, A; Oganesian, S

2001-01-01

It was found that "sound" electromagnetic radiations of extremely high frequencies (53.5-68 GHz) or millimeter waves (wavelength range of 4.2-5.6 mm) of low intensity (power density 0.01 mW) have a bactericidal effect on Escherichia coli bacteria. It was shown that exposure to irradiation of extremely high frequencies increases the electrokinetic potential and surface change density of bacteria and decreases of membrane potential. The total secretion of hydrogen ions was suppressed, the H+ flux from the cytoplasm to medium decreased, and the flux of N,N'-dicyclohexylcarbodiimide-sensitive potassium ions increased, which was accompanied by changes in the stoichiometry of these fluxes and an increase in the sensitivity of H+ ions to N,N'-dicyclohexylcarbodiimide. The effects depended on duration of exposure: as the time of exposure increased, the bactericidal effect increased, whereas the membranotropic effects decreased. The effects also depended on growth phase of bacteria: the irradiation affected the cells in the stationary but not in the logarithmic phase. It is assumed that the H(+)-ATPase complex F0F1 is involved in membranotropic effects of electromagnetic radiation of extremely high frequencies. Presumably, there are some compensatory mechanisms that eliminate the membranotropic effects.

The human body odor compound androstadienone leads to anger-dependent effects in an emotional Stroop but not dot-probe task using human faces.

PubMed

Hornung, Jonas; Kogler, Lydia; Wolpert, Stephan; Freiherr, Jessica; Derntl, Birgit

2017-01-01

The androgen derivative androstadienone is a substance found in human sweat and thus is a putative human chemosignal. Androstadienone has been studied with respect to effects on mood states, attractiveness ratings, physiological and neural activation. With the current experiment, we aimed to explore in which way androstadienone affects attention to social cues (human faces). Moreover, we wanted to test whether effects depend on specific emotions, the participants' sex and individual sensitivity to smell androstadienone. To do so, we investigated 56 healthy individuals (thereof 29 females taking oral contraceptives) with two attention tasks on two consecutive days (once under androstadienone, once under placebo exposure in pseudorandomized order). With an emotional dot-probe task we measured visuo-spatial cueing while an emotional Stroop task allowed us to investigate interference control. Our results suggest that androstadienone acts in a sex, task and emotion-specific manner as a reduction in interference processes in the emotional Stroop task was only apparent for angry faces in men under androstadienone exposure. More specifically, men showed a smaller difference in reaction times for congruent compared to incongruent trials. At the same time also women were slightly affected by smelling androstadienone as they classified angry faces more often correctly under androstadienone. For the emotional dot-probe task no modulation by androstadienone was observed. Furthermore, in both attention paradigms individual sensitivity to androstadienone was neither correlated with reaction times nor error rates in men and women. To conclude, exposure to androstadienone seems to potentiate the relevance of angry faces in both men and women in connection with interference control, while processes of visuo-spatial cueing remain unaffected.

The human body odor compound androstadienone leads to anger-dependent effects in an emotional Stroop but not dot-probe task using human faces

PubMed Central

Kogler, Lydia; Wolpert, Stephan; Freiherr, Jessica; Derntl, Birgit

2017-01-01

The androgen derivative androstadienone is a substance found in human sweat and thus is a putative human chemosignal. Androstadienone has been studied with respect to effects on mood states, attractiveness ratings, physiological and neural activation. With the current experiment, we aimed to explore in which way androstadienone affects attention to social cues (human faces). Moreover, we wanted to test whether effects depend on specific emotions, the participants' sex and individual sensitivity to smell androstadienone. To do so, we investigated 56 healthy individuals (thereof 29 females taking oral contraceptives) with two attention tasks on two consecutive days (once under androstadienone, once under placebo exposure in pseudorandomized order). With an emotional dot-probe task we measured visuo-spatial cueing while an emotional Stroop task allowed us to investigate interference control. Our results suggest that androstadienone acts in a sex, task and emotion-specific manner as a reduction in interference processes in the emotional Stroop task was only apparent for angry faces in men under androstadienone exposure. More specifically, men showed a smaller difference in reaction times for congruent compared to incongruent trials. At the same time also women were slightly affected by smelling androstadienone as they classified angry faces more often correctly under androstadienone. For the emotional dot-probe task no modulation by androstadienone was observed. Furthermore, in both attention paradigms individual sensitivity to androstadienone was neither correlated with reaction times nor error rates in men and women. To conclude, exposure to androstadienone seems to potentiate the relevance of angry faces in both men and women in connection with interference control, while processes of visuo-spatial cueing remain unaffected. PMID:28369152

Association between non-melanoma and melanoma skin cancer rates, vitamin D and latitude

PubMed Central

Rivas, Miguel; Rojas, Elisa; Calaf, Gloria M.; Barberán, Marcela; Liberman, Claudio; De Paula Correa, Marcelo

2017-01-01

Vitamin D synthesis takes place in the skin due to solar ultraviolet-B (UVB) radiation. Several studies have shown the association between low sun exposure, non-melanoma skin cancer (NMSC) and a lack of vitamin D synthesis. Since such synthesis in the body depends on the exposure of the skin to solar UVB radiation (290–320 nm), experimental measurements of this type of solar radiation are important. Tarapaca University in Arica, Chile, established a solar UV radiation laboratory in 2006 and since then this laboratory has performed systematic experimental solar UVB measurements using a calibrated biometer instrument. The results, which are presented in the current study, showed the association between NMSC and MSC rates, and the time required to produce 1,000 IU vitamin D with latitudinal variation. Solar UV index (UVI) levels reported in 6 cities from the north to the south of Chile indicated that the UVI ratio of monthly mean values was 1.8 times higher in Arica than in Punta Arenas in January (summer in Chile), whereas it was 14 times higher in June (winter). This factor is an important consideration, since vitamin D synthesis is directly associated with the exposure of individuals to solar UVB radiation. A similar trend was observed in Antofagasta, Santiago, Concepcion, Valdivia and Punta Arenas. It can be concluded from these data that there is a direct association between NMSC rates and mortality, and UVB radiation, meaning that this type of cancer would not depend on vitamin D synthesis and therefore on calcium uptake. By contrast, MSC rates increased with decreased levels of vitamin D, and thus calcium uptake, in all cities, with the only exception being Punta Arenas. PMID:28521479

Profiling Lipid Metabolites Yields Unique Information on Sex- and Time-dependent Responses of Fathead Minnows (Pimephales promelas) Exposed to 17α-Ethynylestradiol

EPA Science Inventory

Alterations in hepatic lipid profiles of fathead minnows (FHM) exposed to the synthetic estrogen 17α-ethynylestradiol (EE2) were determined using 1H-NMR spectroscopy-based metabolite profiling. The exposures were conducted using either 10 ng/l or 100 ng/l EE2 via a continuous flo...

Superinfection exclusion of the ruminant pathogen anaplasma marginale in the tick vector is dependent on time between exposures to the strains

USDA-ARS?s Scientific Manuscript database

The remarkable genetic diversity of vector-borne pathogens allows for the establishment of superinfection in the mammalian host. To have a long-term impact on population strain structure, the introduced strains must also be transmitted by a vector population that has been exposed to the existing pri...

A two-step method for developing a control rod program for boiling water reactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taner, M.S.; Levine, S.H.; Hsiao, M.Y.

1992-01-01

This paper reports on a two-step method that is established for the generation of a long-term control rod program for boiling water reactors (BWRs). The new method assumes a time-variant target power distribution in core depletion. In the new method, the BWR control rod programming is divided into two steps. In step 1, a sequence of optimal, exposure-dependent Haling power distribution profiles is generated, utilizing the spectral shift concept. In step 2, a set of exposure-dependent control rod patterns is developed by using the Haling profiles generated at step 1 as a target. The new method is implemented in amore » computer program named OCTOPUS. The optimization procedure of OCTOPUS is based on the method of approximation programming, in which the SIMULATE-E code is used to determine the nucleonics characteristics of the reactor core state. In a test in cycle length over a time-invariant, target Haling power distribution case because of a moderate application of spectral shift. No thermal limits of the core were violated. The gain in cycle length could be increased further by broadening the extent of the spetral shift.« less

Changes in the quaternary structure of phosphoenolpyruvate carboxylase induced by ionic strength affect its catalytic activity.

PubMed

Wagner, R; Gonzalez, D H; Podesta, F E; Andreo, C S

1987-05-04

Phosphoenolpyruvate carboxylase from maize leaves dissociated into dimers and/or monomers when exposed to increasing ionic strength (e.g. 200-400 mM NaCl) as indicated by gel filtration experiments. Changes in the oligomerization state were dependent on pH, time of preincubation with salt and protein concentration. A dissociation into dimers and monomers was observed at pH 8, while at pH 7 dissociation into the dimeric form only was observed. Exposure of the enzyme to higher ionic strength decreased the activity in a time-dependent manner. Turnover conditions and glucose 6-phosphate protected the carboxylase from the decay in activity, which was faster at pH 7 than at pH 8. The results suggest that changes in activity of the enzyme, following exposure to high ionic strength, are the consequence of dissociation. Tetrameric and dimeric forms of the phosphoenolpyruvate carboxylase seemingly reveal different catalytic properties. We suggest that the distinct catalytic properties of the different oligomeric species of phosphoenolpyruvate carboxylase and changes in the equilibrium between them could be the molecular basis for an effective regulation of metabolite levels by this key enzyme of C4 plants.

Cyclic Failure Mechanisms of Thermal and Environmental Barrier Coating Systems Under Thermal Gradient Test Conditions

NASA Technical Reports Server (NTRS)

Zhu, Dongming; Lee, Kang N.; Miller, Robert A.

2002-01-01

Plasma-sprayed ZrO2-8wt%Y2O3 and mullite+BSAS/Si multilayer thermal and environmental barrier coating (TBC-EBC) systems on SiC/SiC ceramic matrix composite (CMC) substrates were thermally cyclic tested under high thermal gradients using a laser high-heat-flux rig in conjunction with furnace exposure in water-vapor environments. Coating sintering and interface damage were assessed by monitoring the real-time thermal conductivity changes during the laser heat-flux tests and by examining the microstructural changes after exposure. Sintering kinetics of the coating systems were also independently characterized using a dilatometer. It was found that the coating failure involved both the time-temperature dependent sintering and the cycle frequency dependent cyclic fatigue processes. The water vapor environments not only facilitated the initial coating conductivity increases due to enhanced sintering and interface reaction, but also promoted later conductivity reductions due to the accelerated coating cracking and delamination. The failure mechanisms of the coating systems are also discussed based on the cyclic test results and are correlated to the sintering and thermal stress behavior under the thermal gradient test conditions.

Drug-induced cellular death dynamics monitored by a highly sensitive organic electrochemical system.

PubMed

Romeo, Agostino; Tarabella, Giuseppe; D'Angelo, Pasquale; Caffarra, Cristina; Cretella, Daniele; Alfieri, Roberta; Petronini, Pier Giorgio; Iannotta, Salvatore

2015-06-15

We propose and demonstrate a sensitive diagnostic device based on an Organic Electrochemical Transistor (OECT) for direct in-vitro monitoring cell death. The system efficiently monitors cell death dynamics, being able to detect signals related to specific death mechanisms, namely necrosis or early/late apoptosis, demonstrating a reproducible correlation between the OECT electrical response and the trends of standard cell death assays. The innovative design of the Twell-OECT system has been modeled to better correlate electrical signals with cell death dynamics. To qualify the device, we used a human lung adenocarcinoma cell line (A549) that was cultivated on the micro-porous membrane of a Transwell (Twell) support, and exposed to the anticancer drug doxorubicin. Time-dependent and dose-dependent dynamics of A549 cells exposed to doxorubicin are evaluated by monitoring cell death upon exposure to a range of doses and times that fully covers the protocols used in cancer treatment. The demonstrated ability to directly monitor cell stress and death dynamics upon drug exposure using simple electronic devices and, possibly, achieving selectivity to different cell dynamics is of great interest for several application fields, including toxicology, pharmacology, and therapeutics. Copyright © 2015 Elsevier B.V. All rights reserved.

Fate dynamics of environmentally exposed explosive traces.

PubMed

Kunz, Roderick R; Gregory, Kerin E; Aernecke, Matthew J; Clark, Michelle L; Ostrinskaya, Alla; Fountain, Augustus W

2012-04-12

The chemical and physical fates of trace amounts (<50 μg) of explosives containing 2,4,6-trinitrotoluene (TNT), hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), and pentaerythritol tetranitrate (PETN) were determined for the purpose of informing the capabilities of tactical trace explosive detection systems. From these measurements, it was found that the mass decreases and the chemical composition changes on a time scale of hours, with the loss mechanism due to a combination of sublimation and photodegradation. The rates for these processes were dependent on the explosive composition, as well as on both the ambient temperature and the size distribution of the explosive particulates. From these results, a persistence model was developed and applied to model the time dependence of both the mass and areal coverage of the fingerprints, resulting in a predictive capability for determining fingerprint fate. Chemical analysis confirmed that sublimation rates for TNT were depressed by UV (330-400 nm) exposure due to photochemically driven increases in the molecular weight, whereas the opposite was observed for RDX. No changes were observed for PETN upon exposure to UV radiation, and this was attributed to its low UV absorbance.

Temporal and spatial features of the formation of DNA adducts in sulfur mustard-exposed skin.

PubMed

Batal, Mohamed; Boudry, Isabelle; Mouret, Stéphane; Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Bérard, Izabel; Cléry-Barraud, Cécile; Douki, Thierry

2013-12-15

Sulfur mustard (SM) is a chemical warfare agent that targets skin where it induces large blisters. DNA alkylation is a critical step to explain SM-induced cutaneous symptoms. We determined the kinetics of formation of main SM-DNA adducts and compare it with the development of the SM-induced pathogenesis in skin. SKH-1 mice were exposed to 2, 6 and 60 mg/kg of SM and treated skin was biopsied between 6h and 21 days. Formation of SM DNA adducts was dose-dependent with a maximum immediately after exposure. However, adducts were persistent and still detectable 21 days post-exposure. The time-dependent formation of DNA adducts was also found to be correlated with the appearance of apoptotic cells. This temporal correlation suggests that these two early events are responsible for the severity of the damage to the skin. Besides, SM-DNA adducts were also detected in areas located next to contaminated zone, thus suggesting that SM diffuses in skin. Altogether, this work provides for the first time a clear picture of SM-induced genotoxicity using DNA adducts as a marker. © 2013.

An investigation into UV light exposure as an experimental model for artificial aging on tensile strength and force delivery of elastomeric chain.

PubMed

Wahab, Siti Waznah; Bister, Dirk; Sherriff, Martyn

2014-02-01

This study investigated the effect of ultraviolet type A light (UVA) exposure on the tensile properties of elastomeric chain. UVA light exposure was used as model for artificial aging, simulating prolonged storage of elastomeric chain. Tensile strength (n = 60) was measured after exposing Ormco, Forestadent and 3M chains to UVA light for 0, 2, 3, and 4 weeks. Force decay was measured (n = 60) using chain exposed for 5, 10, and 14 days. The chains were subsequently stretched at a constant distance and the resulting forces measured at 0, 1, 24 hours and 7, 14, 21, and 28 days. This test simulated a clinical scenario of pre-stretching and subsequent shortening of elastomeric chain. Tensile strength had statistically significant difference and was directly related to the duration of ultraviolet (UV) light exposure. Forestadent chain, which had the second highest value for the 'as received' product, showed the most consistent values over time with the lowest degradation. Ormco showed the lowest values for 'as received' as well as after UV exposure; 3M chain had the highest loss of tensile strength. Force decay was also significantly different. UV light exposure of 10 days or more appears to mark a 'watershed' between products: 3M had most survivors, Forestadent chain had some survivors, depending on the time the chain was stretched for. None of the Ormco product survived UV light exposure for more than 5 days. UVA light exposure may be used as a model for artificial aging as it reduces force delivery and tensile strength of exposed chains.

Effects of 50 Hz electric currents on mood and verbal reasoning skills.

PubMed Central

Stollery, B T

1986-01-01

Seventy-six male volunteers were studied in a crossover trial to assess the impact on the central system of electric currents such as might be induced by exposure to an intense power frequency electric field. Currents totalling 500 microamperes (50 Hz) were passed through electrodes attached to the head, upper arms, and feet, simulating exposure of and average man to a vertical electric field of about 36 kV/m. Exposure was continuous for a single day (5.5 hours) and the experiment was based on a double blind, counterbalanced, within subject design. A series of psychological tests examining self reports of both stress and arousal (mood checklist) and performance tests of memory, attention, and verbal skills were administered. Although the double blind conditions were compromised to some extent by reported sensations at electrode sites, the duration of these sensations was small in relation to the overall exposure or sham exposure time and did not interact with the effects apparently associated with exposure that were found. No significant difference between the exposed and sham-exposed groups was found on the first day, but on the second day the sham exposed group felt more aroused at the end of the day and their response times had improved more on the complex problems of a syntactic reasoning test. No exposure effects were apparent in self reports of stress or in performance in a semantic reasoning test, although both showed some influence of sensations. Interpretation of the exposure effects is complicated by their apparent restriction of the second test day, which may indicate some type of state dependent transfer phenomenon. PMID:3707872

Evaluation of the toxicity of graphene oxide exposure to the eye.

PubMed

Wu, Wei; Yan, Liang; Wu, Qian; Li, Yijian; Li, Qiyou; Chen, Siyu; Yang, Yuli; Gu, Zhanjun; Xu, Haiwei; Yin, Zheng Qin

2016-11-01

Graphene and its derivatives are the new carbon nanomaterials with the prospect for great applications in electronics, energy storage, biosensors and medicine. However, little is known about the toxicity of graphene or its derivatives in the case of occasional or repeated ocular exposure. We performed in vitro and in vivo studies to evaluate the toxicity of graphene oxide (GO) exposure to the eye. Primary human corneal epithelium cells (hCorECs) and human conjunctiva epithelium cells (hConECs) were exposed to GO (12.5-100 μg/mL). Acute GO exposure (2 h) did not induce cytotoxicity to hCorECs. However, short-term GO exposure (24 h) exerted significant cytotoxicity to hCorECs and hConECs with increased intracellular reactive oxygen species (ROS). Glutathione (GSH) reduced the GO-induced cytotoxicity. We further performed acute eye irritation tests in albino rabbits according to the Organization for Economic Cooperation and Development (OECD) guidelines, and the rabbits did not exhibit corneal opacity, conjunctival redness, abnormality of the iris, or chemosis at any time point after the instillation of 100 μg/mL of GO. However, 5-day repeated GO exposure (50 and 100 μg/mL) caused reversible mild corneal opacity, conjunctival redness and corneal epithelium damage to Sprague-Dawley rats, which was also alleviated by GSH. Therefore, our study suggests that GO-induced time- and dose-dependent cytotoxicity to hCorECs and hConECs via oxidative stress. Occasional GO exposure did not cause acute eye irritation; short-term repeated GO exposure generally resulted in reversible damage to the eye via oxidative stress, which may be alleviated by the antioxidant GSH.

Effects of yohimbine and drug cues on impulsivity and attention in cocaine-dependent men and women and sex-matched controls.

PubMed

Moran-Santa Maria, M M; Baker, N L; McRae-Clark, A L; Prisciandaro, J J; Brady, K T

2016-05-01

Deficits in executive function have been associated with risk for relapse. Data from previous studies suggest that relapse may be triggered by stress and drug-paired cues and that there are significant sex differences in the magnitude of these responses. The aim of this study was to examine the impact of the pharmacological stressor and alpha-2 adrenergic receptor antagonist yohimbine and cocaine cues on executive function in cocaine-dependent men and women. In a double-blind placebo controlled cross-over study, cocaine-dependent men (n=12), cocaine-dependent women (n=27), control men (n=31) and control women (n=25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Participants performed the Connors' Continuous Performance Test II prior to medication/placebo administration and immediately after each cue exposure session Healthy controls had a significant increase in commission errors under the yohimbine condition [RR (95% CI)=1.1 (1.0-1.3), χ(2)1=2.0, p=0.050]. Cocaine-dependent individuals exhibited a significant decrease in omission errors under the yohimbine condition [RR (95% CI)=0.6 (0.4-0.8), χ(2)1=8.6, p=0.003]. Cocaine-dependent women had more omission errors as compared to cocaine-dependent men regardless of treatment [RR (95% CI)=7.2 (3.6-14.7), χ(2)1=30.1, p<0.001]. Cocaine-dependent women exhibited a slower hit reaction time as compared to cocaine-dependent men [Female 354 ± 13 vs. Male 415 ± 14; t89=2.6, p=0.012]. These data add to a growing literature demonstrating significant sex differences in behaviors associated with relapse in cocaine-dependent individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

In-residence, multiple route exposures to chlorpyrifos and diazinon estimated by indirect method models

NASA Astrophysics Data System (ADS)

Moschandreas, D. J.; Kim, Y.; Karuchit, S.; Ari, H.; Lebowitz, M. D.; O'Rourke, M. K.; Gordon, S.; Robertson, G.

One of the objectives of the National Human Exposure Assessment Survey (NHEXAS) is to estimate exposures to several pollutants in multiple media and determine their distributions for the population of Arizona. This paper presents modeling methods used to estimate exposure distributions of chlorpyrifos and diazinon in the residential microenvironment using the database generated in Arizona (NHEXAS-AZ). A four-stage probability sampling design was used for sample selection. Exposures to pesticides were estimated using the indirect method of exposure calculation by combining measured concentrations of the two pesticides in multiple media with questionnaire information such as time subjects spent indoors, dietary and non-dietary items they consumed, and areas they touched. Most distributions of in-residence exposure to chlorpyrifos and diazinon were log-normal or nearly log-normal. Exposures to chlorpyrifos and diazinon vary by pesticide and route as well as by various demographic characteristics of the subjects. Comparisons of exposure to pesticides were investigated among subgroups of demographic categories, including gender, age, minority status, education, family income, household dwelling type, year the dwelling was built, pesticide use, and carpeted areas within dwellings. Residents with large carpeted areas within their dwellings have higher exposures to both pesticides for all routes than those in less carpet-covered areas. Depending on the route, several other determinants of exposure to pesticides were identified, but a clear pattern could not be established regarding the exposure differences between several subpopulation groups.

Detection of leachables and cytotoxicity after exposure to methacrylate- and epoxy-based root canal sealers in vitro.

PubMed

Lodienė, Greta; Kopperud, Hilde M; Ørstavik, Dag; Bruzell, Ellen M

2013-10-01

Root canal sealing materials may have toxic potential in vitro depending on the cell line, cytotoxicity assay, material chemistry, and degree of polymer curing. The aims of the present study were to detect leaching components from epoxy- or methacrylate-based root canal sealers and to investigate the degree of cytotoxicity after exposure to extracts from these materials. Qualitative determination of substances released from the materials was performed by gas- and liquid chromatography/mass spectrometry. Submandibular salivary gland acinar cell death (apoptosis/necrosis) was determined using a fluorescence staining/microscopy technique. The major leachable monomer from the epoxy-based material was bisphenol-A diglycidyl ether (BADGE), whereas leachables from the methacrylate-based materials were mainly triethylene glycol dimethacrylate (TEGDMA), urethane dimethacrylate (UDMA), hydroxyethyl methacrylate (HEMA), and polyethyleneglycol dimethacrylate (PEGDMA). Exposure to diluted extracts of cured methacrylate-based materials caused a postexposure time-dependent increase in cell death. This effect was not demonstrated as a result of exposure to undiluted extract of cured epoxy-based material. Extracts of all fresh materials induced apoptosis significantly, but at lower dilutions of the epoxy- than the methacrylate-based materials. The degree of leaching, determined from the relative chromatogram peak heights of eluates from the methacrylate-based sealer materials, corresponded with the degree of cell death induced by extracts of these materials. © 2013 Eur J Oral Sci.

Emotion self-regulation and empathy depend upon longer stimulus exposure.

PubMed

Ikezawa, Satoru; Corbera, Silvia; Wexler, Bruce E

2014-10-01

Observation of others in pain induces positive elevation (pain effect) in late event-related potentials (ERP). This effect is associated with top-down attention regulating processes. It has previously been shown that stimulus exposure duration can affect top-down attentional modulation of response to threat-related stimuli. We investigated the effect of exposure duration on ERP response to others in pain. Two late ERP components, P3 and late positive potentials (LPP), from 18 healthy people were measured while they viewed pictures of hands in painful or neutral situations for either 200 or 500 ms, during two task conditions (pain judgment and counting hands). P3 and LPP pain effects during the pain judgment condition were significantly greater with 500 ms than 200 ms stimulus presentation. Ours is the first study to suggest that engagement of empathy-related self-regulatory processes reflected in late potentials requires longer exposure to the pain-related stimulus. Although this is important information about the relationship between early sensory and subsequent brain processing, and about engagement of self-regulatory processes, the neural basis of this time-dependence remains unclear. It might be important to investigate the relationship between stimulus duration and empathic response in clinical populations where issues of self-regulation, empathic response and speed of information processing exist. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

AN EXPERIMENTAL STUDY OF THE EFFECTS OF CHEMICALLY DISPERSED OIL ON FEATHER STRUCTURE AND WATERPROOFING IN COMMON MURRES ( URIA AALGE).

PubMed

Whitmer, Emily R; Elias, Becky A; Harvey, Danielle J; Ziccardi, Michael H

2018-04-01

Following an oil spill in the marine environment, chemical dispersants, which increase oil droplet formation and distribution into the water column, are assumed to provide a net benefit to seabirds by reducing the risk of exposure to oil on the water surface. However, few data are available regarding acute, external impacts of exposure to dispersed oil. We evaluated the effects of known concentrations of dispersant and crude oil in artificial seawater on live Common Murres ( Uria aalge). Waterproofing and microscopic feather geometry were evaluated over time and compared to pre-exposure values. Birds exposed to a high concentration of dispersant experienced an immediate, life-threatening loss of waterproofing and buoyancy, both of which resolved within 2 d. Birds exposed to oil, or a dispersant and oil mixture, experienced dose-dependent waterproofing impairment without resolution over 2 d. Alterations in feather geometry were observed in oil-exposed or dispersant- and oil-exposed birds and were associated with increased odds of waterproofing impairment compared to control birds. At a given contaminant concentration, there were no significant differences in waterproofing between oil-exposed and dispersant- and oil-exposed birds. We found that acute, external effects of oil and dispersed oil exposure are comparable and dose-dependent. Our results also indicate that a zero-risk assumption should not be used when seabirds are present within the dispersant application zone.

Cancer mortality and occupational exposure to aromatic amines and inhalable aerosols in rubber tire manufacturing in Poland.

PubMed

de Vocht, Frank; Sobala, Wojciech; Wilczynska, Urszula; Kromhout, Hans; Szeszenia-Dabrowska, Neonila; Peplonska, Beata

2009-08-01

Most data on carcinogenic risk in the rubber industry are based on data from Western countries. This study assessed cancer risks in a retrospective cohort in a Polish tire manufacturing plant, relying on quantified exposure to inhalable aerosols and aromatic amines instead of job titles or external comparisons. Cumulative exposure for all exposures was assigned to cohort members based on estimates from a company-specific JEM. Cancer risks associated with cumulative exposure adjusted for co-exposures, gender and year of birth were calculated. Exposure levels were higher for women than for men. Aromatic amine exposure was significantly associated with increased urinary bladder cancer risk (RR=7.32-8.27), depending on exposure level, and prostate cancer at low levels only (RR=5.86). In women, increased risks were found for all cancers (RR=2.50) and of the digestive organs and peritoneum (RR=4.54) at low level only, while an exposure-response association with breast cancer risk was found. Inhalable aerosol exposure was associated with cancers of the liver and intrahepatic bile ducts in a dose-dependent manner, while dose-dependent reduced risks were found for respiratory cancers (most notably the larynx) and cancer of the colon. Increased risks for specific cancer sites in this rubber plant were similar to Western Europe and the US. However, several cancer risks were gender-specific which could relate to higher exposure levels in women or to differences in exposures to chemicals not assessed in this study.

Prenatal Particulate Air Pollution and Neurodevelopment in Urban Children: Examining Sensitive Windows and Sex-specific Associations

PubMed Central

Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Coull, Brent A.; Bellinger, David C.; Kloog, Itai; Schwartz, Joel; Wright, Robert O.; Wright, Rosalind J.

2015-01-01

Background Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex. Objectives We implemented innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter≤2.5μm (PM2.5) and children’s neurodevelopment. Methods We assessed 267 full-term urban children’s prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors [OEs], commission errors [CEs], hit reaction time [HRT], and HRT standard error [HRT-SE] on the Conners’ CPT-II), and memory (general memory [GM] index and its components - verbal [VEM] and visual [VIM] memory, and attention-concentration [AC] indices on the WRAML-2) assessed at age 6.5±0.98 years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined. Results Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12 years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31–38 weeks with lower IQ, at 20–26 weeks gestation with increased OEs, at 32–36 weeks with slower HRT, and at 22–40 weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18–26 weeks with reduced VIM, at 12–20 weeks with reduced GM). Conclusions Increased PM2.5 exposure in specific prenatal windows was associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups. PMID:26641520

Prenatal particulate air pollution and neurodevelopment in urban children: Examining sensitive windows and sex-specific associations.

PubMed

Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Coull, Brent A; Bellinger, David C; Kloog, Itai; Schwartz, Joel; Wright, Robert O; Wright, Rosalind J

2016-02-01

Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex. We implemented innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter ≤ 2.5 μm (PM2.5) and children's neurodevelopment. We assessed 267 full-term urban children's prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors [OEs], commission errors [CEs], hit reaction time [HRT], and HRT standard error [HRT-SE] on the Conners' CPT-II), and memory (general memory [GM] index and its components - verbal [VEM] and visual [VIM] memory, and attention-concentration [AC] indices on the WRAML-2) assessed at age 6.5±0.98 years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined. Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12 years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31-38 weeks with lower IQ, at 20-26 weeks gestation with increased OEs, at 32-36 weeks with slower HRT, and at 22-40 weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18-26 weeks with reduced VIM, at 12-20 weeks with reduced GM). Increased PM2.5 exposure in specific prenatal windows may be associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups. Copyright © 2015 Elsevier Ltd. All rights reserved.

Real-time measurement of individual occupational radon exposures in tombs of the Valley of the Kings, Egypt.

PubMed

Gruber, E; Salama, E; Rühm, W

2011-03-01

The active radon exposure meter developed recently at the German Research Center for Environmental Health (Helmholtz Zentrum München) was used to measure radon concentrations in 12 tombs located in the Valley of the Kings, Egypt. Radon concentrations in air between 50 ± 7 and 12 100 ± 600 Bq m(-3) were obtained. The device was also used to measure individual radon exposures of those persons working as safeguards inside the tombs. For a measurement time of 2-3 d, typical individual radon exposures ranged from 1800 ± 400 to 240 000 ± 13 000 Bq h m(-3), depending on the duration of measurement and radon concentration in the different tombs. Based on current ICRP dose conversion conventions for workers and on equilibrium factors published in the literature for these tombs, individual effective dose rates that range from 1.5 ± 0.3 to 860 ± 50 µSv d(-1) were estimated. If it is assumed that the climatic conditions present at the measurement campaign persist for about half a year, in this area, then effective doses up to ∼ 66 mSv could be estimated for half a year, for some of the safeguards of tombs where F-values were known. To reduce the exposure of the safeguards, some recommendations are proposed.

Exposure to volatile organic compounds for individuals with occupations associated with potential exposure to motor vehicle exhaust and/or gasoline vapor emissions.

PubMed

Jo, W K; Song, K B

2001-03-26

Workers who work near volatile organic compounds (VOCs) source(s), motor vehicle exhausts and/or gasoline vapor emissions, are suspected to be exposed to highly-elevated VOC levels during their work-time. This study confirmed this suspicion and evaluated the work-time exposure VOCs for traffic police officers, parking garage attendants, service station attendants, roadside storekeepers and underground storekeepers, by measuring the concentrations of six aromatic VOCs in workplace air, or personal air and breath samples. For nearly all target VOCs, the post-work breath concentrations of the workers were slightly or significantly higher than the pre-work breath concentrations, depending on the compound and occupation. Furthermore, both the pre- and post-work breath concentrations of the workers showed elevated levels compared with a control group of college students. The post-work breath concentrations were significantly correlated with the personal air concentrations, while the pre-work breath concentrations were not. Smoking workers were not always exposed to higher aromatic VOC levels than non-smoking workers. The breath and personal air concentrations for all the target compounds were both higher for underground parking garage attendants than for ground-level parking attendants. For all the target compounds except toluene, storekeepers exhibited similar levels of exposure for all store types. Print shopkeepers recorded the highest toluene exposure.

Exposure to Sub-lethal 2,4-Dichlorophenoxyacetic Acid Arrests Cell Division and Alters Cell Surface Properties in Escherichia coli.

PubMed

Bhat, Supriya V; Kamencic, Belma; Körnig, André; Shahina, Zinnat; Dahms, Tanya E S

2018-01-01

Escherichia coli is a robust, easily adaptable and culturable bacterium in vitro , and a model bacterium for studying the impact of xenobiotics in the environment. We have used correlative atomic force - laser scanning confocal microscopy (AFM-LSCM) to characterize the mechanisms of cellular response to the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D). One of the most extensively used herbicides world-wide, 2,4-D is known to cause hazardous effects in diverse non-target organisms. Sub-lethal concentrations of 2,4-D caused DNA damage in E. coli WM1074 during short exposure periods which increased significantly over time. In response to 2,4-D, FtsZ and FtsA relocalized within seconds, coinciding with the complete inhibition of cell septation and cell elongation. Exposure to 2,4-D also resulted in increased activation of the SOS response. Changes to cell division were accompanied by concomitant changes to surface roughness, elasticity and adhesion in a time-dependent manner. This is the first study describing the mechanistic details of 2,4-D at sub-lethal levels in bacteria. Our study suggests that 2,4-D arrests E. coli cell division within seconds after exposure by disrupting the divisome complex, facilitated by dissipation of membrane potential. Over longer exposures, 2,4-D causes filamentation as a result of an SOS response to oxidative stress induced DNA damage.

Differential neurotoxic effects of in utero and lactational exposure to hydroxylated polychlorinated biphenyl (OH-PCB 106) on spontaneous locomotor activity and motor coordination in young adult male mice.

PubMed

Haijima, Asahi; Lesmana, Ronny; Shimokawa, Noriaki; Amano, Izuki; Takatsuru, Yusuke; Koibuchi, Noriyuki

2017-01-01

We investigated whether in utero or lactational exposure to 4-hydroxy-2',3,3',4',5'-pentachlorobiphenyl (OH-PCB 106) affects spontaneous locomotor activity and motor coordination in young adult male mice. For in utero exposure, pregnant C57BL/6J mice received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from gestational day 10 to 18. For lactational exposure, the different groups of dams received 0.05 or 0.5 mg/kg body weight of OH-PCB 106 or corn oil vehicle via gavage every second day from postpartum day 3 to 13. At 6-7 weeks of age, the spontaneous locomotor activities of male offspring were evaluated for a 24-hr continuous session in a home cage and in an open field for 30-min. Motor coordination function on an accelerating rotarod was also measured. Mice exposed prenatally to OH-PCB 106 showed increased spontaneous locomotor activities during the dark phase in the home cage and during the first 10-min in the open field compared with control mice. Mice exposed lactationally to OH-PCB 106, however, did not show a time-dependent decrease in locomotor activity in the open field. Instead, their locomotor activity increased significantly during the second 10-min block. In addition, mice exposed lactationally to OH-PCB 106 displayed impairments in motor coordination in the rotarod test. These results suggest that perinatal exposure to OH-PCB 106 affects motor behaviors in young adult male mice. Depending on the period of exposure, OH-PCB 106 may have different effects on neurobehavioral development.

Exposure to nanoscale particles and fibers during machining of hybrid advanced composites containing carbon nanotubes

NASA Astrophysics Data System (ADS)

Bello, Dhimiter; Wardle, Brian L.; Yamamoto, Namiko; Guzman deVilloria, Roberto; Garcia, Enrique J.; Hart, Anastasios J.; Ahn, Kwangseog; Ellenbecker, Michael J.; Hallock, Marilyn

2009-01-01

This study investigated airborne exposures to nanoscale particles and fibers generated during dry and wet abrasive machining of two three-phase advanced composite systems containing carbon nanotubes (CNTs), micron-diameter continuous fibers (carbon or alumina), and thermoset polymer matrices. Exposures were evaluated with a suite of complementary instruments, including real-time particle number concentration and size distribution (0.005-20 μm), electron microscopy, and integrated sampling for fibers and respirable particulate at the source and breathing zone of the operator. Wet cutting, the usual procedure for such composites, did not produce exposures significantly different than background whereas dry cutting, without any emissions controls, provided a worst-case exposure and this article focuses here. Overall particle release levels, peaks in the size distribution of the particles, and surface area of released particles (including size distribution) were not significantly different for composites with and without CNTs. The majority of released particle surface area originated from the respirable (1-10 μm) fraction, whereas the nano fraction contributed 10% of the surface area. CNTs, either individual or in bundles, were not observed in extensive electron microscopy of collected samples. The mean number concentration of peaks for dry cutting was composite dependent and varied over an order of magnitude with highest values for thicker laminates at the source being >1 × 106 particles cm-3. Concentration of respirable fibers for dry cutting at the source ranged from 2 to 4 fibers cm-3 depending on the composite type. Further investigation is required and underway to determine the effects of various exposure determinants, such as specimen and tool geometry, on particle release and effectiveness of controls.

The 2008-2009 recession and alcohol outcomes: differential exposure and vulnerability for Black and Latino populations.

PubMed

Zemore, Sarah E; Mulia, Nina; Jones-Webb, Rhonda J; Liu, Huiguo; Schmidt, Laura

2013-01-01

We examined whether race/ethnicity was related to exposure to acute economic losses in the 2008-2009 recession, even accounting for individual-level and geographic variables, and whether it influenced associations between economic losses and drinking patterns and problems. Data were from the 2010 National Alcohol Survey (N = 5,382). Surveys assessed both severe losses (i.e., job and housing loss) and moderate losses (i.e., reduced hours/pay and trouble paying the rent/mortgage) attributed to the 2008-2009 recession. Alcohol outcomes included total annual volume, monthly drunkenness, drinking consequences, and alcohol dependence (based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition). Compared with Whites, Blacks reported significantly greater exposure to job loss and trouble paying the rent/mortgage, and Latinos reported greater exposure to all economic losses. However, only Black-White differences were robust in multivariate analyses. Interaction tests suggested that associations between exposure to economic loss and alcohol problems were stronger among Blacks than Whites. Given severe (vs. no) loss, Blacks had about 13 times the odds of both two or more drinking consequences and alcohol dependence, whereas the corresponding odds ratios for Whites were less than 3. Conversely, associations between economic loss and alcohol outcomes were weak and ambiguous among Latinos. Results suggest greater exposure to economic loss for both Blacks and Latinos (vs. Whites) and that the Black population may be particularly vulnerable to the negative effects of economic hardship on the development and/or maintenance of alcohol problems. Findings extend the economic literature and signal policy makers and service providers that Blacks and Latinos may be at special risk during economic downturns.

Impact of exposure time, particle size and uptake pathway on silver nanoparticle effects on circulating immune cells in mytilus galloprovincialis.

PubMed

Bouallegui, Younes; Ben Younes, Ridha; Turki, Faten; Oueslati, Ridha

2017-12-01

Nanomaterials have increasingly emerged as potential pollutants to aquatic organisms. Nanomaterials are known to be taken up by hemocytes of marine invertebrates including Mytilus galloprovincialis. Indeed, assessments of hemocyte-related parameters are a valuable tool in the determination of potentials for nanoparticle (NP) toxicity. The present study assessed the effects from two size types of silver nanoparticles (AgNP: <50 nm and <100 nm) on the frequency of hemocytes subpopulations as immunomodulation biomarkers exposed in a mollusk host. Studies were performed using exposures prior to and after inhibition of potential NP uptake pathways (i.e. clathrin- and caveolae-mediated endocytosis) and over different durations of exposure (3, 6 and 12 h). Differential hemocyte counts (DHC) revealed significant variations in frequency of different immune cells in mussels exposed for 3 hr to either AgNP size. However, as exposure duration progressed cell levels were subsequently differentially altered depending on particle size (i.e. no significant effects after 3 h with larger AgNP). AgNP effects were also delayed/varied after blockade of either clathrin- or caveolae-mediated endocytosis. The results also noted significant negative correlations between changes in levels hyalinocytes and acidophils or in levels basophils and acidophils as a result of AgNP exposure. From these results, we concluded AgNP effects on mussels were size and duration of exposure dependent. This study highlighted how not only was NP size important, but that differing internalization mechanisms could be key factors impacting on the potential for NP in the environment to induce immunomodulation in a model/test sentinel host like M. galloprovincialis.

Effects of developmental exposure to bisphenol A and ethinyl estradiol on spatial navigational learning and memory in painted turtles (Chrysemys picta).

PubMed

Manshack, Lindsey K; Conard, Caroline M; Johnson, Sarah A; Alex, Jorden M; Bryan, Sara J; Deem, Sharon L; Holliday, Dawn K; Ellersieck, Mark R; Rosenfeld, Cheryl S

2016-09-01

Developmental exposure of turtles and other reptiles to endocrine disrupting chemicals (EDCs), including bisphenol A (BPA) and ethinyl estradiol (EE2, estrogen present in birth control pills), can induce partial to full gonadal sex-reversal in males. No prior studies have considered whether in ovo exposure to EDCs disrupts normal brain sexual differentiation. Yet, rodent model studies indicate early exposure to these chemicals disturbs sexually selected behavioral traits, including spatial navigational learning and memory. Thus, we sought to determine whether developmental exposure of painted turtles (Chrysemys picta) to BPA and EE2 results in sex-dependent behavioral changes. At developmental stage 17, turtles incubated at 26⁰C (male-inducing temperature) were treated with 1) BPA High (100μg /mL), 2) BPA Low (0.01μg/mL), 3) EE2 (0.2μg/mL), or 4) vehicle or no vehicle control groups. Five months after hatching, turtles were tested with a spatial navigational test that included four food containers, only one of which was baited with food. Each turtle was randomly assigned one container that did not change over the trial period. Each individual was tested for 14 consecutive days. Results show developmental exposure to BPA High and EE2 improved spatial navigational learning and memory, as evidenced by increased number of times spent in the correct target zone and greater likelihood of solving the maze compared to control turtles. This study is the first to show that in addition to overriding temperature sex determination (TSD) of the male gonad, these EDCs may induce sex-dependent behavioral changes in turtles. Copyright © 2016 Elsevier Inc. All rights reserved.

Time series analysis and mortality model of dog bite victims presented for treatment at a referral clinic for rabies exposure in Monrovia, Liberia, 2010-2013.

PubMed

Olarinmoye, Ayodeji O; Ojo, Johnson F; Fasunla, Ayotunde J; Ishola, Olayinka O; Dakinah, Fahnboah G; Mulbah, Charles K; Al-Hezaimi, Khalid; Olugasa, Babasola O

2017-08-01

We developed time trend model, determined treatment outcome and estimated annual human deaths among dog bite victims (DBVs) from 2010 to 2013 in Monrovia, Liberia. Data obtained from clinic records included victim's age, gender and site of bite marks, site name of residence of rabies-exposed patients, promptness of care sought, initial treatment and post-exposure-prophylaxis (PEP) compliance. We computed DBV time-trend plot, seasonal index and year 2014 case forecast. Associated annual human death (AHD) was estimated using a standardized decision tree model. Of the 775 DBVs enlisted, care seeking time was within 24h of injury in 328 (42.32%) DBVs. Victim's residential location, site of bite mark, and time dependent variables were significantly associated with treatment outcome (p< 0.05). The equation X^ t =28.278-0.365t models the trend of DBVs. The high (n=705, 90.97%) defaulted PEP and average 155 AHD from rabies implied urgent need for policy formulation on national programme for rabies prevention in Liberia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Withanolide A Prevents Neurodegeneration by Modulating Hippocampal Glutathione Biosynthesis during Hypoxia

PubMed Central

Baitharu, Iswar; Jain, Vishal; Deep, Satya Narayan; Shroff, Sabita; Sahu, Jayanta Kumar; Naik, Pradeep Kumar; Ilavazhagan, Govindasamy

2014-01-01

Withania somnifera root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer. Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)–related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner. PMID:25310001

Withanolide A prevents neurodegeneration by modulating hippocampal glutathione biosynthesis during hypoxia.

PubMed

Baitharu, Iswar; Jain, Vishal; Deep, Satya Narayan; Shroff, Sabita; Sahu, Jayanta Kumar; Naik, Pradeep Kumar; Ilavazhagan, Govindasamy

2014-01-01

Withania somnifera root extract has been used traditionally in ayurvedic system of medicine as a memory enhancer. Present study explores the ameliorative effect of withanolide A, a major component of withania root extract and its molecular mechanism against hypoxia induced memory impairment. Withanolide A was administered to male Sprague Dawley rats before a period of 21 days pre-exposure and during 07 days of exposure to a simulated altitude of 25,000 ft. Glutathione level and glutathione dependent free radicals scavenging enzyme system, ATP, NADPH level, γ-glutamylcysteinyl ligase (GCLC) activity and oxidative stress markers were assessed in the hippocampus. Expression of apoptotic marker caspase 3 in hippocampus was investigated by immunohistochemistry. Transcriptional alteration and expression of GCLC and Nuclear factor (erythroid-derived 2)-related factor 2 (Nrf2) were investigated by real time PCR and immunoblotting respectively. Exposure to hypobaric hypoxia decreased reduced glutathione (GSH) level and impaired reduced gluatathione dependent free radical scavenging system in hippocampus resulting in elevated oxidative stress. Supplementation of withanolide A during hypoxic exposure increased GSH level, augmented GSH dependent free radicals scavenging system and decreased the number of caspase and hoescht positive cells in hippocampus. While withanolide A reversed hypoxia mediated neurodegeneration, administration of buthionine sulfoximine along with withanolide A blunted its neuroprotective effects. Exogenous administration of corticosterone suppressed Nrf2 and GCLC expression whereas inhibition of corticosterone synthesis upregulated Nrf2 as well as GCLC. Thus present study infers that withanolide A reduces neurodegeneration by restoring hypoxia induced glutathione depletion in hippocampus. Further, Withanolide A increases glutathione biosynthesis in neuronal cells by upregulating GCLC level through Nrf2 pathway in a corticosterone dependenet manner.

Modeling toxicodynamic effects of trichloroethylene on liver in mouse model of autoimmune hepatitis.

PubMed

Gilbert, Kathleen M; Reisfeld, Brad; Zurlinden, Todd J; Kreps, Meagan N; Erickson, Stephen W; Blossom, Sarah J

2014-09-15

Chronic exposure to industrial solvent and water pollutant trichloroethylene (TCE) in female MRL+/+mice generates disease similar to human autoimmune hepatitis. The current study was initiated to investigate why TCE-induced autoimmunity targeted the liver. Compared to other tissues the liver has an unusually robust capacity for repair and regeneration. This investigation examined both time-dependent and dose-dependent effects of TCE on hepatoprotective and pro-inflammatory events in liver and macrophages from female MRL+/+mice. After a 12-week exposure to TCE in drinking water a dose-dependent decrease in macrophage production of IL-6 at both the transcriptional and protein level was observed. A longitudinal study similarly showed that TCE inhibited macrophage IL-6 production. In terms of the liver, TCE had little effect on expression of pro-inflammatory genes (Tnfa, Saa2 or Cscl1) until the end of the 40-week exposure. Instead, TCE suppressed hepatic expression of genes involved in IL-6 signaling (Il6r, gp130, and Egr1). Linear regression analysis confirmed liver histopathology in the TCE-treated mice correlated with decreased expression of Il6r. A toxicodynamic model was developed to estimate the effects of TCE on IL-6 signaling and liver pathology under different levels of exposure and rates of repair. This study underlined the importance of longitudinal studies in mechanistic evaluations of immuntoxicants. It showed that later-occurring liver pathology caused by TCE was associated with early suppression of hepatoprotection rather than an increase in conventional pro-inflammatory events. This information was used to create a novel toxicodynamic model of IL-6-mediated TCE-induced liver inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.