Biotransformation Potential of Cationic Surfactants in Fish Assessed with Rainbow Trout Liver S9 Fractions

Biotransformation may substantially reduce the extent to which organic environmental contaminants accumulate in fish. Presently, however, relatively little is known regarding the biotransformation of ionized chemicals, including cationic surfactants, in aquatic organisms. To address this deficiency, a rainbow trout liver S9 substrate depletion assay (RT-S9) was used to measure in vitro intrinsic clearance rates (CLint; ml min–1 g liver–1) for 22 cationic surfactants that differ with respect to alkyl chain length and degree of methylation on the charged nitrogen atom. None of the quaternary N,N,N-trimethylalkylammonium compounds exhibited significant clearance. Rapid clearance was observed for N,N-dimethylalkylamines, and slower rates of clearance were measured for N-methylalkylamine analogs. Clearance rates for primary alkylamines were generally close to or below detectable levels. For the N-methylalkylamines and N,N-dimethylalkylamines, the highest CLint values were measured for C10–C12 homologs; substantially lower clearance rates were observed for homologs containing shorter or longer carbon chains. Based on its cofactor dependency, biotransformation of C12–N,N-dimethylamine appears to involve one or more cytochrome P450–dependent reaction pathways, and sulfonation. On a molar basis, N-demethylation metabolites accounted for up to 25% of the N,N-dimethylalkylamines removed during the 2-h assay, and up to 55% of the removed N-methylalkylamines. These N-demethylation products possess greater metabolic stability in the RT-S9 assay than the parent structures from which they derive and may contribute to the overall risk of ionizable alkylamines. The results of these studies provide a set of consistently determined CLint values that may be extrapolated to whole trout to inform in silico bioaccumulation assessments

Cigarette smoking and estrogen-related cancer

Cigarette smoking is a known cause of many cancers, yet epidemiologic studies have found protective associations with the risk of four “estrogen-related” malignancies: endometrial cancer, endometrioid and clear cell ovarian cancers, and thyroid cancer. This review considers epidemiologic and biological aspects of these associations, focusing particularly on estrogen signaling, and contrasts them with those for breast cancer, another estrogen-related malignancy. The observational findings regarding the inverse associations are consistent and remain after adjustment for possible confounding factors. In general, women who smoke do not have lower circulating estrogen levels than nonsmokers, eliminating one possible explanation for reduced risks of these malignancies. For endometrial and endometrioid ovarian cancer, the negative associations could plausibly be explained by interference with signaling through the estrogen receptor α. However, this is unlikely to explain the lower risks of thyroid and clear cell ovarian cancers. For thyroid cancer, an anti-inflammatory effect of nicotine and reduced TSH levels from smoking have been proposed explanations for the inverse association, but both lack convincing evidence. While the overall impact of cigarette smoking is overwhelmingly negative, protective associations such as those discussed here can provide potential clues to disease etiology, treatment, and prevention

Outcomes after assisted reproductive technology in women with cancer: A systematic review and meta-Analysis

STUDY QUESTION: What are the associations between a history of cancer and outcomes after ART? SUMMARY ANSWER: Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer and a lower likelihood of clinical pregnancy and live birth after ART. WHAT IS KNOWN ALREADY: Small, single-institution studies have suggested that cancer and its treatment may negatively affect ART outcomes. STUDY DESIGN, SIZE, DURATION: We conducted a systematic review with meta-Analysis of studies comparing ART outcomes between women with and without cancer. PubMed, Embase and Scopus were searched for original, English-language studies published up to June 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria required reporting of ART outcomes after controlled ovarian stimulation (COS) among women with a history of cancer compared to women without cancer who used ART for any indication. Outcomes of interest ranged from duration of COS to likelihood of live birth after embryo transfer. Random-effects meta-Analysis was used to calculate mean differences and odds ratios (ORs) with 95% CIs and 95% prediction intervals (PIs). We assessed heterogeneity by age-Adjustment, referent group indication for ART, study location and among women with breast cancer and women who initiated ART before cancer treatment. We used visual inspection, Egger's test and the trim-And-fill method to assess funnel plot asymmetry. MAIN RESULTS AND THE ROLE OF CHANCE: Of 6094 unique records identified, 42 studies met inclusion criteria, representing a median per study of 58 women with cancer (interquartile range (IQR) = 159) and 114 women without cancer (IQR = 348). Compared to women without cancer, on average, women with cancer had a lower return for embryo transfer (OR: 0.22; 95% CI: 0.07, 0.74; 95% PI: 0.00, 64.98); lower likelihood of clinical pregnancy (OR: 0.51; 95% CI: 0.35, 0.73; 95% PI: 0.19, 1.35); and lower likelihood of live birth (OR: 0.56; 95% CI: 0.38, 0.83; 95% PI: 0.19, 1.69). Substantial among-study heterogeneity was observed for COS duration, gonadotropin dose, cycle cancellation, total oocytes and mature oocytes. Fertilization percentage showed less heterogeneity, but study-specific estimates were imprecise. Similarly, number of embryos showed less heterogeneity, and most studies estimated minimal differences by cancer history. Funnel plot asymmetry was observed for estradiol peak and oocyte maturation percentage. LIMITATIONS, REASONS FOR CAUTION: Appreciable confounding is possible in 11 studies that lacked adequate control for group differences in age, and among-study heterogeneity was observed for most outcomes. Lack of data limited our ability to assess how cancer clinical factors (e.g. cancers other than breast, cancer stage and treatment) and ART cycle characteristics (e.g. fresh versus frozen embryo transfers and use of gestational carriers) may affect outcomes. WIDER IMPLICATIONS OF THE FINDINGS: Women with cancer may be less likely to achieve pregnancy and live birth after embryo transfer. Further examination of reproductive outcomes and sources of heterogeneity among studies is warranted to improve evidence of the expected success of ART after a cancer diagnosis. STUDY FUNDING/COMPETING INTEREST(S): This research was supported in part by R01 CA211093 and P30 ES010126. C.M. was supported by the University of North Carolina Lineberger Cancer Control Education Program (T32 CA057726) and the National Cancer Institute (F31 CA260787). J.A.R.-H. was supported by the National Cancer Institute (K08 CA234333, P30 CA016672). J.A.R.-H. reports receiving consulting fees from Schlesinger Group and Guidepoint. The remaining authors declare no competing interests. REGISTRATION NUMBER: N/A

Pavement Treatment Effectiveness, 1995 SPS-3 and SPS-4 Site Evaluations: National Report

DTFH61-93-C-00060This report presents an evaluation of the performance SHRP SPS-3 and SPS-4 experiment sites based on field reviews after 5 years of performance. Condition evaluation of the section and Expert Task Group performance estimates are the basis for treatment assessments

Hazardous air pollutants and telomere length in the Sister Study

Background: Telomeres are vital for genomic integrity, and telomere length has been linked to many adverse health outcomes. Some hazardous air pollutants or air toxics increase oxidative stress and inflammation, two possible determinants of shortened telomere length. No studies have examined air toxic-Telomere length associations in a nonoccupational setting. Methods: This study included 731 Sister Study participants (enrolled 2003-2007) who were randomly selected to assess telomere length in baseline blood samples. Multiplex qPCR was used to determine telomere to single copy gene (T/S) ratios. Census tract concentration estimates of 29 air toxics from the 2005 National Air Toxics Assessment were linked to baseline residential addresses. Air toxics were classified into tertile-based categories of the exposure. Multivariable linear regression was used to estimate β coefficients and 95% confidence intervals (CIs) in single-pollutant models. Multipollutant groups were identified with regression trees. Results: The average T/S ratio was 1.24. Benzidine (T3 versus T1 β =-0.08; 95% CI =-0.14,-0.01) and 1,4-dioxane (T3 versus T1 β =-0.06; 95% CI =-0.13, 0.00) in particular, as well as carbon tetrachloride, chloroprene, ethylene dibromide, and propylene dichloride, were associated with shorter relative telomere length. Benzidine (P = 0.02) and 1,4-dioxane (P = 0.06) demonstrated some evidence of a monotonic trend. The regression tree identified age, BMI, physical activity, ethylene oxide, acrylonitrile, ethylidene dichloride, propylene dichloride, and styrene in multipollutant groups related to telomere length. Conclusions: In this first study of air toxics and telomere length in a nonoccupational setting, several air toxics, particularly 1,4-dioxane and benzidine, were associated with shorter relative telomere length

Strategies for Developing and Documenting Products of Public Scholarship in Research and Creative Activity

This guidance is Part 1 of an intended 3 part series with the remaining guides to focus on strategies to document public and community-engaged scholarship as excellence in Teaching followed by Service.This document builds on the IUPUI Concept Paper on Public Scholarship and provides a planning and documentation tool to aid faculty in preparing their dossier for promotion and tenure. Candidates can use this document to aid in their planning and gathering of evidence. Primary and unit committees can use this guidance in mentoring junior colleagues. The specific guidance in this document focuses on planning for and documenting their public and community-engaged scholarship as research and creative activity as is adapted from prior work by Jordan (2007)

Disparities in the use of assisted reproductive technologies after breast cancer: a population-based study

Purpose: Equitable access to oncofertility services is a key component of cancer survivorship care, but factors affecting access and use remain understudied. Methods: To describe disparities in assisted reproductive technology (ART) use among women with breast cancer in California, we conducted a population-based cohort study using linked oncology, ART, and demographic data. We identified women age 18–45 years diagnosed with invasive breast cancer between 2000 and 2015. The primary outcome was ART use—including oocyte/embryo cryopreservation or embryo transfer—after cancer diagnosis. We used log-binomial regression to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) to identify factors associated with ART use. Results: Among 36,468 women with invasive breast cancer, 206 (0.56%) used ART. Women significantly less likely to use ART were age 36–45 years at diagnosis (vs. 18–35 years: PR = 0.17, 95% CI 0.13–0.22); non-Hispanic Black or Hispanic (vs. non-Hispanic White: PR = 0.31, 95% CI 0.21–0.46); had at least one child (vs. no children: adjusted PR [aPR] = 0.39, 95% CI 0.25–0.60); or lived in non-urban areas (vs. urban: aPR = 0.28, 95% CI 0.10–0.75), whereas women more likely to use ART lived in high-SES areas (vs. low-/middle-SES areas: aPR = 2.93, 95% CI 2.04–4.20) or had private insurance (vs. public/other insurance: aPR = 2.95, 95% CI 1.59–5.49). Conclusion: Women with breast cancer who are socially or economically disadvantaged, or who already had a child, are substantially less likely to use ART after diagnosis. The implementation of policies or programs targeting more equitable access to fertility services for women with cancer is warranted

Radio emission and jets from microquasars

To some extent, all Galactic binary systems hosting a compact object are potential `microquasars', so much as all galactic nuclei may have been quasars, once upon a time. The necessary ingredients for a compact object of stellar mass to qualify as a microquasar seem to be: accretion, rotation and magnetic field. The presence of a black hole may help, but is not strictly required, since neutron star X-ray binaries and dwarf novae can be powerful jet sources as well. The above issues are broadly discussed throughout this Chapter, with a a rather trivial question in mind: why do we care? In other words: are jets a negligible phenomenon in terms of accretion power, or do they contribute significantly to dissipating gravitational potential energy? How do they influence their surroundings? The latter point is especially relevant in a broader context, as there is mounting evidence that outflows powered by super-massive black holes in external galaxies may play a crucial role in regulating the evolution of cosmic structures. Microquasars can also be thought of as a form of quasars for the impatient: what makes them appealing, despite their low number statistics with respect to quasars, are the fast variability time-scales. In the first approximation, the physics of the jet-accretion coupling in the innermost regions should be set by the mass/size of the accretor: stellar mass objects vary on 10^5-10^8 times shorter time-scales, making it possible to study variable accretion modes and related ejection phenomena over average Ph.D. time-scales. [Abridged]Comment: 28 pages, 13 figures, To appear in Belloni, T. (ed.): The Jet Paradigm - From Microquasars to Quasars, Lect. Notes Phys. 794 (2009

Immersed boundary-finite element model of fluid-structure interaction in the aortic root

It has long been recognized that aortic root elasticity helps to ensure efficient aortic valve closure, but our understanding of the functional importance of the elasticity and geometry of the aortic root continues to evolve as increasingly detailed in vivo imaging data become available. Herein, we describe fluid-structure interaction models of the aortic root, including the aortic valve leaflets, the sinuses of Valsalva, the aortic annulus, and the sinotubular junction, that employ a version of Peskin's immersed boundary (IB) method with a finite element (FE) description of the structural elasticity. We develop both an idealized model of the root with three-fold symmetry of the aortic sinuses and valve leaflets, and a more realistic model that accounts for the differences in the sizes of the left, right, and noncoronary sinuses and corresponding valve cusps. As in earlier work, we use fiber-based models of the valve leaflets, but this study extends earlier IB models of the aortic root by employing incompressible hyperelastic models of the mechanics of the sinuses and ascending aorta using a constitutive law fit to experimental data from human aortic root tissue. In vivo pressure loading is accounted for by a backwards displacement method that determines the unloaded configurations of the root models. Our models yield realistic cardiac output at physiological pressures, with low transvalvular pressure differences during forward flow, minimal regurgitation during valve closure, and realistic pressure loads when the valve is closed during diastole. Further, results from high-resolution computations demonstrate that IB models of the aortic valve are able to produce essentially grid-converged dynamics at practical grid spacings for the high-Reynolds number flows of the aortic root