Tobacco product-derived aldehydes: effects on circulating angiogenic cells & implications for cardiovascular disease.

Cardiovascular disease (CVD) is the leading cause of death worldwide. Tobacco smoke is the most significant modifiable risk factor in CVD development and contains numerous toxic compounds, including aldehydes, which have been linked to CVD. Formaldehyde, acetaldehyde, acrolein, and crotonaldehyde have been identified as significant contributors to cigarette-induced health effects, but the mechanism of these effects is not well understood. These aldehydes are also found in aerosols produced by e-cigarettes (e-cigs). The goal of this dissertation was to explore the systemic, hematological, and endothelium-related effects of exposure to tobacco products and constituent aldehydes and to identify potential mechanisms of injury. In the Louisville Healthy Heart Study, hematological measures and circulating angiogenic cells (CACs) were assessed against tobacco product use categories. In murine studies, male and female C57BL/6J, transient receptor potential ankyrin 1 (TRPA1)-null, and/or extracellular superoxide dismutase-transgenic (ecSOD-Tg) mice were exposed to mainstream cigarette smoke (MCS), e-cig aerosol, humectants, or constituent aldehydes for varying durations and concentrations. Hematological measures, plasma biomarkers, and levels of CACs were assessed. Chapter III of this dissertation describes findings from the Louisville Healthy Heart Study. E-cig or dual users showed significantly increased levels of leukocytes and of CAC-3, an early endothelial progenitor cell population, compared with never smokers. Chapter IV describes systemic and vascular changes induced by exposure to MCS, e-cig aerosol, or humectants, finding significant decreases in leukocytes after all exposures and decreases in CACs in female mice exposed to JUUL Mango aerosol. Chapter V describes effects of exposure to formaldehyde and acetaldehyde, finding that formaldehyde induces significant hematological and vascular changes. Chapter VI describes effects of exposure to acrolein and crotonaldehyde, presenting novel evidence implicating chronic crotonaldehyde exposure as a risk factor for CVD. Finally, chapter VII explores the roles of ecSOD and TRPA1 in tobacco product-related CVD, demonstrating that the effects of unsaturated aldehydes are mediated by TRPA1. This dissertation presents novel data investigating associations between CACs and e-cigs in a human cohort, examining the role of tobacco products and individual constituent aldehydes in the development of CVD, and demonstrating the role of TRPA1 in the CVD effects related to tobacco products

Novel statistical methodology reveals that hip shape is associated with incident radiographic hip osteoarthritis among African American women

Hip shape is a risk factor for the development of hip osteoarthritis (OA), and current methods to assess hip shape from radiographs are limited; therefore this study explored current and novel methods to assess hip shape

What is the status of the Lee’s Lane Landfill Superfund Site?

The Lee’s Lane Landfill is located in western Louisville, KY along the Ohio River (Fig. 1) [1]. The site was used as a quarry in the 1940s before being repurposed as a landfill from 1948 to 1975 (Fig. 2). At least 212,400 tons of municipal and industrial waste were disposed of in the landfill during this period. In 1980, the Kentucky Department of Hazardous Materials and Waste Management discovered approximately 400 drums of hazardous waste within the landfill; these drums were removed by the landfill owners in the fall of 1981, but the remaining drums of non-hazardous material, as well as any empty drums, were buried in place on the landfill. The buried and capped landfill waste covers an area of 112 acres. The United States Environmental Protection Agency (EPA) placed the Lee’s Lane Landfill site on the National Priorities List (NPL) in 1983. Cleanup efforts concluded in 1988 and monitoring of the site has continued since. This white paper summarizes reports published from 2013 through 2018 documenting Lee’s Lane Landfill site conditions and the effectiveness of the cap and other remedies put in place to protect human health. The condition of the site must be reviewed every five years by the EPA, and those results are made available to the public in what is referred to as a Five-Year Review (FYR). The Lee’s Lane Landfill FYR relies on information provided to the EPA by the Kentucky State Department of Environmental Protection (KDEP), information collected by the Lee’s Lane Landfill Group, monitoring data and conclusions from the Louisville and Jefferson County Metropolitan Sewer District’s (MSD) Conceptual Site Model (CSM) report, [2] and other interim communications. Using the information in these reports as well as relevant current and historical research documents, we identify questions that remain unanswered and need to be addressed in order to confirm that the contaminants present on the site do not pose a risk to public health and to determine whether the site is ready for re-use. We conclude by proposing several next steps to fill the identified gaps in information and confirm the conclusions in the reports

A new reference genome assembly for the microcrustacean Daphnia pulex

Comparing genomes of closely related genotypes from populations with distinct demographic histories can help reveal the impact of effective population size on genome evolution. For this purpose, we present a high quality genome assembly of Daphnia pulex (PA42), and compare this with the first sequenced genome of this species (TCO), which was derived from an isolate from a population with >90% reduction in nucleotide diversity. PA42 has numerous similarities to TCO at the gene level, with an average amino acid sequence identity of 98.8 and >60% of orthologous proteins identical. Nonetheless, there is a highly elevated number of genes in the TCO genome annotation, with similar to 7000 excess genes appearing to be false positives. This view is supported by the high GC content, lack of introns, and short length of these suspicious gene annotations. Consistent with the view that reduced effective population size can facilitate the accumulation of slightly deleterious genomic features, we observe more proliferation of transposable elements (TEs) and a higher frequency of gained introns in the TCO genome

Canonically conjugate pairs and phase operators

For quantum mechanics on a lattice the position (``particle number'') operator and the quasi-momentum (``phase'') operator obey canonical commutation relations (CCR) only on a dense set of the Hilbert space. We compare exact numerical results for a particle in simple potentials on the lattice with the expectations, when the CCR are assumed to be strictly obeyed. Only for sufficiently smooth eigenfunctions this leads to reasonable results. In the long time limit the use of the CCR can lead to a qualitativel wrong dynamics even if the initial state is in the dense set.Comment: 4 pages, 5 figures. Phys. Rev. A, in pres

Variations in Hip Shape Are Associated with Radiographic Knee Osteoarthritis : Cross-sectional and Longitudinal Analyses of the Johnston County Osteoarthritis Project

Acknowledgment We thank our funding sources, as well as the staff and participants in the Johnston County Osteoarthritis Project, without whom this work would not be possible. Funding was provided in part by the US National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) K23 AR061406 (Nelson); US National Institutes of Health (NIH)/NIAMS P60AR30701 (Jordan/Renner/Schwartz); US Centers for Disease Control/Association of Schools of Public Health S043 and S3486 (Jordan/Renner); K24-AR04884, P50-AR063043, and P50-AR060752 (Lane); and NIH/National Center for Advancing Translational Sciences KL2TR001109 (Golightly).Peer reviewedPostprin