Digital Commons Network^™

Novel Strategies In Antithrombotic Therapy: Targeting Thrombosis While Preserving Hemostasis, Martha M. S. Sim, Semekidus Shiferawe, Jeremy P. Wood

Saha Cardiovascular Research Center Faculty Publications

Antithrombotic therapy is a delicate balance between the benefits of preventing a thrombotic event and the risks of inducing a major bleed. Traditional approaches have included antiplatelet and anticoagulant medications, require careful dosing and monitoring, and all carry some risk of bleeding. In recent years, several new targets have been identified, both in the platelet and coagulation systems, which may mitigate this bleeding risk. In this review, we briefly describe the current state of antithrombotic therapy, and then present a detailed discussion of the new generation of drugs that are being developed to target more safely existing or newly identified …

A Blunted Th17 Cytokine Signature In Women With Mild Cognitive Impairment: Insights From Inflammatory Profiling Of A Community-Based Cohort Of Older Adults, Adam D. Bachstetter, Jenny Lutshumba, Edric D. Winford, Erin L. Abner, Barbra J. Martin, Jordan P. Harp, Linda J. Van Eldik, Frederick A. Schmitt, Donna M. Wilcock, Ann M. Stowe, Gregory A. Jicha, Barbara S. Nikolajczyk

Markey Cancer Center Faculty Publications

People with dementia have an increase in brain inflammation, caused in part by innate and adaptive immune cells. However, it remains unknown whether dementia-associated diseases alter neuro-immune reflex arcs to impact the systemic immune system. We examined peripheral immune cells from a community-based cohort of older adults to test if systemic inflammatory cytokine signatures associated with early stages of cognitive impairment. Human peripheral blood mononuclear cells were cultured with monocyte or T-cell-targeted stimuli, and multiplex assays quantitated cytokines in the conditioned media. Following T-cell-targeted stimulation, cells from women with cognitive impairment produced lower amounts of TH17 cytokines compared with cells …

Dense Granule Protein 3 Of Toxoplasma Gondii Plays A Crucial Role In The Capability Of The Tissue Cysts Of The Parasite To Persist In The Presence Of Anti-Cyst Cd8+ T Cells During The Chronic Stage Of Infection, Rajesh Mani, Mohamed H. Abdelaziz, Eri Ochiai, Qila Sa, Barbara A. Fox, David J. Bzik, Yasuhiro Suzuki

Markey Cancer Center Faculty Publications

Toxoplasma gondii establishes chronic infection by forming tissue cysts, and this chronic infection is one of the most common parasitic infections in humans. Our recent studies revealed that whereas CD8 + T cells of genetically resistant BALB/c mice have the capability to remove the tissue cysts of the parasite through their perforin-mediated activities, small portions of the cysts are capable of persisting in the presence of the anti-cyst CD8+ T cells. It is currently unknown how those small portions of the cysts resist or escape the T-cell immunity and persist in the hosts. In the present study, we discovered that …

Effects Of Interfraction Dose Variations Of Target And Organs At Risk On Clinical Outcomes In High Dose Rate Brachytherapy For Cervical Cancer, Brien Washington, Dennis C. Cheek, Denise Fabian, Mahesh R. Kudrimoti, Damodar Pokhrel, Chi Wang, Cameron Thayer-Freeman, Wei Luo

Markey Cancer Center Faculty Publications

Meeting dose prescription is critical to control tumors in radiation therapy. Interfraction dose variations (IDVs) from the prescribed dose in high dose rate brachytherapy (HDR) would cause the target dose to deviate from the prescription but their clinical effect has not been widely discussed in the literature. Our previous study found that IDVs followed a left-skewed distribution. The clinical effect of the IDVs in 100 cervical cancer HDR patients will be addressed in this paper. An in-house Monte Carlo (MC) program was used to simulate clinical outcomes by convolving published tumor dose response curves with IDV distributions. The optimal dose …

Elongation Of Very Long Chain Fatty Acids-3 (Elovl3) Is Activated By Zhx2 And Is A Regulator Of Cell Cycle Progression, Kate Townsend Creasy, Hui Ren, Jieyun Jiang, Martha L. Peterson, Brett T. Spear

Markey Cancer Center Faculty Publications

Zinc fingers and homeoboxes 2 (Zhx2) are transcriptional regulators of liver gene expression with key functions in embryonic development as well as tissue regeneration in response to damage and disease, presumably through its control of target genes. Previous microarray data suggested that elongation of very long chain fatty acids-3 (Elovl3), a member of the ELOVL family of enzymes that synthesize very long chain fatty acids (VLCFAs), is a putative Zhx2 target gene. VLCFAs are core component of ceramides and other bioactive sphingolipids that are often dysregulated in diseases and regulate key cellular processes including proliferation. Since several previously identified Zhx2 …

Proteasome Inhibition Protects Blood–Brain Barrier P-Glycoprotein And Lowers Aβ Brain Levels In An Alzheimer’S Disease Model, Milica Vulin, Yu Zhong, Bryan J. Maloney, Björn Bauer, Anika M. S. Hartz

Markey Cancer Center Faculty Publications

Background Loss of P-glycoprotein (P-gp) at the blood–brain barrier contributes to amyloid-β (Aβ) brain accumulation in Alzheimer’s disease (AD). Using transgenic human amyloid precursor protein (hAPP)-overexpressing mice (Tg2576), we previously showed that Aβ triggers P-gp loss by activating the ubiquitin–proteasome pathway, which leads to P-gp degradation. Furthermore, we showed that inhibiting the ubiquitin-activating enzyme (E1) prevents P-gp loss and lowers Aβ accumulation in the brain of hAPP mice. Based on these data, we hypothesized that repurposing the FDA-approved proteasome inhibitor, bortezomib (Velcade®; BTZ), protects blood–brain barrier P-gp from degradation in hAPP mice in vivo.

Methods We treated hAPP mice with …

Stat3 Modulates Cd4+ T Mitochondrial Dynamics And Function In Aging, Emelia Zukowski, Marco Sannella, Jack Donato Rockhold, Gabriella Kalantar, Jingting Yu, Sara Santacruz-Calvo, Madison K. Kuhn, Nasun Hah, Ling Ouyang, Tzu-Wen Wang, Lyanne Murphy, Heather Marszalkowski, Kaleigh Gibney, Micah J. Drummond, Elizabeth A. Proctor, Hatice Hasturk, Barbara S. Nikolajczyk, Leena P. Bharath

Markey Cancer Center Faculty Publications

Aging promotes numerous intracellular changes in T cells that impact their effector function. Our data show that aging promotes an increase in the localization of STAT3 to the mitochondria (mitoSTAT3), which promotes changes in mitochondrial dynamics and function and T-cell cytokine production. Mechanistically, mitoSTAT3 increased the activity of aging T-cell mitochondria by increasing complex II. Limiting mitoSTAT3 using a mitochondria-targeted STAT3 inhibitor, Mtcur-1 lowered complex II activity, prevented age-induced changes in mitochondrial dynamics and function, and reduced Th17 inflammation. Exogenous expression of a constitutively phosphorylated form of STAT3 in T cells from young adults mimicked changes in mitochondrial dynamics and …

2023 Final Report For Databases In The 2022 Traffic Records Improvement Plan: Facilitating The Development Of Projects To Attain The Goals In The Implementation Plan For The 2022-26 Traffic Records Strategic Plan, Lenahan O'Connell, Samantha Wright, Reginald Souleyrette

Kentucky Transportation Center Research Report

During fiscal year 2023, with financial support (Grant #M3Da-2022-04) from the Kentucky Office of Highway Safety, the Kentucky Transportation Center (KTC)-continued its work with traffic database officials to facilitate successful attainment of the remaining goals from the 2017-21 Traffic Records Strategic Plan (TRSP), which goals are in the 2022-26 TRSP Transportation Records Improvement Plan (TRIP). For most databases, some new goals were developed; this required further refinement of some projects or strategies to improve database performance. Projects to complete the goals in the TRIP were continued and some completed for the following databases: CRASH, Citation/Adjudication, Injury Surveillance (KIPRC and EMS), …

Development Of A Spatial And Statistical Diagnostic Tool To Prioritize Pfas Sample Locations In Kentucky Surface Waters, Ariel Robinson, Angela Gutierrez, Kelly G. Pennell

Kentucky Water Resources Annual Symposium

No abstract provided.

Karst Watershed Planning For The Jennings Creek/Lost River Watershed In South-Central Kentucky To Improve Water Quality And Community Awareness, Jason S. Polk, Adam Desloge, Brittany Pekara, Trayson Lawler, Shreya Pandey, Kara Brunot, Mara Neace, Meghan Forbes, Matt Powell

Kentucky Water Resources Annual Symposium

No abstract provided.

Antibiotic-Resistant E.Coli In Kentucky Watersheds Impacted By Various Land Uses, Jayden Hamlet, Jason Marion, Travis Altheide

Kentucky Water Resources Annual Symposium

No abstract provided.

Full Program Proceedings For 2023 Kentucky Water Resources Symposium, Kentucky Water Research Institute

Kentucky Water Resources Annual Symposium

No abstract provided.

Equine In Vivo Metabolite Profiling Of The Selective Androgen Receptor Modulator Lgd-3303 For Doping Control, Malin Nilsson Broberg, Heather Knych, Ulf Bondesson, Curt Pettersson, Börje Tidstedt, Scott Stanley, Mario Thevis, Mikael Hedeland

UK CARES Faculty Publications

LGD-3303 is a Selective Androgen Receptor Modulator (SARM) that is prohibited in both equine and human sports due to its anabolic properties. The aim of this study was to investigate the equine in vivo metabolite profile of LGD-3303 and identify drug metabolites that can be suitable as new and improved analytical targets for equine doping control. This was performed by an oral administration of 0.05 mg⋅kg 1 LGD-3303 to horses, where blood and urine samples were collected up to 96 h after administration. The in vivo samples consisting of plasma, urine and hydrolyzed urine were analyzed utilizing ultra-high performance liquid …

Membrane Functionalization Approaches Toward Per- And Polyfluoroalkyl Substances And Selected Metal Ion Separations, Francisco Cecil Léniz-Pizarro, Holly E. Rudel, Nicolas J. Briot, Julie B. Zimmerman, Dibakar Bhattacharyya

UK CARES Faculty Publications

Adsorption and ion exchange technologies are two of the most widely used approaches to separate pollutants from water; however, their intrinsic diffusion limitations continue to be a challenge. Pore functionalized membranes are a promising technology that can help overcome these challenges, but the extents of their competitive benefits and broad applicability have not been systematically evaluated. Herein, three types of adsorptive/ion exchange (IX) polymers containing strong/weak acid, strong base, and iron-chitosan complex groups were synthesized in the pores and partially on the surface of microfiltration (MF) membranes and tested for the removal of organic and inorganic cations and anions from …

A Lamprey Neural Cell Type Atlas Illuminates The Origins Of The Vertebrate Brain, Francesco Lamanna, Francisca Hervas-Sotomayor, A. Phillip Oel, David Jandzik, Daniel Sobrido-Cameán, Gabriel N. Santos-Durán, Megan L. Martik, Jan Stundl, Stephen A. Green, Thoomke Brüning, Katharina Mößinger, Julia Schmidt, Celine Schneider, Mari Sepp, Florent Murat, Jeramiah J. Smith, Marianne E. Bronner, María Celina Rodicio, Antón Barreiro-Iglesias, Daniel M. Medeiros, Detlev Arendt, Henrik Kaessmann

Markey Cancer Center Faculty Publications

The vertebrate brain emerged more than ~500 million years ago in common evolutionary ancestors. To systematically trace its cellular and molecular origins, we established a spatially resolved cell type atlas of the entire brain of the sea lamprey—a jawless species whose phylogenetic position affords the reconstruction of ancestral vertebrate traits—based on extensive single-cell RNA-seq and in situ sequencing data. Comparisons of this atlas to neural data from the mouse and other jawed vertebrates unveiled various shared features that enabled the reconstruction of cell types, tissue structures and gene expression programs of the ancestral vertebrate brain. However, our analyses also revealed …

Syne1 Mutation Is Associated With Increased Tumor Mutation Burden And Immune Cell Infiltration In Ovarian Cancer, Laura M. Harbin, Nan Lin, Frederick R. Ueland, Jill M. Kolesar

Markey Cancer Center Faculty Publications

SYNE1, a nuclear envelope protein critical for cellular structure and signaling, is downregulated in numerous malignancies. SYNE1 alterations are found in 10% of gynecologic malignancies and 5% of epithelial ovarian cancers. Previous studies demonstrated an association between SYNE1 mutation, increased tumor mutation burden (TMB), and immunotherapy response. This study evaluates the SYNE1 mutation frequency, association with TMB, and downstream effects of SYNE1 mutation in ovarian cancer. Genetic information, including whole-exome sequencing, RNA analysis, and somatic tumor testing, was obtained for consenting ovarian cancer patients at an academic medical center. Mutation frequencies were compared between the institutional cohort and The Cancer …

Kentucky Traffic Collision Facts 2022 Report, Paul Ross, Eric Green, Christopher Blackden, Kenneth R. Agent, Christopher Van Dyke

Kentucky Transportation Center Research Report

Kentucky’s Traffic Collision Facts is based on collision reports submitted to the Kentucky State Police Records Branch. As required by Kentucky Revised Statute 189.635: “Every law enforcement agency whose officers investigate a vehicle accident of which a report must be made...shall file a report of the accident...within ten days after investigation of the accident upon forms supplied by the bureau.” The stated purpose of this requirement is to utilize data on traffic collisions to improve the Commonwealth’s traffic safety program. Unless otherwise noted, data in this publication are for public roads only. Data contained in this report are based solely …

Inspection Training Course On Bridge Preventive Maintenance Activities, Danny Wells, Sudhir Palle

Kentucky Transportation Center Research Report

Despite over 30 percent of bridges in the United States having exceeded their 50-year design lives, most state departments of transportation (DOTs) lack the funding needed to replace bridges on a large scale. In response, agencies have increasingly turned to bridge preventive maintenance activities to prolong bridge service lives. These activities provide a safe and cost-effective way to slow the rate at which structures deteriorate, mitigate the effects of aging, and improve bridge functional condition. The Kentucky Transportation Cabinet (KYTC) has become increasingly reliant on preventive maintenance to preserve and extend the service lives of its steel and concrete bridges. …

2023 Safety Belt Usage Survey In Kentucky, Erin Lammers-Staats, Derek S. Young, Kenneth R. Agent, Aidan Elias

Kentucky Transportation Center Research Report

Data and results of a statewide observational survey used to establish the statewide usage rate for safety belts in Kentucky.

Analysis Of Traffic Crash Data In Kentucky 2018-2022, Paul Ross, Eric Green, Christopher Blackden, Christopher Van Dyke

Kentucky Transportation Center Research Report

This report documents analysis of traffic crash data in Kentucky. A primary objective of this study was to determine average crash statistics for Kentucky highways. Where used, rates were calculated for various highway types and for counties and cities. Difference criteria were used for exposure. Average and critical numbers, SPFs, and crash rates were calculated for various highway types in rural and urban areas. These metrics rely on crashes identified on highways where Annual Average Daily Traffic (AADT) volumes were available. Data in this report may be used to help identify problem areas. The other primary objective of this study …

Association Between Insurer Connectivity In Appalachian Population Health Networks And Preventable Hospitalizations: Evidence From Kentucky, Rachel Hogg-Graham, Kelsey R. Gatton, Rick Ingram, Glen P. Mays

Journal of Appalachian Health

Introduction: Addressing complex health and social needs requires cross-sector collaboration to deliver medical, social, and population health services at the community level. Capacity in community health and social services networks may be constrained in regions like Appalachia due to the combined effects of rurality and persistently poor health and social outcomes. One way that cross-sector networks serving low-resource communities can expand their capacity is by engaging partners, like health insurers, who can leverage resources from outside the local area.

Purpose: This study examines insurer connectivity in cross-sector networks across Kentucky’s geographic regions and the association between connectivity and the probability …

The Ninth Myth Of Appalachia, Randolph Wykoff

Journal of Appalachian Health

Many stereotypes afflict our much-maligned region, and the Jonesborough­­–Washington County History Museum displays eight of these "myths of Appalachia." Here, our Editor-in-Chief suggests a ninth—that the people of Appalachia "do not care" about their health—and argues that regional health disparities result not from apathy but from a confluence of socioeconomic factors.

Patient Engagement In Patient Portals In Appalachia V. Surrounding U.S. Census Regions: An Analysis Of Hints (Health Information National Trends Survey) Data, 2017–2020, Heather Lea Tudor, Rick Ingram, Sarah Wackerbarth

Journal of Appalachian Health

Introduction: Those living in the Appalachian Region face a greater number of significant health disparities than residents of other areas of the U.S. Patient portals can decrease disparities, increase health literacy, and improve health outcomes.

Purpose: This study explores if those living in the Appalachian Region are offered access to and use their patient portals differently than those in the surrounding U.S. Census regions. Additionally, the study aims to determine if there was a difference in reported reasons for the non-use of patient portals.

Methods: A secondary analysis was completed using data from the National Cancer Institute's Health Information National …

Self-Reported Consumption Of Bottled Water V. Tap Water In Appalachian And Non-Appalachian Kentucky, Jason W. Marion

Journal of Appalachian Health

Introduction: Quantitative studies on drinking water perceptions in Appalachia are limited. High-profile water infrastructure failures in the U.S. and Eastern Kentucky, coupled with human-made and natural disasters in the Appalachian Region, have likely impacted opinions regarding tap water.

Purpose: To use existing unexplored data to describe baseline tap water v. bottled water consumption in Kentucky.

Methods: Telephone-based cross-sectional data were obtained from the 2013 Kentucky Health Issues Poll (KHIP) directed by the Foundation for a Healthy Kentucky. Among many items in KHIP, self-reported consumption of bottled water over tap water, reasons for bottled water use, and demographic data were obtained. …

The Appalachian Gap In Preventable Hospitalizations: Are We Seeing Any Progress?, Rachel Hogg-Graham, Juan Lang, Teresa M. Waters

Journal of Appalachian Health

Introduction: Previous studies have documented geographic variation in preventable hospitalizations between rural and urban areas, but much less is known about preventable hospitalization patterns between heterogeneous rural areas. Unique challenges related to access of care and poverty may put the rural Appalachian Region at risk for higher rates of preventable hospitalizations.

Purpose: This study examines whether within-rural differences in Kentucky’s preventable hospitalization rates exist and how these differences may be changing over time.

Methods: Longitudinal and geographic trends in county-level preventable hospitalization rates were examined using Kentucky hospital discharge data from 2016 to 2019. Regression models were run to determine …

Evaluation Of A Faculty Fellows Program In Science Communication, Stacy Stanifer, Beverly Delidow, Kathy Rademacher, Luz Huntington-Moskos, Kelly Kennoy, Amanda Thaxton-Wiggins, Craig Wilmhoff, Ellen J. Hahn

Journal of Appalachian Health

Introduction: Science communication plays a crucial role in tackling pressing regional, national, and global health issues. Effective communication with various audiences is integral to dissemination of science findings.

Purpose: This study evaluates changes in self-efficacy and attitudes toward science communication skills over time and also assesses program outcomes and satisfaction with a Faculty Fellows in Science Communication (FFSC) program among faculty (N = 30) with interest in environmental health science and/or education in Appalachia Kentucky.

Methods: A mixed methods program evaluation was employed using longitudinal data on behaviors, attitudes, and program outcomes from three cohorts of Faculty Fellows who participated …

Impact Of Interprofessional Student Teams At A Remote Area Medical Event In Rural Appalachia, Emily K. Flores, Karilynn Dowling, Caroline Abercrombie Md, Rick L. Wallace

Journal of Appalachian Health

Introduction: Education in interprofessional collaboration is vital to expand healthcare access, especially in areas of higher disparity. To address this need, interprofessional faculty collaborators incorporated undergraduate and graduate health profession students into teams at an annual Remote Area Medical event in rural Appalachia between 2017 and 2020.

Purpose: This article evaluates the impact of an interprofessional student teams model on both patient care experience and students’ interprofessional collaboration attitudes and behaviors.

Methods: Student volunteers completed pre- and post-event surveys containing questions about demographics, open-ended questions, and questions from two instruments: the Student Perceptions of Interprofessional Clinical Education-Revised Instrument, Version 2 …

Scale Model Experiments Of Toxic Gas Production From The Combustion Of Polymers When Applied With Different Droplet Sizes Of Water Mist, Nicharee Thinnakornsutubutr, Masayuki Mizuno, Kazunori Kuwana

Progress in Scale Modeling, an International Journal

This research experimentally investigated the combustion of polymeric materials with water mist application in an enclosure, with an emphasis on the production of toxic gases. Two different diameters, ~100 and ~260 μm, were tested. The experimental conditions were determined based on Froude similarity laws for low drop Reynolds number conditions. Droplets and polymers’ physical and chemical properties influence the burning/extinguishing behavior and toxic-gas evolution. In general, larger droplets can extinguish a fire in a shorter time, and toxic gas concentrations in a test chamber decreased more rapidly. However, the large droplets tended to cause the flame expansion phenomenon for thermoplastics …

Unknown Rectal Lesions: A Case Of Severe Proctitis Secondary To Mpox In The Setting Of Concomitant Hiv, Syphilis, Hsv, And Chlamydia, Nicole Robertson Mph, James Crosby Do, Cynthia R. Young Md, Msc, Anne E. Sayers Md, Nicholas J. Van Sickles Md

ePublications of Emerging Medical Research Scholars

Introduction:

Mpox emerged as a public health crisis with limited research describing co-occurring HIV and sexually transmitted infections (STIs). We present a case of severe proctitis secondary to Mpox with concomitant HIV (Human Immunodeficiency Virus), syphilis, HSV (Herpes Simplex Virus), and chlamydia and review presentation, diagnosis, treatment, and prevention of Mpox with concurrent STIs.

Case Presentation:

34-year-old male living with HIV (LWH) presenting with worsening rectal pain, multiple anal papules, and fever. His laboratory workup revealed simultaneous positive results for orthopoxvirus, chlamydia, and HSV-1 PCR. We initiated tecovirimat due to rectal involvement and uncontrolled pain. He subsequently developed lesions on …

The Victorian Volcanic Plains Grassland: Past, Present And Future, Steve G. Clark, J. Crosthwaite, J. Dorrough, J. R. Hirth, Y. Ingeme, J. Mavromihalis, V. Turner

IGC Proceedings (1977-2023)

The Grasslands of the Victorian Volcanic Plains have been replaced with introduced pastures and crops since European settlement with the loss of many plant and animal species. What remains, on public and private land, has high conservation value and needs urgent protection.