Digital Commons Network^™

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …

Circular Rna Circnol10 Inhibits Lung Cancer Development By Promoting Sclm1-Mediated Transcriptional Regulation Of The Humanin Polypeptide Family, Aruo Nan, Lijian Chen, Nan Zhang, Yangyang Jia, Xin Li, Hanyu Zhou, Yihui Ling, Zhishan Wang, Chengfeng Yang, Sijin Liu, Yiguo Jiang

Toxicology and Cancer Biology Faculty Publications

circNOL10 is a circular RNA expressed at low levels in lung cancer, though its functions in lung cancer remain unknown. Here, the function and molecular mechanism of circNOL10 in lung cancer development are investigated using in vitro and in vivo studies, and it is shown that circNOL10 significantly inhibits the development of lung cancer and that circNOL10 expression is co‐regulated by methylation of its parental gene Pre‐NOL10 and by splicing factor epithelial splicing regulatory protein 1 (ESRP1). circNOL10 promotes the expression of transcription factor sex comb on midleg‐like 1 (SCML1) by inhibiting transcription factor ubiquitination and thus also affects regulation …

Cytochrome P450s And Uses Thereof, Joseph Chappell, Lyle F. Ralston

Pharmaceutical Sciences Faculty Patents

The invention relates to isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention relates to uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.

Multi-Ancestry Study Of Blood Lipid Levels Identifies Four Loci Interacting With Physical Activity, Tuomas O. Kilpeläinen, Amy R. Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, Thomas W. Winkler, Hermina Jakupović, Daniel I. Chasman, Alisa Manning, Ioanna Ntalla, Hugues Aschard, Michael R. Brown, Lisa De Las Fuentes, Nora Franceschini, Xiuqing Guo, Dina Vojinovic, Stella Aslibekyan, Mary F. Feitosa, Minjung Kho, Solomon K. Musani, Melissa Richard, Heming Wang, Zhe Wang, Traci M. Bartz, Lawrence F. Bielak, Archie Campbell, Rajkumar Dorajoo, Virginia Fisher, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL …

Cytochrome P450s And Uses Thereof, Joseph Chappell, Lyle F. Ralston

Pharmaceutical Sciences Faculty Patents

The invention relates to isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention relates to uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.

Implantation Of Left Ventricular Assist Device In The Setting Of Heavily Calcified Left Ventricular Apex Using An Apex Preserving Technique, Ismael A. Salas De Armas, Mehmet H. Akay, Jayeshkumar A. Patel, Chandni Patel, Manish K. Patel, Bindu Akkanti, Biswajit Kar, Igor D. Gregoric

The VAD Journal

A heavily calcified ventricular apex represents a challenging, rare and unique situation in LVAD implantation. A 44-year-old male was admitted with myocardial infarction. Left heart catheterization was complicated by episodes of ventricular fibrillation. After an acute stabilization with veno-arterial extracorporeal membrane oxygenation (VA-ECMO), an LVAD implantation was approved. Pre-operative work-up had shown a heavily calcified ventricular apex and an intraventricular thrombus, which was confirmed intraoperatively. To retain a viable ventricular geometry, the decision was made to preserve the calcified apex rather than to excise the entire calcified left ventricular aneurysm. Sutures for the inlet cannula were placed around the calcific …

Hemodynamic, Therapeutic, And Clinical Outcomes Of Ambulatory Pressure-Guided Heart Failure Management, Jacob Abraham, Lian Wang, Rebecca Lewis, Katherine Callis, Joshua Remick, Kateri J. Spinelli

The VAD Journal

Background: Heart failure (HF) management guided by CardioMEMS™ pulmonary artery pressure (PAP) monitoring reduces PAP and HF hospitalizations. The objective of this project was to characterize the relationship between medication adjustments, PAP change, and outcomes for all patients at an advanced HF center.

Methods: We retrospectively analyzed medication changes and hospitalizations for 32 consecutive patients implanted with the CardioMEMS™ sensor at a single HF center and related these outcomes to PAP data from the Merlin.net (Abbott) database. Absolute change in PAP from baseline was estimated using area under the curve normalized to days monitored.

Results: Patients had an average change …

Upcoming Events [2019], Christopher D. Teutsch, Christi L. Forsythe, Rehanon Pampell

Forage Symposium at the Kentucky Cattlemen’s Convention

No abstract provided.

Economics Of Grazing Cover Crops, Edward N. Ballard

Forage Symposium at the Kentucky Cattlemen’s Convention

Feed costs represent the major cost in most livestock production systems. A completed analysis of 225 Standardized Performance Analysis (SPA) Beef Cow Records on herds in Illinois and Iowa showed that feed cost was the overriding factor determining profitability, explaining over 57 percent of the herd-to-herd variation.

2018 Long-Term Summary Of Kentucky Forage Variety Trials, Gene L. Olson, S. Ray Smith, Jimmy C. Henning, Christopher D. Teutsch

Forage Symposium at the Kentucky Cattlemen’s Convention

Forage crops occupy approximately 7 million acres in Kentucky. Forages provide a majority of the nutrition for beef, dairy, horse, goat, sheep, and wildlife in the state. In addition, forage crops play an environmentally friendly role in soil conservation, water quality, and air quality. There are over 60 forage species adapted to the climate and soil conditions of Kentucky. Only 10 to 12 of these species occupy the majority of the acreage, but within these species there is a tremendous variation in varieties.

This publication was developed to provide a user-friendly guide to choosing the best variety for producers based …

Cancer Screening For Transgender Patients: An Online Case-Based Module, Devin Oller

Internal Medicine Faculty Publications

Introduction: Guidelines recommend that primary care providers complete organ-based routine cancer screening for all transgender patients. Training on critical transgender health topics like cancer screening, as well as residents' confidence in addressing issues their transgender patients may face, remains limited among graduate medical education (GME) programs. Online case-based modules are an effective tool for skills improvement in GME, but their application to transgender health topics has not been assessed.

Methods: I developed a brief online module on cancer screening for transgender patients using Google Forms and offered it to first-year internal medicine residents. The module was optional and asynchronous with …

Use Of A Cross-Sectional Survey In The Adult Population To Characterize Persons At High-Risk For Chronic Obstructive Pulmonary Disease, Roy A. Pleasants, Khosrow Heidari, Jill Ohar, James F. Donohue, Njira Lugogo, Chelsea L. Richard, Sarojina Kanotra, David M. Mannino, Monica Kraft, Winston Liao, Charlie Strange

Internal Medicine Faculty Publications

Rationale/Objective: The Behavioral Risk Factor Surveillance System (BRFSS) health survey has been used to describe the epidemiology of chronic obstructive pulmonary disease (COPD) in the US. Through addressing respiratory symptoms and tobacco use, it could also be used to characterize COPD risk. Methods: Four US states added questions to the 2015 BRFSS regarding productive cough, shortness of breath, dyspnea on exertion, and tobacco duration. We determined COPD risk categories: provider-diagnosed COPD as self-report, high-risk for COPD as ≥ 10 years tobacco smoking and at least one significant respiratory symptom, and low risk was neither diagnosed COPD nor high risk. Disease …

Coatings On Mammalian Cells: Interfacing Cells With Their Environment, Kara A. Davis, Pei-Jung Wu, Calvin F. Cahall, Cong Li, Anuhya Gottipati, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

The research community is intent on harnessing increasingly complex biological building blocks. At present, cells represent a highly functional component for integration into higher order systems. In this review, we discuss the current application space for cellular coating technologies and emphasize the relationship between the target application and coating design. We also discuss how the cell and the coating interact in common analytical techniques, and where caution must be exercised in the interpretation of results. Finally, we look ahead at emerging application areas that are ideal for innovation in cellular coatings. In all, cellular coatings leverage the machinery unique to …

Excluding Ptv From Lung Volume May Better Predict Radiation Pneumonitis For Intensity Modulated Radiation Therapy In Lung Cancer Patients, Yinnan Meng, Haihua Yang, Wei Wang, Xingni Tang, Caiping Jiang, Yichao Shen, Wei Luo

Radiation Medicine Faculty Publications

Background: Lung dose-volume histogram (DVH) in radiotherapy could be calculated from multiple normal lung definitions. The lung dosimetric parameters generated from various approaches are significantly different. However, limited evidence shows which definition should be used to more accurately predict radiation pneumonitis (RP). We aimed to compare the RP prediction accuracy of dosimetric parameters from three lung volume methods in lung cancer patients treated with Intensity-Modulated Radiation Therapy (IMRT).

Methods: We retrospectively reviewed 183 consecutive lung cancer patients treated with IMRT from January 2014 to October 2017. The normal lungs were defined by total bilateral lung volume (Total Lung), excluding PTV …

Patterns And Predictors Of Chronic Opioid Use In Older Adults: A Retrospective Cohort Study, Gyeon Oh, Erin L. Abner, David W. Fardo, Patricia R. Freeman, Daniela C. Moga

Epidemiology and Environmental Health Faculty Publications

Background

Given the controversy around the effectiveness of opioid treatment for chronic pain and the lack of detailed guidance for prescribing opioids in older adults, the objectives of this study were to estimate the trajectories and predictors of opioid use in older adults.

Methods

Data were extracted from the National Alzheimer’s Coordinating Center (2005–2017). Group-based trajectory modeling was used to identify the patterns of opioid use (any or strong) among participants age 65+. We used multivariable logistic regression with backward selection to evaluate demographics and comorbidities as potential predictors of trajectory membership.

Results

Among 13,059 participants, four trajectories were identified …

The Politics Of Richard Wright, Jane Anna Gordon, Cyrus Ernesto Zirakzadeh

Civil Rights

A pillar of African American literature, Richard Wright is one of the most celebrated and controversial authors in American history. His work championed intellectual freedom amid social and political chaos. Despite the popular and critical success of books such as Uncle Tom's Children (1938), Black Boy (1945), and Native Son (1941), Wright faced staunch criticism and even censorship throughout his career for the graphic sexuality, intense violence, and communist themes in his work. Yet, many political theorists have ignored his radical ideas.

In The Politics of Richard Wright, an interdisciplinary group of scholars embraces the controversies surrounding Wright as …

Antisense Oligonucleotides Targeting Angiotensinogen: Insights From Animal Studies, Chia-Hua Wu, Ya Wang, Murong Ma, Adam E. Mullick, Rosanne M. Crooke, Mark J. Graham, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the unique substrate of all angiotensin peptides. We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. The scope of the research findings not only opens doors for potentially new therapeutics of hypertension and many other diseases, but also provides insights into understanding critical physiological and pathophysiological roles mediated by AGT.

Allogeneic Hematopoietic Cell Transplantation Provides Effective Salvage Despite Refractory Disease Or Failed Prior Autologous Transplant In Angioimmunoblastic T-Cell Lymphoma: A Cibmtr Analysis, Narendranath Epperla, Kwang W. Ahn, Carlos Litovich, Sairah Ahmed, Minoo Battiwalla, Jonathon B. Cohen, Parastoo Dahi, Nosha Farhadfar, Umar Farooq, Cesar O. Freytes, Nilanjan Ghosh, Bradley Haverkos, Alex Herrera, Mark Hertzberg, Gerhard C. Hildebrandt, David Inwards, Mohamed A. Kharfan-Dabaja, Farhad Khimani, Hillard Lazarus, Aleksandr Lazaryan, Lazaros Lekakis, Hemant Murthy, Sunita Nathan, Taiga Nishihori, Attaphol Pawarode, Tim Prestidge, Praveen Ramakrishnan, Andrew R. Rezvani, Rizwan Romee, Nirav N. Shah

Internal Medicine Faculty Publications

Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016.

Results: The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 …

Bishydrazone-Based Antifungal Agents, Sylvie Garneau-Tsodikova, David S. Watt

Pharmaceutical Sciences Faculty Patents

Hydrazone compounds and pharmaceutical compositions including same are disclosed as having antifungal activity. Such compounds are useful for treating or preventing fungal conditions in a subject in need thereof by administering same.

Plasmodium Para-Aminobenzoate Synthesis And Salvage Resolve Avoidance Of Folate Competition And Adaptation To Host Diet, Joachim Michael Matz, Mutsumi Watanabe, Mofolusho Falade, Takayuki Tohge, Rainer Hoefgen, Kai Matuschewski

Pharmaceutical Sciences Faculty Publications

Folate metabolism is essential for DNA synthesis and a validated drug target in fast-growing cell populations, including tumors and malaria parasites. Genome data suggest that Plasmodium has retained its capacity to generate folates de novo. However, the metabolic plasticity of folate uptake and biosynthesis by the malaria parasite remains unresolved. Here, we demonstrate that Plasmodium uses an aminodeoxychorismate synthase and an aminodeoxychorismate lyase to promote the biogenesis of the central folate precursor para-aminobenzoate (pABA) in the cytoplasm. We show that the parasite depends on de novo folate synthesis only when dietary intake of pABA by …

Disruption Of The Hippocampal And Hypothalamic Blood-Brain Barrier In A Diet-Induced Obese Model Of Type Ii Diabetes: Prevention And Treatment By The Mitochondrial Carbonic Anhydrase Inhibitor, Topiramate, Therese S. Salameh, William G. Mortell, Aric F. Logsdon, D. Allan Butterfield, William A. Banks

Chemistry Faculty Publications

Background: Type II diabetes is a vascular risk factor for cognitive impairment and increased risk of dementia. Disruption of the blood–retinal barrier (BRB) and blood–brain barrier (BBB) are hallmarks of subsequent retinal edema and central nervous system dysfunction. However, the mechanisms by which diet or metabolic syndrome induces dysfunction are not understood. A proposed mechanism is an increase in reactive oxygen species (ROS) and oxidative stress. Inhibition of mitochondrial carbonic anhydrase (mCA) decreases ROS and oxidative stress. In this study, topiramate, a mCA inhibitor, was examined for its ability to protect the BRB and BBB in diet-induced obese type II …

Star-Related Lipid Transfer Protein 10 (Stard10): A Novel Key Player In Alcohol-Induced Breast Cancer Progression, Andrea Floris, Jia Luo, Jacqueline A. Frank, Jennifer Zhou, Sandro Orrù, Michela Biancolella, Sabina Pucci, Augusto Orlandi, Paolo Campagna, Antonella Balzano, Komal Ramani, Maria Lauda Tomasi

Pharmacology and Nutritional Sciences Faculty Publications

Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35–40% of ERBB2-positive breast …

Maternal Work Hours And Childhood Obesity: Evidence Using Instrumental Variables Related To Sibling School Eligibility, Charles J. Courtemanche, Rusty Tchernis, Xilin Zhou

Economics Faculty Publications

This study exploits plausibly exogenous variation derived from the youngest sibling’s school eligibility to estimate the effects of maternal work on the weight outcomes of older children. We first show that mothers’ work hours increase gradually along both the extensive and intensive margins as the age of the youngest child rises, whereas mothers’ spouses’ work hours do not appear to be responsive. We develop an instrumental-variables model that shows that mothers’ work hours lead to larger increases in children’s body mass index z-scores and probabilities of being overweight/obese than those identified in previous studies. Subsample analyses find that the …

Toward An Understanding Of Behavioral And Sensory Experiences When Living With Dementia And Related Disorders: An Environmental Gerontology Perspective, Elizabeth K. Rhodus

Theses and Dissertations--Gerontology

Behavioral and psychological symptoms of dementia create challenges for those living with neurodegenerative cognitive impairment and their care partners. Pharmacological approaches for treatment of challenging behaviors seen in dementia have limited success and serious side effects. Because of this, nonpharmacological approaches are being investigated with increasing frequency. Of particular interest are nonpharmacological approaches involving environmental stimulation to change behaviors. Success of such approaches relies on sensory processing systems, personal preferences, and environmental congruence. There is limited evidence describing behaviors of persons with cognitive impairment in relation to these components. Currently, there is no guiding model for implementation of environmental and …

Process Sustainability Evaluation For Manufacturing Of A Component With The 6r Application, Ana E. Bonilla Hernández, Tao Lu, Tomas Beno, Claes Fredriksson, Ibrahim S. Jawahir

Institute for Sustainable Manufacturing Faculty Publications

Sustainability in manufacturing can be evaluated at product, process and system levels. The 6R methodology for sustainability enhancement in manufacturing processes includes: reduced use of materials, energy, water and other resources; reusing of products/components; recovery and recycling of materials/components; remanufacturing of products; and redesigning of products to utilize recovered materials/resources. Although manufacturing processes can be evaluated by their productivity, quality and cost, process sustainability assessment makes it a complete evaluation. This paper presents a 6R-based evaluation method for sustainable manufacturing in terms of specific metrics within six major metrics clusters: environmental impact, energy consumption, waste management, cost, resource utilization and …

Special Problems In Agricultural Economics, Alexander Ogden Swartz

Theses and Dissertations--Agricultural Economics

According to the USDA Economic Research service, farm-level prices are on the decline. This decline in prices particularly hurts smaller scale operators with many needing to rely on off-farm income in order to ensure they remain in operation. This thesis studies two problems of key interest to the Southeast region and the State of Kentucky by investigating dairy management practices and the environmental benefits of hemp production. As dairy prices have been on the decline and dairy co-ops have tightened their restrictions on somatic cell count (SCC) levels, dairy farmers and farm managers must decide the best course of action …

Two Essays In Fertilizer Management For Improved Profitability, Shelby Dawn Wade

Theses and Dissertations--Agricultural Economics

Corn production in the United States has become increasingly efficient over the years. The use of nitrogen fertilizers has played a substantial role in this efficiency. Nitrogen drives biomass production which leads to increased yields. Unlike other nutrients, nitrogen is more mobile making it easier to lose through leaching and volatilization. The first part of this analysis uses an econometric model to examine the relationship between nitrogen usage and weather data. This relationship leads to farm management decisions to reduce nitrogen fertilization expenses. In addition to the use of nitrogen fertilizers, farmers in Kentucky take advantage of an abundance of …

Two Essays On Input Substitution And Optimal Decision Making In Crop And Livestock Production Systems, John T. Allison Jr.

Theses and Dissertations--Agricultural Economics

The thesis presented consists of two essays that analyze input substitution and decision making in crop and livestock production systems. The first essay consists of a whole-farm analysis that sought to optimize feed mixes and enterprise combinations for an organic dairy operation in the Southeastern United States. This was accomplished through mathematical programming where whole-farm net returns were maximized, and total feed costs were minimized simultaneously for four milk production level cases. Additionally, the sensitivity of the system and break-even milk price were explored. Results suggest substitutability in ration components where an increase in supplemental feeds is justified by additional …

Standardizing The Law On Working Animals, Mallie A. Myers

Kentucky Journal of Equine, Agriculture, & Natural Resources Law

No abstract provided.

Residual Next-Day Effects Of Alprazolam On Psychomotor Performance And Simulated Driving In Healthy Normal Volunteers, Marion A. Coe

Theses and Dissertations--Pharmacology and Nutritional Sciences

The prevalence of drugged driving has increased in the United States, and some prescription medications (e.g., zolpidem) cause impairment after the predicted duration of therapeutic action has elapsed. The aim of this study is to determine if bedtime administration of alprazolam similarly impacts driving performance the following day.

Volunteers were 14 healthy adults (6 males) who completed a double-blind, double-dummy within-subjects design study examining the effects of alprazolam (0.5, 1, & 2mg), zolpidem (10mg), and placebo administered at bedtime on driving performance the following day. The positive control condition was alprazolam (1mg) administered on the test morning. Driving simulator measures, …