Sex Dimorphism In Hematopoiesis And Bone Marrow Niche, Xiaojing Cui

Theses and Dissertations--Toxicology and Cancer Biology

Hematopoietic stem cells (HSC), which are a rare population of cells existing in human circulating blood and bone marrow, can form the whole-blood system by their self-renewal capacity and differentiation ability. Sex dimorphism can be found in hematopoietic stem and progenitor cells, and in the development of hematopoietic lineages. Also, males are at higher risk and have a worse prognosis for most hematologic malignancies than females. Under normal conditions, the number of circulating progenitor cells in women is lower than in men. Furthermore, female mice have a higher rate of HSC division than male mice. A dramatic gender difference exists …

A Pathway For Inclusive Innovation In Pediatric Mental Health: Prevention And Intervention Using Technology, Kate Corinne Bennett

DSW Capstone Projects

It is no secret that access to quality healthcare is difficult for citizens to achieve in the United States. Racism, discrimination, and oppression further exist at the root of compounding social problems, including limits in minority access to mental health services. The COVID-19 pandemic has also exacerbated mental health problems for young children, especially those who are already underserved and at risk. For these reasons, it is imperative that the social work profession emphasizes innovative approaches to equitable treatment access, including a focus on early intervention and the use of technology. Product one of this capstone engages a systematic review …

Apoe Genotype And Sex Modulate Ketogenic Diet Enhancements To Metabolism And Gut Microbiome In Young Mice, Andrew T. Yackzan

Theses and Dissertations--Medical Sciences

The apolipoprotein ε (APOE) allele in humans has been associated with risk for development of Alzheimer’s disease (AD). There are predominately three variations of the allele – ε2 (E2), ε3 (E3), and ε4 (E4) – with E4 contributing the greatest risk of AD development. Recent research has unveiled evidence of neurometabolic and neurovascular deficits in E4 carriers present decades before the onset of dementia; it is believed these chronic defects play a major role in the development of AD, thus making them a potential target for preventative intervention. The purpose of this study was to examine the effect of a …

Novel Mechanism Of Endogenous Pancreatic Cancer Cell Expression Of Immune Checkpoint Programmed Cell-Death 1 Protein (Pd-1) Inducing Epithelial-To-Mesenchymal Transition (Emt) Through The Met Pathway And Promoting Cancer Progression In An Immune-Independent Process, Megan M. Harper

Theses and Dissertations--Clinical and Translational Science

Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers with few treatment options, necessitating an urgent need for novel therapeutics. Immuno-oncologic (IO) therapies have revolutionized anti-cancer regimens in the past decade but typically involve reactivation of adaptive immune responses. In particular, immune checkpoint PD-1 is traditionally expressed only on immune cells while PD-L1 (PD-1 ligand) is overexpressed on cancer cells. When tumor-endogenous PD-L1 binds the PD-1 receptor on T-cells, the immune cells undergo anergy resulting in self-tolerance and cancer cell immune evasion. However, contrary to standard dogma, we previously demonstrated tumor-endogenous PD-1 expression in PDAC. Our data indicated that …

Progressive Endoscopic Approach To Balloon Dilation For Benign Esophageal Strictures, Chad J. Cooper

Theses and Dissertations--Clinical and Translational Science

Benign esophageal strictures are a frequently encountered problem in clinical practice. The management of benign esophageal strictures have slowly evolved over the decades based on “expert opinion.” Despite vast amounts of data about the efficacy and safety of dilation, unfortunately there is no consensus on a systematic and safe approach that is efficient, limits complications and provides long lasting improvement of dysphagia. Our group designed a progressive approach to endoscopic balloon dilation based on tailoring certain technical aspects of the dilation process.

Most studies in the literature concluded that endoscopic dilation is safe and effective in relieving dysphagia caused by …

Investigating The Uncertainties In Ct Non-Small Cell Lung Cancer Radiomics, Gary Ge

Theses and Dissertations--Radiation Medicine

Radiomics is a technique that extracts quantitative features, termed radiomic features, from medical images using data-characterization algorithms. These radiomic features can be used to identify tissue characteristics and radiologic phenotyping that are not observable by clinicians in a non-invasive, low-cost manner, potentially generating image biomarkers for clinical decision. To date, there are still many uncertainties involved in radiomics which limit its clinical implementation. Herein, we propose to explore the impact of each component in the radiomics pipeline on predicting clinical outcomes. In Chapter II, we conduct a thorough review of CT lung cancer radiomics studies to examine the typical feature …

A Plague Of Their Own: Injury Incidence Remains Elevated In The 2021 Major League Baseball Season Compared To Pre-Covid-19 Seasons, Brooks N. Platt, Breanna Sullivan, Shawn Dripchak, Timothy L. Uhl, Aaron Sciascia, William B. Kibler, Austin V. Stone

Orthopaedic Surgery and Sports Medicine Faculty Publications

Background Significant increases in injuries were observed in the 2020 Major League Baseball (MLB) season; these were attributed to an increased acute to chronic workload due to the interrupted preseason and compressed season during the coronavirus disease of 2019 (COVID-19) pandemic. In 2021, the MLB resumed its regular schedule.

Hypothesis/Purpose The purpose of this study was to determine the injury incidence and epidemiology of the 2021 MLB season compared to the injury incidence in the 2020 season and pre-COVID-19 seasons. The hypothesis was that, with the return to normal preseason training, injury incidence in 2021 would return to pre-COVID-19 rates. …

Social And Biological Determinants Of Pregnancy-Related Mortality And Morbidity In A Rural, Underserved Population, Anna Hansen

Theses and Dissertations--Sociology

Cases of severe maternal morbidity (SMM) and pregnancy-related mortality (PRM) are increasing in the US. Research concerning SMM and PRM has neglected women in Central Appalachia; a largely rural, health-disparate population. The aims of this study are two-fold: (1) Examine patient-level and place-based predictors of SMM/PRM via hierarchical logistic regression modeling, and (2) Elucidate Appalachian healthcare patients’ and providers’ experiences with SMM/PRM, perceptions of contributing factors, and insights on points of intervention.

This study uses a mixed methods approach guided by the WHO’s conceptual framework for action on social determinants of health to identify determinants of SMM and PRM among …

Examining Psychological And Knowledge Barriers To Colorectal Cancer Screening In Rural Appalachian Kentucky, Caroline Jenkins, Matthew Rutledge, Lauren Hudson, Nathan L. Vanderford, Nancy Schoenberg

Markey Cancer Center Faculty Publications

While recent rates of colorectal cancer (CRC) screening have improved in Appalachian Kentucky due to public health efforts, they remain lower compared to both KY as a whole, and the USA. Suboptimal screening rates represent a missed opportunity to engage in early detection and prevention. The purpose of this study is to determine the impact that lack of knowledge has on psychological barriers (e.g., fear and embarrassment) to CRC screening as well as the potential effect of a psychosocial intervention to reduce these barriers. Participants were recruited through faith-based organizations and other community sites. After randomizing participants to either an …

Increasing Staff Compliance With Routine Hcv Screening And Improving Linkage To Care Among Patients Testing Hepatitis C Positive In The Emergency Department, Carson G. Swartz

DNP Projects

Background: Hepatitis C virus (HCV) is a blood-borne pathogen that can cause severe liver disease, cancer, and death and is a significant source of morbidity and mortality in the United States. Several academic medical centers including University of Kentucky Healthcare have implemented routine HCV screening for patients presenting to the emergency department (ED) and have discovered a large viral burden amongst patients who are often symptomatic.

Purpose: The purpose of this doctoral project is to increase staff compliance, confidence, and education regarding the HCV screening process in an urban, Level I emergency department, as well as to evaluate whether an …

The Use Of A Pediatric Palliative And Hospice Education Module To Enhance The Knowledge And Practice Of Emergency Room Providers, Morgan Garrett

DNP Projects

Background: Palliative and hospice care resources are underutilized in pediatric patients with chronic and life-limiting illnesses. One contributing factor is the lack of formalized education for medical providers regarding the differences and scope of palliative and hospice care models. Without adequate education about these services, providers are not able to effectively utilize otherwise available resources to provide holistic care.

Purpose: The purpose of this study was to assess the current perception of knowledge among providers pertaining to pediatric palliative and hospice care. The study investigated improvements in educational outcomes in ten categories after participation in a web-based training. A secondary …

Evaluation Of A Beverage Educational Intervention For Latino Parents Of Infants And Children Ages Nine Months To Five Years, Natalie Chelf

DNP Projects

Background: The Latino population has the highest rate of childhood obesity in the United States. Sugar-sweetened beverage (SSB) consumption has a positive correlation with increased rates of childhood obesity. Current research shows a deficit in culturally sensitive methods to reduce SSB consumption in the pediatric Latino population.

Purpose: The purpose of this project is to empower parents of Latino infants and young children with the knowledge to reduce or eliminate the consumption of SSBs in their child’s diet.

Methods: The project was a one group pre-test post-test quasi-experimental study design occurring in one pediatric outpatient clinic. The Information-Motivation-Behavioral Skills (IMB) …

Addressing The Inpatient Penicillin Allergy: Implementing A Nurse-Driven Allergy Assessment Tool To Enhance Antimicrobial Stewardship., Shelby Ryan Bliss

DNP Projects

Background: In an acute care setting, more than half the inpatient population receives antibiotics. Approximately 10% of the general population reports an allergy to penicillin. It has been replicated in the literature with data that of those who report a penicillin allergy, up to 95% are incorrectly identified. When a patient is admitted to the hospital with a penicillin allergy on their electronic health record, they are at higher risk for adverse events such as a hospital acquired infection, the occurrence of an antibiotic resistant bacteria related to receiving broader therapy and increased healthcare utilization.

Purpose: The purpose of this …

The Effect Of Education On The Nida Modified Assist (Nmassist) Tool On Knowledge And Screening For Substance Use Disorder Among Clinicians, Victoria Page Arnold

DNP Projects

Background: Substance use disorder (SUD) is a disparity affecting nearly 24 million individuals in the U.S., nearly 10% of the total population. Oftentimes, the emergency department (ED) is the only medical care this population receives. There is often a lack of screening for SUD in ED’s, therefore referred care may be limited for these individuals. The National Institute on Drug Abuse Modified Assist (NMASSIST) is an evidence-based tool developed to educate and screen for SUD. This tool can be completed in a timely manner and aid in the recommended referral of care for this select population.

Purpose: The purpose of …

Promotion Of Early Recognition Of Depression To Improve Health Related Quality Of Life In Pediatric Oncology Patients, Jennifer Blankenship

DNP Projects

Background: Depression and anxiety are serious complications of cancer and deemed a challenging diagnosis due to the symptoms of depression mimicking common side effects of chemotherapy and radiation. Signs/symptoms frequently are underrecognized thus appropriate treatment is delayed, compromising the health-related quality of life (HRQOL) for pediatric oncology patients.

Purpose: Analyze existing physician and Advanced Practice Provider (APP) clinical practice regarding depression, via a pre- and post-survey and educational PowerPoint on the use of the Center for Epidemiological Studies Depression Scale for Children (CES-DC) to promote early recognition of depression.

Methods: A prospective, single-arm, study was completed in the Kentucky Children’s …

Single-Cell Analysis Of Aneurysmal Aortic Tissue In Patients With Marfan Syndrome Reveals Dysfunctional Tgf-Β Signaling, Ashley Dawson, Yanming Li, Yang Li, Pingping Ren, Hernan G. Vasquez, Chen Zhang, Kimberly R. Rebello, Waleed Ageedi, Alon R. Azares, Aladdein Burchett Mattar, Mary Burchett Sheppard, Hong S. Lu, Joseph S. Coselli, Lisa A. Cassis, Alan Daugherty, Ying H. Shen, Scott A. Lemaire

Saha Cardiovascular Research Center Faculty Publications

The molecular and cellular processes leading to aortic aneurysm development in Marfan syndrome (MFS) remain poorly understood. In this study, we examined the changes of aortic cell populations and gene expression in MFS by performing single-cell RNA sequencing (scRNA seq) on ascending aortic aneurysm tissues from patients with MFS (n = 3) and age-matched non-aneurysmal control tissues from cardiac donors and recipients (n = 4). The expression of key molecules was confirmed by immunostaining. We detected diverse populations of smooth muscle cells (SMCs), fibroblasts, and endothelial cells (ECs) in the aortic wall. Aortic tissues from MFS showed alterations …

Through The Lens: Youth Experiences With Cancer In Rural Appalachian Kentucky Using Photovoice, Katie Gaines, Courtney Martin, Chris Prichard, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Rural Appalachian Kentucky experiences disproportionately high cancer incidence and mortality rates. This cancer burden is due to social determinants of health and cultural factors prominent in the region. The firsthand experiences of community members—especially young people—can highlight these factors and identify areas for improvement. The purpose of this study was to encourage Appalachian Kentucky youth to consider determinants of cancer and visualize the effects that cancer has on their families or communities by asking them to take photographs of cancer-related objects around them. Content analysis was performed on 238 photographs submitted by 25 students, and photographs were organized into themes, …

Typical Sounding Atypical Diagnostic Conundrum -- A Rare Case Of Mycobacterium Avium Complex (Mac) Presenting With Multiple Cranial Nerve Involvement, Ashwini Kini, Karl Echiverri, Edward J. Escott, Padmaja Sudhakar

Neurology Faculty Publications

Background

MAC infections rarely cause symptomatic systemic infection in immunocompetent healthy individuals. This case brings to light a rare such presentation that gives us a learning point about keeping a strong pre-clinical suspicion for this condition in patients whom lung imaging reveals suspicious cavitary lesions. Starting empiric therapy while awaiting culture results may be considered after weighing risks and benefits in order to achieve the morbidity and mortality associated with the disease.

Case report

A 54 year-old white male presented for evaluation of progressively worsening vertigo, imbalance, vertical diplopia, facial diplegia, bilateral hyperacusis followed by hearing loss, dysphagia, and dysarthria …

Genetic Contributors Of Incident Stroke In 10,700 African Americans With Hypertension: A Meta-Analysis From The Genetics Of Hypertension Associated Treatments And Reasons For Geographic And Racial Differences In Stroke Studies, Nicole D. Armstrong, Vinodh Srinivasasainagendra, Amit Patki, Rikki M. Tanner, Bertha A. Hidalgo, Hemant K. Tiwari, Nita A. Limdi, Ethan M. Lange, Leslie A. Lange, Donna K. Arnett, Marguerite R. Irvin

Epidemiology and Environmental Health Faculty Publications

Background: African Americans (AAs) suffer a higher stroke burden due to hypertension. Identifying genetic contributors to stroke among AAs with hypertension is critical to understanding the genetic basis of the disease, as well as detecting at-risk individuals.

Methods: In a population comprising over 10,700 AAs treated for hypertension from the Genetics of Hypertension Associated Treatments (GenHAT) and Reasons for Geographic and Racial Differences in Stroke (REGARDS) studies, we performed an inverse variance-weighted meta-analysis of incident stroke. Additionally, we tested the predictive accuracy of a polygenic risk score (PRS) derived from a European ancestral population in both GenHAT and REGARDS AAs …

Late-Life Exercise Mitigates Skeletal Muscle Epigenetic Aging, Kevin A. Murach, Andrea L. Dimet-Wiley, Yuan Wen, Camille R. Brightwell, Christine M. Latham, Cory M. Dungan, Christopher S. Fry, Stanley J. Watowich

Center for Muscle Biology Faculty Publications

There are functional benefits to exercise in muscle, even when performed late in life, but the contributions of epigenetic factors to late-life exercise adaptation are poorly defined. Using reduced representation bisulfite sequencing (RRBS), ribosomal DNA (rDNA) and mitochondrial-specific examination of methylation, targeted high-resolution methylation analysis, and DNAge™ epigenetic aging clock analysis with a translatable model of voluntary murine endurance/resistance exercise training (progressive weighted wheel running, PoWeR), we provide evidence that exercise may mitigate epigenetic aging in skeletal muscle. Late-life PoWeR from 22–24 months of age modestly but significantly attenuates an age-associated shift toward promoter hypermethylation. The epigenetic age of muscle …

The Efficacy Of Sequential Biologic Agents In Refractory Rheumatoid Arthritis After Failure Of Initial Dmard And Anti-Tumor Necrosis Factor Therapy, Antonio Giovanni Versace, Caterina Oriana Aragona, Daniela La Rosa, Marianna Chiappalone, Maria Concetta Tringali, Alberta De Gaetano, Charles Frederick Moore Jr., Donatella Sangari, William Neal Roberts, Gianluca Bagnato

Internal Medicine Faculty Publications

Introduction/Objective: The efficacy of biologic therapy in the treatment of rheumatoid arthritis (RA) has been well-established but, in practice, a quarter of patients will either not respond to the first biologic agent or will suffer an adverse event requiring a switch to a different drug. While clinical guidelines exist to help guide therapy and previous studies have examined sequential use of anti-TNF agents, there is little data to inform a multiple switch strategy. Our aim was to measure the efficacy of multiple switches of biologic in severe refractory RA. Methods: We enrolled 111 patients whose therapy with one anti-TNF agent …

Does Anyone Remember "Fingerprints On An X-Ray?", Vincent L. Sorrell

Gill Heart & Vascular Institute Faculty Publications

No abstract provided.

Can Activated Titanium Interbody Cages Accelerate Or Enhance Spinal Fusion? A Review Of The Literature And A Design For Clinical Trials, Nathaniel Toop, Connor Gifford, Rouzbeh Motiei-Langroudi, Arghavan Farzadi, Daniel Boulter, Reza Forghani, H. Francis Farhadi

Neurosurgery Faculty Publications

While spinal interbody cage options have proliferated in the past decade, relatively little work has been done to explore the comparative potential of biomaterial technologies in promoting stable fusion. Innovations such as micro-etching and nano-architectural designs have shown purported benefits in in vitro studies, but lack clinical data describing their optimal implementation. Here, we critically assess the pre-clinical data supportive of various commercially available interbody cage biomaterial, topographical, and structural designs. We describe in detail the osteointegrative and osteoconductive benefits conferred by these modifications with a focus on polyetheretherketone (PEEK) and titanium (Ti) interbody implants. Further, we describe the rationale …

A Step-By-Step Guide To Implementing A Multidisciplinary Endocarditis Team, Sami El-Dalati, Daniel Cronin, James Riddell, Michael Shea, Richard L. Weinberg, Emily Stoneman, Twisha Patel, Kirra Ressler, George Michael Deeb

Internal Medicine Faculty Publications

Over the last several years multiple studies, primarily from European centers have demonstrated the clinical and outcomes benefits of multidisciplinary endocarditis teams. Despite this literature, adoption of this approach to patient care has been slower in the United States. While there is literature outlining the optimal composition of an endocarditis team, there is little information to guide providers as they attempt to transform practice from a fragmented, disjointed process to an efficient, collaborative care model. In this review, the authors will outline the steps they took to create and implement a successful multidisciplinary endocarditis team at the University of Michigan. …

Persistent Polypharmacy And Fall Injury Risk: The Health, Aging And Body Composition Study, Lingshu Xue, Robert M. Boudreau, Julie M. Donohue, Janice C. Zgibor, Zachary A. Marcum, Tina Costacou, Anne B. Newman, Teresa M. Waters, Elsa S. Strotmeyer

Health Management and Policy Faculty Publications

Background

Older adults receive treatment for fall injuries in both inpatient and outpatient settings. The effect of persistent polypharmacy (i.e. using multiple medications over a long period) on fall injuries is understudied, particularly for outpatient injuries. We examined the association between persistent polypharmacy and treated fall injury risk from inpatient and outpatient settings in community-dwelling older adults.

Methods

The Health, Aging and Body Composition Study included 1764 community-dwelling adults (age 73.6 ± 2.9 years; 52% women; 38% black) with Medicare Fee-For-Service (FFS) claims at or within 6 months after 1998/99 clinic visit. Incident fall injuries (N = 545 in …

Role Of Serum Amyloid A In Abdominal Aortic Aneurysm And Related Cardiovascular Diseases, Preetha Shridas, Avery C. Patrick, Lisa R. Tannock

Internal Medicine Faculty Publications

Epidemiological data positively correlate plasma serum amyloid A (SAA) levels with cardiovascular disease severity and mortality. Studies by several investigators have indicated a causal role for SAA in the development of atherosclerosis in animal models. Suppression of SAA attenuates the development of angiotensin II (AngII)-induced abdominal aortic aneurysm (AAA) formation in mice. Thus, SAA is not just a marker for cardiovascular disease (CVD) development, but it is a key player. However, to consider SAA as a therapeutic target for these diseases, the pathway leading to its involvement needs to be understood. This review provides a brief description of the pathobiological …

A Case Of Unintentional Isopropanol Poisoning Via Transdermal Absorption Delayed By Weekly Hemodialysis, Andrew R. Chavez, Michael T. Sweeney, Peter Akpunonu

Emergency Medicine Faculty Publications

BACKGROUND Isopropanol toxicity is the most common reported toxic alcohol ingestion in the United States and is well known to emergency physicians. Most toxicities result from unintentional ingestion of rubbing alcohol; however, an under-recognized mechanism of unintentional toxicity is transdermal absorption. Additionally, hemodialysis effectively removes isopropanol and its metabolites from circulation, so that in patients receiving regular hemodialysis, the manifestation of toxicity can be delayed.

CASE REPORT A 67-year-old woman with end-stage renal disease secondary to insulin-dependent type II diabetes on once-weekly hemodialysis presented to the Emergency Department via the Emergency Medical Service with acute encephalopathy, severe hypoglycemia, and hypothermia. …

Deletion Of Sa Β-Gal+ Cells Using Senolytics Improves Muscle Regeneration In Old Mice, Cory M. Dungan, Kevin A. Murach, Christopher J. Zdunek, Zuo Jian Tang, Georgia L. Vonlehmden, Camille R. Brightwell, Zachary Hettinger, Davis A. Englund, Zheng Liu, Christopher S. Fry, Antonio Filareto, Michael Franti, Charlotte A. Peterson

Physical Therapy Faculty Publications

Systemic deletion of senescent cells leads to robust improvements in cognitive, cardiovascular, and whole-body metabolism, but their role in tissue reparative processes is incompletely understood. We hypothesized that senolytic drugs would enhance regeneration in aged skeletal muscle. Young (3 months) and old (20 months) male C57Bl/6J mice were administered the senolytics dasatinib (5 mg/kg) and quercetin (50 mg/kg) or vehicle bi-weekly for 4 months. Tibialis anterior (TA) was then injected with 1.2% BaCl₂ or PBS 7- or 28 days prior to euthanization. Senescence-associated β-Galactosidase positive (SA β-Gal+) cell abundance was low in muscle from both young and old mice …

The Efficacy Of Plant-Based Dietary Program In Patients With Diabetes: A Pilot Study, Reuben Adatorwovor, Nisha Sharma, Dakota Mccoy, Sharon Wasserstrom, Matthew Robinson, Jacquelyn Nyenhuis, Sowmya Suryanarayanan

Biostatistics Faculty Publications

Dietary choices play a key role in insulin sensitivity among diabetes patients. An 8-week pilot study was conducted to evaluate whether a mostly plant-based dietary program will lead to improvement in biochemical markers in adults with diabetes. The dietary program included educational presentations, weekly cooking demonstrations and small group discussions. A sample of thirty-two adults with diabetes (types 1 and 2) were recruited and seventeen (53%) completed the study. Matched-pair tests and Fishers exact tests were used to compare the changes in means and proportion of the participants’ responses. There were changes in HbA1c, lipids, CRP (mg/L), cholesterol (mg/dL), HDL …

Defining Disparities In Cochlear Implantation Through The Social Determinants Of Health, Marissa Schuh, Matthew L. Bush

Otolaryngology--Head & Neck Surgery Faculty Publications

Hearing loss is a global public health problem with high prevalence and profound impacts on health. Cochlear implantation (CI) is a well-established evidence-based treatment for hearing loss; however, there are significant disparities in utilization, access, and clinical outcomes among different populations. While variations in CI outcomes are influenced by innate biological differences, a wide array of social, environmental, and economic factors significantly impact optimal outcomes. These differences in hearing health are rooted in inequities of health-related socioeconomic resources. To define disparities and advance equity in CI, there is a pressing need to understand and target these social factors that influence …