Medicine and Health Sciences Commons^™

Impaired Meningeal Lymphatic Vessel Development Worsens Stroke Outcome, Pavel Yanev, Katherine Poinsatte, Devon Hominick, Noor Khurana, Kielen R. Zuurbier, Marcus Berndt, Erik J. Plautz, Michael T. Dellinger, Ann M. Stowe

Neurology Faculty Publications

The discovery of meningeal lymphatic vessels (LVs) has sparked interest in identifying their role in diseases of the central nervous system. Similar to peripheral LVs, meningeal LVs depend on vascular endothelial growth factor receptor-3 (VEGFR3) signaling for development. Here we characterize the effect of stroke on meningeal LVs, and the impact of meningeal lymphatic hypoplasia on post-stroke outcomes. We show that photothrombosis (PT), but not transient middle cerebral artery occlusion (tMCAo), induces meningeal lymphangiogenesis in young male C57Bl/J6 mice. We also show that Vegfr3^wt/mut mice develop significantly fewer meningeal LVs than Vegfr3^wt/wt mice. Again, meningeal lymphangiogenesis occurs in …

A Population-Based Investigation Of Health-Care Needs And Preferences In American Adults With Multiple Sclerosis, Chungyi Chiu, Malachy Bishop, Bradley Mcdaniels, Byung-Jin Kim, Lebogang Tiro

Early Childhood, Special Education, and Counselor Education Faculty Publications

Background: Comprehensive and effective multiple sclerosis (MS) health care requires understanding of patients’ needs, preferences, and priorities. Objective: To evaluate priorities of patients with MS for their MS care. Methods: Participants included 3003 Americans with MS recruited through the National MS Society and the North American Research Committee on Multiple Sclerosis patient registry. Participants completed a comprehensive questionnaire on aspects of their health-care experiences. Results: Participants identified the top 3 health-care priorities as (1) the affordability of MS health care, (2) ensuring that non-MS health-care providers have more education about MS and how it can interact with other conditions, and …

Lung Metastasis Postradioembolization Of Hepatocellular Carcinoma With Tumor In Vein, Harit Kapoor, Sreeja Sanampudi, Joseph W. Owen, Driss Raissi

Radiology Faculty Publications

Transarterial radioembolization (TARE) is one of the few treatment options available for infiltrative hepatocellular carcinoma with tumor in vein. This is backed by the published data showing marginally favorable toxicity profile compared with other locoregional and systemic therapies. Although lung shunt fraction studies are performed to prevent radiation injury to the lungs, TARE-induced embolization/metastasis to the lungs has not been reported before. We report an intriguing case of new lung metastases within 1 month after TARE for infiltrative hepatocellular carcinoma with a tumor in the vein, with only a slightly elevated but acceptable lung shunt fraction. This report brings to …

Protein Tyrosine Phosphatase 4a3 (Ptp4a3/Prl-3) Drives Migration And Progression Of T-Cell Acute Lymphoblastic Leukemia In Vitro And In Vivo, Min Wei, Meghan G. Haney, Dylan R. Rivas, Jessica S. Blackburn

Molecular and Cellular Biochemistry Faculty Publications

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive blood cancer. There are no immunotherapies and few molecularly targeted therapeutics available for treatment of this malignancy. The identification and characterization of genes and pathways that drive T-ALL progression are critical for the development of new therapies for T-ALL. Here, we determined that the protein tyrosine phosphatase 4A3 (PTP4A3 or PRL-3) plays a critical role in T-ALL initiation and progression by promoting leukemia cell migration. PRL-3 is highly expressed in patient T-ALL samples at both the mRNA and protein levels compared to normal lymphocytes. Knock-down of PRL-3 expression using short-hairpin RNA (shRNA) …

Short-Chain Fatty Acids Improve Poststroke Recovery Via Immunological Mechanisms, Rebecca Sadler, Julia V. Cramer, Steffanie Heindl, Sarantos Kostidis, Dene Betz, Kielen R. Zuurbier, Bernd H. Northoff, Marieke Heijink, Mark P. Goldberg, Erik J. Plautz, Stefan Roth, Rainer Malik, Martin Dichgans, Lesca M. Holdt, Corinne Benakis, Martin Giera, Ann M. Stowe, Arthur Liesz

Neurology Faculty Publications

Recovery after stroke is a multicellular process encompassing neurons, resident immune cells, and brain-invading cells. Stroke alters the gut microbiome, which in turn has considerable impact on stroke outcome. However, the mechanisms underlying gut–brain interaction and implications for long-term recovery are largely elusive. Here, we tested the hypothesis that short-chain fatty acids (SCFAs), key bioactive microbial metabolites, are the missing link along the gut–brain axis and might be able to modulate recovery after experimental stroke. SCFA supplementation in the drinking water of male mice significantly improved recovery of affected limb motor function. Using in vivo wide-field calcium imaging, we observed …

Psychosocial Mediators Of Perceived Stigma And Suicidal Ideation Among Transgender Women, Krishna Kiran Kota, Laura F. Salazar, Rachel E. Culbreth, Richard A. Crosby, Jamal Jones

Health, Behavior & Society Faculty Publications

BACKGROUND: Transgender women (TGW) in the U.S. experience high rates of stigma, depression, and elevated rates of suicide. This study examined correlates of suicidal ideation and estimated the conditional indirect effects of perceived stigma and psychosocial mediators on suicidal ideation.

METHODS: Using a cross-sectional study design, TGW (N = 92) were recruited through snowball sampling in Atlanta, Georgia. Structured interviews were conducted. Suicidal ideation was assessed by combining two variables that measured suicidal thoughts. Logistic regression models were performed to identify the potential risk and protective factors for suicidal ideation. We examined hypothesized psychosocial factors, including anxiety, depression, psychosocial impact …

Identification Of Ebsulfur Analogues With Broad-Spectrum Antifungal Activity, Sylvie Garneau-Tsodikova, Huy X. Ngo, Sanjib K. Shrestha

Pharmaceutical Sciences Faculty Patents

The invention relates to novel ebsulfur analogues and novel pharmaceutical compositions comprising ebsulfur analogues. The invention also relates to novel methods of treating infections caused by fungal species comprising administration of ebselen, ebsulfur, and ebsulfur analogues.

A Brief Educational Intervention Enhances Basic Cancer Literacy Among Kentucky Middle And High School Students, Lauren Hudson, Kerrigan M. Samons, Haley E. Dicken, Chris Prichard, L. Todd Weiss, Jean Edward, Robin C. Vanderpool, Nathan L. Vanderford

Markey Cancer Center Faculty Publications

Kentucky experiences the highest overall cancer incidence and mortality rates in the USA with the greatest burden in the eastern, Appalachian region of the state. Cancer disparities in Kentucky are driven in part by poor health behaviors, poverty, lack of health care access, low education levels, and low health literacy. Individuals with inadequate health literacy are less likely to participate in preventive measures such as obtaining screenings and making healthy lifestyle choices, thus increasing their chances of developing and dying from cancer. By increasing cancer literacy among youth and adults, it may be possible to decrease cancer disparities across Kentucky. …

Reviewer Acknowledgments For 2019, F. Douglas Scutchfield Md, Erin N. Haynes, Erin Bouldin, Robert M. Shapiro Ii, Tim Marema, Charlotte S. Seidman

Journal of Appalachian Health

The Editorial Team extends a heart-felt “thank you” to those who have given their time and expertise in the past year to participate in this process with the Journal of Appalachian Health. We know that you have many competing pressures on your time, and that you are not financially compensated for the time you spend reviewing manuscripts. We hope that there are other forms of compensation that make the sacrifice worth the effort.

A Healthy Attitude: Rural Leaders In Tn County Organize To Address Well-Being In Appalachia, Tim Marema, Erin Bouldin

Journal of Appalachian Health

When it came to formal philanthropy, Grundy County was not on the map. That changed with the 2012 establishment of South Cumberland Community Fund, which serves the plateau portions of Grundy, Franklin, and Marion counties.

The Nuclear Legacy In Appalachia, Michele Morrone, Harold Perkins

Journal of Appalachian Health

Nestled in the rolling hills of Appalachia Ohio is a reminder of the role that the region played in winning the Cold War. For more than 40 years in rural Pike County, the 3,700-acre Portsmouth Gaseous Diffusion Plant (PORTS), or the “A-Plant” as the locals refer to it, enriched uranium for use in nuclear weapons. While the facility produced nuclear fuel for national security, it simultaneously exposed plant workers to chemicals and radiation and discharged pollution into the surrounding community. The A-Plant is now being demolished and the site repurposed. However, the site continues to affect the community as, for …

Appalachian Environmental Health Literacy: Building Knowledge And Skills To Protect Health, Anna G. Hoover, Annie Koempel, W. Jay Christian, Kimberly I. Tumlin, Kelly G. Pennell, Steven Evans, Malissa Mcalister, Lindell E. Ormsbee, Dawn Brewer

Journal of Appalachian Health

Environmental health literacy (EHL) is an emerging, multidisciplinary field that promotes understanding of how environmental exposures can affect human health. After discussing the regional relevance of environmental health knowledge and skills, this article describes three ongoing Appalachian projects that are focused on measuring and building EHL.

Development And Early Outcomes Of The Watauga Compassionate Community Initiative, North Carolina, Tim Marema, Erin Bouldin

Journal of Appalachian Health

Addressing adverse childhood experiences has become a public health imperative, and communities across the United States are working to develop and implement programs and policies to both prevent childhood trauma and support adults who experienced trauma as children. Here we describe the development of the Watauga Compassionate Community Initiative (WCCI) in Watauga, County, North Carolina.

Access To Autism Spectrum Disorder Services For Rural Appalachian Citizens, Angela Scarpa, Laura S. Jensen, Denis Gracanin, Sharon L. Ramey, Angela V. Dahiya, L. Maria Ingram, Jordan Albright, Alyssa J. Gatto, Jen P. Scott, Lisa Ruble

Journal of Appalachian Health

Background: Low-resource rural communities face significant challenges regarding availability and adequacy of evidence-based services.

Purposes: With respect to accessing evidence-based services for Autism Spectrum Disorder (ASD), this brief report summarizes needs of rural citizens in the South-Central Appalachian region, an area notable for persistent health disparities.

Methods: A mixed-methods approach was used to collect quantitative and qualitative data during focus groups with 33 service providers and 15 caregivers of children with ASD in rural southwest Virginia.

Results: Results supported the barriers of availability and affordability of ASD services in this region, especially relating to the need for more ASD-trained providers, …

Introduction To The New “Early Reports Of Innovation” Section, Erin Bouldin, Tim Marema

Journal of Appalachian Health

The Journal of Appalachian Health is introducing a new section this issue. While the journal is centralizing some of the best research and commentary on Appalachian health, the editorial team felt that practice-focused groups, organizations, and agencies may not be fully represented in the publication.

Barn-Raising On The Digital Frontier: The L.A.U.N.C.H. Collaborative, Bradford W. Hesse, David Ahern, Michele Ellison, Eliah Aronoff-Spencer, Robin C. Vanderpool, Karen Onyeije, Michael C. Gibbons, Timothy W. Mullett, Ming-Yuan Chih, Victoria Attencio, Grant Patterson, Jessica Boten, Christopher Hartshorn, Ben Bartolome, Katie Gorscak, Melanie Mccomsey, Alexandra Hubenko, Bin Huang, Corey Baker, Don Norman

Journal of Appalachian Health

A meta-analysis of oncology papers from around the world revealed that cancer patients who lived more than 50 miles away from hospital centers routinely presented with more advanced stages of disease at diagnosis, exhibited lower adherence to prescribed treatments, presented with poorer diagnoses, and reported a lower quality of life than patients who lived nearer to care facilities. Connected health approaches—or the use of broadband and telecommunications technologies to evaluate, diagnose, and monitor patients beyond the clinic—are becoming an indispensable tool in medicine to overcome the obstacle of distance.

Introducing The L.A.U.N.C.H. Collaborative, F. Douglas Scutchfield Md, Kevin Patrick

Journal of Appalachian Health

The L.A.U.N.C.H. Collaborative: Linking & Amplifying User-Centered Networks through Connected Health: A Demonstration of Broadband-Enabled Connected Health and Community-Based Co-Design brings together a group of organizations that are eager to use Appalachian Kentucky as a site for the development of a project aimed at creating an environment that addresses two of the nation’s major concerns about cancer. First, individuals who live in rural and remote areas are more likely to die of cancer than those who live in urban or suburban settings. And second, geographic obstacles hinder their ability to access evidence-based strategies that can prevent cancer or treat it …

Students’ Perceptions Of Justice: Application Of Sanctions, Guilt, And Responsibility In Campus Sexual Assault Cases, Diane R. Follingstad, Caihong R. Li, Jaspreet K. Chahal, Claire M. Renzetti

CRVAW Faculty Journal Articles

Despite growing attention to adjudication of campus sexual assault cases, little is known how students perceive “justice” for such cases. The present study examined whether victim, perpetrator, and assault characteristics influenced students’ perceptions of: whether a sanctionable violation occurred; the type of sanction to be applied; perceived severity of the sanction; proportion of guilt attributable to the victim and perpetrator; and level of responsibility of the victim and perpetrator. Fourteen factors pertaining to potential negative evaluation of rape victims were derived; thus, a non-factorial vignette survey design focusing only on each main effect was employed. 846 college students responded to …

Mentoring Multi-College Bystander Efficacy Evaluation – An Approach To Growing The Next Generation Of Gender-Based Interpersonal Violence Intervention And Prevention (Vip) Researchers, Ann L. Coker, Danielle Davidov, Heather M. Bush, Emily R. Clear

Obstetrics and Gynecology Faculty Publications

The Centers for Disease Control and Prevention provided funding (U01 CE002668) to evaluate bystander program efficacy to reduce gender-based violence on college campuses (Aim 1) and to create a mentoring network (Aim 2) for young campus-based researchers interested in violence intervention or prevention (VIP). While an evaluation of this mentoring program is ongoing, our purpose here was to document the strategies used to create, implement, and begin evaluation of this national multi-college mentoring network. As each public college was recruited into this evaluation named multi-college Bystander Efficacy Evaluation (mcBEE), each college was invited to nominate a researcher interested in receiving …

Review Of Alterations In Perlecan-Associated Vascular Risk Factors In Dementia, Amanda L. Trout, Ibolya Rutkai, Ifechukwude J. Biose, Gregory J. Bix

Neurology Faculty Publications

Perlecan is a heparan sulfate proteoglycan protein in the extracellular matrix that structurally and biochemically supports the cerebrovasculature by dynamically responding to changes in cerebral blood flow. These changes in perlecan expression seem to be contradictory, ranging from neuroprotective and angiogenic to thrombotic and linked to lipid retention. This review investigates perlecan's influence on risk factors such as diabetes, hypertension, and amyloid that effect Vascular contributions to Cognitive Impairment and Dementia (VCID). VCID, a comorbidity with diverse etiology in sporadic Alzheimer's disease (AD), is thought to be a major factor that drives the overall clinical burden of dementia. Accordingly, changes …

Expression Of Cytokines And Chemokines As Predictors Of Stroke Outcomes In Acute Ischemic Stroke, Sarah R. Martha, Qiang Cheng, Justin F. Fraser, Liyu Gong, Lisa A. Collier, Stephanie M. Davis, Doug Lukins, Abdulnasser Alhajeri, Stephen Grupke, Keith R. Pennypacker

Institute for Biomedical Informatics Faculty Publications

Introduction: Ischemic stroke remains one of the most debilitating diseases and is the fifth leading cause of death in the US. The ability to predict stroke outcomes within the acute period of stroke would be essential for care planning and rehabilitation. The Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC; clinicaltrials.gov NCT03153683) study collects arterial blood immediately distal and proximal to the intracranial thrombus at the time of mechanical thrombectomy. These blood samples are an innovative resource in evaluating acute gene expression changes at the time of ischemic stroke. The purpose of this study was to identify inflammatory genes and …

Hypercholesterolemia Accelerates Both The Initiation And Progression Of Angiotensin Ii-Induced Abdominal Aortic Aneurysms, Jing Liu, Hisashi Sawada, Deborah A. Howatt, Jessica J. Moorleghen, Olga A. Vsevolozhskaya, Alan Daugherty, Hong S. Lu

Pharmacology and Nutritional Sciences Faculty Publications

Objective: This study determined whether hypercholesterolemia would contribute to both the initiation and progression of angiotensin (Ang)II-induced abdominal aortic aneurysms (AAAs) in mice.

Methods and Results: To determine whether hypercholesterolemia accelerates the initiation of AAAs, male low-density lipoprotein (LDL) receptor -/- mice were either fed one week of Western diet prior to starting AngII infusion or initiated Western diet one week after starting AngII infusion. During the first week of AngII infusion, mice fed normal diet had less luminal expansion of the suprarenal aorta compared to those initiated Western diet after the first week of AngII infusion. The two groups …

Carcinoma In Situ Involving Sclerosing Adenosis On Core Biopsy: Diagnostic Pearls To Aid The Practicing Clinician And Avoid Overtreatment, Dana Richards, Alberto A. Ayala, Yun Wu, Lavinia P. Middleton

Pathology and Laboratory Medicine Faculty Publications

INTRODUCTION: Involvement of pre-existing benign lesions by ductal carcinoma in situ (DCIS) or lobular neoplasia (LN) can present difficult diagnostic challenges, and can easily cause misdiagnosis of invasive carcinoma and over-management of localized disease. Our objective was to gather the largest case series of DCIS and LN involving sclerosing adenosis (SA), and to report the characteristic features of these lesions, in order to provide histologic criteria for the diagnostician.

METHODS: Our database was searched for core biopsy material diagnosed as carcinoma in situ involving adenosis. Glass slides and pathology reports were reviewed. The cases were studied for salient features, and …

Frontotemporal Dementia Nonsense Mutation Of Progranulin Rescued By Aminoglycosides, Lisha Kuang, Kei Hashimoto, Eric J. Huang, Matthew S. Gentry, Haining Zhu

Molecular and Cellular Biochemistry Faculty Publications

Frontotemporal dementia (FTD) is an early onset dementia and is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5-26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its function under physiological and pathological conditions remains to be defined. Many FTD-causing nonsense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy.

Aminoglycosides are a class of antibiotics that possess a less known function …

Immune-Mediated Genetic Pathways Resulting In Pulmonary Function Impairment Increase Lung Cancer Susceptibility, Linda Kachuri, Mattias Johansson, Sara R. Rashkin, Rebecca E. Graff, Yohan Bossé, Venkata Manem, Neil E. Caporaso, Maria Teresa Landi, David C. Christiani, Paolo Vineis, Geoffrey Liu, Ghislaine Scelo, David Zaridze, Sanjay S Shete, Demetrius Albanes, Melinda C. Aldrich, Adonina Tardón, Gad Rennert, Chu Chen, Gary E. Goodman, Jennifer A. Doherty, Heike Bickeböller, John K. Field, Michael P Davies, M. Dawn Teare, Lambertus A. Kiemeney, Stig E. Bojesen, Aage Haugen, Shanbeh Zienolddiny, Stephen Lam, Loïc Le Marchand, Iona Cheng, Matthew B. Schabath, Eric J. Duell, Angeline S. Andrew, Jonas Manjer, Philip Lazarus, Susanne M. Arnold, James D. Mckay, Nima C. Emami, Matthew T. Warkentin, Yonathan Brhane, Ma'en Obeidat, Richard M. Martin, Caroline Relton, George Davey Smith, Philip C. Haycock, Christopher I. Amos, Paul Brennan, John S. Witte, Rayjean J. Hung

Markey Cancer Center Faculty Publications

Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV₁: r_g = 0.098, p = 2.3 × 10^-8) and the ratio of FEV₁ to forced vital capacity (FEV₁/FVC: r_g = 0.137, p = 2.0 × 10^-12). Mendelian randomization analyses demonstrate that …

Energy Compensation With Exercise Is Not Dependent On Dose, H. Michael Hays

Theses and Dissertations--Nutrition and Food Systems

Background: Exercise induced weight loss is often less than expected due to a coordinated set of compensatory mechanisms that serve to maintain energy homeostasis. The extent to which exercise frequency, duration, intensity and exercise energy expenditure (ExEE) influences the compensatory response to an exercise-induced energy deficit (energy compensation) is controversial. Determining how these variables impact energy compensation would help health care providers prescribe exercise with greater probability of creating a sustained negative energy balance and subsequent weight loss.

Methods: 44 Overweight/obese men and women (BMI=25-35kg/m²) aged 18 to 40 years were randomized to perform aerobic exercise 2 or 6 days/week …

Tolerance Intervals For Time Series Models And Specifying Trimming/Winsorizing Cutoffs, Kedai Cheng

Theses and Dissertations--Statistics

Confidence intervals are used to capture a parameter of interest, usually a mean or a quantile, at a specified confidence level. Prediction intervals are another practical interval that aim at making sound predictions of future values with some confidence. Although these are useful inference tools, neither of them gives people a plausible range of the sampled population. Tolerance intervals are such an inference tool that captures a specified proportion of the sampled population at a predetermined confidence level. In this dissertation, tolerance intervals for an autoregressive process with order p are constructed. In addition, a method of utilizing tolerance interval …

Clinical Measurements Of The Posterior Shoulder Endurance Test (Pset), Neil A. Evans

Theses and Dissertations--Rehabilitation Sciences

Of the intrinsic factors responsible for non-traumatic shoulder pain, muscular endurance is often not measured by rehabilitation professionals due to the lack of available shoulder endurance measures. Measurement properties of the PSET have not been adequately assessed in previous studies. The purpose of this dissertation was to develop the clinical measurement properties of the Posterior Shoulder Endurance Test (PSET) so that it might be used as a clinical measure of shoulder muscular endurance.

Electromyography (EMG) offers the ability to identify which muscles in the posterior shoulder girdle are fatiguing during the PSET. Surface EMG of upper trapezius (UT), middle trapezius …

Psychosocial Predictors Of Chronic Pain And Pain-Related Disability 12 Months After Lower Extremity Fracture, Joshua Judson Van Wyngaarden

Theses and Dissertations--Rehabilitation Sciences

Over 700,000 lower extremity fractures occur each year with a large portion of these patients developing adverse long-term pain and disability outcomes. Current literature indicates that 39% to 62.7% of all patients report continued pain long after traumatic lower extremity fracture. Concurrent physical limitations and reduced quality of life are common, with nearly one-third of all patients reporting pain-related disability seven years after limb threatening trauma, and approximately 50% of these patients having limitations in functional mobility and activities of daily living at long-term follow-up. These poor long-term injury-related pain and disability outcomes are alarming and require further action to …

Mast Cells As Novel Effector Cells In The Pathogenesis Of Chronic Graft-Versus-Host Disease, Ethan Strattan

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Hematopoietic stem cell transplantation (HSCT) is most commonly a treatment for inborn defects of hematopoiesis or acute leukemias. Widespread use of HSCT, a potentially curative therapy, is hampered by onset of graft-versus-host-disease (GVHD), a condition wherein the donor cells recognize the patient tissues as non-self. GVHD can manifest anywhere from weeks to decades post-transplant and is classified as either acute or chronic GVHD, both of which are significant causes of transplant-related morbidity and mortality.

However, GVHD is a complex, multifactorial, and enigmatic disease. The factors driving GVHD at the cellular and molecular level are incompletely understood. Immunosuppression targeting T-cells has …