Medicine and Health Sciences Commons^™

The Effects Of Huntingtin-Lowering: What Do We Know So Far?, William F. Kaemmerer, Richard C. Grondin

Neuroscience Faculty Publications

Therapies targeting mutant huntingtin DNA, mRNA, and protein have a chance at becoming the first disease-modifying treatments for Huntington’s disease, a fatal inherited neurodegenerative disorder for which only symptom management treatments are available today. This review focuses on evidence addressing several key questions pertinent to huntingtin-lowering, ranging from the functions of wild-type huntingtin (wtHTT) that may be disrupted by huntingtin-lowering treatments through the various ways huntingtin can be lowered, the tolerability of wtHTT-lowering in mice and primates, what has been found in the Ionis Pharmaceutical safety trial of a huntingtin-lowering therapy, and to the question of how much mutant huntingtin …

Operationalization Of Bi-Directional Screening For Tuberculosis And Diabetes In Private Sector Healthcare Clinics In Karachi, Pakistan, Mashal S. Basir, Shifa Salman Habib, Syed M A. Zaidi, Saira Khowaja, Hamidah Hussain, Rashida A. Ferrand, Aamir J. Khan

Community Health Sciences

Background: Many countries are facing overlapping epidemics of tuberculosis (TB) and diabetes mellitus (DM). Diabetes increases the overall risk of developing Tuberculosis (TB) and contributes to adverse treatment outcomes. Active screening for both diseases can reduce TB transmission and prevent the development of complications of DM. We investigated bi-directional TB-DM screening in Karachi, Pakistan, a country that ranks fifth among high TB burden countries, and has the seventh highest country burden for DM.
Methods: Between February to November 2014, community-based screeners identified presumptive TB and DM through verbal screening at private health clinics. Individuals with presumptive TB were referred for …

Treating Latent Tuberculosis Infection In Newly Arriving Refugees: An Advanced Practice Nurse Initiative At The University Of Louisville Global Health Center, Linda Goss, Dawn Balcom, Karen Mutsch, Ruth Carrico, Rahel Bosson

Journal of Refugee & Global Health

Background: A review of newly arriving refugees referred to the local health department for latent tuberculosis infection (LTBI) treatment during 2013-2015 revealed a treatment gap of 73%, supporting the need to identify new approaches to treat vulnerable populations and mirrored results in the literature.

Objectives: 1) Describe an advanced practice registered nurse (APRN) led alternative approach to LTBI treatment in the refugee population; and 2) evaluate the impact of a 12-week regimen for LTBI on treatment acceptance, adherence and completion.

Methods: During the initial health screening visit, treatment options were provided for those identified with LTBI consisting of either a …

Dennd5b Regulates Intestinal Triglyceride Absorption And Body Mass, Scott M. Gordon, Edward B. Neufeld, Zhihong Yang, Milton Pryor, Lita A. Freeman, Xiao Fan, Iftikhar J. Kullo, Leslie G. Biesecker, Alan T. Remaley

Saha Cardiovascular Research Center Faculty Publications

Regulation of lipid absorption by enterocytes can influence metabolic status in humans and contribute to obesity and related complications. The intracellular steps of chylomicron biogenesis and transport from the Endoplasmic Reticulum (ER) to the Golgi complex have been described, but the mechanisms for post-Golgi transport and secretion of chylomicrons have not been identified. Using a newly generated Dennd5b^−/− mouse, we demonstrate an essential role for this gene in Golgi to plasma membrane transport of chylomicron secretory vesicles. In mice, loss of Dennd5b results in resistance to western diet induced obesity, changes in plasma lipids, and reduced aortic atherosclerosis. In …

‘We Can Now Fear Huntington’S Disease Less’: Reflections On The 14th Therapeutics Conference, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Extracellular Vesicles From Thyroid Carcinoma: The New Frontier Of Liquid Biopsy, Germana Rappa, Caterina Puglisi, Mark F. Santos, Stefano Forte, Lorenzo Memeo, Aurelio Lorico

College of Osteopathic Medicine (TUN) Publications and Research

The diagnostic approach to thyroid cancer is one of the most challenging issues in oncology of the endocrine system because of its high incidence (3.8% of all new cancer cases in the US) and the difficulty to distinguish benign from malignant non-functional thyroid nodules and establish the cervical lymph node involvement during staging. Routine diagnosis of thyroid nodules usually relies on a fine-needle aspirate biopsy, which is invasive and often inaccurate. Therefore, there is an urgent need to identify novel, accurate, and non-invasive diagnostic procedures. Liquid biopsy, as a non-invasive approach for the detection of diagnostic biomarkers for early tumor …

Gait Alterations In Peripheral Arterial Disease Are Not Worsened By The Presence Of Diabetes, Hafizur Rahman

UNO Student Research and Creative Activity Fair

Peripheral arterial disease (PAD) is a vascular disease where atherosclerotic blockages restrict blood flow to muscles in the lower extremities. Diabetes is a common co-morbid condition in PAD and has been shown to increase the risk of lower extremity amputation compared to PAD without diabetes. Although there is a clear pathological relationship between diabetes and PAD, the gait mechanics involved remain indistinct. Therefore, the purpose of this study was to determine whether the presence of diabetes in addition to PAD results in greater functional impairment during ambulation. Twenty-three subjects with PAD and twelve controls consented to participate in the research. …

The Effects Of A 12-Week Jump Rope Exercise Program On Abdominal Adiposity, Vasoactive Substances, Inflammation & Vascular Function In Prehypertensive Adolescent Girls, Ronald Headid

UNO Student Research and Creative Activity Fair

Childhood obesity is strongly associated with cardiovascular disease (CVD) development. It is necessary to combat unfavorable outcomes of obesity at a young age by utilizing effective interventions, such as exercise. Purpose: We sought to examine the effects of a jump rope exercise program on CVD risk factors, including body composition, vasoactive substances, inflammation, and vascular function in prehypertensive adolescent girls. Methods: Forty girls (age 14-16) were recruited and randomly assigned to a jump rope exercise group (EX, n=20) or control group (CON, n=20). Body composition, nitrate and nitrite levels, endothelin-1 (ET-1), c-reactive protein (CRP), systolic blood pressure and diastolic blood …

The Effects Of Swimming Training On Arterial Stiffness, Muscular Strength And Cardiorespiratory Endurance In Postmenopausal Women With Stage 2 Hypertension, Steven Scott

UNO Student Research and Creative Activity Fair

Objective:

Aging is associated with progressive decreases in arterial health and function as well as overall fitness. It is crucial to prevent or reduce the negative effects of aging on vasculature and fitness components by implementing appropriate lifestyle interventions, such as exercise training. We examined the effects of a swimming (SWM) regimen on arterial stiffness (pulse wave velocity, PWV), blood pressure (BP), wave reflection (AIx), muscle strength and aerobic capacity in postmenopausal women with stage 2 hypertension.

Methods:

Using a parallel experimental design, participants were randomly assigned to either a SWM (n=52) or non-exercising control group (n=48) for 20 weeks. …

Impacts Of Dietary Nitrate On Endothelial Function, Arterial Stiffness, And Systemic Vascular Pressure In Peripheral Arterial Disease, Elizabeth J. Pekas, Steven D. Scott, Ronald J. Headid Iii, Michael D. Shukis, Jeonghwa Shin, Jiwon Song, Song-Young Park

UNO Student Research and Creative Activity Fair

Peripheral arterial disease (PAD) is the manifestation of atherosclerotic plaque in the larger arteries of the legs, which results in impaired blood flow to the lower extremities. Markers of vascular health, including endothelial function and arterial stiffness, have been shown to be attenuated in PAD.

Purpose: We sought to examine the effects of a nitrate supplement (body mass-normalized dosage of beetroot juice) on vascular function measurements such as endothelial function, arterial stiffness, and central and peripheral blood pressure in patients with PAD. We hypothesized that acute intake of a nitrate supplement would improve vascular function.

Methods: PAD patients (stage II-III, …

Large Scale Dynamical Model Of Macrophage/Hiv Interactions, Sean T. Bresnahan, Matthew M. Froid

UNO Student Research and Creative Activity Fair

Properties emerge from the dynamics of large-scale molecular networks that are not discernible at the individual gene or protein level. Mathematical models - such as probabilistic Boolean networks - of molecular systems offer a deeper insight into how these emergent properties arise. Here, we introduce a non-linear, deterministic Boolean model of protein, gene, and chemical interactions in human macrophage cells during HIV infection. Our model is composed of 713 nodes with 1583 interactions between nodes and is responsive to 38 different inputs including signaling molecules, bacteria, viruses, and HIV viral particles. Additionally, the model accurately simulates the dynamics of over …

Femoral Vein Transposition Arteriovenous Fistula Is A Feasible Option In "Selected" Patients As Hemodialysis Access, Zia Ur Rehman, Asfia Arham, Ziad Sophie

Section of Cardiothoracic Surgery

Introduction: Lower extremity hemodialysis access is offered to the patients who have severe central venous stenosis. Femoral vein transposition arteriovenous fistula (FV tAVF) is an alternative to lower leg arteriovenous prosthetic grafts. Its safety and patency is under observation.
Materials and Methods: This is a retrospective review of patients who had FV tAVF between January 2011 and March 2016. Preoperative clinical findings, intraoperative findings, postoperative complications, and patency of the AVF were noted and analyzed.
Results: There were 7 patients who underwent FV tAVF during this study period. Most patients were female (6 : 1), with mean …

Joint Association Of Urinary Sodium And Potassium Excretion With Cardiovascular Events And Mortality: Prospective Cohort Study, Martin O'Donnell, Andrew Mente, Sumathy Rangarajan, Matthew J. Mcqueen, Neil O'Leary, Lu Yin, Xiaoyun Liu, Sumathi Swaminathan, Rasha Khatib, Romaina Iqbal

Community Health Sciences

Objective: To evaluate the joint association of sodium and potassium urinary excretion (as surrogate measures of intake) with cardiovascular events and mortality, in the context of current World Health Organization recommendations for daily intake (<2.0 g sodium, >3.5 g potassium) in adults.
Design: International prospective cohort study.
Setting: 18 high, middle, and low income countries, sampled from urban and rural communities.
Participants: 103 570 people who provided morning fasting urine samples.
Main outcome measures: Association of estimated 24 hour urinary sodium and potassium excretion (surrogates for intake) with all cause mortality and major cardiovascular events, using multivariable Cox regression. A six category …

Investigating The Role Of Free Radicals In Huntington's Disease Using Drosophila Melanogaster, Jennifer Libov

Honors Program: Senior Projects (Public)

During normal cell metabolism, reactive oxygen species (ROS) are produced as a byproduct of oxidative phosphorylation. ROS are utilized in the cell as a signaling molecule and can be maintained at healthy levels by cellular antioxidants. However, when the cell experiences oxidative stress due to environmental or genetic conditions, levels of ROS can exceed healthy levels and inhibit necessary life functions by damaging biomolecules and cellular structures. This loss of function can lead to physiological decline and neurodegeneration, such as in diseases like Alzheimer’s, amyotrophic lateral sclerosis (ALS), and, potentially, Huntington’s disease. The following experiments use the model genetic organism …

Chdi’S Chief Scientist: ‘Not A Time For The Huntington's Community To Rest Its Laurels', Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

Continued Progress, But Also Caution, In The Fight Against Huntington's Disease, Kenneth P. Serbin

At Risk for Huntington's Disease

No abstract provided.

A Survey Study Of Self-Rated Patients' Knowledge About Aki In A Post-Discharge Aki Clinic, Victor M. Ortiz-Soriano, Joseph L. Alcorn Iii, Xilong Li, Madona Elias, Taha Ayach, B. Peter Sawaya, Hartmut H. Malluche, Ron Wald, Samuel A. Silver, Javier A. Neyra

Internal Medicine Faculty Publications

Background: Survivors of acute kidney injury (AKI) are at risk of adverse outcomes. Post-discharge nephrology care may improve patients’ AKI knowledge and prevent post-AKI complications.

Objective: The purpose of this study was to examine patients’ awareness about their AKI diagnosis and self-rated knowledge and severity of AKI before and after their first post-discharge AKI Clinic encounter.

Design: We conducted a pre- and post-survey study among AKI survivors who attended a post-discharge AKI Clinic.

Setting: AKI Clinic at the University of Kentucky Medical Center (October 2016 to December 2017). Education about AKI was based on transformative learning theory and provided through …

Apolipoprotein E4 Alters Astrocyte Fatty Acid Metabolism And Lipid Droplet Formation, Brandon C. Farmer, Jude Kluemper, Lance A. Johnson

Physiology Faculty Publications

Lipid droplets (LDs) serve as energy rich reservoirs and have been associated with apolipoprotein E (APOE) and neurodegeneration. The E4 allele of APOE (E4) is the strongest genetic risk factor for the development of late onset Alzheimer’s disease (AD). Since both E4 carriers and individuals with AD exhibit a state of cerebral lipid dyshomeostasis, we hypothesized that APOE may play a role in regulating LD metabolism. We found that astrocytes expressing E4 accumulate significantly more and smaller LDs compared to E3 astrocytes. Accordingly, expression of perilipin-2, an essential LD protein component, was higher in E4 astrocytes. We then …

Social Ecological Predictors Of Risky Sexual Behavior Among Young Adults, Maureen Muchimba

Journal of Social, Behavioral, and Health Sciences

Most studies on sexual behavior outcomes are restricted to adolescents. However, rates of sexually transmitted diseases (STDs) are highest among young adults. This study examined social–ecological predictors in adolescence that predict risky sexual behavior in young adulthood. Using longitudinal data, logistic regression was used to determine social–ecological factors that predict early sexual debut and a high number of lifetime sexual partners among 3,109 young adults. Risk-taking was associated with early sexual debut and a high number of lifetime sexual partners. Father–child connectedness decreased the odds of early sexual debut and a high number of lifetime sexual. School connectedness also decreased …

Health Literacy And Type 2 Diabetes In Barbados, Coralene Quimby-Worrell

The Qualitative Report

In this qualitative instrumental single case study, I explored how patients living with Type 2 diabetes (T2D) in Barbados manage the disease and what role health literacy might play. Purposeful sampling aided in selecting the sample for the study. The sample was 23 participants who were 40 years and older, diagnosed with T2D, living in Barbados, and attending the Endocrine Center for treatment. Participants responded to 13 open ended questions used to answer the research questions. Information was coded using NVivo 10 software and the software provided the themes based on the participants’ responses to the interview questions. The themes …

Innovation And Competition In Advanced Therapy Medicinal Products, Enrique Seoane-Vazquez, Vaishali Shukla, Rosa Rodriguez-Monguio

Pharmacy Faculty Articles and Research

"Advanced therapy medicinal products (ATMPs), including gene therapy, cell therapy, and tissue engineering products, represent a paradigm shift in health care as they have great potential for preventing and treating many diseases (Food and Drug Administration (FDA), 2013). By way of example, only 367 (8.0%) of the 4,603 rare diseases and conditions listed by the NIH Genetic and Rare Diseases Information Center had at least one FDA-approved drug therapy in early 2018. An estimated 3,038 (66.0%) of those rare diseases and conditions are congenital and genetic diseases that could potentially be treated by gene therapy. There are already ATMPs under …

Management Of Patients With Brain Metastases From Non-Small Cell Lung Cancer And Adverse Prognostic Features: Multi-National Radiation Treatment Recommendations Are Heterogeneous, Minesh Mehta

All Publications

No abstract provided.

Sepsis: Triage Triggers, Outcomes Quicker, Rylee Ainge, Mackenzie Flaws, Natalie Heim, Emily Herndon, Hayley Norris, Amy L. Scott

Posters

No abstract provided.

Transforming Growth Factor-Β1 Decreases Β2-Agonist–Induced Relaxation In Human Airway Smooth Muscle, Christie A. Ojiaku, Elena Chung, Vishal Parikh, Jazmean K. Williams, Anthony Schwab, Ana Lucia Fuentes, Maia L. Corpuz, Victoria Lui, Sam Paek, Natalia M. Bexiga, Shreya Narayan, Francisco J. Nunez, Kwangmi An, Rennolds S. Ostrom, Steven S. An, Reynold A. Pannettieri Jr.

Pharmacy Faculty Articles and Research

Helper T effector cytokines implicated in asthma modulate the contractility of human airway smooth muscle (HASM) cells. We have reported recently that a profibrotic cytokine, transforming growth factor (TGF)-β1, induces HASM cell shortening and airway hyperresponsiveness. Here, we assessed whether TGF-β1 affects the ability of HASM cells to relax in response to β₂-agonists, a mainstay treatment for airway hyperresponsiveness in asthma. Overnight TGF-β1 treatment significantly impaired isoproterenol (ISO)-induced relaxation of carbachol-stimulated, isolated HASM cells. This single-cell mechanical hyporesponsiveness to ISO was corroborated by sustained increases in myosin light chain phosphorylation. In TGF-β1–treated HASM cells, ISO evoked markedly lower …

Early Dexamethasone Administration In Adults With Suspected Meningitis Lowers Morbidity And Mortality, Dana Siegel

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of de Gans J, van de Beek D, Investigators EDiABMS. Dexamethasone in adults with bacterial meningitis. New Eng J Med. 2002;347(20):1549-1556. doi: 10.1056/NEJMoa021334.

Rethinking Intravenous Catheter Size And Location For Computed Tomography Pulmonary Angiography, Travis Marshall, Nae Meng Chen, Eric Nguyen, David E. Slattery, Tony Zitek

School of Medicine Faculty Research

Introduction: Computed tomography pulmonary angiography (CTPA) is the test of choice for diagnosis of pulmonary embolism (PE) in the emergency department (ED), but this test may be indeterminate for technical reasons such as inadequate contrast filling of the pulmonary arteries. Many hospitals have requirements for intravenous (IV) catheter size or location for CTPAs to reduce the chances of inadequate filling, but there is a lack of clinical data to support these requirements. The objective of this study was to determine if a certain size or location of IV catheter used for contrast for CTPA is associated with an increased chance …

An In Vitro And In Vivo Evaluation Of The Anticancer Potential Of Resveratrol And Pterostilbene Against Hpv-E6 Positive Cancers, Kaushiki Chatterjee

Dissertations, Theses, and Capstone Projects

Cervical cancer remains as one of the most prevalent cancers effecting women globally. Lack of awareness and affordable prophylactic and therapeutic options in developing countries drive the need for alternative low-cost approaches. Dietary polyphenols have gained increased attention as possible anti-cancer agents. Our study aims to investigate whether two natural structural analogs, resveratrol and pterostilbene, exhibit anti-HPV (Human papillomavirus) activity in cervical cancer. To determine the efficacy of these polyphenols, extensive in vitro and in vivo analyses were carried out. For the in vitro studies we utilized human HeLa cells (HPV18 positive) and murine TC1 cells (HPV 16 oncogene positive). …

The Master Synaptic Regulator: Activity Regulated Cytoskeleton Associated Protein, Arc, In Normal Aging And Diseases With Cognitive Impairment, Amber Khan

Dissertations, Theses, and Capstone Projects

Alzheimer’s disease (AD) is a progressive neurodegenerative disease with complex underlying pathogenic mechanisms. Epidemiological studies have forecasted that in the next 3 decades, the number of AD cases will rise to epidemic proportions with enormous medical, emotional and financial burdens impacting individuals affected and society. Among many risk factors for AD, advancing age is clearly essential and necessary. Revelation of molecular changes in synaptic activities leading to the prodromal, mild cognitive impairment (MCI) stage may help illuminate the course of pathogenic progression and its cause-effect relationship with various targets thereby enabling target-driven disease-modifying therapeutic agents for AD.

Activity-regulated cytoskeleton-associated (Arc) …

Green Tea Extract, Epigallocatechin Gallate, Protect Against Methamphetamine-Induced Striatal Neurotoxicity In Mice, Allen L. Pan

Dissertations, Theses, and Capstone Projects

Methamphetamine (METH) is a strong psychostimulant and its exposure can lead to serious neurological complications. METH-induced neuronal injury is the result of a complex interplay of different factors including dopamine (DA) overflow, oxidative stress and neuroinflammation. Although the mechanisms of METH-induced neurotoxicity have been extensively studied, there is still no effective therapeutic treatment. Therefore, it is essential to study potential drug candidates that can treat METH-induced neurotoxicity. Green tea extract, epigallocatechin gallate (EGCG), has emerged as a neuroprotective agent that can protect against several neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Recently, our lab has shown that EGCG prevents …

Ck2 Negatively Regulates 5-Ht4 Receptor Signaling In The Prefrontal Cortex And Mediates Depression-Like Behaviors, Julia Castello Saval

Dissertations, Theses, and Capstone Projects

The serotonergic system has been the major candidate in the pathophysiology of mood related disorders such as anxiety and major depressive disorder (MDD). Unfortunately, current antidepressant drugs are ineffective in 50% of the population and require chronic administration for a period of 3-6 weeks before the onset of therapeutic response. 5-HT4 receptor (5-HT₄R) agonists have emerged as potential candidates for fast antidepressant action, since an antidepressant response can be achieved after 3 days of pharmacological administration in rodents.

This dissertation aims to investigate the role of casein kinase 2 (CK2) as a regulator of 5-HT₄R expression …