Therapeutics Commons^™

Metabolic Responses To Freund’S Adjuvants And Oncolytic Viruses: Implications On Vaccines And Tumor Immunity, Kiruthiga Mone

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Freund’s adjuvants have been extensively used in experimental research, and they modulate immune responses through various mechanisms. While both complete Freund’s adjuvant (CFA) and incomplete Freund’s adjuvant (IFA) contain the same mineral oil base, CFA contains the killed extract of Mycobacterium tuberculosis (M. tb) as an additional ingredient. Because the CFA contains mycobacterial content similar to that of Bacillus Calmette-Guérin (BCG), which induces trained immunity (TI), we tested the hypothesis that CFA may elicit TI-like features. To test this hypothesis, we investigated the metabolic and epigenetic reprogramming induced by CFA, with IFA and BCG as controls, in inbred …

Defining The Causal Contribution Of The Gut Microbiota To Cardiomyopathy Pathogenesis As A Basis For Developing Microbiome-Targeted Therapies, Xu Shi

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Heart failure (HF) is a leading cause of morbidity and mortality worldwide, placing substantial clinical and economic burdens on society. Although advances in therapy have improved patient outcomes, the biological mechanisms that drive HF onset and progression remain incompletely understood. Increasing evidence suggests that the gut microbiota, the trillions of microorganisms residing in the gastrointestinal tract, plays a key role in some forms of heart disease, especially cardiovascular disease. Moreover, gut microbial dysbiosis has been associated with systemic inflammation, metabolic imbalance, and immune dysregulation, all of which contribute to the pathophysiology of HF. Cardiomyopathy, a primary disorder of the heart …

Chronic Pain After Traumatic Brain Injury: Treatment Experiences And Effects On Cognition And Functioning, Rachael L. Snyder

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Traumatic brain injury (TBI) can contribute to changes in cognitive and emotional functioning, quality of life, and psychosocial reintegration. Chronic pain is a common consequence of TBI which can uniquely impact such outcomes. Still, the exact nature of the contribution of pain on post-TBI outcomes remains unclear, and there are few existing studies exploring the treatment journey for chronic pain and injury rehabilitation through qualitative methods, specifically individual interviews with TBI survivors. This study aimed to document these narratives and to identify precisely how the experiences of TBI survivors seeking treatments, rather than the treatments themselves, impact outcomes. It also …

Assessing Sleep Quality In A Preclinical Model Of Low Back Pain Through Novel Noninvasive Methods, Lydia C. Saltz

Department of Agricultural and Biological Systems Engineering: Dissertations, Theses, and Student Research

Chronic low back pain (LBP) has widespread negative impacts on quality of life. Current treatments for chronic LBP fail to provide long-term efficacy and motivate the need to understand key drivers of poor patient outcomes. Mounting evidence indicates that sleep disturbances and chronic LBP have a strong reciprocal relationship. Women may be particularly vulnerable to the negative impacts of the sleep-pain axis, exhibiting greater prevalence in both conditions. However, the relationship between sleep, pain, and sex remains understudied. Preclinical models can be used to parse out characteristic sleep features that degrade with pain, which can be further broken out by …

Nanoparticle-Based Approaches To Brain Injury And Studies For Improved Detectability Toward Better Delivery Characterization, Hunter A. Miller

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

The clinical translation of nanoparticle (NP) therapeutics for brain injury has been slow despite preclinical promise. The causes of disconnect between preclinical and clinical outcomes is multifactorial, but insufficient delivery is noteworthy. Preclinical delivery characterization often lacks, obscuring mechanisms of failure, slowing development. Multimodal imaging is a promising strategy to improve delivery characterization, combining the strengths of various modalities. Magnetic resonance imaging (MRI) and luminescence imaging are a suitable combination for multimodal imaging, expanding the spatial and temporal resolution of either alone, but further material development is needed to enhance detectability. One problem is the interference of cellular autofluorescence in …

Development Of A Durable And Low-Dose Universal Vaccine Against Swine Influenza A Virus, Erika Petro-Turnquist

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Swine Influenza A Virus (IAV-S) imposes a significant burden on the pork industry and poses a great threat to public health due to its zoonotic potential. Susceptibility to human, avian, and swine influenza make pigs the ultimate mixing vessels for reassorted influenza A virus strains. Current vaccination strategies induce short-lived and strain-specific responses against IAV-S. Further, the substantial genetic diversity of IAV-S necessitates consistent revaccination and updating of commercial vaccines. Computational platforms have recently emerged as a promising strategy to develop new-age vaccines against infectious diseases in livestock animals. Here, we describe a computationally derived set of vaccine immunogens, called …

Data-Driven Drug Repurposing For Immune System-Related Diseases, Sabyasachi Mohanty

Department of Biochemistry: Dissertations, Theses, and Student Research

In this research, we explore a data-driven approach for drug repurposing to enhance the immunomodulatory effect by integrating pattern-based search and genome-scale metabolic modeling. This research helps to find a solution to the preexisting problems of drug discovery which includes expenses and a high amount of time consumption. By leveraging the pre-existing data of the approved drugs to identify the major metabolic pathway changes, we can find new drugs with similar effects with less off-target effects.

The focus on the immune system modulating drugs is due to the high prevalence of immune system-involved diseases and the growing demand for effective …

Applying The Evidence: Taste Manipulation As A Dysphagia Management Strategy, Ross M. Westemeyer, Angela M. Dietsch, Rachel W. Mulheren

Department of Special Education and Communication Disorders: Faculty Publications

Purpose: This narrative review aims to summarize the evidence regarding taste manipulation as a dysphagia management strategy within the evidence-based practice framework, with a focus on clinical application for speech-language pathologists.

Method: First, we present background information on the physiology of taste and swallowing. A summary of research evidence on the effect of taste on swallowing is presented, followed by suggested methods for incorporating taste into swallowing evaluation and intervention. An overview of individual factors that can impact taste perception is provided. Finally, we discuss methods of clinical application and future directions for clinicians.

Conclusions: Although taste …

Instrumental Assessment Of Aero-Resistive Expiratory Muscle Strength Rehabilitation Devices, Angela M. Dietsch, Rahul Krishnamurthy, Kelsey Young, Steven M. Barlow

Department of Special Education and Communication Disorders: Faculty Publications

Purpose

Expiratory muscle strength training (EMST) is increasingly being used to treat voice, cough, and swallowing deficits in a wide range of conditions. However, a multitude of aero-resistive EMST models are commercially available, and the absence of side-by-side comparative data interferes with clinicians’ ability to assess which model is best suited to a particular client’s needs. The primary aim of this research was to test and compare the pressure and flow parameters of six currently available EMST models to help inform clinical decision making.

Method

We identified and tested five devices of each of six different EMST models to generate …

Evaluation Of Protective Efficacy Of Viral Vector Based Swine Influenza Vaccine And A Method For B Cell Culture For Monoclonal Antibody Generation, Sushmita Kumari

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Influenza A virus of the swine (IAV-S) is an economically important swine pathogen that has the potential to spread to humans, thus posing an ongoing public health concern due to its zoonotic potential. Hemagglutinin (HA), the most abundant viral envelope protein, is known to be the key protective antigen. Anti-HA antibodies alone, have been shown to prevent IAV infection. In this study we evaluated the feasibility of a recombinant tri segmented Pichinde virus (PICV) as a viral vector to deliver IAV-S hemagglutinin antigen in pigs. Four groups of weaned pigs (T01-04) were immunized twice with PBS, rPICV-GFP as a vector …

Development Of Vaccines And Antivirals Against Zika Virus, Aryamav Pattnaik

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The re-emergence of Zika virus (ZIKV), an arbovirus, poses a major global human health concern because of its ability to cause congenital abnormalities and neurological diseases. While many candidate vaccines and antiviral drugs are in the developmental pipeline, none have been approved for use against ZIKV infection. This dissertation describes the characterization of one vaccine and two antiviral drug candidates against ZIKV infection. A bacterial ferritin-based nanoparticle vaccine, termed zDIII-F, is designed to display multiple copies of ZIKV E protein domain III on its surface. These stable nanoparticles are shown to induce robust antibody-mediated protection against lethal ZIKV infection in …

Cardiorespiratory Fitness, Balance And Walking Improvements In An Adolescent With Cerebral Palsy (Gmfcs Ii) And Autism After Motor-Assisted Elliptical Training, Guilherme Manna Cesar, Thad W. Buster, Judith M. Burnfield

Department of Mechanical and Materials Engineering: Faculty Publications

Purpose: To quantify the impact of motor-assisted elliptical (ICARE) training on cardiorespiratory fitness, balance and walking function of an adolescent with walking limitations due to cerebral palsy.

Materials and methods: A thirteen-year-old boy with hemiplegic cerebral palsy (Gross Motor Function Classification System II) and autism participated. Peak oxygen consumption (peak VO₂, primary outcome measure), oxygen cost of walking, Pediatric Balance Scale (PBS), modified Timed Up and Go (mTUG), 2-Minute Walk Test (2MWT), and gait characteristics (speed, cadence, step length, single support time) were assessed prior to and after completion of 24 sessions of moderate- to vigorous- intensity ICARE …

Dr. Seuss Fine Motor Development Club, Nicole Borcyk, Madelyn Beck

Honors Program: Expanded Learning Clubs

After school club that helps students develop fine motor skills by doing hands-on activities relating to Dr. Seuss's most popular books.

Type 2 Bovine Viral Diarrhea Virus NPro Suppresses Type I Interferon Pathway Signaling In Bovine Cells And Augments Bovine Respiratory Syncytial Virus Replication, Abdulrahman Abdulaziz A. Alkheraif

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

Bovine viral diarrhea virus (BVDV) and bovine respiratory syncytial virus (BRSV) infections contribute to the bovine respiratory disease complex (BRDC), which is a multi-factorial disorder involving co-infections of viruses and bacteria including mycoplasma. BRDC causes great economic losses to the United States feedlot industry. BVDV infection induces immunosuppression in infected animals. BVDV N^pro binds and degrades the transcription factor interferon regulatory factor-3 (IRF-3) and effectively blocks type I interferon (type I IFN) expression in host cells. BRSV nonstructural proteins, NS1 and NS2, block activation of IRF-3. In calves, concurrent infection with BVDV and BRSV resulted in more severe clinical …

Prebiotics And Inflammatory Bowel Disease, Heather Rasmussen, Bruce R. Hamaker

Department of Nutrition and Health Sciences: Faculty Publications

Inflammatory bowel disease risk factors include poor diet, and corresponding low intake of dietary fiber, specifically prebiotics, which is fermented by the gut microbiota. Dietary fibers, many of which are potential prebiotics, have hundreds to thousands of unique chemical structures that may promote bacteria or bacterial groups to provide beneficial health effects. In vitro and in vivo animal models provide some support for the use of prebiotics for inflammatory bowel disease through inflammation reduction. Studies using prebiotics in patients with inflammatory bowel disease are limited and focus on only a select few prebiotic substances.

Keywords: Inflammatory bowel disease, Ulcerative colitis, …

Stabilization Of Gp120 Outer Domain For Hiv-1-1 Vaccine Immunogen Design, Duoyi Hu

School of Veterinary and Biomedical Sciences: Dissertations, Theses, and Student Research

The sole envelope glycoprotein spike on the surface of Human Immunodeficiency Virus (HIV-1) is composed of two subunits: gp120 and gp41. The gp120 consists of three domains: the inner domain, outer domain and bridging sheet, to which the viral primary receptor CD4 binds and induces a conformational change in gp120 to expose the co-receptor binding site. Previous studies have found that the outer domain of gp120 is relatively more stable than the inner domain and bridging sheet. When superimposed, the co-crystal structures of CD4-gp120 complex and VRC01-gp120 complex revealed that the CD4-binding site (CD4-BS) antibody VRC01 actually mainly bound to …

Beyond Bloodletting: Fda Gives Leeches A Medical Makeover, Carol Rados

Harold W. Manter Laboratory of Parasitology: Library Materials

In June 2004, the Food and Drug Administration cleared the first application for leeches (Hirudo medicinalis) to be used in modern medicine as medical devices. By definition, a medical device is an article intended to diagnose, cure, treat, prevent, or mitigate a disease or condition, or to affect a function or structure of the body, that does not achieve its primary effect through a chemical action and is not metabolized.