Analytical, Diagnostic and Therapeutic Techniques and Equipment Commons^™

Helical Remodeling Augments 5-Lipoxygenase Activity In The Synthesis Of Proinflammatory Mediators, Eden M. Gallegos, Tanner D. Reed, Forge A. Mathes, Nelson V. Guevara, David B. Neau, Wei Huang, Marcia E. Newcomer, Nathaniel C. Gilbert

School of Medicine Faculty Publications

The synthesis of proinflammatory leukotrienes implicated in asthma, allergic rhinitis, and atherosclerosis is initiated by the enzyme 5-lipoxygenase (5-LOX). The crystal structure of human Stable-5-LOX revealed a conformation where the catalytic iron was inaccessible to bulk solvent as two aromatic residues on a conserved helix-α2 (Hα2) plugged the substrate access portal. Whether 5-LOX can also adopt a more open conformation has not been resolved. Here, we present a new conformation of 5-LOX where Hα2 adopts an elongated conformation equivalent to that described in other animal lipoxygenase structures. Our observation of the sigmoidal kinetic behavior of 5-LOX, which is indicative of …

Healthy Exosomes And Their Effects On Diabetic Cardiomyocytes, Miguel A. Garza, Genaro A. Ramírez-Correa, Maria Lourdes Garza-Rodríguez, Andres J. Medina

MEDI 9331 Scholarly Activities Clinical Years

Extracellular Vesicles, and more specifically, exosomes, are essential for effective cell-to-cell communication in a wide variety of tissues. In the last couple of decades, these nanovesicles have been proven to be active participants and regulators in many disease processes; therefore, their therapeutic effects have been widely studied and proven in various cardiovascular diseases both, in vitro and in vivo. Thus, this study aims at assessing the effects of running healthy mice exosomes on cardiomyocyte and cardiac tissue samples obtained from diabetic mice. Here, we successfully extract exosomes from mice plasma and detect their presence through the use of anti-CD9 and …

Artificial Intelligence In The Radiomic Analysis Of Glioblastomas: A Review, Taxonomy, And Perspective, Ming Zhu, Sijia Li, Yu Kuang, Virigina B. Hill, Amy B. Heimberger, Lijie Zhai, Shenjie Zhai

Electrical & Computer Engineering Faculty Research

Radiological imaging techniques, including magnetic resonance imaging (MRI) and positron emission tomography (PET), are the standard-of-care non-invasive diagnostic approaches widely applied in neuro-oncology. Unfortunately, accurate interpretation of radiological imaging data is constantly challenged by the indistinguishable radiological image features shared by different pathological changes associated with tumor progression and/or various therapeutic interventions. In recent years, machine learning (ML)-based artificial intelligence (AI) technology has been widely applied in medical image processing and bioinformatics due to its advantages in implicit image feature extraction and integrative data analysis. Despite its recent rapid development, ML technology still faces many hurdles for its broader applications …

Cell-Free Dna Sequencing In Multiple Myeloma, Russell Irwin

Dissertations and Theses (Open Access)

Multiple myeloma (MM) is an incurable plasma cell dyscrasia. Recent advances in MM therapy, including CAR-T therapy, have increased survival and shown the value of assessing treatment response with great sensitivity, both in acute and long-term settings. Cell-free DNA, DNA fragments which are released into circulation as a part of normal cellular turnover, is a useful and dynamic biomarker in cancer patients due to the presence of circulating tumor DNA (ctDNA), which is readily identified using next generation sequencing. Here we report the analytical sensitivity, applicability, consistency, and prognostic ability of M5Seq, a novel hybrid capture panel designed for MM …

Development Of Advanced Mr-Guided Adaptive Radiation Therapy Methods For Head & Neck Cancers On The 1.5t Mr-Linac, Brigid Mcdonald

Dissertations and Theses (Open Access)

The 1.5T hybrid MRI/linear accelerator (MR-linac) has recently been introduced into clinical practice and used for the treatment of head and neck cancers (HNC). This device enables on-line adaptive radiation therapy (ART) based on anatomical changes throughout treatment and variations in patient position. This novel technology also has the potential for advanced ART strategies such as dose-optimized ART, in which the treatment plan is optimized based on the accumulated dose over previous fractions, or biological image-guided ART, in which the plan is adapted based on individual tumor response as measured through quantitative imaging techniques such as diffusion-weighted imaging (DWI). The …

Neuropsychology Of Primary Headache Disorders: A Meta-Analysis, Jasmin H. Pizer

Graduate Theses and Dissertations (2019 - present)

Objective: A meta-analysis was conducted comparing cognition on clinical measures between individuals with a primary headache disorder (PHD) and healthy controls (HC). Data Selection: The University of South Alabama Libraries’ OneSearch and PubMed, with a uniform search-strategy, were used to locate original research comparing cognition between PHD and HC samples. Analyses were modeled under random effects. Hedge’s g was used as a bias-corrected estimate of effect size. Between-study heterogeneity was assessed using Cochran’s Q and I2. Data Synthesis: The initial search interval spanned inception–May 2021 and yielded 6692 results. Fifty-seven studies were analyzed. Meta-analysis showed a significant combined effect size …

Inflammatory Response Following Hemorrhagic Stroke: The Role Of Cytokines, Patrick Devlin

Theses and Dissertations (ETD)

Hemorrhagic stroke is a dangerous form of stroke resulting from the rupturing of weakened blood vessels, releasing blood that increases intracranial pressure and causes the death of surrounding tissue. Treatment options are improving but remain limited, as evidenced by this condition being characterized by high rates of mortality as well as long-term morbidity. Unregulated inflammatory responses that occur following injury may be partially to blame for these poor outcomes. In response to any injury, the immune system releases cytokines to recruit immune cell activation and promote inflammation. But after hemorrhagic stroke, whether aneurysmal subarachnoid hemorrhage (aSAH) or intracerebral hemorrhage (ICH), …

Heart To Heart, Mom To Mom, Karis L. Tekwani

Journal of Patient-Centered Research and Reviews

This essay describes the human connection forged between two young moms, one the physician and one the patient, when their paths collided one night in the emergency department of a busy hospital. It describes a challenging and most memorable care experience in the career of a young emergency physician, the clinical outcome, and the patient’s appreciative follow-up message years later.

The Short-Term Effects Of Fine Airborne Particulate Matter And Climate On Covid-19 Disease Dynamics, El Hussain Shamsa, Kezhong Zhang

Medical Student Research Symposium

Background: Despite more than 60% of the United States population being fully vaccinated, COVID-19 cases continue to spike in a temporal pattern. These patterns in COVID-19 incidence and mortality may be linked to short-term changes in environmental factors.

Methods: Nationwide, county-wise measurements for COVID-19 cases and deaths, fine-airborne particulate matter (PM_2.5), and maximum temperature were obtained from March 20, 2020 to March 20, 2021. Multivariate Linear Regression was used to analyze the association between environmental factors and COVID-19 incidence and mortality rates in each season. Negative Binomial Regression was used to analyze daily fluctuations of COVID-19 cases …

Multicolor Fluorescence Guided Surgery For Head And Neck Cancer, Dani Szafran-Reeder

University Honors Theses

This project aims to take a novel, NIR nerve-specific fluorophore LGW05-75⁴ and test its compatibility with a tumor-targeting affibody molecule, ABY-029⁶ that has been labeled with IRDye800CW. The overall goal is to show that these two molecules can be co-administered to show the nerves and tumor cells in real-time to better assist surgeons in a full resection while avoiding iatrogenic nerve damage.

Targeting Myeloid Protein Kinase C Signaling To Overcome Immune Suppression And Improve Immunotherapy In Cancer, Mehdi Chaib

Theses and Dissertations (ETD)

Checkpoint immunotherapy unleashes T cell antitumor potential which has revolutionized cancer treatment showing unprecedented long-term responses. However, most patients do not respond to immunotherapy which often correlates with a dysfunctional or immunosuppressive myeloid compartment. Immunosuppressive myeloid cells comprise Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) and can suppress T cells via production of immunosuppressive factors. Conversely, efficient cytotoxic T cell priming is dependent on the ability of antigen-presenting cells (APCs), mainly conventional dendritic cells (cDCs) and macrophages, to present or cross-present tumor antigens to T cells. Thus, targeting immunosuppressive myeloid cells while simultaneously enhancing APCs represents a promising strategy …

The Role And Immunogenicity Of Cbfa2t3-Glis2 In Pediatric Acute Megakaryoblastic Leukemia, Elizabeth A. Garfinkle

Theses and Dissertations (ETD)

CBFA2T3-GLIS2 is the most prevalent fusion oncogene in pediatric acute megakaryoblastic leukemia in patients without Down syndrome (non-DS-AMKL) and is associated with an event free survival of only 8% even with high intensity chemotherapy and stem cell transplant in first remission. A cryptic inversion event on chromosome 16 joins the three nervy homology regions (NHR) of CBFA2T3 to the five zinc fingers of GLIS2. This configuration enables the encoded chimeric transcription factor to bind GLIS consensus sequences throughout the genome and recruit transcriptional activators and repressors to alter gene expression and enhance self-renewal capability. Few cooperating mutations have been identified …

Rates And Perceptions Of Covid-19 Vaccination From University Of Mississippi Students, Josie Parham

Honors Theses

The trials, tribulations and triumphs of the global COVID-19 pandemic are impacted by and are a product of behaviors that occur at the level of nations, states, cities and, ultimately, communities. In the wake of the development of safe and effective vaccines against SARS-CoV2, the virus responsible for the pandemic, the significance of the vaccine is closely linked to the number of individuals that receive the vaccine. To date, surveys have measured sizable variations in vaccination rates between nations, states, cities, and communities. Focusing on events that have transpired in one such local community, the present study (i) measured the …

The Role Of Corticothalamic Projections (Prelimbic Cortex To Nucleus Reuniens) In Working Memory, Phillip Kumpf, Paul C. Kumpf, S. D. Dunn, Evan Ciacciarelli, T. Gohar, Timothy Sloand, Mark Niedringhaus, Elizabeth West

Rowan-Virtua Research Day

Working memory (WM) is the ability to store information for short periods of time and is used to execute tasks

WM has been understood to work via the medial prefrontal cortex (mPFC) and dorsal hippocampus (dHPC), but they do not directly project to each other

The nucleus reuniens of the thalamus (Re) is a “middle man” between the mPFC and dHPC

There are projections between the prelimbic cortex (PrL) and Re that may be used during WM

To test the connection of the PrL to Re, a delayed nonmatch to position (DNMTP) task was performed

A Suspected Case Of Vaccine Induced Thrombosis With Thrombocytopenia Following Sars Cov2 Vaccine, Maryam Soliman

Rowan-Virtua Research Day

With the new development of the SARS-CoV vaccine and the majority of the population receiving this vaccine, it is important to recognize some of the rare side effects associated with it.

VITT is a rare complication of the COVID vaccine

Diagnostic criteria: COVID vaccine 4-24 days prior to symptom onset, any venous or arterial thrombosis, thrombocytopenia < 150, positive PF4 HIT ELISA, markedly elevated D-dimer >4x ULN.

Vaccine Induced Thrombosis with Thrombocytopenia is a potentially life-threatening diagnosis that must be recognized and treated correctly to prevent poor outcomes.

Alternate Site Pacing And The Impact On Intracellular Calcium Handling During The Post-Extrasystolic Cardiac Cycle, Kent Ozcan, Lawrence Mulligan

Rowan-Virtua Research Day

Objective: Previous work has shown that alternate site (RV apex) results in myocardial dysfunction. With the development of tools to place endocardial pacing leads in locations that create physiological pacing activation, we sought to evaluate how ventricular trans-septal or left ventricular apical placement pacing differs from right atrial pacing. We will evaluate how these chronic pacing modes impact the PR and RF at baseline, 0, and 16 weeks in the canine heart.

Methods: Quantitative analysis will be performed on previously generated data. The data set includes pacing of 15 dogs total (8 with trans-septal leads & 7 with left ventricular …

Interaction Of Fluorescent Probes With Sirtuin Proteins, James Fusco, Brian P Weiser

Rowan-Virtua Research Day

Sirtuins are a class of proteins belonging to the Sir2 (Silencing information regulator 2) family of NAD+ dependent protein lysine deacylases. Different Isoforms (SIRT1-SIRT7) differ in their specific deacylase activity and cellular location. They have roles in DNA repair, glucose metabolism, and cellular proliferation which make them highly desirable targets for carcinoma therapeutics. We previously used 1-aminoanthracene’s (AMA) fluorescent properties when bound with SIRT2 (Kd of 37 μM) to develop a high-throughput screen to identify novel ligands that inhibit SIRT2’s enzymatic activities. We hope to reveal other potential probes for future high-throughput screening with all the sirtuin isotopes. 1-AMA’s fluorescence …

Cases From A Community Hospital… Jchimp Series #1: 55-Year-Old Male With Acute Pe Who Developed Persistent Epistaxis., Jerrica N. Mueller, Bobby Mathew, Douglas D. Reh, Joseph Fuscaldo

Journal of Community Hospital Internal Medicine Perspectives

This is the first in a new series of case reports that will present real scenarios from our community hospital. The cases are chosen to highlight clinical dilemmas and offer review and perspective on what is currently known about the topic. We present the case of a 55-year-old Caucasian male who presented to the emergency department of our community hospital for worsening dyspnea. Evaluation in the Emergency department revealed a diagnosis of extensive pulmonary emboli in the pulmonary vasculature. The patient was admitted to the ICU. A clinical decision was made to initiate treatment with low-dose tissue plasminogen activator (tpa) …

Targeting Metabolic Adaptations To Anti-Angiogenic Therapy In Ovarian Cancer, Deanna M. Glassman, Deanna Glassman

Dissertations and Theses (Open Access)

ABSTRACT

Background: Ovarian cancer is the most lethal gynecologic malignancy. Despite modest clinical improvements with anti-VEGF antibody (AVA) therapy, adaptive resistance is nearly ubiquitous and additional therapeutic options are limited. A dependence on glutamine metabolism, via the enzyme glutaminase (GLS), is a known mechanism of adaptive resistance.

Purpose: To assess the efficacy of a glutaminase inhibitor as a means of exploiting the metabolic vulnerability of glutamine dependence that develops as a result of adaptive resistance to AVA therapy.

Experimental Design: We used a glutaminase inhibitor (GLSi) synthesized at MD Anderson Cancer Center for all in vitro and in vivo experiments. …

Nanoparticles For Biomedical Applications, Joseph Kim

Dissertations and Theses (Open Access)

This thesis presents development and evaluation of the potential of three new nanoparticles for biomedical applications. With the rapid growth of the field of nanoscience, researchers have explored developing nanoparticles for various biomedical applications, including imaging, therapy, and drug delivery. This thesis demonstrates the development of two C­₆₀ fullerene based nanoparticles and one boron based nanoparticle to answer key questions related to their biological potential.

In the first part of the thesis, we describe synthesis and characterization of a pure boron nanoparticle containing asolectin phospholipid-based liposome construct prepared using a water-in-oil emulsion method, as a novel alternative agent for …

Early Detection Of Atypical Motor And Neurobehavior Of Infants At Risk Secondary To Opioid Exposure: A Prospective Study, Kara Boynewicz

Electronic Theses and Dissertations

Prenatal opioid exposure has been studied in relation to infants' medical outcomes. However, large gaps exist in the literature supporting early identification of atypical neurobehavior and motor development of infants with prenatal opioid exposure. The purpose of the study was to investigate whether prenatal opioid exposure has a negative influence on a newborn infant’s neurobehavior and motor development to aid in the early identification of potential delays. Using a prospective quasi experimental design, infants motor development using the Test of Infant Motor Performance (TIMP) and neurobehavior using the NICU Neonatal Network Scale (NNNS) was assessed on 58 infants in a …

Synthesis, Structural Characterization, And In Vitro Biological Assessment Of Trans- Platinum (Ii) Thionate Complexes As Potent Anticancer Agents, Mia Alshami

Chemistry & Biochemistry Undergraduate Honors Theses

The content of this thesis has been originally reported in our published paper, “trans-Platinum (II) Thionate Complexes: Synthesis, Structural Characterization, and in vitro Biological Assessment as Potent Anticancer Agents” ChemPlusChem 2019 84, 1525-1535, DOI: 10.1002/cplu.201900394, in which I served as coauthor. Cancer caused 9.6 million deaths in 2018 worldwide, with 18.1 million new diagnoses during that same year.The most widely used metal in anticancer drugs is platinum (Pt), and these drugs are used to treat almost 50% of cancer patients. To optimize drug effectiveness, trans-configured Pt(II) complexes have been introduced as a strategy to potentially overcome the …

A Neurophysiological Investigation Of Listening Effort In Normal Hearing Adults Using Fnirs And Pupillometry, Jessica Defenderfer

Theses and Dissertations (ETD)

Real-world conversations are often accompanied by some sort of interference that challenges the clarity of the speaker’s message, causing listeners to exert more effort to understand speech. Previous research has demonstrated that when listening to speech becomes difficult, various regions of the brain are recruited beyond those which engage during optimal listening conditions. However, the neural correlates that underly listening effort are not fully understood. Importantly, the pupillary response can be used to index listening effort, such that pupil size increases with increasing cognitive demand. I proposed that pupillometry can be used to characterize the cortical response, such that changes …

Gene Therapy And Biomedical Applications, Sarah Dundore, Leena Pattarkine

Harrisburg University Research Symposium: Highlighting Research, Innovation, & Creativity

Gene therapy has many uses today through the new treatment options and its potential to treat uncurable diseases. (Class Project)

Stroke Network Of Wisconsin (Snow) Scale Predicts Large Vessel Occlusion Stroke In The Prehospital Setting, Kessarin Panichpisal, Sarah Erpenbeck, Paul Vilar, Reji P. Babygirija, Maharaj Singh, M. Riccardo Colella, Richard A. Rovin

Journal of Patient-Centered Research and Reviews

Purpose: In previous trials, the Stroke Network of Wisconsin (SNOW) scale accurately predicted large vessel occlusion (LVO) stroke in the hospital setting. This study evaluated SNOW scale performance in the prehospital setting and its ability to predict LVO or distal medium vessel occlusion (DMVO) in patients suspected of having acute ischemic stroke (AIS), a scenario in which transport time to an endovascular treatment-capable facility (ECSC) is critical.

Methods: All potential AIS patients with last-known-well time of ≤ 24 hours were assessed by Milwaukee County Emergency Medical Services for LVO using SNOW. Patients with a positive SNOW score were transferred to …

Psycho-Emotional Education For Occupational Therapists Supporting Individuals Assuming The Role Of Family-Caregiver For People With A Traumatic Brain Injury (Tbi), Laura Dawn Lippman, Caitlyn E. Baird, Natalie L. Billharz

2022 Celebration of Scholarly Works

The purpose of this research was to identify the psycho-emotional needs of family-caregivers of individuals who sustained a traumatic brain injury (TBI), and measure if there was a change in knowledge among occupational therapists, and occupational therapy students following a two-hour seminar covering topics identified in the literature. The topics covered in the seminar included the concept of ambiguous loss, the importance of validating emotions, the caregiver grieving process, and the importance of providing caregiver resources. To measure the change in knowledge, researchers utilized primarily a quantitative research design using pre- and post-test questionnaires with Likert- scale questions. The questionnaire …

Immunomodulatory Roles Of The Lysosomal Sialidase Neuraminidase 1, Leigh Ellen Fremuth

Theses and Dissertations (ETD)

Background Sialic acids are key sugar moieties located at the non-reducing terminals of glycan chains on glycoproteins and glycolipids. By virtue of their location, they influence the functions and biochemical properties of the macromolecules they are bound to. Removal of sialic acids in mammalian cells is carried out by four sialidases, which are differentially expressed and localized in distinct subcellular compartments. Neuraminidase 1 (NEU1), the most abundant and ubiquitous of the four sialidases, functions primarily in the acidic environment of the lysosomes, but can hydrolyze substrates at the plasma membrane, at least in certain cell types. The enzyme initiates the …

Succinic Semialdehyde Dehydrogenase Deficiency (Ssadhd): Qualitative Needs Assessment For Patients With A Rare Neurological Disorder, Cassandra Bovee, Kayla Woodring

Annual Research Symposium

No abstract provided.

Seroprevalence Of Covid-19 Igg Antibody In Resident And Fellow Physicians In Milwaukee, Wisconsin: Analysis Of A Cross-Sectional Survey, Dennis J. Baumgardner, Alexander Schwank, Jessica J. F. Kram, Wilhelm Lehmann, Jacob Bidwell, Tricia La Fratta, Kenneth Copeland

Journal of Patient-Centered Research and Reviews

Purpose: Medical trainees are likely at differential risk of exposure to COVID-19 per respective clinical activity. We sought to determine the seroprevalence of COVID-19 antibody (Ab) among resident and fellow physicians with varying degrees of exposure to COVID-19.

Methods: A cross-sectional study of Milwaukee-based resident and fellow physicians, encompassing December 2019–June 2020, was conducted. Relevant variables of interest were ascertained by survey and payroll data, and Abbott ARCHITECT Ab test (index cut-off of ≥ 1.4) was performed. Descriptive statistics were generated, with 95% CI calculated for the study’s primary outcome of seroprevalence.

Results: Among survey respondents (92 of 148, 62%), …

Breadth Of Vaccinated Cancer Patient Humoral Response To Sars-Cov-2 Spike Protein And Rbd Variants, Julia Corman, Joey Breckenridge Jr., Adrienne M. Bushau-Sprinkle, Krystal T. Hamorsky, Joshua L. Fuqua

Posters-at-the-Capitol

SARS-CoV-2, the virus responsible for the COVID-19 of which several variants have emerged, such as the B.1.351 SARS-CoV-2 variant. The Receptor Binding Domain (RBD), located within the Spike protein is an immunogenic epitope for potent neutralizing antibodies. Current mRNA vaccines encode for the Spike protein, allowing the body to build antigen-specific antibodies. Assays measuring protective antibodies are essential to manage the COVID-19 pandemic and can be used as a platform for variant screening. RBD-foldon 2.2 is a novel antigen produced by fusing RBD with the trimerization domain Fibritin from Bacteriophage T4. Its amino acid sequence is based on the original …