Medicine and Health Sciences Commons^™

In Patients With Cardiac Arrest, Does Early Defibrillation Reduce Mortality?, Nicholas Lueddecke

Theses and Graduate Projects

Background: Cardiac arrest is a devastating disorder that affects millions of people each year. Often having a sudden onset, cardiac arrest is almost certainly lethal if prompt treatment is not started. In hopes to both better understand how treatment of cardiac arrest has evolved and to quantitatively measure the outcome of defibrillation, multiple pieces of literature have been reviewed.

Methods: Articles were found that were pertinent by using PubMed and Google Scholar. Literature was obtained that researched a wide spectrum of topics relating to defibrillation and cardiac arrest that did not focus on traumatic cardiac arrests as it is beyond …

Speech-Evoked Brain Activity Is More Robust To Competing Speech When It Is Spoken By Someone Familiar, Emma Holmes, Ingrid S. Johnsrude

Communication Sciences and Disorders Publications

When speech is masked by competing sound, people are better at understanding what is said if the talker is familiar compared to unfamiliar. The benefit is robust, but how does processing of familiar voices facilitate intelligibility? We combined high-resolution fMRI with representational similarity analysis to quantify the difference in distributed activity between clear and masked speech. We demonstrate that brain representations of spoken sentences are less affected by a competing sentence when they are spoken by a friend or partner than by someone unfamiliar—effectively, showing a cortical signal-to-noise ratio (SNR) enhancement for familiar voices. This effect correlated with the familiar-voice …

The Immunoregulation Of Autoimmune Diabetes, Hao Hu

Arts & Sciences Electronic Theses and Dissertations

How autoimmune diseases are regulated is a long-term research topic in the autoimmunity field. We use autoimmune diabetes as a model to study this. Autoimmune diabetes is a T cell-dependent autoimmune syndrome. The functions of T cells are regulated during their development and activation. Developmentally, T cells will undergo a stringent thymic selection: a process that self-reactive T cells are tolerized to become thymic derived Tregs or can be deleted by apoptosis based on binding affinity and avidity between the TCRs and self-peptide:MHC complexes. After T cells mature, they can also be tolerized in the periphery in many other ways, …

Exploring Β-Cell Function And Heterogeneity In Obese Sm/J Mice, Mario Alejandro Miranda

Arts & Sciences Electronic Theses and Dissertations

Pancreatic β-cells perform glucose-stimulated insulin secretion, a process required to maintain systemic glucose homeostasis. Obesity promotes glycemic and inflammatory stress, causing β-cell death and dysfunction, resulting in diabetes. Efforts to improve β-cell function in obesity have been hampered by observations that β-cells are highly heterogeneous, varying in morphology, function, and gene expression. There is great need to understand the breadth of β-cell heterogeneity in health and obesity to improve diabetic therapies.High fat-fed SM/J mice spontaneously transition from hyperglycemic-obese to normoglycemic-obese with age, providing a unique opportunity to study β-cell adaptation. Here, we show that as they resolve hyperglycemia, obese SM/J …

Investigation Of Ifnγ-Induced Control Of Intracellular Pathogens, Michael Mcallaster

Arts & Sciences Electronic Theses and Dissertations

Genes required for the lysosomal degradation pathway of autophagy play key roles in topologically distinct cellular processes with significant physiologic importance. One of the first-described of these ATG gene-dependent processes is the requirement for a subset of ATG genes in interferon-γ (IFNγ)-induced inhibition of norovirus and Toxoplasma gondii replication. In this dissertation we identified novel components that are required for or that negatively regulate this immune mechanism. Enzymes involved in the conjugation of UFM1 to target proteins including UFC1 and UBA5, negatively regulated IFNγ-induced inhibition of norovirus replication via effects of Ern1. We identified and confirmed that IFNγ-induced inhibition of …

Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell

Arts & Sciences Electronic Theses and Dissertations

Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. …

Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang

Arts & Sciences Electronic Theses and Dissertations

Macrophages are innate immune cells that protect against pathogens and maintain tissue integrity. In vertebrates, macrophages reside in every tissue where they perform specific functions from early development through adulthood. While macrophages provide important functions across all tissues, a major focus in recent years has been the role of resident brain macrophages, known as microglia, in neurodegeneration. As microglia have been shown to affect brain development, homeostasis, and disease, they demonstrate how immune cells critically mediate neurological health and point to the broader significance of neuroimmune interactions, or the coordinated actions of the nervous and immune systems for maintaining tissue …

Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy

Arts & Sciences Electronic Theses and Dissertations

The microtubule-binding protein tau is associated with neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy, and a subset of frontotemporal dementias. In these tauopathies, tau becomes hyperphosphorylated and forms intracellular neurofibrillary tau tangles, contributing to synaptic dysfunction, neuronal death, and severe astrogliosis. Tau can be classified as having a 3-repeat (3R) or 4-repeat (4R) structure, resulting from alternative splicing of exon 10 within the MAPT gene. While the higher deposition of 4R tau characterizes many primary tauopathies, the role of 4R tau in neurodegenerative disease pathogenesis remains unclear. To investigate the role of tau isoforms in disease, we created tau …

Phenotyping And Preclinical Meta-Analysis Of Behavioral Outcomes From Complete Freund’S Adjuvant-Induced Inflammatory Pain In The Rodent Hind-Paw, Dominika J. Burek

Arts & Sciences Electronic Theses and Dissertations

Pain and opioid use disorder prevalence, diagnoses of mental health disorders, and rate of suicide have all skyrocketed over the last 30 years as a matrix of public health crises. Each reduces quality of life and installs risk of the others; together, they have burdened our country with nearly unmanageable healthcare challenges. Although the critical demand for novel and more effective therapeutics has been clear for decades, relatively little progress has been made to address pain and its comorbidities. Repeated clinical trial failures have called into question the preclinical evidence upon which they are based. Preclinical models of pain-induced negative …

Does Transitioning To An Omi/Nomi Model For The Evaluation Of Acute Coronary Syndrome In Adult Emergency Department Patients Improve Outcomes Compared To Contemporary Stemi/Nstemi Model?, Ismar Terzic

Theses and Graduate Projects

Acute coronary syndrome (ACS) continues to be the most common cause of death in the United States, and nearly every 34 seconds one American has a coronary event. Based on 12- lead electrocardiogram (ECG) findings myocardial infarction (MI) patients are treated, according to guidelines, emergently with reperfusion therapy if presenting with ST elevation myocardial infarction (STEMI), versus delayed revascularization if presenting with non-ST elevation myocardial infarction (NSTEMI). However, the evidence shows there is a lack of recognition of which patients require immediate catherization utilizing the current guidelines. In recent years, approximately 70% of acute MI (AMI) patients are classified as …

Blood-Based Multi-Cancer Detection Using A Novel Variant Calling Assay (Deepgentm): Early Clinical Results, Rebecca M. Tuttle, Frederic Ris, Minia Hellan, Jonathan Douissard, Jorge J. Nieva, Frederic Triponez, Yanghee Woo, David Geller, Nicolas C. Buchs, Leo Buehler, Stefan Moenig, Christope E. Iselin, Wolfram Karenovics, Patrick Petignat, Giang Thanh Lam, Manuela Undurraga Malinervo, James R. Ouellette, Debashish Bose, Nael Ismail, Christian Toso

Department of Surgery Faculty Publications

This is an early clinical analysis of the DEEPGENTM platform for cancer detection. Newly diagnosed cancer patients and individuals with no known malignancy were included in a prospective open-label case-controlled study (NCT03517332). Plasma cfDNA that was extracted from peripheral blood was sequenced and data were processed using machine-learning algorithms to derive cancer prediction scores. A total of 260 cancer patients and 415 controls were included in the study. Overall, sensitivity for all cancers was 57% (95% CI: 52, 64) at 95% specificity, and 43% (95% CI: 37, 49) at 99% specificity. With 51% sensitivity and 95% specificity for all stage …

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Graft In The Treatment Of Multivessel Coronary Artery Disease On Diabetes Mellitus Patients, Nguyen Vu

Theses and Graduate Projects

Objectives: This systemic review is conducted to compare between Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Graft (CABG) in the revascularization strategy of patients with diabetes mellitus (DM) and multivessel coronary artery disease (CAD) based on clinical outcomes.

Background: Diabetes mellitus approached epidemic proportions globally and was recognized as a risk factor of aggressive and multivessel CAD [1,2]. The controversy over the optimal revascularization strategy for patients with DM and multivessel CAD has been hotly debated for more than 10 years. Numerous studies and data analysis were conducted to compare between PCI and CABG based on clinical outcomes of …

Platelet-Rich Plasma Vs. Traditional Surgical And Nonsurgical Interventions For Rotator Cuff Tendinopathies, Nick Slingerland

Theses and Graduate Projects

Background: Rotator cuff tendinopathies present as one of the most common musculoskeletal injuries of the upper extremity. The rotator cuff consists of four muscles: the supraspinatus, infraspinatus, teres minor, and subscapularis with the supraspinatus the most injured of the group. Over time, variations regarding treatment through surgical or nonsurgical interventions have remained constant. In recent years, the use of platelet-rich plasma (PRP) as an additional alternative has become popular to promote healing and improve functionality of the shoulder. The purpose of this clinical review using various study designs is to assess if the platelet-rich plasma injections are more effective when …

Movement Patterns During Functional Activities In People With Chronic Low Back Pain, Quenten Lowell Hooker

Arts & Sciences Electronic Theses and Dissertations

People with chronic LBP display an altered movement pattern where the lumbar spine moves more readily than other joints that can contribute to the activity. The pattern is of particular clinical relevance because across multiple studies the magnitude of altered pattern is associated with LBP and function. One session of motor skill training (MST) during functional activities can improve the altered pattern. However, of the few studies investigating MST for people with LBP, none have examined the short-term or long-term effects of MST on the altered pattern. Additionally, no study has systematically examined if person-specific characteristics moderate the altered pattern …

Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt

Arts & Sciences Electronic Theses and Dissertations

Cytosolic nucleic acid sensing and interferon (IFN) signaling are central to the host immune response to microbial pathogens. However, dysregulation of immunological pathways such as these can result in devastating autoimmune disease. In order to provide a robust immune response to pathogen without causing harm to self, the host immune system must engage in a delicate balancing act, interacting with microbes and determining whether they are commensal or pathogenic. The cGAS-STING pathway is a key regulator of host-microbe interactions by cytosolic nucleic sensing and IFN signaling. Loss of function in the cGAS-STING pathway leads to increased susceptibility to pathogenic threats, …

Exploring Contextual Differences In Environment And Policy Strategies To Promote Physical Activity In Disadvantaged Communities, Natalicio Hector Serrano

Arts & Sciences Electronic Theses and Dissertations

The benefits of physical activity for health are far reaching, including the reduced risk of several chronic diseases. However, only about 24% of US adults meet recommended guidelines of physical activity, with traditionally disadvantaged populations such as rural residents and persons of color facing even lower rates. Ecological models of health behavior help to understand correlates of physical activity that impact population health, but may not be as useful in disadvantaged populations where the evidence base is either lacking or not as rigorous. Furthermore, measures and methods may be underdeveloped in disadvantaged populations and there is a lack of understanding …

Community Based Participatory Research Informed Manualization And Piloting Of E-Training Of A Modified Dialectical Behavior Therapy Intervention, Annika M. Miyamoto

Doctoral Dissertations

This study explores the efficacy of delivering modified dialectical behavior therapy (m-DBT) to direct support staff who work with seriously mentally ill patients with neurocognitive deficits using remote web-based technology. The partnering facility for this study is a residential skilled-nursing facility that provides 24-hour care to individuals under conservatorship. Using a previously piloted m-DBT protocol, qualitative feedback was gathered from four participants with background training in psychology and varying experiences with DBT. All participants had direct knowledge of the treatment environment and experience working with the patient population. Gathered feedback was used to revise the m-DBT protocol to be used …

The Adequacy Of Pa Didactic Psychiatric Education, Dean Berzins

Theses and Graduate Projects

With a shortage of mental health specialists, primary care providers, which increasingly include physician assistants (PAs), must be able to adequately recognize, diagnose, and treat common mental health disorders. Unfortunately, providers are not currently able to meet this challenge and frequently underdiagnose and undertreat psychiatric conditions. This paper examined the amount of didactic education in psychodiagnostics PA students receive compared to the amount of didactic psychodiagnostics training psychotherapists students receive in graduate school. Results indicated that while psychotherapists have, on average, more classroom time, the difference in seat time between PAs and psychotherapists is less than double, but the assigned …

What Is The Most Effective Management For Patients With Concomitant Gallstones And Bile Duct Stones?, Stephanie Mccarney

Theses and Graduate Projects

Background: Gallstone disease is common with a high prevalence in developed nations and is expected to rise as the obesity and metabolic syndrome epidemic worsens. The associated relationship between gallstone and biliary tract disease is complex. The most effective treatment approach for patients with concomitant gallstones and bile duct stones is controversial. Multiple different combinations of one-step and two-step endoscopic and/or surgical techniques exist. Advancements in laparoscopic and endoscopic methods have paved the way for a minimally invasive approach to managing cholecystocholedocholithiasis (CCL).

Methods: A literature review was conducted via systematic search of Google Scholar and PubMed to …

Concentrations Of Lead, Mercury, Arsenic, Cadmium, Manganese, And Aluminum In The Blood Of Pakistani Children With And Without Autism Spectrum Disorder And Their Associated Factors, Mohammad H. Rahbar, Shahnaz H. Ibrahim, Syed Iqbal Azam, Manouchehr Hessabi, Fatima Karim, Sori Kim, Jing Zhang, Nasreen Gulzar Ali, Katherine A. Loveland

Department of Paediatrics and Child Health

Background: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with early onset in utero or childhood. Environmental exposure to six metals (Pb, Hg, As, Cd, Mn, Al) is believed to be associated with ASD directly or interactively with genes. Objective: To assess the association of ASD among Pakistani children with the six metals and genotype frequencies of three GST genes (GSTP1, GSTM1, GSTT1).
Methods: We enrolled 30 ASD cases, age 2-12 years old, and 30 age- and sex-matched typically developing (TD) controls in Karachi, Pakistan. We assessed associations of ASD status with various factors using …