Honoring Veterans’ Wishes: Efficacy Of An Evidence-Based Shared Decision-Making Tool In Va Icu Goals-Of-Care Discussions, Stephanie Alexander, Anna Astashchanka Md, Venktesh Ramnath Md

Doctor of Nursing Practice Final Manuscripts

Abstract

Introduction: This Doctor of Nursing Practice project aimed to enhance the knowledge and confidence of the San Diego Veterans Health Administration’s (VASD) Intensive Care Unit (ICU) medical providers in goals-of-care discussions (GOCD). Additionally, this project aimed to improve the documentation of these discussions.

Background: Delays in GOCD can lead to futile medical and surgical interventions, inappropriate antibiotic use, and higher rates of mental health conditions in patients and their loved ones. Earlier GOCD are associated with lower ventilation and resuscitation rates, earlier hospice enrollment, reduced ICU admissions, lower financial costs, and better patient and caregiver quality of life. However, …

Cord Blood-Derived Invariant Natural Killer T Cells As A Platform For Allogeneic Chimeric Antigen Receptor Cell Therapy, Maison Grefe

Dissertations & Theses (Open Access)

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematopoietic malignancies achieving >50% complete response rates in numerous refractory/relapsed B cell malignancies. However, there are challenges that hinder CAR-T efficacy and bar the broader use of this therapy in patients. One approach to address these challenges is to create a safe allogeneic CAR cell product by using cells that do not cause graft versus host disease (GvHD). Invariant natural killer T (iNKT) cells are an ideal candidate as they are restricted to the monomorphic CD1d protein in contrast to HLA restricted αβ-T cells and therefore are safe in …

Telehealth Utilization In Clinical Trials: Facilitators, Barriers, And Future Directions, Michael Carpenter

MUSC Theses and Dissertations

Purpose: Telehealth implementation in clinical trials is not as well developed as compared to telehealth utilization in other areas of medical care. The focus of this project will explore the factors that foster and hinder the effective use of telehealth in clinical trials and how these insights can inform future strategies and policies.

Method: The project synthesizes empirical research and theoretical literature on the integration of telehealth into clinical trial. The research utilizes an online survey via REDCap to gauge the level of acceptance, perceived effectiveness, and potential barriers to the implementation of telehealth in clinical research.

Results: The responses …

Developing Radiosensitizers To Enhance Radiotherapy In Treating Gastroenteropancreatic Neuroendocrine Tumor, Zeta Chow

Theses and Dissertations--Clinical and Translational Science

Gastroenteropancreatic Neuroendocrine Tumor (GEP-NET) is a heterogeneous group of malignancies arising from multipotent neuroendocrine stem cells in the gastrointestinal tract. The incidence of GEP-NET continues to rise, possibly due to the advancement of imaging and biomarkers available for diagnosis. However, even though the majority of patients are diagnosed with low-grade and localized disease, a significant percentage of patients present with advanced-stage metastatic disease with poor prognosis in months to a few years. These advanced-stage GEP-NET patients can also present with a variety of debilitating symptoms that significantly impact their quality of life. The role of palliative-intent surgery is limited, and …

Modulating The Mtor Pathway Using Inducible Retrogradely Transported Aavs As A Novel Approach To Improve Motor Recovery In Spinal Cord Injury, Christopher Bosse-Joseph

Theses and Dissertations--Medical Sciences

Spinal cord injury poses multiple regeneration barriers, including neuronal-intrinsic and extrinsic factors. Overcoming these barriers has stood as a longstanding challenge in neuroscience. A well-studied mechanism to promote spinal cord regeneration and locomotor recovery is activating the PI3K/mTOR pathway by knocking out phosphatase and tensin homolog protein (PTEN). PTEN knockout (PTEN-KO) studies have traditionally used adeno-associated virus (AAV) viral vectors to improve functional recovery. The use of traditional AAV serotypes to induce PTEN-KO has shown promise to improve functional recovery in rodent models; however, these approaches show significant limitations for translational utility. Firstly, the use of traditional AAV serotypes to …

Sex And Gender Differences In Arthritis Health Information, Tania Al-Jilawi

Electronic Thesis and Dissertation Repository

Arthritis is a common disorder that may result in pain and inflammation, making it challenging to move or continue being active. Arthritis comes in a variety of forms. The two studies of this thesis aimed to identify the influence of intersectionality, especially sex and gender, in arthritis. The first study, a structured review, evaluated the inclusion of sex/gender and intersectional identities in patient resources of three arthritis societies: the Canadian Arthritis Society, the American Arthritis Foundation, and the National Rheumatoid Arthritis Society. The appraisal tool, the Sex/Gender and Intersectional Considerations in Patient/Consumer Health Information Appraisal Tool was used to evaluate …

A Multi-Modal Imaging Analysis Of Inter-Community Hub Nodes In Subjective Cognitive Decline Linking Longitudinal Hub Function Disruption To White Matter Integrity Kurtosis, Duncan Nowling

MUSC Theses and Dissertations

Subjective Cognitive Decline (SCD) has garnered much interest as a potential identifiable preclinical stage and indicator of risk for cognitive decline in Alzheimer’s Disease and related dementias (ADRD). Identification of individuals in this stage though is difficult, as they present with objectively normal cognitive evaluation scores, relying instead upon self-report of concern about decline in cognitive abilities. The use of non-invasive in-vivo imaging methods like BOLD functional imaging and diffusion tensor have allowed for complex mapping of both the functional and structural network features unique to this condition. This study furthers this network biomarker map of SCD by investigating the …

Early Development Of C3ar1-Targeting Chimeric Antigen Receptor T Cells For The Treatment Of Glioblastoma Multiforme, Cameron Fraser

Electronic Theses, Projects, and Dissertations

Glioblastoma multiforme is the most aggressive type of glioma, demonstrating extremely low long-term survival despite modern therapies. Chimeric antigen receptor T cells have shown extreme levels of success in the treatment of B cell lymphomas through persistent anti-tumor activity. Prior research has demonstrated the therapeutic potential in targeting the C3a-C3aR1 pathway as it acts in an autocrine loop, maintaining the proliferation and survival of cancer stem cells within the tumor. Here, we reorient the treatment to target C3aR1 for the treatment of glioblastoma multiforme. In order to achieve this, Jurkat immortalized T cells will express various chimeric antigen receptor designs …

The Importance Of Contrast Sensitivity, Color Vision, And Electrophysiological Testing In Clinical And Occupational Settings, Frances Silva

Theses & Dissertations

Visual acuity (VA) is universally accepted as the gold standard metric for ocular vision and function. Contrast sensitivity (CS), color vision, and electrophysiological testing for clinical and occupational settings are warranted despite being deemed ancillary and minimally utilized by clinicians. These assessments provide essential information to subjectively and objectively quantify and obtain optimal functional vision. They are useful for baseline data and monitoring hereditary and progressive ocular conditions and cognitive function. The studies in this dissertation highlight the value of contrast sensitivity, color vision, and cone specific electrophysiological testing, as well as the novel metrics obtained with potential practical clinical …

Shedding Light On Hearing In Coma: Investigating The Applicability Of Functional Near-Infrared Spectroscopy For Assessing Auditory Function And Aiding Prognosis In Patients With Acute Disorders Of Consciousness, Reza Moulavi Ardakani

Electronic Thesis and Dissertation Repository

There is a critical need for a bedside neuroimaging tool to aid in the prediction of functional recovery outcomes for patients with acute disorders of consciousness (DoC) in the early days following severe brain injury. Current neurobehavioral examinations and prognosis tools have limitations in predicting good outcomes, leading to potential mistreatment or premature withdrawal of life support. Functional near-infrared spectroscopy (fNIRS) is a viable candidate for such purposes due to its portability and cost-effectiveness. Auditory processing, viewed as a multi-level and multifaceted brain function, could provide a sensitive and specific marker of residual cognitive function in unresponsive patients. This study …

The Effect Of Kidney Preservation At 10°C With Hemopure And Hydrogen Sulfide Donor, Sodium Thiosulfate, In A Syngeneic Model Of Rat Renal Transplantation, Maria Abou Taka

Electronic Thesis and Dissertation Repository

Kidney transplantation is preferred for patients with end-stage renal disease. The current gold standard for preserving kidneys is static cold storage (SCS) at 4°C in University of Wisconsin (UW) solution. However, SCS contributes to ischemia-reperfusion injury (IRI), which involves cell death and inflammation. Our group showed that SCS of kidneys with hydrogen sulfide donors, like sodium thiosulfate (STS), that reduce tissue injury enhanced kidney survival. Though, there is still a risk of cold renal IRI at 4°C. Recent evidence suggests that preserving organs at 10°C enhanced graft function and survival. Therefore, this thesis will evaluate the effect of 10°C kidney …

Building Up Cal Poly Global Brigades Student Group: Reflections On Designing And Implementing One Undergraduate-Led Community Info Session, Caroline Nicole Smith, Jafra D. Thomas

Kinesiology and Public Health

Intro: Global Brigades, an international non-profit organization, trains college students and other pre-professionals in community-based health promotion by mobilizing community service trips around the world, which are taught and led by local community groups. Cal Poly’s Global Brigades student group was founded in 2018, and thus far, they have carried out three annual, medically-focused brigades to Honduras (two in-person, one virtual).

Purpose: The aim of this report is to present the findings of one experiential senior project to promote Cal Poly’s Global Brigades student group^[1] (conducted January to March 2023).

Methods: The student designed material for …

Social Dominance Alters Stress-Induced Neural Activity And Generates Individual Differences In Stress Vulnerability, Jenna Lee Laymon

Masters Theses

Identifying the physiological and behavioral mechanisms that underlie stress vulnerability is a crucial step toward identifying novel targets for the prevention and treatment of stress-related disorders. Social status is a key environmental factor that contributes to individual variations in stress vulnerability. In particular, achieving a subordinate social status has been shown to produce susceptibility to anxiety-like and depressive-like behavior. In this project, our aim was to identify neural ensembles regulating how dominance status modulated stress-induced changes in avoidant behavior in male and female Syrian hamsters. Using a viral vector that codes for robust activity marker (RAM), we investigated whether stress-induced …

Kir-Based Inhibitory Cars Overcome Car-Nk Cell Trogocytosis-Mediated Fratricide And Tumor Escape, Ye Nmn Li

Dissertations & Theses (Open Access)

Trogocytosis is an active process that transfers surface material from targeted to effector cells. Using multiple in vivo tumor models and clinical data, we report that chimeric antigen receptor (CAR) activation in natural killer (NK) cells promoted the transfer of the CAR-cognate-antigen from tumor to NK cells, resulting in (1) lower tumor antigen density, thus impairing the ability of CAR-NK cells to engage with their targets, (2) induced self-recognition and continuous CAR-mediated engagement, resulting in fratricide of trogocytic antigen expressing NK cells (NK^TROG+) and NK cell hyporesponsiveness. This phenomenon could be offset by a dual-CAR system incorporating both …

Immobilization And Its Effects On Functional Recovery After Spinal Cord Injury., William H. Gregory

College of Arts & Sciences Senior Honors Theses

Recovery, or rather the failure to recover, is a perplexing issue of spinal cord injury that is currently being investigated. This issue becomes more puzzling when investigating models in which spinal cord injury (SCI) is studied. There appears to be greater functional recovery experienced by animals within these models after injury as compared to patients in the clinical setting. While many things could contribute to this disparity, one difference that stands out when comparing the basic research model and clinical experience of SCI is the inactivity and limb disuse after the injury. This same level of immobility is rarely accounted …

Targeting Metabolic Alterations Associated With Smooth Muscle Α-Actin Pathogenic Variant Attenuates Moyamoya-Like Cerebrovascular Disease, Anita Kaw

Dissertations & Theses (Open Access)

Heterozygous pathogenic variants in ACTA2, encoding smooth muscle α-actin (α-SMA), predispose to thoracic aortic aneurysms and dissections. De novo missense variants disrupting ACTA2 arginine 179 (p.Arg179) cause a multisystemic disease termed smooth muscle dysfunction syndrome (SMDS), which is characterized by early onset thoracic aortic disease and moyamoya disease-like (MMD) cerebrovascular disease. The MMD-like cerebrovascular disease in SMDS patients is marked by bilateral steno-occlusive lesions in the distal internal carotid arteries (ICAs) and their branches. To study the molecular mechanisms that underlie the ACTA2 p.Arg179 variants, a smooth muscle-specific Cre-lox knock-in mouse model of the heterozygous Acta2 R179C variant, termed …

Modeling Antihypertensive Therapeutic Inertia And Intensification To Support Clinical Action Toward Hypertension Control, Benjamin Martin

All Dissertations

Background

Hypertension is the leading modifiable risk factor for cardiovascular disease and consequent mortality worldwide. In the U.S., more than half of hypertension cases remain uncontrolled, despite availability of effective pharmaceutical treatment options. Evidence suggests that therapeutic inertia, defined as clinician failure to initiate or increase therapy when treatment goals are unmet, is the most influential barrier to improving hypertension control. Substantial rates of therapeutic inertia have been reported in ambulatory primary care settings where hypertension is typically treated and managed. Understanding and overcoming the forces driving therapeutic inertia in hypertension management is a critical strategy to reach population health …

Application Of Informatics Tools To Facilitate The Practice Of Precision Medicine With Genomic Testing And Clinical Data, Michael Sayer

Pharmaceutical Sciences (PhD) Dissertations

The practice of precision medicine considers a variety of sources of information to optimize patient care. Factors such as patient demographics, clinical history, and lab test values have well understood effects on treatment outcomes and influence decision making. However, effective inclusion of biomolecular data such as protein expression and DNA sequencing data within the practice of precision medicine needs continued study. Informatics tools offer solutions to allow these complex data sources to be effectively embraced. Utilization of informatics tools to visualize data pertaining to the gene selection practices of pharmacogenomic (PGx) tests effectively communicated large amounts of information into concise …

Regenerative Medicine For Tendon/Ligament Injuries: De Novo Equine Tendon/Ligament Neotissue Generation And Application, Takashi Taguchi

LSU Doctoral Dissertations

Tendon and ligament injuries are debilitating conditions across species. Poor regenerative capacities of these tissues limit restoration of original functions. The first study evaluated the effect of cellular administration on tendon/ligament injuries in horses using meta-analysis. The cellular administration was effective in restoring ultrasonographic echogenicity and increasing vascularity during early phase of healing. Additionally, it improved microstructural organization of healed tissue in terms of cellularity and fiber alignment. However, the study did not support its use for increasing rate of return to performance, expression/deposition of tendon-specific genes/proteins, or mechanical properties.

The findings led to the second study that engineered implantable …

Mir125a As Molecular Target Of Vitamin D Mediated Inhibition Of Cd4+ T Cell Differentiation Into Th17 Cells In Mrl/Lpr Lupus-Prone Mice, Miranda Hilt

Undergraduate Distinction Papers

The dynamic function of vitamin D in an array of immunomodulatory and anti-inflammatory mechanisms and its implication in the pathogenesis of autoimmune diseases has been the topic of much recent scholarship. Here I attempt to elucidate the molecular mechanism of vitamin D-mediated inhibition of the differentiation of CD4+ T cells into pro-inflammatory Th17 cells in MRL/lpr lupus prone mice by investigating how miR-125a expression is affected by dietary modulation of cholecalciferol (vitamin D₃). MRL/MpJ and MRL/lpr mice were split into three experimental groups and fed specially formulated diets that varied in their concentrations of vitamin D. …

Leveraging Bio-Inspired Molecules For Cancer Theranostics, Douglas S. Macpherson

Dissertations, Theses, and Capstone Projects

A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Alzheimer’S Disease Genetics And Short-Chain Fatty Acid Treatment In Studies Of The Murine Gut Microbiome, Diana Zajac

Theses and Dissertations--Physiology

Elucidating the relationship of the gut microbiome in Alzheimer's Disease (AD) risk and pathogenesis is an area of intense interest. Since 60 to 80% of AD risk is related to genetics and APOE alleles represent the most impactful genetic risk factors for AD, their mechanism(s) of action are under intense scrutiny.

First, I conducted a study on APOE targeted replacement mice to investigate the impact of APOE alleles on the murine gut microbiome. The relative abundance of bacteria from the family Ruminococacceae and related genera increased with APOE2 status. The relative abundance of the class Erysipelotrichia increased with APOE4 status, …

Physical Activity Promotion, Assessment, And Engagement In Clinical Settings In The United States, Kristin A. Grogg

Graduate Theses, Dissertations, and Problem Reports

Physical inactivity is an important contributor to morbidity and all-cause mortality and the 2018 Physical Activity Guidelines Advisory Committee recommended that physicians increase their role in physical activity assessment and promotion to combat physical inactivity and related comorbidities. Healthcare providers are increasingly called upon to initiate physical activity promotion with their patients to manage conditions like obesity, diabetes, and cardiovascular diseases. Still, recent reports indicate that less than half of primary care visits include some type of physical activity promotion. Although the National Physical Activity Plan includes some recommendations for clinicians and the healthcare sector on physical activity promotion, it …

Role Of Histone Deacetylase (Hdac) In Epithelial To Mesenchymal Transition (Emt) In A Human Cholangiocyte Model Of Ischemic Cholangiopathy, Priyanshi Pragnesh Parikh

Theses and Dissertations

Organ transplants are a vital intervention for many diseases that result in end stage organ failure. Currently, the donation pool is not meeting the demands of the transplant list. Expanding this pool to include donation after cardiac death (DCD) is highly sought-after. However, the use of DCD livers can lead to increased odds of graft failure and ischemic cholangiopathy. The loss of epithelialization and fibrosis that occurs during ischemic cholangiopathy is characteristic of these cells undergoing epithelial-to-mesenchymal transition (EMT). The biological changes the cell experiences enhance migratory capacity, invasiveness, and increased resistance to apoptosis. Our earlier studies have shown differential …

Age-Associated Collagen Crosslinking And Its Role In Skeletal Muscle Regeneration, Lucas C. Olson

Theses and Dissertations

Advanced glycation end-products (AGEs) non-enzymatically accumulate on skeletal muscle collagen in old age via the Maillard reaction, causing an increase in intramuscular collagen and a stiffening of the muscle’s microenvironment. AGEs abrogate muscle regeneration through stiffening the muscle stem cell (MuSC) microenvironment and by binding to the receptor for advanced glycation end products (RAGE). Stiffer substrates promote MuSC proliferation at the expense of differentiation, and soluble AGEs are known to abrogate myogenic differentiation. Previously our group has demonstrated that decellularized muscle matrix (DMM), a type of extracellular matrix (ECM) scaffold extracted from skeletal muscle, encourages regeneration in a challenging rat …

Assessment Of The Interplay Between Regional Β-Amyloid Burden And White Matter Hyperintensities On Cognition And Default Mode Network In Clinically Normal Older Participants, Doaa G. Ali

Theses and Dissertations--Clinical and Translational Science

Objective: Alzheimer’s disease (AD) and subcortical vascular dementia are considered the most common pathologic contributors to dementia in the aging population. Both frequently coexist in over 80% of community dwelling adults with dementia. The neuropathological development of AD arguably begins with β-amyloid (Aβ) deposition in the brain. This series of studies aims to test the hypothesis that early focal regional amyloid deposition in the brain is associated with cognitive performance in specific cognitive domain scores in preclinical AD (pAD) (study1). Since mixed dementia is widely recognized as the norm rather than the exception, the second study aimed to explore the …

The Role Of Generative Adversarial Networks In Bioimage Analysis And Computational Diagnostics., Ahmed Naglah

Electronic Theses and Dissertations

Computational technologies can contribute to the modeling and simulation of the biological environments and activities towards achieving better interpretations, analysis, and understanding. With the emergence of digital pathology, we can observe an increasing demand for more innovative, effective, and efficient computational models. Under the umbrella of artificial intelligence, deep learning mimics the brain’s way in learn complex relationships through data and experiences. In the field of bioimage analysis, models usually comprise discriminative approaches such as classification and segmentation tasks. In this thesis, we study how we can use generative AI models to improve bioimage analysis tasks using Generative Adversarial Networks …

Contributions Of Asymmetry And Instability To Transfer And Retention Following Locomotor Adaptation, Daniel L. Gregory

Doctoral Dissertations

Gait asymmetry resulting from neurological injury is more costly and less stable than healthy gait. Split-belt treadmills, which drive limbs at different speeds, lead to spatial and temporal gait asymmetries, and perturb walking balance, have been used to study locomotor adaptability and learning related to asymmetry and stability. This knowledge may be leveraged to design more effective rehabilitation protocols. In experiment 1, we asked how constraining stride-rates away from preferred during split-belt walking influences learning revealed in a retention test. We found that constraints to stride rate during asymmetric walking uncovered the capacity to leverage redundant degrees-of-freedom for walking control, …

Emergency Care For Youth Who Experience Suicidality And Identify As Lesbian Gay Bisexual Transgender Queer/Questioning (Lgbtq+): An Interpretive Phenomenology, Theresa Schultz

Electronic Theses and Dissertations

Purpose: Suicide is a leading cause of death in children; youth who identify as LGBTQ+ are at an exponentially higher risk of suicide. The purpose of this study was to explore the lived experiences of young adults who identify as LGBTQ+ and sought emergency care for suicidality when they were adolescents.

Methods: Heideggerian hermeneutics phenomenology is the research method used in this study. Youth, ages 18-25 years, who identify as LGBTQ+ and sought emergency treatment for suicidality when they were adolescents (13-17 years) were recruited to participate;fifteen youth enrolled. Individuals ranged in age from 20 to 25 years. Participants described …