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2022

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Full-Text Articles in Medicine and Health Sciences

Monitoring Intraventricular Hemorrhage In Preterm Infants, Lilian Mn Kebaya Dec 2022

Monitoring Intraventricular Hemorrhage In Preterm Infants, Lilian Mn Kebaya

Electronic Thesis and Dissertation Repository

Germinal Matrix-Intraventricular hemorrhage (GMH-IVH) remains a significant cause of adverse neurodevelopmental outcomes in preterm infants. Current management options for GMH-IVH rely on serial 2-dimensional cranial ultrasound (2D cUS) ventricular measurements and clinical signs. A need exists for reliable biomarkers to aid in the early detection of posthemorrhagic ventricular dilatation (PHVD) and cerebral palsy (CP). We incorporated 3-dimensional cranial US (3D cUS) and functional infrared spectroscopy (fNIRS) to monitor ventricle volumes (VV) and spontaneous functional connectivity (sFC) in preterm infants with GMH-IVH. Infants with severe GMH-IVH who underwent cerebrospinal fluid diversion showed larger VV, which correlated with decreased sFC. Our findings …


Transcranial Direct Current Stimulation Of Frontal/Occipital Cortices Modulates Neural Correlates Of Cognition In Healthy Young Adults, Yasra Arif Dec 2022

Transcranial Direct Current Stimulation Of Frontal/Occipital Cortices Modulates Neural Correlates Of Cognition In Healthy Young Adults, Yasra Arif

Theses & Dissertations

An exponential rise in the use of transcranial direct current stimulation (tDCS) to modify the human brain and behavior has been observed over the last 20 years, with studies often yielding mixed outcomes. Such heterogeneity is partially attributed to the lack of a concise understanding of the underlying mechanisms. Though considered to exert modulatory effects by changing neuronal membrane polarization and synaptic efficacy, the interactive effects of offline tDCS and the neural underpinnings of cognition, both at the regional and network-level, are yet to be fully understood. Using High-Definition tDCS (HD-tDCS), Magnetoencephalography (MEG), a range of well-established cognitive paradigms, and …


Empowering Nurses To Recognize Post-Stroke Depression In The African American Community, Deidra Frisbie, Robin Simon Dec 2022

Empowering Nurses To Recognize Post-Stroke Depression In The African American Community, Deidra Frisbie, Robin Simon

Doctor of Nursing Practice Projects

African Americans (AA) have the highest prevalence of stroke and death compared to other racial groups in the United States. Post-stroke depression (PSD) affects approximately 1/3 of all stroke patients and is underdiagnosed in the African American community.

Aim: By using a mHealth mobile app and a Psychiatry provider list at discharge, PSD can be identified, and interventions initiated, thus decreasing the sequela of PSD in AA.

Methods: Nurses were provided education on PSD, expressions of depression in African-Americans, cultural humility, implicit bias, and the importance of the nurse's role in developing a therapeutic relationship.

Results: Quantitative analysis revealed the …


Secretion Of Salivary Proteins And Their Interactions, Karla Tonelli Bicalho Crosara Dec 2022

Secretion Of Salivary Proteins And Their Interactions, Karla Tonelli Bicalho Crosara

Electronic Thesis and Dissertation Repository

Saliva’s clinical application for disease diagnosis and monitoring is limited by incomplete knowledge of salivary protein interactions, the effect of stimulation on the salivary proteome, and if these factors impact protein identification. This thesis expands knowledge of the salivary interactome and effects of stimulation intensity and duration on parotid saliva’s proteome. First, previous in vitro studies identified 43 proteins in the histatin 1-protein network and demonstrated histatin 1’s increased stability in whole saliva when interacting with amylase. We hypothesized that protein-protein-interaction databases could enlarge the histatin 1-protein network. A comprehensive histatin 1-protein network was created using STRING database, merging previous …


The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland Dec 2022

The Effects Of Nmda Antagonism On Neuronal Activity And Neurovascular Coupling In Non-Human Primate Cortex, Benjamin Thomas Acland

Arts & Sciences Electronic Theses and Dissertations

The N-methyl-D-aspartate receptor (NMDAR) plays a variety of important roles in the development and function of primate central nervous systems. This thesis describes three nonhuman primate studies that, together, demonstrate that pharmacologically reducing NMDAR activity not only causes dramatic changes in neural activity in cortex, but also changes the relationship between that activity and a key signal often used as its proxy in human studies, the blood-oxygen-level-dependent (BOLD) signal. The first study reveals that NMDA antagonism is sufficient to induce powerful low-frequency modulation of spiking activity and extracellular local field potential (LFP) and discusses the implications of this finding for …


Contributions Of Specific Retinal Circuits And Their Respective Projections To Visual Behaviors, Jenna Mackenzie Krizan Dec 2022

Contributions Of Specific Retinal Circuits And Their Respective Projections To Visual Behaviors, Jenna Mackenzie Krizan

Arts & Sciences Electronic Theses and Dissertations

The survival of a species is inextricably linked to its ability to successfully navigate and interact with its surroundings, whether to seek safety from predators or gain sustenance from prey. Both functions are performed by mice, guided by vision, and rely on intricate processing in the retina and subcortical targets in the brain. This dissertation addresses how specific features of the visual environment and specific retinal ganglion cell circuits that sample a particular space in the visual environment are used to guide efficient predation in mice.Recent studies have begun to link the ability to detect, track, and ultimately capture prey …


Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones Dec 2022

Sik3 & Wnk Signals Through Fray To Regulate Glial K+ Buffering And Seizure Susceptibility In Drosophila Models Of Hyperexcitability, Lorenzo Laronn Lones

Arts & Sciences Electronic Theses and Dissertations

K+ homeostasis is important for maintaining healthy, physiological levels of neuronal activity. Glial cells play a central role in maintaining homeostatic ion gradients. In previous work from our lab, we unravel a glial K+ buffering program that is centered on a key kinase, salt-inducible kinase 3 (SIK3). SIK3-HDAC4 signaling in glial regulates the transcription of channels and transporters involved in water and ion transport. Defects in this pathway lead to peripheral nerve edema, neuronal hyperactivity, and seizure sensitivity. In an hyperexcitability mutant, eag Shaker, we show this pathway is downregulated and genetic activation suppresses seizure behavior. In this thesis, I …


The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan Dec 2022

The Bidirectional Relationship Between The Circadian Clock And Alzheimer’S Disease, Patrick Sheehan

Arts & Sciences Electronic Theses and Dissertations

The circadian clock and inflammation have a well-described bidirectional relationship in the peripheral immune system: the circadian clock regulates inflammatory responses, but inflammation also impacts oscillatory gene transcription controlled by the clock. The purpose of this thesis work is to understand if manipulation of the circadian clock can impact Alzheimer’s disease pathology, and if pathology itself can alter the circadian clock and its outputs. Here, I show that astrocyte-specific disruption of the circadian clock via deletion of the clock gene Bmal1 surprisingly decreased intra-neuronal protein pathologies. Further investigation found that deletion of the circadian clock resulted in a transcriptomic profile …


Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard Dec 2022

Extensive Behavioral Phenotyping Of Williams Syndrome Locus Relevant Mouse Models To Assess Contributions Of Oxytocin And Gtf2ird1, Kayla Rose Nygaard

Arts & Sciences Electronic Theses and Dissertations

The Williams Syndrome Critical Region (WSCR) at chromosome 7q11.23 provides a unique opportunity to untangle the relationship between genotype and phenotype in complex behaviors, from fear and anxiety to sociability and sensorimotor processing. Copy number variations (CNVs) in this region result in two syndromes, Williams Syndrome (WS) and Duplication 7q11.23 Syndrome (Dup7), which display phenotypes that may align, indicating a common disruption of a system, or diverge, reflecting an underlying gene dosage-dependent effect. While case studies of atypical deletions resulting in WS have implicated telomeric genes Gtf2ird1 and Gtf2i in the cognitive and behavioral profiles of WS, proving causation requires …


Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer Dec 2022

Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer

Arts & Sciences Electronic Theses and Dissertations

The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …


Simulated And Experimental Approaches To The Development Of Novel Test Phantoms For Radiofrequency Heating Of Implanted Medical Devices, Amgad M. Louka Dec 2022

Simulated And Experimental Approaches To The Development Of Novel Test Phantoms For Radiofrequency Heating Of Implanted Medical Devices, Amgad M. Louka

Electronic Thesis and Dissertation Repository

Magnetic resonance imaging (MRI) has cemented itself as the gold standard for imaging of soft tissues and is only increasing in popularity. Given the rising number of MRI scanners and medical device being implanted into patients, it is becoming increasingly likely that patients undergoing MRI will have an implanted medical device (IMD). The presence of an elongated metallic IMD inside a scanner could result in dangerous interactions with the radiofrequency fields during MRI, thus some of these IMDs preclude the patients from being scanned.

Orthopedic devices typically fall into this category due to their high potential for RF induced heating, …


Noninvasive Quantification Of Tissue Sodium Concentration In The Kidney Disease Spectrum Using 23na Magnetic Resonance Imaging, Fabio R. Salerno Dec 2022

Noninvasive Quantification Of Tissue Sodium Concentration In The Kidney Disease Spectrum Using 23na Magnetic Resonance Imaging, Fabio R. Salerno

Electronic Thesis and Dissertation Repository

Chronic kidney disease (CKD), especially when requiring kidney replacement therapy (hemodialysis (HD) and peritoneal dialysis (PD)), is associated with extracellular water expansion with increased total body sodium. Sodium can also be accumulated in tissues independently of extracellular water. Sodium-23 magnetic resonance imaging (23Na MRI) can quantify the concentration of sodium nuclei in tissues. Applied to the human leg, quantification of tissue sodium concentrations mainly at the skin and muscle level is possible. We hypothesized that increased tissue sodium concentrations exert toxic effects in CKD and dialysis. We aimed to (1) compare tissue sodium concentrations in adults, children and …


Autopsy V. Virtopsy: A New Approach For Postmortem Forensic Examination, Nicole Elaine Lawson Dec 2022

Autopsy V. Virtopsy: A New Approach For Postmortem Forensic Examination, Nicole Elaine Lawson

Honors Projects

Virtopsy as a potential new standard in forensic science investigation in the place of a conventional autopsy. In recent years there have been new advancements across the forensic field and in the scientific world as a whole. These advancements have changed many approaches bringing new capabilities and new challenges and pushback. This report takes a specific interest in the evolution of forensic autopsy. With improvements such as magnetic resonance imaging (MRI), computed tomography scan (CT), X-Rays, and other approaches a new term and technique have been coined Virtopsy. As this new potential approach has come to light the resistance against …


Data-Driven Neuroanatomical Subtypes In Various Stages Of Schizophrenia: Linking Cortical Thickness, Glutamate, And Language Functioning, Liangbing Liang Dec 2022

Data-Driven Neuroanatomical Subtypes In Various Stages Of Schizophrenia: Linking Cortical Thickness, Glutamate, And Language Functioning, Liangbing Liang

Electronic Thesis and Dissertation Repository

The considerable variation in the spatial distribution of cortical thickness changes has been used to parse heterogeneity in schizophrenia. We aimed to recover a ‘cortical impoverishment’ subgroup with widespread cortical thinning. We applied hierarchical cluster analysis to cortical thickness data of three datasets in different stages of psychosis and studied the cognitive, functional, neurochemical, language and symptom profiles of the observed subgroups. Our consensus-based clustering procedure consistently produced a subgroup characterized by significantly lower cortical thickness. This ‘cortical impoverishment’ subgroup was associated with a higher symptom burden in a clinically stable sample and higher glutamate levels with language impairments in …


Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita Dec 2022

Computer-Aided Drug Discovery For Helicobacter Pylori, Nicole Ann Vita

Theses and Dissertations (ETD)

Helicobacter pylori is a high-priority drug-resistant pathogen and is currently the only bacteria considered to be a class I carcinogen and there is a critical need to identify novel chemical matter to treat H. pylori infections. Hp is responsible for greater than 60% of gastric cancer related deaths and 89% of all gastric cancer morbidities. In a previous study, our lab identified novel Hp thienopyrmidine inhibitors that target respiratory complex I, an essential enzyme in respiration. Respiratory complex I is a large asymmetric multidomain and membrane bound enzyme and due to these innate features, it is not practical for biophysical …


Quantifying The Magnitude Of Total Dose Deviation Caused By Various Sources Of Error Among Iroc Phantom Irradiation Results, Sharbacha S. Edward Dec 2022

Quantifying The Magnitude Of Total Dose Deviation Caused By Various Sources Of Error Among Iroc Phantom Irradiation Results, Sharbacha S. Edward

Dissertations & Theses (Open Access)

The Imaging and Radiation Oncology Core (IROC) phantoms are used as an end-to-end test of an institution’s radiotherapy processes, and for clinical trial credentialing. Phantoms are treated like patients, and evaluation of the doses received by the thermoluminescent dosimeters (TLDs) inside the phantom, reflects the accuracy with which an institution can image, plan and irradiate a phantom or patient. Recent phantom results show that among the hundreds of various IROC phantoms irradiated annually, 8-17% of institutions fail this test. The purpose of this work was to investigate the various types of errors that may occur during the treatment process and …


Patient Care Management Of Hypertension Through Improving Follow-Up And Reducing Missed Appointments In A Primary Care Clinic: A Qi Project, Victoria Idubor Dec 2022

Patient Care Management Of Hypertension Through Improving Follow-Up And Reducing Missed Appointments In A Primary Care Clinic: A Qi Project, Victoria Idubor

Doctor of Nursing Practice

Background. Missed follow-up appointments constitute significant problems clinics and health centers face nationwide. A significant portion of primary care providers’ patients will require follow-up appointments to manage their chronic illnesses. About 20 to 40% of patients seen at this clinic have a history of hypertension. Uncontrolled hypertension has been shown to increase the risk of certain cardiovascular disease events and mortality. Follow-up appointments are crucial for patients with hypertension to monitor for more life-threatening signs and manage their overall care. Purpose. The purpose of this project is to improve the timely management of care for patients with hypertension …


The Association Of Lower Medication Adherence And Increased Medical Spending, Ryan A. Fuchs Dec 2022

The Association Of Lower Medication Adherence And Increased Medical Spending, Ryan A. Fuchs

Capstone Experience

Medical prescribing is a common occurrence in daily clinical practice. According to the Centers for Disease Control and Prevention, in 2015-2016 45.8% of the U.S. population used prescription drugs in the past 30 days. (CDC, 2019) Although drug therapy can be effective in treating disease, full benefits are often not realized because many patients do not take their medications as prescribed. There is quite a bit of research out there about non-adherence to medication. Some studies focus on the financial impacts of non-adherence, but most of the studies examine the reasons for medication non-adherence. A gap exists in research about …


Methods Development In Inflammatory Bowel Disease, Andrew B. Steimke Dec 2022

Methods Development In Inflammatory Bowel Disease, Andrew B. Steimke

Theses and Dissertations (ETD)

Inflammatory bowel disease (IBD) is a disease that is classified into two subtypes: ulcerative colitis (UC) and Crohn’s disease (CD). Symptoms can range from mild discomfort to requiring surgical intervention and affects approximately 1-in-200 adults in America alone, with global incidence rates increasing. While many treatments exist for IBD, perhaps the main reason for the lack of a cure is that there are many different pathogeneses that all lead to a very similar expression of symptoms. Over 240 IBD loci have been identified to date, yet the causative allele that drives the association has only been identified in ~60 of …


The Impact Of Alzheimer Disease On Semantic Knowledge, Maileen G. Ulep Dec 2022

The Impact Of Alzheimer Disease On Semantic Knowledge, Maileen G. Ulep

UNLV Theses, Dissertations, Professional Papers, and Capstones

The research furthers the understanding of the impact of Alzheimer disease (AD) on cognition and the organization of semantic knowledge in the brain, which might contribute to the development of diagnostic and staging tools, and interventions to palliate cognitive deficits. The disruption of semantic knowledge in AD is well documented in the literature. Much of the existing research focuses on the general impact AD has on semantic knowledge. This study explores the impact of AD on specific domains of knowledge, chiefly, living kinds and artifacts, critical to ordinary functioning. The content, organization and structure of the investigated domains of knowledge …


Development Of A Low-Dose Radiation Therapy Device For Acute Respritory Distress Syndrome, Thomas Heath Davis Dec 2022

Development Of A Low-Dose Radiation Therapy Device For Acute Respritory Distress Syndrome, Thomas Heath Davis

Masters Theses

This research focuses on the development of a low dose radiotherapy (LD-RT) device for treatment of acute respiratory distress syndrome (ARDS), a respiratory illness that affects millions of people a year. The use of orthovoltage (200 – 500 keV) X-ray energy provides many advantages over traditional radiotherapy delivery with linear accelerators, such as low cost and greater accessibility. In addition, X-ray tubes have been shown throughout history to provide good treatment outcomes for pneumonia, and research has shown LD-RT to be just as effective with ARDS. This proposal summarizes my efforts in determining the dosimetric properties of a LD-RT system …


A Cloning-Free Recyclable System For Crispr-Cas9 Mediated Mutant And Reversion Construction In Candida Albicans Clinical Isolates, Amanda K. Vogel Dec 2022

A Cloning-Free Recyclable System For Crispr-Cas9 Mediated Mutant And Reversion Construction In Candida Albicans Clinical Isolates, Amanda K. Vogel

Theses and Dissertations (ETD)

Candida albicans is a ubiquitous opportunistic fungal pathogen and one of the most prevalent causes of fungal diseases worldwide. The reference isolate SC5314 is one of the most widely used strains for both experimental and genetic studies, but it is becoming increasingly evident that genetic diversity in clinical isolates plays an important role in antifungal resistance, virulence, and pathogenicity. These recent discoveries highlight the need for genetic tools that are capable of investigating genes in multiple strain backgrounds. Here we build on the SAT1-flipper method and combine it with CRISPR-Cas9 technology to achieve cloning-free homozygous deletion in a single transformation …


Examining The Effects Of Npra Antagonist Anantin On Sci-Induced Ployuria., Lindsey Zipperer Dec 2022

Examining The Effects Of Npra Antagonist Anantin On Sci-Induced Ployuria., Lindsey Zipperer

Electronic Theses and Dissertations

Polyuria, or the over production of urine, is a prevalent condition that significantly impacts the quality of life in individuals suffering from a spinal cord injury (SCI). Post-SCI induced polyuria is thought to have been associated with altered levels of vasopressin (AVP), atrial natriuretic peptide (ANP), and natriuretic peptide receptor A (NPRA). In the present study, the function of NPRA was analyzed in the rat contusion model using anantin, an NPRA antagonist. A daily dose of either 100 µg of anantin or vehicle was administered intraperitoneally immediately following the SCI surgery and continued until termination, 4 weeks post injury (wpi). …


Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury Dec 2022

Bayesian Methods For Graphical Models With Neighborhood Selection., Sagnik Bhadury

Electronic Theses and Dissertations

Graphical models determine associations between variables through the notion of conditional independence. Gaussian graphical models are a widely used class of such models, where the relationships are formalized by non-null entries of the precision matrix. However, in high-dimensional cases, covariance estimates are typically unstable. Moreover, it is natural to expect only a few significant associations to be present in many realistic applications. This necessitates the injection of sparsity techniques into the estimation method. Classical frequentist methods, like GLASSO, use penalization techniques for this purpose. Fully Bayesian methods, on the contrary, are slow because they require iteratively sampling over a quadratic …


Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum Dec 2022

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …


Identifying And Minimizing Underspecification In Breast Cancer Subtyping, Jonathan Cheuk-Kiu Tang Dec 2022

Identifying And Minimizing Underspecification In Breast Cancer Subtyping, Jonathan Cheuk-Kiu Tang

Master's Theses

In the realm of biomedical technology, both accuracy and consistency are crucial to the development and deployment of these tools. While accuracy is easy to measure, consistency metrics are not so simple to measure, especially in the scope of biomedicine where prediction consistency can be difficult to achieve. Typically, biomedical datasets contain a significantly larger amount of features compared to the amount of samples, which goes against ordinary data mining practices. As a result, predictive models may fail to find valid pathways for prediction during training on such datasets. This concept is known as underspecification.

Underspecification has been more accepted …


Markers Of Neuroinflammatory And Degenerative Processes In Professional Athletes With Traumatic Encephalopathy Syndrome, Brooke Conway Kleven Dec 2022

Markers Of Neuroinflammatory And Degenerative Processes In Professional Athletes With Traumatic Encephalopathy Syndrome, Brooke Conway Kleven

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: The clinical criteria for Traumatic encephalopathy syndrome (ccTES) were developed to improve the diagnosis of Chronic traumatic encephalopathy (CTE). This study aimed to determine whether there was an association between a clinical diagnosis of Traumatic encephalopathy syndrome (TES) and changes in serum biomarkers, balance, neuroimaging, and cognition among athletes in the Professional Athletes Brain Health Study (PABHS).Methods: Of the cohort, 130 professional fighters met age or retirement criteria and went to a consensus conference, with 52 fighters (40%) meeting the criteria for TES. A generalized linear model with generalized estimating equations was utilized to assess the odds of disease …


Dimensionality Of Natural Auditory Scene Perception: A Factor Analysis Study, Margaret A. Mcmullin Dec 2022

Dimensionality Of Natural Auditory Scene Perception: A Factor Analysis Study, Margaret A. Mcmullin

UNLV Theses, Dissertations, Professional Papers, and Capstones

Theories of auditory and visual scene analysis suggest the perception of scenes relies on the identification and segregation of objects within it, resembling a detail-oriented processing style, but it is possible that a global-oriented process also occurs while evaluating auditory scenes. There is evidence for global properties that enable rapid recognition of visual scenes, even without recognizing the individual objects comprising the scene. It is our understanding that a similar line of research has not been explored in the auditory domain; therefore, we evaluated the contributions of high-level global and low-level acoustic information to auditory scene perception. A secondary aim …


T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones Dec 2022

T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones

Biomedical Sciences Theses & Dissertations

Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …


Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema Dec 2022

Risk-Factor Induced Changes In The Breast Microenvironment Facilitate Inflammatory Breast Cancer Progression And Lymphovascular Invasion, Wintana Balema, Wintana Balema

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) is a rapidly progressing, rare and highly lethal form of breast cancer. IBC is a clinical diagnosis, requiring >1/3 involvement on the affected breast and/or skin by erythema, and disease onset of < 6 months. The clinical symptoms of IBC vary in severity and presentation, these include redness, warmth, skin thickening and bruised or pink/purple discoloration appearance and skin changes such as peau d’orange. These skin symptoms are not attributed to inflammation, rather IBC is characterized by florid lymphovascular tumor emboli clogging dermal lymphatics. This leads to “classic” symptoms of breast swelling and skin edema or discoloration. To date, unique genomic drivers which differentiate IBC from non-IBC invasive breast cancers have not been identified highlighting a role for the microenvironment. Several epidemiological studies have unveiled subtype-specific risk factors associated with IBC that are known to alter the microenvironment. Obesity is an established risk factor for all subtypes of IBC. Never-breastfeeding increases risk for developing the most aggressive, triple-negative IBC. Further, never breastfeeding is associated with later clinical stage and worse outcomes. We worked to model these overlapping risk factors to understand microenvironment changes that may lead to the lymphatic change’s indicative of IBC.

First, we investigated the association of a “classic” triad of clinical IBC signs with overall survival among patients to demonstrate the most overt clinical findings of lymphatic involvement were impacting prognosis. We evaluated a triad of IBC signs, including swollen involved breast, nipple change, and diffuse skin change, using breast medical photographs from patients enrolled on a prospective IBC registry. We reported that the …