Medicine and Health Sciences Commons^™

The Quantified Elf, Umico Niwa

Theses and Dissertations

The Quantified Elf is an ongoing collection of scientific, medical, archaeological articles and excerpts from my personal journal. It is a way by which I explore the various ways Western notions of personhood subsume human life into constructs of sexuality and gender, overlooking the various other modes of unbridled existence: plant, microbial. fungal, animal, celestial bodies. The speculative medical papers propose novel forms of body modification to combat gender dysphoria.

The Impact Of Aging And Mechanical Injury On Alveolar Epithelial And Macrophage Responses In Acute Lung Injury And Inflammation, Michael S. Valentine

Theses and Dissertations

Patients with severe lung pathologies, such as Acute Respiratory Distress Syndrome (ARDS), often require mechanical ventilation as a clinical intervention; however, this procedure frequently exacerbates the original pulmonary issue and produces an exaggerated inflammatory response that potentially leads to sepsis, multisystem organ failure, and mortality. This acute lung injury (ALI) condition has been termed Ventilator-Induced Lung Injury (VILI). Alveolar overdistension, cyclic atelectasis, and biotrauma are the primary injury mechanisms in VILI that lead to the loss of alveolar barrier integrity and pulmonary inflammation. Stress and strains during mechanical ventilation are believed to initiate alveolar epithelial mechanotransduction signaling mechanisms that contribute …

Epigenetic Regulation Of Drug Metabolizing Enzymes In Normal Aging, Mohamad M. Kronfol

Theses and Dissertations

Geriatric populations are at a higher risk for adverse drug reactions (ADRs). This may be partly due to changes in drug metabolism in old age, but the underlying mechanisms are poorly understood. Prior research in humans and mice has shown age-associated changes to the expression of several genes involved in drug metabolism. Furthermore, studies of human blood showed that epigenetic regulation of genes encoding drug metabolizing enzymes change with age. However, it is unknown if genes in the liver are similarly affected. Therefore, we hypothesize that genes encoding drug metabolizing enzymes may show differential epigenetic regulation in the liver with …

3-D Homology Modeling Of Organic Anion Transporters (Oats): Defining The Biochemical Basis For Oat-Substrate Interactions, Christopher Jay

Theses and Dissertations

A goal in the drug development process, as indicated by the FDA, is to evaluate a drug’s ADME profile, as potential drug interactions could exist, leading to adverse drug reactions or loss of efficacy. Transport proteins, specifically organic anion transporters (OATs) are involved in the absorption, distribution, and elimination of small, negatively charged compounds. Although there is an exhaustive list of structurally diverse organic anions which interact with OATs, interactions at a molecular level are still shrouded in mystery particularly due to the lack of a solved crystal structure. Therefore, in silico homology models (hOAT1, 2, 3) were generated using …

Signaling Mechanism Responsible For 5-Ht2a Receptor Tolerance To Psychedelic Induced Head-Twitch Behavior In Mice, Audrey R. Mcmurtrie

Theses and Dissertations

In recent years, there has been a growing interest in psychedelic compounds stemming from their promising use as therapeutic agents and research tools that can be used to treat and study several neuropsychiatric disorders. Psychedelics have proven useful in a broad range of these diseases - they serve as models for psychosis in schizophrenia but have also had promising results in treating major depressive disorder, anxiety, and other common disorders. Decreased stigmatization surrounding psychedelics has further increased their use in research and clinical settings. In light of these trends and the promising nature of their use, a thorough understanding of …

Effects Of Gestational Ozone Exposure On Privileged Placental And Brain Barrier Integrity, Alexander I. Hamm

Theses and Dissertations

Ambient outdoor ozone, a common of component of photochemical smog and urban air pollution, is linked to various neurological and vascular pathologies. Its immediate reaction with lung surfactant after inhalation results in complete reactivity of the gas, with no active ozone passing into circulation. This indicates the presence of secondary and tertiary mediators in ozone-related systemic pathologies after pulmonary insult. In vasculature, ozone exposure is associated with an acute hypertensive phenotype apparent at least 24 hours after dose, such as experienced on a hot summer afternoon in a large metropolitan area like Los Angeles or Mexico City. However, the effects …

An Identification Of Tgf-B'S Role In Ischemic Cholangiopathy, Courtney Chmielewski

Theses and Dissertations

Organ transplants are a necessary intervention for many diseases that result in end stage organ failure. The donation pool cannot match the demands of the transplant list, so expanding the pool to include donation after cardiac death (DCD) is desired. However, there are increased odds of graft failure and ischemic cholangiopathy leading to inferior outcomes when DCD livers are used. Ischemic cholangiopathy consists of multiple diffuse strictures and fibrosis of the bile ducts leading to a loss of epithelialization and fibrosis. The cellular mechanism is proposed to be epithelial-to-mesenchymal transition (EMT). TGF-�� is seen as a key initiator of EMT, …

Modeling Gardnerella Host-Pathogen Interaction: Characterization Of Vaginolysin And The Opacity Phenotype, Erin M. Garcia

Theses and Dissertations

Bacterial vaginosis (BV) describes a dysbiotic state of the vaginal mucosa, during which the dominance by beneficial lactobacilli species is lost, the vaginal pH increases, and the flora comprising the vaginal microbiome becomes more diverse. Bacterial taxa associated with this dysbiotic state interact to form a dense polymicrobial biofilm on the surface of the vaginal epithelium. This shift in the vaginal microflora is clinically important, even when symptoms are not noted, as women with BV are at increased risk for acquisition of other sexually transmitted infections, including HIV, and are more than two times as likely to experience preterm birth. …

New Persistent And Chronic Opioid Use In Cancer Survivors After Curative Intent Radiation, Elena V. Fernández

Theses and Dissertations

Background: Emerging evidence suggests that as more patients are surviving cancer, new persistent opioid use (no prior exposure to opioids before cancer therapy but requiring opioid prescriptions after curative intent treatment; NPOU) is of greater concern. In patients receiving curative intent radiation (definitive radiation therapy and as treatment for cure; CIR), the extent to which patients develop NPOU or continue opioid use (COU) following CIR is not known. Neither are factors associated with NPOU or COU, opioid doses, or time to discontinuation (TTD) of opioids in 5CS known. Objectives: Describe longitudinal trends opioid use in cancer survivors who received CIR, …

Estimating Response Status In Sequential Multiple Assignment (Smar)-Like Trials, Keighly Bradbrook

Theses and Dissertations

Sequential, multiple assignment, randomized trials (SMARTs) allow investigators to develop and compare experimental treatment regimens in which individuals are successively randomized to different treatments based on some set of predetermined rules. The rules used to make decisions on when and how to switch treatments are based on a chosen set of tailoring variables. Although not always true, intermediate response is commonly used as the primary tailoring variable as it is often predictive of future treatment success. As such, successful implementation depends on identifying patients who respond to treatment, though in some situations such mechanisms may not exist. Further, patient-level covariates …

Data Science Methods For Standardization, Safety, And Quality Assurance In Radiation Oncology, Khajamoinuddin Syed

Theses and Dissertations

Radiation oncology is the field of medicine that deals with treating cancer patients through ionizing radiation. The clinical modality or technique used to treat the cancer patients in the radiation oncology domain is referred to as radiation therapy. Radiation therapy aims to deliver precisely measured dose irradiation to a defined tumor volume (target) with as minimal damage as possible to surrounding healthy tissue (organs-at-risk), resulting in eradication of the tumor, high quality of life, and prolongation of survival. A typical radiotherapy process requires the use of different clinical systems at various stages of the workflow. The data generated in these …

Model-Based In-Vitro Pk/Pd Profiling Of Novel Synthetic Allosteric Effectors Of Hemoglobin (Aeh) As Potential Sickle Cell Disease (Scd) Therapeutics, Xiaomeng Xu

Theses and Dissertations

Introduction: Allosteric effectors of hemoglobin (AEH) represent a class of synthetic aromatic aldehydes that transiently form covalent interactions (Schiff-base) with hemoglobin (Hb) to form Hb-AEH adduct, preventing the HbS polymerization and sickling of red blood cells (RBC). The overall objective of this research was to aid in the optimization of novel AEH by understanding their target-site disposition of AEH in relevant biological matrices, e.g., HbA solution, whole blood (WB) and human liver cytosol (HLC), a surrogate of aldehyde dehydrogenase (ALDH)-mediated oxidative metabolism.

Methods: A “universal” HPLC-UV/Vis assay method was developed for the quantitation of HbA-AEH adduct for chemically …

Recovery From Visual Dysfunction Following Mild Traumatic Brain Injury Is Associated With Adaptive Reorganization Of Retinal Inputs To Lateral Geniculate Nucleus In The Mouse Model Utilizing Central Fluid Percussion Injury., Vishal C. Patel

Theses and Dissertations

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality nationwide. Prevalence of mild TBI (mTBI) vastly outnumbers more severe forms however the associated morbidity has only recently gained public attention. Visual dysfunction is a significant component of mTBI associated morbidity with recovery of function linked with improvement in global outcomes. Examination of sensory and motor pathways in other brain injury paradigms support that recovery is largely dependent on adaptive plasticity of remaining connections. Current examinations of visual function recovery following mTBI is limited to identifying evidence for recovery and objective evidence for adaptive plasticity is limited. Therefore, …

Integration Of Multi-Omic Platforms To Understand The Regulation Of Genes In Human Disease, Eva Lancaster

Theses and Dissertations

Epigenetic mechanisms have been hypothesized to modify gene expression (GE) in response to both genetic variation and environmental exposures, ultimately contributing to the development of complex traits. Epigenome-wide association studies (EWAS) aim to test the theory that marks of DNA methylation (DNAm) have downstream consequences that result in the development of complex diseases. Although these methods have been successful in identifying DNAm patterns in complex traits, specific molecular mechanisms involved in the etiology of complex diseases remain unidentified. This knowledge gap does not originate from a lack of DNAm-trait associations, but rather stems from study design issues that affect the …

The Impact Of The Fda Warning On Post-Tonsillectomy Opioid Prescribing In Publicly And Privately Insured Children, Dianna J. Soelberg

Theses and Dissertations

Due to reports of significant adverse events, the U.S. FDA placed a Boxed Warning on the opioid codeine in February 2013 – contraindicating its use in pediatric patients undergoing tonsillectomy and/or adenoidectomy. Studies conducted in privately insured children showed a reduction in codeine prescribing and a slight increase in alterative opioid prescribing following the FDA warning, yet the extent to which the FDA warning impacted prescribing in publicly insured children is unknown. Using a quasi-experimental interrupted time series design, this study evaluated codeine and alternative opioid prescribing before and after the FDA warning in both publicly and privately insured children …

The Impact Of Occupational Therapy Acute Care Services On Readmission Rates For Patients In Medicare’S Hospital Readmission Reduction Program, Jessica M. Edelstein

Theses and Dissertations

The United States (US) health care system is faced with the daunting challenge to make healthcare payments commensurate with quality of care provided. To assess quality, metrics for reimbursement have been established by Medicare. One such quality metric is hospital readmissions (readmissions). Readmissions are associated with poor patient outcomes and costly. Associated poor patient outcomes include higher risk for mortality, deconditioning, nutritional issues and cognitive impairments. As a result, readmissions cost Medicare $26 billion annually. Current strategies for reducing readmissions in the US are fragmented and hospital-specific. While specific strategies may vary, hospitals that have low readmissions rates tend to …

The Effect Of The Senolytic Abt-263 On Androgen Deprivation-Induced Senescent Prostate Tumor Cells, So Min Lee

Theses and Dissertations

Prostate cancer (PCa) is one of the leading causes of cancer-related deaths in men. Although standard treatments such as androgen deprivation therapies (ADT) and antiandrogens have increased survival for many patients, most men placed on these therapies will develop castration-resistant disease (CRPC). Previous studies have shown that these treatments have limited cytotoxicity and instead promote cell growth arrest. Our current work demonstrates that prostate tumor cells grown in the absence of androgens by using charcoal-stripped serum undergo senescence-mediated or senescent-like growth arrest, based on the cellular expression of senescence-associated-beta-galactosidase (SA-β-Gal). Our studies further suggest that this senescence is transient and …

Black Women And Body Image: Implications Of The Racialized Beauty Aesthetic, Rachel L. Boutte

Theses and Dissertations

Black women have the highest prevalence of overweight and obesity relative to any other demographic group in the United States, however current weight management interventions appear least effective for them. Although several hypotheses have been proposed to explain these outcomes, few studies have collected data to evaluate how well they fit the lived experiences of Black women. In particular, the potential roles of body image and body dissatisfaction in the development and maintenance of overweight and obesity in Black women are not well understood. Extant literature largely reports that Black women are inoculated from body dissatisfaction due to cultural factors, …

Exosomes As Systemic Mediators Of Nanotube Induced Neurotoxicity, Christopher G. Canal

Theses and Dissertations

Extra-pulmonary effects of nanoparticle inhalation have been well documented; however, mechanisms for conveying peripheral bioactivity remain elusive. Recent studies point to indirect molecular mediators shed into the circulation. Protein and lipid alternatives to cytokines or chemokines have been proposed, yet the diversity among responses suggests a broader assemblage of factors. Recently we have proposed proteolytic fragment peptides as an additional source of bioactivity, which interestingly were significantly associated with exosomal proteins after enrichment analysis. Here we tested whether modeled exposure to multi-walled carbon nanotubes (MWCNT) could alter the composition and bioactivity of circulating exosomes. Male C57BL/6 mice were exposed by …

Investigation Of Molecular Mechanisms Of Liver Preservation Injury: A Complication Preceding Organ Transplantation, Ria C. Fyffe-Freil

Theses and Dissertations

Of the over 108,000 American awaiting a life-saving organ transplant today, over 12,000 (11%) of those need a new liver (OPTN, 2020). Last year, only 35% of patients on the waiting list for an organ were transplanted. Improving the quality of marginal organs by preventing or reversing preservation injury could vastly increase the number of transplants performed. Washout of circulating blood during liver procurement with cold University of Wisconsin solution flushes out any endogenous pro-survival signaling molecules. We investigated lysophospholipid (LPL) surface receptors (G-protein coupled receptors for lysophosphatidic acid (LPA) and sphingosine- 1-phosphate (S1P)) and their role in protecting hepatocytes …

Development And Validation Of Predictive Risk And Multiple Criteria Decision Analysis Models To Evaluate Cardiovascular Outcomes Among Cancer Patients, Purva N. Parab

Theses and Dissertations

Objective: The objectives of our study were to characterize the study population with cancer and cardiovascular diseases (CVD) both as compared to those without and to build a predictive model using machine learning (ML) algorithms that can predict the risk of CVD in cancer patients. In addition, our objective was also to evaluate characteristics associated with cardiotoxic adverse events of breast cancer therapies and develop a multiple criteria decision analysis (MCDA) model to conduct benefit-risk assessment of breast cancer therapy regimens. Methods: We used Medical Expenditure Panel Survey (MEPS) and FDA Adverse Events Reporting System (FAERS) 2005-2015 files along with …

Differential Identification Of Hyperacusis And Misophonia: Implications Of Discrete Decreased Sound Tolerance (Dst) Condition Subtypes, Rachel E. Wallace

Theses and Dissertations

Hyperacusis and misophonia are two conditions of decreased sound tolerance (DST) studied in the psychological literature due to their association with psychological symptoms and mechanisms. DSTs are differentiated from normal sound sensitivity due to the reported impairment and distress individuals experience. Researchers suggest that DSTs are differentiated by types of sounds and emotional reactions elicited, such that hyperacusis is a fear and pain response to ordinary environmental sounds perceived as uncomfortably loud, and misophonia is an anger and disgust response to human-made sounds, but these distinctions, and associated characteristics, have not been empirically demonstrated. Undergraduate students (N = 1572) …

Development Of A Screening Assay For Type Iii Secretion System Inhibitors And High Throughput Screening Campaign Of Inhibitors Of Prp Of Staphylococcus Aureus, Heather A. Pendergrass

Theses and Dissertations

Antibiotics inhibit the growth or survival of bacteria by targeting their essential functions.¹ Due to weaknesses in traditional antibiotics and the increasing prevalence of antibiotic resistance genes, virulence factors are being targeted for therapeutic treatment of bacterial infection.² We have developed an assay to quantify and observe type III secretion system (T3SS) activity. The type III secretion system (T3SS) is a virulence factor present in some Gram-negative pathogens including enteropathogenic and enterohemorrhagic E. coli (EPEC and EHEC, respectively),³ and others.^4–9 The T3SS between EPEC and EHEC are highly conserved and share over 90% sequence identity with …

Covid-19 Sampling From The Middle Ear And Mastoid: A Case Report, George B Wanna, Zachary G Schwam, Vivian F Kaul, Maura K Cosetti, Enrique Perez, Peter Filip, Waleed Javaid, Avi Kandel, Alberto Paniz-Mondolfi, Satish Govindaraj, Eric M Genden

Faculty, Staff and Student Publications

No abstract provided.

Kinematic And Coordination Variability In Runners With And Without Patellofemoral Pain, Jessica Mutchler, Klarie Macias, Barry Munkasy, Samuel J. Wilson, John C. Garner Iii, Li Li

Health Sciences & Kinesiology: Faculty Publications

Background: Patellofemoral pain (PFP) is a common overuse injury that has been suggested to cause abnormal gait kinematics and variability in runners with PFP. Conflicting results have been presented as to the variability of joint kinematics and joint coordination. Objective: The purpose of this study was to examine the variability of lower extremity kinematics and joint coordination in the presence of PFP and exertion. Methods: Six female runners with PFP and matched controls (CON) ran at a self-selected pace on an instrumented treadmill until exertion or pain criteria was met. Sixteen anatomical retroreflective markers and seven tracking clusters were placed …

Microbiotyping The Sinonasal Microbiome, Ahmed Bassiouni, Sathish Paramasivan, Arron Shiffer, Matthew R Dillon, Emily K Cope, Clare Cooksley, Mahnaz Ramezanpour, Sophia Moraitis, Mohammad Javed Ali, Benjamin S Bleier, Claudio Callejas, Marjolein E Cornet, Richard G Douglas, Daniel Dutra, Christos Georgalas, Richard J Harvey, Peter H Hwang, Amber U Luong, Rodney J Schlosser, Pongsakorn Tantilipikorn, Marc A Tewfik, Sarah Vreugde, Peter-John Wormald, J Gregory Caporaso, Alkis J Psaltis

Faculty, Staff and Student Publications

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based …

Educational Case: Systemic Mastocytosis With An Associated Hematological Neoplasm, Brenda Mai, Md A Wahed, Lei Chen, Nghia D Nguyen, Xiaohong Iris Wang, Zhihong Hu

Faculty, Staff and Student Publications

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1

Operability, Acceptability, And Usefulness Of A Mobile App To Track Routine Immunization Performance In Rural Pakistan: Interview Study Among Vaccinators And Key Informants, Shehla Zaidi, Saqib Ali Shaikh, Saleem Sayani, Abdul Momin Kazi, Adeel Khoja, Syed Shahzad Hussain, Rabia Najmi

Community Health Sciences

Background: There has been a recent spate of mobile health (mHealth) app use for immunizations and other public health concerns in low- and middle-income countries. However, recent evidence has largely focused on app development or before-and-after effects on awareness or service coverage. There is little evidence on the factors that facilitate adoption of mHealth programs, which is critical to effectively embed digital technology into mainstream health systems.

Objective: This study aimed to provide the qualitative experiences of frontline health staff and district managers while engaging with real-time digital technology to improve the coverage of routine childhood immunization in an underserved …

Non-Thrust Cervical Manipulations Reduce Short-Term Pain And Decrease Systolic Blood Pressure During Intervention In Mechanical Neck Pain: A Randomized Clinical Trial, Emmanuel Yung, Cheongeun Oh, Michael Wong, Jason K. Grimes, Erica M. Barton, Muhammad I. Ali, Allison Breakey

Physical Therapy Faculty Publications

Objectives: To evaluate the association of resting blood pressure with pain response and evaluate the cardiovascular effects of anterior-to-posterior [AP] versus lateral [LAT] techniques of cervical spine non-thrust manipulation [NTM].

Methods: Forty-three (23 females) participants with non-chronic neck pain (mean age 29.00 ± SD 9.09 years) randomly received AP or LAT NTM to the cervical spine. Blood pressure and heart rate were measured before, during, and after the intervention. Disability and pain were measured pre- and post-intervention.

Results: Resting systolic blood pressure (SBP) was significantly associated with average pain reduction two days later on univariate and multivariate analyses (coefficients −0.029 …

Sustained Acoustic Medicine Combined With A Diclofenac Ultrasound Coupling Patch For The Rapid Symptomatic Relief Of Knee Osteoarthritis: Multi-Site Clinical Efficacy Study, Alex Madzia, Chirag Agrawal, Paddy Jarit, Stephanie Petterson, Kevin Plancher, Ralph Ortiz

Physical Therapy Faculty Publications

Background:

Sustained Acoustic Medicine (SAM) is an emerging, non-invasive, non-narcotic, home-use ultrasound therapy for the daily treatment of joint pain. The aim of this multi-site clinical study was to examine the efficacy of long-duration continuous ultrasound combined with a 1% diclofenac ultrasound gel patch in treating pain and improving function in patients with knee osteoarthritis.

Methods:

The Consolidated Standards of Reporting Trials (CONSORT) were followed. Thirty-two (32) patients (18-males, 14-females) 54 years of average age with moderate to severe knee pain and radiographically confirmed knee osteoarthritis (Kellgren-Lawrence (KL) grade II/III) were enrolled for treatment with the SAM device and diclofenac …