Medicine and Health Sciences Commons^™

Accounting For The Uncertainty Due To Chemicals Below The Detection Limit In Mixture Analysis, Paul M. Hargarten

Theses and Dissertations

Humans are exposed to multiple chemicals every day. Epidemiological studies have shown that chemical mixtures are associated with cancers, allergies, neurodevelopmental disorders, and other adverse health effects. To assess these associations, investigators are increasingly using chemical mixture approaches like weighted quantile sum (WQS) regression. In these studies, the research objectives are to determine whether a mixture of correlated chemicals is associated with an adverse health outcome and to identify the important chemicals. However, as experimental equipment measures each exposure to a chemical-specific detection limit, the exposures are unknown between zero and the detection limit. Indeed, the number of exposures below …

Use Of Pefloxacin As A Surrogate Marker To Detect Ciprofloxacin Susceptibility In Salmonella Enterica Serotypes Typhi And Paratyphi A, Safia Moin, Mohammad Zeeshan, Sidra Laiq, Ahmed Raheem, Afia Zafar

Department of Pathology and Laboratory Medicine

Objective: To determine the use of pefloxacin as a surrogate marker to detect fluoroquinolone (ciprofloxacin) susceptibility against Salmonella enterica serotypes Typhi and Paratyphi A.
Methods: The prospective, descriptive cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from September 2016 to March 2018, and comprised Salmonella Typhi and Paratyphi A isolates of blood cultures. Disk susceptibility tests and broth microdilution to test minimum inhibitory concentration were performed as per standard guidelines. Data was analysed using SPSS 21.
Results: Of the 138 isolates, 91(66%) were intermediate resistant to ciprofloxacin but were resistant to pefloxacin, 42(30%) were resistant to both …

Evaluation Of A Concussion Management And Discharge Education Training Module For Emergency Department Nurses, Carmen Frede

DNP Projects

Purpose: The purpose of this project was to improve the Emergency Department (ED) nurses’ knowledge on identifying patients at risk for concussions and delivering effective concussion discharge education using an educational training intervention.

Methods: This project used a descriptive, non-randomized pre-post survey design. Participation involved three stages: a pre-education survey to assess baseline concussion education knowledge, an educational intervention consisting of a narrated PowerPoint presentation, and a post-education survey to evaluate knowledge on concussion discharge education. The intervention was delivered online via the UK Canvas educational platform.

Results: The majority of nursing staff participants were female (97%) and had a …

Don't Just Check The Box: Check Your Athlete's Heart: Adding A 12-Lead Ecg To Pre-Participation Screening To Identify High Risk Of Sudden Cardiac Arrest In Male High School Athletes, Shannon King

DNP Projects

PURPOSE: Sudden cardiac arrest (SCA) continues to be the leading cause of death in male high school athletes participating in competitive sports. There is gap in the current preventative screening practice of history and physical alone. The purpose of this project is to evaluate adding a 12-lead electrocardiogram (ECG) to pre-participation screening captures cardiac abnormalities that identify male athletes at a higher risk for developing SCA. METHODS: A descriptive secondary analysis design to determine the incidence of cardiac abnormalities detected with the addition of a 12-lead ECG during pre-participation screenings (annual sports physical) of high school-aged male athletes. The study …

Law, Structural Racism, And The Covid-19 Pandemic, Ruqaiijah Yearby, Seema Mohapatra

All Faculty Scholarship

Racial and ethnic minorities have always been the most impacted by pandemics because of: disparities in exposure to the virus; disparities in susceptibility to contracting the virus; and disparities in treatment. This article explains how structural racism, the ways in which laws are used to advantage the majority and disadvantage racial and ethnic minorities, has caused these disparities. Specifically, this article focuses on how employment, housing, health care, and COVID-19 relief laws have been manipulated to disadvantage racial and ethnic minorities, making minorities more susceptible to COVID-19 infection and death. This article uses Blumenshine’s 2008 framework to outline how structural …

Predictive Factors For Identifying Macrolide Responder In Treating Chronic Rhinosinusitis, Kachorn Seresirikachorn

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: A low-dose macrolide (LDM) has antineutrophilic activity, so they should not work for eosinophilic inflammation. Clinical predictors are required to select favorable patients for LDM therapy appropriately. This study aims to assess individual predictive factors and propose suitable multiple predictive factors for identifying a macrolide responder in treating CRS. Methodology: Prospective cohort study was done in adult CRS patients. Clinical data collection, Lund-Mackay CT score, visual analog scale (VAS), and sino-nasal outcome test 22 (SNOT-22) were assessed. Patients received 150 mg of roxithromycin once daily plus saline irrigation for 12 weeks. VAS was evaluated at every visit. If the …

Characterization Of Bone Pathology In Sickle Cell Disease And Therapeutic Strategies, Mykel D. Green

Dissertations and Theses

Sickle cell disease (SCD) is a genetic hemoglobinopathy that has grown into a global health concern. While the advances in medical treatment and management of SCD during childhood have drastically improved the overall survival of children, the transition from pediatric to adult services is significantly inadequate in comparison. Life expectancies of patients with SCD in first world countries such as the United States are shortened to averages of 42 and 48 years for men and women, respectively. Despite the increasing number of people living with SCD, remarkably, few detailed studies have described the clinical course and complications of the disease …

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 …

Molecular And Behavioral Mechanisms Mediated Paclitaxel-Induced Changes In Affect-Like Behavior In Mice, Julia Meade

Theses and Dissertations

Paclitaxel and oxaliplatin are two chemotherapeutics that cause acute neurotoxicity and chemotherapy-induce peripheral neuropathy (CIPN) in 70-90% of cancer patients. Chemotherapy-induced sensory changes are correlated with depression and anxiety. We characterized the effects of these drugs on sensation and various mood-related behaviors in mice, to determine if changes in sensation are associated with depression-like behavior, to explore putative mechanisms of chemotherapy-induced depression-like behavior (Aim 1), and to develop a mouse model of chemotherapy-induced operant responding deficit (Aim 2). In Aim 1, we observed that a cumulative dose of 32 mg/kg paclitaxel induced mechanical hypersensitivity and transiently reduced preference for sucrose …

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT_2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …

Artificial Neural Network For Pulmonary Rifampicin Resistant Tuberculosis Screening Indonesia : A Study In Accuracy And Cost-Effectiveness Analysis Of The Model, Bumi Zulheri Herman

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Diagnosis of Pulmonary Rifampicin Resistant Tuberculosis (RR-TB) with the Drug-Susceptibility Test (DST) is costly and time-consuming, and the GeneXpert for rapid diagnosis is not widely available in Indonesia. This study aims to develop an Artificial Neural Network model and evaluate the deployed model performance for RR-TB screening. Methods: A cross-sectional study involved suspected RR-TB patients with complete sputum Lowenstein Jensen DST (reference) and 19 clinical, laboratory, and radiology parameter results, retrieved from medical records in hospitals under the Faculty of Medicine, Hasanuddin University Indonesia, from January 2015-December 2019. The Artificial Neural Network (ANN) models were built along with other …

Variation Of Tuberculosis Prevalence Across Diagnostic Approaches And Geographical Areas Of Indonesia, Alvera Noviyani

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Tuberculosis (TB) has contributed a significant disease burden and economic loss worldwide. Given no gold standard for diagnosis, early identification of TB infection has been challenging. This study aimed to comparatively investigate the prevalence of TB across diagnostic approaches (sputum AFB, sputum culture, sputum genetic test, and chest x-ray) and geographical areas in Indonesia. Methods: Participant demographic variables and TB screening test results were obtained from the Tuberculosis Unit, Health Research and Development Agency, Ministry of Health (HRDA-MoH). Variations across geographical areas and diagnostic approaches are expressed as prevalence rate and 95%CI. Results: A total of 67,944 records were …

Effect Of Peak Plantar Presure On Plantar Corn Size, Milintorn Wongchinchai

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Corn and callus are one of the most common problems faced by dermatologists in dermatology clinic. Repeated local irritation to plantar skin results in the thickening of traumatized skin. Corn and callus are often overlooked, and this becomes longstanding problem causing pain when walking and standing up. There is no study explore the correlation between plantar pressure and size of corn. Objectives: To explore the correlation between peak plantar pressure and size of corn Materials and methods: 30 participants with plantar corn were recruited in this study. Their plantar corns were measured in millimetre using a dermoscope. Each participant …

Modelling Of Cholangiocarcinogenesis By Using Pluripotent Stem Cell, Natthida Kittimawikrom

Chulalongkorn University Theses and Dissertations (Chula ETD)

The exome sequencing study of cholangiocarcinoma (CCA) revealed SMAD4 mutation was frequently observed. The role of SMAD4 to cholangiocarcinogenesis as well as cell origin of CCA are not fully understand. According to current CCA model including cell lines and animal models, it still limited in resembling human cells and early event during carcinogenesis. The objective of this study was to study the role of SMAD4 signaling disruption in cholangiocyte progenitors. To clarify these questions, we used induced pluripotent stem cells (iPSCs) to differentiate into cholangiocyte organoids by using growth factors induction in this study. The result demonstrated that cholangiocyte organoids …

The Effectiveness Of Cannabidiol In Rheumatic Disease Pain: A Systematic Review, Mary C. Wiczek

All Graduate Theses, Dissertations, and Other Capstone Projects

Cannabinoids have long been a part of human culture and medicine, and more recently have been rediscovered for their potential use in the management of rheumatic disease pain. The objective of this review was to evaluate the known clinical effectiveness of cannabidiol treatment for rheumatic disease related pain. The legality and current regulation of these products was also reviewed to establish the current status of federal and state rules regarding their clinical use. Basic definitions of the terms used to differentiate cannabidiol from other cannabinoid products was also outlined. A systematic literature search was then conducted to explore the current …

Probiotics And The Prevention Of Clostridioides Difficile: A Review Of Existing Systematic Reviews, Andrea L. Onstad

All Graduate Theses, Dissertations, and Other Capstone Projects

Clostridioides difficile is the leading cause of infectious diarrhea (Vernaya et al., 2017). Probiotics have been proposed to provide a protective benefit against Clostridioides difficile infection (CDI). The objective of this literature review was to examine the research evidence pertaining to the use of probiotics for the prevention of CDI in individuals receiving antibiotic therapy. A systematic literature review of studies published between 2015 and 2019 was performed. Five databases were searched, which yielded 10 systematic reviews that met strict inclusion criteria. Overall, the majority of evidence indicated that probiotics versus no treatment, placebo, or usual care have the potential …

Tunable Multiphase Dynamics Of Arginine And Lysine Liquid Condensates, Rachel S. Fisher, Shana Elbaum-Garfinkle

Advanced Science Research Center

Liquid phase separation into two or more coexisting phases has emerged as a new paradigm for understanding subcellular organization, prebiotic life, and the origins of disease. The design principles underlying biomolecular phase separation have the potential to drive the development of novel liquid-based organelles and therapeutics, however, an understanding of how individual molecules contribute to emergent material properties, and approaches to directly manipulate phase dynamics are lacking. Here, using microrheology, we demonstrate that droplets of poly-arginine coassembled with mono/polynucleotides have approximately 100 fold greater viscosity than comparable lysine droplets, both of which can be finer tuned by polymer length. We …

Assessing Morphology Of Iprgcs After Traumatic Brain Injury, Brian Foresi, Matt Smith

Williams Honors College, Honors Research Projects

ipRGCs are retinal ganglion cells that project to visual processing centers of the brain for nonimage forming visual functions. The relation of ipRGCs to tramatic brain injury (TBI) is emerging as data has been published describing ipRGC functional changes in TBI affected military veterans. Major symptomologies of concussions, a mild form of TBI, also overlap with the function governed by sites in the brain with major ipRGC projection percentages. Assesing if a morphological change is occuring in the ipRGCs after a TBI could support the idea of a pathological mechanism of the injury. This study could also indicate further relevance …

Cardiovascular Tissue Remodeling Of Preeclampsia, Rachel Metz

Williams Honors College, Honors Research Projects

Preeclampsia is a hypertensive disorder of pregnancy that leads to a multitude of problems for the mother and fetus during and after pregnancy. While the effects on the mother's body after pregnancy are often overlooked, preeclamptic mothers are prone to cardiovascular diseases from the great deal of stress experienced through the duration of a preeclamptic pregnancy. The associated high blood pressure causes cardiac muscle to work a great deal harder in an attempt to successfully perfuse tissues adequately. This increase in prolonged stress leads to remodeling of the cardiovascular tissues-significantly increasing the risk of heart issues in life beyond the …

Investigating The Morphology Of Iprgcs In Control Vs. Glaucomatous Retinas, Samantha Cook

Williams Honors College, Honors Research Projects

Glaucoma is a build-up of pressure in the eye that leads to the gradual loss of sight. The intention of this study was to investigate how glaucoma affects intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). These cells contain melanopsin, a photopigment, that enables the cells to react to light. Four-month-old control and five-month-old glaucoma mice retinas were dissected, stained using primary and secondary antibodies, then traced using ImageJ’s Simple Neurite Tracer. There were no significant differences in soma size, total dendritic length, dendritic field size, and dendritic field diameter between control and glaucoma ipRGCs. However, further research is needed to provide …

A Rare Case Of Herpes Zoster Ophthalmicus After Photodynamic Therapy, Madison Bradley, Sonal Muzumdar, Neda Shahriari, Marti J. Rothe, Madina Falcone

Biology Undergraduate Publications

Dear Editors:

Topical photodynamic therapy (PDT) is frequently used in dermatology to treat actinic keratoses (AKs) and superficial nonmelanoma skin cancers (Ibbotson et al., 2019). Herein, we present an extremely rare case of herpes zoster ophthalmicus (HZO) after PDT.

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …

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 …

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, …

Process Factors Affecting Reperfusion Time In Patients Presenting With St-Segment Elevation Myocardial Infarction (Stemi), Richard R. Wall

Theses and Dissertations

Abstract PROCESS FACTORS AFFECTING REPERFUSION TIME IN PATIENTS

PRESENTING WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION (STEMI) By Richard R. Wall MSRS, RT(R)(CT)(CI), RCIS

A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University.

Virginia Commonwealth University, 2020.

Dissertation Chair: Jeffrey S. Legg Ph.D. Associate Professor and Chair, Department of Radiation Sciences

An ST-segment myocardial infarction (STEMI) occurs when the blood flow to the myocardium is suddenly and completely blocked causing the myocardium to become ischemic. A STEMI is a life-threatening condition that necessitates emergent medical treatment. Research has shown that longer …

Prevalence And Predictors Of Chronic Pain Intensity And Disability Among Adults With Sickle Cell Disease, Nadine Matthie, Coretta Jenerette, Ashley Gibson, Sudeshna Paul, Melinda Higgins, Lakshmanan Krishnamurti

Faculty, Staff and Student Publications

Among 170 adults with sickle cell disease, we evaluated chronic pain impact and disability prevalence, assessed age and gender differences, and identified psychosocial predictors of chronic pain intensity and disability. Most participants had a high level of disability. Chronic pain intensity and disability were significantly associated with pain catastrophizing and chronic pain self-efficacy, and worsened with age. Further research is needed to confirm study findings and develop interventions, including palliative care approaches that address catastrophizing and disability, particularly for young women and middle-aged adults with sickle cell disease. Moreover, consistent clinical assessment of chronic pain and psychosocial health should be …

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.

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 …

Covid-19: A Simple Curve Approximation Tool, Jane Courtney

Articles

In the current COVID-19 pandemic, much focus is put on ‘flattening the curve’. This ‘curve’ refers to the cases versus time graph, which shows the rise of a disease to its peak before descending. The aim in a pandemic is to flatten this curve by reducing the peak and spreading out the timeline. However, the models used to predict this curve are often not clearly outlined, no model parameters are given, and models are not tested against real data. This lack of detail makes it difficult to recreate the curve from these models. What is much needed is a simple …

Optimisation Of Estrogen Receptor Subtype-Selectivity Of A 4-Aryl-4h-Chromene Scaffold Previously Identified By Virtual Screening, Miriam Carr, Andrew Knox, Daniel Nevin, Niamh O'Boyle, Shu Wang, Billy Egan, Thomas Mccabe, Brendan Twamley, Daniela Zisterer, David Lloyd, Mary Meegan

Articles

4-Aryl-4H-Chromene derivatives have been previously shown to exhibit anti-proliferative, apoptotic and anti-angiogenic activity in a variety of tumor models in vitro and in vivo generally via activation of caspases through inhibition of tubulin polymerisation. We have previously identified by Virtual Screening (VS) a 4-aryl-4H-chromene scaffold, of which two examples were shown to bind Estrogen Receptor α and β with low nanomolar affinity and <20-fold selectivity for α over β and low micromolar anti-proliferative activity in the MCF-7 cell line. Thus, using the 4-aryl-4H-chromene scaffold as a starting point, a series of compounds with a range of basic arylethers at C-4 and modifications at the C3-ester substituent of the benzopyran ring were synthesised, producing some potent ER antagonists in the MCF-7 cell line which were highly selective for ERα (compound 35; 350-fold selectivity) or ERβ (compound 42; 170-fold selectivity).