Medicine and Health Sciences Commons^™

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.

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 …

Modeling Genetic Risk Factor Of Alzheimer's Disease "Sorl1" Using Patient Specific Pluripotent Stem Cells, Kamonchanok Kongsri

Chulalongkorn University Theses and Dissertations (Chula ETD)

Alzheimer’s disease is the most common neurodegenerative; cause of dementia and trends to increase in elder society. There is still not cure. A new strategy development for treatment is needed. SORL1 is a major genetic risk factor associated with sporadic AD. It correlates with degrading amyloid beta (Aβ) by sorting to lysosome. SORL1 overexpression has been reported that reduce Aβ production. However, the molecular mechanism that regulate in neurons is still unclear. The purpose of this study is to generate an effective drug discovery platform for identifying molecules that can modulate SORL1 level in human neurons by using induced pluripotent …

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 …

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 …

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 …

Role Of Nurd In Acute Leukemia Cell Survival, Javeria Aijaz

Theses and Dissertations

Depletion of the ATPase component of the Nucleosome Remodeling and Deacetylase (NuRD) complex, CHD4, reduces acute myeloid leukemia (AML) cell survival. This study identified other NuRD components, as potential therapeutic targets for disrupting protein-protein interactions within NuRD. In addition to AML, we established that T-cell Acute Lymphoblastic Leukemia (T-ALL) cell lines responded similarly to CHD4 depletion.

Greater than 90% depletion of either MBD2 or MBD3 (the mutually exclusive two DNA binding NuRD paralogues) – was unremarkable, but complete depletion of MBD3 increased apoptosis and genotoxic sensitivity. Combined depletion of MBD-NuRD proteins augmented apoptosis observed with complete MBD3 depletion - indicating …

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 …

Investigating The Role Of Oncogene C-Terminal Binding Protein (Ctbp) In Pancreatic Ductal Adenocarcinoma, Kranthi Kumar Chougoni

Theses and Dissertations

The transcriptional coregulator CtBP2 has been implicated as an oncogene in colon, prostate, breast and ovarian cancers. Previously, we reported overexpression of CtBP2 in human PDAC specimens. However, its exact role in PDAC is still unclear. In the current study, we attempt to delineate the oncogenic role CtBP2 in PDAC growth and metastasis. Using an orthotopic syngeneic pancreatic tumor mouse model (CKP), we found that deletion of Ctbp2 decreases PDAC tumor growth, proliferation, metastasis, EMT and significantly prolongs survival. Further, we identified significant downregulation of Erbb3 mRNA levels upon deletion of Ctbp2 in CKP PDAC cells As ErbB3 signaling was …

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 …

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 …

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, …

Vaccine Hesitancy: Experimentalism As Regulatory Opportunity, Ana Santos Rutschman, Timothy L. Wiemken

All Faculty Scholarship

This symposium on patient innovation has prompted us to explore problems related to departures from official vaccination schedules. At a time in which vaccine confidence has been plummeting across the world, we argue that a more granular understanding—and ultimately a more finely tuned regulatory framework—is needed to reflect the current behavioral heterogeneity among indicated patients who choose to forego or delay administration of recommended vaccines. In particular, we focus on a phenomenon we term “vaccine staggering:” a departure from vaccination schedules in the form of delays in receiving one or more vaccines, which is motivated by the desire to boost …

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 …

Boron Trifluoride Etherate Promoted Microwave Assisted Synthesis Of Antimalarial Acridones, Papireddy Kancharla, Rozalia A. Dodean, Yuexin Li, Jane X. Kelly

Chemistry Faculty Publications and Presentations

A microwave-assisted, rapid and efficient method using boron trifluoride etherate (BF3.Et2O) for the synthesis of acridones, via an intramolecular acylation of N-phenylanthranilic acid derivatives, has been developed. The reaction proceeds under solvent-free conditions, tolerates a wide range of functional groups, and provides rapid access to a range of acridones in good to excellent yields. Several of the synthesized acridones exhibited potent antimalarial activities against CQ sensitive and multi-drug resistant (MDR) parasites.

Knowledge Of Breast Cancer And Screening Methods Among Rural Women In Southwest Nigeria: A Mixed Method Analysis, Rowland Edet, Oluwayimika Ekundina, Obasanjo Afolabi Bolarinwa, Julianah Babajide, Juliet Amarachukwu Nwafor

Department of Sociology: Faculty Publications

The objective of this study was to assess the awareness of rural women on breast cancer and its screening methods in Southwest Nigeria. Descriptive cross-sectional survey design with the aid of a semi-structured questionnaire was used to generate data among 422 rural women in selected communities in Egbeda local government area of Ibadan. The qualitative data was generated through in-depth interviews among rural women and key informant interviews among health workers in the communities. The study revealed that only 63.7% were aware of breast cancer screening methods compared to 31.6% who were not aware of it. The commonly known screening …

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).

Concordant Peripheral Lipidome Signatures In Two Large Clinical Studies Of Alzheimer’S Disease, Kevin Huynh, Wei Ling Florence Lim, Corey Giles, Kaushala S. Jayawardana, Agus Salim, Natalie A. Mellett, Adam Alexander T. Smith, Gavriel Olshansky, Brian G. Drew, Pratishtha Chatterjee, Ian Martins, Simon M. Laws, Ashley I. Bush, Christopher C. Rowe, Victor L. Villemagne, David Ames, Colin L. Masters, Matthias Arnold, Kwangsik Nho, Andrew J. Saykin, Rebecca Baillie, Xianlin Han, Rima Kaddurah-Daouk, Ralph N. Martins, Peter J. Meikle

Research outputs 2014 to 2021

© 2020, The Author(s). Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for detailed lipid separation and characterisation. In this study we examined peripheral samples of two cohorts (AIBL, n = 1112 and ADNI, n = 800). We are able to identify concordant peripheral signatures associated with prevalent AD arising from lipid pathways including; ether lipids, sphingolipids (notably GM3 gangliosides) and lipid …

Evaluation Of A Remote Symptom Assessment And Management (Sam) System For People Receiving Adjuvant Chemotherapy For Breast Or Colorectal Cancer: Mixed Methods Study, Lisa Whitehead, Laura Emery, Deborah Kirk, Diane Twigg, Deborah Brown, Joanna Dewar

Research outputs 2014 to 2021

©Lisa Whitehead, Laura Emery, Deborah Kirk, Diane Twigg, Deborah Brown, Joanna Dewar. Background: The Symptom Assessment and Management (SAM) program is a structured, online, nurse-supported intervention to support symptom self-management in people receiving adjuvant chemotherapy post surgery for breast or colorectal cancer. Objective: The objective of this study was to describe the development, implementation strategy, and evaluation of the SAM system. Methods: The development of the SAM program involved 3 phases. In phase 1, the web app was developed through consultation with consumers and clinicians and of the literature to ensure that the system was evidence-based and reflected the realities …

The Prognostic Impact Of Circulating Tumour Dna In Melanoma Patients Treated With Systemic Therapies—Beyond Braf Mutant Detection, Gabriela Marsavela, Peter A. Johansson, Michelle R. Pereira, Ashleigh C. Mcevoy, Anna L. Reid, Cleo Robinson, Lydia Warburton, Muhammad A. Khattak, Tarek M. Meniawy, Benhur Amanuel, Michael Millward, Nicholas K. Hayward, Melanie R. Ziman, Elin S. Gray, Leslie Calapre

Research outputs 2014 to 2021

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In this study, we evaluated the predictive value of circulating tumour DNA (ctDNA) to inform therapeutic outcomes in metastatic melanoma patients receiving systemic therapies. We analysed 142 plasma samples from metastatic melanoma patients prior to commencement of systemic therapy: 70 were treated with BRAF/MEK inhibitors and 72 with immunotherapies. Patient-specific droplet digital polymerase chain reaction assays were designed for ctDNA detection. Plasma ctDNA was detected in 56% of patients prior to first-line anti-PD1 and/or anti-CTLA-4 treatment. The detection rate in the immunotherapy cohort was comparably lower than those with BRAF inhibitors …

Effects Of A Single Mutation In Chikungunya Virus Non-Structural Protein On Virus Infection In Aedes Albopictus And Mammalian Cell Lines, Yin Ling Jolene Fu

Student Works (2020-2029)

Chikungunya virus (CHIKV) has caused large-scale epidemics of fever, rash and arthritis since 2004. This unprecedented re-emergence has been mainly associated with mutations in genes encoding structural envelope proteins, providing increased fitness in the secondary vector Aedes (Ae.) albopictus. In the 2008-2013 CHIKV outbreaks across Southeast Asia, an R82S mutation in non-structural protein 4 (nsP4) emerged early in Malaysia or Singapore and quickly became predominant. To determine whether this nsP4-R82S mutation provides a selective advantage in host cells which may have contributed to the epidemic, the fitness of infectious clone-derived CHIKV with nsP4- 82R and nsP4-82S were compared in Ae. …

Functional Characterisation Of Cancer-Associated Fibroblasts From Nasopharyngeal Carcinoma, Wee Lin Wong

Student Works (2020-2029)

Nasopharyngeal carcinoma (NPC) remains a major health issue in Southern China and Southeast Asia where the disease is endemic. Whilst the cure rate for early stage NPC is high, patients often present with late stage diseases and have a 5-year survival rate of less than 50%. NPC patients often suffer from severe treatment side effects because of the location of the tumours that is in proximity to various important organs in the head and neck region. Therefore, alternative therapeutic approaches are needed to improve the treatment outcomes and reduce patient morbidity. Targeted therapies are not in routine use to treat …

Improving Access To Hepatitis C Treatment For Uninsured Patients In Southeast Georgia, Bonzo K. Reddick, Marianna O'Ree

Journal of the Georgia Public Health Association

Background: In this brief report, we discuss enhancing access to hepatitis C treatment for uninsured patients in Southeast Georgia.

Methods: Through our screening program for hepatitis C virus (HCV) infections in a local safety net emergency department, the Comprehensive AIDS Resources Emergency (CARE) Initiative studied the rates of linkage to care for newly diagnosed patients with HCV and sought ways to improve linkage to care for those who did not have health insurance.

Results: Our multidisciplinary team partnered with a local federally qualified health center (FQHC) and a wholesale laboratory service to offer affordable care options, thus increasing the percent …

Cardiometabolical Risk Factors Associated With Renal Function In Apparently Healthy Young Students: A Cross-Sectional Study, Lucia M. Perez-Navarro, Rafael Valdez-Ortiz, Araceli Alegria-Diaz, Miguel Murgia-Romero, Rafael Jimenez-Flores, Rafael Villalobos-Molina, Srinivas Mummidi, Ravindranath Duggirala, Juan C. Lopez-Alvarenga

School of Medicine Publications

Background: Cardiometabolic risk factors (CMRFs) appear decades before developing chronic kidney disease (CKD) in adulthood.

Objective: The objective of the study was to identify the prevalence and association between CMRFs and kidney function in apparently healthy young adults (18-25 years old).

Methods: We included 5531 freshman year students. Data collected on CMRFs included central obesity, high body mass index (hBMI >25), blood pressure, glycemia, lipids, uric acid (UA >6.8 mg/dL), and insulin. Glomerular filtration rate (GFR) was estimated by CKD-Epidemiology Collaboration formula. We used logistic regression and a log linear for odds ratio (OR) (95% confidence level) and probabilities.

Results: …