Diseases Commons^™

Vitamin B12 Deficiency Does Not Stimulate Amyloid-Beta Toxicity In A Ceanorhabditis Elegans Model Of Alzheimer’S Disease, Opeyemi F. Showemimo

Electronic Theses and Dissertations

Alzheimer’s disease (AD) is symptomized by amyloid-beta plaques in the brain and accounts for more than 65 percent of dementia cases. Vitamin B12 (cobalamin) deficiency can result in similar cognitive impairment and roughly 15% of the elderly are vitamin B12 deficient. Vitamin B12 deficiency results in the accumulation of toxic methylmalonic acid and homocysteine. Hyperhomocysteinemia is a strong risk factor for AD. To test if vitamin B12 deficiency stimulates amyloid-beta toxicity, Caenorhabditis elegans expressing amyloid-beta in muscle were fed either vitamin B12-deficient OP50-1 or vitamin B12-rich HT115(DE3) E. coli bacteria. Increased amyloid-beta toxicity was found in worms fed the …

Chikungunya Outbreak In Karachi Pakistan 2016-2017: An Analysis Of Viral Isolates, Dhani Prakoso, Kelli Barr, Kehkashan Imtiaz, Joveria Farooqi, Erum Khan, Maureen Long

Department of Pathology and Laboratory Medicine

In December 2016 physicians in Karachi, Pakistan,witnessed an increase in patients presenting with febrile illness and severe polyarthralgia. Subsequently, chikungunya virus (CHIKV)) was isolated from three patients. This virus was sequenced and compared with other isolates of CHIKV obtained in India and Pakistan during recent outbreaks. Phylogenetic analysis indicated that the Karachi isolates were most similar to the East Central South African CHIKV lineage and showed sequence homology to isolates obtained in other parts of Pakistan and India. More importantly, two of the CHIKV isolates had a nucleotide substitution in the E1 gene corresponding to an amino acid change at …

Muc13 Enhances Colorectal Cancer Metastasis, Kyle Doxtater

Theses and Dissertations (ETD)

Colorectal cancer (CRC) is one of the most prevalent cancer worldwide with a 5% lifetime incidence in developed countries. It is third most common cause of cancer related death in the United States and the second deadliest when men and women are combined. Encouragingly due to changes in dietary lifestyle, screening colonoscopy, and advancement in treatments the mortality has decreased in recent years. Most sporadic CRCs develop from polyploid adenomas and are preceded by intramucosal carcinomas (stage 0), which can progress into more malignant forms. This developmental process is known as the adenoma-carcinoma sequence. Early detection and endoscopic removal are …

Delineating The Upc2a Regulon In Candida Glabrata, Yu Li

Theses and Dissertations (ETD)

Candida glabrata is the second most common cause of invasive candidiasis. Intrinsic resistance has greatly limited the utility of the triazole antifungal, fluconazole, in the treatment of invasive fungal infection. The transcription factor Upc2 regulates the expression of sterol biosynthesis genes in yeast. Disrupting UPC2A in C. glabrata greatly increases its susceptibility to fluconazole (FLU) in both FLU-susceptible and -resistant clinical isolates. Therefore, the Upc2A and its target genes represent a potential pathway for overcoming FLU resistance in C. glabrata. We aimed to delineate the Upc2A regulon to determine its target genes involved in FLU resistance. Transcriptome sequencing (RNA-seq) analysis …

Sarcopenia Screening By Registered Dietitian Nutritionists (Rdns) In The United States (U.S.), Madison Marcom

Electronic Theses and Dissertations

Sarcopenia is a disease of muscle wasting primarily seen in older adults. Although this term was first coined over three decades ago, there is a lack of consensus on a definition, screening criteria, and treatment protocol for sarcopenia. The primary purpose of this study is to determine whether registered dietitian nutritionists (RDNs) in the United States (U.S.) screen for sarcopenia. Study participants were recruited through a randomized email list and included RDNs throughout the U.S. Respondents completed a survey questioning knowledge of sarcopenia, screening tools and company protocols in place, and the need and desire for sarcopenia education. Data revealed …

Optimizing Empiric Vancomycin Use In Febrile Neutropenia Patients, Nicole Tadros, Erika Dittmar, Radhan Gopalani

All Publications

Introduction: Febrile neutropenia (FN) is a complication of chemotherapy resulting in a temperature 100.4⁰F or greater plus an absolute neutrophil count (ANC) below 500 cells/mm³ or an ANC below 1000 cells/mm³ and expected to decrease below 500 cells/mm³ within 48 hours. Timely administration of broad-spectrum antimicrobial therapy is a cornerstone for the initial management of FN. However, prolonged empiric antimicrobial treatment can lead to resistance and toxicity. National guidelines and published literature do not support vancomycin as a routine part of empiric antimicrobial regimens in FN; it is only recommended in patients with specific clinical indications. This …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

Using Deep Learning To Automate The Diagnosis Of Skin Melanoma, Akhil Reddy Alasandagutti

Honors Theses

Machine learning and image processing techniques have been widely implemented in the field of medicine to help accurately diagnose a multitude of medical conditions. The automated diagnosis of skin melanoma is one such instance. However, a majority of the successful machine learning models that have been implemented in the past have used deep learning approaches where only raw image data has been utilized to train machine learning models, such as neural networks. While they have been quite effective at predicting the condition of these lesions, they lack key information about the images, such as clinical data, and features that medical …

Headache-Related Disability Among Individuals With And Without Migraine Aura, Delora Denney

Honors Theses

Migraine is a neurological disease marked by recurrent headache and migraine attacks. Migraine is one of the most common diseases in the world, and as a result of high prevalence and symptoms, migraine is also quite disabling. One-third of people who have migraine experience aura, and these individuals have a greater risk for stroke, psychiatric comorbidities, and suicide attempts. The present study aimed to evaluate if there was a difference in headache-related disability between those who have migraine with and without aura, and any headache or psychiatric factors that may account for observed difference in disability.

The present study is …

Imaging Based Prediction Of Pathology In Adult Diffuse Glioma With Applications To Therapy And Prognosis, Evan Gates

Dissertations and Theses (Open Access)

The overall aggressiveness of a glioma is measured by histologic and molecular analysis of tissue samples. However, the well-known spatial heterogeneity in gliomas limits the ability for clinicians to use that information to make spatially specific treatment decisions. Magnetic resonance imaging (MRI) visualizes and assesses the tumor. But, the exact degree to which MRI correlates with the actual underlying tissue characteristics is not known.

In this work, we derive quantitative relationships between imaging and underlying pathology. These relations increase the value of MRI by allowing it to be a better surrogate for underlying pathology and they allow evaluation of the …

Investigating Diffusion Tensor Imaging Correlates Of Cognitive Impairment In Idiopathic Normal Pressure Hydrocephalus And Alzheimer's Disease, Omar Hasan, Omar Hasan

Dissertations and Theses (Open Access)

Modest expansion of the human brain cerebrospinal fluid (CSF)-filled ventricles is normal with aging, and because of this, it can be difficult for physicians to accurately diagnose and treat enlarged ventricles (ventriculomegaly), called hydrocephalus¹ (fluid or water in the brain) Ventriculomegaly occurs due to an obstruction (such as a blood clot or tumor), or a change in CSF absorption². Primary hydrocephalus, also called idiopathic normal pressure hydrocephalus (iNPH), is non-obstructive and may be comorbid with other neurodegenerative diseases such as Alzheimer’s disease (AD) or frontotemporal dementia (FTD). Clinically, it can be difficult to tell whether the pathophysiological …

Cervical Cancer-Associated Suffering: Estimating The Palliative Care Needs Of A Highly Vulnerable Population, Eric L. Krakauer, Xiaoxiao Kwete, Khadidjatou Kane, Gauhar Afshan, Lisa Bazzett-Matabele, Danta Dona Ruthnie Bien-Aimé, Sarah Byrne-Martelli, Stephen Connor, Raimundo Correa, C R Beena Devi C R Beena Devi

Department of Anaesthesia

Purpose: To enable design of optimum palliative care for women with cervical cancer, we studied the most common types of suffering and their severity, prevalence, and duration.
Methods: We first reviewed the literature on the major types, severity, prevalence, and duration of suffering associated with cervical cancer. We then conducted a modified Delphi process with experts in cervical cancer care to supplement the literature. For each type of suffering, we distinguished between decedents (those who die from cervical cancer in a given year) and nondecedents (those who have cervical cancer in a given year but do not die). By applying …

Impact Of Proton Pump Inhibitor Use On Effectiveness Of Immune Checkpoint Inhibitors In Advanced Cancer Patients, Ken Chen

Capstone Experience: Master of Public Health

Background: Gut microbiome plays a critical role in modulating therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) may affect the gut microbiome by altering gut pH.

Objective: To evaluate if concurrent use of PPI 0-30 days before or after initiation of ICIs (nivolumab or pembrolizumab) is associated with poorer overall survival (OS) and progression-free survival (PFS) for patients with stage IV non-small cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma or head and neck squamous cell carcinoma compared with no PPI use.

Methods: This was a single-center retrospective cohort study of advanced cancer patients …

Climate Change And Vaccines: Distrust Of Science In Politics And The Media, Natalie Montalbano

Senior Honors Projects

Distrust in science and the scientific process has increased significantly over the last fifty years, and this distrust is particularly apparent in the fields of climate change and vaccination. Climate change, a relatively new scientific issue, has become one of the hottest topics discussed in both U.S and world politics. The existence and real threat of anthropogenic global warming was publicly declared by National Geographic in 2004, but climate scientists had acknowledged that humans were causing the warming of our Earth as early as the 1980’s. Vaccines, despite being safe and effective in curbing the spread of infectious diseases, have …

Criterion Validity Of The Ohio State University Traumatic Brain Injury Identification Method In A Criminal Justice Sample, Sarah M. Monaghan

Student Theses

The purpose of the current study was to determine the clinical utility of the Ohio State University Traumatic Brain Injury Identification Method (OSU-TBI-ID) in a criminal justice sample, by evaluating the criterion-related validity of this instrument. It was hypothesized that this tool could differentiate between incarcerated individuals with or without a history of Traumatic Brain Injury (TBI) on measures evaluating important TBI-related sequalae. The sample consisted of 95 incarcerated men detained at a private correctional facility in a Mid-Atlantic state. Measures used in this study to evaluate executive functioning difficulties, psychiatric difficulties, substance use problems, institutional misconduct and recidivism were …

Impact Of Acne On Quality Of Life In Young Pakistani Adults And Its Relationship With Severity: A Multicenter Study, Shaheen Naveed, Sadia Masood, Atiya Rahman, Safia Awan, Saadia Tabassum

Department of Medicine

Objectives: The current study aimed to determine the effect of acne vulgaris on quality of life of young adults and to assess the correlation between acne severity and impairment of quality of life (QOLI).
Methods: In this multi-center cross-sectional study, 163 young adults with acne vulgaris were assessed for severity and quality of life impairment between December 2016 and May 2017 at three tertiary care hospitals. Cardiff Acne Disability Index (CADI) was used to assess the quality of life while the severity of acne measured by Global Acne Grading System (GAGS). Data were collected on standardized forms, with CADI, GAGS …

Inclusion Of Olive Or Coconut Oil In A High-Fructose High-Fat Diet Increases Liver Injury In A Pig Model Of Pediatric Nafld, Kayla A. Dillard

Master's Theses

Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to investigate the effect of partial substitution of dietary lard by an isocaloric amount of olive or coconut oil on endpoints of NAFLD. Thirty-eight 15-d-old Iberian pigs housed in pens balanced for weight and sex were randomly assigned to receive 1 of 3 hypercaloric high-fructose high-fat (HFF) diets for 10 weeks: 1) lard (LAR; n=5 pens), 2) lard + olive oil (OLI, n=10), and 3) lard + coconut oil (COC; n=10). Additional pigs (BSL, n=4) were …

Social Worker’S Adjustment And Perception When Dealing With Double-Exposure During A Natural Disaster, Magaly Santos

Electronic Theses, Projects, and Dissertations

Limited research captures the perceptions and adjustments of social workers living and providing treatment in the same communities during a disaster. Few studies have captured the stressors and responsibilities put on social workers during an ongoing disaster. This paper reports the findings of the double-exposure captured using a qualitative approach in collecting interviews from nine mental health professionals who continued working during the outbreak of the COVID-19 pandemic. A constructivist paradigm was used to capture each participant’s reality. Participants described the sudden change to remote work as difficult when having to find the balance between work and life demands, providing …

How Covid-19 Has Fundamentally Changed Clinical Research In Global Health, Jay J H. Park, Robin Mogg, Gerald E. Smith, Etheldreda Nakimuli-Mpungu, Fyezah Jehan, Craig R. Rayner, Jeanine Condo, Eric H. Decloedt, Jean B. Nachega, Gilmar Reis, Edward J. Mills

Department of Paediatrics and Child Health

COVID-19 has had negative repercussions on the entire global population. Despite there being a common goal that should have unified resources and efforts, there have been an overwhelmingly large number of clinical trials that have been registered that are of questionable methodological quality. As the final paper of this Series, we discuss how the medical research community has responded to COVID-19. We recognise the incredible pressure that this pandemic has put on researchers, regulators, and policy makers, all of whom were doing their best to move quickly but safely in a time of tremendous uncertainty. However, the research community's response …

Exploring Equity In Health And Poverty Impacts Of Control Measures For Sars-Cov-2 In Six Countries, Sedona Sweeney, Theo Prudencio Juhani Capeding, Rosalind Eggo, Maryam Huda, Mark Jit, Don Mudzengi, Nichola R. Naylor, Simon Procter, Matthew Quaife, Lela Serebryakova

Community Health Sciences

Background: Policy makers need to be rapidly informed about the potential equity consequences of different COVID-19 strategies, alongside their broader health and economic impacts. While there are complex models to inform both potential health and macro-economic impact, there are few tools available to rapidly assess potential equity impacts of interventions.
Methods: We created an economic model to simulate the impact of lockdown measures in Pakistan, Georgia, Chile, UK, the Philippines and South Africa. We consider impact of lockdown in terms of ability to socially distance, and income loss during lockdown, and tested the impact of assumptions on social protection coverage …

Referral Pattern And Outcomes Of Neonates From Secondary Care Setting Of Aga Khan University Hospital To Tertiary Care Centers In Pakistan, Suneeta Khemani, Nazia Shamim, Adnan Mirza, Nadia Mohammad, Safdar Kagazwala, Shakeel Ahmed

Department of Paediatrics and Child Health

Objective: To determine the reasons of neonatal referrals from secondary-care to tertiary-care setting, and to assess neonatal outcomes for the referred cases.
Methods: The retrospective study was conducted at the Aga Khan University Hospital, Karachi, and comprised data from July 2015 to June 2019 Related to all neonates born after 32 weeks of gestation at the satellite secondary-care centres in Kharadar, Garden and Karimabad who had been referred to the main tertiary care hospital. The reason for referral, need of mechanical ventilation, referral place and neonatal outcome were noted. Data was analysed using SPSS 22.
Results: Of the 348 cases, …

Gastrointestinal Complications In Critically Ill Children: Experience From A Resource-Limited Country, Sidra Ishaque, Mariam Shakir, Asma Akbar Ladak, Anwar Ul Haque

Department of Paediatrics and Child Health

Objectives: To determine the frequency and predictors of outcome of gastrointestinal complications (GIC) in critically ill children.
Methods: This descriptive study was prospectively conducted in The Pediatric Intensive Care Unit (PICU), The Aga Khan University Hospital (AKUH), Karachi, from September 2015 to January 2017. After obtaining approval from the Ethical Review Committee of AKUH and informed consent from the parents, all children (aged one month to 18 years), of either gender, admitted to the Pediatric Intensive Care Unit (PICU) during the study period were included. The frequency of the defined GIC: vomiting, high gastric residue volume (GRV), diarrhea, constipation, and …

Mitophagy Deficiency Increases Nlrp3 To Induce Brown Fat Dysfunction In Mice, Myoung Seok Ko, Ji Young Yun, In-Jeoung Baek, Jung Eun Jang, Jung Jin Hwang, Seung Eun Lee, Seung-Ho Heo, David A Bader, Chul-Ho Lee, Jaeseok Han, Jong-Seok Moon, Jae Man Lee, Eun-Gyoung Hong, In-Kyu Lee, Seong Who Kim, Joong Yeol Park, Sean M Hartig, Un Jung Kang, David D Moore, Eun Hee Koh, Ki-Up Lee

Faculty, Staff and Students Publications

Although macroautophagy/autophagy deficiency causes degenerative diseases, the deletion of essential autophagy genes in adipocytes paradoxically reduces body weight. Brown adipose tissue (BAT) plays an important role in body weight regulation and metabolic control. However, the key cellular mechanisms that maintain BAT function remain poorly understood. in this study, we showed that global or brown adipocyte-specific deletion of pink1, a Parkinson disease-related gene involved in selective mitochondrial autophagy (mitophagy), induced BAT dysfunction, and obesity-prone type in mice. Defective mitochondrial function is among the upstream signals that activate the NLRP3 inflammasome. NLRP3 was induced in brown adipocyte precursors (BAPs) from pink1 …

Temporal Changes And Institutional Variation In Use Of Percutaneous Coronary Intervention For St-Elevation Myocardial Infarction With Multivessel Coronary Artery Disease In The United States: An Ncdr Research To Practice Project, Eric A Secemsky, Neel Butala, Aishwarya Raja, Rohan Khera, Yongfei Wang, Jeptha P Curtis, Thomas M Maddox, Salim S Virani, Ehrin J Armstrong, Kendrick A Shunk, Ralph G Brindis, Deepak Bhatt, Robert W Yeh

Faculty, Staff and Students Publications

IMPORTANCE: After disparate results from observational and small randomized studies, the COMPLETE trial demonstrated superiority of multivessel (MV) percutaneous coronary intervention (PCI) over culprit-only PCI for ST-elevation myocardial infarction (STEMI).

OBJECTIVE: To describe temporal trends and institutional variation of MV PCI use for STEMI in the United States to inform how new evidence may influence clinical practice.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study included STEMI admissions involving MV disease from 1598 institutions in the National Cardiovascular Data Registry CathPCI Registry from the third quarter of 2009 to the first quarter of 2018. An MV PCI was defined as a …

Genetics Of Atrial Fibrillation, Jitae A Kim, Mihail G Chelu, Na Li

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Atrial fibrillation is the most common sustained cardiac arrhythmia. In addition to traditional risk factors, it is increasingly recognized that a genetic component underlies atrial fibrillation development. This review aims to provide an overview of the genetic cause of atrial fibrillation and clinical applications, with a focus on recent developments.

RECENT FINDINGS: Genome-wide association studies have now identified around 140 genetic loci associated with atrial fibrillation. Studies into the effects of several loci and their tentative gene targets have identified novel pathways associated with atrial fibrillation development. However, further validations of causality are still needed for many …

The Effects Of Differences In Vaccination Rates Across Socioeconomic Groups On The Size Of Measles Outbreaks, Elizabeth Hunter, John D. Kelleher

Conference papers

Vaccination rates are often presented at the level of a country or region. However, within those areas there might be geographic or demographic pockets that have higher or lower vaccination rates. We use an agent-based model designed to simulate the spread of measles in Irish towns to examine if the effectiveness of vaccination rates to reduce disease at a population level is sensitive to the uniformity of vaccinations across socioeconomic groups. We find that when vaccinations are not applied evenly across socioeconomic groups we see more outbreaks and outbreaks with larger magnitudes.

Enabling Precision Medicine In Cancer Care Through A Molecular Data Warehouse: The Moffitt Experience, Steven A Eschrich, Jamie K Teer, Phillip Reisman, Erin Siegel, Chandan Challa, Patricia Lewis, Katherine Fellows, Everin Malpica, Rodrigo Carvajal, Guillermo Gonzalez, Scott Cukras, Miguel Betin-Montes, Garrick Aden-Buie, Melissa Avedon, Daniel Manning, Aik Choon Tan, Brooke L Fridley, Travis Gerke, Mattias Van Looveren, Amilcar Blake, Jennifer Greenman, Dana E Rollison

Faculty, Staff and Students Publications

PURPOSE: The use of genomics within cancer research and clinical oncology practice has become commonplace. Efforts such as The Cancer Genome Atlas have characterized the cancer genome and suggested a wealth of targets for implementing precision medicine strategies for patients with cancer. The data produced from research studies and clinical care have many potential secondary uses beyond their originally intended purpose. Effective storage, query, retrieval, and visualization of these data are essential to create an infrastructure to enable new discoveries in cancer research.

METHODS: Moffitt Cancer Center implemented a molecular data warehouse to complement the extensive enterprise clinical data warehouse …

Prospective Patient-Reported Symptom Profiles Associated With Pediatric Acute Lymphoblastic Leukemia Relapse, Austin L Brown, Kimberly P Raghubar, Olga A Taylor, Melanie Brooke Bernhardt, Lisa S Kahalley, Wei Pan, Philip J Lupo, Marilyn J Hockenberry, Michael E Scheurer

Faculty, Staff and Students Publications

PURPOSE: Despite improvements in frontline pediatric acute lymphoblastic leukemia (ALL) treatment, relapse remains a concern. Research in adult cancer patients suggests that patient-reported symptoms may predict survival, but the relationship between symptoms and relapse for pediatric ALL has received little attention.

METHODS: Pediatric patients with ALL (age 2-18 years) and/or their primary caregivers completed symptom surveys at the end of induction, start of delayed intensification (DI), start of maintenance cycle 1 (MC1), and start of maintenance cycle 2 (MC2). Symptom clusters for co-occurring fatigue, pain, sleep disruptions, and nausea were defined using latent profile analysis. Hazard ratios (HR) and 95% …

Soluble Angiotensin-Converting Enzyme 2, Cardiac Biomarkers, Structure, And Function, And Cardiovascular Events (From The Atherosclerosis Risk In Communities Study), Aliza Hussain, Olive Tang, Caroline Sun, Xiaoming Jia, Elizabeth Selvin, Vijay Nambi, Aaron Folsom, Gerardo Heiss, Faiez Zannad, Thomas Mosley, Salim S Virani, Josef Coresh, Eric Boerwinkle, Bing Yu, Jonathan W Cunningham, Amil M Shah, Scott D Solomon, James A De Lemos, Ron C Hoogeveen, Christie M Ballantyne

Faculty, Staff and Students Publications

Membrane-bound angiotensin-converting enzyme 2 is important in regulation of the renin-angiotensin-aldosterone system, but the association of cleaved soluble ACE2 (sACE2) with cardiovascular disease (CVD) is unclear. We evaluated the association of sACE2 with cardiac biomarkers, structure, and function and cardiovascular events in the Atherosclerosis Risk in Communities Study. sACE2 was measured in a subset of 497 participants (mean age 78±5.4 years, 53% men, 27% black); Cox regression analyses assessed prospective associations of sACE2 with time to first CVD event at median 6.1-year follow-up. sACE2 was higher in men, blacks, and participants with prevalent CVD, diabetes, or hypertension. Higher sACE2 levels …

Acetyl-Coa And Metabolite Fluxes Regulate White Adipose Tissue Expansion, Jessica B Felix, Aaron R Cox, Sean M Hartig

Faculty, Staff and Students Publications

White adipose tissue (WAT) depends on coordinated regulation of transcriptional and metabolic pathways to respond to whole-body energy demands. We highlight metabolites that contribute to biosynthetic reactions for WAT expansion. Recent studies have precisely defined how byproducts of carbohydrate and lipid metabolism affect physiological and endocrine functions in adipocytes. We emphasize the critical emerging roles of short-chain fatty acids (SCFAs) and tricarboxylic acid (TCA) cycle metabolites that connect lipogenesis to WAT energy balance and endocrine functions. These insights address how adipocytes use small molecules generated from central carbon metabolism to measure responses to nutritional stress.