Digital Commons Network^™

Hypoxia-Inducible Factor (Hif)-2Α Reprograms Liver Macrophages To Protect Against Acute Liver Injury Via The Production Of Interleukin-6, Rachel Y Gao, Meng Wang, Qihui Liu, Dechun Feng, Yankai Wen, Yang Xia, Sean P Colgan, Holger K Eltzschig, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Acetaminophen (APAP) overdose represents the most frequent cause of acute liver failure, resulting in death or liver transplantation in more than one third of patients in the United States. The effectiveness of the only antidote, N-acetylcysteine, declines rapidly after APAP ingestion, long before patients are admitted to the clinic with symptoms of severe liver injury. The direct hepatotoxicity of APAP triggers a cascade of innate immune responses that may exacerbate or limit the progression of tissue damage. A better understanding of this complex mechanism will help uncover targets for therapeutic interventions.

APPROACH AND RESULTS: We observed that …

Beyond An Updated Graded Prognostic Assessment (Breast Gpa): A Prognostic Index And Trends In Treatment And Survival In Breast Cancer Brain Metastases From 1985 To Today, Paul W Sperduto, Shane Mesko, Jing Li, Daniel Cagney, Ayal Aizer, Nancy U Lin, Eric Nesbit, Tim J Kruser, Jason Chan, Steve Braunstein, Jessica Lee, John P Kirkpatrick, Will Breen, Paul D Brown, Diana Shi, Helen A Shih, Hany Soliman, Arjun Sahgal, Ryan Shanley, William Sperduto, Emil Lou, Ashlyn Everett, Drexell Hunter Boggs, Laura Masucci, David Roberge, Jill Remick, Kristin Plichta, John M Buatti, Supriya Jain, Laurie E Gaspar, Cheng-Chia Wu, Tony J C Wang, John Bryant, Michael Chuong, James Yu, Veronica Chiang, Toshimichi Nakano, Hidefumi Aoyama, Minesh P Mehta

Faculty, Staff and Student Publications

PURPOSE: Brain metastases are a common sequelae of breast cancer. Survival varies widely based on diagnosis-specific prognostic factors (PF). We previously published a prognostic index (Graded Prognostic Assessment [GPA]) for patients with breast cancer with brain metastases (BCBM), based on cohort A (1985-2007, n = 642), then updated it, reporting the effect of tumor subtype in cohort B (1993-2010, n = 400). The purpose of this study is to update the Breast GPA with a larger contemporary cohort (C) and compare treatment and survival across the 3 cohorts.

METHODS AND MATERIALS: A multi-institutional (19), multinational (3), retrospective database of 2473 …

Discovery Of A Selective Inhibitor Of Doublecortin Like Kinase 1, Fleur M Ferguson, Behnam Nabet, Srivatsan Raghavan, Yan Liu, Alan L Leggett, Miljan Kuljanin, Radha L Kalekar, Annan Yang, Shuning He, Jinhua Wang, Raymond W S Ng, Rita Sulahian, Lianbo Li, Emily J Poulin, Ling Huang, Jost Koren, Nora Dieguez-Martinez, Sergio Espinosa, Zhiyang Zeng, Cesear R Corona, James D Vasta, Ryoma Ohi, Taebo Sim, Nam Doo Kim, Wayne Harshbarger, Jose M Lizcano, Matthew B Robers, Senthil Muthaswamy, Charles Y Lin, A Thomas Look, Kevin M Haigis, Joseph D Mancias, Brian M Wolpin, Andrew J Aguirre, William C Hahn, Kenneth D Westover, Nathanael S Gray

Faculty, Staff and Students Publications

Doublecortin like kinase 1 (DCLK1) is an understudied kinase that is upregulated in a wide range of cancers, including pancreatic ductal adenocarcinoma (PDAC). However, little is known about its potential as a therapeutic target. We used chemoproteomic profiling and structure-based design to develop a selective, in vivo-compatible chemical probe of the DCLK1 kinase domain, DCLK1-IN-1. We demonstrate activity of DCLK1-IN-1 against clinically relevant patient-derived PDAC organoid models and use a combination of RNA-sequencing, proteomics and phosphoproteomics analysis to reveal that DCLK1 inhibition modulates proteins and pathways associated with cell motility in this context. DCLK1-IN-1 will serve as a versatile tool …

Acute Maltodextrin Supplementation During Resistance Exercise, Dylan T Wilburn, Steven B Machek, Thomas D Cardaci, Paul S Hwang, Darryn S Willoughby

Faculty, Staff and Students Publications

Most of the research investigating the ergogenic enhancing mechanisms of carbohydrate have been conducted using aerobic based exercise. Therefore, the purpose of this study was to investigate the effects of pre-exercise maltodextrin ingestion on resistance exercise performance, serum insulin, epinephrine, glucose, and muscle glycogen concentrations. In a double blind, cross over, repeated measures design, participants completed four sets to failure at 70% of 1-RM with 45s rest on the angled leg press with or without pre-exercise maltodextrin (2g/kg) after a 3hr fast. Serum glucose, epinephrine, and insulin were assessed at baseline, 30 min post-ingestion, immediately after, and 1hr post-exercise with …

Emergency Potassium Normalization Treatment Including Sodium Zirconium Cyclosilicate: A Phase Ii, Randomized, Double-Blind, Placebo-Controlled Study (Energize), W Frank Peacock, Zubaid Rafique, Konstantin Vishnevskiy, Edward Michelson, Elena Vishneva, Tatiana Zvereva, Rajaa Nahra, Dao Li, Joseph Miller

Faculty, Staff and Students Publications

OBJECTIVES: Sodium zirconium cyclosilicate (SZC) is a novel, highly selective potassium binder currently approved in the United States and European Union for treatment of hyperkalemia. This pilot evaluation explored the efficacy of SZC with insulin and glucose as hyperkalemia treatment in the emergency department (ED).

METHODS:This exploratory, phase II, multicenter, randomized, double‐blind, placebo‐controlled study (NCT03337477) enrolled adult ED patients with blood potassium ≥ 5.8 mmol/L. Patients were randomized 1:1 to receive SZC 10 g or placebo, up to three times during a 10‐hour period, with insulin and glucose. The primary efficacy outcome was the mean change in serum …

Pooled Crispr Screens With Imaging On Microraft Arrays Reveals Stress Granule-Regulatory Factors, Emily C Wheeler, Anthony Q Vu, Jaclyn M Einstein, Matthew Disalvo, Noorsher Ahmed, Eric L Van Nostrand, Alexander A Shishkin, Wenhao Jin, Nancy L Allbritton, Gene W Yeo

Faculty, Staff and Students Publications

Genetic screens using pooled CRISPR-based approaches are scalable and inexpensive, but restricted to standard readouts, including survival, proliferation and sortable markers. However, many biologically relevant cell states involve cellular and subcellular changes that are only accessible by microscopic visualization, and are currently impossible to screen with pooled methods. Here we combine pooled CRISPR-Cas9 screening with microraft array technology and high-content imaging to screen image-based phenotypes (CRaft-ID; CRISPR-based microRaft followed by guide RNA identification). By isolating microrafts that contain genetic clones harboring individual guide RNAs (gRNA), we identify RNA-binding proteins (RBPs) that influence the formation of stress granules, the punctate protein-RNA …

Rapid And Efficient Synthetic Assembly Of Multiplex Luciferase Reporter Plasmids For The Simultaneous Monitoring Of Up To Six Cellular Signaling Pathways, Alejandro Sarrion-Perdigones, Yezabel Gonzalez, Koen J T Venken

Faculty, Staff and Students Publications

High-throughput cell-based screening assays are valuable tools in the discovery of chemical probes and therapeutic agents. Such assays are designed to examine the effects of small compounds on targets, pathways, or phenotypes participating in normal and disease processes. While most cell-based assays measure single quantities, multiplexed assays seek to address these limitations by obtaining multiple simultaneous measurements. The signals from such measurements should be independently detectable and cover large dynamic ranges. Luciferases are good candidates for generation of such signals. They are genetically encoded, versatile, and cost-effective, and their output signals can be sensitively detected. We recently developed a multiplex …

Simultaneous Examination Of Cellular Pathways Using Multiplex Hextuple Luciferase Assaying, Alejandro Sarrion-Perdigones, Lyra Chang, Yezabel Gonzalez, Tatiana Gallego-Flores, Damian W Young, Koen J T Venken

Faculty, Staff and Students Publications

Multiplex experimentation that can assay multiple cellular signaling pathways in the same cells requires orthogonal genetically encoded reporters that report over large dynamic ranges. Luciferases are cost-effective, versatile candidates whose output signals can be sensitively detected in a multiplex fashion. Commonly used dual luciferase reporter assays detect one luciferase that is coupled to a single cellular pathway, and a second that is coupled to a control pathway for normalization purposes. We expanded this approach to multiplex hextuple luciferase assaying that can report on five cellular signaling pathways and one control, each of which is encoded by a unique luciferase. Light …

Decomposing Loss Aversion From Gaze Allocation And Pupil Dilation, Feng Sheng, Arjun Ramakrishnan, Darsol Seok, Wenjia Joyce Zhao, Samuel Thelaus, Puti Cen, Michael Louis Platt

Faculty, Staff and Student Publications

Loss-averse decisions, in which one avoids losses at the expense of gains, are highly prevalent. However, the underlying mechanisms remain controversial. The prevailing account highlights a valuation bias that overweighs losses relative to gains, but an alternative view stresses a response bias to avoid choices involving potential losses. Here we couple a computational process model with eye-tracking and pupillometry to develop a physiologically grounded framework for the decision process leading to accepting or rejecting gambles with equal odds of winning and losing money. Overall, loss-averse decisions were accompanied by preferential gaze toward losses and increased pupil dilation for accepting gambles. …

Myeloma Cells Shift Osteoblastogenesis To Adipogenesis By Inhibiting The Ubiquitin Ligase Murf1 In Mesenchymal Stem Cells, Zhiqiang Liu, Huan Liu, Jin He, Pei Lin, Qiang Tong, Jing Yang

Faculty, Staff and Students Publications

The suppression of bone formation is a hallmark of multiple myeloma. Myeloma cells inhibit osteoblastogenesis from mesenchymal stem cells (MSCs), which can also differentiate into adipocytes. We investigated myeloma-MSC interactions and the effects of such interactions on the differentiation of MSCs into adipocytes or osteoblasts using single-cell RNA sequencing, in vitro co-culture, and subcutaneous injection of MSCs and myeloma cells into mice. Our results revealed that the α4 subunit of integrin on myeloma cells stimulated vascular cell adhesion molecule 1 (VCAM1) on MSCs, leading to the activation of protein kinase C β1 (PKCβ1) signaling and repression of the muscle ring-finger …

Age-Dependent Involvement Of Gut Mast Cells And Histamine In Post-Stroke Inflammation, Maria Pilar Blasco, Anjali Chauhan, Pedram Honarpisheh, Hilda Ahnstedt, John D'Aigle, Arunkumar Ganesan, Sriram Ayyaswamy, Frank Blixt, Susan Venable, Angela Major, David Durgan, Anthony Haag, Julia Kofler, Robert Bryan, Louise D Mccullough, Bhanu Priya Ganesh

Faculty, Staff and Students Publications

BACKGROUND: Risk of stroke-related morbidity and mortality increases significantly with age. Aging is associated with chronic, low-grade inflammation, which is thought to contribute to the poorer outcomes after stroke seen in the elderly. Histamine (HA) is a major molecular mediator of inflammation, and mast cells residing in the gut are a primary source of histamine.

METHODS: Stroke was induced in male C57BL/6 J mice at 3 months (young) and 20 months (aged) of age. Role of histamine after stroke was examined using young (Yg) and aged (Ag) mice; mice underwent MCAO surgery and were euthanized at 6 h, 24 h, …

Tfeb Regulates Murine Liver Cell Fate During Development And Regeneration, Nunzia Pastore, Tuong Huynh, Niculin J Herz, Alessia Calcagni', Tiemo J Klisch, Lorenzo Brunetti, Kangho Ho Kim, Marco De Giorgi, Ayrea Hurley, Annamaria Carissimo, Margherita Mutarelli, Niya Aleksieva, Luca D'Orsi, William R Lagor, David D Moore, Carmine Settembre, Milton J Finegold, Stuart J Forbes, Andrea Ballabio

Faculty, Staff and Students Publications

It is well established that pluripotent stem cells in fetal and postnatal liver (LPCs) can differentiate into both hepatocytes and cholangiocytes. However, the signaling pathways implicated in the differentiation of LPCs are still incompletely understood. Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is known to be involved in osteoblast and myeloid differentiation, but its role in lineage commitment in the liver has not been investigated. Here we show that during development and upon regeneration TFEB drives the differentiation status of murine LPCs into the progenitor/cholangiocyte lineage while inhibiting hepatocyte differentiation. Genetic interaction studies show that …

Communication Strategies To Address Vaccine Hesitancy In Healthcare Settings And On Social Media, Lindy U. Mcgee Md, Jinny Suh Jd

Journal of Applied Research on Children: Informing Policy for Children at Risk

Abstract

Vaccine hesitancy is now recognized as a threat to global health. Its causes are complex, and it is defined by a resistance to or questioning of immunization. It is important to address vaccine hesitancy directly before people who are hesitant become vaccine refusers or anti-vaccine. Fortunately, with evidence-based information delivered with a compassionate communication style many of those who are hesitant to vaccinate can be persuaded to ultimately vaccinate. This paper aims to explain successful communication strategies used to address vaccine hesitancy in healthcare settings and on social media. Vaccine hesitant parents frequently list their child’s healthcare provider as …

Knowledge About The Human Papillomavirus Vaccine Among Employees At A Tertiary Cancer Center: Room For Improvement, Kristina R. Dahlstrom, Erich M. Sturgis, Ronald A. Depinho, Ernest Hawk, George P. Baum, Elenita Tamez, Rosalind S. Bello, Lori D. Stevens, Lois M. Ramondetta

Journal of Applied Research on Children: Informing Policy for Children at Risk

Introduction: The human papillomavirus (HPV) vaccine is recommended by the U.S. Centers for Disease Control and Prevention for routine vaccination of boys and girls to protect against HPV-related cancers and genital warts. To meet the Healthy People 2020 target for HPV vaccination, health care providers must understand the importance of strongly recommending the HPV vaccine to all eligible adolescents. We sought to determine HPV vaccination patterns among employees at a tertiary cancer center and their children and attitudes regarding HPV vaccination among the employees.

Methods: All employees at a tertiary cancer center were invited to participate in a cross-sectional survey …

Proteolysis-Targeting Chimera (Protac) For Targeted Protein Degradation And Cancer Therapy, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

Proteolysis-targeting chimera (PROTAC) has been developed to be a useful technology for targeted protein degradation. A bifunctional PROTAC molecule consists of a ligand (mostly small-molecule inhibitor) of the protein of interest (POI) and a covalently linked ligand of an E3 ubiquitin ligase (E3). Upon binding to the POI, the PROTAC can recruit E3 for POI ubiquitination, which is subjected to proteasome-mediated degradation. PROTAC complements nucleic acid-based gene knockdown/out technologies for targeted protein reduction and could mimic pharmacological protein inhibition. To date, PROTACs targeting ~ 50 proteins, many of which are clinically validated drug targets, have been successfully developed with several …

A Goldenbraid Cloning System For Synthetic Biology In Social Amoebae, Peter Kundert, Alejandro Sarrion-Perdigones, Yezabel Gonzalez, Mariko Katoh-Kurasawa, Shigenori Hirose, Peter Lehmann, Koen J T Venken, Gad Shaulsky

Faculty, Staff and Students Publications

GoldenBraid is a rapid, modular, and robust cloning system used to assemble and combine genetic elements. Dictyostelium amoebae represent an intriguing synthetic biological chassis with tractable applications in development, chemotaxis, bacteria-host interactions, and allorecognition. We present GoldenBraid as a synthetic biological framework for Dictyostelium, including a library of 250 DNA parts and assemblies and a proof-of-concept strain that illustrates cAMP-chemotaxis with four fluorescent reporters coded by one plasmid.

T​He​ E​Ffect​ ​Of​ U​Nconventional​ G​As​ ​And​ O​Il​ D​Rilling​ E​Missions​ ​On​ A​Sthma​ ​And​ R​Espiratory D​Iseases​ ​In​ ​The​ B​Arnett​ S​Hale​ ​Of​ T​Exas, Stella A. Okoroafor

Dissertations and Theses (Open Access)

Unconventional gas and oil drilling (UGOD) has increased substantially in the United States for more than a decade. The resultant environmental unsafe air pollution effects of UGOD both locally and regionally have been well documented in the literature. Despite the dramatic increase in unconventional well drilling and the toxicant exposure, the health consequences of UGOD remain largely uncertain. This study assesses the relationship between active wells and healthcare use for respiratory diseases by zip code from 2004 to 2008 in the Barnett shale area of Texas. The first modern shale gas well was drilled in the Barnett shale area of …

Utility Of Plasma Biomarkers In The Validation Of Reported Loc & Pta For Gcs 13-15 Patients: A Track-Tbi Pilot Study, Jeffrey Brennan

Dissertations and Theses (Open Access)

Depending on a brain injury patient to accurately report their duration of unconsciousness and amnesia is clearly flawed. We constructed biomarker-based models to validate these self-reported measurements using a GCS 13-15 subset of participants from TRACK-TBI, a multi-institutional study on traumatic brain injury. Potential covariates were assessed for significant interactions with biomarker level. We report that the predictions of LOC and PTA failed. GFAP exhibited the most consistent serum level increase between categories of both LOC and PTA. Given a number of issues with the study sample, we recommend continued investigation on the prediction of LOC and PTA using a …

Effects Of Penfluridol On Integrin-Fak Signaling And Tumor Cell Killing In Combination With Oncolytic Hsv In Glioblastoma, Mitra Nair

Dissertations and Theses (Open Access)

Integrins are known to play an important role in activating multiple intracellular pathways, one of which is focal adhesion kinase (FAK). Phosphorylation of FAK can lead to the activation of various downstream signaling pathways that can increase tumor cell growth and proliferation, making it an ideal target for cancer therapeutics. Due to the fact that many FAK inhibitors are limited in their penetration of the blood brain barrier, we investigated the use of Penfluridol, an antipsychotic drug known to attenuate integrin expression at a transcriptional level, in combination with oncolytic herpes simplex I virus (oHSV) in a glioblastoma model. We …

Table-To-Text: Generating Descriptive Text For Scientific Tables From Randomized Controlled Trials, Qiang Wei

Dissertations and Theses (Open Access)

Unprecedented amounts of data have been generated in the biomedical domain, and the bottleneck for biomedical research has shifted from data generation to data management, interpretation, and communication. Therefore, it is highly desirable to develop systems to assist in text generation from biomedical data, which will greatly improve the dissemination of scientific findings. However, very few studies have investigated issues of data-to-text generation in the biomedical domain. Here I present a systematic study for generating descriptive text from tables in randomized clinical trials (RCT) articles, which includes: (1) an information model for representing RCT tables; (2) annotated corpora containing pairs …

Caregivers Of Medically Fragile Children With Technology Needs, Vuong Prieto

Dissertations and Theses (Open Access)

Background: Medically fragile children (MFC) with technology needs have complex and challenging health care needs in the home setting. Providing care can have both negative and positive psychological and social impacts on the caregivers’ health related quality of life (HRQOL).

Aims: a) To examine the relationship between caregiver burden, caregiving satisfaction, and HRQOL in caregivers of MFC with technology needs. b) To identify caregiver and child related variables of caregiver burden and caregiving satisfaction.

Methods: A cross sectional study was conducted over four months at a children’s hospital and outpatient clinics. Caregivers completed three one-time surveys (Zarit Burden Interview, Caregiving …

Maternal And Newborn Outcomes For Women Living With Hiv In Adapted Group Prenatal Care, Jodi Behr

Dissertations and Theses (Open Access)

Background: For women living with HIV (WLWH), managing HIV and their pregnancy can be challenging. WLWH have been identified at risk for lower adherence to prenatal care, increased maternal HIV Plasma RNA levels, decreased newborn gestational age, and newborn birth weight. Improved outcomes have been found with group prenatal care. Maternal and newborn outcomes for WLWH and their newborns in group prenatal care compared to WLWH and their newborns in individual care have not been evaluated.

Purpose: The aims of this study were to evaluate group differences between WLWH who attended individual prenatal care appointments (IC) compared to WLWH who …

A Partial Likelihood Approach To Longitudinal Categorical Data Using A Continuous Time Semi-Markov Chain Model, Kusha A. Mohammadi

Dissertations and Theses (Open Access)

Longitudinal studies have been critical in understanding the characteristics of chronic diseases or interventions. Since many processes have natural multi-categorical responses over time, multi-state stochastic models have been used to estimate the transition rates between stages. Some multi-state models applied in practice assume the Markov property. The Markov property constrains the sojourn distribution to be exponentially distributed. While useful theoretical properties arise by the Markov assumption, we will consider a more flexible framework by allowing arbitrarily distributed waiting times. This describes a semi-Markov process which has already been applied to various fields in Public Health. Similar to Markov model developments, …

Statistical Methods For Functional Annotation-Based Rare Variant Association Analysis, Yiding Ma

Dissertations and Theses (Open Access)

Despite ongoing large-scale population-based whole-genome sequencing (WGS) projects such as the TOPMed program, WGS-based association analysis of complex traits remains a tremendous challenge. External biological knowledge, such as functional annotations based on the ENCODE, Epigenomics Roadmap and GTEx projects, may be helpful in distinguishing causal rare variants from neutral ones; however, each functional annotation can only provide certain aspects of the biological functions. Our knowledge for selecting informative annotations a priori is limited and incorporating non-informative annotations will introduce noise and lose power. In the first part of this dissertation, we propose FunSPU, a versatile and adaptive test that incorporates …

The Intersection Of Diet, Health And The Environment: Plant Based Diets And Public Health, Christine E. Jovanovic

Dissertations and Theses (Open Access)

Both globally and within the United States, chronic disease has become a major driver of mortality and morbidity. In the United States in 2017, the top ten causes of mortality accounted for 74% of all deaths [2]; of these causes, half are closely linked to diet (heart disease, cancer, stroke, Alzheimer’s and diabetes). [3] In 2013, Ioannidis estimated that 26% of deaths and 14% of disability adjusted life years (DALYs) in the United States may be attributable to dietary risk factors, controlling for obesity. [4] At the same time, diet also has an important impact on the environment. Direct emissions …

Exploring Community-Based Weight Loss Initiatives, Retention, And Motivation, Miriam Martinez

Dissertations and Theses (Open Access)

Obesity puts individuals at risk of developing diabetes, cardiovascular disease, and cancer. Traditionally obesity was primarily perceived as a personal disorder requiring treatment at the individual level. Strategies to prevent obesity have shifted to an ecological approach. Organizations such as the World Health Organization recommend population based community approaches that connect people, families, schools, and municipalities. Community programs to facilitate weight loss are an effective strategy to reach large populations. The overall goal of this study is to assess community programs, factors associated with retention, and motivation for completing a community weight-loss initiative. A systematic review was conducted to characterize …

A Mixed- Methods Examination Of The Healthcare, Social Support, And Religious Needs Of Sexual And Gender Minority (Sgm) Older Adults In Texas, Jennifer Lynn Holcomb

Dissertations and Theses (Open Access)

Shared historical and social contexts influence a generational group’s needs, risk factors, and resiliency mechanisms. Sexual and gender minority (SGM) older adults have experienced structural exclusion and systematic discrimination throughout their lifetime. The minority stress model posits that SGM individuals experience stressors, like discrimination, unique to their social status which affect physical and mental health. SGM older adults experience worse physical and mental health outcomes than their heterosexual peers suggesting unique needs for SGM older adults. Research also points to resiliency mechanisms that offset the impact of stressors on SGM older adults. The examination of these needs and resiliency mechanisms …

Consider Us: Analysis Of National Mammography Screening Recommendations On African American Women, Gayla M. Ferguson

Dissertations and Theses (Open Access)

Breast cancer is the second most common cause of cancer related death in women in the United States with one in eight women expected to develop the disease in their lifetime. Unfortunately, breast cancer is the leading cause of cancer related death among African American women. African American women are four times more likely to die from breast cancer that Caucasian women. Mammography screenings are the most effective method of reducing breast cancer mortality in African American women. This study aimed to determine if the changes made to the mammography screening recommendations put forth by the U.S. Preventive Services Task …

The Role Of Dna Methylation In White Matter Hyperintensity Burden: An Integrative Approach, Yunju Yang

Dissertations and Theses (Open Access)

Cerebral white matter hyperintensities (WMH) on MRI are an indicator of cerebral small vessel disease, a major risk factor for vascular dementia and stroke. DNA methylation may contribute to the molecular underpinnings of WMH, which are highly heritable. We performed a meta-analysis of 11 epigenome-wide association studies in 6,019 middle-aged to elderly subjects, who were free of dementia and stroke and were of African (AA) or European (EA) descent. In each study, association between WMH volume and each CpG was tested within ancestry using a linear mixed model, adjusted for age, sex, total intracranial volume, white blood cell count, technical …

Exploration Of Breastfeeding As A Protective Factor For Breast Cancer In South African Women: A Nested Case-Control Study, Booker S. Quiera

Dissertations and Theses (Open Access)

Background. South African’s (SA) breast cancer incidence rate is continually increasing (39 per 100,000 (2012) versus 46.2 per 100,000 (2018) with trends towards later-stage diagnosis. In previous literature, breastfeeding has been assessed as a protective factor for breast cancer; however, the SA population experiences inconsistent breastfeeding trends, rates, and support services. Therefore, this study will evaluate the inverse association between breast cancer and breastfeeding history. Methods. Cases (breast cancer) and controls (mastalgia) were matched 1:1 on clinical visit from May-August 2019 at Groote Schuur Hospital (GSH) in Cape Town, Western Cape, South Africa. Breastfeeding history, breast carcinoma diagnosis, and clinically …