Open Access. Powered by Scholars. Published by Universities.®

Medicine and Health Sciences Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 30 of 290

Full-Text Articles in Medicine and Health Sciences

Frequency Of Complications Following Spinal Fusion In Children With Cerebral Palsy, Nili S. Amir May 2020

Frequency Of Complications Following Spinal Fusion In Children With Cerebral Palsy, Nili S. Amir

GSBS Dissertations and Theses

Background:

Neuromuscular Scoliosis is a frequent complication of Cerebral Palsy that requires surgical management including spinal fusion. The objective of this observational study was to describe differences in the frequency of postoperative complications in children with Cerebral Palsy following spinal fusion surgery compared to children with Idiopathic Scoliosis.

Methods:

The 2016 Kids’ Inpatient Database was queried to identify pediatric patients (old) with concurrent diagnoses of Cerebral Palsy and Neuromuscular Scoliosis undergoing spinal fusion surgery. Cases were compared to children without Cerebral Palsy and with a diagnosis of Idiopathic Scoliosis undergoing the same procedure. Fitted Poisson regression analysis with robust variance ...


Association Of Race/Ethnicity And Population Density With Disparities In Timeliness Of Rectal Cancer Therapy, Susanna S. Hill Apr 2020

Association Of Race/Ethnicity And Population Density With Disparities In Timeliness Of Rectal Cancer Therapy, Susanna S. Hill

GSBS Dissertations and Theses

Objective:

Access to care is key to effective rectal cancer treatment. We hypothesized that ethnic/racial minorities living in high population density areas would have the greatest delays in cancer care compared to whites living in medium population density areas.

Methods:

Using 2004-2016 National Cancer DataBase data, we identified stage I-III patients with invasive rectal adenocarcinoma who underwent surgery. The data were analyzed by race/ethnicity (whites, blacks, or Hispanics) and population density (metropolitan or urban/rural). Multivariable ANCOVA was performed to evaluate the duration of time from diagnosis to surgery.

Results:

The study population consisted of 76,131 patients ...


Optimizing Crispr/Cas9 For Gene Silencing Of Sod1 In Mouse Models Of Als, Zachary C. Kennedy Aug 2019

Optimizing Crispr/Cas9 For Gene Silencing Of Sod1 In Mouse Models Of Als, Zachary C. Kennedy

GSBS Dissertations and Theses

Mutations in the SOD1 gene are the best characterized genetic cause of amyotrophic lateral sclerosis (ALS) and account for ~20% of inherited cases and 1-3% of sporadic cases. The gene-editing tool Cas9 can silence mutant genes that cause disease, but effective delivery of CRISPR-Cas9 to the central nervous system (CNS) remains challenging. Here, I developed strategies using canonical Streptococcus pyogenes Cas9 to silence SOD1. In the first strategy, I demonstrate effectiveness of systemic delivery of guide RNA targeting SOD1 to the CNS in a transgenic mouse model expressing human mutant SOD1 and Cas9. Silencing was observed in both the brain ...


Comprehensive Computational Assessment And Evaluation Of Epstein Barr Virus (Ebv) Variations, Mirnas, And Ebers In Ebl, Aml And Across Cancers, Mercedeh J. Movassagh Apr 2019

Comprehensive Computational Assessment And Evaluation Of Epstein Barr Virus (Ebv) Variations, Mirnas, And Ebers In Ebl, Aml And Across Cancers, Mercedeh J. Movassagh

GSBS Dissertations and Theses

Viruses are known to be associated with 20% of human cancers. Epstein Barr virus (EBV) in particular is the first virus associated with human cancers. Here, we computationally detect EBV and explore the effects of this virus across cancers by taking advantage of the fact that EBV microRNAs (miRNAs) and Epstein Barr virus small RNAs (EBERs) are expressed at all viral latencies. We identify and characterize two sub-populations of EBV positive tumors: those with high levels of EBV miRNA and EBERS expression and those with medium levels of expression.

Based on principal component analysis (PCA) and hierarchical clustering of viral ...


Gene Therapy For Amyotrophic Lateral Sclerosis: An Aav Mediated Rnai Approach For Autosomal Dominant C9orf72 Associated Als, Gabriela Toro Mar 2019

Gene Therapy For Amyotrophic Lateral Sclerosis: An Aav Mediated Rnai Approach For Autosomal Dominant C9orf72 Associated Als, Gabriela Toro

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is a terminal neurodegenerative disease that affects motor neurons causing progressive muscle weakness and respiratory failure. In 2011, the presence of a hexanucleotide repeat expansion within chromosome 9 open reading frame 72(C9ORF72) was identified in ALS patient samples, becoming the major known genetic cause for ALS and frontotemporal dementia (FTD). Carriers of this mutation present reduced levels of C9ORF72 mRNA, RNA foci produced by the aggregating expansion and toxic dipeptides generated through repeat-associated non-ATG translation. These findings have led to multiple hypotheses on the pathogenesis of C9ORF72: 1) Haploinsufficiency, 2) RNA gain-of-function, 3) RAN Translation ...


Religiosity And Patient Activation And Health Outcomes Among Hospital Survivors Of An Acute Coronary Syndrome, Hawa Ozien Abu Mar 2019

Religiosity And Patient Activation And Health Outcomes Among Hospital Survivors Of An Acute Coronary Syndrome, Hawa Ozien Abu

GSBS Dissertations and Theses

Background: Religious involvement is widespread and may influence patient engagement with their healthcare (patient activation) and health outcomes. This dissertation examined the association between religiosity and patient activation, changes in health-related quality of life (HRQOL), readmissions, and survival after hospitalization for acute coronary syndrome (ACS).

Methods: We recruited 2,174 patients hospitalized for ACS in Georgia and Central Massachusetts (2011-2013) in a prospective cohort study. Participants self-reported three items assessing religiosity – strength/comfort from religion, petition prayers for health, and awareness of intercessory prayers by others. Patient activation was measured using the 6-item Patient Activation Measure. Generic HRQOL was assessed ...


Understanding The Experience And Evaluating The Occurrence Of Depression In A Sample Of Pregnant Veterans, Aimee R. Kroll-Desrosiers Jan 2019

Understanding The Experience And Evaluating The Occurrence Of Depression In A Sample Of Pregnant Veterans, Aimee R. Kroll-Desrosiers

GSBS Dissertations and Theses

Background: The Veterans Health Administration (VHA) encourages depression screening and treatment for pregnant veterans; however, rates of depression symptoms and treatment utilization during pregnancy have not been well-studied.

Methods: We used data from the Maternity Care Coordination for Women Veterans cohort study. Specifically, our aims were to: 1) examine rates and correlates of depression symptoms in a sample of pregnant veterans; 2) understand mental health care treatment utilization and explore the experiences of veterans accessing mental health care at the VHA during pregnancy; and 3) examine VHA mental health provider's perspectives on depression screening and treatment in the perinatal ...


Characterization Of The Caspase-3 Cleavage Motif Of The Salmonella Typhimurium Effector Protein Sifa And Its Role In Pathogenesis, Samir Patel Nov 2018

Characterization Of The Caspase-3 Cleavage Motif Of The Salmonella Typhimurium Effector Protein Sifa And Its Role In Pathogenesis, Samir Patel

GSBS Dissertations and Theses

Salmonella enterica serovar Typhimurium (S. Typhimurium) is a Gram-negative facultative anaerobe that induces severe inflammation resulting in gastroenteritis. In the case of S. Typhimurium infection, induction of an inflammatory response has been linked to its primary virulence mechanism, the type III secretion system (T3SS). The T3SS secretes protein effectors that exploit the host’s cell biology to facilitate bacterial entry and intracellular survival, and to modulate the host immune response.

One such effector, SifA, is a bi-functional T3SS effector protein that plays an important role in Salmonella virulence. The N-terminal domain of SifA binds SifA-Kinesin-Interacting-Protein (SKIP), and via an interaction ...


Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry Oct 2018

Tumor-Stroma Interactions Differentially Alter Drug Sensitivity Based On The Origin Of Stromal Cells, Benjamin D. Landry

GSBS Dissertations and Theses

Tumor heterogeneity observed between patients has made it challenging to develop universal or broadly effective cancer therapies. Therefore, an ever-growing movement within cancer research aims to tailor cancer therapies to individual patients or specific tumor subtypes. Tumor stratification is generally dictated by the genomic mutation status of the tumor cells themselves. Importantly, non-genetic influences – such as interactions between tumor cells and other components of the tumor microenvironment – have largely been ignored. Therefore, in an effort to increase treatment predictability and efficacy, we investigated how tumor-stroma interactions contribute to drug sensitivity and drug resistance.

I designed a high throughput co-culture screening ...


Fus And Excitotoxicity Cross Paths In Als: New Insights Into Cellular Stress And Disease, Maeve Tischbein Aug 2018

Fus And Excitotoxicity Cross Paths In Als: New Insights Into Cellular Stress And Disease, Maeve Tischbein

GSBS Dissertations and Theses

Amyotrophic lateral sclerosis (ALS) is an incurable and fatal neurodegenerative disease characterized by motor neuron loss. Although pathological mutations exist in >15 genes, the mechanism(s) underlying ALS are unknown. FUS is one such gene and encodes the nuclear RNA-binding protein (RBP), fused in sarcoma (FUS), which actively shuttles between the nucleus and cytoplasm. Intriguingly, nearly half of the ALS mutations identified in FUS cause this protein to mislocalize, suggesting that FUS localization is relevant to disease.

Here, we found that excitotoxicity, a neuronal stress caused by aberrant glutamate signaling, induces the rapid redistribution of FUS and additional disease-linked RBPs ...


Predictors Of Patient Activation At Acs Hospital Discharge And Health Care Utilization In The Subsequent Year, Rebecca L. Kinney Aug 2018

Predictors Of Patient Activation At Acs Hospital Discharge And Health Care Utilization In The Subsequent Year, Rebecca L. Kinney

GSBS Dissertations and Theses

Background. AHA guidelines have been established to reduce Acute Coronary Syndrome (ACS)-related morbidity, mortality and recurrent events post-discharge. These recommendations emphasize the patient as an engaged member of the health care team in secondary prevention efforts. Patients with high levels of activation are more likely to perform activities that will promote their own health and are more likely to have their health care needs met. Despite evidence and strong expert consensus supporting patients as active collaborators in their own ACS care, the complexity and unexpected realities of self-managing one’s care at home are often underestimated. This study seeks ...


National Trends In Elective Ileal Pouch-Anal Anastomosis For Ulcerative Colitis, Chau Maggie Hoang Jun 2018

National Trends In Elective Ileal Pouch-Anal Anastomosis For Ulcerative Colitis, Chau Maggie Hoang

GSBS Dissertations and Theses

Background: Recent national trends and distribution of ileal pouch-anal anastomosis (IPAA) procedures for patients with ulcerative colitis (UC) are unknown. We examined the frequency of use of elective IPAA procedures among patients with UC and the distribution of IPAA procedures across more than 140 U.S. academic medical centers and their affiliates.

Methods: Data were obtained from the University HealthSystem Consortium for patients with a primary diagnosis of UC admitted electively between 2012 and 2015.

Results: The mean age of the study population (n=6,875) was 43 years and 57% were men. Among these, one-third (n=2,307) underwent ...


Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti May 2018

Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti

GSBS Dissertations and Theses

Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.

We established that cholesterol-conjugated siRNAs passively associate ...


A Suite Of Computational Tools To Interrogate Sequence Data With Local Haplotype Analysis Within Complex ​Plasmodium​ Infections And Other Microbial Mixtures, Nicholas J. Hathaway Mar 2018

A Suite Of Computational Tools To Interrogate Sequence Data With Local Haplotype Analysis Within Complex ​Plasmodium​ Infections And Other Microbial Mixtures, Nicholas J. Hathaway

GSBS Dissertations and Theses

The rapid development of DNA sequencing technologies has opened up new avenues of research, including the investigation of population structure within infectious diseases (both within patient and between populations). In order to take advantage of these advances in technologies and the generation of new types of data, novel bioinformatics tools are needed that won’t succumb to artifacts introduced by the data generation, and thus provide accurate and precise results. To achieve this goal I have create several tools.

First, SeekDeep, a pipeline for analyzing targeted amplicon sequencing datasets from various technologies, is able to achieve 1-base resolution even at ...


Clostridium Difficile Colonization And Infection In The Elderly And Associations With The Aging Intestinal Microbiome, John P. Haran Mar 2018

Clostridium Difficile Colonization And Infection In The Elderly And Associations With The Aging Intestinal Microbiome, John P. Haran

GSBS Dissertations and Theses

The widespread use of antibiotics has led to dramatic increases in the incidence and severity of Clostridium difficile infection (CDI). No group of patients suffers more from CDI than the elderly. Nursing homes (NH) represent the perfect storm of a vulnerable group of frail elders living in confined communities. Nursing home residents suffer from increased morbidity and mortality from CDI and corresponding high rates of C. difficile colonization. Upwards of 40 to 50% of CDI current cases originate from NHs and the prevalence of colonization rates remain high within these facilities, with as many as half of the residents being ...


Identification Of Novel Genetic Variations For Amyotrophic Lateral Sclerosis (Als), Guang Xu Feb 2018

Identification Of Novel Genetic Variations For Amyotrophic Lateral Sclerosis (Als), Guang Xu

GSBS Dissertations and Theses

A list of genes have been identified to carry mutations causing familial ALS such as SOD1, TARDBP, C9orf72. But for sporadic ALS, which is 90% of all ALS cases, the underlying genetic variants are still largely unknown. There are multiple genome-wide association study (GWAS) for sporadic ALS, but usually a large number nominated SNP can hardly be replicated in larger cohort analysis. Also majority of GWAS SNP lie within noncoding region of genome, imposing a huge challenge to study their biological role in ALS pathology. With the rapid development of next-generation sequencing technology, we are able to sequence exome and ...


Investigating The Structural Basis For Human Disease: Apobec3a And Profilin, Tania V. Silvas Jan 2018

Investigating The Structural Basis For Human Disease: Apobec3a And Profilin, Tania V. Silvas

GSBS Dissertations and Theses

Analyzing protein tertiary structure is an effective method to understanding protein function. In my thesis study, I aimed to understand how surface features of protein can affect the stability and specificity of enzymes. I focus on 2 proteins that are involved in human disease, Profilin (PFN1) and APOBEC3A (A3A). When these proteins are functioning correctly, PFN1 modulates actin dynamics and A3A inhibits retroviral replication. However, mutations in PFN1 are associated with amyotrophic lateral sclerosis (ALS) while the over expression of A3A are associated with the development of cancer. Currently, the pathological mechanism of PFN1 in this fatal disease is unknown ...


Barriers To Healthcare Access And Patient Outcomes After A Hospitalization For An Acute Coronary Syndrome And Other Acute Conditions, Nathaniel A. K. Erskine Nov 2017

Barriers To Healthcare Access And Patient Outcomes After A Hospitalization For An Acute Coronary Syndrome And Other Acute Conditions, Nathaniel A. K. Erskine

GSBS Dissertations and Theses

Background: Guideline-concordant therapies for survivors of an acute coronary syndrome (ACS) hospitalization require healthcare access, something that millions of Americans lack.

Methods and Results: Using data from a prospective cohort study of over 2,000 survivors of a hospitalization for an ACS in central Massachusetts and Georgia from 2011 to 2013, the first two aims of this thesis sought to identify the post-discharge consequences for survival and health status of having: 1) financial barriers to healthcare, 2) no usual source of care, and 3) transportation barriers. We found that patients lacking a usual source of care and having a transportation ...


Investigating The Peptide-Mhc Specificity Of Alloreactive T Cells And Natural T Regulatory Cells Using A Self-Peptide Display Library, Brian R. Duke Nov 2017

Investigating The Peptide-Mhc Specificity Of Alloreactive T Cells And Natural T Regulatory Cells Using A Self-Peptide Display Library, Brian R. Duke

GSBS Dissertations and Theses

T cells use their highly variable T cell receptor (TCR) to engage major histocompatibility molecules (MHC) presenting peptides on the surface of antigen presenting cells during an immune response. The TCR repertoire of developing T cells is shaped by thymic selection, resulting in a self-tolerant and foreign peptide specific naïve T cell population. However, naive T cells are alloreactive and generate immune responses towards foreign MHC alleles in clinical settings involving transplantation. While T cell immune responses towards foreign pathogens are peptide specific, the overall specificity of allo-responses is still debated.

Under normal circumstances, immune system homeostasis and self-tolerance is ...


Characterization Of Adipose Tissue Inflammation In Alcoholic Liver Disease, Melissa A. Fulham Nov 2017

Characterization Of Adipose Tissue Inflammation In Alcoholic Liver Disease, Melissa A. Fulham

GSBS Dissertations and Theses

Adipose tissue inflammation has an impact on liver health and it has been demonstrated that chronic alcohol consumption leads to the expression of pro-inflammatory markers in the adipose tissue. A thorough characterization of alcohol-induced adipose inflammation is lacking, and is important to understand in order to identify immune-related mechanisms that drive this phenomenon. Current therapeutic regimens for alcoholic liver disease are ineffective. It is critical to understand how other organs influence liver injury in this disease when developing novel and effective therapies in the future.

Alcoholic liver disease exhibits a sexual dimorphism; women are more susceptible to liver injury than ...


Dosage Compensation Of Trisomy 21 And Its Implications For Hematopoietic Pathogenesis In Down Syndrome, Jen-Chieh Chiang Nov 2017

Dosage Compensation Of Trisomy 21 And Its Implications For Hematopoietic Pathogenesis In Down Syndrome, Jen-Chieh Chiang

GSBS Dissertations and Theses

Down Syndrome (DS), the most common aneuploidy seen in live-borns, is caused by trisomy for chromosome 21. DS imposes high risks for multiple health issues involving various systems of the body. The genetic complexity of trisomy 21 and natural variation between all individuals has impeded understanding of the specific cell pathologies and pathways involved. In addition, chromosomal disorders have been considered outside the hopeful progress in gene therapies for single-gene disorders. Here we test the feasibility of correcting imbalanced expression of genes across an extra chromosome by expression of a single gene, XIST, the key player in X chromosome inactivation ...


Innate Immunity As Mediator Of Cell Death And Inflammation In Alcoholic Liver Disease, Arvin Iracheta-Vellve Nov 2017

Innate Immunity As Mediator Of Cell Death And Inflammation In Alcoholic Liver Disease, Arvin Iracheta-Vellve

GSBS Dissertations and Theses

Central driving forces in the pathogenesis of liver disease are hepatocyte death and immune cell-driven inflammation. The interplay between outcomes, stemming from these two major cell types, is present from the earliest ethanol exposure, and are both determinants in advanced stages of liver disease particularly in alcoholic liver disease (ALD). The complexities associated with advanced ALD are many and therapies are limited. Due to the liver’s role in ethanol metabolism and filtering gut-derived products, it is becoming increasingly clear that innate immunity plays a central role in triggering activation of cell death and inflammatory pathways in ALD. We identified ...


Investigating Structural And Functional Defects In Als-Causing Profilin 1 Variants, Sivakumar Boopathy Sep 2017

Investigating Structural And Functional Defects In Als-Causing Profilin 1 Variants, Sivakumar Boopathy

GSBS Dissertations and Theses

Mutations in profilin 1 (PFN1) cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease that targets motor neurons. PFN1 is a 15 kDa protein that is best known for its role in actin dynamics. However, little is known about the pathological mechanisms of PFN1 in ALS. In this dissertation, it is demonstrated that certain familial ALS-linked mutations severely destabilize the native conformation of PFN1 in vitro and cause accelerated turnover of the PFN1 protein in neuronal cells. This mutation-induced destabilization can account for the high propensity of ALS-linked variants to aggregate and also provides rationale for their reported functional defects ...


A Two-Pronged Approach To Preeclampsia: Understanding Gene Expression And Targeting Sflt1 Using Rnai, Ami Ashar-Patel Jul 2017

A Two-Pronged Approach To Preeclampsia: Understanding Gene Expression And Targeting Sflt1 Using Rnai, Ami Ashar-Patel

GSBS Dissertations and Theses

Preeclampsia (PE) is a disorder affecting 2-10% of pregnancies worldwide. Clinical signs include high blood pressure (HBP) and proteinuria in the mother after the 20th week of pregnancy. Currently, the only cure for PE is delivery of the fetus, which is often necessary preterm and thus dangerous for both mother and fetus. Maternal symptoms of PE are caused by excess anti-angiogenic proteins of placental origin called soluble Flt1s (sFlt1s). sFlt1 mRNA isoforms are produced by alternative polyadenylation (APA) of full-length Flt1 (fl-Flt1) pre- mRNA. While fl-Flt1 encodes a transmembrane protein, sFlt1s encode truncated proteins that are soluble. Multiple sFlt1 isoforms ...


Inhibiting Axon Degeneration In A Mouse Model Of Acute Brain Injury Through Deletion Of Sarm1, Nils Henninger May 2017

Inhibiting Axon Degeneration In A Mouse Model Of Acute Brain Injury Through Deletion Of Sarm1, Nils Henninger

GSBS Dissertations and Theses

Traumatic brain injury (TBI) is a leading cause of disability worldwide. Annually, 150 to 200/1,000,000 people become disabled as a result of brain trauma. Axonal degeneration is a critical, early event following TBI of all severities but whether axon degeneration is a driver of TBI remains unclear. Molecular pathways underlying the pathology of TBI have not been defined and there is no efficacious treatment for TBI.

Despite this significant societal impact, surprisingly little is known about the molecular mechanisms that actively drive axon degeneration in any context and particularly following TBI. Although severe brain injury may cause ...


Characterization Of Severe Malaria In Liberian Children 5 Years Old And Younger, Patricia A. Mcquilkin May 2017

Characterization Of Severe Malaria In Liberian Children 5 Years Old And Younger, Patricia A. Mcquilkin

GSBS Dissertations and Theses

Malaria continues to be a challenging problem in the developing world, and the burden of this life threatening disease continues to be borne by young children living in Sub Saharan Africa. One of the biggest challenges to the prevention and control of this problem lies in accurately diagnosing malaria, and distinguishing it from the many other febrile illnesses which present in children in this age group.

Liberia is a West African country with a high burden of malaria. Very little is known about the presentation of severe malaria in children aged 5 years old and younger in Liberia. We undertook ...


Exploring New Therapeutic Strategies For Osteoarthritis: From Genetic Manipulation Of Skeletal Tissues To Chemically-Modified Synthetic Hydrogels, Henry Huang Mar 2017

Exploring New Therapeutic Strategies For Osteoarthritis: From Genetic Manipulation Of Skeletal Tissues To Chemically-Modified Synthetic Hydrogels, Henry Huang

GSBS Dissertations and Theses

Osteoarthritis (OA), a degenerative disease of articular joints, is the leading cause of chronic disability in the US and affects more than a third of adults over 65 years old. Due to the obesity epidemic and an aging population, the prevalence of OA is expected to rise in both young and old adults. There are no disease modifying OA drugs. Therefore, providing any treatment options that delay the onset or progression of OA is highly desirable. The scope of this dissertation examines two different strategies to promote translational therapies for OA. The first approach investigated whether Smad ubiquitin regulatory factor ...


Impact Of Intra-Articular Injection Use On Patient-Reported Outcomes Among Patients With Knee Osteoarthritis, Shao-Hsien Liu Mar 2017

Impact Of Intra-Articular Injection Use On Patient-Reported Outcomes Among Patients With Knee Osteoarthritis, Shao-Hsien Liu

GSBS Dissertations and Theses

Background: Knee osteoarthritis (OA) is the most common type of OA and is a major cause of pain and thus results in disability for daily activities among persons living in the community. OA currently has no cure. In addition to the conflicting recommendations from clinical guidelines, evidence about the extent to which long-term use of intra-articular injections improves patient outcomes is also lacking.

Methods: Using data from the Osteoarthritis Initiative (OAI), marginal structural models (MSMs) applying inverse probability treatment weights (IPTW) were used to examine the effectiveness of intra-articular injections and changes in symptoms over time. The specific aims of ...


Patient And Social Determinants Of Health Trajectories Following Coronary Events, Lisa Nobel Mar 2017

Patient And Social Determinants Of Health Trajectories Following Coronary Events, Lisa Nobel

GSBS Dissertations and Theses

More than 1.2 million Americans are hospitalized annually with an acute coronary syndrome (ACS); many impaired quality of life after discharge with an ACS. This dissertation focuses on two novel aspects of patient health status (PHS) after ACS: how it can be predicted based on the socioeconomic status (SES) of the patient, and how it evolves over time. We used data from TRACE-CORE, a longitudinal prospective cohort of patients hospitalized with ACS. We measured PHS using both the SF-36 mental and physical component subscales (MCS and PCS) and the Seattle Angina Questionnaire (SAQ) health-related quality of life (HRQoL) and ...


Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles In Cardiac Progenitor Cells, Sara L. Lewandowski Dec 2016

Histone Deacetylase 3 Coordinates Heart Development Through Stage-Specific Roles In Cardiac Progenitor Cells, Sara L. Lewandowski

GSBS Dissertations and Theses

Disruptions in cardiac development cause congenital heart disease, the most prevalent and deadly congenital malformation. Genetic and environmental factors are thought to contribute to these defects, however molecular mechanisms remain largely undefined. Recent work highlighted potential roles of chromatin- modifying enzymes in congenital heart disease pathogenesis. Histone deacetylases, a class of chromatin-modifying enzymes, have developmental importance and recognized roles in the mature heart. This thesis aimed to characterize functions of Hdac3 in cardiac development. We found loss of Hdac3 in the primary heart field causes precocious progenitor cell differentiation, resulting in hypoplastic ventricular walls, ventricular septal defect, and mid- gestational ...