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Full-Text Articles in Medicine and Health Sciences

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 ...


Trends, Predictors, And Consequences Of Child Undernutrition In India, Apurv Soni Apr 2019

Trends, Predictors, And Consequences Of Child Undernutrition In India, Apurv Soni

GSBS Dissertations and Theses

Background: India has the highest number of undernourished children worldwide. Understanding trends, predictors, and consequences of child undernutrition is important to inform strategy for addressing this public health crisis.

Methods: We used data from four National Family Health Surveys (1992-93, 1998-99, 2005-6, 2015-16 NFHS) to examine trends of undernutrition before and after the 2005 implementation of the National Rural Health Mission, India’s flagship public health initiative (Aim 1). We used the 2016 NFHS to build a predictive model that identifies infants at-risk for child undernutrition (Aim 2). Lastly, we used data from the 2005 and 2012 India Human Development ...


Physiological And Psychological Stressors Associated With Glucose Metabolism In The Boston Puerto Rican Health Study, Andrea A. Lopez-Cepero Mar 2019

Physiological And Psychological Stressors Associated With Glucose Metabolism In The Boston Puerto Rican Health Study, Andrea A. Lopez-Cepero

GSBS Dissertations and Theses

Background: Puerto Ricans experience high prevalence of type 2 diabetes (diabetes). Stress is a risk factor for diabetes. The allostatic load (AL) model explains how stress influences disease through a chain of physiological changes. Puerto Ricans experience psychological and physiological (obesity and high glycemic load (GL)) stressors linked with diabetes, yet how these stressors impact the AL chain and how their interplay affects glucose metabolism remains unknown.

Methods: Using data from the Boston Puerto Rican Health Study, this thesis sought to examine: 1) the relationship between GL and primary AL markers, 2) the interaction between perceived stress and GL on ...


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 ...


Interpersonal Discrimination, Gendered Race, And Cardiovascular Disease Inequities: Application Of The Emerging Identity Pathology Model, Ganga S. Bey Mar 2019

Interpersonal Discrimination, Gendered Race, And Cardiovascular Disease Inequities: Application Of The Emerging Identity Pathology Model, Ganga S. Bey

GSBS Dissertations and Theses

An emerging framework, the Identity Pathology (IP) model, partially addresses persistent uncertainties about the primary causes of disparities in cardiovascular health (CVH) between black and white women and men through outlining how identity beliefs associated with social group membership lead to predictable differences in the health-damaging effects of discrimination exposure. Using data from the CARDIA cohort, this doctoral thesis seeks to: 1) propose a novel psychosocial characteristic, identity pathology, that drives the distribution of reported race and gender discrimination in health-relevant ways, 2) assess whether there are group differences in the effects of multiple versus single forms of discrimination on ...


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 ...


Factors Associated With Weight Management Counseling During Primary Care Clerkships, Karen M. Ashe Jan 2019

Factors Associated With Weight Management Counseling During Primary Care Clerkships, Karen M. Ashe

GSBS Dissertations and Theses

Background: The United States Preventive Services Task Force guidelines support screening and provision of intensive multi-component behavioral counseling for adults who have obesity. One barrier to providing such counseling is lack of training in medical school. Not much is known about factors associated with medical students’ perceived weight management counseling (WMC) skills or whether preceptors model or teach WMC during primary care clerkships.

Methods: A mixed methods approach addressed factors affecting WMC training during primary care clerkships. A secondary analysis of 3rd year medical students (n=730) described students’ perceived WMC skills, attitudes and frequency of engagement in 5As ...