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Sirna Therapy In Glioblastoma Stem Cells: Identification Of Target Genes And Potential Therapeutic Implications., Benjamin Himes

Yale Medicine Thesis Digital Library

Glioblastoma multiforme (GBM), the most common primary brain malignancy, carries a grim prognosis; survival statistics have scarcely improved in decades. Even with the development of temozolomide, the current front-line chemotherapeutic agent for GBM, improvement in long-term survival has been minimal, with recurrence virtually assured. One explanation for the persistence of this disease is the presence of a stem-like cell population within GBM (glioblastoma stem cells, or GSCs). These cells are capable of self-renewal, tumor initiation, and are resistant to chemotherapy. We hypothesized that derangement in the expression of genes critical for the maintenance of GSCs could eliminate these cells outright, …

Correlations Between Intracranial Aneurysms And Thoracic Aortic Aneurysms, Gregory Kuzmik

Yale Medicine Thesis Digital Library

This project investigates the clinical occurrence of concurrent thoracic aortic aneurysms (TAA) and intracranial aneurysms (ICA). We hypothesized that patients with a TAA have an increased risk of harboring a concurrent ICA, and likewise that patients with an ICA have an increased risk of harboring a concurrent TAA relative to the general population. In a separate arm of this project, we hypothesized that a pre-defined gene expression profile, based on the expression levels of 41 specific genes measured in peripheral blood cells, will exhibit a characteristic expression pattern in ICA patients and thereby have utility in detecting the presence of …

Pravastatin Does Not Prevent Antiphospholipid Antibody Effects On Human First Trimester Trophoblast Function, Ebele Odiari

Yale Medicine Thesis Digital Library

Women with antiphospholipid syndrome (APS) have circulating antiphospholipid antibodies (aPL) and are at risk for recurrent pregnancy loss and late pregnancy complications due placental dysfunction. Recent research has demonstrated that aPL directly alter human first trimester trophoblast function by up–regulating inflammatory cytokines, limiting cell migration, and altering angiogenic factor production. Due to their anti–inflammatory properties, Statins have been tested both in vitro, using human trophoblast, and In vivo, using a mouse model, for the treatment of APS-associated pregnancy complications and preeclampsia. In vivo mouse studies showed that statins prevent aPL–mediated fetal loss, whereas in vitro human studies suggest that statins, …

Radiation Therapy And Expander-Implant Breast Reconstruction: Analysis Of Timing And Complications, Rachel Lentz

Yale Medicine Thesis Digital Library

The optimal timing of expander-implant exchange in the setting of post mastectomy radiation remains unclear with prior reports yielding inconsistent and variable results. The purpose of this study was to characterize complications associated with the sequencing of expander-implant breast reconstruction before or after radiation therapy and to compare the outcomes between early (< 4 months) and late (>4 months) expander-implant exchange in the subset of patients who received radiation prior to exchange.

The medical records of all patients receiving post-mastectomy radiation therapy in the setting of tissue expander-implant breast reconstruction between June 2004 - June 2011 at Yale-New Haven hospital were reviewed retrospectively. Patients …

Ambient Air Pollutant Pm10 And The Risk Of Preterm Birth In Lanzhou, China, Nan Zhao

Public Health Theses

ABSTRACT

Background: Early studies have inconsistently linked ambient air pollutant PM₁₀ exposure during pregnancy to the risk of preterm birth. However, majority of early studies were based on registry data which could result in misclassification of exposure due to the lack of detailed home and work addresses, as well as failed to collect information on potential confounders. China has the world's most polluted cities and suffers the second largest burden of preterm births. Very few studies, however, have been conducted in China to investigate the association between PM₁₀ exposure and preterm birth. Building upon a birth cohort study …

Future Expectations And Resiliency Among Adolescents: The Possible Moderating Role Of Future Expectations., Brigette Aliece Davis

Public Health Theses

Background: Future expectations are the extent to which an individual believes certain events will occur in their lifetime. Positive expectations for the future are well understood to be independently protective for both risk factors in times of transition--specifically adolescence--and for health outcomes in the future. Resiliency theory suggests that certain protective factors may interact with baseline risk to weaken or eliminate the association between risks and poor outcomes, providing enhanced protection for at-risk youth. This study aimed to determine if future expectations can moderate the association between high-risk adolescent behaviors and adult outcomes; specifically if high expectations can be a …

Methylation Of The Brca1 Promoter And Breast Cancer In Shift Workers., Christian Ramos

Public Health Theses

A search of the cancer literature reveals the strong association between long-term nighttime shiftwork and increased risk of breast cancer in female workers. Since 2007, the International Agency for Research on Cancer (IARC) has categorized shiftwork as "probably carcinogenic to humans", a Group 2A carcinogen1. Evidence from epigenetic studies shows that differential methylation of genes is one possible mechanism by which long-term shiftwork disrupts the expression patterns of the genes responsible for maintaining a cancer free status.

This study builds upon the work initiated by Zhu et al and investigates the association between shiftwork dependent methylation of the NBR2-BRAC1 promoter …

Impact Of Marital Stress On Medication Adherence And Physician Follow-Up After Acute Myocardial Infarction, Dante Cammarata

Public Health Theses

Introduction: Coronary Heart Disease (CHD) is the leading cause of death worldwide. While different types of stress have been linked to CHD development and prognosis, literature regarding the effect of marital stress on positive health behaviors in the early recovery period following myocardial infarction (MI) is limited.

Objective: The present analysis was undertaken to explore the relationship between marital stress and medication adherence and physician follow up, two important components of early post-MI recovery.

Methods: VIRGO study participants who reported either being married or in a committed relationship at the time of study enrollment or at a 30-day follow-up interview …

Inflammation And Cancer-Related Fatigue In Breast Cancer Survivors, Kelly Foss

Public Health Theses

Purpose: Cancer-related fatigue negatively impacts quality of life and possible recurrence and overall mortality in breast cancer survivors. This study aimed to investigate the associations between inflammation and cancer-related fatigue in breast cancer survivors using methods of systematic review and quantitative assessment of the Hormones and Physical Exercise (HOPE) Study in a high-risk population.

Methods: A PubMed search was conducted to identify peer-reviewed studies that assessed the associations among inflammatory markers, CRP, IL-6, and TNF-α, and cancer-related fatigue in breast cancer survivors. The HOPE Study was a randomized control trial in 121 postmenopausal Stage I-IIIC breast cancer survivors, who were …

Calcifying Nanoparticles As Novel Etiologic Agents Of Idiopathic Preterm Birth And Preterm Premature Rupture Of The Membranes, Lydia Shook

Yale Medicine Thesis Digital Library

Preterm birth (PTB) is a leading cause of neonatal morbidity and mortality. In many cases, preterm birth is preceded by preterm premature rupture of the membranes (PPROM) without any identifiable cause. Pathological calcification, i.e. the deposition of hydroxyapatite (HA) in non-skeletal tissue, has been implicated in degenerative diseases of soft tissue, such as atherosclerosis. Multiple pathogenic mechanisms have been described, including the aberrant aggregation of HA into calcifying nanoparticles (CNPs) and the HA-induced differentiation of mesenchymal cells into osteoblasts in a process called ectopic osteogenesis. The objective of this thesis was to explore the possibility that CNPs form in human …

Urinary Biomarkers And Association With Recovery From Severe Aki, Rahul Agarwal

Yale Medicine Thesis Digital Library

Few studies have examined the ability of urinary biomarkers to associate with recovery from acute kidney injury (AKI), a common complication for hospitalized patients that is independently associated with severe morbidity and mortality. We hypothesized that urinary biomarkers of kidney injury (NGAL, IL-18) or repair (YKL-40) would be associated with renal recovery in patients with severe AKI.

We prospectively enrolled 48 patients admitted at Yale New Haven Hospital with severe AKI (AKIN Stage 3). Daily morning urine samples were collected (until recovery up to max of 9 days). Levels of urinary YKL-40, NGAL, and IL-18 were measured. The primary exposures …

Less Intensive Therapy For Older Aml Patients, William Thomas Clarke

Yale Medicine Thesis Digital Library

Specific aims: This single-center, retrospective study compared overall survival and hospitalization in older patients with acute myeloid leukemia (AML) receiving first-line treatment with standard induction chemotherapy and decitabine therapy.

Methods: Between January 2000 and December 2009, 36 patients at Yale-New Haven Hospital age 65 years and older with newly diagnosed AML received standard induction chemotherapy (n=11), decitabine therapy (n=11), or supportive care only (n=14). Data obtained included baseline characteristics, achievement of remission, overall survival, inpatient and outpatient visits, and early death.

Results: When compared to standard induction chemotherapy, decitabine patients were significantly older (77 vs 69 years, P = .020) …

Natural History Of Tricuspid Regurgitant Jet Velocity And A New Association With Proteinuria In Children With Sickle Cell Disease, Suzanne Jaqueth Forrest

Yale Medicine Thesis Digital Library

Given the morbidity and mortality associated with pulmonary hypertension and progressive renal failure in sickle cell disease, recognition of both organ dysfunctions during childhood should allow for improved management of patients and early treatment for both. The definitive diagnosis of pulmonary hypertension is made on cardiac catheterization, however measurement of tricuspid regurgitant jet velocity (TRV) on echocardiogram can be used to estimate pulmonary artery systolic pressures and can be used as a screening modality for pulmonary hypertension. Pulmonary hypertension is defined as TRV ≥2.5m/sec and occurs in 16-30% of children with sickle cell disease on screening echocardiograms. Two studies were …

Altered Circulating Follicular Helper T Cell Phenotype In Systemic Lupus Erythematosus, Hsi-En Ho

Yale Medicine Thesis Digital Library

Autoreactive B cells in Systemic Lupus Erythematosus (SLE) undergo autoantigen selection, suggesting a requirement for germinal center follicular helper T (Tfh) cells in their maturation. However, evidence for dysregulation of Tfh cells in SLE and their contribution to disease activity remains unclear. Recently, blood CXCR5hi CD4 T cells, a heterogeneous pool consisting of functionally distinct Th1-, Th2-, Th17-like subsets, have been proposed to be the circulating counterpart of Tfh cells. The purpose of this study was to examine the hypothesis that Tfh dysregulation, as reflected in altered phenotype of blood CXCR5hi population, was associated with SLE disease activity. Blood samples …

Novel Strategies In The Prevention And Treatment Of Childhood Obesity: The Importance Of Lifestyle Counseling And Psychological Resiliency, Stacey Kallem

Yale Medicine Thesis Digital Library

Efforts to prevent and treat childhood obesity have had only modest results. Novel strategies are needed. The aims and hypotheses of this thesis are to: 1) Document the self-reported receipt of lifestyle counseling from physicians and other health care providers by BMI status. We hypothesize that despite recommendations for universal lifestyle counseling, few children will be counseled by their health care providers, though children who are obese will report receiving the most counseling. 2) Test the hypothesis that psychological resiliency (i.e., "shift and persist") protects low socioeconomic status children from obesity. Physical assessments and health surveys were collected from two …

Biological And Clinical Markers Of Neuronal Injury In Primary And Chronic Hiv-1 Infection, Michael Peluso

Yale Medicine Thesis Digital Library

The use of antiretroviral therapy (ART) has shifted the neurological manifestations of HIV-1 infection toward mild but debilitating HIV-associated neurocognitive disorder (HAND). Through two studies, we sought to characterize neuronal injury during primary and chronic HIV infection and to describe its relationship with HAND.

The aim of the first study was to quantify cerebrospinal fluid (CSF) and neuroimaging biomarkers of neuronal injury in primary HIV infection (PHI). We compared CSF levels of neurofilament light chain (NFL), tau, and amyloid proteins in 92 subjects with PHI and 25 controls and examined relationships with disease progression and neuroinflammation, neuropsychological testing, and proton-magnetic …

Spatial Distribution Of Alitta Virens And Clymenella Torquata With Respect To Rigid Boundaries In Mud And Sand, Kevin T. Du Clos, Sara M. Lindsay, Peter A. Jumars

Journal of Marine Research

Recent advances in understanding of sediment material properties and of burrowing mechanics suggest likely differences in the behavior of organisms burrowing in mud and sand. The path of least resistance in the mud may lead an infaunal organism to burrow along a rigid wall. By contrast, in sand, force chains may prevent a burrowing organism from reaching a rigid wall. Burrowing in mud occurs primarily by the propagation of cracks. Cracks, and hence burrows, tend to propagate along rigid walls. In sand, force chains comprise collections of particles that experience much more stress than their neighbors. Stress chains tend to …

Instability Of A Tidal Mixing Front In The Presence Of Realistic Tides And Mixing, K. H. Brink

Journal of Marine Research

Instability and lateral eddy fluxes associated with a tidal mixing front are studied using idealized primitive equation numerical model runs. The front itself develops as a result of turbulence associated with imposed tidal currents over a sloping bottom. Thus, the model includes realistic levels of turbulence and time-dependence in the base-state conditions. In all of the 21 configurations considered, the front is unstable to fluctuations that usually draw energy primarily from the potential energy pool. Scalings are developed to parameterize a) the location of the tidal mixing front; b) the eddy kinetic energy; and c) the lateral eddy coefficients. In …

Medicine@Yale March 2013 Volume 9, Issue 1, Yale School Of Medicine Office Of Communications

Medicine@Yale - development newsletter

Medicine@Yale : advancing biomedical science, education and health care was a print and online newsletter which published news about academics, research and philanthropy for alumni, donors, faculty, students and the general public. It was initially published 6 times a year and then changed to a quarterly schedule. The first issue came out June/Jul. 2005. The final issue was published in May/June 2022, vol. 17, issue 1. Published by Yale School of Medicine, Office of Communications.

Bulletin Of Yale University School Of Nursing 2013-2014, Yale School Of Nursing

Yale School of Nursing Bulletins and Catalogues

Series 109, Number 15

September 5, 2013

Marker Characterization Of Ecp-Induced Monocyte-Derived Dendritic Cells, Kristina Liu

Yale Medicine Thesis Digital Library

Extracorporeal photopheresis (ECP) in the treatment of cutaneous T-cell lymphoma, GVHD and autoimmune conditions continues to spur the question of how ECP is capable of inducing immunogenicity and tolerance. We previously demonstrated that ECP treatment leads to large-scale conversion of peripheral blood monocytes into functionally competent leukocytes with dendritic cell phenotypes, which may play key roles in the immunomodulatory capabilities of ECP. To characterize this population of cells on a molecular level, we assessed for differential surface expression of selected gene-products on monocytes after treatment with a model-ECP apparatus. Five gene-products (CXCL16, SIRPa, ICAM1, TNFR1, PLAUR) showed significant increases in …

Nutrient Supply In The Southern East China Sea After Typhoon Morakot, Chin-Chang Hung, Chih-Ching Chung, Gwo-Ching Gong, Sen Jan, Yaling Tsai, Kuo-Shu Chen, Wen Chen Chou, Ming-An Lee, Yi Chang, Meng-Hsien Chen, Wen-Rong Yang, Chiung-Jung Tseng, Glen Gawarkiewicz

Journal of Marine Research

Recent studies show that typhoons have profound effects on phytoplankton assemblages along their tracks, but it is difficult to quantitatively estimate nutrient supply after a typhoon's passage due to a lack of nutrient information before and after the arrival of a typhoon. During the passage of Typhoon Morakot (July 22 to Aug. 26, 2009), we conducted pre- and post-typhoon field cruises to study nutrient supply in the Southern East China Sea (SECS). The results showed nitrate and phosphate supplies to the water column in the SECS after the typhoon's passage were 5.6 × 10¹¹ g-N/day and 7.8 × 10 …

Gender Differences In Adult Child Caregiving Patterns: Associations With Care-Recipients' Physical And Mental Health And Cognitive Status, Ying Liu

Public Health Theses

Purpose of the study: To examine differences related to gender of adult child primary caregivers, caregiving patterns, and the association with care-recipients' physical and mental health and cognitive status.

Design and Method: A secondary analysis of the most recent national cross-sectional survey (National Health and Aging Trends Study (NHATS)) was conducted on 5616 community dwelling older adults (65 years of age or older). The relationships between gender of their adult child caregivers and intensity and duration of care, type of care provided, care-recipients' physical and mental health (self-reported health status, number of chronic diseases, depression and anxiety) and cognitive status …

Environmental Risk Assessment Of Community Acquired Legionellosis From Recycled Water Use In Los Angeles County California, Luis Lozano

Public Health Theses

Abstract

Legionellosis is caused by Legionella pneumophila, resulting in 8,000-18,000 yearly hospitalizations and 4,000 deaths in the United States (Bouwknegt, 2012) (Toshiaki, 2004) (World Health Organization, 2012). L. pneumophila may persist in the built environment due to unique intracellular characteristics. Although the mode of transmission of L. pneumophila is inhalation of aerosolized contaminated water, this bacterium is not transmitted human to human (World Health Organization, 2012). L. pneumophila infection may be facilitated by the increased use of recycled water in Los Angeles County. In a water stressed area such as Los Angeles County, a limited potable water supply may not …

Gender Differences In Linguistic Indicators Of Communion And Agency: Associations With Caregiver Stress, Hannah-Rose Mitchell

Public Health Theses

This study examined gender differences in caregivers' use of agentic and communal words when talking about their care recipients' suffering and how this related to their stress, in terms of cardiovascular reactivity and self-reported negative emotion. Seventy-six older adult caregivers of spouses with chronic pain were recorded while describing an incident of their spouses' suffering. Caregivers' heart rate (HR) was continuously monitored during their speeches, and they reported their emotions (distress and anger) after their speeches. In addition, respiratory sinus arrhythmia (RSA) was calculated using HR. Results indicated that male caregivers were more likely to talk about a relational episode …

The Impact Of Intimate Partner Violence On Breastfeeding: A Demographic And Health Surveys Analysis Of India, Nepal And Timor-Leste, Aliya Cecilia Roginiel

Public Health Theses

Objective: The objective of this study is to evaluate the association between lifetime experience of intimate partner violence (IPV) and breastfeeding in India, Nepal and Timor-Leste.

Methods: Women respondents, between the ages of 15 and 49 years, whose last child was under or equal to 2 years of age and a singleton birth and who were applied the domestic violence module, were included in the final study sample for each country. Logistic regression analyses were used to investigate any unadjusted associations between any lifetime IPV, any physical IPV, any sexual IPV or both and the following breastfeeding outcomes: early breastfeeding …

The Role Of Race In The Association Between Weight Status And Risk Behaviors Among United States Adolescents, Jennifer M. Sanderson

Public Health Theses

Objective: To evaluate whether race and ethnicity moderate the association between weight status and risk behaviors in a nationally-representative sample of adolescents.

Methods: The 2009 and 2011 Youth Risk Behavior Surveys were combined (N = 25,550), and used to compare substance use, risky sexual behaviors, and violent behaviors between healthy weight, overweight, and obese adolescents. In both overall and race-stratified samples, chi-square tests and logistic regression were used to determine associations between weight status and engagement in risk behaviors among White, Black, and Hispanic adolescents. These analyses were performed separately in males and females.

Results: Overweight and obese adolescents had …

Effect Of Exercise On Vo2max In Breast Cancer Survivors Taking Aromatase Inhibitors: The Hormones And Physical Exercise (Hope) Study, Mia Sorkin

Public Health Theses

Purpose: The purpose of this study was to investigate the effects of a yearlong exercise intervention compared to usual care on cardiorespiratory fitness in sedentary breast cancer survivors who were taking aromatase inhibitors and experiencing arthralgia.

Methods: Participants were randomized to either an exercise intervention group that met twice weekly with a personal trainer or usual care. Participants completed self-administered questionnaires, including reporting demographic and personal characteristics, and a graded treadmill test using a modified Branching protocol at baseline and at the end of the 12-month study. T-tests and chi-squared analyses were used to assess change in cardiorespiratory fitness, measured …

Mdi-Specific Igg Exposure Biomarker And Role Of Intervention, Ann Y. Teng

Public Health Theses

Background:

Diisocyanates are sensitizing agents that are used in many industries in the production of polyurethane foams, coatings and other products. Methylene diphenyl diisocyanate (MDI) exposure can occur through dermal and inhalation routes resulting in sensitization and leading to isocyanate asthma. MDI-specific IgG (MDI-IgG) bio-monitoring has been proposed to be used as a predictor of exposure.

Methods:

A prospective longitudinal study was used to assess annual MDI- IgG serum markers in 223 workers in a fabric-coating company. Kaplan Meir Survival Analysis determined whether there was a difference in seroconversion based on exposure level. A Cox proportional hazard model was used …

Age Differences In Social Support And Mental Health In Male Veterans, Melissa Rachel Weiner

Public Health Theses

Psychological concerns among United States veterans of all ages are considerable, however social support may help improve the mental health of these individuals. The protective effect of social support on mental health has been observed in older and younger samples of veterans, but it is unclear whether social support may be more beneficial at certain life stages. By assessing cross-sectional survey data from a large sample of veterans using an extreme groups approach (EGA), the impact of perceived support, structural support, and community integration on mental health difficulty and screening positive for a mental disorder was assessed. The effect of …