Improving Nk Cell Therapy For Osteosarcoma, Jennifer Foltz

Dissertations and Theses (Open Access)

Osteosarcoma (OS) is the most common primary bone tumor. Despite new treatment options, 5-year survival for metastatic OS has remained at only 30% for the last 30 years. Adoptive transfer of Natural Killer (NK) cells holds promise for a new, non-toxic therapy for OS. NK cells are part of the innate immune system and readily kill metastatic and chemotherapy-resistant OS in vitro and in murine models. However, there is little data regarding their efficacy in animal models with an intact immune system. In addition, the OS tumor microenvironment is highly suppressive, producing TGFβ which impedes NK cell killing of solid …

Image Registration To Map Endoscopic Video To Computed To Mography For Head And Neck Radiotherapy Patients, William S. Ingram

Dissertations and Theses (Open Access)

The purpose of this work was to explore the feasibility of registering endoscopic video to radiotherapy treatment plans for patients with head and neck cancer without physical tracking of the endoscope during the examination. Endoscopy-CT registration would provide a clinical tool that could be used to enhance the treatment planning process and would allow for new methods to study the incidence of radiation-related toxicity.

Endoscopic video frames were registered to CT by optimizing virtual endoscope placement to maximize the similarity between the frame and the virtual image. Virtual endoscopic images were rendered using a polygonal mesh created by segmenting the …

Preclinical Development Of Therapeutic Strategies Against Triple-Negative And Inflammatory Breast Cancer, Angie M. Torres-Adorno

Dissertations and Theses (Open Access)

Triple-negative (TNBC) and inflammatory (IBC) breast cancer are the most aggressive forms of breast cancer, accounting for 20% and 10% of cancer-related deaths, respectively. Among IBC cases, 30% are additionally classified with TNBC molecular pathology, a diagnosis that significantly worsens patient’s prognosis. The current lack of TNBC and IBC molecular understanding prevents the development of effective therapeutic strategies. To identify effective treatments, we explored aberrant apoptosis pathways and cell membrane fluidity as novel therapeutic targets.

We first identified an effective therapeutic strategy against TNBC and IBC by pro-apoptotic protein NOXA-mediated inhibition of the anti-apoptotic protein MCL1 following inhibition of histone …

Investigating The Role Of Prmt1 And Arginine Methylation Of Hsp70 In Human Pancreatic Cancer, Liang Wang

Dissertations and Theses (Open Access)

Protein arginine methyltransferase 1 (PRMT1) is the major arginine methyltransferase, which catalyzes the addition of one or two methyl groups to the arginine residues of its substrate proteins. The best-known substrate for PRMT1 is histone, while more and more non-histone proteins are now found to be methylated by PRMT1. Dysregulation of PRMT1 is reported in several human cancer types. However, its biological roles in human pancreatic cancer initiation and development are still unclear. In the first part of this study, I found that the expression level of PRMT1 was elevated in both human and mouse pancreatic cancer tissues in immunohistochemistry …

Structural And Functional Effect Of Phosphorylation On Ampa Receptors, Caitlin E. Nurik

Dissertations and Theses (Open Access)

Structural and Functional Effect of Phosphorylation on AMPA Receptors

Cailtin Edmunds show you, BA

Advisory Professor: Vasanthi Jayaraman, Ph. D.

The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor is the primary contributor to neuronal fast excitatory transmission, and plays a key role in learning and memory. Previous studies have established that residues S818, S831, and T840 in the C-terminal segment of GluA1 homomeric AMPA receptor are phosphorylated by PKC, and phosphorylation at these sites leads to an increase in receptor conductance. We show that the domain inclusive of those sites alters its secondary structure due to phosphorylation (using glutamate substitution as a mimic) …

Improvements In Four-Dimensional And Dual Energy Computed To Mography, Rachael M. Martin

Dissertations and Theses (Open Access)

Dual energy and 4D computed tomography (CT) seek to address some of the limitations in traditional CT imaging. Dual energy CT, among other purposes, allows for the quantification and improved visualization of contrast materials, and 4D CT is often used in radiation therapy applications as it allows for the visualization and quantification of object motion. While much research has been done with these technologies, areas remain for potential improvement, both in preclinical and clinical settings, which will be explored in this dissertation. Preclinical dual energy cone-beam CT (CBCT) can benefit from wider separation between the peak energy of the two …

Hsp27 And Chemotherapy-Induced Autophagy As Biomarkers In Osteosarcoma, John Andrew Livingston

Dissertations and Theses (Open Access)

Survival for patients with osteosarcoma has not improved for > 30 years. Despite aggressive multi-agent chemotherapy combined with surgical resection, a significant fraction of patients with localized disease relapse after optimal treatment. We evaluated the occurrence of cytoplasmic LC3B (light chain 3B)-positive puncta (a marker of autophagy) and presence of HSP27 (heat shock protein 27) in cancer cells within pre-treatment biopsy, post-treatment surgical resection, and metastatic osteosarcoma specimens by immunohistochemistry in 260 patients. LCB3+ puncta expression was seen in 34% of pre-treatment. 50% of resection, and 67% of metastasis samples. Sixty-six percent of all specimens were scored positive for HSP27 (85% …

Mechanisms Underlying The Sensitivity And Resistance Of Gastric Cancer Cells To Met Inhibitors, Rebecca Schroeder

Dissertations and Theses (Open Access)

MET amplification has been clinically credentialed as a therapeutic target in gastric cancer, but the molecular mechanisms underlying sensitivity and resistance to MET inhibitors are still not well understood. Using whole-genome mRNA expression profiling, we identified autophagy as a top molecular pathway that was activated by the MET inhibitor crizotinib in drug-sensitive human gastric cancer cells, and functional studies confirmed that crizotinib increased autophagy levels in the drug sensitive cells in a concentration-dependent manner. We then used chemical and molecular approaches to inhibit autophagy in order to define its role in cell death. The clinically available inhibitor of autophagy, chloroquine, …

Pharmacologic And Genetic Manipulations Of Angiotensin Signaling In Thoracic Aortic Disease Models, Andrew M. Peters

Dissertations and Theses (Open Access)

Thoracic aortic aneurysms and dissections (TAAD) are a major cause of morbidity and mortality in patients. Many different risk factors have been associated TAAD, but hypertension is the largest risk factor. Subsets of TAAD patients have identifiable syndromic genetic diseases, yet a number of genetic non-syndromic patients have been identified. Infusion of angiotensin II into mouse models causes aortic disease through inflammation and fibrosis. An angiotensin type I receptor (AT1R) blocker (ARB) or an angiotensin converting enzyme (ACE) inhibitor (ACEi) can reverse aortic pathology in some mouse models. I set out to better understand the relationship between angiotensin and TAAD …

General And Emotion-Specific Alterations To Cognitive Control In Women With A History Of Childhood Abuse, Kristen L. Mackiewicz Seghete, Roselinde H. Kaiser, Anne P. Deprince, Marie T. Banich

Psychology: Faculty Scholarship

Background

Although limited, the literature suggests alterations in activation of cognitive control regions in adults and adolescents with a history of childhood abuse. The current study examined whether such alterations are increased in the face of emotionally-distracting as compared to emotionally neutral information, and whether such alterations occur in brain regions that exert cognitive control in a more top-down sustained manner or a more bottom-up transient manner.

Methods

Participants were young adult women (ages 23–30): one group with a history of childhood physical or sexual abuse (N = 15) and one with no trauma exposure (N = 17), as assessed …

Sex Differences In Spatial Accuracy Relate To The Neural Activation Of Antagonistic Muscles In Young Adults, Agostina Casamento-Moran, Sandra K. Hunter, Yen-Ting Chen, Min-Hyuk Kwon, Emily J. Fox, Basma Yacoubi, Evangelos A. Christou

Exercise Science Faculty Research and Publications

Sex is an important physiological variable of behavior, but its effect on motor control remains poorly understood. Some evidence suggests that women exhibit greater variability during constant contractions and poorer accuracy during goal-directed tasks. However, it remains unclear whether motor output variability or altered muscle activation impairs accuracy in women. Here, we examine sex differences in endpoint accuracy during ankle goal-directed movements and the activity of the antagonistic muscles. Ten women (23.1 ± 5.1 years) and 10 men (23 ± 3.7 years) aimed to match a target (9° in 180 ms) with ankle dorsiflexion. Participants performed 50 trials and we …

Home Care Nurses' Perceptions Of Telemedicine, Carla Puckett

Nursing Masters

Introduction: Congestive heart failure (CHF) is a progressive and disabling illness with high healthcare utilization costs. Due to its complexity and the large number of patients diagnosed with CHF, telemedicine has been increasingly incorporated as part of CHF management. Many studies support its benefits in improving patient outcomes and its practicality to be used in the home care setting. However, more research is needed to investigate home care nurses’ perceptions of telemedicine and how those perceptions affect its implementation.

Objectives: To explore home care nurses’ perceptions of telemedicine and how these perceptions could affect how telemedicine is implemented in home-care. …

U.S. Public Perception And Knowledge Of Lung Cancer Screening, Jessica Luciano

Nursing Masters

The purpose of this study was to evaluate the U.S. public’s attitude toward and knowledge of lung cancer screening per the U.S. Preventative Task Force’s (USPSTF) 2013 guideline. A questionnaire addressing cancer screening perception, lung cancer risk perception, and agreeability to lung cancer screening and surgical resection of detected lung cancer was adapted from Flynn, Peters, and Morgan (2013). The electronic questionnaire was posted to the primary investigator’s Facebook page and snowball sampling was employed. Of the 92 eligible adult respondents, 40% were current or former smokers and 3.3% were eligible for lung cancer screening. The majority of participants believed …

Effects Of Lactobacillus Rhamnosus Mrs6an On Intestinal Gpat3 Pathway Involved In The Lipid Transport In Enterocytes, Ayodeji Oludare Ipinmoroti

Electronic Theses and Dissertations

Accumulation of triglyceride (TG) in enterocytes of the small intestine follows two specific absorption pathways: the monoacylglycerol acyltransferase pathway (MGAT) and glycerol acyltransferase pathway (GPAT), the latter (GPAT) is usually found in the small intestine. In this study, we investigated the effects of Lactobacillus rhamnosus MRS6AN, an isolate from “amabere amaruranu” a Kenyan traditional cultured milk, on triglyceride accumulation and expression of GPAT3, I-FABP, MTP and NPC1L1 in Caco-2 cell enterocyte model. Intracellular triglyceride level (TG) of Caco2 cells was significantly reduced by live L. rhamnosus (LB) compared with other bacterial products. MTP expression in Caco2 cells was minimally reduced …

Development Of A Comprehensive And Sustainable Gynecologic Oncology Training Program In Western Kenya, A Low Resource Setting, Barry Rosen, Peter Itsura, Philip Kipkirui Tonui, Allan L. Covens, Luc Van Lonkhuijzen, Elkanah Omenge

Obstetrics and Gynaecology, East Africa

To provide information on the development of a gynecologic oncology training program in a low-resource setting in Kenya.

This is a review of a collaboration between Kenyan and North American physicians who worked together to develop a gynecologic oncology training in Kenya. We review the published data on the increase of cancer incidence in sub-Saharan Africa and outline the steps that were taken to develop this program.

The incidence of cervical cancer in Kenya is very high and is the leading cause of cancer mortality in Kenya. WHO identifies cancer as a new epidemic affecting countries in sub-Saharan Africa. In …

Differential And Joint Effects Of Metformin And Statins On Overall Survival Of Elderly Patients With Pancreatic Adenocarcinoma: A Large Population-Based Study., Jian-Yu E, Shou-En Lu, Yong Lin, Judith M. Graber, David Rotter, Lanjing Zhang, Gloria M. Petersen, Kitaw Demissie, Grace Lu-Yao, Xiang-Lin Tan

Department of Medical Oncology Faculty Papers

Background: Published evidence indicates that individual use of metformin and statin is associated with reduced cancer mortality. However, their differential and joint effects on pancreatic cancer survival are inconclusive.Methods: We identified a large population-based cohort of 12,572 patients ages 65 years or older with primary pancreatic ductal adenocarcinoma (PDAC) diagnosed between 2008 and 2011 from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database. Exposure to metformin and statins was ascertained from Medicare Prescription Drug Event files. Cox proportional hazards models with time-varying covariates adjusted for propensity scores were used to assess the association while controlling for potential confounders.Results: Of 12,572 …

The Whole Is Not The Sum Of Its Parts: Specific Types Of Positive Affect Influence Sleep Differentially, Sarah D. Pressman, Brooke N. Jenkins, Tara L. Kraft, Heather Rasmussen, Michael F. Scheier

Psychology Faculty Articles and Research

Given the known detrimental effects of poor sleep on an array of psychological and physical health processes, it is critical to understand the factors that protect sleep, especially during times of stress when sleep particularly suffers. Positive affect (PA) arises as a variable of interest given its known associations with health and health behaviors and its ability to buffer stress. In two studies, we examined which types of PA (distinguished by arousal level and trait/state measurement) were most beneficial for sleep and whether these associations varied depending on the stress context. In Study 1, college students (N = 99) reported …

Outcomes Of An Integrated Approach To Speed And Strength Training With An Elite-Level Sprinter, Eric D. Magrum

Electronic Theses and Dissertations

The purpose of this study was to observe changes in sprint velocity, ground contact time, and peak force demonstrated by a competitive sprinter following an integrated approach to speed development and strength training. As part of an ongoing monitoring procedure the participant completed 20m sprint testing through an optical measurement system and isometric-strength testing before and after each phase of training. Sprint velocity, ground contact time and peak force were analysed using Tau-U, smallest worthwhile and percent change statistics. Results indicate sprinting velocity statistically improved while changes in peak force were practically significant and ground contact time remained trivial throughout …

The Efficacy Of Pressure Ulcer Treatment With Cathodal And Cathodal-Anodal High-Voltage Monophasic Pulsed Current: A Prospective, Randomized, Controlled Clinical Trial, Anna Polak, Luther C. Kloth, Edward Blaszczak, Jakub Taradaj, Agnieszka Nawrat-Szoltysik, Tomasz Ickowicz, Ewa Hordynska, Andrzej Franek, Cezary Kucio

Physical Therapy Faculty Research and Publications

Background. Studies show that anode and cathode electrical stimulation (ES) promotes the healing of wounds, but specific protocols for both electrodes are not available.

Objective. To compare the effectiveness of cathodal versus cathodal+anodal ES in the treatment of Category II-IV pressure ulcers (PrUs).

Design. Prospective, randomized, controlled, clinical study.

Setting. Three nursing and care centers.

Patients. Sixty-three participants with PrUs were randomly formed into a cathodal ES group (CG: N = 23; mean age of 79.35; SD 8.48), a cathodal+anodal ES group (CAG: N = 20; mean age of 79.65; SD 11.44) and a placebo ES group (PG: N = …

Physical Activity Modulates Corticospinal Excitability Of The Lower Limb In Young And Old Adults, Hamidollah Hassanlouei, Christopher W. Sundberg, Ashleigh E. Smith, Andrew Kuplic, Sandra K. Hunter

Exercise Science Faculty Research and Publications

Aging is associated with reduced neuromuscular function, which may be due in part to altered corticospinal excitability. Regular physical activity (PA) may ameliorate these age-related declines, but the influence of PA on corticospinal excitability is unknown. The purpose of this study was to determine the influence of age, sex, and PA on corticospinal excitability by comparing the stimulus-response curves of motor evoked potentials (MEP) in 28 young (22.4 ± 2.2 yr; 14 women and 14 men) and 50 old adults (70.2 ± 6.1 yr; 22 women and 28 men) who varied in activity levels. Transcranial magnetic stimulation was used to …

The Impact Of Faculty Academic Mentoring On First-Generation Undergraduate Students : A Mixed Method Design, Gustavo Salazar Ii

Dissertations

The quality of the relationship between mentors and mentees has gained considerable research interest in business-related fields but little ground in the academic sphere. This study examined the effectiveness of an existing faculty mentoring program that had been underway for several years at a small, private, religiously affiliated university. A convergent, parallel, mixed methods design was used to collect quantitative and qualitative data. Current and former undergraduate participants of the mentoring program were invited to volunteer for online surveys assessing the quality of their mentoring relationship in the program. That same pool was also invited to volunteer for group interviews. …

Utilizing Modular Labs In Human Anatomy And Physiology: Lessons Learned From A First Time Experience, Jennifer Zitzner

Biology: Faculty Publications and Other Works

Anatomy and physiology laboratory experiences build upon concepts that are presented in the lecture part of the course. Our anatomy and physiology laboratory class meets weekly for approximately three hours and includes a compilation of activities that are to be completed during the laboratory period. While exercises are built off of topics presented in lecture and predominantly hands-on in nature, many students were not taking advantage of the self-directed learning experiences, especially those employing anatomical models. Some students were content to simply take photographs of models with their cell phones and complete only the graded portions of the laboratory assignment …

Supporting Nurse Education In The Implementation Of A Pediatric Delirium Assessment Protocol In The Pediatric Intensive Care Unit, Lucy Camarena, Rn, Bsn, Cnl, Cpn, Phn

Master's Projects and Capstones

Delirium has historically been under studied, more so in the pediatric population, despite its long term effects on patients’ health. The deficit in knowledge of delirium leads to an increase in hospital stays and unnecessary unit expenses. My intention with this change project is to increase the awareness of delirium in the pediatric delirium by providing an educational intervention to the PICU nurses. After conducting a root cause, SWOT and cost analysis, I determined that successful education of the PICU nurses about delirium could substantially decrease its incidence. Using Ronald Lippitt’s Change Theory and the CNL competencies as guides I …

Knowledge, Attitude And Perceptions Of Muslim Cancer Patients Regarding Cancer Treatment During Ramadan: Results From A Tertiary Care Hospital Karachi, Afshan Asghar Rasheed, Yasmin Abdul Rashid, Farah Tahir Pirzada, Fawad Haroon, Adnan Jabbar, Ahmed Raheem Buksh

Department of Radiation Oncology

Objective: To assess the knowledge and attitude of Muslim cancer patients regarding cancer treatment during Ramadan.
Methods: This cross-sectional study was conducted at the Aga Khan University Hospital, Karachi, from July to August 2015, and comprised cancer patients. .Adult Muslim cancer patients receiving active oncological treatment or on surveillance were included. Patients on only supportive treatment were excluded. SPSS 19 was used for data analysis.
Results: Of the 265 patients, 87(32.8%) were males and 178(67.2%) were females. The overall mean age was 49±13.87 years. Besides, 184(70.9%) patients belonged to the middle class. Breast cancer was the most common cancer 106(40.6%). …

Driving Organizational Change From The Bedside: The Aacn Clinical Scene Investigator Academy., Susan R. Lacey, Caryl Goodyear-Bruch, Adrienne Olney, Dave Hanson, Marian S. Altman, Natasha S. Varn-Davis, Debbie Brinker, Ramón Lavandero, Karen S. Cox

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Staff nurses are pivotal in leading change related to quality improvement efforts, although many lack skills to steer change from the bedside. The American Association of Critical-Care Nurses (AACN) staff nurse leadership program, Clinical Scene Investigator (CSI) Academy, teaches and empowers staff nurses in leadership skills and change concepts to translate evidence into practice affecting patient outcomes.

OBJECTIVES: To describe the curriculum of the AACN CSI Academy that provides staff nurses with the leadership skills required to create unit-based change projects that positively impact patient/family outcomes.

METHODS: The curriculum of the Academy included leadership topics, communication, change concepts, quality …

Community Education Of The Nurse Practitioner Role In Healthcare, Lisa M. Kemp

Nursing Masters

Introduction: The existing primary care physician shortage in the United States is predicted to increase following the passage of the Patient Protection and Affordable Care Act (ACA), growth of the aging population, and physician specialization. This will reduce patient access to quality care. The integration of the nurse practitioner role in primary healthcare delivery models can increase access to quality healthcare services for patients. Efforts must be in place to assist communities in adapting and accepting the nurse practitioner role in the primary care setting.

Purpose: The purpose of this project was to develop and evaluate an educational program on …

The Hurdles Of The Handoff: A Study Of Why Picu Nurses Are Not Utilizing The Handoff Tool And How To Improve Utilization, Lindsay C. Kraus

Nursing Masters

Abstract

Background: Adverse patient events have been linked to communication errors during handoff. The Joint Commission has estimated that 65% of adverse patient events are associated with issues in communication. This, coupled with mandated electronic medical record (EMR) adoption in 2009, has complicated the implementation of effective handoffs. Many EMR systems are ill equipped to provide effective handoff tools, leading to staff non-compliance and a system of varied handoff procedures.

Purpose: To determine the barriers to nurses utilization of the EMR based handoff tool in the pediatric intensive care unit (PICU).

Methods: This study was a longitudinal pre-post analysis design, …

Assessment Of Risk Of Dengue And Yellow Fever Virus Transmission In Three Major Kenyan Cities Based On Stegomyia Indices, Sheila B. Agha, David P. Tchouassi, Armanda D.S. Bastos, Rosemary Sang

All Peer-Reviewed Publications

Dengue (DEN) and yellow fever (YF) are re-emerging in East Africa, with contributing drivers to this trend being unplanned urbanization and increasingly adaptable anthropophilic Aedes (Stegomyia) vectors. Entomological risk assessment of these diseases remains scarce for much of East Africa and Kenya even in the dengue fever-prone urban coastal areas. Focusing on major cities of Kenya, we compared DEN and YF risk in Kilifi County (DEN-outbreak-prone), and Kisumu and Nairobi Counties (no documented DEN outbreaks). We surveyed water-holding containers for mosquito immature (larvae/pupae) indoors and outdoors from selected houses during the long rains, short rains and dry seasons (100 houses/season) …

Electromyographical Comparison Of A Traditional, Suspension Device, And Towel Pull-Up, Ronald L. Snarr, Ashleigh V. Hallmark, Jason C. Casey, Michael R. Esco

Health Sciences & Kinesiology: Faculty Publications

Strengthening muscles of the back may have various implications for improving functions of daily living, aiding in the transfer of power in throwing, and assist in injury prevention of the shoulder complex. While several versions of the pull-up exist, there is currently no literature comparing their differences. The purpose of this investigation was to compare the electromyographical activity of the latissimus dorsi, posterior deltoid, middle trapezius, and biceps brachii while performing three variations of the pull-up. Resistance-trained men and women (n = 15, age = 24.87 ± 6.52 years) participated in this study by performing traditional pull-ups, suspension device pull-ups, …

Optimal Echo Time For Functional Mri Of The Infant Brain Identified In Response To Noxious Stimulation, Sezgi Goksan, Caroline Hartley, Samuel A. Hurley, Anderson M. Winkler, Eugene P. Duff, Mark Jenkinson, Richard Rogers, Stuart Clare, Rebeccah Slater

School of Medicine Publications

Purpose: Blood oxygen level dependent (BOLD) brain activity, measured using functional MRI (fMRI), is dependent on the echo time (TE) and the reversible spin-spin relaxation time constant ( T2*) that describes the decay of transverse magnetization. Use of the optimal TE during fMRI experiments allows maximal sensitivity to BOLD to be achieved. Reports that T2* values are longer in infants (due to higher water concentrations and lower lipid content) have led to the use of longer TEs during infant fMRI experiments; however, the optimal TE has not been established.

Methods: In this study, acute experimental mildly noxious stimuli were applied …