Medicine and Health Sciences Commons^™

The Morbidity & Mortality Of Prevalent Heart Failure, Jennifer Kwon

Loma Linda University Electronic Theses, Dissertations & Projects

The first study population included 292 unselected consecutive patients from the LLUMC heart failure clinic who were enrolled in the study from January to July 2006 and were followed up through the end of December 2010. The treatment policy at the clinic was to uptitrate dosages of beta-adrenergic blockade (β-blockers), angiotensin-converting-enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) to the most tolerable levels in order to reach target dosages, as recommended by the Heart Failure Society of America (HFSA). Patients were classified into systolic heart failure (ejection fraction (EF) < 40%) or diastolic heart failure (EF≥40%). All dosages of β-blockers, ACEi and ARB were extracted through chart reviews and were used as the main predictors of the patients' survival. Results from analyses showed that reaching target dosages of β-blockers and ACEi/ARB may increase survival when compared to not reaching target among the systolic HF population (HR_{β_biockers}= 0.64, 95% CI 0.26-1.56 and HR_ACEi/ARB=0.50, …

Mrp4 Is A Crucial Regulator Of Testosterone Biosynthesis, Jessica Ann Morgan

Theses and Dissertations (ETD)

The physiological role of multidrug resistance protein 4 (Mrp4) in the testes is unknown. It was discovered that Mrp4 is expressed primarily in mouse and human Leydig cells; however, there is no current evidence that Mrp4 regulates testosterone biosynthesis. The role of Mrp4 was investigated in Leydig cells where testosterone production is regulated by cAMP, an intracellular second messenger formed when the luteinizing hormone (LH) receptor (Lhr) is activated. As Mrp4 regulates cAMP, we compared testosterone levels in our Mrp4 WT and KO mice. Prepubertal KO mice had significantly reduced testicular testosterone, impaired gametogenesis, and disrupted cAMP homeostasis, resulting in …

Sociosexuality, Mate Preferences, And Sex Steroid Hormone Levels Among Breastfeeding Women In Manila, Michelle Escasa

UNLV Theses, Dissertations, Professional Papers, and Capstones

This project investigates the influence of lactation on female sociosexuality and mate preferences in urban Manila, a population with long-term breastfeeding, low contraceptive use, and quick return to ovulatory cycling. Physiological and evolutionary considerations suggest that lactating women face important life history allocation trade-offs between mating and parenting effort that may be manifest in their sociosexual behavior and mate preferences. Breastfeeding (n=155) and control (n=105) women were recruited to provide a saliva sample (for testosterone and estradiol analyses), complete a questionnaire, and complete a face and voice preference task to determine preferences for masculinity. Breastfeeding women reported differences in commitment …

Frictional Forces Of A Fixed, Esthetic Orthodontic Appliance System, Brady Michael Nance

UNLV Theses, Dissertations, Professional Papers, and Capstones

Purpose: The demands of an all esthetic fixed orthodontic appliance system are ever increasing in today's world. Frictional values of an esthetic, fixed orthodontic appliance system are needed to evaluate their clinical effectiveness for orthodontic treatment. The aim of this study is to evaluate the frictional values of various esthetic orthodontic archwires ligated to an esthetic orthodontic bracket.

Methods: Three types of stainless steel and nickel titanium alloy (niti) esthetic orthodontic archwires (epoxy, poly, plastic) in four sizes (.016, .018, .017 x .025, .019 x .025 inches) were ligated to both a stainless steel bracket system and a ceramic (esthetic) …

Optimization Of Chiral Separation Of Nadolol By Simulated Moving Bed Technology, Nesma Nehad Hashem

Electronic Thesis and Dissertation Repository

Simulated Moving Bed (SMB) technology has gained increasing attention as one of the most powerful techniques for chromatographic separations due to its cost-effectiveness and efficiency. Application of SMB technology is especially important in the pharmaceutical industry for production of enantiopure drugs, as required under strict FDA regulations, to avoid possible adverse effects of racemic drugs. In this study, the performance of the SMB process in separation of racemic nadolol on a perphenyl carbamoylated beta cyclodextrin (β-CD) stationary phase was investigated. The equilibrium dispersive model coupled with bi-Langmuir adsorption isotherm and lumped kinetic approximation, constitute the mathematical model used to simulate …

Experimental And Computational Analysis Of The Structure And Dynamics Of Intrinsically Disordered Proteins, Elio Anthony Cino

Electronic Thesis and Dissertation Repository

Intrinsically disordered proteins (IDPs) are abundant in cells and have central roles in

protein-protein interaction networks. Many are involved in cancer, aging and

neurodegenerative diseases. The structure and dynamics of IDPs is intimately related to their

interactions with binding partners. Because IDPs are inherently flexible and do not have a

single conformation, conventional methods and conditions for determining structure and

dynamics of globular proteins may not be directly applicable. Nuclear magnetic resonance

(NMR) spectroscopy is one of the primary techniques characterizing the structures and

dynamics of IDPs, but one cannot rely solely on NMR data. A primary aim of this …

The Role Of The Yxxφ Motif In Cd82 Trafficking And Function, Mekel Marie Richardson

Theses and Dissertations (ETD)

CD82, a tetraspanin, is a tumor metastasis suppressor. Tetraspanins are membrane spanning proteins that play critical roles in diverse biological and pathological processes, e.g., the regulation of cancer metastasis. CD82 is ubiquitously expressed in various types of tissues, but its expression becomes down-regulated or lost in a majority of metastatic tumors. It inhibits tumor metastasis without affecting primary tumor growth. Cancer patients whose tumors contain CD82 exhibit minimal metastasis. We know that CD82 functions as a tumor metastasis suppressor but the mechanism by which this occurs is largely unknown. CD82 can be found on the plasma membrane as well as …

Nrf2 Activation By Dimercaptopropanol Attenuates Mutant Huntingtin Toxicity, Kyle M. Dailey

Electronic Thesis and Dissertation Repository

Huntington’s disease (HD) is a fatal neurodegenerative disorder resulting from the expansion of a trinucleotide repeat within the HD gene. At the cellular level mutant HTT (mHTT) aggregates perturb cellular metabolism, intracellular trafficking and mitochondrial function, resulting in the increased production of reactive oxygen species (ROS) an event closely linked with nerve cell death. Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-sensitive transcription factor responsible for transcribing neuroprotective genes under the control of the antioxidant response element (ARE), which work to counteract high intracellular ROS levels. I have identified significant increases in cell viability, NRF2 nuclear localization, and …

Discovery Of Dihydroartemisinin And Dasatinib Drug Combination To Cure Pooroutcome Bcr-Abl+ Acute Lymphoblastic Leukemia, Harpreet Singh

Theses and Dissertations (ETD)

Oncogenic signaling by the Philadelphia chromosome-encoded BCR-ABL fusion kinase initiates and drives both Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and chronic myelogenous leukemia (CML). Food and Drug Administration (FDA)- approved BCR-ABL-specific kinase inhibitors (BCR-ABL–KIs) imatinib, dasatinib and nilotinib induce prolonged remissions in CML but poor leukemia-reduction and relapse-control in Ph+ ALL. The relative primary BCR-ABL–KI-resistance in Ph+ ALL patients carrying predominantly BCR-ABLWT disease cannot be attributed to drug-resistant BCR-ABL mutations (BCR-ABLMUTANTS), and remains poorly understood.

We established a cell-based platform to evaluate the modulation of anti-Ph+ ALL activity of drugs by both tumor-extrinsic cytokines normally present in the leukemia …

Identification Of Persistent Long Range Interactions In GA95 And GB95 Through Thermal Unfolding Simulations, Milen Redai Tesfamariam

Chemistry & Biochemistry Theses & Dissertations

For over five decades, different experiments have been performed to research how proteins attain their native three dimensional structures. However, the folding problem continues to be a puzzle in modern science. The design of two proteins that have maximal sequence identity but different folds and functions is one method that is being used to study the relationship between protein structure and amino acid sequence. In particular, mutant proteins of Streptococcus protein G, G_A and G_B, have 95% sequence identity and a 3a helix fold and β4/a fold, respectively. Molecular dynamics simulations of G_A95 …

A Study Of Histone Deacetylase Inhibitors: Determination Of The Binding Energetics Of Suberoylanilide Hydroxamic Acid With Zinc And Cobalt And Preliminary Screening Of Nitric Oxide Donors, Erin Gallagher

College of Science and Health Theses and Dissertations

Inhibiting histone deacetylases (HDACs) can suppress tumor cell growth eventually leading to their death, makeing HDACs an important drug target. Therefore, understanding the mechanism behind inhibiting HDACs is imperative. To determine the thermodynamic parameters for the interaction of a known competitive HDAC inhibitor, suberoylanilide hydroxamic acid (SAHA), with zinc(II), the metal ion in the HDAC active site, and cobalt(II), isothermal titration calorimetry (ITC) was used. The results showed that SAHA binds to zinc(II) more strongly than it does to cobalt(II) as the equilibrium binding constants were 4.3 ± 0.5 x 10² M^-1 and 2.0 ± 0.5 x 10 …

The Effects Of Nicotine Administration On Behavior And Markers Of Brain Plasticity In A Rodent Model Of Psychosis, Marla K. Perna

Electronic Theses and Dissertations

Schizophrenia affects about 1% of the population. A hallmark of the disorder is increased dopamine D2 receptor sensitivity in the brain. Studies have shown that schizophrenics smoke cigarettes at approximately 4 times the rate of the general population. It has been suggested that nicotine use is a form of self-medication for symptoms in schizophrenia. Smoking behaviors typically begin in adolescence. We assessed effects of nicotine on behavior and brain plasticity in an adolescent rodent model of schizophrenia with the goal of identifying targets for smoking cessation. Methods: Rats were neonatally treated with quinpirole (a D2/D3 agonist) or saline and sensitized …

Acetaldehyde And Epithelial Junctions: Role Of Pp2a And Occludin Phosphorylation, Mitzi Dunagan

Theses and Dissertations (ETD)

Chronic alcohol consumption causes health problems including cancers, liver damage, and cirrhosis.These problems are exacerbated by endotoxins from the bacterial population of the colon, which can enter the bloodstream when gastrointestinal tight junctions, protein complexes that prevent paracellular passage of molecules, are compromised. The mechanisms of this barrier disruption are the subject of current study.

Acetaldehyde, produced as a result of ethanol breakdown by intestinal microflora as well as intestinal epithelia, is a known carcinogen. It compromises the barrier function of intestinal epithelial cells by causing irregularities in the phosphorylation of tight junction proteins. It also reacts with proteins, lipids, …

Arsenic Contamination In Groundwater In Vietnam: An Overview And Analysis Of The Historical, Cultural, Economic, And Political Parameters In The Success Of Various Mitigation Options, Thuy M. Ly

Pomona Senior Theses

Although arsenic is naturally present in the environment, 99% of human exposure to arsenic is through ingestion. Throughout history, arsenic is known as “the king of poisons”; it is mutagenic, carcinogenic, and teratogenic. Even in smaller concentrations, it accumulates in the body and takes decades before any physical symptoms of arsenic poisoning shows. According to the World Health Organization (WHO), the safe concentration of arsenic in drinking water is 10 µg/L. However, this limit is often times ignored until it is decades too late and people begin showing symptoms of having been poisoned.

This is the current situation for Vietnam, …

Chemosensitization Of Hepatocellular Carcinoma To Gemcitabine By Non-Invasive Radiofrequency Field-Induced Hyperthermia, Mustafa Raoof

Dissertations & Theses (Open Access)

Gemcitabine is a potent nucleoside analogue against solid tumors however drug resistance rapidly emerges. Removal of gemcitabine incorporated in the DNA by repair mechanisms could potentially contribute to resistance in chemo-refractory solid tumors. In this study, we evaluated homologous recombination repair of gemcitabine-stalled replication forks as a potential mechanism contributing to resistance. We also studied the effect of hyperthermia on homologous recombination pathway to explain the previously reported synergy between gemcitabine and hyperthermia. We found that hyperthermia degrades and inhibits localization of Mre11 to gemcitabine-stalled replication forks. Furthermore, gemcitabine-treated cells that were also treated with hyperthermia demonstrate a prolonged passage …

The Molecular Basis Of Fitness And Transmissibility Of Neuraminidase Inhibitor Resistant Influenza A Viruses, Susu Duan

Theses and Dissertations (ETD)

Neuraminidase (NA) inhibitors including oral oseltamivir and inhaled zanamivir are among the first line of defense against influenza virus infection. Development of resistance to NA inhibitors is a huge drawback for limited options for the control of influenza. During the first decade of NA inhibitor use, the detection rates of resistance to both NA inhibitors had remained low in circulating influenza viruses. However, the 2008~2009 season was marked by a radical increase of prevalence of oseltamvir resistance from <1% to >90% in worldwide surveillance in less than a year. The resistance was solely linked to NA H275Y variants of seasonal H1N1 viruses, …

Increased Geranylgeranylated K-Ras Contributes To Antineoplastic Effects Of Farnesyltransferase Inhibitors., Mandy A. Hall

Dissertations & Theses (Open Access)

The Ras family of small GTPases (N-, H-, and K-Ras) is a group of important signaling mediators. Ras is frequently activated in some cancers, while others maintain low level activity to achieve optimal cell growth. In cells with endogenously low levels of active Ras, increasing Ras signaling through the ERK and p38 MAPK pathways can cause growth arrest or cell death. Ras requires prenylation – the addition of a 15-carbon (farnesyl) or 20-carbon (geranylgeranyl) group – to keep the protein anchored into membranes for effective signaling. N- and K-Ras can be alternatively geranylgeranylated (GG’d) if farnesylation is inhibited but are …

Ferrocene Constrained Helical Peptides Via On-Resin Cyclization, Thomas A. Mcteague

Senior Theses and Projects

Previous research within the Curran group has demonstrated that ferrocene may be used as an organometallic constraint to induce the formation of α-helices in short peptides which traditionally possess undefined conformations. Through strategic placement of lysine residues at the i and i+3 positions within the peptide, such a constraint was accomplished via the crosslinking of the lysine side chains to ferrocene dicarboxylic acid chloride in solution phase synthesis. The aim of this work was to develop a method for solid phase peptide synthesis (SPPS) for the synthesis of these ferrocene-constrained helices. In particular, we seek to develop a method in …

A Mechanistic Study Of S-Adenosyl-L-Methionine Protection Against Acetaminophen Hepatotoxicity, James Michael Brown

Theses, Dissertations and Capstones

Acetaminophen (APAP) toxicity remains the leading cause of drug induced liver failure in the United States. The current therapy for APAP toxicity is N-acetylcysteine (NAC). NAC must be administered within eight hours of APAP overdose for maximum efficacy. That, coupled with the fact that APAP toxicity may not be overtly evident, makes an alternative therapeutic intervention worth exploring. Previous work by our laboratory has demonstrated that S-adenosyl-L-methionine (SAMe) prevents APAP toxicity when given following APAP overdose in C57Bl/6 mice at a level comparable to NAC. The focus of the current work was to examine the mechanistic aspects of this protection …

Does The Use Of An Oral Lipase Inhibitor (Orlistat) Increase Appetite?, Sandra Boyd

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: To determine whether or not Orlistat ingested prior to a meal causes an increased appetite response.

STUDY DESIGN: A Review of three randomized controlled trials studies from 2003-2008 that were in the English language.

DATA RESOURCES: Randomized controlled trials comparing the effect of Orlistat on satiety were found using PubMed, OVID, and Cochrane databases.

OUTOMES MEASURED: Outcomes measured in the studies were: sensation of appetite, hunger, fullness, nausea, bloating, heartburn, belching, epigastric burning, and prospective food consumption. Each study measured individual patient responses using a VAS (visual analogue scale). Demarchi et al (2004) used a gastric barostat to measure …

Is Intravenous Ramosetron 0.3 Mg Effective In The Prevention Of Postoperative Nausea And Vomiting In Women Undergoing Gynecologic Surgery?, Keith S. Elsner

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not intravenous ramosetron 0.3 mg is effective in the prevention of postoperative nausea and vomiting (PONV) in women undergoing gynecologic surgery.

STUDY DESIGN: Review of three English language primary research articles published later than 1995.

DATA SOURCES: Randomized, double-blinded, controlled clinical trials comparing intravenous ramosetron to placebo or other control groups were identified using Ovid MEDLINE and Cochrane Library databases.

OUTCOMES MEASURED: Measured outcomes include a complete response to the intervention within the first 24-48 hours, the incidence of postoperative nausea and vomiting, need for rescue antiemetic, …

Does Tadalafil Improve Exercise Capacitance In Patients Over 12 Years Old With Pulmonary Hypertension?, Erin Chesnavich

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this systematic review is to determine whether or not the oral Phosphodiesterase inhibitor Tadalafil improves exercise capacitance in those over 12 years with pulmonary hypertension.

Study Design: Review of three primary research materials published in English language in 2009. Data Sources: Randomized, controlled, double blind clinical trials found using PubMed, OVID and COCHRANE databases.

Outcome measured: Trials measured 6-minute walking distance and health related quality of life measurements which included: SF-36 (a measure of self reported health status), and the EQ-5D (a patient reported health related quality of life measure), WHO functional class, clinical worsening, and …

Does The Use Of Intravenous Zoledronic Acid, In Combination With Chemotherapy Regimens, Arrest The Development And Spread Of Cancer Cells To Increase Disease-Free Survival In Breast Cancer Patients?, Dara Colasurdo

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the use of intravenous zoledronic acid, in combination with chemotherapy regimens, arrest the development and spread of cancer cells to increase disease-free survival in breast cancer patients.“

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2009 and 2010.

DATA SOURCES: Randomized controlled trials and open label, randomized, phase 2 trial comparing the use of zoledronic acid in combination with chemotherapy to the use of chemotherapy alone were found using Medline/PubMed and Cochrane Databases

OUTCOMES MEASURED: The outcomes measured were incidence …

Is Afrin (Oxymetazoline) A Safe And Effective Drug In Normal, Healthy Adults With Reference To Nasal Congestion And The Nasal Response?, Allie Rubinstein

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not, “Is Afrin (Oxymetazoline) a safe and effective drug in normal, healthy adults with reference to nasal congestion and the nasal response?”

STUDY DESIGN: Review of three English language primary studies published in 1997, 1999, 2003.

DATA SOURCES: Randomized, controlled studies (double-blind, placebo-controlled) testing the efficacy and safeness of Afrin in comparison to a placebo group, were found using the PubMed database.

OUTCOMES MEASURED: Nasal patency, congestion, degree of nasal blockage, and symptoms (quantity, consistency, color of nasal secretions, turbinate size/color) were measured through patient diary card …

Is Asenapine More Effective Than Other Interventions In The Treatment Of Adult Patients With Bipolar I Disorder?, Mary H. Tsakiris

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Asenapine is more effective than other interventions in the treatment of adult patients with bipolar I disorder.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published from 2009-2010.

DATA SOURCES: Three randomized controlled trials studying the effectiveness of Asenapine in the treatment of mania in adult patients with bipolar I disorder in comparison to other interventions.

OUTCOME MEASURED: Outcomes measured were reduction in severity of manic symptoms and tolerability of the medication. The severity of manic symptoms was measured using the Young …

Is Aspirin Effective In Helping To Prevent Breast Cancer In Women Ages 45 Years And Older?, Kristen M. Quartuccio

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not aspirin is effective in helping to prevent breast cancer in women ages 45 years and older.

STUDY DESIGN: Review of three English language primary studies published in 2005, 2007, and 2008

DATA SOURCES: Two randomized, double blind, placebo controlled clinical trials and one prospective, population based cohort study comparing aspirin to placebo were found using PubMed and Cochrane databases.

OUTCOMES MEASURED: Breast cancer development was measured in several ways. Tumor characteristics were measured at diagnosis, including size, metastasis to lymph nodes, histology of the mass, histology …

Is Ceftobiprole A Safe And Effective Treatment For Skin And Skin Structure Infections?, Laura Thompson

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this systematic review is to determine whether or not ceftobiprole is a safe and effective treatment for complicated skin and skin structure infections

STUDY DESIGN: Review of all English language primary randomized controlled trials from 1996-2010

DATA SOURCES: Three randomized controlled trials were found using Pubmed and Cochrane databases

OUTCOMES MEASURES: Skin or skin-structure infection cure with ceftobiprole intervention and adverse effects of this new pharmaceutical. Cure or failure to cure skin infection was determined based on both clinical and microbiological assessment. Adverse events were measured based on patient reports, clinician reports, labs, and vital sign …

Is Fixed-Combination Prostaglandin Analog/Β-Blocker Therapy Safe And More Effective Than Β-Blocker Monotherapy In The Prevention Of Disease Progression In Adults With Open-Angle Glaucoma?, My-Hang Pham

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether fixed-combination prostaglandin analog/β-blocker therapy is safe and more effective than β-blocker monotherapy in the prevention of disease progression in adults with open-angle glaucoma.

Study Design: Review of three English language randomized controlled trials published in 2008 and 2010.

Data sources: 3 randomized, controlled, double-blind trials comparing fixed-combination prostaglandin analog/β-blocker therapy to β-blocker monotherapy were found using Pubmed, Medline, and Cochrane databases.

Outcome Measured: Disease progression/regression was assessed by post-baseline measurement of IOP during three follow-up visits throughout the trials. The safety profile of each therapy was …

Is Rivastigmine Effective In The Treatment Of Alzheimer’S Disease?, Beena Patel

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not rivastigmine is effective for the treatment of Alzheimer’s Disease.

STUDY DESIGN: Review of two trials in the English language published in 2007 and 2010, and an open-label, singlearm, multi-center study from 2008.

DATA SOURCES: Randomized, double-blind, placebo-controlled trials comparing rivastigmine to a visually-matched capsule (placebo) was found using PubMed and Cochrane databases.

OUTCOMES MEASURED: Overall global performance using the Alzheimer’s Disease Assessment Scale (ADAS-cog), ability to perform activities of daily living, cognitive function using the mini mental status exam (MMSE), and neuropsychiatric symptoms using BEHAVE-AD.

RESULTS: …

Is Tesamorelin A Safe And Effective Drug To Treat Lipodystrophy In Hiv Patients?, Jazmine A. Cole

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not Tesamorelin is a safe and effective drug to treat lipodystrophy in HIV patients.

Study Design: Review of three English language primary randomized controlled trials published between 2005-2010.

Data Sources: Randomized, placebo-controlled, double-blind clinical trials comparing Tesamorelin to a visually matched placebo were found using PubMed.

Outcome(s) Measured: Each of the three clinical trials assessed the improvement of lipodystrophy (accumulation of visceral adipose tissue) in HIV patients. In addition, they noted how the improvement in lipodystrophy would impact patient's self body image and quality of life. Prior …