Sixth Undergraduate Research Conference
April 3 – April 4, 2008
St. Mary’s Hall
School of Nursing and Health Studies
Georgetown University
Washington, DC

Antibiotic Resistant Microbes: The Fault of Modern Medicine
Albanese, Claire, Dooley, Bridget, Lucy, Catie, Robacynski, Katie, Round, Caroline & Angerio, Allan Ph.D.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

This research focuses on the rise, physiology, history, transmission, and treatment of various antibiotic resistant microbes. In particular we concentrate on methicillin-resistant staphylococcus aureus, vancomycin-resistant enterococcus, and antibiotic-resistant tuberculosis. Two case studies presented exemplify the transmission and course of one such microbe, MRSA.
Section I delves into the biological processes of antibiotic resistance and how the chromosomal make-up of bacteria lends itself to easy replication and transmission of resistant genes. Section II explains the transmission of the identified microbes and the immune response to infection. Section III will describe the effects of resistance in the field of medicine throughout the rise of antibiotic use. Section IV clarifies the difference between community-acquired and hospital-acquired MRSA, VRE, and antibiotic-resistant TB, as well as major risk factors. Lastly, section V will go through preventative method, treatment for each mentioned infection, and a review of commonly used antibiotics.

Ubiquitin-Proteasomal Pathways in Disease
Ali, Mohammed, Furino, Emily, Keegan, Bethany, Leland, Naomi, Angerio, Alan, Ph.D.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Proteasomes are complexes in the body essential to the degradation of abnormal proteins, and are thus naturally tied with several disease processes.  The complex consists of two end-caps and two enzymatic rings, stacked in a barrel shaped manner to facilitate form with function.  Abnormal proteins in the body are first tagged to be degraded by the protein ubiquitin before they can be recognized by the proteasome cap. Once recognized, the ubiquitin-proteasome system, or UPS, ultimately decomposes the abnormal proteins into chains of amino acids as they move along the internal core. The promotion and utility of UPS plays an essential role in disease processes such as neurodegenerative disorders, cancers, and prion-related illnesses. Neurodegenerative diseases are characterized by clumps of accumulated abnormal proteins that are unable to be broken down by the UPS. Similarly, prion-related diseases employ a mechanism that triggers abnormal aggregation of proteins, impairing the proteolytic activity of the UPS. Within the context of cancers, proteasome promotion and inhibition both play instrumental roles in the clinical prognosis. Potent viruses, such as HPV have adapted ways to fool proteasomes into destroying the body’s own benefactors, tumor suppressor proteins, thereby prevailing over the cell’s proteolytic defenses. The extent of the faculties of the UPS and its roles in disease termination and prevention have yet to be fully investigated.

Regioselective Copper-Catalyzed Amination of Bromobenzoic Acids Using Aliphatic and Aromatic Amines
August, Adam & Casimir, Michael.
Department of Chemistry, Georgetown University

A chemo- and regioselective copper-catalyzed cross-coupling procedure for amination of 2-bromobenzoic acids was tested.  This reaction method eliminates the need for acid protection and produces N-aryl and N-alkyl anthranilic acid derivatives in up to 99% yield.  Anthranilic acids have applications in the pharmaceutical industry as non-steroidal anti-inflammatory drugs and are useful in the development of antimalarial and anticancer drugs.  N-(1-Pyrene) anthranilic acid has been employed in metal ion-selective fluorosensing. Titration experiments showed that this pyrene-derived amino acid forms an equimolar complex with Hg(II) in water resulting in selective fluorescence quenching even in the presence of other metal ions such as Zn(II) and Cd(II).

Mercury: Effects on the Human Nervous System
Battle, Molly, Brown, Francesca, Pratt, Louisa, Yates, Theresa, Dorrance, Carter & Angerio, Allan Ph.D.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

This article outlines the types of mercury found in nature, their natural presentation, and how they are incorporated into the body.  The most common type of mercury is methyl mercury, which most prominently affects the nervous system.  Methyl mercury affects the microglial cells and the mitochondria in the neurons.  The neurotransmitter glutamine has altered uptake and transport, which triggers opening of the NMDA channels in the mitochondria.  This increases membrane permeability of the mitochondria, and allows for the leaking of cytochrome c.  Cytochrome c is necessary for apoptosis stimulation, and with increased concentrations leads to cell death within the nervous system.  Mercury poisoning presents with many neurological symptoms including tremors, memory loss, and sensory impairment.

Estrogen Mimicking Compounds In the Environment
Bernal, Linda, Critz,  Julianna, Tran, Jennifer & Marrinan, Jaclyn.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Using the 1997 Silent Spring Institute’s report, The Cape Cod Breast Cancer and Environmental Study: Result of the First Three Years of Study, this paper investigates the physiological effects of estrogen mimicking compounds on mammary cells and the consequent increase of breast cancer incidence on Cape Cod, Massachusetts. Substantial amounts of environmental estrogens were found in groundwater contamination resulting from the past use of pesticides in the Cape Cod region, most notably by the Massachusetts Military Reservation (MMR). This paper assesses the role of estrogen in breast cancer pathogenesis as a foundation to understand the role of estrogen mimicking compounds in breast cancer development. The results of this study provide evidence that supports the idea that there is a higher incidence rate of breast cancer in areas where there is more exposure to estrogen mimicking compounds.

Identification of linkages between novel HIV-1 genotypic mutations and drug-resistant mutations
Boyd, Allison, C.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Mutations in the protease and reverse transcriptase genes in HIV-1 can result in resistance to antiretroviral (ARV) therapy. Mutations occurring in these two regions that are not currently recognized to be associated with resistance are considered novel mutations. Due to the complexity of ARV therapy it is likely that more HIV genomic mutations are associated with resistance than are currently identified. Some of the novel mutations alone or in combination with other mutations may modulate drug resistance. The purpose of the study is to identify mathematical correlations between novel mutations in both the protease and reverse transcriptase region and known ARV resistance mutations. Chi squared and Fisher exact tests detected 49 novel mutations in the reverse transcriptase region that correlate with at least one known drug resistance mutation, and 32 novel mutations in the protease region that are correlated with at least one known drug resistance mutation (P < 0.05). A mathematical correlation between two mutations does not necessarily correspond with a biological correlation. Therefore the next step in this research would be to identify the role that each of the novel mutations that are correlated with known ARV resistance mutations actually play in ARV resistance.

The Cellular Effect of Lead Poisoning and Its Clinical Picture
Brochin, Robert, Leone, Siena, Phillips, Dylan, Shepard, Nicholas & Zisa, Diane.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Purpose: To investigate the effect of the lead ion on the human body, specifically its effect on cells and to research its clinical picture.
Results: Lead intoxication affects many systems of the body including the cardiovascular, renal, and reproductive systems.  Its most detrimental effects occur in the nervous system where lead blocks the receptor know as N-methyl-D-aspartate, an effective receptor involved in the maturation of brain plasticity. The toxicity of lead plays a major role in the communication between astrocytes and endothelial cells. By disrupting the blood-brain barrier, it causes encephalopathy and edema that primarily affects the cerebellum. Fetus astrocytes in utero are at an especially high risk of lead intoxication because the immature endothelial cells that form the capillaries of the brain offer a decreased resistance to lead, and thereby easily allow Pb2+ to enter the brain. Intracellularly, lead replaces calcium as a second messenger, binding with calmodulin more readily than calcium, resulting in an alteration in protein conformation. This altered conformation leads protein kinases to phosphoylate and activate substrate molecules, which alter various cellular processes leading to the clinical picture of lead poisoning. In order to prevent the deleterious effects that Pb has on the human system it is important to understand the various means by which it is introduced into the body. Environmental and domestic sources of Pb are the most often seen causes for the disease, but with proper precautionary measures it is easily possible to adequately reduce the level of risk associated with lead poisoning.

Styrofoam Trays and Standardized Tests: ELL Students, School Lunches, and Obesity
Burnes, Sara.
Edmund A Walsh School of Foreign Service, Georgetown University

Links between nutrition and achievement in public schools (measured by results on standardized tests, graduation rates, and similar means) have long been noted. These links have led to the creation of initiatives such as the District of Columbia s universal free breakfast program. Now, as evidence of an American childhood obesity epidemic–especially prevalent in the Hispanic community– comes to light, schools are being called upon to not just to feed students, but to feed them nutritious meals that will encourage healthy habits for life. Are schools feeding students meals that boost their body-mass indexes along with their test scores?
This paper attempts to link these concepts by analyzing the English Language Learner DC senior high school student population with a special focus on Hispanic students, using District of Columbia Public Schools data. According to both public school and private sources, there is a significant correlation between the percentage of English Language Learners and high reduced or free lunch program participation in urban schools. Based on school-reported enrollment data on English Language Learners and Number Receiving Free or Reduced Price Lunch, as well as national data to create plausible estimates for the number of ELL students receiving Free or Reduced Lunch in Washington, this paper will examine the effects of the USDA’s National School Lunch Program and Breakfast Program guidelines. To do so, the author will review the nutritional value of guideline-following meals, as well as the health of Hispanic ELL students through BMI and diabetes statistics.
Conclusion: School meals may include calorie-dense foods and allow many exceptions for foods of dubious nutritional value, contributing to unhealthy habits. Yet other snacks in schools, as well as genetics and reduced physical activity among children, also contribute to obesity in the examined population.

The Role of Microglial Cells in Neurodegenerative Diseases
Chang, Haeseon, Iyengar, Swathi, Mulholland, Erin, Maloney, Caitlin, Jansen, Sierra & Angerio, Allan Ph.D.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Microglia are a group of functionally supportive neuroglia in the central nervous system; they provide immunity by phagocytizing foreign substances and aid in the overall health of the CNS. However, as overall health in the CNS deteriorates, the microglia become activated and become detrimental to the entire system.  The microglia become activated by inflammation, trauma, ischemic/infarctive conditions, and neurodegenerative diseases. With increased activity of these cells, there is a precipitous rise in output of cytotoxins associated with microglial metabolism.  This ultimately causes cellular impairment and death. Our research aim is to determine the extent of microglial involvement in basal gangliar degenerative diseases, focusing on Huntingdon s Chorea and Parkinson s Disease.

Microglia play a prominent role in basal ganglia dysfunction. In the case of Huntington’s Chorea, proinflammatory cytokines released by the microglia directly correlate to the disease progression. In Parkinson’s Disease, a neurodegenerative disease similar to Huntington’s Chorea, cytokines released by the activated microglia contribute to disease progression.  However, in Parkinson’s, dopamine deficiency is a key cause of  disease progression. The research into the exact role of microglia in neurodegenerative diseases is still in its formative years, but based on the results of research involving microglial stem cells and rodent microglia, scientists are uncovering the myriad roles of microglia in both normal and pathological physiology.

Confronting Religion: Perceptions and Health-Seeking Behaviors of Devout Adolescents when Faced with a Sexually Transmitted Infection in Ghana
Crommett, Matthew C.
Department of International Health, School of Nursing and Health Studies, Georgetown University

This study investigates the health-seeking behaviors of adolescents in three communities in Ghana when confronted with a sexually transmitted infection (STI). It looks into the reasons why adolescents (aged 10-19 years) choose certain sexual health services and support outlets over others and the general perceptions attached to an adolescent who has contracted a sexually transmitted infection. As religion has often been considered an important force in the formation of attitudes and practice toward sexual behavior, this study pays particular attention to the effect that religion has on the decisions made following the contraction of a sexually transmitted infection. Data for this study was gathered through in-depth interviews, focus group discussions (FGDs) and the administering of a survey. 152 subjects were included in the study over a two month period. The results show that adolescents harbor negative perceptions of other adolescents who have contracted a STI. Adolescents would seek care and support for a STI, but sometimes from non-formal routes that have unusual and sometimes unreliable treatment programs. Sexual health care was perceived as being too expensive for adolescents at the health facility. Transport to the nearest health facility was not a problem, but the public nature of the facility drew concerns from adolescents. Individual knowledge of STIs and their symptoms was very low and taught by insufficient sources. Religion, be it Christianity or Islam, affected the knowledge levels and perceptions of adolescents on a number of sexual health topics. A large majority (84%) believed that abstinence was the only way to prevent STIs. Nearly all subjects considered themselves devout and regarded very highly the recommendations of their religious leader. As all adolescents attend religious gatherings multiple times per week, these gatherings are seen as potential forums for dissemination of information about sexual health.

HIV-1 genotypic mutations associated with transmitted drug resistance in Washington, DC
Dickinson, Katie, Yarlagadda, Sunaina, Boyd, Allison, Herzberg, Emily, Lamparello, Nicole, de Leon, Miguel, Porter, Allison, Rohr, Kaileen, Smith, Staceyann.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Background: When HIV-1 positive individuals engage in high-risk behaviors, the possibility of transmitting drug resistant variants of the HIV-1 virus increases. Varying rates of HIV-1 mutations resulting in reduced viral susceptibility to anti-retroviral drugs (ARV) among treatment-naïve individuals (those who have never been treated with ARV) are being reported in metropolitan areas internationally. Previous investigations within the US have reported transmitted drug resistance (TDR) within 8-22.5% of HIV-1 individuals. This study is the first to define rates of genotypic resistance among treatment-naïve HIV-1 infected individuals in Washington, DC, the area with the highest rate of HIV/AIDS in the US. DC reports 128 AIDS cases annually per 100,000 people whereas the US records 14. Methods: From January 1, 2005 to December 31, 2006, a Washington, DC cohort of 142 HIV-1 treatment-naïve patients was identified with genotypic analyses of their HIV-1 virus to identify the presence of mutations associated with TDR. Results: Results indicate that treatment naïve individuals in Washington, DC are infected with drug resistant HIV-1 virus strains. Analysis of the rates of clinically relevant mutations with respect to high-risk behaviors and demographic variables revealed p-values greater than 0.05, indicating no significant statistical correlation. This demonstrates that the pattern of HIV-1 drug resistance is similar to that observed in other metropolitan areas. Those who belong to a specific demographic or who participate in a risk behavior are no more likely to acquire TDR than those who do not. Conclusions: These results show the rates of ARV resistance in Washington, DC, are comparable to those reported in other major cities across the US. Genotypic ARV mutations resulting in TDR do not correlate to specific risk factors or demographics. However, because of increasing TDR rates, significant public health implications remain that validate the need for further investigation.

Antibiotic Resistant Microbes and Superbugs: What to do?
Dickson, Natalie, Gaine, Shannon, Devitt, Erin, Perkowski, Katelyn & Angerio, Allan Ph.D.
Department of Human Science and Department of Professional Nursing, School of Nursing and Health Studies, Georgetown University

We investigated the rise of antibiotic resistant microbes and their growing effects in the medical realm.  It was observed that in the future, people who are antibiotic resistant to certain bacteria will most likely die immediately after exposure.  This is due to the limited number of antibiotics left to treat patients, unless there is an advance in research.  Two antibiotic resistant bacteria s, methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus faecium, are among those bacteria that are threatening the population.  These bacteria attack the cell walls; thus, preventing the bacterial cell from making proteins and attacking the antigen.  It has been studied that antibiotics such as vancomycin and linezolid are the last resort for people who have become infected with the above mentioned bacteria.  Therefore, researchers are attempting to find new solutions for treatment; these include synthesizing antibiotics from non-natural means, or xenobiotics, administering Platensimycin, a recently discovered antibiotic, and sequencing the bacterial genome in order to identify new targets for antibiotics. While these results may look promising, it is important for clinicians to be aware of correct antibiotic usage and to avoid spreading infections by washing their hands.  Antibiotic resistant microbes pose a threat to the population unless steps are taken immediately to prevent this problem.

Surgery for Trachoma Trichiasis in the Highlands Region of Chiapas, Mexico
Doran, Shannon.
Department of International Health, School of Nursing and Health Studies, Georgetown University

Aims: This study looks at the roots of the discontent expressed by operated patients with trachoma trichiasis in the highlands region of Chiapas, the common reasons why persons in this area refuse surgery for trachoma trichiasis, and the other factors that influence a person’s decision to accept/refuse surgery.
Methods: Interviews were conducted with persons in two study groups: persons with trachoma trichiasis who had been operated on in the past and persons with trachoma trichiasis who had never been operated on. During the interview, a questionnaire was completed and an eye exam was conducted.
Results: Population characteristics across the study groups were very similar- most were poor, rural farmers or housewives around the age of 65. The only major dissimilarity was the number of men and women- 4 and 12 respectively. Within the two study groups, 3 persons currently accept surgery for trachoma trichiasis while 13 do not. No significant relationship was found between knowledge, attitudes, perceptions, and experiences and acceptance/rejection of the surgery. However, other important qualitative findings were discovered. Post-operative care was found to be lacking- 7 out of 8 patients did not receive any acetominaphen, tetracycline, or bandages after surgery. For people who did not accept surgery, the most common reason given for the rejection was fear. Also, 8 of 13 persons who did not accept the surgery did not feel that their trachoma was serious.
Conclusions: From the results of this study, it is unclear if knowledge, attitudes, perceptions, and experiences affect a person’s decision to have surgery for trachoma trichiasis. The most significant finding was that only one of the patients who had the surgery was given any type of treatment afterward. Better post-operative care must be implemented and further study is needed to investigate what influences the decision to accept/reject surgery for trachoma trichiasis.

The Relationship Between the Priod Protein Related Diseases and Neurodegenerative Parkinsonian Disorders
Emhof, Margi, Feldman, Chelsea, Hsieh, Jerry, Raheem, Anam, Robbins, Leah & Angerio, Allan Ph.D.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Parkinson’s Disease is a neurodegenerative disorder affecting the neurons of the substantia nigra, thus disrupting dopamine and norepinephrine production in this region of the brain.  The disease is characterized by the presence of alpha-synuclein protein aggregates, termed Lewy bodies, within the affected neurons, which closely resemble aggregates formed in prion protein related diseases.  While it is clear that the presence of these amyloids have a detrimental effect on the neurons, the origin of their toxicity remains hotly debated in the scientific community.  Effective treatments against neurodegenerative disorders, such as Parkinson’s disease and prion-related diseases cannot be developed until the toxicity of these protein aggregates is better understood.  Based on a thorough review of relevant literature, we have proposed that both the actual amyloid fibers, as well as the soluble oligomers associated with amyloidosis, are responsible for the damage done to the neurons that ultimately leads to the cell death associated with these neurodegenerative diseases.

Anabolic-Androgenic Steroids: A Review of the Physiologic Effects and Emerging Cardiovascular Risks
Esmaili, Armond M., Bench, Elias M., Herb, Brandon D., Carroll, Erin M. & Angerio, Allan Ph.D.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Anabolic-androgenic steroids (AAS) are synthetic derivatives of testosterone used for athletic, clinical, and cosmetic purposes. Endogenous testosterone serves two key functions in the human body; it is androgenic, promoting the development of male secondary sexual characteristics, and it is anabolic, stimulating muscle growth and protein synthesis. AAS seek to maximize testosterone’s anabolic effects while reducing its androgenic action. However, clinical studies have demonstrated that complete separation of these two effects cannot be achieved, and thus no purely  anabolic steroids currently exist. Supraphysiologic levels of testosterone and its metabolites received orally, transdermally, or parenterally have numerous physiologic side effects throughout the body. While athletes, both competitive and recreational, have used AAS to exploit their effects on increasing muscle strength and lean body mass, negative action on the reproductive, endocrine, hepatic, integumentary, neurological, and cardiovascular systems consequently result. Specifically, recent case studies have revealed several adverse cardiovascular effects, including left ventricular hypertrophy, blood vessel plaquing, and impaired blood vessel elasticity. These alterations have been implicated in increasing the risk of thrombosis, atherosclerosis, and sudden cardiac death among users of anabolic-androgenic steroids.

Popular Perceptions of Environmental Health Concerns in the Dominican Republic
Frangos, Stephanie.
Edmund A. Walsh School of Foreign Service, Georgetown University

The environmental health of a community plays a large role in determining a population’s public health status.  Environmentally-mediated disease makes up a large percentage of the global disease burden and is especially high across developing nations.  Communities in the developing world must be educated in order to take action to improve the health of their environment with respect to drinking water, sanitation, and waste management.  This community action will, in turn, positively impact public health status.  In order to create effective policy and public health measures that will successfully involve community members, the knowledge and attitudes of populations must be analyzed.  This study analyzes the affect of socioeconomic status, education and age on the knowledge and attitudes surrounding water, sanitation, waste management services, and the connections between public health and the environment in Jarabacoa and El Callejón, a small town and a rural community in the Dominican Republic.  The study was completed using a mixed methodology, which employed structured oral interviews of household residents, in-depth interviews with healthcare professionals and government officials, and observation in the respective communities.  Socioeconomic status, education, and age were all found to impact the knowledge and attitudes surrounding the environmental and public health issues in question.  Data suggests that lower socioeconomic groups, individuals with fewer completed years of education, and the elderly should be most targeted when implementing programs and policies to improve drinking water practices, change sanitation habits, and involve the public in waste management of similar communities throughout the Dominican Republic and the developing world.

Links between obesity and cancer
Gabrio, Jenna, Menser, Natalie, Elsener, Kathleen, Rogan, Katherine, & Angerio, Alan Ph.D.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

The emerging obesity epidemic has serious health consequences. Obesity is a risk factor for certain cancers, particularly those cancers that are associated with hormones. Excess adipose tissue can adversely affect the metabolic pathways leading to oxidative stress, store lipposoluble carcinogens, and act as an endocrine organ that disrupts homeostasis. A preventive approach that combats obesity through exercise, a balanced diet rich in antioxidants, and weight control, could reduce the risk of developing certain cancers.

Type I Alpha-2b Interferons and their Role in Chronic Hepatitis C
Henry, Carolyn, Iyer, Tara, Lambert, Megan, & Pereira, Karen.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

In order to inhibit viral replication in the body, interferons act rapidly by binding to intercellular receptors and signaling protein synthesis, which function to decelerate cell growth or most often to trigger apoptosis. Through basic biochemical pathways involving signal transduction and phosphorylation, type 1 IFN-α stimulate the transcription of specific genes in the nucleus. The proteins produced affect the translation initiation factor as well as enzymatically degrade the viral RNA itself to yield their antiviral effects. Like other viruses, Hepatitis C has evolved to develop mechanisms to evade interferons by blocking synthesis and prevent cellular action. Thus, recent research of the virus-host interactions and the cellular antiviral response indicates that interferons alpha-2a and alpha-2b, as well as the new interferon alfacon-1 are the most effective therapies. In addition, pairing the pegylated interferon alpha-2b and the nucleoside ribavirin in a combination therapy has recently proven more valuable in continuing type 1 interferons cellular functions in the presence of various strains of chronic Hepatitis C. Although the treatment with ribavirin produces a myriad of adverse effects while enhancing the IFNs effects, it most efficiently inhibits chronic Hepatitis C’s viral replication and aids in pegylated interferon alpha-2b s immunomodulatory effects.

Use of erectile dysfunction drugs (PDE-5 inhibitors) among HIV-positive individuals in medical care
Herzberg, Emily M.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Background: Prevention in HIV-positive individuals is has been shown to influence risk behavior outcomes.  The use of drugs to treat erectile dysfunction, PDE-5 inhibitors, among HIV-positive individuals to enhance their sexual experience has recently been demonstrated between 6%-42% of populations, creating important implications in terms of prevention in HIV-positive persons.  Use of PDE-5 inhibitors has been found to lead to significant increases in risk behaviors capable of transmitting HIV, including an increased number of sexual partners and increased rates of unprotected insertive and receptive anal sex.  Recent documented use of PDE-5 inhibitors may be due to self-identified erectile (ED) dysfunction among HIV-positive men.  While data exists for a multitude of metropolitan areas, no data has been reported for the District of Columbia
Methodology: This data is part of a larger study of the prevalence of a variety of risk behaviors among HIV-positive individuals at an urban HIV clinic in Washington, DC.  Interviews were conducted using hand-held PDAs with HAPI software.  A convenience sample of 126 HIV-positive individuals receiving medical care at an urban HIV clinic in Washington, DC was recruited between Jan.   July 2007.  Participants responded to questions about demographics, sexual risk behaviors, drug and alcohol use, use of the internet for sex, use of PDE-5 inhibitors, depression, and partner violence.
Results: Initial results from a subset of 92 study participants from one clinic site indicate that HIV-positive individuals in DC are using PDE-5 inhibitors to enhance sexual experience.  Overall, no heterosexual participants used PDE-5 inhibitors during sex.  Out of 42 MSM who took the survey, 39 answered these questions.  25% (n=8) of the 39 MSM reported using PDE-5 inhibitors, with about half obtaining the drugs through a prescription and half through other means (friend/neighbor, internet, off the street, etc.)
Discussion: Further analysis is necessary to determine significant correlations between PDE5-inhibitors and other demographic and risk behavior variables.  However, initial results place Washington, DC within published literature in terms of PDE-5 inhibitor use among HIV-positive persons.

Evaluating Resistance Mechanisms in MRSA
H. Holcomb1, K. Durbin2, N. Darling2, M. Cho2, K. Choi1, and Dr. Allan Angerio1, Ph.D.
Departments of Human Science1 and International Health2, School of Nursing and Health Studies, Georgetown University

Bacterial resistance to antibiotics is a significant issue in both healthcare and community settings, causing increases in morbidity and mortality.  Bacterial resistance can be induced through random genetic mutations, the improper use of antibiotics or the uptake of plasmid DNA from foreign cells. Any bacterium can evolve resistance, however due to the broad spectrum of antibiotics it exhibits resistance to, and its enhanced virulence, this paper focuses on Methicillin Resistant Staphylococcus Aureus (MRSA).
MSRA can be acquired nosocomially, through extended hospital stays or the use of invasive devices. It can also be acquired in the community, with outbreaks generally occurring in schools, gyms and other crowded settings. Community Acquired MRSA (CA-MRSA) typically colonizes either the nasal passages or the skin. It usually presents with various cutaneous disorders, and can become invasive, leading to acute systemic infections. On a cellular level, MRSA secretes a variety of toxins related to pathogenesis, including Panton-Valentine Leukocidin (PVL), a toxin targeting leukocytes for lysis. Secretion of PVL is also associated with strains of staphylococcus aureus displaying antibiotic resistance.
MRSA has acquired a variety of immune evasion strategies including the production of superantigens, the formation of biofilms, and the invasion of leukocytes. Several vaccine models have shown promise as effective tools for the management of MRSA, including a genetic vaccine and one that uses surface proteins to elicit a cell specific immune response.

Prions and Parkinson’s Disease
Janiszewski, Kristen , McDaniel, Lauren, Pryor, Antonia, Zehentbauer, Kendra & Angerio, Allan Ph.D.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Parkinson s Disease, a degenerative disease of the central nervous system, occurs when neurons in the substantia nigra, which normally produce dopamine, die or become impaired. The absence of dopamine, a critical neurotransmitter, results in the characteristic symptoms of Parkinson’s Disease: muscle rigidity, particularly in the limbs and trunk; tremor of the hands, legs, jaw, or head; and impaired balance. Deterioration of the neurons of the substantia nigra corresponds strongly to the accumulation of fibrillar aggregates called amyloid plaques and the presence of cytoplasmic protein inclusions known as Lewy bodies. Linked to the formation of these amyloid plaques and Lewy bodies are prions, infectious proteins found in many neurodegenerative disorders, including Parkinson’s disease. The most predominant prion in the central nervous system, PrPc, is a normal, protease-sensitive prion, while PrPsc is an abnormal protease-resistant form of PrPc. The conversion of PrPc to PrPsc is a post-translational event that results in the accumulation of PrPsc as amyloid plaque deposits. These amyloid plaques from the conversion of PrPsc are neurotoxic to the dopaminergic neurons of the substantia nigra. Amyloid plaques also contribute to the deposition of Lewy bodies in the brain. Lewy bodies are intracytoplasmic inclusions made of fibrillar alpha-synuclein and an aggregated neurofilament, such as an amyloid plaque. Missense mutations predispose the alpha-synuclein to aggregate while mutations in genes lead to the deposition of amyloid plaques. The accumulation of the alpha-synuclein fibers and amyloid plaques resulting in the formation of Lewy bodies is detrimental to the cell, leading to mitochondrial damage, activation of inflammatory processes and further aggregation of misfolded proteins.

Pax3/7 Expression Coincides with MRF Genes During Acute Skeletal Muscle Hypertrophy
Kander, Lizzie.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Recent evidence implicates Pax3 and Pax7 as upstream transcriptional regulators of muscle regulatory factors (e.g., MyoD) in skeletal muscle. Pax3 and Pax7 are thought to direct muscle precursor (satellite) cell proliferation and self-renewal and also commit adult stem cells (non-satellite cells) into a myogenic lineage. We functionally overloaded (FO) the plantaris muscle in adult rats via surgical ablation of the gastrocnemius muscle and then assessed whole-muscle Pax3, Pax7, and MyoD protein content after 12h, 1, 2, 3, and 7 days using western blot analysis. Relative to control rats, FO muscle mass increased ~7 and 12% on day 3 and 7, respectively (P< 0.05). Pax3, Pax7, and MyoD expression rose at 12h and 1 day (P> 0.05) and peaked on days 2 and 3 (P< 0.05). Day 2 expression for Pax3, Pax7, and MyoD were ~4-, 4-, and 2-fold higher in FO than control rats, respectively. Day 3 expression for Pax3, Pax7, and MyoD were ~7-, ~6-, and ~2-fold higher in FO than control rats, respectively, and returned to baseline by day 7. These results indicate that Pax3 and Pax7 proteins follow a similar temporal pattern of expression as a muscle regulatory factor (MyoD) known to be important for muscle hypertrophy. Our next objective is to discriminate whether satellite cells or adult stem cells are the principal source of Pax3 and Pax7 expression in hypertrophying skeletal muscle.

The Inflammatory Effect of a Mixture of Bioactive Constituents
McElroy, Kaitlyn.
Georgetown College visiting student, spring semester 2008
Bates College Biology Department, Lewiston ME 2007-12-14

Juniperus Virginiana (Eastern Red Cedar) has been used in indigenous medicine for the treatment of colds and rheumatism. In the present study, the anti-inflammatory properties of a juniper tree extract were investigated. All properties of the tree were extracted with hexane followed by acetone. The extraction was then tested for anti-inflammatory activity on Carrageenin induced hind paw edema in the rat. The extraction exhibited a dose (0.2, 0.3, 0.6mg/ml) and time dependent increase in inflammation at 1, 3, and 5hrs after injection of Carrageenin, indicating a pro-inflammatory response due to the extract.

HPV Vaccine: Mandatory Healthcare vs. Individual Rights
Moher, Justin & King, Kathryn. *
Department of Human Science, School of Nursing and Health, Georgetown University* & Department of Biology, Georgetown College#

In June of 2006, the Federal Drug Administration (FDA) approved Gardasil for use as a vaccination against Human Papillomavirus (HPV) strains 6, 11, 16, and 181; the strains  responsible for more than 70 percent of cervical cancers 2. With an estimated 493,000 new cases of cervical cancer each year, of which the United States claims 11,0003, Gardasil’s proven near 100% success rate for preventing female genital lesions and warts makes it an extremely beneficial drug. The possibility for dramatic benefits has sparked a debate in the United States as to whether Gardasil vaccinations should be mandatory; in essence, should the health of the public stand above the autonomy of the individual? Conclusion: The government will continually have to redraw and re-evaluate the line between public welfare and individual autonomy.

Antiestrogen Resistant Breast Cancer and IRF-1
Mulla, Jennifer E.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Fulvestrant (ICI 182,780) is an example of a steroidal estrogen receptor inhibitor and pure antagonist used in the treatment of breast cancers that express the estrogen receptor (ER+).  ICI 182,780 (ICI) is a commonly used treatment for postmenopausal women, although ICI resistance has become a barrier to treatment for many patients. The Clarke lab seeks to understand the mechanism of antiestrogen resistance and develop methods for restoring antiestrogen sensitivity. To study antiestrogen resistance, we have developed LCC1, an ER+ breast cancer cell line that does not require estrogen for growth, from ER+ MCF7 breast cancer cells. LCC9 cells were then selected in vitro for cross resistance to Tamoxifen and ICI.
Using proteome and transcriptome analysis, we have identified a number of genes that are differentially expressed between antiestrogen sensitive LCC1 cells and resistant LCC9 cells. One of these proteins, Interferon Regulatory Factor 1 (IRF-1) showed a marked decrease in protein expression, mRNA levels, and transcriptional activity in LCC9 cells versus precursor LCC1 cells. IRF-1 is a nuclear transcription factor known to play a role in cellular immunity and tumor prevention. Down regulation of IRF-1 is indicated in several cancers, and is also associated with an upregulation of prosurvival protein Bcl-2. We therefore hypothesize that the down regulation of IRF-1 may play a role in the mechanism antiestrogen resistance.
Preliminary studies show that IRF-1 levels can be restored in LCC9 cells by treatment ranging from 10 to 1000 IU/mL with type two interferon (IFN-γ). This restoration of IRF-1 is accompanied by a down regulation of Bcl-2 in LCC9. It has also been verified that co-treatment of LCC9 cells with IFN-γ and ICI causes a greater decrease in proliferation than treatment with ICI or IFN- γ; alone. An optimum combined dose of 100IU/mL of IFN- γ; and 10-100 μg/mL has been identified and will be used in annexin V assays to determine the level of apoptosis in comparison to ICI or IFN- γ treatment alone and no treatment.
To further study the affect of IRF-1 on ICI mediated cell death, we have stably transfected wild-type IRF-1, dominant negative IRF-1 (dnIRF-1) and an empty vector into MCF7 cells. These cells represent a model of IRF-1 knockdown and over expression and are currently being screened to select clones with the highest transfection efficiency. These clones will be analyzed using annexin V, proliferation, and western blot analysis to determine the affect of IRF-1 over expression and knockdown on ICI induced apoptosis, Bcl-2 levels, and proliferation.

Burkina Faso’s Experience with the International Coordinating Group (ICG) during the 2007 Meningococcal Meningitis Epidemic: Successes, Challenges, and Future Outlook
Nihara, Aki.
Department of International Health, School of Nursing and Health Studies, Georgetown University

Purpose: Burkina Faso was the most severely affected country in the sub-Saharan African meningitis belt in 2007; the 25,961 cases of meningococcal meningitis in Burkina Faso represent 69.2% of the total number of cases in all 13 countries. The International Coordinating Group on Vaccine Provision for Epidemic Meningitis (ICG) ensures rapid access to vaccines for countries experiencing meningitis epidemics. The purpose of this study is to examine successes and challenges experienced by Burkina Faso in requesting and receiving vaccines from the ICG for districts with meningococcal meningitis epidemics in 2007.
Results: Burkina Faso made 4 requests to the ICG for 5,817,552 doses during the epidemic season.  The total number of doses that Burkina Faso received from all sources was 4,758,700, of which 2,700,400 were received from the ICG.  Information provided in the requests varied by district only with regards with laboratory confirmations.  Most districts implemented vaccination campaigns using vaccines from the national stock or previous requests.  This study found Burkina Faso to be resourcefulness with the supply of vaccines received, yet major problems of delayed request submission and vaccination campaign implementation remain.
Conclusion: It is necessary for Burkina Faso to update population information, improve documentation practices, utilize the alert threshold as a signal to request, and continue efforts to enhance national laboratory capacity.  The ICG should consider working to align its threshold definitions more closely with those of severely affected countries and to develop a comprehensive evaluation system that examines countries experiences with the request process.  While time and cooperation constraints hindered fulfillment of all the objectives of the study, it is clear that the ICG contributes positively to Burkina Faso’s fight against meningitis.

Microglial Cells In Health and Disease
Gaelan Ritter, Kelsey Schweiberger, Kathryn Tucker, Margaret Vose, Ja-Rei Wang
Department of Human Science, School of Nursing and Health Studies, Georgetown University

The purpose of this paper is to examine the role of the brain’s primary immune cell, microglia, and to assess their dual role as helpful and harmful agents in disease pathogenesis. Microglia cells are one of the four major types of neuroglia present in the central nervous system and make up five to fifteen percent of the total cell population. Scattered throughout the CNS, their main functions are to provide structural support and to phagocytice foreign substances as part of the brain s immune protection. When microglial cells become activated, their metamorphosis entails changes significant in the brain s self defense. In the instances of trauma or infection, microglial cells rapidly transform into an activated state. The activation constitutes a graded process involving a general reaction pattern of cellular responses, recruitment of other cells to the site of injury or invasion, and a variety of functional changes. Activated microglia secrete various mediators such as cytokines, chemokines, proteases, and amyloid precursor proteins. When microglia activation is prolonged, the microglia continually secrete mediators which cause chronic neuroinflammation in the brain. In Alzheimers disease, the presence of amyloid-beta containing extracellular plaques (A?) in the brain stimulates microglial cells to secrete neurotoxic substances that promotes neurodegeneration.  The aging of microglia promotes cell dystrophy, which creates a vicious cycle that contributes to Alzheimers pathogenesis.  Human immunodeficiency virus-1 (HIV-1) causes activation of microglia, which leads to more infected cells crossing the blood-brain-barrier and amplified neurotoxin production, especially chemokines.  Consequent microglia-mediated inflammation causes cognitive, behavioral and motor dysfunction characteristic of HIV-1-associated dementia.

Trochlear Contact Pressures After Straight Anteriorization of the Tibial Tuberosity
Rue, Jon-Paul M.D., MC USN1, Colton, Anne, M.D. 2, Zare, Stephanie 3, Shewman, Elizabeth M.S. 3, Farr, Jack M.D. 4, Bach, Bernard Jr., M.D. 3, Cole, Brian M.D., M.B.A. 3, 5 LCDR
3 Division of Sports Medicine, Department of Orthopaedic Surgery Rush University Medical Center, Chicago, IL5 Director, The Rush Cartilage Repair Center, 1 Department of Orthopaedic Surgery, National Naval Medical Center, Bethesda, MD, 2 Surgical Orthopedic Associates, Broomall, PA, 4 OrthoIndy Cartilage Restoration Center of Indiana and Indiana University School of Medicine, Indianapolis, IN.

Background: Anteromedialization of the tibial tuberosity has been shown to decrease mean total contact pressures of the lateral trochlea and to shift contact pressures to the medial trochlea.
Hypothesis: Modifying the AMZ osteotomy to a straight anteriorization osteotomy of the tibial tuberosity can decrease trochlear contact pressures without a resultant medial shift of forces to the medial trochlear contact area.
Study Design: Descriptive Laboratory Study
Methods: Ten cadavers were tested before and after straight anteriorization tibial tuberosity osteotomy by loading the extensor mechanism with 89.1N and 178.2N at 0, 30, 60 and 90 degrees of flexion following a validated patellofemoral joint loading protocol. Contact pressures were measured with electroresistive pressure sensors placed directly on the trochlea.
Results: The mean trochlear contact pressures following osteotomy decreased significantly (p < .05) for loads of 89.1N and 178.2N at both 30_ (23%, 20%) and 60_ (18.7%, 31.9%) of knee flexion. The peak contact pressures decreased significantly (p < 0.05) for loads of 89.1N and 178.2N at 30_ (24.3%,27.0%) and 60_ (31.9 , 24.5%), and for loads of 89.1 N at 90_ (13.4%) of knee flexion.
Conclusion: We demonstrated significantly decreased trochlear contact forces following straight anteriorization osteotomy of the tibial tuberosity, without a significant resultant medial shift of the center of force.
Clinical Relevance: Straight anteriorization of the tibial tuberosity may be a useful adjunct for patients with medial articular defects of the patellar or trochlea in whom anteromedialization would be otherwise contraindicated.
Key Terms: Trochlea, Contact Pressures, Tibial Tuberosity (aka, Tubercle) Osteotomy, Anteriorization

Survival of Human Prostate Carcinoma Cells after Treatment with NSAIDs and Exposure to Single and Fractionated Radiation
Singh, Jaskaran, Palayoor, Sanjeewani T., Aryankalayil, Moly, Cerna, David &
Coleman, C. Norman.
Department: Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892; Student of Georgetown University School of Nursing and Health Studies, Department of Health Systems Administration

The Department of Defense states that prostate cancer is the most commonly diagnosed cancer in men, accounting for 30 percent of all cancers.  Prostate cancer is the second leading cause of cancer death in men.  Additionally, there is no cure for locally advanced or metastatic prostate cancer.
Treatment for prostate cancer currently includes external-beam radiation therapy, and radical prostatectomy. Radiation therapy treatment is generally delivered in 1.8-2 Gray (Gy) fractions to the prostate over 7 to 8 weeks for a total of 65-75 Gy. Since the curative potential of radiation therapy has yet to be maximized, there remains a challenge to enhance prostate tumor control by identifying effective strategies for improving radiation sensitivity of tumors.
Purpose of Study:
1) Mimic clinical radiation therapy protocol and compare the survival of human prostate carcinoma cells following fractionated dose irradiation (2Gy x 5 and 1Gy x 10) and single dose (10Gy) irradiation in vitro using PC3 and DU prostate cancer cell lines.
2) Investigate the effect of Ibuprofen, a non steroidal anti-inflammatory drug (NSAID) on cancer cell radiation survival.
Results and Conclusion:
The data shows that higher concentrations of ibuprofen (0.5mM) alone decrease survival of PC3 and DU cells, while lower concentrations have little effect. The surviving fractions of cells irradiated with fractionated dose schedules were higher than the single dose treatment for both cell lines. 10 Gy single dose eliminated cell survival in PC3 cells almost entirely and decreased survival greatly for DU cells. There was not a significant difference in cell survival between 1Gy x 10 and 2Gy x 5 fractionation. The ibuprofen did not enhance radiosensitivity of the cells at the concentrations used in the present study. PC3 cells showed a higher level of sensitivity towards radiation and ibuprofen than DU cells.

The Role of Interferon in the Immune Response
Treacy, Lauren E.
Georgetown University

In 1940 scientists discovered that certain viruses interfered with the growth of other viruses in tissues.  It was not until 1950 that scientists discovered this interference to be caused by the action of the affected cell.   When a cell is attacked by an invader, the cell produces interferon to fight off the invader.  Interferon disrupts protein synthesis, which ultimately disrupts viral replication.  Interferon is also produced as a response to stress; in this way interferon assists in the body’s homeostatic properties.  Interferon is an antiviral innate immune response.  Interferon can be categorized into alpha, beta and gamma; alpha, beta and gamma interferon are all produced by different cells and perform different tasks. Interferon can have adverse affects if not properly regulated, but interferon can also be used for treatment of many viruses, such as Viral Hepatitis.

Comparative Pharmacokinetic Parameters of Intravenously Administered Ravuconazole in Healthy and Immunocompromised Infected Rabbits
Wallach, Caitlin.
Department of Human Science, School of Nursing and Health Studies, Georgetown University

Aspergillus fumigatus is an airborne fungi that is extremely dangerous to immunosuppressed patients.  There are poor success rates and toxicity associated with the drugs used to treat this infection.  A promising new drug is the triazole antifungal ravuconazole; its effectiveness and safeness give hope to better treatment for this infection.  In order to learn more about the behavior of this new drug in vivo, this research focuses on the pharmacokinetic parameters that result when ravuconazole is administered intravenously to two groups of rabbits: 1) healthy and 2) immunocompromised and infected with aspergillus.
Results: I have calculated and analyzed the pharmacokinetic parameters of ravuconazole over 24 hours when it is administered to healthy rabbits at different doses: 5, 10, 20, and 40 mg/kg body weight.  I have also drawn comparisons between the pharmacokinetic parameters observed in healthy versus immunocompromised, infected rabbits in dosage groups of 5 and 10 mg/kg body weight over 24 hours.
Conclusion: The information that I have calculated can be used in order to gain insight about how this new drug behaves.  Pharmacokinetic parameters such as clearance rate and half-life are useful in perfecting dosage regimens.  It is only through the gathering of data through research like this that physicians will one day be able to use ravuconazole as therapy for immunosuppressed patients who are suffering from fungal infections.  In my comparison of the healthy versus the immunocompromised, infected rabbits, I found the behavior of ravuconazole and the pharmacokinetic parameters to be very different between the two groups.  This finding is significant because it shows that the pharmacokinetics of ravuconazole must be studied in immunocompromised, infected models in order to perfect dosage regimens for these patients.

In-Vitro Dopamine Sensing Capabilities of Polycarbazole Film-Modified Platinum Electrodes
White, Bradley M.
Department of Human Science, School of Nursing and Health Studies & Department of Chemistry, Georgetown University

Many benefits arise from understanding the intricate functions of the human brain.  Analyzing neurological pathways and processes is necessary to better understand neurological diseases, such as Alzheimer s disease and Parkinson s disease. We investigated the ongoing development of chemical sensor technology using polycarbazole coated platinum electrodes. Our results suggest that polycarbazole electrodes meet and possibly surpass the sensitivity, selectivity and durability of current polymer electrodes used for detecting neurotransmitters. Experiments performed in the areas of sensitivity, selectivity, and durability have demonstrated that polycarbazole electrodes can detect physiological concentrations of dopamine (DA), can detect DA concentration changes in the presence of ascorbic acid, and can produce similar results when used for multiple days of experimentation. Therefore, we suggest that polycarbazole electrodes may act as accurate detectors for in vivo neurotransmitter detection experiments.

The Impact of Organizational Capacity on the Targeted Mass Distribution of Free Insecticide Treated Bed Nets Through the Public Sector in Rural Uganda
Young, Darwin.
Department of International Health, School of Nursing and Health Studies, Georgetown University & the Ugandan Ministry of Health

Malaria accounts for a significant portion of Sub-Saharan Africa’s disease burden.  Though many studies have shown the effectiveness of insecticide treated bed nets in reducing all-cause child mortality, no research has been done measuring the impact of operational capacity on ITN distribution through the public sector.  Using data collected as part of a multi-national study on the efficacy of 5 community-directed initiatives, this study explores the impact of operational capacity at both the district and community levels in rural Uganda.  A multivariate logistic regression revealed that district policy, transportation budget for supervision, and a high percentage of facilities that sent reports to the district were found to be the best predictors for ITN coverage.  Recommendations include allocating resources to support capacity building alongside ITN distribution programs and increased operational research.