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The Antibiotic Revolution, Alyssa Olsen

Spring 2013, Kuhn's Philosophy of Science

In 1928, Alexander Fleming discovered Penicillin, which revolutionized the way infections were treated. This discovery was revolutionary because it impacted the scientific field, the medical field, the pharmaceutical industry, and all of humanity. Alexander Fleming’s discovery of Penicillin sparked the development of antibiotics, which has continued to save people’s lives since the revolution. Thomas Kuhn would qualify the discovery of Penicillin by Alexander Fleming as a revolution because it led to a paradigm shift. Prior to the discovery of Penicillin, patients died from trivial injuries and infections. Fleming’s discovery of Penicillin is revolutionary because it changed the worldview of the …

A Magnetic-Resonance-Imaging-Compatible Remote Catheter Navigation System., Mohammad Ali Tavallaei, Yogesh Thakur, Syed Haider, Maria Drangova

Medical Biophysics Publications

A remote catheter navigation system compatible with magnetic resonance imaging (MRI) has been developed to facilitate MRI-guided catheterization procedures. The interventionalist's conventional motions (axial motion and rotation) on an input catheter - acting as the master - are measured by a pair of optical encoders, and a custom embedded system relays the motions to a pair of ultrasonic motors. The ultrasonic motors drive the patient catheter (slave) within the MRI scanner, replicating the motion of the input catheter. The performance of the remote catheter navigation system was evaluated in terms of accuracy and delay of motion replication outside and within …

Fibromyalgia Syndrome: A Pathoneurological Basis Of Disease, Alex D. Hamilton

Senior Honors Theses

Fibromyalgia (also known as fibromyalgia syndrome, or FMS) is a condition which causes its victims to suffer a wide range of symptoms, most notably chronic musculoskeletal pain. Although the causes of fibromyalgia remain unknown, recent advances help elucidate the underlying pathophysiologies of this condition, and show that it is likely not a musculoskeletal condition, but rather a pathoneurological condition.

Competition For Antigen At The Level Of The Apc Is A Major Determinant Of Immunodominance During Memory Inflation In Murine Cytomegalovirus Infection., Lila A Farrington, Tameka A Smith, Finn Grey, Ann B Hill, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

The unique ability of CMV to drive the expansion of virus-specific T cell populations during the course of a lifelong, persistent infection has generated interest in the virus as a potential vaccine strategy. When designing CMV-based vaccine vectors to direct immune responses against HIV or tumor Ags, it becomes important to understand how and why certain CMV-specific populations are chosen to inflate over time. To investigate this, we designed recombinant murine CMVs (MCMVs) encoding a SIINFEKL-enhanced GFP fusion protein under the control of endogenous immediate early promoters. When mice were infected with these viruses, T cells specific for the SIINFEKL …

Genomics Unbound: The Scientific And Legal Case Against Patents Based On Naturally Occurring Dna Sequences, Fazal Khan

Scholarly Works

While there have been mixed opinions as to whether gene patents were dead in light of Prometheus,this Article argues that a proper understanding of patent law, genomics, and public policy concerns should lead to no other result. The primary focus of this piece is to rebut certain vested interests in the biotechnology industry and affirm the normative claim that gene patents improperly fetter genomics research and development. First, through the lens of the Myriad case, we will recount why there was such a strong public interest movement against recognizing such patents. Specifically, we will show how patents on naturally occurring …

Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky

Dartmouth Scholarship

Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence …

A Semantic-Based Method For Extracting Concept Definitions From Scientific Publications: Evaluation In The Autism Phenotype Domain, Saeed Hassanpour, Martin J. O’Connor, Amar K. Das

Dartmouth Scholarship

Background: A variety of informatics approaches have been developed that use information retrieval, NLP and text-mining techniques to identify biomedical concepts and relations within scientific publications or their sentences. These approaches have not typically addressed the challenge of extracting more complex knowledge such as biomedical definitions. In our efforts to facilitate knowledge acquisition of rule-based definitions of autism phenotypes, we have developed a novel semantic-based text-mining approach that can automatically identify such definitions within text.

Results: Using an existing knowledge base of 156 autism phenotype definitions and an annotated corpus of 26 source articles containing such definitions, we evaluated and …

An Ethical Analysis Of Incentives As “Nudges” Toward Better Health Outcomes: A Case Study Of Seva Mandir’S Immunization Program In Rural Udaipur, Julika Kaplan

Independent Study Project (ISP) Collection

Seva Mandir, a non-governmental organization working on tribal development issues in the Udaipur District of India, offers pregnant women and mothers one kilogram of lentils for every visit they make to the organization’s monthly immunization camps. This study assesses whether it is ethical to use incentive-based systems, as opposed to empowerment through health education, to “nudge” the rural poor in Udaipur toward immunization. The information presented in this study is based on twenty-nine interviews with pregnant women and mothers of children less than two years old conducted during six field visits to Seva Mandir’s immunization camps. Through data obtained from …

Reduction In Phencyclidine Induced Sensorimotor Gating Deficits In The Rat Following Increased System Xc − Activity In The Medial Prefrontal Cortex, Victoria Lutgen, Krista Qualmann, Jon M. Resch, Linghai Kong, Sujean Choi, David A. Baker

Biomedical Sciences Faculty Research and Publications

Rationale: Aspects of schizophrenia, including deficits in sensorimotor gating, have been linked to glutamate dysfunction and/or oxidative stress in the prefrontal cortex. System x_c ⁻, a cystine–glutamate antiporter, is a poorly understood mechanism that contributes to both cellular antioxidant capacity and glutamate homeostasis.

Objectives: Our goal was to determine whether increased system x_c ⁻ activity within the prefrontal cortex would normalize a rodent measure of sensorimotor gating.

Methods: In situ hybridization was used to map messenger RNA (mRNA) expression of xCT, the active subunit of system x_c ⁻, in the prefrontal cortex. Prepulse inhibition was …

Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani

Community Health Sciences

Background

In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting.

Methods

We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total …

Vitamin D Supplementation Practices During Pregnancy And Infancy Among A Sample Of Muslim Women In Ireland And Saudi Arabia, Imann Khadrawi

Masters

Vitamin D is a steroid hormone, a group of fat-soluble pro-hormones, which encourages the absorption and metabolism of calcium and phosphorous. The requirement for the nutrient is high at particular stages of the lifecycle especially during pregnancy and infancy. Severe vitamin D deficiency during pregnancy may increase the risk of developing preeclampsia and gestational diabetes in pregnancy and rickets in the child. While vitamin D supplementation has been a policy recommendation in Ireland since 2007, at the time of this study, it was not a policy recommendation in Saudi Arabia. The present quantitative cross-sectional survey was conducted to determine the …

The Effects Of Mindfulness Meditation On Rumination In Depressed People, Rachel A. Sluder

Honors Theses and Capstones

Mindfulness meditation is a practice of focus, awareness, and non-judgmental acceptance of one's thoughts (Deyo et al., 2009; Kenny et al., 2007). Rumination is a maladaptive pattern of thought that is common in people with depression and other mood disorders. It can lead to further episodes of depression, and can be very destructive in that way (Nolen-Hoeksema, 2008). This paper reviews several studies on mindfulness meditation, depression, and rumination, with a focus on certain areas and phenomena such as alpha asymmetry (Keune et al 2013) and gamma band activity (Berkovich-Ohana et al., 2012). Modalities such as fMRI and EEG are …

Relationship Between Exercise Induced Dyspnea And Functional Capacity With Doppler-Derived Diastolic Function, Sumera Nasim, Najaf Nadeem, Aysha Zahidie, Tabbasum Sharif

Community Health Sciences

Background

Dyspnea is the frequent cause of exercise intolerance and physical inactivity among patients referred for exercise tolerance test. Diastolic dysfunction has shown significant correlation with exercise capacity and exercise induced dyspnea. To find out the frequency of diastolic dysfunction (DD) and the relationships between impaired exercise capacity and exercise induced dyspnea with DD by Doppler-derived indices among patients referred for stress test in a tertiary care hospital of Karachi.

Methods

For this study 135 consecutive patients who were referred for stress test at our non-invasive lab were screened for eligibility. Patients with valvular pathology, atrial fibrillation (AF) and coronary …

Study Of The Insulin Mimetic Sodium Orthovanadate In Glucosamine Induced Insulin Resistnace In Primary Rat Hepatocytes, Kalan Mcpherson

Masters Theses

Insulin resistance and type II diabetes is a disease state characterized by a lack of sensitivity of insulin to provoke a proper response in insulin sensitive tissues. Currently, we utilize glucosamine to increase flux through the Hexosamine Biosynthetic Pathway (HBP) to induce an insulin resistance like state in primary rat hepatocytes. We tested the effectiveness of the insulin mimetic sodium orthovanadate to determine if it could elicit an insulin-like response under these conditions. Mixed results were obtained on the effectiveness of vanadate as an insulin mimetic in this insulin resistant model.

The Investigation Of Microbe-Nematode Interactions, Chelsea K. Crepeau

Honors Theses and Capstones

No abstract provided.

Drug-Induced Linear Iga Bullous Dermatosis, Luis A. Soro Do, Tanya Ermolovich Do

Department of Medicine

No abstract provided.

Improving Health Outcomes For Children (Ihoc) First Steps Phase I Initiative: Improving Immunizations For Children And Adolescents, Kimberley S. Fox Mpa, Carolyn E. Gray Mph

Population Health & Health Policy

This report, co-authored by Kimberley Fox and Carolyn Gray, provides a final evaluation of the initial phase of First STEPS (Strengthening Together Early Preventive Services), a learning collaborative led by Maine Quality Counts to support 24 pediatric and family practices in improving their childhood immunization rates. The evaluation found that all participating practices had higher immunization rates after participating in First STEPS. On average, overall child immunization rates increased by 5.1% at 12 months and 7.1% at 15 months, and average immunization rates across practices increased significantly from 74.2% to 81.3%. Practices also reported significant improvement in the use of …

Fiber-Free White Flour With Fructose Offers A Better Model Of Metabolic Syndrome, Faridah Amin, Anwar Hassan Gilani

Department of Biological & Biomedical Sciences

BACKGROUND: The metabolic syndrome (MS) is a combination of metabolic abnormalities that lead to an increased risk of cardiovascular diseases. Due to its rising incidence and demanding life-long use of multiple drugs, there is a growing interest in testing and developing new allopathic, complementary and alternative therapies for controlling or curing disorders of MS. The discovery of new therapeutic modalities requires animal models of disease and currently available models have limitations. Developing an appropriate animal model for MS to achieve various therapeutic targets remains a challenge and this study aims to develop a rat model which closely depicts MS in …

An Informational Algorithm As The Basis For Perception-Action Control Of The Instantaneous Axes Of The Knee, Wangdo Kim, Margarida M. Espanha, António P. Veloso, Duarte Araújo, Filipa João, Luis Carrão, Sean S. Kohles

Mechanical and Materials Engineering Faculty Publications and Presentations

Traditional locomotion studies emphasize an optimization of the desired movement trajectories while ignoring sensory feedback. We propose an information based theory that locomotion is neither triggered nor commanded but controlled. The basis for this control is the information derived from perceiving oneself in the world. Control therefore lies in the human-environment system. In order to test this hypothesis, we derived a mathematical foundation characterizing the energy that is required to perform a rotational twist, with small amplitude, of the instantaneous axes of the knee (IAK). We have found that the joint’s perception of the ground reaction force may be replaced …

Principles Of Quantitative Fluid And Cation Replacement In Extreme Hyperglycemia, Antonios H. Tzamaloukas, Yijuan Sun, Nikifor K. Konstantinov, Richard I. Dorin, Todd S. Ing, Deepak Malhorta, Glenn H. Murata, Joseph I. Shapiro M.D.

Biochemistry and Microbiology

Hyperglycemia may cause profound deficits of water, sodium and potassium through osmotic diuresis, which continues during treatment as long as there is glucosuria. Replacement fluids should cover both the deficits at presentation and the ongoing losses during treatment. At presentation with hyperglycemia, quantitative estimates of the deficits in water, sodium and potassium are based on rapid body weight changes, which indicate changes in body water, and on the serum sodium concentration corrected to a normal serum glucose level. The corrected serum sodium concentration provides a measure of the water deficit relative to the cation deficit (sodium, plus potassium) that is …

Flagellar Motility Is A Key Determinant Of The Magnitude Of The Inflammasome Response To Pseudomonas Aeruginosa, Yash R. Patankar, Rustin R. Lovewell, Matthew E. Poynter, Jeevan Jyot, Barbara I. Kazmierczak, Brent Berwin

Dartmouth Scholarship

We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of bacterial motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association and ingestion of P. aeruginosa by phagocytes both in vitro and in vivo. Since bacterial interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation by P. aeruginosa, we hypothesized that reduced bacterial association with phagocytes due to loss of bacterial motility, independent of flagellar expression, will lead to reduced inflammasome activation. Here we report …

The Role Of Nicotinic Acetylcholine Receptors In Ethanol Responsive Behaviors And Drinking, Anton Dawson

Theses and Dissertations

The high co-morbidity between alcohol (ethanol) and nicotine abuse suggests that nicotinic acetylcholine receptors (nAChRs), which are thought to underlie nicotine dependence, may also be involved in alcohol dependence. A genomic region that encodes the Alpha5* nAChR subtype has recently been shown to be associated with alcohol dependence phenotypes in humans. Therefore, the aim of this study was to determine the role of Alpha5* nAChRs in ethanol-responsive behaviors upon acute administration in mice as well as in their drinking behavior. We conducted tests in mice lacking the Alpha5 coding gene (Chrna5) in ethanol-induced hypothermia, hypnosis, anxiolysis, and conditioned place preference. …

Infective Endocarditis In The U.S., 1998–2009: A Nationwide Study, David H. Bor, Steffie Woolhandler, Rachel Nardin, David Brusch, David U. Himmelstein

Publications and Research

Background
Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates.

Methods and Findings
Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients …

Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood

Dartmouth Scholarship

There has been extensive research regarding T cell recognition of Epstein-Barr virus-transformed cells; however, less is known regarding the recognition of B cells immortalized by gamma-2 herpesviruses. Here we show that B cells immortalized by murine gammaherpesvirus 68 (MHV-68, γHV-68) can be controlled by either CD4 or CD8 T cells in vivo. We present evidence for the direct recognition of infected B cells by CD4 and CD8 T cells. These data will help in the development of immunotherapeutic approaches combating gamma-2 herpesvirus-related disease.

Marked Improvement Of Cytotoxic Effects Induced By Docetaxel On Highly Metastatic And Androgen-Independent Prostate Cancer Cells By Downregulating Macrophage Inhibitory Cytokine-1., M Mimeault, Sonny L. Johansson, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND: Overexpression of macrophage inhibitory cytokine-1 (MIC-1) frequently occurs during the progression of prostate cancer (PC) to androgen-independent (AI) and metastatic disease states and is associated with a poor outcome of patients.

METHODS: The gain- and loss-of-function analyses of MIC-1 were performed to establish its implications for aggressive and chemoresistant phenotypes of metastatic and AI PC cells and the benefit of its downregulation for reversing docetaxel resistance.

RESULTS: The results have indicated that an enhanced level of secreted MIC-1 protein in PC3 cells is associated with their acquisition of epithelial-mesenchymal transition features and higher invasive capacity and docetaxel resistance. Importantly, …

Loss Of Fbp1 By Snail-Mediated Repression Provides Metabolic Advantages In Basal-Like Breast Cancer, Chenfang Dong, Tingting Yuan, Yadi Wu, Yifan Wang, Teresa W-M Fan, Sumitra Miriyala, Yiwei Lin, Jun Yao, Jian Shi, Tiebang Kang, Pawel Lorkiewicz, Daret St. Clair, Mien-Chie Hung, B. Mark Evers, Binhua P. Zhou

Toxicology and Cancer Biology Faculty Publications

The epithelial-mesenchymal transition (EMT) enhances cancer invasiveness and confers tumor cells with cancer stem cell (CSC)-like characteristics. We show that the Snail-G9a-Dnmt1 complex, which is critical for E-cadherin promoter silencing, is also required for the promoter methylation of fructose-1,6-biphosphatase (FBP1) in basal-like breast cancer (BLBC). Loss of FBP1 induces glycolysis and results in increased glucose uptake, macromolecule biosynthesis, formation of tetrameric PKM2, and maintenance of ATP production under hypoxia. Loss of FBP1 also inhibits oxygen consumption and reactive oxygen species production by suppressing mitochondrial complex I activity; this metabolic reprogramming results in an increased CSC-like property and tumorigenicity by enhancing …

Drugs, Devices, And Desires: A Problem-Based Learning Course In The History Of Medicine, Sarah Levitt, Anne Mckeage, P. K. Rangachari

Interdisciplinary Journal of Problem-Based Learning

Problem-based learning (PBL) is well suited for courses in the history of medicine, where multiple perspectives exist and information has to be gleaned from different sources. A student, an archivist, and a teacher offer three perspectives about a senior level course where students explored the antecedents and consequences of medical technology. Two active learning strategies were used: (a) PBL to explore the historical basis of procedures used to diagnose, prevent and treat a single disease, tuberculosis, and (b) a concurrent inquiry-based component that permitted individual exploration of other medical technologies and demonstration of learning through diverse options (book reviews, conversations, …

Uncovering The Molecular Pathways Of Mbd5 In Neurodevelopmental Disorders, Sureni Mullegama

Theses and Dissertations

Neurodevelopmental disorders (NDs) are a growing public health concern. These complex disorders cause failure of normal brain development, which leads to intellectual disability (ID) or autism in 3% of children. Accurate diagnosis of NDs is difficult due to complex overlapping phenotypes. Moreover, associations between phenotypically similar NDs and their overlapping molecular mechanisms remain unidentified. The chromosome 2q23.1 region is a newly discovered disease region. We have recently identified a novel ND, 2q23.1 deletion syndrome. The phenotype includes severe ID, significantly delayed speech, behavioral problems, seizures and short stature. This syndrome shares characteristics in common with other genetic syndromes, including Smith-Magenis …

Just Beautiful Portrays Of The Mind? The Relevance Of Aesthetic Strategies On Knowledge Creation In Neuroscience, Valerie Kummer

The Transdisciplinary STEAM+ Journal

We live in the age of big data. All types of data are being generated at an increasing rate but theories about the strategies and methods to visualize them is lagging. One of the main challenges we face today in research is to keep up with the massive amounts of data we produce (Allen, Elena A. et.al, 2012). Especially in the field of neuroscience and its use of imaging technologies, the vast array of data has risen to such a high number that it is impossible to grasp the inherent information without additional software tools and intelligent interfaces. Only through …

Health-Related Resource Use And Costs In Elderly Adults With And Without Mild Cognitive Impairment, Carolyn Zhu, Peter J. Whitehouse, Marian B. Patterson

Faculty Scholarship

Objectives To assess differences in resource use and cost between older adults with and without mild cognitive impairment (MCI) over time. Design Multicenter, longitudinal study. Setting Sixty-eight Alzheimer's Disease Cooperative Study (ADCS) sites in the United States. Participants Two hundred fifty-nine individuals diagnosed with MCI and 107 cognitively normal elderly adults followed annually for 3 years. Measurements The Resource Use Instrument (RUI) was used to capture medical and nonmedical care use. Generalized linear latent and mixed models were used to estimate differences in resource use and costs in older adults with and without MCI after controlling for clinical and demographic …