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Advances In The Diagnosis Of Human Opisthorchiasis: Development Of Opisthorchis Viverrini Antigen Detection In Urine, Chanika Worasith, Christine Kamamia, Anna Yakovleva, Kunyarat Duenngai, Chompunoot Wangboon, Jeffrey M. Bethony, +8 Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Background

Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated "heavy" infections in single villages to widespread "light" OV infections distributed over wide geographical areas. Currently, the "gold standard" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV …

Carcinogenic Parasite Secretes Growth Factor That Accelerates Wound Healing And Potentially Promotes Neoplasia., Michael J. Smout, Javier Sotillo, Thewarach Laha, Atiroch Papatpremsiri, Gabriel Rinaldi, Rafael N. Pimenta, Paul J. Brindley, +11 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Infection with the human liver fluke Opisthorchis viverrini induces cancer of the bile ducts, cholangiocarcinoma (CCA). Injury from feeding activities of this parasite within the human biliary tree causes extensive lesions, wounds that undergo protracted cycles of healing, and re-injury over years of chronic infection. We show that O. viverrini secreted proteins accelerated wound resolution in human cholangiocytes, an outcome that was compromised following silencing of expression of the fluke-derived gene encoding the granulin-like growth factor, Ov-GRN-1. Recombinant Ov-GRN-1 induced angiogenesis and accelerated mouse wound healing. Ov-GRN-1 was internalized by human cholangiocytes and induced gene and protein expression changes associated …

Parasite Manipulation Of The Invariant Chain And The Peptide Editor H2-Dm Affects Major Histocompatibility Complex Class Ii Antigen Presentation During Toxoplasma Gondii Infection, Louis-Philippe Leroux, Manami Nishi, Sandy El-Hage, Barbara A. Fox, David I Bzik, Florence Dzierszinsk

Dartmouth Scholarship

Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4(+) T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, …

Tracing The Human Healthcare Roots Of Antibiotic Resistance In India: Causes, Challenges, And Promising Solutions, Kelsey Matteson

Independent Study Project (ISP) Collection

The rapid development of biological defense mechanisms by bacteria, or antibiotic resistance, is a dangerously progressing public health concern worldwide. The spread of antibiotic resistant pathogens are not only a threat to the security of healthcare facilities and the stability of modern medicine across the globe, but this phenomenon also creates a particular burden on countries with a high prevalence of infectious disease such as India. This study attempts to explore India’s unique human healthcare causes of the emergence and spread of antibiotic resistance, comprehend the obstacles that have created roadblocks to change, and outline possible solutions to overcome these …

Human Polyclonal Antibodies Produced Through Dna Vaccination Of Transchromosomal Cattle Provide Mice With Post-Exposure Protection Against Lethal Zaire And Sudan Ebolaviruses., Callie E Bounds, Steven A Kwilas, Ana I Kuehne, Jennifer M Brannan, Russell R Bakken, John M Dye, Jay W Hooper, Lesley C Dupuy, Barry Ellefsen, Drew Hannaman, Hua Wu, Jin-An Jiao, Eddie J Sullivan, Connie S Schmaljohn, Matthias J. Schnell

Department of Medicine Faculty Papers

DNA vaccination of transchromosomal bovines (TcBs) with DNA vaccines expressing the codon-optimized (co) glycoprotein (GP) genes of Ebola virus (EBOV) and Sudan virus (SUDV) produce fully human polyclonal antibodies (pAbs) that recognize both viruses and demonstrate robust neutralizing activity. Each TcB was vaccinated by intramuscular electroporation (IM-EP) a total of four times and at each administration received 10 mg of the EBOV-GPco DNA vaccine and 10 mg of the SUDV-GPco DNA vaccine at two sites on the left and right sides, respectively. After two vaccinations, robust antibody responses (titers > 1000) were detected by ELISA against whole irradiated EBOV or SUDV …

The Controversy Of Vaccinations, Nicholas G. Aboreden

The Kabod

Recently vaccination has become a controversial topic. There is a growing number of people who believe that vaccines carry great health risks to patients and therefore refuse to be vaccinated or to vaccinate their children. This ill-informed view of immunizations is beginning to cause serious problems in the United States as growing numbers of disease cases are being seen. A closer look into the science of vaccines and the benefits they have brought, clearly show that not only do vaccines carry very little risk to patients, but they are responsible for the eradication and reduction of multiple debilitating diseases.

Differential Expression Of Mrna Encoding Cytokines And Chemokines In The Reproductive Tract After Infection Of Mice With Chlamydia Trachomatis, Katheryn L. Cerny, Maranda Van Fleet, Anatoly Slepenkin, Ellena M. Peterson, Phillip J. Bridges

Animal and Food Sciences Faculty Publications

Infection with Chlamydia trachomatis targets epithelial cells within the genital tract which respond by secreting chemokines and cytokines. Persistent inflammation can lead to fibrosis, tubal infertility and/or ectopic pregnancy; many infections are asymptomatic. Most studies have investigated the inflammatory response in the initial stages of infection, less is known about the later stages of infection, especially with a low, potentially asymptomatic, bacterial load. Our objective was to determine the inflammatory mediators involved in clearance of low-grade infection and the potential involvement in chronic inflammation. Six to eight week old C3H/HeJ mice were pretreated with 2.5 mg medroxyprogesterone acetate on day …

The Role Of Perlecan And Endorepellin In The Control Of Tumor Angiogenesis And Endothelial Cell Autophagy., Stephen Douglass, Atul Goyal, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

During tumor growth and angiogenesis there is a dynamic remodeling of tissue architecture often accompanied by the release of extracellular matrix constituents full of biological activity. One of the key constituents of the tumor microenvironment is the large heparan sulfate proteoglycan perlecan. This proteoglycan, strategically located at cell surfaces and within basement membranes, is a well-defined pro-angiogenic molecule when intact. However, when partially processed by proteases released during cancer remodeling and invasion, the C-terminal fragment of perlecan, known as endorepellin, has opposite effects than its parent molecule. Endorepellin is a potent inhibitor of angiogenesis by exerting a dual receptor antagonism …

The Conserved G-Protein Coupled Receptor Fshr-1 Regulates Protective Host Responses To Infection And Oxidative Stress, Elizabeth V. Miller, Leah N. Grandi, Jennifer A. Giannini, Joseph D. Robinson, Jennifer R. Powell

Biology Faculty Publications

The innate immune system’s ability to sense an infection is critical so that it can rapidly respond if pathogenic microorganisms threaten the host, but otherwise maintain a quiescent baseline state to avoid causing damage to the host or to commensal microorganisms. One important mechanism for discriminating between pathogenic and non-pathogenic bacteria is the recognition of cellular damage caused by a pathogen during the course of infection. InCaenorhabditis elegans, the conserved G-protein coupled receptor FSHR-1 is an important constituent of the innate immune response. FSHR-1 activates the expression of antimicrobial infection response genes in infected worms and delays accumulation …

Trim21 Regulates Nmi-Ifi35 Complex-Mediated Inhibition Of Innate Antiviral Response, Anshuman Das, Phat X. Dinh, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

In this study, using an immunoprecipitation coupled with mass spectrometry approach, we have identified the E3 ubiquitin ligase Trim21 as an interacting partner of IFI35 and Nmi. We found that this interaction leads to K63-linked ubiquitination on K22 residue of Nmi, but not IFI35. Using domain deletion analysis, we found that the interaction is mediated via the coiled-coil domain of Nmi and the carboxyl-terminal SPRY domain of Trim21. Furthermore, we show that depletion of Trim21 leads to significantly reduced interaction of Nmi with IFI35, which results in the abrogation of the negative regulatory function of the Nmi-IFI35 complex on innate …

Week Of August 24, 2015, New York Medical College

InTouch

• School of Medicine Class of 2019 Embarks on their Journey to Medicine at the White Coat Ceremony
• NYMC Celebrates Walkway Ribbon Cutting
• NYMC Celebrates Faculty Authorship
• D.P.T. Class of 2015 Achieves 100 Percent First-Time Passing Rate on the National Licensure Exam
• GSBMS Welcomes New Cohort of Ph.D. Candidates

The Right Tool For The Job: Detection Of Soil-Transmitted Helminths In Areas Co-Endemic For Other Helminths, Maria V. Periago, Renata C. Diniz, Simone A. Pinto, Anna Yakovleva, Rodrigo Correa-Oliveira, David J. Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Due to the recent increased use of the McMaster (MM) fecal egg counting method for assessing benzimidazole drug efficacy for treating soil-transmitted helminth (STH) infections, the aim of the current study was to determine the operational value of including the MM method alongside the Kato-Katz (KK) fecal thick smear to increase the diagnostic sensitivity when STHs are co-endemic with trematode helminths (e.g., Schistosoma mansoni).

Methods

A cross-sectional study was conducted in school-aged children aged 4-18 years in the northeastern region of the State of Minas Gerais (Brazil), where Necator americanus, Ascaris lumbricoides, Trichuris trichiura, and S …

Amikacin Concentrations Predictive Of Ototoxicity In Multidrug-Resistant Tuberculosis Patients, Chawangwa Modongo, Jotam G. Pasipanodya, Nicola M. Zetola, Scott M. Williams

Dartmouth Scholarship

Aminoglycosides, such as amikacin, are used to treat multidrug-resistant tuberculosis. However, ototoxicity is a common problem and is monitored using peak and trough amikacin concentrations based on World Health Organization recommendations. Our objective was to identify clinical factors predictive of ototoxicity using an agnostic machine learning method. We used classification and regression tree (CART) analyses to identify clinical factors, including amikacin concentration t

hresholds that pre- dicted audiometry-confirmed ototoxicity among 28 multidrug-resistant pulmonary tuberculosis patients in Botswana. Amika- cin concentrations were measured for all patients. The quantitative relationship between predictive factors and the probability of ototoxicity were then identified using …

Week Of July 27, 2015, New York Medical College

InTouch

• Public Health Program Passes the Test... with Flying Colors
• School of Medicine Class of 2017 Transitions to the Clinical Years
• NYMC Hosts 16th Pediatric Cancer Research Foundation Memorial Lectureship
• NYMC Reaches Out to Nepal
• NYMC Hosts Open Door Family Medical Centers Summer Students
• Lawrence Shapiro, M.D., Is Named Professor Emeritus of Pediatrics

B Lymphocytes Are Required During The Early Priming Of Cd4+ T Cells For Clearance Of Pneumocystis Infection In Mice, Michael M. Opata, Melissa L. Hollifield, Frances E. Lund, Troy D. Randall, Robert Dunn, Beth A. Garvy, David J. Feola

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B cells play a critical role in the clearance of Pneumocystis. In addition to production of Pneumocystis-specific Abs, B cells are required during the priming phase for CD4⁺ T cells to expand normally and generate memory. Clearance of Pneumocystis was found to be dependent on Ag specific B cells and on the ability of B cells to secrete Pneumocystis-specific Ab, as mice with B cells defective in these functions or with a restricted BCR were unable to control Pneumocystis infection. Because Pneumocystis-specific antiserum was only able to partially protect B cell–deficient mice from infection, we …

A Self-Lysis Pathway That Enhances The Virulence Of A Pathogenic Bacterium, Kirsty A. Mcfarland, Emily L. Dolben, Michele Leroux, Tracy K. Kambara, Kathryn Ramsey, Robin Kirkpatrick, Joseph Mougous, Deborah Hogan, Simon Dove

Dartmouth Scholarship

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of …

Bacterially-Based Immune Challenges And Trauma Elicit Terminal Investment In Male Aedes Aegypti, Molly K. Schumacher

Theses and Dissertations

Investment in life history traits such as immune function and reproduction is constrained by finite available resources. A cost-of-immunity trade-off may occur in response to infection when resources are diverted away from reproductive effort and into an immune response. Alternatively, an infected individual may enhance reproductive effort to maximize terminal reproductive success in response to the survival threat inherent to infection (terminal investment). We measured male Aedes aegypti reproductive behavior following inoculations with: living bacteria; killed bacteria as an immune elicitor; and a sham control. Mating competitiveness relative to naïve males was also determined through a binary mate choice experiment …

Neurocysticercosis, Abigail Hill

Nursing Student Class Projects (Formerly MSN)

Neurocysticercosis (NCC) is one of the most common parasitic infections of the central nervous system in humans and is the most serious clinical manifestation of cysticercosis. NCC is caused by the ingestion of the larval form of the pork tapeworm Taenia solium. NCC is endemic in low income developing countries where pigs are commonly raised, including the countries of Central America, South America, and parts of Africa and Asia. (Naddaf, Seeger, & Stafstrom, 2014). The parasite Taenia solium encysts in the brain and can express a broad range of symptoms including seizures, headache, hydrocephalus, encephalitis, stroke and mental health and …

Chagas Disease: Immigrating Into The United States, Angela Metzger

Nursing Student Class Projects (Formerly MSN)

Chagas Disease is starting to make a profound entrance into our communities within the United States. The influx of the immigrant population is the principal cause of the accumulation in the number of reported cases. (Center for Disease Control and Prevention, 2014). The Trypanosoma cruzi is a parasite that causes Chagas disease. The triatomine blood sucking insect enjoys the mucosal membranes of their pray, both humans and animals. The most common regions of the penetrating bite are the conjunctiva of the eye or around the mouth. It is through the feces of the vector entering the inoculation site that initiates …

Exploring The Pathophysiological Concepts Of Ebola Virus, Andrew T. Wasson

Nursing Student Class Projects (Formerly MSN)

The Ebola virus is a member of the filoviridae family. Five distinctive species of ebolavirus have been identified, four of which are known to cause disease in humans (Martines, Ng, Greer, Rollin, and Zaki, 2014). The specific species known to cause disease in humans are Zaire, Sudan, Ivory Coast, and Bundibugyo (Bray & Chertow, 2014). Bah et al. (2015) report that the Zaire ebolavirus (EBOV) was the cause of the most recent West African outbreak and carries the highest human mortality rate among the five known species, with up to 90% of cases being fatal. Ebola is a filamentous, enveloped, …

Chikungunya Virus: More Than A Mosquito Bite, Abigail Shaw

Nursing Student Class Projects (Formerly MSN)

Chikungunya fever is a viral infection caused by the Chikungunya virus (CHIKV). Although seldom fatal, CHIKV causes high fevers, polyarthralgia, and rash. The mosquito-borne virus has spread rapidly in the last ten years, causing over three million cases of CHIKV worldwide (Powers, 2015). The recent outbreak initiated in Africa and the islands of the Indian Ocean in 2004 has quickly spread to Asia, Europe and the Americas (CDC, 2015). According to the CDC (2015), until 2014, cases in the United States had only been linked to foreign travel outside of the Americas. As the outbreak has grown, cases of local …

Lyme Disease, Jared Hostetler

Nursing Student Class Projects (Formerly MSN)

Lyme disease is the most common vector borne illness found in the United States. Each year 30,000 people are diagnosed with the disease, with many more cases going unreported (Centers for Disease Control and Prevention, 2015). The vector responsible for spreading the disease is the deer tick. The infection itself is caused by the spirochete Borrelia burgdorferi. This bacteria is transmitted through the saliva from the bite of a deer tick. Diagnosis can be challenging due to the fact that multiple systems of the body can be affected with different severities. Early diagnosis and treatment is critical in the prevention …

Lyme Disease: A Tick’S Risky Bite, Jana Keller

Nursing Student Class Projects (Formerly MSN)

Lyme Disease is a bacterial infection transmitted primarily by the deer tick and is commonly seen in the United States. It is an infectious disease caused by the bacterium Borrelia burgdorferi, which is a spirochete (Pearson, 2014). Lyme disease’s prevalence is confirmed by the Centers for Disease Control and Preventions whom estimates that 30,000 people per year are diagnosed with Lyme disease in the Unites States (Moore, 2015). It is imperative that primary health care workers (such as Nurse Practitioners) are familiar with this disease and the early signs and symptoms. If early signs and symptoms go unnoticed or misdiagnosed …

Chikungunya Virus: A Case Study Of The Emerging Vector-Borne Disease, Lindsay D. Sullivan

Nursing Student Class Projects (Formerly MSN)

The Chikungunya virus (CHIKV) has spread like a wildfire in the Americas. Since its emergence in Sub-Saharan Africa as early at the 18th century, CHIKV has caused many isolated outbreaks in Africa, Southeast Asia, and Australia. Over the last decade, the vector-borne disease has inflicted millions of people on islands in the Indian Ocean, India, and now the Americas with the aid of viral mutations and international travel (Weaver and Lecuit, 2015). The first case of local CHIKV transmission in the Western Hemisphere was fairly recent. On the island of St. Martin in October 2013, an individual carrying an Asian …

Tuberculosis, Lindsay Mackey

Nursing Student Class Projects (Formerly MSN)

Tuberculosis (TB) is an infectious bacterial disease caused by Mycobacterium tuberculosis and mostly affects the lungs and sometimes other organs such as the kidneys, spine, and brain (Center for Disease Control and Prevention, 2015). In 2013, the CDC (2015) estimated that approximately 9 million people were infected with Mycobacterium tuberculosis worldwide and approximately 1.5 million deaths were a result of TB. Tuberculosis is an airborne infection which can be spread through the air from an infected individuals cough, sneeze, or speech. Individuals infected with TB can either have latent or active stage. Latent TB is when an individual becomes infected …

Congenital Cytomegalovirus (Cmv), Patty Fleming

Nursing Student Class Projects (Formerly MSN)

Cytomegalovirus (CMV) is a common herpes virus infection that is usually harmless and belongs to a group of herpes viruses that includes the herpes simplex viruses, varicella-zoster virus (which causes chickenpox and shingles), and the Epstein-Barr virus (which causes infectious mononucleosis). Once CMV is in a person's body, it stays there throughout their life. (Centers for Disease Control and Prevention, 2010). CMV is shed in various bodily secretions, especially urine and saliva (Congenital Cytomegalovirus Foundation, 2014). According to the Centers for Disease Control and Prevention (CDC), the majority of otherwise healthy children and adults infected with CMV are asymptomatic while …

Implications Of Underlying Pathophysiology Of Osteomyelitis In Diabetics For Nursing Care, Danielle Spencer

Nursing Student Class Projects (Formerly MSN)

Osteomyelitis is an infection of the bone caused by either bacteria, fungi, parasites, viruses or mycobacteria (McCance, et. al., 2014). The infection can enter bone either through an outside source or through the blood from a blood borne infection (McCance, et. al., 2014). The most common bacteria involved with osteomyelitis is Staphylococcus aureus (Hatzenbuehler & Pulling, 2011, p. 1027). Recently, at Dublin Methodist Hospital there has been an increase in the number of osteomyelitis cases in chronic uncontrolled diabetic patients requiring below the knee amputations. Two of the cases specifically were linked to chronic diabetic foot ulcers. Each of these …

Clostridium Difficile, Kristen Johnson

Nursing Student Class Projects (Formerly MSN)

Clostridium difficile (CD) is an infectious disease that has a direct impact on our healthcare resources. “Clostridium difficile, an anaerobic, spore forming, toxin-forming, gram-positive bacillus, has become the leading cause of health care—associated infectious diarrhea (Walters & Zuckerbraun, 2014, p. 329).” I chose this topic because CD is a hypervirulent organism that is not only affecting hospitalized patients but is now emerging as a community acquired infection. Healthcare treatments and costs are on the rise due to persistent and recurrent CD infections. Understanding the pathogenesis, risk factors, diagnostic testing, and management strategies are important in reducing the spread of CD …

Differences In Health-Related Behaviors And Attitudes Between Urban, Rural, And Isolated Households In Western West Virginia, Michael Newsome Phd, Tim Hazelett, Monika Sawhney Phd, Msw

Economics Faculty Research

This study uses data from a 2013 survey of 275 randomly sampled households across nine counties in western West Virginia to examine the significant differences between the health behaviors and attitudes of rural and isolated populations. The results show that age, education, and income are significant factors in explaining differences in health-related behaviors and attitudes for all urban, rural and isolated respondents. However, after controlling for socio-demographic differences, isolation is found to have only a few significant effects, and some of the effects run counter to stereotypes of isolated populations. Rural respondents are significantly more likely than isolated respondents to …

Levels Of 8-Oxodg Predict Hepatobiliary Pathology In Opisthorchis Viverrini Endemic Settings In Thailand., Prasert Saichua, Anna Yakovleva, Christine Kamamia, Amar R. Jariwala, Paul J. Brindley, Jeffrey M. Bethony, + 8 More

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini is distinct among helminth infections as it drives a chronic inflammatory response in the intrahepatic bile duct that progresses from advanced periductal fibrosis (APF) to cholangiocarcinoma (CCA). Extensive research shows that oxidative stress (OS) plays a critical role in the transition from chronic O. viverrini infection to CCA. OS also results in the excision of a modified DNA lesion (8-oxodG) into urine, the levels of which can be detected by immunoassay. Herein, we measured concentrations of urine 8-oxodG by immunoassay from the following four groups in the Khon Kaen Cancer Cohort study: (1) O. viverrini negative individuals, (2) …