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Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S Mhashilkar, Sai L Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R Palli, H. Lee Woodcock Iii, Thomas R Unnasch

Chemistry Faculty Publications

BACKGROUND: A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

METHODOLOGY/ PRINCIPAL FINDINGS: Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at sub-micromolar concentrations. …

Identification Of Ecdysone Hormone Receptor Agonists As A Therapeutic Approach For Treating Filarial Infections, Amruta S. Mhashilkar, Sai L. Vankayala, Canhui Liu, Fiona Kearns, Priyanka Mehrotra, George Tzertzinis, Subba R. Palli, H. Lee Woodcock, Thomas R. Unnasch

Entomology Faculty Publications

Background A homologue of the ecdysone receptor has previously been identified in human filarial parasites. As the ecdysone receptor is not found in vertebrates, it and the regulatory pathways it controls represent attractive potential chemotherapeutic targets.

Methodology/ Principal Findings Administration of 20-hydroxyecdysone to gerbils infected with B. malayi infective larvae disrupted their development to adult stage parasites. A stable mammalian cell line was created incorporating the B. malayi ecdysone receptor ligand-binding domain, its heterodimer partner and a secreted luciferase reporter in HEK293 cells. This was employed to screen a series of ecdysone agonist, identifying seven agonists active at …

Controlled, Pulsatile Release Of Thermostabilized Inactivated Polio Vaccine From Plga-Based Microspheres, Stephany Y. Tzeng, Rohiverth Guarecuco, Kevin J. Mchugh, Evan M. Rosenberg, Yingying Zeng, Robert Langer, Ana Jaklenec

Vaccine Technology VI

Many vaccines, such as the inactivated polio vaccine (IPV), must be administered in several doses for full efficacy. Because patient access is a major challenge for vaccination efforts in developing countries, administering multiple doses per patient is impractical in those areas. Single-administration vaccines would greatly improve efforts to vaccinate populations in Third World countries, and the World Health Organization (WHO) Expanded Program for Immunization describes an ideal vaccine as one that is heat-stable, requires only one shot, and is easy to administer. Although already existing technologies, such as microspheres composed of poly(lactic-co-glycolic acid) (PLGA), are able to encapsulate …

What's Happening: June 13, 2016, Maine Medical Center

What's Happening

No abstract provided.

Il-4 Sensitivity Shapes The Peripheral Cd8+ T Cell Pool And Response To Infection, Kristin R. Renkema, June-Yong Lee, You Jeong Lee, Sara E. Hamilton, Kristin A. Hogquist, Stephen C. Jameson

Peer Reviewed Articles

Previous studies have revealed that a population of innate memory CD8⁺ T cells is generated in response to IL-4, first appearing in the thymus and bearing high expression levels of Eomesodermin (Eomes) but not T-bet. However, the antigen specificity and functional properties of these cells is poorly defined. In this study, we show that IL-4 regulates not only the frequency and function of innate memory CD8⁺ T cells, but also regulates Eomes expression levels and functional reactivity of naive CD8⁺ T cells. Lack of IL-4 responsiveness attenuates the capacity of CD8⁺ T cells to mount a …

Medical School Watercooler Newsletter - June 12, 2016, Lindsey Lyle

Watercooler Newsletter

This is the June 12, 2016 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents Include:

• USA Pediatric Cardiology Clinic Receives Echocardiography Accreditation by the IAC
• Med School Café - Expert Advice for the Community
• USA, Greek Community Dedicate Hippocrates Park
• Class of 2018 Medical Students to Receive White Coats June 19

Vaccines: Reaching For Higher Branches After The Low Hanging Fruit Has Been Picked, Michael G. Kurilla

Vaccine Technology VI

Vaccines represent one of the most significant advances by medicine in addressing infectious diseases being responsible for the elimination of a few and the virtual eradication of several other scourges. In addition, medicine is also beginning to appreciate the potential applicability of vaccines beyond infectious diseases to areas such as oncology. During any emerging infectious disease public health event, availability of a vaccine figures prominently in the assessment of the capability to address the threat most effectively. A more rapid deployment of new vaccines would enable more effective management of emerging threats. Efforts to streamline manufacture and production of vaccines …

Conference Program (Vaccine Technology Vi), Laura A. Palomares, Tarit Mukhopadhyay, Manon Cox, Nathalie Garçon

Vaccine Technology VI

No abstract provided.

Lack Of An Association Or An Inverse Association Between Low-Density-Lipoprotein Cholesterol And Mortality In The Elderly: A Systematic Review, Uffe Ravnskov, Rokura Hama, Tomohito Hamazaki, Paul J. Rosch, Tore Schersten, Ralf Sundberg

NYMC Faculty Publications

OBJECTIVE: It is well known that total cholesterol becomes less of a risk factor or not at all for all-cause and cardiovascular (CV) mortality with increasing age, but as little is known as to whether low-density lipoprotein cholesterol (LDL-C), one component of total cholesterol, is associated with mortality in the elderly, we decided to investigate this issue.

SETTING, PARTICIPANTS AND OUTCOME MEASURES: We sought PubMed for cohort studies, where LDL-C had been investigated as a risk factor for all-cause and/or CV mortality in individuals ≥60 years from the general population.

RESULTS: We identified 19 cohort studies including 30 cohorts with …

Guidelines Are Not Evidence, James P. Meza Md, Phd, Nicholus H. Yee Md

Clinical Research in Practice: The Journal of Team Hippocrates

Guidelines are inherently flawed when caring for an individual patient, because they apply to populations, not individuals. A strong competency in reading and interpreting clinical research gives doctors the power to evaluate guidelines and make appropriate shared decisions with their patients.

Improving Influenza Vaccination Rates In The Hiv Population At An Academic Clinic, Anusha G. Govinda, Md, Anita Modi, Md, Emma Biegacki, Bryan Hess, Md

House Staff Quality Improvement and Patient Safety Conference (2016-2019)

AIM:

Performance measure: Percentage of HIV-infected patients with documentation of influenza vaccination in Allscripts.

Numerator: Number of HIV-infected patients who have obtained an influenza vaccine during influenza season.

Denominator: Total number of HIV-infected patients at the Jefferson Infectious Disease (ID) Clinic

Patient exclusions: Those who are allergic to eggs or have had allergic reactions to the influenza vaccine in the past

Goal: "75% of HIV-infected patients at the Jefferson ID clinic will be vaccinated against influenza and documented in Allscripts during influenza season"

Medication Errors And Hospital Admissions, A Tale Of Woe, Allison Greco, Md, René Daniel, Md, Raymond Janowski, Md, Bracken Babula, Md

House Staff Quality Improvement and Patient Safety Conference (2016-2019)

Goal for Improvement:

To improve proper medication regimens for patients as they transition between healthcare settings

So that patients achieve improved outcomes and reduced hospital admissions caused by medication errors

SMART aim is to decrease teh number of discrepancies between discharge medication lists and pill bottles or blister packs produced at one-week follow up with Jefferson PCP by 10% within six months.

A Survey Of Tuberculosis Infection Control Practices At The Nih/Niaid/Daids-Supported Clinical Trial Sites In Low And Middle Income Countries., Catherine Godfrey, Gail Tauscher, Sally Hunsberger, Melissa Austin, Lesley Scott, Jeffrey T. Schouten, Anne F. Luetkemeyer, Constance Benson, Robert Coombs, Susan Swindells

Journal Articles: Infectious Diseases

BACKGROUND: Health care associated transmission of Mycobacterium tuberculosis (TB) is well described. A previous survey of infection control (IC) practices at clinical research sites in low and middle income countries (LMIC) funded by the National Institute of Allergy and Infectious Diseases (NIAID) conducting HIV research identified issues with respiratory IC practices. A guideline for TB IC based on international recommendations was developed and promulgated. This paper reports on adherence to the guideline at sites conducting or planning to conduct TB studies with the intention of supporting improvement.

METHODS: A survey was developed that assessed IC activities in three domains: facility …

Mcb Faculty Member Mario Grijalva Travels To Ecuador For Grand Opening Of New Research Facility, Ohio University College Of Arts & Sciences

All Forum Articles

No abstract provided.

Prolonged Morphine Exposure Induces Increased Firm Adhesion In An In Vitro Model Of The Blood-Brain Barrier., Marianne Strazza, Vanessa Pirrone, Brian Wigdahl, Will Dampier, Wei Lin, Rui Feng, Monique E Maubert, Babette Weksler, Ignacio A Romero, Pierre-Olivier Couraud, Michael R Nonnemacher

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

The blood-brain barrier (BBB) has been defined as a critically important protective barrier that is involved in providing essential biologic, physiologic, and immunologic separation between the central nervous system (CNS) and the periphery. Insults to the BBB can cause overall barrier damage or deregulation of the careful homeostasis maintained between the periphery and the CNS. These insults can, therefore, yield numerous phenotypes including increased overall permeability, interendothelial gap formation, alterations in cytokine and chemokine secretion, and accelerated cellular passage. The current studies expose the human brain microvascular endothelial cell line, hCMEC/D3, to prolonged morphine exposure and aim to uncover the …

The Smoluchowski Equation In Population Dynamics And The Spread Of Infection, Satomi Sugaya

Physics & Astronomy ETDs

This dissertation is a report on an interdisciplinary investigation consisting of an application of random walk techniques to problems in ecology, particularly to the spread of Hantavirus epidemic among rodents that live on an open terrain. The population of mice that we consider is made up of infectious disease-carrying mice and susceptible mice that are disease-free, and each mouse has its own home range around which it executes a random walk. We describe an event of infection transmission in such a population via reaction-diffusion theory. Our simple model consists of two mice, one infected and the other susceptible, the disease …

Differential Interactions Of Lipopolysaccharides With Lipid Bilayers: Applications For Pathogen Detection, Loreen R. Stromberg

Biomedical Engineering ETDs

This dissertation describes the development of new tailored methods for the discriminative detection of amphiphilic lipopolysaccharide (LPS) antigens, so as to improve screening methodologies for food-safety applications, and detection of amphiphiles in general. LPS is associated with the outer membrane of Gram-negative bacteria, and is a primary virulence biomarker of several pathogens. Direct detection of amphiphilic LPS in the aqueous matrices of the host/sample requires an appreciation of the complex biochemistry of the molecule, and forms the basis for this research. The unique structure of this molecule can be used for identification of both the serogroup and strain of pathogen. …

Exploring The Opioid Epidemic: Barriers To Adequate Patient Care, Laurie Geddes

Nursing Capstones

No abstract provided.

School-Located Influenza Vaccination Program Effectiveness: An Observational, Descriptive Case Study., Dorcas E. Kunkel

DNP and Student Works

Children have the highest influenza infection rates of all population groups. The Advisory Committee on Immunization Practices (ACIP) recommends annual universal influenza vaccination of all persons ≥ 6 months of age. Many school-aged children do not receive recommended vaccinations and experience influenza, which results in poor health, absences from school, and transmission of infection to family and community members. The purpose of this evaluation was to determine the effectiveness of a school located influenza vaccination program planned and operated by public health nurses.

Mimicking The Bioactivation Of The Antitubercular Agent Ethionamide Using Peracetic Acid, Isabelle E. Logan

University Honors Theses

Tuberculosis still affects a large number of the world’s population and drug resistance is becoming an increasing problem. Second line of defense antitubercular agents such as ethionamide (ETD) are thus becoming increasingly important. Since ethionamide is a prodrug, its metabolization through oxidation by a monooxygenase was successfully mimicked using peracetic acid. The reaction was found to be biphasic, with a fast initial oxidation to yield ethionamide sulfoxide (ETD-SO), which was relatively stable and was successfully isolated. We derived a bimolecular rate constant of 3.08 ± 0.72 × 10² M^-1 s^-1 for this initial phase of the reaction. …

The Feasibility Of Community Level Interventions For Pre-Eclampsia In South Asia And Sub-Saharan Africa: A Mixed-Methods Design, Asif Raza Khowaja, Rahat Najam Qureshi, Diane Sawchuck, Olufemi T. Oladapo, Olalekan O. Adetoro, Elizabeth A. Orenuga, Mrutyunjaya Bellad, Ashalata Mallapur, Umesh Charantimath, Esperanca Sevene

Department of Paediatrics and Child Health

Background: Globally, pre-eclampsia and eclampsia are major contributors to maternal and perinatal mortality; of which the vast majority of deaths occur in less developed countries. In addition, a disproportionate number of morbidities and mortalities occur due to delayed access to health services. The Community Level Interventions for Pre-eclampsia (CLIP) Trial aims to task-shift to community health workers the identification and emergency management of pre-eclampsia and eclampsia to improve access and timely care. Literature revealed paucity of published feasibility assessments prior to initiating large-scale community-based interventions. Arguably, well-conducted feasibility studies can provide valuable information about the potential success of clinical trials …

Mrsa Causing Infections In Hospitals In Greater Metropolitan New York: Major Shift In The Dominant Clonal Type Between 1996 And 2014, Maria Pardos De La Gandara, Judith Berger, David Burstein, Phyllis Della-Latta, Guiqing Wang, Alexander Tomasz

NYMC Faculty Publications

A surveillance study in 1996 identified the USA100 clone (ST5/SCCmecII)-also known as the "New York/Japan" clone-as the most prevalent MRSA causing infections in 12 New York City hospitals. Here we update the epidemiology of MRSA in seven of the same hospitals eighteen years later in 2013/14. Most of the current MRSA isolates (78 of 121) belonged to the MRSA clone USA300 (CC8/SCCmecIV) but the USA100 clone-dominant in the 1996 survey-still remained the second most frequent MRSA (25 of the 121 isolates) causing 32% of blood stream infections. The USA300 clone was most common in skin and soft tissue infections (SSTIs) …

Repurposing Atovaquone: Targeting Mitochondrial Complex Iii And Oxphos To Eradicate Cancer Stem Cells., Marco Fiorillo, Rebecca Lamb, Herbert B Tanowitz, Luciano Mutti, Marija Krstic-Demonacos, Anna Rita Cappello, Ubaldo E. Martinez-Outshoorn, Federica Sotgia, Michael P Lisanti

Kimmel Cancer Center Papers, Presentations, and Grand Rounds

Atovaquone is an FDA-approved anti-malarial drug, which first became clinically available in the year 2000. Currently, its main usage is for the treatment of pneumocystis pneumonia (PCP) and/or toxoplasmosis in immune-compromised patients. Atovaquone is a hydroxy-1,4-naphthoquinone analogue of ubiquinone, also known as Co-enzyme Q10 (CoQ10). It is a well-tolerated drug that does not cause myelo-suppression. Mechanistically, it is thought to act as a potent and selective OXPHOS inhibitor, by targeting the CoQ10-dependence of mitochondrial complex III. Here, we show for the first time that atovaquone also has anti-cancer activity, directed against Cancer Stem-like Cells (CSCs). More specifically, we demonstrate that …

Extracellular Proteins: Novel Key Components Of Metal Resistance In Cyanobacteria?, Joaquín Giner-Lamia, Sara B. Pereira, Miquel Bovea-Marco, Matthias E. Futschik, Paula Tamagnini, Paulo Oliveira

School of Biomedical Sciences

No abstract provided.

Stellar Works: Searching For The Lives Of Women In Science, Jennifer Elizabeth Woodman

Dissertations and Theses

While women have had a profound impact in the world of science, they struggle to gain an equal foothold in many science, technology, engineering, and mathematics (STEM) fields today. This has led to considerable public and private sector efforts to recruit women into these arenas. In order to understand how schools and nonprofits engage today's young women in STEM studies, this account includes time spent both in high school science classrooms and with ChickTech -- a Portland-based organization that works to provide a pathway into tech careers for high school-aged girls.

A historical perspective reveals that modern women aren't treading …

Nih Launches $9 Million Program To Train Workers On Infectious Disease Safety, Staff

Browse All News

No abstract provided.

Childhood Health Status And Adulthood Cardiovascular Disease Morbidity In Rural China: Are They Related?, Qing Wang, Jay Shen

School of Public Health Faculty Research

Cardiovascular diseases (CVDs) are among the top health problems of the Chinese population. Although mounting evidence suggests that early childhood health status has an enduring effect on late life chronic morbidity, no study so far has analyzed the issue in China. Using nationally representative data from the 2013 China Health and Retirement Longitudinal Study (CHARLS), a Probit model and Two-Stage Residual Inclusion estimation estimator were applied to analyze the relationship between childhood health status and adulthood cardiovascular disease in rural China. Good childhood health was associated with reduced risk of adult CVDs. Given the long-term effects of childhood health on …

Enterocyte-Associated Microbiome Of The Hadza Hunter-Gatherers, S. Turroni, S Rampelli, M Centanni, S. L. Schnorr, C. Consolandi, M. Severgnini, C. Peano, M. Soverini, M. Falconi, Alyssa Crittenden, A. G. Henry, P. Brigidi, M. Candela

Anthropology Faculty Research

By means of a recently developed non-invasive ex vivo minimal model based on the interaction of the human enterocyte-like HT29 cell line and fecal slurries, we explored the enterocyte-associated microbiome of 21 Hadza hunter-gatherers and nine urban living Italians. Though reductionist, this model allows inferring the microbiota structural and functional arrangement as it interacts with enterocytes. Microbial suspensions obtained from Hadza or Italian stools were first evaluated for structural integrity by high resolution-scanning electron microscopy and co-incubated with HT29 cell monolayers. The enterocyte adherent microbiota fraction was then characterized by 16S rRNA gene sequencing and predictive functional profiling using PICRUSt. …

Enterocyte Associated Microbiome Of The Hadza Hunter-Gatherers, Silvia Turroni, Simone Rampelli, Manuela Centanni, Stephanie L. Schnorr, Clarissa Consolandi, Marco Severgnini, Clelia Peano Matteo, Soverini, Mirella Falconi, Alyssa N. Crittenden Amanda, G. Henry, Patrizia Brigidi, Marco Candela

Anthropology Faculty Research

By means of a recently developed non-invasive ex vivo minimal model based on the interaction of the human enterocyte-like HT29 cell line and fecal slurries, we explored the enterocyte-associated microbiome of 21 Hadza hunter-gatherers and nine urban living Italians. Though reductionist, this model allows inferring the microbiota structural and functional arrangement as it interacts with enterocytes. Microbial suspensions obtained from Hadza or Italian stools were first evaluated for structural integrity by high resolution-scanning electron microscopy and co-incubated with HT29 cell monolayers. The enterocyte adherent microbiota fraction was then characterized by 16S rRNA gene sequencing and predictive functional profiling using PICRUSt. …

Design Of Trials For Interrupting The Transmission Of Endemic Pathogens, Mariabeth Silkey, Tobias Homan, Nicolas Maire, Alexandra Hiscox, Richard Mukabana, Willem Takken, Thomas A. Smith

All Peer-Reviewed Publications

Background: Many interventions against infectious diseases have geographically diffuse effects. This leads to contamination between arms in cluster-randomized trials (CRTs). Pathogen elimination is the goal of many intervention programs against infectious agents, but contamination means that standard CRT designs and analyses do not provide inferences about the potential of interventions to interrupt pathogen transmission at maximum scale-up. Methods: A generic model of disease transmission was used to simulate infections in stepped wedge cluster-randomized trials (SWCRTs) of a transmission-reducing intervention, where the intervention has spatially diffuse effects. Simulations of such trials were then used to examine the potential of such designs …