Medicine and Health Sciences Commons^™

Advances In Developing Therapies To Combat Zika Virus: Current Knowledge And Future Perspectives, Ashok Munjal, Rekha Khandia, Kuldeep Dharma, Swati Sachan, Kumaragurubaran Karthik, Ruchi Tiwari, Yashpal S. Malik, Deepak Kumar, Raj K. Singh, Hafiz M. N. Iqbal, Sunil K. Joshi

Bioelectrics Publications

Zika virus (ZIKV) remained largely quiescent for nearly six decades after its first appearance in 1947. ZIKV reappeared after 2007, resulting in a declaration of an international “public health emergency” in 2016 by the World Health Organization (WHO). Until this time, ZIKV was considered to induce only mild illness, but it has now been established as the cause of severe clinical manifestations, including fetal anomalies, neurological problems, and autoimmune disorders. Infection during pregnancy can cause congenital brain abnormalities, including microcephaly and neurological degeneration, and in other cases, Guillain-Barré syndrome, making infections with ZIKV a substantial public health concern. Genomic and …

A Variant Pfcrt Isoform Can Contribute To Plasmodium Falciparum Resistance To The First-Line Partner Drug Piperaquine, Satish K. Dhingra, Devasha Redhi, Jill M. Combrinck, Tomas Yeo, John Okombo, Philipp P. Henrich, Annie N. Cowell, Purva Gupta, Matthew L. Stegman, Jonathan M. Hoke, Roland A. Cooper, Elizabeth Winzeler, Sachel Mok, Timothy J. Egan, David A. Fidock

Biological Sciences Faculty Publications

Current efforts to reduce the global burden of malaria are threatened by the rapid spread throughout Asia of Plasmodium falciparum resistance to artemisinin-based combination therapies, which includes increasing rates of clinical failure with dihydroartemisinin plus piperaquine (PPQ) in Cambodia. Using zinc finger nuclease-based gene editing, we report that addition of the C101F mutation to the chloroquine (CQ) resistance-conferring PfCRT Dd2 isoform common to Asia can confer PPQ resistance to cultured parasites. Resistance was demonstrated as significantly higher PPQ concentrations causing 90% inhibition of parasite growth (IC₉₀) or 50% parasite killing (50% lethal dose [LD₅₀]). This mutation …

Defining The Risk Of Zika And Chikungunya Virus Transmission In Human Population Centers Of The Eastern United States, Carrie A. Manore, Richard S. Ostfeld, Folashade B. Agusto, Holly Gaff, Shannon L. Ladeau

Biological Sciences Faculty Publications

The recent spread of mosquito-transmitted viruses and associated disease to the Americas motivates a new, data-driven evaluation of risk in temperate population centers. Temperate regions are generally expected to pose low risk for significant mosquito-borne disease; however, the spread of the Asian tiger mosquito (Aedes albopictus) across densely populated urban areas has established a new landscape of risk. We use a model informed by field data to assess the conditions likely to facilitate local transmission of chikungunya and Zika viruses from an infected traveler to Ae. albopictus and then to other humans in USA cities with variable human …

Impact Of Disease On The Survival Of Three Commercially Fished Species, John M. Hoenig, Maya L. Groner, Matthew W. Smith, Wolfgang K. Vogelbein, David M. Taylor, Donald F. Landers Jr., John T. Swenarton, David T. Gauthier

Biological Sciences Faculty Publications

Recent increases in emergent infectious diseases have raised concerns about the sustainability of some marine species. The complexity and expense of studying diseases in marine systems often dictate that conservation and management decisions are made without quantitative data on population-level impacts of disease. Mark-recapture is a powerful, underutilized, tool for calculating impacts of disease on population size and structure, even in the absence of etiological information. We applied logistic regression models to mark-recapture data to obtain estimates of disease-associated mortality rates in three commercially important marine species: snow crab (Chionoecetes opilio) in Newfoundland, Canada, that experience sporadic epizootics …

Exosomes Serve As Novel Modes Of Tick-Borne Flavivirus Transmission From Arthropod To Human Cells And Facilitates Dissemination Of Viral Rna And Proteins To The Vertebrate Neuronal Cells, Wenshuo Zhou, Michael Woodson, Biswas Neupane, Fengwei Bai, Michael B. Sherman, Kyung H. Choi, Girish Neelakanta, Hameeda Sultana

Biological Sciences Faculty Publications

Molecular determinants and mechanisms of arthropod-borne flavivirus transmission to the vertebrate host are poorly understood. In this study, we show for the first time that a cell line from medically important arthropods, such as ticks, secretes extracellular vesicles (EVs) including exosomes that mediate transmission of flavivirus RNA and proteins to the human cells. Our study shows that tick-borne Langat virus (LGTV), a model pathogen closely related to tick-borne encephalitis virus (TBEV), profusely uses arthropod exosomes for transmission of viral RNA and proteins to the human- skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed the presence of purified arthropod/neuronal exosomes …

A Neighborhood-Wide Association Study (Nwas): Example Of Prostate Cancer Aggressiveness, Shannon M. Lynch, Nandita Mitra, Michelle Ross, Craig Newcomb, Karl Dailey, Tara Jackson, Charnita M. Zeigler-Johnson, Harold Riethman

School of Medical Diagnostics & Translational Sciences Faculty Publications

Purpose

Cancer results from complex interactions of multiple variables at the biologic, individual, and social levels. Compared to other levels, social effects that occur geospatially in neighborhoods are not as well-studied, and empiric methods to assess these effects are limited. We propose a novel Neighborhood-Wide Association Study(NWAS), analogous to genome-wide association studies(GWAS), that utilizes high-dimensional computing approaches from biology to comprehensively and empirically identify neighborhood factors associated with disease.

Methods

Pennsylvania Cancer Registry data were linked to U.S. Census data. In a successively more stringent multiphase approach, we evaluated the association between neighborhood (n = 14,663 census variables) and prostate …

Neonatal Hypoglycemia In Diabetic Mothers: A Systematic Review, Brook T. Alemu, Olaniyi Olayinka, Hind A. Baydoun, Matthew Hoch, Muge Akpinar-Elci

Community & Environmental Health Faculty Publications

Hypoglycemia occurs in approximately 8-30% of neonates born to mothers with diabetes. The full extent of the individual and contextual risk factors of hypoglycemia remains unclear and no systematic review of the available studies exists to date. We identified published studies using PubMed and EBSCO host search engines. A modified STROBE statement was used to assess studies' strengths, weaknesses, and generalizability. A total of 16 articles were eligible for full text review. The clinical risk factors in these studies were broadly classified into two: infant-related and mother-related risk factors. The identified infant-related risk factors were SGA, macrosomia, prematurity, lower cord …

Effects Of Instrument Handle Design On Dental Hygienists' Forearm Muscle Activity During Scaling, Jessica R. Suedbeck, Susan L. Tolle, Gayle Mccombs, Martha L. Walker, Daniel M. Russell

Dental Hygiene Faculty Publications

Purpose: The purpose of this study was to determine the effects of 4 different commercially available instrument handle designs (A. 16 grams and 12.7 mm diameter, B. 23 grams and 11.1 mm diameter, C. 21 grams and 7.9 mm diameter and D. 18 grams and 6.35 mm diameter) on the muscle activity of four forearm muscles during a simulated scaling experience.

Methods: A convenience sample of 27 (n=27) dental hygienists used a Columbia 13/14 curet with four different instrument handles to scale artificial calculus from typodont teeth. Each participant's muscle activity was measured using surface electromyography (sEMG).

Results: Similar muscle …