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A Distinct Difference Between Air And Mucosal Temperatures In Human Respiratory Tract, Mehdi Khosravi, Ruei-Lung Lin, Ashish P. Maskey, Subodh Pandey, An-Hsuan Lin, Lu-Yuan Lee

Internal Medicine Faculty Publications

xtensive evidence indicates that several types of temperature-sensitive ion channels are abundantly expressed in the sensory nerves innervating airway mucosa. Indeed, airway temperature is known to play an important role in regulating respiratory functions. However, the actual airway mucosal temperature and its dynamic changes during the respiratory cycle have not been directly measured. In previous studies, airway tissue temperature was often estimated by indirect measurement of the peak exhaled breath temperature (PEBT). In view of the poor thermal conductivity of air, we believe that the airway tissue temperature cannot be accurately determined by the exhaled air temperature, and this study …

A Narrative Review On The Unexplored Potential Of Colostrum As A Preventative Treatment And Therapy For Diarrhea In Neonatal Dairy Calves, Havelah S. M. Carter, David L. Renaud, Michael A. Steele, Amanda J. Fischer-Tlustos, Joao H. C. Costa

Animal and Food Sciences Faculty Publications

Diarrhea is the leading cause of morbidity and mortality in pre-weaned dairy calves and, as such, represents a significant animal health and welfare concern. Furthermore, digestive disease early in life is associated with several long-term consequences such as reduced growth rate and decreased milk yield during the first lactation, thus generating severe economic losses. The majority of diarrheic cases in young calves are treated with antimicrobials; however, it is necessary to develop alternative treatments, as excessive antimicrobial usage can lead to antimicrobial resistance and can negatively impact the gut microflora of a calf. Bovine colostrum is abundant in immune and …

Establishing Peer Recovery Support Services To Address The Central Appalachian Opioid Epidemic: The West Virginia Peers Enhancing Education, Recovery, And Survival (Wv Peers) Pilot Program, Stephen M. Davis, Amanda Stover, Herb Linn, Jon Dower, Dan Mccawley, Erin Winstanley, Judith Feinberg

Journal of Appalachian Health

Introduction: Central Appalachia has been disproportionately affected by the opioid epidemic and overdose fatalities. We developed West Virginia Peers Enhancing Education, Recovery, and Survival (WV PEERS), a program based on peer recovery support, to engage individuals using opioids and link them with a range of services.

Methods: Community partners providing services to individuals with opioid use disorder (OUD) were identified and collaborations were formalized using a standardized memorandum of understanding. The program was structured to offer ongoing peer recovery support specialist (PRSS) services, not just a one-time referral. A website and cards describing the WV PEERS program were developed and …

Real-World Applications For Analytics Teaching And Learning, Anita Lee-Post

Marketing & Supply Chain Textbook Gallery

This document provides learning-by-doing materials for Analytics software skill development using SAS JMP. It integrates Analytics concepts and techniques with real-world scenarios based on the COVID-19 pandemic to illustrate how real-world data can be transformed into actionable insights to offer decision support for COVID-19 related issues. A holistic treatment of the Analytics process from data acquisition and cleansing to data analysis and interpretation is emphasized using five studies:

1. Characterize COVID-19 mortality demographic risk factors,
2. Visualize COVID-19 mortality demographics,
3. Conduct COVID-19 mortality time series forecasting,
4. Predict COVID-19 mortality, and
5. Analyze COVID-19 vaccine acceptance, uptake, and experiences.

Each study is structured with …

Longitudinal Pre-Exposure Prophylaxis (Prep) Acceptability, Initiation And Adherence Among Criminal Justice-Involved Adults In The Usa: The Southern Prep Cohort Study (Specs) Protocol, Katherine Lemasters, Carrie B. Oser, Mariah Cowell, Katie Mollan, Kathryn Nowotny, Lauren Brinkley-Rubinstein

Sociology Faculty Publications

INTRODUCTION: HIV prevalence among criminal justice (CJ)-involved adults is five times higher than the general population. Following incarceration, CJ-involved individuals experience multilevel barriers to HIV prevention. Pre-exposure prophylaxis (PrEP) is a widely available, daily medication efficacious in preventing HIV. Little is known about PrEP knowledge, acceptability, initiation and sustained use among CJ-involved persons or about how these outcomes vary by multilevel factors. The Southern Pre-Exposure Prophylaxis Study (SPECS) will investigate barriers and facilitators for PrEP initiation and sustained use among CJ-involved adults, building a foundation for PrEP interventions for this underserved population.

METHODS AND ANALYSIS: SPECS uses a mixed-methods sequential …

Human Apobec3 Variations And Viral Infection, Shiva Sadeghpour, Saeideh Khodaee, Mostafa Rahnama, Hamzeh Rahimi, Diako Ebrahimi

Plant Pathology Faculty Publications

Human APOBEC3 (apolipoprotein B mRNA-editing catalytic polypeptide-like 3) enzymes are capable of inhibiting a wide range of endogenous and exogenous viruses using deaminase and deaminase-independent mechanisms. These enzymes are essential components of our innate immune system, as evidenced by (a) their strong positive selection and expansion in primates, (b) the evolution of viral counter-defense mechanisms, such as proteasomal degradation mediated by HIV Vif, and (c) hypermutation and inactivation of a large number of integrated HIV-1 proviruses. Numerous APOBEC3 single nucleotide polymorphisms, haplotypes, and splice variants have been identified in humans. Several of these variants have been reported to be associated …

Rapid Development Of Methicillin-Resistant Staphylococcus Aureus (Mrsa) Purulent Pericarditis In The Setting Of Endocarditis, Samiullah Arshad, Naoki Misumida

Internal Medicine Faculty Publications

Methicillin-resistant Staphylococcus aureus (MRSA) purulent pericarditis is a rare but potentially fatal complication of MRSA bacteremia. We describe a case of a 27-year-old patient with active intravenous drug use, who presented with fever, chills, and dyspnea and was found to have tricuspid valve endocarditis. Echocardiogram on admission showed no pericardial effusion. The patient became hypotensive, with worsening dyspnea, in the following 3 days. A computed tomography scan of the chest was repeated and showed a large pericardial effusion. The patient underwent pericardiocentesis and pericardial drain placement. Antibiotics were continued, with resolution of effusion. Early pericardiocentesis of a large purulent pericardial …

Identification Of A Ruminant Origin Group B Rotavirus Associated With Diarrhea Outbreaks In Foals, Tirth Uprety, Chithra C. Sreenivasan, Ben M. Hause, Ganwu Li, Solomon O. Odemuyiwa, Stephan Locke, Jocelynn Morgan, Li Zeng, William F. Gilsenan, Nathan Slovis, Laurie Metcalfe, Craig N. Carter, Peter J. Timoney, David W. Horohov, Dan Wang, Erdal Erol, Emma Adam, Feng Li

Maxwell H. Gluck Equine Research Center Faculty Publications

Equine rotavirus group A (ERVA) is one of the most common causes of foal diarrhea. Starting in February 2021, there was an increase in the frequency of severe watery to hemorrhagic diarrhea cases in neonatal foals in Central Kentucky. Diagnostic investigation of fecal samples failed to detect evidence of diarrhea-causing pathogens including ERVA. Based on Illumina-based metagenomic sequencing, we identified a novel equine rotavirus group B (ERVB) in fecal specimens from the affected foals in the absence of any other known enteric pathogens. Interestingly, the protein sequence of all 11 segments had greater than 96% identity with group B …

Association Of Nonacute Opioid Use And Cardiovascular Diseases: A Scoping Review Of The Literature, Jade H. Singleton, Erin L. Abner, Peter D. Akpunonu, Anna M. Kucharska-Newton

Epidemiology and Environmental Health Faculty Publications

BACKGROUND

In this scoping review, we identified and reviewed 23 original articles from the PubMed database that investigated the relationship between nonacute opioid use (NOU) and cardiovascular outcomes.

METHODS AND RESULTS

We defined NOU to include both long-term opioid therapy and opioid use disorder. We summarized the association between NOU and 5 classes of cardiovascular disease, including infective endocarditis, coronary heart disease (including myocardial infarction), congestive heart failure, cardiac arrythmia (including cardiac arrest), and stroke. The most commonly studied outcomes were coronary heart disease and infective endocarditis. There was generally consistent evidence of a positive association between community prevalence of …

Pharmacotherapy In Coronavirus Disease 2019 And Risk Of Secondary Infections: A Single-Center Case Series And Narrative Review, Michael Behal, Brooke Barlow, Breanne Mefford, Melissa L. Thompson Bastin, J. Chris Donaldson, Melanie Laine, Brittany D. Bissell

Pharmacy Practice and Science Faculty Publications

OBJECTIVES: Since the onset of the coronavirus disease 2019 pandemic, immune modulators have been considered front-line candidates for the management of patients presenting with clinical symptoms secondary to severe acute respiratory syndrome coronavirus 2 infection. Although heavy emphasis has been placed on early clinical efficacy, we sought to evaluate the impact of pharmacologic approach to coronavirus disease 2019 within the ICU on secondary infections and clinical outcomes.

DATA SOURCES: PubMed (inception to March 2021) database search and manual selection of bibliographies from selected articles.

STUDY SELECTION AND DATA EXTRACTION: Articles relevant to coronavirus disease 2019, management of severe acute respiratory …

Effect Of Clinical Isolate Or Cleavage Site Mutations In The Sars-Cov-2 Spike Protein On Protein Stability, Cleavage, And Cell-Cell Fusion, Chelsea T. Barrett, Hadley E. Neal, Kearstin Edmonds, Carole L. Moncman, Rachel Thompson, Jean M. Branttie, Kerri Beth Boggs, Cheng-Yu Wu, Daisy W. Leung, Rebecca E. Dutch

Molecular and Cellular Biochemistry Faculty Publications

The trimeric severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein (S) is the sole viral protein responsible for both viral binding to a host cell and the membrane fusion event needed for cell entry. In addition to facilitating fusion needed for viral entry, S can also drive cell-cell fusion, a pathogenic effect observed in the lungs of SARS-CoV-2-infected patients. While several studies have investigated S requirements involved in viral particle entry, examination of S stability and factors involved in S cell-cell fusion remain limited. A furin cleavage site at the border between the S1 and S2 subunits (S1/S2) has …

The Impact Of Contact Tracing On The Spread Of Covid-19: An Egocentric Agent-Based Model, Andrew Pilny, Lin Xiang, Corey Huber, Will Silberman, Sean Goatley-Soan

Communication Faculty Publications

At its core, contact tracing is a form of egocentric network analysis (ENA). One of the biggest obstacles for ENA is informant accuracy (i.e., amount of true contacts identified), which is even more prominent for interaction-based network ties because they often represent episodic relational events, rather than enduring relational states. This research examines the effect of informant accuracy on the spread of COVID-19 through an egocentric, agent-based model. Overall when the average person transmits COVID-19 to 1.62 other people (i.e., the R₀), they must be, on average, 75% accurate with naming their contacts. In higher transmission contexts (i.e., …

Solar Disinfection Of Turbid Hygiene Waters In Lexington, Ky, Usa, Atena Amirsoleimani, Gail M. Brion

Civil Engineering Faculty Publications

Solar disinfection (SODIS) could be a key to providing a clean, hygiene water for birthing uses, but the recommended climate zone is limited, the microbial indicators are related to gastrointestinal illness and not wound infections. SODIS feasibility was investigated to remove Escherichia coli from turbid water at temperatures less than 50 °C in Lexington, KY. Increasing turbidity from 0 to 200 NTU decreased E. coli inactivation from 5 to 1 log. With the same experimental protocol, more than 4-log inactivation of Staphylococcus aureus and Staphylococcus epidermidis (common human-skin microorganisms related to serious post-partum infections of both mother and child) was …

Report Of The Pathogenesis And Pathophysiology Of Lyme Disease Subcommittee Of The Hhs Tick Borne Disease Working Group, Sam T. Donta, Leith J. States, Wendy A. Adams, Troy Bankhead, Nicole Baumgarth, Monica E. Embers, Robert B. Lochhead, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

An understanding of the pathogenesis and pathophysiology of Lyme disease is key to the ultimate care of patients with Lyme disease. To better understand the various mechanisms underlying the infection caused by Borrelia burgdorferi, the Pathogenesis and Pathophysiology of Lyme Disease Subcommittee was formed to review what is currently known about the pathogenesis and pathophysiology of Lyme disease, from its inception, but also especially about its ability to persist in the host. To that end, the authors of this report were assembled to update our knowledge about the infectious process, identify the gaps that exist in our understanding of …

Integrated Research To Reduce Poisoning From Oxytropis And Astragalus Spp In U.S.A., Michael H. Ralphs, B. L. Stegelmeier, K. E. Panter, Dale R. Gardner, J. A. Pfister, S. E. Lee, L. F. James, K. C. Mcdaniel, Rebecca Creamer, J. R. Valdez, D. R. Child

IGC Proceedings (1977-2023)

No abstract provided.

Dating App Use Among Rural Men Who Have Sex With Men And Its Relationship To Hiv Prevention And Risk Behaviors: A Mixed-Methods Analysis, Lauren Bineau, Danielle Lambert, Natalia Truszczynski, Nathan Hansen, Carolyn Lauckner

Center for Health Equity Transformation Faculty Publications

INTRODUCTION: Men who have sex with men (MSM) in rural areas have limited access to HIV prevention and education resources. Given the growing usage of mobile dating apps among the wider MSM population, this research sought to explore their use among MSM in rural areas and their potential for delivering HIV prevention information.

METHODS: Participants were recruited from different areas of the rural Southern USA. This mixed-methods study consisted of an online survey (n=85) and follow-up qualitative phone interviews with 20 survey respondents. The survey assessed dating app use, sexual behaviors, and pre-exposure prophylaxis (PrEP) awareness, usage, and attitudes among …

Serological Survey Of Leptospira Infection In Arabian Horses In Poland, Bernard Wasiński, Katarzyna Paschalis-Trela, Jan Trela, Michał Czopowicz, Jerzy Kita, Monika Żychska, Anna Cywińska, Iwona Markowska-Daniel, Craig N. Carter, Lucjan Witkowski

Veterinary Diagnostic Laboratory Faculty Publications

Leptospirosis is one of the most common zoonotic infections worldwide, including in most livestock, some companion animals, horses, wildlife, and humans. Epidemiological estimation of its prevalence in all species is difficult due to the variety of clinical presentations and challenges regarding laboratory diagnosis. The purpose of this study was to measure the seroprevalence of leptospiral infection in Arabian horses kept in the largest breeding farms in Poland, representing over 15% of the Polish Arabian horse population. Leptospira antibodies were detected by MAT (cut-off 1:100) in 33.2% of serum samples (204 of 615 animals) (CI 95%: 29.6–37.0%), most frequently reacting with …

Yeast Particle Encapsulation Of Scaffolded Terpene Compounds For Controlled Terpene Release, Ernesto R. Soto, Florentina Rus, Hanchen Li, Carli Garceau, Jeffrey Chicca, Mostafa Elfawal, David Gazzola, Martin K. Nielsen, Joseph F. Urban Jr., Raffi V. Aroian, Gary R. Ostroff

Maxwell H. Gluck Equine Research Center Faculty Publications

Terpenes are naturally occurring compounds produced by plants that are of great commercial interest in the food, agricultural, cosmetic, and pharmaceutical industries due to their broad spectra of antibacterial, antifungal, anthelmintic, membrane permeation enhancement, and antioxidant biological activities. Applications of terpenes are often limited by their volatility and the need for surfactants or alcohols to produce stable, soluble (non-precipitated) products. Yeast particles (YPs) are hollow, porous microspheres that have been used for the encapsulation of terpenes (YP terpenes) by passive diffusion of terpenes through the porous YP cell walls. We here report the development of a second generation YP encapsulated …

Green Versus Green: When The Economic Needs Of Minority Communities Clash With Environmental Justice Concerns, Rhoda J. Yen

Journal of Natural Resources & Environmental Law

No abstract provided.

Water Exchange Rate Across The Blood-Brain Barrier Is Associated With Csf Amyloid-Β 42 In Healthy Older Adults, Brian T. Gold, Xingfeng Shao, Tiffany L. Sudduth, Gregory A. Jicha, Donna M. Wilcock, Elayna R. Seago, Danny J. J. Wang

Sanders-Brown Center on Aging Faculty Publications

INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function.

METHODS: Forty cognitively normal older adults (67–86 years old) were scanned with diffusion‐prepared, arterial spin labeling (DP‐ASL), which estimates water exchange rate across the BBB (k_w). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores.

RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid …

Exploring Covid-19 Case Fatality In Relation To The Prevalence Of Chronic Conditions And Health Behaviors In Appalachian Kentucky, W. Jay Christian

Journal of Appalachian Health

Background: Research has demonstrated that common chronic conditions, especially those related to cardiovascular health, are important risk factors for severe COVID-19 symptoms or hospitalization. Population prevalence rates of such conditions have not previously been examined in relation to COVID-19 case fatality rates in the Central Appalachian region.

Purpose: This study examined prevalence rates of selected chronic conditions and COVID-19 case fatality rates to determine whether the relationship between them is consistent across Appalachian and non-Appalachian regions of Kentucky.

Methods: Data from Kentucky’s Behavioral Risk Factor Survey (KyBRFS) were used to calculate prevalence rates of asthma, diabetes, influenza vaccination, hypertension, obesity, …

Application Of Eh-Ph Diagrams On Acid Leaching Systems For The Recovery Of Rees From Bastnaesite, Monazite And Xenotime, Peijia Lin, Xinbo Yang, Joshua M. Werner, Rick Q. Honaker

Mining Engineering Faculty Publications

Bastnaesite, monazite and xenotime are rare earth minerals (REMs) that are typical sources for rare earth elements (REEs). To advance the understanding of their leaching and precipitation behavior in different hydrometallurgical processes, Eh-pH diagrams were constructed and modified using the HSC 9.9 software. The aqueous stability of rare earth elements in H₂O and acid leaching systems, i.e., the REE-Ligands-H₂O systems, were depicted and studied based on the Eh-pH diagrams. This study considers the most relevant lixiviants, their resulting equilibrium states and the importance in the hydrometallurgical recovery of rare earth elements (REMs). A literature review was …

Feeding Cannabidiol (Cbd)-Containing Treats Did Not Affect Canine Daily Voluntary Activity, Elizabeth M. Morris, Susanna E. Kitts-Morgan, Dawn M. Spangler, Jessica Gebert, Eric S. Vanzant, Kyle R. Mcleod, David L. Harmon

Animal and Food Sciences Faculty Publications

Growing public interest in the use of cannabidiol (CBD) for companion animals has amplified the need to elucidate potential impacts. The purpose of this investigation was to determine the influence of CBD on the daily activity of adult dogs. Twenty-four dogs (18.0 ± 3.4 kg, 9 months−4 years old) of various mixed breeds were utilized in a randomized complete block design with treatments targeted at 0 and 2.5 mg (LOW) and at 5.0 mg (HIGH) CBD/kg body weight (BW) per day split between two treats administered after twice-daily exercise (0700–0900 and 1,700–1,900 h). Four hours each day [1,000–1,200 h (a.m.) …

The Public’S Perceptions Of Government Officials’ Communication In The Wake Of The Covid-19 Pandemic, Shaniece B. Bickham, Diane B. Francis

Communication Faculty Publications

Early news coverage in the US about the COVID-19 pandemic focused on information released from local, state and federal government officials. With an emphasis on US government at these levels, this study examined whether the public’s credibility perceptions and trust in government, along with message exposure, influenced their adherence to information from the government about (a) stay-at-home orders, (b) social distancing and (c) COVID-19 testing. Source credibility theory and situational crisis communication theory provided the theoretical framework for this study. Through the survey data analysis, we investigated communication preferences in the wake of the pandemic and whether credibility perceptions differed …

Insects Provide Unique Systems To Investigate How Early-Life Experience Alters The Brain And Behavior, Rebecca R. Westwick, Clare C. Rittschof

Entomology Faculty Publications

Early-life experiences have strong and long-lasting consequences for behavior in a surprising diversity of animals. Determining which environmental inputs cause behavioral change, how this information becomes neurobiologically encoded, and the functional consequences of these changes remain fundamental puzzles relevant to diverse fields from evolutionary biology to the health sciences. Here we explore how insects provide unique opportunities for comparative study of developmental behavioral plasticity. Insects have sophisticated behavior and cognitive abilities, and they are frequently studied in their natural environments, which provides an ecological and adaptive perspective that is often more limited in lab-based vertebrate models. A range of cues, …

Method For Designing Compounds And Compositions Useful For Targeting High Stoichiometric Complexes To Treat Conditions, Including Treatment Of Viruses, Bacteria, And Cancers Having Acquired Drug Resistance, Peixuan Guo, Dan Shu

Pharmaceutical Sciences Faculty Patents

A method is described for the identification o f multi-subunit biocomplex drug targets. The method includes identifying a target that performs a biological function, wherein the target comprises one or more subunits, wherein a minimum number of the one or more subunits is inactivated to inhibit the biological function. The method includes selecting a drug that binds specifically to each subunit of the one or more subunits with a target probability. The method describes a relationship between inhibition efficiency of the drug and total number of the one or more subunits using a binomial distribution, wherein the inhibition efficiency comprises …

Efficacy And Safety Of Vancomycin Loading Doses In Critically Ill Patients With Methicillin-Resistant Staphylococcus Aureus Infection, Alexander H. Flannery, Katie L. Wallace, Christian N. Rhudy, Allison S. Olmsted, Rachel C. Minrath, Stuart M. Pope, Aaron M. Cook, David S. Burgess, Peter E. Morris

Pharmacy Practice and Science Faculty Publications

Background: While vancomycin loading doses may facilitate earlier pharmacokinetic–pharmacodynamic target attainment, the impact of loading doses on clinical outcomes remains understudied. Critically ill patients are at highest risk of morbidity and mortality from methicillin resistant Staphylococcus aureus (MRSA) infection and hypothesized to most likely benefit from a loading dose. We sought to determine the association between receipt of a vancomycin loading dose and clinical outcomes in a cohort of critically ill adults.

Methods: Four hundred and forty-nine critically ill patients with MRSA cultures isolated from blood or respiratory specimens were eligible for the study. Cohorts were established by receipt of …

An Inactivated Bacterium (Paraprobiotic) Expressing Bacillus Thuringiensis Cry5b As A Therapeutic For Ascaris And Parascaris Spp. Infections In Large Animals, Joseph F. Urban, Martin K. Nielsen, David Gazzola, Yue Xie, Ethiopia Beshah, Yan Hu, Hanchen Li, Florentina Rus, Kelly Flanagan, Austin Draper, Sridhar Vakalapudi, Robert W. Li, Gary R. Ostroff, Raffi V. Aroian

Maxwell H. Gluck Equine Research Center Faculty Publications

Ascaris and Parascaris are important parasites in the family Ascarididae, large, ubiquitous intestinal-dwelling nematodes infecting all classes of vertebrates. Parasitic nematode drug resistance in veterinary medicine and drug recalcitrance in human medicine are increasing worldwide, with few if any new therapeutic classes on the horizon. Some of these parasites are zoonotic, e.g., Ascaris is passed from humans to pigs and vice versa. The development of new therapies against this family of parasites would have major implications for both human and livestock health. Here we tested the therapeutic ability of a paraprobiotic or dead probiotic that expresses the Bacillus …

Stage-Specific Action Of Juvenile Hormone Analogs, Ramaseshadri Parthasarathy, Subba Reddy Palli

Entomology Faculty Publications

The discovery of juvenile hormones (JH) and their synthetic analogs (JHA) generated excitement and hope that these compounds will replace first- and second-generation insecticides that have not so desirable environmental and human safety profiles. However, JHAs used commercially during the past four decades did not meet these expectations. The recent availability of advanced molecular and histological methods and the discovery of key players involved in JH action provided some insights into the functioning of JHA in a stage and species-specific manner. In this review, we will summarize recent findings and stage-specific action of JHA, focusing on three commercially used JHA, …

Selecting An Anti-Malarial Clinical Candidate From Two Potent Dihydroisoquinolones, Yizhe Chen, Fangyi Zhu, Jared T. Hammill, Gloria Holbrook, Lei Yang, Burgess Freeman, Karen L. White, David M. Shackleford, Kathleen G. O'Loughlin, Susan A. Charman, Jon C. Mirsalis, R. Kiplin Guy

Pharmaceutical Sciences Faculty Publications

BACKGROUND: The ongoing global malaria eradication campaign requires development of potent, safe, and cost-effective drugs lacking cross-resistance with existing chemotherapies. One critical step in drug development is selecting a suitable clinical candidate from late leads. The process used to select the clinical candidate SJ733 from two potent dihydroisoquinolone (DHIQ) late leads, SJ733 and SJ311, based on their physicochemical, pharmacokinetic (PK), and toxicity profiles is described.

METHODS: The compounds were tested to define their physicochemical properties including kinetic and thermodynamic solubility, partition coefficient, permeability, ionization constant, and binding to plasma proteins. Metabolic stability was assessed in both microsomes and hepatocytes derived …