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Detection Of (1,3)-Β-D-Glucan In Cerebrospinal Fluid In Histoplasma Meningitis, Thein Myint, Felicia C. Chow, Karen C. Bloch, Luke Raymond-Guillen, Thomas E. Davis, Patty W. Wright, Laila Woc-Colburn, Raed N. Khairy, Alan C. Street, Tomotaka Yamamoto, Amanda Albers, L. Joseph Wheat, Chadi A. Hage Oct 2018

Detection Of (1,3)-Β-D-Glucan In Cerebrospinal Fluid In Histoplasma Meningitis, Thein Myint, Felicia C. Chow, Karen C. Bloch, Luke Raymond-Guillen, Thomas E. Davis, Patty W. Wright, Laila Woc-Colburn, Raed N. Khairy, Alan C. Street, Tomotaka Yamamoto, Amanda Albers, L. Joseph Wheat, Chadi A. Hage

Internal Medicine Faculty Publications

The diagnosis of central nervous system (CNS) histoplasmosis is often difficult. Although cerebrospinal fluid (CSF) (1,3)-β-d-glucan (BDG) is available as a biological marker for the diagnosis of fungal meningitis, there are limited data on its use for the diagnosis of Histoplasma meningitis. We evaluated CSF BDG detection, using the Fungitell assay, in patients with CNS histoplasmosis and controls. A total of 47 cases and 153 controls were identified. The control group included 13 patients with a CNS fungal infection other than histoplasmosis. Forty-nine percent of patients with CNS histoplasmosis and 43.8% of controls were immunocompromised. The median CSF …


Systemic Immunosuppression And Risk Of Age-Related Macular Degeneration, Harpal S. Sandhu, Joshua Lambert, Yan Xu, Henry J. Kaplan Sep 2018

Systemic Immunosuppression And Risk Of Age-Related Macular Degeneration, Harpal S. Sandhu, Joshua Lambert, Yan Xu, Henry J. Kaplan

Applied Statistics Laboratory Faculty Publications

A local immune response has been implicated in the pathogenesis of age-related macular degeneration (AMD), but it is unclear if systemic immunosuppressive/immunomodulatory therapy (IMT) protects against the onset and/or progression of AMD. We performed a retrospective cohort study using a Cox proportional hazards model of two cohorts. Cohort 1 included patients with stage V chronic kidney disease (CKD) status post kidney transplantation, on at least one IMT agent, and older than 50. Cohort 2 included patients with stage IV or V CKD who had not undergone kidney transplantation, were not on IMT, and were older than 50. The main outcomes …


Better Than Deet Repellent Compounds Derived From Coconut Oil, Junwei J. Zhu, Steven C. Cermak, James A. Kenar, Gary Brewer, Kenneth F. Haynes, Dave Boxler, Paul D. Baker, Desen Wang, Changlu Wang, Andrew Y. Li, Rui-De Xue, Yuan Shen, Fei Wang, Natasha M. Agramonte, Ulrich R. Bernier, Jaires G. De Oliveira Filho, Ligia M. F. Borges, Kristina Friesen, David B. Taylor Sep 2018

Better Than Deet Repellent Compounds Derived From Coconut Oil, Junwei J. Zhu, Steven C. Cermak, James A. Kenar, Gary Brewer, Kenneth F. Haynes, Dave Boxler, Paul D. Baker, Desen Wang, Changlu Wang, Andrew Y. Li, Rui-De Xue, Yuan Shen, Fei Wang, Natasha M. Agramonte, Ulrich R. Bernier, Jaires G. De Oliveira Filho, Ligia M. F. Borges, Kristina Friesen, David B. Taylor

Entomology Faculty Publications

Hematophagous arthropods are capable of transmitting human and animal pathogens worldwide. Vector-borne diseases account for 17% of all infectious diseases resulting in 700,000 human deaths annually. Repellents are a primary tool for reducing the impact of biting arthropods on humans and animals. N,N-Diethyl-meta-toluamide (DEET), the most effective and long-lasting repellent currently available commercially, has long been considered the gold standard in insect repellents, but with reported human health issues, particularly for infants and pregnant women. In the present study, we report fatty acids derived from coconut oil which are novel, inexpensive and highly efficacious repellant compounds. These coconut …


Latent Tuberculosis Infection Is Associated With Increased Unstimulated Levels Of Interferon-Gamma In Lima, Peru, Moises A. Huaman, David Henson, Paola L. Rondan, Eduardo Ticona, Gustavo Miranda, Richard J. Kryscio, Raquel Mugruza, Ernesto Aranda, Cesar Ticona, Susan Abarca, Paula Heredia, Andres Aguirre, Timothy R. Sterling, Beth A. Garvy, Carl J. Fichtenbaum Sep 2018

Latent Tuberculosis Infection Is Associated With Increased Unstimulated Levels Of Interferon-Gamma In Lima, Peru, Moises A. Huaman, David Henson, Paola L. Rondan, Eduardo Ticona, Gustavo Miranda, Richard J. Kryscio, Raquel Mugruza, Ernesto Aranda, Cesar Ticona, Susan Abarca, Paula Heredia, Andres Aguirre, Timothy R. Sterling, Beth A. Garvy, Carl J. Fichtenbaum

Internal Medicine Faculty Publications

Background

We previously reported increased unstimulated blood levels of interferon-gamma in persons with latent tuberculosis infection (LTBI) in the United States, suggesting enhanced immune activation in LTBI. To investigate this further in a TB-endemic setting, we assessed interferon-gamma levels in persons with and without LTBI in Peru.

Methods

We analyzed data from patients with and without a recent type 1 (spontaneous) acute myocardial infarction (AMI) who were enrolled from two public hospital networks in Lima, Peru, and underwent LTBI testing using the QuantiFERON® TB Gold In-tube (QFT) assay. Participants with a positive QFT test were defined as having LTBI, whereas …


Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel Sep 2018

Interfering With Dna Decondensation As A Strategy Against Mycobacteria, Enzo M. Scutigliani, Edwin R. Scholl, Anita E. Grootemaat, Sadhana Khanal, Jakub A. Kochan, Przemek M. Krawczyk, Eric A. Reits, Atefeh Garzan, Huy X. Ngo, Keith D. Green, Sylvie Garneau-Tsodikova, Jan M. Ruijter, Henk A. Van Veen, Nicole N. Van Der Wel

Pharmaceutical Sciences Faculty Publications

Tuberculosis is once again a major global threat, leading to more than 1 million deaths each year. Treatment options for tuberculosis patients are limited, expensive and characterized by severe side effects, especially in the case of multidrug-resistant forms. Uncovering novel vulnerabilities of the pathogen is crucial to generate new therapeutic strategies. Using high resolution microscopy techniques, we discovered one such vulnerability of Mycobacterium tuberculosis. We demonstrate that the DNA of M. tuberculosis can condense under stressful conditions such as starvation and antibiotic treatment. The DNA condensation is reversible and specific for viable bacteria. Based on these observations, we hypothesized …


The Conquest Of Pus -- A History Of Bitumen, Creosote And Carbolic Acid, Charles T. Ambrose Sep 2018

The Conquest Of Pus -- A History Of Bitumen, Creosote And Carbolic Acid, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

In the Western world from antiquity on, open wounds were treated topically with petroleum-derived substances, such as bitumen, asphalt, pitch, and tar. The immediate aim was to stifle bleeding and ease pain but a potential benefit was preventing local corruption with pus formation. In the early 19th century, creosote was recovered from bitumen and found to reduce suppuration. Carbolic acid was later isolated from creosote and recognized as an underlying active agent. In the 1860s, carbolic acid was first employed by Jules Lemaire to treat local skin infections and later by Joseph Lister to prevent the suppuration in compound fractures. …


Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson Aug 2018

Transcriptomic Insights On The Virulence-Controlling Csra, Badr, Rpon, And Rpos Regulatory Networks In The Lyme Disease Spirochete, William K. Arnold, Christina R. Savage, Kathryn G. Lethbridge, Trever C. Smith, Catherine A. Brisette, Janakiram Seshu, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Borrelia burgdorferi, the causative agent of Lyme disease, survives in nature through a cycle that alternates between ticks and vertebrates. To facilitate this defined lifestyle, B. burgdorferi has evolved a gene regulatory network that ensures transmission between those hosts, along with specific adaptations to niches within each host. Several regulatory proteins are known to be essential for the bacterium to complete these critical tasks, but interactions between regulators had not previously been investigated in detail, due to experimental uses of different strain backgrounds and growth conditions. To address that deficit in knowledge, the transcriptomic impacts of four critical …


Temporal Trends And Predictors Of Antimicrobial Resistance Among Staphylococcus Spp. Isolated From Canine Specimens Submitted To A Diagnostic Laboratory, Julia G. Conner, Jackie Smith, Erdal Erol, Stephan Locke, Erica Phillips, Agricola Odoi Aug 2018

Temporal Trends And Predictors Of Antimicrobial Resistance Among Staphylococcus Spp. Isolated From Canine Specimens Submitted To A Diagnostic Laboratory, Julia G. Conner, Jackie Smith, Erdal Erol, Stephan Locke, Erica Phillips, Agricola Odoi

Veterinary Diagnostic Laboratory Faculty Publications

Background

Resistance to commonly used antimicrobials is a growing concern in both human and veterinary medicine. Understanding the temporal changes in the burden of the problem and identifying its determinants is important for guiding control efforts. Therefore, the objective of this study was to investigate temporal patterns and predictors of antimicrobial resistance among Staphylococcus spp. isolated from canine specimens submitted to the University of Kentucky Veterinary Diagnostic Laboratory (UKVDL) between 1993 and 2009.

Methods

Retrospective data of 4,972 Staphylococcus isolates assessed for antimicrobial susceptibility using the disk diffusion method at the UKVDL between 1993 and 2009 were included in the …


Gut Inflammatory Diseases, Infection, And Nutrition, Helieh S. Oz, Sung-Ling Yeh, Amedeo Amedei Jul 2018

Gut Inflammatory Diseases, Infection, And Nutrition, Helieh S. Oz, Sung-Ling Yeh, Amedeo Amedei

Internal Medicine Faculty Publications

No abstract provided.


Incidence Of Acute Kidney Injury Among Patients Treated With Piperacillin-Tazobactam Or Meropenem In Combination With Vancomycin, Wilbur Cliff Rutter, David S. Burgess Jul 2018

Incidence Of Acute Kidney Injury Among Patients Treated With Piperacillin-Tazobactam Or Meropenem In Combination With Vancomycin, Wilbur Cliff Rutter, David S. Burgess

Pharmacy Practice and Science Faculty Publications

Acute kidney injury (AKI) increases during empirical antimicrobial therapy with the combination of piperacillin-tazobactam (TZP) and vancomycin (VAN) compared to the number of incidences with monotherapy or the combination of cefepime and VAN. Limited data regarding the impact of meropenem (MEM) combined with VAN exist. This study examined the AKI incidence among patients treated with MEM plus VAN (MEM+VAN) or TZP+VAN. Data were collected from the University of Kentucky Center for Clinical and Translational Science Enterprise Data Trust from September 2007 through October 2015. Adults without previous renal disease who received MEM+VAN or TZP+VAN for at least 2 days were …


Isolated Sporothrix Schenckii Monoarthritis, Aram Barbaryan, Wissam El Atrouni, Stefania Bailuc, Matthew W. Jones, Maharshi Bhakta, Khaldoun Haj Mahmoud, Aibek E. Mirrakhimov Jun 2018

Isolated Sporothrix Schenckii Monoarthritis, Aram Barbaryan, Wissam El Atrouni, Stefania Bailuc, Matthew W. Jones, Maharshi Bhakta, Khaldoun Haj Mahmoud, Aibek E. Mirrakhimov

Internal Medicine Faculty Publications

Sporothrix schenkii sensu lato is a rare cause of arthritis. Its course is indolent with lack of constitutional symptoms resulting in delayed presentation and diagnosis. It is a dimorphic fungus found ubiquitously in sphagnum moss, decaying vegetation, soil, and hay. Inoculation of dirt into the skin and soft tissues and, in rare instances, inhalation of aerosolized conidia from soil and plants can lead to infection. Subacute and chronic involvement of skin and subcutaneous tissues is the most common manifestation of sporotrichosis in immunocompetent hosts. In patients with underlying risk factors (HIV, alcoholism, diabetes mellitus, organ transplant patients, immunosuppressive medications, steroids, …


Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson Jun 2018

Borrelia Burgdorferi Spovg Dna- And Rna-Binding Protein Modulates The Physiology Of The Lyme Disease Spirochete, Christina R. Savage, Brandon L. Jutras, Aaron Bestor, Kit Tilly, Patricia A. Rosa, Yvonne Tourand, Philip E. Stewart, Catherine A. Brissette, Brian Stevenson

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The SpoVG protein of Borrelia burgdorferi, the Lyme disease spirochete, binds to specific sites of DNA and RNA. The bacterium regulates transcription of spoVG during the natural tick-mammal infectious cycle and in response to some changes in culture conditions. Bacterial levels of spoVG mRNA and SpoVG protein did not necessarily correlate, suggesting that posttranscriptional mechanisms also control protein levels. Consistent with this, SpoVG binds to its own mRNA, adjacent to the ribosome-binding site. SpoVG also binds to two DNA sites in the glpFKD operon and to two RNA sites in glpFKD mRNA; that operon encodes genes necessary for glycerol catabolism …


Shifts In Assemblage Of Foraging Bats At Mammoth Cave National Park Following Arrival Of White-Nose Syndrome, Marissa M. Thalken, Michael J. Lacki, Joseph S. Johnson Jun 2018

Shifts In Assemblage Of Foraging Bats At Mammoth Cave National Park Following Arrival Of White-Nose Syndrome, Marissa M. Thalken, Michael J. Lacki, Joseph S. Johnson

Forestry and Natural Resources Faculty Publications

The arrival of white-nose syndrome (WNS) to North America in 2006, and the subsequent decline in populations of cave-hibernating bats have potential long-term implications for communities of forest-dwelling bats in affected regions. Severe declines in wintering populations of bats should lead to concomitant shifts in the composition and relative abundance of species during the staging, maternity, and swarming seasons in nearby forested habitats. We examined capture rates of bats collected in mist nets from 2009 to 2016 to evaluate summer patterns in abundance of species pre- and post-arrival of WNS to Mammoth Cave National Park, KY. The data demonstrated a …


First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma, Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, John L. Villano May 2018

First Results On Survival From A Large Phase 3 Clinical Trial Of An Autologous Dendritic Cell Vaccine In Newly Diagnosed Glioblastoma, Linda M. Liau, Keyoumars Ashkan, David D. Tran, Jian L. Campian, John E. Trusheim, Charles S. Cobbs, Jason A. Heth, Michael Salacz, Sarah Taylor, Stacy D. D'Andre, Fabio M. Iwamoto, Edward J. Dropcho, Yaron A. Moshel, Kevin A. Walter, Clement P. Pillainayagam, Robert Aiken, Rekha Chaudhary, Samuel A. Goldlust, Daniela A Bota, Paul Duic, Jai Grewal, Heinrich Elinzano, Steven A. Toms, Kevin O. Lillehei, Tom Mikkelsen, Tobias Walbert, Steven R. Abram, Andrew J. Brenner, Steven Brem, Matthew G. Ewend, John L. Villano

Internal Medicine Faculty Publications

Background: Standard therapy for glioblastoma includes surgery, radiotherapy, and temozolomide. This Phase 3 trial evaluates the addition of an autologous tumor lysate-pulsed dendritic cell vaccine (DCVax®-L) to standard therapy for newly diagnosed glioblastoma.

Methods: After surgery and chemoradiotherapy, patients were randomized (2:1) to receive temozolomide plus DCVax-L (n = 232) or temozolomide and placebo (n = 99). Following recurrence, all patients were allowed to receive DCVax-L, without unblinding. The primary endpoint was progression free survival (PFS); the secondary endpoint was overall survival (OS).

Results: For the intent-to-treat (ITT) population (n = 331), median OS (mOS) was 23.1 months …


Protozoal Coinfection In Horses With Equine Protozoal Myeloencephalitis In The Eastern United States, Sarah Schale, Daniel Howe, Michelle Yeargan, Jennifer K. Morrow, Amy Graves, Amy L. Johnson May 2018

Protozoal Coinfection In Horses With Equine Protozoal Myeloencephalitis In The Eastern United States, Sarah Schale, Daniel Howe, Michelle Yeargan, Jennifer K. Morrow, Amy Graves, Amy L. Johnson

Maxwell H. Gluck Equine Research Center Faculty Publications

Background: Infection by 2 or more protozoa is linked with increased severity of disease in marine mammals with protozoan encephalitis.

Hypothesis/Objectives: To assess whether horses with equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona also have evidence of infection with Neospora hughesi or Toxoplasma gondii. We hypothesized that horses with EPM would be more likely than horses with cervical vertebral stenotic myelopathy (CVSM) to be positive for antibodies to multiple protozoan parasites.

Animals: One hundred one horses with neurologic disease: 49 with EPM and 52 with CVSM.

Methods: Case review. Archived serum and cerebrospinal fluid (CSF) from 101 horses …


In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian May 2018

In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian

Veterinary Science Faculty Publications

Background

The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define the …


Serum Lipidomics Of Bovine Paratuberculosis: Disruption Of Choline-Containing Glycerophospholipids And Sphingolipids, Paul L. Wood, Erdal Erol, Glen F. Hoffsis, Margaret Steinman, Jeroen Debuck May 2018

Serum Lipidomics Of Bovine Paratuberculosis: Disruption Of Choline-Containing Glycerophospholipids And Sphingolipids, Paul L. Wood, Erdal Erol, Glen F. Hoffsis, Margaret Steinman, Jeroen Debuck

Veterinary Science Faculty Publications

Objectives: Bovine paratuberculosis is a devastating infection with Mycobacterium avium subspecies paratuberculosis that ultimately results in death from malnutrition. While the infection is characterized by a long (2–4 years) subclinical phase with immune activation, ultimately host defense mechanisms fail and the bacteria spread from the small intestine to other organs. Since both the gastrointestinal tract and liver are essential for the biosynthesis of structural glycerophospholipids, we investigated the circulating levels of these lipids in field infections and experimentally infected cattle.

Methods: Serum lipidomics of control and M. avium subspecies paratuberculosis–infected cattle were performed utilizing high-resolution mass spectrometry.

Results: In …


Bioprospecting Deep-Sea Actinobacteria For Novel Anti-Infective Natural Products, Dongbo Xu, Linna Han, Chunhui Li, Qi Cao, Duolong Zhu, Nolan H. Barrett, Dedra Harmody, Jing Chen, Haining Zhu, Peter J. Mccarthy, Xingmin Sun, Guojun Wang Apr 2018

Bioprospecting Deep-Sea Actinobacteria For Novel Anti-Infective Natural Products, Dongbo Xu, Linna Han, Chunhui Li, Qi Cao, Duolong Zhu, Nolan H. Barrett, Dedra Harmody, Jing Chen, Haining Zhu, Peter J. Mccarthy, Xingmin Sun, Guojun Wang

Molecular and Cellular Biochemistry Faculty Publications

The global prevalence of drug resistance has created an urgent need for the discovery of novel anti-infective drugs. The major source of antibiotics in current clinical practice is terrestrial actinobacteria; the less-exploited deep-sea actinobacteria may serve as an unprecedented source of novel natural products. In this study, we evaluated 50 actinobacteria strains derived from diverse deep water sponges and environmental niches for their anti-microbial activities against a panel of pathogens including Candida albicans, Clostridium difficile, Staphylococcus aureus, and methicillin-resistant S. aureus (MRSA), and Pseudomonas aeruginosa. More than half of the tested strains (27) were identified as …


How Much Do We Spend? Creating Historical Estimates Of Public Health Expenditures In The United States At The Federal, State, And Local Levels, Jonathon P. Leider, Beth Resnick, David Bishai, F. Douglas Scutchfield Apr 2018

How Much Do We Spend? Creating Historical Estimates Of Public Health Expenditures In The United States At The Federal, State, And Local Levels, Jonathon P. Leider, Beth Resnick, David Bishai, F. Douglas Scutchfield

Health Management and Policy Faculty Publications

The United States has a complex governmental public health system. Agencies at the federal, state, and local levels all contribute to the protection and promotion of the population's health. Whether the modern public health system is well situated to deliver essential public health services, however, is an open question. In some part, its readiness relates to how agencies are funded and to what ends. A mix of Federalism, home rule, and happenstance has contributed to a siloed funding system in the United States, whereby health agencies are given particular dollars for particular tasks. Little discretionary funding remains. Furthermore, tracking how …


Neutrophils From Both Susceptible And Resistant Mice Efficiently Kill Opsonized Listeria Monocytogenes, Michelle G. Pitts, Travis A. Combs, Sarah E. F. D'Orazio Apr 2018

Neutrophils From Both Susceptible And Resistant Mice Efficiently Kill Opsonized Listeria Monocytogenes, Michelle G. Pitts, Travis A. Combs, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Inbred mouse strains differ in their susceptibility to infection with the facultative intracellular bacterium Listeria monocytogenes, largely due to delayed or deficient innate immune responses. Previous antibody depletion studies suggested that neutrophils (polymorphonuclear leukocytes [PMN]) were particularly important for clearance in the liver, but the ability of PMN from susceptible and resistant mice to directly kill L. monocytogenes has not been examined. In this study, we showed that PMN infiltrated the livers of BALB/c/By/J (BALB/c) and C57BL/6 (B6) mice in similar numbers and that both cell types readily migrated toward leukotriene B4 in an in vitro chemotaxis assay. However, …


Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza Apr 2018

Early Relapse After Autologous Hematopoietic Cell Transplantation Remains A Poor Prognostic Factor In Multiple Myeloma But Outcomes Have Improved Over Time, Shaji K. Kumar, Angela Dispenzieri, Raphael Fraser, Fei Mingwei, Gorgun Akpek, Robert Cornell, Mohamed Kharfan-Dabaja, Cesar Freytes, Shahrukh Hashmi, Gerhard C. Hildebrandt, Leona Holmberg, Robert Kyle, Hillard Lazarus, Cindy Lee, Jospeh Mikhael, Taiga Nishihori, Jason Tay, Saad Usmani, David Vesole, Ravi Vij, Baldeep Wirk, Amrita Krishnan, Cristina Gasparetto, Tomer Mark, Yago Nieto, Parameswaran Hari, Anita D'Souza

Internal Medicine Faculty Publications

Duration of initial disease response remains a strong prognostic factor in multiple myeloma (MM) particularly for upfront autologous hematopoietic cell transplant (AHCT) recipients. We hypothesized that new drug classes and combinations employed prior to AHCT as well as after post-AHCT relapse may have changed the natural history of MM in this population. We analyzed the Center for International Blood and Marrow Transplant Research database to track overall survival (OS) of MM patients receiving single AHCT within 12 months after diagnosis (N=3256) and relapsing early post-AHCT (< 24 months), and to identify factors predicting for early vs late relapses (24−48 months post-AHCT). Over three periods (2001–2004, 2005–2008, 2009–2013), patient characteristics were balanced except for lower proportion of Stage III, higher likelihood of one induction therapy with novel triplets and higher rates of planned post-AHCT maintenance over time. The proportion of patients relapsing early was stable over time at 35–38%. Factors reducing risk of early relapse included lower stage, chemosensitivity, transplant after 2008 and post-AHCT maintenance. Shorter post-relapse OS was associated with early relapse, IgA MM, Karnofsky < 90, stage III, > 1 line of induction and lack of maintenance. Post-AHCT early relapse remains …


Microbial Co-Infection Alters Macrophage Polarization, Phagosomal Escape, And Microbial Killing, Nikita H. Trivedi, Jieh-Juen Yu, Chiung-Yu Hung, Richard P. Doelger, Christopher S. Navara, Lisa Y. Armitige, Janakiram Seshu, Anthony P. Sinai, James P. Chambers, M. Neal Guentzel, Bernard P. Arulanandam Apr 2018

Microbial Co-Infection Alters Macrophage Polarization, Phagosomal Escape, And Microbial Killing, Nikita H. Trivedi, Jieh-Juen Yu, Chiung-Yu Hung, Richard P. Doelger, Christopher S. Navara, Lisa Y. Armitige, Janakiram Seshu, Anthony P. Sinai, James P. Chambers, M. Neal Guentzel, Bernard P. Arulanandam

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Macrophages are important innate immune cells that respond to microbial insults. In response to multi-bacterial infection, the macrophage activation state may change upon exposure to nascent mediators, which results in different bacterial killing mechanism(s). In this study, we utilized two respiratory bacterial pathogens, Mycobacterium bovis (Bacillus Calmette Guẻrin, BCG) and Francisella tularensis live vaccine strain (LVS) with different phagocyte evasion mechanisms, as model microbes to assess the influence of initial bacterial infection on the macrophage response to secondary infection. Non-activated (M0) macrophages or activated M2-polarized cells (J774 cells transfected with the mouse IL-4 gene) were first infected with BCG for …


The Role Of Nutrition In Influencing Mechanisms Involved In Environmentally Mediated Diseases, Bernhard Hennig, Michael C. Petriello, Mary V. Gamble, Young-Joon Surh, Laura A. Kresty, Norbert Frank, Nuchanart Rangkadilok, Mathuros Ruchirawat, William A. Suk Mar 2018

The Role Of Nutrition In Influencing Mechanisms Involved In Environmentally Mediated Diseases, Bernhard Hennig, Michael C. Petriello, Mary V. Gamble, Young-Joon Surh, Laura A. Kresty, Norbert Frank, Nuchanart Rangkadilok, Mathuros Ruchirawat, William A. Suk

Superfund Research Center Faculty Publications

Human exposure to environmental contaminants such as persistent chlorinated organics, heavy metals, pesticides, phthalates, flame retardants, electronic waste and airborne pollutants around the world, and especially in Southeast Asian regions, are significant and require urgent attention. Given this widespread contamination and abundance of such toxins as persistent organic pollutants (POPs) in the ecosystem, it is unlikely that remediation alone will be sufficient to address the health impacts associated with this exposure. Furthermore, we must assume that the impact on health of some of these contaminants results in populations with extraordinary vulnerabilities to disease risks. Further exacerbating risk; infectious diseases, poverty …


Poster Session 1, Kentucky Water Resources Research Institute, University Of Kentucky Mar 2018

Poster Session 1, Kentucky Water Resources Research Institute, University Of Kentucky

Kentucky Water Resources Annual Symposium

  1. The Ecological Importance of Perched Aquifers and Their Hydrological Connectivity to Ridge Top Ephemeral Wetlands in Daniel Boone National Forest
  2. Water Bugs and Bacteria: Creating a Water Quality Monitoring Program for the Wheeling Creek Watershed in the Northern Panhandle of West Virginia
  3. Use of eDNA to Detect Salamander Species in Central Kentucky Streams
  4. Hydrogeological Properties of Natural and Constructed Wetlands in Kentucky’s Daniel Boone National Forest
  5. Use of eDNA in Multiple Species Fish Biomass Determinations in Small to Mid-sized Lotic Systems
  6. Rainfall Runoff Model Development Using HSPF for a Flood Control Reservoir System to Examine Long Term Benefits
  7. Examining the …


Comparative Analysis Of Microbial Sensing Molecules In Mucosal Tissues With Aging, Octavio A. Gonzalez, Sreenatha S. Kirakodu, Michael John Novak, A. J. Stromberg, L. Orraca, J. Gonzalez-Martinez, A. Burgos, Jeffrey L. Ebersole Mar 2018

Comparative Analysis Of Microbial Sensing Molecules In Mucosal Tissues With Aging, Octavio A. Gonzalez, Sreenatha S. Kirakodu, Michael John Novak, A. J. Stromberg, L. Orraca, J. Gonzalez-Martinez, A. Burgos, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Host-bacterial interactions at mucosal surfaces require recognition of the bacteria by host cells enabling targeted responses to maintain tissue homeostasis. It is now well recognized that an array of host-derived pattern recognition receptors (PRRs), both cell-bound and soluble, are critical to innate immune engagement of microbes via microbial-associated molecular patterns (MAMP). This report describes the use of a nonhuman primate model to evaluate changes in the expression of these sensing molecules related to aging in healthy gingival tissues. Macaca mulatta aged 3-24 years were evaluated clinically and gingival tissues obtained, RNA isolated and microarray analysis conducted for gene expression of …


A Comparison Of Oral And Intravenous Mouse Models Of Listeriosis, Michelle G. Pitts, Sarah E. F. D'Orazio Mar 2018

A Comparison Of Oral And Intravenous Mouse Models Of Listeriosis, Michelle G. Pitts, Sarah E. F. D'Orazio

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Listeria monocytogenes is one of several enteric microbes that is acquired orally, invades the gastric mucosa, and then disseminates to peripheral tissues to cause systemic disease in humans. Intravenous (i.v.) inoculation of mice with L. monocytogenes has been the most widely-used small animal model of listeriosis over the past few decades. The infection is highly reproducible and has been invaluable in deciphering mechanisms of adaptive immunity in vivo, particularly CD8+ T cell responses to intracellular pathogens. However, the i.v. model completely bypasses the gut phase of the infection. Recent advances in generating both humanized mice and murinized bacteria, as well …


Streptococcus Equi Infections In Horses: Guidelines For Treatment, Control, And Prevention Of Strangles—Revised Consensus Statement, A. G. Boyle, John F. Timoney, J. R. Newton, M. T. Hines, A. S. Waller, B. R. Buchanan Mar 2018

Streptococcus Equi Infections In Horses: Guidelines For Treatment, Control, And Prevention Of Strangles—Revised Consensus Statement, A. G. Boyle, John F. Timoney, J. R. Newton, M. T. Hines, A. S. Waller, B. R. Buchanan

Maxwell H. Gluck Equine Research Center Faculty Publications

This consensus statement update reflects our current published knowledge and opinion about clinical signs, pathogenesis, epidemiology, treatment, complications, and control of strangles. This updated statement emphasizes varying presentations in the context of existing underlying immunity and carrier states of strangles in the transmission of disease. The statement redefines the “gold standard” for detection of possible infection and reviews the new technologies available in polymerase chain reaction diagnosis and serology and their use in outbreak control and prevention. We reiterate the importance of judicious use of antibiotics in horses with strangles. This updated consensus statement reviews current vaccine technology and the …


Central Nervous System Histoplasmosis: Multicenter Retrospective Study On Clinical Features, Diagnostic Approach And Outcome Of Treatment, Joseph Wheat, Thein Myint, Ying Guo, Phebe Kemmer, Chadi A. Hage, Colin Terry, Marwan M. Azar, James Riddell, Peter Ender, Sharon Chen, Kareem Shehab, Kerry Cleveland, Eden Esguerra, James Johnson, Patty Wright, Vanja Douglas, Pascalis Vergidis, Winnie Ooi, John Baddley, David Bamberger, Raed N. Khairy, Holenarasipur R. Vikram, Elizabeth Jenny-Avital, Geetha Sivasubramanian, Karen Bowlware, Barbara Pahud, Juan Sarria, Townson Tsai, Maha Assi, Satish Mocherla Mar 2018

Central Nervous System Histoplasmosis: Multicenter Retrospective Study On Clinical Features, Diagnostic Approach And Outcome Of Treatment, Joseph Wheat, Thein Myint, Ying Guo, Phebe Kemmer, Chadi A. Hage, Colin Terry, Marwan M. Azar, James Riddell, Peter Ender, Sharon Chen, Kareem Shehab, Kerry Cleveland, Eden Esguerra, James Johnson, Patty Wright, Vanja Douglas, Pascalis Vergidis, Winnie Ooi, John Baddley, David Bamberger, Raed N. Khairy, Holenarasipur R. Vikram, Elizabeth Jenny-Avital, Geetha Sivasubramanian, Karen Bowlware, Barbara Pahud, Juan Sarria, Townson Tsai, Maha Assi, Satish Mocherla

Internal Medicine Faculty Publications

Central nervous system (CNS) involvement occurs in 5 to 10% of individuals with disseminated histoplasmosis. Most experience has been derived from small single center case series, or case report literature reviews. Therefore, a larger study of central nervous system (CNS) histoplasmosis is needed in order to guide the approach to diagnosis, and treatment.

A convenience sample of 77 patients with histoplasmosis infection of the CNS was evaluated. Data was collected that focused on recognition of infection, diagnostic techniques, and outcomes of treatment.

Twenty nine percent of patients were not immunosuppressed. Histoplasma antigen, or anti-Histoplasma antibodies were detected in the …


Rural/Urban Disparities In Pneumococcal Vaccine Service Delivery Among The Fee-For-Service Medicare Population, Jeffery C. Talbert, Aric Schadler, Patricia R. Freeman Feb 2018

Rural/Urban Disparities In Pneumococcal Vaccine Service Delivery Among The Fee-For-Service Medicare Population, Jeffery C. Talbert, Aric Schadler, Patricia R. Freeman

Rural & Underserved Health Research Center Publications

Overview of Key Findings

  • In 2014, the overall mean vaccination rate in urban areas was 4.66 compared to a mean vaccination rate of 2.81 in rural areas, indicating a 40% lower mean vaccination rate in rural communities.
  • The majority of pneumococcal vaccine services delivered to fee-for-service Medicare beneficiaries were provided by primary care providers, although pharmacy providers delivered close to one-fourth (22.2%) of these services.
  • The proportion of pneumococcal vaccine services delivered by pharmacy providers was significantly greater in rural versus urban counties (29.4% vs. 21.1%).
  • Consistent with previous literature, county characteristics positively associated with pneumococcal vaccine service delivery include …


An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi Jan 2018

An Aged Canid With Behavioral Deficits Exhibits Blood And Cerebrospinal Fluid Amyloid Beta Oligomers, Clare Rusbridge, Francisco J. Salguero, Monique Antoinette David, Kiterie M. E. Faller, Jose T. Bras, Rita J. Guerreiro, Angela C. Richard-Londt, Duncan Grainger, Elizabeth Head, Sebastian G. P. Brandner, Brian Summers, John Hardy, Mourad Tayebi

Pharmacology and Nutritional Sciences Faculty Publications

Many of the molecular and pathological features associated with human Alzheimer disease (AD) are mirrored in the naturally occurring age-associated neuropathology in the canine species. In aged dogs with declining learned behavior and memory the severity of cognitive dysfunction parallels the progressive build up and location of Aβ in the brain. The main aim of this work was to study the biological behavior of soluble oligomers isolated from an aged dog with cognitive dysfunction through investigating their interaction with a human cell line and synthetic Aβ peptides. We report that soluble oligomers were specifically detected in the dog's blood and …