Organisms Commons^™

Tailoring The Gut Microbiome Through Diet To Target Short Chain Fatty Acids And Trimethylamine N-Oxide For Heart Failure Prevention, Julia M. Gabel

PANDION: The Osprey Journal of Research and Ideas

The number of people diagnosed with heart failure is on the rise—it’s becoming an epidemic. There are treatment options available for heart failure, but unfortunately there is not a cure. However, most cases of heart failure can be prevented. One mechanism that provides promise for preventing heart failure is the implementation of a heart healthy diet. However, not in the context that most are familiar with. In this case, a heart healthy diet is in reference to the ability of diet to tailor the gut microbiome in order to target specific metabolites that are associated with heart failure. Diet plays …

The Discovery, Characterization, And Engineering Of Autolytic Enzymes As Antimicrobials, Jacob M. Furlon

Dartmouth College Ph.D Dissertations

In an age of rising levels of antibiotic resistance, we are quickly running out of tools to address some of the most virulent and widespread infectious bacteria. One group of enzymes that show significant potential for use as next-generation antibiotics are antimicrobial peptidoglycan hydrolases, often referred to as lysins. These enzymes are responsible for the breakdown of peptidoglycan within the bacterial cell wall, and, when exogenously applied, can result in dramatic destabilization of the cell wall leading to rapid lysis of the bacteria. While phage endolysins have been widely investigated as potential antimicrobials, the therapeutic potential of endogenous autolysins from …

Additive Effects Of Cyclic Peptide [R4w4] When Added Alongside Azithromycin And Rifampicin Against Mycobacterium Avium Infection, Melissa Kelley, Kayvan Sasaninia, Arbi Abnousian, Ali Badaoui, James Owens, Abrianna Beever, Nala Kachour, Rakesh Kumar Tiwari, Vishwanath Venketaraman

Pharmacy Faculty Articles and Research

Mycobacterium avium (M. avium), a type of nontuberculous mycobacteria (NTM), poses a risk for pulmonary infections and disseminated infections in immunocompromised individuals. Conventional treatment consists of a 12-month regimen of the first-line antibiotics rifampicin and azithromycin. However, the treatment duration and low antibiotic tolerability present challenges in the treatment of M. avium infection. Furthermore, the emergence of multidrug-resistant mycobacterium strains prompts a need for novel treatments against M. avium infection. This study aims to test the efficacy of a novel antimicrobial peptide, cyclic [R4W4], alongside the first-line antibiotics azithromycin and rifampicin in reducing M. avium survival. Colony-forming unit (CFU) …

Analyzing Pseudomonas Aeruginosa With Bacteriophage Tags Using Photoacoustic Flow Cytometry, Jennifer C. Schinke

Electronic Theses and Dissertations

The number of daily bacterial infections is climbing and the CDC explains that this is due to the antibiotic-resistant threat in the United States. Finding a faster way of bacterial identification is necessary as it currently takes 1-4 days for a medical lab to culture and identify bacteria. Photoacoustic flow cytometry (PAFC) can be used as an alternative method resulting in swift identification within an hour (Edgar, 2019). Pseudomonas aeruginosa, cell line PA01, will be coated in up to a few hundred red dyed phages making it detectible by the photoacoustic flow cytometry system. Bacteriophages (phages) are viruses that …

Two Structurally Defined Aβ Polymorphs Promote Different Pathological Changes In Susceptible Mice, Ruben Gomez-Gutierrez, Ujjayini Ghosh, Wai-Ming Yau, Nazaret Gamez, Katherine Do, Carlos Kramm, Hamid Shirani, Laura Vegas-Gomez, Jonathan Schulz, Ines Moreno-Gonzalez, Antonia Gutierrez, K Peter R Nilsson, Robert Tycko, Claudio Soto, Rodrigo Morales

Faculty, Staff and Student Publications

Misfolded Aβ is involved in the progression of Alzheimer's disease (AD). However, the role of its polymorphic variants or conformational strains in AD pathogenesis is not fully understood. Here, we study the seeding properties of two structurally defined synthetic misfolded Aβ strains (termed 2F and 3F) using in vitro and in vivo assays. We show that 2F and 3F strains differ in their biochemical properties, including resistance to proteolysis, binding to strain-specific dyes, and in vitro seeding. Injection of these strains into a transgenic mouse model produces different pathological features, namely different rates of aggregation, formation of different plaque types, …

Neurotropic Manifestations As A Potential Risk Factor For Schizophrenia Following In Utero Exposure To Sars-Cov-2, Mir Ali R Talpur, Omar H. Elsayed, Rif S. El-Mallakh

The University of Louisville Journal of Respiratory Infections

Background: COVID-19 infection is associated with neurologic and psychiatric morbidity that suggests a direct effect of the virus or secondary effect of an inflammatory process. These neuropsychiatric consequences may increase the likelihood of schizophrenia in the offspring of women who become infected with COVID-19 during their pregnancy.

Methods: We performed a directed narrative review of the literature focusing on the proposed pathophysiological processes that lead to schizophrenia and known pathological consequences of COVID-19 infection.

Results: Schizophrenia in adult offspring has been associated with maternal infections during pregnancy by a wide range of respiratory and neurotropic pathogens. Spikes in the incidence …

Outpatient Sexually Transmitted Infection Testing And Treatment Patterns In The United States: A Real-World Database Study, Rebecca Lillis, Louis Kuritzky, Zune Huynh, Rodney Arcenas, Avneet Hansra, Roma Shah, Baiyu Yang, Stephanie N. Taylor

School of Medicine Faculty Publications

Background: Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most common notifiable sexually transmitted infections (STIs) in the United States. Because symptoms of these infections often overlap with other urogenital infections, misdiagnosis and incorrect treatment can occur unless appropriate STI diagnostic testing is performed in clinical settings. The objective of this study was to describe STI diagnostic testing and antimicrobial treatment patterns and trends among adolescent and adult men and women with lower genitourinary tract symptoms (LGUTS). Methods: We analyzed insurance claims data from the IBM® MarketScan® Research Databases. Patients included were between 14 and 64 years old with …

Vitamin B2 Enables Regulation Of Fasting Glucose Availability, Peter M Masschelin, Pradip Saha, Scott A Ochsner, Aaron R Cox, Kang Ho Kim, Jessica B Felix, Robert Sharp, Xin Li, Lin Tan, Jun Hyoung Park, Liping Wang, Vasanta Putluri, Philip L Lorenzi, Alli M Nuotio-Antar, Zheng Sun, Benny Abraham Kaipparettu, Nagireddy Putluri, David D Moore, Scott A Summers, Neil J Mckenna, Sean M Hartig

Faculty, Staff and Students Publications

Flavin adenine dinucleotide (FAD) interacts with flavoproteins to mediate oxidation-reduction reactions required for cellular energy demands. Not surprisingly, mutations that alter FAD binding to flavoproteins cause rare inborn errors of metabolism (IEMs) that disrupt liver function and render fasting intolerance, hepatic steatosis, and lipodystrophy. In our study, depleting FAD pools in mice with a vitamin B2-deficient diet (B2D) caused phenotypes associated with organic acidemias and other IEMs, including reduced body weight, hypoglycemia, and fatty liver disease. Integrated discovery approaches revealed B2D tempered fasting activation of target genes for the nuclear receptor PPARα, including those required for gluconeogenesis. We also found …

On The Respiratory Syncytial Virus Vaccine, Forest W. Arnold

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Time Is Ticking For Cervical Cancer, Vijay Kumar, Caitlin Bauer, John H. Stewart

School of Medicine Faculty Publications

Cervical cancer (CC) is a major health problem among reproductive-age females and comprises a leading cause of cancer-related deaths. Human papillomavirus (HPV) is the major risk factor associated with CC incidence. However, lifestyle is also a critical factor in CC pathogenesis. Despite HPV vaccination introduction, the incidence of CC is increasing worldwide. Therefore, it becomes critical to understand the CC tumor immune microenvironment (TIME) to develop immune cell-based vaccination and immunotherapeutic approaches. The current article discusses the immune environment in the normal cervix of adult females and its role in HPV infection. The subsequent sections discuss the alteration of different …

Mirnas Signature As Potential Biomarkers For Cervical Precancerous Lesions In Human Papillomavirus Positive Women, Martha I. González-Ramírez, Yurley T. Cardona, María C. Agudelo, Carolina López, Juan J. Florez-Acosta, Samuel Agudelo-Gamboa, Jone Garai, Li Li, Carlos A. Orozco-Castaño, Jovanny Zabaleta, Gloria I. Sánchez

School of Medicine Faculty Publications

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by …

Elucidating The Impact Of Sos-Response Timing In On Escherichia Coli Survival Following Treatment With Fluoroquinolone Topoisomerase Inhibitors, Stephanie Schofield

Honors Scholar Theses

Antibiotic treatment failure is a public health crisis, with a 2019 report stating that roughly 35,000 deaths occur in the United States yearly due to bacterial infections that are unresponsive to antibiotics (1). One complication in the treatment of bacterial infection is antibiotic persistence which further compromises our battle to effectively treat infection. Bacterial persisters can exist in clonal bacterial cultures and can tolerate antibiotic treatment by undergoing reversible phenotypic changes. They can survive drug concentrations that their genetically identical kin cannot. Some persisters remain in a slow growing state and are difficult to target with current antibiotics. A specific …

Center Based Cardiac Rehabilitation Outcomes Associated With Covid-19 Pandemic: A Retrospective Comparative Cohort Study, Haley Williams, Kayla Woodworth

Doctor of Nursing Practice Projects: College of Nursing

Background: Traditional cardiac rehabilitation (CR) is a multidisciplinary, multifaceted program for cardiac patients. Throughout the Covid-19 pandemic, health care, including center-based CR (CBCR) programs, were closed to in-person sessions. Even with the return to CBCR participation, patient outcomes may have been affected by this disruption in care. The goal of this study was to determine if CR participation outcomes differed before and after CBCR program closure due to Covid-19.

Methods: A retrospective comparative cohort design was used to examine CR participant outcome data before and after the Covid-19 pandemic. Convenience sampling of CR participants at a large, urban …

Echinomycin As A Promising Therapeutic Agent Against Kshv-Related Malignancies, Jungang Chen, Zhen Lin, Jiao Song, Karlie Plaisance-Bonstaff, Jennifer James, Shengyu Mu, Steven R. Post, Lu Dai, Zhiqiang Qin

School of Medicine Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiologic agent of several human cancers, including Kaposi’s sarcoma (KS) and primary effusion lymphoma (PEL), which preferentially arise in immunocompromised patients while lack of effective therapeutic options. Oncoproteins Myc and hypoxia-inducible factor-1α (HIF1α) have been found closely related to KSHV infection, replication and oncogenesis. However, the strategies of dual targeting these two oncoproteins have never been developed and tested for treatments of KSHV-related malignancies. In the current study, we report that treatment of echinomycin dramatically regresses cell growth both in vitro-cultured KSHV + tumor cells and in vivo KS or PEL xenograft mice models, …

An Overview Of Viruses And The Infamous Sars-Cov-2, Jake Sun

The Confluence

Background information on viruses is first presented which include topics like evolution, ecology, history, identification, structure, and application. The novel SARS-CoV-2, which causes COVID-19, pandemic originated in Wuhan, China in December 2019. Millions of people were infected with the virus in a short time period causing urgent concern worldwide. The purpose of this review is to provide a brief and general understanding of the SARS-CoV-2 to increase awareness and actions toward preventive measures. COVID-19 is a (+) ssRNA spherical enveloped virion that causes primarily respiratory illnesses. The S protein interacts with ACE-2 receptors on the host cell to gain entry …

Effect Of Temperature On The Microbiome Of A Laboratory Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna Mitchell

Poster Presentations

Honors research poster.

Haemaphysalis longicornis is a species of tick native to eastern Asia, including eastern China, Japan, eastern Russia, and Korea. To date, it has invaded and has now established its existence in Australia, New Zealand, and several of the Pacific Islands. This species of tick has recently been introduced to the United States, having a confirmed sighting in November 2017 on a sheep farm in New Jersey and since establishing populations in 18 states along the east coast and Appalachia. Based on the existing locations of H. longicornis in its native regions, as well as in the United …

Sexual Dimorphism Of Glomerular Capillary Morphology In Rats, Zackarias Coker

Undergraduate Honors Theses

Chronic kidney disease (CKD) progresses faster in males than females; however, the underlying mechanisms remain poorly understood. Sex differences in glomerular capillary morphology has been hypothesized to contribute, in part, to the increased susceptibility to hypertension-induced renal injury and CKD progression in males, but this has not been investigated. The goal of the present study was to assess glomerular capillary morphology in male vs. female rats with intact kidneys and after uninephrectomy (UNX). We hypothesized that glomerular capillary radii (R_CAP) and length (L_CAP) would be greater in male rats.

Male (n=4) and female (n=4) with intact …

Effect Of Temperature On The Microbiome Of A Laboratory-Reared Colony Of Haemaphysalis Longicornis Ticks, Brianna L. Mitchell

Honors Theses

Haemaphysalis longicornis ticks are invasive to the United States with potential to transmit several tick-borne pathogens that are native to the United States. Based on existing locations of H. longicornis in its native regions in Asia, as well as its invasive populations that are established in the United States, several geographic range prediction models have been produced to help understand future range expansion and distribution of this invasive tick in North America. Unfortunately, these models do not all agree and there is uncertainty associated with the potential geographic range expansion of H. longicornis ticks in North America. Climate can affect …

Identification Of Molecular Markers Associated With Copd In Non-Smokers And Smokers: A Bioinformatics Analysis, Agede O. Ayodele, Isa M. Wasagu, Ademola E. Fawibe, Alakija K. Salami

The University of Louisville Journal of Respiratory Infections

Background

Even though the proportional burden of COPD among never-smokers is significant in both developing and developed nations, accounting for around 30% of all COPD in the community, there is little awareness of the prevalence of COPD in this population. Understanding the molecular processes that underlie COPD in nonsmokers is essential.

Methods

Dataset (GSE146560) was acquired from the Gene Expression Omnibus (GEO). The limma and clusterProfiler software tools were used to identify differentially expressed genes (DEGs) and conduct a functional enrichment analysis respectively.

Results

In all, 10,583 DEGs were found, of which 1,065 were up-regulated and 9,518 were down-regulated. The …

Diagnosis Of Urinary Tract Infections And Rapid Molecular Characterization Of Antibiotic Resistance, Mohammed Harris

All Dissertations

Urinary tract infections (UTIs) are one of the most common infectious clinical entities in both community and hospital settings. They have a broad range of clinical severity yet inflict large epidemiological burden of morbidity and mortality on patients and the healthcare system with billions of dollars in cost of treatment. Understanding what methods are optimal for diagnosing UTIs are critical to mitigate the marked impact and cost of these infections.

Chapter 1 and 2 in this work surveys the broad array of diagnostic modalities for UTIs and highlights their advantages and limitations in the context of the current standard of …

The Characterization Of The Sars-Cov-2 Receptor Binding Domain Interaction With The Human Ace2 Receptor And Potential Small Molecule Inhibitors, Camryn Carter

Honors Theses

In December 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV-2), was identified in Wuhan, China after numerous patients experienced pneumonia symptoms, but existing medicinal treatments were ineffective.1 The global spread of the SARS-CoV-2 virus caused an outbreak of the infectious disease, coronavirus disease 2019 (COVID-19), which was soon after declared a pandemic by the World Health Organization, referred to as the COVID-19 pandemic. According to John Hopkins University, over 1,000,000 people have died from SARS-CoV-2 infection and about 104,000,000 cases have been confirmed in the United States (US). An infection of the SARS-CoV-2 virus is caused by the …

Exploring The Possible Phenomenon Of Viral Interference Between The Novel Coronavirus And Common Respiratory Viruses, Spencer Deleveaux, Alexandria Clarke-Kregor, Xavier Fonseca-Fuentes, Essam Mekhaiel

Journal of Patient-Centered Research and Reviews

At the peak of the 2021 wave of the SARS-CoV-2 alpha variant in North America, there was concern for a superimposed wave of viral respiratory infections. There was, however, an apparent shift in the usual epidemiology of these pathogens, especially during the traditional influenza season from approximately October 2020 to March 2021. This article seeks to briefly describe the epidemiology of notable respiratory pathogens during the first wave of the COVID-19 pandemic and to focus on one possible factor for the trends observed. There are many contributory elements to the observed viral trends, but in particular, we present a synopsis …

Independent Effects Of Hiv And Antiretroviral Therapy On The Oral Microbiome Identified By Multivariate Analyses, Clifford J. Beall, Elizabeth A. Lilly, Carolina Granada, Kelly Treas, Kenneth R. Dubois, Shahr B. Hashmi, Jose A. Vazquez, Michael E. Hagensee, Ann L. Griffen, Eugene J. Leys, Paul L. Fidel

School of Dentistry Faculty Publications

The oral microbiome is an important predictor of health and disease. We recently reported significant yet modest effects of HIV under highly active antiretroviral therapy (ART) on the oral microbiome (bacterial and fungal) in a large cohort of HIV-positive (HIV+) and matched HIV-negative (HIV-) individuals. As it was unclear whether ART added to or masked further effects of HIV on the oral microbiome, the present study aimed to analyze the effects of HIV and ART independently, which also included HIV- subjects on preexposure prophylaxis (PrEP) therapy. Cross-sectional analyses of the effect of HIV devoid of ART (HIV+ ART- versus matched …

Investigating The Antibacterial And Immunomodulatory Properties Of Lactobacillus Acidophilus Postbiotics, Rachael M. Wilson

Graduate School of Biomedical Sciences Theses and Dissertations

Probiotics are nonpathogenic microorganisms that have been extensively studied for their ability to prevent various infectious, gastrointestinal, and autoimmune diseases. The mechanisms underlying these probiotic effects have not been elucidated. However, we and other researchers have evidence suggesting that probiotic bacteria secrete metabolites that are antimicrobial and anti-inflammatory. As such, we developed a methodology to collect the secreted metabolites from a probiotic bacterium, Lactobacillus acidophilus, and tested this cell free filtrate (CFF) both in vitro and in vivo. Using this CFF, we have demonstrated that L. acidophilus secretes a molecule(s) that has specific bactericidal activity against the opportunistic pathogen, Pseudomonas …

Topical Anesthetic Gel Interferes With Antibacterial Efficacy Of Povidone-Iodine Both In Vitro And In Vivo, Cecilly Kelleher Bs, Jacob Im Md, Linda Kang Bs, Aleksey Mishulin Md, Sukhvinder Singh Phd, Ashok Kumar Phd

Medical Student Research Symposium

Purpose: To evaluate the effects of viscous lidocaine gel on the antimicrobial efficacy of povidone-iodine (PI) and their order of application in both in vitro and in vivo models.

Methods: In vitro antibacterial effects were tested against Staphylococcus aureus (S. aureus) with disc diffusion methods for application of lidocaine alone, PI alone, PI before lidocaine, and lidocaine before PI. Zones of inhibition were measured after incubation at 37°C overnight. Mouse eyes were colonized with S. aureus for in vivo study to which PI and/or lidocaine were applied in various combinations. Eyes were then rinsed with saline, and …

Longitudinal Ultrasound Imaging And Network Modeling In Rats Reveal Sex-Dependent Suppression Of Liver Regeneration After Resection In Alcoholic Liver Disease, Benjamin K. Barnhart, Toshiki Kan, Ankita Srivastava, Corinne E. Wessner, John Waters, Manju Ambelil, John R. Eisenbrey, Jan B. Hoek, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Liver resection is an important surgical technique in the treatment of cancers and transplantation. We used ultrasound imaging to study the dynamics of liver regeneration following two-thirds partial hepatectomy (PHx) in male and female rats fed via Lieber-deCarli liquid diet protocol of ethanol or isocaloric control or chow for 5–7 weeks. Ethanol-fed male rats did not recover liver volume to the pre-surgery levels over the course of 2 weeks after surgery. By contrast, ethanol-fed female rats as well as controls of both sexes showed normal volume recovery. Contrary to expectations, transient increases in both portal and hepatic artery blood flow …

Performance Of A Sars-Cov-2 Rt-Pcr Assay With Non-Traditional Specimen Types, Subathra Marimuthu, Holly Aliesky, Heather Ness, Daniya Sheikh, Sathya Rashmit, Dawn Balcom, Leslie A. Wolf

The University of Louisville Journal of Respiratory Infections

During the first two years of the coronavirus disease 2019 (COVID-19) pandemic, nasopharyngeal (NP) specimens were the gold standard for clinical diagnostic testing. As information about the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the pandemic continued to be shared, it was clear that the virus could be detected in other specimen types during an active infection. The University of Louisville Infectious Diseases Laboratory accepted non-traditional specimen types, most without a paired, positive NP result, for research purposes only to support local epidemiology efforts. A real-time reverse transcription-polymerase chain reaction (RT-PCR) assay originally validated for NP specimens was used …

What? Now A Respiratory Syncytial Virus Epidemic, Aya Allam, Steven B Lippmann

The University of Louisville Journal of Respiratory Infections

No abstract provided.

Endogenous Mirna-Based Innate-Immunity Against Sars-Cov-2 Invasion Of The Brain, Walter J. Lukiw, Aileen I. Pogue

School of Medicine Faculty Publications

The severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19, possesses an unusually large positive-sense, single-stranded viral RNA (ssvRNA) genome of about ~29,903 nucleotides (nt). In many respects, this ssvRNA resembles a very large, polycistronic messenger RNA (mRNA) possessing a 5′-methyl cap (m7GpppN), a 3′- and 5′-untranslated region (3′-UTR, 5′-UTR), and a poly-adenylated (poly-A+) tail. As such, the SARS-CoV-2 ssvRNA is susceptible to targeting by small non-coding RNA (sncRNA) and/or microRNA (miRNA), as well as neutralization and/or inhibition of its infectivity via the human body’s natural complement of about ~2650 miRNA species. Depending on host cell and tissue …

Subacute Cutaneous Lupus Erythematosus After Mrna-Based Sars-Cov-2 Vaccination, Sarah Rimmer, Long Ly, Erin Boh

School of Medicine Faculty Publications

No abstract provided.