Organisms Commons^™

Formulation Development Of Dual-Compartment Topical Inserts Combining Tenofovir Alafenamide And Elvitegravir For Flexible On-Demand Hiv Prevention, Vivek Agrahari, M. Melissa Peet, Neelima Chandra, Prakash Ramalingam, Pardeep K. Gupta, Sriramakamal Jonnalagadda, Onkar N. Singh, Timothy J. Mccormick, Gustavo F. Doncel, Meredith R. Clark

Department of Obstetrics & Gynecology Faculty Publications

Pre-exposure prophylaxis (PrEP) has emerged as a prominent approach for the prevention of HIV infections. While the latest advances have resulted in effective oral and injectable product options, there are still gaps in on-demand, event-driven, topical products for HIV prevention that are safe and effective. Here we describe the formulation development of a dual-compartment topical insert containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) that may be administered when needed, vaginally or rectally, pre- or post-coitus, for flexible HIV prophylaxis. Specifically, we describe the lab-scale formulation development, preclinical mucosal safety and pharmacokinetics (PK) testing in rabbits, long-term stability, and scale-up …

Chronic Administration Of A Cannabis-Derived Mixture At An Antihyperalgesic Dose Does Not Significantly Enhance Hepatotoxicity Or The Development Of Metabolic Dysfunction-Associated Steatohepatitis In Male Mice, Kim B. Pedersen, Tomislav Jelesijevic, Tamara M. Morris, Sarah M. Melton, Ashley S. Henderson, John F. Glenn, Gregory J. Davenport, Martin J.J. Ronis, Peter J. Winsauer

School of Medicine Faculty Publications

Cannabis and cannabinoid mixtures have been linked to a variety of health benefits including pain mitigation, suppression of nausea produced by chemotherapeutic agents, anti-inflammatory effects, and effects on energy homeostasis, glucose, and lipid metabolism. The latter properties have led to the suggestion that these products could have therapeutic effects on the development of metabolic dysfunction-associated steatohepatitis (MASH) - a severe type of liver pathology in obese and diabetic patients. However, varying agonist and antagonistic properties of different cannabinoids on the endogenous cannabinoid system make prediction regarding hepatic effects and diet interactions difficult. The current study was designed to examine hepatic …

The Ptp4a3 Inhibitor Kvx-053 Reduces Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Virulence, Inflammation, And Development Of Acute Lung Injury In K18-Hace2 Mice, Ruben M. L. Colunga-Biancatelli, Pavel A. Solopov, Caitlin M. Woodson, Irving Coy Allen, Ivan Akhrymuk, Maryna Akhrymuk, Brittany N. Heath, Hannah M. Ivester, Tierney Day, Dan E. Austin, Kylene Kehn-Hall, John S. Lazo, Elizabeth R. Sharlow, John D. Catravas

Bioelectrics Publications

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a global health crisis, marked by high transmissibility and virulence. Despite widespread vaccination efforts, effective treatments for COVID-19, particularly for severe cases leading to Acute Respiratory Distress Syndrome (ARDS), remain limited. This study investigates the efficacy of KVX-053, a protein tyrosine phosphatase type IVA (PTP4A3) small molecule inhibitor, in modulating SARS-CoV-2-induced inflammation and lung injury using in vitro cell models and in vivo K18-hACE2 transgenic mice. KVX-053 reduced in vitro pro-inflammatory cytokine expression, including TNFα, CXCL10, and CXCL11, without impacting viral replication or cell viability. K18-hACE2 mice treated with KVX-053 demonstrated …

Identification Of Benzothiophene-Derived Inhibitors Of Flaviviruses By Targeting Rna-Dependent Rna Polymerase, Leah Liu Wang, Shazeed-Ul Karim, Aidan Hand, Ryan Brunkhorst, Mackenna Petersen, Sarah Altam, Yi Liu, Luwen Zhang, Fengwei Bai, Shi-Hua Xiang

School of Biological Sciences: Faculty Publications

Flaviviruses such as Dengue, West Nile, and Zika viruses are mosquito-borne RNA viruses that can cause serious diseases in humans. To develop effective drugs for treating these viruses’ infections, we create a new approach for developing common or shared drugs that may work for several different viral species of flaviviruses. It is based on the conserved RNA-dependent RNA polymerase (RdRp), which is the key enzyme for viral replication. We built up a common structure of RdRps (POLcon) from their consensus sequence. A conserved Triple-D structural motif was identified at the active site of POLcon that has been used for virtual …

A Case Displaying The Importance Of Jak1 And Jak2 Gene Transcription In Antifungal Defense Against Coccidioidomycosis, Jennifer K. Priessnitz, Taylor Colore, Nelson Nicolasora

Department of Medicine Faculty Publications

This case report explores the consequences of ruxolitinib via inhibition janus kinase 1 (JAK1) and JAK2 pathways in the context of fungal defense in a patient diagnosed with pulmonary coccidioidomycosis during ruxolitinib therapy for polycythemia vera. The patient experienced a relapse of pulmonary coccidioidomycosis after antifungal treatment was discontinued while continuing ruxolitinib use. This case illustrates the heightened risk of discontinuing antifungal therapy in endemic regions, emphasizing the critical need for continued monitoring. Furthermore, this case underscores the vital role of the JAK1 and JAK2 signaling cascade, particularly the interferon-gamma (INF-γ)-JAK1 and JAK2-signal transducer and activator of transcription 1 (STAT) …

Blood Culture Utilization: How Many Follow-Up Cultures Are Needed?, George Jones, Jennifer Hanrahan

Department of Medicine Faculty Publications

Background: Follow-up blood cultures (BCx) are ordered after an initial positive culture in many instances. The number of follow-up cultures needed is not clear. Obtaining unnecessary BCx may cause unintended consequences. The optimal balance between stewardship and patient safety warrants investigation. We sought to assess the frequency with which a third set is positive after a negative second BCx. Methods: We conducted a retrospective study of BCx submitted to the microbiology laboratory from 1/1/18-11/1/23. We included all patients ≥18 years who had at least two follow-up BCx drawn 24-72 hours after an initial positive culture. Data were collected from electronic …

Zika Virus Modulates Arthropod Histone Methylation For Its Survival In Mosquito Cells, Telvin Harrell

Biological Sciences Faculty Publications

Zika virus (ZIKV) is a mosquito-borne human pathogen that causes mild febrile illness in adults and severe neurological complications and microcephaly in newborns. Studies have reported that ZIKV modulates methylation of human and viral RNA critical for its replication in vertebrate cells. In this study, we show that ZIKV modulates mosquito S-adenosyl methionine (SAMe)-synthase, an enzyme involved in the production of SAMe (methyl donor), and histone methylation for its survival in mosquito cells. Reverse transcription quantitative PCR followed by immunoblotting analysis showed increased amounts of SAMe synthase at both RNA and protein levels, respectively, in C6/36 mosquito cells infected with …

Development Of A Streptococcus Mutans Biofilm Model On A Typodont Platform To Investigate Its Dynamics In Orthodontics, Hibah Chughtai

Theses & Dissertations

Introduction: Biofilm formation plays a significant role in dental health, resulting in plaque accumulation, which can lead to caries and oral diseases. Streptococcus mutans (S. mutans) is a key bacterium involved in this process. The goal of this study was to establish a protocol for the development of an S. mutans biofilm on dental typodont teeth to analyze the effects of orthodontic brackets on biofilm formation. Understanding these dynamics is critical for developing strategies to mitigate biofilm accumulation during orthodontic treatment. Methods: S. mutans biofilms were cultivated under three conditions: 96-well tissue culture plates, S. mutans inoculated non-bracketed …

Design, Synthesis, And Nmr-Guided Characterization Of A Targeted Covalent Inhibitor-Like Molecule Against Ivyp1 From P. Aeruginosa, Samuel Taylor Moore

Master's Theses

Multi-drug resistance poses a serious threat to future generations and historical antibiotic pipelines; consequently, the medical and economic burdens associated with treating multidrug-resistant bacteria are substantiated. In this context, P. aeruginosa (PA) emerges as one of the most significant healthcare challenges, being a leading cause of resistance-associated mortality worldwide. Despite modern efforts to combat these poor outcomes, drug-resistant cases continue to rise, and the need for novel antibiotic treatment is apparent. To this end, we investigated relevant resistance mechanisms and past antibiotic targets within PA, and in doing so, we identified relationships between peptidoglycan biology and a periplasmic protein, Inhibitor …

Impact Of Pathogenic E. Coli In Drinking Water On The Well-Being Of Children, Aysha Khatoon

CBER Conference

Despite global advancements, unsafe drinking water is a major cause of illness, ranked as the eighth highest worldwide (Forouzanfar et al., 2015). Studies indicate that even improved water sources, can harbour faecal contamination (Shaheed et al., 2014; Bain et al., 2014b). Globally, 1.8 billion people rely on drinking water contaminated with faecal matter (Bain et al., 2014a), with pathogenic E. coli being a primary concern. In Pakistan, the situation is dire. About 25 million people, particularly children, suffer due to open defecation, leading to 53,000 child deaths annually from diarrhoea (UNICEF, 2021). Pathogenic E. coli is a significant contributor to …

Proteolytic Manipulation Of Neutrophil Responses And The Efferocytic Synapse By Porphyromonas Gingivalis., Kelley N. Cooper

Electronic Theses and Dissertations

Porphyromonas gingivalis (Pg) is etiologically associated with chronic periodontitis, a highly prevalent chronic inflammatory disease characterized by the destruction of hard and soft tissues of the periodontium. Pg is adapted to live in the human oral subgingival niche, a hostile environment dominated by excessive numbers of activated neutrophils and antimicrobial mediators. Its survival is contingent upon prompt and effective inactivation of neutrophil effector functions. In this dissertation, I uncover a novel pathogenic mechanism employed by Pg that disarms the antimicrobial capacity of live neutrophils and simultaneously sequesters them within macrophages. Mechanistically, RgpB, a cysteine protease produced by Pg …

Investigation Of Reproductive Inhibition During Chronic Heat Stress In C. Elegans, Macy Makenna Nielander

Theses and Dissertations

Nearly all organisms experience heterogeneity in environmental conditions that can negatively impact fitness. A common adaptive strategy to reduce the impact of this stress is called facultative diapause, where development and reproduction are temporarily arrested to promote survival. Facultative diapause is characterized by three major criteria, the arrest must be (i) induced by an unfavorable environmental condition, (ii) reversible, and (iii) driven by genetically regulated mechanisms. The aim of this thesis was to determine whether chronic heat-induced inhibition of egg laying in Caenorhabditis elegans represents a novel form of facultative diapause. It was found that the inhibition of egg-laying is …

An Assessment Of The Impact Of Fentanyl On Post-Mortem Interval From A Decomposition And Biochemical Perspective, Kaylene Mcdonald

Senior Honors Theses

In the realm of body decomposition, bodies undergo a plethora of different metabolic and chemical changes. The human body follows a very consistent pattern and predictable time frame, with the exclusion of extenuating circumstances. The presence of fentanyl at the time of death provides the possibility of changes in decomposition rates, potentially skewing the time of death estimations. This research analyzes the varying decompositional stages of a body and their subsequent close relations with activity in the environment around it, specifically investigating the impacts of fentanyl on those surroundings and postmortem interval estimation determinations. This research found evidence that fentanyl …

Enhancing Immune Response And Survival In Hepatocellular Carcinoma With Novel Oncolytic Jurona Virus And Immune Checkpoint Blockade, Mulu Z. Tesfay, Yuguo Zhang, Khandoker U. Ferdous, Mika A. Taylor, Aleksandra Cios, Randal S. Shelton, Camila C. Simoes, Chelsae R. Watters, Oumar Barro, Natalie M. Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L. Graham, Charity L. Washam, Duah Alkam, Allen Gies, Stephanie D. Byrum, Emmanouil Giorgakis, Steven R. Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y. Chabu, Martin E. Fernandez-Zapico, Dan G. Duda, Lewis R. Roberts, Rang Govindarajan, Mitesh J. Borad, Martin J. Cannon, Et Al

School of Medicine Faculty Publications

Members of the Vesiculovirus genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model. Proteogenomic analysis of JURV-treated, murine HCC tumors demonstrates that the therapeutic effects of the combination of JURV and anti-PD-1 are predominantly driven by …

Enhancing Immune Response And Survival In Hepatocellular Carcinoma With Novel Oncolytic Jurona Virus And Immune Checkpoint Blockade, Mulu Z. Tesfay, Yuguo Zhang, Khandoker U. Ferdous, Mika A. Taylor, Aleksandra Cios, Randal S. Shelton, Camila C. Simoes, Chelsae R. Watters, Oumar Barro, Natalie M. Elliott, Bahaa Mustafa, Jean Christopher Chamcheu, Alicia L. Graham, Charity L. Washam, Duah Alkam, Allen Gies, Stephanie D. Byrum, Emmanouil Giorgakis, Steven R. Post, Thomas Kelly, Jun Ying, Omeed Moaven, Chiswili Y. Chabu, Martin E. Fernandez-Zapico, Dan G. Duda, Lewis R. Roberts, Rang Govindarajan, Mitesh J. Borad, Martin J. Cannon, Et Al

School of Graduate Studies Faculty Publications

Members of the Vesiculovirus genus including Jurona virus (JURV) have emerged as promising immunotherapeutic agents, characterized by their tumor selectivity, fast kinetics, low seroprevalence, and minimal toxicity in humans. Here, we demonstrate that the administration of JURV leads to tumor regression in both hepatocellular carcinoma (HCC) xenograft and syngeneic models. Furthermore, our findings indicate that combining JURV and anti-PD-1 therapy reduced tumor burden and improved survival rates over JURV or anti-PD-1 alone in an orthotopic HCC model. Proteogenomic analysis of JURV-treated, murine HCC tumors demonstrates that the therapeutic effects of the combination of JURV and anti-PD-1 are predominantly driven by …

Improving Treatment Outcomes For Bacterial Vaginosis By Affecting The Vaginal Microbiome, Aleya Devries, Jyotsna Chawla Assistant Professor, Microbiology, Jackeline Moljo Assistant Professor, Family Medicine

HCA-NSU MD Research Day

Objective: The goal of this review is to educate providers about the importance of maintaining the balance of the vaginal microbiome (VMB) and how modifiable factors may be used to improve treatment outcomes of patients with bacterial vaginosis. Background: Bacterial vaginosis (BV) is the most common vaginal infection in women of reproductive age and is treated with Metronidazole, which has a high recurrent infection rate. Preliminary studies highlighted the balance of VMB species affects the development of BV and therapeutic outcomes of Metronidazole. Furthermore, previous studies have described how VMB composition can be shaped by various factors. Methods: Here, we …

Flexor Tenosynovitis Of The Wrist And Hand Due To Non-Tuberculous Mycobacteria, Mariafe Reyes, Tatevik Malisetyan, Skylar Harmon, Mohammadali M. Shoja Md, Gary B. Schwartz Md

HCA-NSU MD Research Day

Title: Flexor Tenosynovitis of the Wrist and Hand Due to Non-tuberculous Mycobacteria Authors: Mariafe Reyes1,Tatevik Malisetyan1, Skylar Harmon1, Mohammadali M. Shoja, MD1 Gary B. Schwartz, MD1 1Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, USA INTRODUCTION: Non-tuberculous mycobacteria (NTM) are a group of bacteria, including Mycobacterium marinum, Mycobacterium kansasii, and Mycobacterium avium intracellulare (MAI), that usually exist in the soil and water sources. The most common site of infection is the lungs, but extra-pulmonary involvement of the skin and rarely the musculoskeletal (MSK) system does occur, especially the hands and wrists. CASE PRESENTATION: A 45-year-old, …

Viral Genome Delivery Across Bacterial Cell Surfaces, Stephano M. Iglesias, Fenglin Li, Federica Briani, Gino Cingolani

Department of Biochemistry and Molecular Biology Faculty Papers

In 1952, Hershey and Chase used bacteriophage T2 genome delivery inside Escherichia coli to demonstrate that DNA, not protein, is the genetic material. Over 70 years later, our understanding of bacteriophage structure has grown dramatically, mainly thanks to the cryogenic electron microscopy revolution. In stark contrast, phage genome delivery in prokaryotes remains poorly understood, mainly due to the inherent challenge of studying such a transient and complex process. Here, we review the current literature on viral genome delivery across bacterial cell surfaces. We focus on icosahedral bacterial viruses that we arbitrarily sort into three groups based on the presence and …

Lupin Root Diseases - Diagnosis And Management, Department Of Primary Industries And Regional Development, Western Australia

Grains and other field crops factsheets

Root, hypocotyl and stem base diseases can be significant problems in lupin crops, reducing stand density, plant vigour and yield. Root disease is present in nearly all narrow leafed lupin (Lupinus angustifolius) paddocks but in the majority of paddocks has only a small impact on crop development. However, in paddocks where high levels of root rot occurs, plant establishment, seedling vigour and crop yield can be significantly affected.

When a root disease is present in a crop very little can be done to manage it in that cropping season. It is therefore vital that the cause is correctly identified to …

Editorial: Predicting, Managing, And Minimizing Mycotoxicosis In Farm Animals, Jesus Adonai Maguey-Gonzalez, Juan D. Latorre, Sergio Gomez-Rosales, Abraham Mendez-Albores

Poultry Science Faculty Publications and Presentations

Editorial on the Research Topic: Predicting, managing, and minimizing mycotoxicosis in farm animals