Digital Commons Network^™

Targeting Sars-Cov-2 Nonstructural Protein 3: Function, Structure, Inhibition, And Perspective In Drug Discovery, Xin Li, Yongcheng Song

Faculty, Staff and Students Publications

As a highly contagious human pathogen, severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has infected billions of people worldwide with more than 6 million deaths. With several effective vaccines and antiviral drugs now available, the SARS-CoV-2 pandemic been brought under control. However, a new pathogenic coronavirus could emerge in the future, given the zoonotic nature of this virus. Natural evolution and drug-induced mutations of SARS-CoV-2 also require continued efforts for new anti-coronavirus drugs. Nonstructural protein (nsp) 3 of CoVs is a large, multifunctional protein, containing a papain-like protease (PLpro) and a macrodomain (Mac1), which are essential for viral replication. Here, we …

Protein Subunit Vaccines: Promising Frontiers Against Covid-19, Vivek P. Chavda, Eswara Naga Hanuma Kumar Ghali, Pankti C. Balar, Subhash Chauhan, Nikita Tiwari, Somanshi Shukla, Mansi Athalye, Vandana Bharat Patravale, Vasso Apostolopoulos, Murali Yallapu

School of Medicine Publications

The emergence of COVID-19 has posed an unprecedented global health crisis, challenging the healthcare systems worldwide. Amidst the rapid development of several vaccine formulations, protein subunit vaccines have emerged as a promising approach. This article provides an in-depth evaluation of the role of protein subunit vaccines in the management of COVID-19. Leveraging viral protein fragments, particularly the spike protein from SARS-CoV-2, these vaccines elicit a targeted immune response without the risk of inducing disease. Notably, the robust safety profile of protein subunit vaccines makes them a compelling candidate in the management of COVID-19. Various innovative approaches, including reverse vaccinology, virus …

Pseudoviruses, A Safer Toolbox For Vaccine Development Against Enveloped Viruses, Syamala R Thimmiraju, Jason T Kimata, Jeroen Pollet

Faculty, Staff and Students Publications

Introduction: Pseudoviruses are recombinant, replication-incompetent, viral particles designed to mimic the surface characteristics of native enveloped viruses. They are a safer, and cost-effective research alternative to live viruses. With the potential emergence of the next major infectious disease, more vaccine scientists must become familiar with the pseudovirus platform as a vaccine development tool to mitigate future outbreaks.

Areas covered: This review aims at vaccine developers to provide a basic understanding of pseudoviruses, list their production methods, and discuss their utility to assess vaccine efficacy against enveloped viral pathogens. We further illustrate their usefulness as wet-lab simulators for emerging mutant variants, …

Correlates Of Transactional Sex Among Black Men And Women Who Misuse Opioids, Shemeka Thorpe, Paige Orphé, Gabriella Pitcher, Kendall Mccleod, Natalie Malone, Danelle Stevens-Watkins

Kinesiology and Health Promotion Faculty Publications

The rise in opioid misuse coincides with increased sexually transmitted infection (STI) and HIV incidence. Transactional sex is an under-researched phenomenon among Black Americans who misuse opioids, and may increase their risk of STI or HIV transmission. Given the disproportionate impact of the opioid epidemic on Black Americans and the risks associated with opioid misuse, the current study aims to investigate sociostructural factors, history of violence, and sexual risk factors associated with transactional sex among Black men and women. A sample of n = 375 Black adult Kentuckians reporting opioid misuse completed a survey including transactional sex, sociostructural, violence history, …

How Individuals’ Opinions Influence Society’S Resistance To Epidemics: An Agent-Based Model Approach, Geonsik Yu, Michael J. Garee, Mario Ventresca, Yuehwern Yih

Faculty Publications

Background: Protecting public health from infectious diseases often relies on the cooperation of citizens, especially when self-care interventions are the only viable tools for disease mitigation. Accordingly, social aspects related to public opinion have been studied in the context of the recent COVID-19 pandemic. However, a comprehensive understanding of the effects of opinion-related factors on disease spread still requires further exploration. Methods: We propose an agent-based simulation framework incorporating opinion dynamics within an epidemic model based on the assumption that mass media channels play a leading role in opinion dynamics. The model simulates how opinions about preventive interventions change over …

Advances In The Clinical Application Of High-Throughput Proteomics, Miao Cui, Fei Deng, Mary L Disis, Chao Cheng, Lanjing Zhang

Faculty, Staff and Students Publications

High-throughput proteomics has become an exciting field and a potential frontier of modern medicine since the early 2000s. While significant progress has been made in the technical aspects of the field, translating proteomics to clinical applications has been challenging. This review summarizes recent advances in clinical applications of high-throughput proteomics and discusses the associated challenges, advantages, and future directions. We focus on research progress and clinical applications of high-throughput proteomics in breast cancer, bladder cancer, laryngeal squamous cell carcinoma, gastric cancer, colorectal cancer, and coronavirus disease 2019. The future application of high-throughput proteomics will face challenges such as varying protein …

Changes In Psychiatric Diagnosis Associated With Sars-Cov-2 Infection And Predicting The Development Of New Psychiatric Illness In Covid Patients By Using Machine Learning Approach: A Study Using The Us National Covid Cohort Collaborative (N3c), Asif Rahman

Graduate Theses, Dissertations, and Problem Reports (ETD)

The enduring impact of COVID-19 extends beyond acute illness, with potential long-term psychiatric consequences raising significant concern among healthcare professionals and researchers alike. Emerging evidence suggests a multifaceted relationship between COVID-19 and the development of different psychiatric illnesses like Schizophrenia Spectrum and Psychotic Disorders (SSPD), Depression, Bipolar disorder, Personality disorder, Trauma, and a range of other mental health conditions. Considering these emerging connections, our study endeavors to rigorously assess the associations between COVID-19 and various psychiatric illnesses while simultaneously employing machine learning techniques to predict the development of new psychiatric disorders in individuals affected by the virus. Leveraging the extensive …

Autophagy Determines Distinct Cell Fates In Human Amnion And Chorion Cells, Mary Elise L Severino, Lauren Richardson, Ananth Kumar Kammala, Enkhtuya Radnaa, Kamil Khanipov, Leslie Michelle M Dalmacio, Indira U Mysorekar, Marian Kacerovsky, Ramkumar Menon

Faculty, Staff and Students Publications

Human fetal membranes (amniochorion) that line the intrauterine cavity consist of two distinct cell layers; single-layer amnion epithelial cells (AEC) and multilayer chorion trophoblast cells (CTC). These layers are connected through a collagen-rich extracellular matrix. Cellular remodeling helps support membrane growth and integrity during gestation and helps to maintain pregnancy. Preterm prelabor rupture of the human amniochorionic (fetal) membrane (pPROM) is antecedent to 40% of all spontaneous preterm birth. Oxidative stress (OS) induced activation of the p38 MAPK due to various maternal risk exposures and the amniochorion cells' senescence are reported pathological features of pPROM. Our transcriptomics analysis implicated dysregulated …

Hospital Surge Capacity In Co-Occurring Mass Casualty Incidents, Carolyn Solimine

Electronic Theses & Dissertations (2024 - present)

The COVID-19 pandemic has brought sweeping disruption and changes across healthcare systems. Examining how these changes have impacted surge capacity and capabilities is necessary to plan for future co-occurring surge-creating events in hospital Emergency Departments (EDs) and Intensive Care Units (ICUs). While there is extensive research on patient surge management, no study has looked at how the presence of a prolonged surge would impact the healthcare system’s ability to handle a concurrent acute patient surge. This study seeks to demonstrate the need for comprehensive planning for co-occurring patient surges in New York State using hospital capacity data from Health and …

Ribosome Hibernation Factor Induces Antibiotic Persisters Of Mycobacterium Tuberculosis In Neutrophil-Rich Lung Lesions, Jamie Corro

Electronic Theses & Dissertations (2024 - present)

Mycobacterium tuberculosis (Mtb), the etiological agent of tuberculosis, is a prescient global health threat and the leading cause of death by an infectious agent. Treatment of Mtb infection involves administering 2-4 antibiotics for a minimum of 6 months. This extended drug regimen is required to target a subpopulation of persistent bacilli. As their name implies, these bacteria can “persist” by acquiring nonhereditary and transient antibiotic tolerance. Although the precise mechanism is unknown, it’s often attributed to slowing cellular growth and metabolic processes. During zinc deprivation, bacteria can remodel their ribosomes by replacing their zinc-binding paralogues containing the CXXC motif (C+) …

Polygenic Scores And Mendelian Randomization Identify Plasma Proteins Causally Implicated In Alzheimer’S Disease, Davis B Cammann, Yimei Lu, Jerome I Rotter, Alexis C Wood, Jingchun Chen

Faculty, Staff and Students Publications

BACKGROUND: An increasing body of evidence suggests that neuroinflammation is one of the key drivers of late-onset Alzheimer's disease (LOAD) pathology. Due to the increased permeability of the blood-brain barrier (BBB) in older adults, peripheral plasma proteins can infiltrate the central nervous system (CNS) and drive neuroinflammation through interactions with neurons and glial cells. Because these inflammatory factors are heritable, a greater understanding of their genetic relationship with LOAD could identify new biomarkers that contribute to LOAD pathology or offer protection against it.

METHODS: We used a genome-wide association study (GWAS) of 90 different plasma proteins (

RESULTS: We identified …

High-Risk Individuals And Naloxone Use: Implications For Thn Programs In Rural Appalachian Communities, Victor Garcia, Lisa Mccann, Erick Lauber, Christian Vaccaro, Melissa Swauger, Alex Daniel Heckert

Journal of Appalachian Health

Introduction: Take-home naloxone (THN) is being made available across rural Appalachia to curb opioid overdose fatalities. Despite this initiative, some opioid users do not possess naloxone, and if they do, do not administer it to others.

Purpose: Research findings on risk factors that contribute to opioid overdose are presented. These factors, identified in a sample of 16 overdose cases, are (1) early onset age of opioid use; (2) progressive opioid use; (3) a transition from pain medication to heroin and fentanyl; (4) fears of being arrested at a naloxone intervention if first responders are contacted, and (5) limited knowledge of …

Spatial Analysis Of The Distribution Of Covid-19 Vulnerable Groups To Covid-19 Cases In Brebes Regency, Fatimatuzzahro Fatimatuzzahro, Rara Warih Gayatri

Preventia: The Indonesian Journal of Public Health

The number of COVID-19 cases in Brebes Regency within a year is still quite high. The elderly, Hypertension and Diabetes Mellitus are the most important COVID-19 vulnerable groups and have the highest risk of death. The purpose of this study is to determine the distribution of COVID-19 vulnerable groups and their spatial relationship to COVID-19 cases in Brebes Regency. This study used a correlation or ecology study design. The data used is secondary data obtained from the Brebes Regency Health Office, namely the number of COVID-19 cases, the number of elderly, people with hypertension and diabetes mellitus in 2021. The …

Systematic Review Of The Relationship Between Hygiene Practice And The Incidence Of Ascaris Lumbricoides Infection In Southeast Asian Children, Anastasia Rouli Alodia, Ririn Arminsih Wulandari

Preventia: The Indonesian Journal of Public Health

Soil-Transmitted Helminth (STH) infection is one of the Neglected Tropical Diseases (NTDs) that affects around 1.5 billion people worldwide, including regions like Southeast Asia. The most common species infecting humans is Ascaris lumbricoides. Preschool-age and school-age children are particularly vulnerable to STH infection due to their living environments in areas where STH is prevalent. Infection of STH, especially Ascaris lumbricoides, can hinder physical and cognitive development and, in severe cases, cause obstruction of the small intestine. Various factors, such as hygiene practices, can influence the transmission of Ascaris lumbricoides infection in children. This study aims to explore the association between …

Parents' Stigmatizing Beliefs About The Hpv Vaccine And Their Association With Information Seeking Behavior And Vaccination Communication Behaviors, Ashley Hedrick Mckenzie, Ross Shegog, Lara S Savas, C Mary Healy, L Aubree Shay, Sharice Preston, Sharon Coan, Travis Teague, Erica Frost, Stanley W Spinner, Sally W Vernon

Faculty, Staff and Student Publications

Parents' stigmatizing beliefs about the HPV vaccine, such as beliefs that it promotes adolescent sexual activity, constitute a notable barrier to vaccine uptake. The purpose of this study is to describe the associations between parents' stigmatizing beliefs about the HPV vaccine, psychosocial antecedents to vaccination, and parents' intentions to vaccinate their children. Parents of vaccine-eligible children (

Disparities In Mortality Between Appalachian And Non-Appalachian Regions Of Kentucky, Sonali S. Salunkhe, Sahal Alzahrani, Beatrice Ugiliweneza

Journal of Appalachian Health

Introduction: In the opioid epidemic, the U.S. faces a significant public health crisis, with some areas of the country, such as rural and Appalachian regions, suffering more than others. The differential regional impact of the crisis in Kentucky—a state with both non-metropolitan/metropolitan and Appalachian/Non-Appalachian statuses—has not yet been documented despite such knowledge being essential to the success of overdose prevention efforts.

Purpose: This study compares all-cause, drug- and opioid-related mortality between counties in different regions of Kentucky: Appalachian non-metropolitan, Appalachian metropolitan, non-Appalachian non-metropolitan, and non-Appalachian metropolitan.

Methods: Age-adjusted mortality data from the Centers for Disease Control and Prevention’s Wide-ranging Online …

Carbapenem-Resistant Enterobacterales—Kentucky, 2013–2020: Challenges And Successes, Mary Issac, Andrea Flinchum, Kevin Spicer

Journal of Appalachian Health

Introduction: Carbapenem-resistant Enterobacterales (CRE) are considered urgent, antibiotic-resistant threats in the U.S. and are of global concern. Active collaboration between public health authorities and healthcare facilities and providers will be necessary to prevent and contain these organisms.

Purpose: To describe the epidemiology of CRE in Kentucky and to discuss challenges and successes with building and sustaining an effective prevention and containment program.

Methods: Retrospective descriptive summary of CRE isolates reported by healthcare providers, facilities, and laboratories in Kentucky from 2013 through 2020. Data available from case reporting forms and laboratory testing are summarized.

Results: From 2013 through 2020, 1805 CRE …

Epidemiologi Difteri Di Indonesia Tahun 2020-2022: Distribusi Kasus, Tingkat Keparahan Gejala, Riwayat Imunisasi Dan Risiko Kematian, Sekar Astrika Fardani, Tri Yunis Miko Wahyono

Jurnal Epidemiologi Kesehatan Indonesia

Difteri menjadi salah satu penyebab utama kematian anak dan dewasa pada era pre-vaksin. Insiden difteri secara global kembali meningkat pada beberapa tahun terakhir dengan case fatality rate (CFR) mencapai 10%. Manusia tidak memiliki kekebalan alami terhadap difteri, sehingga pemberian imunisasi sangat penting untuk memberikan perlindungan terhadap infeksi difteri, mengurangi tingkat keparahan dan risiko kematian. Penelitian ini bertujuan memberikan gambaran distribusi kasus, tingkat keparahan gejala, riwayat imunisasi difteri dan risiko kematian pada penderita difteri di Indonesia tahun 2020 s.d 2022. Penelitian dilakukan dengan desain studi cross-sectional dengan menggunakan data sekunder laporan kasus difteri nasional tahun 2020 s.d 2022. Dari 563 responden, …

Situation Analysis Of Health Problems In Depok City In 2021, Murti Utami Putri, Asri C. Adisasmita, Hidayat Nuh Ghazali Djajuli

Jurnal Epidemiologi Kesehatan Indonesia

Based on 2021 data, from the results of problem identification, 16 health problems in Depok City were assessed. Maternal mortality was selected as a priority problem with 65 cases of maternal death or 155.58 per 100,000 live births. COVID-19 infection is the most common cause of maternal death. This study aims to provide an overview of maternal death circumstances in Depok because of prioritization following situation analysis of health problems. This situation analysis was conducted in Depok with a quantitative and qualitative approach analyzed using the PAHO-adapted Hanlon involving the participation of 17 respondents from the Health Office and the …

Estimasi Biaya Produktivitas Yang Hilang Akibat Kematian Dini Pasien Covid-19 Di Rs Pku Muhammadiyah Gamping, Yuni Andriani, Sugiyono Sugiyono

Jurnal Ekonomi Kesehatan Indonesia

COVID-19 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 virus infection has had an impact on the global health and economic system, including in developing countries. This research is an observational study by estimating the indirect costs of lost productivity due to premature deaths in COVID-19 patients at PKU Muhammadiyah Gamping Hospital in 2021 and knowing the characteristics of the patients. This hospital was chosen as the research site because the percentage of Bed Occupancy Rate (BOR) was the highest in Sleman Regency in 2021, reaching 68.94%. The results of the research show …

Genital Tract Infections, The Vaginal Microbiome And Gestational Age At Birth Among Pregnant Women In South Africa: A Cohort Study Protocol, Ranjana M.S. Gigi, Mandisa M. Mdingi, Hyunsul Jung, Shantelle Claassen-Weitz, Lukas Bütikofer, Jeffrey D. Klausner, Christina A. Muzny, Christopher M. Taylor, Janneke H.H.M. Van De Wijgert, Remco P.H. Peters, Nicola Low

School of Medicine Faculty Publications

Introduction Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth. Methods and analysis This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and …

Determinants Of Immunization In Polio Super High-Risk Union Councils Of Pakistan, Ahmad Khan, Imtiaz Hussain, Dale A. Rhoda, Muhammad Umer, Uzair Ansari, Imran Ahmed, Caitlin Clary, Rana Muhammad Safdar, Sajid Bashir Soofi

Centre of Excellence in Women and Child Health

Background: The current polio epidemiology in Pakistan poses a unique challenge for global eradication as the country is affected by ongoing endemic poliovirus transmission. Across the country, 40 union councils (UCs) which serve as core reservoirs for poliovirus with continuous incidences of polio cases are categorized as super-high-risk union councils (SHRUCs).
Methodology: A cross-sectional survey was conducted in 39 SHRUCs using a two-stage stratified cluster sampling technique. 6,976 children aged 12-23 months were covered. A structured questionnaire was used for data collection. Data were analyzed using STATA version 17.
Results: Based on both vaccination records and recall, 48.3% of children …

Para-Infectious Brain Injury In Covid-19 Persists At Follow-Up Despite Attenuated Cytokine And Autoantibody Responses, Benedict D Michael, Cordelia Dunai, Edward J Needham, Kukatharmini Tharmaratnam, Robyn Williams, Yun Huang, Sarah A Boardman, Jordan J Clark, Parul Sharma, Krishanthi Subramaniam, Greta K Wood, Ceryce Collie, Richard Digby, Alexander Ren, Emma Norton, Maya Leibowitz, Soraya Ebrahimi, Andrew Fower, Hannah Fox, Esteban Tato, Mark A Ellul, Geraint Sunderland, Marie Held, Claire Hetherington, Franklyn N Egbe, Alish Palmos, Kathy Stirrups, Alexander Grundmann, Anne-Cecile Chiollaz, Jean-Charles Sanchez, James P Stewart, Michael Griffiths, Tom Solomon, Gerome Breen, Alasdair J Coles, Nathalie Kingston, John R Bradley, Patrick F Chinnery, Jonathan Cavanagh, Sarosh R Irani, Angela Vincent, J Kenneth Baillie, Peter J Openshaw, Malcolm G Semple, Covid-Cns Consortium, Isaric4c Investigators, Leonie S Taams, David K Menon

Faculty, Staff and Student Publications

To understand neurological complications of COVID-19 better both acutely and for recovery, we measured markers of brain injury, inflammatory mediators, and autoantibodies in 203 hospitalised participants; 111 with acute sera (1-11 days post-admission) and 92 convalescent sera (56 with COVID-19-associated neurological diagnoses). Here we show that compared to 60 uninfected controls, tTau, GFAP, NfL, and UCH-L1 are increased with COVID-19 infection at acute timepoints and NfL and GFAP are significantly higher in participants with neurological complications. Inflammatory mediators (IL-6, IL-12p40, HGF, M-CSF, CCL2, and IL-1RA) are associated with both altered consciousness and markers of brain injury. Autoantibodies are more common …

Assessment Of Deficits In Specific Cognitive Domains In Older Adults Living With Hiv., Andrea Reyes-Vega, Harideep Samanapally, Rishikesh Rijal, Stephen P. Furmanek, Christopher B. Shields, Brandon C. Dennis, Smita Ghare, Shirish Barve

Faculty and Staff Scholarship

A significant proportion of people living with HIV (PLWH) have cognitive impairment. Moreover, approximately 70% of PLWH in the United States will be ≥50 years old by 2030, raising concerns of a higher incidence of dementia as they age. Accordingly, there is a clinical need to monitor their cognitive status. The aim of this study was to delineate specific cognition areas impacted in OALWH with a clinical diagnosis of neurocognitive impairment. We used a comprehensive set of tests (paper and NIH Toolbox Cognition Battery), to assess different cognitive domains in a total of 25 OALWH ≥ 50 years. 64% were …

Simvastatin In Critically Ill Patients With Covid-19, Thomas E Hills, Elizabeth Lorenzi, Lindsay R Berry, Murali Shyamsundar, Farah Al-Beidh, Djillali Annane, Yaseen Arabi, Diptesh Aryal, Carly Au, Abigail Beane, Zahra Bhimani, Marc Bonten, Charlotte A Bradbury, Frank M Brunkhorst, Aidan Burrell, Meredith Buxton, Carolyn S Calfee, Maurizio Cecconi, Allen C Cheng, Matthew E Cove, Michelle A Detry, Lise J Estcourt, Mark Fitzgerald, Ewan C Goligher, Herman Goossens, Cameron Green, Rashan Haniffa, David A Harrison, Madiha Hashmi, Alisa M Higgins, Christopher Horvat, David T Huang, Nao Ichihara, Deva Jayakumar, Peter S Kruger, François Lamontagne, Lamprini Lampro, Patrick R Lawler, John C Marshall, Alexina J Mason, Anna Mcglothlin, Shay Mcguinness, Zoe K Mcquilten, Bryan J Mcverry, Paul R Mouncey, Srinivas Murthy, Matthew D Neal, Alistair D Nichol, Cecilia M O'Kane, Rachael L Parke, Jane C Parker, Ebenezer Rabindrarajan, Luis F Reyes, Kathryn M Rowan, Hiroki Saito, Marlene Santos, Christina T Saunders, Christopher W Seymour, Manu Shankar-Hari, Pratik Sinha, B Taylor Thompson, Alexis F Turgeon, Anne M Turner, Frank Van De Veerdonk, Sebastian Weis, Ian S Young, Ryan Zarychanski, Roger J Lewis, Colin J Mcarthur, Derek C Angus, Scott M Berry, Lennie P G Derde, Steve A Webb, Anthony C Gordon, Daniel F Mcauley

Faculty, Staff and Student Publications

BACKGROUND: The efficacy of simvastatin in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear.

METHODS: In an ongoing international, multifactorial, adaptive platform, randomized, controlled trial, we evaluated simvastatin (80 mg daily) as compared with no statin (control) in critically ill patients with Covid-19 who were not receiving statins at baseline. The primary outcome was respiratory and cardiovascular organ support-free days, assessed on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support through day 21 in survivors; the analyis used a Bayesian hierarchical ordinal model. The adaptive design included prespecified statistical …

Evaluation Of A Targeted Covid-19 Community Outreach Intervention: Case Report For Precision Public Health, Isela De La Cerda, Cici X Bauer, Kehe Zhang, Miryoung Lee, Michelle Jones, Arturo Rodriguez, Joseph B Mccormick, Susan P Fisher-Hoch

Faculty, Staff and Student Publications

BACKGROUND: Cameron County, a low-income south Texas-Mexico border county marked by severe health disparities, was consistently among the top counties with the highest COVID-19 mortality in Texas at the onset of the pandemic. The disparity in COVID-19 burden within Texas counties revealed the need for effective interventions to address the specific needs of local health departments and their communities. Publicly available COVID-19 surveillance data were not sufficiently timely or granular to deliver such targeted interventions. An agency-academic collaboration in Cameron used novel geographic information science methods to produce granular COVID-19 surveillance data. These data were used to strategically target an …

The Potential For Development Of Clinically Relevant Microbial Resistance To Rifaximin-Α: A Narrative Review, Herbert L Dupont

Faculty, Staff and Student Publications

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. …

Association Of Covid-19 Coinfection With Increased Mortality Among Patients With Pseudomonas Aeruginosa Bloodstream Infection In The Veterans Health Administration System, Leila S. Hojat, Brigid M. Wilson, Federico Perez, Maria F. Mojica, Mendel E. Singer, Robert A. Bonomo

Faculty Scholarship

Objective: Pseudomonas aeruginosa bloodstream infection (PA-BSI) and COVID-19 are independently associated with high mortality. We sought to demonstrate the impact of COVID-19 coinfection on patients with PA-BSI. Design: Retrospective cohort study. Setting: Veterans Health Administration. Patients: Hospitalized patients with PA-BSI in pre-COVID-19 (January 2009 to December 2019) and COVID-19 (January 2020 to June 2022) periods. Patients in the COVID-19 period were further stratified by the presence or absence of concomitant COVID-19 infection. Methods: We characterized trends in resistance, treatment, and mortality over the study period. Multivariable logistic regression and modified Poisson analyses were used to determine the association between COVID-19 …

Dna Methylation-Based Epigenetic Biomarkers In Cell-Type Deconvolution And Tumor Tissue Of Origin Identification, Ze Zhang

Dartmouth College Ph.D Dissertations

DNA methylation is an epigenetic modification that regulates gene expression and is essential to establishing and preserving cellular identity. Genome-wide DNA methylation arrays provide a standardized and cost-effective approach to measuring DNA methylation. When combined with a cell-type reference library, DNA methylation measures allow the assessment of underlying cell-type proportions in heterogeneous mixtures. This approach, known as DNA methylation deconvolution or methylation cytometry, offers a standardized and cost-effective method for evaluating cell-type proportions. While this approach has succeeded in discerning cell types in various human tissues like blood, brain, tumors, skin, breast, and buccal swabs, the existing methods have major …

Towards A Mode Of Action For The Anti-Schistosomal Aryl Hydantoins, Thomas Schulze

Theses & Dissertations

Schistosomiasis is a significant human disease caused by the helminth parasite Schistosoma mansoni. Praziquantel remains the only clinically used treatment, yet it is rapidly metabolized and only effective against the adult stage worm infection. Ro 13-3978 (AR02) is a potent antischistosomal compound with activity against multiple S. mansoni life stages; however, it manifests anti-androgenic activity. Additionally, the mechanism of action for worm clearance remains unknown. The structure of Ro 13-3979 was used to generate optimized derivatives, including AR102, that show increased potency towards worms, reduced off-target anti-androgen effects, and extended half-life thereby increasing the feasibility for a single-dose curative treatment. …