Medicine and Health Sciences Commons^™

Frequency Of Bystander Exposure To Antibiotics For Enteropathogenic Bacteria Among Young Children In Low-Resource Settings, Elizabeth T. Rogawski Mcquade, Stephanie A. Brennhofer, Sarah E. Elwood, Timothy L. Mcmurry, Joseph A. Lewnard, Estomih R. Mduma, Sanjaya Shrestha, Najeeha Talat Iqbal, Pascal O. Bessong, Gagandeep Kang

Department of Paediatrics and Child Health

Children in low-resource settings carry enteric pathogens asymptomatically and are frequently treated with antibiotics, resulting in opportunities for pathogens to be exposed to antibiotics when not the target of treatment (i.e., bystander exposure). We quantified the frequency of bystander antibiotic exposures for enteric pathogens and estimated associations with resistance among children in eight low-resource settings. We analyzed 15,697 antibiotic courses from 1,715 children aged 0 to 2 y from the MAL-ED birth cohort. We calculated the incidence of bystander exposures and attributed exposures to respiratory and diarrheal illnesses. We associated bystander exposure with phenotypic susceptibility of E. coli isolates in …

Whole-Genome Sequencing Links Clostridium (Clostridioides) Difficile In A Single Hospital To Diverse Environmental Sources In The Community, Su-Chen Lim, Deirdre Collins, Korakrit Imwattana, Daniel R. Knight, Sicilia Perumalsamy, Natasza M.R. Hain-Saunders, Papanin Putsathit, David Speers, Thomas Riley

Research outputs 2022 to 2026

Aims

To investigate if Clostridium (Clostridioides) difficile infection (CDI), traditionally thought of as hospital-acquired, can be genomically linked to hospital or community environmental sources, and to define possible importation routes from the community to the hospital.

Methods and Results

In 2019, C. difficile was isolated from 89/300 (29.7%) floor and 96/300 (32.0%) shoe sole samples at a tertiary hospital in Western Australia. Non-toxigenic C. difficile ribotype (RT) 010 predominated among floor (96.6%) and shoe sole (73.2%) isolates, while toxigenic RT 014/020 was most prevalent among contemporaneous clinical cases (33.0%) at the hospital. Whole-genome sequencing and high-resolution core genome …

Using A One Health Approach For The Assessment Of Rabies Control In Rural Victoria Falls, Zimbabwe, Ryan Lapenna

Electronic Thesis and Dissertation Repository

Rabies, a viral zoonotic disease, is widespread in Zimbabwe, with human fatalities reported annually in the country. To supplement the Government’s effort on rabies control, the Victoria Falls Wildlife Trust and Veterinarians for Animal Welfare Zimbabwe have joined forces to carry out dog rabies vaccinations in rural communities adjacent to the major tourist attraction of The Victoria Falls. A One Health approach was used to 1) determine the level of protective rabies antibodies among a sample of rural dogs and 2) collect information and describe the knowledge, attitudes, and practices related to rabies among dog owners. In 2020, blood was …

Igg Antibodies To Sars-Cov-2 In Asymptomatic Blood Donors At Two Time Points In Karachi, Muhammad Hasan, Bushra Moiz, Shama Qaiser, Kiran I. Masood, Zara Ghous, Areeba Hussain, Natasha Bahadur Ali, Syed Hani Abidi, Kulsoom Ghias, Erum Khan, Zahra Hasan

Department of Pathology and Laboratory Medicine

Introduction: An estimated 1.5 million cases were reported in Pakistan until 23 March, 2022. However, SARS-CoV-2 PCR testing capacity has been limited and the incidence of COVID-19 infections is unknown. Volunteer healthy blood donors can be a control population for assessment of SARS-CoV-2 exposure in the population. We determined COVID-19 seroprevalence during the second pandemic wave in Karachi in donors without known infections or symptoms in 4 weeks prior to enrollment.
Materials and methods: We enrolled 558 healthy blood donors at the Aga Khan University Hospital between December 2020 and February 2021. ABO blood groups were determined. Serum IgG reactivity …

Behavioural Support And Nicotine Replacement Therapy For Smokeless Tobacco Cessation: Protocol For A Pilot Randomised-Controlled Multi-Country Trial, Faraz Siddiqui, Linda Bauld, Ray Croucher, Cath Jackson, Ian Kellar, Mona Kanaan, Subhash Pokhrel, Rumana Huque, Romaina Iqbal, Javaid Ahmed Khan

Community Health Sciences

Background: Smokeless tobacco (ST) is consumed globally by more than 350 million people, with approximately 85% of all users based in South and Southeast Asia. In this region, ST products are cheap and easily accessible. Evidence-based interventions to people quit ST use are lacking. This study aims to test the feasibility of conducting a future definitive trial of ST cessation, using a culturally adapted behavioural intervention, and/or nicotine replacement therapy (NRT) in three South Asian countries.
Methods: We will conduct a factorial design, randomised-controlled pilot trial in Bangladesh, India and Pakistan. Daily ST users will be recruited from primary health …

Functional Characterization Of A High-Throughput In Vitro Model To Predict Faecal Microbiota Transplantation (Fmt) Donor Success, Catherine M. Andary

Undergraduate Student Research Internships Conference

Faecal microbiota transplantation (FMT) involves the administration of donor faecal matter to a diseased recipient with the goal of remodeling the host microbiome to provide health benefits. In recent years, FMT has emerged as a potential therapy for a variety of microbiome-associated diseases such as atherosclerosis. Trimethylamine (TMA) is an atherosclerosis-linked metabolite generated by the gut microbiota from dietary precursors which is then oxidized to trimethylamine N-oxide (TMAO) by the liver, contributing to increased gut permeability. It has been shown that FMT may alter or restore the gut microbiome of recipients to reduce plasma TMAO levels. Despite its potential, the …

The Sars-Cov-2 Differential Genomic Adaptation In Response To Varying Uvindex Reveals Potential Genomic Resources For Better Covid-19 Diagnosis And Prevention, Naveed Iqbal, Muhammad Rafiq, Masooma Ali, Sanaullah Tareen, Maqsood Ahmad, Faheem Nawaz, Sumair Khan, Rida Riaz, Ting Yang, Ambrin Fatima

Department of Biological & Biomedical Sciences

Coronavirus disease 2019 (COVID-19) has been a pandemic disease reported in almost every country and causes life-threatening, severe respiratory symptoms. Recent studies showed that various environmental selection pressures challenge the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infectivity and, in response, the virus engenders new mutations, leading to the emergence of more virulent strains of WHO concern. Advance prediction of the forthcoming virulent SARS-CoV-2 strains in response to the principal environmental selection pressures like temperature and solar UV radiation is indispensable to overcome COVID-19. To discover the UV-solar radiation-driven genomic adaption of SARS-CoV-2, a curated dataset of 2,500 full-grade genomes from …

Cyclic Di-Gmp Regulates Motility, Biofilm Formation, And Desiccation Tolerance In Acinetobacter Baumannii, Garrett Reynolds

Electronic Theses and Dissertations

Acinetobacter baumannii is an increasingly multidrug-resistant pathogen contributing to hospital-acquired infections necessitating the discovery of novel treatments. A bacterial second messenger, cyclic diguanosine monophosphate (cyclic di-GMP), can regulate various persistence factors that are potentially advantageous for survival in hospital environments. Cyclic di-GMP–modulating enzymes and cyclic di-GMP–binding effectors predictively are encoded in the Acinetobacter baumannii genome. I hypothesized that cyclic di-GMP controls motility, biofilm formation, and desiccation tolerance in Acinetobacter baumannii. Disrupting cyclic di-GMP–modulating enzymes or cyclic di-GMP–binding effectors should alter the regulatory effectiveness of these phenotypes. I tested the multidrug-resistant isolate Acinetobacter baumannii strain AB5075 and identified several transposon …

Bacterial Chondronecrosis With Osteomyelitis In Broilers: Genomics, Phylogenomics, And Methods To Detect Specific Pathogens During Outbreaks., Abdulkarim Abdulaziz A. Shwani

Graduate Theses and Dissertations

Lameness is a major issue in animal welfare and the broiler industry. Bacterial chondronecrosis with osteomyelitis (BCO) is one of the main causes of lameness. Many staphylococcal species, including Staphylococcus agnetis isolate 908, have been isolated from the bones and blood of lame broilers at the University of Arkansas. Staphylococcus agnetis is a coagulase-variable, Gram-positive bacterial species that has been previously associated with subclinical or mild clinical cases of mastitis in dairy cattle. The annotated complete genome of hypervirulent strain 908 was published at NCBI. In this study, it has been compared to nine genomes we assembled for hypervirulent isolates …

Microplastics In Freshly Fallen Snow: How May It Adversely Impact Human Health And Exacerbate The Covid-19 Crisis?, Ayesha Liaquat, Aleena Kashif, Sushma Rathi, Alishba Raza

Medical College Documents

No abstract provided.

Tetr Family Regulator Farr Variation Controls Antimicrobial Fatty Acid Efflux In Staphylococcus Aureus, Camryn M. Bonn

Electronic Thesis and Dissertation Repository

To colonize human skin and survive within abscesses, Staphylococcus aureus has evolved mechanisms to evade host innate defenses. USA300 has become the predominate community-acquired methicillin-resistant S. aureus (CA-MRSA) clone, which can be in part attributed to detoxification of unsaturated free fatty acids (uFFA) found in sebum and the nares. Our lab has previously identified the TetR family regulator FarR responsible for induction of the resistance-nodulation-division (RND) superfamily efflux pump FarE to promote efflux of toxic uFFA. However, RND family efflux pumps remain poorly characterized in Gram-positive species and the mechanism by which FarR regulates FarE has yet to be determined. …

Regulation Of Mhc Ii Trafficking And Expression By Host And Viral Factors, Alex Lac

Electronic Thesis and Dissertation Repository

Antigen presentation by major histocompatibility complex class II (MHC II) to the adaptive immune system is crucial for mounting sterilizing immune responses. This central role has made antigen presentation a target for antagonism by many pathogens. Notably, infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) decrease MHC II expression in several immune cells. The mechanisms responsible for this suppression are unknown but involves either redirecting MHC II molecules away from the cell surface or inhibiting MHC II expression. To understand how pathogens manipulate intracellular MHC II trafficking, we first investigated the role of the Golgi trafficking regulator, ERC1, in …

A Conserved Mechanism For Hormesis In Molecular Systems, Sharon N. Greenwood, Regina G. Belz, Brian P. Weiser

Rowan-Virtua School of Osteopathic Medicine Faculty Scholarship

Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this …

Molecular Mechanisms Underlying Mucosal Attachment And Colonization By Clostridioides Difficile, Ben Sidner

Department of Food Science and Technology: Dissertations, Theses, and Student Research

Clostridioides difficile is a Gram-positive, spore-forming, anaerobic bacterium which causes gastrointestinal disease and is a leading cause of nosocomial infections. Although infection typically occurs following antibiotic therapy, in recent years there has been an increase in infections which are not preceded by antibiotic use. Additionally, community-associated infections and rates of disease recurrence have increased. While it is understood that a healthy gastrointestinal microbiota provides protection against infection, the molecular mechanisms which underly C. difficile's ability to colonize and persist in the gut are mostly unknown. Building on work from others that suggests C. difficile associates with the outer mucus …

Jatropha Tanjorensis A Flora Of Southeast Nigeria: Isolation And Characterization Of Naringenin And Validation Of Bio-Enhanced Synergistical Activity Of Α- Tocopherol Toward Clinical Isolates Of Resistant Bacterial, Ikechukwu Kingsley Ijoma, Vincent Ishmael Egbulefu Ajiwe

Makara Journal of Science

Jatropha tanjorensis is among the rich floras of Southeast Nigeria and used by ethnic people to treat infections and manage health conditions. Ethnomedicine has long been employed in the treatment of ailments caused by bacterial pathogens. Studies showed that the incorporation of synthetic α-tocopherol to an antibacterial agent improves its activity. However, knowledge about the antibacterial-enhanced activity of plant-based α-tocopherols, especially those isolated from Jatropha tanjorensis, is limited because of the different bioactivities of synthetic and natural α-tocopherols. To determine the phytochemicals in J. tanjorensis, we carried out the structural elucidation of its leaf extracts. Naringenin and α-tocopherol …

Presence Of Blaper-1 And Blaveb-1 Beta-Lactamase Genes Among Isolates Of Pseudomonas Aeruginosa From Burn And Trauma Hospital Peshawar, Pakistan, Suleman Khan, Samiyah Tasleem, Alfarah Rehmat Ullah,, Sarwat Moon, Saad Alghamdi, Raina Saad Suliman, Muhammad Ateeq, Muhmmad Salman, Anas S. Dablool,, Banan Atwah, Farkad Bantun

Journal of Bioresource Management

Pseudomonas aeruginosa spp are the most prevalent bacteria that cause nosocomial infections in hospitals. Most antibiotics, including novel new β-lactams, are already resistant to them, and they can become resistant during treatment, which can make the treatment fail. P. aeruginosa isolates from ICU patients who had Per-1 and VEB-1 were the main focus of this study. These two ESBLs are the two most common in ICU patients who had them. 50 isolates were gathered from Peshawar's LRH ICU facilities in the year 2021. The antibiotic susceptibility test was conducted in accordance with the Clinical and Laboratory Standards Institute's standards (CLSI). …

The Role Of The Gut-Brain Axis In Alzheimer's Disease: A Narrative Review, Leila Karout

University Honors Theses

The importance of the gut microbiome in health has become increasingly recognized as more research points to the strong association between an imbalanced gut microbial composition and a diseased state. Alzheimer's Disease burdens millions, and the rate of growth is expected to increase. However, current treatment methods are less than ideal and do not offer a substantial benefit to patients' quality of life. Additionally, there are gaps in the current understanding of Alzheimer's Disease pathogenesis. Research on the relationship between gut microbiota and neurodegeneration provides a different perspective on the pathogenesis and treatment methods for dementia, such as Alzheimer's Disease. …

Biowill - Characterising Willow Bark Bio-Actives For Skin Therapies, Arnold Marisa

ORBioM (Open Research BioSciences Meeting)

Willow bark is considered as a disposable by-product when processing willow for biomass. Willow (Salix) is known to contain high value bioactive compounds which include salicin and its derivatives, and other phytochemicals of interest such as polyphenols and flavonoids. The plant is historically known as the primary source of salicylates to which the well-known drug aspirin is derived from. The work forms part of the Interreg project BioWILL, which is focused on integrated “Zero Waste” biorefinery utilising all fractions of willow feedstock for the production of biochemicals and renewable energy. This project aims to investigate the crude and …

Effect Of Sub-Inhibitory Concentrations Of Nitrofurantoin, Ciprofloxacin And Trimethoprim On In-Vitro Biofilm Formation In Uropathogenic Escherichia Coli, Shane Whelan

ORBioM (Open Research BioSciences Meeting)

The purpose of the current study was to determine the effect of sublethal concentrations of nitrofurantoin, ciprofloxacin and trimethoprim on biofilm formation in 57 uropathogenic Escherichia coli strains (UPEC).

The MIC of nitrofurantoin, ciprofloxacin and trimethoprim was determined for 57 UPEC isolates. Biofilm formation for each isolate with and without sub-lethal concentrations of each antibiotic was then quantified, and the statistical significance of changes in biofilm formation was ascertained by way of a Dunnett's test.

The effects of sub-MIC antibiotics on biofilm formation of UPEC were variable. A total of 22.8% of strains were induced to form biofilm by nitrofurantoin, …

Resolving The Repression Pathway Of Virulence Gene Hila In Salmonella, Alexandra King, Lon Chubiz Phd, Brenda Pratte, Lauren Daugherty

Undergraduate Research Symposium

Salmonella is a relatively abundant, virulent species of bacteria that is most known for spreading gastrointestinal diseases through food. These illnesses result in approximately 1.35 million infections, including over 25,000 hospitalizations each year, in the U.S. alone (CDC.gov). As antibiotic resistance becomes an increasingly urgent public health problem, the importance of developing alternative treatment methods is only becoming more crucial. One of the genes responsible for this virulence is known as hilA. HilA is the main transcriptional regulator of Salmonella Pathogenicity Island-1 gene (UniProt). SPI-1 plays an important role in the invasion of Salmonella into epithelial cells. The proteins encoded …

Factors Affecting The Antibacterial Activity Of Cefiderocol On Klebsiella Pneumoniae With Diverse Characteristics, Lana Jamal Rashed Daoud

Theses

Antimicrobial resistance (AMR) is a growing serious threat that poses a burden on the healthcare system. Spread of AMR bacteria limits treatment options; thus, new antimicrobial agents are required. Cefiderocol (CFDC) is a novel siderophore cephalosporin, approved by the FDA in 2019 for use in treating infections caused by multi-drug resistant (MDR) pathogens; but it is not yet in clinical use in the UAE. CFDC is equipped with stabilizers against β-lactamases as well as a siderophore side chain that allows it to penetrate the outer membrane of bacteria through the iron uptake pathways. The aim of this study is to …

Flippase Inhibitors As Antimicrobial Agents, Robert Tancer

Seton Hall University Dissertations and Theses (ETDs)

Drug resistant microbes are a considerable challenge for modern medicine to overcome. The research described in this dissertation involved development of lipid flippase inhibitors and investigating their potential as antimicrobial agents against various drug resistant microbes. The microbes primarily investigated were methicillin resistant Staphylococcus aureus (MRSA) & Cryptococcus neoformans. Chapter 1 reviews the historical perspective and summarizes the current state of the field of research. In Chapter 2, the design space of an antimicrobial peptide known as humimycin was explored and the effects of modifications on its structure were observed against MRSA. Several key observations resulted. Most notably, the …

Identification Of Pneumococcal Membrane Proteins Involved In Colonization/Biofilm Formation And Cognate Host Cellular Receptors, Yoonsung Hu

Theses and Dissertations

Colonization is prerequisite for infection and transmission of Streptococcus pneumoniae, or pneumococcus. Currently available pneumococcal conjugate and pneumococcal polysaccharide vaccines can provide protection against a limited number of capsular serotypes. Implementation of vaccines has decreased the frequency of invasive pneumococcal disease and their colonization rates, but only in a serotype-dependent manner. This has led to serotype replacement in pneumococcal ecology and increased invasive disease caused by non-vaccine serotypes. Development of conserved protein-based vaccine that can provide protection against all pneumococcal serotypes is needed. Numerous surface proteins are conserved in all serotypes, and some are known to be involved in …

Eskape Pathogens: The Clinical Prevalence And Molecular Mechanisms Of Antibiotic Resistance, Anusha Attre

Honors Scholar Theses

The ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are the leading cause of all nosocomial, or healthcare-associated (HAI), infections (Navidinia, 2016). The purpose of this research study is to determine the burden of ESKAPE infections on healthcare and study the antibiotic resistance in these high-risk pathogens to provide direction for researchers to develop new antimicrobial innovations to reduce ESKAPE infectivity and improve patient outcomes. To study the burden of ESKAPE infections, this review analyzes the current statistics explaining the clinical prevalence of each pathogen in causing HAIs. Additionally, each pathogen is …

Gut Commensals Modulate Siv/Shiv Pathogenesis And Therapeutics, Samuel Johnson

Theses & Dissertations

Despite significant advancements in combination antiretroviral therapy (cART), ongoing inflammation in the brain and gut remain two of the most significant hurdles in the health of people living with human immunodeficiency virus (HIV). Additionally, a viral reservoir in each compartment inhibits cure efforts by allowing rapid viral rebound following cART interruption. Emerging understanding of the gut-brain axis (GBA) implicates each compartment in the modulation of the other in a complex bi-directional interaction mediated by vagus innervation, circulating lymphocytes, and microbiome composition and biproducts. Using multiple models of the simian (and simian-human) immunodeficiency virus (SIV/SHIV) and therapeutic intervention, I present how …

Cdk8 Kinase Module Modifies Expression Of Specific Translation-Related Proteins Before And After Stress, Brittany Friedson, Katrina Cooper

Rowan-Virtua Research Day

Translation is tightly coupled to growth status. Efficient protein synthesis is necessary for cell growth in nutrient rich environments, while global translation inhibition combined with selective translation of stress-responsive mRNAs helps limit growth in times of stress. Environmental stress cues which inhibit the nutrient-sensing complex TORC1 are known to reduce general translation, but how does the cell alter protein synthesis machinery to adapt to these conditions? A few mechanisms to promote cell survival in nitrogen starvation include post-translational modification and selective degradation of specific mRNA-binding translation factors, as well as inhibition of activators of genes whose products are required for …

Cat Covid, Cmv And Chemokines, Oh My!, Trevor Hancock

Doctoral Dissertations

Cytomegalovirus (CMV) is an important pathogen infecting most humans worldwide. CMV infection within immunocompromised individuals can cause severe morbidity and potential mortality. Disease during CMV infection is due to virus dissemination and subsequent inflammation. Host immune cells lie at the intersection potentially mediating both. The CMV-encoded viral chemokine vCXCL-1 is a proposed virulence factor in mouse models increasing immune cell recruitment and disease. However, the primary immune cell mediator is undetermined. To identify targets, Chapter 2 examines CXCR2 expression (receptor for vCXCL-1) among various mouse tissues and human peripheral blood under steady-state conditions. In vitro, isoforms of HCMV’s vCXCL-1 …

Investigation Of Genomic Instability Induced By G-Quadruplexes In The Absence Of Functional Topoisomerase 1 In Yeast, Alexandra Berroyer

Dissertations & Theses (Open Access)

Topoisomerase 1 (Top1) is an enzyme that removes transcriptionally generated negative supercoils by binding and nicking DNA. Since transcription of guanine-rich DNA leads to the formation of G-quadruplex (G4) structures, Top1’s function likely suppresses G4-formation. In support of this, Top1 significantly reduces co-transcriptional G4 DNA-associated genomic instability at a model G4-motif in Saccharomyces cerevisiae. However, whether Top1 suppresses G4-formation on a genome-wide scale in yeast remains unexplored. Therefore, I aimed to uncover if deletion of Top1 enhances genome-wide G4-formation in S. cerevisiae. As an approach to quantify global G4-formation, I expressed the G4-specific antibody BG4 from a yeast …

Time Course Investigation Of The Dermal Leukocyte Response To Lipoteichoic Acid In Chickens, Ian Gilbert

Animal Science Undergraduate Honors Theses

Lipoteichoic acid (LTA) is component of the cell wall of Gram-positive bacteria that stimulates inflammation during bacterial infection. However, few studies have investigated the in vivo immune response to LTA, and none of the in vivo studies done have been performed in birds. For this project, the pulp (a skin-derivative) of growing feathers (GFs) of chickens were used as a test site to investigate the in vivo effects of intradermally injected LTA. In Study 1, the pulp of 12 GFs of 11-week-old Light-brown Leghorn (LBL) males were injected with 10 μL of differing concentrations of LTA (0.1, 1.0, 10, 100 …

The Effect Of Cognitive Status And Residency On Oral Health In Patients With Dementia, Nicole Stephens

Dissertations & Theses (Open Access)

Poor oral health is a predictor of cognitive decline in elderly populations and has been shown to precede dementia. As cognitive decline progresses, patients are likely to move from the community into nursing facilities. We hypothesize that severity of dementia and residency type will impact the oral health of patients with dementia. Fifty-two participants of two dementia levels were recruited from the UTHealth Neurocognitive Disorders Center and two Houston-area nursing homes. A standardized oral health assessment, plaque index, and oral bacteria analysis determined participants’ oral health status. Further, data was collected on participants’ medical history, oral hygiene habits, dietary habits, …