Digital Commons Network^™

A Curious Case Of Medium-Vessel Vasculitis, Nisa N Ilsin, Haleigh D Stafford, Anna Catinis, Theodore Rosen

Faculty, Staff and Students Publications

Vasculitis, or the inflammation of vessels due to primary or secondary causes, may arise from numerous etiologies, often leading to diagnostic uncertainty. Delayed treatment due to diagnostic or etiologic uncertainty presents a significant clinical risk, with consequences including organ failure and mortality. We describe a case of a 58-year-old male with a history including ankylosing spondylitis who presented with painful ulcers involving the bilateral lower extremities following a trip to the southern Texas border. Histopathology revealed medium-vessel vasculitis; however, the search for a likely etiology in the setting of a unique combination of potential vasculitis precipitants, including glochid inoculation, a …

Retinoblastoma Malignance And Exosome Mechanisms Facilitating Optic Nerve Head Metastatic Niche Formation, Cui Shi

Dissertations, Theses, and Capstone Projects

Retinoblastoma (RB) is a rare pediatric ocular tumor that occurs before five years of age and it is the most common intraocular cancer of childhood with more than 300 children in the United States and 8000 diagnosed globally each year. RB arises from the proliferation of cone photoreceptor precursor cells in the retina as a result of mutations in the RB1 gene. The influence of RB secreted factors on cells in the retinal environment has not been fully elucidated. Cancer cell released exosomes have been shown to transform their microenvironment through transfer of metastasis promoting molecular cargo. Cancer cell extracellular …

Understanding Primate Immunity To African Trypanosomes Through The Characterization Of Trypanosome Lytic Factor Formation And Function, Sara Fresard

Dissertations, Theses, and Capstone Projects

African trypanosomes cause an annual loss of over 1 billion USD due to their economic and agricultural burden in Sub-Saharan Africa. These parasites are unicellular, extracellular parasites, that infect humans, cattle, and other livestock. Humans and some non-human primates are protected against most species of trypanosomes due to an innate immunity factor, Trypanosome Lytic Factor (TLF). This modified High Density Lipoprotein (HDL) contains two unique proteins, Haptoglobin Related Protein (HPR), a ligand to a trypanosome surface receptor, and Apolipoprotein-L1 (APOL1), the lytic component. Our overall goal is to use our understanding of primate immunity to create genetically modified cattle that …

A Case Of Persistent Intra-Abdominal Stenotrophomonas Maltophilia Infection Despite Bacteriophage Therapy, Grace D Cullen, Keiko Christine Salazar, Austen Lee Terwilliger, Saima Aslam, Justin R Clark, Anthony W Maresso, Paul L Bollyky, Jenny R Aronson

Faculty, Staff and Students Publications

Multidrug resistant infections are a challenge in the health care setting and a cause of patient morbidity and mortality. Bacteriophages (phages) are viruses that target and kill bacteria and have been used in patients to treat bacterial infections. We present a case of disseminated Stenotrophomonas maltophilia infection, with pulmonary, intra-abdominal and bloodstream involvement. The patient was treated with a combination of antibiotics and personalized phage therapy, administered daily for 12 days both intravenously as well as via intra-abdominal drains. Phage therapy was well-tolerated, the patient cleared S. maltophilia from their bloodstream and their intra-abdominal abscesses were stable or decreased in …

Unraveling The Multilevel Dynamics Of Water, Sanitation, And Child Anthropometry In Indonesia, Rifa Kirana, Ahmad Komarulzaman

Makara Journal of Health Research

Background: Anthropometrics, reflecting nutritional status, growth, and development, are crucial elements that can predict a person’s health and well-being. However, low anthropometric measures among children under 5 years remain a significant issue in Indonesia, often influenced by various factors at the household and community levels. Access to clean water and adequate sanitation has been identified as major determinants of these adverse health outcomes. This study analyzes the relationship between anthropometric measures and access to water and sanitation at household and community levels using a multilevel analysis approach.

Methods: The study employs cross-sectional data from the Indonesian Family Life …

Exploring Berberine As A Novel Therapeutic Agent Against Staphylococcus Aureus Infections: Targeting Inflammation And Antibiotic Resistance, Daniel Kopulos

NYMC Student Theses and Dissertations

Staphylococcus aureus is a versatile Gram-positive bacterium commonly found on human skin. While often harmless, it can cause various infections when the skin is compromised, ranging from minor issues to life-threatening conditions in immunocompromised individuals.

The bacterium’s ability to resist antibiotics, particularly methicillin, underscores its clinical challenge. Staphylococcus aureus can also acquire vancomycin resistance. It evades immune responses through multiple mechanisms, including capsule formation, interference with immune proteins like staphylococcal protein A, and secretion of toxins such as Panton-Valentine Leukocidin. Understanding these mechanisms is crucial for developing effective strategies against Staphylococcus aureus infections.

The immune response to Staphylococcus aureus infections …

Antibiotic-Resistant Gram-Negative Bacteria In A Local Wastewater Treatment Plant In North Georgia, Nou Moua, Lindsay Mccuen, Sarah White, Swapna Bhat, Margi Flood, Jeanelle Morgan

Georgia Journal of Science

Antibiotics are some of the most essential lifesaving drugs currently available to us against infectious diseases. Several pathogens are developing resistance to these drugs and many have become resistant to multiple antibiotics. Such multi-drug resistance is becoming a global issue and has been found in many environments including wastewater treatment plants (WWTPs). In this study, we sampled a local WWTP for antibiotic-resistant bacteria. This WWTP is in North Georgia and runs directly into Lake Lanier, which is the main source of drinking water for the Atlanta area as well as a popular spot for water recreation. We obtained treated and …

Combination Therapy Of Ido1 Inhibition And Anti-Pd1 Mediates Anti-Tumor Immunity By Promoting Memory Immunity Development And Cytotoxicity Of Γδ T And Nk Cells Via Il-2 Signaling And By Overcoming Pro-Tumor Effects Of Tgf-Β Signaling, Hyuk Jee

Dartmouth College Master’s Theses

Cutaneous melanoma is the most aggressive form of skin cancer even though it takes only about 1% of all skin cancers. Even among all cutaneous melanomas, NRAS-mutant melanoma is more aggressive than any other, and about 10-25% of all cutaneous melanoma cases have mutations in NRAS. NRAS is a member of the RAS family of proto-oncogenic GTPase proteins, and it plays a key role in signal transduction pathways responsible for cellular survival, proliferation, and metabolism. Immunotherapy is the first line of defense against NRAS-mutant melanoma because, despite tremendous efforts made for decades, it has not been successful to develop small …

The Prospect Of Indonesian Herbal As An Alternative Treatment For Covid-19 Patient: A Literature-Based Study, Hadi Sunaryo, Wahyu Hidayati

Indonesian Journal of Medical Chemistry and Bioinformatics

Coronavirus disease 2019 (COVID-19) is a new disease caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The disease has several symptoms from mild to severe and could lead to death for comorbidities and the elderly. Therefore, the infections and mortality cases keep growing day by day, moreover many authorities are trying to suppress it by applying several health protocols, including medicines. Several studies were conducted on drug discovery from plants to cure the disease. The article aimed to do a narrative review about the prospect of JAMU becoming an alternative medicine to cure COVID-19 by mapping …

Antimicrobial Studies Of Novel Pyrazole And Thiazole-Based Antibacterial Agents, Hansa Raj Kc

Student Theses and Dissertations

In recent years, the rise of antibiotic-resistant bacteria has become a global concern, resulting in fewer effective antibiotics. Several conventional antibacterial agents are ineffective against these, necessitating novel molecules with enhanced efficacy and diverse actions. We developed pyrazole and thiazole-based antibacterial agents and demonstrated that they have significant potency (minimum inhibitory concentration as low as 0.39 µg/mL) against antibiotic-resistant and susceptible bacteria, as well as promising anti-biofilm and anti-persister activity. In vivo toxicity tests on Caenorhabditis elegans showed no significant harm to this model host organism at low compound concentrations. These compounds rescued C. elegans from methicillin-resistant Staphylococcus aureus (MRSA) …

Neutralization Escape, Infectivity, And Membrane Fusion Of Jn1-Derived Sars-Cov-2 Slip, Flirt, And Kp2 Variants, Pei Li, Julia N Faraone, Cheng Chih Hsu, Michelle Chamblee, Yi-Min Zheng, Claire Carlin, Joseph S Bednash, Jeffrey C Horowitz, Rama K Mallampalli, Linda J Saif, Eugene M Oltz, Daniel Jones, Jianrong Li, Richard J Gumina, Kai Xu, Shan-Lu Liu

Faculty, Staff and Student Publications

We investigate JN.1-derived subvariants SLip, FLiRT, and KP.2 for neutralization by antibodies in vaccinated individuals, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients, or class III monoclonal antibody S309. Compared to JN.1, SLip, KP.2, and especially FLiRT exhibit increased resistance to bivalent-vaccinated and BA.2.86/JN.1-wave convalescent human sera. XBB.1.5 monovalent-vaccinated hamster sera robustly neutralize FLiRT and KP.2 but have reduced efficiency for SLip. All subvariants are resistant to S309 and show decreased infectivity, cell-cell fusion, and spike processing relative to JN.1. Modeling reveals that L455S and F456L in SLip reduce spike binding for ACE2, while R346T in FLiRT and KP.2 strengthens …

Anatolian Medicinal Plants As Potential Antiviral Agents: Bridging Traditional Knowledge And Modern Science In The Fight Against Covid-19 And Related Viral Infections, Engi̇n Ti̇lkat, Israt Jahan, Ayşe Hoşer, Alevcan Kaplan, Oğuzhan Özdemi̇r, Ahmet Onay

Turkish Journal of Biology

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the worldwide coronavirus illness 2019 (COVID-19), often known as the coronavirus pandemic. Since December 2020 however, COVID-19 vaccines have been extensively administered in numerous countries. In addition to new antiviral medications, the treatment regimen also encompasses symptom management. In spite of sustained research efforts, the outbreak remains uncontrolled, with affected patients still lacking proper treatment. Consequently, this review serves as a valuable asset for researchers and practitioners aiming to delve into the yet unexplored potential of Anatolian flora in the fight against COVID-19 and other viral infections. Numerous …

Molecular Docking, Pharmacological Profiling, And Molecular Dynamics Simulation Of Potential Antihyperuricemic Agent From Secondary Metabolites Of Dillenia Philippinensis Rolfe (Dilleniaceae), Louie Rince C. Suyo, John P. Paulin, Nicole Clarence Louise L. Gapaz, Markus Brent S. Arevalo, Vince Tyrell P. Yongco, Librado A. Santiago

Karbala International Journal of Modern Science

Crystal accumulation in the joints due to increased serum uric acid (sUA) may lead to an inflammatory condition called gout. Increased sUA is caused by the excessive reabsorption of the urate anion transporter-1 (URAT-1). Therefore, URAT-1 inhibition will promote uric acid excretion and reduce the risk of having gout. Dillenia philippinensis Rolfe, often known as katmon, is an endemic plant in the Philippines with bioactive compounds associated with several therapeutic benefits. The present study represents the first scientific inquiry into the antihyperuricemic potential of compounds isolated from D. philippinensis. This study aimed to assess the interaction of URAT-1 with …

Development Of A Urothelial Cell Line Expressing A Caspase-1 Biosensor To Measure Cellular Inflammatory Responses To Potential Uropathogens, Nikita Riya Kesav

Master's Theses

Urinary tract infections are one of the most common bacterial infections, historically implicating Escherichia coli as the causative pathogen. However, it is now known that there are a variety of bacteria that exist within the urinary tract, acting as either beneficial uroprotectives or opportunistic uropathogens. Furthermore, there are significant gaps in our understanding as to how these bacteria interact with the urothelium and what role each plays in maintaining or disrupting homeostasis. Research has shown that Toll-like receptor 4 (TLR4) signaling and Nod-like Receptor Protein 3 play a role in inflammasome activation during infection, triggering caspase-1 activation and inducing release …

Testing Strategies To Develop A Mucosal T Cell Inducing Vaccine For Hiv-1, Reynolds Boone

Master's Theses

Despite numerous efforts, HIV vaccine is still not available. Because HIV Envelop protein varies among subtypes and isolates, it is impossible for one vaccine against HIV Env to induce neutralizing antibodies against all subtypes and isolates. Previous vaccine attempts inducing HIV-specific CD4+ T cells have even been shown to enhance the HIV infection because HIV preferentially infects activated CD4+ T cells. It is known that CD8+ cytotoxic T cells (CTLs) play an important role in controlling HIV infections. We hypothesize that a vaccine inducing only CD8+ CTLs but not CD4+ T cells will be effective in preventing HIV infections. Thus, …

The Anti-Inflammatory Properties Of Exopolysaccharide From Bacillus Subtilis, Nikolay Todorov

Master's Theses

Commensal microorganisms can be used therapeutically to ameliorate a variety of diseases. The laboratory of Dr. Katherine L. Knight studies these therapeutic properties in the commensal microorganism known as Bacillus subtilis. Previously, the Knight lab has demonstrated that B. subtilis can protect against colitis caused by Citrobacter rodentium suggesting that B. subtilis possesses anti-inflammatory properties. These properties are specific to the polysaccharide capsule of the microorganism known as exopolysaccharide or EPS. EPS can be produced and purified for study. EPS has been demonstrated to be protective in a variety of diseases such as allergic eosinophilia, sepsis, Graft versus Host disease, …

Characterization Of Cd11c-Expressing Gut-Associated T Cells, Ana Cvetkovic

Master's Theses

Our immune system is a remarkable defense network that protects our bodies from a range of threats. Its’ intricate machinery comprises of messenger and effector cells that work together to coordinate an effective immune response. Traditionally, T lymphocytes have been considered effectors: they receive instructions from messengers, known as Antigen Presenting Cells (APCs), that alter T-cell activation state and behavior. In the gut, Dendritic Cells (DCs) are the APCs that most often instruct T cells. To accomplish their messenger role, DCs express CD11c at high levels, a surface marker involved in cell-to-cell signaling and phagocytosis. As such, CD11c expression has …

Investigating The Roles Of Sirtuins During Cvb3 Infection And Innate Immunity, Bridget M. Hulsebosch

Master's Theses

Coxsackievirus B3 (CVB3) is an enterovirus that chronically infects heart tissue, leading to dilated cardiomyopathy. However, no vaccines or antivirals exist for CVB3 infection or to treat CVB3-induced dilated cardiomyopathy, except for a heart transplant. Sirtuins (SIRTs), class III lysine deacetylases, have diverse and complex roles in cellular functions, contributing to energy production, NF-κB signaling, cell cycle regulation, and inflammation. Previous studies showed that SIRTs are essential for hepatitis B and A viral replication and regulate the IFN response during viral infection. However, the role of SIRT1 and 2 during CVB3 infection is entirely unknown. CVB3-infected SIRT1 and SIRT2 knockout …

Design, Synthesis, And Evaluation Of Oleyl-Wrh Peptides For Sirna Delivery, Mrigank Shekhar Rai, Muhammad Imran Sajid, Jonathan Moreno, Keykavous Parang, Rakesh Kumar Tiwari

Pharmacy Faculty Articles and Research

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silence a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1–4) peptides. The peptide/siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide/siRNA complexes showed serum …

The Experience Of Homelessness And Its Effects On Gut Eubiosis, Kamerin Villagomez

University Honors Theses

Microorganisms which populate the human gastrointestinal tract (GIT) have a profound effect on overall human health. The relationship between host health and eubiosis, or balance, of the GIT microbiome is symbiotic and can have reciprocal relationships with quality of sleep, quality of diet, stress and mental health, and the experience of pain. These specific aspects of health are unique in populations experiencing homelessness due to the multi-dimensional and complex nature of their lived experience. Very few studies explore populations experiencing homelessness, with even fewer investigating the intersection between this population and the human GIT microbiome. It is important to do …

Histories Of Stress: A Life Course Approach To Population Health In Late Medieval And Early Modern Berlin, Emily Brennan

Theses and Dissertations

Given our current climate crisis and urban population increases, researchers are increasingly interested in the health outcomes at the intersection of climate change and urbanization. Since climate change and urbanization affects human health in a variety of ways, more work is needed in diverse cultural contexts to understand temporal and geographic variations of such phenomena more fully. Using skeletal individuals from 13^th – 18^th century Berlin (n = 387), this project analyses demographic and health trends from the founding of the city in the late medieval period (c. 1200 – 1500) to the early modern period, when the …

Germline Genetic Determinates Of Cancer And Pre-Malignant Conditions, Jie Liu

Arts & Sciences Graduate Student Theses and Dissertations

Cancer is a genetic disease stemming from a combination of inherited and acquired mutations. In my thesis, we sought to characterize how germline genetic variation affects acquired clonal expansions in normal tissues and its progression to malignancy. In Chapter 2, we studied the impact of germline genetic variation on clonal hematopoiesis (CH) in 731,835 individuals. We identified 22 novel CH predisposition genes, most of which predispose to CH driven by specific mutational events. CH predisposition genes contribute to unique somatic landscapes reflecting the influence of germline genetic backdrop on gene-specific CH fitness. Correspondingly, somatic-germline interactions influence the risk of CH …

Preventive Effects Of Quercetin On The Leaky Gut By Suppression Of Il-1beta-Induced Transcription Factors Involved In An Inflammatory Pathway In Colonic Epithelial Cells, Wannaporn Chayalak, Sumpun Thammacharoen, Chatsri Deachapunya, Sutthasinee Poonyachoti

The Thai Journal of Veterinary Medicine

Flavonol quercetin (Q), found in vegetables and fruits, demonstrates the most potent anti-inflammatory effect. The preventive effect and cellular mechanisms of Q (Q1, Q10, and Q100 µM) on IL-1β induced leaky gut via the signaling molecules of inflammatory pathway, NF-κB p65-iκB/or p38/ERK1/2/MLCK/phospho(p)-MLC were investigated in Caco-2 cells. The cytotoxic effect of Q was initially determined by MTT assay. Transepithelial electrical resistance (TER) and apical-to-basolateral fluorescein isothiocyanate-labeled dextran (FD-4) flux were used to determine paracellular permeability. The protein expression of signaling molecules was examined by Western blot analysis, and their target MLCK mRNA expression was determined using real-time PCR. All Q …

Declined Lawsonia Intracellularis In Feces By Phytogenic Feed Additive Supplementation In Fattening Pigs In Different Herds System, Morakot Nuntapaitoon

The Thai Journal of Veterinary Medicine

The objective of the present study was to determine the efficacy of phytogenic feed additives on the number of L. intracellularis in feces and incidence of diarrhea in fattening pigs in different herds system. The present study was carried out in two commercial swine farms located in the northern (Herd A) and western (Herd B) parts of Thailand. In total, 80 fattening pigs (12-week-olds) were randomly allocated into two groups, including the Control group (n=40) and the Treatment group (n=40). The pigs in each group were fed with a conventional diet (Control) and the same diet supplemented with 2 kg/ton …

Molecular Characterization And Antibiogram Of Riemerella Anatipestifer In Ducklings In Upper Egypt, Mohamed Sabry Ahmed, Amal Abd El-Ghani Batahi, Ahmed Ibrahim Ahmed, Nabila Osman

The Thai Journal of Veterinary Medicine

Riemerella anatipestifer infection represents a great threat to the duck industry worldwide and it is considered the major cause of death in the backyard rearing system of ducks in Egypt. The disease is characterized by diarrhea, respiratory signs and loss of weight. The present study was conducted during the period between July 2019 and January 2021 to examine the prevalence rate, the antibiogram patterns of the different antibiotics and the pathogenicity of R. anatipestifer in Qena province. One-hundred samples were collected from diseased and freshly dead backyard ducklings. A tentative characterization of R. anatipestifer was done depending on the phenotypic …

Alternative Approaches To Live Attenuated Oral Rotavirus Vaccines, Makoye Mhozya Kanyema, Junhong Wang, Gui-Lian Yang, Xin Cao, Chunfeng Wang

The Thai Journal of Veterinary Medicine

Oral attenuated rotavirus vaccine is safe and effective in developed countries but, however, it is less effective in low income countries such as African and Asian countries. Low vaccine effectiveness in low-income countries is arising from a variety of sources such as maternal antibodies, chronic enteropathy and other enteric diseases such as cholera, typhoid, and parasitic diseases, as well as the microbiota. There is increasingly evidence related to the risk of intussusception for the oral vaccine. The development of effective and safer rotavirus vaccines, particularly, non-living candidates, is critical. The aim of this review therefore is to explore some of …

In Vitro Antibacterial, Antibiofilm Activities, And Phytochemical Properties Of Posidonia Oceanica (L) Delile: An Endemic Mediterranean Seagrass, Ertugrul Ozbil, Mehmet Ilktac, Sultan Ogmen, Ovgu Isbilen, Jesus M Duran Ramirez, Jana Gomez, Jennifer N Walker, Ender Volkan

Faculty, Staff and Student Publications

In the antibiotic resistance era, utilizing understudied sources for novel antimicrobials or antivirulence agents can provide new advances against antimicrobial resistant pathogens. In this study, we aimed to investigate antibacterial and antibiofilm activities of Posidonia oceanica (L.) Delile against Enterococcus faecalis ATCC 29212, Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 700603 and several S. aureus clinical isolates obtained from medical devices, including patient urinary catheters and breast implant infections, with varying antibiotic recalcitrance profiles. The ethanolic and methanolic extracts from P. oceanica rhizome exhibited significant antibacterial activity against E. faecalis and S. aureus, as well …

Sounding The Alarm: Local Cues That Drive Functional Specialization Of Brain Resident Memory T Cells, Shawn Christopher Musial Jr.

Dartmouth College Ph.D Dissertations

Resident memory T cells are a unique subset of memory T cells that persist within tissues throughout the body, including the brain, optimally positioned to exert local immune activation. Broadly, T cells in the CNS are implicated in a range of neurologic disorders, can protect against reinfection, and even participate in normal CNS homeostasis. Despite this, there remain significant gaps in knowledge about how T cells, specifically resident memory T cells (T_RM), are regulated and function in the unique CNS environment. Here, we leverage a mouse model of acute viral infection to dissect the diversity of brain T …

An Indirect Elisa Using A Recombinant Envelope Protein For Detecting Antibody Against Duck Tembusu Virus Infection, Thaweesak Songserm

The Thai Journal of Veterinary Medicine

Duck Tembusu virus (DTMUV) belonging to Flavivirus group, causes severe central nervous system disorders and decreased egg production as found in Thailand. To detect antibody against the DTMUV infection, we developed an indirect enzyme-linked immunosorbent assay (ELISA) based on the recombinant envelop (E) protein for coating antigen. The E protein coding gene of KPS54A61DTMUV was cloned into pPICzαA vector and expressed by using 2% (v/v) of absolute methanol as inducer in Pichia pastoris expression. The recombinant E protein was detected in the culture medium at a concentration of 4.55 mg/ml and analyzed a protein expected size by SDS-PAGE at 65 …

Regulatory Complexity Of Cellular Differentiation In Candida Albicans Revealed Through Systematic Screening Of Protein Kinase Mutants, Michael C Lorenz

Faculty, Staff and Student Publications

A recent study in mBio reports the construction and preliminary screening of a library containing mutants of 99 of the 119 predicted protein kinases in Candida albicans (the majority of the remaining 20 are probably essential) (J. Kramara, M.-J. Kim, T. L. Ollinger, L. C. Ristow, et al., mBio e01249-24, 2024, https://doi.org/10.1128/mbio.01249-24). Using a quantitative competition assay in 10 conditions that represent nutritional, osmotic, cell wall, and pH stresses that are considered to model various aspects of the host environment allowed them to phenotypically cluster kinases, which highlight both the integration and specialization of signaling pathways, suggesting novel functions …