Digital Commons Network^™

"The In-Betweeners": The Lived Experience Of Adult Cochlear Implant Users, Aylah Sroloff

Antioch University Dissertations & Theses

This phenomenological study explored the lived experiences of adult cochlear implant (CI) users, implanted prior to the age of 10-years-old. Seven adult CI users were recruited. In-depth, semi-structured, qualitative interviews were conducted to explore participants’ experiences and identities as CI users. Transcripts were analyzed using interpretative phenomenological analysis, through which six group experimental themes were generated: (a) CIs and identity,” (b) social isolation, (c) advocacy, (d), costs and benefits of integration into the hearing world, and (e) “the future of CIs.” This study’s findings highlighted participants’ perspectives on living with CIs, the challenges they face, their process of identity exploration, …

Voluntary Wheel Running Prevents Formation Of Membrane Attack Complexes And Myelin Degradation After Peripheral Nerve Injury, Suzanne M Green-Fulgham, Michael J Lacagnina, Kendal F Willcox, Jiahe Li, Michael E Harland, Adriano Polican Ciena, Igor R Correia Rocha, Jayson B Ball, Renee A Dreher, Younus A Zuberi, Joseph M Dragavon, Marucia Chacur, Steven F Maier, Linda R Watkins, Peter M Grace

Faculty, Staff and Student Publications

Regular aerobic activity is associated with a reduced risk of chronic pain in humans and rodents. Our previous studies in rodents have shown that prior voluntary wheel running can normalize redox signaling at the site of peripheral nerve injury, attenuating subsequent neuropathic pain. However, the full extent of neuroprotection offered by voluntary wheel running after peripheral nerve injury is unknown. Here, we show that six weeks of voluntary wheel running prior to chronic constriction injury (CCI) reduced the terminal complement membrane attack complex (MAC) at the sciatic nerve injury site. This was associated with increased expression of the MAC inhibitor …

Hypoxia-Adenosine Axis As Therapeutic Targets For Acute Respiratory Distress Syndrome, Katherine Figarella, Jieun Kim, Wei Ruan, Tingting Mills, Holger Klaus Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

The human respiratory and circulatory systems collaborate intricately to ensure oxygen delivery to all cells, which is vital for ATP production and maintaining physiological functions and structures. During limited oxygen availability, hypoxia-inducible factors (HIFs) are stabilized and play a fundamental role in maintaining cellular processes for hypoxia adaptation. First discovered during investigations of erythropoietin production regulation, HIFs influence physiological and pathological processes, including development, inflammation, wound healing, and cancer. HIFs promote extracellular adenosine signaling by enhancing adenosine generation and receptor signaling, representing an endogenous feedback mechanism that curbs excessive inflammation, supports injury resolution, and enhances hypoxia tolerance. This is especially …

First Evidence Of Microplastic Inhalation Among Free-Ranging Small Cetaceans, Miranda K Dziobak, Andreas Fahlman, Randall S Wells, Ryan Takeshita, Cynthia Smith, Austin Gray, John Weinstein, Leslie B Hart

Faculty, Staff and Student Publications

Plastic is a ubiquitous environmental contaminant, resulting in widespread exposure across terrestrial and marine spaces. In the environment, plastics can degrade into microparticles where exposure has been documented in a variety of fauna at all trophic levels. Human epidemiological studies have found relationships between inhaled microplastics and oxidative stress and inflammation. Previous studies of bottlenose dolphins (Tursiops truncatus) have reported prevalent exposure to plasticizing chemicals (e.g., phthalates) as well as particle loads in gastrointestinal tracts, but exposure from inhalation has not yet been studied. The objective of this study was to determine if inhalation is a viable route of microplastic …

In Vivo Scanning Laser Fundus And High-Resolution Oct Imaging Of Retinal Ganglion Cell Injury In A Non-Human Primate Model With An Activatable Fluorescent-Labeled Tat Peptide Probe, Xudong Qiu, Seth T Gammon, Carol Rasmussen, Federica Pisaneschi, Charlene B Y Kim, James Ver Hoeve, Steven W Millward, Edward M Barnett, T Michael Nork, Paul L Kaufman, David Piwnica-Worms

Faculty, Staff and Student Publications

The optical imaging agent TcapQ488 has enabled imaging of retinal ganglion cell (RGC) injury in vivo in rodents and has potential as an effective diagnostic probe for early detection and intervention monitoring in glaucoma patients. In the present study, we investigated TcapQ488 in non-human primates (NHPs) to identify labeling efficacy and early signals of injured RGC, to determine species-dependent changes in RGC probe uptake and clearance, and to determine dose-limiting toxicities. Doses of 3, 6, and 12 nmol of TcapQ488 were delivered intravitreally to normal healthy NHP eyes and eyes that had undergone hemiretinal endodiathermy axotomy (HEA) in the inferior …

Case Report: Early Acute Kidney Failure In An 11-Year-Old Boy With Dent Disease Type 1, Nicolette Murphey, Craig Authement, Paul Hillman, Samhar I Al-Akash, Kate Richardson

Faculty, Staff and Student Publications

Dent disease type 1 (Dent 1) is a rare X-linked genetic condition which impacts kidney function and is caused by pathogenic variants in CLCN5. Affected males typically develop low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and other symptoms. Kidney failure often occurs between the third to fifth decade of life. Here, we report an 11-year-old boy with Dent 1 and a severe kidney disease phenotype. The patient presented with flank pain, nocturnal enuresis, foamy urine, and increased urinary frequency. He was found to have nephrotic-range proteinuria, without hypoalbuminemia, and a significantly decreased estimated glomerular filtration rate at presentation. Further, he …

Meta-Analysis Of The Vmp-Like Sequences Of Lyme Disease Borrelia: Evidence For The Evolution Of An Elaborate Antigenic Variation System, Steven J Norris, Kalvis Brangulis

Faculty, Staff and Student Publications

VMP-like sequence (vls) antigenic variation systems are present in every Lyme disease Borrelia strain with complete genome sequences. The linear plasmid-encoded vls system consists of a single expression site (vlsE) and contiguous array(s) of silent cassettes that have ~90% identity with the central cassette region of the cognate vlsE gene; antigenic variation occurs through random, segmental, and unidirectional recombination of vls silent cassette sequences into the vlsE expression site. Automated annotation programs do not accurately recognize vls silent cassette sequences, so these regions are not correctly annotated in most genomic sequences. In this study, the vls …

Tissue Transglutaminase: A Multifunctional And Multisite Regulator In Health And Disease, Zhouzhou Yao, Yuhua Fan, Lizhen Lin, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Tissue transglutaminase (TG2) is a widely distributed multifunctional protein involved in a broad range of cellular and metabolic functions carried out in a variety of cellular compartments. In addition to transamidation, TG2 also functions as a Gα signaling protein, a protein disulfide isomerase (PDI), a protein kinase, and a scaffolding protein. In the nucleus, TG2 modifies histones and transcription factors. The PDI function catalyzes the trimerization and activation of heat shock factor-1 in the nucleus and regulates the oxidation state of several mitochondrial complexes. Cytosolic TG2 modifies proteins by the addition of serotonin or other primary amines and in this …

Fa4sans-Gan: A Novel Machine Learning Generative Adversarial Network To Further Understand Ophthalmic Changes In Spaceflight Associated Neuro-Ocular Syndrome (Sans), Sharif Amit Kamran, Khondker Fariha Hossain, Joshua Ong, Ethan Waisberg, Nasif Zaman, Salah A Baker, Andrew G Lee, Alireza Tavakkoli

Faculty, Staff and Student Publications

PURPOSE: To provide an automated system for synthesizing fluorescein angiography (FA) images from color fundus photographs for averting risks associated with fluorescein dye and extend its future application to spaceflight associated neuro-ocular syndrome (SANS) detection in spaceflight where resources are limited.

DESIGN: Development and validation of a novel conditional generative adversarial network (GAN) trained on limited amount of FA and color fundus images with diabetic retinopathy and control cases.

PARTICIPANTS: Color fundus and FA paired images for unique patients were collected from a publicly available study.

METHODS: FA4SANS-GAN was trained to generate FA images from color fundus photographs using 2 …

From Mitochondria To Tumor Suppression: Acat1’S Crucial Role In Gastric Cancer, Wei He, Yanfang Li, Song-Bai Liu, Ying Chang, Shiyuan Han, Xingyu Han, Zixin Ma, Hesham M Amin, Yao-Hua Song, Jin Zhou

Faculty, Staff and Student Publications

Acetyl CoA acetyltransferase 1 (ACAT1), a mitochondrial enzyme, is mainly involved in the formation and decomposition of ketones, isoleucine, and fatty acids. Previous clinical studies showed that mutations in the ACAT1 gene lead to ketoacidosis, Notably the role of ACAT1 in human cancer' pathogenesis varies depending on cancer type, and its specific role in gastric cancer remains largely unknown. In the current study, we found that the expression of ACAT1 in primary late-stage gastric cancer tumor tissues was significantly lower than in early-stage tumors. This observation was further confirmed in high-grade gastric cancer cell line MKN45. The expression of CD44 …

Dysregulation Of Epigenetic Modifications In Inborn Errors Of Immunity, Zhongyao Xiao, Rongjing He, Zihan Zhao, Taiping Chen, Zhengzhou Ying

Faculty, Staff and Student Publications

Inborn errors of immunity (IEIs) are a group of typically monogenic disorders characterized by dysfunction in the immune system. Individuals with these disorders experience increased susceptibility to infections, autoimmunity and malignancies due to abnormal immune responses. Epigenetic modifications, including DNA methylation, histone modifications and chromatin remodeling, have been well explored in the regulation of immune cell development and effector function. Aberrant epigenetic modifications can disrupt gene expression profiles crucial for immune responses, resulting in impaired immune cell differentiation and function. Dysregulation of these processes caused by mutations in genes involving in epigenetic modifications has been associated with various IEIs. In …

Sustained Pain And Macrophage Infiltration In A Mouse Muscle Contusion Model, Ibdanelo Cortez, Caitlyn M Gaffney, Caitlin V Crelli, Eric Lee, James M Nichols, Hoang Vu Pham, Syed Mehdi, Jelena M Janjic, Andrew J Shepherd

Faculty, Staff and Student Publications

Introduction/aims: Prior studies have emphasized the role of inflammation in the response to injury and muscle regeneration, but little emphasis has been placed on characterizing the relationship between innate inflammation, pain, and functional impairment. The aim of our study was to determine the contribution of innate immunity to prolonged pain following muscle contusion.

Methods: We developed a closed-impact mouse model of muscle contusion and a macrophage-targeted near-infrared fluorescent nanoemulsion. Closed-impact contusions were delivered to the lower left limb. Pain sensitivity, gait dysfunction, and inflammation were assessed in the days and weeks post-contusion. Macrophage accumulation was imaged in vivo by injecting …

Invasion Of Superbugs: Cockroach-Driven Outbreak Of Multidrug-Resistant Enterobacter In An Icu, Jennifer Hanrahan, Nicholas Schouten, Steven H. Fyffe, Annette Jencson, Stephanie Stroever

Department of Medicine Faculty Publications

Objective: To describe factors in an outbreak of multidrug-resistant Enterobacter cloacae (MRE) in an intensive care unit (ICU) over a 20-month period including the likely contribution of cockroaches to the outbreak.

Design: This is a retrospective descriptive study.

Setting: ICU in an urban hospital.

Patients: All patients admitted to the ICU during the 20-month outbreak period were included in the study.

Interventions: Infection prevention interventions included contact isolation, hand hygiene, dedicated patient equipment, environmental cultures, and pest control.

Results: 25 patients were identified as being colonized or infected with MRE. Relatedness of the outbreak strain and strains found in cockroaches …

In Vivo Measurement Of Nadh Fluorescence Lifetime In Skeletal Muscle Via Fiber-Coupled Time-Correlated Single Photon Counting, Kathryn M. Priest, Jacob V. Schluns, Nathania Nischal, Colton L. Gattis, Jeffery C. Wolchok, Timothy J. Muldoon

Biomedical Engineering Faculty Publications and Presentations

Nicotinamide adenine dinucleotide (NADH) is a cofactor that serves to shuttle electrons during metabolic processes such as glycolysis, the tricarboxylic acid cycle, and oxidative phosphorylation (OXPHOS). NADH is autofluorescent, and its fluorescence lifetime can be used to infer metabolic dynamics in living cells. Fiber-coupled time-correlated single photon counting (TCSPC) equipped with an implantable needle probe can be used to measure NADH lifetime in vivo, enabling investigation of changing metabolic demand during muscle contraction or tissue regeneration. This study illustrates a proof of concept for point-based, minimally-invasive NADH fluorescence lifetime measurement in vivo. Volumetric muscle loss (VML) injuries were …

Usp22 Overexpression Fails To Augment Tumor Formatiaon In Mmtv-Erbb2 Mice But Loss Of Function Impacts Mmtv Promoter Activity, Xianghong Kuang, Andrew Salinger, Fernando Benavides, William J Muller, Sharon Y R Dent, Evangelia Koutelou

Faculty, Staff and Student Publications

The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting …

Multiple Unfolded Protein Response Pathways Cooperate To Link Cytosolic Dsdna Release To Stimulator Of Interferon Gene Activation, Tiancheng Hu, Yiping Liu, Jeremy Fleck, Cason King, Elaine Schalk, Zhenyu Zhang, Andrew Mehle, Judith A Smith

Faculty, Staff and Student Publications

The double-stranded DNA (dsDNA) sensor STING has been increasingly implicated in responses to "sterile" endogenous threats and pathogens without nominal DNA or cyclic di-nucleotide stimuli. Previous work showed an endoplasmic reticulum (ER) stress response, known as the unfolded protein response (UPR), activates STING. Herein, we sought to determine if ER stress generated a STING ligand, and to identify the UPR pathways involved. Induction of IFN-β expression following stimulation with the UPR inducer thapsigargin (TPG) or oxygen glucose deprivation required both STING and the dsDNA-sensing cyclic GMP-AMP synthase (cGAS). Furthermore, TPG increased cytosolic mitochondrial DNA, and immunofluorescence visualized dsDNA punctae in …

Image-Guided Deployment And Monitoring Of A Novel Tungsten Nanoparticle-Infused Radiopaque Absorbable Inferior Vena Cava Filter In A Swine Model, Erin Marie San Valentin, Jossana A Damasco, Marvin Bernardino, Karem A Court, Biana Godin, Gino Martin Canlas, Adam Melancon, Gouthami Chintalapani, Megan C Jacobsen, William Norton, Rick R Layman, Natalie Fowlkes, Stephen R Chen, Steven Y Huang, Marites P Melancon

Faculty, Staff and Student Publications

PURPOSE: To improve radiopacity of radiolucent absorbable poly-p-dioxanone (PPDO) inferior vena cava filters (IVCFs) and demostrate their effectiveness in clot-trapping ability.

MATERIALS AND METHODS: Tungsten nanoparticles (WNPs) were incorporated along with polyhydroxybutyrate (PHB), polycaprolactone (PCL), and polyvinylpyrrolidone (PVP) polymers to increase the surface adsorption of WNPs. The physicochemical and in vitro and in vivo imaging properties of PPDO IVCFs with WNPs with single-polymer PHB (W-P) were compared with those of WNPs with polymer blends consisting of PHB, PCL, and PVP (W-PB).

RESULTS: In vitro analyses using PPDO sutures showed enhanced radiopacity with either W-P or W-PB coating, without compromising the …

Diet-Stimulated Marrow Adiposity Fails To Worsen Early, Age-Related Bone Loss, Cody Mcgrath, Sarah E Little-Letsinger, Gabriel M Pagnotti, Buer Sen, Zhihui Xie, Gunes Uzer, Guniz B Uzer, Xiaopeng Zong, Martin A Styner, Janet Rubin, Maya Styner

Faculty, Staff and Student Publications

Introduction: Longitudinal effect of diet-induced obesity on bone is uncertain. Prior work showed both no effect and a decrement in bone density or quality when obesity begins prior to skeletal maturity. We aimed to quantify long-term effects of obesity on bone and bone marrow adipose tissue (BMAT) in adulthood.

Methods: Skeletally mature, female C57BL/6 mice (n = 70) aged 12 weeks were randomly allocated to low-fat diet (LFD; 10% kcal fat; n = 30) or high-fat diet (HFD; 60% kcal fat; n = 30), with analyses at 12, 15, 18, and 24 weeks (n = 10/group). Tibial microarchitecture was analyzed …

Single-Cell Rna Sequencing Analysis Identifies Acute Changes In The Tumor Microenvironment Induced By Interferon Α Gene Therapy In A Murine Bladder Cancer Model, Alexis R Steinmetz, Morgan Pierce, Alberto Martini, Come Tholomier, Ganiraju Manyam, Yan Chen, Akshay Sood, Jonathan J Duplisea, Burles A Johnson, Bogdan A Czerniak, Byron H Lee, Chinnaswamy Jagannath, Seppo Yla-Herttuala, Nigel R Parker, David J Mcconkey, Colin P Dinney, Sharada Mokkapati

Faculty, Staff and Student Publications

Introduction: Nadofaragene firadenovec (Ad-IFNα/Syn3) is now approved for BCG-unresponsive bladder cancer (BLCA). IFNα is a pleiotropic cytokine that causes direct tumor cell killing via TRAIL-mediated apoptosis, angiogenesis inhibition, and activation of the innate and adaptive immune system. We established an immunocompetent murine BLCA model to study the effects of murine adenoviral IFNα (muAd-Ifnα) gene therapy on cancer cells and the tumor microenvironment using a novel murine equivalent of Nadofaragene firadenovec (muAd-Ifnα).

Methods: Tumors were induced by instilling MB49 cells into the bladders of mice; luciferase imaging confirmed tumor development. Mice were treated with adenovirus control (Ad-Ctrl; empty vector), or muAd-Ifnα …

Documentation Of International Classification Of Headache Disorders Criteria In Patient Medical Records: A Retrospective Cohort Analysis., Michelle Pershing, Omkar Hirekhan, Azfar Syed, John O Elliott, Jonathan Toot

Ambulatory and Primary Care Articles

OBJECTIVE: To determine headache diagnosis and treatment patterns in the outpatient setting, focusing on documentation of the International Classification of Headache Disorders (ICHD) criteria.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort data were collected from electronic medical records of adults aged 18-35 who presented to resident-staffed family medicine outpatient clinics in the Midwest, USA, for a new or worsening headache between 2015 and 2016. Diagnosis codes were used to summarize the overall nature and prevalence of headaches. A random subset of 30 patients each for migraine headache (MGH) with and without aura and tension-type headache (TTH) were reviewed to determine how …

Pathophysiology Of Pain And Mechanisms Of Neuromodulation: A Narrative Review (A Neuron Project)., Marcin Karcz, Alaa Abd-Elsayed, Krishnan Chakravarthy, Mansoor M Aman, Natalie Strand, Mark N Malinowski, Usman Latif, David Dickerson, Tolga Suvar, Timothy Lubenow, Evan Peskin, Ryan D'Souza, Eric Cornidez, Andrew Dudas, Christopher Lam, Michael Farrell Ii, Geum Yeon Sim, Mohamad Sebai, Rosa Garcia, Lucas Bracero, Yussr Ibrahim, Syed Jafar Mahmood, Marco Lawandy, Daniel Jimenez, Leili Shahgholi, Kamil Sochacki, Mohamed Ehab Ramadan, Vinicius Tieppo Francio, Dawood Sayed, Timothy Deer

Neuroscience Articles

Pain serves as a vital innate defense mechanism that can significantly impact an individual's quality of life. Understanding the physiological effects of pain well plays an important role in developing novel pain treatments. Nociceptor neurons play a key role in pain and inflammation. Interactions between nociceptors and the immune system occur both at the site of injury and within the central nervous system. Modulating chemical mediators and nociceptor activity offers promising new approaches to pain management. Essentially, the sensory nervous system is essential for modulating the body's protective response, making it critical to understand these interactions to discover new pain …

Risk Stratification And Prediction Of Severity Of Covid-19 Infection In Patients With Preexisting Cardiovascular Disease, Stanislava Matejin, Igor D Gregoric, Rajko Radovancevic, Slobodan Paessler, Vladimir Perovic

Faculty, Staff and Student Publications

Introduction: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a highly contagious viral disease. Cardiovascular diseases and heart failure elevate the risk of mechanical ventilation and fatal outcomes among COVID-19 patients, while COVID-19 itself increases the likelihood of adverse cardiovascular outcomes.

Methods: We collected blood samples and clinical data from hospitalized cardiovascular patients with and without proven COVID-19 infection in the time period before the vaccine became available. Statistical correlation analysis and machine learning were used to evaluate and identify individual parameters that could predict the risk of needing mechanical ventilation and patient survival.

Results: Our results confirmed that COVID-19 …

Therapeutic Efficacy Of A Potent Anti-Venezuelan Equine Encephalitis Virus Antibody Is Contingent On Fc Effector Functionslc6a1 Variant Pathogenicity, Molecular Function And Phenotype: A Genetic And Clinical Analysis, Jennifer L Schwedler, Maxwell A Stefan, Christine E Thatcher, Peter R Mcilroy, Anupama Sinha, Ashlee M Phillips, Christopher A Sumner, Colleen M Courtney, Christina Y Kim, Dina R Weilhammer, Brooke Harmon

Faculty, Staff and Student Publications

The development of specific, safe, and potent monoclonal antibodies (Abs) has led to novel therapeutic options for infectious disease. In addition to preventing viral infection through neutralization, Abs can clear infected cells and induce immunomodulatory functions through engagement of their crystallizable fragment (Fc) with complement proteins and Fc receptors on immune cells. Little is known about the role of Fc effector functions of neutralizing Abs in the context of encephalitic alphavirus infection. To determine the role of Fc effector function in therapeutic efficacy against Venezuelan equine encephalitis virus (VEEV), we compared the potently neutralizing anti-VEEV human IgG F5 (hF5) Ab …

Enhancing Breast Cancer Treatment: Mesoporous Dopamine Nanoparticles In Synergy With Chrysin For Photothermal Therapy, Jing Zhu, Heng Zhang, Haomiao Lan, Bing Bi, Xianfeng Peng, Dandan Li, Haili Wang, Ke Zhu, Fuqiang Shao, Minggang Yin

Research outputs 2022 to 2026

Introduction: Breast cancer is one of the most prevalent cancers, primarily affecting women. Among its subtypes, estrogen receptor-positive (ER+) breast cancer is particularly common. Inhibiting estrogen's effects is crucial for treating ER+ breast cancer, but current therapies often have significant side effects and limitations. Chrysin, a natural flavonoid, has shown potential in reducing estrogen receptor expression, but its poor water solubility hampers clinical application. This study explores the use of mesoporous dopamine nanoparticles (mPDA) to enhance the delivery and efficacy of Chrysin, combined with photothermal therapy (PTT), for breast cancer treatment. Methods: Chrysin-loaded mPDA nanoparticles (Chrysin@mPDA) were synthesized and characterized …

Preclinical Evaluation Of A Novel Antibiotic-Eluting Bioenvelope For Cied Infection Prevention, Zerelda Esquer Garrigos, John N Catanzaro, Daniel Deegan, Ji Zhang, M Rizwan Sohail

Faculty, Staff and Students Publications

The risk of infection remains a significant concern with cardiovascular implantable electronic devices, necessitating the development of new strategies. This study explores the efficacy of a novel antibiotic-eluting biologic envelope designed to mitigate infection risk through localized antibiotic delivery while preserving the regenerative properties of biological matrix. Antibiotics, rifampin and minocycline, are released through polymer discs, ensuring extended drug release. Utilizing an established model of infection in a New Zealand White rabbit, the study assessed performance against Gram-positive bacterial strains, including common pathogens such as Staphylococcus aureus and S. epidermidis associated with CIED infections, and Gram-negative bacterial strains. Results demonstrated …

Detection Of Invasive Bartonella Infections With Next-Generation Sequencing Of Microbial Cell-Free Dna, Fernando H Centeno, Ahmed M Hamdi, Todd M Lasco, Mayar Al Mohajer

Faculty, Staff and Students Publications

We report 9 patients with invasive Bartonella infections, including 5 with endocarditis, who were diagnosed with microbial cell-free DNA next-generation sequencing and Bartonella serology studies. Diagnosis with plasma mcfDNA NGS enabled a faster clinical and laboratory diagnosis in 8 patients. Prompt diagnosis impacted antibiotic management in all 9 patients.

The Uterine Secretome Initiates Growth Of Gynecologic Tissues In Ectopic Locations, Jan Sunde, Morgan Wasickanin, Tiffany A Katz, Laurel Gillette, Sanam Bidadi, Derek O'Neil, Ramya Masand, Richard O Burney, Kathleen A Pennington

Faculty, Staff and Students Publications

Endosalpingiosis (ES) and endometriosis (EM) refer to the growth of tubal and endometrial epithelium respectively, outside of their site of origin. We hypothesize that uterine secretome factors drive ectopic growth. To test this, we developed a mouse model of ES and EM using tdTomato (tdT) transgenic fluorescent mice as donors. To block implantation factors, progesterone knockout (PKO) tdT mice were created. Fluorescent lesions were present after oviduct implantation with and without WT endometrium. Implantation was increased (p<0.05) when tdt oviductal tissue was implanted with endometrium compared to oviductal tissue alone. Implantation was reduced (p<0.0005) in animals implanted with minced tdT oviductal tissue with PKO tdT endometrium compared to WT endometrium. Finally, oviductal tissues was incubated with and without a known implantation factor, leukemia inhibitory factor (LIF) prior to and during implantation. LIF promoted lesion implantation. In conclusion, endometrial derived implantation factors, such as LIF, are necessary to initiate ectopic tissue growth. We have developed an animal model of ectopic growth of gynecologic tissues in a WT mouse which will potentially allow for development of new prevention and treatment modalities.

Single Cell Analysis Of Short-Term Dry Eye Induced Changes In Cornea Immune Cell Populations, Jehan Alam, Ebru Yaman, Gerda Cristal Villalba Silva, Rui Chen, Cinita S De Paiva, Mary Ann Stepp, Stephen C Pflugfelder

Faculty, Staff and Students Publications

BACKGROUND: Dry eye causes corneal inflammation, epitheliopathy and sensorineural changes. This study evaluates the hypothesis that dry eye alters the percentages and transcriptional profiles of immune cell populations in the cornea.

METHODS: Desiccating stress (DS) induced dry eye was created by pharmacologic suppression of tear secretion and exposure to drafty low humidity environment. Expression profiling of corneal immune cells was performed by single-cell RNA sequencing (scRNA-seq). Cell differentiation trajectories and cell fate were modeled through RNA velocity analysis. Confocal microscopy was used to immunodetect corneal immune cells. Irritation response to topical neurostimulants was assessed.

RESULTS: Twelve corneal immune cell populations …

Inhibition Of Src-3 As A Potential Therapeutic Strategy For Aggressive Mantle Cell Lymphoma, Imani Bijou, Yang Liu, Dong Lu, Jianwei Chen, Shelby Sloan, Lapo Alinari, David M Lonard, Bert W O'Malley, Michael Wang, Jin Wang

Faculty, Staff and Students Publications

Mantle cell lymphoma (MCL) has a poor prognosis and high relapse rates despite current therapies, necessitating novel treatment regimens. Inhibition of SRC-3 show effectiveness in vivo and in vitro in other B cell lymphomas. Additionally, previous studies have shown that SRC-3 is highly expressed in the lymph nodes of B cell non-Hodgkin's lymphoma patients, suggesting SRC-3 may play a role in the progression of B cell lymphoma. This study aimed to investigate novel SRC-3 inhibitors, SI-10 and SI-12, in mantle cell lymphoma. The cytotoxic effects of SI-10 and SI-12 were evaluated in vitro and demonstrated dose-dependent cytotoxicity in a panel …

Β2-Glycoprotein I Promotes The Clearance Of Circulating Mitochondria, Swapan Kumar Dasgupta, Jahnavi Gollamudi, Stefanie Rivera, Ross A Poche, Rolando E Rumbaut, Perumal Thiagarajan

Faculty, Staff and Students Publications

β2-glycoprotein I (β2-Gp1) is a cardiolipin-binding plasma glycoprotein. It is evolutionarily conserved from invertebrates, and cardiolipin-bound β2-Gp1 is a major target of antiphospholipid antibodies seen in autoimmune disorders. Cardiolipin is almost exclusively present in mitochondria, and mitochondria are present in circulating blood. We show that β2-Gp1 binds to cell-free mitochondria (CFM) in the circulation and promotes its phagocytosis by macrophages at physiological plasma concentrations. Exogenous CFM had a short circulation time of less than 10 minutes in mice. Following infusion of CFM, β2-Gp1-deficient mice had significantly higher levels of transfused mitochondria at 5 minutes (9.9 ± 6.4 pg/ml versus 4.0 …