Medicine and Health Sciences Commons^™

Mirnas Signature As Potential Biomarkers For Cervical Precancerous Lesions In Human Papillomavirus Positive Women, Martha I. González-Ramírez, Yurley T. Cardona, María C. Agudelo, Carolina López, Juan J. Florez-Acosta, Samuel Agudelo-Gamboa, Jone Garai, Li Li, Carlos A. Orozco-Castaño, Jovanny Zabaleta, Gloria I. Sánchez

School of Medicine Faculty Publications

Biomarkers to identify women at risk of cervical cancer among those with high-risk HPV infection (hrHPV+) are needed. Deregulated expression of microRNAs (miRNAs) contributes to hrHPV-induced cervical carcinogenesis. We aimed at identifying miRNAs with the capacity to distinguish high (CIN2+) and low (≤ CIN1) grade cervical lesions. We sequenced miRNA libraries from Formalin-Fixed Paraffin-Embedded (FFPE) tissues from women with CIN2+ (n = 10) and age-matched women with ≤ CIN1 (n = 10), randomly and retrospectively selected from a trial that followed women for 24 months after a hrHPV+ test at the screening visit. Five miRNAs differentially expressed were validated by …

7-Ketocholesterol Promotes Retinal Pigment Epithelium Senescence And Fibrosis Of Choroidal Neovascularization Via Iqgap1 Phosphorylation-Dependent Signaling, Haibo Wang, Aniket Ramshekar, Thaonhi Cung, Chris Wallace-Carrete, Chandler Zaugg, Jasmine Nguyen, Gregory J. Stoddard, M. Elizabeth Hartnett

School of Medicine Faculty Publications

Accumulation of 7-ketocholesterol (7KC) occurs in age-related macular degeneration (AMD) and was found previously to promote fibrosis, an untreatable cause of vision loss, partly through induction of endothelial-mesenchymal transition. To address the hypothesis that 7KC causes mesenchymal transition of retinal pigment epithelial cells (RPE), we exposed human primary RPE (hRPE) to 7KC or a control. 7KC-treated hRPE did not manifest increased mesenchymal markers, but instead maintained RPE-specific proteins and exhibited signs of senescence with increased serine phosphorylation of histone H3, serine/threonine phosphorylation of mammalian target of rapamycin (p-mTOR), p16 and p21, β-galactosidase labeling, and reduced LaminB1, suggesting senescence. The cells …

Gata6-As1 Regulates Intestinal Epithelial Mitochondrial Functions, And Its Reduced Expression Is Linked To Intestinal Inflammation And Less Favourable Disease Course In Ulcerative Colitis, Katya E Sosnovski, Tzipi Braun, Amnon Amir, Danielle Moshel, Marina Benshoshan, Kelli L Vandussen, Nina Levhar, Haya Abbas-Egbariya, Katia Beider, Rakefet Ben-Yishay, Syed Asad Ali, Sean R Moore, Subra Kugathasan, Ifat Abramovich, Efrat Glick Saar, Batya Weiss, Iris Barshack, Eyal Gottlieb, Tamar Geiger, Shomron Ben-Horin, Igor Ulitsky, Jeffrey S Hyams, Lee A Denson, Yael Haberman

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Widespread dysregulation of long non-coding RNAs [lncRNAs] including a reduction in GATA6-AS1 was noted in inflammatory bowel disease [IBD]. We previously reported a prominent inhibition of epithelial mitochondrial functions in ulcerative colitis [UC]. However, the connection between reduction of GATA6-AS1 expression and attenuated epithelial mitochondrial functions was not defined.

METHODS: Mucosal transcriptomics was used to conform GATA6-AS1 reduction in several treatment-naïve independent human cohorts [n=673]. RNA pull-down followed by mass spectrometry was used to determine the GATA6-AS1 interactome. Metabolomics and mitochondrial respiration following GATA6-AS1 silencing in Caco-2 cells were used to elaborate on GATA6-AS1 functions.

RESULTS: GATA6-AS1 …

Targeting Energy Intake And Circadian Biology To Engage Mechanisms Of Aging In Older Adults With Obesity: Calorie Restriction And Time-Restricted Eating, Satchidananda Panda, Geraldine Maier, Dennis T Villareal

Faculty, Staff and Students Publications

With the rise in obesity across age groups, it has been a hindrance to engaging in physical activity and mobility in older adults. Daily calorie restriction (CR) up to 25% has been the cornerstone of obesity management even though the safety in older adults remains incompletely understood. Although some adults can follow CR with clinically significant weight loss and improved health metrics, CR faces 2 obstacles-many fail to adopt CR and even among those who can adopt it short term, long-term compliance can be difficult. Furthermore, there is a continuing debate about the net benefits of CR-induced weight loss in …

Coronavirus Disease 2019 Convalescent Plasma Outpatient Therapy To Prevent Outpatient Hospitalization: A Meta-Analysis Of Individual Participant Data From 5 Randomized Trials, Adam C Levine, Yuriko Fukuta, Moises A Huaman, Jiangda Ou, Barry R Meisenberg, Bela Patel, James H Paxton, Daniel F Hanley, Bart J A Rijnders, Arvind Gharbharan, Casper Rokx, Jaap Jan Zwaginga, Andrea Alemany, Oriol Mitjà, Dan Ouchi, Pere Millat-Martinez, Valerie Durkalski-Mauldin, Frederick K Korley, Larry J Dumont, Clifton W Callaway, Romina Libster, Gonzalo Perez Marc, Diego Wappner, Ignacio Esteban, Fernando Polack, David J Sullivan

Faculty, Staff and Students Publications

BACKGROUND: Outpatient monoclonal antibodies are no longer effective and antiviral treatments for coronavirus disease 2019 (COVID-19) disease remain largely unavailable in many countries worldwide. Although treatment with COVID-19 convalescent plasma (CCP) is promising, clinical trials among outpatients have shown mixed results.

METHODS: We conducted an individual participant data meta-analysis from outpatient trials to assess the overall risk reduction for all-cause hospitalizations by day 28 in transfused participants. Relevant trials were identified by searching Medline, Embase, medRxiv, World Health Organization COVID-19 Research Database, Cochrane Library, and Web of Science from January 2020 to September 2022.

RESULTS: Five included studies from 4 …

Transmembrane Stem Factor Nanodiscs Enhanced Revascularization In A Hind Limb Ischemia Model In Diabetic, Hyperlipidemic Rabbits, Eri Takematsu, Miles Massidda, Gretchen Howe, Julia Goldman, Patricia Felli, Lei Mei, Gregory Callahan, Andrew Sligar, Richard Smalling, Aaron Baker

Faculty, Staff and Student Publications

Therapies to revascularize ischemic tissue have long been a goal for the treatment of vascular disease and other disorders. Therapies using stem cell factor (SCF), also known as a c-Kit ligand, had great promise for treating ischemia for myocardial infarct and stroke, however clinical development for SCF was stopped due to toxic side effects including mast cell activation in patients. We recently developed a novel therapy using a transmembrane form of SCF (tmSCF) delivered in lipid nanodiscs. In previous studies, we demonstrated tmSCF nanodiscs were able to induce revascularization of ischemia limbs in mice and did not activate mast cells. …

Tonb-Dependent Receptor Protein Displayed On Spores Of Bacillus Subtilis Stimulates Protective Immune Responses Against Acinetobacter Baumannii, Nor-Aziyah Matrahim, Kathryn Marie Jones, Brian P Keegan, Ulrich Strych, Bin Zhan, Hai-Yen Lee, Sazaly Abubakar

Faculty, Staff and Students Publications

The emergence of antibiotic-resistant Acinetobacter baumannii strains with limited treatment options has become a significant global health concern. Efforts to develop vaccines against the bacteria have centred on several potential protein targets, including the TonB-dependent receptors (TBDRs). In the present study, TBDRs from A. baumannii were displayed on the surface of Bacillus subtilis spores. The immunogenicity of the recombinant spores was evaluated in orally vaccinated mice. None of the immunized mice demonstrated signs of illness and were observed to be healthy throughout the study. Sera and the intestinal secretions from the recombinant spores-treated mice demonstrated mucosal and humoral antibody responses …

Lifelong Fitness In Ambulatory Children And Adolescents With Cerebral Palsy Ii: Influencing The Trajectory, Susan V. Duff, Justine D. Kimbel, Marybeth Grant-Beuttler, Theresa Sukal-Moulton, Noelle G. Moreau, Kathleen M. Friel

Physical Therapy Faculty Articles and Research

Physical activity of at least moderate intensity in all children contributes to higher levels of physical and psychological health. While essential, children with cerebral palsy (CP) often lack the physical capacity, resources, and knowledge to engage in physical activity at a sufficient intensity to optimize health and well-being. Low levels of physical activity place them at risk for declining fitness and health, contributing to a sedentary lifestyle. From this perspective, we describe a framework to foster a lifelong trajectory of fitness in ambulatory children with CP (GMFCS I–III) as they progress into adolescence and adulthood, implemented in conjunction with a …

Incubation With Porcine Urinary Bladder Matrix Yields A Late-Stage Wound Transcriptome In Endothelial Cells And Keratinocytes Isolated From Both Diabetic And Non-Diabetic Subjects, John T. Paige, Daniel J. Lightell, Hunter F. Douglas, Natasha C. Klingenberg, Thaidan Pham, T. Cooper Woods

School of Medicine Faculty Publications

Proper wound closure requires the functional coordination of endothelial cells (ECs) and keratinocytes. In the late stages of wound healing, keratinocytes become activated and ECs promote the maturation of nascent blood vessels. In diabetes mellitus, decreased keratinocyte activation and impaired angiogenic action of ECs delay wound healing. Porcine urinary bladder matrix (UBM) improves the rate of wound healing, but the effect of exposure to UBM under diabetic conditions remains unclear. We hypothesized that keratinocytes and ECs isolated from both diabetic and non-diabetic donors would exhibit a similar transcriptome representative of the later stages of wound healing following incubation with UBM. …

Contribution Of The Oral And Gastrointestinal Microbiomes To Bloodstream Infections In Leukemia Patients, Stephanie Mcmahon, Pranoti Sahasrabhojane, Jiwoong Kim, Samantha Franklin, Chia-Chi Chang, Robert R Jenq, Andrew E Hillhouse, Samuel A Shelburne, Jessica Galloway-Peña

Faculty, Staff and Student Publications

Bloodstream infections (BSIs) pose a significant mortality risk for acute myeloid leukemia (AML) patients. It has been previously reported that intestinal domination (>30% relative abundance [RA] attributed to a single taxon) with the infecting taxa often precedes BSI in stem cell transplant patients. Using 16S rRNA amplicon sequencing, we analyzed oral and stool samples from 63 AML patients with BSIs to determine the correlation between the infectious agent and microbiome composition. Whole-genome sequencing and antimicrobial susceptibilities were performed on all BSI isolates. Species-level detection of the infectious agent and presence of antibiotic resistance determinants in the stool (

Hematopoietic Progenitor Kinase 1 Inhibits The Development And Progression Of Pancreatic Intraepithelial Neoplasia, Hua Wang, Rohan Moniruzzaman, Lei Li, Baoan Ji, Yi Liu, Xiangsheng Zuo, Reza Abbasgholizadeh, Jun Zhao, Guangchao Liu, Ruiqi Wang, Hongli Tang, Ryan Sun, Xiaoping Su, Tse-Hua Tan, Anirban Maitra, Huamin Wang

Faculty, Staff and Student Publications

Ras plays an essential role in the development of acinar-to-ductal metaplasia (ADM) and pancreatic ductal adenocarcinoma (PDAC). However, mutant Kras is an inefficient driver for PDAC development. The mechanisms of the switching from low Ras activity to high Ras activity that are required for development and progression of pancreatic intraepithelial neoplasias (PanINs) are unclear. In this study, we found that hematopoietic progenitor kinase 1 (HPK1) was upregulated during pancreatic injury and ADM. HPK1 interacted with the SH3 domain and phosphorylated Ras GTPase-activating protein (RasGAP) and upregulated RasGAP activity. Using transgenic mouse models of HPK1 or M46, a kinase-dead mutant of …

Microbiome Alterations Driven By Trypanosoma Cruzi Infection In Two Disjunctive Murine Models, Sergio Castañeda, Marina Muñoz, Peter J Hotez, Maria Elena Bottazzi, Alberto E Paniz-Mondolfi, Kathryn M Jones, Rojelio Mejia, Cristina Poveda, Juan David Ramírez

Faculty, Staff and Students Publications

Alterations caused by Trypanosoma cruzi in the composition of gut microbiome may play a vital role in the host-parasite interactions that shapes physiology and immune responses against infection. Thus, a better understanding of this parasite-host-microbiome interaction may yield relevant information in the comprehension of the pathophysiology of the disease and the development of new prophylactic and therapeutic alternatives. Therefore, we implemented a murine model with two mice strains (BALB/c and C57BL/6) to evaluate the impact of Trypanosoma cruzi (Tulahuen strain) infection on the gut microbiome utilizing cytokine profiling and shotgun metagenomics. Higher parasite burdens were observed in cardiac and intestinal …

High-Resolution Transcriptomic And Epigenetic Profiling Identifies Novel Regulators Of Copd, Uwe Schwartz, Maria Llamazares Prada, Stephanie T Pohl, Mandy Richter, Raluca Tamas, Michael Schuler, Corinna Keller, Vedrana Mijosek, Thomas Muley, Marc A Schneider, Karsten Quast, Joschka Hey, Claus P Heußel, Arne Warth, Hauke Winter, Özdemirhan Serçin, Harry Karmouty-Quintana, Soma Sk Jyothula, Manish K Patel, Felix Herth, Ina Koch, Giuseppe Petrosino, Alexandru Titimeaua, Balca R Mardin, Dieter Weichenhan, Tomasz P Jurkowski, Charles D Imbusch, Benedikt Brors, Vladimir Benes, Birgit Jung, David Wyatt, Heiko F Stahl, Christoph Plass, Renata Z Jurkowska

Faculty, Staff and Student Publications

Patients with chronic obstructive pulmonary disease (COPD) are still waiting for curative treatments. Considering its environmental cause, we hypothesized that COPD will be associated with altered epigenetic signaling in lung cells. We generated genome-wide DNA methylation maps at single CpG resolution of primary human lung fibroblasts (HLFs) across COPD stages. We show that the epigenetic landscape is changed early in COPD, with DNA methylation changes occurring predominantly in regulatory regions. RNA sequencing of matched fibroblasts demonstrated dysregulation of genes involved in proliferation, DNA repair, and extracellular matrix organization. Data integration identified 110 candidate regulators of disease phenotypes that were linked …

The Effectiveness Of Disinfection Protocols In Medical School Osteopathic Manipulative Medicine Labs., Harrison A. Patrizio, Riley Phyu, Thomas Boyle, Todd Schachter

Rowan-Virtua School of Osteopathic Medicine Departmental Research

CONTEXT: In light of the COVID-19 pandemic, healthcare-associated infections have taken center stage. Healthcare has adjusted workflows to accommodate for more robust disinfecting regiments to help protect the community. This has resulted in the need for medical institutions to reevaluate the current disinfection protocols down to the student level. The osteopathic manipulative medicine (OMM) laboratory provides an optimal avenue for assessing the effectiveness of medical students' ability to clean examination tables. With OMM laboratories having a high level of interaction, adequate disinfection is important for the health and safety of students and teaching faculties.

OBJECTIVES: This study will evaluate the …

Her3-Targeted Therapeutic Antibodies And Antibody–Drug Conjugates In Non-Small Cell Lung Cancer Refractory To Egfr-Tyrosine Kinase Inhibitors, Margaret E. Larsen, Hui Lyu, Bolin Liu

School of Medicine Faculty Publications

Human epidermal growth factor receptor 3 (HER3) is a unique member of the human epidermal growth factor receptor (HER/EGFR) family, since it has negligible kinase activity. Therefore, HER3 must interact with a kinase-proficient receptor to form a heterodimer, leading to the activation of signaling cascades. Overexpression of HER3 is observed in various human cancers, including non-small cell lung cancer (NSCLC), and correlates with poor clinical outcomes in patients. Studies on the underlying mechanism demonstrate that HER3-initiated signaling promotes tumor metastasis and causes treatment failure in human cancers. Upregulation of HER3 is frequently observed in EGFR-mutant NSCLC treated with EGFR-tyrosine kinase …

Investigating Interpersonal And Community Drivers Of Taenia Solium Prevention To Reduce Acquired Seizure Disorders In Northern Peru: An Analysis Of Social Networks, Social Capital, And Community-Identified Barriers And Facilitators, Angela Gayle Spencer

Dissertations and Theses

Background: In Northern Peru and other low- and middle-income countries (LMICs) worldwide, the Taenia solium parasite causes an estimated 30% of acquired epilepsy -- an entirely preventable disease burden. Sanitation development and pork production regulation would reduce infection risk in endemic communities, but large-scale systemic improvements are not likely to occur in the near future. In the meantime, communities can reduce infection risk by adopting protective behaviors. Social networks can provide role modeling and support for health-promoting behaviors, and deliver social capital in the form of trusting relationships, norms of reciprocity, and information exchange in support of T. solium control. …

Relative And Quantitative Characterization Of The Bovine Bacterial Ocular Surface Microbiome In The Context Of Suspected Ocular Squamous Cell Carcinoma, Hannah B. Gafen, Chin-Chi Liu, Nikole E. Ineck, Clare M. Scully, Melanie A. Mironovich, Lauren Guarneri, Christopher M. Taylor, Meng Luo, Marina L. Leis, Erin M. Scott, Renee T. Carter, Andrew C. Lewin

School of Medicine Faculty Publications

The ocular surface microbiome is altered in certain disease states. The aim of this study was to characterize the bovine bacterial ocular surface microbiome (BBOSM) in the context of ocular squamous cell carcinoma (OSCC). The conjunctiva of normal (n = 28) and OSCC (n = 10) eyes of cows aged 2 to 13 years from two farms in Louisiana and Wyoming were sampled using individual sterile swabs. DNA extraction followed by 16S ribosomal ribonucleic acid (rRNA) gene sequencing and real-time polymerase chain reaction (RT-PCR) were performed to, respectively, assess the relative and absolute BBOSM. Discriminant analysis (DA) was performed using …

Troponin In Acute Chest Pain To Risk Stratify And Guide Effective Use Of Computed Tomography Coronary Angiography (Target-Ctca): A Randomised Controlled Trial, Kuan Ken Lee, David Lowe, Rachel O'Brien, Ryan Wereski, Anda Bularga, Caelan Taggart, Matthew T H Lowry, Amy V Ferry, Michelle C Williams, Giles Roditi, John Byrne, Chris Tuck, Denise Cranley, Praveen Thokala, Steve Goodacre, Catriona Keerie, John Norrie, David E Newby, Alasdair J Gray, Nicholas L Mills

Faculty, Staff and Student Publications

BACKGROUND: The majority of patients with suspected acute coronary syndrome presenting to the emergency department will be discharged once myocardial infarction has been ruled out, although a proportion will have unrecognised coronary artery disease. In this setting, high-sensitivity cardiac troponin identifies those at increased risk of future cardiac events. In patients with intermediate cardiac troponin concentrations in whom myocardial infarction has been ruled out, this trial aims to investigate whether outpatient computed tomography coronary angiography (CTCA) reduces subsequent myocardial infarction or cardiac death.

METHODS: TARGET-CTCA is a multicentre prospective randomised open label with blinded endpoint parallel group event driven trial. …

Antitumor Efficacy Of Dual Blockade With Encorafenib + Cetuximab In Combination With Chemotherapy In Human Brafv600e-Mutant Colorectal Cancer, Stefania Napolitano, Melanie Woods, Hey Min Lee, Vincenzo De Falco, Giulia Martini, Carminia Maria Della Corte, Erika Martinelli, Vincenzo Famiglietti, Davide Ciardiello, Amanda Anderson, Natalie Wall Fowlkes, Oscar Eduardo Villareal, Alexey Sorokin, Preeti Kanikarla, Olu Coker, Van Morris, Lucia Altucci, Josep Tabernero, Teresa Troiani, Fortunato Ciardiello, Scott Kopetz

Faculty, Staff and Student Publications

PURPOSE: Encorafenib + cetuximab (E+C) is an effective therapeutic option in chemorefractory BRAFV600E metastatic colorectal cancer (mCRC). However, there is a need to improve the efficacy of this molecular-targeted therapy and evaluate regimens suitable for untreated BRAFV600E in patients with mCRC.

EXPERIMENTAL DESIGN: We performed a series of in vivo studies using BRAFV600E mCRC tumor xenografts. Mice were randomized to receive 5-fluoruracil (5-FU), irinotecan, or oxaliplatin regimens (FOLFIRI or FOLFOX), (E+C) or the combination. Patients received long-term treatment until disease progression, with deescalation strategies used to mimic maintenance therapy. Transcriptomic changes after progression on cytotoxic chemotherapy or targeted therapy were …

Targeted Therapy With The Mutant Idh2 Inhibitor Enasidenib For High-Risk Idh2-Mutant Myelodysplastic Syndrome, Courtney D Dinardo, Sangeetha Venugopal, Curtis Lachowiez, Koichi Takahashi, Sanam Loghavi, Guillermo Montalban-Bravo, Xuemei Wang, Hetty Carraway, Mikkael Sekeres, Ameenah Sukkur, Danielle Hammond, Kelly Chien, Abhishek Maiti, Lucia Masarova, Koji Sasaki, Yesid Alvarado, Tapan Kadia, Nicholas J Short, Naval Daver, Gautam Borthakur, Farhad Ravandi, Hagop M Kantarjian, Bhumika Patel, Amy Dezern, Gail Roboz, Guillermo Garcia-Manero

Faculty, Staff and Student Publications

The isocitrate dehydrogenase enzyme 2 (IDH2) gene is mutated in ∼5% of patients with myelodysplastic syndrome (MDS). Enasidenib is an oral, selective, mutant IDH2 inhibitor approved for IDH2-mutated (mIDH2) relapsed/refractory acute myeloid leukemia. We designed a 2-arm multicenter study to evaluate safety and efficacy of (A) the combination of enasidenib with azacitidine for newly diagnosed mIDH2 MDS, and (B) enasidenib monotherapy for mIDH2 MDS after prior hypomethylating agent (HMA) therapy. Fifty patients with mIDH2 MDS enrolled: 27 in arm A and 23 in arm B. Median age of patients was 73 years. The most common adverse events were neutropenia (40%), …

Development Of A Biomarker Panel For Assessing Cardiovascular Risk In Diabetic Patients With Chronic Limb-Threatening Ischemia (Clti): A Prospective Study, Elisabetta Nardella, Federico Biscetti, Maria Margherita Rando, Andrea Leonardo Cecchini, Maria Anna Nicolazzi, Enrica Rossini, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Medicine Faculty Papers

BACKGROUND: Lower-extremity endovascular revascularization (LER) is often required for diabetic patients with chronic limb threatening ischemia (CLTI). During the post-revascularization period patients may unpredictably experience major adverse cardiac events (MACE) and major adverse limb events (MALE). Several families of cytokines are involved in the inflammatory process that underlies the progression of atherosclerosis. According to current evidence, we have identified a panel of possible biomarkers related with the risk of developing MACE and MALE after LER. The aim was to study the relationship between a panel of biomarkers - Interleukin-1 (IL-1) and 6 (IL-6), C-Reactive Protein (CRP), Tumor Necrosis Factor-α (TNF-α), …

Patiromer Utility As An Adjunct Treatment In Patients Needing Urgent Hyperkalaemia Management (Platinum): Design Of A Multicentre, Randomised, Double-Blind, Placebo-Controlled, Parallel-Group Study, Zubaid Rafique, Jeffrey Budden, Carol Moreno Quinn, Youyou Duanmu, Basmah Safdar, Jason J Bischof, Brian E Driver, Charles A Herzog, Matthew R Weir, Adam J Singer, Stephen Boone, Karina M Soto-Ruiz, W Frank Peacock

Faculty, Staff and Students Publications

INTRODUCTION: Hyperkalaemia is common, life-threatening and often requires emergency department (ED) management; however, no standardised ED treatment protocol exists. Common treatments transiently reducing serum potassium (K

METHODS AND ANALYSIS: PLATINUM is a Phase 4, multicentre, randomised, double-blind, placebo-controlled study in participants who present to the ED at approximately 30 US sites. Approximately 300 adult participants with hyperkalaemia (K

ETHICS AND DISSEMINATION: A central Institutional Review Board (IRB) and Ethics Committee provided protocol approval (#20201569), with subsequent approval by local IRBs at each site, and participants will provide written consent. Primary results will be published in peer-reviewed manuscripts promptly following study …

Posttreatment Lyme Disease Syndrome And Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Systematic Review And Comparison Of Pathogenesis, Natalie Bai, Christie Richardson

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Lyme disease is the most common vector-borne illness in the United States and has been causing significant morbidity since its discovery in 1977. It is well-documented that about 10% of patients properly treated with antibiotics never fully recover, but instead go on to develop a chronic illness dubbed, posttreatment Lyme disease syndrome (PTLDS) characterized by severe fatigue, cognitive slowing, chronic pain, and sleep difficulties. This review includes 18 studies that detail the symptoms of patients with PTLDS and uses qualitative analysis to compare them to myalgic encephalitis/chronic fatigue syndrome (ME/CFS), a strikingly similar syndrome. In the majority of the PTLDS …

Tumor Microenvironment As A Therapeutic Target In Melanoma Treatment, Naji Kharouf, Thomas W. Flanagan, Sofie Yasmin Hassan, Hosam Shalaby, Marla Khabaz, Sarah Lilly Hassan, Mosaad Megahed, Youssef Haikel, Simeon Santourlidis, Mohamed Hassan

School of Graduate Studies Faculty Publications

The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic …

Complement System In Multiple Sclerosis: Its Role In Disease Course And Potential As A Therapeutic Target, Michael R. Linzey

Dartmouth College Ph.D Dissertations

Multiple sclerosis (MS) is a clinically heterogeneous neurological condition characterized by neuroinflammation and neurodegeneration. Relapsing-remitting MS, defined by inflammatory attacks, is the most common initial form of MS and there are currently 23 FDA-approved treatments for these patients. These therapies work primarily by reducing inflammation in the CNS; they do not work well in progressive disease. Therefore, an unmet medical need exists for effective therapeutic options to treat progressive MS (PMS).

In MS, intrathecal immunoglobulins synthesis (IIgS) correlates with disease progression. My goals for this dissertation were to establish the pathological role of IIgS and identify new potential therapeutic …

Chronic Obstructive Pulmonary Disease Is Associated With Worse Oncologic Outcomes In Early-Stage Resected Pancreatic And Periampullary Cancers, Rachel Huang, Emma Hammelef, Matthew Sabitsky, Carolyn Ream, Saed Khalilieh, Nitzan Zohar, Harish Lavu, Wilbur B. Bowne, Charles J. Yeo, Avinoam Nevler

Department of Surgery Faculty Papers

Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer mortality in the United States. Hypoxic and hypercapnic tumor microenvironments have been suggested to promote tumor aggressiveness. The objective of this study was to evaluate the association between chronic obstructive pulmonary disease (COPD) and oncologic survival outcomes in patients with early-stage PDAC and periampullary cancers. In this case-control study, patients who underwent a pancreaticoduodenectomy during 2014–2021 were assessed. Demographic, perioperative, histologic, and oncologic data were collected. A total of 503 PDAC and periampullary adenocarcinoma patients were identified, 257 males and 246 females, with a mean age of 68.1 (±9.8) …

Whole Genome Analysis For 163 Grnas In Cas9-Edited Mice Reveals Minimal Off-Target Activity, Kevin A Peterson, Sam Khalouei, Nour Hanafi, Joshua A Wood, Denise G Lanza, Lauri G Lintott, Brandon J Willis, John R Seavitt, Robert E Braun, Mary E Dickinson, Jacqueline K White, K C Kent Lloyd, Jason D Heaney, Stephen A Murray, Arun Ramani, Lauryl M J Nutter

Faculty, Staff and Students Publications

Genome editing with CRISPR-associated (Cas) proteins holds exceptional promise for "correcting" variants causing genetic disease. To realize this promise, off-target genomic changes cannot occur during the editing process. Here, we use whole genome sequencing to compare the genomes of 50 Cas9-edited founder mice to 28 untreated control mice to assess the occurrence of S. pyogenes Cas9-induced off-target mutagenesis. Computational analysis of whole-genome sequencing data detects 26 unique sequence variants at 23 predicted off-target sites for 18/163 guides used. While computationally detected variants are identified in 30% (15/50) of Cas9 gene-edited founder animals, only 38% (10/26) of the variants in 8/15 …

An Aerobic Exercise Intervention To Improve Metabolic Health Among People Living With Hiv With At-Risk Alcohol Use: The Alive-Ex Research Study Protocol, Liz Simon, Stefany D. Primeaux, Danielle E. Levitt, Brianna Bourgeois, Neil M. Johannsen, Adrianna Peters, Jameel Ahmed, Richard H. Marshall, Alexandra H. Fairchild, Tekeda F. Ferguson, Patricia E. Molina

School of Medicine Faculty Publications

Background: Effective antiretroviral therapy (ART) in people living with HIV (PLWH) has improved life expectancy and increased risk of age-associated cardiometabolic comorbidities. At-risk alcohol use is more frequent among PLWH and increases the risk of health challenges. PLWH with at-risk alcohol use are more likely to meet criteria for prediabetes/diabetes and this is associated with impaired whole-body glucose-insulin dynamics. Methods: The Alcohol & Metabolic Comorbidities in PLWH: Evidence Driven Interventions Study (ALIVE-Ex Study, NCT03299205) is a longitudinal, prospective, interventional study to determine the effects of an aerobic exercise protocol on improving dysglycemia among PLWH with at-risk alcohol use. The intervention …

Preparation And Immunofluorescence Staining Of Bundles And Single Fiber Cells From The Cortex And Nucleus Of The Eye Lens, Michael P Vu, Catherine Cheng

Faculty, Staff and Student Publications

The lens is a transparent and ellipsoid organ in the anterior chamber of the eye that changes shape to finely focus light onto the retina to form a clear image. The bulk of this tissue comprises specialized, differentiated fiber cells that have a hexagonal cross section and extend from the anterior to the posterior poles of the lens. These long and skinny cells are tightly opposed to neighboring cells and have complex interdigitations along the length of the cell. The specialized interlocking structures are required for normal biomechanical properties of the lens and have been extensively described using electron microscopy …

Early Postpartum Hba1c After Hyperglycemia First Detected In Pregnancy-Imperfect But Not Without Value, Ankia Coetzee, David R Hall, Mari Van De Vyver, Magda Conradie

Faculty, Staff and Student Publications

BACKGROUND: South African women of childbearing age are disproportionally affected by obesity and at significant risk of Type 2 Diabetes Mellitus (T2DM). Unless pregnant, they do not readily undergo screening for T2DM. With a local focus on improved antenatal care, hyperglycemia is often first detected in pregnancy (HFDP). This may erroneously be attributed to Gestational Diabetes Mellitus (GDM) in all without considering T2DM. Glucose evaluation following pregnancy is essential for early detection and management of women with T2DM in whom persistent hyperglycemia is to be expected. Conventional testing with an oral glucose tolerance test (OGTT) is cumbersome, prompting investigation for …