Digital Commons Network^™

Closing The Gaps In Care Of Dyslipidemia: Revolutionizing Management With Digital Health And Innovative Care Models, Samuel J Apple, Rachel Clark, Jonathan Daich, Macarena Lopez Gonzalez, Robert J Ostfeld, Peter P Toth, Vera Bittner, Seth S Martin, Jamal S Rana, Khurram Nasir, Michael D Shapiro, Salim S Virani, Leandro Slipczuk

Faculty, Staff and Students Publications

Although great progress has been made in the diagnostic and treatment options for dyslipidemias, unawareness, underdiagnosis and undertreatment of these disorders remain a significant global health concern. Growth in digital applications and newer models of care provide novel tools to improve the management of chronic conditions such as dyslipidemia. In this review, we discuss the evolving landscape of lipid management in the 21st century, current treatment gaps and possible solutions through digital health and new models of care. Our discussion begins with the history and development of value-based care and the national establishment of quality metrics for various chronic conditions. …

Development Of Thermosensitive Hydrogel Of Amphotericin-B And Lactoferrin Combination-Loaded Plga-Peg-Pei Nanoparticles For Potential Eradication Of Ocular Fungal Infections, Sammar Fathy Elhabal, Shrouk A Ghaffar, Raghda Hager, Nahla A Elzohairy, Mohamed Mansour Khalifa, Passant M Mohie, Rania A Gad, Nasreen N Omar, Mohammed H Elkomy, Mohammad Ahmad Khasawneh, Nashwa Abdelaal

Faculty, Staff and Students Publications

The most prevalent conditions among ocular surgery and COVID−19 patients are fungal eye infections, which may cause inflammation and dry eye, and may cause ocular morbidity. Amphotericin-B eye drops are commonly used in the treatment of ocular fungal infections. Lactoferrin is an iron-binding glycoprotein with broad-spectrum antimicrobial activity and is used for the treatment of dry eye, conjunctivitis, and ocular inflammation. However, poor aqueous stability and excessive nasolacrimal duct draining impede these agens' efficiency. The aim of this study was to examine the effect of Amphotericin-B, as an antifungal against Candida albicans, Fusarium, and Aspergillus flavus, and Lactoferrin, …

Development Of Canagliflozin Nanocrystals Sublingual Tablets In The Presence Of Sodium Caprate Permeability Enhancer: Formulation Optimization, Characterization, Sammar Fathy Elhabal, Mohamed A El-Nabarawi, Nashwa Abdelaal, Mohamed Fathi Mohamed Elrefai, Shrouk A Ghaffar, Mohamed Mansour Khalifa, Passant M Mohie, Dania S Waggas, Ahmed Mohsen Elsaid Hamdan, Samar Zuhair Alshawwa, Essa M Saied, Nahla A Elzohairy, Tayseer Elnawawy, Rania A Gad, Nehal Elfar, Hanaa Mohammed, Mohammad Ahmad Khasawneh

Faculty, Staff and Students Publications

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor (SGLT2) that lowers albuminuria in type-2 diabetic patients, cardiovascular, kidney, and liver disease. CFZ is classified as class IV in the Biopharmaceutical Classification System (BCS) and is characterized by low permeability, solubility, and bioavailability, most likely attributed to hepatic first-pass metabolism. Nanocrystal-based sublingual formulations were developed in the presence of sodium caprate, as a wetting agent, and as a permeability enhancer. This formulation is suitable for children and adults and could enhance solubility, permeability, and avoid enterohepatic circulation due to absorption through the sublingual mucosa. In the present study, formulations containing various surfactants …

Case Sampling Vs Universal Review For Evaluating Hospital Postoperative Mortality In Us Surgical Quality Improvement Programs, Vivi W Chen, Alexis P Chidi, Tracey Rosen, Yongquan Dong, Peter A Richardson, Jennifer Kramer, David A Axelrod, Laura A Petersen, Nader N Massarweh

Faculty, Staff and Students Publications

IMPORTANCE: Representative surgical case sampling, rather than universal review, is used by US Department of Veterans Affairs (VA) and private-sector national surgical quality improvement (QI) programs to assess program performance and to inform local QI and performance improvement efforts. However, it is unclear whether case sampling is robust for identifying hospitals with safety or quality concerns.

OBJECTIVE: To evaluate whether the sampling strategy used by several national surgical QI programs provides hospitals with data that are representative of their overall quality and safety, as measured by 30-day mortality.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study was a national, hospital-level …

The Brd4-Nut Fusion Alone Drives Malignant Transformation Of Nut Carcinoma, R Taylor Durall, Julianna Huang, Luke Wojenski, Yeying Huang, Prafulla C Gokhale, Brittaney A Leeper, Joshua O Nash, Pedro L Ballester, Scott Davidson, Adam Shlien, Emmanuel Sotirakis, Fabien Bertaux, Vincent Dubus, Jia Luo, Catherine J Wu, Derin B Keskin, Kyle P Eagen, Geoffrey I Shapiro, Christopher A French

Faculty, Staff and Students Publications

NUT carcinoma (NC) is an aggressive squamous carcinoma defined by the BRD4-NUT fusion oncoprotein. Routinely effective systemic treatments are unavailable for most NC patients. The lack of an adequate animal model precludes identifying and leveraging cell-extrinsic factors therapeutically in NC. Here, we created a genetically engineered mouse model (GEMM) of NC that forms a Brd4::NUTM1 fusion gene upon tamoxifen induction of Sox2-driven Cre. The model displayed complete disease penetrance, with tumors arising from the squamous epithelium weeks after induction and all mice succumbing to the disease shortly thereafter. Closely resembling human NC (hNC), GEMM tumors (mNC) were poorly differentiated squamous …

Ezh2 Cooperates With Brd4-Nut To Drive Nut Carcinoma Growth By Silencing Key Tumor Suppressor Genes, Yeying Huang, R Taylor Durall, Nhi M Luong, Hans J Hertzler, Julianna Huang, Prafulla C Gokhale, Brittaney A Leeper, Nicole S Persky, David E Root, Praju V Anekal, Paula D L M Montero Llopis, Clement N David, Jeffery L Kutok, Alejandra Raimondi, Karan Saluja, Jia Luo, Cynthia A Zahnow, Biniam Adane, Kimberly Stegmaier, Catherine E Hawkins, Christopher Ponne, Quan Le, Geoffrey I Shapiro, Madeleine E Lemieux, Kyle P Eagen, Christopher A French

Faculty, Staff and Student Publications

NUT carcinoma (NC) is an aggressive carcinoma driven by the BRD4-NUT fusion oncoprotein, which activates chromatin to promote expression of pro-growth genes. BET bromodomain inhibitors (BETi) are a promising treatment for NC that can impede BRD4-NUT’s ability to activate genes, but the efficacy of BETi as monotherapy are limited. Here, we demonstrated that EZH2, which silences genes through establishment of repressive chromatin, is a dependency in NC. Inhibition of EZH2 with the clinical compound tazemetostat (taz) potently blocked growth of NC cells. Epigenetic and transcriptomic analysis revealed that taz reversed the EZH2-specific H3K27me3 silencing mark and restored expression of multiple …

Microbial Stimulation Of Oxytocin Release From The Intestinal Epithelium Via Secretin Signaling, Heather A Danhof, Jihwan Lee, Aanchal Thapa, Robert A Britton, Sara C Di Rienzi

Faculty, Staff and Students Publications

Intestinal microbes impact the health of the intestine and organs distal to the gut. Limosilactobacillus reuteri is a human intestinal microbe that promotes normal gut transit, the anti-inflammatory immune system, wound healing, normal social behavior in mice, and prevents bone reabsorption. Oxytocin impacts these functions and oxytocin signaling is required for L. reuteri-mediated wound healing and social behavior; however, the events in the gut leading to oxytocin stimulation and beneficial effects are unknown. Here we report evolutionarily conserved oxytocin production in the intestinal epithelium through analysis of single-cell RNA-Seq datasets and imaging of human and mouse intestinal tissues. Moreover, …

Idiographic Coping Outcomes In Youth With Autism Spectrum Disorder And Co-Occurring Anxiety: Results From The Taasd Study, Lesley A Norris, Jonathan C Rabner, Eric A Storch, Jeffrey J Wood, Connor Kerns, Adam B Lewin, Brent J Small, Philip C Kendall

Center for Medical Ethics and Health Policy Staff Publications

Versions of cognitive behavioral therapy (Coping Cat, CC; Behavioral Interventions for Anxiety in Children with Autism, BIACA) have shown efficacy in treating anxiety among youth with autism spectrum disorder. Measures of efficacy have been primarily nomothetic symptom severity assessments. The current study examined idiographic coping outcomes in the Treatment of Anxiety in Autism Spectrum Disorder study (N = 167). Longitudinal changes in coping with situations individualized to youth fears (Coping Questionnaire) were examined across CC, BIACA and treatment as usual (TAU) in a series of multilevel models. CC and BIACA produced significantly greater improvements than TAU in caregiver-reported coping. Youth …

A Heritable Iron Memory Enables Decision-Making In Escherichia Coli, Souvik Bhattacharyya, Nabin Bhattarai, Dylan M Pfannenstiel, Brady Wilkins, Abhyudai Singh, Rasika M Harshey

Faculty, Staff and Student Publications

The importance of memory in bacterial decision-making is relatively unexplored. We show here that a prior experience of swarming is remembered when Escherichia coli encounters a new surface, improving its future swarming efficiency. We conducted >10,000 single-cell swarm assays to discover that cells store memory in the form of cellular iron levels. This “iron” memory preexists in planktonic cells, but the act of swarming reinforces it. A cell with low iron initiates swarming early and is a better swarmer, while the opposite is true for a cell with high iron. The swarming potential of a mother cell, which tracks with …

Chimeric Antigen Receptor T Cells To Target Cd79b In B-Ceall Lymphomas, Fuliang Chu, Jingjing Cao, Jingwei Liu, Haopeng Yang, Timothy J Davis, Shao-Qing Kuang, Xiaoyun Cheng, Zheng Zhang, Swathi Karri, Long T Vien, Laura Bover, Ryan Sun, Francisco Vega, Michael Green, Richard Eric Davis, Sattva S Neelapu

Faculty, Staff and Student Publications

BACKGROUND: Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent and durable effects in B-cell malignancies. However, antigen loss or downregulation is a frequent cause of resistance. Here, we report development of a novel CAR T-cell therapy product to target CD79b, a pan B-cell antigen, widely expressed in most B-cell lymphomas.

METHODS: We generated a novel anti-CD79b monoclonal antibody by hybridoma method. The specificity of the antibody was determined by testing against isogenic cell lines with human CD79b knock-in or knock-out. A single-chain variable fragment derived from the monoclonal antibody was used to make a panel of CD79b-targeting CAR …

Lactic Acid Bacterial Surface Display Of Scytovirin Inhibitors For Anti-Ebolavirus Infection, Joshua Wiggins, Ngan Nguyen, Wenzhong Wei, Leah Liu Wang, Haley Hollingsead Olson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, …

The Implications Of Ferroptosis In Antibiotic Resistance, Marysol Hohl

Senior Honors Theses

Bacterial infections in the United States are becoming increasingly resistant to existing antibiotic treatments. Due to projected increases in resistance and the recent decrease in novel antibacterials, experts have determined that the United States is in the “post-antibiotic era.” The scientific community has failed to resolve resistance despite the continual discovery of new antibiotic compounds. In the past decade, a novel form of cell death called ferroptosis has been implicated in antibiotic treatment by employing the use of nanotechnology. This literature review will describe the problem of bacterial resistance and demonstrate how current research is pioneering a new age of …

Glial Cell Adhesion Molecule (Glialcam) Determines Proliferative Versus Invasive Cell States In Glioblastoma, Arpan De, John M Lattier, John E Morales, Jack R Kelly, Xiaofeng Zheng, Zhihua Chen, Sumod Sebastian, Zahra Nassiri Toosi, Jason T Huse, Frederick F Lang, Joseph H Mccarty

Faculty, Staff and Student Publications

The malignant brain cancer glioblastoma (GBM) contains groups of highly invasive cells that drive tumor progression as well as recurrence after surgery and chemotherapy. The molecular mechanisms that enable these GBM cells to exit the primary mass and disperse throughout the brain remain largely unknown. Here we report using human tumor specimens and primary spheroids from male and female patients that glial cell adhesion molecule (GlialCAM), which has normal roles in brain astrocytes and is mutated in the developmental brain disorder megalencephalic leukoencephalopathy with subcortical cysts (MLC), is differentially expressed in subpopulations of GBM cells. High levels of GlialCAM promote …

Stratification Of Risk For Emergent Intracranial Abnormalities In Children With Headaches: A Pediatric Emergency Care Applied Research Network (Pecarn) Study Protocol, Daniel S Tsze, Nathan Kuppermann, T Charles Casper, Bradley J Barney, Lawrence P Richer, Danica B Liberman, Pamela J Okada, Claudia R Morris, Sage R Myers, Jane K Soung, Rakesh D Mistry, Lynn Babcock, Sandra P Spencer, Michael D Johnson, Eileen J Klein, Kimberly S Quayle, Dale W Steele, Andrea T Cruz, Alexander J Rogers, Danny G Thomas, Jacqueline M Grupp-Phelan, Tiffani J Johnson, Peter S Dayan, Pediatric Emergency Care Applied Research Network (Pecarn)

Faculty, Staff and Students Publications

INTRODUCTION: Headache is a common chief complaint of children presenting to emergency departments (EDs). Approximately 0.5%-1% will have emergent intracranial abnormalities (EIAs) such as brain tumours or strokes. However, more than one-third undergo emergent neuroimaging in the ED, resulting in a large number of children unnecessarily exposed to radiation. The overuse of neuroimaging in children with headaches in the ED is driven by clinician concern for life-threatening EIAs and lack of clarity regarding which clinical characteristics accurately identify children with EIAs. The study objective is to derive and internally validate a stratification model that accurately identifies the risk of EIA …

A Conceptual Framework For Nomenclatural Stability And Validity Of Medically Important Fungi: A Proposed Global Consensus Guideline For Fungal Name Changes Supported By Abp, Asm, Clsi, Ecmm, Escmid-Efisg, Eucast-Afst, Fdlc, Idsa, Isham, Mmsa, And Msgerc, Sybren De Hoog, Thomas J Walsh, Sarah A Ahmed, Ana Alastruey-Izquierdo, Barbara D Alexander, Maiken Cavling Arendrup, Esther Babady, Feng-Yan Bai, Joan-Miquel Balada-Llasat, Andrew Borman, Anuradha Chowdhary, Andrew Clark, Robert C Colgrove, Oliver A Cornely, Tanis C Dingle, Philippe J Dufresne, Jeff Fuller, Jean-Pierre Gangneux, Connie Gibas, Heather Glasgow, Yvonne Gräser, Jacques Guillot, Andreas H Groll, Gerhard Haase, Kimberly Hanson, Amanda Harrington, David L Hawksworth, Randall T Hayden, Martin Hoenigl, Vit Hubka, Kristie Johnson, Julianne V Kus, Ruoyu Li, Jacques F Meis, Michaela Lackner, Fanny Lanternier, Sixto M Leal, Francesca Lee, Shawn R Lockhart, Paul Luethy, Isabella Martin, Kyung J Kwon-Chung, Wieland Meyer, M Hong Nguyen, Luis Ostrosky-Zeichner, Elizabeth Palavecino, Preeti Pancholi, Peter G Pappas, Gary W Procop, Scott A Redhead, Daniel D Rhoads, Stefan Riedel, Bryan Stevens, Kaede Ota Sullivan, Paschalis Vergidis, Emmanuel Roilides, Amir Seyedmousavi, Lili Tao, Vania A Vicente, Roxana G Vitale, Qi-Ming Wang, Nancy L Wengenack, Lars Westblade, Nathan Wiederhold, Lewis White, Christina M Wojewoda, Sean X Zhang

Faculty, Staff and Student Publications

The rapid pace of name changes of medically important fungi is creating challenges for clinical laboratories and clinicians involved in patient care. We describe two sources of name change which have different drivers, at the species versus the genus level. Some suggestions are made here to reduce the number of name changes. We urge taxonomists to provide diagnostic markers of taxonomic novelties. Given the instability of phylogenetic trees due to variable taxon sampling, we advocate to maintain genera at the largest possible size. Reporting of identified species in complexes or series should where possible comprise both the name of the …

Tulathromycin Metaphylaxis Increases Nasopharyngeal Isolation Of Multidrug Resistant Mannheimia Haemolytica In Stocker Heifers, William B. Crosby, Brandi B. Karisch, Lari M. Hiott, Lee J. Pinnell, Alexandra Pittman, Jonathan G. Frye, Charlene R. Jackson, John Dustin Loy, William B. Epperson, John Blanton Jr., Sarah F. Capik, Paul S. Morley, Amelia R. Woolums

School of Veterinary and Biomedical Sciences: Faculty Publications

Bovine respiratory disease (BRD) is a leading cause of disease in feedlot and stocker calves with Mannheimia haemolytica (MH) as one of the most common etiologies. One of the most effective means of controlling BRD is through metaphylaxis, which involves administering antimicrobials to all animals at high risk of developing BRD. However, increasing prevalence of multidrug resistant (MDR) MH may reduce efficacy of metaphylaxis due to decreased susceptibility to drugs used for metaphylaxis. Primarily, this study aimed to determine the effect of tulathromycin metaphylaxis and subsequent BRD treatment on antimicrobial resistance (AMR) in MH isolated from stocker calves. Secondary objectives …

Intouch Week Of November 20, 2023, New York Medical College

InTouch

• SOM Class of 2027Celebrates Friendsgiving
• GSBMS Pens Conditional Admittance and Guaranteed Interview Agreements with TUCOM
• NYMC Raises More than $5,000 for Victims of the Israeli-Palestinian Conflict

Vaginal Microbial Dynamics And Pathogen Colonization In A Humanized Microbiota Mouse Model, Marlyd E Mejia, Vicki Mercado-Evans, Jacob J Zulk, Samantha Ottinger, Korinna Ruiz, Mallory B Ballard, Stephanie W Fowler, Robert A Britton, Kathryn A Patras

Faculty, Staff and Students Publications

Vaginal microbial composition is associated with differential risk of urogenital infection. Although Lactobacillus spp. are thought to confer protection against infection, the lack of in vivo models resembling the human vaginal microbiota remains a prominent barrier to mechanistic discovery. Using 16S rRNA amplicon sequencing of C57BL/6J female mice, we found that vaginal microbial composition varies within and between colonies across three vivaria. Noting vaginal microbial plasticity in conventional mice, we assessed the vaginal microbiome of humanized microbiota mice (

Mechanism Of Stepwise Electron Transfer In Six-Transmembrane Epithelial Antigen Of The Prostate (Steap) 1 And 2, Kehan Chen, Lie Wang, Jiemin Shen, Ah-Lim Tsai, Ming Zhou, Gang Wu

Faculty, Staff and Student Publications

Six transmembrane epithelial antigen of the prostate (STEAP) 1-4 are membrane-embedded hemoproteins that chelate a heme prosthetic group in a transmembrane domain (TMD). STEAP2-4, but not STEAP1, have an intracellular oxidoreductase domain (OxRD) and can mediate cross-membrane electron transfer from NADPH via FAD and heme. However, it is unknown whether STEAP1 can establish a physiologically relevant electron transfer chain. Here, we show that STEAP1 can be reduced by reduced FAD or soluble cytochrome b5 reductase that serves as a surrogate OxRD, providing the first evidence that STEAP1 can support a cross-membrane electron transfer chain. It is not clear whether …

Dietary Analysis For Hashimoto’S Thyroiditis: An Integrative Review, Evan Thompson, Alison Hultquist

Master of Science in Nursing Final Projects

Abstract

Hashimoto’s Thyroiditis (HT) is the leading cause of primary hypothyroidism in the United States. In HT, there is an infiltration by lymphocytes which leads to the production of autoantibodies against the thyroid gland. Throughout this integrative review, the aim was to evaluate the effectiveness of micronutrient supplementation and dietary management as adjunct treatments in HT. The purpose was to assist primary care providers in the development of a more holistic plan of care. Literature published within the past seven years was gathered and reviewed from PubMed, CINAHL, and Cochrane Library. Findings indicate that many patients with HT may benefit …

Perceptions Of Nigerian Medical Students Regarding Their Preparedness For Precision Medicine: A Cross-Sectional Survey In Lagos, Nigeria, Chibuzor Ogamba, Alero Roberts, Sharon Ajudua, Mosopefoluwa Akinwale, Fuhad Jeje, Festus Ibe, Moses Afolayan, Yetunde Kuyinu

Einstein Health Papers

BACKGROUND: Advances in precision medicine in Nigeria suggest improving genomics education and competency among healthcare practitioners to facilitate clinical translation. Due to the scarcity of research in this area, this study aimed to assess Nigerian medical students' perceptions about their preparedness to integrate precision medicine into their future clinical practice.

METHODS: This was an institution-based cross-sectional study of medicine and surgery students in their clinical years attending the two fully accredited colleges of medicine in Lagos, Nigeria, between April and October 2022 using an adapted tool administered via Google Forms. The survey assessed their awareness, perceptions about knowledge, ability, and …

Pmca Screening Of Retropharyngeal Lymph Nodes In White-Tailed Deer And Comparisons With Elisa And Ihc, Rebeca Benavente, J Hunter Reed, Mitch Lockwood, Rodrigo Morales

Faculty, Staff and Student Publications

Chronic wasting disease (CWD) is a prion disease affecting cervids. CWD diagnosis is conducted through enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) in retropharyngeal lymph nodes. Unfortunately, these techniques have limited sensitivity against the biomarker (CWD-prions). Two in vitro prion amplification techniques, real-time quaking-induced conversion (RT-QuIC) and protein misfolding cyclic amplification (PMCA), have shown promise in detecting CWD-prions in tissues and bodily fluids. Recent studies have demonstrated that RT-QuIC yields similar results compared to ELISA and IHC. Here, we analyzed 1003 retropharyngeal lymph nodes (RPLNs) from Texas white-tailed deer. PMCA detected CWD at a higher rate compared to ELISA/IHC, identified …

Rapid, High Throughput, Automated Detection Of Sars-Cov-2 Neutralizing Antibodies Against Wuhan-Wt, Delta And Omicron Ba1, Ba2 Spike Trimers, Narayanaiah Cheedarla, Hans P Verkerke, Sindhu Potlapalli, Kaleb Benjamin Mclendon, Anamika Patel, Filipp Frank, William Henry O'Sick, Suneethamma Cheedarla, Tyler Jon Baugh, Gregory L Damhorst, Huixia Wu, Daniel Graciaa, Fuad Hudaib, David N Alter, Janetta Bryksin, Eric A Ortlund, Jeanette Guarner, Sara Auld, Sarita Shah, Wilbur Lam, Dawn Mattoon, Joseph M Johnson, David H Wilson, Madhav V Dhodapkar, Sean R Stowell, Andrew S Neish, John D Roback

Faculty, Staff and Student Publications

Traditional cellular and live-virus methods for detection of SARS-CoV-2 neutralizing antibodies (nAbs) are labor- and time-intensive, and thus not suited for routine use in the clinical lab to predict vaccine efficacy and natural immune protection. Here, we report the development and validation of a rapid, high throughput method for measuring SARS-CoV-2 nAbs against native-like trimeric spike proteins. This assay uses a blockade of human angiotensin converting enzyme 2 (hACE-2) binding (BoAb) approach in an automated digital immunoassay on the Quanterix HD-X platform. BoAb assays using Wuhan-WT (vaccine strain), delta (B.1.167.2), omicron BA1 and BA2 variant viral strains showed strong correlation …

Loss Of Cftr Function In Macrophages Alters The Cell Transcriptional Program And Delays Lung Resolution Of Inflammation, Dianne Wellems, Yawen Hu, Scott Jennings, Guoshun Wang

School of Graduate Studies Faculty Publications

Cystic fibrosis (CF) is an autosomal recessive genetic disorder caused by mutations in the CF Transmembrane-conductance Regulator (CFTR) gene. The most severe pathologies of CF occur in the lung, manifesting as chronic bacterial infection, persistent neutrophilic inflammation, and mucopurulent airway obstruction. Despite increasing knowledge of the CF primary defect and the resulting clinical sequelae, the relationship between the CFTR loss of function and the neutrophilic inflammation remains incompletely understood. Here, we report that loss of CFTR function in macrophages causes extended lung inflammation. After intratracheal inoculation with Pseudomonas aeruginosa, mice with a macrophage-specific Cftr-knockout (Mac-CF) were able to mount an …

Candida Auris-Macrophage Cellular Interactions And Transcriptional Response, Pedro Miramón, Andrew W Pountain, Michael C Lorenz

Faculty, Staff and Student Publications

The pathogenic yeast Candida auris represents a global threat of the utmost clinical relevance. This emerging fungal species is remarkable in its resistance to commonly used antifungal agents and its persistence in the nosocomial settings. The innate immune system is one the first lines of defense preventing the dissemination of pathogens in the host. C. auris is susceptible to circulating phagocytes, and understanding the molecular details of these interactions may suggest routes to improved therapies. In this work, we examined the interactions of this yeast with macrophages. We found that macrophages avidly phagocytose C. auris; however, intracellular replication is …

Baseline Extracellular Vesicle Mirna-30c And Autophagic Ctcs Predict Chemoradiotherapy Resistance And Outcomes In Patients With Lung Cancer, Diego De Miguel-Perez, Francisco Gabriel Ortega, Rosario Guerrero Tejada, Antonio Martínez-Única, Christine B Peterson, Alessandro Russo, Muthukumar Gunasekaran, Andres F Cardona, Victor Amezcua, Jose Antonio Lorente, Jose Expósito Hernández, Christian Rolfo, Maria Jose Serrano

Faculty, Staff and Student Publications

Concurrent chemoradiotherapy (cCRT) is the mainstay of treatment for patients diagnosed with locally advanced non-small cell lung cancer (NSCLC). One significant challenge in the effectiveness of this therapy is the potential development of resistance mechanisms, where autophagy up-regulation has been proposed as a key contributing factor. However, there is a lack of reliable biomarkers to predict outcomes on these patients. Interestingly, for addressing this gap, extracellular vesicles (EVs) and circulating tumor cells (CTCs) have emerged as potential sources of such biomarkers. In this study, we investigated EV-associated miRNAs and presence of autophagic CTCs in prospectively collected serial samples from 38 …

Association Of Cardiovascular Disease And Pancreatitis: What Came First, The Chicken Or The Egg?, Bing Chen, Aleena Moin, Hafeez Ul Hassan Virk, Hani Jneid, Salim S Virani, Chayakrit Krittanawong

Faculty, Staff and Students Publications

Background: Recent studies suggest an association between pancreatitis and cardiovascular disease. This article aims to review the available evidence linking cardiovascular disease with acute and chronic pancreatitis.

Methods: A comprehensive search was conducted on the PubMed/MEDLINE database from inception to April 2022 using Medical Subject Heading and keywords related to pancreatitis and cardiovascular disease. The search was limited to English-language literature involving human subjects, and various study types, including observational studies, case-control studies, cohort studies, and clinical trials, were screened for eligibility. Following data extraction, the authors conducted a narrative synthesis of the studies.

Results: Longitudinal studies indicate that a …

The Increasing Vulnerability Of African Youths To Mental Health Disorders: Risk Factors, Advocacy And Recommendations, Fidelis Ikechukwu Edeh, Abdullateef Ridwanullah Olamide

International Journal of Health and Allied Sciences

There is no abstract for this article type.

Mechanisms And Treatment Options For Hyperthyroid-Induced Osteoporosis: A Narrative Review, Robert M. Branstetter 4th, Rahib K. Islam, Collin A. Toups, Amanda N. Parra, Zachary Lee, Shahab Ahmadzadeh, Giustino Varrassi, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Normal thyroid hormone levels are crucial for the homeostasis of many metabolic cycles and processes throughout the human body. Thyroid dysfunction, such as thyrotoxicosis, can result from many different etiologies, including Graves' disease (GD), toxic multinodular goiter (MNG), and toxic adenoma. These hyperthyroid disease states can cause devastating complications and disease, including the disruption of the bone remodeling cycle and skeletal development, which can result in osteoporosis. Osteoporosis is characterized by a decrease in bone mineral density and a propensity for fragility fractures. In addition to patients with overt hyperthyroidism, studies have provided evidence of other high-risk patient demographics, such …

Gasdermin D Permeabilization Of Mitochondrial Inner And Outer Membranes Accelerates And Enhances Pyroptosis, Rui Miao, Cong Jiang, Winston Y Chang, Haiwei Zhang, Jinsu An, Felicia Ho, Pengcheng Chen, Han Zhang, Caroline Junqueira, Dulguun Amgalan, Felix G Liang, Junbing Zhang, Charles L Evavold, Iva Hafner-Bratkovič, Zhibin Zhang, Pietro Fontana, Shiyu Xia, Markus Waldeck-Weiermair, Youdong Pan, Thomas Michel, Liron Bar-Peled, Hao Wu, Jonathan C Kagan, Richard N Kitsis, Peng Zhang, Xing Liu, Judy Lieberman

Faculty, Staff and Student Publications

Gasdermin D (GSDMD)-activated inflammatory cell death (pyroptosis) causes mitochondrial damage, but its underlying mechanism and functional consequences are largely unknown. Here, we show that the N-terminal pore-forming GSDMD fragment (GSDMD-NT) rapidly damaged both inner and outer mitochondrial membranes (OMMs) leading to reduced mitochondrial numbers, mitophagy, ROS, loss of transmembrane potential, attenuated oxidative phosphorylation (OXPHOS), and release of mitochondrial proteins and DNA from the matrix and intermembrane space. Mitochondrial damage occurred as soon as GSDMD was cleaved prior to plasma membrane damage. Mitochondrial damage was independent of the B-cell lymphoma 2 family and depended on GSDMD-NT binding to cardiolipin. Canonical and …