Translational Medical Research Commons^™

Design Of The Strive-Ipf Trial-Study Of Therapeutic Plasma Exchange, Rituximab, And Intravenous Immunoglobulin For Acute Exacerbations Of Idiopathic Pulmonary Fibrosis, Tejaswini Kulkarni, Gerard Criner, Daniel Kass, Ivan Rosas, Mary Beth Scholand, Daniel Dilling, Ross Summer, Steven Duncan

Division of Pulmonary and Critical Care Medicine Faculty Papers

BACKGROUND: Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) affect a significant proportion of patients with IPF. There are limited data to inform therapeutic strategies for AE-IPF, despite its high mortality. We discuss the rationale and design of STRIVE-IPF, a randomized, multi-center, open-label Phase IIb clinical trial to determine the efficacy of combined therapeutic plasma exchange (TPE), rituximab, and intravenous immunoglobulin (IVIG), in comparison to treatment as usual (TAU), among patients with acute IPF exacerbations.

METHODS: The STRIVE-IPF trial will randomize 51 patients among five sites in the United States. The inclusion criteria have been designed to select a study population …

Increase In Hnrnpa1 Expression Suffices To Kill Motor Neurons In Transgenic Rats, Xionghao Liu, Tingting Zhang, Qinxue Wu, Cao Huang, Xu-Gang Xia, Hongxia Zhou, Bo Huang

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

A dominant mutation in hnRNPA1 causes amyotrophic lateral sclerosis (ALS), but it is not known whether this mutation leads to motor neuron death through increased or decreased function. To elucidate the relationship between pathogenic hnRNPA1 mutation and its native function, we created novel transgenic rats that overexpressed wildtype rat hnRNPA1 exclusively in motor neurons. This targeted expression of wildtype hnRNPA1 caused severe motor neuron loss and subsequent denervation muscle atrophy in transgenic rats that recapitulated the characteristics of ALS. These findings demonstrate that the augmentation of hnRNPA1 expression suffices to trigger motor neuron degeneration and the manifestation of ALS-like phenotypes. …

Evaluation Of A Novel Lupus Anticoagulant Assay Designed To Reduce False Positive Results Due To Anticoagulation: A Retrospective Study At A Single Health System, Jessica D. Anderson, Tamara Sabih, Yuying Xing, Lili Zhao, Marc D. Smith

Conference Presentation Abstracts

Introduction: Lupus anticoagulants (LA) are antibodies directed against phospholipids/phospholipid-protein complexes involved in coagulation and are associated with thrombotic events and recurrent fetal loss. There is no gold standard test for LA, therefore at least two LA-specific tests are recommended before excluding LA. Potential testing methods involve dilute Russell viper venom time (dRVVT) and hexagonal phase phospholipid assays (HPPA); however, many of these tests are susceptible to interference with anticoagulant therapy which can lead to false positive results. In this study, we compared the performance of our current HPPA, StaClot LA (SCLA), with a novel assay reported to have relatively minimal …

Increased Glucose Availability Sensitizes Pancreatic Cancer To Chemotherapy, Ali Vaziri-Gohar, Jonathan J. Hue, Ata Abbas, Hallie J. Graor, Omid Hajihassani, Mehrdad Zarei, George Titomihelakis, John Feczko, Moeez Rathore, Sylwia Chelstowska, Alexander W. Loftus, Rui Wang, Mahsa Zarei, Maryam Goudarzi, Renliang Zhang, Belinda Willard, Li Zhang, Adam Kresak, Joseph E. Willis, Gi-Ming Wang, Curtis Tatsuoka, Joseph M. Salvino, Ilya Bederman, Henri Brunengraber, Costas A. Lyssiotis, Jonathan R. Brody, Jordan M. Winter

Student Papers, Posters & Projects

Pancreatic Ductal Adenocarcinoma (PDAC) is highly resistant to chemotherapy. Effective alternative therapies have yet to emerge, as chemotherapy remains the best available systemic treatment. However, the discovery of safe and available adjuncts to enhance chemotherapeutic efficacy can still improve survival outcomes. We show that a hyperglycemic state substantially enhances the efficacy of conventional single- and multi-agent chemotherapy regimens against PDAC. Molecular analyses of tumors exposed to high glucose levels reveal that the expression of GCLC (glutamate-cysteine ligase catalytic subunit), a key component of glutathione biosynthesis, is diminished, which in turn augments oxidative anti-tumor damage by chemotherapy. Inhibition of GCLC phenocopies …

A Review Of Isomirs In Colorectal Cancer, Molly A. Lausten, Bruce M. Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

As advancements in sequencing technology rapidly continue to develop, a new classification of microRNAs has occurred with the discovery of isomiRs, which are relatively common microRNAs with sequence variations compared to their established template microRNAs. This review article seeks to compile all known information about isomiRs in colorectal cancer (CRC), which has not, to our knowledge, been gathered previously to any great extent. A brief overview is given of the history of microRNAs, their implications in colon cancer, the canonical pathway of biogenesis and isomiR classification. This is followed by a comprehensive review of the literature that is available on …

Particle Arc Single-Isocenter Stereotactic Radiosurgery Of Multiple Brain Metastases, L Volz, S Mein, T Tessonnier, Peilin Liu, A Mairani, M Durante, Xuanfeng Ding, C Graeff, T Li

Conference Presentation Abstracts

Purpose: To develop spot-scanning proton (SPArc) and heavy ion (SHArc) arc therapy for single-isocenter stereotatic radiosurgery (SISRS) of multiple brain metastases (MBMs). First results achieved with dedicated planning infrastructure are compared to state-of-the -art volumetric modulated photon arc therapy (HA-VMAT). Methods: A multi-institutional collaboration was established to develop bespoke SPArc and SHArc SISRS infrastructure with available research and commercial treatment planning systems. Devised planning and delivery methods considered dedicated energy, spot, and multi-arc selection strategies. SPArc and SHArc (carbon and helium ions) plans were generated for MBM patients exhibiting 3-12 intracranial lesions with GTV volumes between 0.03ccm and 19.8ccm, at …

An Analytic Model Of The External Beam Dose Rate Effect On Immune Cells In Blood Dosimetry, Lili Zhao, Peilin Liu, G Liu, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: Radiation therapy is a double-edged sword with regard to its immunomodulatory effect. It is critical to find how it is affected by dose rate. Thus, we developed an analytic model for calculating the number of immune cells receiving radiation. Methods: Suppose the blood is received radiation by constant dose rate. The blood is one-way flow without circulation in the radiation delivery at a constant velocity. Two kinds of lung treatment regimens were considered standard delivery 2Gy per fx total 30fx and hypo-fractionation SBRT 12 Gy per fx total 5 fx. Two different dose rates were simulated for standard treatment: …

Integrative Analysis Of Metabolome And Methylome Identifies The Correlation Of Aminoacyl-Trna Biosynthesis Metabolitesand Sepsecs Gene Methylation In Huntington’S Disease Brain Tissue, Sangeetha Vishweswaraiah, Ali Yilmaz, Nadia Ashrafi, Nazia Saiyed, Abdulla Khalid, Purvesh R. Koladiya, Xiaobei Pan, Shirin Macias, Uppala Radhakrishna, Stewart F. Graham

Conference Presentation Abstracts

No abstract provided.

Does Proton Arc Therapy Has Potential Clinical Benefits For Hepatocellular Carcinoma?, Peilin Liu, R Dalfsen, M Soukup, Shupeng Chen, Lili Zhao, Z Wang, X S. Gao, Thomas Quinn, Craig Stevens, Rohan Deraniyagala, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To investigate the potential clinical benefits and dose-averaged Linear Energy Transfer (LETd) sparing, utilizing proton arc plan for Hepatocellular carcinoma (HCC) patients in comparison with Intensity Modulated Proton Therapy (IMPT). Methods: Ten HCC patients have been retrospectively selected. Two planning groups were created: Proton Arc plans using Monaco ver. 6 and the clinical IMPT plan. Both planning groups used the same robustness parameters. The prescription dose is 67.5 Gy (RBE) in 15 fractions/ 66 GyE in 10 fractions of the Clinical Target Volume (CTV) following clinical IMPT plan. Robustness evaluations were performed to ensure target dose coverage. Normal Tissue …

Investigate The Delivery Efficiency Improvement For Sparc Compared To Impt, Peilin Liu, B A. De Jong, S Chang, Lili Zhao, G Liu, Craig Stevens, Rohan Deraniyagala, E W. Korevaar, J A. Langendijk, Xiaoqiang Li, Xuanfeng Ding

Conference Presentation Abstracts

Purpose: To assess the efficiency improvement of SPArc compared to IMPT in proton clinical operation.Methods: A random clinical operation day at a proton therapy center with a two room system. Aa total of 10 Head & Neck cancer cases treated on Jan 6th, 2021were selected and SPArc plans were generated for all the cases with similar target coverage and dose constraints of organ at risk (OARs). 3% range uncertainties and 3mm setup uncertainties were applied for robust optimization. The log files of clinical IMPT were exported to calculate true treatment delivery time. The machine-specific delivery sequence model was utilized to …

Test-Retest Reliability Of Virtual Reality Devices In Quantifying For Relative Afferent Pupillary Defect, Prithul Sarker, Nasif Zaman, Joshua Ong, Phani Paladugu, Molly Aldred, Ethan Waisberg, Andrew G. Lee, Alireza Tavakkoli

Student Papers, Posters & Projects

Background: The swinging flashlight test (SFT) is one of the most prominent clinical tests for detecting the relative afferent pupillary defect (RAPD). A positive RAPD localizes the lesion to the affected afferent pupil pathway and is a critical part of any ophthalmic exam. Testing for an RAPD, however, can be challenging (especially when small), and there is significant intrarater and interrater variability.

Methods: Prior studies have shown that the pupillometer can improve the detection and measurement of RAPD. In our previous research, we have demonstrated an automatic SFT by utilizing virtual reality (VR), named VR-SFT. We applied our methods to …

A Comprehensive Investigation Of Linear Energy Transfer Optimization Effectiveness In Intensity-Modulated Proton Therapy Via Alternating Direction Method Of Multipliers (Impt Let-Admm), Q Fan, G Liu, Lili Zhao, Xiaoqiang Li, Xuanfeng Ding, S Dai

Conference Presentation Abstracts

Linear energy transfer (LET)-guided optimization in intensity-modulated proton therapy (IMPT) via alternating direction method of multipliers (ADMM) has the potential to improve its biological effectiveness (IMPTLET- ADMM), in which the LET distribution in target can be escalated, while the LET distribution in the organs at risk can be mitigated. This study aims to quantitatively investigate the effectiveness of LET optimization in IMPT via ADMM with different solvers in its iteration loop. Methods: The clinical dose-volume-histogram (DVH) constraint noted dose sub-problem and clinical LET -volume-histogram (LVH) constraint noted LET sub-problem are combined to generate a composite objective function, which is available …

Urinary Cytokines As Potential Biomarkers Of Mild Cognitive Impairment And Alzheimer’S Disease: A Pilot Study, Nadia Ashrafi, Sumeyya Akyol, Sangeetha Vishweswaraiah, Abhishek Maiti, Ilyas Ustun, Sarah Bartolone, Travonia Brown-Hughes, Roland Thorpe Jr, Tammy Osentoski, Stacey Ruff, Amita Pai, Michael E. Maddens, Zaid Imam, Stewart Graham

Conference Presentation Abstracts

No abstract provided.

Protocol Of A Multicentre Randomised Controlled Trial Assessing Transperineal Prostate Biopsy To Reduce Infectiouscomplications, Jim Hu, Alec Zhu, Andrew Vickers, Mohamad Ezzeddine Allaf, Behfar Ehdaie, Anthony Schaeffer, Christian Pavlovich, Ashley E. Ross, David A. Green, Gerald Wang, Serge Ginzburg, Jeffrey S. Montgomery, Arvin George, John N. Graham, Benjamin T. Ristau, Andres Correa, Jonathan E. Shoag, Keith J. Kowalczyk, Tenny R. Zhang, E.M. Schaeffer

Einstein Health Papers

Introduction Approximately one million prostate biopsies are performed annually in the USA, and most are performed using a transrectal approach under local anaesthesia. The risk of postbiopsy infection is increasing due to increasing antibiotic resistance of rectal flora. Single-centre studies suggest that a clean, percutaneous transperineal approach to prostate biopsy may have a lower risk of infection. To date, there is no high-level evidence comparing transperineal versus transrectal prostate biopsy. We hypothesise that transperineal versus transrectal prostate biopsy under local anaesthesia has a significantly lower risk of infection, similar pain/discomfort levels and comparable detection of non-low-grade prostate cancer.

Methods and …

Persistently Elevated Hbv Viral-Host Junction Dna In Urine As A Biomarker For Hepatocellular Carcinoma Minimum Residual Disease And Recurrence: A Pilot Study, Selena Y Lin, Dina Halegoua-De Marzio, Peter Block, Yu-Lan Kao, Jesse M. Civan, Fwu-Shan Shieh, Wei Song, Hie-Won Hann, Ying-Hsiu Su

Department of Medicine Faculty Papers

Hepatitis B virus (HBV)-host junction sequences (HBV-JSs) has been detected in the urine of patients with HBV infection. This study evaluated HBV-JSs as a marker of minimum residual disease (MRD) and tumor recurrence after treatment in HBV-hepatocellular carcinoma (HCC) patients. Archived serial urine DNA from two HBV–HCC with recurrence as confirmed by MRI and four HBV-related cirrhosis (LC) patients were used. Urinary HBV-JSs were identified by an HBV-targeted NGS assay. Quantitative junction-specific PCR assays were developed to investigate dynamic changes of the most abundant urinary HBV-JS. Abundant urinary HBV-JSs were identified in two cases of tumor recurrence. In case 1, …

Glut1 Is Redundant In Hypoxic And Glycolytic Nucleus Pulposus Cells Of The Intervertebral Disc, Shira N. Johnston, Elizabeth S. Silagi, Vedavathi Madhu, Duc H. Nguyen, Irving M. Shapiro, Makarand V. Risbud

Department of Orthopaedic Surgery Faculty Papers

Glycolysis is central to homeostasis of nucleus pulposus (NP) cells in the avascular intervertebral disc. Since the glucose transporter, GLUT1, is a highly enriched phenotypic marker of NP cells, we hypothesized that it is vital for the development and postnatal maintenance of the disc. Surprisingly, primary NP cells treated with 2 well-characterized GLUT1 inhibitors maintained normal rates of glycolysis and ATP production, indicating intrinsic compensatory mechanisms. We showed in vitro that NP cells mitigated GLUT1 loss by rewiring glucose import through GLUT3. Of note, we demonstrated that substrates, such as glutamine and palmitate, did not compensate for glucose restriction resulting …

Expansion Of The Detrusor Muscular Ring Surrounding The Bladder Neck On Mri: Moving Beyond The Prostate As An Etiology Of Lower Urinary Tract Symptoms Due To Benign Prostatic Hyperplasia, Kiran Nandalur, David Walker, Hong Ye, Sayf A. Al-Katib, Brian Seifman, David Gangwish, Abhay Dhaliwal, Connor Ervin, Kayla Dobies, Channing Sesoko, Sirisha Nandalur, Bernadette Zwaans, Jennifer Nguyen, Jason Hafron

Conference Presentation Abstracts

Purpose: The etiology of lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) remains uncertain. The purpose of our study was to quantitatively analyze pelvic anatomic characteristics on magnetic resonance imaging (MRI) to assess for independent factors for symptoms.
*Methods and Materials: This retrospective single-institution study evaluated treatment-naïve men who underwent prostate MRI within 3 months of International Prostate Symptom Score (IPSS) from June 2021 to February 2022. Factors measured on MRI included: detrusor muscular ring surrounding the bladder neck measured as area and alternatively diameter, central gland (CG) mean apparent diffusion coefficient (ADC), levator hiatus (LH) volume, intrapelvic …

Regulation Of Airway Smooth Muscle Cell Proliferation By Diacylglycerol Kinase: Relevance To Airway Remodeling In Asthma, Miguel Angel Hernandez-Lara, Santosh K Yadav, Sushrut D. Shah, Mariko Okumura, Yuichi Yokoyama, Raymond B. Penn,, Taku Kambayashi, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

Airway remodeling in asthma involves the hyperproliferation of airway smooth muscle (ASM) cells. However, the molecular signals that regulate ASM growth are not completely understood. Gq-coupled G protein-coupled receptor and receptor tyrosine kinase signaling regulate ASM cell proliferation via activation of phospholipase C, generation of inositol triphosphate (IP3) and diacylglycerol (DAG). Diacylglycerol kinase (DGK) converts DAG into phosphatidic acid (PA) and terminates DAG signaling while promoting PA-mediated signaling and function. Herein, we hypothesized that PA is a pro-mitogenic second messenger in ASM, and DGK inhibition reduces the conversion of DAG into PA resulting in inhibition of ASM cell proliferation. We …

Grk2 Regulates Adp Signaling In Platelets Via P2y1 And P2y12., Xuefei Zhao, Matthew Cooper, James V Michael, Yanki Yarman, Aiden Baltz, J Kurt Chuprun, Walter J Koch, Steven E. Mckenzie, Maurizio Tomaiuolo, Timothy J Stalker, Li Zhu, Peisong Ma

Department of Medicine Faculty Papers

The critical role of G protein-coupled receptor kinase 2 (GRK2) in regulating cardiac function has been well documented for >3 decades. Targeting GRK2 has therefore been extensively studied as a novel approach to treating cardiovascular disease. However, little is known about its role in hemostasis and thrombosis. We provide here the first evidence that GRK2 limits platelet activation and regulates the hemostatic response to injury. Deletion of GRK2 in mouse platelets causes increased platelet accumulation after laser-induced injury in the cremaster muscle arterioles, shortens tail bleeding time, and enhances thrombosis in adenosine 5'-diphosphate (ADP)-induced pulmonary thromboembolism and in FeCl3-induced carotid …

Characterization And Assessment Of Barriers And Facilitators To The Decision-Making Process For Blood And Blood Donor Safety In The United States: A Collective Case Study, Lauren A. Crowder

Doctor of Philosophy in Translational Health Sciences Dissertations

Background: Over 16 million blood components are transfused to patients in need every year in the United States (Jones et al., 2021). Because of the reliance on human blood donors, the donation and transfusion of blood will always be associated with some level of risk for both donors and recipients; the tolerability of these risks may vary from stakeholder to stakeholder. While the U.S. Food and Drug Administration (FDA) concedes that attaining a blood supply with zero risk for transmission of infectious diseases may be unattainable (U.S. Food and Drug Administration, 2019), they continue to strive for the lowest …

Augmented Immunomodulation Of Endogenous Marrow-Derived Stem Cells In The Setting Of Acl Rupture, Mackenzie Fleischer, Michael Newton, Samantha Hartner, John A. Driscoll, Anthony Arveschoug, Chritopher C. Vasileff, Kevin Baker

Conference Presentation Abstracts

PURPOSE: Augmentation of MSC immunomodulation is an unexplored, potentially useful therapeutic to combat PTOA following ACLR. Lower kynurenine-to-tryptophan ratios observed in synovial fluid of ACL rupture (ACLR) rats suggests decreased activity of tryptophan metabolizing enzyme, Ido, known to be secreted by MSCs to promote T-reg expansion and Th17 suppression. This study aims to characterize the immunomodulatory capacity of pharmacologically mobilized MSCs in conjunction with exogenously delivered Ido. METHODS: Rats (N = 48) underwent ACLR to evaluate the effects of mobilized MCSs on Ido1 and inflammatory cytokine expression profiles in the synovial fluid. Additionally, rats (N = 160) underwent ACLR to …

Path To Publication: A Peer Mentorship Model For Student-Lead Surgical Research, Usama Waqar, Hareem Rauf, Muskaan Abdul Qadir, Hina Inam

Medical College Documents

Early and sustained involvement in research is imperative for medical students to ensure better career prospects in addition to provision of high-quality, evidence-based care to patients. However, involvement of students in surgical research still remains limited, owing to inadequate research training. The current paper was planned to describe the structure of the "Path to Publication" series, incorporating peer mentorship with capacity-building research workshops for medical students. A total of 25 students were grouped into 8 surgical subspecialty groups to conduct research, supervised by experienced student research and faculty mentors. In addition, a series of research workshops were organized in synchronization …

Ogr1-Dependent Regulation Of The Allergen-Induced Asthma Phenotype, Ajay P Nayak, Deepak A. Deshpande, Phd, Sushrut D. Shah, Dominic R Villalba, Roslyn Yi, Nadan Wang, Raymond B. Penn

Division of Pulmonary and Critical Care Medicine Faculty Papers

The proton-sensing receptor, ovarian cancer G protein-coupled receptor (OGR1), has been shown to be expressed in airway smooth muscle (ASM) cells and is capable of promoting ASM contraction in response to decreased extracellular pH. OGR1 knockout (OGR1KO) mice are reported to be resistant to the asthma features induced by inhaled allergen. We recently described certain benzodiazepines as OGR1 activators capable of mediating both procontractile and prorelaxant signaling in ASM cells. Here we assess the effect of treatment with the benzodiazepines lorazepam or sulazepam on the asthma phenotype in wild-type (WT) and OGR1KO mice subjected to inhaled house dust mite (HDM; …

Adult Spiny Mice (Acomys) Exhibit Endogenous Cardiac Recovery In Response To Myocardial Infarction, Hsuan Peng, Kazuhiro Shindo, Renée R. Donahue, Erhe Gao, Brooke M. Ahern, Bryana M. Levitan, Himi Tripathi, David Powell, Ahmed Noor, Garrett A. Elmore, Jonathan Satin, Ashley W. Seifert, Ahmed K. Abdel-Latif

Physiology Faculty Publications

Complex tissue regeneration is extremely rare among adult mammals. An exception, however, is the superior tissue healing of multiple organs in spiny mice (Acomys). While Acomys species exhibit the remarkable ability to heal complex tissue with minimal scarring, little is known about their cardiac structure and response to cardiac injury. In this study, we first examined baseline Acomys cardiac anatomy and function in comparison with commonly used inbred and outbred laboratory Mus strains (C57BL6 and CFW). While our results demonstrated comparable cardiac anatomy and function between Acomys and Mus, Acomys exhibited a higher percentage of cardiomyocytes displaying …

Development Of A Novel Mir-3648-Related Gene Signature As A Prognostic Biomarker In Esophageal Adenocarcinoma, Donglei Zhang, Hang Yin, Thomas L. Bauer, Michael P. Rogers, Jeffrey B. Velotta, Clinton T. Morgan, Weijia Du, Ping Xu, Xiaozhe Qian

Surgery Faculty Publications

Background: Esophageal adenocarcinoma (EA) is a typical immunogenic malignant tumor with a dismal 5-year survival rate lower than 20%. Although miRNA-3648 (miR-3648) is expressed abnormally in EA, its impact on the tumor immune microenvironment remains unknown. In this study, we sought to identify immune-related genes (IRGs) that are targeted by miR-3648 and develop an EA multigene signature.

Methods: The gene expression data of 87 EA tumor samples and 67 normal tissue samples from The Cancer Genome Atlas (TCGA) database and the Genotype-Tissue Expression (GTEx) database were downloaded, respectively. Weighted gene co-expression network analysis (WGCNA), the CIBERSORT algorithm, and Cox regression …

The Contribution Of Patient Reported Outcome Measures To Shared Decision-Making In Radiation Oncology At A Midwestern Comprehensive Cancer Center, Kellie Bodeker

Doctor of Philosophy in Translational Health Sciences Dissertations

Background. Chronic diseases, such as lung cancer, require a provider-patient relationship developed over time. This relationship fosters shared decision-making (SDM), a collaborative, dynamic information exchange and analysis between provider and patient regarding treatment and desired outcomes. Established benefits to SDM include an improved quality of life and decreased anxiety and depression. Despite established benefits, recent research suggests radiation oncologists are not engaging in SDM. A decision-aid tool utilizing patient reported outcome measures may increase SDM between radiation oncologists and patients with lung cancer. Patient-reported outcome measures, wherein the patient provides direct assessment of their health and quality of life, …

Apoε4 Lowers Energy Expenditure In Females And Impairs Glucose Oxidation By Increasing Flux Through Aerobic Glycolysis, Brandon C. Farmer, Holden C. Williams, Nicholas A. Devanney, Margaret A. Piron, Grant K. Nation, David J. Carter, Adeline E. Walsh, Rebika Khanal, Lyndsay E. A. Young, Jude C. Kluemper, Gabriela Hernandez, Elizabeth J. Allenger, Rachel Mooney, Lesley R. Golden, Cathryn T. Smith, J. Anthony Brandon, Vedant A. Gupta, Philip A. Kern, Matthew S. Gentry, Josh M. Morganti, Ramon C. Sun, Lance A. Johnson

Physiology Faculty Publications

BACKGROUND: Cerebral glucose hypometabolism is consistently observed in individuals with Alzheimer's disease (AD), as well as in young cognitively normal carriers of the Ε4 allele of Apolipoprotein E (APOE), the strongest genetic predictor of late-onset AD. While this clinical feature has been described for over two decades, the mechanism underlying these changes in cerebral glucose metabolism remains a critical knowledge gap in the field.

METHODS: Here, we undertook a multi-omic approach by combining single-cell RNA sequencing (scRNAseq) and stable isotope resolved metabolomics (SIRM) to define a metabolic rewiring across astrocytes, brain tissue, mice, and human subjects expressing APOE4.

RESULTS: Single-cell …

Circumcision As An Intervening Strategy Against Hiv Acquisition In The Male Genital Tract, Adhikarimayum Lakhikumar Sharma, Joseph Hokello, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Unsafe sex with HIV-infected individuals remains a major route for HIV transmission, and protective strategies, such as the distribution of free condoms and pre-or post-prophylaxis medication, have failed to control the spread of HIV, particularly in resource-limited settings and high HIV prevalence areas. An additional key strategy for HIV prevention is voluntary male circumcision (MC). International health organizations (e.g., the World Health Organization, UNAIDS) have recommended this strategy on a larger scale, however, there is a general lack of public understanding about how MC effectively protects against HIV infection. This review aims to discuss the acquisition of HIV through the …

Chloroquine: Autophagy Inhibitor, Antimalarial, Bitter Taste Receptor Agonist In Fight Against Covid-19, A Reality Check?, Pawan Sharma, Kielan D. Mcalinden, Saeid Ghavami, Deepak A. Deshpande

Center for Translational Medicine Faculty Papers

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate …

Timing Of Preoperative Surgical Antibiotic Prophylaxis Prior To One-To-Three Level Elective Lumbar Fusion, Akash Singh, Gregory Schroeder, Md, Jose Canseco, Md, Alexander Vaccaro, Md, Parthik Patel, Md, Ariana Reyes, Md

Phase 1

Introduction: Surgical site infections (SSIs) in patients who have undergone lumbar fusion surgery can be a devastating complication. The aim of this study was to examine the relationship between timing of preoperative antibiotic prophylaxis and adverse outcomes such as SSIs with subgroup analysis stratified by antibiotic type.

Methods: This retrospective cohort included patients having undergone a 1-3 level lumbar fusion who were allocated into 5 groups based on the time from antibiotic administration to incision (Group A = 0-15 min, Group B = 16-30 min, Group C = 31-45 min, Group D = 46 – 60 min, and Group …