Medicine and Health Sciences Commons^™

Methionyl-Trna Synthetase Synthetic And Proofreading Activities Are Determinants Of Antibiotic Persistence, Whitney N. Wood, Miguel Angel Rubio, Lorenzo Eugenio Leiva, Gregory J. Phillips, Michael Ibba

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Bacterial antibiotic persistence is a phenomenon where bacteria are exposed to an antibiotic and the majority of the population dies while a small subset enters a low metabolic, persistent, state and are able to survive. Once the antibiotic is removed the persistent population can resuscitate and continue growing. Several different molecular mechanisms and pathways have been implicated in this phenomenon. A common mechanism that may underly bacterial antibiotic persistence is perturbations in protein synthesis. To investigate this mechanism, we characterized four distinct metG mutants for their ability to increase antibiotic persistence. Two metG mutants encode changes near the catalytic site …

Biomarkers For Managing Neurodegenerative Diseases, Lara Cheslow, Adam E. Snook, Scott A. Waldman

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track responses to therapy, and parse the causality of molecular events to identify novel targets for further clinical investigation. …

Correction: The Novel Phosphatase Nudt5 Is A Critical Regulator Of Triple-Negative Breast Cancer Growth, Jing Qian, Yanxia Ma, William M Tahaney, Cassandra L Moyer, Amanda Lanier, Jamal Hill, Darian Coleman, Negar Koupaei, Susan G Hilsenbeck, Michelle I Savage, Brent D G Page, Abhijit Mazumdar, Powel H Brown

Faculty, Staff and Student Publications

No abstract provided.

Integration Of Kupffer Cells Into Human Ipsc-Derived Liver Organoids For Modeling Liver Dysfunction In Sepsis, Yang Li, Yunzhong Nie, Xia Yang, Yang Liu, Xiaoshan Deng, Yoshihito Hayashi, Riana Plummer, Qinglin Li, Na Luo, Toshiharu Kasai, Takashi Okumura, Yu Kamishibahara, Takemasa Komoto, Takuya Ohkuma, Satoshi Okamoto, Yumiko Isobe, Kiyoshi Yamaguchi, Yoichi Furukawa, Hideki Taniguchi

Faculty, Staff and Student Publications

Maximizing the potential of human liver organoids (LOs) for modeling human septic liver requires the integration of innate immune cells, particularly resident macrophage Kupffer cells. In this study, we present a strategy to generate LOs containing Kupffer cells (KuLOs) by recapitulating fetal liver hematopoiesis using human induced pluripotent stem cell (hiPSC)-derived erythro-myeloid progenitors (EMPs), the origin of tissue-resident macrophages, and hiPSC-derived LOs. Remarkably, LOs actively promote EMP hematopoiesis toward myeloid and erythroid lineages. Moreover, supplementing with macrophage colony-stimulating factor (M-CSF) proves crucial in sustaining the hematopoietic population during the establishment of KuLOs. Exposing KuLOs to sepsis-like endotoxins leads to significant …

Hdx-Ms Finds That Partial Unfolding With Sequential Domain Activation Controls Condensation Of A Cellular Stress Marker, Ruofan Chen, Hendrik Glauninger, Darren N Kahan, Julia Shangguan, Joseph R Sachleben, Joshua A Riback, D Allan Drummond, Tobin R Sosnick

Faculty, Staff and Students Publications

Eukaryotic cells form condensates to sense and adapt to their environment [S. F. Banani, H. O. Lee, A. A. Hyman, M. K. Rosen, Nat. Rev. Mol. Cell Biol. 18, 285–298 (2017), H. Yoo, C. Triandafillou, D. A. Drummond, J. Biol. Chem. 294, 7151–7159 (2019)]. Poly(A)-binding protein (Pab1), a canonical stress granule marker, condenses upon heat shock or starvation, promoting adaptation [J. A. Riback et al., Cell 168, 1028–1040.e19 (2017)]. The molecular basis of condensation has remained elusive due to a dearth of techniques to probe structure directly in condensates. We apply hydrogen–deuterium exchange/mass spectrometry to investigate the mechanism of …

Space (Swift Phenotypic Analysis Of Cells): An Open-Source, Single Cell Analysis Of Cell Painting Data, Fabio Stossi, Pankaj K Singh, Michela Marini, Kazem Safari, Adam T Szafran, Alejandra Rivera Tostado, Christopher D Candler, Maureen G Mancini, Elina A Mosa, Michael J Bolt, Demetrio Labate, Michael A Mancini

Faculty, Staff and Students Publications

Phenotypic profiling by high throughput microscopy has become one of the leading tools for screening large sets of perturbations in cellular models. Of the numerous methods used over the years, the flexible and economical Cell Painting (CP) assay has been central in the field, allowing for large screening campaigns leading to a vast number of data-rich images. Currently, to analyze data of this scale, available open-source software ( i.e. , CellProfiler) requires computational resources that are not available to most laboratories worldwide. In addition, the image-embedded cell-to-cell variation of responses within a population, while collected and analyzed, is usually averaged …

A Therapeutically Targetable Positive Feedback Loop Between Nc-Hlx-2-7, Hlx, And Myc That Promotes Group 3 Medulloblastoma, Keisuke Katsushima, Kandarp Joshi, Menglang Yuan, Brigette Romero, Mona Batish, Stacie Stapleton, George Jallo, Elayaraja Kolanthai, Sudipta Seal, Olivier Saulnier, Michael D Taylor, Robert J Wechsler-Reya, Charles G Eberhart, Ranjan J Perera

Faculty, Staff and Students Publications

Recent studies suggest that long non-coding RNAs (lncRNAs) contribute to medulloblastoma (MB) formation and progression. We have identified an lncRNA, lnc-HLX-2-7, as a potential therapeutic target in group 3 (G3) MBs. lnc-HLX-2-7 RNA specifically accumulates in the promoter region of HLX, a sense-overlapping gene of lnc-HLX-2-7, which activates HLX expression by recruiting multiple factors, including enhancer elements. RNA sequencing and chromatin immunoprecipitation reveal that HLX binds to and activates the promoters of several oncogenes, including TBX2, LIN9, HOXM1, and MYC. Intravenous treatment with cerium-oxide-nanoparticle-coated antisense oligonucleotides targeting lnc-HLX-2-7 (CNP-lnc-HLX-2-7) inhibits tumor growth by 40%-50% in an intracranial MB xenograft mouse …

Identifying Potential Dietary Treatments For Inherited Metabolic Disorders Using Drosophila Nutrigenomics, Felipe Martelli, Jiayi Lin, Sarah Mele, Wendy Imlach, Oguz Kanca, Christopher K Barlow, Jefferson Paril, Ralf B Schittenhelm, John Christodoulou, Hugo J Bellen, Matthew D W Piper, Travis K Johnson

Faculty, Staff and Students Publications

Inherited metabolic disorders are a group of genetic conditions that can cause severe neurological impairment and child mortality. Uniquely, these disorders respond to dietary treatment; however, this option remains largely unexplored because of low disorder prevalence and the lack of a suitable paradigm for testing diets. Here, we screened 35 Drosophila amino acid disorder models for disease-diet interactions and found 26 with diet-altered development and/or survival. Using a targeted multi-nutrient array, we examine the interaction in a model of isolated sulfite oxidase deficiency, an infant-lethal disorder. We show that dietary cysteine depletion normalizes their metabolic profile and rescues development, neurophysiology, …

Ly6c+ Monocytes In The Skin Promote Systemic Alphavirus Dissemination, Autumn C Holmes, Cormac J Lucas, Morgan E Brisse, Brian C Ware, Heather D Hickman, Thomas E Morrison, Michael S Diamond

2020-Current year OA Pubs

Alphaviruses are mosquito-transmitted pathogens that induce high levels of viremia, which facilitates dissemination and vector transmission. One prevailing paradigm is that, after skin inoculation, alphavirus-infected resident dendritic cells migrate to the draining lymph node (DLN), facilitating further rounds of infection and dissemination. Here, we assess the contribution of infiltrating myeloid cells to alphavirus spread. We observe two phases of virus transport to the DLN, one that occurs starting at 1 h post infection and precedes viral replication, and a second that requires replication in the skin, enabling transit to the bloodstream. Depletion of Ly6C

Efficacy And Feasibility Of Short-Stretch Compression Therapy For Filarial Lymphedema In Sri Lanka, Jaimee M Hall, Nirmitha Lalindi De Silva, Janaka Ruben, Sandani S Thilakarathne, Thishan Channa Yahathugoda, Philip J Budge

2020-Current year OA Pubs

The WHO-recommended essential package of care (EPC) for filarial limb lymphedema consists of daily limb washing, entry lesion management, limb protection, exercises, and elevation. Decongestive therapy (DT) with compression bandaging by trained lymphedema therapists adds additional benefit but is unavailable for most in low- and middle-income countries (LMICs). To determine whether DT using self-adjustable, short-stretch compression garments (SSCG), prefitted using portable, three-dimensional infrared imaging (3DII), would be effective and feasible in LMIC settings, we conducted a pilot 6-week, interventional, single-group, open-label pilot study in Galle, Sri Lanka. Ten participants with Dreyer stage 3 lymphedema used SSCG for 2 weeks after …

Impact Of Imaging Frequency On Progression-Free Survival In Alliance Trials Enrolling Patients With Follicular Lymphoma, Sarah C Rutherford, Jun Yin, Levi D Pederson, Kristie A Blum, Peter Martin, Sin-Ho Jung, Barbara Grant, Cara Rosenbaum, Bruce D Cheson, Nancy L Bartlett, Sumithra J Mandrekar, John P Leonard

2020-Current year OA Pubs

No abstract provided.

Targeting Cxcr4, Vla-4, And Cxcr2 For Hematopoietic Stem Cell Mobilization, Daniel Cancilla, Michael P Rettig, Darja Karpova, Haresh Thakellapalli, Megh Singh, Marvin J Meyers, Peter G Ruminski, Stephanie Christ, Ezhilarasi Chendamarai, Feng Gao, Leah Gehrs, Julie K Ritchey, Michael Prinsen, John F Dipersio

2020-Current year OA Pubs

No abstract provided.

Phase 2 Study Of Add-On Parsaclisib For Patients With Myelofibrosis And Suboptimal Response To Ruxolitinib: Final Results, Abdulraheem Yacoub, Stephen T Oh, Et Al.

2020-Current year OA Pubs

Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib. Eligible patients remained on a stable ruxolitinib dose and received add-on parsaclisib 10 or 20 mg, once daily for 8 weeks, and once weekly thereafter (daily-to-weekly dosing; n = 32); or parsaclisib 5 or 20 mg, once daily for 8 weeks, …

Intergenerational Protective Anti-Gut Commensal Immunoglobulin G Originates In Early Life, Brigida Rusconi, Adina K Bard, Ryan Mcdonough, Angel M Kindsvogel, Jacqueline D Wang, Sreeram Udayan, Keely G Mcdonald, Rodney D Newberry, Phillip I Tarr

2020-Current year OA Pubs

Maternal immunoglobulins of the class G (IgGs) protect offspring from enteric infection, but when, where, and how these antibodies are physiologically generated and confer protection remains enigmatic. We found that circulating IgGs in adult mice preferentially bind early-life gut commensal bacteria over their own adult gut commensal bacteria. IgG-secreting plasma cells specific for early-life gut bacteria appear in the intestine soon after weaning, where they remain into adulthood. Manipulating exposure to gut bacteria or plasma cell development before, but not after, weaning reduced IgG-secreting plasma cells targeting early-life gut bacteria throughout life. Further, the development of this anti-gut commensal IgG …

The Genomic And Evolutionary Landscapes Of Anaplastic Thyroid Carcinoma, Peter Y F Zeng, Stephenie D Prokopec, Stephen Y Lai, Nicole Pinto, Michelle A Chan-Seng-Yue, Roderick Clifton-Bligh, Michelle D Williams, Christopher J Howlett, Paul Plantinga, Matthew J Cecchini, Alfred K Lam, Iram Siddiqui, Jianxin Wang, Ren X Sun, John D Watson, Reju Korah, Tobias Carling, Nishant Agrawal, Nicole Cipriani, Douglas Ball, Barry Nelkin, Lisa M Rooper, Justin A Bishop, Cathie Garnis, Ken Berean, Norman G Nicolson, Paul Weinberger, Ying C Henderson, Christopher M Lalansingh, Mao Tian, Takafumi N Yamaguchi, Julie Livingstone, Adriana Salcedo, Krupal Patel, Frederick Vizeacoumar, Alessandro Datti, Liu Xi, Yuri E Nikiforov, Robert Smallridge, John A Copland, Laura A Marlow, Martin D Hyrcza, Leigh Delbridge, Stan Sidhu, Mark Sywak, Bruce Robinson, Kevin Fung, Farhad Ghasemi, Keith Kwan, S Danielle Macneil, Adrian Mendez, David A Palma, Mohammed I Khan, Mushfiq Shaikh, Kara M Ruicci, Bret Wehrli, Eric Winquist, John Yoo, Joe S Mymryk, James W Rocco, David Wheeler, Steve Scherer, Thomas J Giordano, John W Barrett, William C Faquin, Anthony J Gill, Gary Clayman, Paul C Boutros, Anthony C Nichols

Faculty, Staff and Student Publications

Anaplastic thyroid carcinoma is arguably the most lethal human malignancy. It often co-occurs with differentiated thyroid cancers, yet the molecular origins of its aggressivity are unknown. We sequenced tumor DNA from 329 regions of thyroid cancer, including 213 from patients with primary anaplastic thyroid carcinomas. We also whole genome sequenced 9 patients using multi-region sequencing of both differentiated and anaplastic thyroid cancer components. Using these data, we demonstrate thatanaplastic thyroid carcinomas have a higher burden of mutations than other thyroid cancers, with distinct mutational signatures and molecular subtypes. Further, different cancer driver genes are mutated in anaplastic and differentiated thyroid …

Quality Improvement In Healthcare: A Practical Guide For Providers (Part 3), Jeremy Ellis

Transformative Medicine

No abstract provided.

Novel Drug Approvals 2023, Emily Wagner, Christina Swiger, Mary Hoang, Maley Zents

Transformative Medicine

This article provides an overview of the novel drugs approved for 2023. The Food and Drug Administration’s (FDA) Center for Drug Evaluation and Research (CDER) provides standards to drug developers. The CDER sets standards for required data needed in the drug development and application process. Every year a variety of new drugs and biological products are approved. Some are new molecular compounds while others are structurally similar to those already on the market. Therefore, products may not have been used in medical practice previously while others have already been used in practice. This article highlights medications that are new in …

“This Ekg Is Concerning For Ischemia!”, Muhammad M. Zafar

Transformative Medicine

No abstract provided.

Aortic Dissection: The Insidious Menace, Muhammad Umer Riaz Gondal, John Lemoine, Mohammad Baig, Prem Parajuli, Zainab Kiyani, Hamza Khan, Hassam Saif

Transformative Medicine

Introduction:

Aortic dissection represents a critical emergency characterized by the cleavage of aortic wall layers, creating a deceptive false lumen. Associated with high mortality rates, prompt diagnosis and intervention are needed to ensure survival.

Case:

A 63-year-old male with no significant medical history presented to the emergency with two days of worsening mid-sternal chest pain. Upon presentation, he was hemodynamically stable. Blood pressure was 130/85 mm Hg (similar in both arms), heart rate 90 bpm, and saturating 98 % on room air. Physical examination did not reveal any new murmurs. EKG showed normal sinus rhythm, no ischemic changes, and a …

New Onset Dyspnea In A Patient With Pacemaker, What Does The Ecg Tracing Show?, Jakob Nypaver, Robert Libera Do, Arun Kundra, Ravi Choxi

Transformative Medicine

Dual chamber pacemakers are programmed to allow for AV synchrony. Whenever a patient with a dual chamber pacemaker with underlying sinus rhythm presents with AV dissociation, the lack of AV synchrony should be questioned. The authors present a case of new onset dyspnea diagnosed as pacemaker syndrome. The diagnosis was initially delayed due to underlying ventricular paced rhythm as misidentified as normal pacemaker behavior.

A 69-year-old female with a past medical history of 2:1 atrioventricular block status post dual-chamber pacemaker implant presented with complaints of new onset shortness of breath and dyspnea. The ECG showed a ventricular rate of 66 …

Autoimmune Hemolytic Anemia: A Rare Presentation Of Mantle Cell Lymphoma, Ian Garrahy, Shoja Rahimian

Transformative Medicine

Autoimmune hemolytic anemia (AIHA) is a well-recognized phenomenon of non-Hodgkin lymphoma, albeit with only few cases described with mantle cell lymphoma (MCL). The characteristics of such cases can improve understanding and management of AIHA in this type of lymphoma. To that end, we describe herein two cases of patients with MCL who presented with AIHA, with comparison to nine previously described cases in literature.

Metformin Continuation Versus Holding Pre And Post Coronary Angiography With Normal Renal Function: A Systematic Review And Meta-Analysis, Mohammad Hamza, Yasar Sattar, Sadaf Fakhra, Neel Patel, Mubashar Karamat, Saman Razzaq, Aamir Saeed, Khaled M. Harmouch, Islam Elgendy, Mamas Mamas, Anand Prasad, Wael Aljaroudi, Ramesh Daggubati, M Chadi Alraies

Transformative Medicine

Background

It is common practice to withhold metformin prior to cardiac catheterization due to fear of developing lactic acidosis in the setting of contrast-associated acute kidney injury (AKI). The evidence behind this recommendation is currently weak.

Methods

We collected 851 articles from PubMed and Embase, of which 3 met our inclusion criteria. Inclusion criteria were age > 18 years, baseline use of long-term metformin with continued or interrupted metformin use in patients during diagnostic or interventional cardiac catheterization. The outcomes studied were differences between post-catheterization and pre-catheterization serum creatinine (SCr) and glomerular filtration rate (GFR). We excluded studies dealing with patients …

Lstm-Based Recurrent Neural Network Predicts Influenza-Like-Illness In Variable Climate Zones, Alfred Amendolara, Christopher Gowans, Joshua Barton, David Sant, Andrew Payne

Annual Research Symposium

Purpose: Influenza virus is responsible for a recurrent, yearly epidemic in most temperate regions of the world. For the 2021-2022 season the CDC reports 5000 deaths and 100,000 hospitalizations, a significant number despite the confounding presence of SARS-CoV-2. The mechanisms behind seasonal variance in flu burden are not well understood. Based on a previously validated model, this study seeks to expand understanding of the impact of variable climate regions on seasonal flu trends. To that end, three climate regions have been selected. Each region represents a different ecological region and provides different weather patterns showing how the climate variables impact …

Dissociating Reading And Auditory Comprehension In Persons With Aphasia, Rachel M. Harrington, Sigfus Kristinsson, Janina Wilmskoetter, Natalie Busby, Dirk Den Ouden, Chris Rorden, Julius Fridriksson Ph.D., Leonardo Bonilha

Faculty Publications

Language comprehension is often affected in individuals with post-stroke aphasia. However, deficits in auditory comprehension are not fully correlated with deficits in reading comprehension and the mechanisms underlying this dissociation remain unclear. This distinction is important for understanding language mechanisms, predicting long-term impairments and future development of treatment interventions. Using comprehensive auditory and reading measures from a large cohort of individuals with aphasia, we evaluated the relationship between aphasia type and reading comprehension impairments, the relationship between auditory versus reading comprehension deficits and the crucial neuroanatomy supporting the dissociation between post-stroke reading and auditory deficits. Scores from the Western Aphasia …

Playful Progress: A Parent's Guide To Growth And Development, Gabriella N. Lawrey

Honors Program: Senior Projects (Public)

This thesis presents a creative project aimed at empowering parents to recognize developmental achievements, as well as address potential developmental delays in their children. Grounded in the principles of child development, this project focuses on creating age-appropriate activities that facilitate the identification of developmental milestones. By utilizing foundational resources in the field of child development, this toolkit of engaging activities has been curated to support parental understanding and observation. The primary objective of this applied knowledge project is to better equip parents with the vocabulary and tools to facilitate their child’s development. Throughout these activities, parents are encouraged to engage …

Increased Nitrate Intake From Beetroot Juice Over 4 Weeks Affects Nitrate Metabolism, But Not Vascular Function Or Blood Pressure In Older Adults With Hypertension, Rebeka Fejes, Martin Lutnik, Stefan Weisshaar, Nina Pilat, Karl-Heinz Wagner, Hans-Peter Stüger, Jonathan M. Peake, Richard J. Woodman, Kevin D. Croft, Catherine P. Bondonno, Jonathan M. Hodgson, Michael Wolzt, Oliver Neubauer

Research outputs 2022 to 2026

The decline in vascular function and increase in blood pressure with aging contribute to an increased cardiovascular disease risk. In this randomized placebo-controlled crossover study, we evaluated whether previously reported cardiovascular benefits of plant-derived inorganic nitrate via nitric oxide (NO) translate into improved vascular function and blood pressure-lowering in 15 men and women (age range: 56-71 years) with treated hypertension. We investigated the effects of a single ∼400 mg-dose at 3 hours post-ingestion (3H POST) and the daily consumption of 2 × ∼400 mg of nitrate through nitrate-rich compared with nitrate-depleted (placebo) beetroot juice over 4 weeks (4WK POST). Measurements …

Smoking Cessation In Primary Care Using The 5 A’S Model Of Motivational Interviewing: A Quality Improvement Project, Lauren M. Violette

DNP Projects

Significance and Background: Tobacco use is one of the leading causes of preventable death in the United States, greatly contributing to morbidity and mortality. Motivational Interviewing (MI), a counseling style, has been shown to increase motivation for change in people. Successful intervention for behavior modification starts with identifying a person’s readiness for change. The 5 A’s model is an established form of motivational interviewing that addresses the five major steps of intervention: Ask, Advise, Assess, Assist, and Arrange. The Center for Disease Control (CDC) endorses the use of the 5 A’s brief tobacco intervention to protect the public’s health from …

Evaluating Drowning Prevention Campaigns - The Challenge Of Getting The Right Information To The Right People At The Right Time: A Response To Calverley, Petrass, And Blitvich, Gemma Crawford, Meg Abercromby, Malena Della Bona, Justine E. Leavy Ph.D.

International Journal of Aquatic Research and Education

Evidence-informed decision making requires timely and readily available research and evaluation for policy and practice. In the context of drowning prevention, evaluation of interventions in the grey and peer reviewed literature is relatively scarce. Lack of evidence and associated barriers to access limits the scope of knowledge translation efforts and the application of research outcomes to initiatives designed to prevent drowning. The paper, Alcohol Focused Drowning Prevention Campaigns: What Do We Know and What Should We Do Now? highlights a lack of specific evaluation for alcohol-focused drowning prevention campaigns. We offer insights as evaluators of a youth water safety program …

Novel Frameless Linac Radiosurgery Solution For Uveal Melanoma, Louis Cappelli, Mehak Khan, Sudheshna Vemula, Christina Hum, Haisong Lui, Yan Yu, Yingxuan Chen, Yechi Zhang, Muhammad Sharif, Wenyin Shi

Department of Radiation Oncology Faculty Papers

INTRODUCTION: Radiation treatment has replaced enucleation as an organ-preservation treatment for patients with uveal melanoma (UM). We developed a novel non-invasive, frameless LINAC based solution for fractionated stereotactic radiosurgery (fSRS) treatment.

METHODS: We designed and constructed the a stereotactic ocular localization box that can be attached and indexed to a stereotactic LINAC tabletop. It contains adjustable LED lights as a gaze focus point and CCD camera for monitoring of the patient's eye position. The device also has 6 infrared spheres compatible with the ExacTRAC IGRT system. Treatment plans were developed using iPLAN Dose version 4.5, with conformal dynamic arcs and …

Odevixibat: A Novel Bile Salt Inhibitor Treatment For Pruritus In Progressive Familial Intrahepatic Cholestasis, Farrah E. Flattmann, Farhan S. Mohiuddin, Anjuni Singh, Anamika Tandon, Stewart J. Lockett, Jon D. Hirsch, Chizoba N. Mosieri, Adam M. Kaye, Giustino Varrassi, Shahab Ahmadzadeh, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Chronic pruritus is defined as an itch lasting greater than six weeks. It can manifest from a wide variety of etiologies, as many different substances can act as pruritogens, such as steroids, histamine, progesterone, endogenous opioids, and serotonin. In the setting of cholestatic liver disease, increased bile acids play a major role in chronic pruritus. The itching in cholestatic liver disease is worsened in intensity at night and localized frequently to the palms, soles, knees, and other pressure sites. It can be hard to manage, affecting the quality of sleep and causing irritability, poor attention, and, in some cases, depression. …