Digital Commons Network^™

Using Micro Satellites To Assess The Impact Of Algae Growth On Global Warming, Hursh, Vanessa

Student Works

Data gathered from microsatellites can inform policymakers and environmental agencies about the impact of algae on global warming. It can guide the development of strategies to mitigate or harness the potential benefits of algae growth.

The Gender Of Gideon, Kathryn A. Sabbeth, Jessica Steinberg

Faculty Publications

This Article makes a simple claim that has been overlooked for decades and yet has enormous theoretical and practical significance: the constitutional guarantee of counsel adopted by the U.S. Supreme Court in Gideon v. Wainwright accrues largely to the benefit of men. In this Article, we present original data analysis demonstrating that millions of women face compulsory and highly punitive encounters with the justice system but do so largely in the civil courts, where no right to counsel attaches. The demographic picture that emerges is one in which the right to counsel skews heavily against women’s interests. As this Article …

The Nightmare Of Dream Advertising, Dustin Marlan

Faculty Publications

Advertisers are attempting to market to us while we dream. This is not science fiction, but rather a troubling new reality. Using a technique dubbed “targeted dream incubation” (TDI), companies have begun inserting commercial messages into people’s dreams. Roughly, TDI works by: (1) creating an association during waking life using sensory cues (for example, a pairing of sounds, visuals, or scents); and (2) as the subject is drifting off to sleep, the association is again introduced with the goal of triggering related dreams with related subject matter. Based on a 2021 American Marketing Association survey, 77 percent of 400 companies …

A Synthesis Of The Science And Law Relating To Eyewitness Misidentifications And Recommendations For How Police And Courts Can Reduce Wrongful Convictions Based On Them, Henry F. Fradella

Seattle University Law Review

The empirical literature on perception and memory consistently demonstrates the pitfalls of eyewitness identifications. Exoneration data lend external validity to these studies. With the goal of informing law enforcement officers, prosecutors, criminal defense attorneys, judges, and judicial law clerks about what they can do to reduce wrongful convictions based on misidentifications, this Article presents a synthesis of the scientific knowledge relevant to how perception and memory affect the (un)reliability of eyewitness identifications. The Article situates that body of knowledge within the context of leading case law. The Article then summarizes the most current recommendations for how law enforcement personnel should—and …

Adapting Grief And Bereavement-Focused Cognitive Behavioral Therapy For Chinese-Identifying Individuals In America: A Cultural Analysis, Ian Tsang

Graduate School of Professional Psychology: Doctoral Papers and Masters Projects

Anti-Asian hate as well as shifting circumstances brought on by current events all around the world highlight the increased need for mental health support and services in an ever-growing Chinese population in the United States, particularly in regard to grief work. Additionally, Chinese Americans demonstrate a disproportionate and lower utilization of mental health services, especially in comparison to the general population in the country. This paper discusses the various factors contributing to this phenomenon before presenting recommendations for culturally adapting evidence-based approaches to grieving individuals in the target population. More specifically, a cultural analysis consisting of topics such as Chinese …

Rethinking Innovation At Fda, Rachel Sachs, W. Nicholson Price Ii, Patricia J. Zettler

Scholarship@WashULaw

In several controversial drug approval decisions in recent years, the Food & Drug Administration (FDA) has publicly justified its decision partly on the ground that approving the drugs in question would support innovation in those fields going forward. To some observers, these arguments were surprising, as the agency’s determination whether a drug is “safe” and “effective” does not seem to depend on whether its approval also supports innovation. But FDA’s use of these innovation arguments in drug approval decisions is just one example of the ways in which the agency has come to make many innovation-related judgments as part of …

Heterologous Mrna-Protein Vaccination With Tc24 Induces A Robust Cellular Immune Response Against Trypanosoma Cruzi, Characterized By An Increased Level Of Polyfunctional Cd8+ T-Cells, Cristina Poveda, Ana Carolina Leão, Chiara Mancino, Francesca Taraballi, Yi-Lin Chen, Rakesh Adhikari, Maria Jose Villar, Rakhi Kundu, Duc M Nguyen, Leroy Versteeg, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Jeroen Pollet, Kathryn M Jones

Faculty, Staff and Students Publications

Tc24 is a Trypanosoma cruzi-derived flagellar protein that, when formulated with a TLR-4 agonist adjuvant, induces a balanced immune response in mice, elevating IgG2a antibody titers and IFN-γ levels. Furthermore, vaccination with the recombinant Tc24 protein can reduce parasite levels and improve survival during acute infection. Although some mRNA vaccines have been proven to elicit a stronger immune response than some protein vaccines, they have not been used against T. cruzi. This work evaluates the immunogenicity of a heterologous prime/boost vaccination regimen using protein and mRNA-based Tc24 vaccines. Mice (C57BL/6) were vaccinated twice subcutaneously, three weeks apart, with …

A Novel Use Of Bar Code Medication Administration Data To Assess Nurse Staffing And Workload, Melissa K Knox, Paras D Mehta, Lynette E Dorsey, Christine Yang, Laura A Petersen

Faculty, Staff and Students Publications

OBJECTIVE: The aim of the study is to introduce an innovative use of bar code medication administration (BCMA) data, medication pass analysis, that allows for the examination of nurse staffing and workload using data generated during regular nursing workflow.

METHODS: Using 1 year (October 1, 2014-September 30, 2015) of BCMA data for 11 acute care units in one Veterans Affairs Medical Center, we determined the peak time for scheduled medications and included medications scheduled for and administered within 2 hours of that time in analyses. We established for each staff member their daily peak-time medication pass characteristics (number of patients, …

Neprilysin Inhibitors In Heart Failure: The Science, Mechanism Of Action, Clinical Studies, And Unanswered Questions, Biykem Bozkurt, Ajith P Nair, Arunima Misra, Claire Z Scott, Jamal H Mahar, Savitri Fedson

Faculty, Staff and Students Publications

This article provides a contemporary review and a new perspective on the role of neprilysin inhibition in heart failure (HF) in the context of recent clinical trials and addresses potential mechanisms and unanswered questions in certain HF patient populations. Neprilysin is an endopeptidase that cleaves a variety of peptides such as natriuretic peptides, bradykinin, adrenomedullin, substance P, angiotensin I and II, and endothelin. It has a broad role in cardiovascular, renal, pulmonary, gastrointestinal, endocrine, and neurologic functions. The combined angiotensin receptor and neprilysin inhibitor (ARNi) has been developed with an intent to increase vasodilatory natriuretic peptides and prevent counterregulatory activation …

Evaluating The Proportion Of Isolated Cases Among A Spectrum Of Birth Defects In A Population-Based Registry, Peter H Langlois, Lisa Marengo, Philip J Lupo, Margaret Drummond-Borg, A J Agopian, Wendy N Nembhard, Mark A Canfield

Faculty, Staff and Students Publications

INTRODUCTION: Because the etiology and outcomes of birth defects may differ by the presence vs. absence of co-occurring anomalies, epidemiologic studies often attempt to classify cases into isolated versus non-isolated groupings. This report describes a computer algorithm for such classification and presents results using data from the Texas Birth Defects Registry (TBDR).

METHODS: Each of the 1,041 birth defects coded by the TBDR was classified as chromosomal, syndromic, minor, or "needs review" by a group of three clinical geneticists. A SAS program applied those classifications to each birth defect in a case (child/fetus), and then hierarchically combined them to obtain …

5-Meo-Dmt For Post-Traumatic Stress Disorder: A Real-World Longitudinal Case Study, Anya Ragnhildstveit, Ryan Khan, Paul Seli, Lisa Claire Bass, River Jude August, Miriam Kaiyo, Nathaniel Barr, Laura Kate Jackson, Michael Santo Gaffrey, Joseph Peter Barsuglia, Lynnette Astrid Averill

Center for Medical Ethics and Health Policy Staff Publications

Psychedelic therapy is, arguably, the next frontier in psychiatry. It offers a radical alternative to longstanding, mainstays of treatment, while exciting a paradigm shift in translational science and drug discovery. There is particular interest in 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)—a serotonergic psychedelic—as a novel, fast-acting therapeutic. Yet, few studies have directly examined 5-MeO-DMT for trauma- or stress-related psychopathology, including post-traumatic stress disorder (PTSD). Herein, we present the first longitudinal case study on 5-MeO-DMT for chronic refractory PTSD, in a 23-year-old female. A single dose of vaporized bufotoxin of the Sonoran Desert Toad (Incilius alvarius), containing an estimated 10−15 mg …

Transcriptomic Profiles Of Multiple Organ Dysfunction Syndrome Phenotypes In Pediatric Critical Influenza, Tanya Novak, Jeremy Chase Crawford, Georg Hahn, Mark W Hall, Simone A Thair, Margaret M Newhams, Janet Chou, Peter M Mourani, Keiko M Tarquinio, Barry Markovitz, Laura L Loftis, Scott L Weiss, Renee Higgerson, Adam J Schwarz, Neethi P Pinto, Neal J Thomas, Rainer G Gedeit, Ronald C Sanders, Sidharth Mahapatra, Bria M Coates, Natalie Z Cvijanovich, Kate G Ackerman, David W Tellez, Patrick Mcquillen, Stephen C Kurachek, Steven L Shein, Christoph Lange, Paul G Thomas, Adrienne G Randolph

Faculty, Staff and Students Publications

BACKGROUND: Influenza virus is responsible for a large global burden of disease, especially in children. Multiple Organ Dysfunction Syndrome (MODS) is a life-threatening and fatal complication of severe influenza infection.

METHODS: We measured RNA expression of 469 biologically plausible candidate genes in children admitted to North American pediatric intensive care units with severe influenza virus infection with and without MODS. Whole blood samples from 191 influenza-infected children (median age 6.4 years, IQR: 2.2, 11) were collected a median of 27 hours following admission; for 45 children a second blood sample was collected approximately seven days later. Extracted RNA was hybridized …

Native Bk Polyomavirus Nephropathy In An Orthotopic Heart Transplant Patient, Zachary M Thompson, George Ajene, Prathit A Kulkarni, Nidhi Aggarwal, Savitri Fedson, Maulin K Shah

Faculty, Staff and Students Publications

BK polyomavirus nephropathy (BKVN) is a common cause of nephropathy in kidney transplant patients and is typically seen within the first year after transplantation. BK polyomavirus nephropathy can occur in the native kidneys of patients with nonrenal solid-organ transplants (NRSOT). However, this is rare, especially outside the early post-transplant period, and BKVN is not usually considered in the differential diagnosis for acute kidney injury in NRSOT patients. We present a case of a 75-year-old man who had undergone orthotopic heart transplant 13 years prior with stable allograft function who developed progressive renal dysfunction in the setting of recent unilateral obstructive …

Pre-Treatment Inflamed Tumor Immune Microenvironment Is Associated With Folfirinox Response In Pancreatic Cancer, Zachary Gao, Sung Wook Kang, Derek Erstad, Joseph Azar, George Van Buren, William Fisher, Zequn Sun, Mark P Rubinstein, Hyun-Sung Lee, E Ramsay Camp

Faculty, Staff and Students Publications

INTRODUCTION: Pancreatic adenocarcinoma (PDAC) is an aggressive tumor with limited response to both chemotherapy and immunotherapy. Pre-treatment tumor features within the tumor immune microenvironment (TiME) may influence treatment response. We hypothesized that the pre-treatment TiME composition differs between metastatic and primary lesions and would be associated with response to modified FOLFIRINOX (mFFX) or gemcitabine-based (Gem-based) therapy.

METHODS: Using RNAseq data from a cohort of treatment-naïve, advanced PDAC patients in the COMPASS trial, differential gene expression analysis of key immunomodulatory genes in were analyzed based on multiple parameters including tumor site, response to mFFX, and response to Gem-based treatment. The relative …

A Population-Based Assessment Of Metastatic Hepatoblastoma In Texas Reveals Ethnic Disparities, Andres F Espinoza, Michael E Scheurer, Tiffany M Chambers, Sanjeev A Vasudevan, Philip J Lupo

Faculty, Staff and Students Publications

BACKGROUND: Hepatoblastoma (HB) is the most common primary liver cancer in children with emerging evidence that incidence is increasing globally. While overall survival for low risk hepatoblastoma is >90%, children with metastatic disease have worse survival. As identifying factors associated with high-risk disease is critical for improving outcomes for these children, a need for a further understanding of the epidemiology of hepatoblastoma is warranted. Therefore, we conducted a population-based epidemiologic study of hepatoblastoma in Texas, a large state characterized by ethnic and geographic diversity.

METHODS: Information on children diagnosed with hepatoblastoma at 0-19 years of age for the period of …

Circulating Tumor Dna Sequencing Of Pediatric Solid And Brain Tumor Patients: An Institutional Feasibility Study, Ross Mangum, Jacquelyn Reuther, Koel Sen Baksi, Ilavarasi Gandhi, Ryan C Zabriskie, Alva Recinos, Robin Raesz-Martinez, Frank Y Lin, Samara L Potter, Andrew C Sher, Stephen F Kralik, Carrie A Mohila, Murali M Chintagumpala, Donna Muzny, Jianhong Hu, Richard A Gibbs, Kevin E Fisher, Juan Carlos Bernini, Jonathan Gill, Timothy C Griffin, Gail E Tomlinson, Kelly L Vallance, Sharon E Plon, Angshumoy Roy, D Williams Parsons

Faculty, Staff and Students Publications

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) …

Nourishing The Brain On Deep Space Missions: Nutritional Psychiatry In Promoting Resilience, Nihar N Pathare, Flavia Fayet-Moore, Jennifer A Fogarty, Felice N Jacka, Philip Strandwitz, Gary E Strangman, Dorit B Donoviel

Faculty, Staff and Students Publications

The grueling psychological demands of a journey into deep space coupled with ever-increasing distances away from home pose a unique problem: how can we best take advantage of the benefits of fresh foods in a place that has none? Here, we consider the biggest challenges associated with our current spaceflight food system, highlight the importance of supporting optimal brain health on missions into deep space, and discuss evidence about food components that impact brain health. We propose a future food system that leverages the gut microbiota that can be individually tailored to best support the brain and mental health of …

Global Regulatory Reforms To Promote Equitable Vaccine Access In The Next Pandemic, Richard Mahoney, Peter J Hotez, Maria Elena Bottazzi

Faculty, Staff and Students Publications

There is broad consensus that the global response to the Covid-19 pandemic was inadequate, leading to unacceptable levels of avoidable morbidity and mortality. Three strategic missteps led to the lack of equitable vaccine access: The heavy reliance on commercial vaccine manufacturers in high-income countries (HICs) versus low- and middle-income countries (LMICs); the emergence of vaccine nationalism restricting and delaying the supply of vaccines to LMICs; and an inadequate support or recognition for LMIC national regulatory authorities. To avoid these inequities in a future pandemic, we focus on three successful vaccine development and technology transfer case studies-the Hepatitis B vaccine produced …

A Systematic Review Of Treatments For Misophonia, Seth A Mattson, Johann D'Souza, Katharine D Wojcik, Andrew G Guzick, Wayne K Goodman, Eric A Storch

Faculty, Staff and Students Publications

Research into misophonia treatments has been limited and it is unclear what treatment approaches may be effective. This systematic review extracted and synthesized relevant treatment research on misophonia to examine the efficacy of various intervention modalities and identify current trends in order to guide future treatment research. PubMed, PsycINFO, Google Scholar, and Cochrane Central were searched 4using the keywords "misophonia," "decreased sound tolerance," "selective sound sensitivity," or "decreased sound sensitivity." Of the 169 records available for initial screening, 33 studied misophonia treatment specifically. Data were available for one randomized controlled trial, one open label trial, and 31 case studies. Treatments …

Corticosteroid-Laba Inhalers Increase Phonation Threshold Pressure (Ptp) And Flow (Ptf) In Rabbits, Christopher Dromey, Kristine Tanner, Heidi J. Robison, Maya Elena Stevens, Ray M. Merrill, Julie Barkmeier-Kraemer, Ben Christensen

Faculty Publications

Objectives: This study examined the effects of a combination corticosteroid plus long-acting beta2-adrenergic agonist inhaler (IC) on rabbit phonation. Methods: White New Zealand male rabbits were assigned randomly to experimental and control groups (n = 11 per group). The experimental group received twice-daily doses of Advair HFA™ (fluticasone propionate 45 mcg and salmeterol 21 mcg) via a veterinary facemask with 1-way valve and spacer; the control group received aerosolized saline. After 8 weeks, animals were euthanized, larynges excised, frozen, and subsequently thawed and mounted on a standard bench apparatus. Phonation was elicited during 15 successive trials, and phonation threshold pressure …

Inhibition Of Yap/Taz-Driven Tead Activity Prevents Growth Of Nf2-Null Schwannoma And Meningioma, Liyam Laraba, Lily Hillson, Julio Grimm De Guibert, Amy Hewitt, Maisie R Jaques, Tracy T Tang, Leonard Post, Emanuela Ercolano, Ganesha Rai, Shyh-Ming Yang, Daniel J Jagger, Waldemar Woznica, Philip Edwards, Aditya G Shivane, C Oliver Hanemann, David B Parkinson

Peninsula Medical School

Schwannoma tumours typically arise on the eighth cranial nerve and are mostly caused by loss of the tumour suppressor Merlin (NF2). There are no approved chemotherapies for these tumours and the surgical removal of the tumour carries a high risk of damage to the eighth or other close cranial nerve tissue. New treatments for schwannoma and other NF2-null tumours such as meningioma are urgently required. Using a combination of human primary tumour cells and mouse models of schwannoma, we have examined the role of the Hippo signalling pathway in driving tumour cell growth. Using both genetic ablation of the Hippo …

Genome-Wide Analysis Of Motor Progression In Parkinson Disease, Carrasco A Martínez, R Real, M Lawton, Reynolds R Hertfelder, M Tan, L Wu, N Williams, C Carroll, J-C Corvol, M Hu, D Grosset, J Hardy, M Ryten, Y Ben-Shlomo, M Shoai, Hr Morris

Peninsula Medical School

Background and Objectives The genetic basis of Parkinson disease (PD) motor progression is largely unknown. Previous studies of the genetics of PD progression have included small cohorts and shown a limited overlap with genetic PD risk factors from case-control studies. Here, we have studied genomic variation associated with PD motor severity and early-stage progression in large longitudinal cohorts to help to define the biology of PD progression and potential new drug targets. Methods We performed a GWAS meta-analysis of early PD motor severity and progression up to 3 years from study entry. We used linear mixed-effect models with additive effects, …

Sociophonetics And Dialectology, Dominic Watt, Margaret E. L. Renwick, Joseph A. Stanley

Faculty Publications

In this chapter we explore how the investigation of phonetic detail in speech seen through a sociolinguistic lens can inform and enhance our understanding of dialectal variation in languages. We begin by examining how sociophonetics can be considered an offshoot of dialectology, later to mature into a free- standing discipline during the late twentieth century. We next discuss the reconvergence of sociophonetics and dialectology as it became clearer that the two approaches to the study of language variation are, in combination, greater than the sum of their parts, even if their agendas may place different emphases on what should be …

Three-Layer Model With Absorption For Conservative Estimation Of The Maximum Acoustic Transmission Coefficient Through The Human Skull For Transcranial Ultrasound Stimulation, David Attali, Thomas Tiennot, Mark Schafer, Elsa Fouragnan, Jérôme Sallet, Charles F. Caskey, Robert Chen, Ghazaleh Darmani, Ellen J. Bubrick, Christopher Butler, Charlotte J. Stagg, Miriam Klein-Flügge, Lennart Verhagen, Seung Schik Yoo, Kim Butts Pauly, Jean Francois Aubry

School of Psychology

Transcranial ultrasound stimulation (TUS) has been shown to be a safe and effective technique for non-invasive superficial and deep brain stimulation. Safe and efficient translation to humans requires estimating the acoustic attenuation of the human skull. Nevertheless, there are no international guidelines for estimating the impact of the skull bone. A tissue independent, arbitrary derating was developed by the U.S. Food and Drug Administration to take into account tissue absorption (0.3 dB/cm-MHz) for diagnostic ultrasound. However, for the case of transcranial ultrasound imaging, the FDA model does not take into account the insertion loss induced by the skull bone, nor …

Bottle With A Message: The Role Of Story Writing As An Engagement Tool To Explore Children's Perceptions Of Marine Plastic Litter, Estelle Praet, Jostein Baeza-Álvarez, Veer D De, Geraldine Holtmann-Ahumada, Jen S. Jones, Sarah Langford, Jessica Michel Dearte, John Schofield, Martin Thiel, Kayleigh J. Wyles

School of Psychology

As human behaviors play a crucial role in addressing the global threat of plastic pollution, it is vital to understand perceptions about marine plastic litter (MPL) and to develop interventions encouraging pro-environmental behaviors (PEBs). This study evaluates story writing as a window to explore perceptions and as an engagement activity to boost PEBs. During the COVID-19 lockdowns, schoolchildren from the East Pacific coast participated in this activity, each creating a story and answering a pre-post survey. Qualitative and quantitative analysis of 81 stories and 79 surveys show awareness of sources and impacts. Participants identified land and local pollution as significant …

Decoding Brain Basis Of Laughter And Crying In Natural Scenes, Lauri Nummenmaa, Tuulia Malèn, Sanaz Nazari-Farsani, Kerttu Seppälä, Lihua Sun, Severi Santavirta, Henry K. Karlsson, Matthew Hudson, Jussi Hirvonen, Mikko Sams, Sophie Scott, Vesa Putkinen

School of Psychology

Laughter and crying are universal signals of prosociality and distress, respectively. Here we investigated the functional brain basis of perceiving laughter and crying using naturalistic functional magnetic resonance imaging (fMRI) approach. We measured haemodynamic brain activity evoked by laughter and crying in three experiments with 100 subjects in each. The subjects i) viewed a 20-minute medley of short video clips, and ii) 30 min of a full-length feature film, and iii) listened to 13.5 min of a radio play that all contained bursts of laughter and crying. Intensity of laughing and crying in the videos and radio play was annotated …

Forging A Future Title Ix, Naomi M. Mann

Faculty Scholarship

Title IX is in transition. Fifty years after its passage, Title IX is at the center of multiple culture wars, notably those around the definition of sex¹ and the contours of due process² in schools. Since 2011, the federal Department of Education (“ED”) has issued multiple guidance documents, containing widely divergent obligations for schools.³ In the last decade, the meaning of Title IX has been highly contested, appearing sometimes more dependent on the administration in power than on the statute’s text and purpose.⁴ This pendulum swing has diverted attention away from Title IX’s core goal: equal …

Phase I Study Of Anti-Epidermal Growth Factor Receptor Antibody-Drug Conjugate Serclutamab Talirine: Safety, Pharmacokinetics, And Antitumor Activity In Advanced Glioblastoma, Benedito A Carneiro, Saiama N Waqar, Et Al.

2020-Current year OA Pubs

BACKGROUND: Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T monotherapy in a phase I, first-in-human, dose-escalation, and dose-expansion study in patients with advanced solid tumors associated with EGFR overexpression.

METHODS: Eligible patients (≥18 years) had advanced, histologically confirmed solid tumors associated with EGFR overexpression (centralized testing). Patients received Ser-T intravenously once every 4 weeks (Q4W; 5-50 μg/kg) in the dose-escalation phase. Herein, preliminary antitumor activity at the recommended phase II dose (RP2D) is reported only for patients with glioblastoma …

Frances Crutchfield Kellers Winthrop And Family Letters Collection - Accession 1821, Frances Crutchfield Kellers

Manuscript Collection

The Frances Crutchfield Kellers Winthrop and Family Letters Collection consists of letters written by Winthrop College graduate, Frances Crutchfield Kellers (1912-1993). Frances attended Winthrop from 1930-1934 and graduated with the Class of 1934. These letters are mostly addressed to her mother and father, describing various aspects of her time at Winthrop, her friends, her dorm-mates, her struggles and various escapades she enjoyed during her school days. The letters begin a few months before attending Winthrop and continue through the end of her junior year. Also included is a pocket calendar from the year 1986 as well as paper slips written …

The Neurotoxin Dsp-4 Dysregulates The Locus Coeruleus-Norepinephrine System And Recapitulates Molecular And Behavioral Aspects Of Prodromal Neurodegenerative Disease, Alexa F. Iannitelli, Michael A. Kelberman, Daniel J. Lustberg, Anu Korukonda, Katharine E. Mccann, Bernard Mulvey, Arielle Segal, L Cameron Liles, Steven A. Sloan, Joseph D. Dougherty, David Weinshenker

2020-Current year OA Pubs

The noradrenergic locus coeruleus (LC) is among the earliest sites of tau and α-synuclein pathology in Alzheimer's disease (AD) and Parkinson's disease (PD), respectively. The onset of these pathologies coincides with loss of noradrenergic fibers in LC target regions and the emergence of prodromal symptoms including sleep disturbances and anxiety. Paradoxically, these prodromal symptoms are indicative of a noradrenergic hyperactivity phenotype, rather than the predicted loss of norepinephrine (NE) transmission following LC damage, suggesting the engagement of complex compensatory mechanisms. Because current therapeutic efforts are targeting early disease, interest in the LC has grown, and it is critical to identify …