Medical Specialties Commons^™

Comparison Of Bivalent And Monovalent Sars-Cov-2 Variant Vaccines: The Phase 2 Randomized Open-Label Covail Trial, Ann R Falsey, Cecilia Losada, Lindsey R Baden, Sharon E Frey, Jennifer A Whitaker, Susan J Little, Evan J Anderson, Emmanuel B Walter, Richard M Novak, Richard Rupp, Lisa A Jackson, Tara M Babu, Angelica C Kottkamp, Anne F Luetkemeyer, Lilly C Immergluck, Rachel M Presti, Martín Bäcker, Patricia L Winokur, Siham M Mahgoub, Paul A Goepfert, Dahlene N Fusco, Elissa Malkin, Jeffrey M Bethony, Edward E Walsh, Daniel S Graciaa, Hady Samaha, Amy C Sherman, Stephen R Walsh, Getahun Abate, Zacharoula Oikonomopoulou, Hana M El Sahly, Thomas C S Martin, Satoshi Kamidani, Michael J Smith, Benjamin G Ladner, Laura Porterfield, Maya Dunstan, Anna Wald, Tamia Davis, Robert L Atmar, Mark J Mulligan, Kirsten E Lyke, Christine M Posavad, Megan A Meagher, David S Stephens, Kathleen M Neuzil, Kuleni Abebe, Heather Hill, Jim Albert, Kalyani Telu, Jinjian Mu, Teri C Lewis, Lisa A Giebeig, Amanda Eaton, Antonia Netzl, Samuel H Wilks, Sina Türeli, Mamodikoe Makhene, Sonja Crandon, David C Montefiori, Mat Makowski, Derek J Smith, Seema U Nayak, Paul C Roberts, John H Beigel, Covail Study Group

Faculty, Staff and Students Publications

Vaccine protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection wanes over time, requiring updated boosters. In a phase 2, open-label, randomized clinical trial with sequentially enrolled stages at 22 US sites, we assessed safety and immunogenicity of a second boost with monovalent or bivalent variant vaccines from mRNA and protein-based platforms targeting wild-type, Beta, Delta and Omicron BA.1 spike antigens. The primary outcome was pseudovirus neutralization titers at 50% inhibitory dilution (ID50 titers) with 95% confidence intervals against different SARS-CoV-2 strains. The secondary outcome assessed safety by solicited local and systemic adverse events (AEs), unsolicited AEs, serious AEs …

Genomic Medicine To Reduce Tobacco And Related Disorders: Translation To Precision Prevention And Treatment, Christopher I Amos, Laura J Bierut

Faculty, Staff and Students Publications

Genomic medicine can enhance prevention and treatment. First, we propose that advances in genomics have the potential to enhance assessment of disease risk, improve prognostic predictions, and guide treatment development and application. Clinical implementation of polygenic risk scores (PRSs) has emerged as an area of active research. The pathway from genomic discovery to implementation is an iterative process. Second, we provide examples on how genomic medicine has the potential to solve problems in prevention and treatment using two examples: Lung cancer screening and evidence-based tobacco treatment are both under-utilized and great opportunities for genomic interventions. Third, we discuss the translational …

Revisiting The Use Of Antibiotics To Prevent Copd Exacerbation: Is Doxycycline The Answer?

Faculty, Staff and Students Publications

No abstract provided.

Il17a Blockade With Ixekizumab Suppresses Muvb Signaling In Clinical Psoriasis, Venkatesh Krishnan, Bruce W Konicek, Ernst R Dow, So Young Park, Sandeep K Agarwal, Neil J Mckenna

Faculty, Staff and Students Publications

Unbiased informatics approaches have the potential to generate insights into uncharacterized signaling pathways in human disease. In this study, we generated longitudinal transcriptomic profiles of plaque psoriasis lesions from patients enrolled in a clinical trial of the anti-IL17A antibody ixekizumab (IXE). This dataset was then computed against a curated matrix of over 700 million data points derived from published psoriasis and signaling node perturbation transcriptomic and chromatin immunoprecipitation-sequencing datasets. We observed substantive enrichment within both psoriasis-induced and IXE-repressed gene sets of transcriptional targets of members of the MuvB complex, a master regulator of the mitotic cell cycle. These gene sets …

Distribution Of Hand Function By Age In Individuals With Rett Syndrome, Jane B Lane, David N Lieberman, Steven A Skinner, Daniel G Glaze, Bernhard Suter, Peter T Heydemann, Arthur A Beisang, Shannon M Standridge, Robin C C Ryther, Richard H Haas, Lloyd J Edwards, Amitha Ananth, Alan K Percy

Faculty, Staff and Students Publications

OBJECTIVE: To determine the longitudinal distribution of hand function skills in individuals with classic Rett Syndrome (RTT), an X-linked dominant neurodevelopmental disorder, and correlate with

METHOD: We conducted a longitudinal study of 946 girls and young women with typical RTT seen between 2006 and 2021 in the US Natural History Study (NHS) featuring a structured clinical evaluation to assess the level of hand function skills. The specific focus in this study was to assess longitudinal variation of hand skills from age 2 through age 18 years in relation to specific

RESULTS: Following the initial regression period, hand function continues to …

Children’S Oncology Group’S 2023 Blueprint For Research: Non-Hodgkin Lymphoma, Robert J Hayashi, Eric J Lowe, Lisa Giulino-Roth, Birte Wistinghausen, Michelle Hermiston, Carl E Allen

Faculty, Staff and Students Publications

Pediatric non-Hodgkin lymphoma (NHL) includes over 30 histologies (many with subtypes), with approximately 800 cases per year in the United States. Improvements in survival in NHL over the past 5 decades align with the overall success of the cooperative trial model with dramatic improvements in outcomes. As an example, survival for advanced Burkitt lymphoma is now >95%. Major remaining challenges include survival for relapsed and refractory disease and long-term morbidity in NHL survivors. Langerhans cell histiocytosis (LCH) was added to the NHL Committee portfolio in recognition of LCH as a neoplastic disorder and the tremendous unmet need for improved outcomes. …

Deficiencies With Cage-Aid Questionnaire In Identifying Nonmedical Opioid Use-A Report Of Two Cases, Tarun Mallipeddi, Olivia Jastrzemski, Matthew D Clark, Joseph Arthur, Akhila Reddy, Eduardo Bruera

Faculty, Staff and Students Publications

Background: The CAGE-AID questionnaire (Cut-down, Annoyed, Guilty, Eye-opener scale Adapted to Include Drugs) is used to screen patients for substance use disorder and nonmedical opioid use (NMOU). Major pain guidelines encourage using such screening tools for all patients including cancer patients before initiating opioids. We present two cases where the CAGE-AID results did not accurately identify the risk for NMOU.

Case description: Patient 1 is a male in his 60s with metastatic prostate cancer was admitted for uncontrolled pain. Imaging revealed extensive spinal metastasis, needing initiation of methadone and hydromorphone. The CAGE-AID score was positive, placing him at risk for …

Incidence Of And Factors Associated With Recurrent Firearm Injury Among Patients Presenting To St. Louis Trauma Centers, 2010 To 2019 : A Cohort Study, Daphne Lew, Rachel Ancona, Joshua M Landman, Marguerite Spruce, Phillip Marotta, David B Liss, Michael A Mancini, Douglas Schuerer, Megan E Ranney, Randi E Foraker

Faculty, Staff and Students Publications

Background: Firearm injuries are a public health crisis in the United States.

Objective: To examine the incidence and factors associated with recurrent firearm injuries and death among patients presenting with an acute (index), nonfatal firearm injury.

Design: Multicenter, observational, cohort study.

Setting: Four adult and pediatric level I trauma hospitals in St. Louis, Missouri, 2010 to 2019.

Participants: Consecutive adult and pediatric patients (n = 9553) presenting to a participating hospital with a nonfatal acute firearm injury.

Measurements: Data on firearm-injured patient demographics, hospital and diagnostic information, health insurance status, and death were collected from the St. Louis Region-Wide …

Perspectives On Contingency Management For Alcohol Use And Alcohol-Associated Conditions Among People In Care With Hiv, James Dziura, Tekeda Ferguson, Lisa M Fucito, Amy C Justice, Stephen Maisto, Vincent C Marconi, Patricia Molina, Manuel Paris, Maria C Rodriguez-Barradas, Michael Simberkoff, Nancy M Petry, David A Fiellin, E Jennifer Edelman

Faculty, Staff and Students Publications

BACKGROUND: Contingency management (CM) is an evidence-based approach for reducing alcohol use; however, its implementation into routine HIV primary care-based settings has been limited. We evaluated perspectives on implementing CM to address unhealthy alcohol use and associated conditions for people with HIV in primary care settings.

METHODS: From May 2021 to August 2021, we conducted two focus groups with staff involved in delivering the intervention (n = 5 Social Workers and n = 4 Research Coordinators) and individual interviews (n = 13) with a subset of participants involved in the multi-site Financial Incentives, Randomization, and Stepped Treatment (FIRST) trial. Qualitative …

Rna Interference Targeting Angptl3 For Triglyceride And Cholesterol Lowering: Phase 1 Basket Trial Cohorts, Patrick A Gladding, David Sullivan, John Baker, Peter Clifton, James Hamilton, Bruce Given, Stacey Melquist, Rong Zhou, Ting Chang, Javier San Martin, Daniel Gaudet, Ira J Goldberg, Joshua W Knowles, Robert A Hegele, Christie M Ballantyne

Faculty, Staff and Students Publications

Elevated triglycerides and non-high-density lipoprotein cholesterol (HDL-C) are risk factors for atherosclerotic cardiovascular disease (ASCVD). ARO-ANG3 is an RNA interference therapy that targets angiopoietin-like protein 3 (ANGPTL3), a regulator of lipoprotein metabolism. This first-in-human, phase 1, randomized, placebo-controlled, open-label trial investigated single and repeat ARO-ANG3 doses in four cohorts of fifty-two healthy participants and one cohort of nine participants with hepatic steatosis, part of a basket trial. Safety (primary objective) and pharmacokinetics (in healthy participants) and pharmacodynamics (secondary objectives) of ARO-ANG3 were evaluated. ARO-ANG3 was generally well tolerated, with similar frequencies of treatment-emergent adverse events in active and placebo groups. …

Global Sumoylation In Mouse Oocytes Maintains Oocyte Identity And Regulates Chromatin Remodeling And Transcriptional Silencing At The End Of Folliculogenesis, Peixin Jiang, Sean M Hartig, Karen Schindler, Stephanie A Pangas

Faculty, Staff and Students Publications

Meiotically competent oocytes in mammals undergo cyclic development during folliculogenesis. Oocytes within ovarian follicles are transcriptionally active, producing and storing transcripts required for oocyte growth, somatic cell communication and early embryogenesis. Transcription ceases as oocytes transition from growth to maturation and does not resume until zygotic genome activation. Although SUMOylation, a post-translational modification, plays multifaceted roles in transcriptional regulation, its involvement during oocyte development remains poorly understood. In this study, we generated an oocyte-specific knockout of Ube2i, encoding the SUMO E2 enzyme UBE2I, using Zp3-cre+ to determine how loss of oocyte SUMOylation during folliculogenesis affects oocyte development. Ube2i Zp3-cre+ female …

A Qualitative Exploration Of Patient Perspectives On Psychosocial Burdens And Positive Factors In Adults With Osteogenesis Imperfecta, Kristin M Kostick, Dianne Nguyen, Sophie C Schneider, Whitney S Shepherd, Hannah Cho, Members Of The Bbdc, Chaya N Murali, Brendan Lee, V Reid Sutton, Eric A Storch

Faculty, Staff and Students Publications

Osteogenesis imperfecta (OI) is a pleiotropic, heritable connective tissue disorder associated with a wide range of health implications, including frequent bone fracture. While progress has been made to understand the spectrum of these physical health implications, the impact of OI on psychosocial well-being, as well as protective factors that buffer against adverse psychosocial outcomes, remain understudied. This present study relies on a qualitative approach to assess patient perspectives on both protective and adverse psychosocial factors specific to OI in 15 adults with varying disease status. Semi-structured interviews were conducted, subsequently coded, and themes extracted. Themes concerning psychosocial burdens (i.e., negative …

Approach To Non-Type 2 Asthma

Faculty, Staff and Students Publications

No abstract provided.

Examining Whether Genetic Variants Moderate The Skeletal Effects Of Selective Serotonin Reuptake Inhibitors In Older Adolescents And Young Adults, Vicki Ellingrod, Chadi A Calarge

Faculty, Staff and Students Publications

Objective: To examine whether serotonin (5-HT) related genetic variants moderate the effects of selective serotonin reuptake inhibitors (SSRIs) on skeletal outcomes. Methods: Trabecular bone mineral density (BMD) at the radius, lumbar spine (LS) BMD, total body less head (TBLH) bone mineral content (BMC) and markers of bone metabolism (osteocalcin, C-terminal telopeptide of type I collagen [CTX-1], and bone specific alkaline phosphatase to CTX-1 ratio) were examined in an observational study, enrolling 15- to 20-year-old participants, unmedicated or within a month of SSRI initiation. Variants in HTR1A (rs6295), HTR1B (rs6296), HTR1D (rs6300), HTR2A (rs6311 and rs6314), HTR2B (rs6736017), and the serotonin …

Anesthesia Care Provider Sedation Versus Conscious Sedation For Endoscopic Ultrasound-Guided Tissue Acquisition: A Retrospective Cohort Study, Kendrick Che, John J Kim, Wasseem Skef

Faculty, Staff and Students Publications

BACKGROUND/AIMS: We aimed to study the effects of sedation on endoscopic ultrasound-guided tissue acquisition.

METHODS: We conducted a retrospective study evaluating the role of sedation in endoscopic ultrasound-guided tissue acquisition by comparing two groups: anesthesia care provider (ACP) sedation and endoscopist-directed conscious sedation (CS).

RESULTS: Technical success was achieved in 219/233 (94.0%) in the ACP group and 114/136 (83.8%) in the CS group (p=0.0086). In multivariate analysis, the difference in technical success between the two groups was not significant (adjusted odds ratio [aOR], 0.5; 95% confidence interval [CI], 0.234-1.069; p=0.0738). A successful diagnostic yield was present in 146/196 (74.5%) in …

Studying Ultra-Rare Variants In Stx1a Uncovers A Novel Neurodevelopmental Disorder

Faculty, Staff and Students Publications

No abstract provided.

Equine Bronchial Epithelial Cells Are Susceptible To Cell Entry With A Sars-Cov-2 Pseudovirus But Reveal Low Replication Efficiency, Bibiana Petri Da Silveira, Jennifer L Fridley, Kelsey M Wells, Numan Oezguen, Robert C Burghardt, Gus A Wright, Jeroen Pollet, Angela I Bordin, Paul De Figueiredo, Julian L Leibowitz, Noah D Cohen

Faculty, Staff and Students Publications

Objective: To examine the susceptibility of cultured primary equine bronchial epithelial cells (EBECs) to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus relative to human bronchial epithelial cells (HBECs).

Sample: Primary EBEC cultures established from healthy adult horses and commercially sourced human bronchial epithelial cells (HBECs) were used as a positive control.

Methods: Angiotensin-converting enzyme 2 (ACE2) expression by EBECs was demonstrated using immunofluorescence, western immunoblot, and flow cytometry. EBECs were transduced with a lentivirus pseudotyped with the SARS-CoV-2 spike protein that binds to ACE2 and expresses the enhanced green fluorescent protein (eGFP) as a reporter. Cells were transduced …

Cardiometabolic Predictors Of High-Risk Ccta Phenotype In A Diverse Patient Population, Sharmila Sarkar, John P Skendelas, Jonathan Daich, Aldo L Schenone, Lili Zhang, Carlos J Rodriguez, Salim S Virani, Piotr J Slomka, Leslee J Shaw, Eric E Williamson, Daniel S Berman, Mario J Garcia, Damini Dey, Leandro Slipczuk

Faculty, Staff and Students Publications

Introduction: Low-attenuation non-calcified plaque (LAP) burden and vascular inflammation by pericoronary adipose tissue (PCAT) measured from coronary CT angiography (CCTA) have shown to be predictors of cardiovascular outcomes. We aimed to investigate the relationships of cardiometabolic risk factors including lipoprotein(a) and epicardial adipose tissue (EAT) with CCTA high-risk imaging biomarkers, LAP and vascular inflammation.

Methods: The patient population consisted of consecutive patients who underwent CCTA for stable chest pain and had a complete cardiometabolic panel including lipoprotein(a). Plaque, PCAT and EAT were measured from CT using semiautomated software. Elevated LAP burden and PCAT attenuation were defined as ≥4% and ≥70.5 …

Is It A True Left Bundle Branch Block Or Not?, Gaurav Upadhyay, Kamil Sedlacek, Pavel Osmancik

Faculty, Staff and Students Publications

No abstract provided.

Fetal Echocardiographic Z Score Pilot Project: Study Design And Impact Of Gestational Age And Variable Type On Reproducibility Of Measurements Within And Across Investigators, Oluwatosin Fatusin, Lindsay R Freud, Whitnee Hogan, Anita Krishnan, Carol Mcfarland, L Luann Minich, Shaine A Morris, Nelangi Pinto, Angela P Presson, Theresa A Tacy, Mary T Donofrio

Faculty, Staff and Students Publications

Background: Fetal echocardiography is widely available, but normative data are not robust. In this pilot study, the authors evaluated (1) the feasibility of prespecified measurements in a normal fetal echocardiogram to inform study design and (2) measurement variability to assign thresholds of clinical significance and guide analyses in larger fetal echocardiographic Z score initiatives.

Methods: Images from predefined gestational age groups (16-20, >20-24, >24-28, and >28-32 weeks) were retrospectively analyzed. Fetal echocardiography expert raters attended online group training and then independently analyzed 73 fetal studies (18 per age group) in a fully crossed design of 53 variables; each observer repeated …

Public Reporting For Coronary Artery Bypass Graft Surgery: The Quest For The Optimal Scorecard, Michael Halkos, Danny Chu, Bradley S Taylor, John Puskas, Deepak L Bhatt, Marco Zenati, John Stulak, Todd Rosengart, Husam H Balkhy, Eugene H Blackstone, Lars G Svensson, Faisal G Bakaeen, Ozgun Erten, Tara Karamlou, Edward G Soltesz, A Marc Gillinov, Anthony Warmuth, Eric E Roselli, Nicholas G Smedira

Faculty, Staff and Students Publications

Objective: A number of publicly available rating algorithms are used to assess hospital performance in coronary artery bypass grafting (CABG). However, concerns remain that these algorithms fail to correlate with each other and inadequately capture the case complexity of individual center practices.

Methods: Composite star ratings for isolated CABG from the Society of Thoracic Surgeons public reporting database were extracted for 2018-2019. U.S. News & World Report Best Hospitals was used to extract CABG ratings as well as overall cardiology and heart surgery ranking, and the Centers for Medicare & Medicaid Services Hospital Compare was used to extract CABG volume …

Characterizing Control Of Memory Cd8 T Cell Differentiation By Btb-Zf Transcription Factor Zbtb20, Chenyang Li, Fred W Kolling, Heidi W Trask, Young-Kwang Usherwood, Chao Cheng, Hildreth R Frost, Edward J Usherwood

Faculty, Staff and Students Publications

Members of the BTB-ZF transcription factor family regulate the immune system. Our laboratory identified that family member Zbtb20 contributes to the differentiation, recall responses, and metabolism of CD8 T cells. Here, we report a characterization of the transcriptional and epigenetic signatures controlled by Zbtb20 at single-cell resolution during the effector and memory phases of the CD8 T cell response. Without Zbtb20, transcriptional programs associated with memory CD8 T cell formation were up-regulated throughout the CD8 T response. A signature of open chromatin was associated with genes controlling T cell activation, consistent with the known impact on differentiation. In addition, memory …

Small-Molecule Chemical Probes For The Potential Therapeutic Targets In Alcoholic Liver Diseases

Faculty, Staff and Students Publications

Alcoholic liver disease (ALD) encompasses a range of conditions resulting from prolonged and excessive alcohol consumption, causing liver damage such as alcoholic fatty liver, inflammation, fibrosis, and cirrhosis. Alcohol consumption contributes to millions of deaths each year. So far, the effective treatments for ALD are limited. To date, the most effective treatment for ALD is still prevention by avoiding excessive alcohol consumption, and only few specialized medicines are in the market for the treatment of patients suffering from ALD. Small molecules targeting various pathways implicated in ALD pathogenesis can potentially be used for effective therapeutics development. In this review, we …

Il17a Blockade With Ixekizumab Suppresses Muvb Signaling In Clinical Psoriasis, Venkatesh Krishnan, Bruce W Konicek, Ernst R Dow, So Young Park, Sandeep K Agarwal, Neil J Mckenna

Faculty, Staff and Students Publications

Unbiased informatics approaches have the potential to generate insights into uncharacterized signaling pathways in human disease. In this study, we generated longitudinal transcriptomic profiles of plaque psoriasis lesions from patients enrolled in a clinical trial of the anti-IL17A antibody ixekizumab (IXE). This dataset was then computed against a curated matrix of over 700 million data points derived from published psoriasis and signaling node perturbation transcriptomic and chromatin immunoprecipitation-sequencing datasets. We observed substantive enrichment within both psoriasis-induced and IXE-repressed gene sets of transcriptional targets of members of the MuvB complex, a master regulator of the mitotic cell cycle. These gene sets …

Revision Tracheotomy Complicated By History Of Follicular B-Cell Lymphoma, Adam R Szymanowski

Faculty, Staff and Students Publications

This case report presents a 65-year-old woman with multiple complications during a revision tracheotomy including subcutaneous emphysema and a pneumothorax. Management of her airway was complicated by a history of recurrent follicular B-cell lymphoma associated with extensive cervical lymphadenopathy. We detail the importance of heightened clinical awareness and the use of intraoperative safety adjuncts when performing revision tracheostomies.

Nurse Leader Perceptions Of Data In The Veterans Health Administration: A Qualitative Evaluation, Melissa K Knox, Sylvia J Hysong, Lynette E Dorsey, Patrick N O'Mahen, Laura A Petersen

Faculty, Staff and Students Publications

Healthcare systems and nursing leaders aim to make evidence-based nurse staffing decisions. Understanding how nurses use and perceive available data to support safe staffing can strengthen learning healthcare systems and support evidence-based practice, particularly given emerging data availability and specific nursing challenges in data usability. However, current literature offers sparse insight into the nature of data use and challenges in the inpatient nurse staffing management context. We aimed to investigate how nurse leaders experience using data to guide their inpatient staffing management decisions in the Veterans Health Administration, the largest integrated healthcare system in the United States. We conducted semistructured …

Oral Delivery Of Rnai For Cancer Therapy, Sheikh Shafin Ahmad, Sandeep K Agarwal, Md Nurunnabi

Faculty, Staff and Students Publications

Cancer is a major health concern worldwide and is still in a continuous surge of seeking for effective treatments. Since the discovery of RNAi and their mechanism of action, it has shown promises in targeted therapy for various diseases including cancer. The ability of RNAi to selectively silence the carcinogenic gene makes them ideal as cancer therapeutics. Oral delivery is the ideal route of administration of drug administration because of its patients' compliance and convenience. However, orally administered RNAi, for instance, siRNA, must cross various extracellular and intracellular biological barriers before it reaches the site of action. It is very …

Closing The Gap For Children With Ocd: A Staged-Care Model Of Cognitive Behavioural Therapy With Exposure And Response Prevention, Lara J Farrell, Allison M Waters, Eric A Storch, Gabrielle Simcock, Iain E Perkes, Jessica R Grisham, Katelyn M Dyason, Thomas H Ollendick

Center for Medical Ethics and Health Policy Staff Publications

Childhood obsessive-compulsive disorder (OCD) is among the most prevalent and disabling mental health conditions affecting children and adolescents. Although the distress and burden associated with childhood OCD are well documented and empirically supported treatments are available, there remains an unacceptable "treatment gap" and "quality gap" in the provision of services for youth suffering from OCD. The treatment gap represents the large number of children who never receive mental health services for OCD, while the quality gap refers to the children and young people who do access services, but do not receive evidence-based, cognitive behavioural therapy with exposure and response prevention …

Safety And Efficacy Of Long-Term Deutetrabenazine Use In Children And Adolescents With Tics Associated With Tourette Syndrome: An Open-Label Extension Study, Joohi Jimenez-Shahed, Barry J Gertz, Elizabeth A Garofalo, David A Stamler, Maria Wieman, Juha-Matti Savola, Eran Harary, Jessica Alexander, Hadas Barkay, Mark Forrest Gordon

Faculty, Staff and Students Publications

BACKGROUND: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by motor and phonic tics.

OBJECTIVE: To assess the safety and efficacy of deutetrabenazine (Teva Neuroscience, Inc, Parsippany, NJ), a vesicular monoamine transporter 2 inhibitor, in children and adolescents with TS.

METHODS: Alternatives for Reducing Tics in TS (ARTISTS) open-label extension (OLE) (NCT03567291) was a 54-week, global, phase 3, open-label extension study of deutetrabenazine (6-48 mg daily) conducted May 28, 2018 to April 3, 2020 with a 2-week randomized withdrawal period. Participants (6-16 years of age) had TS and active tics causing distress or impairment. Safety (primary outcome) was assessed by …

Analysis And Modeling Of Early Estradiol-Induced Greb1 Single Allele Gene Transcription At The Population Level, Ayse Koksoy, Michael A Mancini, Fabio Stossi, Robert Azencott

Faculty, Staff and Students Publications

Single molecule fluorescence in situ hybridization (smFISH) can be used to visualize transcriptional activation at the single allele level. We and others have applied this approach to better understand the mechanisms of activation by steroid nuclear receptors. However, there is limited understanding of the interconnection between the activation of target gene alleles inside the same nucleus and within large cell populations.

Using the GREB1 gene as an early estrogen receptor (ER) response target, we applied smFISH to track E2-activated GREB1 allelic transcription over early time points to evaluate potential dependencies between alleles within the same nucleus. We compared two types …