Chemicals and Drugs Commons^™

Radial Glia Integrin Avb8 Regulates Cell Autonomous Microglial Tgfβ1 Signaling That Is Necessary For Microglial Identity, Gabriel Mckinsey, Nicolas Santander, Xiaoming Zhang, Kilian Kleemann, Lauren Tran, Aditya Katewa, Kaylynn Conant, Matthew Barraza, Kian Waddell, Carlos Lizama, Marie La Russa, Ji Hyun Koo, Hyunji Lee, Dibyanti Mukherjee, Helena Paidassi, E. S. Anton, Kamran Atabai, Dean Sheppard, Oleg Butovsky, Thomas Arnold

Department of Medicine Faculty Papers

Microglial diversity arises from the interplay between inherent genetic programs and external environmental signals. However, the mechanisms by which these processes develop and interact within the growing brain are not yet fully understood. Here, we show that radial glia-expressed integrin beta 8 (ITGB8) activates microglia-expressed TGFβ1 to drive microglial development. Domain-restricted deletion of Itgb8 in these progenitors results in regionally restricted and developmentally arrested microglia that persist into adulthood. In the absence of autocrine TGFβ1 signaling, microglia adopt a similar phenotype, leading to neuromotor symptoms almost identical to Itgb8 mutant mice. In contrast, microglia lacking the canonical TGFβ signal transducers …

A Case Of Turmeric-Induced Hepatotoxicity With Hyperferritinemia, Nina R. Spitofsky, Albert A. Huang, Aria Jalalian, Stefanie Gallagher, Scott Fink

Department of Medicine Faculty Papers

Introduction: We present the first published case of turmeric-associated drug-induced liver injury (DILI) accompanied by significant ferritin elevation. Case Presentation: Our patient, a 59-year-old female with DILI caused by long-term ingestion of oral turmeric supplements, presented with painless jaundice on an annual exam. The patient’s liver function tests exhibited a hepatocellular pattern and hyperferritinemia (>2,000 ng/dL). Additional testing was negative except for heterozygosity for the H63D allele associated with hemochromatosis. A liver biopsy indicated acute hepatitis without fibrosis or stainable iron. Conclusion: Upon discontinuation of the supplement, liver enzymes normalized within a month. This case highlights the potential for …

Association Of Inflammatory Biomarkers With New Functional Morbidity At Hospital Discharge In Children Who Survive Severe Sepsis, Mallory Perry-Eaddy, Walter Faig, Martha Curley, Scott Weiss

Department of Pediatrics Faculty Papers

OBJECTIVE: New functional morbidity is common in critically ill children who survive sepsis; yet, the underlying biological mechanisms, particularly the impact of inflammation, remain unknown. We sought to test the hypothesis that increased levels of inflammatory biomarkers during the acute phase of pediatric sepsis are associated with new functional morbidity at hospital discharge.

METHODS: We conducted a post hoc secondary analysis of the MitoPSe clinical study, including N = 119 critically ill children who survived sepsis. Data collected included demographic and clinical variables and 31 inflammatory biomarkers collected at three distinct timepoints (within days 1-2 of PICU admission, days 3-5, …

Long-Term Safety And Comparative Efficacy Of Il-17 Inhibitors In Treating Ankylosing Spondylitis, Alyssa L. Sepulveda, Yolanda V. Gutierrez, Ronald A. Shaju

Research Symposium

Background:
Ankylosing Spondylitis (AS) is a chronic inflammatory disease affecting the axial skeleton, characterized by spinal stiffness, sacroiliitis, and potential vertebral fusion. While nonsteroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor (TNF) inhibitors are first-line treatments, IL-17 inhibitors, such as secukinumab and ixekizumab, are used in patients with inadequate response or contraindications to TNF inhibitors. These targeted therapies address IL-17’s role in driving inflammation and structural damage in AS.

Methods:
A systematic review was conducted using PubMed, Science Direct, and Cochrane to identify studies published between 2000 and 2025. Keywords included “Ankylosing spondylitis” and “IL-17 inhibitors” and “efficacy.” Inclusion criteria …

Immunogenetic Studies In Patients With Gad-Positive Stiff-Person Syndrome Reveal Novel Lymphocytic Genes And Klk10 -Gene Variants, Popianna Tsiortou, Harry Alexopoulos, Konstantinos Kyriakidis, Michalis Kosmidis, Chrysanthi Barba, Sofia Akrivou, Ioannis Michalopoulos, Panagiotis Politis, Marinos Dalakas

Department of Neurology Faculty Papers

BACKGROUND AND OBJECTIVES: The aim of this study was to identify genetic markers and immunologic characteristics of glutamic acid decarboxylase (GAD) antibody-positive patients with stiff-person syndrome (SPS).

METHODS: We conducted systemic immunogenetic studies in 11 GAD-positive patients: 8 with sporadic SPS and 3 from a three-generation family with very high GAD-ab titers but diverse symptomatology (one with GAD-epilepsy and SPS and 2 only with diabetes), by performing complete immunologic profile and whole-exome sequencing analysis.

RESULTS: Two genes expressed in immune and neuronal tissues were identified: the ORAI1 that codes for a calcium release–activated channel protein with a role in the …

Terlipressin-Induced Hyponatremic Seizures In A Patient With Congenital Hepatic Fibrosis, Luca Gauci, Jorge Gafa, Suzanne Cauchi, Jurgen Gerada

HCA Healthcare Journal of Medicine

Introduction

Acute variceal bleeding from portal hypertension is one of the most serious complications with a mortality rate of 15% to 25%. Terlipressin is a vasopressor that controls variceal bleeding by lowering the portal pressure and reducing blood flow to the varices.

Case Presentation

We report a case of a patient with acute variceal bleeding, treated endoscopically and with terlipressin, who developed severe hyponatremia and seizures requiring admission to intensive care. Clinical and biochemical improvements were noticeable upon the cessation of terlipressin, with an eventual discharge from the hospital.

Conclusion

Prompt management of acute variceal bleeding with both endoscopic and …

Alcohol And Cannabis Use For Pain Management: Translational Findings Of Relative Risks, Benefits, And Interactions, Sumin Lee, Scott Edwards

School of Medicine Faculty Publications

Chronic pain affects over 20% of the global population and contributes to the vast burden of psychiatric illness. While effective treatments for chronic pain remain limited, both alcohol and cannabis have been used for centuries to manage pain and closely associated negative affective symptoms. However, persistent misuse of alcohol and/or cannabis in such a negative reinforcement fashion is hypothesized to increase the risk of severity of substance use disorders (SUDs). The current review describes neurobiological evidence for the analgesic efficacy of alcohol and primary cannabis constituents and how use or co-use of these substances may influence SUD risk.

Refractory Dermatitis Evolving Into Lupus Spectrum Disease In The Setting Of Dupilumab Use, Jonathan M. Joseph, Jacob Kilgore, Nicholas Culotta

School of Medicine Faculty Publications

Cutaneous lupus erythematosus (CLE) encompasses a broad range of clinical and histopathologic variants that can overlap with other dermatologic entities, complicating accurate diagnosis. We report the case of a 42-year-old male patient who initially presented with a diffuse pruritic eruption presumed to be atopic dermatitis, for which dupilumab was initiated. Within the following weeks, the patient developed a fever of unknown origin and diarrhea, raising concern for an atypical drug-related reaction or an unmasked autoimmune process. Subsequent biopsies demonstrated evolving histopathologic features, including superficial and deep perivascular dermatitis suggestive of drug eruption. In addition, a dermal mucin deposition with mixed …

Bilateral Carotid Body Paragangliomas With Succinate Dehydrogenase Complex Subunit D Gene Mutation, Abdul R. Khan, Kelvin Li, Neel D. Gupta, Jagan D. Gupta, Mohammed M. Ansari, Triet M. Do, Enrique Palacios

School of Medicine Faculty Publications

No abstract provided.

Silencing Faf2 Mitigates Alcohol-Induced Hepatic Steatosis By Modulating Lipolysis And Pcsk9 Pathway, Nazmul Huda, Praveen Kusumanchi, Yanchao Jiang, Hui Gao, Themis Thoudam, Ge Zeng, Nicholas J. Skill, Zhaoli Sun, Suthat Liangpunsakul, Jing Ma, Zhihong Yang

School of Medicine Faculty Publications

BACKGROUND: Chronic alcohol consumption leads to lipid accumulation, oxidative stress, cellular damage, and inflammation in the liver, collectively referred to as alcohol-associated liver disease (ALD). FAF2/UBXD8/ETEA (Fas-associated factor 2) is a ubiquitin ligase adaptor protein that plays a crucial role in the ubiquitin-mediated degradation of misfolded proteins in the endoplasmic reticulum. A recent genome-wide association study indicated an association between FAF2 and ALD; however, the exact contribution of FAF2 to ALD pathogenesis remains unclear. METHODS: FAF2 was knocked down using AAV-delivered shRNA in C57/BL6 mice. Mice were subjected to a chronic-plus-single binge ethanol feeding (NIAAA) model. Nine hours after gavage, …

Effect Of Steroids On The Progression Of Alzheimer's Dementia: A Retrospective Chart Review., Julijana Zoran Conic, Alexandra Chetty, Lily Chen, Audrey Marsh, Sean Barry, Rodney Pattabhi, Thomas Reske, Erwin Aguilar, Lobna Ali

School of Medicine Faculty Publications

Objectives: Alzheimer's disease (AD) is a prevalent age‐related neurodegenerative disease that affects millions of individuals in the United States. Neuroinflammation is a driver of the neurodegenerative changes that characterize AD, prompting interest in how inflammation can be modulated for treatment and prevention. Methods: ICD‐10 codes were quarried from electronic medical records to identify patients diagnosed with AD from 2012 to 2020. The patients were then divided into those who used systemic steroids and those who did not before the progression of their disease. Data on medication prescribed was used to measure the disease's progression. Clinical findings and laboratory results were …

The Unfolding Story Of Protein Misfolding Causing Alzheimer Disease In Recipients Of Human Pituitary Growth Hormone, Evan G. Graber, Sayed M. Hadi Hosseini, Darrell M. Wilson, Alan D. Rogol

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Human growth hormone (hGH) has been in clinical use for children with GH deficiency (GHD) since the late 1950s. The original formulations were considered very safe with few adverse events reported. That changed remarkably in 1985 when the first patients with GHD, who had been treated with cadaveric hGH, were diagnosed with Creutzfeldt-Jakob disease (CJD). Fortunately, that same year a robust supply of recombinant hGH was released to the market whose adverse event profile did not include CJD. Patients who had received National Hormone and Pituitary Program hGH have been continuously followed since 1985. It is clear that prions are …

Jarisch-Herxheimer Reaction After Benzathine Penicillin G Treatment In Adults With Early Syphilis: Secondary Analysis Of A Randomized Clinical Trial., Jodie A. Dionne, Chunming Zhu, Jorge Mejia-Galvis, Kimberly Workowski, Teresa A. Batteiger, Julia C. Dombrowski, Kenneth H. Mayer, Candice J. Mcneil, Arlene C. Seña, Stephanie Taylor, Harold C. Wiesenfeld, Matthew M. Hamill, Charlotte Perlowski, Edward W. Hook Iii

School of Medicine Faculty Publications

Key Points: Question: What proportion of patients with early syphilis have symptoms of the Jarisch-Herxheimer reaction (JHR) after treatment with benzathine penicillin G, and what are the associated characteristics? Findings: This prespecified secondary analysis of a multisite US randomized clinical trial found that, among 249 adults with early syphilis, JHR symptoms occurred after benzathine penicillin G treatment in 59 participants (23.7%). Onset of JHR was within 12 hours of treatment for 86.0% of participants, and JHR was associated with successful treatment response, secondary syphilis, and absence of HIV. Meaning: This study suggests that patients treated with benzathine penicillin G for …

A Galleria Mellonella Study: Protective Effects Of Sulforaphane On Immune Function In Binge Alcohol Exposure, Robert Kento Darby, Braydon Black, Vincent Tran, Dallen James, Scott Quimby

Annual Research Symposium

Alcohol is associated with increased mortality and morbidity. Pulmonary infections with opportunistic pathogens can occur in healthy humans; however, hazardous alcohol exposure like binge alcohol intoxication (≥ 0.08% BAC) is a major risk factor. We’ve previously investigated the efficacy of Sulforaphane (SFN) prophylaxis in protecting human and murine alveolar macrophage function against opportunistic infections when exposed to binge alcohol conditions in vitro. However, an in vivo model investigating SFN and hazardous alcohol exposure in the context of infection is not well understood. The aim of this study is to 1) establish a G. mellonella larvae model by determining the LD50 …

Glucagon-Like Peptide-1 Receptor Agonists Improve Metabolic Dysfunction-Associated Steatotic Liver Disease Outcomes, Brandon Havranek, Rebecca Loh, Beatriz Torre, Rachel Redfield, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the leading cause of chronic liver disease and is associated with significant cardiovascular morbidity and mortality. This study aims to investigate the association of glucagon-like peptide-1 (GLP-1) agonists with major cardiovascular events, clinically significant portal hypertension events, and all-cause mortality in patients with MASLD. A large, population-based retrospective cohort study was conducted using the TriNetX platform, which provided real-time access to electronic health records of 634,265 adult patients with MASLD/MASH. Propensity score matching (PSM) was employed to create two cohorts: A GLP-1 agonists group and a control group without GLP-1 agonists usage. Hazard …

Quantitative Characterization And Prediction Of The Binding Determinants And Immune Escape Hotspots For Groups Of Broadly Neutralizing Antibodies Against Omicron Variants: Atomistic Modeling Of The Sars-Cov-2 Spike Complexes With Antibodies, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Nishank Raisinghani, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

A growing body of experimental and computational studies suggests that the cross-neutralization antibody activity against Omicron variants may be driven by the balance and tradeoff between multiple energetic factors and interaction contributions of the evolving escape hotspots involved in antigenic drift and convergent evolution. However, the dynamic and energetic details quantifying the balance and contribution of these factors, particularly the balancing nature of specific interactions formed by antibodies with epitope residues, remain largely uncharacterized. In this study, we performed molecular dynamics simulations, an ensemble-based deep mutational scanning of SARS-CoV-2 spike residues, and binding free energy computations for two distinct groups …

An Open-Label Study To Determine The Maximum Tolerated Dose Of Oral Esk-440 Administered As A Single Agent In Patients With Advanced Or Metastatic Solid Tumors, Russell J. Schilder, Drew Rasco, Manish R. Sharma

Kimmel Cancer Center Faculty Papers

PURPOSE: Anaplastic lymphoma kinase (ALK) dysregulation is implicated in numerous cancers. Tyrosine kinase inhibitors (TKIs) targeting ALK have improved disease outcomes, but resistance mechanisms are common. This first-in-human trial evaluates ESK-440, a dual inhibitor of ALK and focal adhesion kinase, as a novel strategy for cancers with resistance to ALK-targeting TKIs.

METHODS: This phase 1, open-label, dose-finding study evaluated the maximum tolerated dose (MTD), safety, efficacy, and pharmacokinetics of ESK-440 in participants with advanced or metastatic solid tumors (ClinicalTrials.gov: NCT01922752). A 3 + 3 dose-escalation design, with daily doses ranging from 25 to 700 mg/day of ESK-440 for each 28-day …

Durable Responses To Immune Checkpoint Inhibitor-Based Regimens For Metastatic Clear Cell Renal Cell Carcinoma Stratified By Imdc Risk Groups: A Pooled Analysis Of Four Randomized Phase 3 Trials, Albert Jang, Jeffrey Y. Zhong, Hamsa L.S. Kumar, Kevin K. Zarrabi, Alec Zhu, Abby L. Grier, Adam Calaway, Jonathan E. Shoag, Laura Bukavina, Angela Y. Jia, Prateek Mendiratta, Iris Y. Sheng, Santosh Rao, Jason R. Brown, Jorge A. Garcia, Seunghee Margevicius, Pingfu Fu, Pedro C. Barata

Department of Medical Oncology Faculty Papers

Background: An immune checkpoint inhibitor (ICI) backbone is a standard of care for frontline metastatic clear cell renal cell carcinoma, involving either ICI doublet or tyrosine kinase inhibitor (TKI) with ICI. These phase 3 trials used a sunitinib control arm. The optimal regimen is uncertain. Objective: To compare long-term responders of these trials using extended follow-up data stratified by International Metastatic RCC Database Consortium risk group. Methods: Phase 3 trial data (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR) with a minimum follow-up of four years was used. Pseudo individual patient data (IPD) was obtained from Kaplan-Meier curves using the graph …

Insilico Evaluation Of The Therapeutic Effects Of N1-(5-(3-Imino-2,4a-Dihydro-3h-Benzo[F]Chromen-2-Yl)-1,3,4-Thiadiazol-2-Yl)-N10-(5-(3-Imino-3h-Benzo[F]Chromen-2-Yl)-1,3,4-Thiadiazol-2-Yl)Decanediamide As Anti-Hepatitis B And C Agent, Moses M. Edim, Njok N. Okam, Nguuma I. Gber, Jessica E. Egbelo, Israel E. Okon, Chiemerie P. Ogbonna, Emmanuel K. Aidoo, Kenneth N. Chisom, Emmanuel Samuel

Polytechnic Journal

Hepatitis B and C viruses are a major cause of cirrhosis and hepatocellular carcinoma, with significantly increasing mortality and morbidity worldwide. This study provides a detailed analysis of the therapeutic effects of N1-(5-(3-imino-2,4a-dihydro-3H-benzo[f]chromen-2-yl)-1,3,4-thiadiazol-2-yl)-N10-(5-(3-imino-3H-benzo[f]chromen-2-yl)-1,3,4-thiadiazol-2-yl) decan diamide (PRO_16) as an anti-hepatitis B and C virus. A computational DFT was applied via the ωB97XD method of theory and a basis set of 6-311G++ (2d, 2p) to evaluate the quantum mechanics of the compound. A time-dependent self-consistent field DFT method with the aforementioned functional and basis set was utilized for UV‒visible evaluation. Additionally, a molecular docking technique and ADMET prediction were used to elucidate …

Development And Validation Of Risk Stratification For Heart Failure After Acute Coronary Syndrome Based On Dynamic S100a8/A9 Levels, Jie Ma, Ke Ma, Jing Chen, Xinying Yang, Fei Gao, Hai Gao, Hui Zhang, Xin-Liang Ma, Jie Du, Ping Li, Yulin Li

Department of Emergency Medicine Faculty Papers

BACKGROUND: The early assessment of heart failure (HF) risk in patients with acute coronary syndrome (ACS) can help reduce mortality. S100A8/A9 is not only rapidly released after myocardial ischemia, but is also involved in reperfusion injury, which is an important predictor of HF after ACS. We attempted to construct a reliable HF risk stratification tool for evaluating patients with ACS after reperfusion therapy based on S100A8/A9 dynamic changes.

METHODS AND RESULTS: This prospective study included 3 independent cohorts of patients with ACS who received reperfusion therapy. The discovery cohort was divided into 2 subgroups: the longitudinal subgroup (n=264) with serum …

Palovarotene In Fibrodysplasia Ossificans Progressiva: Review And Perspective, Vincent Verheij, Robert Diecidue, Esmée Botman, Joseph Harrington, Nobuhiko Haga, Alberto Hidalgo-Bravo, Patricia Delai, Vrisha Madhuri, Mona Al Mukaddam, Keqin Zhang, Tae-Joon Cho, Rolf Morhart, Richard Keen, Carmen De Cunto, Clive Friedman, Zvi Grunwald, Michael Zasloff, J. Coen Netelenbos, Edward Hsiao, Frederick Kaplan, Robert Pignolo, Christiaan Scott, Elisabeth Marelise Eekhoff

Department of Oral and Maxillofacial Surgery Faculty Papers

INTRODUCTION: Palovarotene is a retinoic acid receptor gamma agonist that was studied in phase-2 and phase-3 clinical trials for the inhibition of new heterotopic ossification (HO) in fibrodysplasia ossificans progressiva (FOP). Despite numerous setbacks and regulatory delays, palovarotene is now the first approved FOP treatment in the U.S.A., Canada and Australia but remains unapproved in Europe where concerns surrounding the drug and its path to regional market authorization persist.

AREAS COVERED: The developmental history of palovarotene and an overview of the clinical trials and the regulatory approval journey are discussed by global FOP experts.

EXPERT OPINION: While post hoc analyses …

Nrf2/Cyclooxygenase 2 Signaling In Cr(Vi)-Induced Carcinogenesis, Lei Zhao, Yi-Fang Wang, Andrea Adamcakova-Dodd, Peter Thorne, Ranakul Islam, Ke Jian Liu, Fei Chen, Jia Luo, Ling-Zhi Liu

Kimmel Cancer Center Faculty Papers

Long-term exposure to hexavalent chromium [Cr(VI)] has been linked to lung cancer, and cyclooxygenase-2 (COX-2) is a well-known inflammatory factor. However, the role and mechanism of COX-2 in Cr(VI)-induced carcinogenesis are not clear yet. To address this question, we employed a mouse model exposed to Cr(VI) through intranasal instillation of particulate zinc chromate (ZnCrO4) for 12 weeks. Metabolomics and RNA-seq assays revealed enhanced activity of the arachidonic acid (AA)/eicosanoid metabolism pathway in lung tissues from mice exposed to Cr(VI). COX-2, the key enzyme of the AA/eicosanoid pathway, was significantly upre- gulated in Cr(VI)-exposed lung tissues, as well as in the …

Bayesian Population Pharmacokinetic Modeling Of Ondansetron For Neonatal Opioid Withdrawal Syndrome, Kevin Lam, John Mondick, Gary Peltz, Manhong Wu, Walter Kraft

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Ondansetron is an anti-emetic 5-HT3 receptor antagonist being investigated for treating neonatal opioid withdrawal syndrome (NOWS). Sparse PK data were analyzed from a multicenter, double-blind clinical trial with 98 mother/neonate dyads. Pregnant women with opioid use disorder were randomized to receive either placebo or ondansetron 8 mg intravenously within 4 h of delivery. Neonates born to mothers who were randomized to ondansetron received 0.07 mg/kg orally once every 24 h for up to five doses. Using current PK data, model parameters from a two-compartmental structural model from the literature (i.e., a priori model) were updated with the Metropolis-Hastings Markov-chain Monte …

Management Of Hip Fracture Patients On Direct Oral Anticoagulants: A Survey Of Orthopaedic Trauma Surgeons, Systematic Review, And Meta-Analysis, Clay Spitler, Robert Rutz, Nigel Blackwood, Meghan Wally, Joseph Johnson, Peter Krause, Jaimo Ahn, Zuhair Mohammed, Mark Mcclure, Rebecca Billings, Ziqing Yu, Matthew Yeager

School of Medicine Faculty Publications

OBJECTIVES: This systematic review examined the literature regarding management of fracture patients who take direct oral anticoagulant (DOAC) medications, with a focus on delay in surgical treatment, and need for transfusions. In addition, a survey of orthopaedic trauma surgeons was conducted to gain insight on current practices. DATA SOURCES: A review of PubMed, Cochrane, Embase, and Scopus databases was performed from inception through March 2024, including English language publications. STUDY SELECTION: Studies were included if they reported time to surgery and transfusion rates among fracture patents who were taking DOAC medications. Additional data points were collected on an "if-reported" basis, …

Il-1Β In Neoplastic Disease And The Role Of Its Tumor-Derived Form In The Progression And Treatment Of Metastatic Prostate Cancer, Yetunde Oyende, Luke Taus, Alessandro Fatatis

Kimmel Cancer Center Faculty Papers

Since its discovery, IL-1β has taken center stage as a key mediator of a very broad spectrum of diseases revolving around immuno-mediated and inflammatory events. Predictably, the pleiotropic nature of this cytokine in human pathology has led to the development of targeted therapeutics with multiple treatment indications in the clinic. Following the accumulated findings of IL-1β's central modulatory role in the immune system and the implication of inflammatory pathways in cancer, the use of IL-1β antagonists was first proposed and then also pursued for oncology disorders. However, this approach has consistently relied on the perceived need of interfering with IL-1β …

Adenosine-Sensitive Upper Septal Fascicular Ventricular Tachycardia Associated With Takotsubo Syndrome, Parker O'Neill, Daniel Underberg, Reginald Ho, Darius Farzad, Gregary Marhefka

Department of Medicine Faculty Papers

We describe a rare case of upper septal fascicular ventricular tachycardia (VT) associated with takotsubo syndrome that failed to convert with synchronized shock but converted to normal sinus rhythm after intravenous adenosine administration. The excess catecholamine state of takotsubo syndrome likely provided substrate for cyclic adenosine monophosphate–mediated triggered activity, causing fascicular VT.

Nitroglycerine For Retained Placenta: A Meta-Analysis Of Randomized Controlled Trials, Alessandro Petrecca, Gabriele Saccone, Vincenzo Berghella

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: To evaluate the effect of nitroglycerine on placenta delivery after retained placenta.

DESIGN: Systematic review with meta-analysis.

DATA SOURCES: MEDLINE, PROSPERO, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library, Scielo were searched from their inception until February 2024.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included all randomized clinical trials comparing use of nitroglycerine (i.e. intervention group) with placebo or with no treatment (i.e. control group) given for retained placenta after vaginal delivery.

DATA SYNTHESIS: The primary outcome was rate of manual removal of the placenta. The summary measures were reported as relative risk (RR) or as mean difference (MD) with …

Residual Traditional Risk In Non-Traditional Atherosclerotic Diseases, Federico Biscetti, Giorgia Polito, Maria Margherita Rando, Maria Anna Nicolazzi, Luis H. Eraso, Paul J. Dimuzio, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Individuals with chronic inflammatory and immune disorders are at an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Despite extensive literature exploring the relationship between "non-traditional" atherosclerotic conditions and CV risk, many aspects remain unresolved, including the underlying mechanisms promoting the "non-traditional CV risk", the development of an innovative and comprehensive CV risk assessment tool, and recommendations for tailored interventions. This review aims to evaluate the available evidence on key "non-traditional" CV risk-enhancer conditions, with a focus on assessing and managing CV risk factors. We conducted a comprehensive review of 412 original articles, narrative and systematic reviews, and …

Tdp43 Autoregulation Gives Rise To Dominant Negative Isoforms That Are Tightly Controlled By Transcriptional And Post-Translational Mechanisms, Megan M. Dykstra, Kaitlin Weskamp, Nicolás B. Gómez, Jacob Waksmacki, Elizabeth Tank, M. Rebecca Glineburg, Allison Snyder, Emile Pinarbasi, Michael Bekier, Xingli Li, Morgan R. Miller, Jen Bai, Shameena Shahzad, Neha Nedumaran, Clare Wieland, Corey Stewart, Sydney Willey, Nikolas Grotewold, Jonathon Mcbride, John J. Moran, Aditya V. Suryakumar, Michael Lucas, Peter M. Tessier, Michael Ward, Peter K. Todd, Sami J. Barmada

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The nuclear RNA-binding protein TDP43 is integrally involved in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Previous studies uncovered N-terminal TDP43 isoforms that are predominantly cytosolic in localization, prone to aggregation, and enriched in susceptible spinal motor neurons. In healthy cells, however, these shortened (s)TDP43 isoforms are difficult to detect in comparison to full-length (fl)TDP43, raising questions regarding their origin and selective regulation. Here, we show that sTDP43 is created as a by-product of TDP43 autoregulation and cleared by nonsense-mediated RNA decay (NMD). sTDP43-encoding transcripts that escape NMD are rapidly degraded post-translationally via the proteasome …

Two-Year Follow-Up Of Gait And Postural Control Following Initiation Of Recombinant Human Tripeptidyl Intracerebroventricular Enzyme Replacement Therapy In Two Atypical Cln2 Patients, Rahul Soangra, Marybeth Grant-Beuttler, Harriet Chang, Raymond Y. Wang

Physical Therapy Faculty Articles and Research

Neuronal ceroid lipofuscinosis type 2 (CLN2) is a rapidly progressive neurodegenerative disorder leading to premature mortality. Ambulatory CLN2 patients typically receive standard of care treatment through biweekly intracerebroventricular (ICV) enzyme replacement therapy (ERT) involving recombinant human tripeptidyl peptidase 1, known as cerliponase alfa (Brineura^®, Biomarin Pharmaceuticals). This study longitudinally assessed the impact of ICV cerliponase alfa ERT on gait, and postural control across a two-year span in two siblings diagnosed with atypical CLN2 disease. Both participants, ID01 (18 years and 8 months old at enrollment) and ID02 (13 years and 3 months old at enrollment), exhibited symptomatic characteristics …