Chemicals and Drugs Commons^™

Fluorine-Containing Isosteres Enable A Structure-Activity Relationship Study Of Gingerol Derivatives, Shelby Cooper, Diarta Kabashi, Marlin Yacoub, Jessica Molen, Osman Farhan, Christina Farley, Samantha Yencha, Michelle Figueiredo, Nidheesh Phadnis, Wynter Henry, Julian Harris, Frank Wilkinson, John Milligan

College of Life Sciences Faculty Papers

A series of fluorinated and non-fluorinated [6]-gingerol, [6]-paradol, [6]-shogaol and ferulate derivatives were synthesized. Testing these analogs in anti-proliferation assays with MCF-7, A549, HCT-116 and HEK-293 cell lines provided insight into the structural features that contribute to the anti-proliferative activity of naturally occurring ginger constituents. In particular, the use of both vinyl and alkyl trifluoromethyl isosteres allowed us to evaluate the structure-activity impact of the enone motif found in shogaols. Our results indicate that enone-containing derivatives have a higher potency, suggesting the conjugated enone motif characteristic of shogaols may be primarily responsible for the anti-cancer activity of the broader natural …

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 …

Moud 2.0: A Clinical Algorithm And Implementation Evaluation Protocol For Sublingual And Injectable Buprenorphine Treatment Of Opioid Use Disorder, Brandon Joa, Eric Fung, Michael Weinstein, Lara Weinstein

Department of Family & Community Medicine Faculty Papers

BACKGROUND: Primary care is the initial contact point for most patients with opioid use disorder (OUD) but lacks tools for guiding treatment. Only a small fraction of patients access evidence-based care. Long-acting injectable buprenorphine has potential to improve medication adherence and program retention in low-barrier primary care treatment settings. We present the first clinical decision support algorithm incorporating long-acting buprenorphine (LAIB) in primary care. We include a protocol for a future evaluation of the algorithm's implementation process, "Medication for Opioid Use Disorder (MOUD) 2.0," at a housing and integrated care clinic at a Federally Qualified Health Center.

METHODS: Literature review …

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 …

Transcription Factor Runx1 Regulates Coagulation Factor Xiii-A (F13a1): Decreased Platelet-Megakaryocyte F13a1 Expression And Clot Contraction In Runx1 Haplodeficiency, Fabiola Del Carpio-Cano, Natthapol Songdej, Liying Guan, Guangfen Mao, Lawrence E. Goldfinger, Jeremy G.T. Wurtzel, Kiwon Lee, Michele P. Lambert, Mortimer Poncz, A. Koneti Rao

Cardeza Foundation for Hematologic Research

BACKGROUND: Germline RUNX1 haplodeficiency (RHD) is associated with thrombocy- topenia, platelet dysfunction, and predisposition to myeloid malignancies. Platelet expression profiling of an RHD patient showed decreased F13A1, encoding for the A subunit of factor (F)XIII, a transglutaminase that cross-links fibrin and induces clot stabilization. FXIII-A is synthesized by hematopoietic cells, megakaryocytes, and monocytes.

OBJECTIVES: o understand RUNX1 regulation of F13A1 expression in platelets/mega- karyocytes and the mechanisms and consequences of decreased F13A1 in RHD.

METHODS: We performed studies in platelets, human erythroleukemia (HEL) cells, and human CD34+ cell-derived megakaryocytes including on clot contraction in cells following small inhibitor RNA knockdown …

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 …

Skeletal And Dental Tissue Mineralization: The Potential Role Of The Endoplasmic Reticulum/Golgi Complex And The Endolysosomal And Autophagic Transport Systems, Irving M. Shapiro, Makarand V. Risbud, Tengteng Tang, William J. Landis

Department of Orthopaedic Surgery Faculty Papers

This paper presents a review of the potential role of the endoplasmic reticulum/Golgi complex and intracellular vesicles in mediating events leading to or associated with vertebrate tissue mineralization. The possible importance of these organelles in this process is suggested by observations that calcium ions accumulate in the tubules and lacunae of the endoplasmic reticulum and Golgi. Similar levels of calcium ions (approaching millimolar) are present in vesicles derived from endosomes, lysosomes and autophagosomes. The cellular level of phosphate ions in these organelles is also high (millimolar). While the source of these ions for mineral formation has not been identified, there …

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 …

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …

Nls-Binding Deficient Kapβ2 Reduces Neurotoxicity Via Selective Interaction With C9orf72-Als/Ftd Dipeptide Repeats, Kevin Kim, Amandeep Girdhar, Maria Elena Cicardi, V. Kankate, Miyuki Hayashi, Ruoyu Yang, Jenny Carey, Charlotte M Fare, James Shorter, Gino Cingolani, Davide Trotti, Lin Guo

Department of Biochemistry and Molecular Biology Faculty Papers

Arginine-rich dipeptide repeat proteins (R-DPRs) are highly toxic proteins found in patients with C9orf72-linked amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). R-DPRs can cause toxicity by disrupting the natural phase behavior of RNA-binding proteins (RBPs). Mitigating this abnormal phase behavior is, therefore, crucial to reduce R-DPR-induced toxicity. Here, we use FUS as a model RBP to investigate the mechanism of R-DPR-induced aberrant RBP phase transition. We find that this phase transition can be mitigated by Kapβ2. However, as a nuclear import receptor and phase modifier for PY-NLS-containing RBPs, the function of WT Kapβ2 could lead to undesired interaction with its …

Tryptophan Kynurenine Pathway-Based Imaging Agents For Brain Disorders And Oncology-From Bench To Bedside, Erik Stauff, Wenqi Xu, Heidi H. Kecskemethy, Sigrid A. Langhans, Vinay V. R. Kandula, Lauren W. Averill, Xuyi Yue

Jefferson Hospital Staff Papers and Presentations

Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of …

Emcreg-International Multidisciplinary Consensus Panel On Management Of Hyperkalemia In Chronic Kidney Disease And Heart Failure, Natalie Kreitzer, Nancy M. Albert, Alpesh N. Amin, Craig J. Beavers, Richard C. Becker, Gregg Fonarow, W. Brian Gibler, Katherine W. Kwon, Robert J. Mentz, Biff F. Palmer, Charles V. Pollack, Iliana L. Piña

Division of Cardiology Faculty Papers

BACKGROUND: Hyperkalemia, generally defined as serum potassium levels greater than 5.0 mEq/L, poses significant clinical risks, including cardiac toxicity and muscle weakness. Its prevalence and severity increase in patients with chronic kidney disease (CKD), diabetes mellitus, and heart failure (HF), particularly when compounded by medications like angiotensin converting inhibitors, angiotensin receptor blockers, and potassium sparing diuretics. Hyperkalemia arises from disruptions in potassium regulation involving intake, excretion, and intracellular-extracellular distribution. In CKD and acute kidney injury, these regulatory mechanisms are impaired, leading to heightened risk. The management of chronic hyperkalemia presents a challenge due to the necessity of balancing effective cardiovascular …

Treatment Sequence With Tebentafusp And Immune Checkpoint Inhibitors In Patients With Metastatic Uveal Melanoma And Metastatic Gna11/Gnaq Mutant Melanocytic Tumors, Florentia Dimitriou, Marlana Orloff, Erica Koch Hein, Phil Cheng, Isaac Hughes, Ester Simeone, Kamaneh Montazeri, Piyush Grover, Inderjit Mehmi, Camille Gerard, Caroline Gaudy-Marqueste, Jean-Jacques Grob, Olivier Michielin, Omid Hamid, Georgina Long, Ryan Sullivan, Ellen Kapiteijn, Douglas Johnson, Paolo Ascierto, Anthony Joshua, Richard Carvajal, Marcus Butler, Jessica Hassel, Reinhard Dummer

Kimmel Cancer Center Faculty Papers

BACKGROUND: Metastatic uveal melanoma (mUM) is rare. Immune checkpoint inhibitors (ICIs) have shown modest efficacy in mUM. Tebentafusp prolonged overall survival (OS) in a phase 3 study. We aimed to investigate the efficacy and safety of the sequence of tebentafusp and ICIs.

METHODS: Patients with HLA-A * 02:01 positive mUM, or metastatic GNA11/GNAQ mutant melanocytic tumors treated with tebentafusp followed by ICIs (group 1) or the inverse sequence (group 2) at any treatment line were retrospectively identified. The primary objective was OS rate at 2 years.

RESULTS: 131 patients were included; 51 in group 1 and 80 in group 2. …

The Complexity And Significance Of Fibroblast Growth Factor (Fgf) Signaling For Fgf-Targeted Cancer Therapies, Anh Nguyen, Caroline Facey, Bruce Boman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Fibroblast growth factors (FGFs) have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis. The goal of this review paper is to (i) deliberate on the role of FGFs and FGF receptors (FGFRs) in different cancers, (ii) present advances in FGF-targeted cancer therapies, and (iii) explore cell signaling mechanisms that explain how FGF expression becomes dysregulated during cancer development. FGF is often mutated and overexpressed in cancer and the different FGF and FGFR isoforms have unique expression patterns and distinct roles in different cancers. Among the FGF members, the FGF 15/19 …

Glucose-Lowering Agents Developed In The Last Two Decades And Their Perioperative Implications, Basavana Goudra, Geno Merli, Michael Green

Department of Anesthesiology Faculty Papers

The last two decades have provided far more options f both patients and their physicians in the treatment of diabetes mellitus. While dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been approved for nearly two decades, sodium-glucose cotransporter 2 inhibitors (SGLT-2is) are relatively new. Of interest to perioperative physicians, these drugs present specific perioperative concerns, prompting many societies to issue guidelines. Retained gastric contents due to slow gastric emptying is a significant drawback of GLP-1RAs, increasing the risk of aspiration. Recommendations include withholding GLP-1RAs for a predefined period of time, performing gastric ultrasound to evaluate gastric …

Nuclear Expression Of Dynamin 2 Is Associated With Tumor Aggressiveness In Bladder Cancer Patients: A Bioinformatics And Experimental Approach, Mahdieh Razmi, Leili Saeednejad Zanjani, Mandana Rahimi, Roya Sajed, Sadegh Safaei, Zahra Madjd, Roya Ghods

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

AIMS: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

METHODS AND RESULTS: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer …

Opa1 And Disease-Causing Mutants Perturb Mitochondrial Nucleoid Distribution, J. Macuada, I. Molina-Riquelme, G. Vidal, N. Pérez-Bravo, C. Vásquez-Trincado, G. Aedo, D. Lagos, P. Yu-Wai-Man, R. Horvath, T. J. Rudge, B. Cartes-Saavedra, V. Eisner

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Optic atrophy protein 1 (OPA1) mediates inner mitochondrial membrane (IMM) fusion and cristae organization. Mutations in OPA1 cause autosomal dominant optic atrophy (ADOA), a leading cause of blindness. Cells from ADOA patients show impaired mitochondrial fusion, cristae structure, bioenergetic function, and mitochondrial DNA (mtDNA) integrity. The mtDNA encodes electron transport chain subunits and is packaged into nucleoids spread within the mitochondrial population. Nucleoids interact with the IMM, and their distribution is tightly linked to mitochondrial fusion and cristae shaping. Yet, little is known about the physio-pathological relevance of nucleoid distribution. We studied the effect of OPA1 and ADOA-associated mutants on …

Akt Kinases As Therapeutic Targets, Dalal Hassan, Craig Menges, Joseph Testa, Alfonso Bellacosa

Student Papers, Posters & Projects

AKT, or protein kinase B, is a central node of the PI3K signaling pathway that is pivotal for a range of normal cellular physiologies that also underlie several pathological conditions, including inflammatory and autoimmune diseases, overgrowth syndromes, and neoplastic transformation. These pathologies, notably cancer, arise if either the activity of AKT or its positive or negative upstream or downstream regulators or effectors goes unchecked, superimposed on by its intersection with a slew of other pathways. Targeting the PI3K/AKT pathway is, therefore, a prudent countermeasure. AKT inhibitors have been tested in many clinical trials, primarily in combination with other drugs. While …

Association Between Various Types Of Corticosteroids And Mortality For Severe Community-Acquired Pneumonia In Adults: A Systematic Review And Network Meta-Analysis, Peng Wang, Jun Wan, Qiaoyu You, Yuxin Zheng, Wenhao Xu, Jialing He, Liyuan Peng, Cuyubamba Dominguez Jorge Luis, Yuning Feng, Ping Xu, Xinrong Li, Weelic Chong, Yang Hai, Lu Jia, Fang Fang, Yu Zhang

Department of Medical Oncology Faculty Papers

OBJECTIVE: This study aims to conduct a systematic review and network meta-analysis to evaluate the efficacy and safety of specific corticosteroids, including but not limited to hydrocortisone, methylprednisolone, prednisolone, and dexamethasone, in the treatment of severe community-acquired pneumonia (SCAP). Efficacy will be assessed using specific outcomes, such as 30-day mortality and the requirement for mechanical ventilation. Safety evaluations will include adverse events like gastrointestinal bleeding and healthcare-associated infections. The study seeks to address the gaps identified in the latest guidelines regarding the optimal use of different corticosteroid types and to provide recommendations for clinical practice.

DATA SOURCES: This study conducted …

Cocaine-Induced Dna-Dependent Protein Kinase Relieves Rnap Ii Pausing By Promoting Trim28 Phosphorylation And Rnap Ii Hyperphosphorylation To Enhance Hiv Transcription, Adhikarimayum Lakhikumar Sharma, Priya Tyagi, Meenata Khumallambam, Mudit Tyagi

Center for Translational Medicine Faculty Papers

Drug abuse continues to pose a significant challenge in HIV control efforts. In our investigation, we discovered that cocaine not only upregulates the expression of the DNA-dependent protein kinase (DNA-PK) but also augments DNA-PK activation by enhancing its phosphorylation at S2056. Moreover, DNA-PK phosphorylation triggers the higher localization of the DNA-PK into the nucleus. The finding that cocaine increases the nuclear localization of the DNA-PK provides further support to our observation of enhanced DNA-PK recruitment at the HIV long terminal repeat (LTR) following cocaine exposure. By activating and facilitating the nuclear localization of the DNA-PK, cocaine effectively orchestrates multiple stages …

Beta-Blocker Use In Patients Undergoing Non-Cardiac Surgery: A Systematic Review And Meta-Analysis, Doménica Herrera Hernández, Bárbara Abreu, Tania S. Xiao, Andreina Rojas, Kevin López Romero, Valentina Contreras, Sol Villa Nogueyra, Zulma Sosa, Samantha M. Alvarez, Camila Sánchez Cruz, Ernesto Calderón Martinez

Department of Radiology Faculty Papers

BACKGROUND: The use of beta-blockers in the perioperative period has been widely investigated due to their potential to reduce the risk of major adverse cardiovascular and cerebrovascular events (MACCE) and mortality; yet their overall impact on various postoperative outcomes remains debated. This study constitutes a systematic review and meta-analysis of the impact of beta-blockers on mortality, MI, stroke, and other adverse effects such as hypotension and bradycardia in patients undergoing non-cardiac surgery.

METHODS: A comprehensive systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Searches were performed across PubMed, Cochrane, Web of Science, Scopus, EMBASE, and CINAHL databases; …

Evaluation Of Sirtuin 1 As A Predictor Of Cardiovascular Outcomes In Diabetic Patients With Limb-Threatening Ischemia, Federico Biscetti, Maria Margherita Rando, Maria Anna Nicolazzi, Enrica Rossini, Michele Santoro, Flavia Angelini, Roberto Iezzi, Luis H. Eraso, Paul J. Dimuzio, Dario Pitocco, Massimo Massetti, Antonio Gasbarrini, Andrea Flex

Department of Surgery Faculty Papers

Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly …

Systemic Effects Of Anti-Vegf Intravitreal Injection In Patients With Age-Related Macular Degeneration: A Multi-Institutional Real-World Study, Tzu-Yi Lin, Yi-Ting Hsieh, Sunir J. Garg, Lee-Jen Chen, Kuan-Jen Chen, Wei-Chi Wu, Chi-Chun Lai, Yih-Shiou Hwang, Eugene Yu-Chuan Kang

Wills Eye Hospital Papers

PURPOSE: In individuals aged >50 years, age-related macular degeneration (AMD) is the leading cause of irreversible blindness. Intravitreal injections of antivascular endothelial growth factor (VEGF) agents (bevacizumab, ranibizumab, and aflibercept) show good efficacy and similar incidences of systemic adverse events (SAEs). However, comparative studies between agents are limited. Our study aimed to compare the real-world SAE risks of bevacizumab, ranibizumab, and aflibercept users.

METHODS: This retrospective cohort study identified new bevacizumab, ranibizumab, and aflibercept users in a multi-institutional database in Taiwan between 2014 and 2019. Inverse probability of treatment weights (IPTW) with propensity scores was conducted to achieve homogeneity among …

Attention Deficit Hyperactivity Disorder, Cannabis Use, And The Endocannabinoid System: A Scoping Review, Jennie Ryan, Mitchell Fruchtman, Andrea Sparr-Jaswa, Amy Knehans, Brooke Worster

Department of Medicine Faculty Papers

There is emerging evidence that the endocannabinoid system (ECS) plays a significant role in the pathophysiology of many psychiatric disorders, including attention deficit hyperactivity disorder (ADHD). Increasing evidence suggests that a number of neurobiological correlates between endogenous cannabinoid function and cognitive dysfunction are seen in ADHD, making the ECS a possible target for therapeutic interventions. Cannabis use and cannabis use disorder are more prevalent in individuals with ADHD, compared to the general population, and there is growing popular perception that cannabis is therapeutic for ADHD. However, the relationship between cannabis use and ADHD symptomology is poorly understood. Further understanding of …

Deoxycholic Acid Injections As A Nonsurgical Treatment For Lipomas In Adiposis Dolorosa (Dercum Disease), Zvi Schwartz, Kayla Brockmeyer, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

Adiposis dolorosa (Dercum disease) is a rare condition characterized by diffuse and recurring painful lipomas on the trunk and extremities. Patients are typically middle-aged females with an elevated BMI presenting with chronic pain. Physical examination reveals soft subcutaneous nodules and masses, tender to palpation. The associated pain significantly impacts quality of life and requires therapeutic intervention. The most common treatment option is surgical excision. Alternative options should be considered for patients with numerous lipomas where surgical management is not practical or is not desired. Deoxycholic acid injections are a viable alternative non-surgical technique. We present a case of a 55-year-old …

Drug-Induced Subacute Cutaneous Lupus Erythematous From Cenobamate: Case Presentation And Review Of The Literature, Safiyyah Bhatti, Daniel Joffe, Timothy Webster, Jason Lee, Neda Nikbakht

Department of Dermatology and Cutaneous Biology Faculty Papers

A 68-year-old woman with a history of seizures on cenobamate presented with an itchy rash all over her body. The rash started about one month prior to her presentation to the dermatology clinic. The rash was initially treated with topical triamcinolone with improvement at one-month follow-up. However, four months later the rash flared and there was concern that cenobamate was the cause. Biopsy was performed showing vacuolar interface dermatitis with atrophy, suggestive of subacute lupus erythematosus. Blood work revealed positive antinuclear antibody, anti-ribonucleoprotein antibody, Sjogren Anti-SS-A and positive histone antibody. Given the worsening rash, positive labs, and cenobamate as the …

Α4 Nicotinic Acetylcholine Receptors In Lipopolysaccharide-Related Lung Inflammation, J. Ritzenthaler, Walter H. Watson, Jesse Roman

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

Sepsis remains an important healthcare challenge. The lungs are often affected in sepsis, resulting in acute lung injury characterized by inflammation. Mechanisms involving lipopolysaccharide (LPS) stimulation of toll-like receptor (TLR) signaling with induction of proinflammatory pathways have been implicated in this process. To date, however, studies targeting these pathways have failed to improve outcomes. We have found that LPS may also promote lung injury through the activation of α4 nicotinic acetylcholine receptors (α4 nAChRs) in immune cells. We observed increased expression of α4 nAChRs in human THP-1 monocytic cells exposed to LPS (100 ng/mL, 24 h). We also observed that …

Apixaban Versus Enoxaparin To Prevent Venous Thromboembolism In Post-Operative Patients With Gynecologic Cancers At An Urban Academic Medical Center, Victoria Diamond, Katherine Gerber, Geno J. Merli, Rebecca J. Mercier, Aaron Shafer, Norman G. Rosenblum

Department of Obstetrics and Gynecology Faculty Papers

OBJECTIVE: A recent clinical trial demonstrated that the use of apixaban was safe and equal to enoxaparin (LMWH) in post-operative gynecologic oncology patients. This study aimed to determine if these findings are applicable in a diverse patient population at a single site urban academic medical center.

METHODS: This was a retrospective cohort study of patients who underwent an exploratory laparotomy for confirmed or presumed gynecologic cancer from the years 2017-2023 at a single-site urban academic medical center. Venous thromboembolism (VTE) prophylaxis with LMWH was standard practice at our institution up until January 2021 after which apixaban became standard for post-operative …

Post-Transcriptional Methylation Of Mitochondrial-Trna Differentially Contributes To Mitochondrial Pathology, Sunita Maharjan, Howard Gamper, Yuka Yamaki, Thomas W. Christian, Robert Y. Henley, Nan-Sheng Li, Takeo Suzuki, Tsutomu Suzuki, Joseph A. Piccirilli, Meni Wanunu, Erin L. Seifert, Douglas C. Wallace, Ya-Ming Hou

Department of Biochemistry and Molecular Biology Faculty Papers

Human mitochondrial tRNAs (mt-tRNAs), critical for mitochondrial biogenesis, are frequently associated with pathogenic mutations. These mt-tRNAs have unusual sequence motifs and require post-transcriptional modifications to stabilize their fragile structures. However, whether a modification that stabilizes a wild-type (WT) mt-tRNA would also stabilize its pathogenic variants is unknown. Here we show that the N¹-methylation of guanosine at position 9 (m¹G9) of mt-Leu(UAA), while stabilizing the WT tRNA, has a destabilizing effect on variants associated with MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes). This differential effect is further demonstrated, as removal of the m¹G9 …