Chemicals and Drugs Commons^™

Economic Value Of Intra-Articular Knee Oa Therapies: A U.S. Perspective, Vinod Dasa, Wilson Ngai, Kevin Steele, Ronald Preblick, Heather Watson, Kevin L. Ong

School of Medicine Faculty Publications

AIMS: This study compared the six-month medical/pharmacy costs and healthcare resource utilization (HCRU) for knee OA patients undergoing intra-articular therapy with different classes of hyaluronic acid (HA) (by molecular weight) or corticosteroid (ICS). MATERIALS AND METHODS: Patients across high molecular weight (HMW) HA, medium molecular weight (MMW) HA, low molecular weight (LMW) HA, and ICS therapy groups were matched from a U.S. claims database (Optum's de-identified Clinformatics Data Mart Database), with a final size of 6,234 patients per group. Adjusted six-month medical/prescription costs per patient per month (PPPM), and HCRU rates and costs, were determined. Secondary endpoints included complication rates …

Impact Of Stereochemical Replacement On Activity And Selectivity Of Membrane-Active Antibacterial And Antifungal Cyclic Peptides, Sandeep Lohan, Anastasia G. Konshina, Eman H. M. Mohammed, Naiera M. Helmy, Srishhti K. Jha, Rakesh Kumar Tiwari, Innokentiy Maslennikov, Roman G. Efremov, Keykavous Parang

Pharmacy Faculty Articles and Research

Herein, we report a library of 7-mer macrocyclic peptides designed by systematically replacing one, multiple, or all L-amino acids with their D-isomers in our previously identified hit compounds. Lead peptides, 15c and 16c, showed broad-spectrum activity against bacteria (Gram-positive minimum inhibitory activity (MIC 1.5–6.2 µg/mL and Gram-negative MIC 6.2–25 µg/mL) and fungi (MIC = 3.1–25 µg/mL). Additionally, peptides 15c and 16c showed rapid kill kinetics and biofilm degradation potential against both bacteria and fungi, while resistance development was not observed. The antimicrobial effect of these macrocyclic peptides was attributed to their membranolytic action, which was confirmed by calcein dye …

Brivaracetam For Spinal Cord Injury-Related Neuropathic Pain: Results Of A Pilot Double-Blinded, Randomized, Placebo-Controlled Clinical Trial, Leslie R. Morse, Ricardo A. Battaglino, Nguyen Nguyen, Brian Devries, Abigail Welch, Ana Lucia Battaglino, Clas Linnman, Michael Stillman, Robert Wudlick, Joda Glossner, Grant Anderton, Richard Goldstein, Scott P. Falci

Department of Medicine Faculty Papers

OBJECTIVE: Assess feasibility, safety, and tolerability of 3 months of oral brivaracetam for severe (9-10/10) spinal cord injury-related neuropathic pain.

METHODS: We conducted a multisite pilot study where adults were randomized to 3 months of brivaracetam (100 mg BID) or placebo. Pain was assessed via the Brief Pain Inventory, the International Spinal Cord Injury Pain Basic Dataset (version 2.0), and a daily pain diary.

RESULTS: We enrolled 24 participants across 2 sites and 14 participants were included in the final analysis (n = 8 placebo, n = 6 brivaracetam). The drug was tolerated with expected, nonserious side effects (nausea if …

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …

Abstract 2587 Recombinant Expression And Purification Of A. Vinelandii Cown In E. Coli, Julie Takei, Cedric P. Owens, Katie Sanders, Neeraja Gajendran

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

The goal of this project is to study the protein CowN in the diazotroph Azotobacter vinelandii (Av) in comparison to CowN in Gluconacetobacter diazotrophicus (Gd). Nitrogenase is an enzyme that catalyzes the reduction of nitrogen gas into ammonia in diazotrophic bacteria. In many diazotrophs, the protein CowN prevents nitrogenase inhibition from the environmental gas carbon monoxide (CO). Previous work studied CowN in the diazotroph G. diazotrophicus. In G. diazotrophicus, CowN binds to nitrogenase and weakens CO binding to its active site. The mechanism of CowN has only been investigated in G. diazotrophicus. Thus, we are interested in determining if CowN's …

Abstract 2853 Prmt7 Negatively Regulates The Expression P53 In Response To Dna Damage, Molly Niswender, Lorenzo Pessi, Cecilia Lopez, Marco Bisoffi

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Protein Arginine Methyltransferase 7 (PRMT7) is the only member of the protein arginine methyltransferase protein family that monomethylates its protein substrates. PRMT7 is found in both the nucleus and cytoplasm of breast cells and is believed to play a robust role in the tumorigenesis and metastasis of breast cancer. The goal of this project is to uncover possible pathways for PRMT7 to promote cancer progression. A preliminary antibody array was performed to determine the regulation of known cancer-related proteins by PRMT7. An early-stage human breast cancer cell line, MCF-7, was transfected with plasmid pCDH1-hPRMT7-GFP to over-express PRMT7. Qualitative and quantitative …

The Multifunctional Ascorbate Peroxidase Moapx1 Secreted By Magnaporthe Oryzae Mediates The Suppression Of Rice Immunity, Muxing Liu, Ziqian Guo, Jiexiong Hu, Yuke Chen, Fang Chen, Weizhong Chen, Wenya Wang, Boyang Ye, Zhixiang Yang, Gang Li, Xinyu Liu, Haifeng Zhang, Ping Wang, Zhengguang Zhang

School of Graduate Studies Faculty Publications

Fungi secrete effector proteins, including extracellular redox enzymes, to inhibit host immunity. Redox enzymes have been hypothesized to inhibit host reactive oxygen species (ROS); however, how they suppress host immunity remains unknown. We characterized an extracellular ascorbate peroxidase (MoApx1) that is secreted into rice chloroplasts by the rice blast fungus Magnaporthe oryzae. MoApx1 displays multifunctional capabilities that significantly contribute to fungal virulence. Firstly, MoApx1 neutralizes host-derived H2O2 within the chloroplast through its peroxidase activity, thereby inhibiting chloroplast ROS (cROS)-mediated defense responses. Secondly, MoApx1 targets the photosystem I subunit OsPsaD, disrupting photosynthetic electron transport to further suppress cROS production. Most importantly, …

Engineering Lipid–Polymer Nanoparticles For Sirna Delivery To Cancer Cells, Arthur Manda, Abdulelah Alhazza, Hasan Uludağ, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Background: RNA interference (RNAi) is a powerful tool that can target many proteins without the expensive and time-consuming drug development studies. However, due to the challenges in delivering RNA molecules, the potential impact of RNAi approaches is yet to be fully realized in clinical settings. Lipid nanoparticles (LNPs) have been the most successful delivery system for nucleic acids, but targeted delivery to a solid tumor still eludes the developed LNPs. We hypothesized that specially designed low-molecular-weight PEIs can partially or completely replace the ionizable lipids for more accommodating vehicles due to the structural flexibility offered by polymers, which could …

Supra Inguinal Fascia Iliac Versus Peng Block For Post-Operative Pain Management Of Hip Arthroplasty: A Narrative Review, Shahab Ahmadzadeh, Megan S. Walker, Mary O'Dell Duplechin, Drake P. Duplechin, Charles J. Fox, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Effective post-operative pain management following hip arthroplasty is critical to improving recovery, reducing opioid consumption, enhancing mobility, and reducing the risk of complications for patients. Multimodal anesthesia strategies, including the supra inguinal fascia iliac block (SIFIB) and the periarticular nerve group (PENG) block have become the new point of focus as opposed to traditional methods previously used. This narrative review compares the SIFIB and the PENG block in their efficacy to treat post-operative pain management. Mechanism of action, safety, patient outcomes, and clinical applications are compared between the two blocks for evaluation. Clinical studies have indicated that both blocks reduce …

Ensemble-Based Binding Free Energy Profiling And Network Analysis Of The Kras Interactions With Darpin Proteins Targeting Distinct Binding Sites: Revealing Molecular Determinants And Universal Architecture Of Regulatory Hotspots And Allosteric Binding, Mohammed Alshahrani, Vedant Parikh, Brandon Foley, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

KRAS is a pivotal oncoprotein that regulates cell proliferation and survival through interactions with downstream effectors such as RAF1. Despite significant advances in understanding KRAS biology, the structural and dynamic mechanisms of KRAS allostery remain poorly understood. In this study, we employ microsecond molecular dynamics simulations, mutational scanning, and binding free energy calculations together with dynamic network modeling to dissect how engineered DARPin proteins K27, K55, K13, and K19 engage KRAS through diverse molecular mechanisms ranging from effector mimicry to conformational restriction and allosteric modulation. Mutational scanning across all four DARPin systems identifies a core set of evolutionarily constrained residues …

Cross-Sectional Analysis Of Wound-Associated Soluble Factors In Early, Established, And Chronic Wounds Of Recessive Dystrophic Epidermolysis Bullosa Patients, Vitali Alexeev, Leonie Huitema, Taylor Phillips, Paras Patel, Mauricio Garza, Franziska Ringpfeil, Julio Salas-Alanis, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Poorly healing wounds represent the primary health-related burden for hereditary recessive dystrophic epidermolysis bullosa (RDEB) patients. Contribution of wound-associated soluble constituents to wound progression remains not well defined.

OBJECTIVE: To conduct cross-sectional analysis of cytokine, chemokine, and growth factor in exudates from RDEB wounds and define changes associated with wound progression.

METHODS: Concentrations of selected cytokines, chemokines, and growth factors were evaluated by multiplex ELISA in eight blister fluids and 66 exudates from early, established, and chronic RDEB and five chronic venous ulcers (VU). A cross-sectional analysis was performed.

RESULTS: Our data demonstrated that proinflammatory CXCL8 and IL-1β tend …

Advances In Molecular Imaging Of Vegfrs: Innovations In Imaging And Therapeutics, Hanieh Karimi, Sarah Lee, Wenqi Xu, Sigrid A. Langhans, David K. Johnson, Erik Stauff, Heidi H. Kecskemethy, Lauren W. Averill, Xuyi Yue

Department of Radiology Faculty Papers

Vascular endothelial growth factor receptors (VEGFRs) are key regulators of angiogenesis, lymphangiogenesis, and vascular permeability, playing essential roles in both physiological and pathological processes. The VEGFR family, including VEGFR-1, VEGFR-2, and VEGFR-3, interacts with structurally related VEGF ligands (VEGFA, VEGFB, VEGFC, VEGFD, and placental growth factor [PlGF]), activating downstream signaling pathways that mediate critical cellular processes, including proliferation, migration, and survival. Dysregulation of VEGFR signaling has been implicated in numerous diseases, such as cancer, cardiovascular conditions, and inflammatory disorders. Targeting VEGFRs with radiopharmaceuticals, such as radiolabeled peptides, antibodies, and specific tracers like 64Cu-bevacizumab and 89Zr-ramucirumab, has emerged as a powerful …

Refine: A Database Of Linked Clinical Data And Genomic Biomarkers In Renal Cell Carcinoma Patients Receiving Immunotherapy-Based Treatment Regimens, Jeffrey Zhong, Albert Jang, Bashar Abuqayas, Arnab Basu, David Benjamin, Vineel Bhatlapenumarthi, Mehmet Asim Bilen, Dhvani Buch, Mark Chang, Erica Chin, Sourat Darabi, Nagendra Dhanikonda, Pooja Ghatalia, Claud Grigg, Abby Grier, Tanya Jindal, Joannah Jung, Deepak Kilari, Hamsa Kumar, Suzanna Lee, Brittany Neelands, Chinmayi Pandya, Jeff Pawalek, Jaimee Staggers, Ahmet Yildirim, Yousef Zakharia, Kevin Zarrabi, Michael Zimmerman, George Sledge, David Spetzler, Andrew Elliott, Rana Mckay, Pedro Barata

Department of Medical Oncology Faculty Papers

The REnal cancer consortium for Focused Investigation of Novel biomarkers and Expression (REFINE) consortium represents an important initiative in integrating clinical data with molecular sequencing in patients with advanced renal cell carcinoma (RCC) treated with immunotherapy-based approaches. By leveraging real-world evidence and genomic analysis, this consortium aims to explore putative predictive biomarkers with the potential to inform personalized treatment strategies. Findings from the REFINE database may further contribute to our understanding of disease courses of immunotherapy-based approaches for various molecular subtypes of RCC, associations of race and ethnicity with RCC treatment and outcomes with representation of patient populations underrepresented in …

Molecular Insights Into The Role Of Estrogen Receptor Beta In Ecdysterone Mediated Anabolic Activity, Syeda Sumayya Tariq, Madiha Sardar, Muhammad Shafiq, Hendrick Heinz, Mohammad Nur-E-Alam, Aftab Ahmad, Zaheer Ul-Haq

Pharmacy Faculty Articles and Research

Ecdysterone, often dubbed a “natural steroid,” has garnered significant attention among athletes for its reputed growth-promoting and anabolic properties. Unlike synthetic anabolic steroids, which are classified as controlled substances, ecdysteroids remain largely unregulated in many countries and are widely marketed as dietary supplements. Notably, ecdysterone has been included in the World Anti-Doping Agency (WADA) monitoring program, highlighting its potential impact on athletic performance and raising questions about its regulation. Emerging evidence indicates that, unlike traditional anabolic steroids that act primarily via the Androgen Receptor (AR), ecdysterone’s anabolic effects may be mediated through Estrogen Receptors (ERs), particularly Estrogen Receptor beta (ERβ). …

June 2025, Swosu Rural Health Center

RURAL ROCKS

• PBM Reform Takes Off in 2025
• Tirzepatide as Compared with Semaglutide for the Treatment of Obesity | New England Journal of Medicine
• Know the ABCs of Diabetic Skin Care
• Updated Recommendations for Pneumococcal Vaccination

Antiarrhythmic Drug Use In Atrial Fibrillation Among Different European Countries – As Determined By A Physician Survey, Espen Fengsrud, Carina Blomström-Lundqvist, A. John Camm, Andreas Goette, Peter R. Kowey, Jose L. Merino, Jonathan P. Piccini, Sanjeev Saksena, James A. Reiffel, Giuseppe Boriani

Department of Medicine Faculty Papers

BACKGROUND: There is limited knowledge of physicians' antiarrhythmic drug (AAD) treatment practices for patients with atrial fibrillation and adherence to guidelines in European countries.

METHODS: An online survey (n = 321) of cardiologists, cardiac electrophysiologists and interventional electrophysiologists was conducted in Germany (DE; n = 83), Italy (IT; n = 95), Sweden (SE; n = 60) and the United Kingdom (UK; n = 83) including 96 questions on treatment practices.

RESULTS: ESC guidelines were the most important non-patient factor influencing treatment practice (55-72 %). However, while amiodarone was frequently (88-93 %) used in heart failure with reduced left ventricular ejection …

Opioid Use Patterns After Nonsurgical Management Of Distal Radius Fractures: A Call For Opioid Stewardship, Sina Ramtin, Sara Khan, Vijay Chhabra, Wali Pirzada, Mohammad Khak, Asif M. Ilyas

Rothman Institute Papers

PURPOSE: While most opioid research focuses on postoperative use, limited data exist on prescribing patterns in nonsurgical management of common injuries such as distal radius fractures (DRFs). This study aimed to assess opioid prescribing trends and identify factors linked to prolonged use in nonsurgically treated DRFs.

METHODS: A retrospective cohort study of 591 patients aged 18-50 with nonsurgically managed DRFs between 2018 and 2024 was conducted. Opioid use was classified as prior opioid use (POU), fracture-related opioid use (FxOU), or delayed opioid use (DOU). Prescription data were obtained from the Prescription Drug Monitoring Program and analyzed for morphine milligram equivalents, …

Neovascular Pruning By Ido1 Inhibitors Can Potentiate Immunogenic Cytotoxicity Of Ischemia-Targeted Agents To Synergistically Enhance Anti-Pd-1 Responsiveness, Shih-Chun Shen, Souvik Dey, James B. Duhadaway, Erika Sutanto-Ward, Maurice T. Hampton, Serguei V. Kozlov, George C. Prendergast, Alexander J. Muller

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

BACKGROUND: Strategies for deploying indoleamine 2,3-dioxygenase 1 (IDO1)-targeted therapies for use against cancer have focused on IDO1's role in promoting peripheral immune tolerance that shields tumors from effector T cells. However, preclinical investigation of both primary and metastatic tumor development in the lungs has uncovered a previously unappreciated role for IDO1 in directing a counterregulatory response to interferon (IFN)-γ that realigns the local inflammatory environment to promote tumor neovascularization. Understanding how to therapeutically leverage the ability of IDO1 inhibitors to subvert inflammatory neovascularization within the tumor microenvironment has potential ramifications for future clinical development of these compounds.

METHODS: Pulmonary metastases …

Molecular Biomarkers Of Glioma, Punsasi Rajakaruna, Stella A. Rios, Hana Elnahas, Ashley Villanueva, David Uribe, Sophia Leslie, Walaa A. Abbas, Larissa Barroso, Stephanie Oyervides, Michael W. Persans, Wendy Innis-Whitehouse, Megan E. Keniry

School of Integrative Biological & Chemical Sciences Faculty Publications

In this review, we discuss how mutations in glioma are associated with prognosis and treatment efficacy. A fascinating characteristic of glioma and all cancers is that while common growth and developmental pathways are altered, the characteristic mutations are distinct depending on the specific type of tumor with concomitant prognoses. Next-generation sequencing, precision medicine, and artificial intelligence are boosting the employment of molecular biomarkers in cancer diagnosis and treatment. Understanding the biological underpinnings of distinct mutations on critical signaling pathways is crucial for developing novel therapies for glioma.

An Exploratory Pharmacogenetic Pilot Study Of Two Reverse Transcriptase Inhibitors, Tenofovir Alafenamide Fumarate And Tenofovir Disoproxil Fumarate, Derek E. Murrell, Benjamin C. Kennard, Maria E. Bertoni, David B. Cluck, Jonathan P. Moorman, Stacy D. Brown, Keshang Wang, Michelle M. Duffourc, Sam Harirforoosh

Pharmacy Faculty Articles and Research

Background and Objectives

The nucleoside reverse transcriptase inhibitors tenofovir alafenamide fumarate and tenofovir disoproxil fumarate are frequently employed in treating human immunodeficiency virus. Further, each form of tenofovir requires laboratory monitoring to determine efficacy and tolerability among patients. This study sought to investigate the relationship, if any, of single nucleotide polymorphisms (SNPs) and selected clinical parameters.

Methods

The study population, predominantly Caucasian males with a median age of 53.0 years [interquartile range 46.0–59.0], was assayed for genetic variations using an iPLEX ADME PGx Pro v1.0 Panel.

Results

Although several SNP relationships were found with both forms of tenofovir, many of …