Therapeutics Commons^™

Microglial Expression Of Serotonin Receptors Reveals Parallel Regulation Of 5-Ht2b And Bdnf In The Rat Hippocampus, Andrei Turkin, Maria Sidorova, Ekaterina Kurilova, Natalia Alenina, Oksana Tuchina, Friederike Klempin

School of Graduate Studies Faculty Publications

Growing evidence suggests that psychiatric disorders are characterized by a prolonged inflammatory state, which may influence the efficacy of compounds targeting serotonin. Serotonin is a key signaling molecule in neuroplasticity of the adult hippocampus and involved in antidepressant action. Recent in vitro studies indicate the neurotransmitter may also facilitate the response to inflammation and potentially modulate microglial function towards neuroprotection. Using Tph2−/− rats depleted of brain serotonin, we examined microglial expression of various serotonin receptors (5-HTRs) in vivo in both the hippocampus and prefrontal cortex and assessed mRNA levels of cytokines and brain-derived neurotrophic factor (BDNF). We observed age-dependent and …

Subgroup Analyses Of The Phase 3 Focus Study Of Melphalan/Hepatic Delivery System In Patients With Unresectable Metastatic Uveal Melanoma, Jonathan S. Zager, Marlana Orloff, Pier Francesco Ferrucci, Junsung Choi, David J. Eschelman, Evan S. Glazer, Aslam Ejaz, Erika Richtig, Sebastian Ochsenreither, Sunil A. Reddy, Michael C. Lowe, Georgia M. Beasley, Anja Gesierich, Martin Gschnell, Reinhard Dummer, Ana Arance, Stephen William Fenwick, Joseph J. Sacco, Johnny John, Matthew Wheater, Christian H. Ottensmeier

Department of Medical Oncology Faculty Papers

PURPOSE: To assess efficacy and safety in subgroups of patients treated with Melphalan/Hepatic Delivery System (melphalan/HDS), a drug/device combination for liver-directed treatment of metastatic UM (mUM) patients. Previously reported FOCUS study results indicated melphalan/HDS treatment provides a clinically meaningful response rate and favorable benefit-risk ratio in patients with unresectable mUM.

METHODS: Patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) every 6-8 weeks for up to 6 cycles. Post hoc analyses of efficacy and safety were conducted for patient subgroups based on demographic and baseline disease characteristics.

RESULTS: 102 patients with mUM were enrolled; treatment was attempted …

Role Of Gut Microbiome In Oncogenesis And Oncotherapies, Renuka Sri Sai Peddireddi, Sai Kiran Kuchana, Rohith Kode, Saketh Khammammettu, Aishwarya Koppanatham, Supriya Mattigiri, Harshavardhan Gobburi, Suresh K. Alahari

School of Graduate Studies Faculty Publications

The gut microbiome has emerged as a key regulator of human health, influencing not only metabolism and immunity but also the development and treatment of cancer. Mounting evidence suggests that microbial dysbiosis contributes to oncogenesis by driving chronic inflammation, producing genotoxic metabolites, altering bile acid metabolism, and disrupting epithelial barrier integrity. At the same time, the gut microbiome significantly modulates the host response to oncotherapies including chemotherapy, radiotherapy, and especially immunotherapy, where microbial diversity and specific taxa determine treatment efficacy and toxicity. This review synthesizes current evidence on the role of the gut microbiome in both oncogenesis and oncotherapies, focusing …

Development And Characterization Of Non-Viral Delivery Systems For Pulmonary Delivery Of Nucleic Acid Therapeutics, Kasturi Siddhanta

Theses & Dissertations

The development of non-viral delivery systems for pulmonary delivery of nucleic acid therapeutics is driven by the need for safer and more accessible approaches to treat lung diseases, while avoiding the systemic side effects and immune responses associated with viral vectors. Such systems encompass both non-invasive inhalation-based platforms, and systemically administered platforms designed to achieve localized lung delivery. These strategies aim to enable high drug concentrations at the site of action, rapid onset of therapeutic effect, and greater therapeutic efficacy than existing treatments. Designing effective pulmonary delivery systems requires precise optimization of particle properties—including size, morphology, surface characteristics, cell-specific targeting, …

P-15 Peptide Enhanced Bone Graft Improves Time To Fusion In Transforaminal Lumbar Interbody Fusion: A Randomized, Controlled, Investigational Device Exemption Study, James S. Harrop, Michael P. Steinmetz, John E. O'Toole, Christopher D Chaput, Rick C. Sasso, K. Brandon Strenge, Greg Maislin, Jeffrey P. Mullin, Thomas B. Freeman, Anthony Guanciale, Howard Lantner, Michael E. Janssen, David G. Schwartz, John M. Small, Wellington K. Hsu, Paul M. Arnold

Department of Neurosurgery Faculty Papers

STUDY DESIGN: Prospective, multicenter, single-blind, randomized, and controlled pivotal study.

OBJECTIVE: Compare time-to-fusion in patients treated with P-15L (PearlMatrix TM P-15 peptide enhanced bone graft) versus local autograft over 24 months and evaluate changes in pain and quality of life at 24 months relative to baseline.

SUMMARY OF BACKGROUND DATA: P-15L, an FDA-designated breakthrough device, is a composite bone graft with P-15, a 15-amino acid polypeptide that promotes cellular adhesion, proliferation, and differentiation to support bone formation.

METHODS: Patients (22-80 y) with degenerative disc disease were randomized to the investigational (P-15L) or control (local autograft) group during single-level transforaminal lumbar …

Ratio Quantification Of Geranium And Rose Essential Oil Mixtures Via Leep Learning Analysis Of Complex Raman Spectra, Jia Wei Tang, Yong Xuan Hong, Jie Chen, Yun Yun Xie, Zhang Wen Ma, Qing Hua Liu, Liang Wang

Research outputs 2022 to 2026

Due to their high economic value, essential oils (EOs) are increasingly subject to adulteration, posing significant challenges for quality assessment and control. Owing to its excellent molecular specificity, Raman spectroscopy has been widely employed for the analysis and evaluation of EO products. In this study, we collected a total of 2700 Raman spectra comprising rose essential oil (REO, n = 900), geranium essential oil (GEO, n = 900), and their mixtures (n = 900). We first constructed a conventional convolutional neural network to distinguish spectra corresponding to varying EO mixing ratios. Interpretability analysis revealed that spectral peaks at 800, 1000, …

Vasoactive Drug Use In Children With Community Acquired Septic Shock In Australia And New Zealand, Elliot Long, Stephen Hearps, Amanda Williams, Ben Gelbart, Warwick Butt, Thomas Rozen, Sarah Mcnab, Meredith Borland, Simon Erickson, Shefali Jani, Marino Festa, Eunicia Tan, Natalie Phillips, Sainath Raman, Amit Kochar, Subodh Ganu, Simon Craig, Anna Lithgow, Arjun Rao, Emma Whyte, Stuart Dalziel, Shane George, Fran Balamuth, Scott Weiss, Nathan Kuppermann, Franz Babl

Department of Medicine Faculty Papers

BACKGROUND: Vasoactive agents are a critical supportive therapy for children with sepsis. We describe the choice and use patterns of vasoactive agents in children with sepsis.

METHODS: Prospective observational study conducted in 11 hospitals in Australia and New Zealand through the Paediatric Research in Emergency Departments International Collaborative (PREDICT) Network from April 2021 to December 2023. Children aged 0-< 18 years with suspected sepsis were included. Children admitted to hospital and treated with parenteral antibiotics and either 1) a provisional diagnosis of sepsis, and/or 2) treatment for suspected sepsis (fluid bolus to treat poor perfusion). The frequency and sequence of use of vasoactive agents, and contributors to the choice of initial vasoactive were collected.

FINDINGS: 6232 children with suspected sepsis were included; median age of 2.1 years (IQR 0.3-7.1 years), in-hospital mortality of 60 (1.0%), in whom a subset of 306 (4.9%) met Phoenix sepsis criteria. Vasoactive agents were used in 179 (2.9%) children overall …

Pediatric Anesthesia And Virtual Reality: Managing Perioperative Pain And Anxiety– A Scoping Review, Moneer Sharafi, Mason Pham, Alec Wiscombe

Doctoral Projects

Pediatric surgery is common, but it often causes considerable anxiety and pain. A staggering percentage of children experience preoperative anxiety, which can heighten pain, delay recovery, and contribute to complications such as emergence delirium and longer-term behavioral issues (Fortier & Kain, 2015). Virtual reality (VR), which immerses users in computer-generated environments, has been proposed as a distraction technique to reduce these challenges. This Doctor of Nursing Practice (DNP) project conducted a scoping review to examine the effectiveness of VR in reducing perioperative pain and anxiety in pediatric patients. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses …

Lycopene, Race And Periodontitis: Disparities In Older Adults, Katherine Kwong, You Lu, Zhuo Huan Li, Susu Luo, Zhaoyu Huang, Zhong Chen, Na Zhao, Tung Sung Tseng

School of Public Health Faculty Publications

Background Periodontitis is a severe gum disease that can be an indicator of other health conditions such as cardiovascular disease and diabetes. Lycopene has been suggested as an adjunct therapy for periodontitis. This study aims to investigate the association between insufficient lycopene intake and the risk of Periodontitis among non-Hispanic White (NHW) and non-Hispanic Black (NHB) older adults. Methods The study included 1,227 adults aged 65–79 years from the National Health and Nutritional Examination Survey (2009–2014). Total lycopene intake from daily diet was studied with age, race, marital status, smoking status, BMI, diabetes, sex, and education as independent variables in …

Treating Atopic Dermatitis: Oral Jak1 Inhibitor Vs. Monoclonal Antibody, Abby Craft, Nicolle Holgate

Physician Assistant Capstones, 2020-current

Objective: To compare symptom management of atopic dermatitis between injectable monoclonal antibodies and an oral Janus kinase 1 (JAK1) inhibitor. Design: Literature review. Methods: Searches were done in PubMed and CINAHL using the following terms: abrocitinib, Cibinqo, dupilumab, Dupixent, and atopic dermatitis. Filters included: randomized controlled trials, clinical trials, and scholarly journal. Results: Three studies met all criteria including Bieber et al, Reich et al, and Huang et al. Conclusion: Oral JAK1 inhibitor abrocitinib has been shown to have similar efficacy in symptom management of moderate-to-severe atopic dermatitis compared to monoclonal antibody dupilumab and should be considered when prescribing treatment.

Dose Adjustment Of The Anti-Seizure Medications Levetiracetam And Lamotrigine During The Postpartum Period. Schedule Plan, Safety And Efficacy, Nadejda Khmelev, Firas Fahoum, Lilach Goldstein

Department of Neurology Faculty Papers

INTRODUCTION: Lamotrigine (LTG) and Levetiracetam (LEV) are anti-seizure medications (ASMs) widely used for treatment of women with epilepsy (WWE) of childbearing age due to low teratogenic potential. Physiological changes during gestation results in enhanced clearance. Drug level monitoring and frequent dose adjustments are required to avoid decline in serum levels and compromised seizure control. Postpartum, physiological changes reverse and ASM clearance trends back to pre-pregnancy rate. Rapid metabolic changes make drug level monitoring and dose adjustments challenging. A delay in dose decrement could result in toxicity. The optimal postpartum dose reduction rate hasn't been established.

METHODS: We retrospectively examined medical …

Application Of Augmented Reality Technology As A Dietary Monitoring And Control Measure Among Adults: A Systematic Review, Gabrielle Victoria Gonzalez, Bingjing Mao, Ruxin Wang, Wen Liu, Chen Wang, Tung Sung Tseng

School of Public Health Faculty Publications

Background/Objectives: Traditional dietary monitoring methods such as 24 h recalls rely on self-report, leading to recall bias and underreporting. Similarly, dietary control approaches, including portion control and calorie restriction, depend on user accuracy and consistency. Augmented reality (AR) offers a promising alternative for improving dietary monitoring and control by enhancing engagement, feedback accuracy, and user learning. This systematic review aimed to examine how AR technologies are implemented to support dietary monitoring and control and to evaluate their usability and effectiveness among adults. Methods: A systematic search of PubMed, CINAHL, and Embase identified studies published between 2000 and 2025 that evaluated …

Electrochemical Sensors For In Situ Monitoring Of Reactive Species During Cold Atmospheric Plasma-Based Therapies, Jonathan Thomas, Suneel Kumar, Gagana Karkada, Julia Sutter, Kristina Pattison, Jason Rainone, Dhruv Patel, Shashank Madhavan, Fred Krebs, Francois Berthiaume, Vandana Miller, Katharina Stapelmann

Kimmel Cancer Center Faculty Papers

Cold atmospheric pressure plasma (CAP) is emerging as a clinically relevant therapy for dermatological conditions such as actinic keratosis, warts, and chronic wounds. However, these therapies lack strategies to monitor CAP delivery in situ and to ensure delivery of an effective CAP dose without unwanted toxicity. CAP acts as a therapeutic agent in these biomedical applications primarily (but not solely) through reactive oxygen and nitrogen species (RONS) generated at transiently high local concentrations. Here we demonstrate the use of bio-electrochemical sensors capable of real-time measurements of key CAP RONS: hydrogen peroxide and oxidation-reduction-potential (ORP). In in vitro scratch assays and …

Identification Of Predictive Pretreatment Biomarkers For Neoadjuvant Chemotherapy Response In Latino Invasive Breast Cancer Patients, Hedda Michelle Guevara-Nieto, Rafael Parra-Medina, Carlos A. Orozco, Sandra Diaz-Casas, Jone Garai, Jovanny Zabaleta, Liliana López-Kleine, Alba L. Combita

School of Medicine Faculty Publications

Background: Breast cancer (BC) exhibits significant heterogeneity in incidence and mortality worldwide. Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced BC; however, its efficacy varies by subtype. This study examined the gene expression profiles associated with NAC response in Colombian women with invasive BC. Methods: RNA sequencing of pre-treatment tissues from 58 patients (29 responders and 29 non-responders) identified differentially expressed genes (DEGs) for each molecular subtype, and prognostic performance was evaluated using risk scores. Results: Functional enrichment analysis highlighted the immune system pathways in non-responders. Changes in cytokine target activity and immune cell populations were analyzed to …

Conservative Vs Invasive Interventions For Temporomandibular Disorders–An Executive Summary Of The Clinical Practice Guideline, Gary D. Klasser, Charles S. Greene

School of Dentistry Faculty Publications

This guideline is based on the International Association for Dental, Oral, and Craniofacial Research (IADR) list of keypoints for the diagnosis and management of TMDs. Clinical Question: Are conservative reversible therapies more effective for TMDs as compared to invasive and irreversible interventions?

Endothelial-Derived Extracellular Vesicles During Exercise In Copd Patients, Samuel C Okpechi, Dorota Wyczechowska, Bennett Deboisblanc, Jessica L Johnson, Mohamed A Ghonim, Natalie Bauer, Hamid A Boulares, Matthew R Lammi

School of Medicine Faculty Publications

Introduction: There are no treatments directly targeting the pulmonary vasculature in chronic obstructive pulmonary disease (COPD), and further characterization of the underlying endothelial cell (EC) abnormalities could be helpful in drug development. Methods: We investigated the influence of exercise and the prostacyclin analog iloprost on extracellular vesicles derived from ECs (eEVs) in 15 moderate–severe COPD patients who were enrolled in a randomized, placebo-controlled crossover trial of iloprost. Results: Active smokers had a profile consistent with inflammatory-derived EVs, while exacerbation-prone COPD subjects had a profile consistent with apoptosis-derived eEVs. There were no significant effects of iloprost on eEV levels. However, there …

Behçet's Disease Unraveled: Insights Into Clinical Manifestations, Diagnosis, And Management, Mansour Alghamdi, Stephen Lindsey

School of Medicine Faculty Publications

Behçet's disease is a rare and recurrent multisystem inflammatory disorder, primarily distinguished by systemic vasculitis that affects veins and arteries of various sizes. Clinically, Behçet's disease is characterized by the presence of recurrent oral and genital ulcers, skin lesions, and uveitis. The prevalence of this condition is significantly elevated along the historical Silk Road, particularly in Turkey; however, epidemiological data indicate variations across different regions and ethnic groups. The diagnosis of Behçet's disease is typically established during the third decade of life, with a more severe prognosis noted when the onset occurs before the age of 25. This review aims …

Urgent Radiotherapy For Superior Vena Cava Syndrome In Metastatic Non-Small Cell Lung Cancer: A Case Report, Arpeet Patel, Nilanjan Haldar, Ida Micaily, Michael Greenberg, Evan Nardone, John A. Lippert, Christopher Fundakowski, Adam C. Mueller

Department of Radiation Oncology Faculty Papers

Superior vena cava (SVC) syndrome is a life-threatening complication of thoracic malignancies, requiring rapid management in the setting of airway compromise or hemodynamic instability. We present a 59-year-old male with metastatic non-small cell lung cancer (NSCLC) who developed superior vena cava syndrome (SVCS) due to compression from a large mediastinal mass identified as metastatic lung adenocarcinoma. His declining respiratory status progressed rapidly, necessitating intensive care. After extensive multidisciplinary collaboration, the patient was determined fit for inpatient radiation therapy and 10 fractions of 300 cGy external beam radiotherapy to the obstructing lesion was planned. However, the patient was unable to lay …

Longitudinal Pharmacokinetic And Safety Studies Of An Antibody-Erythropoietin Fusion Protein For Alzheimer's Disease, Rudy Chang, Devaraj Venkatapura Chandrashekar, G. Chuli Roules, Nataraj Jagadeesan, Emi Iwasaki, Adenike Oyegbesan, Hayk Davtyan, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

Erythropoietin (EPO) shows promise for Alzheimer's disease (AD) but has poor brain penetration, necessitating high doses that cause hematopoietic side effects. To improve brain delivery, EPO was fused to a transferrin receptor monoclonal antibody (TfRMAb), and this study evaluated the pharmacokinetics (PK), safety, and efficacy of repeated TfRMAb-EPO dosing in mice to further its preclinical development. C57BL/6J male mice (10 weeks old, n = 4–5/dose) received subcutaneous (SQ) low (1 mg/kg), mid (3 and 6 mg/kg), or high (20 mg/kg) TfRMAb-EPO doses for 4 weeks. The 1 mg/kg dose showed no adverse effects and resulted in sustained brain and plasma …

Ceftriaxone Use Evaluation At The Medical Ward, Jigme Dorji Wangchuck National Referral Hospital In Bhutan: A Retrospective Analytical Study, Kezang Tshering, Mongal Singh Gurung, Sonam Wangda, Pelden Chejor

Research outputs 2022 to 2026

Objectives Ceftriaxone is the most commonly prescribed cephalosporin antibiotic in hospital settings. The overall prescribing compliance with the national antibiotic guidelines remained unassessed at Jigme Dorji Wangchuk National Referral Hospital (JDWNRH), Bhutan. Methods A retrospective analytical study was conducted by evaluating the medical records of patients who received ceftriaxone between January and December 2020 in the Medical Ward, JDWNRH. Data were analyzed using the Statistical Package for the Social Sciences, version 26. Results A total of 201 (17.82%) patients, with a mean age of 54.83 years (SD ± 20.93), received ceftriaxone, and pneumonia (49.25%) was the most frequently documented indication. …