Medical Specialties Commons^™

Specific Barriers To Athletic Trainers’ Familiarity With And Attitudes Toward Concussion Biomarkers: A Phenomenological Qualitative Study, Te Mccormick, Jm Allen, Kgs Swindell, Tr Campbell

Clinical Practice in Athletic Training

Context: The diagnosis of concussions is largely reliant on subjective information in conjunction with objective measures that might not be the most valid and/or reliable. There is now new research being performed evaluating the use of biological indicators, or biomarkers in the diagnosis and management of concussion. However, the amount of knowledge about biomarkers among athletic trainers is unknown. Additionally, the barriers preventing ATs from using such biomarkers has yet to be studied. Therefore, the purpose of this study is to examine athletic trainers’ familiarity with and their attitude towards concussion biomarkers, while evaluating specific barriers preventing their use in …

The Analysis Of Ground Kinematics In Tie-Down Ropers, M Watts, A Chelette, J Sandford, K Mata

Clinical Practice in Athletic Training

Context: Tie-down roping, an event in rodeo, occurs when the athlete ropes a calf while on horseback, quickly dismounts from the horse and ties three legs of the calf together. Injuries to the knee and lower body have occurred with athletes in the tie-down roping event. Previous research with college rodeo athletes has shown the knee to be the most frequently injured area of the body. The athlete’s lower body movements during the dismount from the horse may increase the risk of injury to the knee. However, these movements have not been previously studied in the tie-down roping event. The …

The Food Environment Of Female Athletes Attending Historically Black Colleges And Universities: A Qualitative Study On The Dimensions Of Food Access And Nutrition, Na Uriegas, Zk Winkelmann, Dm Emerson

Clinical Practice in Athletic Training

Context: Student-athletes are a subset of college students who face additional stressors related to the demands of their sport and academic workload. The food choices of student-athletes may be influenced by the unique food environment they are in. Further challenges may present for Historically Black Colleges and Universities (HBCUs) student-athletes as their institutions tend to be in low food access areas. We aimed to assess food security and explore the lived experiences of HBCU female student-athletes surrounding their food environment and ability to access food based on the five dimensions of food access: availability, accessibility, affordability, accommodation, and acceptability. Methods: …

Use Of An External Dynamic Arm Stabilizer In A Collegiate Baseball Player With Valgus Extension Overload: A Case Report., Jp Goza, Ap Jacobsen

Clinical Practice in Athletic Training

Background: A 21-year-old, male, collegiate baseball player reported to the athletic training staff complaining of pain along the posteromedial aspect of the right elbow. The patient reported a previous history of a grade I ulnar collateral ligament sprain that had been rehabilitated until he was able to return to full pain free activities. The patient could not recall a specific mechanism of injury. Physical examination revealed a loss of terminal elbow extension, and pain along the posteromedial aspect of the elbow. The patient reported no neurological symptoms during or after throwing. Valgus Stress, Milking, and Posterolateral Rotary Drawer tests were …

Weighted Ball Programs And Medial Elbow Injury In Youth Baseball Pitchers, M Sobolewski, K Pritchard

Clinical Practice in Athletic Training

Introduction: Weighted ball programs have been proven to increase pitching velocity, however a combination of poor musculature and body mechanics with increased elbow valgus can heighten the incidence of medial elbow overuse injuries in the youth population. Clinical Question: Can youth baseball pitchers who use weighted ball programs increase their pitching velocity without causing an increased risk of medial elbow injury? Methods: The literature was explored to discover studies that investigated medial elbow injuries using weighted ball programs in youth baseball pitchers. Articles included weighted ball programs as an intervention, kinetics/injury mechanics, youth elbow injuries, and prevention of overuse injuries. …

A Systematic Review Of The Timing Of Therapeutic Anticoagulation In Adult Patients With Acute Traumatic Brain Injury: Narrative Synthesis Of Observational Studies, Sophie Samuel, Jennifer Cortes, Eugene Uh, Huimahn Alex Choi

Library Staff Publications

Traumatic brain injury (TBI) presents complex management scenarios, particularly in patients requiring anticoagulation for concurrent conditions such as venous thromboembolism (VTE) or atrial fibrillation (AF). A systematic search of PubMed/MEDLINE, Embase, and the Cochrane Library databases was conducted to identify relevant studies. Inclusion criteria encompassed studies assessing the effects of anticoagulation therapy on outcomes such as re-hemorrhage, hematoma expansion, thrombotic events, and hemorrhagic events in TBI patients with subdural hematomas (SDH). This systematic review critically addresses two key questions: the optimal timing for initiating anticoagulation therapy and the differential impact of this timing based on the type of intracranial bleed, …

Association Between Unmet Needs And Happiness In Women Living With Breast Cancer In A Multiethnic, Middle-Income Setting, Nithiya Sinarajoo

Student Works (2020-2029)

While improved breast cancer survival rates are commendable, healthcare professionals and stakeholders must acknowledge potential strains on the healthcare system and society if optimal support and survivorship programs are not established. A global shift towards personalized, holistic patient care is crucial. However, implementing such care in a low- and middle-income country like Malaysia faces significant barriers. Positive psychology, which focuses on fostering positive emotions, has shown promise in promoting better health and longevity in healthy populations. However, research on the concept of happiness, both as a predictor of health outcomes and as a patient-reported outcome in cancer settings, remains limited. …

Small Gtp-Binding Protein Gdp Dissociation Stimulator Influences Cisplatin-Induced Acute Kidney Injury Via Perk-Dependent Er Stress, Yuxue Yang, Ting Xiong, Ti Wang, Xiwei Chen, Ziwei Ma, Bangyun Zuo, Dong Ning, Ruilong Song, Xuesong Liu, Daxin Wang

Children’s Nutrition Research Center Staff Publications

Cisplatin is a common anticancer drug, but its frequent nephrotoxicity limits its clinical use. Small GTP-binding protein GDP dissociation stimulator (smgGDS), a small GTPase chaperone protein, was considerably downregulated during cisplatin-induced acute kidney injury (CDDP-AKI), especially in renal tubular epithelial cells. SmgGDS-knockdown mice was established and found that smgGDS knockdown promoted CDDP-AKI, as demonstrated by an increase in serum creatine, blood urea nitrogen levels and the appearance of tubular patterns. RNA sequencing suggested that protein kinase RNA-like ER kinase (PERK), which bridges mitochondria-associated ER membranes, was involved in smgGDS knockdown following CDDP-AKI, and then identified that smgGDS knockdown increased phosphorylated-PERK …

An International Consensus Panel On The Potential Value Of Digital Surgery, Jamie Erskine, Payam Abrishami, Jean Christophe Bernhard, Richard Charter, Richard Culbertson, Jo Carol Hiatt, Ataru Igarashi, Gretchen Purcell Jackson, Matthew Lien, Guy Maddern, Joseph Soon Yau Ng, Anita Patel, Koon Ho Rha, Prasanna Sooriakumaran, Scott Tackett, Giuseppe Turchetti, Anastasia Chalkidou

School of Public Health Faculty Publications

OBJECTIVES: The use of digital technology in surgery is increasing rapidly, with a wide array of new applications from presurgical planning to postsurgical performance assessment. Understanding the clinical and economic value of these technologies is vital for making appropriate health policy and purchasing decisions. We explore the potential value of digital technologies in surgery and produce expert consensus on how to assess this value. DESIGN: A modified Delphi and consensus conference approach was adopted. Delphi rounds were used to generate priority topics and consensus statements for discussion. SETTING AND PARTICIPANTS: An international panel of 14 experts was assembled, representing relevant …

90y Sir-Spheres Activity Measurement With New Siros D-Vial Delivery Kit, Benjamin P Lopez, S Cheenu Kappadath

Faculty, Staff and Student Publications

A new 90Y SIR-Spheres delivery kit (SIROS D-vial and shield) has been introduced with a different physical form from the legacy V-Vial kit. Here, we establish the dose calibrator settings and exposure-rate-to-activity conversion factor to assay 90Y SIR-Spheres activity in the new SIROS kit.

Methods: Eight D-vials with initial 90Y activities from 1.2 to 6.6 GBq within acrylic shields were assayed with dose calibrators and exposure-rate meters until activities decayed to approximately 0.1 GBq. The dose calibrator settings resulting in the lowest median activity errors and the best-fit slope of exposure rate versus activity were identified.

Results: SIROS D-vial 90Y …

The Scaffolding Function Of Lsd1 Controls Dna Methylation In Mouse Escs, Sandhya Malla, Kanchan Kumari, Carlos A García-Prieto, Jonatan Caroli, Anna Nordin, Trinh T T Phan, Devi Prasad Bhattarai, Carlos Martinez-Gamero, Eshagh Dorafshan, Stephanie Stransky, Damiana Álvarez-Errico, Paulina Avovome Saiki, Weiyi Lai, Cong Lyu, Ludvig Lizana, Jonathan D Gilthorpe, Hailin Wang, Simone Sidoli, Andre Mateus, Dung-Fang Lee, Claudio Cantù, Manel Esteller, Andrea Mattevi, Angel-Carlos Roman, Francesca Aguilo

Faculty, Staff and Student Publications

Lysine-specific histone demethylase 1 (LSD1), which demethylates mono- or di- methylated histone H3 on lysine 4 (H3K4me1/2), is essential for early embryogenesis and development. Here we show that LSD1 is dispensable for mouse embryonic stem cell (ESC) self-renewal but is required for mouse ESC growth and differentiation. Reintroduction of a catalytically-impaired LSD1 (LSD1MUT) recovers the proliferation capability of mouse ESCs, yet the enzymatic activity of LSD1 is essential to ensure proper differentiation. Indeed, increased H3K4me1 in Lsd1 knockout (KO) mouse ESCs does not lead to major changes in global gene expression programs related to stemness. However, ablation of LSD1 but …

Targeting Igf2 To Reprogram The Tumor Microenvironment For Enhanced Viro-Immunotherapy, Min Hye Noh, Jin Muk Kang, Alexandra A Miller, Grace Nguyen, Minxin Huang, Ji Seon Shim, Alberto J Bueso-Perez, Sara A Murphy, Kimberly A Rivera-Caraballo, Yoshihiro Otani, Eunju Kim, Seung-Hee Yoo, Yuanqing Yan, Yeshavanth Banasavadi-Siddegowda, Hiroshi Nakashima, E Antonio Chiocca, Balveen Kaur, Zhongming Zhao, Tae Jin Lee, Ji Young Yoo

Faculty, Staff and Student Publications

BACKGROUND: The FDA approval of oncolytic herpes simplex-1 virus (oHSV) therapy underscores its therapeutic promise and safety as a cancer immunotherapy. Despite this promise, the current efficacy of oHSV is significantly limited to a small subset of patients largely due to the resistance in tumor and tumor microenvironment (TME).

METHODS: RNA sequencing (RNA-Seq) was used to identify molecular targets of oHSV resistance. Intracranial human and murine glioma or breast cancer brain metastasis (BCBM) tumor-bearing mouse models were employed to elucidate the mechanism underlying oHSV therapy-induced resistance.

RESULTS: Transcriptome analysis identified IGF2 as one of the top-secreted proteins following oHSV treatment. …

Transcatheter Closure Of Complex Multifenestrated Atrial Septal Defect Using Three Septal Occluders: Is Three Too Many?, Hussam Al Hennawi, Appa Bandi, Ahmad Abulshamat, Shaurya Srivastava, Mohammed Qintar

Abington Jefferson Health Papers

Atrial septal defects (ASDs) are a common form of adult congenital heart disease, with surgical or transcatheter closure being the mainstay of treatment in patients with hemodynamic or clinical complications. Transcatheter repair of secundum ASD is safe and effective. Complex secundum ASDs with multifenestrated defects pose a unique challenge to transcatheter repair. We report a successful but complex transcatheter closure of an ASD using three overlapping Amplazter devices.

Clinical Practice Guideline-Inconsistent Chemotherapy-Induced Vomiting Prophylaxis In Pediatric Cancer Patients In Community Settings: A Children's Oncology Group Study, Aaron J. Sugalski, Allison C. Grimes, Michelle M. Nuño, Subhash Ramakrishnan, Melissa P. Beauchemin, Paula D. Robinson, Nancy Santesso, Alexandra M. Walsh, Andrea R. Wrightson, Lolie C. Yu, Susan K. Parsons, Lillian Sung, L. Lee Dupuis

School of Medicine Faculty Publications

Background: This study aimed to determine the proportion of patients receiving clinical practice guideline (CPG)-inconsistent care related to chemotherapy-induced vomiting (CIV) prophylaxis, and to describe the association between CPG-inconsistent care and site size. The association between delivery of CPG-inconsistent care and patient outcomes (CIV control, admission prolongation, and unplanned healthcare visits) was also described. Methods: This was a retrospective study conducted at Children's Oncology Group (COG) National Cancer Institute Community Oncology Research Program (NCORP) sites. Eligible patients received highly (HEC) or moderately emetogenic chemotherapy (MEC) as inpatients from January 2014 through December 2015, and were previously enrolled in a COG …

Tulips Decorate The Three-Dimensional Genome Of Pfa Ependymoma, Michael J Johnston, John J Y Lee, Bo Hu, Ana Nikolic, Elham Hasheminasabgorji, Audrey Baguette, Seungil Paik, Haifen Chen, Sachin Kumar, Carol C L Chen, Selin Jessa, Polina Balin, Vernon Fong, Melissa Zwaig, Kulandaimanuvel Antony Michealraj, Xun Chen, Yanlin Zhang, Srinidhi Varadharajan, Pierre Billon, Nikoleta Juretic, Craig Daniels, Amulya Nageswara Rao, Caterina Giannini, Eric M Thompson, Miklos Garami, Peter Hauser, Timea Pocza, Young Shin Ra, Byung-Kyu Cho, Seung-Ki Kim, Kyu-Chang Wang, Ji Yeoun Lee, Wieslawa Grajkowska, Marta Perek-Polnik, Sameer Agnihotri, Stephen Mack, Benjamin Ellezam, Alex Weil, Jeremy Rich, Guillaume Bourque, Jennifer A Chan, V Wee Yong, Mathieu Lupien, Jiannis Ragoussis, Claudia Kleinman, Jacek Majewski, Mathieu Blanchette, Nada Jabado, Michael D Taylor, Marco Gallo

Faculty, Staff and Students Publications

Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in …

Cyp3a-Mediated Carbon-Carbon Bond Cleavages In Drug Metabolism, Junhui Zhou, Xuan Qin, Shenzhi Zhou, Kevin R Mackenzie, Feng Li

Faculty, Staff and Students Publications

Cytochrome P450 enzymes (P450s) play a critical role in drug metabolism, with the CYP3A subfamily being responsible for the biotransformation of over 50% of marked drugs. While CYP3A enzymes are known for their extensive catalytic versatility, one intriguing and less understood function is the ability to mediate carbon-carbon (C-C) bond cleavage. These uncommon reactions can lead to unusual metabolites and potentially influence drug safety and efficacy. This review focuses on examining examples of C-C bond cleavage catalyzed by CYP3A, exploring the mechanisms, physiological significance, and implications for drug metabolism. Additionally, examples of CYP3A-mediated ring expansion via C-C bond cleavages are …

Rna Interacts With Topoisomerase I To Adjust Dna Topology, Mannan Bhola, Kouki Abe, Paola Orozco, Homa Rahnamoun, Pedro Avila-Lopez, Elijah Taylor, Nefertiti Muhammad, Bei Liu, Prachi Patel, John F Marko, Anne C Starner, Chuan He, Eric L Van Nostrand, Alfonso Mondragón, Shannon M Lauberth

Faculty, Staff and Students Publications

Topoisomerase I (TOP1) is an essential enzyme that relaxes DNA to prevent and dissipate torsional stress during transcription. However, the mechanisms underlying the regulation of TOP1 activity remain elusive. Using enhanced cross-linking and immunoprecipitation (eCLIP) and ultraviolet-cross-linked RNA immunoprecipitation followed by total RNA sequencing (UV-RIP-seq) in human colon cancer cells along with RNA electrophoretic mobility shift assays (EMSAs), biolayer interferometry (BLI), and in vitro RNA-binding assays, we identify TOP1 as an RNA-binding protein (RBP). We show that TOP1 directly binds RNA in vitro and in cells and that most RNAs bound by TOP1 are mRNAs. Using a TOP1 RNA-binding mutant …

Neoadjuvant Parpi Or Chemotherapy In Ovarian Cancer Informs Targeting Effector Treg Cells For Homologous-Recombination-Deficient Tumors, Yikai Luo, Yu Xia, Dan Liu, Xiong Li, Huayi Li, Jiahao Liu, Dongchen Zhou, Yu Dong, Xin Li, Yiyu Qian, Cheng Xu, Kangjia Tao, Guannan Li, Wen Pan, Qing Zhong, Xingzhe Liu, Sen Xu, Zhi Wang, Ronghua Liu, Wei Zhang, Wanying Shan, Tian Fang, Siyuan Wang, Zikun Peng, Ping Jin, Ning Jin, Shennan Shi, Yuxin Chen, Mengjie Wang, Xiaofei Jiao, Mengshi Luo, Wenjian Gong, Ya Wang, Yue Yao, Yi Zhao, Xinlin Huang, Xuwo Ji, Zhaoren He, Guangnian Zhao, Rong Liu, Mingfu Wu, Gang Chen, Li Hong, Cocpo Consortium, Ding Ma, Yong Fang, Han Liang, Qinglei Gao

Faculty, Staff and Student Publications

Homologous recombination deficiency (HRD) is prevalent in cancer, sensitizing tumor cells to poly (ADP-ribose) polymerase (PARP) inhibition. However, the impact of HRD and related therapies on the tumor microenvironment (TME) remains elusive. Our study generates single-cell gene expression and T cell receptor profiles, along with validatory multimodal datasets from >100 high-grade serous ovarian cancer (HGSOC) samples, primarily from a phase II clinical trial (NCT04507841). Neoadjuvant monotherapy with the PARP inhibitor (PARPi) niraparib achieves impressive 62.5% and 73.6% response rates per RECIST v.1.1 and GCIG CA125, respectively. We identify effector regulatory T cells (eTregs) as key responders to HRD …

Developing A Stand-Alone Children’S Hospital In Southern Nevada: Improving Pediatric Care And Diversifying The Regional Economy, The Lincy Institute

Lincy Institute Events

Southern Nevada is the largest metropolitan region in the country without a stand-alone children's hospital. The absence of such a facility results in poor health outcomes for children, fragmented and inadequate specialized care, and a shortage of pediatric medical professionals. Currently ranked last in clinical care nationwide, Nevada urgently needs a centralized, academic-based children's hospital to improve health services.

The Lincy Institute hosted a community forum to release the findings of a new report conducted by Tripp Umbach detailing why Southern Nevada needs a stand-alone children’s hospital. Tripp Umbach is a recognized industry leader, with 30 years of successful partnerships …

Developing A Stand-Alone Children’S Hospital In Southern Nevada: Needs, Opportunities, And Economic Development Considerations, Tripp Umbach

Policy Briefs and Reports

This independent study developed by Tripp Umbach demonstrates how an independent, research-intensive, stand-alone children’s teaching hospital can significantly enhance the health status of Southern Nevada’s children, reduce outmigration, attract children from neighboring states, and stimulate the healthcare economy. Tripp Umbach evaluated the need for a children’s hospital, the barriers to overcoming its absence, and the advantages of establishing a stand-alone children’s hospital in Southern Nevada for diverse audiences throughout Nevada and nationally.

Chylopericardium And Superior Vena Cava Syndrome Caused By Central Venous Occlusion From Indwelling Hemodialysis Catheters, Daniel Underberg, Nicholas Demario, Sebastian Rodriguez, Khulkar Mirzozoda, Mark Decaro, Gregary Marhefka

Division of Cardiology Faculty Papers

Chylopericardium is a rare condition. Causes include superior vena cava syndrome resulting from indwelling catheters. We present a case of this condition in a 42-year-old man with end-stage renal disease treated with hemodialysis through a right subclavian vein catheter. He underwent successful endovascular stenting with resolution of his symptoms and chylopericardium.

A 6-Month, Prospective, Randomized Controlled Trial Of Customized Adherence Enhancement Versus A Bipolar-Specific Educational Control In Poorly Adherent Adolescents And Young Adults Living With Bipolar Disorder, Jennifer B. Levin, Molly Mcvoy, Joy Yala, Jessica Black, Carla Conroy, Martha Sajatovic

Faculty Scholarship

Objective: Few studies have addressed medication adherence in adolescents and young adults (AYAs) with bipolar disorder (BD). This 6-month prospective randomized-controlled trial (RCT) tested customized adherence enhancement for adolescents and young adults (CAE-AYA), a behavioral intervention for AYAs versus enhanced treatment as usual (ETAU). Methods: Inclusion criteria were AYAs age 13–21 with BD type I or II with suboptimal adherence defined as missing ≥20% of medications. Assessments were conducted at Screening, Baseline, and weeks 8, 12 and 24. Primary outcome was past 7 day self-reported Tablets Routine Questionnaire (TRQ) validated by electronic pillbox monitoring (SimpleMed). Symptom measures included the Hamilton …

Transorbital Alternating Current Stimulation In A Double-Masked Randomized Clinical Trial: Visual Functional Effect And Quality Of Life, Maria De Los Angeles Ramos Cadena, Ashley Sohn, Heather Livengood, Ting-Fang Lee, Batsheva Rubin, Jiyuan Hu, Bernhard A. Sabel, Rachel Matayev, Joseph Panarelli, Gadi Wollstein, Joel S. Schuman

Wills Eye Hospital Papers

PURPOSE: To determine the efficacy and safety of repetitive transorbital alternating current stimulation (rtACS) treatment by assessing vision-related quality of life and visual function outcome in subjects treated with rtACS versus sham-control.

STUDY DESIGN: Double masked, randomized, sham-controlled clinical trial (NCT03188042).

SUBJECTS: Sixteen subjects with moderate-to-advanced glaucoma (visual field [VF] mean deviation [MD] ≤-6.00 decibels) randomized into sham (9 subjects) or rtACS intervention (7 subjects) groups.

METHODS: Subjects underwent 10 rtACS sessions over 2 weeks. All subjects had comprehensive ocular examination at baseline, 1-week, and 4-weeks posttreatment.

MAIN OUTCOME MEASURES: Visual acuity (VA), contrast sensitivity (CS), VF MD, number of …

Single-Cell And Spatial Proteo-Transcriptomic Profiling Reveals Immune Infiltration Heterogeneity Associated With Neuroendocrine Features In Small Cell Lung Cancer, Ying Jin, Yuefeng Wu, Alexandre Reuben, Liang Zhu, Carl M Gay, Qingzhe Wu, Xintong Zhou, Haomin Mo, Qi Zheng, Junyu Ren, Zhaoyuan Fang, Teng Peng, Nan Wang, Liang Ma, Yun Fan, Hai Song, Jianjun Zhang, Ming Chen

Faculty, Staff and Student Publications

Small cell lung cancer (SCLC) is an aggressive pulmonary neuroendocrine malignancy featured by cold tumor immune microenvironment (TIME), limited benefit from immunotherapy, and poor survival. The spatial heterogeneity of TIME significantly associated with anti-tumor immunity has not been systemically studied in SCLC. We performed ultra-high-plex Digital Spatial Profiling on 132 tissue microarray cores from 44 treatment-naive limited-stage SCLC tumors. Incorporating single-cell RNA-sequencing data from a local cohort and published SCLC data, we established a spatial proteo-transcriptomic landscape covering over 18,000 genes and 60 key immuno-oncology proteins that participate in signaling pathways affecting tumorigenesis, immune regulation, and cancer metabolism across 3 …

Screening Of Anti-Prion Compounds Using The Protein Misfolding Cyclic Amplification Technology, Sandra Pritzkow, Isaac Schauer, Ananya Tupaki-Sreepurna, Rodrigo Morales, Claudio Soto

Faculty, Staff and Student Publications

Prion diseases are 100% fatal infectious neurodegenerative diseases affecting the brains of humans and other mammals. The disease is caused by the formation and replication of prions, composed exclusively of the misfolded prion protein (PrPSc). We invented and developed the protein misfolding cyclic amplification (PMCA) technology for in vitro prion replication, which allow us to replicate the infectious agent and it is commonly used for ultra-sensitive prion detection in biological fluids, tissues and environmental samples. In this article, we studied whether PMCA can be used to screen for chemical compounds that block prion replication. A small set of compounds previously …

A Clinician’S Perspective On The New Organ Mesentery And Non-Vascular Mesenteropathies, Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Mesentery was discovered as a new organ in 2017. It is a continuous membranous tissue from the duodenojejunal flexure to the anorectal junction. It has distinct anatomy, physiology, and disease states. Primary mesenteropathies include vascular and non-vascular diseases. Some of them are common, and some of them are rarely seen in clinical practice. Secondary mesenteropathies occur when infection or malignancy in another organ spreads to the mesentery. Each entity has specific diagnostic and treatment protocols. Increased awareness of different mesenteropathies and an understanding of their various presentations at different stages of life can help in early diagnosis and improved clinical …

Tranq Dope: Characterization Of An Ed Cohort Treated With A Novel Opioid Withdrawal Protocol In The Era Of Fentanyl/Xylazine, Kory London, Yutong Li, Jennifer Kahoud, Davis Cho, Jamus Mulholland, Sebastian Roque, Logan Stugart, Jeffrey Gillingham, Elias Borne, Benjamin Slovis

Department of Emergency Medicine Faculty Papers

BACKGROUND: Treating opioid use disorder has reached a new level of challenge. Synthetic opioids and xylazine have joined the non-medical opioid supply, multiplying the complexities of caring for individuals in emergency departments (ED). This combination, known as 'tranq dope,' is poorly described in literature. Inadequate withdrawal treatment results in a disproportionately high rate of patient-directed discharges (also known as against medical advice dispositions, or AMA). This study aimed to describe a cohort of individuals who received a novel order set for suspected fentanyl and xylazine withdrawal in the ED.

METHODS: This is a descriptive study evaluating a cohort of ED …

Intracellular Islatravir-Triphosphate Half-Life Supports Extended Dosing Intervals, Xiaowei Zang, Wendy Ankrom, Walter K. Kraft, Ryan Vargo, S Aubrey Stoch, Marian Iwamoto, Randolph P Matthews

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Antiretroviral therapy has substantially reduced morbidity, mortality, and disease transmission in people living with HIV. Islatravir is a nucleoside reverse transcriptase translocation inhibitor that inhibits HIV-1 replication by multiple mechanisms of action, and it is in development for the treatment of HIV-1 infection. In preclinical and clinical studies, islatravir had a long half-life (t½) of 3.0 and 8.7 days (72 and 209 hours, respectively); therefore, islatravir is being investigated as a long-acting oral antiretroviral agent. A study was conducted to definitively elucidate the terminal t½ of islatravir and its active form islatravir-triphosphate (islatravir-TP). A single-site, open-label, non-randomized, single-dose phase 1 …

G Protein Selectivity Profile Of Gpr56/Adgrg1 And Its Effect On Downstream Effectors, Raida Jallouli, Ana L Moreno-Salinas, Andréanne Laniel, Brian Holleran, Charlotte Avet, Joan Jacob, Trang Hoang, Christine Lavoie, Kendra S Carmon, Michel Bouvier, Richard Leduc

Faculty, Staff and Student Publications

GPR56, an adhesion G-protein coupled receptor (aGPCRs) with constitutive and ligand-promoted activity, is involved in many physiological and pathological processes. Whether the receptor's constitutive or ligand-promoted activation occur through the same molecular mechanism, and whether different activation modes lead to functional selectivity between G proteins is unknown. Here we show that GPR56 constitutively activates both G12 and G13. Unlike constitutive activation and activation with 3-α-acetoxydihydrodeoxygedunin (3αDOG), stimulation with an antibody, 10C7, directed against GPR56's extracellular domain (ECD) led to an activation that favors G13 over G12. An autoproteolytically deficient mutant, GPR56-T383A, was also activated by 10C7 indicating that the tethered …

Crizotinib Enhances Parp Inhibitor Efficacy In Ovarian Cancer Cells And Xenograft Models By Inducing Autophagy, Janice M Santiago-O'Farrill, Alicia Blessing Bollu, Hailing Yang, Vivian Orellana, Marc Pina, Xudong Zhang, Jinsong Liu, Robert C Bast, Zhen Lu

Faculty, Staff and Student Publications

Poly (ADP-ribose) polymerase inhibitors (PARPi) can encounter resistance through various mechanisms, limiting their effectiveness. Our recent research showed that PARPi alone can induce drug resistance by promoting autophagy. Moreover, our studies have revealed that anaplastic lymphoma kinase (ALK) plays a role in regulating the survival of ovarian cancer cells undergoing autophagy. Here, we explored whether the ALK-inhibitor crizotinib could enhance the efficacy of PARPi by targeting drug-induced autophagic ovarian cancer cell and xenograft models. Our investigation demonstrates that crizotinib enhances the anti-tumor activity of PARPi across multiple ovarian cancer cells. Combination therapy with crizotinib and olaparib reduced cell viability and …