Medicine and Health Sciences Commons^™

Adverse Events And Complications After Primary Acl Reconstruction With Quadriceps Tendon Autograft: A Systematic Review, Garrett R Jackson, Enzo S Mameri, Trevor Tuthill, Morgan Wessels, Shaan Asif, Joan Sugrañes, Anjay K Batra, Johnathon R Mccormick, Obianuju A Obioha, Daniel J Kaplan, Derrick M Knapik, Nikhil N Verma, Jorge Chahla

2020-Current year OA Pubs

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) surgery with quadriceps tendon (QT) grafts, both with and without a patellar bone plug, have gained popularity in recent years in the primary and revision settings. Postoperative complications occur with the use of QT autografts.

PURPOSE: To systematically review the incidence of postoperative complications after primary ACLR QT autograft and compare complication rates in patients undergoing all-soft tissue QT grafts versus QT grafts with a patellar bone plug (QTPB).

STUDY DESIGN: Systematic review; Level of evidence, 4.

METHODS: A literature search using the 2020 PRISMA guidelines was performed by querying PubMed, Embase, and Scopus …

Endothelial Adam10 Utilization Defines A Molecular Pathway Of Vascular Injury In Mice With Bacterial Sepsis, Danielle N. Alfano, Mark J. Miller, Juliane Bubeck-Wardenburg

2020-Current year OA Pubs

The endothelium plays a critical role in the host response to infection and has been a focus of investigation in sepsis. While it is appreciated that intravascular thrombus formation, severe inflammation, and loss of endothelial integrity impair tissue oxygenation during sepsis, the precise molecular mechanisms that lead to endothelial injury remain poorly understood. We demonstrate here that endothelial ADAM10 was essential for the pathogenesis of Staphylococcus aureus sepsis, contributing to α-toxin-mediated (Hla-mediated) microvascular thrombus formation and lethality. As ADAM10 is essential for endothelial development and homeostasis, we examined whether other major human sepsis pathogens also rely on ADAM10-dependent pathways in …

Purification Of Modified Mammalian Actin Isoforms For In Vitro Reconstitution Assays, David J Kast, Silvia Jansen

2020-Current year OA Pubs

In vitro reconstitution assays using purified actin have greatly improved our understanding of cytoskeletal dynamics and their regulation by actin-binding proteins. However, early purification methods consisted of harsh conditions to obtain pure actin and often did not include correct maturation and obligate modification of the isolated actin monomers. Novel insights into the folding requirements and N-terminal processing of actin as well as a better understanding of the interaction of actin with monomer sequestering proteins such as DNaseI, profilin and gelsolin, led to the development of more gentle approaches to obtain pure recombinant actin isoforms with known obligate modifications. This review …

Firearm Injury Among People Experiencing Homelessness: Cross-Sectional Evidence From A National Survey Of United States Emergency Departments, Nathaniel A Dell, Michael G Vaughn, Christopher P Salas-Wright

2020-Current year OA Pubs

OBJECTIVES: Persons experiencing homelessness (PEH) are at high risk for violent victimization. This study leverages unique data from a national study in the United States of America to provide estimates of non-fatal firearm injury among PEH and to describe the contexts related to injury, such as substance use, intent of the injury, and precipitating interpersonal factors.

STUDY DESIGN: Cross-sectional.

METHODS: Data from the 1993-2020 National Electronic Injury Surveillance System-Firearm Injury Surveillance Study (NEISS-FISS) were used to describe the context and characteristics of non-fatal firearm injury among PEH aged 16 years or older. Homeless status and substance use data were extracted …

The Heart Of Rett Syndrome: A Quantitative Analysis Of Cardiac Repolarization, Michael P Collins, Mark C Johnson, Robin C Ryther, Judith L Weisenberg, Peter T Heydemann, Colleen M Buhrfiend, William A Scott, Dallas M M Armstrong, Haley M Kern, Hoang H Nguyen

2020-Current year OA Pubs

BACKGROUND: Rett syndrome (RTT) is a developmental encephalopathy disorder that is associated with a high incidence of sudden death presumably from cardiorespiratory etiologies. Electrocardiogram (ECG) abnormalities, such as prolonged heart-rate corrected QT (QTc) interval, are markers of cardiac repolarization and are associated with potentially lethal ventricular arrhythmias. This study investigates the cardiac repolarization characteristics of RTT patients, including QTc and T-wave morphology characteristics.

METHODS: A retrospective quantitative analysis on 110 RTT patients and 124 age and sex-matched healthy controls was conducted.

RESULTS: RTT patients had longer QTc, more abnormal T-wave morphology, and greater heterogeneity of cardiac repolarization parameters compared to …

Denoising Task-Related Fmri: Balancing Noise Reduction Against Signal Loss, M E Hoeppli, M A Garenfeld, C K Mortensen, H Nahman-Averbuch, C D King, R C Coghill

2020-Current year OA Pubs

Preprocessing fMRI data requires striking a fine balance between conserving signals of interest and removing noise. Typical steps of preprocessing include motion correction, slice timing correction, spatial smoothing, and high-pass filtering. However, these standard steps do not remove many sources of noise. Thus, noise-reduction techniques, for example, CompCor, FIX, and ICA-AROMA have been developed to further improve the ability to draw meaningful conclusions from the data. The ability of these techniques to minimize noise while conserving signals of interest has been tested almost exclusively in resting-state fMRI and, only rarely, in task-related fMRI. Application of noise-reduction techniques to task-related fMRI …

Conserved And Divergent Gene Regulatory Programs Of The Mammalian Neocortex, Nathan R Zemke, Daofeng Li, Xiaoyu Zhuo, Vincent Xu, Ting Wang, Et Al.

2020-Current year OA Pubs

Divergence of cis-regulatory elements drives species-specific traits

Multi-Ancestry Genome-Wide Association Study Of Cannabis Use Disorder Yields Insight Into Disease Biology And Public Health Implications, Daniel F Levey, Emma C Johnson, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (n

Recombinant Human Perlecan Dv And Its Lg3 Subdomain Are Neuroprotective And Acutely Functionally Restorative In Severe Experimental Ischemic Stroke, Ifechukwude Joachim Biose, Ibolya Rutkai, Bryan Clossen, Gary Gage, Kenneth Schechtman, H Davis Adkisson 4th, Gregory J Bix

2020-Current year OA Pubs

Despite recent therapeutic advancements, ischemic stroke remains a major cause of death and disability. It has been previously demonstrated that  ~ 85-kDa recombinant human perlecan domain V (rhPDV) binds to upregulated integrin receptors (α2β1 and α5β1) associated with neuroprotective and functional improvements in various animal models of acute ischemic stroke. Recombinant human perlecan laminin-like globular domain 3 (rhPDV

Kat6a Mutations In Arboleda-Tham Syndrome Drive Epigenetic Regulation Of Posterior Hoxc Cluster, Meghna Singh, Sarah J Spendlove, Angela Wei, Leroy M Bondhus, Aileen A Nava, Francisca N De L Vitorino, Seth Amano, Jacob Lee, Gesenia Echeverria, Dianne Gomez, Benjamin A Garcia, Valerie A Arboleda

2020-Current year OA Pubs

Arboleda-Tham Syndrome (ARTHS) is a rare genetic disorder caused by heterozygous, de novo mutations in Lysine(K) acetyltransferase 6A (KAT6A). ARTHS is clinically heterogeneous and characterized by several common features, including intellectual disability, developmental and speech delay, and hypotonia, and affects multiple organ systems. KAT6A is the enzymatic core of a histone-acetylation protein complex; however, the direct histone targets and gene regulatory effects remain unknown. In this study, we use ARTHS patient (n = 8) and control (n = 14) dermal fibroblasts and perform comprehensive profiling of the epigenome and transcriptome caused by KAT6A mutations. We identified differential chromatin accessibility within …

Single-Cell Analysis Of Chromatin Accessibility In The Adult Mouse Brain, Songpeng Zu, Yang Eric Li, Et Al.

2020-Current year OA Pubs

Recent advances in single-cell technologies have led to the discovery of thousands of brain cell types; however, our understanding of the gene regulatory programs in these cell types is far from complete

Endoscopic Management Of Tracheoesophageal Prosthesis-Induced Esophageal Mucosal Bridge, Mahmoud Y. Madi, Matthew Peller, Michael Presti, Ahmad Najdat Bazarbashi

2020-Current year OA Pubs

No abstract provided.

Lasofoxifene Versus Fulvestrant For Er+/Her2- Metastatic Breast Cancer With An Esr1 Mutation: Results From The Randomized, Phase Ii Elaine 1 Trial, M P Goetz, N A Bagegni, Et Al.

2020-Current year OA Pubs

BACKGROUND: Acquired estrogen receptor alpha (ER/ESR1) mutations commonly cause endocrine resistance in ER+ metastatic breast cancer (mBC). Lasofoxifene, a novel selective ER modulator, stabilizes an antagonist conformation of wild-type and ESR1-mutated ER-ligand binding domains, and has antitumor activity in ESR1-mutated xenografts.

PATIENTS AND METHODS: In this open-label, randomized, phase II, multicenter, ELAINE 1 study (NCT03781063), we randomized women with ESR1-mutated, ER+/human epidermal growth factor receptor 2 negative (HER2-) mBC that had progressed on an aromatase inhibitor (AI) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) to oral lasofoxifene 5 mg daily or IM fulvestrant 500 mg (days 1, 15, and 29, …

Phase 1/1b Open-Label, Dose-Escalation Study Of Fruquintinib In Patients With Advanced Solid Tumors In The United States, Andrea Wang-Gillam, William Schelman, Stacey Ukrainskyj, Caly Chien, Martha Gonzalez, Zhao Yang, Marek Kania, Heather Yeckes-Rodin

2020-Current year OA Pubs

This open-label, phase 1/1b study was conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of fruquintinib in United States (U.S.) patients to confirm the recommended phase 2 dose (RP2D) established in China. Patients with advanced solid tumors who had progressed on approved systemic therapy, were enrolled into 2 successive dose escalation cohorts, fruquintinib 3 mg (n = 7) or 5 mg (n = 7), orally, once daily (QD), 3 weeks on and 1 week off (3/1) with a 3 + 3 design followed by a dose expansion cohort at the RP2D 5 mg dose (n = 6). PK samples …

Programmable And Reversible Integrin-Mediated Cell Adhesion Reveals Hysteresis In Actin Kinetics That Alters Subsequent Mechanotransduction, Zheng Zhang, Guy M Genin, Et Al.

2020-Current year OA Pubs

Dynamically evolving adhesions between cells and extracellular matrix (ECM) transmit time-varying signals that control cytoskeletal dynamics and cell fate. Dynamic cell adhesion and ECM stiffness regulate cellular mechanosensing cooperatively, but it has not previously been possible to characterize their individual effects because of challenges with controlling these factors independently. Therefore, a DNA-driven molecular system is developed wherein the integrin-binding ligand RGD can be reversibly presented and removed to achieve cyclic cell attachment/detachment on substrates of defined stiffness. Using this culture system, it is discovered that cyclic adhesion accelerates F-actin kinetics and nuclear mechanosensing in human mesenchymal stem cells (hMSCs), with …

Trpv4 Differentially Controls Inflammatory Cytokine Networks During Static And Dynamic Compression Of The Intervertebral Disc, Garrett W D Easson, Alireza Savadipour, Christian Gonzalez, Farshid Guilak, Simon Y Tang

2020-Current year OA Pubs

BACKGROUND: The ion channel transient receptor potential vanilloid 4 (TRPV4) critically transduces mechanical forces in the IVD, and its inhibition can prevent IVD degeneration due to static overloading. However, it remains unknown whether different modes of loading signals through TRPV4 to regulate the expression of inflammatory cytokines. We hypothesized that TRPV4 signaling is essential during static and dynamic loading to mediate homeostasis and mechanotransduction.

METHODS: Mouse functional spine units were isolated and either cyclically compressed for 5 days (1 Hz, 1 h, 10% strain) or statically compressed (24 h, 0.2 MPa). Conditioned media were monitored at 6 h, 24 h, …

Increasing Energetic Demands On Photoreceptors In Diabetes Corrects Retinal Lipid Dysmetabolism And Reduces Subsequent Microvascular Damage, Sheng Zhang, Xiaochao Wei, Megan Bowers, Sebastian Jessberger, Marcin Golczak, Clay F Semenkovich, Rithwick Rajagopal

2020-Current year OA Pubs

Mechanisms responsible for the pathogenesis of diabetic retinal disease remain incompletely understood, but they likely involve multiple cellular targets, including photoreceptors. Evidence suggests that dysregulated de novo lipogenesis in photoreceptors is a critical early target of diabetes. Following on this observation, the present study aimed to determine whether two interventions shown to improve diabetic retinopathy in mice-pharmacologic visual cycle inhibition and prolonged dark adaptation-reduce photoreceptor anabolic lipid metabolism. Elevated retinal lipid biosynthetic signaling was observed in two mouse models of diabetes, with both models showing reduced retinal AMP-activated kinase (AMPK) signaling, elevated acetyl CoA carboxylase (ACC) signaling, and increased activity …

The Persistency Index: A Novel Screening Tool For Identifying Myofascial Pelvic Floor Dysfunction In Patients Seeking Care For Lower Urinary Tract Symptoms, A Lenore Ackerman, Michele Torosis, Nicholas J Jackson, Ashley T Caron, Melissa R Kaufman, Jerry L Lowder, Jonathan C Routh

2020-Current year OA Pubs

BACKGROUND: Patients with myofascial pelvic floor dysfunction often present with lower urinary tract symptoms, such as urinary frequency, urgency, and bladder pressure. Often confused with other lower urinary tract disorders, this constellation of symptoms, recently termed myofascial urinary frequency syndrome, is distinct from other lower urinary tract symptoms and optimally responds to pelvic floor physical therapy. A detailed pelvic floor myofascial examination performed by a skilled provider is currently the only method to identify myofascial urinary frequency syndrome. Despite a high influence on quality of life, low awareness of this condition combined with no objective diagnostic testing leads to the …

Core Warming Of Coronavirus Disease 2019 Patients Undergoing Mechanical Ventilation: A Pilot Study, Nathaniel P Bonfanti, Nicholas M Mohr, David C Willms, Roger J Bedimo, Emily Gundert, Kristina L Goff, Erik B Kulstad, Anne M Drewry

2020-Current year OA Pubs

Fever is a recognized protective factor in patients with sepsis, and growing data suggest beneficial effects on outcomes in sepsis with elevated temperature, with a recent pilot randomized controlled trial (RCT) showing lower mortality by warming afebrile sepsis patients in the intensive care unit (ICU). The objective of this prospective single-site RCT was to determine if core warming improves respiratory physiology of mechanically ventilated patients with coronavirus disease 2019 (COVID-19), allowing earlier weaning from ventilation, and greater overall survival. A total of 19 patients with mean age of 60.5 (±12.5) years, 37% female, mean weight 95.1 (±18.6) kg, and mean …

Recurrent Adrenergic Stress Provokes Persistent Myocarditis In Pd-1-Deficient Mice, Tomohiro Hayashi, Kenji Rowel Q Lim, Attila Kovacs, Douglas L Mann

2020-Current year OA Pubs

It is unclear how the immune system initiates effective tissue repair responses without also simultaneously activating adaptive immune responses to self-antigens released by damaged or necrotic cells. We studied the role of repetitive adrenergic mediated stress on cardiac injury wild-type and programmed death-1-deficient (PD-1

Longitudinal Lipidomic Profiles During Pregnancy And Associations With Neonatal Anthropometry: Findings From A Multiracial Cohort, Yiqing Song, Ruijin Lu, Guoqi Yu, Mohammad L Rahman, Liwei Chen, Yeiyi Zhu, Michael Y Tsai, Oliver Fiehn, Zhen Chen, Cuilin Zhang

2020-Current year OA Pubs

BACKGROUND: Maternal lipidomic profiling offers promise for characterizing lipid metabolites during pregnancy, but longitudinal data are limited. This study aimed to examine associations of longitudinal lipidomic profiles during pregnancy with multiple neonatal anthropometry using data from a multiracial cohort.

METHODS: We measured untargeted plasma lipidome profiles among 321 pregnant women from the NICHD Fetal Growth Study-Singletons using plasma samples collected longitudinally during four study visits at gestational weeks (GW) 10-14, 15-26, 23-31, and 33-39, respectively. We evaluated individual lipidomic metabolites at each study visit in association with neonatal anthropometry. We also evaluated the associations longitudinally by constructing lipid networks using …

Beyond The Single-Outcome Approach: A Comparison Of Outcome-Wide Analysis Methods For Exposome Research, Augusto Anguita-Ruiz, Chongliang Luo, Et Al.

2020-Current year OA Pubs

Outcome-wide analysis can offer several benefits, including increased power to detect weak signals and the ability to identify exposures with multiple effects on health, which may be good targets for preventive measures. Recently, advanced statistical multivariate techniques for outcome-wide analysis have been developed, but they have been rarely applied to exposome analysis. In this work, we provide an overview of a selection of methods that are well-suited for outcome-wide exposome analysis and are implemented in the R statistical software. Our work brings together six different methods presenting innovative solutions for typical problems arising from outcome-wide approaches in the context of …

Bintrafusp Alfa Versus Pembrolizumab In Patients With Treatment-Naive, Programmed Death-Ligand 1-High Advanced Nsclc: A Randomized, Open-Label, Phase 3 Trial, Byoung Chul Cho, Clifford Robinson, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Bintrafusp alfa, a first-in-class bifunctional fusion protein composed of the extracellular domain of TGF-βRII (a TGF-β "trap") fused to a human immunoglobulin G1 monoclonal antibody blocking programmed death-ligand 1 (PD-L1), has exhibited clinical activity in a phase 1 expansion cohort of patients with PD-L1-high advanced NSCLC.

METHODS: This adaptive phase 3 trial (NCT03631706) compared the efficacy and safety of bintrafusp alfa versus pembrolizumab as first-line treatment in patients with PD-L1-high advanced NSCLC. Primary end points were progression-free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 per independent review committee and overall survival.

RESULTS: Patients (N = …

Physiological And Biomechanical Response To Indoor Cycling With And Without The Ability To Sway, Alina P. Swafford

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Bicycles have been around since the early 19th century. Since the invention of the bicycle, it has taken on several purposes. People have used bicycles as a means of transportation, leisure, exercise, and sport. The number of individuals who participate in a cycling event per year has increased. With the increase in popularity, research related to cycling has also increased. Research related to the physiology and biomechanics of cycling are of particular areas of interest. Balance is a crucial component of understanding why we cycle a certain way. Some research has labeled balancing on a bicycle as cycling sway. …

Exploring The Influence Of Technology-Supported Immersive Experiences: The Case Of Golf Simulators As A Way Of Relieving Stress In The Workplace, Luka Van Der Merwe

UNLV Theses, Dissertations, Professional Papers, and Capstones

This study explores the impact of immersive technology, specifically golf simulators, on relieving work-related stress among hotel industry employees. The purpose of the current study was to examine how hotel employees perceive the use of immersive technology as a form of stress relief. The study was developed to learn whether hotel employees experience work-related stress, and if so, how they cope with it. The study also aimed to determine whether they would be interested in utilizing a golf simulator as a new form of stress relief if it were offered to them free of charge by their employer. Interviewing hotel …

A Multisociety Delphi Consensus Statement On New Fatty Liver Disease Nomenclature, Mary E Rinella, Jeffrey V Lazarus, Vlad Ratziu, Sven M Francque, Arun J Sanyal, Fasiha Kanwal, Diana Romero, Manal F Abdelmalek, Quentin M Anstee, Juan Pablo Arab, Marco Arrese, Ramon Bataller, Ulrich Beuers, Jerome Boursier, Elisabetta Bugianesi, Christopher D Byrne, Graciela E Castro Narro, Abhijit Chowdhury, Helena Cortez-Pinto, Donna R Cryer, Kenneth Cusi, Mohamed El-Kassas, Samuel Klein, Wayne Eskridge, Jiangao Fan, Samer Gawrieh, Cynthia D Guy, Stephen A Harrison, Seung Up Kim, Bart G Koot, Marko Korenjak, Kris V Kowdley, Florence Lacaille, Rohit Loomba, Robert Mitchell-Thain, Timothy R Morgan, Elisabeth E Powell, Michael Roden, Manuel Romero-Gómez, Marcelo Silva, Shivaram Prasad Singh, Silvia C Sookoian, C Wendy Spearman, Dina Tiniakos, Luca Valenti, Miriam B Vos, Vincent Wai-Sun Wong, Stavra Xanthakos, Yusuf Yilmaz, Zobair Younossi, Ansley Hobbs, Marcela Villota-Rivas, Philip N Newsome, Nafld Nomenclature Consensus Group

Faculty, Staff and Students Publications

The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content experts and patient advocates were in favour of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panellists from 56 countries participated in 4 …

Complicated Extubation In A Patient With An Obstructing Tracheobronchial Thrombus, Milan Terzic, Daniel Aintabi, Omar Hegazy

Graduate Medical Education Research Journal

Endotracheal intubation is an effective and rapid technique used as a standard practice for airway management. Airway injury or complications could be a significant cause of morbidity and mortality for patients. Tracheobronchial obstruction secondary to thrombus formation are life threatening complications of traumatic intubations. We present a case of complicated extubation resulting in cardiac arrest in a patient with an obstructing tracheobronchial thrombus. The patient, an 83-year-old female, with atrial fibrillation presented for neck pain. During CT imaging, she developed ventricular fibrillation cardiac arrest. Return of spontaneous circulation (ROSC) was achieved after three cycles of compressions and defibrillation and the …

Medical School Watercooler Newsletter - November 30, 2023, Lindsey Lyle

Watercooler Newsletter

This is the November 30, 2023 edition of the Frederick P. Whiddon College of Medicine's newsletter - Watercooler.

Contents Include:

• Pediatric interventional radiologist joins radiology faculty
• USA researchers identify potential biomarkers for detection and treatment of triple-negative breast cancer
• Now accepting nominations for USA Medical Alumni Awards
• Register now: Tools for Teaching in Medical Education
• Center for Healthy Communities to host community health worker forum

Access To A Regular Primary Care Physician Among Young People With Early Psychosis In Ontario, Canada, Rebecca Rodrigues, Jennifer N S Reid, Joshua C. Wiener, Suzanne Archie, Richard G Booth, Chiachen Cheng, Arlene G Macdougall, Lena Palaniyappan, Bridget L Ryan, Aristotle Voineskos, Paul Kurdyak, Saadia Hameed Jan, Kelly K. Anderson

Epidemiology and Biostatistics Publications

AIM: Access to a primary care physician in early psychosis facilitates help-seeking and engagement with psychiatric treatment. We examined access to a regular primary care physician in people with early psychosis, compared to the general population, and explored factors associated with access.

METHODS: Using linked health administrative data from Ontario (Canada), we identified people aged 14-35 years with a first diagnosis of nonaffective psychotic disorder (n = 39 449; 2005-2015). We matched cases to four randomly selected general population controls based on age, sex, neighbourhood, and index date (n = 157 796). We used modified Poisson regression to estimate prevalence …

Promoting Patient Mobility To Decrease Hospital Length Of Stay, Saira Kinuthia

Student Scholarly Projects

Practice Problem: Promoting patient mobility may reduce hospital-acquired complications and length of stay (LOS). Evidence-based studies have established that there is a correlation between immobility and an increased length of stay in the hospital. How can nurse-driven mobility interventions effectively increase patient mobility and reduce the risk of complications and length of hospital stay?

PICOT: The PICOT question that guided this project was: For veteran patients in the Progressive Care unit (PCU) of a medical center (P), will using the Johns Hopkins Highest Level of Mobility tool (JH-HLM) (I) compared to not using a mobility tool (C) decrease hospital length …