Anatomy Commons^™

Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis In The Management Of Intermediate-Risk Pulmonary Embolism: Primary Results Of The Peerless Randomized Controlled Trial, Wissam A. Jaber, Carin F. Gonsalves Md, Stefan Stortecky, Samuel Horr, Ripal T. Gandhi, Keith Pereira, Jay Giri, Sameer J. Khandhar, Khawaja Afzal Ammar, David M. Lasorda, Brian Stegman, Lucas Busch, David J. Dexter, Ezana M. Azene, Nikhil Daga, Fakhir Elmasri, Chandra R. Kunavarapu, Mark E. Rea, Joseph S. Rossi, Joseph Campbell, Jonathan Lindquist, Adam Raskin, Jason C. Smith, Thomas M. Tamlyn, Gabriel A. Hernandez, Parth Rali, Torrey R. Schmidt, Jeffrey T. Bruckel, Juan C. Camacho, Jun Li, Samy Selim, Catalin Toma, Sukhdeep Singh Basra, Brian A. Bergmark, Bhavraj Khalsa, David M. Zlotnick, Jordan Castle, David J. O'Connor, C. Michael Gibson, For The Peerless Committees And Investigators

Department Surgery Faculty Publications

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

METHODS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation …

Protonic Capacitor Cell Energetics: Transmembrane-Electrostatically Localized Protons/Cations, James Weifu Lee

Chemistry & Biochemistry Faculty Publications

The transmembrane-electrostatically localized protons/cations charges (TELPs/TELCs) theory can serve as a theoretical framework to better explain cell electrophysiology and elucidate bioenergetic systems including both delocalized and localized protonic coupling. According to the TELCs model, the excess positive charges of TELCs at one side of the membrane are balanced by the excess negative charges of transmembrane-electrostatically localized hydroxides anions (TELAs) at the other side of the membrane. Through the TELCs-membrane-TELAs capacitor model, the energetics of oxidative phosphorylation have recently been better elucidated in mitochondria and alkalophilic bacteria, leading to the identification of a novel Type-B energetic process. Both the TELCs model …

Astrocyte Specific Enhancers In The Cortex And Striatum Of Mice, Mikaela Kottelich

Williams Honors College, Honors Research Projects

Among glial cells, astrocytes have a prevalent influence on supporting neuronal function and overall brain health. Specifically targeting this cell type for disease treatment is an existing issue. Other cell types tend to express the desired treatment, which is not always wanted and can lead to unintended, negative consequences. Astrocytes contribute largely to maintaining the blood brain barrier, which is disrupted in Parkinson’s disease. Certain genes are thought to be the reason for this disruption, so if they can be specifically targeted in astrocytes with a specific enhancer, the disruption of the disease could be reversed. In our experiment, we …

Impact Of Tetrahydrocannabinol (Thc) On Daphnia Magna Heart Rate, Ashley Cosgrave

Williams Honors College, Honors Research Projects

Marijuana (Cannabis) is currently federally illegal within the United States and classified as a Schedule I drug. This leaves a large research gap on the impacts of Tetrahydrocannabinol (THC) use. Daphnia magna are frequently used as a model organism for the human heart and toxicology screenings due to their myogenic heart, similarities in physiological pathways, and sensitivity to toxins. As such, in order to bridge the research gap and uncover potential use of Daphnia magna as a model organism for humans in regard to impact on heart rate, we hypothesized that if Daphnia magna possess CB1 receptors or an equivalent …

Neurotensin Regulates Primate Ovulation Via Multiple Neurotensin Receptors, Andrew C. Pearson, Jessica S. Miller, Hannah J. Jensen, Ketan Shrestha, Thomas E. Curry Jr., Diane M. Duffy

Department of Biomedical and Translational Sciences Faculty Publications

Neurotensin (NTS), a small neuropeptide, was recently established as a key paracrine mediator of ovulation. NTS mRNA is highly expressed by granulosa cells in response to the luteinizing hormone (LH) surge, and multiple NTS receptors are expressed by cells of the ovulatory follicle. To identify the role of NTS receptors NTSR1 and SORT1 in ovulation in vivo, the dominant follicle of cynomolgus macaques (Macaca fascicularis) was injected with either vehicle control, the general NTS receptor antagonist SR142948, the NTSR1-selective antagonist SR48692, or the SORT1-selective antagonist AF38469. Human chorionic gonadotropin (hCG) was then administered to initiate ovulatory events. …

Ambulatory Arterial Stiffness Index: Regression Method Comparison And Its Association With Pulse Pressure And Circadian Patterns, José R. Ayala-Hernández, Cristina López-Sánchez, Orlando M. Ayala, Camilo E. Palencia-Tejedor

Engineering Technology Faculty Publications

The Arterial Stiffness Index (AASI) is a calculation obtained through Ambulatory Blood Pressure Monitoring (ABPM), and is an indirect measure of the elastic properties of the arterial wall; but there is heterogeneity in its scope as a predictor of vascular wall health. A comparison is made between linear regression and exponential regression of the AASI, as well as an analysis of variance, according to circadian patterns and pulse pressure (PP) values. This work is an analytical observational study in 106 individuals, most of them women (63%) with a mean age of 53 ± 17.32 years. The coefficient of determination (r2) …

Cochlear Electrode Insertion Training Model, Sarah Powell, Kaelyn E. Kraley, Nathan J. Smith

Williams Honors College, Honors Research Projects

Cochlear implant surgery is a delicate procedure performed by Otolaryngologists (ENTs) to implant an electronic device into the inner ear to provide a sense of sound for people who are profoundly deaf or hard of hearing. The current practices of training involve cadavers and 3D-printed models. Cadavers are commonly used but are expensive, single-use, and do not provide visual and haptic feedback, which are essential for medical students. 3D printed models are less commonly used and are hard to fabricate and not as realistic. If medical students are not properly trained for this delicate procedure, then risks are significantly increased …

Perceived Shoulder Discomfort In Adolescent Swimmers, Abigail Daniel

Williams Honors College, Honors Research Projects

Competitive swimming is a sport that athletes traditionally start at a young age, training for many years to build up an aerobic base, learn the best techniques of the sport, and gain experience racing. While this increases the ability to perform and adapt to training in the sport, it also can lead to shoulder tightness, soreness, and even injury. PURPOSE: To investigate any correlation between the perceived shoulder discomfort of adolescents to flexion and extension measurements. METHODS: Participants (N=25) were recruited in person from a swimming club. Swimmers were between 13-18 years old and varied in participation level from recreational …

Adult Human Rib Variation Of Symmetry Among Many Populations, Madison Irish

Williams Honors College, Honors Research Projects

Human rib morphology is a central focus within the exploration of ribcage biomechanical properties and thoracic traumas, with the use of anatomical models being crucial in clinical, academic, and forensic settings. Despite the significance, there is little existing research on bilateral asymmetry of the ribcage, and many models use the assumption of symmetry between right and left rib pairs. This study investigates morphological right and left rib pair asymmetries using high-resolution imaging and 3D reconstruction techniques among a diverse population of sex, age, and populations. Symmetry was tested using three variables: pitch, radius of curvature, and roll among rib pairs …

Categorizing Clinical Response To Mepolizumab For Patients With Chronic Rhinosinusitis With Nasal Polyps: Synapse Trial, Claire Hopkins, Larry Borish, Jared Silver, Peter Howarth, Robert Chan, Priya Dsilva, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

[Introduction] Chronic rhinosinusitis with nasal polyps (CRSwNP) can substantially affect quality of life (QoL), and is often challenging to manage.¹ First-line treatment for the management of CRSwNP involves intranasal corticosteroids, with short courses of systemic corticosteroids (SCS) for exacerbations, and sinus surgery for uncontrolled disease.² Biologics targeting type 2 inflammation (eg, dupilumab, omalizumab, and mepolizumab) have become a treatment option for refractory CRSwNP. With the advent of disease-modifying treatments such as biologics, control, defined as patients reporting no/low-symptom levels, has increasingly become the treatment goal for CRSwNP.³ However, the optimal use of biologics for symptom control in individual patients remains …

Acute Exacerbations Of Chronic Rhinosinusitis, Robert M. Frederick, Kent Lam, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

Purpose of Review

We aim to highlight recent advancements on the evolving chronic rhinosinusitis (CRS) phenotype: acute exacerbations of chronic rhinosinusitis (AECRS). We focused on studies that expanded the current understanding of its pathophysiology, patient characteristics, and disease burden.

Recent findings

Defining AECRS has been a topic of discussion for many years. A recent regulatory definition of AECRS in the literature incorporates a > 3 day requirement of worsened symptoms and an escalation of treatment. It is important not to rely on patient-reported rescue medication frequency as it was recently demonstrated these are only obtained for 1/3 of reported AECRS episodes. …

Biomechanics Of The Atherosclerotic Lipidome: (Un)Expected Statin Interactions And Membrane Remodelling, Ethan M. Fong

Pomona Senior Theses

Statins interact with lipid membranes in ways that shape their pharmacokinetics, off-target effects, and pleiotropic actions, yet these interactions' mechanical and biophysical consequences remain poorly understood. This thesis employs a combination of surface plasmon resonance (SPR), quartz crystal microbalance with dissipation monitoring (QCM-D), and rheological modelling to characterize how representative statins intercalate within biomimetic supported lipid bilayers (SLBs) of healthy and diseased composition. SPR reveals that lipophilic statins exhibit higher apparent affinities and slower dissociation kinetics, especially in cholesterol- and anionic lipid-rich membranes. QCM-D analyses demonstrate that statins alter membrane mass, dissipation, and interfacial stiffness in a statin- and membrane-dependent …

Cardiac Timing Effects On Response Speed Are Modulated By Blood Pressure But Not Heart Rate Variability In Healthy Young Adults, Xiao Yang, Catalina Roldan, Michael Gazzanigo, Yasmine Nabulsi, Fang Fang

Research and Infrastructure Service Enterprise (RISE) Faculty Publications

Cardiac timing effects reflect the dynamic interplay between interoceptive and exteroceptive processes. Human information processing tends to be facilitated during cardiac diastole and inhibited during systole, reflecting autonomic regulation and the neuromodulation by baroreceptor afferents. Thus, blood pressure (BP) and vagally-mediated heart rate variability (vmHRV) are potential modulators of those effects. Additionally, cognitive control appears to play a critical role in the processes. However, whether cardiac timing effects are influenced by those factors remains unclear. The present study aimed to clarify these relationships. Fifty-one healthy young adults completed three experimental sessions to assess BP, short-term HRV, and cardiac timing effects. …

Interaction Of Cardiac Leiomodin With The Native Cardiac Thin Filament, Madison Little, Cristina M. Risi, Tania M. Larrinaga, Mason D. Summers, Tyler Nguyen, Garry E. Smith Jr., Jennifer Atherton, Carol C. Gregorio, Alla S. Kostyukova, Vitold E. Galkin

Department of Biomedical and Translational Sciences Faculty Publications

Every heartbeat depends on cyclical contraction-relaxation produced by the interactions between myosin-containing thick and actin-based thin filaments (TFs) arranged into a crystalline-like lattice in the cardiac sarcomere. Therefore, the maintenance of thin filament length is crucial for myocardium function. The thin filament is comprised of an actin backbone, the regulatory troponin complex and tropomyosin that controls interactions between thick and thin filaments. Thin filament length is controlled by the tropomodulin family of proteins; tropomodulin caps pointed ends of thin filaments, and leiomodin (Lmod) promotes elongation of thin filaments by a “leaky-cap” mechanism. The broader distribution of Lmod on the thin …

Cannabinoid-2 Receptor Activation Attenuates Sulfur Mustard Analog 2-Chloroethyl-Ethyl-Sulfide-Induced Acute Lung Injury In Mice, Gregory Nicholson, Nicholas Richards, Janette Lockett, My Boi Ly, Raj V. Nair, Woong-Ki Kim, K. Yaragudri Vinod, Nagaraja Nagre

Department of Biomedical and Translational Sciences Faculty Publications

Background: Exposure to sulfur mustard (SM; 2,2′-dichlorodiethyl sulfide) causes toxicity in the human body, particularly the lungs. The molecular mechanisms of SM-induced lung damage are elusive, and no effective treatments exist. This study explores the anti-inflammatory potential of cannabinoid receptor 2 (CB2R) activation in mitigating acute lung injury (ALI) and inflammation induced by 2-chloroethyl ethyl sulfide (CEES), a structural analog of SM. Methods: C57BL/6J mice were exposed to CEES via intratracheal administration to model ALI. CB2R activation was achieved through the intraperitoneal administration of HU308, a selective synthetic agonist. ALI and inflammation were evaluated at 48 h post-exposure to CEES. …

Cellular And Molecular Mechanisms Of Lung Regeneration, Repair, And Fibrosis, Volume Ii, Yong Qiu, Xiao Xiao Tang, Shigeyuki Shichino, Prem Prakash Kushwaha, Yan Y. Sanders, Remo Castro Russo, Chunheng Mo

Department of Biomedical and Translational Sciences Faculty Publications

[Introduction] Organ fibrosis represents a substantial a major contributor to global disease burden, implicated in over 30% of cases leading to disability-associated and fatal conditions. Among these conditions, idiopathic pulmonary fibrosis (IPF) stands as a progressive and frequently fatal interstitial lung disease characterized by aberrant extracellular matrix deposition and parenchymal scarring. The prognosis for IPF patients is poor, with a median survival time of just 3–5 years (Bhattacharya and Ramachandran, 2023; Lederer and Martinez, 2018, Ma et al., 2024, Wei et al., 2024). Current FDA-approved therapeutics, Pirfenidone and Nintedanib, demonstrate capacity to attenuate functional decline in pulmonary fibrosis but remain …

Swinging Lever Mechanism Of Myosin Directly Shown By Time-Resolved Cryo-Em, David P. Klebl, Sean N. Mcmillan, Cristina Risi, Eva Forgacs, Betty Virok, Jennifer L. Atherton, Sarah A. Harris, Michele Stofella, Donald A. Winkelmann, Frank Sobott, Vitold E. Galkin, Peter J. Knight, Stephen P. Muench, Charlotte A. Scarfi, Howard D. White

Department of Biomedical and Translational Sciences Faculty Publications

Myosins produce force and movement in cells through interactions with F-actin¹. Generation of movement is thought to arise through actin-catalysed conversion of myosin from an ATP-generated primed (pre-powerstroke) state to a post-powerstroke state, accompanied by myosin lever swing²,³. However, the initial, primed actomyosin state has never been observed, and the mechanism by which actin catalyses myosin ATPase activity is unclear. Here, to address these issues, we performed time-resolved cryogenic electron microscopy (cryo-EM)⁴ of a myosin-5 mutant having slow hydrolysis product release⁵,⁶. Primed actomyosin was predominantly captured 10 ms after …

Deletion Of Chop In Beta Cell Protects Mice From Cardiovascular Complications In Type 2 Diabetes: Evidence From A Pre-Clinical Mouse Model, Balaji Srinivas, Kiran Alluri, Nour-Eddine Rhaleb, Khalid Matrougui

Department of Biomedical and Translational Sciences Faculty Publications

Introduction

Cardiovascular complications are the leading cause of morbidity and mortality in patients with type 2 diabetes (T2D), which is recognized as a major independent risk factor for coronary artery disease, stroke, peripheral vascular disease, and heart failure. The interrelationship between metabolic dysfunction and cardiovascular disease is complex and multifactorial, involving hyperglycemia, insulin resistance, inflammation, and oxidative stress. Evidence indicates that endoplasmic reticulum (ER) stress and induction of the unfolded protein response (UPR) contribute to metabolic dysregulation and vascular dysfunction. However, the specific role of beta cell-derived UPR mediators, particularly C/EBP homologous protein (CHOP), in coordinating this interorgan axis between …

Phenotype Specific Nuclear Lamina Remodeling In Hipsc Derived Cardiomyocytes Bearing Tnnt2 Sarcomeric Variants, Isabella Leite Coscarella, Olalekan H. Usman, Lili Wang, Maicon Landim-Vieira, Lillian Wirstiuk, Amber N. Brown, Diego A. R. Zorio, Brian K. Washburn, Cynthia Vied, Bjorn C. Knollmann, Christopher Solís, Vitold E. Galkin, P. Bryant Chase, J. Travis Hinson, Jerome Irianto, Jose Renato Pinto

Department of Biomedical and Translational Sciences Faculty Publications

[Summary] Cardiomyocytes endure physical stress from the myocardium environment while generating their own mechanical strains. The force generated by sarcomeres is transmitted both longitudinally to adjacent sarcomeres and laterally to the cytoskeleton via intermediate filaments. This mechanical stimulus impacts other organelles, including the nucleus, thus playing a vital role in sensing and signaling nuclear adaptations. However, there is limited understanding of how changes in cardiac contractility affect nuclear mechanics. Here, we sought to investigate the effects of hyper- and hypo-contractility in nuclei of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) bearing TNNT2 pathogenic variants associated with hypertrophic (HCM) or dilated …

Closing Racial And Ethnic Disparity Gaps In Pediatric Asthma Follow Up Care - A Quality Improvement Initiative, Ayodele Ayeko

Graduate Theses, Dissertations, and Problem Reports (ETD)

ABSTRACT

Closing racial and ethnic disparity gaps in pediatric asthma follow up care - A quality improvement initiative

Ayodele Ayeko

Introduction/Background: Inadequate management of asthma significantly contributes to poor asthma control, poor quality of life (QOL), and high hospitalization rates among pediatric patients. The Global Initiative for Asthma (GINA) guidelines offer recommendations designed to enhance asthma control and improve the quality of life for those affected (2015), including recommendations for close follow up care. At WVU Medicine Children’s Hospital (WVUMCH), insufficient asthma control has been associated with lower clinic follow-up rates and an increase in hospitalization. Although educational initiatives …