Anatomy Commons^™

Optimization Of Serum And Salivary Cortisol Interpolation For Time-Dependent Modeling Frameworks In Healthy Adult Males, Nathaniel T. Berry, Travis Anderson, Christopher K. Rhea, Laurie Wideman

Rehabilitation Sciences Faculty Publications

Cortisol is an important marker of hypothalamic-pituitary-adrenal function and follows robust circadian and diurnal rhythms. However, biomarker sampling protocols can be labor-intensive and cost-prohibitive. Objectives: Explore analytical approaches that can handle differing biological sampling frequencies to maximize these data in more detailed and time-dependent analyses. Methods: Healthy adult males [N = 8; 26.1 (±3.1) years; 176.4 (±8.6) cm; 73.1 (±12.0) kg)] completed two 24 h admissions: one at rest and one including a high-intensity exercise session on the cycle ergometer. Serum and salivary cortisol were sampled every 60 and 120 min, respectively. Six alternative sampling profiles were defined by downsampling …

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 …

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. …

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. …

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 …

Protein Marker-Dependent Drug Discovery Targeting Breast Cancer Stem Cells, Ashley V. Huang, Yali Kong, Kan Wang, Milton L. Brown, David Mu

Department of Biomedical and Translational Sciences Faculty Publications

Breast cancer is one of the most common cancers globally. Unfortunately, many patients with breast cancer develop resistance to chemotherapy and tumor recurrence, which is primarily driven by breast cancer stem cells (BCSCs). BCSCs behave like stem cells and can self-renew and differentiate into mature tumor cells, enabling the cancer to regrow and metastasize. Key markers like CD44 and aldehyde dehydrogenase-1 (ALDH1), along with pathways like Wingless-related integration site (Wnt), Notch, and Hedgehog, are critical to regulating this stem-like behavior of BCSCs and, thus, are being investigated as targets for various new therapies. This review summarizes marker-dependent strategies for targeting …

Anaplastic Large Cell Lymphoma In Children And Adolescents, Eric J. Lowe, Wilhelm Woessmann

Department of Pediatrics Faculty Publications

Anaplastic lymphoma kinase (ALK)-positive anaplastic large-cell lymphoma (ALCL) accounts for >95% of ALCL cases in children and adolescents. The first description of ALCL as a CD30-positive lymphoma in 1985 was followed by the detection of chromosomal translocations involving the ALK gene at chromosome 2p23. The pathogenesis of ALK-positive ALCL is based on signalling from the constitutive active ALK kinase. The clinical characteristics, therapy regimens and outcome data were reported in the 1990s and 2000s. Different chemotherapy regimens led to astonishingly similar long-term event-free survival rates of 70%, independent of the drugs, doses and duration of therapy. Additionally, patients with relapsed …

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 …

The Central Role For Troponin C Amino-Terminal ⍺-Helix In Vertebrate Thin Filiment Ca²⁺-Activation, Yun Shi, Lauren A. Blackwell, Ryan K. Schroy, B. Max Cleland, Cristina M. Risi, Michelle S. Parvatiyar, Jose R. Pinto, Vitold E. Galkin, P. Bryant Chase

Department of Biomedical and Translational Sciences Faculty Publications

Troponin C (TnC) is the Ca²⁺-sensing subunit of troponin that is responsible for activating thin filaments in striated muscle, and, in turn, for regulating the systolic and diastolic contractile function of cardiac muscle. The secondary structure of vertebrate TnC is mainly composed of α-helices, with nine helices named sequentially, starting from the amino terminus, from N to A–H. The N-helix is a 12-residue-long α-helix located at the extreme amino terminus of the protein and is the only helical structure that does not participate in forming Ca²⁺-binding EF-hands. Evolutionarily, the N-helix is found only in TnC from mammalian species and most …

Epigenetic Regulation In Fibrosis, Qingping Wei, Xiaoru Hu, Yan Sanders

Department of Biomedical and Translational Sciences Faculty Publications

[Introduction] Fibrosis is one of the pathological conditions underlying the progression of numerous chronic diseases, and it contributes substantially to morbidity and mortality worldwide. Increasing amounts of evidence indicate that epigenetic mechanisms—including DNA methylation, histone modifications, RNA modifications, and non-coding RNAs—play pivotal roles in epithelial cell injury and maladaptive tissue repair, inflammatory cell and fibroblast activation, and extracellular matrix remodeling and accumulation. Compared to genetic alterations, epigenetic changes are relatively reversible, positioning them as promising therapeutic targets. The articles collected in this Research Topic highlight recent advances in understanding how epigenetic regulation shapes fibrotic processes across multiple organ systems and …

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 …

Left Ventricular Assist Device Destination Therapy: A Journey To Home And Beyond, Mian Z. Munir, Marissa C. Galicia-Castillo, Mia Achitoov, Amin Yehya

Department of Medicine Faculty Publications

[Case] Mr H is a 74-year-old man with history of end-stage heart failure (ESHF) secondary to hereditary transthyretin cardiac amyloidosis. Our patient underwent placement of a HeartMate II (Abbott) left ventricular assist device (LVAD) as destination therapy (DT) at an outside hospital and later came to us (Sentara Heart Hospital) for continued management because he resided in the area. Over a 2-year period, the patient experienced multiple hospital admissions for acute heart failure (HF) exacerbations, delirium, and recurrent low-flow alarms. During his last hospitalization, the palliative medicine team was consulted to facilitate goals-of-care discussions with the patient and his family, …

The Pre-Polarization And Concentration Of Cells Near Micro-Electrodes Using Ac Electric Fields Enhances The Electrical Cell Lysis In A Sessile Drop, Kishor Kaphle, Dharmakeerthi Nawarathna

Electrical & Computer Engineering Faculty Publications

Cell lysis is the starting step of many biomedical assays. Electric field-based cell lysis is widely used in many applications, including point-of-care (POC) applications, because it provides an easy one-step solution. Many electric field-based lysis methods utilize micro-electrodes to apply short electric pulses across cells. Unfortunately, these cell lysis devices produce relatively low cell lysis efficiency as electric fields do not reach a significant portion of cells in the sample. Additionally, the utility of syringe pumps for flow cells in and out of the microfluidics channel causes cell loss and low throughput cell lysis. To address these critical issues, we …

Enhancing Bone Regeneration Using Kaempferol As An Osteoprotective Compound: Signaling Mechanisms, Delivery Strategies, And Potential Applications, Mojdeh Salehi Namini, Sanam Mohandesnezhad, Sadaf Mohandesnezhad, Vahid Mansouri, Lobat Tayebi, Nima Beheshtizadeh

Electrical & Computer Engineering Faculty Publications

Various plants, including fruits, vegetables, and spices, contain kaempferol, a bioflavonoid compound with diverse medicinal effects, such as antioxidant, antibacterial, and anti-inflammatory characteristics. Furthermore, this compound exhibits multiple health-promoting properties, including osteoprotection and osteogenesis, primarily by modulating various cell-signaling pathways. This review aims to illustrate the medical advantages of kaempferol and its role in regulating bone metabolism through cell signaling mechanisms. Numerous studies have demonstrated the bone-protective properties of kaempferol and its encapsulated form. Further research is needed to clarify the optimal dosages, toxicity, safety, and other potential mechanisms of action. This review demonstrates that several signaling pathways, including nuclear …

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 …