Medical Physiology Commons^™

Impact Of Alcohol On Bone Health In People Living With Hiv: Integrating Clinical Data From Serum Bone Markers With Morphometric Analysis In A Non-Human Primate Model, Alexandra Denys, Allison Norman, Daniel S. Perrien, Larry J. Suva, Liz Simon, Lee S. Mcdaniel, Tekeda Ferguson, Kim Pedersen, David Welsh, Patricia E. Molina, Martin J.J. Ronis

School of Medicine Faculty Publications

People living with HIV (PLWH) represent a vulnerable population to adverse musculoskeletal outcomes due to HIV infection, antiretroviral therapy (ART), and at-risk alcohol use. Developing measures to prevent skeletal degeneration in this group requires a grasp of the relationship between alcohol use and low bone mass in both the PLWH population and its constituents as defined by sex, age, and race. We examined the association of alcohol use with serum biochemical markers of bone health in a diverse cohort of PLWH enrolled in the New Orleans Alcohol Use in HIV (NOAH) study. To explore the effects of alcohol on bone …

Capture At The Er-Mitochondrial Contacts Licenses Ip, Máté Katona, Ádám Bartók, Zuzana Nichtova, György Csordás, Elena Berezhnaya, David Weaver, Arijita Ghosh, Péter Várnai, David I. Yule, György Hajnóczky

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualize the capture of motile IP3 receptors (IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and metabolism. IP3Rs are of particular interest because their presence provides a scaffold for ERMCs that mediate local calcium signaling, and their function outside of ERMCs depends on their motility. Unexpectedly, in a cell model with little ERMC Ca2+ coupling, IP3Rs …

Motoneuron Excitability Dysfunction In Als: Pseudo-Mystery Or Authentic Conundrum?, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

In amyotrophic lateral sclerosis (ALS), abnormalities in motoneuronal excitability are seen in early pathogenesis and throughout disease progression. Fully understanding motoneuron excitability dysfunction may lead to more effective treatments. Yet decades of research have not produced consensus on the nature, role or underlying mechanisms of motoneuron excitability dysfunction in ALS. For example, contrary to Ca excitotoxicity theory, predictions of motoneuronal hyper-excitability, normal and hypo-excitability have also been seen at various disease stages and in multiple ALS lines. Accordingly, motoneuron excitability dysfunction in ALS is a disputed topic in the field. Specifically, the form (hyper, hypo or unchanged) and what role …

Ctpathway: A Crosstalk-Based Pathway Enrichment Analysis Method For Cancer Research, Haizhou Liu, Mengqin Yuan, Ramkrishna Mitra, Xu Zhou, Min Long, Wanyue Lei, Shunheng Zhou, Yu-E Huang, Fei Hou, Christine M. Eischen, Wei Jiang

Department of Cancer Biology Faculty Papers

Background: Pathway enrichment analysis (PEA) is a common method for exploring functions of hundreds of genes and identifying disease-risk pathways. Moreover, different pathways exert their functions through crosstalk. However, existing PEA methods do not sufficiently integrate essential pathway features, including pathway crosstalk, molecular interactions, and network topologies, resulting in many risk pathways that remain uninvestigated.

Methods: To overcome these limitations, we develop a new crosstalk-based PEA method, CTpathway, based on a global pathway crosstalk map (GPCM) with >440,000 edges by combing pathways from eight resources, transcription factor-gene regulations, and large-scale protein-protein interactions. Integrating gene differential expression and crosstalk effects in …

Lysine Methyltransferase Nsd1 And Cancers: Any Role In Melanoma?, Imène Krossa, Thomas Strub, Andrew E Aplin, Robert Ballotti, Corine Bertolotto

Department of Cancer Biology Faculty Papers

Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of NSD1 in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or …

Stones, Bones, And Groans With Cancerous Overtones - A Rare Case Of Diffuse Large B Cell Lymphoma Presenting As Hypercalcemia, Evan Becker, Caitlyn Moss, Steve Chung

Advances in Clinical Medical Research and Healthcare Delivery

Diffuse large B cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma that can present in a variety of ways including fever, weight loss, weakness, and drenching night sweats. Uncommonly, hypercalcemia of malignancy can be associated with DLBCL through multiple mechanisms that include synthesis of parathyroid hormone related peptide (PTHrP) or elevated calcitriol levels. It is estimated that hypercalcemia in the setting of DLBCL is present in 18% of newly diagnosed cases. This report details a case of an 80-year-old man with history of chronic anemia and CKD stage 3b that presented with weakness, decreased oral intake, and self-reported weight …

A Case Of Intractable Hyperhidrosis In Spinal Cord Injury: Role Of Stellate Ganglion Block, Soun Sheen, Hemant Kalia, Victoria Kung

Advances in Clinical Medical Research and Healthcare Delivery

Objective:

Autonomic dysreflexia (AD) in spinal cord injury (SCI) can present as hyperhidrosis due to sudomotor dysfunction. Hyperhidrosis can also occur without an identifiable etiology. There are no standard treatment guidelines for refractory hyperhidrosis in the setting of persistent noxious stimulation. Stellate ganglion blockade may prevent hyperhidrosis by inhibiting profound sympathetic surge and vasoconstriction.

Case:

58-year-old female with C7 ASIA-A quadriplegia was admitted to the hospital for episodes of profuse sweating in the setting of autonomic dysreflexia secondary to underlying T7-8 discitis. Despite conservative treatment of discitis, patient continued experience 50-60 episodes of profuse sweating daily. Stellate ganglion block was …

Non-Invasive Transcutaneous Spinal Dc Stimulation As A Neurorehabilitation Als Therapy In Awake G93a Mice: The First Step To Clinical Translation, Morgan M. Highlander, Sherif M. Elbasiouny

Neuroscience, Cell Biology & Physiology Faculty Publications

Spinal direct current stimulation (sDCS) modulates motoneuron (MN) excitability beyond the stimulation period, making it a potential neurorehabilitation therapy for amyotrophic lateral sclerosis (ALS), a MN degenerative disease in which MN excitability dysfunction plays a critical and complex role. Recent evidence confirms induced changes in MN excitability via measured MN electrophysiological properties in the SOD1 ALS mouse during and following invasive subcutaneous sDCS (ssDCS). The first aim of our pilot study was to determine the clinical potential of these excitability changes at symptom onset (P90-P105) in ALS via a novel non-invasive transcutaneous sDCS (tsDCS) treatment paradigm on un-anesthetized SOD1-G93A mice. …

Suppression Of Store-Operated Calcium Entry Channels And Cytokine Release By Cannabinoids, J. Ashot Kozak

Neuroscience, Cell Biology & Physiology Faculty Publications

No abstract provided.

Healthy Exosomes And Their Effects On Diabetic Cardiomyocytes, Miguel A. Garza, Genaro A. Ramírez-Correa, Maria Lourdes Garza-Rodríguez, Andres J. Medina

MEDI 9331 Scholarly Activities Clinical Years

Extracellular Vesicles, and more specifically, exosomes, are essential for effective cell-to-cell communication in a wide variety of tissues. In the last couple of decades, these nanovesicles have been proven to be active participants and regulators in many disease processes; therefore, their therapeutic effects have been widely studied and proven in various cardiovascular diseases both, in vitro and in vivo. Thus, this study aims at assessing the effects of running healthy mice exosomes on cardiomyocyte and cardiac tissue samples obtained from diabetic mice. Here, we successfully extract exosomes from mice plasma and detect their presence through the use of anti-CD9 and …

Cellular Bioenergetics: Experimental Evidence For Alcohol-Induced Adaptations, Liz Simon, Patricia E. Molina

School of Medicine Faculty Publications

At-risk alcohol use is associated with multisystemic effects and end-organ injury, and significantly contributes to global health burden. Several alcohol-mediated mechanisms have been identified, with bioenergetic maladaptation gaining credence as an underlying pathophysiological mechanism contributing to cellular injury. This evidence-based review focuses on the current knowledge of alcohol-induced bioenergetic adaptations in metabolically active tissues: liver, cardiac and skeletal muscle, pancreas, and brain. Alcohol metabolism itself significantly interferes with bioenergetic pathways in tissues, particularly the liver. Alcohol decreases states of respiration in the electron transport chain, and activity and expression of respiratory complexes, with a net effect to decrease ATP content. …

Energy Drink Usage By Students Attending An Online University, Jodi Lynn Hutak, Ali Boolani, Lauri O. Byerley

School of Medicine Faculty Publications

Objective: This study determined the frequency, reasons for, and side effects of energy drinks (ED) consumption among online students. Participants: Students attending an online university. Methods: Participants were recruited by email and completed a 59-question survey about their prior months ED practices using a combination of validated surveys previously published examining similar constructs in on-campus students. Results: 307 students (age = 32.4 ± 6.5yrs) completed the survey, and 88% reported consuming EDs. Students’ reasons for consuming ED included school (p < .001), work (p < .001), an event/competition (p < .001), pick me up (p < .001), lack of rest (p < .001), more energy (p < .001), and staying awake while driving (p < .001). Only individuals who consumed > 10 ED/month reported side effects of headaches (p = .01) and speeding (p=.01). Conclusions: In our sample, a majority of …

Steap1-4 (Six-Transmembrane Epithelial Antigen Of The Prostate 1-4) And Their Clinical Implications For Prostate Cancer, Michael Xu, Latese Evans, Candice L Bizzaro, Fabio Quaglia, Cecilia E Verrillo, Li Li, Julia Stieglmaier, M J Schiewer, Lucia R Languino, William Kevin Kelly

Department of Urology Faculty Papers

Six-Transmembrane Epithelial Antigen of the Prostate 1-4 (STEAP1-4) compose a family of metalloproteinases involved in iron and copper homeostasis and other cellular processes. Thus far, five homologs are known: STEAP1, STEAP1B, STEAP2, STEAP3, and STEAP4. In prostate cancer, STEAP1, STEAP2, and STEAP4 are overexpressed, while STEAP3 expression is downregulated. Although the metalloreductase activities of STEAP1-4 are well documented, their other biological functions are not. Furthermore, the properties and expression levels of STEAP heterotrimers, homotrimers, heterodimers, and homodimers are not well understood. Nevertheless, studies over the last few decades have provided sufficient impetus to investigate STEAP1-4 as potential biomarkers and therapeutic …

Are We Compulsively Chasing Rainbows?, Olivier George, Serge H. Ahmed, Nicholas W. Gilpin

School of Medicine Faculty Publications

No abstract provided.

Health Promoting Self-Care: Evaluating The Impact Of Food And Fitness Challenge On The Physical And Psychological Health Of Healthcare Workers, Giancarlo Lyle-Edrosolo, Gena Oppenheim, Emily Enos, Marlon G Saria

2022 Southern California Nursing Research Conference

Background: The unprecedented rates of burnout, stress, and turnover amongst healthcare workers following the COVID-19 pandemic highlighted the importance of prioritizing caregiver physical and mental health. Despite a direct correlation between nurses with multiple health problems and turnover intention, literature searched over the last two decades yielded minimal results using terms such as, nurses and diet, fitness or exercise therapy. A recent study, which focused on female nurses, found an improvement in psychological health by addressing diet, while another found a decrease in occupational stress with an aerobics program. There is even less data to support the use of a …

Pathophysiology Of Aortic Stenosis, Melissa Lee

Nursing Student Class Projects (Formerly MSN)

Pathophysiology of Aortic Stenosis

Melissa J. Lee

Department of Nursing, Otterbein University

NURS 6810: Advanced Pathophysiology for the Advanced Practice Nurse

Dr. Deana Batross & Dr. Shivani Bhatnagar

July 29, 2022

Pathophysiology of Aortic Stenosis

Proper evaluation of co-morbidities is imperative for patient safety and successful outcomes for patients undergoing anesthesia. Aortic stenosis (AS) is one of the most complex diseases encountered in anesthesia, affecting five percent of older adults and ten percent of the 80-89-year-old-cohort (Joseph et al., 2017). The pathophysiological development of AS is the end result of an inflammatory process caused by endothelial damage from mechanical stress, …

Perioperative Risks Of The Patient With Heart Failure, Gabrielle Metoyer

Nursing Student Class Projects (Formerly MSN)

Perioperative Risks of the Patient with Heart Failure

Gabrielle Metoyer

Department of Nursing, Otterbein University

NURS 6810 – Advanced Pathophysiology

Dr. Deanna Batross and Dr. Shivani Bhatnagar

August 5, 2022

Abstract

According to the CDC (2020), heart failure occurs when the heart cannot pump enough blood and oxygen to support other organs in your body. Heart failure is an epidemic disease affecting 1-2% of the population worldwide (Schwinger, 2020). It is one of the leading causes of morbidity and mortality worldwide with an estimated 6.5 million adults with heart failure in the United States (Lo et al., 2021). Medical advances …

The Role Of Microglia In Neuroinflammation Of The Spinal Cord After Peripheral Nerve Injury, Tana S. Pottorf, Travis M. Rotterman, William M. Mccallum, Zoë A. Haley-Johnson, Francisco J. Alvarez

Neuroscience, Cell Biology & Physiology Faculty Publications

Peripheral nerve injuries induce a pronounced immune reaction within the spinal cord, largely governed by microglia activation in both the dorsal and ventral horns. The mechanisms of activation and response of microglia are diverse depending on the location within the spinal cord, type, severity, and proximity of injury, as well as the age and species of the organism. Thanks to recent advancements in neuro-immune research techniques, such as single-cell transcriptomics, novel genetic mouse models, and live imaging, a vast amount of literature has come to light regarding the mechanisms of microglial activation and alluding to the function …

Sinus Pauses And Asystole As A Rare Presentation Of Thyrotoxic Crisis: A Case Report, Christian Akem Dimala, Charnjeet Sandhu, Oreoluwa Oladiran, Agnieszka Mochon, William Finneran Iii

Transformative Medicine

Introduction

Thyroid crisis is a rare and life-threatening endocrine emergency characterized by exaggerated clinical manifestations of hyperthyroidism with cardiovascular manifestations being the most severe. Rhythm disturbances, sinus tachycardia and atrial fibrillation, are the commonest cardiac manifestations of severe thyrotoxicosis; however, asystole remains a very atypical and uncommon presentation. We present a case of thyrotoxicosis due to Grave’s disease complicated by multiple episodes of asystole.

Case Presentation

A 65-year-old female recently diagnosed with Grave’s disease presented to the hospital with recurrent episodes of syncope. Her hospital course was significant for atrial fibrillation with subsequent progression to sinus pauses and asystole spontaneously …

Lysosomal Zn 2+ Release Triggers Rapid, Mitochondria-Mediated, Non-Apoptotic Cell Death In Metastatic Melanoma, Wanlu Du, Mingxue Gu, Meiqin Hu, Timothy Nold, Prateeksunder Pinchi, Wei Chen, Michael Ryan, Ahmed Bannaga, Haoxing Xu

Medical Student Research Symposium

During tumor progression, lysosome function is often maladaptively upregulated to match the high energy demand required for cancer cell hyper-proliferation and invasion. Here, we report that mucolipin TRP channel 1 (TRPML1), a lysosomal Ca2+ and Zn2+ release channel that regulates multiple aspects of lysosome function, is dramatically upregulated in metastatic melanoma cells compared with normal cells. TRPML-specific synthetic agonists (ML-SAs) are sufficient to induce rapid (within hours) lysosomal Zn2+-dependent necrotic cell death in metastatic melanoma cells while completely sparing normal cells. ML-SA-caused mitochondria swelling and dysfunction lead to cellular ATP depletion. While pharmacological inhibition or genetic silencing of TRPML1 in …

Il-10 And Tgf-Β Increase Connexin-43 Expression And Membrane Potential Of Hl-1 Cardiomyocytes Coupled With Raw 264.7 Macrophages, Cora B. Cox, Mike Castro, Thomas L. Brown, Nancy J. Bigley

Neuroscience, Cell Biology & Physiology Faculty Publications

Cardiac resident macrophages facilitate electrical conduction by interacting with cardiomyocytes via connexin-43 (Cx43) hemichannels. Cx43 is critical for impulse propagation and coordination between muscle contractions. Cardiomyocyte electrophysiology can be altered when coupled with noncardiomyocyte cell types such as M2c tissue-resident macrophages. Using cocultures of murine HL-1 cardiomyocytes and RAW 264.7 macrophages, we examined the hypothesis that cytokine signals, TGF-β1 and IL-10, upregulate Cx43 expression at points of contact between the two cell types. These cytokine signals maintain the macrophages in an M2c anti-inflammatory phenotype, mimicking cardiac resident macrophages. The electrophysiology of cardiomyocytes was examined using di-8-ANEPPS potentiometric dye, which reflects …

Antigen Staining For Detection Of Muc13 And Muc16 Expression In Carcinoma Tissue, Jose A. Benitez

MEDI 9331 Scholarly Activities Clinical Years

MUC13 and MUC16 are epithelial expressed proteins implicated in various carcinomas. Overexpression of these biomarkers appear to play a role in tumor growth; this discovery has paved a road for multiple studies discussing the potential of targeting mucin proteins and optimize immunotherapy approaches against carcinomas. Our study serves to investigate the level of expression of MUC13 and MUC16 in cancerous and normal tissue and to discuss the implications our findings may have for the utilization of these biomarkers for cancer therapy.

Alcohol Impairs Immunometabolism And Promotes Naïve T Cell Differentiation To Pro-Inflammatory Th1 Cd4+ T Cells, Patrick M. Mcternan, Danielle E. Levitt, David A. Welsh, Liz Simon, Robert W. Siggins, Patricia E. Molina

School of Medicine Faculty Publications

CD4+ T cell differentiation to pro-inflammatory and immunosuppressive subsets depends on immunometabolism. Pro-inflammatory CD4+ subsets rely on glycolysis, while immunosuppressive Treg cells require functional mitochondria for their differentiation and function. Previous pre-clinical studies have shown that ethanol (EtOH) administration increases pro-inflammatory CD4+ T cell subsets; whether this shift in immunophenotype is linked to alterations in CD4+ T cell metabolism had not been previously examined. The objective of this study was to determine whether ethanol alters CD4+ immunometabolism, and whether this affects CD4+ T cell differentiation. Naïve human CD4+ T cells were plated on anti-CD3 coated plates with soluble anti-CD28, and …

Modulating Cardiac Remodeling After Myocardial Infarction, Upendra Chalise

Theses & Dissertations

Cardiac remodeling after myocardial infarction (MI) is indicated by infarct wall thinning, reduced ejection fraction, and dilation of the left ventricle (LV). Inflammation presides in the early days of MI as a key event in cardiac wound healing. Infiltration of inflammatory cells, predominantly neutrophils and macrophages, is stimulated by ischemic cardiomyocytes that secrete inflammatory cues. This dissertation focused on identifying factors that influence cardiac remodeling after MI. S100A9 is a neutrophil-derived factor identified that exacerbated infarct wall thinning and cardiac dilation by increasing neutrophil and macrophage infiltration. Similarly, murinoglobulin 1 (Mug1) and galectin (Lgals)3 were macrophage-derived factors identified that regulate …

Tourniquet-Induced Ischemia-Reperfusion Injury, Junliang Qian

Theses & Dissertations

Ischemia-reperfusion (IR) is a pathological condition characterized by an initial restriction of blood supply to an organ followed by subsequent restoration of reperfusion associated with exacerbation of tissue damage. For pre-hospital emergency situations and surgical procedures, tourniquet or femoral artery ligation are widely used to stop extremity hemorrhage or create a bloodless operating field. To fully evaluate the underlying mechanisms in IR pathophysiology and potential therapeutic options, we compared tourniquet- and femoral artery ligation-induced IR injuries in the hindlimb of mice. We found that tourniquet/IR-induced acute hindlimb injuries are more severe than those induced by femoral artery ligation/IR, including alteration …

Admission Pao2 And Mortality Among Pediatric Icu Patients And Critically Ill Subgroups, Cara Holton

Research Days

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Background and Objectives: Studies analyzing the association between hyperoxia and mortality in critically ill pediatric patients and those admitted after cardiac arrest are conflicting and limited by small sample sizes. The aim of this study is to evaluate the association between PaO2 on admission to the pediatric ICU and mortality in a heterogeneous, multicenter cohort and among subgroups of critically ill patients.

Methods/Design: A retrospective cohort study was conducted using data from Virtual Pediatric Systems (VPS) database. VPS is a clinical pediatric critical care database with over 135 participating hospitals in North America. All VPS …

Diurnal Regulation Of Exercise-Induced Myocardial Signaling And Transcription, Charli Aguilar

UNLV Theses, Dissertations, Professional Papers, and Capstones

Introduction: Exercise is well known for its many benefits on the body and most notably the heart. Recent emphasis, and significant resources, have been dedicated to elucidating the molecular mechanisms through which exercise exerts its pluripotent beneficial effects on health and the prevention of disease. A continuous evolution in this field has sought to modulate and optimize exercise in various ways to maximize the benefits. In recent years, a growing appreciation for the impact of circadian rhythms has gained traction and their influence on many essential biological functions have been integrated into exercise physiology (i.e. - chrono-exercise), as well as …

A Neurophysiological Investigation Of Listening Effort In Normal Hearing Adults Using Fnirs And Pupillometry, Jessica Defenderfer

Theses and Dissertations (ETD)

Real-world conversations are often accompanied by some sort of interference that challenges the clarity of the speaker’s message, causing listeners to exert more effort to understand speech. Previous research has demonstrated that when listening to speech becomes difficult, various regions of the brain are recruited beyond those which engage during optimal listening conditions. However, the neural correlates that underly listening effort are not fully understood. Importantly, the pupillary response can be used to index listening effort, such that pupil size increases with increasing cognitive demand. I proposed that pupillometry can be used to characterize the cortical response, such that changes …

Sight Deprivation And Metabolic Effects During The Ymca Bench Press Test, Kyle Cruz

UNLV Theses, Dissertations, Professional Papers, and Capstones

Several studies have investigated the effect of sensory deprivation, particularly sight. However, very few have demonstrated the impact of sight deprivation while exercising to cadence blindfolded. This study aimed to determine exercise performance during a common muscular endurance evaluation, the YMCA Bench Press Test (YBPT), while blindfolded compared to a sighted condition. Twenty-five healthy participants (11 male, 14 female, 168 ± 7.7cm, 68 ± 11.7kg, 23 ± 7.5% fat mass) were recruited from the University of Nevada, Las Vegas student populations and communities. After a YBPT familiarization session, participants completed testing in a counterbalanced order, following the same procedures. A …

At-Home Aerobic Exercise Improves Functional Ability Of Patients With Rheumatoid Arthritis With Limited Exercise Options, Daniel Harris

Clinical Research in Practice: The Journal of Team Hippocrates

A clinical decision report using

Neuberger GB, Aaronson LS, Gajewski B, et al. Predictors of exercise and effects of exercise on symptoms, function, aerobic fitness, and disease outcomes of rheumatoid arthritis. Arthritis Rheum. 2007;57(6):943-952. https://doi.org/10.1002/art.22903

and its application for a patient with rheumatoid arthritis.