Medical Sciences Commons^™

Outcomes Of Mechanical Thrombectomy In Anticoagulated Patients With Acute Distal And Medium Vessel Stroke, Hamza Salim, Basel Musmar, Nimer Adeeb, Vivek Yedavalli, Dhairya Lakhani, Sahibjot Singh Grewal, Kareem El Naamani, Nils Henninger, Sri Hari Sundararajan, Anna Luisa Kühn, Jane Khalife, Sherief Ghozy, Luca Scarcia, Benjamin Yq Tan, Robert W Regenhardt, Jeremy J Heit, Nicole M Cancelliere, Joshua D Bernstock, Aymeric Rouchaud, Jens Fiehler, Sunil Sheth, Ajit S Puri, Christian Dyzmann, Marco Colasurdo, Xavier Barreau, Leonardo Renieri, João Pedro Filipe, Pablo Harker, Răzvan Alexandru Radu, Mohamad Abdalkader, Piers Klein, Thomas R Marotta, Julian Spears, Takahiro Ota, Ashkan Mowla, Pascal Jabbour, Arundhati Biswas, Frédéric Clarençon, James E Siegler, Thanh N Nguyen, Ricardo Varela, Amanda Baker, Muhammed Amir Essibayi, David Altschul, Nestor R Gonzalez, Markus A Möhlenbruch, Vincent Costalat, Benjamin Gory, Christian Paul Stracke, Mohammad Ali Aziz-Sultan, Constantin Hecker, Hamza Shaikh, David S Liebeskind, Alessandro Pedicelli, Andrea M Alexandre, Illario Tancredi, Tobias D Faizy, Erwah Kalsoum, Boris Lubicz, Aman B Patel, Vitor Mendes Pereira, Adrien Guenego, Adam A Dmytriw, Mad Mt Investigators

Faculty, Staff and Student Publications

Background: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood.

Methods: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, …

Ecological And Pathological Applications Of The Heat Shock Response, Taylor Rae Stanley

Theses and Dissertations

The heat shock response (HSR) is a cytoprotective stress response pathway that regulates cellular proteostasis. The HSR is an evolutionarily conserved pathway that is essential for normal cellular functioning. Here, we explore the broad ecological and pathological impacts of the HSR. In an ecological context, we perform gene level analysis of the transcriptomes of two closely related sunfish. We found that the more invasive bluegill sunfish has gene expansions in two HSR gene families, the HSP70 family and the HSP90 family compared to the redear sunfish. These gene expansions were also observed in several other teleost fish species and were …

Blood Biomarkers In Down Syndrome: Facilitating Alzheimer's Disease Detection And Monitoring, Melissa Petersen, Lisi Flores-Aguilar, Elizabeth Head, Laia Montoliu-Gaya, Andre Strydom, Sarah Pape, Juan Fortea, Nicholas Ashton, Chinedu Momoh, Sid O'Bryant

Brain and Mind Institute

Blood-based biomarkers continue to be explored for disease detection, monitoring of progression, and therapeutic outcomes as the diagnostic determination of Alzheimer's Disease in Down Syndrome (DS-AD) remains challenging in clinical settings. This perspective highlights the current status of this effort. Overall, amyloid (A), tau (T), and neurodegeneration (AT[N]) blood-based biomarkers have been shown to increase with disease pathology for individuals with DS. Phosphorylated tau biomarkers (p-tau217, p-tau181) have been consistently shown to track disease progression for DS-AD and are likely good candidates for use in clinical settings. Biomarkers of inflammation (glial fibrillary acidic protein) also show promise; however, additional work …

Cardiomegaly Status After Open Repair Of An Arch Aneurysm, Lucas Ribé Bernal, Rana O Afifi, Anthony L Estrera

Faculty, Staff and Student Publications

This report describes a patient with a thoracic aortic aneurysm who presented with chest pain and dyspnea. Preoperative studies revealed a massive cardiomediastinal silhouette. Within hours after the operation, a profound reduction in cardiomegaly was observed. Herein, we describe the distinctive imaging and technical aspects of the surgical procedure.

Endovascular Thrombectomy For Childhood Stroke (Save Childs Pro): An International, Multicentre, Prospective Registry Study, Peter B Sporns, Kartik Bhatia, Todd Abruzzo, Lisa Pabst, Stuart Fraser, Melissa G Chung, Warren Lo, Ahmed Othman, Sebastian Steinmetz, Ulf Jensen-Kondering, Stefan Schob, Daniel P O Kaiser, Wolfgang Marik, Christina Wendl, Ilka Kleffner, Hans Henkes, Hermann Kraehling, Thi Dan Linh Nguyen-Kim, René Chapot, Umut Yilmaz, Furene Wang, Muhammad Ubaid Hafeez, Flavio Requejo, Nicola Limbucci, Birgit Kauffmann, Markus Möhlenbruch, Omid Nikoubashman, Peter D Schellinger, Patricia Musolino, Ali Alawieh, Jenny Wilson, Dominik Grieb, Alexandra S Gersing, Thomas Liebig, Martin Olivieri, Jaroslava Paulasova Schwabova, Ales Tomek, Panagiotis Papanagiotou, Grégoire Boulouis, Olivier Naggara, Christine K Fox, Kirill Orlov, Alexandra Kuznetsova, Carmen Parra-Farinas, Prakash Muthusami, Robert W Regenhardt, Adam A Dmytriw, Tanja Burkard, Mesha Martinez, Daniel Brechbühl, Maja Steinlin, Lisa R Sun, Ameer E Hassan, André Kemmling, Sarah Lee, Heather J Fullerton, Jens Fiehler, Marios-Nikos Psychogios, Moritz Wildgruber

Faculty, Staff and Student Publications

Background: Emerging evidence suggests that endovascular thrombectomy is beneficial for treatment of childhood stroke, but the safety and effectiveness of endovascular thrombectomy has not been compared with best medical treatment. We aimed to prospectively analyse functional outcomes of endovascular thrombectomy versus best medical treatment in children with intracranial arterial occlusion stroke.

Methods: In this prospective registry study, 45 centres in 12 countries across Asia and Australia, Europe, North America, and South America reported functional outcomes for children aged between 28 days and 18 years presenting with arterial ischaemic stroke caused by a large-vessel or medium-vessel occlusion who received either endovascular …

Biomechanics And Clinical Implications Of Fontan Upsizing, Vijay Govindarajan, Akshita Sahni, Emily Eickhoff, Peter Hammer, David M Hoganson, Rahul H Rathod, Pedro J Del Nido

Faculty, Staff and Student Publications

Background: The Fontan operation, a palliative procedure for single ventricle patients, has evolved to improve outcomes and reduce complications. While extracardiac conduit (ECC) is favored for its simplicity and potential hemodynamic benefits, concerns arise about conduit size adequacy over time. Undersized ECC conduits may cause hemodynamic inefficiencies and long-term complications, while oversizing can lead to flow disturbances, stagnation, and thrombosis, necessitating surgical revision or upsizing to optimize hemodynamics.

Objectives: The study aimed to predict the impact of upsizing by developing a patient-specific workflow using cardiac magnetic resonance-based imaging and computational fluid dynamics to assess Fontan hemodynamic changes and determine the …

Resolution Of Painful Trichodysplasia Spinulosa With Topical Cidofovir: Case Report, Kevin M Burningham, Ritu N Swali, Peter L Rady, Anisha B Patel, Stephen K Tyring

Faculty, Staff and Student Publications

Purpose: Trichodysplasia spinulosa (TS) is a rare, disfiguring skin condition which presents with widespread asymptomatic or pruritic, skin-colored papules with white protruding keratin spiculations in immunocompromised individuals. Due to its rarity, there is little data to guide treatment decisions. The purpose of this article is to report a case of TS that completely resolved after treatment with topical cidofovir.

Materials and methods: A 19-year-old immunosuppressed female presented with widespread painful, itchy bumps on the nose and face. Upon examination, there were erythematous papules with hyperkeratinized spicules affecting the central face. Biopsy of the lesions was consistent with TS which was …

Genetic Testing And Anorexia Nervosa: Knowledge, Attitudes And Awareness, Sarah Ramsay

All Dissertations

This dissertation consists of three parts, each building on the results of the former, evaluating the treatment and research of anorexia nervosa (AN) from a healthcare genetics perspective. These three parts are bookended by an introduction and a conclusion summarizing key findings and providing suggestions for future work. First, in order to assess how Severe and Enduring Anorexia Nervosa (SE-AN) is defined in the literature, and inclusion of those with SE-AN in genetics research, a comprehensive literature review was performed. The review found a lack of consistent identification and inclusion of the SE-AN subtype in AN genetic study participants. Second, …

Chatgpt Vs Expert-Guided Care Pathways For Postesophagectomy Symptom Management, Mohamad K Abou Chaar, Giovanna Grigsby-Rocca, Ming Huang, Shanda H Blackmon

Faculty, Staff and Student Publications

BACKGROUND: The objective of this study was to compare generative artificial intelligence-initiated care pathways, using ChatGPT, with expert-guided consensus-initiated care pathways from AskMayoExpert (AME) for symptom management of esophageal cancer patients after esophagectomy.

METHODS: A formal protocol for development of 9 AME care pathways was followed for specific patient-identified domains after esophagectomy for esophageal cancer. Domain scores were measured and assessed through the Upper Digestive Disease tool. These care pathways were developed by experts validated by a consensus-driven methodology. ChatGPT was used to answer specific questions similar to the AME care pathway on April 9, 2023, and March 28, 2024. …

Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior

Saha Cardiovascular Research Center Faculty Publications

Abstract The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity. APOA2 likewise increased the cholesterol efflux capacity of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up …

Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler

Saha Cardiovascular Research Center Faculty Publications

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein …

Tissue Plasminogen Activator Associated Pulmonary Hemorrhage In Patient With Acta2-Associated Arteriopathy, Travis G. Hughes, Mark A. Wurth, Mary Burchett Sheppard

Saha Cardiovascular Research Center Faculty Publications

Pulmonary hemorrhage after administration of tissue plasminogen activator (tPA) is a rare complication. We present a 15- year-old boy with a heterozygous pathogenic variant in ACTA2 who presented with right brachial artery aneurysm thrombosis treated initially with tPA, resulting in pulmonary hemorrhage. We hypothesize that the underlying pulmonary abnormalities caused by the pathogenic ACTA2 variant may be a risk factor for pulmonary hemorrhage after tPA administration. (J Vasc Surg Cases Innov Tech 2024;10:101558.)

Cyp1b1-Rmdn2 Alzheimer’S Disease Endophenotype Locus Identified For Cerebral Tau Pet, Kwangsik Nho, Shannon L. Risacher, Liana G. Apostolova, Paula J. Bice, Jared R. Brosch, Rachael Deardorff, Kelley Faber, Martin R. Farlow, Tatiana Foroud, Sujuan Gao, Thea Rosewood, Jun Pyo Kim, Kelly Nudelman, Meichen Yu, Paul Aisen, Reisa Sperling, Basavaraj Hooli, Sergey Shcherbinin, Diana Svaldi, Clifford R. Jack, William J. Jagust, Susan Landau, Aparna Vasanthakumar, Tenielle Porter, Vincent Doré, Simon M. Laws

Research outputs 2022 to 2026

Determining the genetic architecture of Alzheimer’s disease pathologies can enhance mechanistic understanding and inform precision medicine strategies. Here, we perform a genome-wide association study of cortical tau quantified by positron emission tomography in 3046 participants from 12 independent studies. The CYP1B1-RMDN2 locus is associated with tau deposition. The most significant signal is at rs2113389, explaining 4.3% of the variation in cortical tau, while APOE4 rs429358 accounts for 3.6%. rs2113389 is associated with higher tau and faster cognitive decline. Additive effects, but no interactions, are observed between rs2113389 and diagnosis, APOE4, and amyloid beta positivity. CYP1B1 expression is upregulated in AD. …

Pain Prevalence, Intensity, And Association With Neuropsychiatric Symptoms Of Dementia In Immigrant And Non-Immigrant Aged Care Residents In Australia, Pelden Chejor, Mustafa Atee, Patricia Cain, Daniel Whiting, Thomas Morris, Davina Porock

Research outputs 2022 to 2026

Pain recognition for culturally diverse people is complex as pain experience is subjective and influenced by cultural background. We compared the prevalence, intensity, and association of pain with neuropsychiatric symptoms (NPS) between immigrants and non-immigrants living with dementia in residential aged care homes (RACHs) who were referred to two Dementia Support Australia programs. Immigrant status was defined by the documented country of birth. Pain and NPS were assessed using PainChek® and the Neuropsychiatric Inventory, respectively. Subgroup analyses were also completed for English-speaking and non-English-speaking immigrants. A total of 17,637 referrals [immigrants, n = 6340; non-immigrants, n = 11,297] from 2792 …

Accelerating Heritability, Genetic Correlation, And Genome-Wide Association Imaging Genetic Analyses In Complex Pedigrees, Brian Donohue, Si Gao, Thomas E. Nichols, Bhim M. Adhikari, Yizhou Ma, Neda Jahanshad, Francis J. Mcmahon, Elizabeth M. Humphries, William Burroughs, John Blangero

School of Medicine Publications

National and international biobanking efforts led to the collection of large and inclusive imaging genetics datasets that enable examination of the contribution of genetic and environmental factors to human brains in illness and health. High-resolution neuroimaging (~104–6 voxels) and genetic (106–8 single nucleotide polymorphic [SNP] variants) data are available in statistically powerful (N = 103–5) epidemiological and disorder-focused samples. Performing imaging genetics analyses at full resolution afforded in these datasets is a formidable computational task even under the assumption of unrelatedness among the subjects. The computational complexity rises as ~N2–3 (where N is the sample size), when …

Genome-Wide Cross-Disease Analyses Highlight Causality And Shared Biological Pathways Of Type 2 Diabetes With Gastrointestinal Disorders, Emmanuel O. Adewuyi, Tenielle Porter, Eleanor K. O’Brien, Oladapo Olaniru, Giuseppe Verdile, Simon M. Laws

Research outputs 2022 to 2026

Studies suggest links between diabetes and gastrointestinal (GI) traits; however, their underlying biological mechanisms remain unclear. Here, we comprehensively assess the genetic relationship between type 2 diabetes (T2D) and GI disorders. Our study demonstrates a significant positive global genetic correlation of T2D with peptic ulcer disease (PUD), irritable bowel syndrome (IBS), gastritis-duodenitis, gastroesophageal reflux disease (GERD), and diverticular disease, but not inflammatory bowel disease (IBD). We identify several positive local genetic correlations (negative for T2D – IBD) contributing to T2D’s relationship with GI disorders. Univariable and multivariable Mendelian randomisation analyses suggest causal effects of T2D on PUD and gastritis-duodenitis and …

Clearance And Transport Of Amyloid Β By Peripheral Monocytes Correlate With Alzheimer’S Disease Progression, Xin Huang, Chris Fowler, Yihan Li, Qiao Xin Li, Jiaqi Sun, Yijun Pan, Liang Jin, Keyla A. Perez, Céline Dubois, Yen Y. Lim, Candace Drysdale, Rebecca L. Rumble, Holly R. Chinnery, Christopher C. Rowe, Ralph N. Martins, Paul Maruff, James D. Doecke, Yong Lin, Abdel A. Belaidi, Kevin J. Barnham, Colin L. Masters, Ben J. Gu

Research outputs 2022 to 2026

Impaired clearance of amyloid β (Aβ) in late-onset Alzheimer’s disease (AD) affects disease progression. The role of peripheral monocytes in Aβ clearance from the central nervous system (CNS) is unclear. We use a flow cytometry assay to identify Aβ-binding monocytes in blood, validated by confocal microscopy, Western blotting, and mass spectrometry. Flow cytometry immunophenotyping and correlation with AD biomarkers are studied in 150 participants from the AIBL study. We also examine monocytes in human cerebrospinal fluid (CSF) and their migration in an APP/PS1 mouse model. The assay reveals macrophage-like Aβ-binding monocytes with high phagocytic potential in both the periphery and …

Impact Of Human Immunoglobulin Genetic Variants On The Expressed Antibody Repertoire., Eric Engelbrecht

Electronic Theses and Dissertations

B cells produce immunoglobulins (IGs; antibodies), which are critical protein components of the immune system. Human IGs are composed of two pairs of identical ‘heavy’ chains and ‘light’ kappa or lambda chains, encoded by genes located at three loci in the genome: the IG heavy chain locus (IGH, chromosome 14), and the IG lambda (IGL, chromosome 22) and kappa (IGK, chromosome 2) loci. Each locus spans ~920-100 kilobase pairs (Kbp) of DNA and harbors families of gene segments that are somatically rearranged during B cell development. The IG loci collectively harbor >180 functional genes, many of which are part of …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Center for Medical Ethics and Health Policy Staff Publications

Introduction: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

Methods: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

Results: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10-8). Subgroup-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and non-coding variants in the region. Common variants in LINC00320 were observed associated with AD in Black individuals (p = 1.9 × 10-9). Finally, we observed rare non-coding variants in the promoter of TOMM40 distinct of APOE in pooled-population analyses (p = 7.2 × 10-8).

Discussion: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

Highlights: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Radiation-Induced Macrovessel/Microvessel Disease, Jun-Ichi Abe, Bryan G Allen, Andreas M Beyer, David Lewandowski, Kranti A Mapuskar, Vikram Subramanian, Michelle R Tamplin, Isabella M Grumbach

Faculty, Staff and Student Publications

Radiation therapy (RT) is a cornerstone in cancer treatment (used in 50% of cases), yet challenges persist because damage to normal tissue through direct impact of radiation or bystander effects is inevitable. Injury of macrovessels by RT manifests as obstructive disease, which is akin to atherosclerotic disease. Historically observed in coronary arteries of patients treated for breast cancer and lymphoma, it also affects patients receiving contemporary therapy for lung and chest cancers. Moreover, radiation at various sites can lead to peripheral vascular disease. An aspect of radiation-induced injury that has received little attention is microvascular injury, which typically results from …

Microbiome Variation In Production Phenotypes And The Role Of Colonization History In Microbiome Establishment, Seidu Adams

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Ruminant-based agriculture is expected to continue to be a major contributor to food security to feed the growing population. At the heart of nutrient degradation of complex organic matter within the rumen are its microbes. These microbes can convert otherwise unusable organic matter into usable protein and energy and can provide up to 50% of the animal’s protein needs and up to 70% of the energy needs. The microbial functional capacity within the rumen determines the nutrients utilized and the end products of fermentation. However, our understanding of microbial functional capacity within the rumen and factors that influence the rumen …

Novel Mouse Models To Study The Role Of T Cells In Cardiac Autoimmunity, Meghna Sur

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Myocarditis patients can chronically develop dilated cardiomyopathy and autoreactive T cells could contribute to the disease pathogenesis, but defining their antigen specificity remains a major challenge. To fill this gap, we generated T cell receptor (TCR) transgenic (Tg) mice specific to cardiac myosin heavy chain (Myhc)-α 334–352 and made a few observations. First, we unexpectedly noted both CD4 and CD8 T cells expressing TCRs specific to Myhc-α 334–352. Second, while Tg T cells from myocarditis-resistant C57BL/6J mice did not respond to Myhc-α 334–352, those from immunized mice responded, indicating that in vivo priming is necessary to break tolerance. Third, upon …

Enhancement Of Zika Virus Infection By West Nile And Dengue Virus Antibody Positive Cord-Blood Samples From Mothers In El Paso-Texas, Jeanette Orbegozo

Open Access Theses & Dissertations

The recent Zika virus (ZIKV) outbreak and its association with microcephaly cases and other neurological syndromes are important public health concerns. A phenomenon known as antibody-dependent enhancement (ADE) involves preexisting flavivirus antibodies to a specific flavivirus that enhances the severity of a second infection with a different flavivirus. Since ZIKV is related to flaviviruses like West Nile virus (WNV) and dengue virus (DENV), prior exposure to these viruses could elicit cross-reactive antibodies that may enhance a subsequent ZIKV infection. Therefore, this study aimed to determine if WNV and DENV antibodies from cord blood enhanced ZIKV infection in vitro. Initially, a …

Novel Therapuetic Approaches For Chagas Disease, Juan Carlos Silva

Open Access Theses & Dissertations

Chagas disease (CD) is caused by the hemoflagellate protozoan Trypanosoma cruzi. This disease is considered one of the 20 neglected tropical diseases (NTD), and it is estimated that 6 to 8 million people worldwide are diagnosed with CD. In the United States, Chagas infection is not reported in all states; however, most reported CD cases are chronic infections. Chagas infection is characterized by two phases: an acute and a chronic phase. Until this present moment, no prophylactic or therapeutic human vaccine is available. However, in a recent study in a murine model, our group showed that the synthetic 20-merpeptide (DAENPGGEVFNDNKKGLSRV) …

Implementing The Methodology To Generate Diagnostic And Therapeutic Antibodies, Andrea Mariana Carlin

Open Access Theses & Dissertations

This research aimed to establish the methodology for developing monoclonal antibodies at The University of Texas at El Paso. Monoclonal antibodies are indispensable across multiple fields, including diagnostics, therapeutics, and biotechnology, yet there is a shortage of commercially available antibodies targeting specific proteins or possessing specialized characteristics. To address this gap, three models were selected: a peptide derived from the intracellular protein Schlafen 8 and two cell surface protein receptors: mouse vascular endothelial growth factor receptor 2 (VEGFR2) and human melanocortin receptor 4 (MC4R). These proteins present unique challenges in antibody generation, including issues of accessibility, expression, and specificity.

Throughout …

Hunting For Heroes: Brain Neurons Mediating Glp-1r Agonists In Obesity Treatment, Yuhan Cao, Qingchun Tong

Faculty, Staff and Student Publications

Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RAs) have proven to be highly effective in reducing obesity across species and ages, gaining unmet popularity in clinical treatments against obesity. Although extensive research efforts have been made to explore how the brain regulates body weight homeostasis including the effect brought up by GLP-1 and its synthetic analogs GLP-1RAs, the identity of neurons and neural pathways that are responsible for the observed anti-obesity effect of GLP-1RAs remain largely elusive. Excitingly, three recent high-profile studies presented compelling evidence that each argues for the importance of GLP-1Rs in the dorsomedial hypothalamus, hindbrain, or lateral septum, …

Nasal Virus Infection Induces Asthma Exacerbation Through B-Cell-Dependent Recruitment Of Inflammatory Monocytes, Kody A Waldstein, Arman Issimov, Maria Ganama, Valerie Jinge, Stephen Tilley, Xiaoyang Hua

Faculty, Staff and Student Publications

Background: Upper respiratory viral infections (URVIs) are responsible for 80% of asthma exacerbation episodes. However, the underlying mechanisms remain poorly understood.

Methods: In this study, we used a mouse model of URVI and examined the impact of URVI on asthma phenotypes and the underlying mechanisms.

Results: Previously, we have reported that nasal-restricted infection with respiratory syncytial virus (RSV) only produces mild sino-nasal inflammation and mucus production, without causing direct lung infection. However, such nasal-restricted infection dramatically enhanced TH2 and TH17 inflammatory responses in the lungs and increased airway hyperresponsiveness (AHR) in mice with house dust mite (HDM)-induced asthma. Additionally, nasal-restricted …

Evaluating Novel In Silico Tools For Accurate Pathogenicity Classification In Epilepsy-Associated Genetic Missense Variants, Ludovica Montanucci, Tobias Brünger, Christian M Boßelmann, Alina Ivaniuk, Eduardo Pérez-Palma, Samden Lhatoo, Costin Leu, Dennis Lal

Faculty, Staff and Student Publications

Objective: Determining the pathogenicity of missense variants in clinical genetic tests for individuals with epilepsy is crucial for guiding personalized treatment. However, achieving a definitive pathogenic classification remains challenging, with most missense variants still classified as variants of uncertain significance (VUS) and with the availability of many computational tools which may provide conflicting predictions. Here, we aim to evaluate the performance of state-of-the-art computational tools in pathogenicity prediction of missense variants in epilepsy-associated genes. This will assist in selecting the most appropriate tool and critically assess their use in clinical setting.

Methods: We assessed the performance of nine in silico …

Brain Gray Matter Changes In Children At Risk For Sudden Unexpected Death In Epilepsy, Bhaswati Roy, Jennifer A Ogren, Luke A Allen, Beate Diehl, Raman Sankar, Samden D Lhatoo, Rajesh Kumar, Ronald M Harper

Faculty, Staff and Student Publications

Background: Potential failing adult brain sites, stratified by risk, mediating Sudden Unexpected Death in Epilepsy (SUDEP) have been described, but are unknown in children.

Methods: We examined regional brain volumes using T1-weighted MRI images in 21 children with epilepsy at high SUDEP risk and 62 healthy children, together with SUDEP risk scores, calculated from focal seizure frequency. Gray matter tissue type was partitioned, maps normalized, smoothed, and compared between groups (SPM12; ANCOVA; covariates, age, sex, and BMI). Partial correlations between regional volumes and seizure frequency were examined (SPM12, covariates, age, sex, and BMI); 67% were at high risk for SUDEP. …

Occluder Device Removal And Total Septation Of "Swiss-Cheese" Ventricular Septal Defects, Andrew K Morse, Julija Dobrila, Damien J Lapar, Jorge D Salazar

Faculty, Staff and Student Publications

"Swiss-cheese" ventricular septal defects present complex treatment challenges. Despite difficult defect visualization and closure, complete septation is the treatment of choice. We present the case of a 2-year-old with residual apical "Swiss-cheese" ventricular septal defects after failed percutaneous device closure with 2 occluder devices. Surgical removal of 1 device and primary closure of the defects via right apical ventriculotomy resulted in successful complete septation.