Digital Commons Network^™

Video Discharge Instructions Increase Patient Understanding For Office-Based Procedures: A Randomized Controlled Study, Jenna Bates Maffei, Jeffrey J Song, Gal Saffati, Mohit Khera

Faculty, Staff and Students Publications

Background: Health literacy significantly influences healthcare outcomes, with poor literacy leading to worse quality of life, increased mortality, and higher readmission rates. Recent efforts to improve post-encounter education include structured teach-back methods, patient preference assessments, and standardized discharge instructions. Studies in emergency departments have shown that incorporating video discharge instructions enhances patient understanding and retention of care information. To address the gap in urology, this study aims to evaluate patient comprehension and satisfaction with video discharge instructions following clinic-based vasectomy procedures.

Methods: We performed an Institutional Review Board approved (#H-51614) unblinded randomized controlled study with written consent from each participant. …

Characterization Of Hepatic Pathology During Azoxymethane-Induced Acute Liver Failure, Shadikchhya Maya Bhattarai, Ashwin Jhawer, Gabriel Frampton, Eleonora Troyanovskaya, Sharon Demorrow, Matthew Mcmillin

Faculty, Staff and Students Publications

Background: Acute liver failure (ALF) is a loss of liver function due to a severe hepatic insult. Studies utilizing the azoxymethane (AOM) mouse model of ALF, which also generates hepatic encephalopathy, have primarily focused on development of neurological deficits. However, the molecular processes that generate liver damage have not been fully characterized. Therefore, a more comprehensive characterization of the hepatic consequences of AOM toxicity is needed to better understand this disease model.

Aim: To identify molecular pathology contributing to hepatic injury during the progression of AOM-induced ALF.

Methods: C57BL/6 mice were injected with AOM to produce ALF and hepatic encephalopathy. …

An In Vivo Screen Identifies Nat10 As A Master Regulator Of Brain Metastasis, Jocelyn F Chen, Peng Xu, Wesley L Cai, Huacui Chen, Emily Wingrove, Xiaojian Shi, Wenxue Li, Giulia Biancon, Meiling Zhang, Amer Balabaki, Ethan D Krop, Elianna Asare, Yangyi Zhang, Mingzhu Yin, Toma Tebaldi, Jordan L Meier, Thomas F Westbrook, Stephanie Halene, Yansheng Liu, Hongying Shen, Don X Nguyen, Qin Yan

Faculty, Staff and Students Publications

Emerging evidence has shown that epigenetic regulation plays a fundamental role in cancer metastasis, the major cause of cancer-related deaths. Here, we conducted an in vivo screen for vulnerabilities of brain metastasis and identified N-acetyltransferase 10 (NAT10) as a driver of brain metastasis. Knockdown of NAT10 restrains cancer cell proliferation and migration in vitro and tumor growth and brain metastasis in vivo. The poorly characterized RNA helicase domain of NAT10 is critical for cell growth in vitro, while both RNA helicase and NAT domains are essential for primary tumor growth and brain metastasis in vivo. Mechanically, NAT10 promotes the …

Combined Targeting Of Glioblastoma Stem Cells Of Different Cellular States Disrupts Malignant Progression, Chenfei Lu, Tao Kang, Junxia Zhang, Kailin Yang, Yang Liu, Kefan Song, Qiankun Lin, Deobrat Dixit, Ryan C Gimple, Qian Zhang, Zhumei Shi, Xiao Fan, Qiulian Wu, Daqi Li, Danyang Shan, Jiancheng Gao, Danling Gu, Hao You, Yangqing Li, Junlei Yang, Linjie Zhao, Zhixin Qiu, Hui Yang, Ningwei Zhao, Wei Gao, Weiwei Tao, Yingmei Lu, Yun Chen, Jing Ji, Zhe Zhu, Chunsheng Kang, Jianghong Man, Sameer Agnihotri, Qianghu Wang, Fan Lin, Xu Qian, Stephen C Mack, Zhibin Hu, Chaojun Li, Michael D Taylor, Ning Liu, Nu Zhang, Ming Lu, Yongping You, Jeremy N Rich, Wei Zhang, Xiuxing Wang

Faculty, Staff and Students Publications

Glioblastoma (GBM) is the most lethal primary brain tumor with intra-tumoral hierarchy of glioblastoma stem cells (GSCs). The heterogeneity of GSCs within GBM inevitably leads to treatment resistance and tumor recurrence. Molecular mechanisms of different cellular state GSCs remain unclear. Here, we find that classical (CL) and mesenchymal (MES) GSCs are enriched in reactive immune region and high CL-MES signature informs poor prognosis in GBM. Through integrated analyses of GSCs RNA sequencing and single-cell RNA sequencing datasets, we identify specific GSCs targets, including MEOX2 for the CL GSCs and SRGN for the MES GSCs. MEOX2-NOTCH and SRGN-NFκB axes play important …

Effects Of Intensive Blood Pressure Treatment On Orthostatic Hypertension: Individual Level Meta-Analysis, Stephen P Juraschek, Jiun-Ruey Hu, Jennifer L Cluett, Carol Mita, Lewis A Lipsitz, Lawrence J Appel, Nigel S Beckett, Barry R Davis, Rury R Holman, Edgar R Miller, Kenneth J Mukamal, Ruth Peters, Jan A Staessen, Addison A Taylor, Jackson T Wright, William C Cushman

Faculty, Staff and Students Publications

Objective: To determine the effects of intensive blood pressure treatment on orthostatic hypertension.

Design: Systematic review and individual participant data meta-analysis.

Data sources: MEDLINE, Embase, and Cochrane CENTRAL databases through 13 November 2023.

Inclusion criteria: Population: ≥500 adults, age ≥18 years with hypertension or elevated blood pressure; intervention: randomized trials of more intensive antihypertensive drug treatment (lower blood pressure goal or active agent) with duration ≥6 months; control: less intensive antihypertensive drug treatment (higher blood pressure goal or placebo); outcome: measured standing blood pressure.

Main outcomes: Orthostatic hypertension, defined as an increase in systolic blood pressure ≥20 mm Hg or …

Haploinsufficiency Of Itsn1 Is Associated With A Substantial Increased Risk Of Parkinson’S Disease, Thomas P Spargo, Chloe F Sands, Isabella R Juan, Jonathan Mitchell, Vida Ravanmehr, Jessica C Butts, Ruth B De-Paula, Youngdoo Kim, Fengyuan Hu, Quanli Wang, Dimitrios Vitsios, Manik Garg, Lawrence Middleton, Michal Tyrlik, Mirko Messa, Guillermo Del Angel, Daniel G Calame, Hiba Saade, Laurie Robak, Ben Hollis, Vishnu A Cuddapah, Huda Y Zoghbi, Joshua M Shulman, Slavé Petrovski, Ismael Al-Ramahi, Ioanna Tachmazidou, Ryan S Dhindsa

Faculty, Staff and Students Publications

Despite its significant heritability, the genetic basis of Parkinson's disease (PD) remains incompletely understood. Here, in analyzing whole-genome sequence data from 3,809 PD cases and 247,101 controls in the UK Biobank, we discover that protein-truncating variants in ITSN1 confer a substantially increased risk of PD (p = 6.1 × 10

Ovarian-Specific Cyp17a1 Overexpression In Female Mice: A Novel Model Of Endogenous Testosterone Excess, Serene Joseph, Vaibhave Ubba, Zhiqiang Wang, Mingxiao Feng, Milan K Dsilva, Sofia Suero, Danielle Waheed, Nathaniel W Snyder, Xiaofeng Yang, Hong Wang, Joanne S Richards, Chemyong J Ko, Sheng Wu

Faculty, Staff and Students Publications

Excessive androgen levels can severely affect female health. However, most existing models of androgen excess rely on exogenous androgen administration, which does not fully capture the effect of elevated local ovarian testosterone on reproductive and metabolic functions. Here, we report the development of a novel hyperandrogenic mouse model, Cyp17TM-625, generated by combining CRISPR-Cas9 and a Tet-On doxycycline system to induce Cyp17A1 overexpression in ovarian theca-interstitial cells. As a result, Cyp17TM-625 mice exhibited significantly elevated Cyp17A1 messenger RNA and protein levels, accompanied by increased testosterone concentrations without alterations in basal levels of estradiol, progesterone, luteinizing hormone, or follicle-stimulating hormone. These mice …

Antimicrobial Performance Of A Novel Drug-Eluting Bioenvelope, Zerelda Esquer Garrigos, Sunil Kapur, Michelle Leroux Williams, M Rizwan Sohail

Faculty, Staff and Students Publications

No abstract provided.

Emerging Clostridioides Difficile Ribotypes Have Divergent Metabolic Phenotypes, Firas S Midani, Heather A Danhof, Nathanael Mathew, Colleen K Ardis, Kevin W Garey, Jennifer K Spinler, Robert A Britton

Faculty, Staff and Students Publications

Clostridioides difficile is a gram-positive spore-forming pathogen that commonly causes diarrheal infections in the developed world. Although C. difficile is a genetically diverse species, certain ribotypes are overrepresented in human infections, and it is unclear if metabolic adaptations are essential for the emergence of these epidemic ribotypes. To identify ribotype-specific metabolic differences, we therefore tested carbon substrate utilization by 88 C. difficile isolates and looked for differences in growth between 22 ribotypes. As expected, C. difficile was capable of growing on a variety of carbon substrates. Further, C. difficile strains clustered by phylogenetic relationship and displayed ribotype-specific and clade-specific …

Author Correction: Generation Of A Tree Shrew Breast Cancer Model Using Lentivirus Expressing Pik3ca-H1047r, Li Zeng, Hong-Yan Zhang, Chuan-Yu Yang, Zhuo Cheng, Qiu-Yun Jiang, Yao Luo, Yi Li, Fu-Bing Li, Ce-Shi Chen

Faculty, Staff and Students Publications

No abstract provided.

Best Practices For Imaging Of Transcatheter Valve Failure: An Update From The Heart Valve Collaboratory, Omar K Khalique, Syed Zaid, Gilbert H L Tang, Mohamed Abdel-Wahab, Miriama Akodad, Vinayak N Bapat, Jeroen J Bax, Daniel J Blackman, Philipp Blanke, Sabine Bleiziffer, Davide Capodanno, Joao L Cavalcante, Lakshmi P Dasi, Ole De Backer, Matthiew De Beuel, Alison Duncan, Marc R Dweck, Miho Fukui, Aakriti Gupta, Kentaro Hayashida, Howard C Herrmann, Tsuyoshi Kaneko, Nicole Karam, Jaffar M Khan, Jan Kovac, Uri Landes, Jonathon A Leipsic, Martin B Leon, Michael J Mack, Mahesh V Madhavan, Moody M Makar, Raj R Makkar, Mouaz Al Mallah, David Meier, Thomas Modine, Atsushi Okada, Roosha K Parikh, Radoslaw Parma, Dhairya Patel, Philippe Pibarot, Bernard Prendergast, Nishath Quader, Michael J Reardon, Toby Rogers, Lucy M Safi, Stephanie L Sellers, Sabah Skaf, Giuseppe Tarantini, Didier Tchetche, Nicolas Van Mieghem, Dee Dee Wang, John G Webb, Stephan Windecker, Steven J Yakubov, Victoria Delgado, Rebecca T Hahn, Hasan Jilaihawi

Faculty, Staff and Students Publications

This updated Heart Valve Collaboratory framework addresses the growing concern for transcatheter valve failure (TVF) following transcatheter aortic valve replacement (TAVR). With the increasing volume of redo-TAV and surgical TAV explantation, there is a critical need for standardized pathways and protocols for evaluating TVF using echocardiography and cardiac computed tomography (CT) angiography. This document clarifies prior definitions of bioprosthetic valve deterioration and bioprosthetic valve failure in a practical, imaging directed context for TAVR. It discusses various imaging modalities for diagnosing TVF, including echocardiography, cardiac CT angiography, cardiac magnetic resonance, and positron emission tomography/CT. Recommendations are provided on the systematic imaging …

The Autophagy Protein Atg14 Safeguards Against Unscheduled Pyroptosis Activation To Enable Embryo Transport During Early Pregnancy, Pooja Popli, Arin K Oestreich, Vineet K Maurya, Marina N Rowen, Yong Zhang, Michael J Holtzman, Ramya Masand, John P Lydon, Shizuo Akira, Kelle Moley, Ramakrishna Kommagani

Faculty, Staff and Students Publications

Recurrent pregnancy loss, characterized by two or more failed clinical pregnancies, poses a significant challenge to reproductive health. In addition to embryo quality and endometrial function, proper oviduct function is also essential for successful pregnancy establishment. Therefore, structural abnormalities or inflammation resulting from infection in the oviduct may impede the transport of embryos to the endometrium, thereby increasing the risk of miscarriage. However, our understanding of the biological processes that preserve the oviductal cellular structure and functional integrity is limited. Here, we report that autophagy-related protein ATG14 plays a crucial role in maintaining the cellular integrity of the oviduct by …

Control Of Clostridioides Difficile Virulence And Physiology By The Flagellin Homeostasis Checkpoint Flic-Fliw-Csra In The Absence Of Motility, Duolong Zhu, Katherine J Wozniak, Firas Midani, Shaohui Wang, Xingmin Sun, Robert A Britton

Faculty, Staff and Students Publications

Mutations affecting Clostridioides difficile flagellin (FliC) have been shown to be hypervirulent in animal models and display increased toxin production and alterations in central metabolism. The regulation of flagellin levels in bacteria is governed by a tripartite regulatory network involving fliC, fliW, and csrA, which creates a feedback system to regulate flagella production. Through genomic analysis of C. difficile clade 5 strains (non-motile), we identified they have jettisoned many of the genes required for flagellum biosynthesis yet retain the major flagellin gene fliC and regulatory gene fliW. We therefore investigated the roles of fliC, fliW …

Navigating The Landscape Of Reinterventions After Tavr, Gilbert H L Tang, Syed Zaid, Ole De Backer

Faculty, Staff and Students Publications

No abstract provided.

A Journey Of Innovation In Mitral Transcatheter Edge-To-Edge Repair: Lessons From The Repair Registry, Gilbert H L Tang, Syed Zaid

Faculty, Staff and Students Publications

No abstract provided.

Lasalocid A Selectively Induces The Degradation Of Myd88 In Lymphomas Harboring The Myd88 L265p Mutation, Wei Li, Ruirui Wang, Junhao Wang, Dafei Chai, Xiaohui Xie, Ken H Young, Ya Cao, Yong Li, Xinfang Yu

Faculty, Staff and Students Publications

Myeloid differentiation primary response protein 88 (MYD88) is a key adaptor molecule in the signaling pathways of toll-like receptor and interleukin-1 receptor. A somatic mutation resulting in a leucine-to-proline change at position 265 of the MYD88 protein (MYD88 L265P) is one of the most prevalent oncogenic mutations found in patients with hematological malignancies. In this study, we used high-throughput screening to identify lasalocid A as a potent small molecule that selectively inhibited the viability of lymphoma cells expressing MYD88 L265P and the associated activation of NF-κB. Further investigations using CRISPR-CRISPR-associated protein 9 genetic screening, proteomics, and biochemical assays revealed that …

Sequence Variants In Hectd1 Result In A Variable Neurodevelopmental Disorder, Gazelle Zerafati-Jahromi, Elias Oxman, Hieu D Hoang, Wu-Lin Charng, Tanvitha Kotla, Weimin Yuan, Keito Ishibashi, Sonia Sebaoui, Kathryn Luedtke, Bryce Winrow, Rebecca D Ganetzky, Anna Ruiz, Carmen Manso-Basúz, Nino Spataro, Peter Kannu, Taryn Athey, Christina Peroutka, Caitlin Barnes, Richard Sidlow, George Anadiotis, Kari Magnussen, Irene Valenzuela, Alejandro Moles-Fernandez, Seth Berger, Christina L Grant, Eric Vilain, Gudny A Arnadottir, Patrick Sulem, Telma S Sulem, Kari Stefansson, Shavonne Massey, Natalie Ginn, Annapurna Poduri, Alissa M D'Gama, Rozalia Valentine, Sara K Trowbridge, Chaya N Murali, Rachel Franciskovich, Yen Tran, Bryn D Webb, Kim M Keppler-Noreuil, April L Hall, Bobbi Mcgivern, Kristin G Monaghan, Maria J Guillen Sacoto, Dustin Baldridge, Gary A Silverman, Sonika Dahiya, Tychele N Turner, Tim Schedl, Joshua G Corbin, Stephen C Pak, Irene E Zohn, Christina A Gurnett

Faculty, Staff and Students Publications

Dysregulation of genes encoding the homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases has been linked to cancer and structural birth defects. One member of this family, the HECT-domain-containing protein 1 (HECTD1), mediates developmental pathways, including cell signaling, gene expression, and embryogenesis. Through GeneMatcher, we identified 14 unrelated individuals with 15 different variants in HECTD1 (10 missense, 3 frameshift, 1 nonsense, and 1 splicing variant) with neurodevelopmental disorders (NDDs), including autism, attention-deficit/hyperactivity disorder, and epilepsy. Of these 15 HECTD1 variants, 10 occurred de novo, 3 had unknown inheritance, and 2 were compound heterozygous. While all individuals in this cohort displayed …

A Comprehensive Atlas Of Aav Tropism In The Mouse, Christopher J Walkey, Kathy J Snow, Jote Bulcha, Aaron R Cox, Alexa E Martinez, M Cecilia Ljungberg, Denise G Lanza, Marco De Giorgi, Marcel A Chuecos, Michele Alves-Bezerra, Carlos Flores Suarez, Sean M Hartig, Susan G Hilsenbeck, Chih-Wei Hsu, Ethan Saville, Yaned Gaitan, Jeff Duryea, Seth Hannigan, Mary E Dickinson, Oleg Mirochnitchenko, Dan Wang, Cathleen M Lutz, Jason D Heaney, Guangping Gao, Stephen A Murray, William R Lagor

Faculty, Staff and Students Publications

Gene therapy with adeno-associated virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of 10 naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10, and AAVrh74) following systemic delivery into male and female mice. A transgene-expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence. Cre-driven activation of tdTomato fluorescence offered superior sensitivity for transduced cells. All serotypes except AAV3B and AAV4 had high liver tropism. Fluorescence activation revealed transduction of unexpected tissues, including adrenals, testes, and ovaries. Rare transduced cells within …

Use Of Robust Norming To Create A Sensitive Cognitive Summary Score In De Novo Parkinson's Disease: An Illustrative Example, Daniel Weintraub, Michael C Brumm, Ryan Kurth, Michele K York

Faculty, Staff and Students Publications

Background: Cognitive impairment is common at all stages of Parkinson's disease (PD), but there is no consensus on which neuropsychological tests to use or how to interpret cognitive battery results. A cognitive summary score (CSS) combines the richness of a neuropsychological battery with the simplicity of a single score.

Objective: The objective of this study was to determine whether a CSS created using robust norming can detect early cognitive deficits in de novo, untreated PD.

Methods: Baseline cognitive data from PD participants and healthy control participants (HCs) in the Parkinson's Progression Markers Initiative were used to (1) create a robust …

Irisin-Mediated Muscle-Renal Crosstalk As A Protective Mechanism Against Contrast-Induced Acute Kidney Injury Via Cgas-Sting Signalling Inhibition, Long Peng, Suhua Li, Qiang Huang, Yuxiang Sun, Juan Sun, Ting Luo, Yanlin Wang, Zhaoyong Hu, Weiyan Lai, Hui Peng

Faculty, Staff and Students Publications

Background: Contrast-induced acute kidney injury (CI-AKI) continues to pose a pressing clinical challenge during invasive cardiovascular procedures due to the limited availability of preventative strategies. We aimed to demonstrate that irisin, a myokine induced by exercise, protects against CI-AKI by inhibiting the cGAS-STING inflammatory pathway.

Methods and results: We explored the relationship between serum irisin levels and CI-AKI incidence in patients administered the contrast media iohexol. Notably, lower serum irisin levels were strongly associated with an increased incidence of CI-AKI following contrast media administration. To establish a causal link between serum irisin levels and CI-AKI, we utilised a mouse model …

Exploration Of Cytokines And Microbiome Among Males And Females With Diarrhea-Predominant Irritable Bowel Syndrome, Li Juen Chen, Anna M Plantinga, Robert Burr, Kevin Cain, Pamela Barney, Tor Savidge, Robert J Shulman, Margaret Heitkemper, Kendra Kamp

Faculty, Staff and Students Publications

Background: Whether pathophysiological factors differ between males and females with irritable bowel syndrome-diarrhea (IBS-D) remains to be tested. To better understand potential sex differences, males with IBS-D were compared to naturally cycling females and to females with IBS-D taking hormonal contraception on plasma levels of cytokines and gut microbiome characteristics.

Methods: Males and females with Rome III IBS-D completed questionnaires and kept a daily symptom diary for 28 days. Blood and stool samples were collected between days 3 and 8 of the daily diary (estrogen-dominant days in naturally cycling females). Blood samples were analyzed for lipopolysaccharide (LPS)-stimulated and unstimulated cytokine …

Early Life Epigenetics And Childhood Outcomes: A Scoping Review, Srirupa Hari Gopal, Theresa Alenghat, Mohan Pammi

Faculty, Staff and Students Publications

Epigenetics is the study of changes in gene expression, without a change in the DNA sequence that are potentially heritable. Epigenetic mechanisms such as DNA methylation, histone modifications, and small non-coding RNA (sncRNA) changes have been studied in various childhood disorders. Causal links to maternal health and toxin exposures can introduce epigenetic modifications to the fetal DNA, which can be detected in the cord blood. Cord blood epigenetic modifications provide evidence of in-utero stressors and immediate postnatal changes, which can impact both short and long-term outcomes in children. The mechanisms of these epigenetic changes can be leveraged for prevention, early …

Cerebrotendinous Xanthomatosis Occurs At High Frequency In Ashkenazi Jews, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous Xanthomatosis (CTX) is a treatable, inborn error of bile acids metabolism caused by pathogenic variants in CYP27A1. CTX is a multi-organ system disorder that progresses over decades. Clinical features include cerebellar dysfunction, pyramidal tract dysfunction, cognitive deficits and decline, peripheral neuropathy, chronic diarrhea, bilateral cataracts, and tendon xanthomas. Treatment is effective when started early, but diagnostic delays often result in individuals not being diagnosed until after the window of highest treatment efficacy. CTX is documented to occur in most global populations, however, no CTX-causing genetic variants have been reported in Ashkenazi Jews. We conducted a systematic review of every …

Anesthetic Management For Proximal Aortic Repair, Thomas R Powell, Emily B Shah, Ali Khalifa, Vicente Orozco-Sevilla, Daniel A Tolpin

Faculty, Staff and Students Publications

Surgical repair of the proximal aorta is a complex endeavor, requiring cardiopulmonary bypass (CPB) and often the use of hypothermic circulatory arrest (HCA). In addition to the normal considerations for patients undergoing cardiopulmonary bypass, additional challenges include cerebral and end-organ protection during periods of circulatory arrest. This review aims to provide an up-to-date, evidence-based review on anesthetic management for proximal aortic repair.

Physicians' Perceptions Of Barriers And Facilitators To The Improvement Of Healthcare Equity For Children Hospitalized With Traumatic Brain Injury: Preliminary Findings From A Pilot Multicenter Pediatric Trauma Study From The United States, Chelsea D Hicks, Heather Barnett, Jennifer Shi, Julia Velonjara, Mauricio A Escobar, Darci Evans, John Fisher, Arnett Klugh Iii, Katrina M Morgan, Morgan K Richards, Sarah Risen, Courtney Robertson, Irim Salik, Dennis W Simon, Arul S Thirumoorthi, Deidre L Wyrick, Bryan J Weiner, Theresa J Hoeft, Monica S Vavilala

Faculty, Staff and Students Publications

Background and objective: Disparities in outcomes for pediatric patients with traumatic brain injuries (TBI) in rural populations and for racial and ethnic minority groups have been documented. In light of this, we examined physician champions' perceptions of healthcare equity for hospitalized children with TBI.

Methods: We surveyed 10 physician TBI champions at 10 US pediatric trauma centers (PTCs) regarding organizational characteristics, barriers, and facilitators (domains and specific) in terms of improving healthcare equity, and priorities to redress inequities.

Results: Level I center TBI champions reported more pediatric beds and higher staffing-to-patient ratios while Level II TBI champions reported more pediatric …

Insulin-Like Growth Factor Binding Protein-3 (Igfbp-3): A Biomarker Of Coronary Artery Disease Induced Myocardial Ischaemia, Jacqui A Lee, Jessika Wise, Sara D Raudsepp, Louise N Paton, Jan Powell, Kieran Jina, Sally Aldous, Richard W Troughton, Philip D Adamson, A Mark Richards, W Frank Peacock, James L Januzzi, Noah Erceg, Luca Koechlin, Jasper Boeddinghaus, Pedro Lopez-Ayala, Christian Mueller, Martin P Than, John W Pickering, Chris J Pemberton

Faculty, Staff and Students Publications

Aims: Among individuals presenting to the emergency department (ED) with chest pain, clinical uncertainty surrounds the appropriate identification of non-myocardial infarction (MI) individuals who would most benefit from objective functional/anatomical testing (e.g. imaging). We applied a proteomic biomarker discovery approach to identify novel candidates reflecting coronary artery disease (CAD) induced ischaemia that could translate to measurement in clinical samples.

Methods and results: Mass spectroscopy (MS) of perfusate from an isolated rat heart model of cardiac ischaemia identified >100 novel protein biomarkers. A prominent candidate, insulin-like growth factor binding protein (IGFBP-3), was then interrogated for its ability to identify CAD-related ischaemia …

Convergence On Camk4: A Key Modulator Of Autism-Associated Signaling Pathways In Neurons, Jacqueline Kaiser, Alana Risteska, Abbey G Muller, Haoxiong Sun, Bethany Lei, Kevin Nay, Anthony R Means, Margot A Cousin, David H Drewry, Jonathan S Oakhill, Bruce E Kemp, Anthony J Hannan, Michael Berk, Mark A Febbraio, Andrew L Gundlach, Elisa L Hill-Yardin, John W Scott

Faculty, Staff and Students Publications

Although the precise underlying cause(s) of autism spectrum disorder remain unclear, more than 1000 rare genetic variations are associated with the condition. For many people living with profound autism, this genetic heterogeneity has impeded the identification of common biological targets for therapy development for core and comorbid traits that include significant impairments in social communication and repetitive and restricted behaviors. A substantial number of genes associated with autism encode proteins involved in signal transduction and synaptic transmission that are critical for brain development and function. CAMK4 is an emerging risk gene for autism spectrum disorder that encodes the CaMK4 (calcium/calmodulin-dependent …

The Glu86 Residue In Tbx4 Proves Critical For Human Lung Development, Przemyslaw Szafranski, Tomasz Gambin, Gail Deutsch, Salma A Nassef, Mary Clay Bailey, Debra L Kearney, Paweł Stankiewicz

Faculty, Staff and Students Publications

T-box transcription factors are a group of evolutionarily conserved T-box-containing regulators of mesoderm specification and development. Heterozygous single nucleotide variants (SNVs) or copy-number variant (CNV) deletions involving dosage-sensitive TBX4 have been associated with pulmonary arterial hypertension (PAH), ischiocoxopodopatellar syndrome with or without PAH, and lethal lung developmental disorders (LLDDs), including acinar dysplasia (AcDys), congenital alveolar dysplasia (CAD), and other unspecified primary pulmonary hypoplasias. Loss- and gain-of-function variants have been proposed to cause pediatric PAH and LLDDs, and adult forms of PAH, respectively. Of more than 50 missense SNVs scattered across the entire TBX4, only three have been reported in patients …

Unveiling Vaginal Fibrosis: A Novel Murine Model Using Bleomycin And Epithelial Disruption, Jennifer M Mccracken, Gisele A Calderon, Felipe Rivas, Dorothea Erxleben, Taylor Moseley, Lishore A Kumar, Daniel E Kennedy, Swathi Balaji, Adam Hall, Julie C E Hakim

Faculty, Staff and Students Publications

Vaginal fibrosis induced by cancer therapy continues to take a physical and psychoemotional burden. To advance the efforts to generate a reproducible and cost-effective animal model, we tested the effect of repeated bleomycin instillations with mucosal layer disruption on induction of vaginal fibrosis. Tissue samples collected at various time points were analyzed for fibrosis-related gene expression changes and collagen content. Low (1.5 U/kg) and high-dose (2.5 U/kg) bleomycin instillations alone did not induce fibrosis, but when high-dose bleomycin was combined with epithelial disruption, increased profibrotic gene expression and trichrome staining were observed. To evaluate spatial and temporal changes in the …

Thalamic Deep Brain Stimulation Improves Movement In A Cerebellar Model Of Lesion-Based Status Dystonicus, Megan X Nguyen, Amanda M Brown, Tao Lin, Roy V Sillitoe, Jason S Gill

Faculty, Staff and Students Publications

Dystonia is the third most common movement disorder and an incapacitating co-morbidity in a variety of neurologic conditions. Dystonia can be caused by genetic, degenerative, idiopathic, and acquired etiologies, which are hypothesized to converge on a "dystonia network" consisting of the basal ganglia, thalamus, cerebellum, and cerebral cortex. In acquired dystonia, focal lesions to subcortical network regions lead to dystonia that can be difficult to manage with canonical treatments, including deep brain stimulation (DBS). While studies in animal models have begun to parse the contribution of individual nodes in the dystonia network, how acquired injury to the cerebellar outflow tracts …