Medical Specialties Commons^™

Network Meta-Analysis To Compare Venaseal With Other Superficial Venous Therapies For Chronic Venous Insufficiency., Raghu Kolluri, Janice Chung, Sue Kim, Nibir Nath, Bhoomika Bajaj Bhalla, Tarun Jain, Joseph Zygmunt, Alun Davies

Heart and Vascular Articles

OBJECTIVE: Several randomized controlled trials (RCTs) have compared different interventions for chronic venous insufficiency (CVI) management, but mixed comparison of these interventions is lacking. The aim of this network meta-analysis was to compare VenaSeal closure system (Medtronic, Minneapolis, Minn) with endovenous laser ablation (EVLA), radiofrequency ablation (RFA), mechanochemical ablation, sclerotherapy, and surgery for management of CVI to achieve anatomic success (complete closure of treated vein within 6 months after intervention) as the primary outcome and health-related quality of life (HRQoL; EuroQol-5 Dimension, Aberdeen Varicose Vein Questionnaire), Venous Clinical Severity Score (VCSS), pain scores, and adverse events as secondary outcomes.

METHODS: …

Structure And Mechanism Of Human Diacylglycerol O-Acyltransferase 1, Lie Wang, Hongwu Qian, Yin Nian, Yimo Han, Zhenning Ren, Hanzhi Zhang, Liya Hu, B V Venkataram Prasad, Arthur Laganowsky, Nieng Yan, Ming Zhou

Faculty, Staff and Students Publications

Diacylglycerol O-acyltransferase-1 (DGAT1) synthesizes triacylglycerides and is required for dietary fat absorption and fat storage in humans1. DGAT1 belongs to the superfamily of membrane-bound O-acyltransferases (MBOAT) that are found in all kingdoms of life and involved in acylation of lipids and proteins2,3. It remains unclear how human DGAT1 (hDGAT1) or other mammalian members of the MBOAT family recognize their substrates and catalyze their reactions. The absence of three-dimensional structures also hampers rational targeting of hDGAT1 for therapeutic purposes. Here we present the structure of hDGAT1 in complex with a substrate oleoyl Coenzyme A solved …

Ubiquitination Of The Dna-Damage Checkpoint Kinase Chk1 By Traf4 Is Required For Chk1 Activation, Xinfang Yu, Wei Li, Haidan Liu, Qipan Deng, Xu Wang, Hui Hu, Zijun Y Xu-Monette, Wei Xiong, Zhongxin Lu, Ken H Young, Wei Wang, Yong Li

Faculty, Staff and Students Publications

BACKGROUND: Aberrant activation of DNA damage response (DDR) is a major cause of chemoresistance in colorectal cancer (CRC). CHK1 is upregulated in CRC and contributes to therapeutic resistance. We investigated the upstream signaling pathways governing CHK1 activation in CRC.

METHODS: We identified CHK1-binding proteins by mass spectrometry analysis. We analyzed the biologic consequences of knockout or overexpression of TRAF4 using immunoblotting, immunoprecipitation, and immunofluorescence. CHK1 and TRAF4 ubiquitination was studied in vitro and in vivo. We tested the functions of TRAF4 in CHK1 phosphorylation and CRC chemoresistance by measuring cell viability and proliferation, anchorage-dependent and -independent cell growth, and mouse …

Catabolic Degradation Of Endothelial Vegfa Via Autophagy, Thomas Neill, Carolyn Chen, Simone Buraschi, Renato V. Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Extracellular matrix-evoked angiostasis and autophagy within the tumor microenvironment represent two critical, but unconnected, functions of the small leucine-rich proteoglycan, decorin. Acting as a partial agonist of vascular endothelial growth factor 2 (VEGFR2), soluble decorin signals via the energy sensing protein, AMP-activated protein kinase (AMPK), in the autophagic degradation of intracellular vascular endothelial growth factor A (VEGFA). Here, we discovered that soluble decorin evokes intracellular catabolism of endothelial VEGFA that is mechanistically independent of mTOR, but requires an autophagic regulator, paternally expressed gene 3 (PEG3). We found that administration of autophagic inhibitors such as chloroquine or bafilomycin A1, or depletion …

Efficacy Of Quality Improvement And Patient Safety Workshops For Students: A Pilot Study, Kevin P Shah, Shreya Goyal, Vignesh Ramachandran, Jaden R Kohn, Jonathan A Go, Zachary Wiley, Anoosha Moturu, Meera K Namireddy, Anjali Kumar, Ryan C Jacobs, Matthew Stampfl, Jesal R Shah, Justin Fu, Weijie V Lin, Brandon Ho, Grace Wey, Sophie Y Lin, Andrew C Caruso, Lindsey Jordan Gay, Diana E Stewart, Sara Andrabi

Faculty, Staff and Students Publications

BACKGROUND: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes.

METHODS: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause …

Association Of Intensive Lifestyle Intervention, Fitness, And Body Mass Index With Risk Of Heart Failure In Overweight Or Obese Adults With Type 2 Diabetes Mellitus: An Analysis From The Look Ahead Trial, Ambarish Pandey, Kershaw V Patel, Judy L Bahnson, Sarah A Gaussoin, Corby K Martin, Ashok Balasubramanyam, Karen C Johnson, Darren K Mcguire, Alain G Bertoni, Dalane Kitzman, Jarett D Berry, Look Ahead Research Group

Faculty, Staff and Students Publications

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher risk for heart failure (HF). The impact of a lifestyle intervention and changes in cardiorespiratory fitness (CRF) and body mass index on risk for HF is not well established.

METHODS: Participants from the Look AHEAD trial (Action for Health in Diabetes) without prevalent HF were included. Time-to-event analyses were used to compare the risk of incident HF between the intensive lifestyle intervention and diabetes support and education groups. The associations of baseline measures of CRF estimated from a maximal treadmill test, body mass index, and longitudinal changes in these …

A Validated Composite Organ And Hematologic Response Model For Early Assessment Of Treatment Outcomes In Light Chain Amyloidosis, Surbhi Sidana, Paolo Milani, Moritz Binder, Marco Basset, Nidhi Tandon, Andrea Foli, Angela Dispenzieri, Morie A Gertz, Suzanne R Hayman, Francis K Buadi, Martha Q Lacy, Prashant Kapoor, Nelson Leung, S Vincent Rajkumar, Giampaolo Merlini, Giovanni Palladini, Shaji K Kumar

Faculty, Staff and Student Publications

Newly diagnosed AL amyloidosis patients were evaluated to develop a model for early assessment of treatment benefit at 6 months, integrating both hematologic (HR) and organ response (OR) assessment (testing cohort, Mayo: n = 473; validation cohort, Pavia: n = 575). Multiple OR were assessed as follows: All OR (AOR): response in all organs, mixed OR (MOR): response in some organs, no OR (NOR)]. AOR rates at 6 months improved with deepening HR; complete response (CR; 38%, 35%), very good partial response (VGPR; 30%, 26%), and partial response (PR; 16%, 21%), respectively. A composite HR/OR (CHOR) model was developed using …

Mechanical Thrombectomy For Acute Ischemic Stroke In The Cardiac Catheterization Laboratory., Steven A Guidera, Sudhir Aggarwal, J Doyle Walton, David Boland, Roy Jackel, Jeffrey D Gould, Brooke Kearins, Joseph Mcgarvey, Yan Qi, Brian Furlong

Department of Radiology & Diagnostic Medical Imaging

OBJECTIVES: The aim of this study was to determine the feasibility of establishing a mechanical thrombectomy (MT) program for acute ischemic stroke in a community hospital using interventional cardiologists working closely with neurologists.

BACKGROUND: American Heart Association/American Stroke Association 2018 guidelines give a Class I (Level of Evidence: A) recommendation for MT in eligible patients with large vessel occlusion stroke. Improvement in neurological outcomes with MT is highly time sensitive. Most hospitals do not have trained neurointerventionalists to perform MT, leading to treatment delays that reduce the benefit of reperfusion therapy.

METHODS: An MT program based in the cardiac catheterization …

Predicting Hemolytic Uremic Syndrome And Renal Replacement Therapy In Shiga Toxin-Producing Escherichia Coli-Infected Children., Ryan S Mckee, David Schnadower, Phillip I Tarr, Jianling Xie, Yaron Finkelstein, Neil Desai, Roni D Lane, Kelly R Bergmann, Ron L Kaplan, Selena Hariharan, Andrea T Cruz, Daniel M Cohen, Andrew Dixon, Sriram Ramgopal, Annie Rominger, Elizabeth C Powell, Jennifer Kilgar, Kenneth A Michelson, Darcy Beer, Martin Bitzan, Christopher M Pruitt, Kenneth Yen, Garth D Meckler, Amy C Plint, Stuart Bradin, Thomas J Abramo, Serge Gouin, April J Kam, Abigail Schuh, Fran Balamuth, Tracy E Hunley, John T Kanegaye, Nicholas E Jones, Usha Avva, Robert Porter, Daniel M Fein, Jeffrey P Louie, Stephen B Freedman

Paediatrics Publications

BACKGROUND: Shiga toxin-producing Escherichia coli (STEC) infections are leading causes of pediatric acute renal failure. Identifying hemolytic uremic syndrome (HUS) risk factors is needed to guide care.

METHODS: We conducted a multicenter, historical cohort study to identify features associated with development of HUS (primary outcome) and need for renal replacement therapy (RRT) (secondary outcome) in STEC-infected children without HUS at initial presentation. Children agedeligible.

RESULTS: Of 927 STEC-infected children, 41 (4.4%) had HUS at presentation; of the remaining 886, 126 (14.2%) developed HUS. Predictors (all shown as odds ratio [OR] with 95% confidence interval [CI]) of HUS included younger age …

Integrating Mouse And Human Genetic Data To Move Beyond Gwas And Identify Causal Genes In Cholesterol Metabolism, Zhonggang Li, James A Votava, Gregory J M Zajac, Jenny N Nguyen, Fernanda B Leyva Jaimes, Sophia M Ly, Jacqueline A Brinkman, Marco De Giorgi, Sushma Kaul, Cara L Green, Samantha L St Clair, Sabrina L Belisle, Julia M Rios, David W Nelson, Mary G Sorci-Thomas, William R Lagor, Dudley W Lamming, Chi-Liang Eric Yen, Brian W Parks

Faculty, Staff and Students Publications

Identifying the causal gene(s) that connects genetic variation to a phenotype is a challenging problem in genome-wide association studies (GWASs). Here, we develop a systematic approach that integrates mouse liver co-expression networks with human lipid GWAS data to identify regulators of cholesterol and lipid metabolism. Through our approach, we identified 48 genes showing replication in mice and associated with plasma lipid traits in humans and six genes on the X chromosome. Among these 54 genes, 25 have no previously identified role in lipid metabolism. Based on functional studies and integration with additional human lipid GWAS datasets, we pinpoint Sestrin1 as …

Acetylation Of Histone H3k27 Signals The Transcriptional Elongation For Estrogen Receptor Alpha, Yujing Gao, Lijia Chen, Yali Han, Fangrui Wu, Wen-Si Yang, Zheng Zhang, Tong Huo, Yingmin Zhu, Chengtai Yu, Hong Kim, Mark Lee, Zhen Tang, Kevin Phillips, Bin He, Sung Yun Jung, Yongcheng Song, Bokai Zhu, Rui-Ming Xu, Qin Feng

Faculty, Staff and Students Publications

As approximately 70% of human breast tumors are estrogen receptor α (ERα)-positive, estrogen and ERα play essential roles in breast cancer development. By interrupting the ERα signaling pathway, endocrine therapy has been proven to be an effective therapeutic strategy. In this study, we identified a mechanism by which Transcription Start Site (TSS)-associated histone H3K27 acetylation signals the Super Elongation Complex (SEC) to regulate transcriptional elongation of the ESR1 (ERα) gene. SEC interacts with H3K27ac on ESR1 TSS through its scaffold protein AFF4. Depletion of AFF4 by siRNA or CRISPR/Cas9 dramatically reduces expression of ESR1 and its target genes, consequently inhibiting …

Principles Of Rna Processing From Analysis Of Enhanced Clip Maps For 150 Rna Binding Proteins, Eric L Van Nostrand, Gabriel A Pratt, Brian A Yee, Emily C Wheeler, Steven M Blue, Jasmine Mueller, Samuel S Park, Keri E Garcia, Chelsea Gelboin-Burkhart, Thai B Nguyen, Ines Rabano, Rebecca Stanton, Balaji Sundararaman, Ruth Wang, Xiang-Dong Fu, Brenton R Graveley, Gene W Yeo

Faculty, Staff and Students Publications

BACKGROUND: A critical step in uncovering rules of RNA processing is to study the in vivo regulatory networks of RNA binding proteins (RBPs). Crosslinking and immunoprecipitation (CLIP) methods enable mapping RBP targets transcriptome-wide, but methodological differences present challenges to large-scale analysis across datasets. The development of enhanced CLIP (eCLIP) enabled the mapping of targets for 150 RBPs in K562 and HepG2, creating a unique resource of RBP interactomes profiled with a standardized methodology in the same cell types.

RESULTS: Our analysis of 223 eCLIP datasets reveals a range of binding modalities, including highly resolved positioning around splicing signals and mRNA …

De Novo Frameshift Variants In The Neuronal Splicing Factor Nova2 Result In A Common C-Terminal Extension And Cause A Severe Form Of Neurodevelopmental Disorder, Francesca Mattioli, Gaelle Hayot, Nathalie Drouot, Bertrand Isidor, Jérémie Courraud, Maria-Victoria Hinckelmann, Frederic Tran Mau-Them, Chantal Sellier, Alica Goldman, Aida Telegrafi, Alicia Boughton, Candace Gamble, Sebastien Moutton, Angélique Quartier, Nolwenn Jean, Paul Van Ness, Sarah Grotto, Sophie Nambot, Ganka Douglas, Yue Cindy Si, Jamel Chelly, Zohra Shad, Elisabeth Kaplan, Richard Dineen, Christelle Golzio, Nicolas Charlet-Berguerand, Jean-Louis Mandel, Amélie Piton

Faculty, Staff and Students Publications

The neuro-oncological ventral antigen 2 (NOVA2) protein is a major factor regulating neuron-specific alternative splicing (AS), previously associated with an acquired neurologic condition, the paraneoplastic opsoclonus-myoclonus ataxia (POMA). We report here six individuals with de novo frameshift variants in NOVA2 affected with a severe neurodevelopmental disorder characterized by intellectual disability (ID), motor and speech delay, autistic features, hypotonia, feeding difficulties, spasticity or ataxic gait, and abnormal brain MRI. The six variants lead to the same reading frame, adding a common proline rich C-terminal part instead of the last KH RNA binding domain. We detected 41 genes differentially spliced after NOVA2 …

Phosphoinositides In Retinal Function And Disease, Theodore G Wensel

Faculty, Staff and Students Publications

Phosphatidylinositol and its phosphorylated derivatives, the phosphoinositides, play many important roles in all eukaryotic cells. These include modulation of physical properties of membranes, activation or inhibition of membrane-associated proteins, recruitment of peripheral membrane proteins that act as effectors, and control of membrane trafficking. They also serve as precursors for important second messengers, inositol (1,4,5) trisphosphate and diacylglycerol. Animal models and human diseases involving defects in phosphoinositide regulatory pathways have revealed their importance for function in the mammalian retina and retinal pigmented epithelium. New technologies for localizing, measuring and genetically manipulating them are revealing new information about their importance for the …

Organizational Guidance For The Care Of Patients With Head-And-Neck Cancer In Ontario., J Irish, J Kim, J Waldron, A C Wei, E Winquist, J Yoo, A Boasie, M Brouwers, E Meertens, S Mcnair, C Walker-Dilks

Paediatrics Publications

Background: At the request of the Head and Neck Cancers Advisory Committee of Ontario Health (Cancer Care Ontario), a working group and expert panel of clinicians with expertise in the management of head-and-neck cancer developed the present guideline. The purpose of the guideline is to provide advice about the organization and delivery of health care services for adult patients with head-and-neck cancer.

Methods: This document updates the recommendations published in the Ontario Health (Cancer Care Ontario) 2009 organizational guideline

Results: To ensure that all patients have access to the highest standard of care available in Ontario, the guideline establishes the …

Sjs/Ten 2019: From Science To Translation., Wan-Chun Chang, Riichiro Abe, Paul Anderson, Wanpen Anderson, Michael R Ardern-Jones, Thomas M Beachkofsky, Teresa Bellón, Agnieszka K Biala, Charles Bouchard, Gianpiero L Cavalleri, Nicole Chapman, James Chodosh, Hyon K Choi, Ricardo R Cibotti, Sherrie J Divito, Karen Dewar, Ulrike Dehaeck, Mahyar Etminan, Diane Forbes, Esther Fuchs, Jennifer L Goldman, James H Holmes, Elyse A Hope, Shuen-Iu Hung, Chia-Ling Hsieh, Alfonso Iovieno, Julienne Jagdeo, Mee Kum Kim, David M Koelle, Mario E Lacouture, Sophie Le Pallec, Rannakoe J Lehloenya, Robyn Lim, Angie Lowe, Jean Mccawley, Julie Mccawley, Robert G Micheletti, Maja Mockenhaupt, Katie Niemeyer, Michael A Norcross, Douglas Oboh, Cristina Olteanu, Helena B Pasieka, Jonathan Peter, Munir Pirmohamed, Michael Rieder, Hajirah N Saeed, Neil H Shear, Christine Shieh, Sabine Straus, Chonlaphat Sukasem, Cynthia Sung, Jason A Trubiano, Sheng-Ying Tsou, Mayumi Ueta, Simona Volpi, Chen Wan, Hongsheng Wang, Zhao-Qing Wang, Jessica Weintraub, Cindy Whale, Lisa M Wheatley, Sonia Whyte-Croasdaile, Kristina B Williams, Galen Wright, Sonia N Yeung, Li Zhou, Wen-Hung Chung, Elizabeth J Phillips, Bruce C Carleton

Paediatrics Publications

Stevens-Johnson syndrome and toxic epidermal necrolysis (SJS/TEN) are potentially life-threatening, immune-mediated adverse reactions characterized by widespread erythema, epidermal necrosis, and detachment of skin and mucosa. Efforts to grow and develop functional international collaborations and a multidisciplinary interactive network focusing on SJS/TEN as an uncommon but high burden disease will be necessary to improve efforts in prevention, early diagnosis and improved acute and long-term management. SJS/TEN 2019: From Science to Translation was a 1.5-day scientific program held April 26-27, 2019, in Vancouver, Canada. The meeting successfully engaged clinicians, researchers, and patients and conducted many productive discussions on research and patient care …

Diabetes And Cardiovascular Disease In Women: Current Challenges And New Hope, Efstratios Koutroumpakis, David Aguilar

The Texas Heart Institute Journal

No abstract provided.

The Comfort Of Destiny, Jeremy A Ross

The Texas Heart Institute Journal

No abstract provided.

Modified Danielson Technique For Prosthetic Aortic Valve Endocarditis And Aortoventricular Discontinuity, Gianfranco Filippone, Claudia Calia, Mario Finazzo, Fabio Fazzari, Giovanni Caruana, Vincenzo Argano

The Texas Heart Institute Journal

Endocarditis is a devastating complication of prosthetic aortic valve replacement. The infective process can destroy aortic annulus tissue, making conventional surgical valve replacement difficult or impossible and causing aortoventricular discontinuity. Several treatment techniques have been proposed. One of these, the Danielson technique, involves translocating the aortic valve to the native ascending aorta, débriding the abscess cavity, closing the coronary ostia, and bypassing the coronary arteries with a Y anastomosis between 2 vein grafts. We describe our use of a modified Danielson technique in a 68-year-old man with advanced prosthetic valve endocarditis that was associated with aortic annulus destruction and aortoventricular …

Robotic-Assisted Percutaneous Coronary Intervention Through Transradial Approach: Experience In 4 Patients With Complex Lesions, Amornpol Anuwatworn, Muhammad Ali Kahn, Tomasz Stys, Marian Petrasko, Adam Stys

The Texas Heart Institute Journal

Robotic-assisted percutaneous coronary intervention can reduce the exposure of interventional cardiologists to radiation and minimize the risk of occupational orthopedic injuries from wearing heavy protective aprons. The PRECISE (Percutaneous Robotically-Enhanced Coronary Intervention) study showed the efficacy and safety of robotic-assisted procedures for relatively low-risk lesions in single coronary arteries. Several reports have described robotic-assisted treatment of complex high-risk lesions, mostly through the transfemoral approach. We report 4 cases of patients in whom we used the transradial approach to treat complex lesions in the left anterior descending coronary artery with bifurcation balloon angioplasty reconstruction (2 cases), in the ostium of the …

Histologic Abnormalities Of The Ascending Aorta: Effects On Aortic Remodeling After Intracardiac Repair Of Tetralogy Of Fallot, Ujjwal Kumar Chowdhury, Lakshmi Kumari Sankhyan, Sheil Avneesh, Ruma Ray, Mani Kalaivani, Suruchi Hasija, Abhinavsingh Chauhan

The Texas Heart Institute Journal

We evaluated aortic tissue specimens from patients undergoing tetralogy of Fallot repair, to determine whether histologic abnormalities affect postsurgical aortic remodeling and other patient-related variables.

Using light microscopy, we studied full-thickness aortic wall tissue operatively excised from 118 consecutive patients undergoing intracardiac repair of tetralogy of Fallot. We performed multiple linear regression analysis to identify independent predictors of change in aortic root dimensions, which we measured with echocardiography after repair and every 3 months thereafter.

Thirty histologically normal specimens were used as controls. Elastic fiber fragmentation was found in 74.6% of the abnormal specimens, mucoid extracellular matrix accumulation in 49.2%, …

Speckle-Tracking Echocardiography In Cardio-Oncology And Beyond, Raymundo A Quintana, Linh P Bui, Rohit Moudgil, Nicolas Palaskas, Saamir Hassan, Jun-Ichi Abe, Elie Mouhayar, Syed Wamique Yusuf, Antonieta Hernandez, Jose Banchs

The Texas Heart Institute Journal

Speckle-tracking echocardiography has enabled clinicians to detect changes in myocardial function with more sensitivity than that afforded by traditional diastolic and systolic functional measurements, including left ventricular ejection fraction. Speckle-tracking echocardiography enables evaluation of myocardial strain in terms of strain (percent change in length of a myocardial segment relative to its length at baseline) and strain rate (strain per unit of time). Both measurements have potential for use in diagnosing and monitoring the cardiovascular side effects of cancer therapy. Regional and global strain measurements can independently predict outcomes not only in patients who experience cardiovascular complications of cancer and cancer …

Pitfalls In Quantitative Myocardial Pet Perfusion I: Myocardial Partial Volume Correction, K Lance Gould, Linh Bui, Danai Kitkungvan, Tinsu Pan, Amanda E Roby, Tung T Nguyen, Nils P Johnson

Faculty, Staff and Student Publications

BACKGROUND: PET quantitative myocardial perfusion requires correction for partial volume loss due to one-dimensional LV wall thickness smaller than scanner resolution.

METHODS: We aimed to assess accuracy of risk stratification for death, MI, or revascularization after PET using partial volume corrections derived from two-dimensional ACR and three-dimensional NEMA phantoms for 3987 diagnostic rest-stress perfusion PETs and 187 MACE events. NEMA, ACR, and Tree phantoms were imaged with Rb-82 or F-18 for size-dependent partial volume loss. Perfusion and Coronary Flow Capacity were recalculated using different ACR- and NEMA-derived partial volume corrections compared by Kolmogorov-Smirnov statistics to standard perfusion metrics with established …

Tortuosity-Powered Microfluidic Device For Assessment Of Thrombosis And Antithrombotic Therapy In Whole Blood, David J Luna, Navaneeth K R Pandian, Tanmay Mathur, Justin Bui, Pranav Gadangi, Vadim V Kostousov, Shiu-Ki Rocky Hui, Jun Teruya, Abhishek Jain

Faculty, Staff and Students Publications

Accurate assessment of blood thrombosis and antithrombotic therapy is essential for the management of patients in a variety of clinical conditions, including surgery and on extracorporeal life support. However, current monitoring devices do not measure the effects of hemodynamic forces that contribute significantly to coagulation, platelet function and fibrin formation. This limits the extent to which current assays can predict clotting status in patients. Here, we demonstrate that a biomimetic microfluidic device consisting stenosed and tortuous arteriolar vessels would analyze blood clotting under flow, while requiring a small blood volume. When the device is connected to an inline pressure sensor …

Cofilin-1-Induced Actin Reorganization In Stored Platelets, Swapan K Dasgupta, Perumal Thiagarajan

Faculty, Staff and Students Publications

BACKGROUND: During platelet storage, there are extensive changes in cytoskeleton and phosphatidylserine exposure. The intrinsic mitochondrial pathway of apoptosis, activated in stored platelets, is a major mediator these changes. Cofilin-1 is an effector of actin reorganization. We examined the effect of cofilin-1 deficiency on cytoskeleton and phosphatidylserine exposure during storage and following activation of apoptosis.

METHODS AND RESULTS: We assessed actin filaments by Alexa-647-phalloidin and phosphatidylserine exposure by fluorescein isothiocyanate-lactadherin by fluorescence microscopy. In fresh platelets, actin filaments are distributed in the subcortical region, and they do not express phosphatidylserine in the outer surface. In stored platelets, there is retraction …

Defining A Taxonomy Of Intracranial Hypertension: Is Icp More Than Just A Number?, W Andrew Kofke, Swarna Rajagopalan, Diana Ayubcha, Ramani Balu, Jovany Cruz-Navarro, Panumart Manatpon, Elizabeth Mahanna-Gabrielli

Faculty, Staff and Students Publications

Intracranial pressure (ICP) monitoring and control is a cornerstone of neuroanesthesia and neurocritical care. However, because elevated ICP can be due to multiple pathophysiological processes, its interpretation is not straightforward. We propose a formal taxonomy of intracranial hypertension, which defines ICP elevations into 3 major pathophysiological subsets: increased cerebral blood volume, masses and edema, and hydrocephalus. (1) Increased cerebral blood volume increases ICP and arises secondary to arterial or venous hypervolemia. Arterial hypervolemia is produced by autoregulated or dysregulated vasodilation, both of which are importantly and disparately affected by systemic blood pressure. Dysregulated vasodilation tends to be worsened by arterial …

Provider Attitudes And Practice Patterns For Direct-Acting Antiviral Therapy For Patients With Hepatocellular Carcinoma, Nicole E Rich, Ju Dong Yang, Ponni V Perumalswami, Naim Alkhouri, Whitney Jackson, Neehar D Parikh, Neil Mehta, Reena Salgia, Andres Duarte-Rojo, Laura Kulik, Mina Rakoski, Adnan Said, Omobonike Oloruntoba, George N Ioannou, Maarouf A Hoteit, Andrew M Moon, Amol S Rangnekar, Sheila L Eswaran, Elizabeth Zheng, Janice H Jou, James Hanje, Anjana Pillai, Ruben Hernaez, Robert Wong, Steven Scaglione, Hrishikesh Samant, Devika Kapuria, Shaun Chandna, Russell Rosenblatt, Veeral Ajmera, Catherine T Frenette, Sanjaya K Satapathy, Parvez Mantry, Prasun Jalal, Binu V John, Oren K Fix, Michael Leise, Christina C Lindenmeyer, Avegail Flores, Nayan Patel, Z Gordon Jiang, Nyan Latt, Renumathy Dhanasekaran, Mobolaji Odewole, Sofia Kagan, Jorge A Marrero, Amit G Singal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) are effective against hepatitis C virus and sustained virologic response is associated with reduced incidence of hepatocellular carcinoma (HCC). However, there is controversy over the use of DAAs in patients with active or treated HCC and uncertainty about optimal management of these patients. We aimed to characterize attitudes and practice patterns of hepatology practitioners in the United States regarding the use of DAAs in patients with HCC.

METHODS: We conducted a survey of hepatology providers at 47 tertiary care centers in 25 states. Surveys were sent to 476 providers and we received 279 responses …

Hepatitis B Virus Hbx Protein Mediates The Degradation Of Host Restriction Factors Through The Cullin 4 Ddb1 E3 Ubiquitin Ligase Complex, Marissa M Minor, F Blaine Hollinger, Adrienne L Mcnees, Sung Yun Jung, Antrix Jain, Joseph M Hyser, Karl-Dimiter Bissig, Betty L Slagle

Faculty, Staff and Students Publications

The hepatitis B virus (HBV) regulatory HBx protein is required for infection, and its binding to cellular damaged DNA binding protein 1 (DDB1) is critical for this function. DDB1 is an adaptor protein for the cullin 4A Really Interesting New Gene (RING) E3 ubiquitin ligase (CRL4) complex and functions by binding cellular DDB1 cullin associated factor (DCAF) receptor proteins that recruit substrates for ubiquitination and degradation. We compared the proteins found in the CRL4 complex immunoprecipitated from uninfected versus HBV-infected hepatocytes from human liver chimeric mice for insight into mechanisms by which HBV and the cell interact within the CRL4 …

Thrombotic, Inflammatory, And Hif-Regulated Genes And Thrombosis Risk In Polycythemia Vera And Essential Thrombocythemia, Radhika Gangaraju, Jihyun Song, Soo Jin Kim, Tsewang Tashi, Brandi N Reeves, Krishna M Sundar, Perumal Thiagarajan, Josef T Prchal

Faculty, Staff and Students Publications

Thrombosis is a major cause of morbidity and mortality in polycythemia vera (PV) and essential thrombocythemia (ET). The pathophysiology of thrombosis in these disorders remains unclear, and we hypothesized that upregulation of thrombotic, inflammatory, and hypoxia-inducible factor (HIF)-regulated genes may play a role in it. We performed unbiased RNA sequencing in granulocytes and platelets of PV patients and found differential expression of several thrombotic, inflammatory, and HIF-regulated genes. The expression of many of these genes positively correlated with JAK2 expression and JAK2V617F allelic burden. We then validated these findings by quantitative polymerase chain reaction analyses of selected gene transcripts in …

Pediatric Resident Knowledge, Experience, Comfort, And Perceived Competency In Providing Sibling Psychosocial Support., David Buchbinder, Sonam Sidhu, Melissa A. Alderfer, Anne Lown, Russ C. Kolarik, Tommy Wang

Department of Pediatrics Faculty Papers

This article is the author’s final published version in International Journal of Medical Education, Volume 11, March 2020, Pages 73-75.

The published version is available at https://doi.org/10.5116/ijme.5e63.6a46. Copyright © Buchbinder et al.