Medical Specialties Commons^™

Incidence Of Primary End Point Changes Among Active Cancer Phase 3 Randomized Clinical Trials, Marcus A Florez, Joseph Abi Jaoude, Roshal R Patel, Ramez Kouzy, Timothy A Lin, Brian De, Esther J Beck, Cullen M Taniguchi, Bruce D Minsky, Clifton D Fuller, J Jack Lee, Michael Kupferman, Kanwal P Raghav, Michael J Overman, Charles R Thomas, Ethan B Ludmir

Faculty, Staff and Student Publications

IMPORTANCE: Primary end point (PEP) changes to an active clinical trial raise questions regarding trial quality and the risk of outcome reporting bias. It is unknown how the frequency and transparency of the reported changes depend on reporting method and whether the PEP changes are associated with trial positivity (ie, the trial met the prespecified statistical threshold for PEP positivity).

OBJECTIVES: To assess the frequency of reported PEP changes in oncology randomized clinical trials (RCTs) and whether these changes are associated with trial positivity.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used publicly available data for complete oncology phase 3 …

The Role Of Transcatheter Aortic Valve Implantation In Patients With Bicuspid Valves In 2023, Milad El Hajj, Zvonimir Krajcer

The Texas Heart Institute Journal

No abstract provided.

Does The Type Of Chronic Heart Failure Impact In-Hospital Outcomes For Aortic Valve Replacement Procedures?, Talha Mubashir, John Zaki, Sin Yeong An, Ismael A Salas De Armas, Yafen Liang, Travis Markham, Han Feng, Mehmet H Akay, Angelo Nascimbene, Bindu Akkanti, George W Williams, Fabricio Zasso, Maria Patarroyo Aponte, Igor D Gregoric, Biswajit Kar

The Texas Heart Institute Journal

Background: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).

Methods: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk.

Results: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF …

Does The Type Of Chronic Heart Failure Impact In-Hospital Outcomes For Aortic Valve Replacement Procedures?, Talha Mubashir, John Zaki, Sin Yeong An, Ismael A Salas De Armas, Yafen Liang, Travis Markham, Han Feng, Mehmet H Akay, Angelo Nascimbene, Bindu Akkanti, George W Williams, Fabricio Zasso, Maria Patarroyo Aponte, Igor D Gregoric, Biswajit Kar

The Texas Heart Institute Journal

Background: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).

Methods: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk.

Results: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF …

The Past, Present, And Future Of Complex Aortic Intervention, Joseph S Coselli

The Texas Heart Institute Journal

No abstract provided.

Does The Type Of Chronic Heart Failure Impact In-Hospital Outcomes For Aortic Valve Replacement Procedures?, Talha Mubashir, John Zaki, Sin Yeong An, Ismael A Salas De Armas, Yafen Liang, Travis Markham, Han Feng, Mehmet H Akay, Angelo Nascimbene, Bindu Akkanti, George W Williams, Fabricio Zasso, Maria Patarroyo Aponte, Igor D Gregoric, Biswajit Kar

The Texas Heart Institute Journal

Background: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).

Methods: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk.

Results: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF …

Does The Type Of Chronic Heart Failure Impact In-Hospital Outcomes For Aortic Valve Replacement Procedures?, Talha Mubashir, John Zaki, Sin Yeong An, Ismael A Salas De Armas, Yafen Liang, Travis Markham, Han Feng, Mehmet H Akay, Angelo Nascimbene, Bindu Akkanti, George W Williams, Fabricio Zasso, Maria Patarroyo Aponte, Igor D Gregoric, Biswajit Kar

The Texas Heart Institute Journal

Background: This study assessed in-hospital outcomes of patients with chronic systolic, diastolic, or mixed heart failure (HF) undergoing transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).

Methods: The Nationwide Inpatient Sample database was used to identify patients with aortic stenosis and chronic HF who underwent TAVR or SAVR between 2012 and 2015. Propensity score matching and multivariate logistic regression were used to determine outcome risk.

Results: A cohort of 9,879 patients with systolic (27.2%), diastolic (52.2%), and mixed (20.6%) chronic HF were included. No statistically significant differences in hospital mortality were noted. Overall, patients with diastolic HF …

Atrioventricular Nodal Ablation Is Not An Effective Treatment Strategy In Catecholaminergic Polymorphic Ventricular Tachycardia, S Yukiko Asaki, David Kessler, Aarushi Nayak, Jeffrey J Kim, Christina Y Miyake

The Texas Heart Institute Journal

Catecholaminergic polymorphic ventricular tachycardia is a rare but lethal heritable arrhythmia syndrome associated with both atrial and ventricular arrhythmias. Treatment includes antiarrhythmics, sympathetic denervation, and implantable cardioverter-defibrillators. The use of atrioventricular nodal ablation as a treatment strategy to prevent ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia was not found in the literature. This report describes a teenager with a presenting rhythm of atrial and ventricular fibrillation and cardiac arrest. Her clinical arrhythmia was predominantly atrial dysrhythmias, which delayed her diagnosis of catecholaminergic polymorphic ventricular tachycardia. Before her diagnosis, she underwent atrioventricular nodal ablation in an effort to prevent ventricular arrhythmias, …

Postpartum Detection Of Diastolic Dysfunction And Nondipping Blood Pressure Profile In Women With Preeclampsia, Marwa Sayed, Mariam Rashed, Ahmed M Abbas, Amr Youssef, Mohamed Abdel Ghany

The Texas Heart Institute Journal

BACKGROUND: Left ventricular diastolic dysfunction and nocturnal "nondipping" of blood pressure detected via ambulatory blood pressure monitoring are predictors of increased cardiovascular morbidity.

METHODS: A prospective cohort study including normotensive women with a history of preeclampsia in their current pregnancy was conducted. All cases were subjected to 24-hour ambulatory blood pressure monitoring and 2-dimensional transthoracic echocardiography 3 months after delivery.

RESULTS: This study included 128 women with a mean (SD) age of 28.6 (5.1) years and a mean (SD) basal blood pressure of 123.1 (6.4)/74.6 (5.9) mm Hg. Among the participants, 90 (70.3%) exhibited an ambulatory blood pressure monitoring profile …

Closed Mitral Valvotomy: Celebrating 100 Years Of Surgical History, Uberto Bortolotti, Igor Vendramin, Aldo Domenico Milano, Ugolino Livi

The Texas Heart Institute Journal

The year 2023 marks the 100th anniversary of the first successful valvotomy for mitral valve stenosis by Elliott C. Cutler in 1923. Closed-chest mitral valve commissurotomy developed further before being replaced by an open procedure after the advent of the heart-lung machine. Currently, because of the almost complete disappearance of rheumatic disease in the Western World, mitral commissurotomies are infrequently performed in those countries, although the procedure-either closed or open-is still performed in developing countries and select patients. This review retraces the 100-year journey from a historic operation to the current era-a milestone in the treatment of patients with mitral …

Meta-Analysis Of The Association Between Atrial Fibrillation, Hypertension, Sleep-Disordered Breathing, And Wake-Up Stroke, Jin Zhou, Jing Xu, Aijuan Cheng, Yimiti Kadier, Xiaoli Liang, Maimaitijiang Mutailipu, Shan Sun

The Texas Heart Institute Journal

BACKGROUND: The occurrence of atrial fibrillation, circadian fluctuation in blood pressure, and oxygen desaturation at night is likely associated with the pathophysiology of wake-up stroke. Whether patients who experience wake-up strokes are candidates for thrombolysis treatment is a serious dilemma. The aim is to investigate the association between risk factors and wake-up stroke and to determine variations that are associated with the pathophysiology of wake-up stroke.

METHODS: Five major electronic databases were searched using a fitted search strategy to identify relevant studies. Odds ratios with 95% CIs were used to calculate estimates, and the Quality Assessment for Diagnostic Accuracy Studies-2 …

Increased Plasma Non-High-Density Lipoprotein Levels And Poor Coronary Collateral Circulation In Patients With Stable Coronary Artery Disease, Fatih Sivri, Banu Öztürk Ceyhan

The Texas Heart Institute Journal

BACKGROUND: This study investigated the relationship between coronary collateral circulation (CCC) and non-high-density lipoprotein cholesterol (non-HDL-C) in patients with stable coronary artery disease (CAD). Coronary collateral circulation plays a critical role in supporting blood flow, particularly in the ischemic myocardium. Previous studies show that non-HDL-C plays a more important role in the formation and progression of atherosclerosis than do standard lipid parameters.

METHODS: A total of 226 patients with stable CAD and stenosis of more than 95% in at least 1 epicardial coronary artery were included in the study. Rentrop classification was used to assign patients into group 1 (n …

Neddylation Inhibition Sensitises Renal Medullary Carcinoma Tumours To Platinum Chemotherapy, Daniel D Shapiro, Niki Millward Zacharias, Durga N Tripathi, Menuka Karki, Jean-Philippe Bertocchio, Melinda Soeung, Rong He, Mary E Westerman, Jianjun Gao, Priya Rao, Truong N A Lam, Eric Jonasch, Luigi Perelli, Emily H Cheng, Alessandro Carugo, Timothy P Heffernan, Cheryl L Walker, Giannicola Genovese, Nizar M Tannir, Jose A Karam, Pavlos Msaouel

Faculty, Staff and Student Publications

BACKGROUND: Renal medullary carcinoma (RMC) is a highly aggressive cancer in need of new therapeutic strategies. The neddylation pathway can protect cells from DNA damage induced by the platinum-based chemotherapy used in RMC. We investigated if neddylation inhibition with pevonedistat will synergistically enhance antitumour effects of platinum-based chemotherapy in RMC.

METHODS: We evaluated the IC50 concentrations of the neddylation‐activating enzyme inhibitor pevonedistat in vitro in RMC cell lines. Bliss synergy scores were calculated using growth inhibition assays following treatment with varying concentrations of pevonedistat and carboplatin. Protein expression was assessed by western blot and immunofluorescence assays. The efficacy of pevonedistat …

Leveraging The Electronic Health Record To Implement Emergency Department Delirium Screening, Anita N Chary, Elise Brickhouse, Beatrice Torres, Ilianna Santangelo, Christopher R Carpenter, Shan W Liu, Kyler M Godwin, Aanand D Naik, Hardeep Singh, Maura Kennedy

Faculty, Staff and Students Publications

OBJECTIVE: The aim of this study is to understand how emergency departments (EDs) use health information technology (HIT), and specifically the electronic health record (EHR), to support implementation of delirium screening.

METHODS: We conducted semi-structured interviews with 23 ED clinician-administrators, representing 20 EDs, about how they used HIT resources to implement delirium screening. Interviews focused on challenges participants experienced when implementing ED delirium screening and EHR-based strategies they used to overcome them. We coded interview transcripts using dimensions from the Singh and Sittig sociotechnical model, which addresses use of HIT in complex adaptive health care systems. Subsequently, we analyzed data …

Development Of A Computable Phenotype Using Electronic Health Records For Venous Thromboembolism In Medical Inpatients: The Medical Inpatient Thrombosis And Hemostasis Study, Ryan M Thomas, Katherine Wilkinson, Insu Koh, Ang Li, Janine S A Warren, Nicholas S Roetker, Nicholas L Smith, Chris E Holmes, Timothy B Plante, Allen B Repp, Mary Cushman, Neil A Zakai

Faculty, Staff and Students Publications

BACKGROUND: Accurate and efficient methods to identify venous thromboembolism (VTE) events in hospitalized people are needed to support large-scale studies. Validated computable phenotypes using a specific combination of discrete, searchable elements in electronic health records to identify VTE and distinguish between hospital-acquired (HA)-VTE and present-on-admission (POA)-VTE would greatly facilitate the study of VTE, obviating the need for chart review.

OBJECTIVES: To develop and validate computable phenotypes for POA- and HA-VTE in adults hospitalized for medical reasons.

METHODS: The population included admissions to medical services from 2010 to 2019 at an academic medical center. POA-VTE was defined as VTE diagnosed within …

Cascade Testing After Exome Sequencing: Retrospective Analysis Of Linked Family Data At 2 Us Laboratories, Julie Stefka, Haley Streff, Pengfei Liu, Meghan Towne, Hadley Stevens Smith

Faculty, Staff and Students Publications

Purpose: Cascade testing, the process of testing a proband's at-risk relatives, is integral to realizing the full value of genomic sequencing. However, there is little empirical evidence on the uptake of cascade testing after a positive exome sequencing (ES) result in a population of probands with diverse clinical indications.

Methods: We retrospectively reviewed administrative data from 2 US clinical laboratories that perform ES. For each proband with a positive ES result, we used linked family data to describe the frequency of relatives' cascade testing performed at the same laboratory, variant detection yield of cascade tests, and characteristics of probands and …

Aspirin And Immunotherapy: A Faustian Bargain?, Eric A Goethe, Amy B Heimberger, Ganesh Rao

Faculty, Staff and Students Publications

Fibrinogen-like protein 1 (FGL1) has been associated with improved survival in hepatocellular carcinoma (HCC). However, recent evidence suggests that FGL1 may bind to surface receptors on lymphocytes and induce immune senescence. In this issue of the JCI, Lin and co-authors show that FGL1 may be acetylated by aspirin and targeted for degradation, which is associated with increased antitumor immunity and improved survival. Similar findings were obtained with inhibitors of sirtuin 2 (SIRT2), a histone deacetylase. These findings expand our current understanding of the role of FGL1 in cancer and provide an impetus for the evaluation of alternative immunotherapy combinations in …

Middle Meningeal Artery Embolization For Chronic Subdural Hematoma: Predictors Of Clinical And Radiographic Failure From 636 Embolizations, Mohamed M Salem, Okkes Kuybu, Alex Nguyen Hoang, Ammad A Baig, Mirhojjat Khorasanizadeh, Cordell Baker, Joshua C Hunsaker, Aldo A Mendez, Gustavo Cortez, Jason M Davies, Sandra Narayanan, C Michael Cawley, Howard A Riina, Justin M Moore, Alejandro M Spiotta, Alexander A Khalessi, Brian M Howard, Ricardo Hanel, Omar Tanweer, Elad I Levy, Ramesh Grandhi, Michael J Lang, Adnan H Siddiqui, Peter Kan, Christopher S Ogilvy, Bradley A Gross, Ajith J Thomas, Brian T Jankowitz, Jan-Karl Burkhardt

Faculty, Staff and Students Publications

Background

Knowledge regarding predictors of clinical and radiographic failures of middle meningeal artery (MMA) embolization (MMAE) treatment for chronic subdural hematoma (CSDH) is limited.

Purpose

To identify predictors of MMAE treatment failure for CSDH.

Materials and Methods

In this retrospective study, consecutive patients who underwent MMAE for CSDH from February 2018 to April 2022 at 13 U.S. centers were included. Clinical failure was defined as hematoma reaccumulation and/or neurologic deterioration requiring rescue surgery. Radiographic failure was defined as a maximal hematoma thickness reduction less than 50% at last imaging (minimum 2 weeks of head CT follow-up). Multivariable logistic regression models …

Alveolar Rhabdomyosarcoma Has Superior Response Rates To Vinorelbine Compared To Embryonal Rhabdomyosarcoma In Patients With Relapsed/Refractory Disease: A Meta-Analysis, Wendy Allen-Rhoades, Philip J Lupo, Michael E Scheurer, Yueh-Yun Chi, John F Kuttesch, Rajkumar Venkatramani, William H Meyer, Leo Mascarenhas

Faculty, Staff and Students Publications

BACKGROUND: Patients with alveolar rhabdomyosarcoma (ARMS) have inferior outcomes compared to patients with embryonal rhabdomyosarcoma (ERMS) and more effective chemotherapy options are needed for these patients. Vinorelbine is a semisynthetic vinca alkaloid that has clinical activity in relapsed rhabdomyosarcoma (RMS) when used alone or in combination with cyclophosphamide.

AIMS: The goal of our study was to evaluate whether RMS histology subtype influences response rate to vinorelbine alone or in combination.

MATERIALS & METHODS: Five Phase 2 trials that enrolled RMS patients were included in the meta-analysis. Two studies evaluated vinorelbine alone, two studies evaluated vinorelbine in combination with low dose …

Genetic Associations Between Modifiable Risk Factors And Alzheimer Disease, Jiao Luo, Jesper Qvist Thomassen, Céline Bellenguez, Benjamin Grenier-Boley, Itziar De Rojas, Atahualpa Castillo, Kayenat Parveen, Fahri Küçükali, Aude Nicolas, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Deckert Jürgen, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Jordi Clarimon, Fermin Moreno, Jordi Pérez-Tur, María J Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Jose Luís Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Teemu Kuulasmaa, Alexandre De Mendonça, Shima Mehrabian, Jakub Hort, Martin Vyhnalek, Sven Van Der Lee, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Delphine Bacq-Daian, Jean-François Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Luisa Benussi, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Sandro Sorbi, Paolo Caffarra, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Carlo Masullo, Gianfranco Spalletta, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick Kehoe, Magda Tsolaki, Giacomina Rossi, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Ole A Andreassen, Mikko Hiltunen, Cornelia Van Duijn, Rebecca Sims, Wiesje Van Der Flier, Agustín Ruiz, Alfredo Ramirez, Jean-Charles Lambert, Ruth Frikke-Schmidt

Faculty, Staff and Students Publications

IMPORTANCE: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.

OBJECTIVE: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for …

Exploration Of Associations Among Dietary Tryptophan, Microbiome Composition And Function, And Symptom Severity In Irritable Bowel Syndrome, Anna M Plantinga, Kendra J Kamp, Qinglong Wu, Li Chen, Linda Yoo, Robert L Burr, Kevin C Cain, Daniel Raftery, Fausto Carnevale Neto, Shyam Badu, Sik Yu So, Tor Savidge, Robert J Shulman, Margaret M Heitkemper

Faculty, Staff and Students Publications

BACKGROUND: Imbalance of the tryptophan (TRP) pathway may influence symptoms among patients with irritable bowel syndrome (IBS). This study explored relationships among different components that contribute to TRP metabolism (dietary intake, stool metabolite levels, predicted microbiome metabolic capability) in females with IBS and healthy controls (HCs). Within the IBS group, we also investigated relationships between TRP metabolic determinants, Bifidobacterium abundance, and symptoms of IBS.

METHODS: Participants with IBS (Rome III) and HCs completed a 28-day diary of gastrointestinal symptoms and a 3-day food record for TRP intake. They provided a stool sample for shotgun metagenomics, 16 S rRNA analyses, and …

The Prevalence And Determinants Of Nafld And Mafld And Their Severity In The Va Primary Care Setting, Aaron P Thrift, Theresa H Nguyen, Codey Pham, Maya Balakrishnan, Fasiha Kanwal, Rohit Loomba, Hao T Duong, David Ramsey, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: A recent panel of international experts proposed the disease acronym metabolic (dysfunction)-associated fatty liver disease (MAFLD) in lieu of nonalcoholic fatty liver disease (NAFLD). We aimed to estimate the burden of and risk factors for NAFLD and MAFLD, and to examine the concordance between definitions in a Veterans population.

METHODS: We conducted a cross-sectional study among randomly selected patients within primary care at the Houston Veterans Affairs (VA) facility. Participants completed a survey, provided blood, and underwent Fibroscan. In the absence of heavy alcohol, hepatitis C virus and hepatitis B virus, a controlled attenuation parameter median ≥290 …

Inhibitory Input Directs Astrocyte Morphogenesis Through Glial Gababr, Yi-Ting Cheng, Estefania Luna-Figueroa, Junsung Woo, Hsiao-Chi Chen, Zhung-Fu Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Communication between neurons and glia plays an important role in establishing and maintaining higher order brain function1. Astrocytes are endowed with complex morphologies which places their peripheral processes in close proximity to neuronal synapses and directly contributes to their regulation of brain circuits2–4. Recent studies have shown that excitatory neuronal activity promotes oligodendrocyte differentiation5–7; whether inhibitory neurotransmission regulates astrocyte morphogenesis during development is unknown. Here we show that inhibitory neuron activity is necessary and sufficient for astrocyte morphogenesis. We found that input from inhibitory neurons functions through astrocytic GABABR and …

Human Papillomavirus Vaccination Prevalence And Disproportionate Cancer Burden Among Us Veterans, Smrithi Chidambaram, Su-Hsin Chang, Vlad C Sandulache, Angela L Mazul, Jose P Zevallos

Faculty, Staff and Students Publications

This cross-sectional study examines the rate of HPV vaccination and the number eligible for this vaccination among younger veterans and civilians.

A Weakly Structured Stem For Human Origins In Africa, Aaron P Ragsdale, Timothy D Weaver, Elizabeth G Atkinson, Eileen G Hoal, Marlo Möller, Brenna M Henn, Simon Gravel

Faculty, Staff and Students Publications

Despite broad agreement that Homo sapiens originated in Africa, considerable uncertainty surrounds specific models of divergence and migration across the continent1. Progress is hampered by a shortage of fossil and genomic data, as well as variability in previous estimates of divergence times1. Here we seek to discriminate among such models by considering linkage disequilibrium and diversity-based statistics, optimized for rapid, complex demographic inference2. We infer detailed demographic models for populations across Africa, including eastern and western representatives, and newly sequenced whole genomes from 44 Nama (Khoe-San) individuals from southern Africa. We infer a reticulated …

Exosomes, Microvesicles, And Other Extracellular Vesicles-A Keystone Symposia Report, Jennifer Cable, Kenneth W Witwer, Robert J Coffey, Aleksandar Milosavljevic, Ariana K Von Lersner, Lizandra Jimenez, Ferdinando Pucci, Maureen M Barr, Niek Dekker, Bahnisikha Barman, Daniel Humphrys, Justin Williams, Michele De Palma, Wei Guo, Nuno Bastos, Andrew F Hill, Efrat Levy, Michael P Hantak, Clair Crewe, Elena Aikawa, Alan M Adamczyk, Tamires M Zanotto, Matias Ostrowski, Tanina Arab, Daniel C Rabe, Aadil Sheikh, Danilo Rodrigues Da Silva, Jennifer C Jones, Chioma Okeoma, Thomas Gaborski, Qin Zhang, Olesia Gololobova

Faculty, Staff and Students Publications

Extracellular vesicles (EVs) are small, lipid-bilayer-bound particles released by cells that can contain important bioactive molecules, including lipids, RNAs, and proteins. Once released in the extracellular environment, EVs can act as messengers locally as well as to distant tissues to coordinate tissue homeostasis and systemic responses. There is a growing interest in not only understanding the physiology of EVs as signaling particles but also leveraging them as minimally invasive diagnostic and prognostic biomarkers (e.g., they can be found in biofluids) and drug-delivery vehicles. On October 30-November 2, 2022, researchers in the EV field convened for the Keystone symposium "Exosomes, Microvesicles, …

Endogenous Interleukin-10 Contributes To Wound Healing And Regulates Tissue Repair, Walker D Short, Meredith Rae, Thomas Lu, Benjamin Padon, Tanuj J Prajapati, Fayiz Faruk, Oluyinka O Olutoye, Ling Yu, Paul Bollyky, Sundeep G Keswani, Swathi Balaji

Faculty, Staff and Students Publications

INTRODUCTION: Interleukin-10 (IL-10) is essential in fetal regenerative wound healing and likewise promotes a regenerative phenotype in adult dermal wounds. However, the role of endogenous IL-10 in postnatal dermal wound healing is not well-established. We sought to determine the function of endogenous IL-10 in murine full thickness excisional wounds that are splinted to prevent contracture and mimic human patterns of wound closure.

METHODS: Full-thickness excisional wounds were made in wildtype (WT) and IL-10

RESULTS: We observed no difference in wound healing rate between WT and IL-10

CONCLUSIONS: These data suggest that endogenous IL-10 expression does not alter closure of full …

Spinal Cord Stimulator Migration And Malfunction In The Setting Of Upper Extremity Complex Regional Pain Syndrome: A Case Report, Mohammed Miniato, Krishna Shah

Faculty, Staff and Students Publications

Background: Common long-term complications for neuromodulation include lead migration, loss of efficacy of therapy, and lead malfunction. The following case describes pitfalls of lead migration and preventative steps to decrease risk of this complication.

Case report: This is an independent case study following the outcome of one patient diagnosed with complex regional pain syndrome that had failed conservative therapy. She underwent implantation of a spinal cord stimulator (SCS) with > 90% relief. Loss of relief was described on follow-up. On reimaging, the SCS had migrated cephalad and this was likely the cause of the malfunction.

Conclusions: Lead migration can occur at …

Prevalence And Risk Factors Of Nonalcoholic Fatty Liver Disease In A General Population, The Hunt Study, Erika R Bjørnå, Martine T Engelsen, Hashem B El-Serag, Eivind Ness-Jensen

Faculty, Staff and Students Publications

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and the metabolic syndrome is the main risk factor. Alanine aminotransferase (ALT) is widely used to screen for NAFLD, and the aims of this study were to assess the prevalence and risk factors of NAFLD in a general population.

Methods: The study was based on the third population-based Trøndelag Health Study (HUNT3), Norway, performed 2006-2008. In HUNT3, ALT and lipids were analyzed, anthropometric measures done, and comorbidity and risk factors reported. Elevated ALT was used to define NAFLD and participants with other diagnosed liver diseases and excessive …

N-Terminal Egfp-Tagging Of Rabbit Apolipoprotein A-I Decreases Expression And Impairs Cholesterol-Efflux Activity, Bradley K Wacker, Lianxiang Bi, Li Liu, Mary G Sorci-Thomas, Philip Ng, Donna J Palmer, Chongren Tang, David A Dichek

Faculty, Staff and Students Publications

No abstract provided.