Digital Commons Network^™

Retrospective Review Of 80 Patients With Chronic Recurrent Multifocal Osteomyelitis Evaluated By Pediatric Orthopaedic Surgeons, Tristen Noble Taylor, Callie Shawhan Bridges, Ekene Uchenna Ezeokoli, Tyler Scott Smith, Nicole Irene Montgomery

Faculty, Staff and Students Publications

Background: Chronic Recurrent Multifocal Osteomyelitis (CRMO) is a rare aseptic autoinflammatory disease with a wide and vague clinical presentation that often mimics infection, malignancy, or benign conditions, leading to a delayed diagnosis. We aimed to evaluate the clinical characteristics, differential diagnoses from evaluating pediatric orthopaedic surgeons, and compared the number of patients that could have avoided a biopsy in 80 patients with CRMO.

Methods: Children diagnosed with CRMO at a single tertiary pediatric hospital in the United States between 2012 and 2022 who were evaluated by a pediatric orthopaedic surgeon were retrospectively reviewed. The differential diagnoses from the surgeons were …

The Nlrp3 Inflammasome Fires Up Heme-Induced Inflammation In Hemolytic Conditions, Suruchi Salgar, Beatriz E Bolívar, Jonathan M Flanagan, Shaniqua J Anum, Lisa Bouchier-Hayes

Faculty, Staff and Students Publications

Overactive inflammatory responses are central to the pathophysiology of many hemolytic conditions including sickle cell disease. Excessive hemolysis leads to elevated serum levels of heme due to saturation of heme scavenging mechanisms. Extracellular heme has been shown to activate the NLRP3 inflammasome, leading to activation of caspase-1 and release of pro-inflammatory cytokines IL-1β and IL-18. Heme also activates the non-canonical inflammasome pathway, which may contribute to NLRP3 inflammasome formation and leads to pyroptosis, a type of inflammatory cell death. Some clinical studies indicate there is a benefit to blocking the NLRP3 inflammasome pathway in patients with sickle cell disease and …

Sumoylation Regulates Functional Properties Of The Oocyte Transcription Factors Sohlh1 And Nobox, Bethany K Patton, Surabhi Madadi, Shawn M Briley, Avery A Ahmed, Stephanie A Pangas

Faculty, Staff and Students Publications

SOHLH1 and NOBOX are oocyte-expressed transcription factors with critical roles in ovary development and fertility. In mice, Sohlh1 and Nobox are essential for fertility through their regulation of the oocyte transcriptional network and cross-talk to somatic cells. Sumoylation is a posttranslational modification that regulates transcription factor function, and we previously showed that mouse oocytes deficient for sumoylation had an altered transcriptional landscape that included significant changes in NOBOX target genes. Here, we show that mouse SOHLH1 is modified by SUMO2/3 at lysine 345 and mutation of this residue alters SOHLH1 nuclear to cytoplasmic localization. In NOBOX, we identify a non-consensus …

Solid Organ Transplantation In Methylmalonic Acidemia And Propionic Acidemia: A Points To Consider Statement Of The American College Of Medical Genetics And Genomics (Acmg), Kuntal Sen, Lindsay C Burrage, Kimberly A Chapman, Ilona Ginevic, George V Mazariegos, Brett H Graham, Acmg Therapeutics Committe

Faculty, Staff and Students Publications

No abstract provided.

Biallelic Variants In Hect E3 Paralogs, Hectd4 And Ube3c, Encoding Ubiquitin Ligases Cause Neurodevelopmental Disorders That Overlap With Angelman Syndrome, Eissa A Faqeih, Malak Ali Alghamdi, Marwa A Almahroos, Essa Alharby, Makki Almuntashri, Amnah M Alshangiti, Prouteau Clément, Daniel G Calame, Leila Qebibo, Lydie Burglen, Martine Doco-Fenzy, Mario Mastrangelo, Annalaura Torella, Filippo Manti, Vincenzo Nigro, Ziegler Alban, Ghadeer Saleh Alharbi, Jamil Amjad Hashmi, Rawya Alraddadi, Razan Alamri, Tadahiro Mitani, Barth Magalie, Zeynep Coban-Akdemir, Bilgen Bilge Geckinli, Davut Pehlivan, Antonio Romito, Vasiliki Karageorgou, Javier Martini, Estelle Colin, Dominique Bonneau, Aida Bertoli-Avella, James R Lupski, Annalisa Pastore, Roy W A Peake, Ashraf Dallol, Majid Alfadhel, Naif A M Almontashiri

Faculty, Staff and Students Publications

Purpose: Pathogenic variants in genes encoding ubiquitin E3 ligases are known to cause neurodevelopmental syndromes. Additional neurodevelopmental disorders associated with the other genes encoding E3 ligases are yet to be identified.

Methods: Chromosomal analysis and exome sequencing were used to identify the genetic causes in 10 patients from 7 unrelated families with syndromic neurodevelopmental, seizure, and movement disorders and neurobehavioral phenotypes.

Results: In total, 4 patients were found to have 3 different homozygous loss-of-function (LoF) variants, and 3 patients had 4 compound heterozygous missense variants in the candidate E3 ligase gene, HECTD4, that were rare, absent from controls as homozygous, …

Aortic Stress Activates An Adaptive Program In Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength And Protects Against Aneurysm And Dissection In Mice, Chen Zhang, Yanming Li, Abhijit Chakraborty, Yang Li, Kimberly R Rebello, Pingping Ren, Wei Luo, Lin Zhang, Hong S Lu, Lisa A Cassis, Joseph S Coselli, Alan Daugherty, Scott A Lemaire, Ying H Shen

Faculty, Staff and Students Publications

BACKGROUND:

When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to angiotensin II (AngII) infusion and determined its importance in protecting against aortic aneurysm and dissection (AAD).

METHODS:

We performed single-cell RNA sequencing (scRNA-seq) and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analyses in a mouse model of sporadic AAD induced by AngII infusion. We also examined the …

Characterizing Mechanism-Based Pain Phenotypes In Patients With Chronic Pancreatitis: A Cross-Sectional Analysis Of The Prospective Evaluation Of Chronic Pancreatitis For Epidemiologic And Translational Studies, Jami L Saloman, Darwin L Conwell, Evan Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Anna Evans Phillips, Mark Topazian, Stephen K Van Den Eeden, Jose Serrano, Dhiraj Yadav

Faculty, Staff and Students Publications

Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N …

Ancillary Documents For Nih Grant Applications: The Pages Beyond The Scienceancillary Documents For Nih Grant Applications: The Pages Beyond The Science, Monica Fahrenholz, Lily S Cheng, Oluyinka Olutoye, Anjali A Degala, Sonya S Keswani, Taylor Lee, Allan M Goldstein, Sundeep G Keswani

Faculty, Staff and Students Publications

Preparing a grant proposal is no small feat, especially for research (R-series) grants from the National Institutes of Health. The National Institutes of Health is the largest public funder of biomedical research in the world, and as such, procuring a research grant from the National Institutes of Health is one of the ultimate benchmarks of success for a surgeon-scientist. Most investigators are familiar with the page limits for most R-series grants (12 pages for an R01 and 6 pages for an R21), with the addition of a single page allotted for the specific aims. Interestingly, despite the usual focus on …

Stanford Type A Aortic Dissection In A Patient With Primary Antiphospholipid Syndrome And Coronavirus Disease 2019, Sarah A Ahmad, Nauman Khalid, Lovely Chhabra, Waleed T Kayani, Tarek Helmy

Faculty, Staff and Students Publications

Acute aortic dissection is one of the most lethal diseases, affecting the lining of the aortic wall. We describe a case of Stanford Type A aortic dissection in a patient with underlying primary antiphospholipid syndrome (APS) complicated by coronavirus disease 2019 (COVID-19). APS is characterized by recurrent venous and/or arterial thrombosis, thrombocytopenia, and rarely vascular aneurysms. The hypercoagulable milieu attributable to APS and the prothrombotic state from COVID-19 posed a challenge in achieving optimal postoperative anticoagulation in our patient.

New Frontiers Of Integration: Convergent Pathways Of Neighborhood Diversification In Metropolitan New York, Kasey Zapatka, Van C. Tran

Publications and Research

This article examines the most recent trends on neighborhood racial integration in New York—the country’s largest metropolitan area in 2019 with a total population of 19.2 million. We ask how the suburbanization of both immigration and poverty have transformed suburbs over the last two decades. We highlight four findings. First, ethnoracial diversification has led to a significant decline in nonintegrated neighborhoods and a sharp rise in integrated neighborhoods, but such a decline is more dramatic in suburbs than in cities. Second, White-integrated neighborhoods remain the most prevalent form of neighborhood integration in both cities and suburbs. Third, immigrant neighborhoods are …

Beyond Varices: Complications Of Cirrhotic Portal Hypertension In Pediatrics, Anna M Banc-Husu, Henry Shiau, Peace Dike, Benjamin L Shneider

Faculty, Staff and Students Publications

Complications of cirrhotic portal hypertension (PHTN) in children are broad and include clinical manifestations ranging from variceal hemorrhage, hepatic encephalopathy (HE), ascites, spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome (HRS) to less common conditions such as hepatopulmonary syndrome, portopulmonary hypertension, and cirrhotic cardiomyopathy. The approaches to the diagnosis and management of these complications have become standard of practice in adults with cirrhosis with many guidance statements available. However, there is limited literature on the diagnosis and management of these complications of PHTN in children with much of the current guidance available focused on variceal hemorrhage. The aim of this review …

Current Challenges And Future Direction In Surveillance For Hepatocellular Carcinoma In Patients With Nonalcoholic Fatty Liver Disease, George Cholankeril, Hashem B El-Serag

Faculty, Staff and Students Publications

The burden for hepatocellular carcinoma (HCC) attributed to nonalcoholic fatty liver disease (NAFLD) continues to grow in parallel with rising global trends in obesity. The risk of HCC is elevated among patients with NAFLD-related cirrhosis to a level that justifies surveillance based on cost-effectiveness argument. The quality of current evidence for HCC surveillance in all patients with chronic liver disease is poor, and even lower in those with NAFLD. For a lack of more precise risk-stratification tools, current approaches to defining a target population in noncirrhotic NAFLD are limited to noninvasive tests for liver fibrosis, as a proxy for liver-related …

Dynamic Errors In Pulse Oximetry Preclude Use Of Correction Factor, Ashraf Fawzy, Valeria S M Valbuena, Christopher F Chesley, Tianshi David Wu, Theodore J Iwashyna

Faculty, Staff and Students Publications

No abstract provided.

Rapid Clinical Expansion And The Fate Of The Hospitalist Educator, Julia B Caton, Shannon K Martin, Marisha Burden, Zaven Sargsyan, Michelle Brooks, Daniel N Ricotta

Faculty, Staff and Students Publications

No abstract provided.

Genetic Variants In Arhgef6 Cause Congenital Anomalies Of The Kidneys And Urinary Tract In Humans, Mice, And Frogs, Verena Klämbt, Florian Buerger, Chunyan Wang, Thomas Naert, Karin Richter, Theresa Nauth, Anna-Carina Weiss, Tobias Sieckmann, Ethan Lai, Dervla M Connaughton, Steve Seltzsam, Nina Mann, Amar J Majmundar, Chen-Han W Wu, Ana C Onuchic-Whitford, Shirlee Shril, Sophia Schneider, Luca Schierbaum, Rufeng Dai, Mir Reza Bekheirnia, Marieke Joosten, Omer Shlomovitz, Asaf Vivante, Ehud Banne, Shrikant Mane, Richard P Lifton, Karin M Kirschner, Andreas Kispert, Georg Rosenberger, Klaus-Dieter Fischer, Soeren S Lienkamp, Mirjam M P Zegers, Friedhelm Hildebrandt

Faculty, Staff and Students Publications

Background: About 40 disease genes have been described to date for isolated CAKUT, the most common cause of childhood CKD. However, these genes account for only 20% of cases. ARHGEF6, a guanine nucleotide exchange factor that is implicated in biologic processes such as cell migration and focal adhesion, acts downstream of integrin-linked kinase (ILK) and parvin proteins. A genetic variant of ILK that causes murine renal agenesis abrogates the interaction of ILK with a murine focal adhesion protein encoded by Parva , leading to CAKUT in mice with this variant.

Methods: To identify novel genes that, when mutated, result in …

Lumasiran For Advanced Primary Hyperoxaluria Type 1: Phase 3 Illuminate-C Trial, Mini Michael, Jaap W Groothoff, Hadas Shasha-Lavsky, John C Lieske, Yaacov Frishberg, Eva Simkova, Anne-Laure Sellier-Leclerc, Arnaud Devresse, Fitsum Guebre-Egziabher, Sevcan A Bakkaloglu, Chebl Mourani, Rola Saqan, Richard Singer, Richard Willey, Bahru Habtemariam, John M Gansner, Ishir Bhan, Tracy Mcgregor, Daniella Magen

Faculty, Staff and Students Publications

Rationale & objective: Lumasiran reduces urinary and plasma oxalate (POx) in patients with primary hyperoxaluria type 1 (PH1) and relatively preserved kidney function. ILLUMINATE-C evaluates the efficacy, safety, pharmacokinetics, and pharmacodynamics of lumasiran in patients with PH1 and advanced kidney disease.

Study design: Phase 3, open-label, single-arm trial.

Setting & participants: Multinational study; enrolled patients with PH1 of all ages, estimated glomerular filtration rate ≤45 mL/min/1.73 m2 (if age ≥12 months) or increased serum creatinine level (if age < 12 months), and POx ≥20 μmol/L at screening, including patients with or without systemic oxalosis.

Intervention: Lumasiran administered subcutaneously; 3 monthly doses followed by monthly or quarterly weight-based dosing.

Outcome: Primary end point: percent change in POx …

Functional And Clinical Studies Reveal Pathophysiological Complexity Of Clcn4-Related Neurodevelopmental Condition, Elizabeth E Palmer, Michael Pusch, Alessandra Picollo, Caitlin Forwood, Matthew H Nguyen, Vanessa Suckow, Jessica Gibbons, Alva Hoff, Lisa Sigfrid, Andre Megarbane, Mathilde Nizon, Benjamin Cogné, Claire Beneteau, Fowzan S Alkuraya, Aziza Chedrawi, Mais O Hashem, Hannah Stamberger, Sarah Weckhuysen, Arnaud Vanlander, Berten Ceulemans, Sulekha Rajagopalan, Kenneth Nunn, Stéphanie Arpin, Martine Raynaud, Constance S Motter, Catherine Ward-Melver, Katrien Janssens, Marije Meuwissen, Diane Beysen, Nicola Dikow, Mona Grimmel, Tobias B Haack, Emma Clement, Amy Mctague, David Hunt, Sharron Townshend, Michelle Ward, Linda J Richards, Cas Simons, Gregory Costain, Lucie Dupuis, Roberto Mendoza-Londono, Tracy Dudding-Byth, Jackie Boyle, Carol Saunders, Emily Fleming, Salima El Chehadeh, Marie-Aude Spitz, Amelie Piton, Bénédicte Gerard, Marie-Thérèse Abi Warde, Gillian Rea, Caoimhe Mckenna, Sofia Douzgou, Siddharth Banka, Cigdem Akman, Jennifer M Bain, Tristan T Sands, Golder N Wilson, Erin J Silvertooth, Lauren Miller, Damien Lederer, Rani Sachdev, Rebecca Macintosh, Olivier Monestier, Deniz Karadurmus, Felicity Collins, Melissa Carter, Luis Rohena, Marjolein H Willemsen, Charlotte W Ockeloen, Rolph Pfundt, Sanne D Kroft, Michael Field, Francisco E R Laranjeira, Ana M Fortuna, Ana R Soares, Vincent Michaud, Sophie Naudion, Sailaja Golla, David D Weaver, Lynne M Bird, Jennifer Friedman, Virginia Clowes, Shelagh Joss, Laura Pölsler, Philippe M Campeau, Maria Blazo, Emilia K Bijlsma, Jill A Rosenfeld, Christian Beetz, Zöe Powis, Kirsty Mcwalter, Tracy Brandt, Erin Torti, Mikaël Mathot, Shekeeb S Mohammad, Ruth Armstrong, Vera M Kalscheuer

Faculty, Staff and Students Publications

Missense and truncating variants in the X-chromosome-linked CLCN4 gene, resulting in reduced or complete loss-of-function (LOF) of the encoded chloride/proton exchanger ClC-4, were recently demonstrated to cause a neurocognitive phenotype in both males and females. Through international clinical matchmaking and interrogation of public variant databases we assembled a database of 90 rare CLCN4 missense variants in 90 families: 41 unique and 18 recurrent variants in 49 families. For 43 families, including 22 males and 33 females, we collated detailed clinical and segregation data. To confirm causality of variants and to obtain insight into disease mechanisms, we investigated the effect on …

Elementary Principal Leadership And Special Education: A Case Study In The United States, Vivian M. Garrison

Dissertations and Theses

School districts have called upon principals to build capacity for inclusive learning environments and prioritize the needs of an increasingly diverse group of students. A principal's work to effectively include students so they are part of the school community and have opportunities to achieve academically has been challenging. As the instructional leader of the school, principals have played an essential role by collaborating with teachers and specialists, removing obstacles to learning, and ensuring that teachers meet the needs of all learners in their classrooms. They have also been held accountable for knowing the laws, policies, and best practices to support …

Raps Sheet, February 2023, Retirement Association Of Portland State

RAPS Sheet: Monthly Newsletter

No abstract provided.

Do Program Practices Matter For Mentors?: How Implementation Of Empirically Supported Program Practices Is Associated With Youth Mentoring Relationship Quality, Thomas E. Keller, Alison L. Drew, Carla Herrera, Hyuny Clark-Shim, Renée Spencer

School of Social Work Faculty Publications and Presentations

This study investigates how the implementation of program-level practices by formal youth mentoring programs is associated with the quality of youth mentoring relationships as contexts for youth development and also examines whether this connection is mediated by the mentor-staff working alliance. Using data from mentors (n = 542) participating in multiple programs (n = 55), multilevel path models examined hypothesized direct and mediated effects. Parallel analyses were conducted with assessments of program practices from staff (n = 219). Greater exposure to program practices was associated with higher ratings of mentoring relationship satisfaction, commitment, and security and lower …

Circadian Clock And Temporal Meal Pattern, Xin Li, Zheng Sun

Faculty, Staff and Students Publications

The central circadian clock in the brain controls the time-of-the-day variations in acute meal responses, with a low glycemic response but a high satiety/thermogenic response to meals consumed at waking compared to other time points. Consistently, studies show that consuming a significant proportion of calories, particularly carbohydrates, in breakfast is beneficial for the chronic management of obesity and its associated metabolic syndrome, compared to consuming identical meals at dinner. Conversely, breakfast skipping or/and late dinner can have unfavorable metabolic outcomes. It remains controversial how meal frequency affects metabolic health. In contrast, irregular meals, especially irregular breakfasts, show consistent adverse metabolic …

Why Does The X Chromosome Lag Behind Autosomes In Gwas Findings?, Ivan P Gorlov, Christopher I Amos

Faculty, Staff and Students Publications

The X-chromosome is among the largest human chromosomes. It differs from autosomes by a number of important features including hemizygosity in males, an almost complete inactivation of one copy in females, and unique patterns of recombination. We used data from the Catalog of Published Genome Wide Association Studies to compare densities of the GWAS-detected SNPs on the X-chromosome and autosomes. The density of GWAS-detected SNPs on the X-chromosome is 6-fold lower compared to the density of the GWAS-detected SNPs on autosomes. Differences between the X-chromosome and autosomes cannot be explained by differences in the overall SNP density, lower X-chromosome coverage …

Potential And Pitfalls Of Pharmacovigilance Databases In Oncology, Ilana Schlam, Michael S Ewer, Sandra M Swain

Duncan NRI Faculty and Staff Publications

No abstract provided.

Serum Biomarkers Correlated With Liver Stiffness Assessed In A Multicenter Study Of Pediatric Cholestatic Liver Disease, Daniel H Leung, Sridevi Devaraj, Nathan P Goodrich, Xinpu Chen, Deepthi Rajapakshe, Wen Ye, Victor Andreev, Charles G Minard, Danielle Guffey, Jean P Molleston, Lee M Bass, Saul J Karpen, Binita M Kamath, Kasper S Wang, Shikha S Sundaram, Philip Rosenthal, Patrick Mckiernan, Kathleen M Loomes, M Kyle Jensen, Simon P Horslen, Jorge A Bezerra, John C Magee, Robert M Merion, Ronald J Sokol, Benjamin L Shneider, Estella Alonso, Lee Bass, Susan Kelly, Mary Riordan, Hector Melin-Aldana, Jorge Bezerra, Kevin Bove, James Heubi, Alexander Miethke, Greg Tiao, Julie Denlinger, Erin Chapman, Ronald Sokol, Amy Feldman, Cara Mack, Michael Narkewicz, Frederick Suchy, Shikha S Sundaram, Johan Van Hove, Benigno Garcia, Mikaela Kauma, Kendra Kocher, Matthew Steinbeiss, Mark Lovell, Kathleen M Loomes, David Piccoli, Elizabeth Rand, Pierre Russo, Nancy Spinner, Jessi Erlichman, Samantha Stalford, Dina Pakstis, Sakya King, Robert Squires, Rakesh Sindhi, Veena Venkat, Kathy Bukauskas, Patrick Mckiernan, Lori Haberstroh, James Squires, Philip Rosenthal, Laura Bull, Joanna Curry, Camille Langlois, Grace Kim, Jeffery Teckman, Vikki Kociela, Rosemary Nagy, Shraddha Patel, Jacqueline Cerkoski, Jean P Molleston, Molly Bozic, Girish Subbarao, Ann Klipsch, Cindy Sawyers, Oscar Cummings, Simon P Horslen, Karen Murray, Evelyn Hsu, Kara Cooper, Melissa Young, Laura Finn, Binita M Kamath, Vicky Ng, Claudia Quammie, Juan Putra, Deepika Sharma, Aishwarya Parmar, Stephen Guthery, Kyle Jensen, Ann Rutherford, Amy Lowichik, Linda Book, Rebecka Meyers, Tyler Hall, Kasper S Wang, Sonia Michail, Danny Thomas, Catherine Goodhue, Rohit Kohli, Larry Wang, Nisreen Soufi, Daniel Thomas, Saul Karpen, Nitika Gupta, Rene Romero, Miriam B Vos, Rita Tory, John-Paul Berauer, Carlos Abramowsky, Jeanette Mcfall, Benjamin L Shneider, Sanjiv Harpavat, Paula Hertel, Daniel Leung, Mary Tessier, Deborah Schady, Laurel Cavallo, Diego Olvera, Christina Banks, Cynthia Tsai, Richard Thompson, Edward Doo, Jay Hoofnagle, Averell Sherker, Rebecca Torrance, Sherry Hall, John Magee, Robert Merion, Cathie Spino, Wen Ye

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Detailed investigation of the biological pathways leading to hepatic fibrosis and identification of liver fibrosis biomarkers may facilitate early interventions for pediatric cholestasis.

APPROACH AND RESULTS: A targeted enzyme-linked immunosorbent assay-based panel of nine biomarkers (lysyl oxidase, tissue inhibitor matrix metalloproteinase (MMP) 1, connective tissue growth factor [CTGF], IL-8, endoglin, periostin, Mac-2-binding protein, MMP-3, and MMP-7) was examined in children with biliary atresia (BA; n = 187), alpha-1 antitrypsin deficiency (A1AT; n = 78), and Alagille syndrome (ALGS; n = 65) and correlated with liver stiffness (LSM) and biochemical measures of liver disease. Median age and LSM …

Structure Of The Lysosomal Mtorc1-Tfeb-Rag-Ragulator Megacomplex, Zhicheng Cui, Gennaro Napolitano, Mariana E G De Araujo, Alessandra Esposito, Jlenia Monfregola, Lukas A Huber, Andrea Ballabio, James H Hurley

Duncan NRI Faculty and Staff Publications

The transcription factor TFEB is a master regulator of lysosomal biogenesis and autophagy1. The phosphorylation of TFEB by the mechanistic target of rapamycin complex 1 (mTORC1)2–5 is unique in its mTORC1 substrate recruitment mechanism, which is strictly dependent on the amino acid-mediated activation of the RagC GTPase activating protein FLCN6,7. TFEB lacks the TOR signalling motif responsible for the recruitment of other mTORC1 substrates. We used cryogenic-electron microscopy to determine the structure of TFEB as presented to mTORC1 for phosphorylation, which we refer to as the ‘megacomplex’. Two full Rag–Ragulator complexes …

Remote Care Adoption In Underserved Congenital Heart Disease Patients During The Covid-19 Era, Ruth M Vaughan, Judson A Moore, Jasmine S Moreno, Karla J Dyer, Abiodun O Oluyomi, Keila N Lopez

Faculty, Staff and Students Publications

The COVID-19 pandemic restricted in-person appointments and prompted an increase in remote healthcare delivery. Our goal was to assess access to remote care for complex pediatric cardiology patients. We performed a retrospective chart review of Texas Children's Hospital (TCH) pediatric cardiology outpatient appointments from March 2020 to December 2020 for established congenital heart disease (CHD) patients 1 to 17 yo. Primary outcome variables were remote care use of telemedicine and patient portal activation. Primary predictor variables were age, sex, insurance, race/ethnicity, language, and location. Descriptive statistics were used to analyze patient demographics. Multivariate logistic regression determined associations with remote care …

A Review Of Stellate Ganglion Block As An Adjunctive Treatment Modality, Kennedy Kirkpatrick, Mashfee H Khan, Yi Deng, Krishna B Shah

Faculty, Staff and Students Publications

Peripheral nerve blocks are becoming increasingly used as adjunctive treatment modalities for a variety of conditions refractory to medical management. Right or left stellate ganglion blocks (SGB) are a specific type of peripheral nerve block that target the sympathetic blockade of neuronal impulses using the injection of local anesthetic and steroids into nerve bundles in the cervical area. This review article is intended to summarize the common uses of stellate ganglion blocks and explain the procedural technique, which has evolved with technological advances in ultrasonography. The similarities between these disease processes are centered around sympathetic hyperactivity. This sympathetic overdrive state …

Magel2 Truncation Alters Select Behavioral And Physiological Outcomes In A Rat Model Of Schaaf-Yang Syndrome, Derek L Reznik, Mingxiao V Yang, Pedro Albelda De La Haza, Antrix Jain, Melanie Spanjaard, Susanne Theiss, Christian P Schaaf, Anna Malovannaya, Theresa V Strong, Surabi Veeraragavan, Rodney C Samaco

Faculty, Staff and Students Publications

Previous studies in mice have utilized Magel2 gene deletion models to examine the consequences of its absence. We report the generation, molecular validation and phenotypic characterization of a novel rat model with a truncating Magel2 mutation modeling variants associated with Schaaf-Yang syndrome-causing mutations. Within the hypothalamus, a brain region in which human MAGEL2 is paternally expressed, we demonstrated, at the level of transcript and peptide detection, that rat Magel2 exhibits a paternal, parent-of-origin effect. In evaluations of behavioral features across several domains, juvenile Magel2 mutant rats displayed alterations in anxiety-like behavior and sociability measures. Moreover, the analysis of peripheral organ …

Anxiety Sensitivity And Cigarette Use On Cannabis Use Problems, Perceived Barriers For Cannabis Cessation, And Self-Efficacy For Quitting Among Adults With Cannabis Use Disorder, Michael F Orr, Luke F Heggeness, Nirvi Mehta, Jacob Moya, Kara Manning, Lorra Garey, Julianna Hogan, Marcel De Dios, Michael J Zvolensky

Faculty, Staff and Students Publications

Many individuals diagnosed with cannabis use disorder (CUD) report a desire to quit using cannabis due to problems associated with use. Yet, successful abstinence is difficult for a large subset of this population. Thus, the present study sought to elucidate potential risk factors for cannabis use problems, perceived barriers for quitting, and diminished self-efficacy for remaining abstinent. Specifically, this investigation examined cigarette user status, anxiety sensitivity, and the interplay between these individual difference factors in terms of cannabis-related problems, perceived barriers for cannabis cessation, and self-efficacy for quitting cannabis use. The sample consisted of 132 adult cannabis users who met …

Comparison Of Postoperative Outcomes Of Laparoscopic Vs Open Inguinal Hernia Repair, Jennie Meier, Audrey Stevens, Miles Berger, Konstantinos I Makris, Athanasios Bramos, Joan Reisch, C Munro Cullum, Simon C Lee, Celette Sugg Skinner, Herbert Zeh, Cynthia J Brown, Courtney J Balentine

Faculty, Staff and Students Publications

Importance: Advocates of laparoscopic surgery argue that all inguinal hernias, including initial and unilateral ones, should be repaired laparoscopically. Prior work suggests outcomes of open repair are improved by using local rather than general anesthesia, but no prior studies have compared laparoscopic surgery with open repair under local anesthesia.

Objective: To evaluate postoperative outcomes of open inguinal hernia repair under general or local anesthesia compared with laparoscopic repair.

Design, setting, and participants: This retrospective cohort study identified 107 073 patients in the Veterans Affairs Surgical Quality Improvement Program database who underwent unilateral initial inguinal hernia repair from 1998 to 2019. …