Digital Commons Network^™

Survey Of Pediatric Critical Care Fellows On Postresuscitation Debriefing, Nicholas A Rossi, Mia Benavidez, Harold S Pine, Shiva Daram, Wasyl Szeremeta

Faculty, Staff and Student Publications

Choanal atresia is a rare congenital airway malformation that presents a unique surgical challenge for pediatric otolaryngologists. Here we report two classic cases of choanal atresia and examine the surgical approaches to this entity. The first case was a four-day-old female with a history of CHARGE syndrome and bilateral mixed membranous and bony choanal atresia confirmed by a CT scan. After undergoing transnasal endoscopic repair, choanal stents were placed for four weeks, and the patient was seen three months postoperatively and found to be doing well with no respiratory concerns. The second case involved a healthy three-year-old female presenting with …

The Nephrocheck Bedside System For Detecting Stage 3 Acute Kidney Injury After Open Thoracoabdominal Aortic Repair, Mark Hwang, Michael H Weisman

Faculty, Staff and Student Publications

No abstract provided.

Changes In Physical Activity Associated With The Covid-19 Pandemic In Individuals With Overweight And Obesity: An Interrupted Time Series Analysis With Historical Controls, Michael C Robertson, Che Young Lee, Ivan Haw-Chong Wu, Yue Liao, Margaret Raber, Nathan Parker, Thuan Le, Leticia Gatus, Karen M Basen-Engquist

Faculty, Staff and Students Publications

The objective of this study was to investigate changes in physical activity patterns associated with the COVID-19 pandemic in individuals with overweight and obesity who were participating in a school district worksite weight loss program. We conducted comparative design interrupted time series analyses on physical activity device (Fitbit) data from the 2018-2019 and 2019-2020 school years (N = 211). We administered a questionnaire in 2020 to supplement device data. After the stay-at-home orders in 2020, participants tended to decrease their weekly step count (B = -1315.7, SE = 627.7, p = .045), decrease their weekly "Lightly active minutes" (B = …

Exposure To Per- And Polyfluoroalkyl Substances And Markers Of Liver Injury: A Systematic Review And Meta-Analysis, Elizabeth Costello, Sarah Rock, Nikos Stratakis, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Dora Cserbik, Todd Jenkins, Stavra A Xanthakos, Rohit Kohli, Stephanie Sisley, Vasilis Vasiliou, Michele A La Merrill, Hugo Rosen, David V Conti, Rob Mcconnell, Leda Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Experimental evidence indicates that exposure to certain pollutants is associated with liver damage. Per- and polyfluoroalkyl substances (PFAS) are persistent synthetic chemicals widely used in industry and consumer products and bioaccumulate in food webs and human tissues, such as the liver.

OBJECTIVE: The objective of this study was to conduct a systematic review of the literature and meta-analysis evaluating PFAS exposure and evidence of liver injury from rodent and epidemiological studies.

METHODS: PubMed and Embase were searched for all studies from earliest available indexing year through 1 December 2021 using keywords corresponding to PFAS exposure and liver injury. For …

Notch-Induced Mdsc Recruitment After Ohsv Virotherapy In Cns Cancer Models Modulates Antitumor Immunotherapy, Yoshihiro Otani, Ji Young Yoo, Cole T Lewis, Samantha Chao, Jessica Swanner, Toshihiko Shimizu, Jin Muk Kang, Sara A Murphy, Kimberly Rivera-Caraballo, Bangxing Hong, Joseph C Glorioso, Hiroshi Nakashima, Sean E Lawler, Yeshavanth Banasavadi-Siddegowda, John D Heiss, Yuanqing Yan, Guangsheng Pei, Michael A Caligiuri, Zhongming Zhao, E Antonio Chiocca, Jianhua Yu, Balveen Kaur

Faculty, Staff and Student Publications

PURPOSE: Oncolytic herpes simplex virus-1 (oHSV) infection of brain tumors activates NOTCH, however the consequences of NOTCH on oHSV-induced immunotherapy is largely unknown. Here we evaluated the impact of NOTCH blockade on virus-induced immunotherapy.

EXPERIMENTAL DESIGN: RNA sequencing (RNA-seq), TCGA data analysis, flow cytometry, Luminex- and ELISA-based assays, brain tumor animal models, and serum analysis of patients with recurrent glioblastoma (GBM) treated with oHSV was used to evaluate the effect of NOTCH signaling on virus-induced immunotherapy.

RESULTS: TCGA data analysis of patients with grade IV glioma and oHSV treatment of experimental brain tumors in mice showed that NOTCH signaling significantly …

Prevalence Of Metabolic Syndrome Among The Adult Population In Western China And The Association With Socioeconomic And Individual Factors: Four Cross-Sectional Studies, Xinyin Xu, Jing Zeng, Wei Yang, Ting Dong, Xin Zhang, Shuwen Cheng, Xiaobo Zhou, Maigeng Zhou, Ling Niu, Guanghui Yi, You Li, Lishi Zhang, Yin Deng, Xianping Wu

Faculty, Staff and Student Publications

Objectives: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation.

Design: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015.

Setting: From 2010 to 2018, 8-15 counties/districts of West China were included.

Participants: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors.

Results: …

Assessment Of Travel Distance For Hyperthermic Intraperitoneal Chemotherapy In Women With Ovarian Cancer, Laura M Chambers, Meng Yao, Molly Morton, Morgan Gruner, Anna Chichura, Anthony B Costales, Max Horowitz, Peter G Rose, Chad M Michener, Robert Debernardo

Faculty, Staff and Students Publications

OBJECTIVE S: To evaluate travel distance in women with advanced or recurrent epithelial ovarian cancer (OC) undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) and the subsequent impact upon outcomes.

METHODS: An IRB-approved single-institution prospective registry was queried for women with OC who underwent HIPEC from 1/1/2009-12/1/2020. Demographic, oncologic, and surgical data were recorded. The patient's home zip code was compared to the institutional zip code to determine travel distance using Google Maps. Patients were divided into three strata for analysis: 1) local: ≤50 miles, 2) regional: 51-99 miles, and 3) distant: ≥100 miles and univariate analysis was performed.

RESULTS: …

Retinal Organoids Derived From Rhesus Macaque Ipscs Undergo Accelerated Differentiation Compared To Human Stem Cells, Antonio Jacobo Lopez, Sangbae Kim, Xinye Qian, Jeffrey Rogers, J Timothy Stout, Sara M Thomasy, Anna La Torre, Rui Chen, Ala Moshiri

Faculty, Staff and Students Publications

PURPOSE: To compare the timing and efficiency of the development of Macaca mulatta, a nonhuman primate (NHP), induced pluripotent stem cell (rhiPSC) derived retinal organoids to those derived from human embryonic stem cells (hESCs).

RESULTS: Generation of retinal organoids was achieved from both human and several NHP pluripotent stem cell lines. All rhiPSC lines resulted in retinal differentiation with the formation of optic vesicle-like structures similar to what has been observed in hESC retinal organoids. NHP retinal organoids had laminated structure and were composed of mature retinal cell types including cone and rod photoreceptors. Single-cell RNA sequencing was conducted at …

Foxo1 Represses Sprouty 2 And Sprouty 4 Expression To Promote Arterial Specification And Vascular Remodeling In The Mouse Yolk Sac, Nanbing Li-Villarreal, Rebecca Lee Yean Wong, Monica D Garcia, Ryan S Udan, Ross A Poché, Tara L Rasmussen, Alexander M Rhyner, Joshua D Wythe, Mary E Dickinson

Faculty, Staff and Students Publications

Establishing a functional circulatory system is required for post-implantation development during murine embryogenesis. Previous studies in loss-of-function mouse models showed that FOXO1, a Forkhead family transcription factor, is required for yolk sac (YS) vascular remodeling and survival beyond embryonic day (E) 11. Here, we demonstrate that at E8.25, loss of Foxo1 in Tie2-cre expressing cells resulted in increased sprouty 2 (Spry2) and Spry4 expression, reduced arterial gene expression and reduced Kdr (also known as Vegfr2 and Flk1) transcripts without affecting overall endothelial cell identity, survival or proliferation. Using a Dll4-BAC-nlacZ reporter line, we found that one of the earliest expressed …

Targeting Calcium-Mediated Inter-Organellar Crosstalk In Cardiac Diseases, Mohit M Hulsurkar, Satadru K Lahiri, Jason Karch, Meng C Wang, Xander H T Wehrens

Faculty, Staff and Students Publications

INTRODUCTION: Abnormal calcium signaling between organelles such as the sarcoplasmic reticulum (SR), mitochondria and lysosomes is a key feature of heart diseases. Calcium serves as a secondary messenger mediating inter-organellar crosstalk, essential for maintaining the cardiomyocyte function.

AREAS COVERED: This article examines the available literature related to calcium channels and transporters involved in inter-organellar calcium signaling. The SR calcium-release channels ryanodine receptor type-2 (RyR2) and inositol 1,4,5-trisphosphate receptor (IP

EXPERT OPINION: Enhanced SR calcium release via RyR2 and reduced SR reuptake via SERCA2a, increased VDAC and MCUC-mediated calcium uptake into mitochondria, and enhanced lysosomal calcium-release via lysosomal TPC and TRPML …

Colonic Epithelial Angiotensin-Converting Enzyme 2 (Ace2) Expression In Blacks And Whites: Potential Implications For Pathogenesis Covid-19 Racial Disparities, Mart De La Cruz, David P Nunes, Vaishali Bhardwaj, Deepika Subramanyan, Caroline Zaworski, Priya Roy, Hemant K Roy

Faculty, Staff and Students Publications

BACKGROUND: Covid-19 toll is disproportionate in Blacks although the mechanisms remain incompletely understood. From a biological perspective, several host proteins have received most attention as logical susceptibility targets. Specifically, angiotensin-converting enzyme 2 (ACE2) serves as the epithelial cell receptor and acts in concert with transmembrane protease serine 2 (TMPRSS2). Intriguingly, ACE2 can also suppress the inflammatory response and therefore may impact the severity of Covid-19 infections (from the exuberant immune response a.k.a. "cytokine storm"). We, therefore, assessed expression of ACE2 and TMPRSS2 in Blacks versus Whites.

METHODS: Archived mucosal biopsies from colonoscopic biopsies of visually normal rectal mucosa without concurrent …

Purpose, Subject, And Consumer Comment On "Perceived Burden Due To Registrations For Quality Monitoring And Improvement In Hospitals: A Mixed Methods Study", Sylvia J Hysong, Patrick O'Mahen, Jochen Profit, Laura A Petersen

Faculty, Staff and Students Publications

Zegers and colleagues’ study codifies the perceived burden of quality monitoring and improvement stemming from the work by clinicians of registering (documenting) quality information in the medical record. We agree with Zegers and colleagues’ recommendation that a smaller, more effective and curated set of measures is needed to reduce burden, confusion, and expense. We further note that focusing on validity of clinical evidence behind individual measures is critical, but insufficient. We therefore extend Zegers and colleagues’ work through a pragmatic, tripartite heuristic. To assess the value of and curate a targeted set of performance measures, we propose concentrating on the …

Comparison Of Endoscopic Ultrasound-Directed Transgastric Endoscopic Retrograde Cholangiopancreatography Outcomes Using Various Technical Approaches, Firas Bahdi, Rollin George, Kavea Paneerselvam, Dang Nguyen, Wasif M Abidi, Mohamed O Othman, Isaac Raijman

Faculty, Staff and Students Publications

Background and study aims  Roux-en-Y gastric bypass presents an anatomic challenge for patients needing ERCP. EUS-directed transgastric ERCP (EDGE) offers high clinical success but carries considerable risk of adverse events (AEs) with no standardized technical approach. In our study, we review the safety and efficacy of our various EDGE technical approaches.

Patients and methods  A retrospective single-center study of all patients who underwent EDGE procedures between February 2018 and November 2019. Primary outcomes included comparing the technical and clinical success, AEs, and lumen-apposing metal stent (LAMS) migration rates per access route (gastrogastric vs jejuno-gastric), number of procedure stages (single-stage vs …

Differences In Covid-19-Related Testing And Healthcare Utilization By Race And Ethnicity In The Veterans Health Administration, Javad Razjouyan, Drew A Helmer, Ang Li, Aanand D Naik, Christopher I Amos, Venkata Bandi, Amir Sharafkhaneh

Faculty, Staff and Students Publications

IMPORTANCE: Recent reports indicate differences in COVID-19-related care and outcomes between Black and White Americans.

OBJECTIVE: We examine the COVID-19-related healthcare utilization and mortality by race and ethnicity of patients tested for SARS-CoV-2 in the Veterans Health Administration (VHA).

DESIGN: A retrospective cohort study.

SETTING: We used the VHA COVID-19 shared data resources between February 1 and June 30, 2020.

PARTICIPANTS: Veterans tested for SARS-CoV-2 virus by VHA.

EXPOSURE(S): Three racial-ethnicity groups of Black, Hispanic, and White (as reference) veterans.

MAIN OUTCOME(S) AND MEASURE(S): Main outcomes are testing rate, positivity rate, hospitalization rate, ICU admission rate, and in-hospital mortality. Controlling …

The Role Of Palmitoleic Acid In Regulating Hepatic Gluconeogenesis Through Sirt3 In Obese Mice, Xin Guo, Xiaofan Jiang, Keyun Chen, Qijian Liang, Shixiu Zhang, Juan Zheng, Xiaomin Ma, Hongmei Jiang, Hao Wu, Qiang Tong

Faculty, Staff and Students Publications

Hepatic gluconeogenesis is a crucial process to maintain glucose level during starvation. However, unabated glucose production in diabetic patients is a major contributor to hyperglycemia. Palmitoleic acid is a monounsaturated fatty acid (16:1n7) that is available from dietary sources. Palmitoleic acid exhibits health beneficial effects on diabetes, insulin resistance, inflammation, and metabolic syndrome. However, the mechanism by which palmitoleate reduces blood glucose is still unclear. SIRT3 is a key metabolism-regulating NAD+-dependent protein deacetylase. It is known that fasting elevates the expression of SIRT3 in the liver and it regulates many aspects of liver’s response to nutrient deprivation, such as fatty …

Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis.

METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up …

Methods For Cross-Cultural Communication In Clinic Encounters, Princess U Ogbogu, Lenora Mendoza Noroski, Kimberly Arcoleo, Benjamin D Reese, Andrea J Apter

Faculty, Staff and Students Publications

Successful cross-cultural communication is critical for adequate exchange of ideas with our patients. Our communities have become more diverse, and thus, the necessity has increased. The murder of George Floyd and other atrocities have sparked recognition of the need to address social injustice and racism and as we fight the ongoing coronavirus disease 2019 (COVID-19) pandemic. Allergist-immunologists are uniquely trained to explain the complex immunology of COVID-19 to patients, but they have less experience discussing issues of health equity. Here, we explore critical components of patient-provider communication: communicating with those for whom English is a second language, advising patients with …

Clinical Presentation, Treatment, And Genetic And Histopathological Analysis Of Juvenile Cataracts And Secondary Glaucoma In A Rhesus Macaque (Macaca Mulatta), M Isabel Casanova, Rui Chen, Laura M Garzel, Katherine J Olstad, Soohyun Kim, Ronald Alan Harris, Yumei Li, Muthuswamy Raveendran, Qingnan Liang, Jun Wang, Glenn Yiu, John Timothy Stout, Jeffrey A Roberts, Jeffrey Rogers, Ala Moshiri, Sara M Thomasy

Faculty, Staff and Students Publications

This report describes the clinical and histological findings, genetic study, and treatment in a 1.3-year-old rhesus macaque with bilateral cataracts and unilateral secondary glaucoma. Intravitreal injection of gentamicin decreased the intraocular pressure from 56 to <2 mm Hg. A putative genetic cause of the cataracts was not identified.

Single-Cell Transcriptional Profiling Of Murine Conjunctival Immune Cells Reveals Distinct Populations Expressing Homeostatic And Regulatory Genes, Jehan Alam, Ghasem Yazdanpanah, Rinki Ratnapriya, Nicholas Borcherding, Cintia S De Paiva, Dequan Li, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Immune cells in the exposed conjunctiva mucosa defend against environmental and microbial stresses. Expression profiling by single-cell RNA sequencing was performed to identify conjunctival immune cell populations expressing homeostatic and regulatory genes. Fourteen distinct clusters were identified, including myeloid cells (neutrophils, monocytes, macrophages), dendritic cells (DC), and lymphoid cells (B, T, γδT, ILC2, and NK) lineages. Novel neutrophil [lipocalin (Lcn2) high and low), and MHCIIlo macrophage (MP) clusters were identified. More than half of the cells map to myeloid and dendritic cell populations with differential expression profiles that include genes with homeostatic and regulatory functions: Serpinb2 (MHCIIlo macrophage), …

Risk Factors Associated With Patient-Reported Fatigue Among Long-Term Oropharyngeal Carcinoma Survivors, Puja Aggarwal, Katherine A Hutcheson, Ryan P Goepfert, Adam S Garden, Naveen Garg, Frank E Mott, Clifton D Fuller, Stephen Y Lai, Gary Brandon Gunn, Mark S Chambers, Ehab Y Hanna, Erich M Sturgis, Sanjay Shete

Faculty, Staff and Students Publications

BACKGROUND: The study objective is to identify risk factors associated with fatigue among long-term OPC survivors.

METHODS: This cross-sectional study included disease-free OPC survivors treated curatively between 2000 and 2013 who were surveyed from September 2015 to July 2016. The outcome variable was patient-reported fatigue. Multivariable logistic regression was used to identify factors associated with moderate to severe fatigue.

RESULTS: Among 863 OPC survivors, 17.4% reported moderate to severe fatigue. Self-reported thyroid problems (OR: 2.01; p = 0.003), current cigarette smoking at time of survey (OR: 3.85; p = 0.001), late lower cranial neuropathy (OR: 3.44; p = 0.002), and …

A Multi-Disciplinary Approach To Chronic Cough In Children, Shraddha S Mukerji, Naga Jaya Smitha Yenduri, Eric Chiou, Siby P Moonnumakal, Joshua R Bedwell

Faculty, Staff and Students Publications

OBJECTIVES: (1) To highlight the important causes of chronic and recurrent cough in children. (2) To discuss multidisciplinary approach to management of chronic/recurrent pediatric cough.

METHODS: Review of scholarly articles, guidelines, expert panels via PubMed and Google Scholar.

CONCLUSION: Chronic cough (CC) in children is mainly attributed to persistent bacterial bronchitis, asthma, nonspecific cough, and gastroesophageal reflux disease (GERD) symptoms. A multi-disciplinary approach is cost-effective and aids with earlier diagnosis and appropriate treatment. Congenital or acquired narrowing of the subglottis is the leading ENT cause for recurrent croup (RC) in children. Laryngeal cleft-type 1 is commonly seen in children with …

Perturbed Hematopoiesis In Individuals With Germline Dnmt3a Overgrowth Tatton-Brown-Rahman Syndrome, Ayala Tovy, Carina Rosas, Amos S Gaikwad, Geraldo Medrano, Linda Zhang, Jaime M Reyes, Yung-Hsin Huang, Tastuhiko Arakawa, Kristen Kurtz, Shannon E Conneely, Anna G Guzman, Rogelio Aguilar, Anne Gao, Chun-Wei Chen, Jean J Kim, Melissa T Carter, Amaia Lasa-Aranzasti, Irene Valenzuela, Lionel Van Maldergem, Lorenzo Brunetti, M John Hicks, Andrea N Marcogliese, Margaret A Goodell, Rachel E Rau

Faculty, Staff and Students Publications

Tatton-Brown-Rahman syndrome (TBRS) is an overgrowth disorder caused by germline heterozygous mutations in the DNA methyltransferase DNMT3A. DNMT3A is a critical regulator of hematopoietic stem cell (HSC) differentiation and somatic DNMT3A mutations are frequent in hematologic malignancies and clonal hematopoiesis. Yet, the impact of constitutive DNMT3A mutation on hematopoiesis in TBRS is undefined. In order to establish how constitutive mutation of DNMT3A impacts blood development in TBRS we gathered clinical data and analyzed blood parameters in 18 individuals with TBRS. We also determined the distribution of major peripheral blood cell lineages by flow cytometric analyses. Our analyses revealed non-anemic macrocytosis, …

A Non-Coding Insertional Mutation Of Grhl2 Causes Gene Over-Expression And Multiple Structural Anomalies Including Cleft Palate, Spina Bifida And Encephalocele, Georgia Pitsava, Marcia L Feldkamp, Nathan Pankratz, John Lane, Denise M Kay, Kristin M Conway, Charlotte Hobbs, Gary M Shaw, Jennita Reefhuis, Mary M Jenkins, Lynn M Almli, Cynthia Moore, Martha Werler, Marilyn L Browne, Chris Cunniff, Andrew F Olshan, Faith Pangilinan, Lawrence C Brody, Robert J Sicko, Richard H Finnell, Michael J Bamshad, Daniel Mcgoldrick, Deborah A Nickerson, James C Mullikin, Paul A Romitti, James L Mills

Faculty, Staff and Students Publications

BACKGROUND: Sacral agenesis (SA) consists of partial or complete absence of the caudal end of the spine and often presents with additional birth defects. Several studies have examined gene variants for syndromic forms of SA, but only one has examined exomes of children with non-syndromic SA.

METHODS: Using buccal cell specimens from families of children with non-syndromic SA, exomes of 28 child-parent trios (eight with and 20 without a maternal diagnosis of pregestational diabetes) and two child-father duos (neither with diagnosis of maternal pregestational diabetes) were exome sequenced.

RESULTS: Three children had heterozygous missense variants in ID1 (Inhibitor of DNA …

Peppermint Oil Effects On The Gut Microbiome In Children With Functional Abdominal Pain, Santosh Thapa, Ruth Ann Luna, Bruno P Chumpitazi, Numan Oezguen, Susan M Abdel-Rahman, Uttam Garg, Salma Musaad, James Versalovic, Gregory L Kearns, Robert J Shulman

Faculty, Staff and Students Publications

Peppermint oil (PMO) is effective in the treatment of functional abdominal pain disorders, but its mechanism of action is unclear. Evidence suggests PMO has microbicidal activity. We investigated the effect of three different doses of PMO on gut microbiome composition. Thirty children (7-12 years of age) with functional abdominal pain provided a baseline stool sample prior to randomization to 180, 360, or 540 mg of enteric coated PMO (10 participants per dose). They took their respective dose of PMO (180 mg once, 180 mg twice, or 180 mg thrice daily) for 1 week, after which the stool collection was repeated. …

Disrupting The Myc-Tfeb Circuit Impairs Amino Acid Homeostasis And Provokes Metabolic Anergy, Mario R Fernandez, Franz X Schaub, Chunying Yang, Weimin Li, Seongseok Yun, Stephanie K Schaub, Frank C Dorsey, Min Liu, Meredith A Steeves, Andrea Ballabio, Alexandar Tzankov, Zhihua Chen, John M Koomen, Anders E Berglund, John L Cleveland

Duncan NRI Faculty and Staff Publications

MYC family oncoproteins are regulators of metabolic reprogramming that sustains cancer cell anabolism. Normal cells adapt to nutrient-limiting conditions by activating autophagy, which is required for amino acid (AA) homeostasis. Here we report that the autophagy pathway is suppressed by Myc in normal B cells, in premalignant and neoplastic B cells of Eμ-Myc transgenic mice, and in human MYC-driven Burkitt lymphoma. Myc suppresses autophagy by antagonizing the expression and function of transcription factor EB (TFEB), a master regulator of autophagy. Mechanisms that sustained AA pools in MYC-expressing B cells include coordinated induction of the proteasome and increases in AA …

Prevalence And Predictors Of Missed Dysplasia On Index Barrett's Esophagus Diagnosing Endoscopy In A Veteran Population, Theresa H Nguyen, Aaron P Thrift, Rollin George, Daniel G Rosen, Hashem B El-Serag, Gyanprakash A Ketwaroo

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Limitations of endoscopic sampling may result in missed dysplasia at the diagnosis of Barrett's esophagus (BE). However, the role of close follow-up endoscopy is unclear. The aim was to evaluate the proportion of patients diagnosed with "missed" dysplasia within 18 months of their index nondysplastic BE (NDBE) diagnosis.

METHODS: This was a retrospective analysis of a cohort of BE patients diagnosed during 1990-2019 at the Houston VA. Patients with BE on index esophagogastroduodenoscopy (EGD) were classified as NDBE, indefinite dysplasia, or dysplastic (low- or high-grade dysplasia) based on initial biopsies. We identified NDBE patients who had follow-up …

Identification Of An Optimal Dose Of Intravenous Ketamine For Late-Life Treatment-Resistant Depression: A Bayesian Adaptive Randomization Trial, Marijn Lijffijt, Nicholas Murphy, Sidra Iqbal, Charles E Green, Tabish Iqbal, Lee C Chang, Colin N Haile, Lorna C Hirsch, Nithya Ramakrishnan, Dylan A Fall, Alan C Swann, Rayan K Al Jurdi, Sanjay J Mathew

Faculty, Staff and Students Publications

Evidence supporting specific therapies for late-life treatment-resistant depression (LL-TRD) is necessary. This study used Bayesian adaptive randomization to determine the optimal dose for the probability of treatment response (≥50% improvement from baseline on the Montgomery-Åsberg Depression Rating Scale) 7 days after a 40 min intravenous (IV) infusion of ketamine 0.1 mg/kg (KET 0.1), 0.25 mg/kg (KET 0.25), or 0.5 mg/kg (KET 0.5), compared to midazolam 0.03 mg/kg (MID) as an active placebo. The goal of this study was to identify the best dose to carry forward into a larger clinical trial. Response durability at day 28, safety and tolerability, and …

Intestinal Deletion Of 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Promotes Expansion Of The Resident Stem Cell Compartment, Alexandria M Doerfler, Jun Han, Kelsey E Jarrett, Li Tang, Antrix Jain, Alexander Saltzman, Marco De Giorgi, Marcel Chuecos, Ayrea E Hurley, Ang Li, Pauline Morand, Claudia Ayala, David R Goodlett, Anna Malovannaya, James F Martin, Thomas Q De Aguiar Vallim, Noah Shroyer, William R Lagor

Faculty, Staff and Students Publications

BACKGROUND: The intestine occupies the critical interface between cholesterol absorption and excretion. Surprisingly little is known about the role of de novo cholesterol synthesis in this organ, and its relationship to whole body cholesterol homeostasis. Here, we investigate the physiological importance of this pathway through genetic deletion of the rate-limiting enzyme.

METHODS: Mice lacking 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) in intestinal villus and crypt epithelial cells were generated using a Villin-Cre transgene. Plasma lipids, intestinal morphology, mevalonate pathway metabolites, and gene expression were analyzed.

RESULTS: Mice with intestine-specific loss of Hmgcr were markedly smaller at birth, but gain …

Derivation And Validation Of A Novel Risk Assessment Tool To Identify Children Aged 2–59 Months At Risk Of Hospitalised Pneumonia-Related Mortality In 20 Countries, Chris A Rees, Tim Colbourn, Shubhada Hooli, Carina King, Norman Lufesi, Eric D Mccollum, Charles Mwansambo, Clare Cutland, Shabir Ahmed Madhi, Marta Nunes, Joseph L Matthew, Emmanuel Addo-Yobo, Noel Chisaka, Mumtaz Hassan, Patricia L Hibberd, Prakash M Jeena, Juan M Lozano, William B Macleod, Archana Patel, Donald M Thea, Ngoc Tuong Vy Nguyen, Cissy B Kartasasmita, Marilla Lucero, Shally Awasthi, Ashish Bavdekar, Monidarin Chou, Pagbajabyn Nymadawa, Jean-William Pape, Glaucia Paranhos-Baccala, Valentina S Picot, Mala Rakoto-Andrianarivelo, Vanessa Rouzier, Graciela Russomando, Mariam Sylla, Philippe Vanhems, Jianwei Wang, Rai Asghar, Salem Banajeh, Imran Iqbal, Irene Maulen-Radovan, Greta Mino-Leon, Samir K Saha, Mathuram Santosham, Sunit Singhi, Sudha Basnet, Tor A Strand, Shinjini Bhatnagar, Nitya Wadhwa, Rakesh Lodha, Satinder Aneja, Alexey W Clara, Harry Campbell, Harish Nair, Jennifer Falconer, Shamim A Qazi, Yasir B Nisar, Mark I Neuman, World Health Organization Prepare Study Group

Faculty, Staff and Students Publications

INTRODUCTION: Existing risk assessment tools to identify children at risk of hospitalised pneumonia-related mortality have shown suboptimal discriminatory value during external validation. Our objective was to derive and validate a novel risk assessment tool to identify children aged 2-59 months at risk of hospitalised pneumonia-related mortality across various settings.

METHODS: We used primary, baseline, patient-level data from 11 studies, including children evaluated for pneumonia in 20 low-income and middle-income countries. Patients with complete data were included in a logistic regression model to assess the association of candidate variables with the outcome hospitalised pneumonia-related mortality. Adjusted log coefficients were calculated for …

Vestibular Rehabilitation For Peripheral Vestibular Hypofunction: An Updated Clinical Practice Guideline From The Academy Of Neurologic Physical Therapy Of The American Physical Therapy Association, Courtney D Hall, Susan J Herdman, Susan L Whitney, Eric R Anson, Wendy J Carender, Carrie W Hoppes, Stephen P Cass, Jennifer B Christy, Helen S Cohen, Terry D Fife, Joseph M Furman, Neil T Shepard, Richard A Clendaniel, J Donald Dishman, Joel A Goebel, Dara Meldrum, Cynthia Ryan, Richard L Wallace, Nakia J Woodward

Faculty, Staff and Students Publications

BACKGROUND: Uncompensated vestibular hypofunction can result in symptoms of dizziness, imbalance, and/or oscillopsia, gaze and gait instability, and impaired navigation and spatial orientation; thus, may negatively impact an individual's quality of life, ability to perform activities of daily living, drive, and work. It is estimated that one-third of adults in the United States have vestibular dysfunction and the incidence increases with age. There is strong evidence supporting vestibular physical therapy for reducing symptoms, improving gaze and postural stability, and improving function in individuals with vestibular hypofunction. The purpose of this revised clinical practice guideline is to improve quality of care …