Medical Specialties Commons^™

Patient-Derived Ipscs Link Elevated Mitochondrial Respiratory Complex I Function To Osteosarcoma In Rothmund-Thomson Syndrome, Brittany E Jewell, An Xu, Dandan Zhu, Mo-Fan Huang, Linchao Lu, Mo Liu, Erica L Underwood, Jun Hyoung Park, Huihui Fan, Julian A Gingold, Ruoji Zhou, Jian Tu, Zijun Huo, Ying Liu, Weidong Jin, Yi-Hung Chen, Yitian Xu, Shu-Hsia Chen, Nino Rainusso, Nathaniel K Berg, Danielle A Bazer, Christopher Vellano, Philip Jones, Holger K Eltzschig, Zhongming Zhao, Benny Abraham Kaipparettu, Ruiying Zhao, Lisa L Wang, Dung-Fang Lee

Faculty, Staff and Student Publications

Rothmund-Thomson syndrome (RTS) is an autosomal recessive genetic disorder characterized by poikiloderma, small stature, skeletal anomalies, sparse brows/lashes, cataracts, and predisposition to cancer. Type 2 RTS patients with biallelic RECQL4 pathogenic variants have multiple skeletal anomalies and a significantly increased incidence of osteosarcoma. Here, we generated RTS patient-derived induced pluripotent stem cells (iPSCs) to dissect the pathological signaling leading to RTS patient-associated osteosarcoma. RTS iPSC-derived osteoblasts showed defective osteogenic differentiation and gain of in vitro tumorigenic ability. Transcriptome analysis of RTS osteoblasts validated decreased bone morphogenesis while revealing aberrantly upregulated mitochondrial respiratory complex I gene expression. RTS osteoblast metabolic assays …

Mission-Based Filters In The Electronic Residency Application Service: Saving Time And Promoting Diversity, Jennifer L Swails, Sasha Adams, Mark Hormann, Emma Omoruyi, Omowunmi Aibana

Faculty, Staff and Student Publications

BACKGROUND: Holistic review promotes diversity, but widespread implementation remains limited.

OBJECTIVE: We aimed to develop a practical approach to incorporate holistic review principles in screening applicants in the Electronic Residency Application Service (ERAS) and to assess the impact on diversity.

METHODS: Three residency programs (internal medicine [IM], pediatrics, and surgery) at McGovern Medical School developed filters to identify applicants with experiences/attributes aligned with the institutional mission. These filters were retroactively applied to each program's 2019-2020 applicant pool using built-in ERAS capabilities to group applicants by user-defined features. We compared the demographics of applicants reviewed during the cycle with those identified …

Resistin Levels Decrease As Insulin Resistance Increases In A Mexican-American Cohort, Absalon D Gutierrez, Carlos A Flores, Sapna Naik, Minjae Lee, Parisa Asgarisabet, Masha Resman, Miryoung Lee, Joseph B Mccormick, Susan P Fisher-Hoch

Faculty, Staff and Student Publications

AIMS: Links between resistin, insulin resistance (IR), and resistin-stimulated cytokine signaling remain unknown in Mexican-Americans. A Mexican-American cohort was examined to determine (1) relationships between circulating resistin and IR, (2) resistin's associations with cytokines and demographic and anthropometric variables, and (3) similar measurements with other adipokines.

METHODS: For cross sectional analyses, 953 adults (367 males and 586 females) in the Cameron County Hispanic Cohort (CCHC) were stratified into three groups: normal glucose tolerance, prediabetes, and diabetes mellitus. Differences in resistin and other adipokine levels were examined using linear regression via unadjusted model (Model 1), model adjusted for cytokines (Model 2), …

Classifying Esophageal Motility By Flip Panometry: A Study Of 722 Subjects With Manometry, Dustin A Carlson, C Prakash Gyawali, Abraham Khan, Rena Yadlapati, Joan Chen, Reena V Chokshi, John O Clarke, Jose M Garza, Anand S Jain, Philip Katz, Vani Konda, Kristle Lynch, Felice H Schnoll-Sussman, Stuart J Spechler, Marcelo F Vela, Jacqueline E Prescott, Alexandra J Baumann, Erica N Donnan, Wenjun Kou, Peter J Kahrilas, John E Pandolfino

Faculty, Staff and Students Publications

INTRODUCTION: Functional luminal imaging probe (FLIP) panometry can evaluate esophageal motility in response to sustained esophageal distension at the time of sedated endoscopy. This study aimed to describe a classification of esophageal motility using FLIP panometry and evaluate it against high-resolution manometry (HRM) and Chicago Classification v4.0 (CCv4.0).

METHODS: Five hundred thirty-nine adult patients who completed FLIP and HRM with a conclusive CCv4.0 diagnosis were included in the primary analysis. Thirty-five asymptomatic volunteers ("controls") and 148 patients with an inconclusive CCv4.0 diagnosis or systemic sclerosis were also described. Esophagogastric junction (EGJ) opening and the contractile response (CR) to distension (i.e., …

Prevalence And Predictors Of Cost-Related Medication Nonadherence In Individuals With Cardiovascular Disease: Results From The Behavioral Risk Factor Surveillance System (Brfss) Survey, Riyad Kherallah, Mahmoud Al Rifai, Ishan Kamat, Chayakrit Krittanawong, Dhruv Mahtta, Michelle T Lee, Jing Liu, Khurram Nasir, Javier Valero-Elizondo, Jaideep Patel, Mouaz H Al-Mallah, Laura A Petersen, Salim S Virani

Faculty, Staff and Students Publications

Medication nonadherence is highly prevalent among patients with chronic cardiovascular disease. Poor adherence has been associated with increased morbidity and mortality. Medication cost is a major driver for medication nonadherence. Utilizing data from the 2016 to 2018 Behavioral Risk Factor Surveillance System (BRFSS) survey, we estimated the prevalence of cost-related medication nonadherence (CRMNA) among the overall population and among individuals who reported a history of diabetes, atherosclerotic cardiovascular disease (ASCVD), or hypertension. We then performed multivariable logistic regression to analyze sociodemographic factors associated with CRMNA. Our study population consisted of 142,577 individuals of whom 24% were older than 65 years, …

The Landscape Of Renal Replacement Therapy In Veterans Affairs Medical Center Intensive Care Units, Chandan Vangala, Maulin Shah, Natasha N Dave, Layth Al Attar, Sankar D Navaneethan, Venkat Ramanathan, Susan Crowley, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

BACKGROUND: Outpatient dialysis is standardized with several evidence-based measures of adequacy and quality that providers aim to meet while providing treatment. By contrast, in the intensive care unit (ICU) there are different types of prolonged and continuous renal replacement therapies (PIRRT and CRRT, respectively) with varied strategies for addressing patient care and a dearth of nationally accepted quality parameters. To eventually describe appropriate quality measures for ICU-related renal replacement therapy (RRT), we first aimed to capture the variety and prevalence of basic strategies and equipment utilized in the ICUs of Veteran Affairs (VA) medical facilities with inpatient hemodialysis capabilities.

METHODS: …

Transient Ascaris Suum Larval Migration Induces Intractable Chronic Pulmonary Disease And Anemia In Mice, Yifan Wu, Evan Li, Morgan Knight, Grace Adeniyi-Ipadeola, Li-Zhen Song, Alan R Burns, Ana Clara Gazzinelli-Guimaraes, Ricardo Fujiwara, Maria Elena Bottazzi, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis is one of the most common infections in the world and associated with significant global morbidity. Ascaris larval migration through the host's lungs is essential for larval development but leads to an exaggerated type-2 host immune response manifesting clinically as acute allergic airway disease. However, whether Ascaris larval migration can subsequently lead to chronic lung diseases remains unknown. Here, we demonstrate that a single episode of Ascaris larval migration through the host lungs induces a chronic pulmonary syndrome of type-2 inflammatory pathology and emphysema accompanied by pulmonary hemorrhage and chronic anemia in a mouse model. Our results reveal that …

Genetic Testing In Ambulatory Cardiology Clinics Reveals High Rate Of Findings With Clinical Management Implications, David R Murdock, Eric Venner, Donna M Muzny, Ginger A Metcalf, Mullai Murugan, Trevor D Hadley, Varuna Chander, Paul S De Vries, Xiaoming Jia, Aliza Hussain, Ali M Agha, Aniko Sabo, Shoudong Li, Qingchang Meng, Jianhong Hu, Xia Tian, Michelle Cohen, Victoria Yi, Christie L Kovar, Marie-Claude Gingras, Viktoriya Korchina, Chad Howard, Daniel L Riconda, Stacey Pereira, Hadley S Smith, Zohra A Huda, Alexandria Buentello, Patricia R Marino, Lee Leiber, Ashok Balasubramanyam, Christopher I Amos, Andrew B Civitello, Mihail G Chelu, Ronald Maag, Amy L Mcguire, Eric Boerwinkle, Xander H T Wehrens, Christie M Ballantyne, Richard A Gibbs

Faculty, Staff and Students Publications

PURPOSE: Cardiovascular disease (CVD) is the leading cause of death in adults in the United States, yet the benefits of genetic testing are not universally accepted.

METHODS: We developed the "HeartCare" panel of genes associated with CVD, evaluating high-penetrance Mendelian conditions, coronary artery disease (CAD) polygenic risk, LPA gene polymorphisms, and specific pharmacogenetic (PGx) variants. We enrolled 709 individuals from cardiology clinics at Baylor College of Medicine, and samples were analyzed in a CAP/CLIA-certified laboratory. Results were returned to the ordering physician and uploaded to the electronic medical record.

RESULTS: Notably, 32% of patients had a genetic finding with clinical …

Variations In Medical Students' Educational Preferences, Attitudes And Volunteerism During The Covid-19 Global Pandemic, Nital P Appelbaum, Sanghamitra M Misra, Jennifer Welch, M Harrison Humphries, Sunthosh Sivam, Nadia Ismail

Faculty, Staff and Students Publications

Public health crises require individuals, often volunteers, to help minimize disasters. The COVID-19 pandemic required such activation of individuals, but little is known about medical students’ preferences of such engagement. We investigated potential variations in medical students’ educational preferences, attitudes, and volunteerism during the COVID-19 pandemic based on socio-demographics to better prepare for future activation scenarios. A web-based, anonymous survey of U.S. medical students at a single institution was conducted in May 2020. Across four training year, 518 (68% response rate) students completed the survey. During the pandemic, 42.3% (n = 215) wanted to discontinue in-person clinical experiences, 32.3% (n …

Predicted Vitamin D Status And Colorectal Cancer Incidence In The Black Women's Health Study, Lauren E Barber, Kimberly A Bertrand, Jessica L Petrick, Hanna Gerlovin, Laura F White, Lucile L Adams-Campbell, Lynn Rosenberg, Hemant K Roy, Julie R Palmer

Faculty, Staff and Students Publications

BACKGROUND: Observational studies, mostly among White populations, suggest that low vitamin D levels increase colorectal cancer risk. African Americans, who are disproportionately burdened by colorectal cancer, often have lower vitamin D levels compared with other populations.

METHODS: We assessed predicted vitamin D score in relation to colorectal cancer among 49,534 participants in the Black Women's Health Study, a cohort of African American women followed from 1995 to 2017 through biennial questionnaires. We derived predicted vitamin D scores at each questionnaire cycle for all participants using a previously validated prediction model based on actual 25-hydroxyvitamin D values from a subset of …

Interaction Between Alcohol Consumption And Pnpla3 Variant In The Prevalence Of Hepatic Steatosis In The Us Population, Mariana Lazo, Usama Bilal, Mack C Mitchell, James Potter, Ruben Hernaez, Jeanne M Clark

Faculty, Staff and Students Publications

BACKGROUND & AIMS: To our knowledge, the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis has not been explored in a representative sample. To examine the interaction between alcohol consumption and PNPLA3 genotype on hepatic steatosis in the US adult population.

METHODS: Cross-sectional study of 4,674 adult participants of the Third National Health and Nutrition Examination Survey, Phase 2 (1991-1994) with data on PNPLA3 genotype, self-reported alcohol consumption, ultrasound-defined hepatic steatosis and socio-demographic characteristics.

RESULTS: In 1991-1994 in the U.S. population, the weighted allele frequency of the G (risk) allele of the rs738409 at PNPLA3 was 25.4%. We …

Associations Of High-Sensitivity Troponin And Natriuretic Peptide Levels With Outcomes After Intensive Blood Pressure Lowering: Findings From The Sprint Randomized Clinical Trial, Jarett D Berry, Vijay Nambi, Walter T Ambrosius, Haiying Chen, Anthony A Killeen, Addison Taylor, Robert D Toto, Elsayed Z Soliman, John W Mcevoy, Ambarish Pandey, Parag H Joshi, Stefan Blankenberg, Dalane W Kitzman, Christie M Ballantyne, James A De Lemos

Faculty, Staff and Students Publications

IMPORTANCE: Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro-B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable.

OBJECTIVE: To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering.

DESIGN, SETTING, AND PARTICIPANTS: This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, …

The Cross-Sectional Association Of Cognition With Diabetic Peripheral And Autonomic Neuropathy–The Grade Study, Joshua I Barzilay, Alokananda Ghosh, Rodica Pop Busui, Andrew Ahmann, Ashok Balasubramanyam, Mary Ann Banerji, Robert M Cohen, Jennifer Green, Faramarz Ismail-Beigi, Catherine L Martin, Elizabeth Seaquist, José A Luchsinger, Grade Research Group

Faculty, Staff and Students Publications

BACKGROUND: Studies examining whether measures of cognition are related to the presence of diabetic peripheral neuropathy (DPN) and/or cardiovascular autonomic neuropathy (CAN) are lacking, as are data regarding factors potentially explaining such associations.

METHODS: Participants were from the Glycemia Reduction Approaches in Diabetes Study (GRADE) that examined 5047 middle-aged people with type 2 diabetes of(memory) were assessed with the Spanish English Verbal Learning Test; frontal executive function and processing speed with the Digit Symbol Substitution Test; and ability to concentrate and organize data with word and animal fluency tests. DPN was assessed with the Michigan Neuropathy Screening Instrument and CAN …

The Emergence Of A Texas Collaboration To Improve Well-Being In Learning Health Systems, Toi B Harris, Anil Nanda, Lilit A Sargsyan, Wei-Jung A Chen, Jennifer G Christner

Faculty, Staff and Students Publications

Prior models of well-being have focused on resolving issues at different levels within a single institution. Changes over time in medicine have resulted in massive turnover and reduced clinical hours that portray a deficit-oriented system. As developments to improve purpose and professional satisfaction emerge, the Texas Medical Association Committee on Physician Health and Wellness (PHW) is committed to providing the vehicle for a statewide collaboration and illuminating the path forward.To describe the existing health and wellness resources in Texas academic medical centers and understand the gaps in resources and strategies for addressing the health and wellness needs in the medical …

Utility Of Blood Cellular Indices In The Risk Stratification Of Patients Presenting With Acute Pulmonary Embolism., Brett Slajus, Yevgeniy Brailovsky, Iman Darwish, Jawed Fareed, Amir Darki

Division of Cardiology Faculty Papers

Pulmonary embolism (PE) clinical manifestations vary widely, and that scope is not fully captured by current all-cause mortality risk models. PE is associated with inflammatory, coagulation, and hemostatic imbalances so blood cellular indices may be prognostically useful. Complete blood count (CBC) data may improve current risk models like the simplified pulmonary embolism severity index (sPESI) for all-cause mortality, offering greater accuracy and analytic ability. Acute PE patients (n = 228) with confirmatory diagnostic imaging were followed for all-cause mortality. Blood cellular indices were assessed for association to all-cause mortality and were supplemented into sPESI using multivariate logistic regression. Multiple blood …

Nutrition, Atherosclerosis, Arterial Imaging, Cardiovascular Risk Stratification, And Manifestations In Covid-19 Framework: A Narrative Review., Smiksha Munjral, Puneet Ahluwalia, Ankush D Jamthikar, Anudeep Puvvula, Luca Saba, Gavino Faa, Inder M Singh, Paramjit S Chadha, Monika Turk, Amer M Johri, Narendra N Khanna, Klaudija Viskovic, Sophie Mavrogeni, John R Laird, Gyan Pareek, Martin Miner, David W Sobel, Antonella Balestrieri, Petros P Sfikakis, George Tsoulfas, Athanasios Protogerou, Prasanna Misra, Vikas Agarwal, George D Kitas, Raghu Kolluri, Jagjit Teji, Mustafa Al-Maini, Surinder K Dhanjil, Meyypan Sockalingam, Ajit Saxena, Aditya Sharma, Vijay Rathore, Mostafa Fatemi, Azra Alizad, Vijay Viswanathan, P K Krishnan, Tomaz Omerzu, Subbaram Naidu, Andrew Nicolaides, Jasjit S Suri

Heart and Vascular Articles

Background: Atherosclerosis is the primary cause of the cardiovascular disease (CVD). Several risk factors lead to atherosclerosis, and altered nutrition is one among those. Nutrition has been ignored quite often in the process of CVD risk assessment. Altered nutrition along with carotid ultrasound imaging-driven atherosclerotic plaque features can help in understanding and banishing the problems associated with the late diagnosis of CVD. Artificial intelligence (AI) is another promisingly adopted technology for CVD risk assessment and management. Therefore, we hypothesize that the risk of atherosclerotic CVD can be accurately monitored using carotid ultrasound imaging, predicted using AI-based algorithms, and reduced …

Case Report: Molecular Diagnosis Of Cystoisospora Belli In A Severely Immunocompromised Patient With Hiv And Kaposi Sarcoma, Roumen Borilov Iordanov, Lauren M Leining, Meng Wu, Galant Chan, Andrew R Dinardo, Rojelio Mejia

Faculty, Staff and Students Publications

Diarrhea in an immunocompromised patient has a broad infectious differential. Diagnosis is difficult despite advances in diagnostic modalities. We report a case of a 45-year-old Nigerian woman who immigrated to the United States 2 years ago. She presented to the hospital with gastrointestinal bleeding, newly diagnosed HIV, and disseminated Kaposi sarcoma. During hospitalization, the patient had an onset of watery diarrhea and high eosinophilia. Subsequent stool analysis using multi-parallel real-time quantitative polymerase chain reaction for 13 parasites was positive for Cystoisospora belli. The patient was treated with trimethoprim-sulfamethoxazole, but had relapsed disease when her antibiotics were stopped prematurely. After restarting …

Case Report: Molecular Diagnosis Of Cystoisospora Belli In A Severely Immunocompromised Patient With Hiv And Kaposi Sarcoma, Roumen Borilov Iordanov, Lauren M Leining, Meng Wu, Galant Chan, Andrew R Dinardo, Rojelio Mejia

Faculty, Staff and Students Publications

Diarrhea in an immunocompromised patient has a broad infectious differential. Diagnosis is difficult despite advances in diagnostic modalities. We report a case of a 45-year-old Nigerian woman who immigrated to the United States 2 years ago. She presented to the hospital with gastrointestinal bleeding, newly diagnosed HIV, and disseminated Kaposi sarcoma. During hospitalization, the patient had an onset of watery diarrhea and high eosinophilia. Subsequent stool analysis using multi-parallel real-time quantitative polymerase chain reaction for 13 parasites was positive for Cystoisospora belli. The patient was treated with trimethoprim-sulfamethoxazole, but had relapsed disease when her antibiotics were stopped prematurely. After restarting …

The Impact Of The Covid-19 Pandemic On Food Distribution At Emergency Food Assistance Organizations In The Southwestern United States: A Qualitative Investigation, Alexandra N Castro, Mamie A White, Ariun Ishdorj, Debbe Thompson, Jayna M Dave

Children’s Nutrition Research Center Staff Publications

This study aimed to identify changes in food distribution operations at emergency food assistance organizations (EFAOs) during the COVID-19 pandemic. EFAOs across the Houston metro area, TX (human service centers and food pantries) as well as the Houston Food Bank (HFB) participated in the qualitative study. Data were collected via individual semi-structured interviews and focus group (December 2020–February 2021), and coded using semi-structured thematic analysis. Categories were pre-identified based on the interview questions. Direct quotes supported subcategories. Directors from 18 EFAOs were interviewed; 8 HFB leadership staff participated in a focus group. Four major categories of change due to COVID-19 …

Enterovirus D68-Associated Acute Respiratory Illness ─ New Vaccine Surveillance Network, United States, July-November 2018-2020., Melisa M. Shah, Ariana Perez, Joana Y. Lively, Vasanthi Avadhanula, Julie A. Boom, James Chappell, Janet A. Englund, Wende Fregoe, Natasha B. Halasa, Christopher J. Harrison, Robert W. Hickey, Eileen J. Klein, Monica M. Mcneal, Marian G. Michaels, Mary Moffatt, Catherine Otten, Leila C. Sahni, Elizabeth Schlaudecker, Jennifer E. Schuster, Rangaraj Selvarangan, Mary A. Staat, Laura S. Stewart, Geoffrey A. Weinberg, John V. Williams, Terry Fan Fei Ng, Janell A. Routh, Susan I. Gerber, Meredith L. Mcmorrow, Brian Rha, Claire M. Midgley

Manuscripts, Articles, Book Chapters and Other Papers

Enterovirus D68 (EV-D68) is associated with a broad spectrum of illnesses, including mild to severe acute respiratory illness (ARI) and acute flaccid myelitis (AFM). Enteroviruses, including EV-D68, are typically detected in the United States during late summer through fall, with year-to-year fluctuations. Before 2014, EV-D68 was infrequently reported to CDC (1). However, numbers of EV-D68 detection have increased in recent years, with a biennial pattern observed during 2014-2018 in the United States, after the expansion of surveillance and wider availability of molecular testing. In 2014, a national outbreak of EV-D68 was detected (2). EV-D68 was also reported in 2016 via …

Spinal Anesthesia Or General Anesthesia For Hip Surgery In Older Adults, Mark D. Neuman, Rui Feng, Jeffrey L. Carson, Lakisha J. Gaskins, Derek Dillane, Daniel I. Sessler, Frederick Sieber, Jay Magaziner, Edward R. Marcantonio, Samir Mehta, Diane Menio, Sabry Ayad, Trevor Stone, Steven Papp, Eric S. Schwenk, Nabil Elkassabany, Mitchell Marshall, J. Douglas Jaffe, Charles Luke, Balram Sharma, Syed Azim, Robert A. Hymes, Ki-Jinn Chin, Richard Sheppard, Barry Perlman, Joshua Sappenfield, Ellen Hauck, Mark A. Hoeft, Mark Giska, Yatish Ranganath, Tiffany Tedore, Stephen Choi, Jinlei Li, M. Kwesi Kwofie, Antoun Nader, Robert D. Sanders, Brian F. S. Allen, Kamen Vlassakov, Stephen Kates, Lee A. Fleisher, James Dattilo, Ann Tierney, Alisa J. Stephens-Shields, Susan S. Ellenberg

Department of Anesthesiology Faculty Papers

Background: The effects of spinal anesthesia as compared with general anesthesia on the ability to walk in older adults undergoing surgery for hip fracture have not been well studied.

Methods: We conducted a pragmatic, randomized superiority trial to evaluate spinal anesthesia as compared with general anesthesia in previously ambulatory patients 50 years of age or older who were undergoing surgery for hip fracture at 46 U.S. and Canadian hospitals. Patients were randomly assigned in a 1:1 ratio to receive spinal or general anesthesia. The primary outcome was a composite of death or an inability to walk approximately 10 ft (3 …

Hematopoiesis Under Telomere Attrition At The Single-Cell Resolution, Natthakan Thongon, Feiyang Ma, Andrea Santoni, Matteo Marchesini, Elena Fiorini, Ashley Rose, Vera Adema, Irene Ganan-Gomez, Emma M Groarke, Fernanda Gutierrez-Rodrigues, Shuaitong Chen, Pamela Lockyer, Sarah Schneider, Carlos Bueso-Ramos, Guillermo Montalban-Bravo, Caleb A Class, Kelly A Soltysiak, Matteo Pellegrini, Ergun Sahin, Alison A Bertuch, Courtney D Dinardo, Guillermo Garcia-Manero, Neal S Young, Karen Dwyer, Simona Colla

Faculty, Staff and Students Publications

The molecular mechanisms that drive hematopoietic stem cell functional decline under conditions of telomere shortening are not completely understood. In light of recent advances in single-cell technologies, we sought to redefine the transcriptional and epigenetic landscape of mouse and human hematopoietic stem cells under telomere attrition, as induced by pathogenic germline variants in telomerase complex genes. Here, we show that telomere attrition maintains hematopoietic stem cells under persistent metabolic activation and differentiation towards the megakaryocytic lineage through the cell-intrinsic upregulation of the innate immune signaling response, which directly compromises hematopoietic stem cells' self-renewal capabilities and eventually leads to their exhaustion. …

Efficacy And Safety Of Fremanezumab In Clinical Trial Participants Aged ≥60 Years With Episodic Or Chronic Migraine: Pooled Results From 3 Randomized, Double-Blind, Placebo-Controlled Phase 3 Studies, Stephanie J. Nahas, Steffen Naegel, Joshua M Cohen, Xiaoping Ning, Lindsay Janka, Verena Ramirez Campos, Lynda J Krasenbaum, Dagny Holle-Lee, David Kudrow, Christian Lampl

Department of Neurology Faculty Papers

Background: Although migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene-related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM).

Methods: This analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and …

Perspectives Of Black And Hispanic Children Living In Under-Resourced Communities On Meal Preparation And Grocery Shopping Behaviors: Implications For Nutrition Education, Chishinga Callender, Denisse Velazquez, Meheret Adera, Jayna M Dave, Norma Olvera, Tzuan A Chen, Shana Alford, Debbe Thompson

Children’s Nutrition Research Center Staff Publications

Minority children living in under-resourced communities are at the greatest risk for obesity and poor diet quality. Child involvement in meal preparation may be a helpful strategy to improve diet quality. This paper explores minority children's perspectives regarding this. Eighteen children participated in a mixed methods study (online surveys, telephone interviews). Descriptive statistics were calculated for child demographic and psychosocial factors. Thematic analysis was used to code and analyze the interviews. Most children reported having cooking experience (83%) and cooking with family (94%) and exhibited high cooking self-efficacy (21.8 ± 2.9) and positive cooking attitudes (25.7 ± 4.4). Children reported …

Construct Validity For The Self-Reported Competency And Sub-Construct Associated Characteristics Of Romanian Physicians In Autism Spectrum Disorder, Mohammad H Rahbar, Iuliana Dobrescu, Shezeen Gillani, Manouchehr Hessabi, Sori Kim, Mihaela Stancu, Florina Rad

Faculty, Staff and Student Publications

BACKGROUND: Lack of physicians' knowledge regarding mental health, including Autism Spectrum Disorder (ASD) could have adverse effects on affected individuals' health and quality of life. The purpose of this study was to provide construct validity for a modified questionnaire in order to determine the self-reported competency for underlying sub-constructs in ASD, make inferences on perceived competence in ASD based on a sample of Romanian physicians, and identify physicians' characteristics associated with these sub-domains of competency.

METHODS: For this survey, we modified a questionnaire that was used in Pakistan and Turkey, and administered it to a sample of 383 practicing physicians …

Attitudes Toward Osteopathic Medicine Scale: Development And Psychometrics, Mohammadreza Hojat Professor, Jennifer Desantis, Robert A Cain, Mark R Speicher, Lynn Bragan, Leonard H Calabrese

Department of Medicine Faculty Papers

Objective: To develop a valid and reliable instrument for measuring attitudes toward osteopathic medicine.

Methods: Participants included 5,669 first-year students from 33 U.S. colleges of osteopathic medicine, who completed an online survey at the beginning of the 2019-2020 academic year. Using data from the nationwide Project in Osteopathic Medical Education and Empathy, we developed a 13-item instrument: Attitudes Toward Osteopathic Medicine Scale (ATOMS) and demonstrated the validity and reliability of its scores. The social desirability response bias was controlled in statistical analyses.

Results: The corrected item-total score correlations were all positive and statistically significant, and the effect sizes of item …

Nrf1 Association With Auts2-Polycomb Mediates Specific Gene Activation In The Brain, Sanxiong Liu, Kimberly A Aldinger, Chi Vicky Cheng, Takae Kiyama, Mitali Dave, Hanna K Mcnamara, Wukui Zhao, James M Stafford, Nicolas Descostes, Pedro Lee, Stefano G Caraffi, Ivan Ivanovski, Edoardo Errichiello, Christiane Zweier, Orsetta Zuffardi, Michael Schneider, Antigone S Papavasiliou, M Scott Perry, Jennifer Humberson, Megan T Cho, Astrid Weber, Andrew Swale, Tudor C Badea, Chai-An Mao, Livia Garavelli, William B Dobyns, Danny Reinberg

Faculty, Staff and Student Publications

The heterogeneous family of complexes comprising Polycomb repressive complex 1 (PRC1) is instrumental for establishing facultative heterochromatin that is repressive to transcription. However, two PRC1 species, ncPRC1.3 and ncPRC1.5, are known to comprise novel components, AUTS2, P300, and CK2, that convert this repressive function to that of transcription activation. Here, we report that individuals harboring mutations in the HX repeat domain of AUTS2 exhibit defects in AUTS2 and P300 interaction as well as a developmental disorder reflective of Rubinstein-Taybi syndrome, which is mainly associated with a heterozygous pathogenic variant in CREBBP/EP300. Moreover, the absence of AUTS2 or mutation in its …

Sedation And Acute Encephalopathy In A Pediatric Patient Following Ingestion Of Delta-8-Tetrahydrocannabinol Gummies, Peter Akpunonu, Regan A. Baum, Andrew Reckers, Blake Davidson, Ross Ellison, Matthew Riley, Jordan Trecki, Roy Gerona

Emergency Medicine Faculty Publications

BACKGROUND Delta-8 tetrahydrocannabinol (delta-8 THC) is an isomer of delta-9-tetrahydrocannabinol (delta-9 THC), the primary psychoactive cannabinoid in the marijuana plant. Typically found at lower concentrations in marijuana, delta-8 THC exhibits psychoactive properties similar to delta-9 THC. Products containing delta-8 THC are readily available across the US and currently there is a lack of available confirmatory testing specific to delta-8 THC as there is cross-reactivity to other naturally occurring cannabinoids in standard immunoassays. Pediatric exposures to this substance are on the rise.

CASE REPORT We present a case with laboratory confirmation of a previously healthy 2-year-old girl ingesting approximately 15 mg/kg …

Postoperative Outcomes In Oesophagectomy With Trainee Involvement., Oesophago-Gastric Anastomosis Study Group (Ogaa) On Behalf Of The West Midlands Research Collaborative

Department of Surgery Faculty Papers

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting.

METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed …

Ultrafiltration Rate And Incident Atrial Fibrillation Among Older Individuals Initiating Hemodialysis, Jennifer E Flythe, Sai Liu, Maria E Montez-Rath, Wolfgang C Winkelmayer, Tara I Chang

Faculty, Staff and Students Publications

BACKGROUND: Higher ultrafiltration (UF) rates are associated with numerous adverse cardiovascular outcomes among individuals receiving maintenance hemodialysis. We undertook this study to investigate the association of UF rate and incident atrial fibrillation in a large, nationally representative US cohort of incident, older hemodialysis patients.

METHODS: We used the US Renal Data System linked to the records of a large dialysis provider to identify individuals ≥67 years of age initiating hemodialysis between January 2006 and December 2011. We applied an extended Cox model as a function of a time-varying exposure to compute adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) …