Digital Commons Network^™

Safety And Efficacy Of Fecal Microbiota Transplantation To Treat And Prevent Recurrent Clostridioides Difficile In Cancer Patients, Hiba Ali, Shruti Khurana, Weijie Ma, Yuanzun Peng, Zhi-Dong Jiang, Herbert Dupont, Hao Chi Zhang, Anusha S Thomas, Pablo Okhuysen, Yinghong Wang

Faculty, Staff and Students Publications

Background: Cancer patients are at increased risk of recurrent Clostridioides difficile infection (rCDI) due to malignancy itself, cancer therapy, and frequent antibiotic use and have a lower response rate to standard oral antibiotics. There are limited data on the safety and efficacy of fecal microbiota transplantation (FMT) for treating rCDI in cancer patients. We aim to describe our experience of using FMT to treat rCDI at a tertiary cancer center.

Methods: We conducted a retrospective study of cancer patients who underwent FMT for rCDI at The University of Texas MD Anderson Cancer Center from June 2017 through January 2020. Baseline …

The Association Of Pre-Kidney Transplant Dialysis Modality With De Novo Posttransplant Heart Failure, Colin R Lenihan, Sai Liu, Medha Airy, Carl Walther, Maria E Montez-Rath, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

BACKGROUND: Heart failure (HF) after kidney transplantation is a significant but understudied problem. Pretransplant dialysis modality could influence incident HF risk through differing cardiac stressors. However, whether pretransplant dialysis modality is associated with the development of posttransplant HF is unknown.

METHODS: We used the US Renal Data System to assemble a cohort of 27,701 patients who underwent their first kidney transplant in the USA between the years 2005 and 2012 and who had Medicare fee-for-service coverage for >6 months preceding their transplant date. Patients with any HF diagnosis prior to transplant were excluded. Detailed baseline patient characteristics and comorbidities were …

Hemoglobin A1c Threshold For Reduction In Bone Turnover In Men With Type 2 Diabetes Mellitus, Sabaa Joad, Elliot Ballato, Fnu Deepika, Giulia Gregori, Alcibiades Leonardo Fleires-Gutierrez, Georgia Colleluori, Lina Aguirre, Rui Chen, Vittoria Russo, Virginia Carolina Fuenmayor Lopez, Clifford Qualls, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

BACKGROUND: Emerging data suggest that type 2 diabetes mellitus (T2D) is associated with an increased risk for fractures despite relatively normal or increased bone mineral density (BMD). Although the mechanism for bone fragility in T2D patients is multifactorial, whether glycemic control is important in generating this impairment in bone metabolism remains unclear. The purpose of our study is to identify a hemoglobin A1c (A1c) threshold level by which reduction in bone turnover begins in men with T2D.

METHOD: A cross-sectional analysis of baseline data was obtained from 217 men, ages 35-65, regardless of the presence or absence of hypogonadism or …

The Bile Acid Induced Hepatokine Orosomucoid Suppresses Adipocyte Differentiation, Sung Ho Lee, Jong Min Choi, Sung Yun Jung, Aaron R Cox, Sean M Hartig, David D Moore, Kang Ho Kim

Faculty, Staff and Students Publications

Bile acids have recently emerged as key metabolic hormones with beneficial impacts in multiple metabolic diseases. We previously discovered that hepatic bile acid overload distally modulates glucose and fatty acid metabolism in adipose tissues to exert anti-obesity effects. However, the detailed mechanisms that explain the salutary effects of serum bile acid elevation remain unclear. Here, proteomic profiling identified a new hepatokine, Orosomucoid (ORM) that governs liver-adipose tissue crosstalk. Hepatic ORMs were highly induced by both genetic and dietary bile acid overload. To address the direct metabolic effects of ORM, purified ORM proteins were administered during adipogenic differentiation of 3T3-L1 cells …

Deep Simulation Of Facial Appearance Changes Following Craniomaxillofacial Bony Movements In Orthognathic Surgical Planning, Lei Ma, Daeseung Kim, Chunfeng Lian, Deqiang Xiao, Tianshu Kuang, Qin Liu, Yankun Lang, Hannah H Deng, Jaime Gateno, Ye Wu, Erkun Yang, Michael A K Liebschner, James J Xia, Pew-Thian Yap

Faculty, Staff and Students Publications

Facial appearance changes with the movements of bony segments in orthognathic surgery of patients with craniomaxillofacial (CMF) deformities. Conventional bio-mechanical methods, such as finite element modeling (FEM), for simulating such changes, are labor intensive and computationally expensive, preventing them from being used in clinical settings. To overcome these limitations, we propose a deep learning framework to predict post-operative facial changes. Specifically, FC-Net, a facial appearance change simulation network, is developed to predict the point displacement vectors associated with a facial point cloud. FC-Net learns the point displacements of a pre-operative facial point cloud from the bony movement vectors between pre-operative …

Genomic Mapping Of Dna-Repair Reaction Intermediates In Living Cells With Engineered Dna Structure-Trap Proteins, Jingjing Liu, Qian Mei, Sadeieh Nimer, Devon M Fitzgerald, Susan M Rosenberg

Faculty, Staff and Students Publications

Diverse DNA structures occur as reaction intermediates in various DNA-damage and -repair mechanisms, most of which results from replication stress. We harness the power of proteins evolutionarily optimized to bind and "trap" specific DNA reaction-intermediate structures, to quantify the structures, and discern the mechanisms of their occurrence in cells. The engineered proteins also allow genomic mapping of sites at which specific DNA structures occur preferentially, using a structure-trapping protein and ChIP-seq- or Cut-and-Tag-like methods. Genome-wide identification of sites with recurrent DNA-damage intermediates has illuminated mechanisms implicated in genome instability, replication stress, and chromosome fragility. Here, we describe X-seq, for identifying …

A Pharmacokinetic Analysis Of Hemodialysis For Metformin-Associated Lactic Acidosis, Stephen A Harding, Rana Biary, Robert S Hoffman, Mark K Su, Mary Ann Howland

Faculty, Staff and Students Publications

OBJECTIVE: Although hemodialysis is recommended for patients with severe metformin-associated lactic acidosis (MALA), the amount of metformin removed by hemodialysis is poorly documented. We analyzed endogenous clearance and hemodialysis clearance in a patient with MALA.

METHODS: A 62-year-old man with a history of type II diabetes mellitus presented after several days of vomiting and diarrhea and was found to have acute kidney injury (AKI) and severe acidemia. Initial serum metformin concentration was 315.34 μmol/L (40.73 μg/mL) (typical therapeutic concentrations 1-2 μg/mL). He underwent 6 h of hemodialysis. We collected hourly whole blood, serum, urine, and dialysate metformin concentrations. Blood, urine, …

Intrapulmonary Administration Of Purified Neil2 Abrogates Nf-Κb-Mediated Inflammation, Nisha Tapryal, Shandy Shahabi, Anirban Chakraborty, Koa Hosoki, Maki Wakamiya, Gobinda Sarkar, Gulshan Sharma, Victor J Cardenas, Istvan Boldogh, Sanjiv Sur, Gourisankar Ghosh, Tapas K Hazra

Faculty, Staff and Students Publications

Aberrant or constitutive activation of nuclear factor kappa B (NF-κB) contributes to various human inflammatory diseases and malignancies via the upregulation of genes involved in cell proliferation, survival, angiogenesis, inflammation, and metastasis. Thus, inhibition of NF-κB signaling has potential for therapeutic applications in cancer and inflammatory diseases. We reported previously that Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase, is involved in the preferential repair of oxidized DNA bases from the transcriptionally active sequences via the transcription-coupled base excision repair pathway. We have further shown that Neil2-null mice are highly sensitive to tumor necrosis factor α (TNFα)- and lipopolysaccharide-induced …

Characteristics And Outcomes Of In-Hospital Cardiac Arrest In Covid-19 A Systematic Review And Meta-Analysis, Lukasz Szarpak, Magdalena Borkowska, Frank W Peacock, Zubaid Rafique, Aleksandra Gasecka, Jacek Smereka, Katarzyna Pytkowska, Marta Jachowicz, Lukasz Iskrzycki, Natasza Gilis-Malinowska, Milosz J Jaguszewski

Faculty, Staff and Students Publications

BACKGROUND: The purpose herein, was to perform a systematic review of interventional outcome studies in patients with in-hospital cardiac arrest before and during the coronavirus disease 2019 (COVID-19) pandemic period.

METHODS: A meta-analysis was performed of publications meeting the following PICOS criteria: (1) participants, patients > 18 years of age with cardiac arrest due to any causes; (2) intervention, cardiac arrest in COVID-19 period; (3) comparison, cardiac arrest in pre-COVID-19 period; (4) outcomes, detailed information for survival; (5) study design, randomized controlled trials, quasi-randomized or observational studies comparing cardiac arrest in COVID-19 and pre-COVID-19 period for their effects in patients with …

Thyroid Storm In A Patient With Covid-19, Angela N Rao, Ruaa Y Al-Ward, Ruchi Gaba

Faculty, Staff and Students Publications

OBJECTIVE: A thyroid storm is a severe exacerbation of thyrotoxicosis that can cause significant morbidity and mortality. The emergence of the novel coronavirus (SARS-CoV-2) that originated in Wuhan, China, has become a worldwide pandemic. We present the first documented case of thyroid storm (as defined by the Burch-Wartofsky criteria) in a patient with COVID-19.

METHODS: Laboratory and diagnostic studies, including thyroid function tests, thyroid antibody testing, SARS-CoV-2 nasopharyngeal polymerase chain reaction testing, and thyroid ultrasound were performed.

RESULTS: A 25-year-old woman presented to the hospital with dry cough, dyspnea, palpitations, weight loss, diarrhea, and anxiety. Physical examination revealed exophthalmos with …

X-Linked Serotonin 2c Receptor Is Associated With A Non-Canonical Pathway For Sudden Unexpected Death In Epilepsy, Cory A Massey, Samantha J Thompson, Ryan W Ostrom, Janice Drabek, Olafur A Sveinsson, Torbjörn Tomson, Elisabeth A Haas, Othon J Mena, Alica M Goldman, Jeffrey L Noebels

Faculty, Staff and Students Publications

Sudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Most monogenic models of Sudden Unexpected Death in Epilepsy invoke a failure of inhibitory synaptic …

Assessment Of The Impact Of Tardive Dyskinesia In Clinical Practice: Consensus Panel Recommendations, Richard Jackson, Matthew N Brams, Leslie Citrome, Amber R Hoberg, Stuart H Isaacson, John M Kane, Rajeev Kumar

Faculty, Staff and Students Publications

PURPOSE: Tardive dyskinesia (TD) is a hyperkinetic movement disorder in which patients experience abnormal involuntary movements that can have profound negative impacts on physical, cognitive, and psychosocial functioning. Use of measures to assess the functional impact of TD in routine clinical practice is lacking. To address this gap, an advisory panel of experts in psychiatry and movement disorder neurology was convened to develop consensus recommendations on assessment of the impact of TD on patients' functioning that can be used in clinical practice.

METHODS: An advisory panel provided recommendations using an iterative process, beginning with a narrative literature review regarding current …

Mucins, Gut Microbiota, And Postbiotics Role In Colorectal Cancer, Ramesh Pothuraju, Sanjib Chaudhary, Satyanarayana Rachagani, Sukhwinder Kaur, Hemant K Roy, Michael Bouvet, Surinder K Batra

Faculty, Staff and Students Publications

An imbalance in the crosstalk between the host and gut microbiota affects the intestinal barrier function, which results in inflammatory diseases and colorectal cancer. The colon epithelium protects itself from a harsh environment and various pathogenic organisms by forming a double mucus layer, primarily comprising mucins. Recent studies are focusing on how dietary patterns alter the gut microbiota composition, which in turn regulates mucin expression and maintains the intestinal layers. In addition, modulation of gut microbiota by microbiotic therapy (involving fecal microbiota transplantation) has emerged as a significant factor in the pathologies associated with dysbiosis. Therefore, proper communication between host …

A Right Para-Tracheal Mass Extending Into The Anterior Mediastinum: An Anesthetic Management Conundrum, Andres Bacigalupo Landa, Kritika Krishnamurthy, Howard S Goldman

Faculty, Staff and Students Publications

The anesthetic management of patients with a mediastinal mass represent a challenge due to the potential for difficult ventilation and intubation, as well as the risk of cardiovascular collapse upon induction of general anesthesia. Different strategies and alternatives have been described. We present the case of a 70-year-old man with a right para-tracheal mass extending into the anterior mediastinum with 90% mid-tracheal lumen obstruction who was successfully managed with venous-venous extra-corporeal membrane oxygenation (ECMO) during mass debulking and tracheal stent placement.

Large-Scale Characterization Of Drug Responses Of Clinically Relevant Proteins In Cancer Cell Lines, Wei Zhao, Jun Li, Mei-Ju M Chen, Yikai Luo, Zhenlin Ju, Nicole K Nesser, Katie Johnson-Camacho, Christopher T Boniface, Yancey Lawrence, Nupur T Pande, Michael A Davies, Meenhard Herlyn, Taru Muranen, Ioannis K Zervantonakis, Erika Von Euw, Andre Schultz, Shwetha V Kumar, Anil Korkut, Paul T Spellman, Rehan Akbani, Dennis J Slamon, Joe W Gray, Joan S Brugge, Yiling Lu, Gordon B Mills, Han Liang

Faculty, Staff and Students Publications

Perturbation biology is a powerful approach to modeling quantitative cellular behaviors and understanding detailed disease mechanisms. However, large-scale protein response resources of cancer cell lines to perturbations are not available, resulting in a critical knowledge gap. Here we generated and compiled perturbed expression profiles of ∼210 clinically relevant proteins in >12,000 cancer cell line samples in response to ∼170 drug compounds using reverse-phase protein arrays. We show that integrating perturbed protein response signals provides mechanistic insights into drug resistance, increases the predictive power for drug sensitivity, and helps identify effective drug combinations. We build a systematic map of "protein-drug" connectivity …

A Steroid Receptor Coactivator Stimulator (Mcb-613) Attenuates Adverse Remodeling After Myocardial Infarction, Lisa K Mullany, Aarti D Rohira, John P Leach, Jong H Kim, Tanner O Monroe, Andrea R Ortiz, Brittany Stork, M Waleed Gaber, Poonam Sarkar, Andrew G Sikora, Todd K Rosengart, Brian York, Yongcheng Song, Clifford C Dacso, David M Lonard, James F Martin, Bert W O'Malley

Faculty, Staff and Students Publications

Progressive remodeling of the heart, resulting in cardiomyocyte (CM) loss and increased inflammation, fibrosis, and a progressive decrease in cardiac function, are hallmarks of myocardial infarction (MI)-induced heart failure. We show that MCB-613, a potent small molecule stimulator of steroid receptor coactivators (SRCs) attenuates pathological remodeling post-MI. MCB-613 decreases infarct size, apoptosis, hypertrophy, and fibrosis while maintaining significant cardiac function. MCB-613, when given within hours post MI, induces lasting protection from adverse remodeling concomitant with: 1) inhibition of macrophage inflammatory signaling and interleukin 1 (IL-1) signaling, which attenuates the acute inflammatory response, 2) attenuation of fibroblast differentiation, and 3) promotion …

Safety And Effectiveness Of Hydroxychloroquine And Azithromycin Combination Therapy For Treatment Of Hospitalized Patients With Covid-19: A Propensity-Matched Study, Henry D Huang, Hani Jneid, Mariam Aziz, Venkatesh Ravi, Parikshit S Sharma, Timothy Larsen, Neal Chatterjee, Basil Saour, Zaid Aziz, Hemal Nayak, Richard G Trohman, Kousik Krishnan

Faculty, Staff and Students Publications

INTRODUCTION: We sought to determine the effectiveness and safety of hydroxychloroquine-azithromycin (HCQ-AZM) therapy in hospitalized patients with COVID-19.

METHODS: This was a retrospective cohort study of 613 patients hospitalized (integrated health system involving three hospitals) for RT-PCR-confirmed COVID-19 infection between March 1, 2020 and April 25, 2020. Intervention was treatment with HCQ-AZM in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Outcomes of interest were in-hospital all-cause mortality, cardiovascular mortality, pulseless electrical activity (PEA) arrest, non-lethal arrhythmias, and length of hospital stay. Secondary measures included in-hospital corrected QT (QTc) interval parameters and serum biomarkers levels.

RESULTS: Propensity-matched …

Inferior St-Elevation Myocardial Infarction Presenting When Urgent Primary Percutaneous Coronary Intervention Is Unavailable: Should We Adhere To Current Guidelines?, Yochai Birnbaum, Glenn N Levine, John French, Juan Carlos Kaski, Dan Atar, Mahboob Alam, David Hasdai, Hani Jneid, Barry F Uretsky

Faculty, Staff and Students Publications

The pivotal studies that led to the recommendations for emergent reperfusion therapy for ST-elevation myocardial infarction (STEMI) were conducted for the most part over 25 years ago. At that time, contemporary standard treatments including aspirin, statin, and even anticoagulation were not commonly used. The 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines and the 2017 European Society of Cardiology guidelines give a class I recommendation (with the level of evidence A) for primary percutaneous coronary intervention (pPCI) in patients with STEMI and ischemic symptoms of less than 12 h. However, if the patient presents to a hospital …

Multivessel Traumatic Coronary Artery Dissection After A Motor Vehicle Accident With Successful Percutaneous Coronary Intervention, Yagya Pandey, Brittany Owen, Gilad Birnbaum, Rashed Tabbaa, Ihab Hamzeh, Nasser Lakkis, Waleed Kayani

Faculty, Staff and Students Publications

Coronary artery dissection is a rare complication of blunt chest wall trauma. We report a case of acute left anterior descending and right coronary artery dissections after a motor vehicle accident. The musculoskeletal injuries obscured the cardiac symptoms. Electrocardiogram and bedside echocardiogram revealed cardiac pathology, which prompted urgent coronary angiography and intervention. (Level of Difficulty: Advanced.)

Inferior St-Elevation Myocardial Infarction Presenting When Urgent Primary Percutaneous Coronary Intervention Is Unavailable: Should We Adhere To Current Guidelines?, Yochai Birnbaum, Glenn N Levine, John French, Juan Carlos Kaski, Dan Atar, Mahboob Alam, David Hasdai, Hani Jneid, Barry F Uretsky

Faculty, Staff and Students Publications

The pivotal studies that led to the recommendations for emergent reperfusion therapy for ST-elevation myocardial infarction (STEMI) were conducted for the most part over 25 years ago. At that time, contemporary standard treatments including aspirin, statin, and even anticoagulation were not commonly used. The 2013 American College of Cardiology Foundation (ACCF)/American Heart Association (AHA) guidelines and the 2017 European Society of Cardiology guidelines give a class I recommendation (with the level of evidence A) for primary percutaneous coronary intervention (pPCI) in patients with STEMI and ischemic symptoms of less than 12 h. However, if the patient presents to a hospital …

The Cancer Patient And Cardiology, José Luis Zamorano, Christer Gottfridsson, Riccardo Asteggiano, Dan Atar, Lina Badimon, Jeroen J Bax, Daniela Cardinale, Antonella Cardone, Elizabeth A M Feijen, Péter Ferdinandy, Teresa López-Fernández, Chris P Gale, John H Maduro, Javid Moslehi, Torbjørn Omland, Juan Carlos Plana Gomez, Jessica Scott, Thomas M Suter, Giorgio Minotti

Faculty, Staff and Students Publications

Advances in cancer treatments have improved clinical outcomes, leading to an increasing population of cancer survivors. However, this success is associated with high rates of short- and long-term cardiovascular (CV) toxicities. The number and variety of cancer drugs and CV toxicity types make long-term care a complex undertaking. This requires a multidisciplinary approach that includes expertise in oncology, cardiology and other related specialties, and has led to the development of the cardio-oncology subspecialty. This paper aims to provide an overview of the main adverse events, risk assessment and risk mitigation strategies, early diagnosis, medical and complementary strategies for prevention and …

Spinal Cord Injury Provider Knowledge And Attitudes Toward Bacteriuria Management And Antibiotic Stewardship, Felicia Skelton, Sarah May, Larissa Grigoryan, Ivy Poon, Sally Ann Holmes, Lindsey Martin, Barbara W Trautner

Faculty, Staff and Students Publications

INTRODUCTION: Bacteriuria, either asymptomatic or urinary tract infection, is common in persons with spinal cord injury or disorder (SCI/D). In the Veterans Health Administration (VHA), conflicting clinical practice guidelines make appropriate bacteriuria management and antibiotic stewardship challenging.

OBJECTIVE: To explore SCI/D provider knowledge, attitudes, and teamwork around bacteriuria management during the VHA SCI/D annual examination.

DESIGN: Mixed methods.

SETTING: VHA SCI/D centers.

PARTICIPANTS: SCI/D staff providers and physical medicine and rehabilitation resident physicians.

MAIN OUTCOME MEASUREMENTS: Knowledge, safety, and teamwork scores on bacteriuria management using a validated questionnaire. Themes on barriers and facilitators to bacteriuria management during the SCI/D annual …

External Stoma Diversion: A Palliative Measure For Peristomal Wound Healing In Resource-Limited Settings, Rachel W Davis, Youmna A Sherif, Catherine Anne Morrison

Faculty, Staff and Students Publications

The provision of intestinal stoma care is challenging in austere settings due to limitations in surgical and wound care access as well as the high cost and sparsity of ostomy supplies. As a result, many surgical patients suffer from ostomy-related complications such as peristomal wounds and are unable to find relief for these complications from standard treatments and measures. This article describes the external stoma diversion, a cost-effective palliative surgical procedure that assists in the healing of peristomal wounds in resource-limited settings.

Model For End-Stage Liver Disease-Sodium Underestimates 90-Day Mortality Risk In Patients With Acute-On-Chronic Liver Failure, Ruben Hernaez, Yan Liu, Jennifer R Kramer, Abbas Rana, Hashem B El-Serag, Fasiha Kanwal

Faculty, Staff and Students Publications

BACKGROUND & AIMS: It is unclear whether the model for end-stage liver disease-sodium (MELD-Na) score captures the clinical severity of acute-on-chronic liver failure (ACLF). We compared observed 90-day mortality in patients with ACLF with expected mortality based on the calculated MELD-Na and examined the consequences of underestimating clinical severity.

METHODS: We identified patients with ACLF during hospitalization for cirrhosis in 127 VA hospitals between 01/01/2004 and 12/31/2014. We examined MELD-Na scores by ACLF presence and grade. We used actual and observed 90-day mortality to estimate a standardized mortality ratio (SMR) by ACLF presence and grade. We used transplant center-specific median …

Postacute Covid-19: An Overview And Approach To Classification, Eva M Amenta, Amy Spallone, Maria C Rodriguez-Barradas, Hana M El Sahly, Robert L Atmar, Prathit A Kulkarni

Faculty, Staff and Students Publications

As the coronavirus disease 2019 (COVID-19) pandemic has progressed, a large volume of literature has developed delineating the clinical manifestations of acute infection. Recent reports have also started to describe persistent symptoms extending beyond the period of initial illness or hospitalization. Anecdotes of different signs and symptoms occurring after acute infection have also arisen in the lay press. Here we describe the current existing medical literature on the emerging concept of postacute COVID-19 and suggest an approach to classifying different manifestations of the syndrome. We also review long-term clinical manifestations observed in patients who recovered from infection due to other …

Stat1 Dissociates Adipose Tissue Inflammation From Insulin Sensitivity In Obesity, Aaron R Cox, Natasha Chernis, David A Bader, Pradip K Saha, Peter M Masschelin, Jessica B Felix, Robert Sharp, Zeqin Lian, Vasanta Putluri, Kimal Rajapakshe, Kang Ho Kim, Dennis T Villareal, Reina Armamento-Villareal, Huaizhu Wu, Cristian Coarfa, Nagireddy Putluri, Sean M Hartig

Faculty, Staff and Students Publications

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes. However, the causal relationship of these events remains unclear. The established dominance of STAT1 function in the immune response suggests an obligate link between inflammation and the comorbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (STAT1a-KO) enhanced mitochondrial function …

Estimates Of Throughput And Utilization At Freestanding Compared To Low-Volume Hospital-Based Emergency Departments, Cedric Dark, Maureen Canellas, Caroline Mangira, Nick Jouriles, Erin L Simon

Faculty, Staff and Students Publications

OBJECTIVE: Our investigation compared throughput metrics and utilization measures for freestanding emergency departments (FSEDs) versus hospital-based emergency departments (HBEDs) of similar volumes in the United States.

METHODS: This study is a cross sectional survey of 183 FSEDs and 317 HBEDs located across the United States using the Emergency Department Benchmarking Alliance (EDBA) Database. We measured common emergency department (ED) throughput metrics. Primary outcomes included overall length of stay, length of stay for admitted, and length of stay for treated and released patients. Outcomes were weighted based on the proportion of ED volume per facility as per a prior pilot study. …

Mouse Models To Study The Pathophysiology Of Combined Methylmalonic Acidemia And Homocystinuria, Cblc Type, Tiffany Chern, Annita Achilleos, Xuefei Tong, Chih-Wei Hsu, Leeyean Wong, Ross A Poché

Faculty, Staff and Students Publications

Combined methylmalonic acidemia and homocystinuria, cblC type, is the most common inherited disorder of cobalamin metabolism and is characterized by severe fetal developmental defects primarily impacting the central nervous system, hematopoietic system, and heart. CblC was previously shown to be due to mutations in the MMACHC gene, which encodes a protein thought to function in intracellular cobalamin trafficking and biosynthesis of adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). These coenzymes are required for the production of succinyl-CoA and methionine, respectively. However, it is currently unclear whether additional roles for MMACHC exist outside of cobalamin metabolism. Furthermore, due to a lack of sufficient …

Depletion Of Essential Isoprenoids And Er Stress Induction Following Acute Liver-Specific Deletion Of Hmg-Coa Reductase, Marco De Giorgi, Kelsey E Jarrett, Jason C Burton, Alexandria M Doerfler, Ayrea Hurley, Ang Li, Rachel H Hsu, Mia Furgurson, Kalyani R Patel, Jun Han, Christoph H Borchers, William R Lagor

Faculty, Staff and Students Publications

HMG-CoA reductase (Hmgcr) is the rate-limiting enzyme in the mevalonate pathway and is inhibited by statins. In addition to cholesterol, Hmgcr activity is also required for synthesizing nonsterol isoprenoids, such as dolichol, ubiquinone, and farnesylated and geranylgeranylated proteins. Here, we investigated the effects of Hmgcr inhibition on nonsterol isoprenoids in the liver. We have generated new genetic models to acutely delete genes in the mevalonate pathway in the liver using AAV-mediated delivery of Cre-recombinase (AAV-Cre) or CRISPR/Cas9 (AAV-CRISPR). The genetic deletion of Hmgcr by AAV-Cre resulted in extensive hepatocyte apoptosis and compensatory liver regeneration. At the biochemical …

Differences In Gynecologic Tumor Development In Amhr2-Cre Mice With Krasg12d Or Krasg12v Mutations, Eucharist H S Kun, Yvonne T M Tsang, Sophia Lin, Sophia Pan, Tejas Medapalli, Anais Malpica, Joanne S Richards, David M Gershenson, Kwong-Kwok Wong

Faculty, Staff and Students Publications

How different KRAS variants impact tumor initiation and progression in vivo has not been thoroughly examined. We hypothesize that the ability of either KRASG12D or KRASG12V mutations to initiate tumor formation is context dependent. Amhr2-Cre mice express Cre recombinase in tissues that develop into the fallopian tubes, uterus, and ovaries. We used these mice to conditionally express either the KRASG12V/+ or KRASG12D/+ mutation. Mice with the genotype Amhr2-Cre Pten(fl/fl) KrasG12D/+(G12D mice) had abnormal follicle structures and developed low-grade serous ovarian carcinomas with 100% penetrance within 18 weeks. In contrast, mice with …