Digital Commons Network^™

Ketamine: Neuroprotective Or Neurotoxic?, Divya Choudhury, Anita E Autry, Kimberley F Tolias, Vaishnav Krishnan

Faculty, Staff and Students Publications

Ketamine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, has been employed clinically as an intravenous anesthetic since the 1970s. More recently, ketamine has received attention for its rapid antidepressant effects and is actively being explored as a treatment for a wide range of neuropsychiatric syndromes. In model systems, ketamine appears to display a combination of neurotoxic and neuroprotective properties that are context dependent. At anesthetic doses applied during neurodevelopmental windows, ketamine contributes to inflammation, autophagy, apoptosis, and enhances levels of reactive oxygen species. At the same time, subanesthetic dose ketamine is a powerful activator of multiple parallel neurotrophic signaling cascades …

Malnutrition In Orthopaedic Sports Medicine: A Review Of The Current Literature, Jihoon T Choi, Brandon Yoshida, Omid Jalali, George F Hatch

Faculty, Staff and Students Publications

CONTEXT: Malnutrition is well-studied in various aspects of the orthopaedic literature, most commonly in relation to arthroplasty, spine surgery, and trauma. However, the management of nutritional deficiencies is commonly overlooked among orthopaedic sports medicine providers. The purpose of this article is to analyze the available sports medicine literature to review the associations between malnutrition and the management of orthopaedic sports medicine patients from a treatment and performance standpoint.

EVIDENCE ACQUISITION: PubMed was searched for relevant articles published from 1979 to 2019.

STUDY DESIGN: Clinical review.

LEVEL OF EVIDENCE: Level 4.

RESULTS: Few studies exist on the implications of macronutrient deficiencies …

Novel Mutations In The Gtpbp3 Gene For Mitochondrial Disease And Characteristics Of Related Phenotypic Spectrum: The First Three Cases From China, Hui-Ming Yan, Zhi-Mei Liu, Bei Cao, Victor Wei Zhang, Yi-Duo He, Zheng-Jun Jia, Hui Xi, Jing Liu, Fang Fang, Hua Wang

Faculty, Staff and Students Publications

Combined Oxidative Phosphorylation Deficiency 23 (COXPD23) caused by mutations in GTPBP3 gene is a rare mitochondrial disease, and this disorder identified from the Chinese population has not been described thus far. Here, we report a case series of three patients with COXPD23 caused by GTPBP3 mutations, from a severe to a mild phenotype. The main clinical features of these patients include lactic acidosis, myocardial damage, and neurologic symptoms. Whole genome sequencing and targeted panels of candidate human mitochondrial genome revealed that patient 1 was a compound heterozygote with novel mutations c.413C > T (p. A138V) and c.509_510del (p. E170Gfs∗42) in GTPBP3 …

Trace Element Concentrations In Blood And Scute Tissues From Wild And Captive Hawaiian Green Sea Turtles (Chelonia Mydas), Katherine R Shaw, Jennifer M Lynch, George H Balazs, T Todd Jones, Jeff Pawloski, Marc R Rice, Amanda D French, Jing Liu, George P Cobb, David M Klein

Faculty, Staff and Students Publications

Sea turtles are exposed to trace elements through water, sediment, and food. Exposure to these elements has been shown to decrease immune function, impair growth, and decrease reproductive output in wildlife. This study compares trace element concentrations in green turtles in captivity at Sea Life Park Hawaii (n = 6) to wild green turtles in Kapoho Bay, HI (n = 5 to 7). Blood and scute samples were collected and analyzed for eleven elements via inductively coupled plasma-mass spectrometry (ICP-MS). Selenium was significantly greater (p < 0.05) in the blood of captive turtles compared to wild turtles, while V, Ni, and Pb were significantly greater in the blood of wild turtles. In scute, V, Cu, Se, and Cr were significantly greater in captive turtles, while As was significantly greater in wild turtles. Pelleted food fed to the captive turtles and representative samples of the wild turtle diet were analyzed via ICP-MS to calculate trophic transfer factors and daily intake values. Wild turtles had greater estimated daily intake than captive turtles for all elements except Cu and Se. Because captive turtles are fed a diet very different from their wild counterparts, captive turtles do not represent control or reference samples for chemical exposure studies in wild turtles. No toxic thresholds are known for sea turtles, but rehabilitation and managed care facilities should monitor sea turtle elemental concentrations to ensure the animals’ health.

Effects Of Intensive Blood Pressure Treatment On Orthostatic Hypotension : A Systematic Review And Individual Participant-Based Meta-Analysis, Stephen P Juraschek, Jiun-Ruey Hu, Jennifer L Cluett, Anthony Ishak, Carol Mita, Lewis A Lipsitz, Lawrence J Appel, Nigel S Beckett, Ruth L Coleman, William C Cushman, Barry R Davis, Greg Grandits, Rury R Holman, Edgar R Miller, Ruth Peters, Jan A Staessen, Addison A Taylor, Lutgarde Thijs, Jackson T Wright, Kenneth J Mukamal

Faculty, Staff and Students Publications

BACKGROUND: Although intensive blood pressure (BP)-lowering treatment reduces risk for cardiovascular disease, there are concerns that it might cause orthostatic hypotension (OH).

PURPOSE: To examine the effects of intensive BP-lowering treatment on OH in hypertensive adults.

DATA SOURCES: MEDLINE, EMBASE, and Cochrane CENTRAL from inception through 7 October 2019, without language restrictions.

STUDY SELECTION: Randomized trials of BP pharmacologic treatment (more intensive BP goal or active agent) that involved more than 500 adults with hypertension or elevated BP and that were 6 months or longer in duration. Trial comparisons were groups assigned to either less intensive BP goals or placebo, …

Distribution Of Calcium Volume, Density, Number, And Type Of Coronary Vessel With Calcified Plaque In South Asians In The Us And Other Race/Ethnic Groups: The Masala And Mesa Studies, Mahmoud Al Rifai, Alka M Kanaya, Namratha R Kandula, Miguel Cainzos-Achirica, Jaideep Patel, Matthew Budoff, Michael H Criqui, Michael J Blaha, Salim S Virani

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: South Asians (SA) experience disproportionately higher rates of atherosclerotic cardiovascular disease (ASCVD) events than non-Hispanic whites (NHW) and several other Asian groups. The coronary artery calcium (CAC) Agatston score may not capture the unique characteristics of coronary plaque in SA. We therefore evaluated the prevalence and patterns of advanced CAC measures (specific coronary vessel involvement, CAC volume and density) in SA versus other race/ethnicities.

METHODS: We combined data from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts. We used multivariable-adjusted linear regression models to compare advanced CAC …

Patient-Perceived Versus Actual Risk Of Cardiovascular Disease And Associated Willingness To Consider And Use Prevention Therapy, Ann Marie Navar, Tracy Y Wang, Shuang Li, Xiaojuan Mi, Zhuokai Li, Jennifer G Robinson, Salim S Virani, Eric D Peterson

Faculty, Staff and Students Publications

BACKGROUND: Cardiovascular prevention guidelines use estimated 10-year atherosclerotic cardiovascular disease (CVD) risk based on the pooled cohort equations to guide treatment decisions and engage patients in shared decision-making. We sought to determine patient perceived versus actual risk of atherosclerotic CVD and associations with willingness for preventive therapy.

METHODS: We evaluated calculated and perceived CVD risk among 4187 patients across 124 sites in the Patient and Provider Assessment of Lipid Management Registry. Ten-year risk was assessed using the pooled cohort equations; risk relative-to-peers was determined based on age-, sex-, and race-based percentiles; and patient estimates of risk were assessed using patient …

Secretion Of Von Willebrand Factor And Suppression Of Adamts-13 Activity By Markedly High Concentration Of Ferritin, Dalia A Bashir, Qi Da, Subhashree Pradhan, Nitin Sekhar, Christian Valladolid, Fong Lam, Danielle Guffey, Jordana Goldman, Moreshwar S Desai, Miguel A Cruz, Carl Allen, Trung C Nguyen, K Vinod Vijayan

Faculty, Staff and Students Publications

Hyperferritinemia is associated with poor outcomes in critically ill patients with sepsis, hemophagocytic lymphohistiocytosis (HLH), macrophage activation syndromes (MAS) and coronavirus disease 19 (COVID-19). Autopsies of hyperferritinemic patients that succumbed to either sepsis, HLH, MAS or COVID-19 have revealed disseminated microvascular thromboses with von Willebrand factor (VWF)-, platelets-, and/or fibrin-rich microthrombi. It is unknown whether high plasma ferritin concentration actively promotes microvascular thrombosis, or merely serves as a prognostic biomarker in these patients. Here, we show that secretion of VWF from human umbilical vein endothelial cells (HUVEC) is significantly enhanced by 100,000 ng/ml of recombinant ferritin heavy chain protein (FHC). …

How Do Red Blood Cells Die?, Perumal Thiagarajan, Charles J Parker, Josef T Prchal

Faculty, Staff and Students Publications

Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive. Red cells undergo several physicochemical changes as they age in the circulation. Several of these changes have been proposed as a recognition tag for macrophages. Most prevalent hypotheses for red cell …

Identification Of Deep-Intronic Splice Mutations In A Large Cohort Of Patients With Inherited Retinal Diseases, Xinye Qian, Jun Wang, Meng Wang, Austin D Igelman, Kaylie D Jones, Yumei Li, Keqing Wang, Kerry E Goetz, David G Birch, Paul Yang, Mark E Pennesi, Rui Chen

Faculty, Staff and Students Publications

High throughput sequencing technologies have revolutionized the identification of mutations responsible for a diverse set of Mendelian disorders, including inherited retinal disorders (IRDs). However, the causal mutations remain elusive for a significant proportion of patients. This may be partially due to pathogenic mutations located in non-coding regions, which are largely missed by capture sequencing targeting the coding regions. The advent of whole-genome sequencing (WGS) allows us to systematically detect non-coding variations. However, the interpretation of these variations remains a significant bottleneck. In this study, we investigated the contribution of deep-intronic splice variants to IRDs. WGS was performed for a cohort …

A Gigantic Uterine Leiomyoma And Big Bilateral Adrenal Myelolipomas As A Result Of Untreated Congenital Adrenal Hyperplasia, Betty La, Celestine Tung, Eugene A Choi, Ha Nguyen

Faculty, Staff and Students Publications

INTRODUCTION: Patients with congenital adrenal hyperplasia (CAH) can present early with salt wasting, adrenal insufficiency, and hyperandrogenism. Late consequences as a result of untreated CAH are now rarely seen. We present a patient with a massive uterine leiomyoma and bilateral adrenal myelolipomas due to longstanding treatment noncompliance.

CASE REPORT: A female patient with CAH was treated with glucocorticoids until the age of 29 years when they stopped with the intention of identifying as a male. The patient then presented with abdominal pain and distension. Computed tomography images of the abdomen and pelvis revealed a 31 × 35 × 31-cm abdominal …

An International Study Of Interobserver Variability Of “String Sign” Of Pancreatic Cysts Among Experienced Endosonographers, Seifeldin Hakim, Emmanuel Coronel, Graciela M Nogueras González, Philip S Ge, Suresh T Chari, Nirav Thosani, Srinivas Ramireddy, Ricardo Badillo, Tomas Davee, Marc F Catalano, Robert J Sealock, Sreeram Parupudi, Lyndon V Hernandez, Virendra Joshi, Atsushi Irisawa, Surinder Rana, Sundeep Lakhtakia, Peter Vilmann, Adrian Saftoiu, Siyu Sun, Marc Giovannini, Matthew H Katz, Michael P Kim, Manoop S Bhutani

Faculty, Staff and Students Publications

BACKGROUND AND OBJECTIVES: No single optimal test reliably determines the pancreatic cyst subtype. Following EUS-FNA, the "string sign" test can differentiate mucinous from nonmucinous cysts. However, the interobserver variability of string sign results has not been studied.

METHODS: An experienced endosonographer performed EUS-FNA of pancreatic cysts on different patients and was recorded on video performing the string sign test for each. The videos were shared internationally with 14 experienced endosonographers, with a survey for each video: "Is the string sign positive?" and "If the string sign is positive, what is the length of the formed string?" Also asked "What is …

An International Study Of Interobserver Variability Of “String Sign” Of Pancreatic Cysts Among Experienced Endosonographers, Wanda Phipatanakul, David T Mauger, Theresa W Guilbert, Leonard B Bacharier, Sandy Durrani, Daniel J Jackson, Fernando D Martinez, Anne M Fitzpatrick, Amparito Cunningham, Susan Kunselman, Lisa M Wheatley, Cindy Bauer, Carla M Davis, Bob Geng, Kirsten M Kloepfer, Craig Lapin, Andrew H Liu, Jacqueline A Pongracic, Stephen J Teach, James Chmiel, Jonathan M Gaffin, Matthew Greenhawt, Meera R Gupta, Peggy S Lai, Robert F Lemanske, Wayne J Morgan, William J Sheehan, Jeffrey Stokes, Peter S Thorne, Hans C Oettgen, Elliot Israel

Faculty, Staff and Students Publications

Asthma remains one of the most important challenges to pediatric public health in the US. A large majority of children with persistent and chronic asthma demonstrate aeroallergen sensitization, which remains a pivotal risk factor associated with the development of persistent, progressive asthma throughout life. In individuals with a tendency toward Type 2 inflammation, sensitization and exposure to high concentrations of offending allergens is associated with increased risk for development of, and impairment from, asthma. The cascade of biological responses to allergens is primarily mediated through IgE antibodies and their production is further stimulated by IgE responses to antigen exposure. In …

Case Report: Dupilumab Successfully Controls Severe Eczema In A Child With Elevated Ige Levels And Recurrent Skin Infections, Tejas P Joshi, Sara Anvari, Meera R Gupta, Carla M Davis, Joud Hajjar

Faculty, Staff and Students Publications

The efficacy of dupilumab in pediatric patients with severe eczema presenting in the setting of elevated immunoglobulin E (IgE) levels and recurrent bacterial skin infections is not well-understood. Here we present the case of a child with elevated IgE levels in whom dupilumab treatment led to remarkable control of his eczema and recurrent skin infections. We also review the use of dupilumab in other patients with molecularly proven cases of hyper IgE (HIGE) syndrome. Our case supports the notion that dupilumab may have a seminal application in treating severe eczema that occurs in the setting of elevated IgE levels and …

Meta-Analysis Comparing Outcomes Of Catheter Ablation For Ventricular Arrhythmia In Ischemic Versus Nonischemic Cardiomyopathy, Indranill Basu-Ray, Dibbendhu Khanra, Sumit K Shah, Anindya Mukherjee, Sudhanva V Char, Bhavna Jain, T Jared Bunch, Michael Gold, Adedayo A Adeboye, Mohammad Saeed

Faculty, Staff and Students Publications

BACKGROUND: Catheter ablation is an effective treatment for ventricular arrhythmia (VA) in ischemic cardiomyopathy (ICM). However, results in non-ICM (NICM) patients are not satisfactory, and studies comparing differences between NICM and ICM are limited. We conducted a meta-analysis of procedural characteristics and long-term outcomes of catheter ablation for VA, comparing results between ICM and NICM.

METHODS: Studies in the PubMed, EMBASE, and Cochrane databases were systematically reviewed. Four studies reporting comparison of catheter ablation of VA between ICM and NICM were examined. The Newcastle-Ottawa Scale was used to appraise study quality. A random-effects model with inverse variance method was used …

Power Washing Pulmonary Alveolar Proteinosis, Tiana R Endicott-Yazdani, Gary S Schwartz, Haiying Zhang, Randall L Rosenblatt, Puneet S Garcha

Faculty, Staff and Students Publications

Pulmonary alveolar proteinosis is an uncommon cause of insidious onset shortness of breath and hypoxemia. It is caused by an accumulation of surfactant within the alveoli. Left untreated, it can be fatal. Standard-of-care treatment is whole-lung lavage; however, in severe cases, the associated hypoxemia can be profound and single-lung ventilation would not be tolerated, potentially preventing a lifesaving treatment. Single cases using veno-venous extracorporeal membrane oxygenation to perform whole-lung lavage have been reported. Here we describe three patients with severe pulmonary alveolar proteinosis who were successfully treated with whole-lung lavage using veno-venous extracorporeal membrane oxygenation for oxygenation support.

Conduction Disorders In The Setting Of Acute Stemi, Kjell Nikus, Yochai Birnbaum, Miquel Fiol-Sala, Jani Rankinen, Antoni Bayés De Luna

Faculty, Staff and Students Publications

ST-elevation myocardial (STEMI) is frequently associated with conduction disorders. Regional myocardial ischemia or injury may affect the cardiac conduction system at various locations, and neural reflexes or changes in the balance of the autonomous nervous system may be involved. Sinoatrial and atrioventricular blocks are more frequent in inferior than anterior STEMI, while new left anterior fascicular block and right bundle branch block indicate proximal occlusion of the left anterior descending coronary artery. New left bundle branch block is associated with multi-vessel disease. Most conduction disorders associated with STEMI are reversible with reperfusion therapy, but they may still impair prognosis because …

Improving Student Confidence With Electronic Health Record Order Entry, Arindam Sarkar, Anjali Aggarwal, Larissa Grigoryan, Susan G Nash, Nidhi Mehrotra, Roger J Zoorob, William Y Huang

Faculty, Staff and Students Publications

INTRODUCTION: Despite near-universal utilization of electronic health records (EHRs) by physicians in practice, medical students in most ambulatory settings gain limited experience with placing EHR orders. In this study, an individual preceptor site investigated the usefulness of a targeted curriculum in improving students' EHR confidence and clinical reasoning skills.

METHODS: Family medicine clerkship students assigned to one community health center were invited to participate in this prospective, survey-based study. In their first week, students observed a preceptor performing EHR tasks. For the remainder of the 4-week clerkship, students utilized decision support tools, assigned a working diagnosis, entered unsigned orders in …

Creating A 'Community Of Inquiry': A Framework For Optimizing The Virtual Education Experience, Betty Lee Ligon, Audrea Burns, Satid Thammasitboon

Faculty, Staff and Students Publications

This article was migrated. The article was marked as recommended.

Background: Medical educators must learn to implement technologic advances to create meaningful learning experiences, implementing media tools that are effective in meeting evolving academic needs and fostering interpersonal engagement. The increasing time constraints in a department of more than 1,600 faculty interspersed throughout a large metropolitan complex served as the catalyst for utilizing technology to create a framework for providing virtual faculty development.

Objective: To use a Community of Inquiry (CoI) as a framework to guide the development of an interactive, virtual writing retreat.

Methods: We used the three elements …

Mitochondrial Regulation Of Diabetic Kidney Disease, Daniel L Galvan, Koki Mise, Farhad R Danesh

Faculty, Staff and Students Publications

The role and nature of mitochondrial dysfunction in diabetic kidney disease (DKD) has been extensively studied. Yet, the molecular drivers of mitochondrial remodeling in DKD are poorly understood. Diabetic kidney cells exhibit a cascade of mitochondrial dysfunction ranging from changes in mitochondrial morphology to significant alterations in mitochondrial biogenesis, biosynthetic, bioenergetics and production of reactive oxygen species (ROS). How these changes individually or in aggregate contribute to progression of DKD remain to be fully elucidated. Nevertheless, because of the remarkable progress in our basic understanding of the role of mitochondrial biology and its dysfunction in DKD, there is great excitement …

Pharmacologically Induced Ex Copula Ejaculation In Horses And Donkeys, Afroza Khanam, Ayman A Swelum, Firdous A Khan

Faculty, Staff and Students Publications

Pharmacologically induced ex copula ejaculation is a method used for collection of semen when the traditional methods of semen collection are not feasible. Common indications for this method include health issues that either preclude the physical act of mating or result in impaired erection and ejaculation. The method also offers an alternative when there is a lack of equipment and facilities required for semen collection using the conventional artificial vagina method. A variety of pharmacological protocols for ex copula ejaculation in stallions have been evaluated in both research and clinical settings with no serious side-effects reported. In general, these protocols …

Lrrtm4 Is A Member Of The Transsynaptic Complex Between Rod Photoreceptors And Bipolar Cells, Melina A Agosto, Theodore G Wensel

Faculty, Staff and Students Publications

Leucine rich repeat transmembrane (LRRTM) proteins are synaptic adhesion molecules with roles in synapse formation and signaling. LRRTM4 transcripts were previously shown to be enriched in rod bipolar cells (BCs), secondary neurons of the retina that form synapses with rod photoreceptors. Using two different antibodies, LRRTM4 was found to reside primarily at rod BC dendritic tips, where it colocalized with the transduction channel protein, TRPM1. LRRTM4 was not detected at dendritic tips of ON-cone BCs. Following somatic knockout of LRRTM4 in BCs by subretinal injection and electroporation of CRISPR/Cas9, LRRTM4 was abolished or reduced in the dendritic tips of transfected …

Small-Molecule Inhibitor Of Af9/Enl-Dot1l/Af4/Aff4 Interactions Suppresses Malignant Gene Expression And Tumor Grow, Fangrui Wu, Shenyou Nie, Yuan Yao, Tong Huo, Xin Li, Xiaowei Wu, Jidong Zhao, Yi-Lun Lin, Yinjie Zhang, Qianxing Mo, Yongcheng Song

Faculty, Staff and Students Publications

Chromosome translocations involving mixed lineage leukemia (MLL) gene cause acute leukemia with a poor prognosis. MLL is frequently fused with transcription cofactors AF4 (~35%), AF9 (25%) or its paralog ENL (10%). The AHD domain of AF9/ENL binds to AF4, its paralog AFF4, or histone-H3 lysine-79 (H3K79) methyltransferase DOT1L. Formation of AF9/ENL/AF4/AFF4-containing super elongation complexes (SEC) and the catalytic activity of DOT1L are essential for MLL-rearranged leukemia. Protein-protein interactions (PPI) between AF9/ENL and DOT1L/AF4/AFF4 are therefore a potential drug target.

Methods: Compound screening followed by medicinal chemistry was used to find inhibitors of such PPIs, which were examined for their biological …

A Novel Statistical Method For Interpreting The Pathogenicity Of Rare Variants, Jun Wang, Hehe Liu, Renae Elaine Bertrand, Alejandro Sarrion-Perdigones, Yezabel Gonzalez, Koen J T Venken, Rui Chen

Faculty, Staff and Students Publications

PURPOSE: To achieve the ultimate goal of personalized treatment of patients, accurate molecular diagnosis and precise interpretation of the impact of genetic variants on gene function is essential. With sequencing cost becoming increasingly affordable, the accurate distinguishing of benign from pathogenic variants becomes the major bottleneck. Although large normal population sequence databases have become a key resource in filtering benign variants, they are not effective at filtering extremely rare variants.

METHODS: To address this challenge, we developed a novel statistical test by combining sequencing data from a patient cohort with a normal control population database. By comparing the expected and …

Kv13 Channel Up-Regulation In Peripheral Blood T Lymphocytes Of Patients With Multiple Sclerosis, Ioannis Markakis, Ioannis Charitakis, Christine Beeton, Melpomeni Galani, Elpida Repousi, Stella Aggeloglou, Petros P Sfikakis, Michael W Pennington, K George Chandy, Cornelia Poulopoulou

Faculty, Staff and Students Publications

Voltage-gated Kv1.3 potassium channels are key regulators of T lymphocyte activation, proliferation and cytokine production, by providing the necessary membrane hyper-polarization for calcium influx following immune stimulation. It is noteworthy that an accumulating body of in vivo and in vitro evidence links these channels to multiple sclerosis pathophysiology. Here we studied the electrophysiological properties and the transcriptional and translational expression of T lymphocyte Kv1.3 channels in multiple sclerosis, by combining patch clamp recordings, reverse transcription polymerase chain reaction and flow cytometry on freshly isolated peripheral blood T lymphocytes from two patient cohorts with multiple sclerosis, as well as from healthy …

Alpha-Single Chains Of Collagen Type Vi Inhibit The Fibrogenic Effects Of Triple Helical Collagen Vi In Hepatic Stellate Cells, Christian Freise, Hyunho Lee, Christopher Chronowski, Doug Chan, Jessica Cziomer, Martin Rühl, Tarkan Dagdelen, Maik Lösekann, Ulrike Erben, Andre Catic, Werner Tegge, Detlef Schuppan, Rajan Somasundaram, Ergun Sahin

Faculty, Staff and Students Publications

The interaction of extracellular matrix (ECM) components with hepatic stellate cells (HSCs) is thought to perpetuate fibrosis by stimulating signaling pathways that drive HSC activation, survival and proliferation. Consequently, disrupting the interaction between ECM and HSCs is considered a therapeutical avenue although respective targets and underlying mechanisms remain to be established. Here we have interrogated the interaction between type VI collagen (CVI) and HSCs based on the observation that CVI is 10-fold upregulated during fibrosis, closely associates with HSCs in vivo and promotes cell proliferation and cell survival in cancer cell lines. We exposed primary rat HSCs and a rat …

Adipocyte-Specific Ablation Of Pu1 Promotes Energy Expenditure And Ameliorates Metabolic Syndrome In Aging Mice, Ke Yun Chen, Alejandra De Angulo, Xin Guo, Aditya More, Scott A Ochsner, Eduardo Lopez, David Saul, Weijun Pang, Yuxiang Sun, Neil J Mckenna, Qiang Tong

Faculty, Staff and Students Publications

Objective: Although PU.1/Spi1 is known as a master regulator for macrophage development and function, we have reported previously that it is also expressed in adipocytes and is transcriptionally induced in obesity. Here, we investigated the role of adipocyte PU.1 in the development of the age-associated metabolic syndrome.

Methods: We generated mice with adipocyte-specific PU.1 knockout, assessed metabolic changes in young and older adult PU.1^fl/fl (control) and AdipoqCre PU.1^fl/fl (aPU.1KO) mice, including body weight, body composition, energy expenditure, and glucose homeostasis. We also performed transcriptional analyses using RNA-Sequencing of adipocytes from these mice.

Results: aPU.1KO mice have elevated energy …

Lifestyle Risk Factors, Quality Of Life, And Intervention Preferences Of Barrett's Esophagus Patients: A Prospective Cohort Study, Xiaotao Zhang, Sharmila Anandasabapathy, Julian Abrams, Mohamed Othman, Hoda J Badr

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: Lifestyle counseling to achieve a healthy weight, quit smoking, and reduce alcohol is a cornerstone in the management of Barrett's Esophagus (BE). However, little is known about whether patients make these recommended lifestyle changes or the impact of non-adherence on their quality of life (QOL). This study characterized the lifestyle risk factors, QOL, and intervention preferences of BE patients as a first step toward developing lifestyle change interventions for this population.

METHODS: Patients with a confirmed BE diagnosis (N = 106) completed surveys at a surveillance endoscopy visit (baseline) and at 3- and 6-month follow-ups. Patients reported …

Helicobacter Pylori Diagnosis And Therapy In The Era Of Antimicrobial Stewardship, Akiko Shiotani, Priya Roy, Hong Lu, David Y Graham

Faculty, Staff and Students Publications

The diagnosis and therapy of Helicobacter pylori infection have undergone major changes based on the use the principles of antimicrobial stewardship and increased availability of susceptibility profiling. H. pylori gastritis now recognized as an infectious disease, as such there is no placebo response allowing outcome to be assessed in relation to the theoretically obtainable cure rate of 100%. The recent recognition of H. pylori as an infectious disease has changed the focus to therapies optimized to reliably achieve high cure rates. Increasing antimicrobial resistance has also led to restriction of clarithromycin, levofloxacin, or metronidazole to susceptibility-based therapies. Covid-19 resulted in …

Colorectal Endoscopic Submucosal Dissection: An Update On Best Practice, Tara Keihanian, Mohamed O Othman

Faculty, Staff and Students Publications

Endoscopic submucosal dissection (ESD) is a method of en-bloc resection of neoplastic colorectal lesions which is less invasive compared to surgical resection. Lesion stratification, architecture recognition and estimation of depth of invasion are crucial for patient selection. Expert endoscopists have integrated a variety of classification systems including Paris, lateral spreading tumor (LST), narrow band imaging (NBI), international colorectal endoscopic (NICE) and Japanese NBI expert team (JNET) in their day-to-day practice to enhance lesion detection accuracy. Major societies recommend ESD for LST-non granular (NG), Kudo-VI type, large depressed and protruded colonic lesions with shallow submucosal invasion. Chance of submucosal invasion enhances …