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Restoration Of Cardiac Function After Myocardial Infarction By Long-Term Activation Of The Cns Leptin-Melanocortin System, Fabio N Gava, Alexandre A Da Silva, Xuemei Dai, Romain Harmancey, Sadia Ashraf, Ana C M Omoto, Mateus C Salgado, Sydney P Moak, Xuan Li, John E Hall, Jussara M Do Carmo

Faculty, Staff and Student Publications

Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca

Racial Disparities In Systemic Sclerosis: Short‐ And Long‐Term Outcomes Among African American Participants Of Sls I And Ii, Elizabeth R Volkmann, Virginia Steen, Ning Li, Michael D Roth, Philip J Clements, Daniel E Furst, Shervin Assassi, Dinesh Khanna, Grace-Hyun J Kim, Jonathan Goldin, Robert M Elashoff, Donald P Tashkin

Faculty, Staff and Student Publications

OBJECTIVE: To evaluate short- and long-term outcomes of African American (AA) participants of Scleroderma Lung Studies (SLS) I and II.

METHODS: SLS I randomized 158 participants with systemic sclerosis-interstitial lung disease (SSc-ILD) to 1 year of oral cyclophosphamide (CYC) versus placebo. SLS II randomized 142 participants with SSc-ILD to 1 year of oral CYC followed by 1 year of placebo versus 2 years of mycophenolate (MMF). Joint models compared the course of forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO) between AA and non-AA, and Cox proportional hazard models assessed long-term morbidity and mortality outcomes.

RESULTS: In …

Restoration Of Cardiac Function After Myocardial Infarction By Long-Term Activation Of The Cns Leptin-Melanocortin System, Fabio N Gava, Alexandre A Da Silva, Xuemei Dai, Romain Harmancey, Sadia Ashraf, Ana C M Omoto, Mateus C Salgado, Sydney P Moak, Xuan Li, John E Hall, Jussara M Do Carmo

Faculty, Staff and Student Publications

Heart failure has a high mortality rate, and current therapies offer limited benefits. The authors demonstrate that activation of the central nervous system leptin-melanocortin pathway confers remarkable protection against progressive heart failure following severe myocardial infarction. The beneficial cardiac-protective actions of leptin require activation of brain melanocortin-4 receptors and elicit improvements in cardiac substrate oxidation, cardiomyocyte contractility, Ca

Mir-9-1 Suppresses Cell Proliferation And Promotes Apoptosis By Targeting Uhrf1 In Lung Cancer, Cheng-You Jia, Wei Xiang, Ji-Bin Liu, Geng-Xi Jiang, Feng Sun, Jian-Jun Wu, Xiao-Li Yang, Rui Xin, Yi Shi, Dan-Dan Zhang, Wen Li, Zavuga Zuberi, Jie Zhang, Gai-Xia Lu, Hui-Min Wang, Pei-Yao Wang, Fei Yu, Zhong-Wei Lv, Yu-Shui Ma, Da Fu

Faculty, Staff and Student Publications

Lung cancer is listed as the most common reason for cancer-related death all over the world despite diagnostic improvements and the development of chemotherapy and targeted therapies. MicroRNAs control both physiological and pathological processes including development and cancer. A microRNA-9 to 1 (miR-9 to 1) overexpression model in lung cancer cell lines was established and miR-9 to 1 was found to significantly suppress the proliferation rate in lung cancer cell lines, colony formation in vitro, and tumorigenicity in nude mice of A549 cells. Ubiquitin-like containing PHD and RING finger domains 1 (UHRF1) was then identified to direct target of miR-9 …

Stress Inoculation Training (Sit-Norcal), Part 1: The Development And Preliminary Evaluation Of A Psychological Performance Training Protocol, Sarah E Jackson, Matthew R Baity, Patrick R Thomas, Douglas Barba, Daniel Jacobson, Madeleine Goodkind, Diane Swick, A Sarah Ivey

Faculty, Staff and Student Publications

Background: Stress inoculation training (SIT) interventions have demonstrated promise within military contexts for human performance enhancement and psychological health applications. However, lack of manualized guidance on core content selection, delivery, and measurement processes has limited their use.

Purpose: The purpose of this study was to develop and evaluate a comprehensive SIT intervention protocol to enhance the performance and health of military personnel engaged in special warfare and first-response activities.

Methods: Multidisciplinary teams of subject matter experts (n = 19) were consulted in protocol generation. The performance improvement/human performance technology (HPT) model was used in the selection, refinement, and measurement of …

Helping Healthcare Teams Save Lives During Covid-19: Insights And Countermeasures From Team Science, Allison M Traylor, Scott I Tannenbaum, Eric J Thomas, Eduardo Salas

Faculty, Staff and Student Publications

As the COVID-19 pandemic has ravaged the United States, health care teams are on the frontlines of this global crisis, often navigating harrowing conditions at work, such as a lack of personal protective equipment and staffing shortages, and distractions at home, including worries about elderly relatives or making childcare arrangements. While the nature and severity of stressors impacting health care teams are in many ways unprecedented, decades of psychological research exploring teamwork in extreme contexts can provide insights to understand and improve outcomes for teams in a crisis. This review highlights the psychological principles that apply to teams in a …

Interscalene Block For Analgesia In Orthopedic Treatment Of Shoulder Trauma: Single-Dose Liposomal Bupivacaine Versus Perineural Catheter, Andrzej P Kwater, Nadia Hernandez, Carlos Artime, Johanna Blair De Haan

Faculty, Staff and Student Publications

BACKGROUND: Interscalene brachial plexus block is frequently utilized to provide perioperative analgesia to patients undergoing shoulder surgery to optimize recovery, minimize opioid consumption, and decrease overall hospital length of stay. The use of an indwelling perineural interscalene catheter provides extended analgesia and is efficacious in managing severe postoperative pain following major shoulder surgery. Currently, the only alternative to perineural catheters for extended analgesia with interscalene block involves the perineural infiltration of liposomal bupivacaine. However, there is limited published data regarding the overall analgesic effectiveness of using interscalene liposomal bupivacaine in the setting of shoulder surgery.

METHODS: We performed a retrospective …

Influenza Vaccination For The Prevention Of Cardiovascular Disease In The Americas: Consensus Document Of The Inter-American Society Of Cardiology And The Word Heart Federation, Álvaro Sosa Liprandi, María Inés Sosa Liprandi, Ezequiel José Zaidel, Gabriel M Aisenberg, Adrián Baranchuk, Eduardo Costa Duarte Barbosa, Gabriela Borrayo Sánchez, Bryce Alexander, Fernando Tomás Lanas Zanetti, Ricardo López Santi, Ana Girleza Múnera-Echeverri, Pablo Perel, Daniel Piskorz, Carlos Enrique Ruiz-Mori, Jorge Saucedo, Osiris Valdez, José Ramón González Juanatey, Daniel José Piñeiro, Fausto J Pinto, Fernando Stuardo Wyss Quintana

Faculty, Staff and Student Publications

BACKGROUND: Cardiovascular mortality is decreasing but remains the leading cause of death world-wide. Respiratory infections such as influenza significantly contribute to morbidity and mortality in patients with cardiovascular disease. Despite of proven benefits, influenza vaccination is not fully implemented, especially in Latin America.

OBJECTIVE: The aim was to develop a regional consensus with recommendations regarding influenza vaccination and cardiovascular disease.

METHODS: A multidisciplinary team composed by experts in the management and prevention of cardiovascular disease from the Americas, convened by the Inter-American Society of Cardiology (IASC) and the World Heart Federation (WHF), participated in the process and the formulation of …

Enhancing Glucose Metabolism Via Gluconeogenesis Is Therapeutic In A Zebrafish Model Of Dravet Syndrome, Rajeswari Banerji, Christopher Huynh, Francisco Figueroa, Matthew T Dinday, Scott C Baraban, Manisha Patel

Faculty, Staff and Students Publications

Energy-producing pathways are novel therapeutic targets for the treatment of neurodevelopmental disorders. Here, we focussed on correcting metabolic defects in a catastrophic paediatric epilepsy, Dravet syndrome which is caused by mutations in sodium channel NaV1.1 gene, SCN1A. We utilized a translatable zebrafish model of Dravet syndrome (scn1lab) which exhibits key characteristics of patients with Dravet syndrome and shows metabolic deficits accompanied by down-regulation of gluconeogenesis genes, pck1 and pck2. Using a metabolism-based small library screen, we identified compounds that increased gluconeogenesis via up-regulation of pck1 gene expression in scn1lab larvae. Treatment with PK11195, a pck1 activator …

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 …

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 …

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 …

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 …

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 …

Mitral Valve Repair Complicated By Left Circumflex Coronary Artery Occlusion: The Vital Role Of The Anesthesiologist, Andres Bacigalupo Landa, Jason Hoyos, Jayanand D'Mello

Faculty, Staff and Students Publications

The anatomical relationship between the mitral valve and the left circumflex coronary artery places this vessel at risk for occlusion during mitral valve repair or replacement. In view of the potential high morbidity and mortality of this complication, the anesthesiologist has a vital role in its prompt diagnosis. We present the case of a 47-year-old man who underwent a minimally invasive mitral valve repair, which was complicated by left circumflex coronary artery occlusion.

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.

A New Aortic Arch Dissection Classification: The Fuwai Classification, Juntao Qiu, Xinjin Luo, Jinlin Wu, Wei Pan, Qian Chang, Xiangyang Qian, Xiaogang Sun, Bo Wei, Liang Zhang, Shen Liu, Wenxiang Jiang, Cuntao Yu

Faculty, Staff and Students Publications

Aims: We describe a new aortic arch dissection (AcD) classification, which we have called the Fuwai classification. We then compare the clinical characteristics and long-term prognoses of different classifications.

Methods: All AcD patients who underwent surgical procedures at Fuwai Hospital from 2010 to 2015 were included in the study. AcD procedures are divided into three types: Fuwai type Cp, Ct, and Cd. Type Cp is defined as the innominate artery or combined with the left carotid artery involved. Type Cd is defined as the left subclavian artery or combined with the left carotid artery involved. All other AcD surgeries are …

Open Problems In Extracellular Rna Data Analysis: Insights From An Ercc Online Workshop, Roger P Alexander, Robert R Kitchen, Juan Pablo Tosar, Matthew Roth, Pieter Mestdagh, Klaas E A Max, Joel Rozowsky, Karolina Elżbieta Kaczor-Urbanowicz, Justin Chang, Leonora Balaj, Bojan Losic, Eric L Van Nostrand, Emily Laplante, Bogdan Mateescu, Brian S White, Rongshan Yu, Aleksander Milosavljevic, Gustavo Stolovitzky, Ryan M Spengler

Faculty, Staff and Students Publications

We now know RNA can survive the harsh environment of biofluids when encapsulated in vesicles or by associating with lipoproteins or RNA binding proteins. These extracellular RNA (exRNA) play a role in intercellular signaling, serve as biomarkers of disease, and form the basis of new strategies for disease treatment. The Extracellular RNA Communication Consortium (ERCC) hosted a two-day online workshop (April 19–20, 2021) on the unique challenges of exRNA data analysis. The goal was to foster an open dialog about best practices and discuss open problems in the field, focusing initially on small exRNA sequencing data. Video recordings of workshop …

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 …

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 …

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 …

Long Noncoding Rnas And Their Therapeutic Promise In Diabetic Nephropathy, Juan D Coellar, Jianyin Long, Farhad R Danesh

Faculty, Staff and Students Publications

Recent advances in large-scale RNA sequencing and genome-wide profiling projects have unraveled a heterogeneous group of RNAs, collectively known as long noncoding RNAs (lncRNAs), which play central roles in many diverse biological processes. Importantly, an association between aberrant expression of lncRNAs and diverse human pathologies has been reported, including in a variety of kidney diseases. These observations have raised the possibility that lncRNAs may represent unexploited potential therapeutic targets for kidney diseases. Several important questions regarding the functionality of lncRNAs and their impact in kidney diseases, however, remain to be carefully addressed. Here, we provide an overview of the main …

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 …

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 …

Buprenorphine For Chronic Pain: A Safer Alternative To Traditional Opioids, Suhani Dalal, Ahish Chitneni, Amnon A Berger, Vwaire Orhurhu, Bilal Dar, Bennett Kramer, Anvinh Nguyen, John Pruit, Charles Halsted, Alan D Kaye, Jamal Hasoon

Faculty, Staff and Students Publications

With the ongoing public health crisis with prescription opioids, there is a need for safer alternatives for medication management in chronic pain patients. Buprenorphine is a partial mu-opioid agonist which is commonly utilized to treat patients with opioid-use disorders. The purpose of this review is to discuss the potential use of this medication for the treatment of chronic pain instead of resorting to more traditional Schedule II opioids. Buprenorphine offers a safer alternative for patients who require opioids to manage chronic pain, given the unique pharmacological properties that allow it to provide adequate analgesia with less abuse potential.

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 …

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 …

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 …