Medicine and Health Sciences Commons^™

Temporal Stability Of The Hemodynamic Response Function Across The Majority Of Human Cerebral Cortex, Haitham Salem, Tung Huynh, Natasha Topolski, Benson Mwangi, Madhukar H Trivedi, Jair C Soares, A John Rush, Sudhakar Selvaraj

Faculty, Staff and Student Publications

BACKGROUND: Artificial intelligence is currently being used to facilitate early disease detection, better understand disease progression, optimize medication/treatment dosages, and uncover promising novel treatments and potential outcomes.

METHODS: Utilizing the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) dataset, we built a machine learning model to predict depression remission rates using same clinical data as features for each of the first three antidepressant treatment steps in STAR*D. We only used early treatment data (baseline and first follow up) in each STAR*D step to temporally analyze predictive features of remission at the end of the step.

RESULTS: Our model showed significant prediction …

Singlet Oxygen Quenching By Resveratrol Derivatives, Charlotte G Monsour, Abegail C Tadle, Bliss J Tafolla-Aguirre, Nidhi Lakshmanan, Jin Hyeok Yoon, Rhemrose B Sabio, Matthias Selke

Faculty, Staff and Student Publications

We investigated the singlet oxygen quenching ability of several derivatives of trans-resveratrol which have been reported to have significant antioxidant ability, including photoprotective activity. We measured the total rate constants of singlet oxygen removal (kT) by the methylated resveratrol derivative 1,3-dimethoxy-5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene, and the partially methylated resveratrol derivatives 4-((E)-2-(3,5-dimethoxyphenyl)ethenyl)phenol (pterostilbene), 5-[(E)-2-(4-methoxyphenyl)ethenyl]benzene-1,3-diol and (2R,3R)-3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)-2,3-dihydrochromen-4-one (dihydromyricetin). A protic solvent system results in higher kT values, except for the completely methylated derivative. We also investigated the ability of trans-resveratrol to directly act as a photosensitizer (rather than via secondary photoproducts resulting from other primary photochemical …

Tubers Affecting The Fusiform Face Area Are Associated With Autism Diagnosis, Alexander L Cohen, Mallory R Kroeck, Juliana Wall, Peter Mcmanus, Arina Ovchinnikova, Mustafa Sahin, Darcy A Krueger, E Martina Bebin, Hope Northrup, Joyce Y Wu, Simon K Warfield, Jurriaan M Peters, Michael D Fox, Acern Study Group

Faculty, Staff and Student Publications

OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with focal brain "tubers" and a high incidence of autism spectrum disorder (ASD). The location of brain tubers associated with autism may provide insight into the neuroanatomical substrate of ASD symptoms.

METHODS: We delineated tuber locations for 115 TSC participants with ASD (n = 31) and without ASD (n = 84) from the Tuberous Sclerosis Complex Autism Center of Excellence Research Network. We tested for associations between ASD diagnosis and tuber burden within the whole brain, specific lobes, and at 8 regions of interest derived from the ASD neuroimaging literature, including the anterior …

Impact Of Time To Treatment On Endovascular Thrombectomy Outcomes In The Early Versus Late Treatment Time Windows, Negar Asdaghi, Kefeng Wang, Hannah Gardener, Angus Jameson, David Z Rose, Ayham Alkhachroum, Carolina M Gutierrez, Hao Ying, Nils Mueller-Kronast, Nicole B Sur, Chuanhui Dong, Gillian Gordon Perue, Marissa Lepain, Sebastian Koch, Nastajjia Krementz, Erika Marulanda-Londoño, Ricardo Hanel, Brijesh Mehta, Dileep R Yavagal, Tatjana Rundek, Ralph L Sacco, Jose G Romano

Faculty, Staff and Student Publications

BACKGROUND: The impact of time to treatment on outcomes of endovascular thrombectomy (EVT) especially in patients presenting after 6 hours from symptom onset is not well characterized. We studied the differences in characteristics and treatment timelines of EVT-treated patients participating in the Florida Stroke Registry and aimed to characterize the extent to which time impacts EVT outcomes in the early and late time windows.

METHODS: Prospectively collected data from Get With the Guidelines-Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. Participants were EVT patients with onset-to-puncture time (OTP) of ≤24 hours and …

Building The Foundation For A Community-Generated National Research Blueprint For Inherited Bleeding Disorders: Research Priorities To Transform The Care Of People With Hemophilia, Duc Q Tran, Craig C Benson, Judith A Boice, Meera Chitlur, Amy L Dunn, Miguel A Escobar, Kalpna Gupta, Jill M Johnsen, James Jorgenson, Scott D Martin, Suzanne Martin, Shannon L Meeks, Alfredo A Narvaez, Doris V Quon, Mark T Reding, Ulrike M Reiss, Brittany Savage, Kim Schafer, Bruno Steiner, Courtney Thornburg, Lena M Volland, Annette Von Drygalski

Faculty, Staff and Student Publications

BACKGROUND: Decades of research have transformed hemophilia from severely limiting children's lives to a manageable disorder compatible with a full, active life, for many in high-income countries. The direction of future research will determine whether exciting developments truly advance health equity for all people with hemophilia (PWH). National Hemophilia Foundation (NHF) and American Thrombosis and Hemostasis Network conducted extensive inclusive all-stakeholder consultations to identify the priorities of people with inherited bleeding disorders and those who care for them.

RESEARCH DESIGN AND METHODS: Working group (WG) 1 of the NHF State of the Science Research Summit distilled the community-identified priorities for …

Transabdominal Cerclage During Pregnancy: A Retrospective Single Operator Series Over A Quarter Century, David R Hall, Mari Van De Vyver

Faculty, Staff and Student Publications

OBJECTIVE: To describe the pregnancy outcomes and complications observed in a series of cases of transabdominal cerclage (TAC), which is reserved for highly selected women with recurrent mid-trimester pregnancy loss, due to cervical insufficiency.

METHODS: A retrospective audit covering 25 years (January 1, 1997 to December 31, 2021) was performed at the Obstetric Special Care division, Tygerberg Academic Hospital in Cape Town, South Africa. All 118 pregnancies from 94 procedures, operated and managed by the principal author were included for descriptive analysis.

RESULTS: Eighty-four (91.3%) of the 92 first pregnancies after first insertion had successful outcomes. All second and third …

Development Of The Illinois Surgical Quality Improvement Collaborative (Isqic): Implementing 21 Components To Catalyze Statewide Improvement In Surgical Care, Karl Y Bilimoria, Michael F Mcgee, Mark V Williams, Julie K Johnson, Amy L Halverson, Kevin J O'Leary, Paula Farrell, Juliana Thomas, Remi Love, Lindsey Kreutzer, Allison R Dahlke, Brianna D'Orazio, Steven Reinhart, Katelyn Dienes, Mark Schumacher, Ying Shan, Christopher Quinn, Vivek N Prachand, Susan Sullivan, Kimberly A Cradock, Kelsi Boyd, William Hopkinson, Colleen Fairman, David Odell, Jonah J Stulberg, Cindy Barnard, Jane Holl, Ryan P Merkow, Anthony D Yang

Faculty, Staff and Student Publications

INTRODUCTION: In 2014, 56 Illinois hospitals came together to form a unique learning collaborative, the Illinois Surgical Quality Improvement Collaborative (ISQIC). Our objectives are to provide an overview of the first three years of ISQIC focused on (1) how the collaborative was formed and funded, (2) the 21 strategies implemented to support quality improvement (QI), (3) collaborative sustainment, and (4) how the collaborative acts as a platform for innovative QI research.

METHODS: ISQIC includes 21 components to facilitate QI that target the hospital, the surgical QI team, and the peri-operative microsystem. The components were developed from available evidence, a detailed …

Gender-Associated Cardiometabolic Risk Profiles And Health Behaviors In Patients With Type 2 Diabetes: A Cross-Sectional Analysis Of The Joint Asia Diabetes Evaluation (Jade) Program, Lee-Ling Lim, Eric S H Lau, Alice P S Kong, Amy W C Fu, Vanessa Lau, Weiping Jia, Wayne H H Sheu, Leorino Sobrepena, K H Yoon, Alexander T B Tan, Yook-Chin Chia, Aravind Sosale, Banshi D Saboo, Jothydev Kesavadev, Su-Yen Goh, Thy Khue Nguyen, Yotsapon Thewjitcharoen, Raymond Suwita, Ronald C W Ma, Elaine Y K Chow, Andrea O Y Luk, Juliana C N Chan

Faculty, Staff and Student Publications

Background

In Asia, diabetes-associated death due to cardiorenal diseases were 2–3 times higher in women than men which might be due to gender disparity in quality of care and health habits.

Methods

Adults with type 2 diabetes (T2D) from 11 Asian countries/areas were assessed using the same protocol (2007–2015). We compared treatment target attainment (HbA_1c < 7%, blood pressure [BP] < 130/80 mmHg, risk-based LDL-cholesterol, lack of central obesity [waist circumference <90 cm in men or <80 cm in women), use of cardiorenal-protective drugs (renin-angiotensin system [RAS] inhibitors, statins), and self-reported health habits including self-monitoring blood glucose (SMBG) by gender. Analyses were stratified by countries/areas, age of natural menopause (<50 vs. ≥50 years), and comorbidities (atherosclerotic cardiovascular disease [ASCVD], heart failure, kidney impairment [eGFR < 60 mL/min/1.73 m²]).

Findings

Among 106,376 patients (53.2% men; median (interquartile range) diabetes duration: 6.0 (2.0–12.0) years; mean ± SD HbA_1c 8.0 ± 1.9%; 27% insulin-treated), women were older and …

A National, Electronic Health Record-Based Study Of Perinatal Hemorrhagic And Ischemic Stroke, Stuart Fraser, Samantha M Levy, Yashar Talebi, Sean I Savitz, Alicia Zha, Gen Zhu, Hulin Wu

Faculty, Staff and Student Publications

BACKGROUND: Perinatal stroke occurs in approximately 1 in 1100 live births. Large electronic health record (EHR) data can provide information on exposures associated with perinatal stroke in a larger number of patients than is achievable through traditional clinical studies. The objective of this study is to assess prevalence and odds ratios of known and theorized comorbidities with perinatal ischemic and hemorrhagic stroke.

METHODS: The data for patients aged 0-28 days with a diagnosis of either ischemic or hemorrhagic stroke were extracted from the Cerner Health Facts Electronic Medical Record (EMR) database. Incidence of birth demographics and perinatal complications were recorded. …

Incidence And Predictors Of Acute Limb Ischemia In Acute Myocardial Infarction Complicated By Cardiogenic Shock., Carlos M Romero, Irfan Shafi, Aadhar Patil, Eric Secemsky, Ido Weinburg, Raghu Kolluri, Huaqing Zhao, Vladimir Lakther, Riyaz Bashir

Heart and Vascular Articles

OBJECTIVE: To describe the incidence and predictors of acute limb ischemia (ALI) in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS).

METHODS: Patients with index hospitalizations for AMI complicated by cardiogenic shock from 2016 to 2019 in the US National Readmission Database were identified. We evaluated the incidence of ALI and its associated mortality, length of stay, and cost of hospitalization. We used multivariable logistic regression to determine independent predictors of ALI in this population.

RESULTS: A total of 84,615 patients had AMI complicated by cardiogenic shock and 1302 (1.54%) developed ALI. The rates of ALI increased …

Lingual Alveolar Soft Part Sarcoma In A 78-Year-Old Woman: A Case Report And Comprehensive Review Of The Literature From 1952 To 2022, Aliaksandr Aksionau, Nestor Enriquez Dela Cruz, Andrew T Meram, Hugo Cuellar-Saenz, Jillian R Aveni, Hidehiro Takei

Faculty, Staff and Student Publications

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare translocation-related soft tissue sarcoma, occurring mainly in the limbs and trunk in young adults and adolescents. ASPS is rarely seen in the head and neck and one fourth of those cases described are tongue primary. Given its nonspecific symptoms, clinical findings, and rarity in this location, lingual ASPS (L-ASPS) has been reported to be commonly misdiagnosed as various benign tumors, leading to adverse outcomes.

METHODS: We report a case of L-ASPS occurring in the oldest (78 years) female patient published to date and comprehensively review the literature from 1952 to 2022. …

Epstein-Barr Virus-Associated Lymphoepithelial Carcinoma Arising In The Parotid Gland: A Case Report And Literature Review, Akinobu Kubota, Nobuyuki Bandoh, Takashi Goto, Ken-Ichi Matsumoto, Tomomi Yamaguchi-Ishochi, Yasutaka Kato, Hiroshi Nishihara, Hidehiro Takei

Faculty, Staff and Student Publications

A 60-year-old woman presented with a 3-year history of a slow-growing, painless mass in their left parotid gland. Ultrasonography revealed a well-circumscribed, lobulated, hypoechoic mass measuring 19x12x10 mm in the left parotid gland. Computed tomography revealed a well-circumscribed, solid mass with homogeneous enhancement. Fluorodeoxyglucose-positron emission tomography revealed uptake by the tumor but no uptake in other organs, including the nasopharynx. The patient underwent superficial parotidectomy with adequate safety margins and selective neck dissection followed by radiotherapy. No facial paralysis or recurrence of the tumor had been observed as of 20 months post-operation. Histologically, the tumor was composed of sheets of …

Independent Associations Of Neighborhood Deprivation And Patient-Level Social Determinants Of Health With Textbook Outcomes After Inpatient Surgery, Susanne Schmidt, Jeongsoo Kim, Michael A Jacobs, Daniel E Hall, Karyn B Stitzenberg, Lillian S Kao, Bradley B Brimhall, Chen-Pin Wang, Laura S Manuel, Hoah-Der Su, Jonathan C Silverstein, Paula K Shireman

Faculty, Staff and Student Publications

OBJECTIVE: Assess associations of Social Determinants of Health (SDoH) using Area Deprivation Index (ADI), race/ethnicity and insurance type with Textbook Outcomes (TO).

SUMMARY BACKGROUND DATA: Individual- and contextual-level SDoH affect health outcomes, but only one SDoH level is usually included.

METHODS: Three healthcare system cohort study using National Surgical Quality Improvement Program (2013-2019) linked with ADI risk-adjusted for frailty, case status and operative stress examining TO/TO components (unplanned reoperations, complications, mortality, Emergency Department/Observation Stays and readmissions).

RESULTS: Cohort (34,251 cases) mean age 58.3 [SD=16.0], 54.8% females, 14.1% Hispanics, 11.6% Non-Hispanic Blacks, 21.6% with ADI>85, and 81.8% TO. Racial and …

Pyroptosis In Neutrophils: Multimodal Integration Of Inflammasome And Regulated Cell Death Signaling Pathways, George R Dubyak, Brandon A Miller, Eric Pearlman

Faculty, Staff and Student Publications

Pyroptosis is a proinflammatory mode of lytic cell death mediated by accumulation of plasma membrane (PM) macropores composed of gasdermin-family (GSDM) proteins. It facilitates two major functions in innate immunity: (i) elimination of intracellular replicative niches for pathogenic bacteria; and (ii) non-classical secretion of IL-1 family cytokines that amplify host-beneficial inflammatory responses to microbial infection or tissue damage. Physiological roles for gasdermin D (GSDMD) in pyroptosis and IL-1β release during inflammasome signaling have been extensively characterized in macrophages. This involves cleavage of GSDMD by caspase-1 to generate GSDMD macropores that mediate IL-1β efflux and progression to pyroptotic lysis. Neutrophils, which …

Properties Of A Combined Measure Of Reading And Writing: The Assessment Of Writing, Self-Monitoring And Reading (Awsm Reader), Anthony R Gioia, Yusra Ahmed, Steven P Woods, Paul T Cirino

Faculty, Staff and Student Publications

There is significant overlap between reading and writing, but no known standardized measure assesses these jointly. The goal of the present study is to evaluate the properties of a novel measure, the Assessment of Writing, Self-Monitoring, and Reading (AWSM Reader), that simultaneously evaluates both reading comprehension and writing. In doing so, we evaluate reliability (Cronbach’s alpha) and various aspects of construct-related validity, including separate criterion measures of reading and writing, and the AWSM Reader’s relations with other variables, including language and executive function (EF), both of which are implicated for both reading and writing. Participants were 377 3rd, 4th, and …

Crk2 Controls Cytoskeleton Morphogenesis In Trypanosoma Brucei By Phosphorylating Β-Tubulin To Regulate Microtubule Dynamics, Kyu Joon Lee, Qing Zhou, Ziyin Li

Faculty, Staff and Student Publications

Microtubules constitute a vital part of the cytoskeleton in eukaryotes by mediating cell morphogenesis, cell motility, cell division, and intracellular transport. The cytoskeleton of the parasite Trypanosoma brucei contains an array of subpellicular microtubules with their plus-ends positioned toward the posterior cell tip, where extensive microtubule growth and cytoskeleton remodeling take place during early cell cycle stages. However, the control mechanism underlying microtubule dynamics at the posterior cell tip remains elusive. Here, we report that the S-phase cyclin-dependent kinase-cyclin complex CRK2-CYC13 in T. brucei regulates microtubule dynamics by phosphorylating β-tubulin on multiple evolutionarily conserved serine and threonine residues to inhibit …

A Look At The Global Impact Of Covid-19 Pandemic On Neurosurgical Services And Residency Training, Cathleen C Kuo, Alexander O Aguirre, Andrea Kassay, Brianna M Donnelly, Hebatalla Bakr, Mohamed Aly, Ahmed A M Ezzat, Mohamed A R Soliman

Faculty, Staff and Student Publications

BACKGROUND: The COVID-19 pandemic has left an indelible effect on healthcare delivery and education system, including residency training. Particularly, neurosurgical departments worldwide had to adapt their operating model to the constantly changing pandemic landscape. This review aimed to quantify the reduction in neurosurgical operative volume and describe the impact of these trends on neurosurgical residency training.

METHODS: We performed a comprehensive search of PubMed and EMBASE between December 2019 and October 2022 to identify studies comparing pre-pandemic and pandemic neurosurgical caseloads as well as articles detailing the impact of COVID-19 on neurosurgery residency training. Statistical analysis of quantitative data was …

Defining The Role Of Ab Externo Xen Gel Stent In Glaucomatous Eyes With Prior Failed Surgical Intervention, Lillian K To, Rupak K Dhoot, Alice Z Chuang, Sam Karimaghaei, Francisco Guevara-Abadia, Ruchi D Shah, Robert M Feldman

Faculty, Staff and Student Publications

PURPOSE: To evaluate the safety and efficacy of Xen45 Gel stent (Xen; Allergan) in eyes that have failed prior surgical intervention, compared to traditional glaucoma drainage device (GDD) or continuous-wave cyclophotocoagulation (CPC). Since this population has low expected success rates with additional surgery, it is vital to compare to standard-of-care surgical options.

METHODS: Retrospective, single-center, case-control study of ab externo transconjunctival Xen shunt in eyes that have previously undergone trabeculectomy and/or GDD surgery. Postoperative data were collected for 18 months. Failure was defined as no light perception, additional glaucoma surgery required, or intraocular pressure (IOP) of < 6 mmHg after 6 weeks postoperatively.

RESULTS: Eighteen Xen eyes …

New Developments In Allergic Fungal Rhinosinusitis Pathophysiology And Treatment, Brian H Cameron, Amber U Luong

Faculty, Staff and Student Publications

Background: Allergic fungal rhinosinusitis (AFRS) is an endotype of chronic rhinosinusitis (CRS) with nasal polyps characterized by eosinophilic mucin laden with fungal hyphae entrapped in expanded sinus cavities with an exaggerated hypersensitivity to fungal elements. The last decade has elucidated fungi-driven inflammatory pathways contributing to the pathophysiology of chronic inflammatory respiratory diseases. In addition, novel therapeutic biologic options have become available for CRS over the last several years.

Objective: To review the current literature examining AFRS, focusing on recent developments in our understanding of its pathophysiology and implications for treatment options.

Methods: Review article.

Results: Fungi-driven respiratory inflammation has been …

Congenital Gastrointestinal Anomalies In Europe 2010–2019: A Geo-Spatiotemporal And Causal Inferential Study Of Epidemiological Patterns In Relationship To Cannabis- And Substance Exposure, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2022 to 2026

Introduction: Congenital anomalies (CA’s) of most of the gastrointestinal tract have been linked causally with prenatal or community cannabis exposure. Therefore, we studied this relationship in Europe. Methods: CA data were from Eurocat. Drug-use data were sourced from the European Monitoring Centre for Drugs and Drug Addiction. Income data were taken from the World Bank. Results: When countries with increasing rates of daily cannabis use were compared with those which were not, the overall rate of gastrointestinal CA’s (GCA’s) was higher in the former group (p = 0.0032). The five anomalies which were related to the metrics of cannabis exposure …

The Australian And New Zealand Society For Sarcopenia And Frailty Research (Anzssfr) Sarcopenia Diagnosis And Management Task Force: Findings From The Consumer Expert Delphi Process, Jesse Zanker, Marc Sim, Kate Anderson, Saliu Balogun, Sharon L. Brennan-Olsen, Elsa Dent, Gustavo Duque, Christian M. Girgis, Mathis Grossmann, Alan Hayes, Tim Henwood, Vasant Hirani, Charles Inderjeeth, Sandra Iuliano, Justin Keogh, Joshua R. Lewis, Gordon S. Lynch, Julie A. Pasco, Steven Phu, Esmee M. Reijnierse, Nicholas Russell, Lara Vlietstra, Renuka Visvanathan, Troy Walker, Debra L. Waters, Solomon Yu, Andrea B. Maier, Robin M. Daly, David Scott

Research outputs 2022 to 2026

Objectives:

To develop guidelines, informed by health-care consumer values and preferences, for sarcopenia prevention, assessment and management for use by clinicians and researchers in Australia and New Zealand.

Methods:

A three-phase Consumer Expert Delphi process was undertaken between July 2020 and August 2021. Consumer experts included adults with lived experience of sarcopenia or health-care utilisation. Phase 1 involved a structured meeting of the Australian and New Zealand Society for Sarcopenia and Frailty Research (ANZSSFR) Sarcopenia Diagnosis and Management Task Force and consumer representatives from which the Phase 2 survey was developed. In Phase 2, consumers from Australia and New Zealand …

Tweak/Fn14 Signalling Regulates The Tissue Microenvironment In Chronic Pancreatitis, N. Dianah B. Abu Bakar, Rodrigo Carlessi, Jully Gogoi-Tiwari, Julia Köhn-Gaone, Vincent Williams, Marco Falasca, John K. Olynyk, Grant A. Ramm, Janina E. E. Tirnitz-Parker

Research outputs 2022 to 2026

Chronic pancreatitis increases the risk of developing pancreatic cancer through the upregulation of pathways favouring proliferation, fibrosis, and sustained inflammation. We established in previous studies that the ligand tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) signals through its cognate receptor fibroblast growth factor-inducible 14 (Fn14) to regulate these underlying cellular processes in the chronic liver injury niche. However, the role of the TWEAK/Fn14 signalling pathway in pancreatic disease is entirely unknown. An analysis of publicly available datasets demonstrated that the TWEAK receptor Fn14 is upregulated in pancreatitis and pancreatic adenocarcinoma, with single cell RNA sequencing revealing pancreatic ductal …

Direct Costs Of Second Aqueous Shunt Implant Versus Transscleral Cyclophotocoagulation (The Assists Trial), Jack X Ma, Alice Z Chuang, Robert M Feldman, Steve L Mansberger, Angelo P Tanna, Lauren S Blieden, Daniel Shoham, Nicholas P Bell, Ronald L Gross, Louis R Pasquale, David S Greenfield, Jeffrey M Liebmann, Robert N Weinreb

Faculty, Staff and Student Publications

PRCIS: The cost of cyclophotocoagulation is less than the cost of a second glaucoma drainage device.

PURPOSE: To compare the total direct costs of implantation of a second glaucoma drainage device (SGDD) with transscleral cyclophotocoagulation (CPC) for patients with inadequately controlled intraocular pressure (IOP) reduction, despite the presence of a preexisting glaucoma drainage device in the ASSISTS clinical trial.

METHODS: We compared the total direct cost per patient, including the initial study procedure, medications, additional procedures, and clinic visits during the study period. The relative costs for each procedure during the 90-day global period and the entire study period were …

Linoleic Acid Improves Piezo2 Dysfunction In A Mouse Model Of Angelman Syndrome, Luis O Romero, Rebeca Caires, A Kaitlyn Victor, Juanma Ramirez, Francisco J Sierra-Valdez, Patrick Walsh, Vincent Truong, Jungsoo Lee, Ugo Mayor, Lawrence T Reiter, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability and atypical behaviors. AS results from loss of expression of the E3 ubiquitin-protein ligase UBE3A from the maternal allele in neurons. Individuals with AS display impaired coordination, poor balance, and gait ataxia. PIEZO2 is a mechanosensitive ion channel essential for coordination and balance. Here, we report that PIEZO2 activity is reduced in Ube3a deficient male and female mouse sensory neurons, a human Merkel cell carcinoma cell line and female human iPSC-derived sensory neurons with UBE3A knock-down, and de-identified stem cell-derived neurons from individuals with AS. We find that loss …

Imaging Features Of Immune Checkpoint Inhibitor-Related Nephritis With Clinical Correlation: A Retrospective Series Of Biopsy-Proven Cases, Muhammad O Awiwi, Ala Abudayyeh, Noha Abdel-Wahab, Adi Diab, Migena Gjoni, Guofan Xu, Raghu Vikram, Khaled Elsayes

Faculty, Staff and Student Publications

OBJECTIVES: Imaging appearances of immune checkpoint inhibitor-related nephritis have not yet been described. The primary objective of this study is to describe the appearances of immunotherapy-related nephritis on computerized tomography (CT) and positron emission tomography (PET). The secondary objectives are to investigate the association of radiologic features with clinical outcomes.

METHODS: CT and PET-CT scans before the initiation of immunotherapy (baseline), at nephritis, and after resolution of pathology-proven nephritis cases were reviewed. Total kidney volume, renal parenchymal SUVmax, renal pelvis SUVmax, and blood pool SUVmean were obtained.

RESULTS: Thirty-four patients were included. The total kidney volume was significantly higher at …

Ninety-Day Mortality Following Transoral Robotic Surgery Or Radiation At Commission On Cancer-Accredited Facilities, James R Janopaul-Naylor, Manali Rupji, Rachel A Tobillo, Joshua W Lorenz, Jeffrey M Switchenko, Sibo Tian, Azeem S Kaka, David C Qian, Ashley J Schlafstein, Conor E Steuer, Jill S Remick, Soumon Rudra, Mark W Mcdonald, Nabil F Saba, William A Stokes, Mihir R Patel, James E Bates

Faculty, Staff and Student Publications

BACKGROUND: Postoperative mortality for oropharynx squamous cell carcinoma (OPSCC) with transoral robotic surgery (TORS) varies from 0.2% to 6.5% on trials; the real-world rate is unknown.

METHODS: NCDB study from 2010 to 2017 for patients with cT1-2N0-2M0 OPSCC with Charleson-Deyo score 0-1. Ninety-day mortality assessed from start and end of treatment at Commission on Cancer-accredited facilities.

RESULTS: 3639 patients were treated with TORS and 1937 with radiotherapy. TORS cohort had more women and higher income, was younger, more often treated at academic centers, and more likely to have private insurance (all p < 0.05). Ninety-day mortality was 1.3% with TORS and 0.7% or 1.4% from start or end of radiotherapy, respectively. From end of therapy, there was no significant difference on MVA between treatment modality.

CONCLUSIONS: There is minimal difference between 90-day mortality …

Ras Nanoclusters Are Cell Surface Transducers That Convert Extracellular Stimuli To Intracellular Signalling, Yong Zhou, John F Hancock

Faculty, Staff and Student Publications

Mutations of rat sarcoma virus (RAS) oncogenes (HRAS, KRAS and NRAS) can contribute to the development of cancers and genetic disorders (RASopathies). The spatiotemporal organization of RAS is an important property that warrants further investigation. In order to function, wild-type or oncogenic mutants of RAS must be localized to the inner leaflet of the plasma membrane (PM), which is driven by interactions between their C-terminal membrane-anchoring domains and PM lipids. The isoform-specific RAS-lipid interactions promote the formation of nanoclusters on the PM. As main sites for effector recruitment, these nanoclusters are biologically important. Since the spatial distribution of lipids is …

Bacterial Division Ring Stabilizing Zapa Versus Destabilizing Slma Modulate Ftsz Switching Between Biomolecular Condensates And Polymers, Begoña Monterroso, Miguel Ángel Robles-Ramos, Marta Sobrinos-Sanguino, Juan Román Luque-Ortega, Carlos Alfonso, William Margolin, Germán Rivas, Silvia Zorrilla

Faculty, Staff and Student Publications

Cytokinesis is a fundamental process for bacterial survival and proliferation, involving the formation of a ring by filaments of the GTPase FtsZ, spatio-temporally regulated through the coordinated action of several factors. The mechanisms of this regulation remain largely unsolved, but the inhibition of FtsZ polymerization by the nucleoid occlusion factor SlmA and filament stabilization by the widely conserved cross-linking protein ZapA are known to play key roles. It was recently described that FtsZ, SlmA and its target DNA sequences (SlmA-binding sequence (SBS)) form phase-separated biomolecular condensates, a type of structure associated with cellular compartmentalization and resistance to stress. Using biochemical …

Eczema Monkeypoxicum In A Female Patient With Atopic Dermatitis, Emma Napoli, Madeline Frizzell, Clark Gravell, Sergio Vallejo, Shasta Theodore, Karen Chen, Huma Siddiqui, Justin Dunn, Dora Marrufo, Jose Cadena, Patrick J Danaher

Faculty, Staff and Student Publications

A female patient with atopic dermatitis who had recently received a tattoo presented with severe right ear pain and several vesiculopustular lesions. Over 1 week, she developed approximately 80 widely distributed lesions. Laboratory testing confirmed mpox (previously monkeypox) virus, and no further lesions developed after initiation of oral tecovirimat.

Invasive Mold Infections Following Hurricane Harvey-Houston, Texas, Mitsuru Toda, Samantha Williams, Brendan R Jackson, Sebastian Wurster, Jose A Serpa, Masayuki Nigo, Carolyn Z Grimes, Robert L Atmar, Tom M Chiller, Luis Ostrosky-Zeichner, Dimitrios P Kontoyiannis

Faculty, Staff and Student Publications

BACKGROUND: Characterizing invasive mold infection (IMI) epidemiology in the context of large flooding events is important for public health planning and clinical decision making.

METHODS: We assessed IMI incidence (per 10 000 healthcare encounters) 1 year before and after Hurricane Harvey at 4 hospitals in Houston, Texas. Potential IMI cases were assigned as proven or probable cases using established definitions, and surveillance cases using a novel definition. We used rate ratios to describe IMI incidence and multivariable logistic regression to examine patient characteristics associated with IMI case status.

RESULTS: IMI incidence was significantly higher posthurricane (3.69 cases) than prehurricane (2.50 …