Internal Medicine Commons^™

Prognostic Value Of Severe Acute Respiratory Syndrome Coronavirus-2 Viral Load And Antibodies In Patients Hospitalized With Covid-19, Rebecca N Bauer, Anastasia Teterina, Haridha Shivram, Jacqueline Mcbride, Carrie M Rosenberger, Fang Cai, Min Bao, Larry Tsai, Oliver Gordon, Ivan T Lee, Jeffrey J Wallin, Danielle Porter, Kavita Juneja, Gregory Camus, Ivan O Rosas, Steffen Wildum

Faculty, Staff and Students Publications

Observational studies have identified the potential prognostic value for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load and anti-SARS-CoV-2 antibodies in coronavirus disease 2019 (COVID-19). However, viral load in nasopharyngeal (NP) swabs produced inconsistent results in prognostic analyses, and the prognostic value of viral load or antibodies has not been confirmed in large clinical trials. COVACTA and REMDACTA were double-blind, randomized, controlled trials with a combined enrollment of 1078 patients hospitalized with COVID-19 treated with tocilizumab or placebo in COVACTA or tocilizumab plus remdesivir or placebo plus remdesivir in REMDACTA. We assessed the potential prognostic value of NP and serum …

Race-Free Estimated Glomerular Filtration Rate Equation In Kidney Transplant Recipients: Development And Validation Study, Marc Raynaud, Solaf Al-Awadhi, Ivana Juric, Gillian Divard, Yannis Lombardi, Nikolina Basic-Jukic, Olivier Aubert, Laurence Dubourg, Ingrid Masson, Christophe Mariat, Dominique Prié, Vincent Pernin, Moglie Le Quintrec, Timothy S Larson, Mark D Stegall, Boris Bikbov, Piero Ruggenenti, Laurent Mesnard, Hassan N Ibrahim, Marie Bodilsen Nielsen, Arthur J Matas, Brian J Nankivell, Stan Benjamens, Robert A Pol, Stephan J L Bakker, Xavier Jouven, Christophe Legendre, Nassim Kamar, Byron H Smith, Hani M Wadei, Antoine Durrbach, Flavio Vincenti, Giuseppe Remuzzi, Carmen Lefaucheur, Andrew J Bentall, Alexandre Loupy

Faculty, Staff and Student Publications

OBJECTIVE: To compare the performance of a newly developed race-free kidney recipient specific glomerular filtration rate (GFR) equation with the three current main equations for measuring GFR in kidney transplant recipients.

DESIGN: Development and validation study SETTING: 17 cohorts in Europe, the United States, and Australia (14 transplant centres, three clinical trials).

PARTICIPANTS: 15 489 adults (3622 in development cohort (Necker, Saint Louis, and Toulouse hospitals, France), 11 867 in multiple external validation cohorts) who received kidney transplants between 1 January 2000 and 1 January 2021.

MAIN OUTCOME MEASURE: The main outcome measure was GFR, measured according to local practice. …

Steroidal Or Non-Steroidal Mras: Should We Still Enable Raasi Use Through K Binders?, L Parker Gregg, Sankar D Navaneethan

Faculty, Staff and Students Publications

Renin-angiotensin-aldosterone system inhibitors (RAASi) and mineralocorticoid receptor antagonists (MRAs) are important interventions to improve outcomes in patients with chronic kidney disease and heart failure, but their use is limited in some patients by the development of hyperkalemia. The risk of hyperkalemia may differ between agents, with one trial showing lower risk of hyperkalemia with the novel non-steroidal MRA finerenone compared with steroidal MRA spironolactone. Novel potassium binders, including patiromer and sodium zirconium cyclosilicate, are available interventions to manage hyperkalemia and enable continuation of RAASi and MRAs in patients who could benefit from these treatments. These agents bind free potassium ions …

Adherence To Opioid Patient Prescriber Agreements At A Safety Net Hospital, Soraira Pacheco, Linh M T Nguyen, John M Halphen, Nikitha N Samy, Nathaniel R Wilson, Gregory Sattler, Shane E Wing, Christine Feng, Rex A D Paulino, Pulin Shah, Supriyanka Addimulam, Riddhi Patel, Curtis J Wray, Joseph A Arthur, David Hui

Faculty, Staff and Student Publications

Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019. We included patients 18 years or older with cancer diagnoses who received opioids. We collected patient characteristics at consultation and information regarding PPA. The …

A Phase 2 Study Of Nivolumab Combined With Ibrutinib In Patients With Diffuse Large B-Cell Richter Transformation Of Cll, Nitin Jain, Jayastu Senapati, Beenu Thakral, Alessandra Ferrajoli, Philip Thompson, Jan Burger, Sreyashi Basu, Tapan Kadia, Naval Daver, Gautam Borthakur, Marina Konopleva, Naveen Pemmaraju, Erin Parry, Catherine J Wu, Joseph Khoury, Carlos Bueso-Ramos, Naveen Garg, Xuemei Wang, Wanda Lopez, Ana Ayala, Susan O'Brien, Hagop Kantarjian, Michael Keating, James Allison, Padmanee Sharma, William Wierda

Faculty, Staff and Student Publications

Richter transformation (RT) is a rare complication of chronic lymphocytic leukemia (CLL) that has dismal outcomes. Upregulation of PD-1/PD-L1 drives immunological evasion in patients with RT. We hypothesized that combining nivolumab, a PD-1 blocking antibody, with the BTK inhibitor (BTKi) ibrutinib could potentiate tumor-cell killing. We conducted an investigator-initiated phase 2 clinical trial to assess the efficacy of combined nivolumab and ibrutinib in patients with diffuse large B-cell lymphoma (DLBCL) RT and CLL. Patients included were ≥18 years of age with adequate hepatic and renal function. Patients received nivolumab every 2 weeks of a 4-week cycle for a maximum of …

Hiv-1 Transmission Among Injecting Drug Users Is Principally Derived From Local Circulating Strains In Guangxi, China, Ping Cen, Hua Yue Liang, Yuan Yang, Fei Zhang, Shi Xiong Yang, Ju Cong Mo, Yi Feng, Jie Gang Huang, Chuan Yi Ning, Chun Yuan Huang, Yao Yang, Na Liang, Bing Yu Liang, Li Ye, Hao Liang

Faculty, Staff and Student Publications

OBJECTIVE: The mode of human immunodeficiency virus (HIV) transmission

METHODS: We performed a molecular epidemiological investigation of infections across Guangxi from 2009 to 2019. Phylogenetic and Bayesian time-geographic analyses of HIV-1 sequences were performed to confirm the characteristics of transmission between IDUs in combination with epidemiological data.

RESULTS: Among the 535 subjects, CRF08_BC (57.4%), CRF01_AE (28.4%), and CRF07_BC (10.7%) were the top 3 HIV strains; 72.6% of infections were linked to other provinces in the transmission network; 93.6% of sequence-transmitted strains were locally endemic, with the rest coming from other provinces, predominantly Guangdong and Yunnan; 92.1% of the HIV transmission …

Parent Perspectives Of School/Daycare Experiences In Young Children Newly Diagnosed With Diabetes, Alexa Stern, Brenda Duran, Randi Streisand, Christine H Wang, Carrie Tully, Lauren Clary, Katherine Gallagher, Fran Cogen, Lefkothea Karaviti, Maureen Monaghan, Marisa E Hilliard

Faculty, Staff and Students Publications

OBJECTIVE: A central part of family adjustment to a new diagnosis of type 1 diabetes (T1D) is integrating T1D management into the child's school/daycare. This may be particularly challenging for young children who rely on adults for their diabetes management. This study aimed to describe parent experiences with school/daycare during the first 1.5 years following a young child's T1D diagnosis.

METHODS: As part of a randomized controlled trial of a behavioral intervention, 157 parents of young children with new-onset (<2 >months) T1D reported on their child's school/daycare experience at baseline and at 9- and 15-month post-randomization. We used a mixed-methods …

Blockchain-Enabled Immutable, Distributed, And Highly Available Clinical Research Activity Logging System For Federated Covid-19 Data Analysis From Multiple Institutions, Tsung-Ting Kuo, Anh Pham, Maxim E Edelson, Jihoon Kim, Jason Chan, Yash Gupta, Lucila Ohno-Machado

Faculty, Staff and Student Publications

OBJECTIVE: We aimed to develop a distributed, immutable, and highly available cross-cloud blockchain system to facilitate federated data analysis activities among multiple institutions.

MATERIALS AND METHODS: We preprocessed 9166 COVID-19 Structured Query Language (SQL) code, summary statistics, and user activity logs, from the GitHub repository of the Reliable Response Data Discovery for COVID-19 (R2D2) Consortium. The repository collected local summary statistics from participating institutions and aggregated the global result to a COVID-19-related clinical query, previously posted by clinicians on a website. We developed both on-chain and off-chain components to store/query these activity logs and their associated queries/results on a blockchain …

Co-Delivery Of Therapeutics And Bioactive Gas Using A Novel Liposomal Platform For Enhanced Treatment Of Acute Arterial Injury, Shao-Ling Huang, Melanie R Moody, Xing Yin, David D Mcpherson, Hyunggun Kim

Faculty, Staff and Student Publications

Atherosclerosis is a complex, multi-stage disease characterized by pathological changes across the vascular wall. Endothelial dysfunction, inflammation, hypoxia, and vascular smooth muscle cell proliferation contribute to its progression. An effective strategy capable of delivering pleiotropic treatment to the vascular wall is essential to limit neointimal formation. Echogenic liposomes (ELIP), which can encapsulate bioactive gases and therapeutic agents, have the potential to deliver enhanced penetration and treatment efficacy for atherosclerosis. In this study, liposomes loaded with nitric oxide (NO) and rosiglitazone, a peroxisome proliferator-activated receptor agonist, were prepared using hydration, sonication, freeze-thawing, and pressurization. The efficacy of this delivery system was …

Sarcopenia And Cardiovascular Diseases, Abdulla A Damluji, Maha Alfaraidhy, Noora Alhajri, Namit N Rohant, Manish Kumar, Christina Al Malouf, Samira Bahrainy, Min Ji Kwak, Wayne B Batchelor, Daniel E Forman, Michael W Rich, James Kirkpatrick, Ashok Krishnaswami, Karen P Alexander, Gary Gerstenblith, Peggy Cawthon, Christopher R Defilippi, Parag Goyal

Faculty, Staff and Student Publications

Sarcopenia is the loss of muscle strength, mass, and function, which is often exacerbated by chronic comorbidities including cardiovascular diseases, chronic kidney disease, and cancer. Sarcopenia is associated with faster progression of cardiovascular diseases and higher risk of mortality, falls, and reduced quality of life, particularly among older adults. Although the pathophysiologic mechanisms are complex, the broad underlying cause of sarcopenia includes an imbalance between anabolic and catabolic muscle homeostasis with or without neuronal degeneration. The intrinsic molecular mechanisms of aging, chronic illness, malnutrition, and immobility are associated with the development of sarcopenia. Screening and testing for sarcopenia may be …

Confidence-Based Laboratory Test Reduction Recommendation Algorithm, Tongtong Huang, Linda T Li, Elmer V Bernstam, Xiaoqian Jiang

Faculty, Staff and Student Publications

BACKGROUND: We propose a new deep learning model to identify unnecessary hemoglobin (Hgb) tests for patients admitted to the hospital, which can help reduce health risks and healthcare costs.

METHODS: We collected internal patient data from a teaching hospital in Houston and external patient data from the MIMIC III database. The study used a conservative definition of unnecessary laboratory tests, which was defined as stable (i.e., stability) and below the lower normal bound (i.e., normality). Considering that machine learning models may yield less reliable results when trained on noisy inputs containing low-quality information, we estimated prediction confidence to assess the …

Functional Neuronal Circuits Promote Disease Progression In Cancer, Anthony C Restaino, Austin Walz, Samuel J Vermeer, Jeffrey Barr, Attila Kovács, Robin R Fettig, Daniel W Vermeer, Hunter Reavis, Caitlin S Williamson, Christopher T Lucido, Tuany Eichwald, Dalia K Omran, Euihye Jung, Lauren E Schwartz, Maria Bell, Desirae M Muirhead, Jody E Hooper, William C Spanos, Ronny Drapkin, Sebastien Talbot, Paola D Vermeer

Faculty, Staff and Student Publications

The molecular and functional contributions of intratumoral nerves to disease remain largely unknown. We localized synaptic markers within tumors suggesting that these nerves form functional connections. Consistent with this, electrophysiological analysis shows that malignancies harbor significantly higher electrical activity than benign disease or normal tissues. We also demonstrate pharmacologic silencing of tumoral electrical activity. Tumors implanted in transgenic animals lacking nociceptor neurons show reduced electrical activity. These data suggest that intratumoral nerves remain functional at the tumor bed. Immunohistochemical staining demonstrates the presence of the neuropeptide, Substance P (SP), within the tumor space. We show that tumor cells express the …

Cord Blood Transplantation For Nonmalignant Disorders: Early Functional Immunity And High Survival, Caridad Martinez, Paibel Aguayo-Hiraldo, Natalia Chaimowitz, Lisa Forbes, Nicholas Rider, Sarah Nicholas, Filiz Seeborg, Javier Chinen, Ivan Chinn, Carla Davis, Howard Roseblatt, Lenora Noroski, Bilal Omer, Tami John, Khaled Yassine, Swati Naik, John Craddock, Saleh Bhar, Carl Allen, Nabil Ahmed, Ghadir Sasa, David Steffin, Erin Doherty, Anil George, Baheyeldin Salem, Brian Friend, Meenakshi Hegde, Malcolm K Brenner, Helen E Heslop, Ann Leen, Amanda Peña, Mengfen Wu, I Celine Hanson, Robert A Krance

Faculty, Staff and Students Publications

There is no consensus on the best donor for children with nonmalignant disorders and immune deficiencies in the absence of a matched related donor (MRD). We evaluated the 2-year overall survival (OS) after umbilical cord blood transplantation (UCBT) in patients with nonmalignant disorders from 2009 to 2020 enrolled in a prospective clinical trial using either 5/6 or 6/6 UCB as the cell source. Patients receive a fully ablative busulfan, cyclophosphamide, and fludarabine without serotherapy. Fifty-five children were enrolled, median age 5 months (range, 1-111 months); primary immune deficiency (45), metabolic (5), hemophagocytic lymphohistiocytosis (1), and hematologic disorders (4). Twenty-six patients …

Perspectives On Non-Prescription Antibiotic Use Among Hispanic Patients In The Houston Metroplex, Lindsey Laytner, Patricia Chen, Susan Nash, Michael K Paasche-Orlow, Richard Street, Roger Zoorob, Barbara Trautner, Larissa Grigoryan

Faculty, Staff and Students Publications

BACKGROUND: Non-prescription antibiotic use includes taking an antibiotic without medical guidance (e.g., leftovers, from friends/relatives, or purchased without a prescription). Non-prescription use contributes to antimicrobial resistance, adverse drug reactions, interactions, superinfection, and microbiome imbalance. Qualitative studies exploring perspectives regarding non-prescription use among Hispanic patients are lacking. We used the Kilbourne Framework for Advancing Health Disparities Research to identify factors influencing patients' non-prescription use and organize our findings.

METHODS: Our study includes Hispanic primary care clinic patients with different types of health insurance coverage in the Houston metroplex who endorsed non-prescription use in a previous survey. Semistructured interviews explored the factors …

Loss Of Lgr5 Through Therapy-Induced Downregulation Or Gene Ablation Is Associated With Resistance And Enhanced Met-Stat3 Signaling In Colorectal Cancer Cells, Tressie A Posey, Joan Jacob, Ashlyn Parkhurst, Shraddha Subramanian, Liezl E Francisco, Zhengdong Liang, Kendra S Carmon

Faculty, Staff and Student Publications

Leucine-rich repeat-containing, G protein-coupled receptor 5 (LGR5) is highly expressed in colorectal cancer and cancer stem cells (CSCs) that play important roles in tumor initiation, progression, and metastasis. Loss of LGR5 has been shown to enhance therapy resistance. However, the molecular mechanisms that mediate this resistance remain elusive. In this study, we demonstrate conversion of LGR5+ colorectal cancer cells to an LGR5- state in response to chemotherapy, LGR5- targeted antibody-drug conjugates (ADCs), or LGR5 gene ablation led to activation of STAT3. Further investigation revealed increased STAT3 activation occurred as a result of increased mesenchymal epithelial transition (MET) factor receptor activity. …

One Thing Leads To Another: Embracing Complexity In Geriatric Cardiology, Ashok Krishnaswami, Min Ji Kwak

Faculty, Staff and Student Publications

No abstract provided.

Patient With Genital Lymphedema, Pain, And Rash, Resa G Magill, Dylan Supak, Rachel Pham, Dustin Luse, Cooper R Benson

Faculty, Staff and Student Publications

No abstract provided.

Neuroendocrine Tumor Of The Ampulla Of Vater: A Case Report, Mohammad S Aman, Bidhan C Das, Aminul Islam, Murshidul Arefin, Satya N Gupta

Faculty, Staff and Student Publications

Neuroendocrine tumors (NETs) of the ampulla of Vater are extremely rare. Here, we discuss the clinical presentation, diagnostic challenges, and treatment options of a recently experienced case of NET of the ampulla of Vater in light of the literature. A 56-year-old woman presented with recurrent upper abdominal pain. Ultrasonography (USG) of the whole abdomen showed multiple gallstones along with a dilated common bile duct (CBD). For evaluating the dilated CBD, a magnetic resonance cholangiopancreatography was performed, which revealed the double-duct sign. Subsequently, an upper gastrointestinal endoscopy showed a bulged-out ampulla of the Vater. Biopsy and histopathological examination of the growth …

Interleukin-33 Facilitates Liver Regeneration Through Serotonin-Involved Gut-Liver Axis, Yankai Wen, Christoph Emontzpohl, Long Xu, Constance L Atkins, Jong-Min Jeong, Yang Yang, Kangho Kim, Chuan Wu, Shizuo Akira, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Insufficient liver regeneration causes post-hepatectomy liver failure and small-for-size syndrome. Identifying therapeutic targets to enhance hepatic regenerative capacity remains urgent. Recently, increased IL-33 was observed in patients undergoing liver resection and in mice after partial hepatectomy (PHx). The present study aims to investigate the role of IL-33 in liver regeneration after PHx and to elucidate its underlying mechanisms.

APPROACH AND RESULTS: We performed PHx in IL-33 -/- , suppression of tumorigenicity 2 (ST2) -/- , and wild-type control mice, and found deficiency of IL-33 or its receptor ST2 delayed liver regeneration. The insufficient liver regeneration could be …

Therapeutic Potential Of Tumor Treating Fields For Malignant Brain Tumors, Youyou Zhou, Xiaoqing Xing, Jinyun Zhou, Han Jiang, Peili Cen, Chentao Jin, Yan Zhong, Rui Zhou, Jing Wang, Mei Tian, Hong Zhang

Faculty, Staff and Student Publications

BACKGROUND: Malignant brain tumors are among the most threatening diseases of the central nervous system, and despite increasingly updated treatments, the prognosis has not been improved. Tumor treating fields (TTFields) are an emerging approach in cancer treatment using intermediate-frequency and low-intensity electric field and can lead to the development of novel therapeutic options.

RECENT FINDINGS: A series of biological processes induced by TTFields to exert anti-cancer effects have been identified. Recent studies have shown that TTFields can alter the bioelectrical state of macromolecules and organelles involved in cancer biology. Massive alterations in cancer cell proteomics and transcriptomics caused by TTFields …

Candidate Biomarkers As Predictors Of Future Kidney Disease And Cardiovascular Dysfunction In Adolescents With Type 2 Diabetes, Fida Bacha, Laure El Ghormli, Barbara H Braffett, Amy S Shah, Santica M Marcovina, Lorraine E Levitt Katz, Steven M Willi, Sonia Caprio, Ruban Dhaliwal, Samuel S Gidding

Faculty, Staff and Students Publications

AIMS: Evaluate changes in circulating biomarkers as predictors of kidney disease, and cardiac/vascular dysfunction in participants from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

METHODS: Candidate biomarkers were assessed annually in 507 participants over a mean follow-up of 6.9 ± 2.4 years. Moderate albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g and hyperfiltration as eGFR ≥ 135 mL/min/1.73 m

RESULTS: At baseline, 35.7% were male, with a mean age 13.9 years, diabetes duration 7.8 months, and HbA1c 6.0%. Higher concentrations of E-selectin and proinsulin were associated with incident moderate albuminuria and hyperfiltration. …

Obstructive Sleep Apnea Modulates Clinical Outcomes Post-Acute Myocardial Infarction: A Large Longitudinal Veterans’ Dataset Report, Ritwick Agrawal, Amir Sharafkhaneh, Vijay Nambi, Ahmed Bahammam, Javad Razjouyan

Faculty, Staff and Students Publications

BACKGROUND: While the longer-term Obstructive Sleep apnea (OSA)-related intermittent hypoxia (IH) leads to various comorbidities, it has become increasingly evident that OSA confers protective advantages during and after acute myocardial infarction (AMI). We hypothesized in patients who were admitted with acute MI, the presence of OSA is associated with lower in-hospital mortality compared to those without a prior diagnosis of OSA.

METHODS: In this nationwide retrospective study utilizing Veterans Health Administration records, we included patients hospitalized for MI with a history of sleep disorders from 1999 to 2020. We divided patients into two cohorts: those with OSA and those without …

Genetic Associations Between Modifiable Risk Factors And Alzheimer Disease, Jiao Luo, Jesper Qvist Thomassen, Céline Bellenguez, Benjamin Grenier-Boley, Itziar De Rojas, Atahualpa Castillo, Kayenat Parveen, Fahri Küçükali, Aude Nicolas, Oliver Peters, Anja Schneider, Martin Dichgans, Dan Rujescu, Norbert Scherbaum, Deckert Jürgen, Steffi Riedel-Heller, Lucrezia Hausner, Laura Molina Porcel, Emrah Düzel, Timo Grimmer, Jens Wiltfang, Stefanie Heilmann-Heimbach, Susanne Moebus, Thomas Tegos, Nikolaos Scarmeas, Jordi Clarimon, Fermin Moreno, Jordi Pérez-Tur, María J Bullido, Pau Pastor, Raquel Sánchez-Valle, Victoria Álvarez, Mercè Boada, Pablo García-González, Raquel Puerta, Pablo Mir, Luis M Real, Gerard Piñol-Ripoll, Jose María García-Alberca, Jose Luís Royo, Eloy Rodriguez-Rodriguez, Hilkka Soininen, Teemu Kuulasmaa, Alexandre De Mendonça, Shima Mehrabian, Jakub Hort, Martin Vyhnalek, Sven Van Der Lee, Caroline Graff, Goran Papenberg, Vilmantas Giedraitis, Anne Boland, Delphine Bacq-Daian, Jean-François Deleuze, Gael Nicolas, Carole Dufouil, Florence Pasquier, Olivier Hanon, Stéphanie Debette, Edna Grünblatt, Julius Popp, Luisa Benussi, Daniela Galimberti, Beatrice Arosio, Patrizia Mecocci, Vincenzo Solfrizzi, Lucilla Parnetti, Alessio Squassina, Lucio Tremolizzo, Barbara Borroni, Benedetta Nacmias, Sandro Sorbi, Paolo Caffarra, Davide Seripa, Innocenzo Rainero, Antonio Daniele, Carlo Masullo, Gianfranco Spalletta, Julie Williams, Philippe Amouyel, Frank Jessen, Patrick Kehoe, Magda Tsolaki, Giacomina Rossi, Pascual Sánchez-Juan, Kristel Sleegers, Martin Ingelsson, Ole A Andreassen, Mikko Hiltunen, Cornelia Van Duijn, Rebecca Sims, Wiesje Van Der Flier, Agustín Ruiz, Alfredo Ramirez, Jean-Charles Lambert, Ruth Frikke-Schmidt

Faculty, Staff and Students Publications

IMPORTANCE: An estimated 40% of dementia is potentially preventable by modifying 12 risk factors throughout the life course. However, robust evidence for most of these risk factors is lacking. Effective interventions should target risk factors in the causal pathway to dementia.

OBJECTIVE: To comprehensively disentangle potentially causal aspects of modifiable risk factors for Alzheimer disease (AD) to inspire new drug targeting and improved prevention.

DESIGN, SETTING, AND PARTICIPANTS: This genetic association study was conducted using 2-sample univariable and multivariable mendelian randomization. Independent genetic variants associated with modifiable risk factors were selected as instrumental variables from genomic consortia. Outcome data for …

Upright Positioning To Maintain Quantitative Measurement Of Higher Right Atrial Pressures, Zaven Sargsyan, Stephanie Sherman

Faculty, Staff and Students Publications

No abstract provided.

Heartworm Adulticide Treatment: A Tropical Perspective, Filipe Dantas-Torres, Jennifer Ketzis, Gabriela Pérez Tort, Andrei Daniel Mihalca, Gad Baneth, Domenico Otranto, Malaika Watanabe, Bui Khanh Linh, Tawin Inpankaew, Pablo Borrás, Sangaran Arumugam, Barend Louis Penzhorn, Adrian Patalinghug Ybañez, Peter Irwin, Rebecca J Traub

Faculty, Staff and Student Publications

Dirofilaria immitis (the canine heartworm) is widespread in the tropics, with prevalence surpassing 30% in high-risk areas. In addition to the suitable climatic conditions that favour mosquito abundance and filarial larva development, there is low compliance with the recommended year-round use of preventives in these transmission hotspots. This represents a major concern, considering that melarsomine (first-line heartworm adulticide) is unavailable in several tropical countries, resulting in the so-called slow-kill protocol being the only available adulticide treatment option. In this article, the members of TroCCAP (Tropical Council for Companion Animal Parasites) review the current distribution of heartworm in the tropics and …

Rapid Escape Of New Sars-Cov-2 Omicron Variants From Ba2-Directed Antibody Responses, Aiste Dijokaite-Guraliuc, Raksha Das, Daming Zhou, Helen M Ginn, Chang Liu, Helen M E Duyvesteyn, Jiandong Huo, Rungtiwa Nutalai, Piyada Supasa, Muneeswaran Selvaraj, Thushan I De Silva, Megan Plowright, Thomas A H Newman, Hailey Hornsby, Alexander J Mentzer, Donal Skelly, Thomas G Ritter, Nigel Temperton, Paul Klenerman, Eleanor Barnes, Susanna J Dunachie, Optic Consortium, Cornelius Roemer, Thomas P Peacock, Neil G Paterson, Mark A Williams, David R Hall, Elizabeth E Fry, Juthathip Mongkolsapaya, Jingshan Ren, David I Stuart, Gavin R Screaton

Faculty, Staff and Student Publications

In November 2021, Omicron BA.1, containing a raft of new spike mutations, emerged and quickly spread globally. Intense selection pressure to escape the antibody response produced by vaccines or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection then led to a rapid succession of Omicron sub-lineages with waves of BA.2 and then BA.4/5 infection. Recently, many variants have emerged such as BQ.1 and XBB, which carry up to 8 additional receptor-binding domain (RBD) amino acid substitutions compared with BA.2. We describe a panel of 25 potent monoclonal antibodies (mAbs) generated from vaccinees suffering BA.2 breakthrough infections. Epitope mapping shows potent …

Redox And Nucleophilic Reactions Of Naphthoquinones With Small Thiols And Their Effects On Oxidization Of H2s To Inorganic And Organic Hydropolysulfides And Thiosulfate, Kenneth R Olson, Kasey J Clear, Yan Gao, Zhilin Ma, Nathaniel M Cieplik, Alyssa R Fiume, Dominic J Gaziano, Stephen M Kasko, Jennifer Luu, Ella Pfaff, Anthony Travlos, Cecilia Velander, Katherine J Wilson, Elizabeth D Edwards, Karl D Straub, Gang Wu

Faculty, Staff and Student Publications

Naphthoquinone (1,4-NQ) and its derivatives (NQs, juglone, plumbagin, 2-methoxy-1,4-NQ, and menadione) have a variety of therapeutic applications, many of which are attributed to redox cycling and the production of reactive oxygen species (ROS). We previously demonstrated that NQs also oxidize hydrogen sulfide (H2S) to reactive sulfur species (RSS), potentially conveying identical benefits. Here we use RSS-specific fluorophores, mass spectroscopy, EPR and UV-Vis spectrometry, and oxygen-sensitive optodes to examine the effects of thiols and thiol-NQ adducts on H2S-NQ reactions. In the presence of glutathione (GSH) and cysteine (Cys), 1,4-NQ oxidizes H2S to both inorganic and organic hydroper-/hydropolysulfides (R2Sn, R=H, Cys, GSH; …

Loss-Of-Function Variants In Mycbp2 Cause Neurobehavioural Phenotypes And Corpus Callosum Defects, Lama Alabdi, Muriel Desbois, Domniţa-Valeria Rusnac, Raashda A Sulaiman, Jill A Rosenfeld, Seema Lalani, David R Murdock, Lindsay C Burrage, Ping Yee Billie Au, Shelley Towner, William G Wilson, Lawrence Wong, Theresa Brunet, Gertrud Strobl-Wildemann, Jennifer E Burton, George Hoganson, Kirsty Mcwalter, Amber Begtrup, Yuri A Zarate, Elyse L Christensen, Karla J Opperman, Andrew C Giles, Rana Helaby, Artur Kania, Ning Zheng, Brock Grill, Fowzan S Alkuraya

Faculty, Staff and Student Publications

The corpus callosum is a bundle of axon fibres that connects the two hemispheres of the brain. Neurodevelopmental disorders that feature dysgenesis of the corpus callosum as a core phenotype offer a valuable window into pathology derived from abnormal axon development. Here, we describe a cohort of eight patients with a neurodevelopmental disorder characterized by a range of deficits including corpus callosum abnormalities, developmental delay, intellectual disability, epilepsy and autistic features. Each patient harboured a distinct de novo variant in MYCBP2, a gene encoding an atypical really interesting new gene (RING) ubiquitin ligase and signalling hub with evolutionarily conserved functions …

Extended Analysis Of Hiv Infection In Cisgender Men And Transgender Women Who Have Sex With Men Receiving Injectable Cabotegravir For Hiv Prevention: Hptn 083, Mark A Marzinke, Jessica M Fogel, Zhe Wang, Estelle Piwowar-Manning, Ryan Kofron, Amber Moser, Pradip Bhandari, Ryann Gollings, Lane R Bushman, Lei Weng, Elias K Halvas, John Mellors, Peter L Anderson, Deborah Persaud, Craig W Hendrix, Marybeth Mccauley, Alex R Rinehart, Marty St Clair, Susan L Ford, James F Rooney, Adeola Adeyeye, Suwat Chariyalertsak, Kenneth Mayer, Roberto C Arduino, Myron S Cohen, Beatriz Grinsztejn, Brett Hanscom, Raphael J Landovitz, Susan H Eshleman

Faculty, Staff and Student Publications

HPTN 083 demonstrated that injectable cabotegravir (CAB) was superior to oral tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) for HIV prevention in cisgender men and transgender women who have sex with men. We previously analyzed 58 infections in the blinded phase of HPTN 083 (16 in the CAB arm and 42 in the TDF-FTC arm). This report describes 52 additional infections that occurred up to 1 year after study unblinding (18 in the CAB arm and 34 in the TDF-FTC arm). Retrospective testing included HIV testing, viral load testing, quantification of study drug concentrations, and drug resistance testing. The new CAB arm infections …

Neurofibroma Of The Internal Carotid Artery Cavernous Sympathetic Plexus: Illustrative Case, Duncan J Trimble, Bryden H Dawes, Hussein A Zeineddine, Katie B Guttenberg, William C Yao, Meenakshi Bhattacharjee, Spiros L Blackburn

Faculty, Staff and Student Publications

BACKGROUND: Intracranial carotid sympathetic plexus (CSP) nerve sheath tumors have rarely been reported in the literature. This study describes the first reported case of a CSP neurofibroma and the first case of a CSP nerve sheath tumor treated via an endoscopic endonasal approach followed by adjuvant radiosurgery.

OBSERVATIONS: A 53-year-old man presented with 3 days of headaches and diplopia and was found to have a complete left abducens nerve palsy. Computed tomography (CT) revealed a smoothly dilated left carotid canal, CT angiography revealed a superiorly displaced left internal carotid artery (ICA), and magnetic resonance imaging revealed a T2-hyperintense and avidly …