Diseases Commons^™

Age-Related Differences In The Mouse Corneal Epithelial Transcriptome And Their Impact On Corneal Wound Healing, Anmar Abu-Romman, Kaitlin K Scholand, Gowthaman Govindarajan, Zhiyuan Yu, Sonali Pal-Ghosh, Mary A Stepp, Cintia S De Paiva

Faculty, Staff and Students Publications

PURPOSE: Aging is a risk factor for dry eye. We sought to identify changes in the aged mouse corneal epithelial transcriptome and determine how age affects corneal sensitivity, re-epithelialization, and barrier reformation after corneal debridement.

METHODS: Corneal epithelium of female C57BL/6J (B6) mice of different ages (2, 12, 18, and 24 months) was collected, RNA extracted, and bulk RNA sequencing performed. Cornea sensitivity was measured with an esthesiometer in 2- to 3-month-old, 12- to 13-month-old, 18- to 19-month-old, and 22- to 25-month-old female and male mice. The 2-month-old and 18-month-old female and male mice underwent unilateral corneal debridement using a …

Pragmatic Strategies To Address Health Disparities Along The Continuum Of Care In Chronic Liver Disease, Mayur Brahmania, Shari Rogal, Marina Serper, Arpan Patel, David Goldberg, Amit Mathur, Julius Wilder, Jennifer Vittorio, Andrew Yeoman, Nicole E Rich, Mariana Lazo, Ani Kardashian, Sumeet Asrani, Ashley Spann, Nneka Ufere, Manisha Verma, Elizabeth Verna, Dinee Simpson, Jesse D Schold, Russell Rosenblatt, Lisa Mcelroy, Sharad I Wadhwani, Tzu-Hao Lee, Alexandra T Strauss, Raymond T Chung, Ignacio Aiza, Rotonya Carr, Jin Mo Yang, Carla Brady, Brett E Fortune

Faculty, Staff and Students Publications

Racial, ethnic, and socioeconomic disparities exist in the prevalence and natural history of chronic liver disease, access to care, and clinical outcomes. Solutions to improve health equity range widely, from digital health tools to policy changes. The current review outlines the disparities along the chronic liver disease health care continuum from screening and diagnosis to the management of cirrhosis and considerations of pre-liver and post-liver transplantation. Using a health equity research and implementation science framework, we offer pragmatic strategies to address barriers to implementing high-quality equitable care for patients with chronic liver disease.

Efficacy And Safety Of Endoscopic Submucosal Dissection For Colorectal Dysplasia In Patients With Inflammatory Bowel Disease: A Systematic Review And Meta-Analysis, Talia F Malik, Vaishnavi Sabesan, Babu P Mohan, Asad Ur Rahman, Mohamed O Othman, Peter V Draganov, Gursimran S Kochhar

Faculty, Staff and Students Publications

BACKGROUND/AIMS: In this meta-analysis, we studied the safety and efficacy of endoscopic submucosal dissection (ESD) for colorectal dysplasia in patients with inflammatory bowel disease (IBD).

METHODS: Multiple databases were searched, and studies were retrieved based on pre-specified criteria until October 2022. The outcomes assessed were resection rates, procedural complications, local recurrence, metachronous tumors, and the need for surgery after ESD in IBD. Standard meta-analysis methods were followed using the random-effects model, and I2% was used to assess heterogeneity.

RESULTS: Twelve studies comprising 291 dysplastic lesions in 274 patients were included with a median follow-up of 25 months. The pooled en-bloc …

Altered Myocardial Lipid Regulation In Junctophilin-2-Associated Familial Cardiomyopathies, Satadru K Lahiri, Feng Jin, Yue Zhou, Ann P Quick, Carlos F Kramm, Meng C Wang, Xander Ht Wehrens

Faculty, Staff and Students Publications

Myocardial lipid metabolism is critical to normal heart function, whereas altered lipid regulation has been linked to cardiac diseases including cardiomyopathies. Genetic variants in the JPH2 gene can cause hypertrophic cardiomyopathy (HCM) and, in some cases, dilated cardiomyopathy (DCM). In this study, we tested the hypothesis that JPH2 variants identified in patients with HCM and DCM, respectively, cause distinct alterations in myocardial lipid profiles. Echocardiography revealed clinically significant cardiac dysfunction in both knock-in mouse models of cardiomyopathy. Unbiased myocardial lipidomic analysis demonstrated significantly reduced levels of total unsaturated fatty acids, ceramides, and various phospholipids in both mice with HCM and …

Predictors And Impact Of Prolonged Vasoplegia After Continuous-Flow Left Ventricular Assist Device Implantation, Harveen K Lamba, Mary Kim, Meng Li, Andrew B Civitello, Ajith P Nair, Leo Simpson, J Patrick Herlihy, O H Frazier, Joseph G Rogers, Gabriel Loor, Kenneth K Liao, Alexis E Shafii, Subhasis Chatterjee

Faculty, Staff and Students Publications

BACKGROUND: Vasoplegia after cardiac surgery is associated with adverse outcomes. However, the clinical effects of vasoplegia and the significance of its duration after continuous-flow left ventricular assist device (CF-LVAD) implantation are less known.

OBJECTIVES: This study aimed to identify predictors of and outcomes from transient vs prolonged vasoplegia after CF-LVAD implantation.

METHODS: The study was a retrospective review of consecutive patients who underwent CF-LVAD implantation between January 1, 2005, and December 31, 2017. Vasoplegia was defined as the presence of all of the following: mean arterial pressure ≤65 mm Hg, vasopressor (epinephrine, norepinephrine, vasopressin, or dopamine) use for >6 hours …

Clinical Outcomes After Acute Coronary Syndromes Or Revascularization Among People Living With Hiv: A Systematic Review And Meta-Analysis, Mohammed Haji, Michael Capilupi, Michael Kwok, Nouran Ibrahim, Gerald S Bloomfield, Christopher T Longenecker, Maria C Rodriguez-Barradas, Chester N Ashong, Eric Jutkowitz, Tracey H Taveira, Michelle Richard, Jennifer L Sullivan, James L Rudolph, Wen-Chih Wu, Sebhat Erqou

Faculty, Staff and Students Publications

IMPORTANCE: Clinical outcomes after acute coronary syndromes (ACS) or percutaneous coronary interventions (PCIs) in people living with HIV have not been characterized in sufficient detail, and extant data have not been synthesized adequately.

OBJECTIVE: To better characterize clinical outcomes and postdischarge treatment of patients living with HIV after ACS or PCIs compared with patients in an HIV-negative control group.

DATA SOURCES: Ovid MEDLINE, Embase, and Web of Science were searched for all available longitudinal studies of patients living with HIV after ACS or PCIs from inception until August 2023.

STUDY SELECTION: Included studies met the following criteria: patients living with …

Performance Of A Stool-Based Quantitative Pcr Assay For The Diagnosis Of Tuberculosis In Adolescents And Adults: A Multinational, Prospective Diagnostic Accuracy Study, Alexander Kay, Anca Vasiliu, Lucia Carratala-Castro, Bariki Mtafya, Jose Euberto Mendez Reyes, Nontobeko Maphalala, Shilzia Munguambe, Durbbin Mulengwa, Tara Ness, Belen Saavedra, Jason Bacha, Gugu Maphalala, Rojelio Mejia, Godwin Mtetwa, Sozinho Acacio, Patricia Manjate, Edson Mambuque, Nosisa Shiba, Nokwanda Kota, Mangaliso Ziyane, Nyanda Elias Ntinginya, Christoph Lange, H Lester Kirchner, Andrew R Dinardo, Alberto L Garcia-Basteiro, Anna Maria Mandalakas, Stool4tb Global Partnership

Faculty, Staff and Students Publications

BACKGROUND: Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens.

METHODS: We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept 21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR …

Chlorthalidone Vs Hydrochlorothiazide For Hypertension Treatment After Myocardial Infarction Or Stroke: A Secondary Analysis Of A Randomized Clinical Trial, Areef Ishani, Cynthia Hau, William C Cushman, Sarah M Leatherman, Robert A Lew, Peter A Glassman, Addison A Taylor, Ryan E Ferguson

Faculty, Staff and Students Publications

IMPORTANCE: Patients with prior myocardial infarction (MI) or stroke have a greater risk of recurrent cardiovascular (CV) events.

OBJECTIVE: To evaluate the association of chlorthalidone (CTD) vs hydrochlorothiazide (HCTZ) with CV outcomes and noncancer deaths in participants with and without prior MI or stroke.

DESIGN, SETTING, AND PARTICIPANTS: This was a prespecified secondary analysis of the Diuretic Comparison Project (DCP), a pragmatic randomized clinical trial conducted within 72 participating Veterans Affairs health care systems from June 2016 to June 2021, in which patients aged 65 years or older with hypertension taking HCTZ at baseline were randomized to continue HCTZ or …

Impact Of Obesity And Age On Mouse Corneal Innervation At The Epithelial-Stromal Interface, Justin A Courson, Rolando E Rumbaut, Alan R Burns

Faculty, Staff and Students Publications

PURPOSE: The corneal epithelium is the most highly innervated structure in the body. Previously, we reported a novel event whereby stromal axons fuse with basal epithelial cells, limiting nerve penetration into the epithelium. Although corneal-epithelial nerves undergo changes in sensitivity and distribution throughout life and in response to an obesogenic diet, it is unknown if neuronal-epithelial cell fusion is altered. Here, we sought to determine if neuronal-epithelial cell fusion frequency correlates with obesogenic diet consumption and age.

METHODS: Corneas were collected from C57BL/6 mice and evaluated for neuronal-epithelial cell fusion frequency using serial block-face scanning electron microscopy. To assess the …

Optimization Of Vagus Nerve Stimulation (Vns) And The Use Of Cervical Vns As A Treatment For Heart Failure With Reduced Ejection Fraction, Misty Owens

Electronic Theses and Dissertations

Vagus nerve stimulation (VNS) is a promising neuromodulatory therapy under investigation for a range of disorders, including heart failure, gastric dysmotility, and migraine. Two primary forms of VNS are currently investigated: cervical VNS (cVNS), involving surgically implantation to activate vagal afferents in the cervical branch in the neck and transcutaneous auricular VNS (taVNS) which subcutaneously stimulates the auricular branch in the outer ear. The nucleus of the solitary tract (NTS) serves as a relay-station receiving 90% of vagal afferents, enabling connections with higher-order brain regions and other brainstem nuclei like the spinal trigeminal nucleus (Sp5) and locus coeruleus (LC), facilitating …

Acute Pain Prediction In Oral Cavity And Oropharyngeal Cancer Patients Receiving Radiation Therapy, Vivian Salama

Dissertations and Theses (Open Access)

Oral-Cavity and oropharyngeal cancers (OC/OPC) are types of head and neck cancers that are increasing in incidence domestically. Radiation therapy (RT) is crucial in OC/OPC management. Pain is a common and challenging symptom for most patients during therapy, as nearly all patients undergoing locoregional RT in OC/OPC require analgesia for acute iatrogenic pain. Moreover, about 45% of long-term survivors report chronic pain, with more than 10% exhibiting severe chronic pain. Pain control is challenging due to the multifactorial clinical, molecular, and cellular etiology of cancer/therapy pain, as well as variation in pain assessment and the non-uniform management of pain between …

Cord Blood-Derived Invariant Natural Killer T Cells As A Platform For Allogeneic Chimeric Antigen Receptor Cell Therapy, Maison Grefe

Dissertations and Theses (Open Access)

Chimeric antigen receptor (CAR) T cells have revolutionized the treatment of hematopoietic malignancies achieving >50% complete response rates in numerous refractory/relapsed B cell malignancies. However, there are challenges that hinder CAR-T efficacy and bar the broader use of this therapy in patients. One approach to address these challenges is to create a safe allogeneic CAR cell product by using cells that do not cause graft versus host disease (GvHD). Invariant natural killer T (iNKT) cells are an ideal candidate as they are restricted to the monomorphic CD1d protein in contrast to HLA restricted αβ-T cells and therefore are safe in …

Inclusion Of Adoption As A Pregnancy Management Option In Prenatal Genetic Counseling Practice, Emma Billings

Dissertations and Theses (Open Access)

Prenatal genetic counselors are essential to providing education, psychosocial support, and guidance on pregnancy options to patients who receive a fetal diagnosis of an anomaly or genetic condition. Therefore, genetic counselors should be well-educated on comprehensive pregnancy management options consisting of parenting, abortion, and adoption. The landscape of adoption education in genetic counseling practice was last characterized in 2010 by Perry and Henry, revealing substantial variability in both the inclusion of adoption-specific education in genetic counseling program (GCP) curricula and the discussion of pregnancy options with patients in prenatal practice. As a result, the authors published a call to action …

Retinoid X Receptor As A Mediator Of Post Stroke Recovery By Reversing Age-Associated Phenotypes Of Microglia/Macrophages, Shun-Ming Ting

Dissertations and Theses (Open Access)

After stroke, microglia (MG) and blood-derived macrophages, together (MF), clear dead cells and cellular debris in the infarcted brain through phagocytosis. However, the phagocytic capability of MF declines with age. Age-related changes in MF phenotype also include overactive inflammatory responses to stroke-induced brain injury, altogether resulting in poor recovery after stroke. Retinoid-X-receptor (RXR) is a pleiotropic transcription factor. Our studies suggest that RXRa enhances MF phagocytic functions, reduces inflammatory responses, and improves post-stroke recovery. To establish phenotypes of aging MF, MG were MACS-sorted from the brains of young adults (2-4 months old) and aged (18-20 months old) mice for transcriptomic …

Interrogating Therapeutic Resistance To Oncogenic Krasg12c-Based Therapies In Colorectal Cancer, Oluwadara Coker

Dissertations and Theses (Open Access)

Colorectal cancer is the second leading cause of cancer-related deaths and the third most common cancer in the United States. Although KRAS is mutated in 50% of patients with metastatic CRC (mCRC), it has historically been a challenging therapeutic target. The recent approval of novel covalent inhibitors selective for KRASG12C mutation have entered the clinic, which has not only marked a major milestone in cancer drug discovery but has also intensified efforts to directly target other KRAS mutations that have also successfully entered the clinic. However, treatment-associated resistance mechanisms have long threatened to attenuate clinical benefit through either adaptive or …

Locally Injectable Peptide Hydrogel For Conversion Of Temozolomide And Codelivery Of Sirna In Glioblastoma Multiforme Treatment, Megan Pitz

All Dissertations

Traditional treatment methods for glioblastoma multiforme (GBM) are largely unsuccessful, with a 5-year survival rate of 5.6%. Temozolomide (TMZ), the only chemotherapy FDA-approved for GBM treatment, is a hydrophobic prodrug that is stable in an acidic pH and begins converting to its active form at a physiological pH of 7.4. However, complete conversion of TMZ is observed only at a higher pH, and only about 30% of administered TMZ reaches the central nervous system. Therefore, there is a need for new treatment methods that maximize TMZ delivery to and efficacy at the tumor site. Self-assembling peptides are a unique class …

A Single Bout Of Vigorous Intensity Exercise Enhances The Efficacy Of Rituximab Against Human Chronic Lymphocytic Leukaemia B-Cells Ex Vivo, Harrison D. Collier-Bain, Annabelle Emery, Adam J. Causer, Frankie F. Brown, Rebecca Oliver, David Dutton, Josephine Crowe, Daniel Augustine, John Graby, Shoji Leach, Rachel Eddy, Daniela Rothschild-Rodriguez, Juliet C. Gray, Mark S. Cragg, Kirstie L. Cleary, Sally Moore, James Murray, James E. Turner, John P. Campbell

Research outputs 2022 to 2026

Chronic lymphocytic leukaemia (CLL) is characterised by the clonal proliferation and accumulation of mature B-cells and is often treated with rituximab, an anti-CD20 monoclonal antibody immunotherapy. Rituximab often fails to induce stringent disease eradication, due in part to failure of antibody-dependent cellular cytotoxicity (ADCC) which relies on natural killer (NK)-cells binding to rituximab-bound CD20 on B-cells. CLL cells are diffusely spread across lymphoid and other bodily tissues, and ADCC resistance in survival niches may be due to several factors including low NK-cell frequency and a suppressive stromal environment that promotes CLL cell survival. It is well established that exercise bouts …

Low Absolute Risk Of Thrombotic And Cardiovascular Events In Outpatient Pregnant Women With Covid-19, Behnood Bikdeli, Darsiya Krishnathasan, Candrika Khairani, Antoine Bejjani, Julia Davies, Nicole Porio, Anthony Tristani, Andre Armero, Ali Assi, Victor Nauffal, Umberto Campia, Zaid Almarzooq, Eric Wei, Marcos Ortiz-Rios, Valeria Zuluaga-Sánchez, Aditya Achanta, Sirus Jesudasen, Bruce Tiu, Geno Merli, Orly Leiva, John Fanikos, Elvira Grandone, Aditya Sharma, Samantha Rizzo, Mariana Pfeferman, Ruth Morrison, Alec Vishnevsky, Judith Hsia, Mark Nehler, James Welker, Marc Bonaca, Brett Carroll, Samuel Goldhaber, Zhou Lan, Gregory Piazza

Division of Cardiology Faculty Papers

INTRODUCTION: Pregnancy may contribute to an excess risk of thrombotic or cardiovascular events. COVID-19 increases the risk of these events, although the risk is relatively limited among outpatients. We sought to determine whether outpatient pregnant women with COVID-19 are at a high risk for cardiovascular or thrombotic events.

MATERIALS & METHODS: We analyzed pregnant outpatients with COVID-19 from the multicenter CORONA-VTE-Network registry. The main study outcomes were a composite of adjudicated venous or arterial thrombotic events, and a composite of adjudicated cardiovascular events. Events were assessed 90 days after the COVID-19 diagnosis and reported for non-pregnant women ≤45 years, and …

Identifying Barriers To Healthcare Access And Utilization Experienced By Lgbtq+ Adults With Chronic Diseases Through The Lens Of The Social Ecological Model, Devin Mottier

Capstone Experience: Master of Public Health

The purpose of this literature review is to comprehensively examine and synthesize existing research on present barriers to health access and utilization that contribute to the disparities in chronic disease prevalence within the adult LGBTQ+ population. In the context of this review, the social-ecological model (SEM) was used to describe the nuanced and multifaceted nature of healthcare access and utilization. This literature review was based upon the following question: ‘Using the social-ecological model, what are the barriers to health access and utilization that contribute to high rates of chronic disease in LGBTQ+ adults?’ Outcome measures of interest included the following …

One Year Follow Up Of A Cross-Sectional Study Of Hookworm Infection And Response To Deworming In Beposo, Ghana, Taylor Clarkson

Capstone Experience: Master of Public Health

Hookworms are soil-transmitted helminths that infect over 500 million people worldwide, primarily those in low-income countries. Infection with hookworm can cause anemia, malnutrition, and stunted physical and cognitive development. Deworming campaigns have attempted to combat hookworm infections in endemic areas for decades. However, there is growing variability in the effectiveness of deworming drugs, and post-treatment reinfections are abundant. There are significant gaps in our understanding of critical host-parasite factors that mediate hookworm infection, reinfection, and response to deworming treatment in endemic communities. A five-year prospective study was undertaken to better understand drivers of hookworm infection in rural Ghana and thus …

Evaluating The Association Of Influenza Vaccination On Long-Term Covid-19 Symptoms In U.S. Adults, Ratnakar Pingili

Capstone Experience: Master of Public Health

Objective. To evaluate the association of influenza vaccination in the past 12 months with Long COVID effects and clinical and sociodemographic factors.

Methods. Cross-sectional study with data from the 2022 Behavioral Risk Factor Surveillance System (BRFSS), covering 415,132 non-institutionalized U.S. adults with a confirmed COVID-19 diagnosis and influenza vaccination reported within the last 12 months. Logistic regression was conducted between influenza vaccination (exposure) and Long COVID (outcome), controlling for demographic variables, pre-existing health conditions, and socioeconomic status.

Results. Of 120,603 participants, 21.89% reported Long COVID symptoms and 42.04% had received an influenza vaccine. Findings indicate a statistically significant 13% reduction …

Exploring Binding Pockets In The Conformational States Of The Sars-Cov-2 Spike Trimers For The Screening Of Allosteric Inhibitors Using Molecular Simulations And Ensemble-Based Ligand Docking, Grace Gupta, Gennady M. Verkhivker

Mathematics, Physics, and Computer Science Faculty Articles and Research

Understanding mechanisms of allosteric regulation remains elusive for the SARS-CoV-2 spike protein, despite the increasing interest and effort in discovering allosteric inhibitors of the viral activity and interactions with the host receptor ACE2. The challenges of discovering allosteric modulators of the SARS-CoV-2 spike proteins are associated with the diversity of cryptic allosteric sites and complex molecular mechanisms that can be employed by allosteric ligands, including the alteration of the conformational equilibrium of spike protein and preferential stabilization of specific functional states. In the current study, we combine conformational dynamics analysis of distinct forms of the full-length spike protein trimers and …

Antihypertensive Medications And Risk Of Melanoma And Keratinocyte Carcinomas: A Systematic Review And Meta-Analysis, Olivia G Cohen, Matthew Taylor, Cassandra Mohr, Kevin T Nead, Candice L Hinkston, Sharon H Giordano, Sinead M Langan, David J Margolis, Mackenzie R Wehner

Faculty, Staff and Student Publications

Some antihypertensive medications are photosensitizing. The implications for skin cancer risk remain unclear because results from prior studies are inconsistent and as new evidence is published. We performed a systematic review and meta-analysis to evaluate the association between antihypertensives and common skin cancers (cutaneous squamous cell carcinoma, basal cell carcinoma, and melanoma) and to evaluate dose-response relationships. Forty-four articles met inclusion criteria, and 42 could be meta analyzed. Increased risks were seen for basal cell carcinoma with calcium channel blockers (relative risk [RR] = 1.17, 95% confidence interval [CI] = 1.11-1.22), diuretics (RR = 1.06, 95% CI = 1.03-1.10), and …

Maternal Diabetes And Intrapartum Fetal Electrocardiogram, Beth A Plunkett, Steven J Weiner, George R Saade, Michael A Belfort, Sean C Blackwell, John M Thorp, Alan T N Tita, Russell S Miller, David S Mckenna, Edward K S Chien, Dwight J Rouse, Yasser Y El-Sayed, Yoram Sorokin, Steve N Caritis, Eunice Kennedy Shriver National Institute Of Child Health And Human Development Maternal-Fetal Medicine Units (Mfmu) Network

Faculty, Staff and Student Publications

Objective:

Fetal electrocardiogram (ECG) ST-changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST-changes by maternal diabetic status and stage of labor.

Methods:

Secondary analysis of a multi-centered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST-changes by stage of labor. ECG tracings were categorized into mutually exclusive groups (ST-depression, ST-elevation without ST-depression or no ST-changes). We compared participants with pre-gestational diabetes mellitus (DM), gestational DM (GDM), and no …

Light Scattering By Vitreous Of Humans With Vision Degrading Myodesopsia From Floaters, Alba M Paniagua-Diaz, Justin H Nguyen, Pablo Artal, Wei Gui, J Sebag

Faculty, Staff and Student Publications

PURPOSE: Vision-degrading myodesopsia (VDM) from vitreous floaters significantly degrades vision and impacts visual quality of life (VQOL), but the relationship to light scattering is poorly understood. This study compared in vitro measures of light scatter and transmission in surgically excised human vitreous to preoperative indexes of vitreous structure, visual function, and VQOL.

METHODS: Pure vitreous collected during vitrectomy from 8 patients with VDM had wide-angle straylight measurements and dark-field imaging, performed within 36 hours of vitrectomy. Preoperative VQOL assessment with VFQ-25, contrast sensitivity (CS) measurements with Freiburg acuity contrast testing, and quantitative ultrasonography were compared to light scattering and transmission …

Sars-Cov-2 Viral Load In The Nasopharynx At Time Of First Infection Among Unvaccinated Individuals: A Secondary Cross-Protocol Analysis Of 4 Randomized Trials, Leigh H Fisher, Jia Jin Kee, Albert Liu, Claudia M Espinosa, April K Randhawa, James Ludwig, Craig A Magaret, Samuel T Robinson, Peter B Gilbert, Ollivier Hyrien, James G Kublin, Nadine Rouphael, Ann R Falsey, Magdalena E Sobieszczyk, Hana M El Sahly, Beatriz Grinsztejn, Glenda E Gray, Karen L Kotloff, Cynthia L Gay, Brett Leav, Ian Hirsch, Frank Struyf, Lisa M Dunkle, Kathleen M Neuzil, Lawrence Corey, Yunda Huang, Paul A Goepfert, Stephen R Walsh, Lindsey R Baden, Holly Janes, Covid-19 Prevention Network (Covpn)

Faculty, Staff and Students Publications

IMPORTANCE: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity.

OBJECTIVE: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease.

DESIGN, SETTING, AND PARTICIPANTS: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline …

Piezo1 Regulates Meningeal Lymphatic Vessel Drainage And Alleviates Excessive Csf Accumulation, Dongwon Choi, Eunkyung Park, Joshua Choi, Renhao Lu, Jin Suh Yu, Chiyoon Kim, Luping Zhao, James Yu, Brandon Nakashima, Sunju Lee, Dhruv Singhal, Joshua P Scallan, Bin Zhou, Chester J Koh, Esak Lee, Young-Kwon Hong

Faculty, Staff and Students Publications

Piezo1 regulates multiple aspects of the vascular system by converting mechanical signals generated by fluid flow into biological processes. Here, we find that Piezo1 is necessary for the proper development and function of meningeal lymphatic vessels and that activating Piezo1 through transgenic overexpression or treatment with the chemical agonist Yoda1 is sufficient to increase cerebrospinal fluid (CSF) outflow by improving lymphatic absorption and transport. The abnormal accumulation of CSF, which often leads to hydrocephalus and ventriculomegaly, currently lacks effective treatments. We discovered that meningeal lymphatics in mouse models of Down syndrome were incompletely developed and abnormally formed. Selective overexpression of …

Multimodal Neurologic Monitoring In Patients Undergoing Extracorporeal Membrane Oxygenation, Khwaja Siddiqui, Muhammad U Hafeez, Ali Ahmad, Syed O Kazmi, Subhasis Chatterjee, Eric Bershad, Mohammad Hirzallah, Chethan Rao, Rahul Damani

Faculty, Staff and Students Publications

Introduction Extracorporeal membrane oxygenation (ECMO) is associated with a high rate of neurologic complications. Multimodal neurologic monitoring (MNM) has the potential for early detection and intervention. We examined the safety and feasibility of noninvasive MNM during ECMO. We hypothesized that survivors and non-survivors would have meaningful differences in transcranial Doppler (TCD) sonography and electroencephalographic (EEG) characteristics, which we aimed to identify. We also investigated adverse neurologic events and attempted to identify differences in EEG and TCD characteristics among patients based on the type of ECMO and the occurrence of these events. Material and methods We performed an observational study on …

Tenapanor As Therapy For Hyperphosphatemia In Maintenance Dialysis Patients: Results From The Optimize Study, Stuart M Sprague, Daniel E Weiner, David P Tietjen, Pablo E Pergola, Steven Fishbane, Geoffrey A Block, Arnold L Silva, Stephen Z Fadem, Robert I Lynn, George Fadda, Lynae Pagliaro, Suling Zhao, Susan Edelstein, David M Spiegel, David P Rosenbaum

Faculty, Staff and Students Publications

KEY POINTS: Tenapanor, a first-in-class local inhibitor of sodium/hydrogen exchanger isoform 3, acts as a phosphate absorption inhibitor by decreasing paracellular phosphate absorption. Tenapanor alone or with phosphate binders achieved

BACKGROUND: OPTIMIZE was a randomized, open-label study evaluating different tenapanor initiation methods. OPTIMIZE evaluated tenapanor alone and in combination with phosphate binders (PBs) to achieve target serum phosphate (P) ≤5.5 mg/dl.

METHODS: Patients with inadequately controlled P receiving maintenance dialysis from 42 US locations who were taking PBs with baseline

RESULTS: By part A end point, 34.4% (

CONCLUSIONS: Tenapanor as monotherapy or in combination with PBs effectively lowered P …

Jak2v617f Reversible Activation Shows Its Essential Requirement In Myeloproliferative Neoplasms, Andrew J Dunbar, Robert L Bowman, Young C Park, Kavi O'Connor, Franco Izzo, Robert M Myers, Abdul Karzai, Zachary Zaroogian, Won Jun Kim, Inés Fernández-Maestre, Michael R Waarts, Abbas Nazir, Wenbin Xiao, Tamara Codilupi, Max Brodsky, Mirko Farina, Louise Cai, Sheng F Cai, Benjamin Wang, Wenbin An, Julie L Yang, Shoron Mowla, Shira E Eisman, Amritha Varshini Hanasoge Somasundara, Jacob L Glass, Tanmay Mishra, Remie Houston, Emily Guzzardi, Anthony R Martinez Benitez, Aaron D Viny, Richard P Koche, Sara C Meyer, Dan A Landau, Ross L Levine

Faculty, Staff and Student Publications

Gain-of-function mutations activating JAK/STAT signaling are seen in the majority of patients with myeloproliferative neoplasms (MPN), most commonly JAK2V617F. Although clinically approved JAK inhibitors improve symptoms and outcomes in MPNs, remissions are rare, and mutant allele burden does not substantively change with chronic therapy. We hypothesized this is due to limitations of current JAK inhibitors to potently and specifically abrogate mutant JAK2 signaling. We therefore developed a conditionally inducible mouse model allowing for sequential activation, and then inactivation, of Jak2V617F from its endogenous locus using a combined Dre-rox/Cre-lox dual-recombinase system. Jak2V617F deletion abrogates MPN features, induces depletion of mutant-specific hematopoietic …