Medicine and Health Sciences Commons^™

Klf4 Enhances Transplantation-Induced Hematopoiesis By Inhibiting Tlrs And Noncanonical Nfκb Signaling At A Steady State, Chun Shik Park, Cory S Bridges, Andrew H Lewis, Taylor J Chen, Saptarsi Shai, Wa Du, Monica Puppi, Barry Zorman, Sumazin Pavel, H Daniel Lacorazza

Faculty, Staff and Students Publications

The transcription factor Krüppel-like factor 4 (KLF4) acts as a transcriptional activator and repressor. KLF4 plays a role in various cellular processes, including the dedifferentiation of somatic cells into induced pluripotent stem cells. Although it has been shown to enhance self-renewal in embryonic and leukemia stem cells, its role in adult hematopoietic stem cells (HSCs) remains underexplored. We demonstrate that conditional deletion of the Klf4 gene in hematopoietic cells led to an increased frequency of immunophenotypic HSCs in the bone marrow, along with a normal distribution of lymphoid and myeloid progenitor cells. Noncompetitive bone marrow transplants showed normal engraftment and …

Words Matter: Destigmatizing The Language Of Medicine Through Research, Training, And Future Directions For Emergency Medicine, Natalie Strokes, Richard Sapp, Meta Carroll, Elizabeth Maxwell Hovis, Mary Mclean, Shannon Markus, Aaryn Hammond, Rosemarie Diaz, Ryan E Tsuchida, Marcia Perry, Edgardo Ordonez

Faculty, Staff and Students Publications

Background: In emergency medicine (EM), language choice significantly impacts patient care and can potentially cause harm, dehumanize patients, and introduce bias. Stigmatizing language in medical settings can affect patient dignity, trust, and outcomes. Despite its importance, there is limited education on avoiding stigmatizing language in EM. This concept paper addresses the need to raise awareness and develop strategies for use of inclusive language in the emergency department (ED).

Methods: A didactic session titled "Words Matter: Destigmatizing the Language of Medicine" was developed and presented at the 2024 Society for Academic Emergency Medicine (SAEM) Annual Meeting. The session involved a collaborative …

Clinical Management And Therapeutic Optimization Of Patients With Heart Failure With Reduced Ejection Fraction And Low Blood Pressure. A Clinical Consensus Statement Of The Heart Failure Association (Hfa) Of The Esc, Hadi Skouri, Nicolas Girerd, Luca Monzo, Mark C Petrie, Michael Böhm, Marianna Adamo, Wilfried Mullens, Gianluigi Savarese, Mehmet Birhan Yilmaz, Offer Amir, Antoni Bayes-Genis, Biykem Bozkurt, Javed Butler, Ovidiu Chioncel, Alexandre Mebazaa, Jose L Merino, Brenda Moura, Piotr Ponikowski, Petar Seferovic, Giuseppe M C Rosano, Marco Metra

Faculty, Staff and Students Publications

Despite major advancements in heart failure (HF) management and guideline recommendations over the past two decades, real-world evidence highlights suboptimal implementation of guideline-directed medical therapy (GDMT) for HF with reduced ejection fraction (HFrEF). Low blood pressure (BP) is common in HFrEF patients and represents a major perceived barrier to implementing life-saving treatments in clinical practice, as physicians are often concerned about symptomatic hypotension and its consequences. Although low BP can be seen in those hospitalized with signs of shock, the most common scenario involves non-severe, asymptomatic hypotension in patients receiving foundational therapy for HFrEF, where premature down-titration or discontinuation of …

Guideline-Directed Medical Therapy And Outcomes In The Ischemia Trial, David J Maron, Jonathan D Newman, Rebecca Anthopolos, Ying Lu, Susanna Stevens, William E Boden, Kreton Mavromatis, Jason Linefsky, Rajesh G Nair, Olga Bockeria, Gilbert Gosselin, Gian P Perna, Elena Demchenko, David Foo, Michael D Shapiro, Mary Ann Champagne, Christie Ballantyne, Peter Mccullough, Jose Luis Lopez-Sendon, Frank Rockhold, Frank Harrell, Yves Rosenberg, Gregg W Stone, Sripal Bangalore, Harmony R Reynolds, John A Spertus, Judith S Hochman

Faculty, Staff and Students Publications

Background: Guideline-directed medical therapy (GDMT) with multiple risk factor goals is recommended for patients with chronic coronary disease (CCD), yet achieving all GDMT goals is uncommon. The relative importance of these goals and timing of their attainment on cardiovascular events is uncertain.

Objectives: This study aims to describe the relationship between achieving specific GDMT goals, when they are achieved, and clinical outcomes.

Methods: This was an observational study of participants with CCD in the ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trial. The primary outcome was cardiovascular (CV) death or myocardial infarction (MI). GDMT goals …

Familial Chylomicronemia Syndrome And Treatments To Target Hepatic Apoc3 Mrna, Eliot A Brinton, Robert H Eckel, Daniel Gaudet, Christie M Ballantyne, Brenda F Baker, Henry N Ginsberg, Joseph L Witztum

Faculty, Staff and Students Publications

Familial chylomicronemia syndrome (FCS) is a rare, recessive monogenic disorder characterized by severely elevated plasma triglyceride (TG) levels due to absent or markedly impaired lipoprotein lipase activity, leading to a greatly increased risk of acute pancreatitis. Naturally occurring very low levels of apoC-III are associated with low TG levels; thus, apoC-III is a target for TG lowering, and therapies have been developed to reduce apoC-III. Strategies to inhibit hepatic apoC-III synthesis include antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs). In the last decade, technologies have been developed to enhance hepatic delivery of these potential therapeutic agents by conjugation of …

Demographic And Clinical Risk Factors Of Developing Clinically Recognized Varicose Veins In Older Adults, Yejin Mok, Shoshana H Ballew, Anna Kucharska-Newton, Kenneth Butler, Peter Henke, Pamela L Lutsey, Maya Salameh, Ron C Hoogeveen, Christie M Ballantyne, Elizabeth Selvin, Kunihiro Matsushita

Faculty, Staff and Students Publications

INTRODUCTION: Varicose veins are common in older adults and are associated with adverse clinical outcomes such as deep venous thrombosis. Established risk factors for varicose veins include female sex, height, and obesity, but other risk factors are relatively uncharacterized.

METHODS: This was a prospective cohort analysis of 6,241 participants aged 66-70 years from the Atherosclerosis Risk in Communities (ARIC) Study. Incident varicose veins were defined as two outpatient encounters (at least a week apart) or inpatient diagnoses through 2018 with ICD-9 code 454 or ICD-10 code I83. Participants with a history of clinically recognized varicose veins at baseline were excluded. …

New Onset Refractory Status Epilepticus: Long-Term Outcomes Beyond Seizures, Poul H Espino, Krista Eschbach, Leah J Blank, Mackenzie C Cervenka, Eyal Muscal, Raquel Farias-Moeller, Emily J Gilmore, Margaret T Gopaul, Hiba A Haider, Aurelie Hanin, Lawrence J Hirsch, Marissa A Kellogg, Gerhard Kluger, Soon-Tae Lee, Alexandria E Melendez-Zaidi, Vincent Navarro, Audrey C Oliger, Elena Pasini, Gitta Reuner, Cynthia M Sharpe, Zubeda B Sheikh, Leon Steigleder, Claude Steriade, Coral M Stredny, Adam Strzelczyk, Olga Taraschenko, Andreas Van Baalen, Sarah A Vinette, Ronny Wickström, Nora W Wong, Jiyeoun Yoo, Teneille E Gofton

Faculty, Staff and Students Publications

We propose and prioritize important outcome domains that should be considered for future research investigating long-term outcomes (LTO) after new onset refractory status epilepticus (NORSE). The study was led by the international NORSE Institute LTO Working Group. First, literature describing the LTO of NORSE survivors was identified using a PubMed search and summarized to identify knowledge gaps. Subsequently, a consensus-building process was performed to prioritize and rank important LTO domains for further research. The prioritization of LTO domains was qualitative, enabling the expert panel to generate ideas, share opinions, and provide reasons for the rankings. A second round took place …

Comparing Rituximab And Cyclophosphamide In Induction Therapy For Childhood-Onset Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: An Archive Registry Cohort Study, Samuel J Gagne, Vidya Sivaraman, Else S Bosman, Brett Klamer, Kimberly A Morishita, Adam Huber, Alvaro Orjuela, Barbara Eberhard, Charlotte Myrup, Dana Gerstbacher, Dirk Foell, Eslam Al-Abadi, Flora Mcerlane, Kathryn Cook, Linda Wagner-Weiner, Melissa Elder, L Nandini Moorthy, Paul Dancey, Rae Yeung, Raju Khubchandani, Samundeeswari Deepak, Sirirat Charuvanij, Stacey Tarvin, Susan Shenoi, Tamara Tanner, Kelly Brown, David A Cabral, Archive Investigators Network Within The Pedvas Initiative

Faculty, Staff and Students Publications

Objective: Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are chronic life-threatening vasculitides requiring substantial immunotherapy. Adult trials identified rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction of GPA and MPA. Disease rarity has limited feasibility of similar trials with pediatric patients. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for patients with childhood GPA and MPA through registry-based comparative evaluation.

Methods: From A Registry of Childhood Vasculitis, we identified patients with GPA and MPA who received induction with RTX or CYC. Pediatric Vasculitis Activity Score (PVAS) and Pediatric Vasculitis Damage Index …

Complete, Sustained Resolution Of Pain With Pseudoarthrectomy For Bertolotti Syndrome: A Case Report, Emanuel Narcis Husu, Nirav Parekh, Jeremy I Simon

Faculty, Staff and Students Publications

Background: Bertolotti syndrome, characterized by lumbar pain due to a lumbosacral (LS) transitional vertebra, is a known but still controversial and overlooked pain generator despite an explosion of information on the condition in the last decade. Current management includes plain radiography, advanced imaging, minimally invasive interventions, and LS fusion.

Case report: We present a unique case of a middle-aged man with Castellvi IIa Bertolotti syndrome consisting of a unilateral enlarged, dysplastic L5 transverse process forming a pseudoarticulation (PA) with the ilium and normal anatomy contralaterally. He was diagnosed on a plain radiograph and following a diagnostic injection of the PA, …

Correction: Citation Issues In The American Academy Of Pediatrics Policy Statement On Transgender And Gender-Diverse Children And Adolescents (Rafferty, 2018), Kathleen Mcdeavitt

Faculty, Staff and Students Publications

No abstract provided.

Psychometric Properties Of The Postpartum Thoughts And Behaviors Checklist, Catherine E Rast, Tracey Dibbs, Caitlin M Pinciotti, Nisha Jagannathan, Jonathan S Abramowitz, Mary C Kimmel, Rashelle Musci, Gerald Nestadt, Paul Nestadt, Lauren M Osborne, Jack Samuels, Eric A Storch

Faculty, Staff and Students Publications

Obsessive compulsive disorder (OCD) has an increased prevalence throughout pregnancy and in the postpartum period relative to non-peripartum periods. While some obsessive-compulsive symptoms in this period present in the same manner to those in non-postpartum OCD, others are more specific to the postpartum period (e.g., obsessions related to sudden infant death syndrome [SIDS]). However, there are few validated scales assessing obsessive-compulsive symptoms during the postpartum period. This study examined the psychometric properties of the Postpartum Thoughts and Behaviors Checklist (PTBC), a semi-structured interview of intrusive thoughts and repetitive, neutralizing behaviors developed to address this gap. In a sample of 257 …

Obesity And Outcomes After Elective Thoracoabdominal Aortic Aneurysm Repair, Sanford Zeigler, Kyle W Blackburn, Ahmad Tabatabaeishoorijeh, Veronica A Glover, Susan Y Green, Marc R Moon, Scott A Lemaire, Joseph S Coselli

Faculty, Staff and Students Publications

Objective: Obesity can complicate surgical repair, but its relationship to outcomes after open thoracoabdominal aortic aneurysm (TAAA) repair remains uncertain. Therefore, we examined whether obesity is associated with greater operative risk after elective TAAA repair.

Methods: We retrospectively evaluated data from 2517 open, elective, single-practice TAAA repairs (from 1986 to 2023) and compared patients without obesity or underweight (body mass index [BMI] 18.6-29.9; n = 1977) with patients with obesity (BMI ≥30; n = 540 [21.5%]). Multivariable logistic regression modeling identified predictors of operative mortality in patients with obesity. We created propensity-matched cohorts (n = 540 pairs) and compared their …

Imaging Considerations For Patients With Chronic Low Back Pain: A Case Report, Kennedy Kirkpatrick, Jay D Shah, Krishna Shah

Faculty, Staff and Students Publications

Background: The incidence of low back pain, a leading cause of global disability, has increased significantly. Spinal cord stimulation (SCS) is US Food and Drug Administration-approved for treating intractable back pain, particularly in patients with prior surgical interventions.

Case report: A 43-year-old woman was referred for SCS implantation following 3 prior lumbar spinal surgeries with continued, right-sided radicular back pain. Additional diagnostic imaging was obtained, and a magnetic resonance imaging with and without contrast revealed a recurrent disc despite 3 lumbar microdiscectomies. The patient was then referred for lumbar spinal fusion, specifically anterior lumbar interbody fusion.

Conclusions: This case underscores …

Defining The Transcriptional Basis Of Organ-Specific Endothelial Cell Specialization, Joshua D. Wythe, James F. Martin

Faculty, Staff and Students Publications

Blood vessels feature extensive phenotypic and functional differences that help them meet the unique nutritive and energetic demands of the specific organ they reside in. Profiling the chromatin and transcriptional landscape of several organs identified novel gene regulatory networks that determine endothelial cell organ specialization in mammals.

Career Choices For Graduates Of Combined Medicine-Pediatrics Residency Programs: A Multi-Year Survey, Anoop Agrawal, Michael Aronica, Michael Kisielewski, Benjamin Doolittle

Faculty, Staff and Students Publications

Background: Combined medicine-pediatrics training was formally established in 1967 by the American Board of Pediatrics and the American Board of Internal Medicine. More than 8000 physicians have completed dual training. Their career choices are not well-described.

Objective: To describe career choices among graduates of combined medicine-pediatrics training programs.

Methods: Nationally representative research surveys conducted each winter from 2017 to 2023 of combined medicine-pediatrics (Med-Peds) residency program directors (PDs), whose programs were (1) of continued accreditation status with the Accreditation Council for Graduate Medical Education (N = 77 to 80) and (2) members of the Medicine Pediatrics Program Directors Association. One …

Foamy Monocytes And Atherogenesis In Mice With Combined Hyperlipidemia And Effects Of Antisense Knockdown Of Apociii, Xueying Peng, Zeqin Lian, Veronica O'Brien, Jing Xiao, Benjamin A Litchfield, Xiao-Yuan Dai Perrard, Lu Xu, Jing Ni, Aparna Mukherjee, Timothy Simmons, Henry Dong, Adam E Mullick, Rosanne Crooke, Henry J Pownall, Scott I Simon, Christie M Ballantyne, Huaizhu Wu

Faculty, Staff and Students Publications

Hypertriglyceridemia (HTG), particularly in combined hyperlipidemia, increases risk for atherosclerotic cardiovascular disease, but the underlying mechanisms remain incompletely understood. We sought to determine contributions of circulating monocytes to atherosclerosis associated with HTG in combined hyperlipidemia, created by transgenic expression of human apoCIII in Ldlr−/− mice (Ldlr−/−ApoCIIItg) fed Western high-fat diet (WD). Tissue culture with THP-1 and primary human monocytes was used to examine effects of triglyceride (TG)-rich lipoproteins on monocytes. Ldlr−/−ApoCIIItg mice were also treated with apoCIII antisense oligonucleotide (ASO) and examined for foamy monocytes and atherosclerosis. Compared to Ldlr−/− mice, Ldlr−/−ApoCIIItg mice fed …

The Association Between County-Level Social Determinants Of Health And Cardio-Kidney-Metabolic Disease Attributed All-Cause Mortality In The Us: A Cross Sectional Analysis, Antoinette Cotton, Pedro Rvo Salerno, Salil V Deo, Salim S Virani, Khurram Nasir, Ian Neeland, Sanjay Rajagopalan, Naveed Sattar, Sadeer Al-Kindi, Yakov E Elgudin

Faculty, Staff and Students Publications

Background: The American Heart Association recently defined cardio-kidney-metabolic (CKM) syndrome as the intersection between metabolic, renal, and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality in the US is essential for developing targeted public interventions.

Methods: We analyzed state-level and county-level CKM-associated all-cause mortality data (2010-2019) from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER). Median and interquartile (IQR) age-adjusted mortality rates (aaMR) per 100,000 were reported and linked with a multi-component metric for social deprivation: the Social Deprivation Index (SDI: range 0 - 100) grouped as: I: 0 - 25, II: 26 - 50, III: 51 …

Primary Prevention Of Cardiovascular Disease In Asia: Challenges: A Narrative Review, Mayank Dalakoti, Norman H Y Lin, Jonathan Yap, Aaysha Cader, Prajapati Dipanker, Derek Lee, Raja Ezman Raja Shariff, Lucky Cuenza, Satoshi Honda, Vorn Malis, Haowen Jiang, Anish Hirachan, Misato Chimura, Tee Joo Yeo, Khung Keong Yeo, Jack Wei Chieh Tan, Jasper Tromp, Poay Huan Loh, Nicholas W S Chew, Scott Wong, Ching-Hui Sia, Benjamin Y Q Tan, Sofian Johar, Gregory Y H Lip, Eugene Yang, Salim S Virani, Steven Hageman, Hueiming Liu, Emanuele Di Angelantonio, Prabhakaran Dorairaj, Angela S Koh, Calvin Chin, Wael Al Mahmeed, Mark Y Chan, Roger Foo

Faculty, Staff and Students Publications

Importance: Asia is home to 60% of the world's population, including the world's 2 most populous countries, India (1.1B) and China (1.2B). With cardiovascular disease burden and mortality increasing, the role of preventive cardiology is increasingly important.

Observations: The challenges in addressing the cardiovascular disease burden in Asia include unique cardiometabolic features of the different populations, heterogeneity of risk factors among Asian countries, differing levels of health literacy and socioeconomic status, suboptimal infrastructure to support preventive care especially in the primary care sector, high out-of-pocket costs, and environmental pollution.

Conclusions: Asia is a large continent that comprises diverse populations with …

Telehealth Is Effective In The Evaluation Of Individuals With Undiagnosed Rare Disorders: An Undiagnosed Diseases Network Study, Queenie K-G Tan, Allyn Mcconkie-Rosell, Rachel Mahoney, Rebecca C Spillmann, Kelly Schoch, Sirisak Chanprasert, Maria T Acosta, Camilo Toro, Jill A Rosenfeld, James P Orengo, Daryl A Scott, Jorge L Granadillo, Kathleen Sisco, Daniel J Wegner, Mustafa Tekin, Stephanie Bivona, Léshon Peart, Lance Rodan, Devon Bonner, Matthew T Wheeler, Jonathan A Bernstein, Maura Ruzhnikov, Undiagnosed Diseases Network, David R Adams, Fuki M Hisama, Vandana Shashi

Faculty, Staff and Students Publications

Patients with undiagnosed and/or rare disorders frequently manifest dysmorphic and neurological features. There is a lack of information on the effectiveness of telehealth in the evaluation of these disorders. We thus compared an unassisted virtual physical examination (PE) with an in-person PE in undiagnosed individuals and also assessed participant telehealth satisfaction. Twenty-six individuals enrolled in the Undiagnosed Diseases Network study underwent an in-home synchronous virtual PE, and a subsequent in-person PE, by the same clinician. The participants completed surveys on telehealth usability and provider empathy. On PE, general appearance and craniofacial features showed near perfect agreement (κ = 0.81-1.00) between …

Effects Of Smoking Behavior On Lung Metastasis In The All Of Us Research Program, Vikram R Shaw, Jinyoung Byun, Younghun Han, Christopher I Amos

Faculty, Staff and Students Publications

Smoking may be associated with an increased risk of lung metastasis in cancers of non-lung origin. We leverage survey and electronic health record data from the diverse All of Us Research Program (AoURP) database to investigate whether smoking and smoking-related behaviors increase the risk of lung metastasis in non-lung primary cancers. The results suggest that cigarette use, measured by four continuous variables, does not increase the risk of lung metastasis in seven common cancer types but demonstrates a small significant effect in a cohort including all types of cancer in the database in both univariable and multivariable analyses. An increased …

The Burden Of Steatotic Liver Disease Before And During The Covid-19 Pandemic: Correspondence To Editorial On “Current Burden Of Steatotic Liver Disease And Fibrosis Among Adults In The United States, 2017–2023”, Donghee Kim, Pojsakorn Danpanichkul, Karn Wijarnpreecha, George Cholankeril, Rohit Loomba, Aijaz Ahmed

Faculty, Staff and Students Publications

No abstract provided.

Neurd Offers Automated Proofreading And Feature Extraction For Connectomics, Brendan Celii, Stelios Papadopoulos, Zhuokun Ding, Paul G Fahey, Eric Wang, Christos Papadopoulos, Alexander B Kunin, Saumil Patel, J Alexander Bae, Agnes L Bodor, Derrick Brittain, Joann Buchanan, Daniel J Bumbarger, Manuel A Castro, Erick Cobos, Sven Dorkenwald, Leila Elabbady, Akhilesh Halageri, Zhen Jia, Chris Jordan, Dan Kapner, Nico Kemnitz, Sam Kinn, Kisuk Lee, Kai Li, Ran Lu, Thomas Macrina, Gayathri Mahalingam, Eric Mitchell, Shanka Subhra Mondal, Shang Mu, Barak Nehoran, Sergiy Popovych, Casey M Schneider-Mizell, William Silversmith, Marc Takeno, Russel Torres, Nicholas L Turner, William Wong, Jingpeng Wu, Szi-Chieh Yu, Wenjing Yin, Daniel Xenes, Lindsey M Kitchell, Patricia K Rivlin, Victoria A Rose, Caitlyn A Bishop, Brock Wester, Emmanouil Froudarakis, Edgar Y Walker, Fabian Sinz, H Sebastian Seung, Forrest Collman, Nuno Maçarico Da Costa, R Clay Reid, Xaq Pitkow, Andreas S Tolias, Jacob Reimer

Faculty, Staff and Students Publications

We are in the era of millimetre-scale electron microscopy volumes collected at nanometre resolution1,2. Dense reconstruction of cellular compartments in these electron microscopy volumes has been enabled by recent advances in machine learning3–6. Automated segmentation methods produce exceptionally accurate reconstructions of cells, but post hoc proofreading is still required to generate large connectomes that are free of merge and split errors. The elaborate 3D meshes of neurons in these volumes contain detailed morphological information at multiple scales, from the diameter, shape and branching patterns of axons and dendrites, down to the fine-scale …

Postoperative Intraocular Lens Tilt From Preoperative Full Crystalline Lens Geometry Using Machine Learning, Eduardo Martinez-Enriquez, Gonzalo Velarde-Rodríguez, Nicolás Alejandre-Alba, Derick Ansah, Sindhu Kishore, Álvaro De La Peña, Ramya Natarajan, Pravin Vaddavalli, Yue Zhao, Joseph O Okudolo, Dylan B Mcbee, Ugur Celik, Mujdat Cetin, Jen-Li Dong, Yuli Lim, Li Wang, Douglas Donald Koch, Scott Macrae, Susana Marcos

Faculty, Staff and Students Publications

In cataract surgery, the opacified crystalline lens is replaced by an artificial intraocular lens (IOL), requiring precise preoperative selection of parameters to optimize postoperative visual quality. Three-dimensional customized eye models, which can be constructed using quantitative data from anterior segment optical coherence tomography, provide a robust platform for virtual surgery. These models enable simulations and predictions of the optical outcomes for specific patients and selected IOLs. A critical step in building these models is estimating the IOL's tilt and position preoperatively based on the available preoperative geometrical information (ocular parameters). In this study, we present a machine learning model that, …

Endothelial Micu1 Protects Against Vascular Inflammation And Atherosclerosis By Inhibiting Mitochondrial Calcium Uptake, Lu Sun, Ruixue Leng, Monan Liu, Meiming Su, Qingze He, Zhidan Zhang, Zhenghong Liu, Zhihua Wang, Hui Jiang, Li Wang, Shuai Guo, Yiming Xu, Yuqing Huo, Clint L Miller, Maciej Banach, Yu Huang, Paul C Evans, Jaroslav Pelisek, Giovanni G Camici, Bradford C Berk, Stefan Offermanns, Junbo Ge, Suowen Xu, Jianping Weng

Faculty, Staff and Students Publications

Mitochondrial dysfunction fuels vascular inflammation and atherosclerosis. Mitochondrial calcium uptake 1 (MICU1) maintains mitochondrial Ca2+ homeostasis. However, the role of MICU1 in vascular inflammation and atherosclerosis remains unknown. Here, we report that endothelial MICU1 prevents vascular inflammation and atherosclerosis by maintaining mitochondrial homeostasis. We observed that vascular inflammation was aggravated in endothelial cell–specific Micu1 knockout mice (Micu1ECKO) and attenuated in endothelial cell–specific Micu1 transgenic mice (Micu1ECTg). Furthermore, hypercholesterolemic Micu1ECKO mice also showed accelerated development of atherosclerosis, while Micu1ECTg mice were protected against atherosclerosis. Mechanistically, MICU1 depletion increased mitochondrial Ca2+ influx, thereby decreasing the expression …

Disease Activity Criteria Impact Dosing Interval Assignment In Neovascular Age-Related Macular Degeneration Trials, Marco A Zarbin, Christina Y Weng, Nikolas J S London, Adrian Hock Chuan Koh, Roberto Gallego-Pinazo, Varun Chaudhary, Audrey Souverain, Ivaylo Stoilov, Philippe Margaron

Faculty, Staff and Students Publications

No abstract provided.

Sialidase Fusion Protein Protects Against Influenza Infection In A Cigarette Smoke-Induced Model Of Copd, Cheng-Yen Chang, Dominique Armstrong, John M Knight, Trevor V Gale, Stephen Hawley, Max Wang, Nancy Chang, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

First- and secondhand smokers are at an increased risk for influenza virus (IFV)-related respiratory failure and death. Despite approved influenza antiviral treatments, there is an unmet need for treatments that can improve outcomes in populations at risk for respiratory failure, including tobacco users with Chronic Obstructive Pulmonary Disease (COPD). Here we show that the sialidase fusion protein, DAS181, reduced viral burden, mitigated inflammation, and attenuated lung function loss, consistent with broad-spectrum anti-influenza responses in a mouse model of COPD and IFV-A infection. Treatment with DAS181 reprogramed the sialic acid-binding immunoglobulin-like lectins (Siglecs) in alveolar macrophages, increased expression of phagocytic marker …

Intestinal Epithelial Serotonin As A Novel Target For Treating Disorders Of Gut-Brain Interaction And Mood, Lin Y Hung, Nuno D Alves, Andrew Del Colle, Ardesheer Talati, Sarah A Najjar, Virginie Bouchard, Virginie Gillet, Yan Tong, Zixing Huang, Kirsteen N Browning, Jialiang Hua, Ying Liu, James O Woodruff, Daniel Juarez, Melissa Medina, Jonathan Posner, Raquel Tonello, Nazli Yalcinkaya, Narek Israelyan, Roey Ringel, Letao Yang, Kam W Leong, Mu Yang, Ji Ying Sze, Tor Savidge, Jay Gingrich, Robert J Shulman, Michael D Gershon, Annie Ouellet, Larissa Takser, Mark S Ansorge, Kara Gross Margolis

Faculty, Staff and Students Publications

Background & aims: Mood disorders and disorders of gut-brain interaction (DGBI) are highly prevalent, commonly comorbid, and lack fully effective therapies. Although selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for these disorders, they may impart adverse effects, including anxiety, anhedonia, dysmotility, and, in children exposed in utero, an increased risk of cognitive, mood, and gastrointestinal disorders. SSRIs act systemically to block the serotonin reuptake transporter and enhance serotonergic signaling in the brain, intestinal epithelium, and enteric neurons. Yet, the compartments that mediate the therapeutic and adverse effects of SSRIs are unknown, as is whether gestational SSRI exposure directly …

Communicating Blood Test Results In Primary Care: A Mixed-Methods Systematic Review, Helen Nankervis, Alyson L Huntley, Penny Whiting, William Hamilton, Hardeep Singh, Sarah Dawson, Rachel O'Donnell, Jane Sprackman, Anna Ferguson Montague, Jessica Watson

Faculty, Staff and Students Publications

Background: Online records access, including test results, was rolled out as part of changes to the GP contract in England in 2023. Blood test result communication is important for patient-centred care, patient safety, and primary care workload. Evidence is needed to ensure that test results are communicated safely and efficiently to patients in primary care.

Aim: To summarise existing evidence for blood test result communication between primary care providers and their patients and carers.

Design and setting: A mixed-methods systematic review was undertaken.

Method: MEDLINE, Embase, PsycInfo (Ovid), CINAHL (EBSCOhost), and the Cochrane Library were searched from January 2013-September 2023. …

Sialidase Fusion Protein Protects Against Influenza Infection In A Cigarette Smoke-Induced Model Of Copd, Cheng-Yen Chang, Dominique Armstrong, John M Knight, Trevor V Gale, Stephen Hawley, Max Wang, Nancy Chang, David B Corry, Farrah Kheradmand

Faculty, Staff and Students Publications

First- and secondhand smokers are at an increased risk for influenza virus (IFV)-related respiratory failure and death. Despite approved influenza antiviral treatments, there is an unmet need for treatments that can improve outcomes in populations at risk for respiratory failure, including tobacco users with Chronic Obstructive Pulmonary Disease (COPD). Here we show that the sialidase fusion protein, DAS181, reduced viral burden, mitigated inflammation, and attenuated lung function loss, consistent with broad-spectrum anti-influenza responses in a mouse model of COPD and IFV-A infection. Treatment with DAS181 reprogramed the sialic acid-binding immunoglobulin-like lectins (Siglecs) in alveolar macrophages, increased expression of phagocytic marker …

Insights Into Protection Against Mycobacterium Tuberculosis Infection: Time To Officially Confirm Another Phenotype?, Todia P Setiabudiawan, Philip C Hill, Andrew R Dinardo, Reinout Van Crevel

Faculty, Staff and Students Publications

Immune correlates of protection against infection with Mycobacterium tuberculosis (Mtb) remain elusive. In this issue of the JCI, Dallmann-Sauer and authors demonstrate that lack of tuberculin skin test (TST) and interferon γ release assay (IGRA) conversion among people with HIV despite years-long Mtb exposure is associated with alveolar lymphocytosis, including specific poly-cytotoxic T cells, and M1-type alveolar macrophages with a stronger ex vivo response to the pathogen. Studies in these rare individuals, termed "TB resisters" and in tuberculosis household contacts who are repeatedly IGRA negative in the months after a specific exposure event (known as "early clearers") help elucidate manipulatable …