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Dementia Research In The Caribbean Hispanic Islands: Present Findings And Future Trends, Daisy Acosta, Jorge J Llibre-Guerra, Ivonne Z Jiménez-Velázquez, Juan J Llibre-Rodríguez

Open Access Publications

During the last decade, the Caribbean Hispanic islands experienced accelerated demographic aging, representing the fastest aging region within Latin America. Age-related non-communicable diseases, including dementia, are now reported at high prevalence. The Caribbean islands share similar genetic ancestry, culture, migration patterns, and risk profiles, providing a unique setting to understand dementia in the Caribbean-Hispanics. This perspective article aimed to describe the impact of dementia in the Caribbean, at a local and regional level and reflect on research strategies to address dementia. We report on 10/66 project findings, described research projects and regional plans for the region. According to our results, …

Sars-Cov-2 Viral Rna Shedding For More Than 87 Days In An Individual With An Impaired Cd8+ T Cell Response, Jackson S Turner, Aaron Day, Wafaa B Alsoussi, Zhuoming Liu, Jane A O'Halloran, Rachel M Presti, Bruce K Patterson, Sean P J Whelan, Ali H Ellebedy, Philip A Mudd

Open Access Publications

Prolonged shedding of viral RNA occurs in some individuals following SARS-CoV-2 infection. We perform comprehensive immunologic evaluation of one individual with prolonged shedding. The case subject recovered from severe COVID-19 and tested positive for SARS-CoV-2 viral RNA repeatedly as many as 87 days after the first positive test, 97 days after symptom onset. The subject did not have any associated rise in anti-Spike protein antibody titers or plasma neutralization activity, arguing against re-infection. This index subject exhibited a profoundly diminished circulating CD8+ T cell population and correspondingly low SARS-CoV-2-specific CD8+ T cell responses when compared with a cohort of other …

Nutrition-Related Symptoms In Adult Survivors Of Critical Illness Who Are Eating Orally: A Scoping Review Protocol., Louise Albrich, Lee Anne S. Chapple, Amelia Nock, Emma J. Ridley, Mary Hickson

School of Health Professions

OBJECTIVE: This review will explore and map the current literature on the nutritional impact of symptoms reported by adult survivors of critical illness who are eating orally after discharge from the intensive care unit (ICU). INTRODUCTION: Survivors of critical care often experience ICU-acquired weakness and poor functional recovery. It is plausible that nutrition interventions throughout their recovery could improve outcomes for these patients. Although a growing number of studies aim to explore the effect of nutrition delivered in the early phases of critical illness, this is also important post-ICU discharge, particularly in already nutritionally compromised patients presenting with muscle loss …

Burden Of Rare Deleterious Variants In Wnt Signaling Genes Among 511 Myelomeningocele Patients, Luke Hebert, Paul Hillman, Craig Baker, Michael Brown, Allison Ashley-Koch, James E Hixson, Alanna C Morrison, Hope Northrup, Kit Sing Au

Faculty, Staff and Student Publications

Genes in the noncanonical WNT signaling pathway controlling planar cell polarity have been linked to the neural tube defect myelomeningocele. We hypothesized that some genes in the WNT signaling network have a higher mutational burden in myelomeningocele subjects than in reference subjects in gnomAD. Exome sequencing data from 511 myelomeningocele subjects was obtained in-house and data from 29,940 ethnically matched subjects was provided by version 2 of the publicly available Genome Aggregation Database. To compare mutational burden, we collapsed rare deleterious variants across each of 523 human WNT signaling genes in case and reference populations. Ten WNT signaling genes were …

Covid-19 Sampling From The Middle Ear And Mastoid: A Case Report, George B Wanna, Zachary G Schwam, Vivian F Kaul, Maura K Cosetti, Enrique Perez, Peter Filip, Waleed Javaid, Avi Kandel, Alberto Paniz-Mondolfi, Satish Govindaraj, Eric M Genden

Faculty, Staff and Student Publications

No abstract provided.

Microbiotyping The Sinonasal Microbiome, Ahmed Bassiouni, Sathish Paramasivan, Arron Shiffer, Matthew R Dillon, Emily K Cope, Clare Cooksley, Mahnaz Ramezanpour, Sophia Moraitis, Mohammad Javed Ali, Benjamin S Bleier, Claudio Callejas, Marjolein E Cornet, Richard G Douglas, Daniel Dutra, Christos Georgalas, Richard J Harvey, Peter H Hwang, Amber U Luong, Rodney J Schlosser, Pongsakorn Tantilipikorn, Marc A Tewfik, Sarah Vreugde, Peter-John Wormald, J Gregory Caporaso, Alkis J Psaltis

Faculty, Staff and Student Publications

This study offers a novel description of the sinonasal microbiome, through an unsupervised machine learning approach combining dimensionality reduction and clustering. We apply our method to the International Sinonasal Microbiome Study (ISMS) dataset of 410 sinus swab samples. We propose three main sinonasal “microbiotypes” or “states”: the first is Corynebacterium-dominated, the second is Staphylococcus-dominated, and the third dominated by the other core genera of the sinonasal microbiome (Streptococcus, Haemophilus, Moraxella, and Pseudomonas). The prevalence of the three microbiotypes studied did not differ between healthy and diseased sinuses, but differences in their distribution were evident based …

An Ecological Momentary Assessment Of Self-Improved And Self-Evaluation Body Comparisons: Associations With College Women's Body Dissatisfaction And Exercise, Rachel I. Macintyre, Kristin E. Heron, Abby L. Braitman, Danielle Arigo

Psychology Faculty Publications

Upward body comparisons are prevalent among college women and associated with body dissatisfaction and disordered eating. However, less is known about distinguishing features of the comparisons themselves as they occur in daily life. The primary purpose of the present study was to examine whether two types of upward body comparisons previously studied experimentally (self-improvement and self-evaluation) are differentially associated with body- and exercise-related outcomes in real-life settings using ecological momentary assessment (EMA). Undergraduate women (N = 74) between 18-25 years (Mage = 20.4, SD = 1.63) completed five surveys on smartphones daily for seven days. EMA measures …

Somatic Symptoms And Binge Eating In Women's Daily Lives, Kelly A. Romano, Kristin E. Heron, Kathryn E. Smith, Ross D. Crosby, Scott G. Engel, Stephen A. Wonderlich, Raina D. Pang, Tyler B. Mason

Psychology Faculty Publications

Objective

The present study aimed to determine whether the momentary severity of women's somatic symptoms was concurrently and prospectively associated with their engagement in binge eating in naturalistic settings.

Method

Thirty women (M_age = 34.13, SD = 13.92) who had engaged in binge eating at least once over the month prior to study entry completed a 14-day ecological momentary assessment (EMA) protocol. During each of the 14 days, participants received five semi-random surveys via text message that assessed momentary somatic symptom severity (i.e., headaches, stomachaches/pain, chest/heart pain, faintness/dizziness, shortness of breath, fatigue) and disordered eating behaviors. Generalized estimating equations …

Transcriptional Insights Into Pathogenesis Of Cutaneous Systemic Sclerosis Using Pathway Driven Meta-Analysis Assisted By Machine Learning Methods, Xiao Xu, Meera Ramanujam, Sudha Visvanathan, Shervin Assassi, Zheng Liu, Li Li

Faculty, Staff and Student Publications

Pathophysiology of systemic sclerosis (SSc, Scleroderma), an autoimmune rheumatic disease, comprises of mechanisms that drive vasculopathy, inflammation and fibrosis. Understanding of the disease and associated clinical heterogeneity has advanced considerably in the past decade, highlighting the necessity of more specific targeted therapy. While many of the recent trials in SSc failed to meet the primary end points that predominantly relied on changes in modified Rodnan skin scores (MRSS), sub-group analysis, especially those focused on the basal skin transcriptomic data have provided insights into patient subsets that respond to therapies. These findings suggest that deeper understanding of the molecular changes in …

Dynamic Conformal Arcs For Lung Stereotactic Body Radiation Therapy: A Comparison With Volumetric-Modulated Arc Therapy., Rasmus Bokrantz, Minna Wedenberg, Peter Sandwall

Oncology Articles

This study constitutes a feasibility assessment of dynamic conformal arc (DCA) therapy as an alternative to volumetric-modulated arc therapy (VMAT) for stereotactic body radiation therapy (SBRT) of lung cancer. The rationale for DCA is lower geometric complexity and hence reduced risk for interplay errors induced by respiratory motion. Forward planned DCA and inverse planned DCA based on segment-weight optimization were compared to VMAT for single arc treatments of five lung patients. Analysis of dose-volume histograms and clinical goal fulfillment revealed that DCA can generate satisfactory and near equivalent dosimetric quality to VMAT, except for complex tumor geometries. Segment-weight optimized DCA …

Adenosine At The Interphase Of Hypoxia And Inflammation In Lung Injury, Xiangyun Li, Nathanial K Berg, Tingting Mills, Kaiying Zhang, Holger K Eltzschig, Xiaoyi Yuan

Faculty, Staff and Student Publications

Hypoxia and inflammation often coincide in pathogenic conditions such as acute respiratory distress syndrome (ARDS) and chronic lung diseases, which are significant contributors to morbidity and mortality for the general population. For example, the recent global outbreak of Coronavirus disease 2019 (COVID-19) has placed viral infection-induced ARDS under the spotlight. Moreover, chronic lung disease ranks the third leading cause of death in the United States. Hypoxia signaling plays a diverse role in both acute and chronic lung inflammation, which could partially be explained by the divergent function of downstream target pathways such as adenosine signaling. Particularly, hypoxia signaling activates adenosine …

The Fms21 (Pila)-Fms20 Locus Encoding One Of Four Distinct Pili Of Enterococcus Faecium Is Harboured On A Large Transferable Plasmid Associated With Gut Colonization And Virulence, Louis Maximilian Buja, Dwayne A Wolf, Bihong Zhao, Bindu Akkanti, Michelle Mcdonald, Laura Lelenwa, Noah Reilly, Giulia Ottaviani, M Tarek Elghetany, Daniel Ocazionez Trujillo, Gabriel M Aisenberg, Mohammad Madjid, Biswajit Kar

Faculty, Staff and Student Publications

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in …

Paclitaxel-Coated Zilver Ptx Drug-Eluting Stent Treatment Does Not Result In Increased Long-Term All-Cause Mortality Compared To Uncoated Devices., Michael D Dake, Gary M Ansel, Marc Bosiers, Andrew Holden, Osamu Iida, Michael R Jaff, Aaron E Lottes, Erin E O'Leary, Alan T Saunders, Marc Schermerhorn, Hiroyoshi Yokoi, Thomas Zeller

Heart and Vascular Articles

PURPOSE: Patient-level data from two large studies of the Zilver PTX drug-eluting stent (DES) with long-term follow-up and concurrent non-drug comparator groups were analyzed to determine whether there was an increased mortality risk due to paclitaxel.

METHODS: Data from the Zilver PTX randomized controlled trial (RCT) and Zilver PTX and bare metal stent (BMS) Japan post-market surveillance studies were analyzed. Five-year follow-up is complete in both DES studies; follow-up for the BMS study was limited to 3 years and is complete. Kaplan-Meier analyses assessed mortality. A Cox proportional hazards model identified significant factors related to mortality.

RESULTS: In the RCT, …

Perioperative Acute Kidney Injury, Sam D Gumbert, Felix Kork, Maisie L Jackson, Naveen Vanga, Semhar J Ghebremichael, Christy Y Wang, Holger K Eltzschig

Faculty, Staff and Students Publications

Perioperative organ injury is among the leading causes of morbidity and mortality of surgical patients. Among different types of perioperative organ injury, acute kidney injury occurs particularly frequently and has an exceptionally detrimental effect on surgical outcomes. Currently, acute kidney injury is most commonly diagnosed by assessing increases in serum creatinine concentration or decreased urine output. Recently, novel biomarkers have become a focus of translational research for improving timely detection and prognosis for acute kidney injury. However, specificity and timing of biomarker release continue to present challenges to their integration into existing diagnostic regimens. Despite many clinical trials using various …

Metaproteomic Analysis Of Human Gut Microbiome In Digestive And Metabolic Diseases, Sheng Pan, Ru Chen

Faculty, Staff and Students Publications

Metaproteomics, as a subfield of proteomics, has quickly emerged as a pivotal tool for global characterization of a microbiome system at a functional level. It has been increasingly applied in studying human digestive and metabolic diseases, and provides information-rich data to identify the dysbiosis of human gut microbiome related to healthy or disease states to elucidate the molecular events underlying host-microbiota interplays. While significant technical challenges still exist, this emerging technology has been demonstrated to provide essential information in interrogating functional changes in the human gut microbiome, complementary to metagenomics and metatranscriptomics. This chapter overviews the overall metaproteomic work flow …

Sleep Duration Is Associated With Vitamin D Deficiency In Older Women Living In Macao, China: A Pilot Cross-Sectional Study, Xiaoying Liu, Liang Ke, Jacky Ho, Myriam Abboud, Elias Mpofu, Tara C. Brennan-Speranza, Rebecca S. Mason, Kaye E. Brock

All Works

© 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Chinese women are known to have both a high prevalence of metabolic syndrome (MetS) and vitamin D deficiency (serum 25-hydroxyvitamin D (25OHD) /l). Associations between sleep duration and circulating 25OHD have recently been reported but, to our knowledge, these associations have not been studied in older Chinese populations. We thus investigated whether sleep duration was associated with vitamin D status in …

Predictors Of Ceasing Or Reducing Statin Medication Following A Large Increase In The Consumer Copayment For Medications: A Retrospective Observational Study, Karla Seamon, Frank Sanfilippo, Max Bulsara, Libby Roughead, Anna Kemp-Casey, Caroline Bulsara, Gerald F. Watts, David Preen

Research outputs 2014 to 2021

OBJECTIVES:

Previous Australian research has shown that following the 21% increase in patient copayments for medications on the Pharmaceutical Benefits Scheme (PBS) in 2005, the use of lipid-lowering therapy declined by 5%. This study aimed to determine the demographic and clinical characteristics of individuals who continued, reduced or ceased their use of statin medication in 2005.

STUDY TYPE:

Retrospective observational study using routinely collected administrative data.

METHOD:

We used pharmaceutical claims, hospital separations and mortality records from 2000 to 2005 for the Western Australian population. The cohort comprised stable users of statin medication in 2004. Based on changes in statin …

Investigating The Effects Of Brainstem Neuronal Adaptation On Cardiovascular Homeostasis., James H Park, Jonathan Gorky, Babatunde Ogunnaike, Rajanikanth Vadigepalli, James S Schwaber

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Central coordination of cardiovascular function is accomplished, in part, by the baroreceptor reflex, a multi-input multi-output physiological control system that regulates the activity of the parasympathetic and sympathetic nervous systems via interactions among multiple brainstem nuclei. Recent single-cell analyses within the brain revealed that individual neurons within and across brain nuclei exhibit distinct transcriptional states contributing to neuronal function. Such transcriptional heterogeneity complicates the task of understanding how neurons within and across brain nuclei organize and function to process multiple inputs and coordinate cardiovascular functions within the larger context of the baroreceptor reflex. However, prior analysis of brainstem neurons revealed …

Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …

2019 Hrs/Ehra/Aphrs/Lahrs Expert Consensus Statement On Catheter Ablation Of Ventricular Arrhythmias, Edmond M Cronin, Phillip Cuculich, Et Al.

2020-Current year OA Pubs

Ventricular arrhythmias are an important cause of morbidity and mortality and come in a variety of forms, from single premature ventricular complexes to sustained ventricular tachycardia and fibrillation. Rapid developments have taken place over the past decade in our understanding of these arrhythmias and in our ability to diagnose and treat them. The field of catheter ablation has progressed with the development of new methods and tools, and with the publication of large clinical trials. Therefore, global cardiac electrophysiology professional societies undertook to outline recommendations and best practices for these procedures in a document that will update and replace the …

Who Benefits From A Prostate Rectal Spacer? Secondary Analysis Of A Phase Iii Trial, Thomas J. Quinn, Walter Bosch, Et Al.

2020-Current year OA Pubs

PURPOSE: Previously a phase III trial of a hydrogel rectal spacer during prostate radiation therapy found decreased toxicity and a clinically significant improvement in bowel quality of life (QOL) at 3 years by the Expanded Prostate Cancer Index. We performed a secondary analysis to identify men less likely to benefit.

METHODS AND MATERIALS: Clinical and dosimetric data for the 222 patients enrolled on the SpaceOAR phase III trial were analyzed. The volume of rectum treated to 70 Gy (V70) and the quantitative analysis of normal tissue effects in the clinic (QUANTEC) rectal dose goals were used as surrogates for clinical …

End Of An Era Of Administering Erythropoiesis Stimulating Agents Among Veterans Administration Cancer Patients With Chemotherapy-Induced Anemia, Shamia Hoque, Brian J. Chen, Martin W. Schoen, Kenneth R. Carson, Jesse Keller, Bartlett J. Witherspoon, Kevin B. Knopf, Y Tony Yang, Benjamin Schooley, Chadi Nabhan, Oliver Sartor, Paul R. Yarnold, Paul Ray, Laura Bobolts, William J. Hrushesky, Michael Dickson, Charles L. Bennett

Open Access Publications

Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and …

Exposure To Covid-19 Patients Increases Physician Trainee Stress And Burnout, Thomas G. Kannampallil, Charles W. Goss, Bradley A. Evanoff, Jaime R. Strickland, Rebecca P. Mcalister, Jennifer Duncan

Open Access Publications

The coronavirus disease 2019 (COVID-19) pandemic has put considerable physical and emotional strain on frontline healthcare workers. Among frontline healthcare workers, physician trainees represent a unique group-functioning simultaneously as both learners and caregivers and experiencing considerable challenges during the pandemic. However, we have a limited understanding regarding the emotional effects and vulnerability experienced by trainees during the pandemic. We investigated the effects of trainee exposure to patients being tested for COVID-19 on their depression, anxiety, stress, burnout and professional fulfillment. All physician trainees at an academic medical center (n = 1375) were invited to participate in an online survey. We …

Integrating A Multidisciplinary Pain Team And Chiropractic Care In A Community Health Center: An Observational Study Of Managing Chronic Spinal Pain, Christopher Prater, Melissa Tepe, Patrick Battaglia

Open Access Publications

BACKGROUND: Chronic spinal pain is one of the most common diseases in the United States. Underserved patients are most affected, and disproportionately may use opioid medications as they lack access to other therapies. It is therefore important to develop systems to treat spinal pain within the primary medical home.

METHODS: We designed a prospective observational pilot study at a community health center to measure the effectiveness of two interventions among an underserved population: a multidisciplinary pain team and chiropractic care. Study outcomes were pain and functional disability measured by the Pain Disability Questionnaire (PDQ), and reduction of opioid dose at …

The Global And National Burden Of Chronic Kidney Disease Attributable To Ambient Fine Particulate Matter Air Pollution: A Modelling Study, Benjamin Bowe, Elena Artimovich, Yan Xie, Yan Yan, Miao Cai, Ziyad Al-Aly

Open Access Publications

Introduction: We aimed to integrate all available epidemiological evidence to characterise an exposure-response model of ambient fine particulate matter (PM

Methods: We collected data from prior studies on the association of PM

Results: The exposure-response function exhibited evidence of an increase in risk with increasing PM

Conclusion: The global burden of CKD attributable to PM

The Longitudinal Parallel Process Analysis Of Biomarkers Of Oxidative Stress, Symptom Clusters, And Cognitive Function In Children With Leukemia, Mary C Hooke, Daniel Hatch, Marilyn J Hockenberry, Susan Whitman, Ida Moore, David Montgomery, Kari Marano, Pauline Mitby, Michael E Scheurer, Olga Taylor, Wei Pan

Faculty, Staff and Students Publications

Background: During treatment for acute lymphoblastic leukemia (ALL), children report co-occurring symptoms of fatigue, sleep disturbance, pain, nausea, and depression as a symptom cluster. Central nervous system–directed ALL therapies also put children at risk for cognitive impairments. Cancer therapies can cause an increase in oxidative stress, which may contribute to treatment-related symptoms. This study examined the longitudinal relationships between biomarkers of oxidative stress in the cerebrospinal fluid, the Childhood Cancer Symptom Cluster–Leukemia (CCSC-L), and cognition, in children over the first year of ALL treatment. Methods: Glutathione (GSH) biomarkers of oxidative stress were measured in cerebrospinal fluid collected during treatment lumbar …

Mitigating Disruptions, And Scalability Of Radiation Oncology Physics Work During The Covid-19 Pandemic, Arash Darafsheh, Hossein Lavvafi, Reza Taleei, Rao Khan

Open Access Publications

PURPOSE: The COVID-19 pandemic has led to disorder in work and livelihood of a majority of the modern world. In this work, we review its major impacts on procedures and workflow of clinical physics tasks, and suggest alternate pathways to avoid major disruption or discontinuity of physics tasks in the context of small, medium, and large radiation oncology clinics. We also evaluate scalability of medical physics under the stress of "social distancing".

METHODS: Three models of facilities characterized by the number of clinical physicists, daily patient throughput, and equipment were identified for this purpose. For identical objectives of continuity of …

Client Processing Is Altered By Novel Myopathy-Causing Mutations In The Hsp40 J Domain, Melanie Y. Pullen, Conrad C. Weihl, Heather L. True

Open Access Publications

The misfolding and aggregation of proteins is often implicated in the development and progression of degenerative diseases. Heat shock proteins (HSPs), such as the ubiquitously expressed Type II Hsp40 molecular chaperone, DNAJB6, assist in protein folding and disaggregation. Historically, mutations within the DNAJB6 G/F domain have been associated with Limb-Girdle Muscular Dystrophy type 1D, now referred to as LGMDD1, a dominantly inherited degenerative disease. Recently, novel mutations within the J domain of DNAJB6 have been reported in patients with LGMDD1. Since novel myopathy-causing mutations in the Hsp40 J domain have yet to be characterized and both the function of DNAJB6 …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …

Myd88-Dependent Influx Of Monocytes And Neutrophils Impairs Lymph Node B Cell Responses To Chikungunya Virus Infection Via Irf5, Nos2 And Nox2, Mary K. Mccarthy, Glennys V. Reynoso, Emma S. Winkler, Matthias Mack, Michael S. Diamond, Heather D. Hickman, Thomas E. Morrison

Open Access Publications

Humoral immune responses initiate in the lymph node draining the site of viral infection (dLN). Some viruses subvert LN B cell activation; however, our knowledge of viral hindrance of B cell responses of important human pathogens is lacking. Here, we define mechanisms whereby chikungunya virus (CHIKV), a mosquito-transmitted RNA virus that causes outbreaks of acute and chronic arthritis in humans, hinders dLN antiviral B cell responses. Infection of WT mice with pathogenic, but not acutely cleared CHIKV, induced MyD88-dependent recruitment of monocytes and neutrophils to the dLN. Blocking this influx improved lymphocyte accumulation, dLN organization, and CHIKV-specific B cell responses. …