Medicine and Health Sciences Commons^™

Glaucoma And Microglia-Induced Neuroinflammation, Makoto Ishikawa, Yukitoshi Izumi, Kota Sato, Taimu Sato, Charles F Zorumski, Hiroshi Kunikata, Toru Nakazawa

2020-Current year OA Pubs

Glaucoma is a multifactorial neurodegenerative disease characterized by a progressive optic neuropathy resulting in visual field defects. Elevated intraocular pressure (IOP) is the greatest risk factor for the development of glaucoma, and IOP reduction therapy is the only treatment currently available. However, there are many cases in which retinal degeneration progresses despite sufficient control of IOP. Therefore, it is important to elucidate the pathophysiology of glaucoma that is resistant to current IOP lowering therapies. Experiments using animal glaucoma models show the relationships between microglial neuroinflammatory responses and damage of retinal ganglion cells (RGCs). Inhibition of neuroinflammatory pathways associated with microglial …

Case Report: Peptide Receptor Radioligand Therapy In Metastatic Pediatric Neuroendocrine Tumors, Khanyisile Hlongwa, Olumayowa Kolade, Abdulilah Alnabulsi, Rachelle Steyn, Anita Brink, Vikas Prasad, Stuart More

2020-Current year OA Pubs

Neuroendocrine tumors (NETs) are not commonly diagnosed in children. Metastatic NETs tend to have poor outcomes, and this is seen in adult and pediatric populations. The role of somatostatin receptor imaging using [

Lymphatic Contractile Dysfunction In Mouse Models Of Cantú Syndrome With Katp Channel Gain-Of-Function, Michael J Davis, Jorge A Castorena-Gonzalez, Hae Jin Kim, Min Li, Maria Remedi, Colin G Nichols

2020-Current year OA Pubs

Cantú Syndrome (CS) is an autosomal dominant disorder caused by gain-of-function (GoF) mutations in the Kir6.1 and SUR2 subunits of K

Plasma And Cerebrospinal Fluid Proteomic Signatures Of Acutely Sleep-Deprived Humans: An Exploratory Study, Ana Vaquer-Alicea, Jinsheng Yu, Haiyan Liu, Brendan P Lucey

2020-Current year OA Pubs

STUDY OBJECTIVES: Acute sleep deprivation affects both central and peripheral biological processes. Prior research has mainly focused on specific proteins or biological pathways that are dysregulated in the setting of sustained wakefulness. This exploratory study aimed to provide a comprehensive view of the biological processes and proteins impacted by acute sleep deprivation in both plasma and cerebrospinal fluid (CSF).

METHODS: We collected plasma and CSF from human participants during one night of sleep deprivation and controlled normal sleep conditions. One thousand and three hundred proteins were measured at hour 0 and hour 24 using a high-scale aptamer-based proteomics platform (SOMAscan) …

How Penalizing Substance Use In Pregnancy Affects Treatment And Research: A Qualitative Examination Of Researchers' Perspectives, Seema K Shah, Leishla Perez-Cardona, Khrystyna Helner, Suena H Massey, Ashish Premkumar, Renee Edwards, Elizabeth S Norton, Cynthia E Rogers, Emily S Miller, Christopher D Smyser, Matthew M Davis, Lauren S Wakschlag

2020-Current year OA Pubs

INTRODUCTION: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood.

METHODS: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis.

RESULTS: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal …

Prospective In Silico Evaluation Of Cone-Beam Computed Tomography-Guided Stereotactic Adaptive Radiation Therapy (Ct-Star) For The Ablative Treatment Of Ultracentral Thoracic Disease, Joshua P Schiff, Eric Laugeman, Hayley B Stowe, Xiaodong Zhao, Jessica Hilliard, Ellie Hawk, Jesiah Watkins, Casey Hatscher, Shahed N Badiyan, Pamela P Samson, Geoffrey D Hugo, Clifford G Robinson, Alex T Price, Lauren E Henke

2020-Current year OA Pubs

PURPOSE: We conducted a prospective, in silico study to evaluate the feasibility of cone-beam computed tomography (CBCT)-guided stereotactic adaptive radiation therapy (CT-STAR) for the treatment of ultracentral thoracic cancers (NCT04008537). We hypothesized that CT-STAR would reduce dose to organs at risk (OARs) compared with nonadaptive stereotactic body radiation therapy (SBRT) while maintaining adequate tumor coverage.

METHODS AND MATERIALS: Patients who were already receiving radiation therapy for ultracentral thoracic malignancies underwent 5 additional daily CBCTs on the ETHOS system as part of a prospective imaging study. These were used to simulate CT-STAR, in silico

RESULTS: Seven patients were accrued, 6 with …

Phantom-Based Quality Assurance Of A Clinical Dose Accumulation Technique Used In An Online Adaptive Radiation Therapy Platform, Borna Maraghechi, Thomas Mazur, Dao Lam, Alex Price, Lauren Henke, Hyun Kim, Geoffrey D Hugo, Bin Cai

2020-Current year OA Pubs

PURPOSE: This study aimed to develop a routine quality assurance method for a dose accumulation technique provided by a radiation therapy platform for online treatment adaptation.

METHODS AND MATERIALS: Two commonly used phantoms were selected for the dose accumulation QA: Electron density and anthropomorphic pelvis. On a computed tomography (CT) scan of the electron density phantom, 1 target (gross tumor volume [GTV]; insert at 6 o'clock), a subvolume within this target, and 7 organs at risk (OARs; other inserts) were contoured in the treatment planning system (TPS). Two adaptation sessions were performed in which the GTV was recontoured, first at …

Designing Implementation Strategies To Improve Identification, Cascade Testing, And Management Of Families With Familial Hypercholesterolemia: An Intervention Mapping Approach, Laney K Jones, Ross C Brownson, Anne C Goldberg, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Familial hypercholesterolemia (FH) is a common inherited cholesterol disorder that, without early intervention, leads to premature cardiovascular disease. Multilevel strategies that target all components of FH care including identification, cascade testing, and management are needed to address gaps that exist in FH care. We utilized intervention mapping, a systematic implementation science approach, to identify and match strategies to existing barriers and develop programs to improve FH care.

METHODS: Data were collected utilizing two methods: a scoping review of published literature, related to any component of FH care, and a parallel mixed method study using interviews and surveys. The scientific …

The Evaluation Of The Delayed Swollen Breast In Patients With A History Of Breast Implants, Grace C Keane, Alexandra M Keane, Ryan Diederich, Kaitlyn Kennard, Eric J Duncavage, Terence M Myckatyn

2020-Current year OA Pubs

Breast implants, whether placed for reconstructive or cosmetic purposes, are rarely lifetime devices. Rupture, resulting from compromised implant shell integrity, and capsular contracture caused by constriction of the specialized scar tissue that normally forms around breast implants, have long been recognized, and remain the leading causes of implant failure. It is apparent, however, that women with breast implants may also experience delayed breast swelling due to a range of etiologic factors. While a majority of delayed seromas associated with breast implants have a benign etiology, this presentation cannot be ignored without an adequate workup as malignancies such as breast implant …

Molecular Techniques Drive Cutting Edge Advancements In Management Of Cutaneous T Cell Lymphoma, Mitchell N Lefebvre, Nicholas Borcherding, Ryan J Reis, Eric Mou, Vincent Liu, Ali Jabbari

2020-Current year OA Pubs

Cutaneous 5T cell lymphoma (CTCL), characterized by malignant T cells infiltrating the skin with potential for dissemination, remains a challenging disease to diagnose and treat due to disease heterogeneity, treatment resistance, and lack of effective and standardized diagnostic and prognostic clinical tools. Currently, diagnosis of CTCL practically relies on clinical presentation, histopathology, and immunohistochemistry. These methods are collectively fraught with limitations in sensitivity and specificity. Fortunately, recent advances in flow cytometry, polymerase chain reaction, high throughput sequencing, and other molecular techniques have shown promise in improving diagnosis and treatment of CTCL. Examples of these advances include T cell receptor clonotyping …

Seventy-Five Years Of Service: An Overview Of The College Of American Pathologists' Proficiency Testing Program In Histocompatibility And Identity Testing, H Cliff Sullivan, Manish J Gandhi, Sujata Gaitonde, Ramya Narasimhan, Ketevan Gendzekhadze, Soumya Pandey, Rhonda K Roby, George C Maha, Harmeet Kaur, Jennifer J Schiller, Julie Mcdowell, Maria Smith, Chang Liu, Gerald P Morris

2020-Current year OA Pubs

The Histocompatibility and Identity Testing Committee offers an overview of the College of American Pathologists' (CAP) Proficiency Testing (PT) program, commemorating its significant 75th anniversary in 2024. The CAP PT program has undergone significant growth and evolution over the years, ultimately achieving Centers for Medicare and Medicaid Services approval. In 1979, CAP's partnership with the American Association for Clinical Histocompatibility Testing marked a pivotal moment, leading to the creation of the first proficiency testing survey in 1980. This laid the foundation for various PT programs managed by the CAP Histocompatibility and Identity Testing Committee, including HLA antibody testing, HLA molecular …

Histopathological Evaluation Of Onchocerca Volvulus Nodules By Microscopy And By Digital Image Analysis For The Study Of Macrofilaricidal Drug Efficacy, Kerstin Fischer, Bettina Dubben, Linda B Debrah, Janina M Kuehlwein, Arcangelo Ricchiuto, Alexander Y Debrah, Achim Hoerauf, Gary J Weil, Peter U Fischer, Ute Klarmann-Schulz

2020-Current year OA Pubs

BACKGROUND: Novel drugs or drug combinations that kill or permanently sterilize adult

MATERIAL AND METHODS: Two expert microscopists independently assessed 605 nodules by direct microscopy. At least two sections with two different stains hematoxylin & eosin (H&E, APR immunostain) of paraffin-embedded, ethanol-fixed whole-nodule cross-sections were analyzed. After variables were identified prone to observer discrepancies, we performed a second study to compare consolidated results for 100 nodules obtained by the two readers by microscopy and by analysis of scanned, high resolution digital images (20x magnification). The last data set analyzed was a quality panel of 100 nodules that has been previously …

The Vacc-Seqqc Project: Benchmarking Rna-Seq For Clinical Vaccine Studies, Johannes B Goll, Richard D Head, Et Al.

2020-Current year OA Pubs

[This corrects the article DOI: 10.3389/fimmu.2022.1093242.].

Designing Home-Based Physical Activity Programs For Rural Cancer Survivors: A Survey Of Technology Access And Preferences, Elizabeth A Salerno, Rohana Gao, Jason Fanning, Neha P Gothe, Lindsay L Peterson, Allison B Anbari, Maura M Kepper, Jingqin Luo, Aimee S James, Edward Mcauley, Graham A Colditz

2020-Current year OA Pubs

BACKGROUND: While technology advances have increased the popularity of remote interventions in underserved and rural cancer communities, less is understood about technology access and preferences for home-based physical activity programs in this cancer survivor population.

PURPOSE: To determine access, preferences, and needs, for a home-based physical activity program in rural cancer survivors.

METHODS: A Qualtrics Research Panel was recruited to survey adults with cancer across the United States. Participants self-reported demographics, cancer characteristics, technology access and usage, and preferences for a home-based physical activity program. The Godin Leisure Time Exercise Questionnaire (GLTEQ) assessed current levels of physical activity. Descriptive statistics …

3′-Sulfated Lewisa/C: An Oncofetal Epitope Associated With Metaplastic And Oncogenic Plasticity Of The Gastrointestinal Foregut, Koushik K Das, Jeffrey W Brown

2020-Current year OA Pubs

Metaplasia, dysplasia, and cancer arise from normal epithelia

Symmetric Data-Driven Fusion Of Diffusion Tensor Mri: Age Differences In White Matter, Andrea Mendez Colmenares, Michelle B Hefner, Vince D Calhoun, Elizabeth A Salerno, Jason Fanning, Neha P Gothe, Edward Mcauley, Arthur F Kramer, Agnieszka Z Burzynska

2020-Current year OA Pubs

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of …

Whole-Brain Imaging Of Freely-Moving Zebrafish, Hamid Hasani, Jipeng Sun, Shuyu I Zhu, Qiangzhou Rong, Florian Willomitzer, Rumelo Amor, Gail Mcconnell, Oliver Cossairt, Geoffrey J Goodhill

2020-Current year OA Pubs

One of the holy grails of neuroscience is to record the activity of every neuron in the brain while an animal moves freely and performs complex behavioral tasks. While important steps forward have been taken recently in large-scale neural recording in rodent models, single neuron resolution across the entire mammalian brain remains elusive. In contrast the larval zebrafish offers great promise in this regard. Zebrafish are a vertebrate model with substantial homology to the mammalian brain, but their transparency allows whole-brain recordings of genetically-encoded fluorescent indicators at single-neuron resolution using optical microscopy techniques. Furthermore zebrafish begin to show a complex …

The Function Of Histone Methylation And Acetylation Regulators In Gbm Pathophysiology, Colin Mccornack, Timothy Woodiwiss, Angela Hardi, Hiroko Yano, Albert H Kim

2020-Current year OA Pubs

Glioblastoma (GBM) is the most common and lethal primary brain malignancy and is characterized by a high degree of intra and intertumor cellular heterogeneity, a starkly immunosuppressive tumor microenvironment, and nearly universal recurrence. The application of various genomic approaches has allowed us to understand the core molecular signatures, transcriptional states, and DNA methylation patterns that define GBM. Histone posttranslational modifications (PTMs) have been shown to influence oncogenesis in a variety of malignancies, including other forms of glioma, yet comparatively less effort has been placed on understanding the transcriptional impact and regulation of histone PTMs in the context of GBM. In …

Down Syndrome And Alzheimer's Disease: A Scoping Review Of Functional Performance And Fall Risk, Selena E Washington, Emily Cler, Cameron Lowery, Susan L Stark

2020-Current year OA Pubs

INTRODUCTION: Alzheimer's disease (AD) occurs in aging adults with Down syndrome (DS) at a higher prevalence and an earlier age than in typical aging adults. As with the general aging adult population, there is an urgent need to understand the preclinical and early phases of AD progression in the adult population with DS. The aim of this scoping review was to synthesize the current state of the evidence and identify gaps in the literature regarding functional activity performance and falls and their significance to disease staging (i.e., mild, moderate, and severe defined staging criteria) in relation to Alzheimer's disease and …

Structural Gray Matter Alterations In Glioblastoma And High-Grade Glioma- A Potential Biomarker Of Survival, Bidhan Lamichhane, Patrick H Luckett, Donna Dierker, Ki Yun Park, Harold Burton, Michael Olufawo, Gabriel Trevino, John J Lee, Andy G S Daniel, Carl D Hacker, Daniel S Marcus, Joshua S Shimony, Eric C Leuthardt

2020-Current year OA Pubs

BACKGROUND: Patients with glioblastoma (GBM) and high-grade glioma (HGG, World Health Organization [WHO] grade IV glioma) have a poor prognosis. Consequently, there is an unmet clinical need for accessible and noninvasively acquired predictive biomarkers of overall survival in patients. This study evaluated morphological changes in the brain separated from the tumor invasion site (ie, contralateral hemisphere). Specifically, we examined the prognostic value of widespread alterations of cortical thickness (CT) in GBM/HGG patients.

METHODS: We used FreeSurfer, applied with high-resolution T1-weighted MRI, to examine CT, evaluated prior to standard treatment with surgery and chemoradiation in patients (GBM/HGG,

RESULTS: Compared to HC …

Amplitudes Of Resting-State Functional Networks - Investigation Into Their Correlates And Biophysical Properties, Soojin Lee, Janine D Bijsterbosch, Fidel Alfaro Almagro, Lloyd Elliott, Paul Mccarthy, Bernd Taschler, Roser Sala-Llonch, Christian F Beckmann, Eugene P Duff, Stephen M Smith, Gwenaëlle Douaud

2020-Current year OA Pubs

Resting-state fMRI studies have shown that multiple functional networks, which consist of distributed brain regions that share synchronised spontaneous activity, co-exist in the brain. As these resting-state networks (RSNs) have been thought to reflect the brain's intrinsic functional organization, intersubject variability in the networks' spontaneous fluctuations may be associated with individuals' clinical, physiological, cognitive, and genetic traits. Here, we investigated resting-state fMRI data along with extensive clinical, lifestyle, and genetic data collected from 37,842 UK Biobank participants, with the object of elucidating intersubject variability in the fluctuation amplitudes of RSNs. Functional properties of the RSN amplitudes were first examined by …

Diffusion Basis Spectrum Imaging As An Adjunct To Conventional Mri Leads To Earlier Diagnosis Of High-Grade Glioma Tumor Progression Versus Treatment Effect, Rowland H Han, Tanner M Johanns, Kaleigh F Roberts, Yu Tao, Jingqin Luo, Zezhong Ye, Peng Sun, Jacob Blum, Tsen-Hsuan Lin, Sheng-Kwei Song, Albert H Kim

2020-Current year OA Pubs

BACKGROUND: Following chemoradiotherapy for high-grade glioma (HGG), it is often challenging to distinguish treatment changes from true tumor progression using conventional MRI. The diffusion basis spectrum imaging (DBSI) hindered fraction is associated with tissue edema or necrosis, which are common treatment-related changes. We hypothesized that DBSI hindered fraction may augment conventional imaging for earlier diagnosis of progression versus treatment effect.

METHODS: Adult patients were prospectively recruited if they had a known histologic diagnosis of HGG and completed standard-of-care chemoradiotherapy. DBSI and conventional MRI data were acquired longitudinally beginning 4 weeks post-radiation. Conventional MRI and DBSI metrics were compared with respect …

Patterns Of Utilization And Clinical Adoption Of 0.35 Tesla Mr-Guided Radiation Therapy In The United States - Understanding The Transition To Adaptive, Ultra-Hypofractionated Treatments, Michael D Chuong, Lauren E Henke, Et Al.

2020-Current year OA Pubs

PURPOSE/OBJECTIVE: Magnetic resonance-guided radiation therapy (MRgRT) utilization is rapidly expanding worldwide, driven by advanced capabilities including continuous intrafraction visualization, automatic triggered beam delivery, and on-table adaptive replanning (oART). Our objective was to describe patterns of 0.35Tesla(T)-MRgRT (MRIdian) utilization in the United States (US) among early adopters of this novel technology.

MATERIALS/METHODS: Anonymized administrative data from all US MRIdian treatment systems were extracted for patients completing treatment from 2014 to 2020. Detailed treatment information was available for all MRIdian linear accelerator (linac) systems and some cobalt systems.

RESULTS: Seventeen systems at 16 centers delivered 5736 courses and 36,389 fractions (fraction details …

Substance Use Treatment Utilization Among Women With And Without Human Immunodeficiency Virus, Ayako W Fujita, Aditi Ramakrishnan, Et Al.

2020-Current year OA Pubs

BACKGROUND: Substance use (SU) contributes to poor health outcomes, yet limited data exist to inform strategies to optimize SU treatment among persons with human immunodeficiency virus (HIV). We describe SU and SU treatment utilization among women with and without HIV in the Women's Interagency HIV Study (WIHS).

METHODS: We included data from women enrolled in WIHS from 2013 to 2020. Current SU was self-reported, nonmedical use of drugs in the past year, excluding use of only marijuana. SU treatment utilization was self-reported use of a drug treatment program in the past year. Multivariable regression models were used to investigate associations …

Neuroinflammation And Amyloid Deposition In The Progression Of Mixed Alzheimer And Vascular Dementia, Chunwei Ying, Peter Kang, Michael M Binkley, Andria L Ford, Yasheng Chen, Jason Hassenstab, Qing Wang, Jeremy Strain, John C Morris, Jin-Moo Lee, Tammie L S Benzinger, Hongyu An

2020-Current year OA Pubs

BACKGROUND: Alzheimer's disease (AD) and vascular contributions to cognitive impairment and dementia (VCID) pathologies coexist in patients with cognitive impairment. Abnormal amyloid beta (Aβ) deposition is the hallmark pathologic biomarker for AD. Neuroinflammation may be a pathophysiological mechanism in both AD and VCID. In this study, we aimed to understand the role of neuroinflammation and Aβ deposition in white matter hyperintensities (WMH) progression and cognitive decline over a decade in patients with mixed AD and VCID pathologies.

METHODS: Twenty-four elderly participants (median [interquartile range] age 78 [64.8, 83] years old, 14 female) were recruited from the Knight Alzheimer Disease Research …

Associations Of Snfl With Clinico-Radiological Measures In A Large Ms Population, Elias S Sotirchos, Robert T Naismith, Min Qiao, Et Al.

2020-Current year OA Pubs

OBJECTIVE: Evaluation of serum neurofilament light chain (sNfL), measured using high-throughput assays on widely accessible platforms in large, real-world MS populations, is a critical step for sNfL to be utilized in clinical practice.

METHODS: Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) is a network of healthcare institutions in the United States and Europe collecting standardized clinical/imaging data and biospecimens during routine clinic visits. sNfL was measured in 6974 MS and 201 healthy control (HC) participants, using a high-throughput, scalable immunoassay.

RESULTS: Elevated sNfL levels for age (sNfL-E) were found in 1238 MS participants (17.8%). Factors associated with …

The Actin-Bundling Protein, Pls3, Is Part Of The Mechanoresponsive Machinery That Regulates Osteoblast Mineralization, Samantha M Chin, Carmela Unnold-Cofre, Teri Naismith, Silvia Jansen

2020-Current year OA Pubs

Plastin-3 (PLS3) is a calcium-sensitive actin-bundling protein that has recently been linked to the development of childhood-onset osteoporosis. Clinical data suggest that PLS3 mutations lead to a defect in osteoblast function, however the underlying mechanism remains elusive. To investigate the role of PLS3 in bone mineralization, we generated MC3T3-E1 preosteoblast cells that are stably depleted of PLS3. Analysis of osteogenic differentiation of control and PLS3 knockdown (PLS3 KD) cells showed that depletion of PLS3 does not alter the first stage of osteoblast mineralization in which a collagen matrix is deposited, but severely affects the subsequent mineralization of that matrix. During …

Interobserver Variability In Target Definition For Stereotactic Arrhythmia Radioablation, Martijn H Van Der Ree, Phillip S Cuculich, Geoffrey D Hugo, Clifford G Robinson, Et Al.

2020-Current year OA Pubs

BACKGROUND: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR.

METHODS: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated …

An Image-Based Modeling Framework For Predicting Spatiotemporal Brain Cancer Biology Within Individual Patients, Kamila M Bond, Lee Curtin, Sara Ranjbar, Ariana E Afshari, Leland S Hu, Joshua B Rubin, Kristin R Swanson

2020-Current year OA Pubs

Imaging is central to the clinical surveillance of brain tumors yet it provides limited insight into a tumor's underlying biology. Machine learning and other mathematical modeling approaches can leverage paired magnetic resonance images and image-localized tissue samples to predict almost any characteristic of a tumor. Image-based modeling takes advantage of the spatial resolution of routine clinical scans and can be applied to measure biological differences within a tumor, changes over time, as well as the variance between patients. This approach is non-invasive and circumvents the intrinsic challenges of inter- and intratumoral heterogeneity that have historically hindered the complete assessment of …

Leishmania Major- Derived Lipophosphoglycan Influences The Host's Early Immune Response By Inducing Platelet Activation And Dkk1 Production Via Tlr1/2, Olivia C Ihedioha, Anutr Sivakoses, Stephen M Beverley, Diane Mcmahon-Pratt, Alfred L M Bothwell

2020-Current year OA Pubs

BACKGROUND: Platelets are rapidly deployed to infection sites and respond to pathogenic molecules via pattern recognition receptors (TLR, NLRP). Dickkopf1 (DKK1) is a quintessential Wnt antagonist produced by a variety of cell types including platelets, endothelial cells, and is known to modulate pro-inflammatory responses in infectious diseases and cancer. Moreover, DKK1 is critical for forming leukocyte-platelet aggregates and induction of type 2 cell-mediated immune responses. Our previous publication showed activated platelets release DKK1 following

RESULTS: Here we probed the role of the key surface virulence glycoconjugate lipophosphoglycan (LPG), on DKK1 production using null mutants deficient in LPG synthesis (

CONCLUSION: …