Digital Commons Network^™

Approach To Vaccinating The Pediatric Solid Organ Transplant Candidate And Recipient, Carol M Kao, Marian G Michaels

2020-Current year OA Pubs

Solid organ transplantation (SOT) candidates and recipients are at increased risk for morbidity and mortality from vaccine-preventable infections. Children are at particular risk given that they may not have completed their primary immunization series at time of transplant or have acquired natural immunity to pathogens from community exposures. Multiple society guidelines exist for vaccination of SOT candidate and recipients, although challenges remain given limited safety and efficacy data available for pediatric SOT recipients, particularly for live-vaccines. After transplant, individual patient nuances regarding exposure risks and net state of immunosuppression will impact timing of immunizations. The purpose of this review is …

Rare Predicted Loss-Of-Function Variants Of Type I Ifn Immunity Genes Are Associated With Life-Threatening Covid-19, Daniela Matuozzo, Megan A. Cooper, Et Al.

2020-Current year OA Pubs

No abstract provided.

Development Of A Goal Setting And Goal Management System: Intervention Mapping, Eunyoung Kang, Erin R Foster

2020-Current year OA Pubs

BACKGROUND: Although goal setting and goal management (GSGM) is a key component of chronic disease management and rehabilitation practice, there is currently no widely used evidence-based intervention system available. This paper describes the theoretical underpinnings and development of a new intervention called MyGoals. MyGoals is designed to guide occupational therapy (OT) practitioners to implement theory-based, client-engaged GSGM for adults with chronic conditions in community-based OT rehabilitation settings.

METHODS: We first developed a planning team with two adults with chronic conditions, two clinicians, and two researchers. As a collaborative team, we co-developed MyGoals by following Intervention Mapping (IM) steps 1-4 and …

Iron Homeostasis And Post-Hemorrhagic Hydrocephalus: A Review, Shelei Pan, Andrew T Hale, Mackenzie E Lemieux, Dhvanii K Raval, Thomas P Garton, Brooke Sadler, Kelly B Mahaney, Jennifer M Strahle

2020-Current year OA Pubs

Iron physiology is regulated by a complex interplay of extracellular transport systems, coordinated transcriptional responses, and iron efflux mechanisms. Dysregulation of iron metabolism can result in defects in myelination, neurotransmitter synthesis, and neuronal maturation. In neonates, germinal matrix-intraventricular hemorrhage (GMH-IVH) causes iron overload as a result of blood breakdown in the ventricles and brain parenchyma which can lead to post-hemorrhagic hydrocephalus (PHH). However, the precise mechanisms by which GMH-IVH results in PHH remain elusive. Understanding the molecular determinants of iron homeostasis in the developing brain may lead to improved therapies. This manuscript reviews the various roles iron has in brain …

Relationship Between Baseline Plasma P-Tau181 And Longitudinal Changes In Cognition And Structural Brain Measures In A Cohort Of Cognitively Unimpaired Older Adults, Marcos V Pais, Chia-Ling Kuo, Beau M Ances, Julie Loebach Wetherell, Eric J Lenze, Breno S Diniz

2020-Current year OA Pubs

INTRODUCTION: Preclinical Alzheimer's disease (AD) affects a significant proportion of cognitively unimpaired (CU) older adults. Currently, blood-based biomarkers detect very early changes in the AD continuum with great accuracy.

METHODS: We measured baseline plasma phosphorylated tau (p-tau)181 using electrochemiluminescence (ECL)-based assay (MesoScale Discovery) in 533 CU older adults. Follow-up lasted up to 18 months. Cognitive performance assessment included memory and cognitive control. Structural brain measures included cortical thickness, which includes the AD magnetic resonance imaging (AD MRI) signature, and hippocampal volume.

RESULTS: In this cohort of CU older adults, baseline plasma p-tau181 levels were not associated with short-term changes in …

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 …

Machine Learning Pipelines Developed For The Prediction Of Cancelation Of Inappropriate Parathyroid Hormone-Related Peptide Orders Demonstrate Poor Performance In Predicting Provider Behavior, Nicholas C. Spies, Christopher W. Farnsworth, Ronald Jackups, Mark A. Zaydman

2020-Current year OA Pubs

No abstract provided.

A Bone To Pick-Cellular And Molecular Mechanisms Of Bone Pain In Sickle Cell Disease, Jahnavi Gollamudi, Kristine A Karkoska, Oluwabukola T Gbotosho, Wei Zou, Hyacinth I Hyacinth, Steven L Teitelbaum

2020-Current year OA Pubs

The bone is one of the most commonly affected organs in sickle cell disease (SCD). Repeated ischemia, oxidative stress and inflammation within the bone is largely responsible for promoting bone pain. As more individuals with SCD survive into adulthood, they are likely to experience a synergistic impact of both aging and SCD on their bone health. As bone health deteriorates, bone pain will likely exacerbate. Recent mechanistic and observational studies emphasize an intricate relationship between bone remodeling and the peripheral nervous system. Under pathological conditions, abnormal bone remodeling plays a key role in the propagation of bone pain. In this …

Evaluating The Efficacy Of Purchased Antisense Oligonucleotides To Reduce Mouse And Human Tau In Vivo, Pranav Vemula, Kathleen M Schoch, Timothy M Miller

2020-Current year OA Pubs

Many preclinical and clinical studies support the use of antisense oligonucleotides (ASOs) as effective therapeutic strategies. However, acquiring ASOs for research purposes may be limited by partnerships with the pharmaceutical companies. Our lab previously developed an effective ASO strategy to lower human tau and reverse pathology in aged tauopathy model mice. Testing the efficacy of purchased tau lowering ASOs would provide support for these reagents as broad research tools. Purchased mouse and human tau lowering ASOs were infused or injected intracerebroventricularly into wildtype and tau transgenic mice. Following treatment, brain tissue evaluated for ASO distribution and levels of tau mRNA, …

Risk And Protection Of Different Rare Protein-Coding Variants Of Complement Component C4a In Age-Related Macular Degeneration, Johanna M Seddon, Dikha De, William Casazza, Shun-Yun Cheng, Claudio Punzo, Mark Daly, Danlei Zhou, Samantha L Coss, John P Atkinson, Chack-Yung Yu

2020-Current year OA Pubs

No abstract provided.

Understanding Tailoring To Support The Implementation Of Evidence-Based Interventions In Healthcare: The Customise Research Programme Protocol, Sheena M Mchugh, Fiona Riordan, Claire Kerins, Geoff Curran, Cara C Lewis, Justin Presseau, Luke Wolfenden, Byron J Powell

2020-Current year OA Pubs

Although there are effective evidence-based interventions (EBIs) to prevent, treat and coordinate care for chronic conditions they may not be adopted widely and when adopted, implementation challenges can limit their impact. Implementation strategies are "methods or techniques used to enhance the adoption, implementation, and sustainment of a clinical program or practice". There is some evidence to suggest that to be more effective, strategies should be

The Association Of Radiation Dose With Overall Survival For Patients Treated With Prostate Stereotactic Body Radiation Therapy, Michael R. Waters, Neal Andruska, Benjamin W. Fischer-Valuck, Temitope Agabalogun, Randall J. Brenneman, Hiram Gay, Jeff M. Michalski, Brian Baumann

2020-Current year OA Pubs

Introduction Stereotactic body radiation therapy (SBRT) for prostate adenocarcinoma (PCa) has demonstrated excellent biochemical recurrence-free survival, with studies showing improved BRFS with higher-dose SBRT. However, current studies have been underpowered to evaluate the relationship of SBRT dose to overall survival (OS). In this retrospective study using the National Cancer Database (NCDB), we hypothesize that, given the low alpha/beta ratio of PCa, a relatively small increase in the dose-per-fraction would be associated with improved survival outcomes for intermediate-risk PCa (IR-PCa) comparing 36.25 Gy/5 fx [biologically equivalent dose (BEDα/β = 1.5 = 211.46 Gy vs. 35 Gy (BED1.5 = 198.33 Gy)]. Materials …

The Mutational Landscape In Chronic Myelomonocytic Leukemia And Its Impact On Allogeneic Hematopoietic Cell Transplantation Outcomes: A Center For Blood And Marrow Transplantation Research (Cibmtr) Analysis, Matthew Mei, Ravi Vij, Et Al.

2020-Current year OA Pubs

Somatic mutations are recognized as an important prognostic factor in chronic myelomonocytic leukemia (CMML). However, limited data are available regarding their impact on outcomes after allogeneic hematopoietic cell transplantation (HCT). In this registry analysis conducted in collaboration with the Center for International Blood and Marrow Transplantation Registry database/sample repository, we identified 313 adult patients with CMML (median age: 64 years, range, 28- 77) who underwent allogeneic HCT during 2001-2017 and had an available biospecimen in the form of a peripheral blood sample obtained prior to the start of conditioning. In multivariate analysis, a CMML-specific prognostic scoring system (CPSS) score of …

Sex-Related Differences In Premature Cardiovascular Disease In Familial Hypercholesterolemia, Anandita Agarwala, Elena Deych, Laney K Jones, Amy C Sturm, Karen Aspry, Zahid Ahmad, Christie M Ballantyne, Anne C Goldberg

2020-Current year OA Pubs

BACKGROUND: Familial hypercholesterolemia (FH) is associated with an increased prevalence of premature atherosclerotic cardiovascular disease (ASCVD), however, little is known about sex-specific differences in premature ASCVD and its risk factors.

OBJECTIVE: The present study seeks to assess the burden and risk factors for premature ASCVD among men and women with FH.

METHODS: In this study we retrospectively examined sex-specific differences in ASCVD prevalence, risk factor burdens, and lipid treatment outcomes in 782 individuals with clinically or genetically confirmed FH treated in 5 U.S. lipid and genetics clinics. A generalized linear model using Binomial distribution with random study site effect and …

An Analysis Of Major Target Deviations In Craniospinal Irradiation Treatment Plans For Patients With Intermediate-Risk Medulloblastoma Within A Phase 3 Clinical Trial (Children's Oncology Group Study Acns0331), Joshua P Schiff, Yimei Lee, Yu Wang, Stephanie M Perkins, Sandy K Kessel, Thomas J Fitzgerald, Nicole A Larrier, Jeff M Michalski

2020-Current year OA Pubs

PURPOSE: Craniospinal irradiation remains an essential and yet difficult part of the treatment of patients with medulloblastoma. Whereas technological advances offer promise of increased conformity, realiance on advanced technology is not without risk, and it remains critical to carefully delineate targets. We describe examples of target deviations (TDs) in craniospinal irradiation treatment plans for postoperative patients with medulloblastoma in a phase 3 clinical trial (ACNS 0331).

METHODS AND MATERIALS: The principal investigator independently performed a review of the treatment plans and portal films of enrolled patients and evaluated the plans for TDs. TDs of dose, dose uniformity, and volume were …

Expanded Analysis Of High-Grade Astrocytoma With Piloid Features Identifies An Epigenetically And Clinically Distinct Subtype Associated With Neurofibromatosis Type 1, Patrick J Cimino, Sonika Dahiya, Et Al.

2020-Current year OA Pubs

High-grade astrocytoma with piloid features (HGAP) is a recently recognized glioma type whose classification is dependent on its global epigenetic signature. HGAP is characterized by alterations in the mitogen-activated protein kinase (MAPK) pathway, often co-occurring with CDKN2A/B homozygous deletion and/or ATRX mutation. Experience with HGAP is limited and to better understand this tumor type, we evaluated an expanded cohort of patients (n = 144) with these tumors, as defined by DNA methylation array testing, with a subset additionally evaluated by next-generation sequencing (NGS). Among evaluable cases, we confirmed the high prevalence CDKN2A/B homozygous deletion, and/or ATRX mutations/loss in this tumor …

#Orthotwitter: Relationship Between Author Twitter Utilization And Academic Impact In Orthopaedic Surgery, Ryan T Halvorson, Sachin Allahabadi, Nicolas Cevallos, Aidan J. Foley, Kelsey Collins, Abel Torres Espin, Brian T. Feeley, Nirav K. Pandya, Jeannie F. Bailey

2020-Current year OA Pubs

Background #OrthoTwitter has evolved to disseminate findings and engage the public. However, the academic impact of Twitter utilization in orthopaedic surgery is unknown. Questions/purposes The purpose of the study was to evaluate relationships between the author and manuscript Twitter activity and citations. Methods Manuscripts in 17 orthopaedic journals from 2018 were identified. Citations, online mentions, impact factors, and subspecialties were obtained. H-index and Twitter account details for authors were obtained for a subset of manuscripts. Relationships between Twitter activity and citations were evaluated. Results 2,473/4,224 (58.5%) manuscripts were mentioned on Twitter (n=29,958 mentions), with Twitter manuscripts cited more frequently (median …

Open-Source Statistical And Data Processing Tools For Wide-Field Optical Imaging Data In Mice, Lindsey M. Brier, Joseph P. Culver

2020-Current year OA Pubs

SIGNIFICANCE: Wide-field optical imaging (WOI) can produce concurrent hemodynamic and cell-specific calcium recordings across the entire cerebral cortex in animal models. There have been multiple studies using WOI to image mouse models with various environmental or genetic manipulations to understand various diseases. Despite the utility of pursuing mouse WOI alongside human functional magnetic resonance imaging (fMRI), and the multitude of analysis toolboxes in the fMRI literature, there is not an available open-source, user-friendly data processing and statistical analysis toolbox for WOI data.

AIM: To assemble a MATLAB toolbox for processing WOI data, as described and adapted to combine techniques from …

Neurobridge: A Prototype Platform For Discovery Of The Long-Tail Neuroimaging Data, Lei Wang, Janine Bijsterbosch, Rick Herrick, Daniel Marcus, Stephen M Moore, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Open science initiatives have enabled sharing of large amounts of already collected data. However, significant gaps remain regarding how to find appropriate data, including underutilized data that exist in the long tail of science. We demonstrate the NeuroBridge prototype and its ability to search PubMed Central full-text papers for information relevant to neuroimaging data collected from schizophrenia and addiction studies.

METHODS: The NeuroBridge architecture contained the following components: (1) Extensible ontology for modeling study metadata: subject population, imaging techniques, and relevant behavioral, cognitive, or clinical data. Details are described in the companion paper in this special issue; (2) A …

A Multicenter Retrospective Study Of Patients Treated In The Thalamus With Responsive Neurostimulation, Madeline C Fields, Jon T Willie, Et Al.

2020-Current year OA Pubs

INTRODUCTION: For drug resistant epilepsy patients who are either not candidates for resective surgery or have already failed resective surgery, neuromodulation is a promising option. Neuromodulatory approaches include responsive neurostimulation (RNS), deep brain stimulation (DBS), and vagal nerve stimulation (VNS). Thalamocortical circuits are involved in both generalized and focal onset seizures. This paper explores the use of RNS in the centromedian nucleus of the thalamus (CMN) and in the anterior thalamic nucleus (ANT) of patients with drug resistant epilepsy.

METHODS: This is a retrospective multicenter study from seven different epilepsy centers in the United States. Patients that had unilateral or …

Applying Hybrid Effectiveness-Implementation Studies In Equity-Centered Policy Implementation Science, Yuka Asada, Aimee Kroll-Desrosiers, Jamie F Chriqui, Geoffrey M Curran, Karen M Emmons, Debra Haire-Joshu, Ross C Brownson

2020-Current year OA Pubs

Policy implementation science (IS) is complex, dynamic, and fraught with unique study challenges that set it apart from biomedical or clinical research. One important consideration is the ways in which policy interacts with local contexts, such as power and social disadvantage (e.g., based on ability, race, class, sexual identity, geography). The complex nature of policy IS and the need for more intentional integration of equity principles into study approaches calls for creative adaptations to existing implementation science knowledge and guidance. Effectiveness-implementation hybrid studies were developed to enhance translation of clinical research by addressing research questions around the effectiveness of an …

Allele-Specific Quantification Of Human Leukocyte Antigen Transcript Isoforms By Nanopore Sequencing, Andrew E O Hughes, Maureen C Montgomery, Chang Liu, Eric T Weimer

2020-Current year OA Pubs

INTRODUCTION: While tens of thousands of HLA alleles have been identified by DNA sequencing, the contribution of alternative splicing to HLA diversity is not well characterized. In this study, we sought to determine if long-read sequencing could be used to accurately quantify allele-specific HLA transcripts in primary human lymphocytes.

METHODS: cDNA libraries were prepared from peripheral blood lymphocytes from 12 donors and sequenced by nanopore long-read sequencing. HLA reads were aligned to donor-specific reference sequences based on the known type of each donor. Allele-specific exon utilization was calculated as the proportion of reads aligning to each allele containing known exons, …

Predictors Of Nonadherence Among Patients With Infectious Complications Of Substance Use Who Are Discharged On Parenteral Antimicrobial Therapy, Shivakumar Narayanan, Patrick R Ching, Edward C Traver, Nivya George, Anthony Amoroso, Shyam Kottilil

2020-Current year OA Pubs

BACKGROUND: The management of invasive infections related to substance use disorder (SUD) needing parenteral antimicrobial therapy is challenging and may have poor treatment outcomes including nonadherence and lack of completion of parenteral antimicrobial therapy.

METHODS: In this retrospective cohort of 201 patients with invasive infections related to SUD, we looked at frequency and determinants of unfavorable outcomes including nonadherence.

RESULTS: Seventy-nine percent of patients with SUD-related infection completed parenteral antibiotic therapy in skilled nursing facilities. A total of 21.5% of patient episodes had documentation of nonadherence. Nonadherence was higher in patients with active injection drug use (IDU) (28.5% versus 15% …

Design Of Effisayil™ 2: A Randomized, Double-Blind, Placebo-Controlled Study Of Spesolimab In Preventing Flares In Patients With Generalized Pustular Psoriasis, Akimichi Morita, Siew Eng Choon, Hervé Bachelez, Milan J Anadkat, Slaheddine Marrakchi, Min Zheng, Tsen-Fang Tsai, Hamida Turki, Harry Hua, Sushmita Rajeswari, Christian Thoma, A David Burden

2020-Current year OA Pubs

INTRODUCTION: Generalized pustular psoriasis (GPP) is a rare autoinflammatory skin disease characterized by flares of widespread erythema with sterile pustules, and can be relapsing with recurrent flares, or persistent with intermittent flares. Spesolimab, a humanized anti-interleukin-36 (IL-36) receptor monoclonal antibody, targets the key IL-36 pathogenetic pathway in GPP. A previous study showed that spesolimab treatment led to rapid pustular and skin clearance in patients with GPP flares, which was sustained for up to 12 weeks. This study investigates the long-term effects of spesolimab on GPP flares, for which no specific treatments are currently available. The Effisayil™ 2 study will assess …

Healthcare-Associated Infections (Hais) During The Coronavirus Disease 2019 (Covid-19) Pandemic: A Time-Series Analysis, John M Sahrmann, Katelin B Nickel, Dustin Stwalley, Erik R Dubberke, Patrick G Lyons, Andrew P Michelson, Kathleen M Mcmullen, Sumanth Gandra, Margaret A Olsen, Jennie H Kwon, Jason P Burnham

2020-Current year OA Pubs

OBJECTIVE: To use interrupted time-series analyses to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on healthcare-associated infections (HAIs). We hypothesized that the pandemic would be associated with higher rates of HAIs after adjustment for confounders.

DESIGN: We conducted a cross-sectional study of HAIs in 3 hospitals in Missouri from January 1, 2017, through August 31, 2020, using interrupted time-series analysis with 2 counterfactual scenarios.

SETTING: The study was conducted at 1 large quaternary-care referral hospital and 2 community hospitals.

PARTICIPANTS: All adults ≥18 years of age hospitalized at a study hospital for ≥48 hours were included in …

Autologous T Cell Therapy For Mage-A4+ Solid Cancers In Hla-A*02+ Patients: A Phase 1 Trial, David S Hong, Brian A Van Tine, Armin Ghobadi, Amanda Cashen, Et Al.

2020-Current year OA Pubs

Affinity-optimized T cell receptors can enhance the potency of adoptive T cell therapy. Afamitresgene autoleucel (afami-cel) is a human leukocyte antigen-restricted autologous T cell therapy targeting melanoma-associated antigen A4 (MAGE-A4), a cancer/testis antigen expressed at varying levels in multiple solid tumors. We conducted a multicenter, dose-escalation, phase 1 trial in patients with relapsed/refractory metastatic solid tumors expressing MAGE-A4, including synovial sarcoma (SS), ovarian cancer and head and neck cancer ( NCT03132922 ). The primary endpoint was safety, and the secondary efficacy endpoints included overall response rate (ORR) and duration of response. All patients (N = 38, nine tumor types) experienced …

A Novel Biosignature Identifies Patients With Dcis With High Risk Of Local Recurrence After Breast Conserving Surgery And Radiation Therapy, Frank A Vicini, G Bruce Mann, Chirag Shah, Sheila Weinmann, Michael C Leo, Pat Whitworth, Rachel Rabinovitch, Mylin A Torres, Julie A Margenthaler, David Dabbs, Jess Savala, Steven C Shivers, Karuna Mittal, Fredrik Wärnberg, Troy Bremer

2020-Current year OA Pubs

PURPOSE: There is an unmet need to identify women diagnosed with ductal carcinoma in situ (DCIS) with a low risk of in-breast recurrence (IBR) after breast conserving surgery (BCS), which could omit radiation therapy (RT), and also to identify those with elevated IBR risk remaining after BCS plus RT. We evaluated a novel biosignature for a residual risk subtype (RRt) to help identify patients with elevated IBR risk after BCS plus RT.

METHODS AND MATERIALS: Women with DCIS treated with BCS with or without RT at centers in the US, Australia, and Sweden (n = 926) were evaluated. Patients were …

Higher Dose Oral Fluconazole For The Treatment Of Aids-Related Cryptococcal Meningitis (Hiflac)--Report Of A5225, A Multicentre, Phase I/Ii, Two-Stage, Dose-Finding, Safety, Tolerability And Efficacy Randomised, Amphotericin B-Controlled Trial Of The Aids Clinical Trials Group, Umesh G. Lalloo, David B. Clifford, Et Al.

2020-Current year OA Pubs

BACKGROUND: The WHO recommended 1200mg/day of fluconazole (FCZ) in the induction phase of cryptococcal meningitis (CM) in HIV prior to 2018 in regions where amphotericin-B (AMB) was unavailable. A 2-stage AMB-controlled, dose-escalation study to determine the maximum tolerated dose and the safety/efficacy of an induction-consolidation strategy of higher doses FCZ (1200mg-2000mg/day), adjusted for weight and renal function (eGFR)in adults with CM was undertaken.

METHODS: In Stage-1, three induction doses of FCZ (1200mg/day, 1600mg/day and 2000mg/day) were tested in sequential cohortsand compared with AMB in a 3:1 ratio. A particular dose was not tested in Stage 2 if there were significant …

Imputation Of Missing Values For Cochlear Implant Candidate Audiometric Data And Potential Applications, Cole Pavelchek, Andrew P. Michelson, Amit Walia, Amanda Ortmann, Jacques Herzog, Craig A. Buchman, Matthew A. Shew

2020-Current year OA Pubs

OBJECTIVE: Assess the real-world performance of popular imputation algorithms on cochlear implant (CI) candidate audiometric data.

METHODS: 7,451 audiograms from patients undergoing CI candidacy evaluation were pooled from 32 institutions with complete case analysis yielding 1,304 audiograms. Imputation model performance was assessed with nested cross-validation on randomly generated sparse datasets with various amounts of missing data, distributions of sparsity, and dataset sizes. A threshold for safe imputation was defined as root mean square error (RMSE) <10dB. Models included univariate imputation, interpolation, multiple imputation by chained equations (MICE), k-nearest neighbors, gradient boosted trees, and neural networks.

RESULTS: Greater quantities of missing data were associated with worse performance. Sparsity in audiometric data is not uniformly distributed, as inter-octave frequencies are less commonly …

Small Molecule Inhibiting Microglial Nitric Oxide Release Could Become A Potential Treatment For Neuroinflammation, Philipp Jordan, Amanda Costa, Et Al.

2020-Current year OA Pubs

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia. We identified a compound (C1) which significantly reduced NO release in a dose-dependent manner, with a low IC50 (252 nM) and no toxic side effects in vitro or …