5 results on '"M. O’Dowd"'
Search Results
2. Human Cytomegalovirus Utilizes Multiple Viral Proteins to Regulate the Basement Membrane Protein Nidogen 1
- Author
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Man I Kuan, Lisa B. Caruso, Anamaria G. Zavala, Pranav S. J. B. Rana, John M. O'Dowd, Italo Tempera, and Elizabeth A. Fortunato
- Subjects
Gene Expression Regulation, Viral ,Viral Proteins ,CCCTC-Binding Factor ,Virology ,Insect Science ,Immunology ,Humans ,Cytomegalovirus ,Microbiology ,Basement Membrane ,Immediate-Early Proteins ,Virus-Cell Interactions - Abstract
Nidogen 1 (NID1) is an important basement membrane protein secreted by many cell types. We previously found that human cytomegalovirus (HCMV) infection rapidly induced chromosome 1 breaks and that the basement membrane protein NID1, encoded near the 1q42 break site, was downregulated. We have now determined that the specific breaks in and of themselves did not regulate NID1, rather interactions between several viral proteins and the cellular machinery and DNA regulated NID1. We screened a battery of viral proteins present by 24 hours postinfection (hpi) when regulation was induced, including components of the incoming virion and immediate early (IE) proteins. Adenovirus (Ad) delivery of the tegument proteins pp71 and UL35 and the IE protein IE1 influenced steady-state (ss) NID1 levels. IE1’s mechanism of regulation was unclear, while UL35 influenced proteasomal regulation of ss NID1. Real-time quantitative PCR (RT-qPCR) experiments determined that pp71 downregulated NID1 transcription. Surprisingly, WF28-71, a fibroblast clone that expresses minute quantities of pp71, suppressed NID1 transcription as efficiently as HCMV infection, resulting in the near absence of ss NID1. Sequence analysis of the region surrounding the 1q42 break sites and NID1 promoter revealed CCCTC-binding factor (CTCF) binding sites. Chromatin immunoprecipitation experiments determined that pp71 and CTCF were both bound at these two sites during HCMV infection. Expression of pp71 alone replicated this binding. Binding was observed as early as 1 hpi, and colocalization of pp71 and CTCF occurred as quickly as 15 min postinfection (pi) in infected cell nuclei. In fibroblasts where CTCF was knocked down, Adpp71 infection did not decrease NID1 transcription nor ss NID1 protein levels. Our results emphasize another aspect of pp71 activity during infection and identify this viral protein as a key contributor to HCMV’s efforts to eliminate NID1. Further, we show, for the first time, direct interaction between pp71 and the cellular genome. IMPORTANCE We have found that human cytomegalovirus (HCMV) utilizes multiple viral proteins in multiple pathways to regulate a ubiquitous cellular basement membrane protein, nidogen-1 (NID1). The extent of the resources and the redundant methods that the virus has evolved to affect this control strongly suggest that its removal provides a life cycle advantage to HCMV. Our discoveries that one of the proteins that HCMV uses to control NID1, pp71, binds directly to the cellular DNA and can exert control when present in vanishingly small quantities may have broad implications in a wide range of infection scenarios. Dysregulation of NID1 in an immunocompetent host is not known to manifest complications during infection; however, in the naive immune system of a developing fetus, disruption of this developmentally critical protein could initiate catastrophic HCMV-induced birth defects.
- Published
- 2023
3. A Decision-Supportive Structured Light Monitoring System for Additive Manufacturing Part Surface Profiling
- Author
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Niall M. O’Dowd, Adam J. Wachtor, and Michael D. Todd
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Digital fringe projection ,Innovation and Infrastructure ,Additive manufacturing ,Industry ,Surface profiling ,Measurement uncertainty quantification - Published
- 2023
4. Electronic Health Record Prompt to Improve Lung Cancer Screening in Primary Care.
- Author
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Steinberg MB, Young WJ, Miller Lo EJ, Bover-Manderski MT, Jordan HM, Hafiz Z, Kota KJ, Mukherjee R, Garthe NE, Sonnenberg FA, O'Dowd M, and Delnevo CD
- Abstract
Introduction: Lung cancer is the leading cause of cancer death in the U.S. Combusted tobacco use, the primary risk factor, accounts for 90% of all lung cancers. Early detection of lung cancer improves survival, yet lung cancer screening rates are much lower than those of other cancer screening tests. Electronic health record (EHR) systems are an underutilized tool that could improve screening rates., Methods: This study was conducted in the Rutgers Robert Wood Johnson Medical Group, a university-affiliated network in New Brunswick, NJ. Two novel EHR workflow prompts were implemented on July 1, 2018. These prompts included fields to determine tobacco use and lung cancer screening eligibility and facilitated low-dose computed tomography ordering for eligible patients. The prompts were designed to improve tobacco use data entry, allowing for better lung cancer screening eligibility identification. Data were analyzed in 2022 retrospectively for the period July 1, 2017 to June 30, 2019. The analyses represented 48,704 total patient visits., Results: The adjusted odds of patient record completeness to determine eligibility for low-dose computed tomography (AOR=1.19, 95% CI=1.15, 1.23), eligibility for low-dose computed tomography (AOR=1.59, 95% CI=1.38, 1.82), and whether low-dose computed tomography was ordered (AOR=1.04, 95% CI=1.01, 1.07) all significantly increased after the electronic medical record prompts were implemented., Conclusions: These findings show the utility and benefit of EHR prompts in primary care settings to increase identification for lung cancer screening eligibility as well as increased low-dose computed tomography ordering., (Copyright © 2023 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)
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- 2023
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5. Methods to derive composite indicators used for quality and safety measurement and monitoring in healthcare: a scoping review protocol.
- Author
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McDonnell T, Cosgrove G, Hogan E, Martin J, McNicholas T, O'Dowd M, Rizoaica F, and McAuliffe E
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- Humans, Quality Improvement, Delivery of Health Care, Systematic Reviews as Topic, Review Literature as Topic, Research Design, Policy
- Abstract
Introduction: Composite indicators of quality and safety in healthcare summarise performance across multiple indicators into a single performance measure. Composite indicators can identify domains and drivers of quality, improve the ability to detect differences, aid prioritisation for quality improvement and facilitate decision making about future healthcare needs. However, the use of composite indicators can be controversial, particularly when used to rank healthcare providers. Many of the concerns around transparency, appropriateness and uncertainty may be addressed by a robust and transparent development and review process.The aim of this scoping review is to describe methodologies used at each of the stages of development of composite indicators of quality and safety in healthcare. This review will provide those tasked with developing or reviewing composite indicators with a valuable consolidated analysis of a substantial and wide-ranging literature., Methods and Analysis: The framework proposed by the Joanna Briggs Institute and enhancements proposed by Peters et al (2015, 2017, 2020) will be used in conducting this scoping review, and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews will guide the reporting. Grey literature and peer-reviewed documents will be in-scope. Electronic databases (PubMed, Embase, CINAHL, ABI/INFORM and SafetyLit) will be searched, and publications will be screened by two reviewers. Discussion, policy and guidance publications will be included if they discuss any aspect of the methods used in the development of a composite indicator of quality or safety in a healthcare setting. The search period ranges from 1 January 2000 to 31 December 2022. Data extraction will capture information on 11 stages of composite indicator development, augmenting a 10-stage framework developed by the European Commission Joint Research Centre., Ethics and Dissemination: Ethical approval is not required. Review findings will be published in a peer-reviewed journal and presented at scientific conferences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
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- 2023
- Full Text
- View/download PDF
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