Browsing by Author "Miller, David W."

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    Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein α-synuclein
    (National Academy of Sciences, 2016-08-23) Wang, Wei; Nguyen, Linh T. T.; Burlak, Christopher; Chegini, Fariba; Guo, Feng; Chataway, Tim; Ju, Shulin; Fisher, Oriana S.; Miller, David W.; Datta, Debajyoti; Wu, Fang; Wu, Chun-Xiang; Landeru, Anuradha; Wells, James A.; Cookson, Mark R.; Boxer, Matthew B.; Thomas, Craig J.; Gai, Wei Ping; Ringe, Dagmar; Petsko, Gregory A.; Hoang, Quyen Q.; Department of Biochemistry & Molecular Biology, IU School of Medicine
    The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well.
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    Incorporating Acupuncture Into American Healthcare: Initiating a Discussion on Implementation Science, the Status of the Field, and Stakeholder Considerations
    (Sage, 2021-08-25) Miller, David W.; Roseen, Eric J.; Stone, Jennifer A.M.; Gardiner, Paula; Olson, Juli; Rosen, Shellie; Wayne, Peter; Davis, Robert; Coeytaux, Remy; Anesthesia, School of Medicine
    Introduction: The field of implementation science is the study of methods that promote the uptake of evidence-based interventions into healthcare policy and practice. While acupuncture has gained significant traction in the American healthcare landscape, its journey has been somewhat haphazard and non-linear. Methods: In June 2019, a group of thirty diverse stakeholders was convened by the Society for Acupuncture Research with the support of a Patient Centered Outcomes Research Institute, Eugene Washington Engagement Award. This group of stakeholders represented a diverse mix of patients, providers, academicians, researchers, funders, allied health professionals, insurers, association leaders, certification experts, and military program developers. The collective engaged in discussion that explored acupuncture's status in healthcare, including reflections on its safety, effectiveness, best practices, and the actual implementation of acupuncture as seen from diverse stakeholder viewpoints. Objectives: A primary goal was to consider how to utilize knowledge from the field of implementation science more systematically and intentionally to disseminate information about acupuncture and its research base, through application of methods known to implementation science. The group also considered novel challenges that acupuncture may present to known implementation processes. Findings: This article summarizes the initial findings of this in-person meeting of stakeholders and the ongoing discussion among the subject matter experts who authored this report. The goal of this report is to catalyze greater conversation about how the field of implementation science might intersect with practice, access, research, and policymaking pertaining to acupuncture. Core concepts of implementation science and its relationship to acupuncture are introduced, and the case for acupuncture as an Evidence Based Practice (EBP) is established. The status of the field and current environment of acupuncture is examined, and the perspectives of four stakeholder groups--patients, two types of professional practitioners, and researchers--are explored in more detail.