25 results on '"Harrington CL"'
Search Results
2. Populating the Universe: Toy Collecting and Adult Lives
- Author
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Bryant, KN, Bielby, DD, and Harrington, CL
- Published
- 2016
3. Soap Operas and Artistic Legitimation: The Role of Critical Commentary
- Author
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Harrington, CL, Scardaville, M, Lippmann, S, and Bielby, DD
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Communication and Media Studies ,Artistic Legitimation ,Reviews ,Television ,Soap Opera ,Critics - Published
- 2015
4. Life course transitions and the future of fandom
- Author
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Harrington, CL, Harrington, CL, Bielby, DD, Bardo, AR, Harrington, CL, Harrington, CL, Bielby, DD, and Bardo, AR
- Abstract
We explore the future of media fandom through integrating insights from gerontology, human development, fan studies, and marketing. Given population aging and the dismantling of the normative 20th-century life course, along with rapid changes in the extent to which our lives are mediated, fandom is undergoing significant modification. We focus on how new findings on emotional maturation over the life course and scholarly identification of self-narrativization as a resource for 21st-century aging suggest ways that fandom may change over time. © The Author(s) 2011.
- Published
- 2011
5. A life course perspective on fandom
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Harrington, CL, Harrington, CL, Bielby, DD, Harrington, CL, Harrington, CL, and Bielby, DD
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In this article we explore a life course perspective on fandom, with particular emphasis on fandom and adult development. While there is growing interest in issues of age and aging within fan studies and within media studies more broadly, there is a tendency in this literature to discuss aging and the life course atheoretically, ignoring a rich body of scholarship in gerontology, sociology, psychology and human development that examines how lives unfold over time. Our goal in this manuscript is to make explicit what is typically rendered implicit in fan studies by drawing directly on life course perspectives to enrich our understanding of long-term and later-life fandom, and to suggest ways that fan studies might more fully account for fandom over time. This article thus synthesizes two bodies of literature that rarely inform one another: fan studies and life course scholarship. © The Author(s), 2010.
- Published
- 2010
6. New directions in fan studies
- Author
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Harrington, CL, Harrington, CL, Bielby, DD, Harrington, CL, Harrington, CL, and Bielby, DD
- Published
- 2005
7. Global television distribution: Implications of TV 'traveling' for viewers, fans, and texts
- Author
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Harrington, CL, Harrington, CL, Bielby, DD, Harrington, CL, Harrington, CL, and Bielby, DD
- Abstract
This article focuses on the sale and purchase of TV programs and formats at international trade fairs and its implications for our understanding of global television audiences, fans, and texts. Through analytic engagement with the core concept of flow, the authors explore three related issues: (a) how viewers and fans are positioned in distribution practices, (b) the ease through which various televisual elements travel through the distribution process, and (c) the limitations of a conceptual reliance on "traveling" discourses to our understanding of global TV trade.
- Published
- 2005
8. Flow, home, and media pleasures
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Harrington, CL, Harrington, CL, Bielby, DD, Harrington, CL, Harrington, CL, and Bielby, DD
- Published
- 2005
9. WHERE DID YOU HEAR THAT - TECHNOLOGY AND THE SOCIAL-ORGANIZATION OF GOSSIP
- Author
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HARRINGTON, CL, HARRINGTON, CL, BIELBY, DD, HARRINGTON, CL, HARRINGTON, CL, and BIELBY, DD
- Published
- 1995
10. Populating the universe: Toy collecting and adult lives
- Author
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Bryant, KN, Bryant, KN, Bielby, DD, Harrington, CL, Bryant, KN, Bryant, KN, Bielby, DD, and Harrington, CL
- Published
- 2014
11. THE MYTHOLOGY OF MODERN LOVE - REPRESENTATIONS OF ROMANCE IN THE 1980S
- Author
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HARRINGTON, CL, HARRINGTON, CL, BIELBY, DD, HARRINGTON, CL, HARRINGTON, CL, and BIELBY, DD
- Published
- 1991
12. Keep your fans to yourself: The disjuncture between sport studies' and pop culture studies' perspectives on fandom
- Author
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Schimmel, KS, Schimmel, KS, Harrington, CL, Bielby, DD, Schimmel, KS, Schimmel, KS, Harrington, CL, and Bielby, DD
- Abstract
This essay explores different understandings of fans and fandom between sport studies and pop culture studies through presentation of survey data originally collected for a study on global fandom/global fan studies. Email surveys from 65 fan scholars around the world reveal important distinctions between sport scholars and pop culture scholars in terms of their basic understandings of fans and fandom, the role of self-reflexivity in fan research, and the location of sport and other pop culture scholarship in the academy. Analysis points to a disjuncture between sport and pop culture fan studies that ultimately limits the ability to fully understand the range of fan experiences and fandoms.
- Published
- 2007
13. Managing culture matters: Genre, aesthetic elements, and the international market for exported television
- Author
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Bielby, DD, Bielby, DD, Harrington, CL, Bielby, DD, Bielby, DD, and Harrington, CL
- Abstract
Our research analyzes the international market for exported television. As a culture industry it is complicated by product uniqueness, culturally-based differences in understandings of desirable product attributes, and the considerable uncertainty of successful reception as programs cross regional, national, and international borders. We draw upon the concept of a culture world to examine both the ways in which matters of cultural production and distribution are "managed" through the business arrangements industry participants rely upon and the ways that the attributes of the products themselves are configured and interpreted by buyers and sellers as they cross borders. © 2004 Elsevier B.V. All rights reserved.
- Published
- 2004
14. Whose stories are they? Fans' engagement with soap opera narratives in three sites of fan activity
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Bielby, DD, Bielby, DD, Harrington, CL, Bielby, WT, Bielby, DD, Bielby, DD, Harrington, CL, and Bielby, WT
- Abstract
Soap opera narratives are subject to multiple and conflicting claims of "ownership" about who is entitled to make evaluative judgments about quality. Our research examines how dedicated fans' claims are mediated within three sites: fan clubs, daytime magazines, and electronic bulletin boards. These sites differ in the frequency and visibility of fan interaction and in the degree to which fan discourse can be managed by producers, which in turn shapes social interaction among fans and the legitimacy with which they can assert claims to the narrative. ©1999 Broadcast Education Association.
- Published
- 1999
15. Bayesian hierarchical vector autoregressive models for patient-level predictive modeling.
- Author
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Feihan Lu, Yao Zheng, Harrington Cleveland, Chris Burton, and David Madigan
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Medicine ,Science - Abstract
Predicting health outcomes from longitudinal health histories is of central importance to healthcare. Observational healthcare databases such as patient diary databases provide a rich resource for patient-level predictive modeling. In this paper, we propose a Bayesian hierarchical vector autoregressive (VAR) model to predict medical and psychological conditions using multivariate time series data. Compared to the existing patient-specific predictive VAR models, our model demonstrated higher accuracy in predicting future observations in terms of both point and interval estimates due to the pooling effect of the hierarchical model specification. In addition, by adopting an elastic-net prior, our model offers greater interpretability about the associations between variables of interest on both the population level and the patient level, as well as between-patient heterogeneity. We apply the model to two examples: 1) predicting substance use craving, negative affect and tobacco use among college students, and 2) predicting functional somatic symptoms and psychological discomforts.
- Published
- 2018
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16. Association of S100A8/A9 with Lipid-Rich Necrotic Core and Treatment with Biologic Therapy in Patients with Psoriasis: Results from an Observational Cohort Study.
- Author
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Berg AR, Hong CG, Svirydava M, Li H, Parel PM, Florida E, O'Hagan R, Pantoja CJ, Lateef SS, Anzenberg P, Harrington CL, Ward G, Zhou W, Sorokin AV, Chen MY, Teague HL, Buckler AJ, Playford MP, Gelfand JM, and Mehta NN
- Subjects
- Humans, Biomarkers, Calgranulin A, Calgranulin B, S100 Proteins, Cohort Studies, Biological Therapy, Necrosis, Lipids, S100A12 Protein, Psoriasis drug therapy, Psoriasis metabolism
- Abstract
Psoriasis is a systemic inflammatory disease with an increased risk of atherosclerotic events and premature cardiovascular disease. S100A7, A8/A9, and A12 are protein complexes that are produced by activated neutrophils, monocytes, and keratinocytes in psoriasis. Lipid-rich necrotic core (LRNC) is a high-risk coronary plaque feature previously found to be associated with cardiovascular risk factors and psoriasis severity. LRNC can decrease with biologic therapy, but how this occurs remains unknown. We investigated the relationship between S100 proteins, LRNC, and biologic therapy in psoriasis. S100A8/A9 associated with LRNC in fully adjusted models (β = 0.27, P = 0.009; n = 125 patients with psoriasis with available coronary computed tomography angiography scans; LRNC analyses; and serum S100A7, S100A8, S100A9, S100A12, and S100A8/A9 levels). At 1 year, in patients receiving biologic therapy (36 of 73 patients had 1-year coronary computed tomography angiography scans available), a 79% reduction in S100A8/A9 levels (‒172 [‒291.7 to 26.4] vs. ‒29.9 [‒137.9 to 50.5]; P = 0.04) and a 0.6 mm
2 reduction in average LRNC area (0.04 [‒0.48 to 0.77] vs. ‒0.56 [‒1.8 to 0.13]; P = 0.02) were noted. These results highlight the potential role of S100A8/A9 in the development of high-risk coronary plaque in psoriasis., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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17. Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in Psoriasis: A Prospective Cohort Study.
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Goyal A, Dey AK, Chaturvedi A, Elnabawi YA, Aberra TM, Chung JH, Belur AD, Groenendyk JW, Lerman JB, Rivers JP, Rodante JA, Harrington CL, Varghese NJ, Sanda GE, Baumer Y, Sorokin AV, Teague HL, Genovese LD, Natarajan B, Joshi AA, Playford MP, Bluemke DA, Chen MY, Alavi A, Pitman RK, Powell-Wiley TM, Tawakol A, Gelfand JM, and Mehta NN
- Subjects
- Adult, Aged, Amygdala diagnostic imaging, Anti-Inflammatory Agents therapeutic use, Asymptomatic Diseases, Cardiovascular Diseases diagnostic imaging, Cardiovascular Diseases physiopathology, Case-Control Studies, Chronic Disease, Computed Tomography Angiography, Coronary Angiography, Cross-Sectional Studies, Female, Fluorodeoxyglucose F18 administration & dosage, Hematopoietic System diagnostic imaging, Humans, Male, Middle Aged, Multidetector Computed Tomography, Predictive Value of Tests, Prospective Studies, Psoriasis diagnostic imaging, Psoriasis drug therapy, Psoriasis physiopathology, Radiopharmaceuticals administration & dosage, Risk Factors, Single Photon Emission Computed Tomography Computed Tomography, Stress, Psychological diagnostic imaging, Stress, Psychological physiopathology, Treatment Outcome, United States epidemiology, Amygdala physiopathology, Cardiovascular Diseases etiology, Hematopoietic System physiopathology, Psoriasis complications, Stress, Psychological etiology
- Abstract
Objectives: This study hypothesized that there is an association between chronic stress (as indexed by resting amygdalar activity [AmygA]), hematopoietic system activity (HMPA), and subclinical cardiovascular indexes (aortic vascular inflammation [VI] and noncalcified coronary plaque burden [NCB]) in psoriasis (PSO). The study also hypothesized that treatment of PSO would improve these parameters., Background: PSO is a stress-related chronic inflammatory condition that is associated with increased prevalence of subclinical cardiovascular disease (CVD). In individuals without PSO, stress has been linked to CVD through a serial biological pathway that involves the amygdala, hematopoietic tissues, and atherosclerotic plaques., Methods: A total of 164 consecutive patients with PSO and 47 healthy volunteers underwent 18-fluorodeoxyglucose positron emission tomography/computed tomography scans for assessment of AmygA, HMPA, and VI, as well as coronary computed tomography angiography scans for quantifying NCB. Furthermore, a consecutive subset of 30 patients with severe PSO (Psoriasis Area Severity Index Score >10) were followed at 1 year to assess the relationship between skin disease improvement and AmygA, HMPA, VI, and NCB., Results: The PSO cohort was middle-aged (mean age: 50 years), had low cardiovascular risk (Framingham risk score: median: 3) and had mild to moderate PSO activity (median Psoriasis Area Severity Index Score: 5.6). AmygA was higher in patients with PSO compared to volunteer participants. AmygA was associated with HMPA (bone marrow activity: β = 0.20, p = 0.01) and subclinical CVD (VI: β = 0.31, p < 0.001; NCB: β = 0.27, p < 0.001) The AmygA-CVD association was in part mediated by HMPA (VI: 20.9%, NCB: 36.7%). Following 1 year of PSO treatment in those with severe disease, improvement in skin disease was accompanied by a reduction in AmygA, bone marrow activity, and VI, with no progression of NCB., Conclusions: In PSO, a chronic inflammatory disease state, AmygA, which is a manifestation of chronic stress, substantially contributes to the risk of subclinical CVD. Additional studies that use psychometric measures of stress are required to explore therapeutic impact., (Published by Elsevier Inc.)
- Published
- 2020
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18. Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study.
- Author
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Elnabawi YA, Dey AK, Goyal A, Groenendyk JW, Chung JH, Belur AD, Rodante J, Harrington CL, Teague HL, Baumer Y, Keel A, Playford MP, Sandfort V, Chen MY, Lockshin B, Gelfand JM, Bluemke DA, and Mehta NN
- Subjects
- Adult, Aged, Arthritis, Psoriatic complications, Arthritis, Psoriatic diagnosis, Arthritis, Psoriatic immunology, Computed Tomography Angiography, Coronary Angiography methods, Coronary Artery Disease diagnostic imaging, Coronary Artery Disease etiology, Coronary Vessels diagnostic imaging, Disease Progression, Female, Humans, Male, Middle Aged, Multidetector Computed Tomography, Necrosis, Prospective Studies, Risk Factors, Severity of Illness Index, Time Factors, Treatment Outcome, Arthritis, Psoriatic drug therapy, Biological Products therapeutic use, Coronary Artery Disease pathology, Coronary Vessels pathology, Plaque, Atherosclerotic
- Abstract
Aims: The use of biologic therapy has increased over the past decade well beyond primary autoimmune diseases. Indeed, a recent trial using an anti-IL-1beta antibody reduced second myocardial infarction (MI) in those who have had MI. Psoriasis is a chronic inflammatory disease often treated with biologics when severe, is associated with increased risk of MI, in part driven by high-risk coronary plaque phenotypes by coronary computed tomography angiography (CCTA). We hypothesized that we would observe a reduction in inflammatory-driven phenotypes of coronary plaque, including non-calcified coronary plaque burden and lipid-rich necrotic core in those treated with biologic therapy after one-year compared with non-biologic therapy., Methods and Results: In a prospective, observational study, 290 participants were recruited from 1 January 2013 through 31 October 2018 with 215 completing one-year follow-up. Of the 238, 121 consecutive participants who were biologic treatment naïve at baseline were included. A blinded reader (blinded to patient demographics, visit and treatment) quantified total coronary plaque burden and plaque subcomponents (calcified and non-calcified) in the three main coronary vessels >2 mm using dedicated software (QAngio, Medis, Netherlands). Psoriasis patients were middle-aged [mean (standard deviation) age, 50.5 (12.1) years], mostly male (n = 70, 58%) with low cardiovascular risk by Framingham score [median (interquartile range, IQR), 3 (1-6)] and had moderate to severe skin disease at baseline [median (IQR) Psoriasis Area Severity Index, PASI, 8.6 (5.3-14.0)]. Biologic therapy was associated with a 6% reduction in non-calcified plaque burden (P = 0.005) reduction in necrotic core (P = 0.03), with no effect on fibrous burden (P = 0.71). Decrease in non-calcified plaque burden in the biologic treated group was significant compared with slow plaque progression in non-biologic treated (Δ, -0.07 mm2 vs. 0.06 mm2; P = 0.02) and associated with biologic treatment beyond adjustment for traditional cardiovascular risk factors (β = 0.20, P = 0.02)., Conclusion: In this observational study, we demonstrate that biologic therapy in severe psoriasis was associated with favourable modulation of coronary plaque indices by CCTA. These findings highlight the importance of systemic inflammation in coronary artery disease and support the conduct of larger, randomized trials., (Published by Oxford University Press on behalf of the European Society of Cardiology 2019. This work is written by US Government employees and is in the public domain in the US.)
- Published
- 2019
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19. Neutrophil Subsets, Platelets, and Vascular Disease in Psoriasis.
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Teague HL, Varghese NJ, Tsoi LC, Dey AK, Garshick MS, Silverman JI, Baumer Y, Harrington CL, Stempinski E, Elnabawi YA, Dagur PK, Cui K, Tunc I, Seifuddin F, Joshi AA, Stansky E, Purmalek MM, Rodante JA, Keel A, Aridi TZ, Carmona-Rivera C, Sanda GE, Chen MY, Pirooznia M, McCoy JP Jr, Gelfand JM, Zhao K, Gudjonsson JE, Playford MP, Kaplan MJ, Berger JS, and Mehta NN
- Abstract
Psoriasis is an inflammatory skin disease associated with increased cardiovascular risk and serves as a reliable model to study inflammatory atherogenesis. Because neutrophils are implicated in atherosclerosis development, this study reports that the interaction among low-density granulocytes, a subset of neutrophils, and platelets is associated with a noncalcified coronary plaque burden assessed by coronary computed tomography angiography. Because early atherosclerotic noncalcified burden can lead to fatal myocardial infarction, the low-density granulocyte-platelet interaction may play a crucial target for clinical intervention.
- Published
- 2019
- Full Text
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20. Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis.
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Sorokin AV, Kotani K, Elnabawi YA, Dey AK, Sajja AP, Yamada S, Ueda M, Harrington CL, Baumer Y, Rodante JA, Gelfand JM, Chen MY, Joshi AA, Playford MP, Remaley AT, and Mehta NN
- Subjects
- Adult, Biomarkers blood, Female, Humans, Lipid Peroxidation, Male, Middle Aged, Plaque, Atherosclerotic diagnostic imaging, Plaque, Atherosclerotic epidemiology, Psoriasis complications, Lipoproteins blood, Plaque, Atherosclerotic blood, Psoriasis blood
- Abstract
Rationale: Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis., Objective: To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis., Methods and Results: Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased body mass index, and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL; P <0.05 for all) with significant association of oxidized LDL (β=0.10; P=0.020) and oxHDL (β=-0.11; P=0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82; P=0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03; P<0.001) and with a concomitant decrease in NCB at 1 year (1.04±0.44 versus 0.95±0.32; P=0.03)., Conclusions: Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.
- Published
- 2018
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21. Effect of 2 Psoriasis Treatments on Vascular Inflammation and Novel Inflammatory Cardiovascular Biomarkers: A Randomized Placebo-Controlled Trial.
- Author
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Mehta NN, Shin DB, Joshi AA, Dey AK, Armstrong AW, Duffin KC, Fuxench ZC, Harrington CL, Hubbard RA, Kalb RE, Menter A, Rader DJ, Reilly MP, Simpson EL, Takeshita J, Torigian DA, Werner TJ, Troxel AB, Tyring SK, Vanderbeek SB, Van Voorhees AS, Playford MP, Ahlman MA, Alavi A, and Gelfand JM
- Subjects
- Adult, Biomarkers blood, Blood Glucose metabolism, Cholesterol, HDL blood, Cross-Over Studies, Double-Blind Method, Female, Fluorodeoxyglucose F18 administration & dosage, Humans, Insulin Resistance, Male, Middle Aged, Positron Emission Tomography Computed Tomography, Predictive Value of Tests, Psoriasis blood, Psoriasis diagnostic imaging, Radiopharmaceuticals administration & dosage, Severity of Illness Index, Time Factors, Treatment Outcome, United States, Vasculitis blood, Vasculitis diagnostic imaging, Adalimumab therapeutic use, Anti-Inflammatory Agents therapeutic use, Inflammation Mediators blood, Psoriasis therapy, Ultraviolet Therapy, Vasculitis therapy
- Abstract
Background: Psoriasis is a chronic inflammatory disease associated with dyslipidemia, cardiovascular events, and mortality. We aimed to assess and compare the effect of treatment of moderate-to-severe psoriasis with adalimumab or phototherapy on vascular inflammation and cardiovascular biomarkers., Methods and Results: Randomized, double-blind, trial of adalimumab, phototherapy, and placebo (1:1:1) for 12 weeks, with crossover to adalimumab for 52 weeks total. Outcomes included vascular inflammation by
18 F-fluorodeoxyglucose positron emission tomography/computed tomography and biomarkers of inflammation, insulin resistance, and lipoproteins. Ninety-seven patients were randomized, 92 completed the randomized controlled trial portion; 81 entered the adalimumab extension with 61 completing 52 weeks of adalimumab. There was no difference in change in vascular inflammation at week 12 in the adalimumab group (change compared with placebo, 0.64%; 95% confidence interval, -5.84% to 7.12%) or the phototherapy group (-1.60%; 95% confidence interval, -6.78% to 3.59%) or after 52-week adalimumab treatment (0.02% compared with initiation; 95% confidence interval, -2.85% to 2.90%). Both adalimumab and phototherapy decreased inflammation by serum CRP, interleukin-6. Only adalimumab reduced tumor necrosis factor and glycoprotein acetylation at 12 and 52 weeks. Neither had an impact on metabolic markers (insulin, adiponectin, and leptin). Only phototherapy increased high-density lipoprotein-p at 12 weeks. At 52-week of adalimumab cholesterol efflux and high-density lipoprotein-p were reduced., Conclusions: Adalimumab reduced key markers of inflammation including glycoprotein acetylation compared with phototherapy with no effect on glucose metabolism and vascular inflammation, and potential adverse effects on high-density lipoprotein. Glycoprotein acetylation improvement may partially explain the beneficial effects of adalimumab seen in observational studies. Larger studies with more detailed phenotyping of vascular disease should assess the comparative differences in the effects of adalimumab and phototherapy seen in our study., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifiers: NCT01866592 and NCT01553058., (© 2018 American Heart Association, Inc.)- Published
- 2018
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22. Visceral Adiposity in Psoriasis is Associated With Vascular Inflammation by 18 F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Beyond Cardiometabolic Disease Risk Factors in an Observational Cohort Study.
- Author
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Rivers JP, Powell-Wiley TM, Dey AK, Rodante JA, Chung JH, Joshi AA, Natarajan B, Sajja AP, Chaturvedi A, Rana A, Harrington CL, Teague HL, Lockshin BN, Ahlman MA, Yao J, Playford MP, Gelfand JM, and Mehta NN
- Subjects
- Adult, Female, Humans, Intra-Abdominal Fat physiopathology, Longitudinal Studies, Male, Middle Aged, Predictive Value of Tests, Prognosis, Psoriasis physiopathology, Psoriasis therapy, Risk Factors, Subcutaneous Fat physiopathology, Time Factors, Vasculitis physiopathology, Vasculitis therapy, Whole Body Imaging, Adiposity, Fluorodeoxyglucose F18 administration & dosage, Intra-Abdominal Fat diagnostic imaging, Positron Emission Tomography Computed Tomography, Psoriasis diagnostic imaging, Radiopharmaceuticals administration & dosage, Subcutaneous Fat diagnostic imaging, Vasculitis diagnostic imaging
- Abstract
Objectives: The authors sought to examine the relationship between visceral adipose tissue (VAT) and vascular inflammation (VI) by
18 F-Fluorodeoxyglucose (18 F-FDG) positron-emission tomography (PET)/computed tomography (CT) in psoriasis (PSO). Furthermore, we evaluated whether treatment of PSO modulated VAT and VI., Background: PSO, a chronic inflammatory skin disease, is associated with VI by18 F-FDG PET/CT and increased cardiometabolic risk including adipose tissue dysregulation. Recently, VI was associated with future cardiovascular events; however, the relationship of visceral and subcutaneous adiposity with VI in PSO has yet to be evaluated., Methods: Consecutive PSO patients (N = 77) underwent18 F-FDG PET/CT scans to measure VI and abdominal adiposity. A subset of PSO patients with severe skin disease was scanned at 1 year following PSO treatment (N = 13)., Results: The cohort was middle aged (51.8 ± 12.6 years), predominantly male (n = 44, 57%), had low cardiovascular risk by Framingham 10-year risk (median 4 years [interquartile range (IQR): 2 to 7 years]), and mild-to-moderate skin disease (5.2 [IQR: 3.0 to 8.5]). PSO disease severity associated with VAT (β = 0.33; p = 0.004) beyond SAT (β = 0.30; p = 0.005). VAT (β = 0.55; p < 0.001), but not SAT (β = 0.15; p = 0.11), associated with VI beyond cardiovascular risk factors. We followed a subset of severe PSO patients treated aggressively for PSO and observed improvement in PSO severity and VAT, which was associated with an improvement in VI at 1 year beyond cardiovascular risk factors (β = 0.53; p = 0.049)., Conclusions: Volume-based CT measurement of VAT may capture metabolic risk associated with VI compared to subcutaneous adipose tissue in PSO. PSO treatment associated with a decrease in VAT as well as decrease in VI suggesting VAT as a relevant biomarker related to VI in PSO., (Published by Elsevier Inc.)- Published
- 2018
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23. Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis.
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Baumer Y, Ng Q, Sanda GE, Dey AK, Teague HL, Sorokin AV, Dagur PK, Silverman JI, Harrington CL, Rodante JA, Rose SM, Varghese NJ, Belur AD, Goyal A, Gelfand JM, Springer DA, Bleck CK, Thomas CL, Yu ZX, Winge MC, Kruth HS, Marinkovich MP, Joshi AA, Playford MP, and Mehta NN
- Subjects
- Adolescent, Animals, Atherosclerosis genetics, Cardiovascular Diseases immunology, Child, Cytokines metabolism, Disease Models, Animal, Dyslipidemias, Female, Foam Cells, Humans, Keratinocytes metabolism, Male, Mice, Mice, Knockout, Multivariate Analysis, Neuropeptides metabolism, Regression Analysis, Superoxide Dismutase metabolism, rac1 GTP-Binding Protein metabolism, Atherosclerosis immunology, Cholesterol metabolism, Inflammation immunology, Macrophages metabolism, Psoriasis immunology, Skin immunology
- Abstract
Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12-/+/Srb1-/-/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis.
- Published
- 2018
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24. Psoriasis as a human model of disease to study inflammatory atherogenesis.
- Author
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Harrington CL, Dey AK, Yunus R, Joshi AA, and Mehta NN
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- Atherosclerosis diagnostic imaging, Cytokines metabolism, Humans, Inflammation diagnostic imaging, Models, Biological, Positron-Emission Tomography, Psoriasis diagnostic imaging, Atherosclerosis pathology, Inflammation pathology, Psoriasis pathology
- Abstract
Inflammation is known to play a significant role in the process of atherogenesis and cardiovascular disease (CVD). Indeed, patients with chronic inflammatory diseases are at increased risk for cardiovascular events. However, the mechanisms linking chronic inflammation and CVD remain poorly understood. Psoriasis, a chronic inflammatory skin disease associated with a greater risk of early cardiovascular events, provides a suitable human model to study the pathophysiology of inflammatory atherogenesis in humans. Additionally, cytokines such as TNF-α, IL-17A, and other immune pathways are the common links between the pathogenesis of psoriasis and atherosclerosis, and hence the approved treatments for psoriasis, which include selective cytokine inhibition (e.g., anti-TNF, anti-IL-17A, and anti-IL-12/23) and immune modulation (e.g., methotrexate or cyclosporine), provide an opportunity to examine the effect of modulating these pathways on atherogenesis. We have been using this human model in a large, prospective cohort study, and this review summarizes our approach and results of using this human model to study inflammatory atherogenesis. Specifically, we review simultaneous multimodal imaging of several vascular beds using
18 fludeoxyglucose positron emission tomography/computed tomography,18 fludeoxyglucose positron emission tomography/MRI, and coronary computed tomography angiography as well as cardiovascular biomarkers to better understand how modulation of inflammation may impact vascular diseases.- Published
- 2017
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25. A defined range of guard cell calcium oscillation parameters encodes stomatal movements.
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Allen GJ, Chu SP, Harrington CL, Schumacher K, Hoffmann T, Tang YY, Grill E, and Schroeder JI
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- Abscisic Acid metabolism, Arabidopsis cytology, Arabidopsis genetics, Electrophysiology, In Vitro Techniques, Mutation, Plant Leaves cytology, Plant Leaves metabolism, Arabidopsis metabolism, Calcium metabolism, Calcium Signaling genetics, Calcium Signaling physiology
- Abstract
Oscillations in cytosolic calcium concentration ([Ca2+]cyt) are central regulators of signal transduction cascades, although the roles of individual [Ca2+]cyt oscillation parameters in regulating downstream physiological responses remain largely unknown. In plants, guard cells integrate environmental and endogenous signals to regulate the aperture of stomatal pores and [Ca2+]cyt oscillations are a fundamental component of stomatal closure. Here we systematically vary [Ca2+]cyt oscillation parameters in Arabidopsis guard cells using a 'calcium clamp' and show that [Ca2+]cyt controls stomatal closure by two mechanisms. Short-term 'calcium-reactive' closure occurred rapidly when [Ca2+]cyt was elevated, whereas the degree of long-term steady-state closure was 'calcium programmed' by [Ca2+]cyt oscillations within a defined range of frequency, transient number, duration and amplitude. Furthermore, in guard cells of the gca2 mutant, [Ca2+]cyt oscillations induced by abscisic acid and extracellular calcium had increased frequencies and reduced transient duration, and steady-state stomatal closure was abolished. Experimentally imposing [Ca2+]cyt oscillations with parameters that elicited closure in the wild type restored long-term closure in gca2 stomata. These data show that a defined window of guard cell [Ca2+]cyt oscillation parameters programs changes in steady-state stomatal aperture.
- Published
- 2001
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