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    Chait, Alan

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    Lipid-lowering in diabetes: An update

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    : Atherosclerotic cardiovascular disease (ASCVD) is accelerated in people with diabetes. Dyslipidemia, hyperglycemia, oxidative stress, and inflammation play a role via a variety of mechanisms operative in the artery wall. In addition, some unique features predispose people with type 1 diabetes to accelerated atherosclerosis. Various organizations have created guidelines that provide advice regarding screening, risk assessment, and roadmaps for treatment to prevent ASCVD in diabetes. Management of dyslipidemia, especially with statins, has proven to be of immense benefit in the prevention of clinical CVD. However, since many patients fail to attain the low levels of low-density lipoproteins (LDL) recommended in these guidelines, supplemental therapy, such as the addition of ezetimibe, bempedoic acid or PCSK9 inhibitors, is often required to reach LDL goals. As a result, the upfront use of combination therapies, particularly a statin plus ezetimibe, is a rational initial approach. The addition to statins of drugs that specifically lower triglyceride levels has not proven beneficial, although the addition of icosapent-ethyl has been shown to be of value, likely by mechanisms independent of triglyceride lowering. Newer treatments in development, including apoC-III and ANGPTL3 inhibitors, seem promising in further reducing apoB-containing lipoproteins

    DIFFERENTIAL EFFECTS OF FATTY ACIDS ON AN IN VITRO MODEL OF HEPATOCYTE STEATOSIS

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    Thesis (Master's)--University of Washington, 2014<bold>Differential Effects of Fatty Acids on an In Vitro Model of Hepatocyte Steatosis</bold> <bold> <italics>Introduction</bold></italics>: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess hepatic fat accumulation in the setting of metabolic syndrome. It ranges from simple hepatic fat accumulation (steatosis), to steatosis with inflammation and fibrosis (steatohepatitis), to end-stage liver disease. Progression of NAFLD has been modeled by a 2 hit hypothesis. The first hit, characterized by triglyceride accumulation, sensitizes the hepatocyte to second hits such as inflammation. Dietary fats are an important contributor to the development of NAFLD. While saturated fatty acids (SFA) tend to promote NAFLD, poly-unsaturated fatty acids (PUFA) and ruminant trans-fatty acids (TFA), such as conjugated linoleic acid (CLA) may be protective. This study aims to investigate the effects of various fatty acids (FA) on hepatocyte triglyceride accumulation, inflammation and insulin sensitivity using an in vitro model. <bold> <italics>Methods</bold></italics>: AML12 hepatocytes were chronically exposed to FAs including Palmitic acid (PA), Oleic acid (OA), Docosahexanoic Acid (DHA) and CLA t10, c12 (CLA 10,12). Hepatic triglyceride content, inflammatory, lipogenic, oxidative stress and ER stress gene expression and insulin signaling proteins were measured. <bold> <italics>Results</bold></italics>: AML12 cells chronically exposed to FA visibly accumulated lipid droplets. Among the various FA treatments, CLA (10,12) induced the greatest triglyceride accumulation. DHA significantly decreased the expression of the lipogenic, inflammatory, oxidative and ER stress genes independent of effects on insulin sensitivity. Interestingly, CLA (10,12) had protective effects on gene expression similar to DHA. <bold> <italics>Conclusion</bold></italics>: Chronic exposure of dietary FA promotes triglyceride accumulation in this in vitro hepatocyte model. DHA and CLA (10,12) have beneficial effects on lipogenesis and inflammatory, oxidative stress and ER stress gene expression despite increasing triglyceride accumulation, indicating that different FA have varying effects on steatotic hepatocyte

    DIFFERENTIAL EFFECTS OF FATTY ACIDS ON AN IN VITRO MODEL OF HEPATOCYTE STEATOSIS

    No full text
    Thesis (Master's)--University of Washington, 2014Differential Effects of Fatty Acids on an In Vitro Model of Hepatocyte Steatosis Introduction: Non-alcoholic fatty liver disease (NAFLD) is characterized by excess hepatic fat accumulation in the setting of metabolic syndrome. It ranges from simple hepatic fat accumulation (steatosis), to steatosis with inflammation and fibrosis (steatohepatitis), to end-stage liver disease. Progression of NAFLD has been modeled by a 2 hit hypothesis. The first hit, characterized by triglyceride accumulation, sensitizes the hepatocyte to second hits such as inflammation. Dietary fats are an important contributor to the development of NAFLD. While saturated fatty acids (SFA) tend to promote NAFLD, poly-unsaturated fatty acids (PUFA) and ruminant trans-fatty acids (TFA), such as conjugated linoleic acid (CLA) may be protective. This study aims to investigate the effects of various fatty acids (FA) on hepatocyte triglyceride accumulation, inflammation and insulin sensitivity using an in vitro model. Methods: AML12 hepatocytes were chronically exposed to FAs including Palmitic acid (PA), Oleic acid (OA), Docosahexanoic Acid (DHA) and CLA t10, c12 (CLA 10,12). Hepatic triglyceride content, inflammatory, lipogenic, oxidative stress and ER stress gene expression and insulin signaling proteins were measured. Results: AML12 cells chronically exposed to FA visibly accumulated lipid droplets. Among the various FA treatments, CLA (10,12) induced the greatest triglyceride accumulation. DHA significantly decreased the expression of the lipogenic, inflammatory, oxidative and ER stress genes independent of effects on insulin sensitivity. Interestingly, CLA (10,12) had protective effects on gene expression similar to DHA. Conclusion: Chronic exposure of dietary FA promotes triglyceride accumulation in this in vitro hepatocyte model. DHA and CLA (10,12) have beneficial effects on lipogenesis and inflammatory, oxidative stress and ER stress gene expression despite increasing triglyceride accumulation, indicating that different FA have varying effects on steatotic hepatocyte

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

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