bet Epigenetic Regulation of Hepatic Lipogenesis: Role in Hepatosteatosis and Diabetes By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 Hepatosteatosis, which is frequently associated with development of metabolic syndrome and insulin resistance, manifests when triglyceride (TG) input in the liver is greater than TG output, resulting in the excess accumulation of TG. Dysregulation of lipogenesis therefore has the potential to increase lipid accumulation in the liver, leading to insulin resistance and type 2 diabetes. Recently, efforts have been made to examine the epigenetic regulation of metabolism by histone-modifying enzymes that alter chromatin accessibility for activation or repression of transcription. For regulation of lipogenic gene transcription, various known lipogenic transcription factors, such as USF1, ChREBP, and LXR, interact with and recruit specific histone modifiers, directing specificity toward lipogenesis. Alteration or impairment of the functions of these histone modifiers can lead to dysregulation of lipogenesis and thus hepatosteatosis leading to insulin resistance and type 2 diabetes. Full Article
bet Remnants of the Triglyceride-Rich Lipoproteins, Diabetes, and Cardiovascular Disease By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 Diabetes is now a pandemic disease. Moreover, a large number of people with prediabetes are at risk for developing frank diabetes worldwide. Both type 1 and type 2 diabetes increase the risk of atherosclerotic cardiovascular disease (CVD). Even with statin treatment to lower LDL cholesterol, patients with diabetes have a high residual CVD risk. Factors mediating the residual risk are incompletely characterized. An attractive hypothesis is that remnant lipoprotein particles (RLPs), derived by lipolysis from VLDL and chylomicrons, contribute to this residual risk. RLPs constitute a heterogeneous population of lipoprotein particles, varying markedly in size and composition. Although a universally accepted definition is lacking, for the purpose of this review we define RLPs as postlipolytic partially triglyceride-depleted particles derived from chylomicrons and VLDL that are relatively enriched in cholesteryl esters and apolipoprotein (apo)E. RLPs derived from chylomicrons contain apoB48, while those derived from VLDL contain apoB100. Clarity as to the role of RLPs in CVD risk is hampered by lack of a widely accepted definition and a paucity of adequate methods for their accurate and precise quantification. New specific methods for RLP quantification would greatly improve our understanding of their biology and role in promoting atherosclerosis in diabetes and other disorders. Full Article
bet Stress-Induced Translational Regulation Mediated by RNA Binding Proteins: Key Links to {beta}-Cell Failure in Diabetes By diabetes.diabetesjournals.org Published On :: 2020-03-20T11:50:28-07:00 In type 2 diabetes, β-cells endure various forms of cellular stress, including oxidative stress and endoplasmic reticulum stress, secondary to increased demand for insulin production and extracellular perturbations, including hyperglycemia. Chronic exposure to stress causes impaired insulin secretion, apoptosis, and loss of cell identity, and a combination of these processes leads to β-cell failure and severe hyperglycemia. Therefore, a better understanding of the molecular mechanisms underlying stress responses in β-cells promises to reveal new therapeutic opportunities for type 2 diabetes. In this perspective, we discuss posttranscriptional control of gene expression as a critical, but underappreciated, layer of regulation with broad importance during stress responses. Specifically, regulation of mRNA translation occurs pervasively during stress to activate gene expression programs; however, the convenience of RNA sequencing has caused translational regulation to be overlooked compared with transcriptional controls. We highlight the role of RNA binding proteins in shaping selective translational regulation during stress and the mechanisms underlying this level of regulation. A growing body of evidence indicates that RNA binding proteins control an array of processes in β-cells, including the synthesis and secretion of insulin. Therefore, systematic evaluations of translational regulation and the upstream factors shaping this level of regulation are critical areas of investigation to expand our understanding of β-cell failure in type 2 diabetes. Full Article
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bet Democratize Trade Policymaking to Better Protect Human Rights By feedproxy.google.com Published On :: Thu, 06 Jun 2019 12:11:18 +0000 12 June 2019 Dr Jennifer Ann Zerk Associate Fellow, International Law Programme There is growing interest in the use of human rights impact assessment to screen proposed trade agreements for human rights risks, and to ensure appropriate risk mitigation steps are taken. 2019-02-15-HumanRightsTradeAgreements-Smaller.jpg Tea pickers walk at dawn through the tea plantations of Munnar, Kerala, on 7 May 2017. Copyright: Pardeep Singh Gill/Getty Images With international trade discourse taking an increasingly transactional and sometimes belligerent tone, it would be easy to overlook the quiet revolution currently under way to bring new voices into trade policy development and monitoring. The traditional division of responsibilities between the executive and legislature – whereby treaties are negotiated and signed by the executive, and the legislature does what is necessary to implement them – may be undergoing some change.Growing awareness of the implications of trade and investment treaties for many aspects of day-to-day life – food standards, employment opportunities, environmental quality, availability of medicines and data protection, just to name a few – is fuelling demands by people and businesses for more of a say in the way these rules are formulated and developed.Various options for enhancing public and parliamentary scrutiny of trading proposals have recently been examined by two UK parliamentary select committees.[1] The reason for this interest is obviously Brexit, which has presented UK civil servants and parliamentarians with the unusual (some would say exciting) opportunity to design an approval and scrutiny process for trade agreements from scratch.Doubtless, EU authorization, liaison and approval procedures (which include a scrutinizing role for the European Parliament) will be influential,[2] as will the European Commission’s experience with stakeholder engagement on trade issues.[3] The recommendations of both UK select committees to include human rights impact assessment processes as part of pre-negotiation preparations[4] echo calls from UN agencies and NGOs for more rigorous and timely analysis of the human rights risks that may be posed by new trading relationships.[5] Again, EU practice with what it terms ‘sustainability impact assessment’ of future trade agreements provides a potential model to draw from.[6] However, process is no substitute for action. Human rights impact assessment is never an end in itself; rather, it is a means to a positive end, in this case a trade agreement which is aligned with the trading partners’ respective human rights obligations and aspirations. It bears remembering, though, that the idea of assessing trade proposals for future human rights risks is a relatively recent one. Do we have the tools and resources to make sure that this is a meaningful compliance and risk management exercise?Thus far there is little evidence that human rights impact assessment and stakeholder engagement exercises are having any real impact on the content of trade agreements.[7] This is the case even in the EU, where practice in these areas is the most advanced and systematic.[8]There are several possible reasons for this. First, the methodological challenges are enormous. Aside from the crystal-ball gazing needed to forecast the social, economic and environmental effects of a trade intervention well into the future, demonstrating causal links between a trade agreement and a predicted adverse impact is often highly problematic given the number of other economic and political factors that may be in play.[9]Secondly, there are many challenges around the need to engage with affected people and listen to their views.[10] The sheer number of possible impacts of a trade agreement on different individuals and communities, as well as the range of rights potentially engaged, makes this a difficult (some would say impossible) task. Some prioritization is always necessary.This makes for difficult decisions about who to engage with and how. Perceived bias or an apparent lack of even-handedness – favouring business compared to civil society, for instance – can sow mistrust about the true aims of such a process, undermining its future effectiveness as participants begin to question whether it is genuine or worthwhile.[11]The challenges are even more acute where impact assessment practitioners are tasked with investigating potential human rights impacts in other countries. Even if it is possible to get past the inevitable political sensitivities,[12] the sort of in-depth consultations required will be beyond the budget and time constraints of most assignments.[13]There are good reasons why trade policy should be subject to greater public and parliamentary scrutiny, and why there should be more opportunities for public participation in the formation of new trading regimes. By building more opportunities for stakeholder consultation at these stages, we can acquire perspectives on trade that are not available from other forms of assessment and analysis.However, policymakers should be wary of overstating the benefits of existing procedural models. Human rights impact assessment processes are still struggling to provide compelling analyses of the relationships between trade agreements and the enjoyment of human rights, let alone a roadmap for policymakers and trade negotiators as to what should be done.[14]And financial and practical barriers to participation in stakeholder engagement exercises mean that, at best, these will provide only a partial picture of stakeholder impacts and views.Experiences with human rights impact assessment of trade agreements so far demonstrate the need for realism about two things: first, the extent to which one can sensibly anticipate and analyse human rights-related risks and opportunities in the preparation stages for a new trading agreement; and, second, the extent to which problems identified in this way can be headed off with the right form of words in the treaty itself.Both recent UK select committee reports place considerable faith in the ability of pre-project transparency and scrutiny processes to flush out potential problems and prescribe solutions. Of course, there may be cases where frontloading the analysis in this way could be useful, for instance where the human rights implications are so clear that they can readily be addressed through upfront commitments by the parties concerned, whether by bespoke or standardized approaches.More often, though, for a trade agreement running many years into the future, human rights impacts and implications will take time to emerge, suggesting the need for robust monitoring and mitigation frameworks designed with longevity in mind. Ideally, pre-signing approval and assessment processes would lay the groundwork for future action by both trading partners, either jointly or separately (though preferably both).To this end, as well as developing ideas for more robust substantive provisions on human rights, policymakers should consider the institutional arrangements required – whether pursuant to the trade agreement or by complementary processes – to ensure that human rights-related risks identified during the planning stages are properly and proactively followed up, that emerging risks are tackled in a timely fashion, and that there are opportunities for meaningful stakeholder contributions to these processes.What needs to happenTrade policymakers can use human rights impact assessment to screen proposed trade treaties for human rights-related risks and to identify possible ways of mitigating those risks, whether through the terms of the agreement itself, domestic law reform or flanking measures.Building more opportunities for stakeholder consultations can enable perspectives on trade to be highlighted that are not available from other forms of assessment.Assessment is complicated, however, by methodological challenges and the difficulties of forecasting a trade agreement’s future impacts. Policymakers need to be realistic about the risks that can be anticipated, and the extent to which many of those identified can be addressed upfront in trade agreements’ terms.These inherent limitations may be overcome to some extent by better ongoing monitoring. Future trade agreements should include more robust human rights risk monitoring and mitigation frameworks, designed with longevity in mind.Notes[1] UK Joint Committee on Human Rights (2019), ‘Human Rights Protections in International Agreements, Seventeenth Report of Session 2017–19’, HC 1833 HL paper 310, 12 March 2019, https://publications.parliament.uk/pa/jt201719/jtselect/jtrights/1833/1833.pdf; and House of Commons International Trade Committee (2018), ‘UK Trade Policy Transparency and Scrutiny, Sixth Report of Session 2017-2019’, HC 1043, 29 December 2018.[2] European Parliament and Directorate General for External Policies (2019), Parliamentary scrutiny of trade policies across the western world, study paper, March 2019, http://www.europarl.europa.eu/RegData/etudes/STUD/2019/603477/EXPO_STU(2019)603477_EN.pdf.[3] European Commission (2019), ‘Trade policy and you’, http://ec.europa.eu/trade/trade-policy-and-you/index_en.htm.[4] See UK Joint Committee on Human Rights (2019), ‘Human Rights Protections in International Agreements’, para 12; and House of Commons International Trade Committee (2018), ‘UK Trade Policy Transparency and Scrutiny’, paras 124–34.[5] OHCHR (2003), Report of the High Commissioner for Human Rights on Human Rights, Trade and Investment, 2 July 2003, E/CN.4/Sub.2/2003/9, Annex, at para 63; UN Economic and Social Council (2017), ‘General Comment No 24 (2017) of the Committee on Economic, Social and Cultural Rights on State obligations under the International Covenant on Economic, Social and Cultural Rights in the context of business activities’, UN Doc. E/C.12/GC/24, 10 August 2017, para 13; and UN General Assembly (2011), ‘Guiding principles on human rights impact assessment of trade and investment agreements’, Report of the Special Rapporteur on the Right to Food, Olivier De Schutter, UN Doc. A/HRC/19/59/Add.5, 19 December 2011.[6] European Commission (2016), Handbook for Sustainability Impact Assessment (2nd ed.), Brussels: European Union, http://trade.ec.europa.eu/doclib/docs/2016/april/tradoc_154464.PDF.[7] Zerk, J. (2019), Human Rights Impact Assessment of Trade Agreements, Chatham House Research Paper, London: Royal Institute of International Affairs, https://www.chathamhouse.org/publication/human-rights-impact-assessment-trade-agreements.[8] Ibid., pp. 11–13. For a detailed explanation of the EU’s approach to human rights impact assessment, see European Commission (2016), Handbook for Sustainability Impact Assessment.[9] Zerk (2019), Human Rights Impact Assessment of Trade Agreements, pp. 14–21.[10] Ibid., pp. 21–22.[11] Ergon Associates (2011), Trade and Labour: Making effective use of trade sustainability impact assessments and monitoring mechanisms, Final Report to DG Employment, Social Affairs and Inclusion European Commission, September 2011; and Gammage, C. (2010), ‘A Sustainability Impact Assessment of the Economic Partnership Agreements: Challenging the Participatory Process’, Law and Development Review, 3(1): pp. 107–34. For a civil society view, see Trade Justice Movement (undated), ‘Trade Justice Movement submission to the International Trade Committee inquiry into UK Trade Policy Transparency and Scrutiny’, https://www.tjm.org.uk/resources/briefings/tjm-submission-to-the-international-trade-committee-inquiry-into-uk-trade-policy-transparency-and-scrutiny, esp. paras 23–32.[12] Zerk (2019), Human Rights Impact Assessment of Trade Agreements, pp. 20–21.[13] Ibid., pp. 21–22.[14] Ibid.This essay was produced for the 2019 edition of Chatham House Expert Perspectives – our annual survey of risks and opportunities in global affairs – in which our researchers identify areas where the current sets of rules, institutions and mechanisms for peaceful international cooperation are falling short, and present ideas for reform and modernization. Full Article
bet Trade, Technology and National Security: Will Europe Be Trapped Between the US and China? By feedproxy.google.com Published On :: Fri, 07 Feb 2020 15:25:01 +0000 Invitation Only Research Event 2 March 2020 - 8:00am to 9:15am Chatham House | 10 St James's Square | London | SW1Y 4LE Event participants Sir Simon Fraser, Managing Partner of Flint Global; Deputy Chairman, Chatham HouseChair: Marianne Schneider-Petsinger, Senior Research Fellow, US and the Americas Programme, Chatham House The US and China have entered into an increasingly confrontational relationship over trade and technology. This may force Europe to make difficult choices between the two economic superpowers – or perform a balancing act. Although the recent US-China phase-1 trade deal has eased the relationship for now, the trade and technology tensions are a structural issue and are likely to persist.The debate over Huawei’s participation in 5G networks is an example of how the UK and other countries may face competing priorities in economic, security and foreign policy. Can Europe avoid a binary choice between the US and China? Is it possible for the EU to position itself as a third global power in trade, technology and standard-setting? What strategies should Europeans adopt to keep the US and China engaged in the rules-based international order and what does the future hold for trade multilateralism?Sir Simon Fraser will join us for a discussion on Europe’s future role between the US and China. Sir Simon is Managing Partner of Flint Global and Deputy Chairman of Chatham House. He previously served as Permanent Secretary at the Foreign and Commonwealth Office (FCO) and Head of the UK Diplomatic Service from 2010 to 2015. Prior to that he was Permanent Secretary at the UK Department for Business, Innovation and Skills. He has also served as Director General for Europe in the FCO and Chief of Staff to European Trade Commissioner Peter Mandelson.We would like to take this opportunity to thank founding partner AIG and supporting partners Clifford Chance LLP, Diageo plc, and EY for their generous support of the Chatham House Global Trade Policy Forum. Event attributes Chatham House Rule Department/project US and the Americas Programme, Global Trade Policy Forum, US Geoeconomic Trends and Challenges US and Americas Programme Email Full Article
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bet Diabetes Core Update – October 2019 By diabetescoreupdate.libsyn.com Published On :: Tue, 24 Sep 2019 18:30:00 +0000 Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals. Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting. This month we review articles on: Nasal Glucagon Incidence of type 2 diabetes in people with a history of hospitalization for major mental illness Achievement of Target A1C <7.0% after treatment with basal insulin in Randomized Controlled Trials and Clinical Practice Metformin effect on Coronary endothelial Dysfunction in prediabetic patients with stable angina Change in cardiovascular health risk and the development of type 2 diabetes and impaired fasting glucose Association between diabetes HbA1c, glycaemia and development of frailty in the elderly For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Abington Jefferson Health Full Article
bet Diabetes Core Update – November 2019 By diabetescoreupdate.libsyn.com Published On :: Fri, 25 Oct 2019 12:46:30 +0000 Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals. Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting. This month we review articles on: Glycemia Reduction Approaches in Diabetes (GRADE) Trial The Effect of Disasters on Patients with Diabetes Fixed Ratio GLP-1/Basal Insulin in Patients Uncontrolled on GLP-1 Mechanisms of CV Protection for SGLT-2 Inhibitors Oral Semaglutide and Cardiovascular Outcomes Trends in Pancreatitis and Pancreatic Cancer in patients started on DPP-4 Inhibitors For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Abington Jefferson Health Full Article
bet Diabetes Core Update – December 2019 By diabetescoreupdate.libsyn.com Published On :: Sun, 24 Nov 2019 20:00:00 +0000 Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals. Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting. This month we review articles on: Combination Basal Insulin/GLP-1 RA vs Basal Bolus for Persons with Very Elevated A1c Changes in Consumption of Sugary Beverages and Artificially Sweetened Beverages and the Risk of Type 2 Diabetes Oral Semaglutide vs. Placebo added to Insulin : The PIONEER 8 Trial Residual Hypertriglyceridemia and Estimated Atherosclerotic CV Risk by Stain Use in U.S. Adults with Diabetes A1c Variability and the Risk of Poor Outcomes in People with Type 2 Diabetes Oral Semaglutide vs. Empagliflozin in Persons with Type 2 Diabetes Uncontrolled on Metformin For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Abington Jefferson Health Full Article
bet Diabetes Core Update – January 2019 By diabetescoreupdate.libsyn.com Published On :: Thu, 26 Dec 2019 20:41:53 +0000 Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals. Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting. This month we review articles on: Linagliptin in Older adults on Insulin Lactic Acidosis from Metformin – FDA analysis Glucagon Receptor Antagonist RV-1502 – Efficacy and Safety Early Identification of MODY SGLT-2 Inhibitors and the Development of Mycotic Infections and UTIs SFLT-2 Inhibitors in Patients with Type 1 Diabetes and the Rate of Diabetic Ketoacidosis For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Abington Jefferson Health Full Article
bet Diabetes Core Update – February 2019 By diabetescoreupdate.libsyn.com Published On :: Sat, 25 Jan 2020 11:33:45 +0000 Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association’s four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 20 minutes long and presents 5-6 recently published articles from ADA journals. Intended for practicing physicians and health care professionals, Diabetes Core Update discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting. This month we review articles on: Efficacy and safety of dapagliflozin in the elderly Lactic Acidosis from Metformin – FDA analysis Economic and Clinical Burden of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes in the United States 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Transitioning to Fixed-Ratio Combination Therapy: Practical Advice General practitioner advice associated with greater physical activity in adults with type 2 diabetes Empagliflozin Effectively Lowers Liver Fat Content For more information about each of ADA’s science and medical journals, please visit www.diabetesjournals.org. Presented by: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Abington Jefferson Health Full Article
