1,221 research outputs found

    Analysis of local extracellular matrix identifies different aetiologies behind bicuspid and tricuspid aortic valve degeneration and suggests therapies

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    Aortic valve degeneration (AVD) is a life-threatening condition that has no medical treatment and lacks individual therapies. Although extensively studied with standard approaches, aetiologies behind AVD are unclear. We compared abundances of extracellular matrix (ECM) proteins from excised valve tissues of 88 patients with isolated AVD of normal tricuspid (TAV) and congenital bicuspid aortic valves (BAV), quantified more than 1400 proteins per ECM sample by mass spectrometry, and demonstrated that local ECM preserves molecular cues of the pathophysiological processes. The BAV ECM showed enrichment with fibrosis markers, namely Tenascin C, Osteoprotegerin, and Thrombospondin-2. The abnormal physical stress on BAV may cause a mechanical injury leading to a continuous Tenascin C-driven presence of myofibroblasts and persistent fibrosis. The TAV ECM exhibited enrichment with Annexin A3 (p = 1.1 x 10(-16) and the fold change 6.5) and a significant deficit in proteins involved in high-density lipid metabolism. These results were validated by orthogonal methods. The difference in the ECM landscape suggests distinct aetiologies between AVD of BAV and TAV; warrants different treatments of the patients with BAV and TAV; elucidates the molecular basis of AVD; and implies possible new therapeutic approaches. Our publicly available database (human_avd_ecm.surgsci. uu.se) is a rich source for medical doctors and researchers who are interested in AVD or heart ECM in general. Systematic proteomic analysis of local ECM using the methods described here may facilitate future studies of various tissues and organs in development and disease

    Episode 42: Calling an Audible

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    Runtime 1:00:12In this episode, Dr. Osterholm and host Chris Dall discuss the latest challenges related to variants of concern, the case for delaying second doses of current vaccines to broaden access to first doses, and double masking

    Episode 43: A Realist Adjusts the Sails

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    Runtime 1:00:00In this episode, Dr. Osterholm and host Chris Dall discuss the current trajectory of the pandemic and inconsistent public health messaging in the US, the latest information on variants and considerations for prioritizing first doses of vaccine, and questions related to the safety of dental and medical care amid the pandemic

    Episode 41: Surrender Is Not an Option

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    Runtime 54:47In this episode, Dr. Osterholm and host Chris Dall discuss the issue of opening schools, updates on variants of concern, and more news on vaccines and their distribution

    Episode 38: Places We've Never Been

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    Runtime 1:03:20In this episode, Dr. Osterholm and host Chris Dall discuss the rotating epidemiology of the pandemic in the US, updates on variants of the virus and what they might mean moving forward, and challenges with the last mile and the last inch of vaccine distribution

    A Research and Development (R&D) roadmap for influenza vaccines: Looking toward the future

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    Improved influenza vaccines are urgently needed to reduce the burden of seasonal influenza and to ensure a rapid and effective public-health response to future influenza pandemics. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was created, through an extensive international stakeholder engagement process, to promote influenza vaccine R&D. The roadmap covers a 10-year timeframe and is organized into six sections: virology; immunology; vaccinology for seasonal influenza vaccines; vaccinology for universal influenza vaccines; animal and human influenza virus infection models; and policy, finance, and regulation. Each section identifies barriers, gaps, strategic goals, milestones, and additional R&D priorities germane to that area. The roadmap includes 113 specific R&D milestones, 37 of which have been designated high priority by the IVR expert taskforce. This report summarizes the major issues and priority areas of research outlined in the IVR. By identifying the key issues and steps to address them, the roadmap not only encourages research aimed at new solutions, but also provides guidance on the use of innovative tools to drive breakthroughs in influenza vaccine R&D

    A Research and Development (R&D) roadmap for influenza vaccines: Looking toward the future

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    Improved influenza vaccines are urgently needed to reduce the burden of seasonal influenza and to ensure a rapid and effective public-health response to future influenza pandemics. The Influenza Vaccines Research and Development (R&D) Roadmap (IVR) was created, through an extensive international stakeholder engagement process, to promote influenza vaccine R&D. The roadmap covers a 10-year timeframe and is organized into six sections: virology; immunology; vaccinology for seasonal influenza vaccines; vaccinology for universal influenza vaccines; animal and human influenza virus infection models; and policy, finance, and regulation. Each section identifies barriers, gaps, strategic goals, milestones, and additional R&D priorities germane to that area. The roadmap includes 113 specific R&D milestones, 37 of which have been designated high priority by the IVR expert taskforce. This report summarizes the major issues and priority areas of research outlined in the IVR. By identifying the key issues and steps to address them, the roadmap not only encourages research aimed at new solutions, but also provides guidance on the use of innovative tools to drive breakthroughs in influenza vaccine R&D.publishedVersio

    Episode 22: Pregnancy in a Pandemic

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    Runtime 1:15:13In this episode, Dr. Osterholm and host Chris Dall discuss herd immunity and the COVID-19 death toll, reports of more reinfections, what is known about pregnancy during the pandemic, and the critical need for data on vaccine safety and effectiveness before approval

    Episode 12: A Tale of Two Countries

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    Runtime 56:32In this episode, Dr. Osterholm and host Chris Dall discuss recent trends in cases across the United States, the public's current perception of this pandemic and its timeline, an outbreak of cases in Beijing, the challenges that might occur if influenza season overlaps with ongoing COVID-19 activity, and the phases of vaccine development
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