Day 1 :
HDR Hôpital de la Salpêtrière, France
Keynote: Value and limits of modern imaging techniques in the evaluation of fibrosis leading to Atrial Fibrillation
Time : 09:30-10:10
Guy Hugues Fontaine has made 15 original contributions at the inception of cardiac pacemakers in the mid-60s. He has identified ARVD as a side work during the beginning of antiarrhythmic surgery in the late 70s. He has published more than 860 scientific papers including 197 book chapters. He was the Reviewer of 17 journals both in clinical and basic Science. He has also served for 5 years as a Member of the Editorial Board of Circulation. He has been invited to give 11 master’s lectures of 90 minutes each during three weeks in the top universities of China (2014).
A group from Paris has attempted to demonstrate a link between fat in the epicardium of atrial tissue to the production of fibrosis as a possible mechanism of atrial fibrillation (AF). In their discussion and conclusion the authors admit that the mechanism of AF is not completely understood. After an excellent review of the CMR techniques available for the identification of fat, fibrosis and water in the heart, they note a lack of spatial resolution of modern imaging techniques that result in their performing ex vivo CMR on two hearts. This However, the modern digital microscope has an optimal resolution which could enable a more precise interpretation of the pathophysiology of AF.
The knowledge accumulated from my study of the histology of ARVD of the right ventricle from 73 patients clearly shows the topographic structure of fat, fibrosis and possible superimposed myocarditis. The atrial structure of the so-called “normal heart” is similar to that observed on the free wall of the right ventricle in ARVD. In addition to epicardial fat, there is fibrosis of two forms, interstitial fibrosis which can be the result of the genetic disorder of the disease or, replacement fibrosis which may be the result of myocarditis generally starting from the epicardium (epicardial-myocarditis as it is known by clinicians). A superimposed myocarditis may have a spectrum of presentation from the fulminant form leading to acute heart failure and death in a few days associated with invasion of both ventricles and atria by lymphocytes to that of a completely healed hyaline fibrosis. There may be intermediate aspects of myocarditis with a variable number of clusters of lymphocytes inside strands of fibrosis called the chronic-active form. Also, there may be a genetic factor now considered to be of increasing importance in the understanding of ventricular cardiomyopathies. In the background of atrial fibrillation these cardiomyopathies can be present but quiescent without arrhythmias in the general population. There can be additional complexity if we consider that myocarditis alone can cause fibrosis and adipocytes. Therefore, myocarditis can produce an arrhythmogenic substrate. In addition, the acute form can be a trigger of arrhythmias associated with an increase of CRP .The same gene that is responsible for the problem in atrial development can also explain the increased susceptibility of these hearts to be affected by myocarditis in a single or in multiple episodes by entero and adeno viruses. Therefore, the prevention or treatment of lone atrial fibrillation may be due to two targets: protection against and/or suppression of viruses and prevention of fibrosis. In the future, the ideal approach to prevention of atrial fibrillation will be the modification of the human genome using the genetic approaches such as the CRISPRcas9. Finally, the results obtained in the treatment of atrial fibrillation may be expanded to the treatment of the whole heart since the atrium and ventricle are two parts of the same embryologic structure as has been recently confirmed by the finding of “atrial dysplasia” .A simple new tool to evaluate patients at risk of atrial fibrillation and to follow the effect of treatment should be the use of the new 16 lead High Definition ECG recorder.
South Carolina State University, USA
Keynote: The stratification system of the United States: Correlations between social class and health
Time : 10:30-11:10
Carol Apt has received her PhD in Sociology from Northeastern University in Boston, Massachusetts, her Master's Degree in Sociology from Boston University in Boston, Massachusetts, and her Bachelor's Degree in Sociology from Indiana University in Indianapolis, Indiana. She also has a certificate of French Studies from Ecole Lemania in Lausanne, Switzerland. She is a Professor of Sociology and the Coordinator of the Sociology Program at South Carolina State University in Orangeburg, South Carolina, where she has been for 20 years. She teaches courses in Human Sexuality, Medical Sociology, Social problems, and the Sociology of Genocide. In 2011, she was honored as the South Carolina State University Professor of the Year. She is a Member of several Editorial Boards and is a Consulting Member of the South Carolina Medical Association Bioethics Committee. In addition to her experience as an author and newspaper and magazine columnist, she is the host of a live, call-in talk radio show entitled, "Talk to Me," which addresses issues of sexuality and relationships. It is broadcast on 90.3 FM, WSSB, an NPR affiliate.
The United States is stratified based on class and there is both upward and downward mobility. An individual's social class is determined by three factors: education, occupation, and income. It is often assumed that there are three social classes in the United States: upper, middle, and lower, but this method of categorization is simplistic and does not give an accurate picture of America in the 21st century. This presentation will explain the stratification system as it currently exists in the United States, and will describe key characteristics of individuals living within each stratum. Specifically, the presentation will focus on the health issues faced by Americans who live in the lower social classes, with emphasis on poverty, obesity, and life expectancy.
Arrowhead Pharmaceuticals, USA
Christine I Wooddell received her Graduate training in Cell and Molecular Biology with an emphasis on transcription and gene regulation. She then worked on development of gene therapy at Mirus Bio, first on the development of therapeutic gene expression vectors and then on delivery of gene therapy for Duchenne muscular dystrophy. Mirus Bio was acquired by Hoffmann-La Roche and then by Arrowhead Pharmaceuticals. She is now the Director of Liver Targeting at Arrowhead where she leads the preclinical research group to develop liver-targeted therapeutics using animal models. Since 2011 her research has focused on the development of RNA interference therapeutics to treat chronic hepatitis B virus infection and liver disease associated with alpha-1 antitrypsin deficiency (AATD). ARC-520 and ARC-521 were developed to treat HBV infection and ARC-AAT to treat AATD liver disease. These three drugs have been advanced to Phase 2 clinical trials.
Statement of the Problem: Worldwide, 250-400 million people are chronically infected with hepatitis B virus (HBV), leading to 800,000 deaths per year from liver cirrhosis, liver failure and hepatocellular carcinoma. Highly expressed viral proteins, thought to be transcribed from viral covalently closed circular DNA (cccDNA), play a role in chronicity. Nucleos (t) ide viral replication inhibitors (NUCs) do not reduce viral proteins. RNA interference (RNAi) therapeutic ARC-520 was developed to reduce all viral proteins and pre-genomic RNA. In human clinical trials, Heparc-2001 with ARC-520, HBV S antigen (HBsAg) was strongly reduced in treatment where naïve patients were positive for HBV e antigen (HBeAg) but was significantly less reduced in patients that were HBeAg negative or had received long-term therapy with NUCs.
Methodology & Theoretical Orientation: The molecular basis for this unexpected differential response was investigated by multiple approaches in chimpanzees chronically infected with HBV and treated with monthly dosing of ARC-520 in the presence of NUCs. Liver HBV mRNA was quantified and sequenced using RT-qPCR, mRNA-seq and Iso-seq. Liver HBV DNA was also quantified and sequenced.
Findings: HBsAg was expressed not only in the episomal cccDNA mini chromosome, but also in transcription of HBV DNA integrated into the host genome, which was a significant source in HBeAg negative chimpanzees. Many of these integrant-derived transcripts lacked target sites for the siRNAs in ARC-520, explaining the reduced response in HBeAg negative chimpanzees and by extension in HBeAg negative patients. Treatment of the HBeAg negative chimpanzees with siRNA hypothesized to target mRNA produced by integrated HBV resulted in deep HBsAg reductions similar to those in the HBeAg positive chimpanzees.
Conclusion & Significance: These results uncover an under-recognized source of HBsAg that may play a key role in maintaining chronicity, a finding expected to alter clinical trial design and endpoint expectations for new HBV therapies. Treatment of chronically HBV-infected chimpanzees with ARC-520.
Armed forces of Netherlands, Netherlands
Stef Stienstra works internationally for several Medical and Biotech companies as Scientific Advisory Board Member and is also an Active Reserve-Officer of the Royal Dutch Navy in his rank as Commander (OF4). For the Dutch Armed Forces. He is CBRNe specialist with focus on Microbiological and Chemical threats and Medical- and Environmental functional specialist within the 1st CMI (Civil Military Interaction) Battalion of the Dutch Armed Forces. For Expertise France he is now managing an EU CBRN CoE public health project in west Africa. In his civilian position, he is at this moment developing with MT-Derm in Berlin (Germany), a novel interdermal vaccination technology as well as a new therapy for cutaneous leishmaniasis for which he has won a Canadian ‘Grand Challenge’ grant. With Hemanua in Dublin (Ireland), he has developed an innovative blood separation unit, which is also suitable to produce convalescent plasma for Ebola virus disese therapy. He has finished both his studies in Medicine and in Biochemistry in The Netherlands with a Doctorate and has extensive practical experience in cell biology, immuno-haematology, infectous diseaases, biodefense and transfusion medicine. His natural business acumen and negotiation competence helps to initiate new successful businesses, often generated from unexpected combinations of technologies.
Public health systems are not always prepared for outbreaks of infectious diseases. Although in the past several public health institutes, like the French ‘Institute Pasteur’ and the Dutch ‘Tropeninstitute, were prominent surveyors of infectious diseases, the investments in worldwide public health have decreased. Now more attention is given to curative healthcare compared to preventive healthcare. The recent Ebola virus disease outbreak in west Africa initiated a new wave of interest to invest in Worldwide Public Health to prevent outbreaks of highly contagious diseases. Zoonotic diseases are threatening as the population does not have natural nor artificial (from vaccination) immune response to new diseases like in the Ebola virus disease outbreak in 2014. The new strain of the Ebola virus in west Africa was slightly less lethal, compared to other Ebola virus strains, but the threat of spreading was far bigger as it had a longer incubation time. Most public health systems are not trained well enough to mitigate highly infectious and deadly disease outbreaks. NGO’s helping to fight the outbreak are often better trained in curative treatments and have less experience with biological (bioweapon) threats for which the military are trained for. The UNMEER mission was unique in this. It was a setting in which military and civilian actors cooperate in fighting a biological threat. Protection is essential for health workers. Smart systems should be developed to prevent further spreading of the disease, but it is not only the biosafety, which should be considered, but also the biosecurity, as misuse of extremely dangerous strains of microorganisms cannot be excluded. Several zoonotic infectious diseases, like anthrax, smallpox and hemorrhagic fevers are listed as potential bioweapons. Therefor both biosafety and biosecurity should be implemented in all measures to fight outbreaks of highly infectious diseases.
Drew University, USA
Keynote: Culture and resistance: Antibiotic resistance in rural china and sociocultural translations of biomedicine
Time : 12:30-13:10
Paul Kadetz holds the Robert Fisher Oxnam Chair of Science and Society at Drew University. He is also a Senior Research Fellow at The University of Liverpool in China and an Associate and Lecturer of the China Centre for Health and Humanity, University College London. Paul is a Medical Anthropologist and a Clinician. In addition to his current research examining sociocultural factors contributing to antimicrobial resistance in rural China, he has conducted and published research concerning: Post-disaster recovery, global health policy, the anthropology of safety, the impact of foreign aid on local healthcare systems and healthcare challenges in China, The Philippines, Cuba, Guatemala, Madagascar and Morocco. His co-edited volume, The Handbook of Welfare in China, was recently published by Edward Elgar.
There is an assumption among biomedical practitioners that biomedicine is always understood and practiced in the same way in every culture and that, somehow, biomedicine is free from sociocultural influences. This mixed-methods pilot research employing structured interviews and observation in clinical settings and retail pharmacies- in rural Anhui, China, funded by the Medical Research Council and Newton Fund (UK) and the National Science Foundation of China identifies how sociocultural translations of biomedicine and local classifications of disease and pharmacotherapies can be imperative, but heretofore unrecognized, factors in antibiotic resistance. In addition to the overuse of antibiotics in livestock, that has entered the general food chain in China, our pilot study has identified misdiagnosis, overuse of antibiotics in treatment, and abundant purchase of antibiotics without prescriptions from retail pharmacies, as potential factors in antibiotic resistance in China. We observed little differentiation between bacterial and viral infections in clinical diagnosis and treatment; with both being commonly categorized as inflammation or infection by physicians, retail pharmacy workers and patients. Similarly, treatment was often for medicine that eliminates infection and for literally resist life medicine. Though physicians may intellectually understand the differential diagnoses between viruses and bacteria, in practice patients are often treated with intravenous antibiotics regardless of the actual etiology. This focus on treating most infections with antibiotics is mirrored in the self-treatment of retail pharmacy customers (almost all of whom were observed purchasing antibiotics without a prescription) and in the recommendations of retail pharmacy workers. These initial findings from the pilot study will guide the main research over the next two years, in which, among other areas, we will further investigate the role of political economy and the pricing and availability of antibiotics in their markedly frequent use.