Podcasts about Shinya

Welcome to the Youtini Canon Book Club! In this episode, Emmi, JG, and Hannah break down their thoughts on The Edge of Balance Vol. 3 by Shima Shinya & Daniel Jose Older, the fourth installment of The High Republic: Edge of Balance series. We get into the incredible horror themes of this manga, the ongoing internal struggle that Azlin Rell faces, and the continued threat of the Nihil and Marchion Ro's mysterious Blight. Pour yourself a cup of caf and enjoy!

Zach and Rashmi conclude their journey through Japanese Horror Cinema with a leap forward in time to that terrifying new metal world as they deep dive Shinya Tsukamoto's 1989 cult classic, TETSUO: THE IRON MAN! Join them as they get lost in Shinya's whirlpool of madness and the many ways this cyber-punk terror piece has shaped the world of horror and cinema at large. PLUS: A SPECIAL ANNOUNCEMENT!

Puroresu France l'hebdo, c'est le meilleur moyen de se tenir au courant de l'actualité du Puroresu, Je vous explique ce qu'il s'est passé, j'analyse les matches et résultat, le podcast est également disponible en version podcast sur toutes les plateformes de podcast. Retrouvez toutes les news de Puroresu France sur le compte twiter : https://twitter.com/PURORESUFR Me suivre : https://twitter.com/CodyMcWildOff https://www.instagram.com/cody.mcwild/ https://twitter.com/ChezCodyMcWild #Puroresu #Wrestling #Catch 00:00 - Intro 00:30 - Yoshinari Ogawa prend sa retraite 02:33 - Nouveau champion KO-D chez DDT 06:53 - Nouveau champion Triple Crown chez AJPW Soutenez-nous sur PayPal !

In the quest for a more sustainable future, technological innovation plays a pivotal role. At the forefront of this movement is Shimizu Shinya, Founder and CEO of Elephantech Inc. With a profound commitment to environmental sustainability and a passion for groundbreaking science, Shimizu is transforming the landscape of electronics manufacturing. His journey from a science enthusiast in Japan to leading an innovative tech company embodies the intersection of cutting-edge technology and ecological responsibility. Join us as we explore Shimizu's vision, the revolutionary technology behind Elephantech, and the company's mission to engineer a greener planet. [01:11] - About Shimizu Shinya Shimizu is the Co-founder and CEO of Elephantech Inc. He started his career as a Business Analyst with McKinsey & Company. --- Support this podcast: https://podcasters.spotify.com/pod/show/tbcy/support

In this episode of Talking HealthTech, host Peter Birch is in Tokyo, Japan, speaking with Shinya Yamamoto, a startup mentor, clinical research innovation professor, and futurist. They delve into the opportunities and challenges in the healthtech industry in Japan, addressing the impact of an ageing population and rising healthcare costs. Shinya provides insightful perspectives on the Japanese healthcare ecosystem, the need for innovation, and the government's increased interest in supporting technology startups.Key Takeaways- Healthcare Challenges in Japan: The discussion highlights the challenges posed by an ageing population and rising healthcare costs in Japan, which creates a need for innovation and technological advancements in the industry.- Role of Small Incubators: Shinya emphasises the significance of small incubators and startups in driving innovation, given the nimbleness and flexibility they offer compared to large organisations.- Government Support and Global Market Entry: Shinya explains the Japanese government's increasing interest in supporting startups, making it an opportune time for entrepreneurs to enter the Japanese market. He also discusses the importance of building with a global mindset for technology startups.Check out the episode and full show notes on the Talking HealthTech website.Loving the show? Leave us a review, and share it with someone who might get some value from it.Keen to take your healthtech to the next level? Become a THT+ Member for access to our online community forum, quarterly summits and more exclusive content. For more information visit talkinghealthtech.com/thtplus

Do you hear that sound? Can you feel it? The cool ocean breeze in your hair, the salt on your tongue. It's the smooth crash of KVGM "The Last Wave", with your host, Hammock. A biweekly VGM podcast bringing you the jammiest video game music from all your favorite composers and consoles. Sit back, relax, and get ready to catch...the Last Wave. We are thrilled to be a part of RadioSEGA's WinterFest 2023 line-up this year and bring you some wintry smooth jams to help you celebrate the holidays in style! We've got a good mix of consoles and composers, including some old favorites and some new friends. Be sure to check out the other shows participating in this year's event! And credit goes to From Ashes To Fire for the event artwork. Playlist Wintersville - Soichi Terada (Ape Escape 3, Sony PlayStation 2) Powder Snow Dance - Hideki Hashimoto (Zutto Issho: With Me Everytime, Sony PlayStation) Victory - Hiroaki Yoshida (Winter Heat, Sega Saturn) Class (Winter) - Starbit Light (Daigaku Gurashi, PC) Snow Mountain - Junya Matsuoka (Tenerezza, Microsoft Xbox) Winter Morning - Zbigniew Siatecki (Ultimate Card Games, Game Boy Advance) Menu 2 - Frank Herrlinger and Gösta Feiweier (RTL Winter Games 2007, Sony PlayStation 2) Tomomi (Winter) - Shoichiro Hirata (Aitakute…Your Smiles in My Heart, Sony PlayStation) Winter Vacation - Shinya Ishikawa (White Album, Sony PlayStation 3) Winter Outside the Window - Naotoshi Nishino (Last Escort 2: Shinya no Amai Toge, Sony PlayStation 2) Special Request A Road Where the Wind Dances - Akari Kaida (Luminous Arc 2, Nintendo DS)

Shinya Tateiwa, a sociologist and professor at Ritsumeikan University, who was known for his essays on the disabled and euthanasia, including a critique of the murder case at a facility for people with disabilities in Sagamihara, passed away at 1:33 p.m. on July 31 at a hospital in Sakyo-ku, Kyoto City due to a malignant lymphoma. He was 62 years old. Please forgive my bad pronunciation of the late Prof. Tateiwa's name, 'Tateiwa'. In the 'English tongue' it is best pronounced as 'Tateh-Ihwa', with the emphasis on the 'ihwa'. I find the name difficult to say. Episode Notes: https://barrierfreejapan.com/2023/08/01/shinya-tateiwa-sociologist-who-researched-people-with-disabilities-dies-aged-62/

•Dieta para prevenir enfermedades del corazón, curar el cáncer, frenar la diabetes •Cómo el amor activa el sistema inmunológico •Cómo fortalecer las defensas de tu cuerpo •Errores de muchas dietas •Cómo ser más saludable •Cómo verte más joven Estos son algunos de los temas de los que habla este libro. ¡A seguir aprendiendo!

•Dieta para prevenir enfermedades del corazón, curar el cáncer, frenar la diabetes •Cómo el amor activa el sistema inmunológico •Cómo fortalecer las defensas de tu cuerpo •Errores de muchas dietas •Cómo ser más saludable •Cómo verte más joven Estos son algunos de los temas de los que habla este libro. ¡A seguir aprendiendo!

Shinya Kakita is a BJJ black belt, coach at Synergy MMA, and the head official of ADCC South East Asia. In this episode we talk about the ADCC schedule this year, training, and a potential rematch of a bjj match we had 10 years ago... Also maybe current ADCC absolute champion Yuri Simões on the podcast next week...? hope you enjoy the conversation

Discover the secret to becoming a successful researcher! According to Shinya Murakami, Professor and Chair of the Periondontal Department at the University of Osaka, Japan, having the right research question is essential for maintaining motivation and reaching new heights in your field. In his inspiring interview with Reinhard Gruber, Murakami shares his personal journey. He talks about how he overcame obstacles to discover the groundbreaking potential of the fibroblast growth factor. This factor was later associated with stimulating the regeneration of periodontal tissue. Learn how he persevered through the tough times and kept his curiosity alive, always on the lookout for the next big question.

An incredible career that deserves to be highlighted.

Shinya Satake - Rank: Member | Price Group: Affiliate Member | Store URL | PV: $0.00 (30D) - $0.00 (90D) | Sales Summary | Order History | From 岡山市北区表町, Okayama | Joined May, 2021 | goshogionlinelesson@gmail.com | +819097398546 https://www.solveres.com/store/shinyasatake #solveres #member #opportunity --- Send in a voice message: https://anchor.fm/jack-bosma3/message Support this podcast: https://anchor.fm/jack-bosma3/support

Do you know who Maku Donaruto is? That name sure sounds familiar, doesn't it? If you have never seen a Maku Donaruto match get ready to have your mind blown, he is a true one of a kind. In this week's episode Maku joins the episode to give his own hilarious review of the match (In Japanese). In addition to that, Jim and Tariq talk about their childhood memories of McDonald's and what ever kid born in the 1970's dreamed of. We also focus on some of the differences between McDonald's as you know it and McDonald's Japan. Jim was salivating for most of that segment. The match this week left both of us speechless, shocking, funny, entertaining, no words did this match any justice. To find out more about Maku Donaruto you can go to his homepage at https://maku-donaruto.com to see his blog, dates and much more. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app Support this podcast: https://anchor.fm/sixmantagpodcast/support

This week, please join author Sean Pokorney and Associate Editor Shinya Goto as they discuss the article "Apixaban for Patients With Atrial Fibrillation on Hemodialysis: A Multicenter Randomized Controlled Trial." Dr Carolyn Lam:               Welcome to Circulation on the Run, your weekly podcast summary and Backstage Pass of the journal and its editors. We're your cohost. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley:            And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Carolyn, this week's feature, very interesting topic. In patients that have end stage renal disease that require dialysis, questions emerged should we anticoagulate them to prevent stroke, but of course, there's a risk of excess bleeding. Well, this feature discussion today is a study comparing apixaban and warfarin for anticoagulation in exactly this patient population. But before we get to those results, how about we grab a cup of coffee and go through some of the other articles in the issue? Would you like to go first? Dr Carolyn Lam:               Absolutely, Greg. So my first paper is a pre-specified analysis of the Paradise MI trial and knowing you'll likely ask me what that was about, Greg, at least to summarize for everyone, the Paradise MI trial compared sacubitril/valsartan with ramipril and its effect on reducing heart failure events after an MI in more than 5,600 patients with an acute myocardial infarction complicated by LV systolic dysfunction, pulmonary congestion, or both. Now in today's paper, what Dr. Mehran and colleagues found was that among patients with a recent AMI and LV systolic dysfunction, heart failure are both, sacubitril/valsartan decreased the risk of coronary related events by 14% as compared with ramipril over a median follow-up of 22 months. The reduction in coronary events occurred with a favorable safety profile. Dr Greg Hundley:            Wow, Carolyn, very interesting. Another indication perhaps for sacubitril/valsartan, especially relative to ACE inhibitors. So what does this mean for us clinically? Dr Carolyn Lam:               Well, the results really cause us to consider if in addition to antiplatelets and lipid lowering therapies, sacubitril/valsartan may be explored as a potential agent to mitigate the residual risk in survivors of AMI. Of course, dedicated studies are necessary to confirm this finding and elucidate its mechanism. Dr Greg Hundley:            Oh, very nice, Carolyn. Well, my first paper comes to us from the World of Preclinical Science and Carolyn, this study evaluated the scavenger receptors stabilin-1 and stabilin-2, proteins that are preferentially expressed by liver sinusoidal endothelial cells. Now, they mediate the clearance of circulating plasma molecules controlling distant organ homeostasis. And studies suggest that stabilin-1 and stabilin-2 may impact atherosclerosis. So in this study, the investigative team led by Professor Cyrill Géraud from the University Medical Center and Medical Faculty in Mannheim, Heidelberg comprehensively studied how targeting stabilin-1 and stabilin-2 affects atherosclerosis. Dr Carolyn Lam:               Huh. All right, nicely explained. And so what did they find, Greg? Dr Greg Hundley:            Right, Carolyn. So inhibition of evolutionary conserved class H scavenger receptors, stabilin-1 and stabilin-2, reduced aortic plaque burden in preclinical models and athero protection was mediated likely through down regulation on transcriptional factor ERG1 in monocytes by multifaceted plasma protein changes. And then finally, Carolyn transforming growth factor beta induced periostin, reelin, and they are novel ligands of stabilin-1 and stabilin-2 and are implicated in the development of atherosclerosis. Dr Carolyn Lam:               Okay. Wow. Could you give us a take home message, please Greg? Dr Greg Hundley:            Right. Carolyn, I knew you had asked me this. So here we go. Monoclonal, anti-stabilin-1 and anti-stabilin-2 antibodies provide a novel approach for the future treatment of atherosclerosis. And in the future, perhaps the plasma proteome composition may serve as a predictive factor, biomarker or surrogate parameter for cardiovascular disease in patients. Dr Carolyn Lam:               Wow. Thanks Greg. My next paper is a true story of discovery. Now I could ask you what you know about the condition hypertension with brachydactyly type E... Greg, I love that expression. I wouldn't be able to answer that too. So let me tell you the story. So hypertension with brachydactyly type E is an autosomal dominant Mendelian disease resembling essential hypertension. Untreated patients die of stroke by the age of 50 years. Now, these authors had previously demonstrated a gain of function phosphodiesterase 3A gene mutations that caused the condition by increasing peripheral vascular resistance. They studied a large family with the condition earlier and were puzzled that cardiac hypertrophy and heart failure did not occur despite the decades of hypertension. And so they hypothesized that in the heart, this phosphodiesterase 3A or PDE3A mutations could be protective. Isn't that neat? And so corresponding authors, Doctors Bader, Klussmann, Bähring and Hübner, all from the Max Delbruck Center for Molecular Medicine in Berlin, Germany. So they studied new patients as well as CRISPR-Cas9 engineered rat models of this condition of hypertension with brachydactyly type E. And they comprehensively phenotyped all of them with the human induced pluripotent stem cells carrying these PDE3A mutations as well. So analyzing all of this from cells to new patients to CRISPR-Cas9 models. Dr Greg Hundley:            Wow, Carolyn, what an interesting story. So what did they find? Dr Carolyn Lam:               So while in vascular smooth muscle, the PDE3A mutations caused hypertension, in the hearts, they conferred protection against hypertension-induced cardiac damage, hypertrophy and heart failure. The mechanism involved long-term adaptations of mRNA and protein expression as well as calcium cycling. Non-selective PDE3A inhibition was a final short term option in heart failure treatment to increase cardiac cyclic AMP and improve contractility. So the data argued that mimicking the effect of PDE3A mutations in the heart rather than non-selective PDE3 inhibition was cardioprotective in the long term. And these findings could indeed facilitate the search for new treatments to prevent hypertension-induced cardiac damage. This is discussed in a really lovely editorial by Dr. Chiong, Houslay, and Lavandero. Dr Greg Hundley:            Very nice, Carolyn. Wow. What another... we have such great articles from the World of Preclinical Science. Beautiful description as well. Well, we have some other articles in the issue, particularly from the Mailbag. And we have a Research Letter from Professor Thiagarajan entitled “Yield of Cardiac MRI in a pre-participation cohort of Young Asian males with T-Wave inversion.” Dr Carolyn Lam:               Interesting. There's an exchange of letters between Dr. Xu and Huang regarding the article associations of dietary cholesterol, serum cholesterol and egg consumption with overall and cause-specific mortality with a systematic review and updated meta-analysis. There is a Perspective piece by Dr. Marcus on Smart watch detected atrial fibrillation, the value in positive predictive value. Isn't that interesting? And now onto that very, very important question of anticoagulation in patients with kidney disease. Can't wait. Let's go, shall we? Dr Greg Hundley:            You bet. Carolyn. Welcome listeners to our December 6th feature discussion. And we have with us today Dr. Sean Pokorney from Duke University in Durham, North Carolina, and our associate editor, Dr. Shinya Goto from Tokai University in Isehara, Japan. Welcome gentlemen. Well, Sean, we're going to start with you. Can you describe for us some of the background information that went into the preparation of your study and what was the hypothesis that you wanted to address? Dr. Sean Pokorney:         Yeah, absolutely. Thanks for having me to discuss the renal AF trial. And so I would say that the background information to the study was that we know that atrial fibrillation is an incredibly common condition in patients with chronic kidney disease. And the decision of anticoagulation in patients with end-stage kidney disease, on hemodialysis is really quite complex because these patients are at high risk for stroke and they're at high risk for bleeding. There are concerns with warfarin around calcific uremic arteriolopathy or calciphylaxis and there have been some data including from the original Aristotle trial that apixaban was even more favorable in terms of bleeding reduction relative to warfarin in patients with more advanced chronic kidney disease. Although patients with creatinine clearance less than 25 were excluded from Aristotle and really all patients with endstage kidney disease on hemodialysis have been excluded from all trials of atrial fibrillation in the past. And so we really wanted to evaluate the safety of apixaban versus warfarin in patients with end-stage kidney disease, on hemodialysis. And the hypothesis was that apixaban was going to be non-inferior to warfarin with respect to safety in terms of major or clinically relevant, non-major bleeding in these patients with atrial fibrillation and end stage kidney disease on hemodialysis. Dr Greg Hundley:            Thanks so much, Sean. And you've mentioned the renal AF trial. So could you describe for us, for your, I guess, substudy, what was the study population? Who did you include and describe for us also your study design? Dr. Sean Pokorney:         Yeah, absolutely. So the trial included patients who had end-stage kidney disease, and/or on hemodialysis, as well as having concomitant atrial fibrillation. And the patients had to have a CHA-VASc score greater than equal to two. All of the patients had to be on hemodialysis for at least three months. So these were chronic hemodialysis patients. And the study design was an open label randomized trial that was 1:1 randomization between apixaban and warfarin with blinded outcome evaluation. And again, the primary endpoint of the study was major or clinically relevant non-major bleeding based on ISTH definitions. And there were secondary endpoints looking at stroke, systemic embolism, death, medication adherence, and I think a really important sub-study looking at PK data. And the goal was to have 50 patients where we included PK data that was going to more represent what chronic apixaban dosing data would look like in these patients with end-stage kidney disease on hemodialysis. And originally the goal of the trial was to include over 700 patients. Originally we were trying to include 762 patients based on our initial power calculations to achieve true non-inferiority. Unfortunately, the trial enrollment was low and so the trial was ultimately stopped prematurely at 154 patients, although we were able to include the original targeted 50 patients in the PK substudy. The dosing that we used in the renal AF trial was 5 mg of apixaban twice daily unless patients had a second dose-reduction criteria in addition to chronic kidney disease. So the fact that they had end-stage kidney disease and were on hemodialysis counted as one dose reduction criteria and patients that were under 60 kilograms or less were 80 years of age or older, who had then a second dose-reduction criteria were treated with the 2.5 mg twice daily dosage. And this was important to note because this is different than the dosage that was used in the AXADIA-AFNET trial. Dr Greg Hundley:            Very nice. And so Sean, what did you find? Dr. Sean Pokorney:         Yeah. So again, a lot of this data is really exploratory because of the limited sample size, we weren't really able to definitively conclude anything about the major or clinically relevant non-major bleeding rates. I would say that some of the key findings that we saw was that there were high rates of major or clinically relevant non-major bleeding in both arms of the trial and one year bleeding event rates were 25% in the warfarin arm and 31% in the apixaban arm. And again, there was no statistically significant difference, although again, this is really exploratory. I would say that some of the other interesting findings that we saw was that there were very low rates of ischemic and hemorrhagic stroke in this patient population. Again, there were 82 patients randomized to apixaban, 72 patients randomized to warfarin. And there was a difference in the randomization because of the stratification by site that was performed with the randomization. And so within the 82 patients that were randomized to apixaban, the patients, there was one ischemic stroke and one hemorrhagic stroke. There were no hemorrhagic strokes in the warfarin population and two ischemic strokes. Another key finding was the high rates of mortality in this patient population. So 26% of the apixaban patients experienced a mortality event, 18% in the warfarin arm. So again, the mortality rates in these patient populations were extremely high. I would also emphasize some of the data from the PK analysis. So we looked at the PK analysis in two different ways. For the patients that were treated with the 5 mg dose of apixaban, the PK data showed that there was consistent overlap in the steady state concentration at one month compared to patients in the Aristotle trial that had really mild to moderate, moderate to severe and severe chronic kidney disease. And so there was a consistent overlap in those steady state concentrations between the end-stage kidney disease population on hemodialysis and the chronic kidney disease population who benefited from a apixaban in the Aristotle trial. Similarly, in the 2.5 mg apixaban dose, the patient who had a second dose reduction criteria in addition to chronic kidney disease, those patients had consistent steady state concentrations of apixaban relative to patients with mild to severe chronic kidney disease. Dr Greg Hundley:            Very nice. Well thank you so much, Sean. And listeners, now we're going to turn to our associate editor, Dr. Shinya Goto. Shinya, can you, sort of, highlight for us some of the interesting findings that you see from these study results that Sean just presented? Dr. Shinya Goto:              Thank you, Greg. Thank you, Sean for your wonderful summary of your study. We had a great discussion with an editor for this paper. As Sean pointed out, this is a kind of underpowered trial or just terminated early, hypothesis was not tested in the trial. But this population of patient clearly needs a real-world clinical trial, patient with atrial fibrillation, end-stage kidney disease, on hemodialysis; things a clinician could do. In some country, nephology society defined warfarin contraindicated in this population. As Sean pointed out, whether the development of this trial include this high-risk population patient. So we had a discussion whether the underpowered trial provided something or nothing may be better than something just provided here. Our consensus finally reached was, this limited trial still provide something like, you have to make a decision to use the anticoagulation. I mean, that the apixaban might be still used due to the PK data. That is the kind of interesting point of this trial. Dr Greg Hundley:            Very nice Shinya. Well, Sean, turning back to you and Shinya with that nice lead in really, Sean, what do you think is the next study that needs to be performed in this sphere of research? Dr. Sean Pokorney:         Yeah, absolutely. I think this is a challenging patient population to study. And again, our trial, the renal AF trial stopped early. Unfortunately, the AXADIA-AFNET 8 study also stopped early, which was also looking at apixaban versus warfarin outside the US and Europe. And so again, it is a challenging patient population to study. But again, I also think it's a really important population to study because one of the main unanswered questions in this population is whether or not they should receive anticoagulation. And so I think that ultimately more work and additional studies trying to determine whether or not these patients truly benefit from anticoagulation or stroke prevention, I think is really one of the critical directions that we need to take the field in. Dr Greg Hundley:            And Shinya, do you have anything to add? Dr. Shinya Goto:              Well, I fully agree with Sean. I mean, this is a very challenging area and still raising the question whether anticoagulation is necessary or not by your study. Maybe next generation oral anticoagulant such as Factor XI inhibitor that is more elevated to contact pathway may be beneficial. So we really need a good clinical study in this very important and known answered area. Dr Greg Hundley:            Very nice. Well listeners, we want to thank Dr. Dr. Sean Pokorney from Duke University in Durham, North Carolina and our own associate editor, Dr. Shinya Goto from Tokai University in Japan for bringing us the results of this randomized open-label trial of apixaban versus warfarin in patients with chronic kidney disease on hemodialysis, revealing high rates of bleeding in both groups, but due to low enrollment, was unable to identify its non-inferiority endpoint. It's important to note, however, as both our author and editorialists have identified further research is really needed in this area to really examine the efficacy of anticoagulation for stroke prevention in this high-risk patient population. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week On The Run. Dr. Greg Hundley:           This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

PHẦN 1: Hãy làm sạch vị tướng, tràng tướng Vị tướng, tràng tướng khỏe đẹp và vị tướng, tràng tướng không khỏe mạnh Thói quen sinh hoạt của người có vị tướng, tràng tướng đẹp Vị tướng, tràng tướng đẹp thường khó mắc bệnh ung thư Đường ruột là “bộ não thứ hai” tự suy nghĩ Thứ nắm giữ gốc rễ của sức khỏe Năm quá trình lưu thông tạo ra “sức khỏe” và bảy phương pháp sống khỏe mạnh Không bỏ qua “tiếng gọi của dạ dày” PHẦN 2: Thói quen ăn uống lành mạnh Hoạt động của enzyme chi phối sức khỏe cơ thể Enzyme trong cơ thể bạn có giảm không? Tự kiểm tra nào Nhai kỹ để tăng lượng enzyme Tỷ lệ bữa ăn lý tưởng: 85% thực vật – 15% động vật Ăn các loại thực phẩm chứa nhiều enzyme Lựa chọn các sản phẩm tự nhiên, tươi mới Ăn các loại ngũ cốc chất lượng tốt như “chưa tinh chế”, “bột mì nguyên chất” Cách hấp thu tốt các chất béo thiết yếu và thịt động vật Uống nước một tiếng, ăn hoa quả 30 phút trước khi ăn Nhiều hóa chất thực vật – nhiều enzyme Không phải là muối ăn, muối biển tự nhiên mới tốt cho cơ thể Ăn bữa tối năm tiếng trước khi ngủ Uống “nước” chứ không phải là các loại “đồ uống” Đừng bỏ sót các dấu hiệu thiếu “nước” Tránh xa thịt động vật vì nó có hại cho dạ dày Các thực phẩm thay thế bơ thực vật, sữa bò, mỡ “Thực phẩm trắng” là thực phẩm không tốt cho cơ thể Nghiêm cấm uống rượu và hút thuốc lá PHẦN 3: Phương pháp thải độc cho cơ thể Tại sao bị táo bón lại không tốt cho cơ thể? Độc tố trong cơ thể bạn đang ở mức nào? Ăn để thải độc Uống nước tốt để thải độc Ngâm bồn hay mát xa có lợi cho lưu thông thể dịch Đào thải độc tố qua phân/ Coffee enamas giúp đại tiện tốt hơn PHẦN 4: Thói quen này giúp tạo ra một cơ thể không bệnh tật Tập thói quen sinh hoạt để cải thiện tình trạng thân nhiệt thấp Vận động “điều độ” tốt hơn “quá mức” Sau khi ăn trưa, ngủ trưa 15 – 20 phút Thở sâu bằng bụng là phương pháp sống khỏe ưu việt Bài tập giãn cơ đơn giản tại văn phòng --- Send in a voice message: https://podcasters.spotify.com/pod/show/taosins/message

Chương 1: SỰ KHÁC NHAU GIỮA “NGƯỜI TRÔNG TRẺ TRUNG” VÀ “NGƯỜI TRÔNG GIÀ CỖI” Tại sao phụ nữ sau khi chồng mất lại trẻ trung đến vậy? Nhìn vào nước da cũng có thể biết được tuổi của đường ruột Tràng tướng của những người sống lâu hơn trăm tuổi ra sao? Dù là bệnh tật hay lão hóa đều có nguyên nhân liên quan đến tình trạng tràng tướng xấu đi “Thức ăn kích thích quá trình lão hóa” chính là đây Thực phẩm thực vật cho một “làn da mochi”, thực phẩm động vật cho một làn da sần sùi Chế độ ăn kiêng atkins làm tràng tướng xấu đi Sự khác biệt giữa béo phì do mỡ nội tạng và béo phì do mỡ dưới da Gan ngỗng vỗ béo thực ra là loại gan nhiễm mỡ quá nhiều dinh dưỡng Hãy nhớ rằng một cốc rượu là một cốc “đánh đổi sự trẻ trung” của bản thân Càng tâm tâm niệm niệm thì bạn lại càng trẻ lâu --- Send in a voice message: https://podcasters.spotify.com/pod/show/taosins/message

CHƯƠNG 1 PHƯƠNG PHÁP SỐNG ĐẠT ĐẾN TUỔI THỌ TỰ NHIÊN Câu nói cửa miệng của mẹ tôi là: “Hãy trở thành một bác sĩ như Hideyo Noguchi!” Đừng sống “bùng nổ để rồi vụt tắt”, hãy sống “bùng nổ nhưng vẫn dài lâu” Đừng để giá trị tuổi thọ trung bình đánh lừa Lý do người dân Okinawa sống lâu dù rất hay ăn thịt lợn Tại sao vẫn có những người có thói quen hút thuốc mà lại sống được đến 90 tuổi? “Cả nhà tôi đều bị ung thư”, chuyện này không phải là số mệnh Bạn nên cẩn thận với các phương pháp chống lão hóa Phương pháp chống lão hóa tốt nhất chính là sống lành mạnh Bí quyết trường thọ và khỏe mạnh mà enzyme chỉ cho chúng ta --- Send in a voice message: https://podcasters.spotify.com/pod/show/taosins/message

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This week, please join author Jonathan Sterne and Associate Editor Shinya Goto as they discuss the article "Association of COVID-19 With Major Arterial and Venous Thrombotic Diseases: A Population-Wide Cohort Study of 48 Million Adults in England and Wales." Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. We're your co-hosts. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, associate editor, director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Oh, Greg, we've got a special treat for everyone today. We have a third co-host and he is none other than Peder Myhre from Norway! Really adding to the diversity of our podcast: me from Asia, you from the US, and Peder from Europe. Welcome, Peder. Dr. Peder Myhre: Thank you so much, Carolyn. It's truly an honor to be here and I'm looking forward to being part of this podcast today. Dr. Carolyn Lam: Awesome. Well, here we go. Looks like we have a feature paper, Greg? Dr. Greg Hundley: Absolutely, Carolyn. Peder, welcome. So, listeners, our feature today will involve COVID-19 and its association with arterial and venous thrombotic diseases. But before we get to that, we're going to all grab a cup of coffee from all over the world and get into some of the other articles in the issue. Peder, Carolyn, how about I go first? My first study involves a prospective cohort of 94,000 individuals from the UK Biobank, who had device-measured physical activity from 2013 to 2015 and were free from myocardial infarction and heart failure. Now, Peder and Carolyn, the study was performed because although objectively measured physical activity has been found associated with acute cardiovascular outcomes, it has not been found associated with heart failure and, of course, a syndrome that's been expanding worldwide. As such this study led by Carlos Celis-Morales from the University of Glasgow aimed to investigate the dose response relationship between device-measured physical activity and heart failure by intensity of the physical activity. Now physical activity was measured with a wrist-worn accelerometer and time spent on light, moderate, and vigorous intensity physical activity was extracted. Incidental heart failure was ascertained from linked hospital and death records. Dr. Peder Myhre: Wow, Greg. That sounds amazing. Tell us, what did they find? Dr. Greg Hundley: You bet, Peder! These investigators found that, compared with participants who undertook no moderate to vigorous intensity physical activity, those who performed 150 to 300 minutes per week of moderate intensity physical activity or 75 to 150 minutes per week of vigorous intensity physical activity were at lower risk of heart failure. Now, interestingly, the association between vigorous intensity physical activity and heart failure was a reverse J-shaped curve with a potentially lower risk reduction above 150 minutes per week. And so, the take-home message for this first paper is that device-measured physical activity, especially moderate intensity physical activity, was associated with a lower risk of heart failure. Probably current vigorous intensity physical activity recommendations should be encouraged, but not necessarily increased. In contrast, increasing moderate intensity physical activity may be beneficial, even among those meeting current recommendations. Dr. Peder Myhre: Wow, Greg. That was a great summary. And the second original research article today is about high density lipoproteins. As you know, raising HDL cholesterol levels to prevent cardiovascular disease remains a hot topic. HDL plays a key role in reverse cholesterol transport and may be cardioprotective and reduce infarct size in the setting of myocardial injury. Lecithin cholesterol acyl transferase, LCAT, is the rate limiting enzyme in the reverse cholesterol transport and a recombinant human LCAT called MEDI6012 has previously been shown to increase HDL cholesterol. So in this study from the corresponding author, Marc Bonaca from University of Colorado School of Medicine, the investigators in the real team is 63B multicenter placebo control trial investigated whether randomized patients to, MEDI6012 or placebo would reduce the infarct size as measured by cardiac MRI, 10 to 12 weeks after the STEMI. Dr. Greg Hundley: Very interesting, Peder. So, MRI assessments of LV mass after PCI. So, what did they find? Dr. Peder Myhre: So, Greg, the authors successfully enrolled 593 patients with a median age of 62 years and 78% males. And the median time from symptom onset to randomization was 146 minutes and only 13 minutes from hospitalization to randomization. And the index MI was anterior in 70% and 65% had TIMI Flow grade 0-1. And then to the main results at 12 weeks, the infarct size did not defer between the treatment group. So that was a 9.7% infarct size for MEDI6012 versus 10.5% for placebo with a P value of 0.79. And there was also no difference in noncalcified black volume. So the authors conclude that enhanced reverse cholesterol transport with recombinant human LCAT did not reduce infarct size or late regression of noncalcified coronary REPL at 12 weeks. Okay, Greg. So tell me about the 3rd paper you have today? Dr. Greg Hundley: Peder, what a great description on that previous paper, beautiful job there. So Peder, this next article pertains to cardio toxicity related to the administration of anthracycline-based chemotherapy. And an example would be Doxorubicin. And this occurs in patients often with certain types of cancer. As you know, Doxorubicin is still utilized for the treatment of leukemia, lymphoma, soft tissue sarcoma and in the setting of adjuvant breast cancer treatment. And so to this end, the authors, led by Lorrie Kirshenbaum from St. Boniface Hospital abstract research, wanted to assess cytokine mediated inflammation in myocellular injury, as a result of some of the inflammation that's induced by the administration of Doxorubicin. So as a little bit of background, cytokines, such as TNF alpha, have been implicated in cardiac dysfunction and toxicity associated with Doxorubicin. Now, while TNF alpha can elicit different cellular responses, including survival or death, the mechanisms underlying these divergent outcomes in the heart really somewhat remain cryptic. The E3 ubiquitin ligase, TRAF2, provides a critical signaling platform for K63 length poly ubiquitin nation of rip K1, crucial for NF-kB activation by TNF alpha and survival. Whether alterations in TNF alpha, TRAF2, NF-kB activation signaling underlie the cardiotoxic effects of Doxorubicin, remains poorly understood. So herein, these authors investigated TRAF2 signaling in the pathogenesis of Doxorubicin cardio toxicity. Dr. Peder Myhre: Oh wow, Greg. So we're talking mitochondrial dysfunction in Doxorubicin cardiomyopathy. So please tell me, what did they find and what were the clinical implications? Dr. Greg Hundley: Very nice. Peder, you remind me of Carolyn, asking me the clinical implications. Okay, so first, in mouse models and in vitro measures in rats, mouse and human pluripotent stem cell derived cardiomyocytes, these investigators monitored TNF alpha levels, LDH, cardiac ultra structure and function, mitochondrial biogenics, as you just suggested, and cardiac cell viability. They found that a novel signaling axis exists that functionally connects the cardiotoxic effects of Doxorubicin to proteasomal degradation of TRAF2. Disruption of the critical TRAF2 survival pathway by Doxorubicin, sensitizes cardiomyocytes to TNF alpha and BNIP3 mediated necrotic cell death. Perhaps, interventions that stabilize TRAF2, so here's the clinical implication, may prove beneficial in mitigating the cardiotoxic effects in cancer patients undergoing anthracycline-based chemotherapy. Dr. Carolyn Lam: So Greg, he may sound like me, but this is me going what an amazing summary and especially in something that is your specialty cardio-oncology, that's amazing. Thank you. Peder, I assume you've got one more paper? Dr. Peder Myhre: So Greg, now I'm going to sound like you and say that we are going to stay within the world of preclinical science. So genome-wide association studies have identified many genetic loci that are robustly associated with coronary artery disease. However, the underlying biological mechanisms are still unknown for most of these loci, hindering the progress to medical translation. And there is evidence to suggest that the genetic influence of coronary artery disease sociability may partly act through vascular smooth muscle cells. So corresponding author, Shu Ye from University of Leicester, performed genotyping, RNA sequencing and cell behavior assays on the large bank of vascular smooth muscle cells with an N of almost 1500. And through these extensive analysis, they saw to identify genes whose expression was influenced by coronary artery disease associated variants. Dr. Greg Hundley: Very nice, Peder. So, more about cardiac gene expression. So, what did they find? Dr. Peder Myhre: Approximately 60% of the known coronary artery disease associated variants show statistically significant effects in vascular smooth muscle cells and the study identified 84 candidate causal genes whose expression quantitative trait, loci signals in vascular smooth muscle cells, significantly co-localized with reported coronary artery disease association signals, of which 38 of them are potentially druggable, so, that was the clinical implications. The authors conclude that a large percentage of coronary artery disease loci can modulate genes, gene expression in vascular smooth muscle cells and influence these cell behavior. Several candidate causal genes identified are likely to be druggable and thus represent potential therapeutic targets. And Greg, accompanying this paper is a beautiful editorial by doctors O'Donnell and Bradner entitled "Bridging the Gap to Translating Genome-Wide Discoveries into Therapies to Prevent and Treat Atherosclerotic Cardiovascular Disease." Dr. Greg Hundley: Very nicely done Peder, very nicely done. Well, as usual, we have some other items, we call it in the mail bag because we receive these wonderful research letters and also research correspondence. So I'll go first. First, Dr. Al-Khatib has a research letter entitled, "Duration of Anticoagulation Interruption before Invasive Procedures and Outcomes in Patients with Atrial Fibrillation Insights from the Aristotle Trial." And also there's a nice ECG analysis by Dr. Tsai entitled, "A Peculiar Wide-Complex Tachycardia During Flecainide Treatment." Dr. Peder Myhre: Nice, Greg, and there's also an exchange on letters to the editors and the response from Professors Zhao and Ding, and again, a response from Professor Zhang regarding the prior letter by Jin et al. pertaining to the previously published article "Micro RNA, 210 Controls, Mitochondrial Metabolism and Protects Heart Function in Myocardial Infarction." Dr. Greg Hundley: Beautifully done, Peder. Oh, wow. Welcome to this team. We're so excited to have you. And now Carolyn, I think we're going to jump over to that feature discussion and learn a little bit more about COVID-19 and arterial and venous thrombotic disease. Dr. Carolyn Lam: You bet! Let's go, Greg and Peder. Now we all know that infection with COVID 19 induces a pro-thrombotic state, but the long term effects of COVID-19 on the incidence of vascular disease, both arterial and venous, remain unclear. That is until today's feature paper. We're so grateful to have corresponding author Dr. Jonathan Stern, from the University of Bristol, as well as our associate editor, Dr. Shinya Goto from Tokai University School of Medicine to join us and discuss this very important paper today. Jonathan, could you start us off on telling us why it's so important to look at this? Haven't we always known that infections, COVID or not, are associated with pro-thrombotic state? So what's so different about what you did and what you found this time? Dr. Jonathan Stern: So, yes, I think we already knew that serious infections, in particular infections leading to hospitalization, can result in thrombotic events, either arterial or venous. And it was also clear from January, February, March 2020, that COVID led to very serious infection and therefore was likely to lead to vascular events. The questions that we set out to address, beyond simply establishing that COVID does indeed do this, was to quantify by how much COVID multiplies the rate at which these thrombotic events occurred, to do that separately for different events, such as myocardial infarction, stroke, venous thromboembolism, pulmonary embolism. And then to importantly, because we analyzed a very large dataset, which we might want to talk about, to try to separate out the amount by which the rating events was multiplied over time and in important subgroups, for example, in hospital people who were hospitalized for their COVID, compared with people who weren't hospitalized for their COVID, by age and sex, and by other demographic characteristics. Dr. Carolyn Lam: I love that, you see, that really set out the novel information this added with, may I add, very important clinical implications, which we'll get to them. You've already teed me up to talk about this 48 million adults that you managed to look at. Oh my goodness! Tell us, how in the world did you do that? Dr. Jonathan Stern: Well, I think the first thing to say is that it's my absolute privilege to talk about this paper on behalf of a really incredible team that put the work together. And a lot of that work, or that work started with really unlocking the power of NHS data because of the COVID pandemic. So in the UK, we have a national health service, free at the point of delivery to everybody. The NHS assembled electronic health records, and there's been a long and proud history of research based on electronic health records in the UK. But for the first time, because of the pandemic, a combined data resource for the whole of England, so that's a population of about 58 million people, was established and that linked primary care data - data from family doctors, data on secondary care hospital admissions, data on COVID testing and subsequently, although it's not the subject of this paper, data on vaccination. So those data were all linked and put into one place within what's called a trusted research environment with very strict controls on what can be output from the environment in order to protect patient privacy. And that was really done during 2020. And then the analyses for this paper took place during 2021, and it was an enormous amount of work by a large and absolutely fantastic team of people across multiple UK universities and national health service institutions. Dr. Carolyn Lam: Wow. Bravo! We talk about big data, we talk about using it. I trained in the NHS system. Who knew that this could come out to reveal such important results? So thank you for that as a background, but now, tell us what you found please? Dr. Jonathan Stern: So we found that rates of these conditions, they were primarily acute lymph infarction and ischemic stroke, which we grouped together with other conditions as arterial thrombotic events, and then deep vein thrombosis and pulmonary embolism, which we grouped together with other conditions as venous events. And we found that rates were substantially multiplied immediately after a diagnosis of COVID by up to 748 times, that the amount by which rates were multiplied diminished with time since COVID, but importantly that even six months to a year after that first diagnosis of COVID, rates of venous events were still about double in people who'd had COVID, compared to people who had COVID. And we found, it seemed quite clear that the persistence of the elevated risk was longer for venous events than for arterial events. Dr. Carolyn Lam: Just really fascinating results and Shinya, could I ask, what are your thoughts on this? And as you were managing this paper, the implications? Dr. Shinya Goto: First of all, thank you very much, Jonathan, for choosing saturation for your great paper. I'm handling quite a lot of papers, but your paper was very attractive. As Carolyn mentioned, it's huge data! 48 million, it's surprising, and also you also pick up booster rate of arterial embolism event for years, and you have also shown adjusted rate is initially increased quite a lot and then decreased gradually. And even after two months, three months still, there is a persisted higher risk. And as you mentioned, for the venous thrombo embolism, it's persisted for more than year to year. It's surprising. COVID-19's a different disease. Perhaps COVID-19 infection cuts to the vascular endarterial cell, perhaps, your research raised a lot of research questions, like endarterial damage induced by COVID-19 in the past 6 months; I would say more than half a year to one year. So that mechanistical insight is very important. And you raise a lot of any clinical questions. Dr. Jonathan Stern: Well, thank you very much for your kind words and you are right, I think we are left with questions about maybe in three areas. Firstly, for how long is there an elevation in risk? I should probably say, for those who haven't read the paper, that these results relate to events that occurred in England and Wales during 2020. And so that is in an era before vaccination and when we were dealing with the original variant, and to some extent, the alpha variant. So we are still waiting to see what the implications were over longer periods, and we will be doing that, we will be extending follow up. In fact, we are at the moment extending those results. I think, secondly, we are left with questions about the mechanisms, which you articulated, and thirdly, there's the question about, well, what are the implications for clinical management of patients with COVID-19? And in particular, for patients who've had severe COVID-19, for example, severe enough to be hospitalized for it? Dr. Shinya Goto: Yeah, you have also showed a very important point that even known hospitalization for COVID-19, the risk of thrombosis becomes high. So it's very surprising. And even non-hospitalized patients have a higher risk of thrombosis. That is probably the huge difference between other virus infections and COVID-19. Dr. Jonathan Stern: Yes. The good news, if you weren't hospitalized for your COVID, is that the elevation in risk declines more rapidly for people with less severe COVID who weren't hospitalized than for people with more severe COVID who were hospitalized. But nonetheless, as you say, particularly in the first week, two weeks, three weeks after COVID, there is a clear elevation in the risk of both arterial and venous events, even if you were not hospitalized for your COVID. We should probably also bear in mind that these results for 2020, when there were severe constraints for some of the time on health service resources. So you probably had to be pretty sick to get hospitalized at that time. Dr. Carolyn Lam: That was a very important caveat that you just highlighted. So thank you for contextualizing those findings for us, Jonathan, but then I kind of wish all podcast guests were like you, and you already asked a question, I was going to ask you. Which is, okay, so what's the clinical implication? Should we all be taking some low dose NOAC or aspirin? Whether you're hospitalized or not? Or if you were in 2020? Because, jokes aside, I know that you found some very important risk factors? Or these events which had clinical implications? Could you expand on it? Dr. Jonathan Stern: So maybe I'd start by saying that we didn't find that these patterns varied dramatically either by sex or by age. And in fact, when we were planning the analyses, I was convinced that we would see dramatic differences in these hazard ratios by age. And, broadly speaking, the facts on a multiplicative scale, the amount by which your rate is multiplied, looked similar across age groups and by sex. On the other hand, we did see the amount by rates of arterial and venous events were multiplied, appeared greater in people of Asian ethnicity or Black ethnicity than in people of White ethnicity. A counterintuitive finding was that the amount by which your rate was multiplied is lower, if you've had a prior event than if you hadn't. Those are the sorts of extents to which we can say something about how your own characteristics predict the consequences once you've had COVID. In terms of management, obviously the pandemic has been tumultuous for medicine and for medical research and things have moved on greatly since the pre-vaccination era, 2020 and early 2021, to which these analyses relate. So the first thing to say is, don't get hospitalized with COVID, and the best way to not be hospitalized with COVID, is to be fully vaccinated for COVID. And that's a message that I think the whole of the medical profession has communicated loudly and clearly for a long time now. So the second thing is, well, okay, what about if, nonetheless, you got COVID, particularly severe COVID, and we discussed this in the team extensively, and I particularly want to mention the senior clinical author, Dr. Will Whiteley from the University of Edinburgh in this regard, and I think the main message here is that risk factor management, cardiovascular risk factor management is always important, but it's probably particularly important in people who've had severe COVID to review risk factor management and make sure that existing guidelines in terms of cholesterol lowering, blood pressure lowering and so on, are being adhered to. We don't... So the most important thing is adherence to existing cardiovascular risk management guidelines. I think we don't have evidence that specific additional interventions are indicated in people who've had COVID, and COVID now in the era of Omicron and widespread vaccination is not the same as COVID during 2020. Dr. Shinya Goto: Jonathan, you have raised a very important issue. I strongly recommend all audiences to read this paper. We have to know persistent or higher risk of myocardial infarction, ischemic stroke, may be controlled more regularly controlled. Don't fear the COVID-19 infection to visiting the healthcare professional. In my country, some of the population stopped coming to the healthcare professional because they fear so much about infection from the hospital or clinic. But it's very important to keep that regular control like static and blood pressure control. Maybe we don't have that data about aspiring or not, but strong message your paper gave is that risk factor control after COVID-19 is very important. Dr. Jonathan Stern: I completely agree. Dr. Carolyn Lam: And I would add to that, remember the days when people were stopping their ACE inhibitors and so on for those fear? So what a great message and thank you for giving us a little bit of a peek into the future of what you're planning next with more follow up, in a population that is vaccinated from a different strain perhaps. And I think this still encourages hopefully more trials and research into this whole area of how we should be managing these patients. Well, thank you so much both of you for discussing this very, very current relevant, important paper. Thank you for publishing it in circulation with us. And to the audience, thank you for joining us today. From Greg and I, you've been listening to Circulation on the Run, and don't forget to tune in again next week. Speaker 6: This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

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Please join authors Christopher Granger and Anthony Carnicelli, as well as Associate Editor & Editorialist Shinya Goto as they discuss the article "Direct Oral Anticoagulants Versus Warfarin in Patients With Atrial Fibrillation: Patient-Level Network Meta-Analyses of Randomized Clinical Trials With Interaction Testing by Age and Sex" and accompanying Editorial "Patient Level Meta-Analysis: End of the Era for DOAC Developmental Trial in AF Patients?" Dr. Carolyn Lam: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts. I'm Dr. Carolyn Nam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr. Greg Hundley: And I'm Dr. Greg Hundley, Associate Editor, Director of the Pauley Heart Center at VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, I'm so excited about our feature discussion today. It is about DOACs versus warfarin in patients with atrial fibrillation, a really important patient-level network meta-analysis of randomized control trials with interaction testing by agent six. So you can already tell something very, very clinically relevant and important discussed by not only the authors, but our dear associate editor and editorialist. Dr. Carolyn Lam: Okay. You just got to tune in, but first I'm going to start us off with some coffee, as well as a description of this first paper in today's issue. The 2018 AHA ACC multi-society cholesterol guidelines states that statin therapy may be withheld or delayed among intermediate risk individuals in the absence of coronary artery calcium. Dr. Carolyn Lam: However, two traditional cardiovascular risk factors associate with incident atherosclerotic cardiovascular disease events among individuals with zero coronary artery calcium over the long term? Well, this is the question that investigators decided to answer in today's paper and they're led by Dr. Virani from Baylor College of Medicine in Houston, Texas. Dr. Carolyn Lam: They studied 3,416 individuals with coronary artery calcium score of zero at baseline from the MESA study, which is a prospective cohort study of individuals free of clinical atherosclerotic cardiovascular disease at baseline. Among these individuals with zero coronary artery calcium, cigarette smoking, diabetes and hypertension were found to be independently associated with incident atherosclerotic cardiovascular disease events over long-term follow up. Dr. Greg Hundley: Ah, very interesting. Another piece of information relating to how we might use coronary artery calcium scores in, it sounds like, a high-risk patient population. So, Carolyn, what's the take-home message here? Dr. Carolyn Lam: Well, even if individuals have a coronary artery calcium of zero, if they are current smokers, if they have diabetes melitis or hypertension, initiation and long-term use of statin therapy, along with a heart healthy lifestyle and risk factor modification may still be warranted as part of the patient/clinician risk discussion. Dr. Greg Hundley: Very interesting Carolyn. Well, I've got a clinical study to tell you about. And, Carolyn, as you know, obesity and diabetes are associated with a higher risk of heart failure and the inner relationships between different measures of adiposity, including overall obesity, central obesity, fat mass, and diabetes status for heart failure risk, are not well established. Dr. Greg Hundley: And so this investigative group, led by Dr. Ambarish Pandey, from UT Southwestern Medical Center, looked at the ARIC, the visit five in ARIC and CHS, the visit one, and cohorts together, and they were obtained from the NHLBI BioLINCC. They were harmonized and pooled for the present analysis, excluding individuals with prevalent heart failure. Dr. Greg Hundley: So using multi-variable adjusted fine-grade model models were created to evaluate the associations of body mass index, waist circumference, and fat mass with risk of heart failure in the overall cohort, as well as among those with, versus without, diabetes at baseline. Dr. Greg Hundley: And the population attributable risk of overall obesity with BMI greater than 30 kilograms per meter squared, abdominal obesity with waist circumference greater than 88 and 102 centimeters in women and men, respectively, and high fat mass above the sex-specific median for incident heart failure, was evaluated among participants with and without diabetes. Dr. Carolyn Lam: Ooh, I'm so in interested in this topic. So what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So a large study, it included 10,387 participants, about 53% from ARIC, 25% had diabetes, and the median age was 74 years. And higher levels of each adiposity measure were significantly associated with higher heart failure risk. The population-attributable risk percentage of overall obesity, abdominal obesity, and high fat mass for incident heart failure was higher among participants with diabetes versus those without diabetes. Dr. Greg Hundley: And so, Carolyn, we can conclude from this research that higher BMI, higher waist circumference and higher fat mass, are strongly associated with greater risk of heart failure among older adults, particularly among those with prevalent diabetes. Dr. Carolyn Lam: So, so nicely done. Thank you, Greg. Well, the next paper talks about common ancestry-specific ion channel variants and how they predispose to drug-induced arrhythmias. Now, we know that multiple reports associate the cardiac sodium channel gene Scn5a variants, and these are the specific variants, S1103Y and R1193Q, with Type 3 congenital long QT syndrome and drug-induced long QT syndrome. Dr. Carolyn Lam: These variants are, however, two common in ancestral populations to be highly arrhythmogenic at baseline. The S1103Y allele frequency, for example, is 8.1% in Africans and the R1193Q is 6.1% prevalent in East Asians. So the investigators, led by Dr. Roden from Vanderbilt University Medical Center in Nashville, Tennessee, and colleagues, determined the effect of the S1103Y variant on QT intervals among 1,479 Africans from a large electronic health record with no confounding medications or diagnosis of heart disease. Dr. Carolyn Lam: Now, while both the specific variants generated increased late sodium current, baseline action potential durations in cardiomyocytes from induced pluripotent stem cells carrying these variants were unexpectedly normal. The re-polarizing potassium current, IKR, was markedly increased in these induced pluripotent stem cells with the variants, accounting for normal baseline action potential duration but, with exposure to an IKR blocker, they displayed exaggerated action potential duration prolongation and after depolarizations. Dr. Greg Hundley: Wow, Carolyn, interesting. So tell us, what are the clinical implications of this really exciting research? Dr. Carolyn Lam: Yeah. So here's the take-home message. These common ancestry-specific variants do not affect baseline re-polarization, despite generating an increased late sodium current. So the authors propose that increased re-polarizing potassium current, IKR, serves to maintain normal re-polarization, but increases the risk of manifest QT prolongation with IKR blocking in these variant carriers. So we need to be aware of that and, further, these findings highlight the need to include ancestral diversity in genomic and pharmacogenomic studies. Dr. Greg Hundley: Oh, wow. Beautifully described, Carolyn. I really appreciate that. Just excellent discussion. Well, Carolyn, my next paper comes to us in an investigation regarding doxorubicin or anthracycline-associated induced cardiotoxicity. So, Carolyn, multiple pharmacogenetic studies have identified the synonymous genomic variant rs7853758 and the intronic variant rs885004 and SLC28A3 as statistically associated with a lower incidence of anthracycline-induced cardiotoxicity. Dr. Greg Hundley: However, the true causal variant, or variance, of this cardioprotective mechanism at this locus, the role of SLC28A3 and other solute carrier transporters in anthracycline-induced cardiotoxicity and the suitability of solute carrier transporters as targets for cardioprotective drugs has not been investigated. Dr. Carolyn Lam: Wow. Got it. So what did these investigators do and find, Greg? Dr. Greg Hundley: Right. So Paul Burridge and his colleagues at Northwestern University found that the patient-specific cardiomyocytes recapitulate the cardioprotective effect of the cGAS-identified SLC28A3 locus, and the authors functionally confirmed for the first time, the role of SLC28A3 in doxorubicin-induced cardiotoxicity. Dr. Greg Hundley: And a novel genetic variant, the rs11140490, is the potential causal variant in the SLC28A3 cardioprotective locus. And finally, Carolyn, the solute carrier transporter inhibitor desipramine protects against doxorubicin-induced cardio toxicity through decreasing the intracellular uptake of doxorubicin into the heart. Dr. Carolyn Lam: Wow. That is a lot of data. Could you summarize it for us, Greg? Dr. Greg Hundley: Right, Carolyn. So these investigators provide two potential therapeutic options to attenuate doxorubicin-induced cardiomyopathy, either repurposing FDA-approved desipramine, or therapy with long non-coding RNA SLC28A3-AS1. Also, Carolyn, they propose that a simple clinical test to detect the presence of rs11140490 can be used to predict that a patient will be less likely to experience doxorubicin-induced cardiomyopathy, and that, perhaps with future clinical trials, it may be possible for these patients to be treated with a longer duration, that is a higher accumulative dose of doxorubicin, to enhance the efficacy of their chemotherapy. Dr. Carolyn Lam: I love the way you took that home for us. Thank you, Greg. Well, also in today's issue is a Research Letter by Dr. Chen on multifaceted spacial and functional zonation of cardiac cells in an adult human heart. Dr. Greg Hundley: Right, Carolyn. And Professor Constantine has a Letter to the Editor entitled Pravastatin Versus Placebo in Pregnancies at High Risk of Term Preeclampsia. Well, Carolyn, how about we get onto that feature article and learn about DOACs versus warfarin in this very large network meta-analysis? Dr. Carolyn Lam: Yes, yes, yes. Let's go, Greg. Thanks. Dr. Greg Hundley: Welcome, listeners, to our feature discussion today. And we're very fortunate. We're going to review the utility of DOACs in patients with atrial fibrillation. And we have with us two of the authors of this original research, Dr. Anthony Carnicelli from Duke University, and Dr. Chris Granger from Duke University. Dr. Greg Hundley: Additionally, we have with us our associate editor, Dr. Shinya Goto, from Japan. Welcome, gentlemen. Anthony, we'll start with you. Describe for us a little of the background information pertaining to your study and what was the hypothesis that you wanted to address? Dr. Anthony Carnicelli: Yeah, thanks so much, Greg, for having us here to discuss this. I started working in the DOAC space when I was a resident at Brigham and Women's Hospital with mentorship from Dr. Bob Guigliano there, and was really fortunate to connect with Dr. Granger when I came to Duke for a fellowship, and we had this unique opportunity to take data out of the four largest trials of anticoagulants in the atrial fibrillation, and take individual patient data from these international centers and combine them to form the combined AF database from which we did this analysis. Dr. Anthony Carnicelli: So a very unique opportunity here to have individual patient-level data from over 70,000 patients, and perform this analysis. And, really, what we aimed to do was to do the kind of highest quality meta-analysis using network meta-analysis methods to investigate the relative safety and efficacy of DOACs versus warfarin and a broad and diverse, but randomized, population of patients with atrial fibrillation. Dr. Greg Hundley: Very good. So you started to describe for us your study population and your study aligns. So tell us a little bit more, who were these patients, and then maybe specifically give us a little bit of the outline of your meta-analysis. Dr. Anthony Carnicelli: Yeah, so these were, again, a very broad patient group, but from kind of 10,000 feet, this was a population of patients with atrial fibrillation who were at risk of stroke, from CHADS score perspective. So there are some nuances from each of the included studies, of course, regarding the individual risk of stroke from one study to the next. But largely, as I mentioned, in patients with non-valvular atrial fibrillation randomized to either DOAC or warfarin. Dr. Anthony Carnicelli: And, from a method standpoint, we are fortunate at Duke and at DCRI, to have an expert in the network, meta-analysis methodology, whom we've worked with, Dr. Bonnie Huang, who helped to put together the analysis here and to proceed with this kind of network methodology. Dr. Anthony Carnicelli: And so, again, our goal was to evaluate the overall safety and efficacy of DOACs versus warfarin, but then also to dive into some specific subgroups, both from a categorical covariant perspective, and then also to evaluate some continuous covariants, specifically age, and to assess gender across the entire spectrum of continuous age in our population, which, of course is a unique opportunity in the individual patient-level data. Dr. Greg Hundley: And, Anthony, you had, gosh, it looks like over 70,000 patients in this particular analysis. Tell us a little bit about the results. Dr. Anthony Carnicelli: Yeah, so interesting, actually, and I agree that the biggest strength of our meta-analysis is the individual patient-level data and also the profound number of randomized patients included. So I think, from a high level, the most important results to highlight are the fact that there is a 19% relative risk reduction in stroke or systemic embolism among patients who are randomized to DOACs compared to warfarin, with an 8% reduction in all-cause death and a 55% reduction in intracranial hemorrhage. Dr. Anthony Carnicelli: So a massive reduction in the most feared complications of both atrial fibrillation and then also those associated with systemic oral anticoagulation. We also found a trend towards less bleeding in patients randomized to the standard-dose DOAC group, as well. Dr. Greg Hundley: Very good. Well, Chris, we're going to turn to you. What an exciting discovery here, and beautiful methodology. I wonder, in addition to what Anthony has shared with us, were there particular outcomes that were pertinent to men versus women or perhaps related to age? Dr. Christopher Granger: Yeah, Greg. So, again, we're proud of this as being really the state-of-the-art ability to evaluate safety and efficacy in this incredibly important population of patients with Afib and at risk for stroke, and to be able to dive into the subgroups and to the individual outcomes, even the less common outcomes. And one of the most striking things, and this really reinforces prior data, but with the greatest confidence of any study ever done, there was this 55% at reduction in intracranial hemorrhage and 19% reduction in total stroke and systemic embolism, really highlighting that these drugs are clearly better than warfarin, from reinforcing the guidelines. Dr. Christopher Granger: And the message with the subgroups is there was really a remarkable amount of consistency. And specifically in the older population where people are really concerned about anticoagulation, there was a clear and consistent major advantage of DOACs over warfarin. Men versus women, clear, clear, compelling benefit of DOACs over warfarin across each of these outcomes, including mortality, by the way, 8%. But highly statistically significant reduction in total mortality. Dr. Christopher Granger: A couple of the interesting ones, there was some effect modification. In other words, some evidence of an even greater benefit in patients who were not previously on a vitamin K antagonist or who had lower creatinine clearance, really important group, right? The renal impairment group. Dr. Christopher Granger: And then there was a greater benefit of lower risk of bleeding for patients with low body weight. And, in fact, the younger population, if anything, had a greater benefit with respect to less bleeding. And the bleeding is so important, Greg and Shinya, right? Because that's the major reason that people are not using anticoagulation, warfarin or DOACs, for this large population of patients who are untreated. And I hope this meta-analysis will be viewed as evidence that have really safe and effective treatments that are underused for this population that we're concerned about bleeding. Dr. Greg Hundley: Excellent. Thanks so much, Chris. Well, Shinya, you see a lot of papers come across your desk. What attracted you to this particular paper? And then can you help us put these results in the context with others that have evaluated the utility of DOACs in patients with atrial fibrillation? Dr. Shinya Goto: Thank you, Greg. Let me congratulate for Anthony and Chris and also group for conducting this great work. I mean, combine AF with amazing success for sharing the clinical trial database. So that all the four with a DOAC available is approved by each country based upon individual trial. Individual trial itself, large enough, right? Include more than 10,000 patient, but this time the [OSA 00:19:49] accumulated all four DOAC trial database together so that it is easy to say clinical trial data sharing provided robust evidence. Dr. Shinya Goto: But it is difficult, actually, to conduct it. I really commended OSA to conduct this success. So the data is predicted, I would say. Individual clinical trial itself shows lower risk of bleeding in DOAC as compared to warfarin. But this paper really provides the first time standard dose of DOAC reduce the risk of stroke and systemic embolism and death as compared to warfarin. Dr. Shinya Goto: So I really commented OSA. So this paper have a strong impact on the medical care. DOAC rapidly change the standard of care already. But superior efficacy was shown only in a few dose of DOAC, like 150 milligram BID of dabigatran, 60 milligram QD edoxaban, and five milligram apixaban. But this combined AF provides a stronger and a trustable robust evidence DOAC is better than warfarin. Dr. Greg Hundley: Very nice. Well, gentlemen, I want to turn back to you. I'll start with Anthony and then Chris, and then Shinya. Anthony, what do you think is the next study to be performed, really, in this space? Dr. Anthony Carnicelli: Well, it may be a bit of a pitch, but I mean, we have many opportunities in the combined AF data set to perform additional analyses, but I think that one of the most important next steps in this space that I'm most excited about is with respect to the newer oral anticoagulants that are coming down the pike. Dr. Anthony Carnicelli: For example, the Factor 11 inhibitor space. I mean, I think that there is another opportunity in the near future to potentially revolutionize the systemic anticoagulation space. And I think that data from combined AF could potentially be used to help continue moving the ball forward, again in the development of newer agents. So I think that's probably the thing that I'm most excited about in this space. Dr. Greg Hundley: Very good. And, Chris? Dr. Christopher Granger: Greg, I think there's so many unanswered questions and I think, as Tony points out, this highlights the fact that we know a lot, but there's a lot of unanswered questions. And those, some of the ones that I'm most interested in are low burden AFib, this AFib that we're detecting now with smart watches and devices, and what we do with that. And patients with renal impairment, including all the way down to renal failure, where those are relatively underrepresented, including in the combined AF data set. Dr. Greg Hundley: Very good. And, Shinya? Dr. Shinya Goto: Yeah. Yeah, Anthony and Chris talked about a little bit the plans to space, but I insist there is a lot of space that also could do with the combined AF database. We can expect a lot of sub-analysis, like you conducted as a continuous variable in this paper, but you can do that with eGFR as continuous variable, PMI as continuous variable. So we can expect a lot of sub-analysis. Probably, this is the end of publication from the individual DOAC development trial. You change the game with the combined AF data set. Dr. Greg Hundley: Very good. Well, listeners, we want to thank Dr. Anthony Carnicelli, Dr. Christopher Granger and our own associate editor, Dr. Shinya Goto, for bringing us this very interesting result from the meta-analysis that, compared to warfarin, DOACs have a more favorable efficacy and safety profile among patients with atrial fibrillation. Well, on behalf of Carolyn and myself, we want to wish you a great week and we will catch you next week on the run. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more, please visit ahajournals.org.

My guest today is Shinya Deguchi. Shinya is the founder of Star Magnolia Capital, a multi-family office and Co-Founder of Gen Z Group. Through Gen Z Group, Gen Z Media creates and promotes educational content (mainly in the medium of graphic novels) in Chinese-speaking regions which is today's focus. In today's conversation, we cover Webtoons and Manga in the context of investor education. It's a little different but an extremely interesting and exciting topic. I hope you enjoy my conversation with Shinya Deguchi.   For the full show notes, transcript, and links to mentioned content, check out the episode page on  https://compoundingpodcast.com/ep29    ------   Show Notes: [00:00:31] - [First question] - Shinya's background [00:03:47] - The influence of Makoto Maki [00:08:00] - Shinya's investing style and how that's changed over time [00:12:11] - Manga and Why start the Gen Z Group? [00:24:14] - Early mistakes? [00:31:07] - When comparing Manga and Webtoons compared to other mediums, why do it? [00:32:21] - What Shinya wished he knew before starting this project  [00:35:55] - And what's next for Gen Z Group? [00:39:10] - Anything else we haven't covered and wrapping up   ------   Connect with Shinya: Connect with Shinya on LinkedIn: https://www.linkedin.com/in/shinya-deguchi-b403908/  Gen Z Group's Website: https://www.genzgroup.org/    ------   Mentioned/Recommended Content: INVEST! Webtoon: https://www.genzgroup.org/new-investor-z  Investor Z IMPACT! Webtoon: https://www.genzgroup.org/investors-z-impact    ------   Stay up to date with the podcast by signing up to the Compounding Curiosity Substack, where I'll email you when the latest episode comes out along with my summary and takeaways, links to mentioned content, graphics and the transcript. Sign up at https://compoundingcuriosity.substack.com/    ------   Connect with Kalani: Visit the Compounding Curiosity PODCAST: https://CompoundingPodcast.com/  Visit the Compounding Curiosity SUBSTACK: https://compoundingcuriosity.substack.com/  Follow Kalani Scarrott on TWITTER: https://twitter.com/ScarrottKalani/  Sign up for Allocators Asia: https://KalaniS.substack.com/  Join the DISCORD: https://discord.gg/NPVNPVsCYb

Welcome to Take Your Time, a podcast by Jonathon Dornbush and Tom Marks where the duo will be playing Persona 5 Royal in real time, playing along with P5R's in-game calendar. Join Tom and Jonathon for episode 31 as we dive into the week of Nov. 1 - 7. As our Persona 5 Royal podcast and playthrough continues, we discuss the first full free week of time during the Sae's palace portion of Persona 5 Royal. Remember, we won't actually discuss P5R's next palace until episode 32, but in the meantime we have plenty to discuss as we make our way through Persona 5's calendar. Jonathon and Tom take their time to discuss the week's scheduled events, including free reading periods, a festival trip with Haru, and some dramatic encounters with Akechi at the train station. We also discuss how we spent our free time with our Persona 5 Royal confidants, including more time with our newest and the final Confidant of P5R, Shinya. We dive a bit into how his story starts, Haru's Confidant ability, and more about the social ties of Persona 5. And at the end of the episode, we discuss Yusuke's entire Confidant line - his powers, his character development, and more. (And don't worry, we save that talk for the very end of the show, so you can listen to the rest of the episode without needing to jump ahead.) Plus, our Persona 5 podcast offers another Pop Quiz question, answers listener questions, and a lot more. Be sure to write in with your thoughts to dornology@gmail.com, or tweet at Jonathon (@jmdornbush) and Tom (@tomrmarks).

La Parole aux Pratiquants avec Shinya Tsuchida, pionnier du Kūdō 空道 en France. C'est à l'âge de 19 ans qu'il découvre le Nippon Kempo alors qu'il recherchait un moyen de ne pas se taire devant une agression physique ou verbale. Il transféra sa pratique dans le Kudo Daidojoku. Et arrivera fin des années 90 en France. Rencontre du sensei, de son parcours, sa pratique des arts martiaux. Le KUDO DAIDO JUKU (空道　大道塾) est un budo de contact autorisant les percussions pieds/poings, les saisies, projection et travail au sol. Issu du Karaté kyokyushinkai, celui-ci a été fondé en 1981 par Azuma TAKASHI jukucho. Son dojo Kudo Paris XII : https://kudoparis12.wixsite.com/kudo-paris-12 Nous sommes un sakagura produisant le saké des temps modernes. Formés au Japon, nous entamons notre seconde année de brassage à Paris, afin de faire partager Wakaze au monde. Tout le monde mérite du bon saké à savourer pendant les repas, avec ses amis et sans contraintes. Saké artisanal : https://www.wakaze-sake.com/fr/ ✅ Toutes nos vidéos en DVD et téléchargement HD avec de grands sensei sur https://www.imaginarts.tv/?utm_source=libsyn&utm_medium=share&utm_term=kudo&utm_content=kudo&utm_campaign=awareness 

Salud - Alimentación

¿Quieres escuchar el audiolibro completo? Visita www.penguinaudio.comCuida tu salud y evita enfermedades, incluye en tu dieta alimentos compatibles con tu cuerpo.Factor microbio presenta un método revolucionario basado en los estudios científicos más recientes que el doctor Hiromi Shinya llama Bioenzima Shinya, una nueva manera de comer y de vivir que puede devolverte la salud y hacer que disfrutes de una vida sana lejos de medicamentos o intervenciones quirúrgicas.En este audiolibro el doctor Shinya te enseña a:-Obtener energía del poder de las plantas.-Aprovechar las bacterias que están presentes en tu cuerpo para estar sano.-Potenciar los sistemas naturales de rejuvenecimiento.-Identificar los cuatro grupos de nutrientes del Bioenzima Shinya.-Descubrir los beneficios de unos intestinos sanos.-Aumentar tu poder inmunológico innato.-Alcanzar tu peso natural y lucir bien.-Escuchar la voz de tu cuerpo. See acast.com/privacy for privacy and opt-out information.

DeAundra Shinya “Dee” “Wyne” Martin Taylor, 35, a native of Whatley and resident of Grove Hill, was born the third child of Janice Morrissette Martin and Leonard Martin on July 29, 1986 in Grove Hill. On Saturday, Aug. 7, 2021, around 3:30 a.m., God and His heavenly angels whispered, “Sweet Child, Come Home to Rest.” “Dee” went home to be with God from Grove Hill Memorial Hospital, along with her sleeping son, Master Jacob Lee Taylor. Shinya left a legacy of love and will forever be affectionately remembered by her family and friends. “Wyne,” as she was affectionately called by...Article Link

¿Quieres escuchar el audiolibro completo? Visita www.penguinaudio.comEn La enzima prodigiosa el doctor Hiromi Shinya ofrecía a los escuchasun tratamiento probado en centenares de pacientes, que fue modificando alo largo de su carrera -más de cincuenta años como profesional de lamedicina-, y que consistía en la generación corporal de una enzima vitala la que ha llamado la "enzima prodigiosa": la clave para una vida largay saludable. A explicar el funcionamiento de esta enzima y por qué estan importante en los seres humanos dedicó su obra, un libro que llevavendidos más de 2.000.000 de ejemplares en el mundo y que harevolucionado el panorama médico. Después del éxito obtenido con Laenzima prodigiosa y movido por la necesidad de seguir explicando losdetalles de un método que está revolucionando el mundo de la salud y queha mejorado la vida de miles de personas, el doctor Hiromi Shinyaregresa al panorama editorial con más fuerza que nunca para insistir enque la clave para la salud está en nosotros mismos. La enzima prodigiosa2 aporta nuevos hábitos saludables que incluir en nuestro día a día paralograr la vitalidad de la juventud en todas las etapas de la vida. Laenzima prodigiosa 2 te enseña: * qué alimentos aceleran elenvejecimiento y cuáles lo previenen. o por qué los primeros signos deenvejecimiento se muestran en la piel. o que el estado de tu piel puededecirte cómo se encuentra tu intestino. * que la falta de agua puedeprovocar cáncer. * que aquellos que sufren dermatitis atópica o alergiahan de beber mucha agua. * que la cafeína acelera el envejecimiento. *que fumar deshidrata. * que dormir no solo sirve para dar descanso alcerebro. * que la comida que es buena para el intestino lo es tambiénpara el cerebro. * que el envejecimiento es la prueba clara de ladisminución de nuestras enzimas. * por qué la vida de los pianistas estan larga. * el maravilloso papel de la mente en todo esto. * que elsexo es el secreto para mantenerse siempre joven. * que nunca es tarde.* que es necesario se feliz, reír, cantar, bailar# para gozar de buenasalud durante toda la vida. See acast.com/privacy for privacy and opt-out information.

Shinya's host Andrew Gaze joins the Dead Set Legends with an Olympic Update. See omnystudio.com/listener for privacy information.

＜お知らせ＞◆Clubhouse イベント：ぜひご参加ください！ ◆６月２１日２０：００~（犬のしつけ・保護犬のことなど：Shinyaさんと何でもお悩み相談！） ⇒　https://bit.ly/3cUmuif ◆６月２２日２０：００~（コロナ禍で増加？分離不安について：なおちゃん先生と語る！） ⇒　https://bit.ly/3gNveI2 ＜夏の熱中症対策＞ ◆熱中症とはどういう状態？ ◆発生のピーク：何月が多い？ ◆熱を発散させる方法が人と違う？ ◆呼吸数を数える ◆温度・湿度設定 など・・ ◆なおちゃん先生のStand.f,チャネル【ゆるっとワントーク＆時々ワーママ子育てバナシ】 ⇒　https://bit.ly/3cXtN8R ◆Clubhouse クラブ【ペットのホリスティックケア】 ⇒　https://bit.ly/3tXtMbn ◆Clubhouse始めました！ ↓ 探してみてネ ↓ アカウント名：ホリスティック獣医Sara (@holistic_sara) 著書： 【ペットのお悩み解決！メール相談室：犬猫に長生きしてもらうためのホームケア】 ◆電子版（Kindle）：https://amzn.to/3cR7kIa ◆一般（ペーパーバック）：https://amzn.to/2W7C94I ◆質問箱を設置しました！ ペットの健康に関する気になることなど、なにかありましたらお気軽にコメントください。 ラジオ番組内でお答えさせていただきます。 ⇒　https://peing.net/ja/sarapa101mayu Attribution: Otologic, https://otologic.jp Dova syndrome, https://dova-s.jp 往診専門 Saraホリスティックアニマルクリニック DVM(獣医師) / 英国VetLFHom　濱田真由美（Sara） ウェブサイト等: https://linktr.ee/holisticvet.sara ーコメント・シェアはお気軽にどうぞー ホリスティック獣医Saraでした

＜お知らせ＞◆Clubhouse イベント：ぜひご参加ください！ ◆６月２１日２０：００~（犬のしつけ・保護犬のことなど：Shinyaさんと何でもお悩み相談！） ⇒　https://bit.ly/3cUmuif ◆６月２２日２０：００~（コロナ禍で増加？分離不安について：なおちゃん先生と語る！） ⇒　https://bit.ly/3gNveI2 ＜夏の熱中症対策＞ ◆熱中症とはどういう状態？ ◆発生のピーク：何月が多い？ ◆熱を発散させる方法が人と違う？ ◆呼吸数を数える ◆温度・湿度設定 など・・ ◆おすすめ配信：himalaya #160. himalaya祭り：水族館のシャチは本当に幸せ？（オススメのDVD） ⇒　https://bit.ly/3iOK0RA ◆Clubhouse クラブ【ペットのホリスティックケア】 ⇒　https://bit.ly/3tXtMbn ◆Clubhouse始めました！ ↓ 探してみてネ ↓ アカウント名：ホリスティック獣医Sara (@holistic_sara) 著書： 【ペットのお悩み解決！メール相談室：犬猫に長生きしてもらうためのホームケア】 ◆電子版（Kindle）：https://amzn.to/3cR7kIa ◆一般（ペーパーバック）：https://amzn.to/2W7C94I ◆質問箱を設置しました！ ペットの健康に関する気になることなど、なにかありましたらお気軽にコメン...

＜お知らせ＞◆Clubhouse イベント：ぜひご参加ください！ ◆６月２１日２０：００~（犬のしつけ・保護犬のことなど：Shinyaさんと何でもお悩み相談！） ⇒　https://bit.ly/3cUmuif ◆６月２１日２０：００~（コロナ禍で増加？分離不安について：なおちゃん先生と語る！） ⇒　https://bit.ly/3gNveI2 ＜イギリスでは映画館に犬も入れる？＞ ワンちゃん・猫ちゃんと一緒に観ると楽しい映画をご紹介！ ◆The secret life of pets ◆101 Dalmatians ◆Bolt ◆Cats & dogs ◆Hachi約束の犬 など・・ 泣くのを我慢できなかった映画とは・・？ ◆おすすめ配信：himalaya #160. himalaya祭り：水族館のシャチは本当に幸せ？（オススメのDVD） ⇒　https://bit.ly/3iOK0RA ◆Clubhouse クラブ【ペットのホリスティックケア】 ⇒　https://bit.ly/3tXtMbn ◆Clubhouse始めました！ ↓ 探してみてネ ↓ アカウント名：ホリスティック獣医Sara (@holistic_sara) 著書： 【ペットのお悩み解決！メール相談室：犬猫に長生きしてもらうためのホームケア】 ◆電子版（Kindle）：https://amzn.to/3cR7kIa ◆一般（ペーパーバック）：https://amzn.to/2W7C94I ◆質問箱を設置しました！ ペ...

＜お知らせ＞◆Clubhouse イベント：ぜひご参加ください！ ◆６月２１日２０：００~（犬のしつけ・保護犬のことなど：Shinyaさんと何でもお悩み相談！） ⇒　https://bit.ly/3cUmuif ◆６月２１日２０：００~（コロナ禍で増加？分離不安について：なおちゃん先生と語る！） ⇒　https://bit.ly/3gNveI2 ＜イギリスでは映画館に犬も入れる？＞ ワンちゃん・猫ちゃんと一緒に観ると楽しい映画をご紹介！ ◆The secret life of pets ◆101 Dalmatians ◆Bolt ◆Cats & dogs ◆Hachi約束の犬 など・・ 泣くのを我慢できなかった映画とは・・？ ◆おすすめ配信：himalaya #160. himalaya祭り：水族館のシャチは本当に幸せ？（オススメのDVD） ⇒　https://bit.ly/3iOK0RA ◆Clubhouse クラブ【ペットのホリスティックケア】 ⇒　https://bit.ly/3tXtMbn ◆Clubhouse始めました！ ↓ 探してみてネ ↓ アカウント名：ホリスティック獣医Sara (@holistic_sara) 著書： 【ペットのお悩み解決！メール相談室：犬猫に長生きしてもらうためのホームケア】 ◆電子版（Kindle）：https://amzn.to/3cR7kIa ◆一般（ペーパーバック）：https://amzn.to/2W7C94I ◆質問箱を設置しました！ ペットの健康に関する気になることなど、なにかありましたらお気軽にコメントください。 ラジオ番組内でお答えさせていただきます。 ⇒　https://peing.net/ja/sarapa101mayu Attribution: Otologic, https://otologic.jp Dova syndrome, https://dova-s.jp 往診専門 Saraホリスティックアニマルクリニック DVM(獣医師) / 英国VetLFHom　濱田真由美（Sara） ウェブサイト等: https://linktr.ee/holisticvet.sara ーコメント・シェアはお気軽にどうぞー ホリスティック獣医Saraでした

Recorded March 31, 2021 On this reimagined Brief edition of Bargain Binge, The Fellas take a dive into the ever-expanding world of reboots, remakes, seboots, soft reboots, sequels, prequels… whatever! They get to the bottom of what makes most reboots so awful and where the concept even came from to begin with. The Fellas also dissect some recent rebominations including Fantasy Island (2020) and Pan (2015). Along the way, they talk about their recent watches, and (this is very exciting) Dylan introduces an exciting new slasher villain into the Bingeverse. What exactly makes a good reboot? What is the origin of the movie reboot as we know it today? And who the hell is this mysterious Screenpeeker taking the world by storm? All this and more on Bargain Binge - the last bastion of physical media and your wallet!   Our stuff this week: Bad Trip (I hate to say it... but Netflix) Alien  6 Film Collection (Blu-ray Box Set) Solid Metal Nightmares: The Films of Shinya Tsukamoto (Arrow Video Blu-ray Box Set)   Find us on the internet here: Website: bargainbingepod.com Email: bargainbingepod@gmail.com Twitter: @BargainBingePod

Shinya Fukumori Trio - For 2 AkisECM | Feb 16, 20181 Hoshi Meguri No Uta 5:032 Silent Chaos 4:403 Ai San San 5:434 For 2 Akis 2:595 The Light Suite 7:12 5.1 Kojo No Tsuki 5.2 Into The Light / The Light 6 No Goodbye 4:577 Spectacular 3:358 Mangetsu No Yube 3:329 Émeraude 5:2110 When The Day Is Done 4:4711 Hoshi Meguri No Uta (Variation) 4:06Design – Sascha KleisDrums – Shinya FukumoriEngineer [Recording] – Gérard De HaroMastered By [Mastering] – Nicolas BaillardPhotography By [Cover Photo] – Woong Chul AnPhotography By [Liner Photos] – Nadia F. RomaniniPiano – Walter LangProducer [Produced By] – Manfred EicherTenor Saxophone – Matthieu BordenaveRecorded March 2017 La Buissonne, Pernes-les-FontainesAn ECM Production© 2018 ECM Records GmbH, München

Nesse oitavo episódio, conversei com Victor Shinya (Arquiteto de soluções em nuvem na IBM). Ele compartilhou conceitos muito importantes sobre o funcionamento da Cloud, deu várias dicas para iniciantes no mercado e ainda sobre o dia a dia de um arquiteto de soluções. Esperamos que você goste do bate papo e se possível, compartilha com todo mundo que é/está começando na área. Encontre a gente: https://linktr.ee/odisseianolinux Contatos Victor: https://www.linkedin.com/in/victorshinya/ https://blog.victorshinya.com.br/ https://twitter.com/victorshinya

It's a true honor to have bass god and ex-Going Steady/Ging Nang Boyz member ABIKO SHINYA on the show this week! We talk with Abiko about his early days playing music and starting a label in the late 90's Tokyo scene, his work on the album BEACH, and the enduring, rejuvenating power of punk rock.

Shinya from Japan would like to invite you to join us at Solveres. https://www.solveres.com/store/shinyasatake/i/8/solveres-opportunities We suggest enrollment as a free affiliate member. Thanks. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/jack-bosma3/message Support this podcast: https://anchor.fm/jack-bosma3/support

Por Elena Kalinnikova. Suscríbete a CesarVidal.TV y escucha este audio antes que nadie y sin publicidad: https://www.cesarvidal.tv

Quando estudamos o cérebro humano, temos a oportunidade de compreender a nós mesmos, mas esbarramos em um grande desafio: como estudar o cérebro durante os estágios iniciais do desenvolvimento em pessoas vivas? A resposta: é muito difícil. Por isso, grande parte das pesquisas nessa área são realizadas em modelos animais ou em tecidos post mortem do cérebro. Então, só nos restou uma opção: recriar o cérebro humano em laboratório. A Engenharia de Tecidos nos permite reconstruir a arquitetura do tecido de interesse em um “pacote” de células que se desenvolverá em um modelo celular mais complexo. Chamamos esses modelos de organoides e, sem dúvida, o mais interessante deles é o organoide cerebral, também chamado de minicérebro. Aperte o play para o conhecer o fascinante mundo dos minicérebros e como eles estão revolucionando a neurociência. ===== Apoie o SciTalk com R$ 5 ou mais: https://apoia.se/scitalk Instagram: https://www.instagram.com/scitalkpodcast Twitter: https://twitter.com/scitalkpodcast E-mail: scitalkpodcast@gmail.com ===== Luiz Hendrix (Host do SciTalk) Twitter: https://twitter.com/LuizHendrix Instagram: https://www.instagram.com/luizghsa ===== Referências - LANCASTER, Madeline A. et al. Cerebral organoids model human brain development and microcephaly. Nature, v. 501, n. 7467, p. 373-379, 2013. - TAKAHASHI, Kazutoshi; YAMANAKA, Shinya. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, v. 126, n. 4, p. 663-676, 2006. - GARCEZ, Patricia P. et al. Zika virus impairs growth in human neurospheres and brain organoids. Science, v. 352, n. 6287, p. 816-818, 2016. - RAJA, Waseem K. et al. Self-organizing 3D human neural tissue derived from induced pluripotent stem cells recapitulate Alzheimer’s disease phenotypes. Plos One, v. 11, n. 9, p. e0161969, 2016. - RASLAN, Ahmed A.; KEE, Yun. Tackling neurodegenerative diseases: animal models of Alzheimer’s disease and Parkinson’s disease. Genes & Genomics, v. 35, n. 4, p. 425-440, 2013. - MANSOUR, Abed AlFatah et al. An in vivo model of functional and vascularized human brain organoids. Nature biotechnology, v. 36, n. 5, p. 432-441, 2018.

Audiolibro

SHINYA / EXTREME IS EVERYTHING INVITES SBMB ON TOXIC SICKNESS / OCTOBER / 2020 by TOXIC SICKNESS OFFICIAL

1 — Hyde, Shinya, Hajime Okano, HIRO - Embryo Burning (Dead-End Cover) 2 — BUCK-TICK - Miu 3 — Naomi Tamura - hikari to kage o dakishimeta mama 4 — SIAM SHADE - sugao no mama de 5 — Heidi - ∞Loop 6 — BUCK-TICK - ROMANCE 7 — Alice Nine - White Prayer 8 — Lycaon - Last Dance 9 — Plastic Tree - Spica 10 — LIN -the end of corruption world- - Silent to my pain 11 — Acid Black Cherry - Tsumi to batsu 12 — Initial'L - VISION 13 — BUCK-TICK - Flame 14 — X Japan - unfinished

本集 Weekly News 内容包含：► 潮流教父藤原浩（Hiroshi Fujiwara）的概念商店「THE CONVENI」将在9月30日关闭，并计划在纽约布鲁克林举办的潮流盛会HYPEFEST，以及北京、上海和成都开设POP-UP 期间限定商店。► LVMH集团正式宣布终止美国珠宝品牌Tiffany & Co.的收购案，Tiffany & Co因此愤而向美国德拉瓦州法院提告，要求LVMH遵守合约完成交易；另一头的LVMH集团也展开反击，反控Tiffany「不诚实」、「营运不当」！► 设计师小冢信哉主导的同名品牌 SHINYA KOZUKA，其创作反映出小冢在伦敦求学期间所邂逅的古着、风景和生活方式，2021春夏便以「COLOUR CHARTS」为题，为工装带来全新的样貌。如果喜欢我们的频道，并且想要获得更多时尚、潮流、艺术与音乐新讯，欢迎订阅并至以下平台追踪我们：️► 网站：LDOPE.com️► 小红书：904963542► Weibo：Watanabe_24Show► Instagram：instagram.com/ldope️► Facebook：facebook.com/LDOPEcom

本集 Daily News 内容包含了木村拓哉首登《SENSE》封面，集结野口强、高桥盾、西山彻、NIGO 与北村信彦等里原大神、川久保玲 Comme des Garçons 联名 NIKE 推出全新 Dunk 鞋款、当代的 19 世纪工装 SHINYA KOZUKA 介绍。如果喜欢我们的频道，欢迎订阅并至以下平台追踪我们：️网站：LDOPE.com️Instagram：instagram.com/ldope️Facebook：facebook.com/LDOPEcom️小红书：904963542️微博：Watanabe_24Show

About Michael Perrine   Michael Perrine is a detoxification consultant, certified colon hydrotherapist, certified holistic health counselor and the founder of Vitality NYC, a nutritional detox studio in New York City offering gravity colon hydrotherapy, whole body cryotherapy, and nutritional coaching. Over the last seventeen years, Michael has performed over 25,000 colonic irrigations and supervised thousands of people through various methods of internal cleansing including fasting, colon cleansing and liver flushing. Michael has also studied natural food preparation, nutritional science and diet philosophy at the Natural Gourmet Institute for Food & Health and The Institute for Integrative Nutrition. Michael is also an instructor at the Natural Gourmet Institute and a member of the American Association of Drugless Practitioners. Before working as a health counselor, he worked for eight years as a natural foods chef at Angelica Kitchen in New York City. His food has been featured in Time Out New York, Vegetarian Times, The Modern Vegetarian Kitchen, and The Angelica Home Kitchen. He is a regular contributor to top fitness and lifestyle blog Bexlife.com and host of the EveryDayDetox Podcast. In this episode, we discuss       Raw food cleanses (the vitality broom cleanse)     How to prepare for a colonic     Juice cleanses     What happens if you break your juice fast incorrectly or too quickly     How to do the sesame seed colon transit time test     The importance of community     Connection matters. Everything we do matters     Why Mike loves cold plunging     What we think of the celery juice craze (is it all hype?)     Some of the things Mike did to heal his Lyme disease     Consistency wins the game! Michael's Resources https://linktr.ee/everydaydetox     References:   Dr. Fred Bishi John Robbins: Diet for a new America The youtube video by Dr. Shinya colonoscopy: https://youtu.be/uJq0YXI-oJk     OTHER RESOURCES Website – https://purejoyplanet.com/ The Pure Joy Podcast Podcast – http://bit.ly/purejoypodcast Free Recipes – https://purejoyplanet.com/recipes Online Superfood & Health Store –https://store.purejoyplanet.com/ Use code PODCAST10 for 10% off storewide for listeners Plant-Keto Lovecamp Program: https://online.purejoyplanet.com/p/plant-based-keto-diet-program-summer GET IN TOUCH  Instagram – https://www.instagram.com/rawchefelainalove/  Twitter – https://twitter.com/ElainaLove  Facebook –https://www.facebook.com/PureJoyAcademy/ Do you have questions, thoughts or feedback for us? Leave your comments below and one of us will reply! If you'd like to support the show's message, please like rate and review on iTunes or wherever you love to listen to podcasts. Subscribe here: http://bit.ly/purejoypodcast

Dr Joseph Hill:                    My name is Joe Hill. I'm the Editor-in-Chief of Circulation and I'm very pleased today to be here today with Professor Daida from Juntendo University in Tokyo, Japan, as well as one of our associate editors, Professor Shinya Goto from Tokai University in Kanagawa, Japan. Dr. Daida is one of the senior authors on a very exciting clinical trial that we're publishing in Circulation. The first and largest trial comparing high-dose versus low-dose statins in Asia. Dr. Daida, would you please tell us more about the study? Dr Hiroyuki Daida:            Yes. Thank you. The trial, called REAL-CAD, is a randomized trial. We compare high-dose statins with low-dose statins in Japanese patients with stable coronary artery disease. The number of the patients is 13,000. It's the largest trial ever comparing high-dose and low-dose statins. We found that with that reduction of the primary end point, which is a composite end point, including cardiovascular death, non-fatal MI, non-fatal stroke, and unstable angina requiring hospitalization.                                                 That is very exciting result because it is the largest trial ever and also the very first trial in Asia. Professor Shinya Goto: Congratulations, Professor Daida, for that great achievement, in the REAL-CAD trial. Could you explain a little bit about the background and that the dose of statins in Japan is generally low, and what was the reason why we kept using low-dose statins, and is care to try change the standard of care in Japan and also East Asia? Could you give a comment on those two topics? Dr Hiroyuki Daida:            Our trial is quite similar to that of PNP trial of comparing Western extensive statin treatment and the Asia statin treatment. However, that extensive statin treatment, intensive statin treatment, is not popular in Asia, so we did that maximum clinical dose of statin, we use this dose in Japan. It is the maximum dose of statin approved in Japan. Dr Joseph Hill:                    So as I understand it, the rationale was the thinking that Asians, East Asians, are unable to tolerate high-dose statin therapy. In this case you used pitavastatin. And, in fact, what you found was there were no increase in serious adversive events in high dose patients. And, just like Caucasians, they derived considerable benefit at multiple points in atherosclerotic cardiovascular disease metrics. Dr Hiroyuki Daida:            Actually, they didn't experience a really high-dose of statin in Japan so government approval is up to 4 mg of pitavastatin, a dose of that about 20. Dr Joseph Hill:                    So, this is not what we would call high-intensity statin therapy but nonetheless, there was a dramatic benefit including an all-cause mortality, irrespective of the starting LDL level at the beginning of the trial? Dr Hiroyuki Daida:            That is right. We found that the effect is similar that the patient, the LDL is greater than 95 or less than 95. So, the effect is independent of the basal based on LDL level. Professor Shinya Goto: The one thing, very exciting just like Joe mentioned, all cause of mortality, especially known cardiovascular caused mortality reduced with the use of high-intensive care of the statin. If any kind of speculation, what is the cause, reduce the inflammation or maybe reduce cancer, something like that. They have any kind of advance to an analysis? Dr Hiroyuki Daida:            We didn't have further analysis but we are not so keen to emphasis the total mortality because maybe that is a chance of the effect but this is the largest trial, so the result is really exciting in this kind of aspect. Dr Joseph Hill:                    So, I would reiterate Shinya's congratulations. This is a monumental piece of work. The largest clinical trial comparing high dose versus low dose statin. The largest ever. The first in Asia. You found a benefit that makes total sense across what we know from other trials and this will change practice. Your work, I believe, will change the way patients with atherosclerotic cardiovascular disease is handled in Japan. Dr Hiroyuki Daida:            Yes, actually the current guideline in Japan for the secondary condition. The condition is LDL less than 100 and for the really high-risk secondary condition listed seventh. We didn't recommend high-dose statin initially, so, this trial result is kind of like this, changing. Dr Joseph Hill:                    I can't resist asking, what comes next? What's your next project? Dr Hiroyuki Daida:            Maybe we need to have a further reduction of LDL. We have another drug, other potent drug recently. We need to investigate all of the new drug such as PCSK9 inhibitor in secondary prevention. Professor Shinya Goto: That's wonderful. Do you have any time to extend observation of the trial? I think the trial is relatively still superior as compared to the global long-standing trial. Really, that's fine, that effect of statin on the cholesterol and even it's different from Japan and other regions of the world. There ought to be intriguing thing, I would like to know, what are you waiting to extend that observation now? Dr Hiroyuki Daida:            Fortunately, we do not intend to extend the follow-up. The whole thing is about four years but we do not plan to extend. We will further analyze the data for some group and our kind of CRP and effect of the baseline. Dr Joseph Hill:                    Lots of secondary analysis underway, undoubtedly. Let me thank both of you for being here, Professor Daida and Professor Goto, I congratulate you again. It's not often that you make a practice-changing intervention in modern-day medicine. I salute you and we are honored and thrilled to publish your outstanding work in Circulation. Thank you both. Dr Hiroyuki Daida:            Thank you very much. Professor Shinya Goto: Thank you very much.  

  Dr. Lam:               Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the Journal and its editors. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Our podcast is taking us to Japan today where we will be talking about aspirin for primary prevention in patients with diabetes. First, here's your summary of this week's issue.                                 The first study provides insight into the development of neurologic injury in patients with single ventricles undergoing staged surgical reconstruction. In this paper by Dr. Fogel and colleagues from the Children's Hospital of Philadelphia, the authors recognize that single ventricle patients experience greater survival with staged surgical procedures culminating in the Fontan operation, but experience high rates of brain injury and adverse neurodevelopmental outcome. They therefore studied 168 single ventricle patients with MRI scans immediately prior to bi-directional Glenn, prior to the Fontan, and then three to nine months after the Fontan reconstruction. They found that significant brain abnormalities were frequently present in these patients and that the detection of these lesions increased as children progressed through staged surgical reconstruction. In addition, there was an inverse association of various indices of cerebral blood flow with these brain lesions. This study therefore suggests that measurement of cerebral blood flow and identification of brain abnormalities may enhance recognition of single ventricle patients at risk for poor outcomes, and possibly facilitate early intervention.                                 The next paper uncovers a unique mechanism underlying arrhythmogenesis and suggests that the anti-epileptic drug valproic acid may possibly be repurposed for anti-arrhythmic applications. In this paper by first authors Dr. Chowdhury and Liu and corresponding author Dr. Wang and colleagues from University of Manchester UK. The authors used mouse models and human induced pluripotent stem cells derived cardiomyocytes to discover a new mechanism linking mitogen activated kinase-kinase 7 deficiency with increased arrhythmia vulnerability in pathologically remodeled hearts. Mechanistically, mitogen activated kinase-kinase-7 deficiency in the hypertrophied hearts left histone deacetylase-2 unphosphorylated, and filamin A accumulated in the nucleus, which then formed an association with kruppel-like factor 4 preventing its transcriptional regulation. Diminished potassium channel reserve caused repolarization delays resulting in ventricular arrhythmias, and the histone deacetylase-2 inhibitor, valproic acid restored potassium channel expression abolishing the ventricular arrhythmias. This study therefore provides exciting insights in developing a new class of anti-arrhythmics specifically targeting signal transduction cascades to replenish repolarization reserve, all for the treatment of ventricular arrhythmias.                                 Does the Mediterranean diet improve HDL function in high risk individuals? Well, the next paper by first author Dr. Hernaiz, corresponding author Dr. Fito and colleagues from Hospital Del Mar Medical Research Institute in Barcelona, Spain addresses this questions. The authors looked at a large sample of 296 volunteers from the PREDIMED study and compared the effects of two traditional Mediterranean diets, one enriched with virgin olive oil, and the other with nuts to a low-fat control diet. They looked at the effects of these diets on the role of HDL particles on reverse cholesterol transport, HDL antioxidant properties, and HDL vasodilatory capacity after one year of dietary intervention. They found that both Mediterranean diets increased cholesterol efflux capacity and improved HDL oxidative status relative to the baseline. In particular, the Mediterranean diet enriched with virgin olive oil decreased cholesterol ester transfer protein activity, and increased HDL ability to esterify cholesterol, paraoxonase-1, arylesterase activity, and HDL vasodilatory capacity. They therefore concluded that adherence to a traditional Mediterranean diet, particularly when enriched with virgin olive oil, improves HDL function in humans.                                 The final study tells us that among hospitalized medically ill patients, extended duration Betrixaban reduces the risk of stroke compared to standard dose enoxaparin. In this retrospective sub-study of the APEX trial, Dr. Gibson and colleagues from Beth Israel Deaconess Medical Center and Harvard Medical School in Boston, Massachusetts randomized 7,513 hospitalized acutely ill patients in a double-dummy, double-blind fashion to either extended duration of the oral Factor Xa inhibitor Betrixaban at 80 mg once daily for 35 to 42 days, or standard dose subcutaneous enoxaparin at 40 mg once daily for 10 days all for venous thromboprophylaxis. They found that the extended duration Betrixaban compared with enoxaparin reduced all cause stroke by almost one half with a relative risk of 0.56 equivalent to an absolute risk reduction of 0.43 percent and number needed to treat of 232. The effect of Betrixaban on stroke was explained by a reduction in ischemic stroke with no difference in hemorrhagic stroke. The reduction in ischemic stroke was confined to patients hospitalized with acute heart failure or non-cardioembolic ischemic stroke.                                 This paper is accompanied by an editorial by Drs. Quinlan, Eikelboom, and Hart in which they articulate three reasons that they think these results are important. First, the results demonstrated an unexpectedly high rate of new or recurrent ischemic stroke during the first three months in hospitalized medical patients receiving standard enoxaparin prophylaxis, the rate being even higher in patients presenting with heart failure or ischemic stroke. Secondly, the data demonstrated for the first time that a NOAC reduces the risk of ischemic strokes in patients without known atrial fibrillation. Thirdly, the effects of Betrixaban on stroke were dose dependent, all of the benefits were seen in those who received the 80 mg dose, whereas the 40 mg dose did not provide advantages compared with enoxaparin or placebo. While these results are encouraging, the editorialists also warn that these are based on a post-hoc analysis and should be considered hypothesis generating.                                 Well, that brings it to the end of our summaries. Now for our feature discussion.                                 Today our feature discussion focuses on the exciting 10-year follow up results of the Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes, or JPAD trial. I am simply delighted to have with me first and corresponding author Dr. Yoshihiko Saito from Nara Medical University, Japan. As well as a familiar voice on this podcast, Dr. Shinya Goto associate editor of Circulation from Tokai University in Japan. Welcome gentlemen! Dr. Goto:             I am very pleased to have this opportunity. I am always enjoy listening your podcast, and this is very interesting topic of aspirin in prevention cardiovascular event in patients with diabetes, type II diabetes. Dr. Lam:               I couldn't agree more, because the burden of cardiovascular disease globally is actually shifting to Asia, and the burden of diabetes especially, is one of the fastest growing in Asia. So a very, highly relevant topic indeed. Could I start, Yoshi, by asking you: these are the 10 year follow up results, what inspired you to take a re-look at the original JPAD results and to report this 10 year result? Dr. Saito:              The American guidelines said that low-dose aspirin is recommended to the type II diabetes patient for the primary prevention of cardiovascular events who are older than 30 years old, and who are not contraindicated to aspirin. That meant that almost all type II diabetes patients were recommended to low dose aspirin. However, at that time there was no direct [inaudible 00:09:49] evidence for it. So we connected the prospective randomized control trial that examined the effects of the low dose aspirin on primary prevention of cardiovascular events in type II diabetes patients without preexisting cardiovascular disease. The name of this trial, JPAD trial, that stand for the Japanese Primary Prevention of Atherosclerosis with aspirin in Diabetes. We enrolled 2,539 patients who were assigned to the low dose asprin group or the no aspirin group. So we followed them with a median follow up period of 4.4 years.                                 The results of the original JPAD trial were that low dose aspirin reduced CV events by about 20%, but the reduction could not reach statistical significance. So I don't know the exact reason, but one is the reason is low statistical power, because event rate was about one-third of the anticipated. Another reason is that low dose aspirin really could not reduce cardiovascular events. So we decided the extension of the follow up of the JPAD trial to elucidate the efficacy and safety of long term therapy with low dose aspirin in type II diabetes patients. This extension study was named the JPAD 2 study. We followed them up to the median follow up period of more than 10 years.                                 In this time the JPAD trial study, we analyzed the patients in a pod protocol method because the randomized control trial was ended after 2008. Finally, we analyzed the 992 patients in the aspirin group, and 1,168 patients in the no aspirin group who retained the original allocations throughout the study period. The primary endpoint were composite endpoint of cardiovascular events including sudden cardiac death, the fatal and the non-fatal coronary artery disease, fatal and non-fatal stroke, peripheral vascular disease, and aortic dissection. This end point is the same as the original JPAD trial. The main results are the primary endpoints, 15.2% of patients occurred primary endpoints in aspirin group, and 14.2% in the no aspirin group occurred in the primary endpoints. So the primary endpoints rate is singular in both groups, with the hazard ratio is 1.14 with a 95% CI is 0.91 to 1.42 with a p value of 0.2 by log-rank test. So the low dose aspirin therapy could not reduce cardiovascular events in the type II diabetes mellitus.                                 We also analyzed these data by intention to treat analysis, the results is singular. Again, the low dose aspirin therapy could not reduce the cardiovascular event in type II diabetes mellitus. However, I was told the hemorrhagic events, total hemorrhagic events was singular in both groups, but gastrointestinal bleeding of about 2% in the aspirin group but only 0.9% in no aspirin group. That means our gastrointestinal bleeding is doubled in the aspirin group compared with no aspirin group. This is the main outcome of the JPAD and JPAD-2 trials. Dr. Lam:               Thank you so much Yoshi, and really congratulations on such a tremendous effort. I completely applaud the idea of looking at the 10 year follow up trying to address the issue of whether or not it was a lack of power that limited JPAD-1, but what you found really reinforced what you found in JPAD-1, which is low dose aspirin did not reduce cardiovascular events in the diabetic group. They're still huge numbers, I'm so impressed that 85% of the treatment assignment was retained. Then furthermore you even showed increased gastrointestinal bleeding with aspirin. So really remarkable results. Can I just ask, are you surprised by the results, and how do you reconcile it with what was found in the general population studies like the Physician Health Study, or the US Preventive Services Task Force, where they really seem to say that primary prevention aspirin works in the general population when your risk is a certain amount? Dr. Saito:              I think that we studied only the type II diabetes patients, so it is not clear that our results are applied to the general population, but our results is very much similar to the current European guidelines and American guidelines. Dr. Lam:               That's a very interesting point about diabetic versus non-diabetic population and the utility of low dose aspirin. Shinya, you brought this up before. What do you think? Dr. Goto:             For the primary prevention population cohort study, aspirin demonstrated 25% reduction of cardiovascular event. We are not recommending aspirin for primary prevention due to the balance of bleeding and cardiovascular protection, absolute risk. In Yoshi's paper, in patients with type II diabetes aspirin evened that [inaudible 00:16:13], and that is very important message he had shown in this long term outcome randomized trial. Dr. Lam:               Do you think that there are some pathophysiologic differences when you study a diabetic versus non-diabetic population? Dr. Goto:             Yes, that is a very important topic, and we have very nice review paper by Dr. Domenico and Fiorito. In patients with diabetes the platelet time over becomes relatively rapid as compared to general population. New platelets come to blood and COX-1 inhibition by aspirin cannot reach to enough level in diabetes patient. Still, this [inaudible 00:16:57] hypothesis, very interesting hypothesis. Dr. Saito:              I think so, I think so. That review that proposed the same concept, their higher dose of aspirin as possibly effective for diabetic patient. Dr. Lam:               That's interesting. Are you planning any future studies Yoshi? Dr. Saito:              Yeah, maybe two times study. Dr. Goto:             But anyway, the event rate is currently very low than the old [inaudible 00:17:28]. So the sample size should be huge. Huge sample size is needed for the primary prevention setting to analyze the effect of aspirin, so the number needed to treat in the primary prevention setting is more than 1000. If diabetes patient, aspirin is resistant to aspirin so the number needed to treat is getting larger. So the sample size is getting larger and larger. That is not practical to perform that clinical trial. Dr. Lam:               That's a very good point that the contemporary trials like yours are really challenged by the low event rates because of improved preventive treatment across the board like high dose statins, like very, very low LDL targets, and so on. That's a good point. Actually, could I ask both of you gentlemen, and maybe Shinya you can start, can you let us know what is it like to perform such a large rigorous clinical trial in Japan? It must be a lot of effort. Could you give us an idea? Dr. Goto:             In Japan, medical care system is a little bit different from the U.S. Every patient covered by the homogeneous health care system so it means it is rather difficult to conduct a clinical trial. I appreciate the effort by Professor Saito, Yoshi, it is extremely difficult to conduct the study. Japan is relatively small island, patient stick to the clinic so the long term follow up with relatively low follow up can be expected. [inaudible 00:19:15] number of patients is a challenge, and Yoshi did succeed it. We can do that and due to the baseline therapy is quite homogenous, impact of the clinical care like this has very strong impact. Dr. Lam:               Exactly, and I share your congratulations once again to Yoshi for really tremendous effort, important results. Thank you so much Shinya for helping with this paper, and for really highlighting how really important it is. Did anyone have anything else to add? Dr. Saito:              Yes, I have one thinking, in respect to the Japanese clinical trials. I think the Japanese evidence, as derived from Japanese clinical studies is getting better and better in quality. Almost all Japanese clinical trials enrolled only Japanese patients, so the way the Japanese not so good at to organize the international clinical trial because of the, one is the language problem, and the other is funding problem. In Japanese funding agency, the AMED, that is similar to the NIH in United States, but AMED is not so strong as NIH so that they cannot give a bigger budget to the Japanese clinicians. That is another problem to organize a big clinical trial. The funding [inaudible 00:20:49] apprenticeship without holding investigators are very, very important to be better clinical situation in Japan, I think so. Dr. Lam:               Thank you for listening to Circulation on the Run, don't forget to tune in next week.  

  Carolyn: Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore.     In just a moment, we are going to be discussing the feature paper on results of the RE-LY trial in patients with valvular heart disease. Yes, you heard me right, this means dabigatran versus warfarin in patients with atrial fibrillation and valvular heart disease. You need to listen to this discussion with first author Dr. Michael Ezekowitz, but first here is a summary of this week's issue.     In the first study, Dr. Norby and colleagues from the School of Public Heath University of Minnesota assessed trajectories of cardiovascular risk factors and the incidence of atrial fibrillation over 25 years in the ARIC study or the Atherosclerosis Risk in Communities Study. They first assessed the trajectories of cardiovascular risk factors in more than 2,400 individuals with incident atrial fibrillation and more than 6,400 matched controls. Next, they determined the association of those risk factor trajectories with the incidence of new atrial fibrillation among more than 10,500 individuals free of atrial fibrillation at baseline.     The main finding was that stroke, myocardial infarction and heart failure risk increase steeply during the time close to diagnosis of atrial fibrillation. All cardiovascular risk factors were elevated in atrial fibrillation cases compared to controls more than 15 years prior to the diagnosis. A trajectory analysis showed not only the presence of the risk factors such hypertension and obesity, but also their duration which was more informative in determining the risk of atrial fibrillation compared to a one time clinical measurement.     Finally, they identified diverse and distinct trajectories for the risk factors findings that carry implications for the different roles of different risk factors in the pathogenesis of atrial fibrillation. The findings of this very significant study also highlight the need to establish preventive strategies that address risk factors decades before atrial fibrillation diagnosis.     The next study is by first author Dr. van der Valk and corresponding author Dr. Strauss from the Academic Medical Center in Amsterdam. These authors aimed to better understand the underlying mechanisms responsible for atherogenicity of lipoprotein a or LPa. The authors achieved this aim by a combination of three approaches. First, in vivo magnetic resonance imaging using 18F-FDG PET/CT and SPECT to measure atherosclerotic burden, arterial wall inflammation and monocyte trafficking to the arterial wall. Secondly, ex vivo analysis of monocytes using facts analysis, inflammatory stimulation assays and trans endothelial migration assays. Third, in vitro studies on monocytes using an in vitro model for trained immunity.     Their main findings were that, firstly, individuals with elevated LPa had increased arterial wall inflammation in vivo. Secondly, that monocytes from these individual remain in a long lasting activated state ex vivo, and finally, that LPa elicited a pro-inflammatory response in healthy monocytes in vitro, an effect that was markedly attenuated by removing or inactivating oxidized phospholipids on LPa.     In summary, this study nicely shows that LPa induces monocyte trafficking to the arterial wall and mediates pro-inflammatory responses through its oxidized phospholipid content. The clinical implications are therefore, that oxidation's specific epitope targeted therapy using for example specific antibodies as single gene antibodies may bear clinical potential to modulate the arthrogenic impact of LPa.     The final study is from first author Dr. Mazen, and corresponding author Dr. Ouzounian from Toronto General Hospital and University of Toronto in Ontario, Canada. These authors sought to compare the long term outcomes of patients undergoing the Ross procedure compared to mechanical aortic valve replacement in a propensity match cohort study of 208 pairs followed for a mean of 14 years.     They found long term survival and freedom from re-intervention were comparable between the Ross procedure and mechanical aortic valve replacement. Of note however, the Ross procedure was associated with improved freedom from cardiac and valve related mortality, as well as a significant reduction in the incidence of stroke and major bleeding. This paper provides important evidence that supports continued used of the Ross procedure in properly selected young adult patients in specialized centers.     What this means is having experienced surgical teams dedicated to mastering the technique and committed to carefully following up the patients for possible late complications. This and more is discussed in a provocative editorial by Dr. Schaff from Mayo Clinic Rochester, Minnesota who provocatively entitled his editorial 'The Ross Procedure: Is it the Preferred Procedure or Double, Double Toil and Trouble?'     Those were all summaries, now for our featured paper.     I am so excited to be joined from all over the world to discuss the featured paper today, and that is on the comparison of dabigatran versus warfarin in patients with atrial fibrillation and valvular heart disease. To discuss this first we have, first and corresponding author, Dr. Michael Ezekowitz from the Sidney Kimmel Medical College at Thomas Jefferson University and Lankenau Medical Center in Philadelphia, as well as from the Cardiovascular Research Foundation in New York. Welcome Michael.   Michael: Thank you very much.   Carolyn: Michael, you're calling from South Africa aren't you?   Michael: I am indeed.   Carolyn: That's wonderful. We're very honored to have Dr. Shinya Goto Sensei, Associate Editor of Circulation from Tokai University Japan. Hello Shinya.   Shinya: Hello Carolyn, thank you very much for your invitation to such an excited podcast. I enjoy podcast every week.   Carolyn: I love this and it is extremely exciting and the most global discussion that we have had so far, with calling in Japan and Singapore and South Africa. Indeed it's because we're discussing a very important problem globally. Michael first, when we talk about the RE-LY trial and the NOAC trials, we're always associating them with non-valvular atrial fibrillation, and yet your topic is discussing valvular heart disease from RE-LY. Can you please start by clarifying that?   Michael: I think the reason we wrote this paper is that there is a misunderstanding of the patient populations that was studied in all the NOAC trials because they were characterized as having non-valvular atrial fibrillation. That's only partially true because in all the trials, patients with mechanical heart valve and hemodynamically significant mitral stenosis were excluded, and yet there were many patients with valvular disease that were included. In the RE-LY trial which is the focus of this particular paper, 25% of the patients had some form of valvular disease that were recruited into the study. So the term non-valvular is misleading.   Carolyn: That is such an important clarification, and it's an issue that I see a lot in Singapore. Frankly, lots of patients with atrial fibrillation have some valve disease even if you exclude prosthetic valves, significant mitral stenosis or valvular heart disease requiring intervention. We're very clear not that this is the patient population you're referring to. Shinya, I want to bring you into this. I see lots of these patients, how about you?   Shinya: The same. Majority of patients have valvular heart disease, small mitral regurgitation is very common. We are excluding only clinically overt mitral stenosis and basically mechanical heart valve in all the newest trials. As Michael pointed out, it is very important to correct misunderstanding. Non-valvular atrial fibrillation, we used in the clinical trial is all atrial fibrillation except clinical overt mitral stenosis and prosthetic for mechanical heart valve.   Carolyn: Exactly. A great foundation for us to get our understand right before we discuss the findings. Michael, could you please give us the top line result and tell us what do the results mean for your own clinical practice?   Michael: Basically, it means that the patients with valvular heart disease that were included in the trial, and these included patients with mitral regurgitation with was the most common lesion, mixed aortic valve disease, tricuspid regurgitation, and also it turned out that there were 192 patients that had mild mitral stenosis. Those with mitral stenosis were presumed to be rheumatic in ideology, and they did have a profile of having rheumatic heart disease, that there were more females, they were younger, there was a high incidence of heart failure and a high incidence of TIA and stroke.     The bottom line here is whether the patients had mild mitral stenosis or the other forms of valvular disease that I just mentioned, that they benefited in an identical fashion from the 150 milligram BID dose of dabigatran and the one 110 milligram BID dose of dabigatran as those patients without any valvular disease. The bottom line is that clinicians can use dabigatran with equal confidence in these patients with valvular disease as in patients without valvular disease.   Carolyn: Thank you Michael, that was very reassuring and something that is very clinically important. Shinya, I'm going to ask a different question. First, maybe your take on the findings, and secondly, what was it like handling this paper across the globe as the Associate Editor Managing this?   Shinya: That is a very important point. The past as Michael pointed out, this paper is very important to remind the clinician of non-valvular atrial fibrillation is not really non-valvular atrial fibrillation, and there is no difference between valvular atrial fibrillation except mitral stenosis and prosthetic valve. The result is similar to non-valvular atrial fibrillation in regard to the effect of dabigatran or by warfarin. That is the one point I have to assure. As a part, it is very important. We are now including many patients not limited in that North America, Europe. We are participating a huge number of patients from Asia. The results is applicable to the global level. We are now leading in that global evidence-based world and RE-LY is one of the good example for the global trial testing the hypothesis with [inaudible 00:13:58] over warfarin.     Michael made a very good summary of that, not only limited to RE-LY, he talked about as our trial like ARISTOTLE and the ROCKET trial. All of the NOAC trial include patient who is valvular heard disease, and the exclusion criteria is a little bit different. Michael beautifully summarized that difference in the table, in his paper.  There is a strong intention to publish this paper integration from all the editorial of old member. This is a very nice paper.   Michael: He's been very kind, that's very nice. That's true. In fact, the results in RE-LY were compared in an indirect fashion with the other trials, ROCKET and ARISTOTLE, through have published similar papers on patients with and without valvular heart disease. Just in summary, the bottom line is that this finding in RE-LY is highly reproducible in the other two trials so this is an important finding that is reproducible and true of the three novel agents that had looked at this in detail.     The other point that was raised is that there were differences in the exclusion criteria in these trials, but at the end of the day, the Europeans and the Americans in terms of guidelines, had fairly similar recommendation. For instance in the United States, it was felt that all patients with valvular disease could be anti-coagulated with the novel agent unless they had rheumatic mitral stenosis, mechanical or bioprosthetic heart valves, or patients that had undergone a prior mitral valve repair. The emphasis was that all other patients could be included.     The Europeans differed slightly and that they agreed that mechanical prosthetic valve and moderate to severe mitral stenosis should be excluded, but they were somewhat more global in recommending inclusions of all other valvular conditions. There is a slight difference then between the European and the American recommendations and guidelines.   Carolyn: On that note of looking across the world at the guidelines and what these results mean, it really leaves me to congratulate you Michael on such an excellent paper, and Shinya for just managing this paper so well.   Michael: Thank you.   Shinya: Thank you very much for your invitation. Bye-bye.   Carolyn: You've been listening to Circulation on the Run. Thank you for joining us today.