Podcast appearances and mentions of chris granger

Ever wondered how to truly embody the love, grace, and truth of Christ in everyday life, far beyond the walls of the church? Discover how every believer is called to carry this significant responsibility, from the workplace to daily routines. Chris Granger challenges the common misconception that only those in formal ministry are tasked with this role, inviting you to embrace your identity as a reflection of Christ in every interaction.For full show note details, go to the episode webpage:

Reclaim the sanctuary of family connection and transform your home into a fortress of love and understanding. Ever feel like the dinner table is more of a battleground than a haven? Join me, Chris Granger, as I promise to guide you through practical strategies for creating a family dynamic that stands strong against the distractions of modern life. Drawing inspiration from timeless sitcoms like "The Andy Griffith Show" and biblical teachings from Proverbs and Ephesians, we'll explore how to forge meaningful bonds during everyday moments. Imagine turning mundane car rides into opportunities for heartfelt conversations and spiritual growth, all while reclaiming your role as the leader of your household.For full show note details, go to the episode webpage:

What if you could transform your physical health while deepening your spiritual journey? Join me, Chris Granger, as we kick off 2025 with a fresh perspective on building both spiritual and physical strength. Through personal reflections from my weight loss journey, I draw parallels between caring for our bodies and restoring classic cars. Guided by 1 Corinthians 6:19-20, we explore the importance of viewing our bodies as temples of the Holy Spirit and the impact of establishing daily habits in praise, prayer, movement, and wisdom. Discover how creating personalized routines can prepare us for life's battles while ensuring our habits are flexible enough to fit our unique lifestyles.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/471-biblical-view-of-health-resolutions/Send us a textThis holiday season, don't face the highs or lows alone. Join The Lion Within Us—a Christian men's community offering genuine connection, encouragement, and growth. From Black Friday through New Year's Eve, save 50% and step into a brotherhood that will inspire and challenge you to become the man God created you to be.Visit TheLionWithin.us today to claim this limited-time offer!Support the showJoin the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffJoin Chris and other members every weekday morning in our app FREE! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Prepare to uncover the transformative implications of Christ's final words, "It is finished." In our latest soul-stirring episode, we delve into the depths of "tetelestai" and its impact on our spiritual lives and leadership. I, Chris Granger, guide you through the events leading up to the cross and how Jesus's ultimate sacrifice establishes a new foundation for our faith as Christian men. As we examine the completion of His work, we'll discover together how to integrate these profound truths into our daily lives and leadership roles.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/380-sko-john-19-30/Get started for free with our 30 Day to Unleash the Lion Within series In just 30 days, you'll embark on a journey of self-discovery and growth. This free resource offers a series of messages, with proven methods to simplify and apply God's Word to your life, empowering you to be an effective leader. Visit thelionwith.us/unleash to get started for free today. Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffJoin Chris and other members every weekday morning in our app FREE! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

As a Christian man, do you often wonder how to navigate your leadership role with faith at the helm? Join me, Chris Granger, along with Pastor Cedric Brown, as we share stories and insights on walking in the divine purpose crafted for you. We kick off with Pastor Cedric's riveting transition from the NFL to the pulpit, a testament that underscores our core message: You are God's masterpiece, designed for extraordinary endeavors. Delving into the nourishing depths of scripture, we tackle the transformative power of the Bible in building mental resilience and the profound joy in giving generously. Our conversation also casts a spotlight on the pivotal roles we play as husbands and fathers, challenging societal norms that attempt to diminish these sacred duties.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/376-building-resilient-communities-fun-friday/Get started for free with our 30 Day to Unleash the Lion Within series In just 30 days, you'll embark on a journey of self-discovery and growth. This free resource offers a series of messages, with proven methods to simplify and apply God's Word to your life, empowering you to be an effective leader. Visit thelionwith.us/unleash to get started for free today. Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffJoin Chris and other members every weekday morning in our app FREE! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Ever wondered how your everyday actions can become a testament to your faith? Join me, Chris Granger, as we traverse the landscape of leading a God-honoring life, from the workplace to the comforts of home with your loved ones. Imagine sitting down to your next meal and asking yourself if it's worthy of being set before the Lord—this episode not only poses such reflective questions but also serves up nourishing advice on how to treat our bodies as temples. And for those of you keeping an eye on your finances, get ready to glean some wisdom for prospering in a bull market, ensuring that your wealth management aligns with divine principles.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/364-fun-friday-living-a-god-honoring-life/Disconnect from the digital world and reconnect with your fellow brothers in Christ around a crackling campfire. Share stories, laughter, and deep conversations that forge lifelong friendships and bonds. April 26-28, 2024 | Stem, NC. Visit https://thelionwithin.us/events/ to register today! Get Free Daily Inspiration With Our Bible App DevotionalsOur devotionals dive deep into the pillars that define The Lion Within Us - health, wealth, and self. Whether you're seeking spiritual growth, financial wisdom, or personal development, these devotionals are tailor-made for you. Connect with The Lion Within Us on YouVersion Bible App. Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffJoin Chris and other members every weekday morning in our app FREE! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Join the ranks of those who dare to live by the powerful teachings of Isaiah 1:17, as we, Chris Granger and The Lion Within Us community, embark on a quest to embrace our divine duties as Christian men. Feel the call to action as we dissect what it truly means to defend the oppressed, champion the fatherless, and support the widow - not simply as choices, but as our sacred response to God's summons. This episode isn't just a discussion; it's a rallying cry to put our faith into fearless action, whether through adoption, fostering, or championing pro-life causes.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/356-sko-isaiah-1-17/Disconnect from the digital world and reconnect with your fellow brothers in Christ around a crackling campfire. Share stories, laughter, and deep conversations that forge lifelong friendships and bonds. April 26-28, 2024 | Stem, NC. Visit https://thelionwithin.us/events/ to register today! Get Free Daily Inspiration With Our Bible App DevotionalsOur devotionals dive deep into the pillars that define The Lion Within Us - health, wealth, and self. Whether you're seeking spiritual growth, financial wisdom, or personal development, these devotionals are tailor-made for you. Connect with The Lion Within Us on YouVersion Bible App. Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffJoin Chris and other members every weekday morning in our app FREE! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Embark on a transformational quest with me, Chris Granger, as we navigate the intricate pathways of discipleship and leadership through the Christian lens. This week, we zero in on how the act of sharpening one another's faith can revolutionize our spiritual journey, with Jesus' own methods as our blueprint. Peek into the compelling dialogue with Jim Halston, where he sheds light on the challenges confronting the church in an era that thirsts for true discipleship and the fulfillment of the Great Commission. Get a dose of motivation with our 'Fun Friday' segment that introduces the 'T' for 'tough' in the SMARTER goals framework, nudging you towards the pursuit of those 'big, hairy, audacious goals' that promise to elevate your role as a steadfast pillar in your family and community.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/355-fun-friday-cultivating-personal-and-communal-growth/Disconnect from the digital world and reconnect with your fellow brothers in Christ around a crackling campfire. Share stories, laughter, and deep conversations that forge lifelong friendships and bonds. April 26-28, 2024 | Stem, NC. Visit https://thelionwithin.us/events/ to register today! Get Free Daily Inspiration With Our Bible App DevotionalsOur devotionals dive deep into the pillars that define The Lion Within Us - health, wealth, and self. Whether you're seeking spiritual growth, financial wisdom, or personal development, these devotionals are tailor-made for you. Connect with The Lion Within Us on YouVersion Bible App. Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffJoin Chris and other members every weekday morning in our app FREE! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Step into courage with me, Chris Granger, as we navigate the bold act of speaking God's truth from the powerful narrative of Daniel 5. Get ready to fortify your resolve and learn how to embrace the criticisms that come with standing firm in your faith. This Fun Friday, we dissect the intricacies of bravery in prayer, finances, and relationships. I'm here to share with you the vitality of forthright prayer to bolster your confidence in God, the advantages of a Roth IRA for your financial health, and the profound impact of deepening your familial bonds. This is about transforming your life, from your spiritual core to the daily interactions that define you.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/337-fun-friday-embracing-courage-and-conviction/Disconnect from the digital world and reconnect with your fellow brothers in Christ around a crackling campfire. Share stories, laughter, and deep conversations that forge lifelong friendships and bonds. April 26-28, 2024 | Stem, NC. Visit https://thelionwithin.us/events/ to register today! Get Free Daily Inspiration With Our Bible App DevotionalsOur devotionals dive deep into the pillars that define The Lion Within Us - health, wealth, and self. Whether you're seeking spiritual growth, financial wisdom, or personal development, these devotionals are tailor-made for you. Connect with The Lion Within Us on YouVersion Bible App. Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffFor only $5 a month, join Chris and other members every weekday morning in our app! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Chris Granger, owner of Seven Oaks Grand Coteau LLC, and Maison Title, joined Discover Lafayette to discuss his growing real estate empire. He is an attorney, a married father of five young boys, and a force to be reckoned with! While Chris worked with an established law firm for 2 1/2 years after graduating from law school, he knew he was never going to work for someone else very long. In 2018 he opened up his own law practice with his wife's cousin, Benjamin Trant, and then Justin Leger became the third business partner. Business took off. The logo/painting of Maison Title was derived from an old painting found in a rental home. Leah Graeff, Maison Title's Marketing and Brand Strategist, redesigned the painting and the logo's font is based upon one found on an old sweet potato label, the significance of which Chris explains, "Grand Coteau is the sweet potato capital of the world. Justin, Ben and I found an artist who came up with the font. Only 35 years old, Chris bought his first property, at $70 thousand with 10% down through a bank closing, as his family residence in Grand Coteau while in his third year of law school. It was a perfect starter home for his wife, Meghan, and their young family to live in. When they needed a larger home for their growing family, Chris decided to rent out the Grand Coteau property, which reappraised at $105K after the improvements they had done. Chris and Meghan Granger pictured with their young family. Photo from Facebook. "The light bulb went off about leveraging the $35K equity in the home. Let's leverage what we already have. What if I scale this thing? I could own 25 rental homes. My initial goal was to have 40 by 40! That was my mantra. But it happened quicker than that." Chris's whole portfolio is based upon leveraging. "You can't put down 10 - 20% equity in each house you buy." Chris's portfolio grew to 25 properties quickly. "I'm a big believer in community banks. Being able to walk in and talk to your local baker and explain a deal is invaluable. But they tend to have a tendency to pause you if you grow too fast. When I got to 25 houses I remember being paused. It's a small circle. The first 25 loans were with two local banks. That lasted two years where I was stalled. So I went head in with my practice with Maison Title." Today, Chris Granger owns several hundred residential and commercial properties, which include the former Jefferson Street Pub, now known as The Jefferson, Abacus, the historic site location of Straw Cove Baking Company at 111 Monroe Street, and 160 units in two apartment complexes in Leesville LA. Chris's thriving real estate title closing agency, Maison Title, is also located in Freetown in the old Petro House on Jefferson Street as well as another branch in Grand Coteau LA. Chris defines himself as a "pedal to the medal guy," doing 90% of the work. He admits, "I need help with the last 10%." He relies on his manager of Seven Oaks Grand Coteau, Casey, to run the property management duties full-time. "Everything in my mind is about rentable doors. We have a few over 425 doors. 140 single family units." When asked about scaling his projects, Chris has learned from experience. "You always need the extra employee before you can afford them. Learning to navigate the cash flow conundrum where you have enough work, but you also have to take a leap of faith to hire them. You always need the help before you can afford them." We discussed the current housing market and the affordability issue. "There is a lack of housing in the $150-250K range in our housing market. Anything above $300K we don't see a lot of in our practice. $200-300K is what we see. There's a national, local, regional housing shortage in real estate." Flood insurance costs are a real issue for rentals. 'You do well when you have quantity. The goal is to net $200 to $250 per month per unit. Throw on a $1,000 flood insurance policy,

Chris Granger: Blaine School District Bond and Levy by KGMI News/Talk 790

Ever wonder what it takes to evolve as a Christian leader in a rapidly changing society? Are you curious about the connections between leadership, faith, and community? Dive into a captivating conversation with Chris Granger, a thought leader in the Christian community who's passionate about helping men unleash their leadership potential rooted in biblical principles. For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/312-new-year-special/Our Black Friday promotion is Live Right Now!We're thrilled to offer you access to our vibrant community at over 50% off! Inside our community, you'll find opportunities to elevate your journey through exclusive spiritual kick-offs, engaging Bible studies, Lion lunches, forums, and so much more. Don't miss out, your journey begins here. Visit thelionwithin.us to join today!Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffFor only $5 a month, join Chris and other members every weekday morning in our app! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Adam Daigle, Business Editor of the Acadiana Advocate, joins Discover Lafayette to discuss the biggest business news of 2023. The #1 story of the year is the incredible strides made in 2023 insofar as job creation is concerned. Iberia Parish is on fire with the recent announcement of First Solar's $1.1 Billion investment to take place on thirty acres at the Acadiana Regional Airport. First Solar will produce high-performance photovoltaic (PV) solar modules. The project is expected to be complete in the first half of 2026 and up to 700 high-paying jobs are anticipated to be created. This enterprise is unique in Louisiana in that it is tied to a new solar training program at UL-Lafayette where students will be educated on designing solar panels. First Solar was founded in 1999 and is among the top 10 solar panel manufacturers in the world. Along with this major announcement, other large regional employers include Amazon at 1300 employees and Stuller at 1500 employees, who have both exceeded projections for local employees. The #2 business story of the year is the large number of local restaurants which closed in early 2023, including the iconic Cafe Vermilionville, Lotus Garden, Grub Burger, The Point Seafood and Steakhouse, BJ's Pizza, and Luna Bar & Grill. By July 2023, the number of closings had settled down. The #3 story of the year is the shake-up at the news desk at KATC, seeing the departure of longtime and popular news anchors Marcelle Fontenot and Jim Hummel who will be joining KADN in January 2024. The move is one being conducted nationally by KATC's owner, E. W. Scripps Co., as a cost-cutting measure. While there will no longer be live news read by anchors at the 5 pm, 6 pm or 10 pm news slots, the company will invest in more reporters to cover breaking news stories throughout the day. Marcelle Fontenot and Jim Hummel recently announced they had resigned from KATC News and will be joining the news desk at KADN in Lafayette. The #4 story is the recently announced departure of Anita Begnaud, CEO of the Lafayette Downtown Development Authority, whose last day will be on December 20, 2023. Anita will be moving on to work with her former boss at One Acadiana, Jason El Koubi, as the Vice President of Marketing and Communications at the Virginia Economic Development Partnership. Under Anita's leadership, the DDA was instrumental in seeing the completion of a myriad of commercial projects in Downtown Lafayette which had languished for years. She brought energy and excitement to her role as CEO and will be sorely missed. Anita Begnaud, CEO of the Lafayette Downtown Development Authority since 2018, recently announce that she will be leaving to work with the Virginia Economic Development Partnership as VP of Marketing and Communications. The #5 business story is the explosive growth occuring in the corridor at Kaliste Saloom Road and Ambassador Caffery Parkway, including the opening this year of Topgolf on December 15 and Dave & Busters which opened November 27. Adam says attracting these type of entertainment venues "brings Lafayette up a class, akin to going from a Double-A to a Triple-A baseball club" as it causes investors to take a closer look at our market and reexamine what is possible in the commercial realm. Other important commercial additions include the recently opened Chimes Restaurant and the development of the Camellia Blvd corridor near Verot School Road which is filling in with medical offices and a new Rouse's, expected to open in early winter. This whole corridor is now serving as the commercial core of Lafayette Parish, is easily accessible by other towns in the parish, and is the economic powerhouse of the Lafayette community generating tax dollars that would have seemed impossible just a few short years ago. As Adam says, "Costco is a sales tax machine!" Discover Lafayette is proud to name attorney Chris Granger as the recipient of our third annual Business Catalyst of the...

Did you know that gratitude can directly contribute to your personal and spiritual growth? That's what we're exploring on this episode of The Lion Within Us, as I, Chris Granger, walk you through the art of purposeful reflection. We'll be sharing some heartfelt points from my own gratitude list and discussing how you can create your own. As we navigate the hustle and bustle of the holiday season, we'll also share some practical steps to ensure you stay on top of your health, manage your wealth, and not forget to practice self-care. For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/298-fun-friday-reflect-and-give-thanks/Our Black Friday promotion is Live Right Now!We're thrilled to offer you access to our vibrant community at over 50% off! Inside our community, you'll find opportunities to elevate your journey through exclusive spiritual kick-offs, engaging Bible studies, Lion lunches, forums, and so much more. Don't miss out, your journey begins here. Visit thelionwithin.us to join today!Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffFor only $5 a month, join Chris and other members every weekday morning in our app! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Then join me, Chris Granger, as I share some inspiring insights and biblical directives specifically in relation to 2 Timothy 3:14-15. Hear how my experiences serving at 2 summer camps had a profound influence on me and the kids there. As Christian men, it's crucial for us to serve - not only in church but also in our homes and communities. Plus, don't miss out on some handy health and wealth tips I have for you, to help you balance your life and be a better husband and father.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/283-fun-friday-finding-hope-in-personal-tragedy/Summit Leadership Development A transformative way to weave the timeless wisdom of God's Word into your leadership style. Amplify your influence in the workforce and the Kingdom with powerful sessions crafted to empower leaders like you. Don't miss this exclusive opportunity to revolutionize your leadership journey. Secure your spot today!Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffFor only $5 a month, join Chris and other members every weekday morning in our app! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Are you ready to revolutionize your leadership style and personal growth by mastering the art of forgiveness? Join me, your host, Chris Granger, as we explore the power of mercy, and unravel the wisdom in Matthew 18:22. We will walk you through practical steps to forgive yourself and others, demonstrating how you can incorporate this virtue into your everyday life to become the best version of yourself. Your comments and thoughts on our deep dive into forgiveness are eagerly awaited.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/259-fun-friday-take-action-by-forgiving/Secure your spot in a Summit Leadership Development Preview Session!Ignite your leadership potential with The Lion Within Us Summit Leadership Development. Join our exclusive preview sessions to experience a transformative journey equipped with biblical principles that empower, inspire, and transform your leadership journey. Register now to become an empowered, purpose-driven leader. Get Free Daily Inspiration With Our Bible App DevotionalsOur devotionals dive deep into the pillars that define The Lion Within Us - health, wealth, and self. Whether you're seeking spiritual growth, financial wisdom, or personal development, these devotionals are tailor-made for you. Connect with The Lion Within Us on YouVersion Bible App. Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffFor only $5 a month, join Chris and other members every weekday morning in our app! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Are you feeling tangled in resentment, grudges, and unforgiveness? Join me, Chris Granger, in the Lion Within Us podcast where we unravel this complicated emotion and explore the essential act of forgiveness, drawing insights from Matthew 18:22. We'll discuss how unforgiveness clouds our joy and creates a foggy barrier between us and others. I'll be sharing perspectives on how forgiveness, rooted in love, can clear this fog and bring back the joy in our lives.For full show note details, go to the episode webpage:https://thelionwithin.us/podcast/257-sko-matthew-18-22/Secure your spot in a Summit Leadership Development Preview Session!Ignite your leadership potential with The Lion Within Us Summit Leadership Development. Join our exclusive preview sessions to experience a transformative journey equipped with biblical principles that empower, inspire, and transform your leadership journey. Register now to become an empowered, purpose-driven leader. Get Free Daily Inspiration With Our Bible App DevotionalsOur devotionals dive deep into the pillars that define The Lion Within Us - health, wealth, and self. Whether you're seeking spiritual growth, financial wisdom, or personal development, these devotionals are tailor-made for you. Connect with The Lion Within Us on YouVersion Bible App. Join the Community TodayThe exclusive community for men who are seeking Truth and Accountability which creates courage to lead, fulfillment and direction. Start your 30-Day Risk-Free trial today!Join the Daily Spiritual Kick OffFor only $5 a month, join Chris and other members every weekday morning in our app! Dive into God's Word and leave with practical ways to simplify and apply it to your daily walk. Join the Daily Spiritual Kick Off today!

Tina and Hillary cover former Missouri State Representative Patricia Derges and former Governor of Louisiana Edwin Edwards. Tina's Story Patricia Derges served as a Missouri state rep beginning in November 2020. BUT when she sold fake cures for Covid she swindled herself out of a job and into jail. Hillary's Story Edwin Edwards served as Louisiana's governor on and off for nearly 25 years. BUT his unscrupulous wheelings and dealings took him from the bayou to a prison cell. Sources Tina's Story KCUR Missouri Rep. Patricia Derges convicted of multiple counts of health care fraud (https://www.kcur.org/news/2022-06-28/missouri-rep-patricia-derges-convicted-of-multiple-counts-of-health-care-fraud)--by Dan Margolies KSMU Former MO lawmaker Tricia Derges is sentenced to 75 months in prison (https://www.ksmu.org/news/2023-03-01/former-mo-lawmaker-tricia-derges-is-sentenced-to-75-months-in-prison)--by Michele Skalicky Med Page Today HCP Busted for Selling Fake Stem Cell Therapy (https://www.medpagetoday.com/special-reports/exclusives/91053)--by Kristina Fiore The New York Post Missouri Rep. Tricia Derges resigns after $900K COVID clinic fraud scheme conviction (https://nypost.com/2022/07/05/rep-tricia-derges-resigns-after-900k-covid-clinic-fraud-scheme-conviction/)--by Danielle Wallace St. Louis Dispatch Sentencing set for ex-Missouri lawmaker in medical fraud case (https://www.stltoday.com/news/local/crime-and-courts/sentencing-set-for-ex-missouri-lawmaker-in-medical-fraud-case/article_576e8761-54b5-5f9c-a860-4660ce17ff46.html)--by Kurt Erickson US Attorney's Office (Western District of Missouri) Jury Convicts State Lawmaker of COVID-19 Fraud Scheme at Springfield Health Care Charity (https://www.justice.gov/usao-wdmo/pr/jury-convicts-state-lawmaker-covid-19-fraud-scheme-springfield-health-care-charity) US Treasury About the CARES Act and the Consolidated Appropriations Act (https://home.treasury.gov/policy-issues/coronavirus/about-the-cares-act#:~:text=The%20Coronavirus%20Aid%2C%20Relief%2C%20and,%2C%20small%20businesses%2C%20and%20industries.) Photos Patricia Derges (https://npr.brightspotcdn.com/dims4/default/86fe407/2147483647/strip/true/crop/1013x1025+0+0/resize/1760x1780!/format/webp/quality/90/?url=http%3A%2F%2Fnpr-brightspot.s3.amazonaws.com%2Fed%2F69%2Fa51418d94d1985c31a04eda11b54%2F032621-mo-triciaderges.png)--from Missouri House of Representatives via KCUR/NPR Derges Ozark Valley Medical Clinic (https://nypost.com/wp-content/uploads/sites/2/2022/07/missouri-republican-fraud-covid-02.jpg?quality=75&strip=all)--from Google Maps via The New York Post Hillary's Story The Advocate 93-year-old Edwin Edwards left all of his assets to his 8-year-old son, according to handwritten will (https://www.theadvocate.com/baton_rouge/news/politics/93-year-old-edwin-edwards-left-all-of-his-assets-to-his-8-year-old/article_6add3c70-7bce-11ec-ae43-47d05790c544.html)--by Tyler Bridges and Mark Ballard Associated Press Ex-Louisiana Gov. Edwin Edwards dies; knew power and prison (https://apnews.com/article/louisiana-edwin-edwards-17a25131ac1a24988e71e60cf701f7f8)--by Kevin McGill Louisiana Secretary of State Edwin Edwards (https://www.sos.la.gov/HistoricalResources/AboutLouisiana/LouisianaGovernors1877-Present/Pages/EdwinWEdwards.aspx) The New York Times Edwin Edwards, Flamboyant Louisiana Governor, Is Dead at 93 (https://www.nytimes.com/2021/07/12/us/politics/edwin-edwards-dead.html)--by Robert D. McFadden nola.com The rise and fall of Gov. Edwin Edwards (https://www.nola.com/300/the-rise-and-fall-of-gov-edwin-edwards/article_25f29b72-8af3-5e68-9c42-37da19577950.html) NPR Edwin Edwards, Ex-Louisiana Guv, Leaves Prison For Halfway House (https://www.npr.org/sections/itsallpolitics/2011/01/13/132908525/edwin-edwards-ex-louisiana-guv-leaves-prison-for-halfway-house)--by Frank James Edwin Edwards: Governor, Convict, Reality TV Star — Congressman? (https://www.npr.org/sections/itsallpolitics/2014/02/20/280234613/edwin-edwards-governor-convict-reality-tv-star-congressman)--by Liz Halloran Ex-Con, Future Congressman? Former Gov. Edwin Edwards Campaigns Again (https://www.npr.org/2014/09/26/351438036/ex-con-future-congressman-former-gov-edwin-edwards-campaigns-again)--by Debbie Elliot (Morning Edition) Louisiana's Edwin Edwards May Be On His Last Political Stand (https://www.npr.org/2014/12/04/368529482/louisianas-edwin-edwards-may-be-on-his-last-political-stand)--by Debbie Elliot (All Things Considered WLRN) Photos Edwin W. Edwards (https://upload.wikimedia.org/wikipedia/commons/7/78/Edwin_Edwards_%281986%29.png)--from 1986 Northwestern State University Potpourri Yearbook via Wikipedia (CC0) 1991 Governor Race Bumper Sticker (https://bloximages.newyork1.vip.townnews.com/theadvocate.com/content/tncms/assets/v3/editorial/e/1a/e1af33c3-7f00-512a-a2fa-ec78f7647c05/60ecb92f731a5.image.jpg?resize=1333%2C888)--photo by Chris Granger via The Advocate Edwards, his wife Trina, and baby (https://www.klfy.com/local/trina-edwards-says-his-last-words-were-to-eli/)--screenshot via KLFY

Don't judge a fish on how to climb a tree.Rylee shares his interview with Chris Granger on "The Lion Within Us". In this episode, Rylee discusses his background in Christianity and entrepreneurship, the King's Council, and what it takes to be a true disciple of Christ. Rylee dives into the kingdom concepts & culture, mindset, and society's indoctrination.Step up and flip some tables. Key takeaways:We are born to be entrepreneursThe meaning of discipleshipBeing a thermostat vs a thermometerBuilding kingdom concepts & culture The cost of being a Good SamaritanValuing your relationship with your spouseThe importance of mindsetKingdom mandate to be fruitful & multiply Quotes:"I just had to, like, get out of the environment that I was in, because I had ultimately become a product of my environment. And we all do, whether we like it or not." - Rylee Meek"I've become a firm believer that as an entrepreneur, we follow opportunities, but always bring our passion with us. And no matter then what the opportunity is, you're going to approach it as a if you are a a follower of Jesus, you're going to approach it, you should at least approach it with an attitude of excellence. Whatever I put my hand to, I'm going to work at it as if I'm working for the Lord, and not for man." - Rylee Meek"We're not given a spirit of fear, we're supposed to be given the spirit of power, love and self control, man, we just live in the spirit of fear where we don't want to take that step. You know, God may be calling us to something but fear is holding us back." - Chris Granger"I love scripture, because I can read the same verse 300 times, and then it's not until I read it that 300 and first time where there's like revelation that takes place, and you do this, you become successful by meditating on the Word of God." - Rylee Meek"We need men around us, right at all times helping us grow. So you can't do this alone, guys." - Chris Granger_ Check the DNA Blueprint, visit: https://kingscouncilcommunity.org/ Text “King” to 727-472-3860 and join the community!-The King's Council's mission is to help you discover and deploy your God-given talents. Our signature coaching program will give you the tools, tactics and strategies to radically change and level up in all areas of your life.Visit https://kingscouncilcommunity.org/ to find out more about unleashing your God-given talents.For the Kingdom Money Principles Cheat Sheet, text “Money” to 727-472-3860.—If you loved what you heard, Follow, Rate and Review this podcast on Apple Podcasts You can also listen to the show on:SpotifyAmazon MusicGoogle PodcastsStitcherSubscribe to our Youtube Channel: https://bit.ly/3pYVALm—Follow the King's Council on Instagram

Please join author Subodh Verma and Guest Editor Christopher Granger as they discuss the article "Empagliflozin and Left Ventricular Remodeling in People Without Diabetes: Primary Results of the EMPA-HEART 2 CardioLink-7 Randomized Clinical Trial." 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-host. I'm Dr. Carolyn Lam, associate editor from the National Heart Center and Duke National University of Singapore. Dr. Peder Myhre: And I'm Dr. Peder Myhre, social media editor and doctor at Akershus University Hospital at University of Oslo in Norway. Dr. Carolyn Lam: Peder, I am so excited to be discussing this issue. So many great articles and a feature discussion coming up on the SGLT2 inhibitor, empagliflozin. And do you think it's got effects on left ventricular remodeling in people without diabetes? Very interesting question. Dr. Peder Myhre: That is so interesting, Carolyn. I can't wait to hear this discussion. Dr. Carolyn Lam: Yep, I agree, but we got to wait till we discuss the other papers in today's issue. I want to go first. So we know that non-vitamin K oral anticoagulants, or NOACs, they've become the standard therapy for preventing stroke and ischemic thromboembolism in most patients with atrial fibrillation. But, what is the effectiveness and safety of NOACs in patients on dialysis? That is hemodialysis. The AXADIA-AFNET 8 study sought to test the hypothesis that apixaban would be non-inferior to vitamin K antagonists in these very patients undergoing hemodialysis. Dr. Peder Myhre: Oh wow. This is really a gap of knowledge that we've been waiting to hear more about. NOACs in patients with hemodialysis. Tell us about this trial, Carolyn. Dr. Carolyn Lam: Sure. So this is from corresponding author, Dr. Reinecke, and colleagues, from University of Munster in Germany. And it's an investigator initiated prospective randomized open-blinded outcome assessment of 97 patients with atrial fibrillation on chronic hemodialysis randomized to either apixaban 2.5 mg BID, or a vitamin K antagonist, aiming for an INR between 2 and 3. Over a median follow-up time of 429 days for apixaban, and 506 days for the vitamin K antagonist, the composite primary safety outcome of first, major bleeding, clinically relevant, non-major bleeding, or all cause death, occurred in 46% of patients on apixaban, and 51% of patients on the vitamin K antagonist. That would be a hazard ratio of 0.91, with a p for non-inferiority being 0.157. How about the primary efficacy outcome? While this was a composite of ischemic stroke, all cause death, myocardial infarction, or deep vein thrombosis, and/or pulmonary embolism, and that occurred in 21% of patients on apixaban and 31% of patients on the vitamin K antagonists. Again, no difference when there was testing. So, in summary, Peder, there were no differences in the safety or efficacy observed between apixaban and vitamin K antagonists in patients with atrial fibrillation on chronic hemodialysis. Of note, however, even receiving oral anticoagulations, these patients remain at very high risk of cardiovascular events. So these data really support the consideration of apixaban for prevention of cardiovascular complications in patients with atrial fibrillation on chronic hemodialysis, but larger studies are definitely needed. Dr. Peder Myhre: Oh wow, Carolyn, that is so clinically relevant. And the next paper is also a clinically relevant paper. And it comes to us from the SPRINT authors. And to remind you, the SPRINT study was a study of intensive systolic blood pressure lowering compared to standard blood pressure lowering. And the results demonstrated that there was a robust reduction in both heart failure endpoints and all cause mortality. And in this sub-study that comes to us from corresponding author Jarett Berry from University of Texas Tyler School of Medicine, these authors look at the mechanisms through which intensive blood pressure lowering reduces the risk of these endpoints. And given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure, and strong association that has been observed between hypertension and levels of cardiac troponin and NT-proBNP, the authors hypothesized that intensive systolic blood pressure lowering would decrease levels of high sensitivity cardiac troponin T and NT-proBNP. Dr. Carolyn Lam: Cool. That's interesting. So how did they do this, and what did they find? Dr. Peder Myhre: So, as expected, Carolyn, the authors found that increases in troponin and NT-proBNP from baseline to 1 year were associated with a higher risk of heart failure and death. And there were really no significant interaction by treatment assignment. But let's look at the changes in troponin. And these results showed that randomization to intensive blood pressure lowering versus standard blood pressure lowering resulted in a significant 3% increase in cardiac troponin T level over 1 year follow up, and a higher proportion of participants with more than 50% increase, and that's with an odds ratio of 1.47. And Carolyn, in contrast, NT-proBNP decreased by 10% in intensive blood pressure arm. And these patients had substantially lower probability of increasing more than 50% in NT-proBNP, with an odds ratio of 0.57 compared to the standard arm. And now, to the most interesting part of this analysis, Carolyn, the association of randomized treatment assignment on changes in troponin was completely attenuated after accounting for changes in eGFR during the follow up, whereas the association of treatment with NT-proBNP changes were completely attenuated after adjusting for changes in systolic blood pressure. So Carolyn, the authors highlight in their discussion the importance of non-cardiac factors influencing variation in cardiac biomarkers, and raise questions about the potential role of cardiac troponin T as a surrogate marker for heart failure or death in blood pressure lowering studies. Dr. Carolyn Lam: Wow, very interesting. Thanks, Peder. Can I tell you now about a preclinical study? Very interesting, because it shows that cardiac inflammation and hypertrophy are regulated by a heart-brain interaction. Dr. Peder Myhre: Wow, Carolyn, a heart-brain interaction. I'm excited to hear more about this. Please explain. Dr. Carolyn Lam: I'd love to, but first some background. Interleukin-1 beta, now that is a pro-inflammatory cytokine that causes cardiac hypertrophy and heart failure. I need to familiarize you with this, the nucleotide-binding domain leucine-rich containing family, pyrin domain-containing-3, NLRP3 for short, which is an inflammasome, which is a cytosolic multiprotein complex that mediates active interleukin-1 beta production. Okay? So you know these terms, and now I want to tell you about the study. This is an elegant series of experiments performed by co-corresponding authors, Dr. Higashikuni, from University of Tokyo, and Dr. Sata, from Tokushima University Graduate School of Medicine, and their colleagues. They first showed that genetic disruption of the NLRP3 inflammasome resulted in significant loss of interleukin-1 beta production, cardiac hypertrophy, and contractile function during pressure overload. Next, a bone marrow transplantation experiment revealed an essential role of NLRP3 inflammasome in cardiac non-immune cells in myocardial interleukin-1 beta production and the cardiac phenotype. It was extracellular ATP released from sympathetic nerve terminals that induced the hypertrophic changes of cardiac cells in an NLRP3 and interleukin-1 beta dependent manner in vitro. And finally, depletion of ATP release from sympathetic efferent nerves, or ablation of cardiac afferent nerves, or a lipophilic beta-blocker, all reduced cardiac extracellular ATP, and inhibited the NLRP3 inflammasome activation, the interleukin-1 beta production, and the adaptive cardiac hypertrophy during pressure overload. So all of this suggests that controlling the neuronal brain signals might have therapeutic potential for the treatment of hypertensive heart disease. Neat, huh? Dr. Peder Myhre: Oh, that is so interesting. The heart and brain interaction. And, Carolyn, we're going to stay in the field of preclinical science. And now we're going to talk about another field that is really interesting, and that is regeneration of cardiomyocytes. Because, Carolyn, developmental cardiac tissue holds remarkable capacity to regenerate after injury, and consists of regenerative mononuclear and deployed cardiomyocytes. Whether reprogramming metabolism promotes persistence of these regenerative mononuclear and deployed cardiomyocytes that enhance cardiac function in repair after injury is unknown. Therefore, these researcher, led by corresponding author, Mohsin Khan, from Temple University School of Medicine, investigated whether the RNA binding protein, LIN28a, which is a master regulator of cellular metabolism, plays a role in cardiac repair following injury. Dr. Carolyn Lam: Wow. That is always, always interesting, regeneration and repair following injury. So what did the authors find? Dr. Peder Myhre: Well, Carolyn, through a number of elegant experiments, the authors made the following key findings. For the first time, they documented a role for RNA binding protein LIN28A in regulating cardiomyocyte turnover in the postnatal and adult heart. And LIN28a overexpression promotes cardiomyocyte cell cycle activity during postnatal development and extends cardiac regenerative ability of the mammalian heart to postnatal day 7. And in the adult heart, the authors could demonstrate that LIN28a drives new myocyte formation, augmenting cardiac structure and function after myocardial injury. And Carolyn, I'm sure you're going to ask the clinical implications of this study. Dr. Carolyn Lam: Indeed. Dr. Peder Myhre: And that is that these results may suggest a novel translational role for LIN28a based strategy to replenish cardiomyocytes in the adult heart after injury. Dr. Carolyn Lam: Very nice, Peder. Thank you. Also in the issue is a Research Letter by Dr. Bick on interleukin-6 receptor polymorphism attenuates clonal hematopoiesis mediated coronary artery disease risk among many individuals in the UK Biobank. There's also Cardiology News by Tracy Hampton, where she highlights few really interesting things, like aging cardiomyocytes accumulate new genetic mutations that was published in Nature Aging, cytokines promote tissue repair after a heart attack in mice, and that was published in Science, and scientists identifying molecular alterations in a failing heart at a single cell resolution, which was published in Nature. Dr. Peder Myhre: And there are a couple of other papers also in this issue, Carolyn. And there's first, an exchange of letters by Drs. Halushka, Lu, and Mayr, regarding the article "Circulating MicroRNA-122-5p is Associated with a Lack of Improvement in Left Ventricular Function after TAVR and Regulates Viability of Cardiomyocytes Through Extracellular Vesicles." And finally, we have an "On My Mind" piece by doctors Monda and Limongelli entitled "An Integrated Sudden Cardiac Risk Prediction Model for Patients with Hypertrophic Cardiomyopathy." Dr. Carolyn Lam: Oh, nice. Nice full issue. Thank you, Peder. Let's go to our feature discussion now. Shall we? Dr. Peder Myhre: Let's go. Dr. Greg Hundley: Welcome listeners to this feature discussion on January 24th. And we have with us Dr. Subodh Verma, from St. Michael's University in Toronto, Canada. And a guest editor, Dr. Christopher Granger, from Duke University in Durham, North Carolina. Welcome gentlemen. Well, Subodh, we will 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. Subodh Verma: First, my great pleasure to be here, and thank you very much for the opportunity to discuss this paper with your viewers. As you know, SGLT2 inhibitors have been truly transformative therapies. From a heart failure perspective, we know that they prevent incident heart failure in people with diabetes who have vascular disease or risk factors. They also have been shown to treat prevalent heart failure in people with heart failure and either a reduced, mildly reduced, or preserved ejection fraction independent of glycemic status. And really, these have been the basis of very strong recommendations to use these agents in the prevention of heart failure in people with diabetes, and also in the treatment of prevalent heart failure in people with and without diabetes. Now, the fact that these drugs have such broad effects in people with heart failure has led to a theory that maybe these drugs could be introduced earlier on in the natural history of heart failure in people who neither have diabetes nor have significant heart failure, the so-called sort of stage A or stage B patient. But there really have been no clinical trials evaluating this question. There've been a lot of translational randomized trials that have provided some mechanistic insights about LV remodeling in people with diabetes or in people with prevalent heart failure. And we hypothesized that maybe the first step to evaluate whether SGLT2 inhibitors may have favorable effects on cardiac remodeling in people without diabetes or without heart failure would be to conduct a randomized double-blind control trial looking at indices of left ventricular remodeling in a population that I've just described. Dr. Greg Hundley: Very nice, Subodh. So you've started us into your study design. Maybe describe that a little more fully, and then who was included in your study population? Dr. Subodh Verma: So EMPA-HEART 2 CardioLink was a multi-center double-blind placebo control randomized trial in which we studied the effects of empagliflozin, an SGLT2 inhibitor, at a dose of 10 mg per day versus placebo in people who did not have type 2 diabetes or significant heart failure. We included people who were adults between the age of 40 and 80 who met 1 of 2 entry criteria. Either they had to have one major criteria, which was an increase in left ventricular mass index by specific echo criteria or MRI criteria, or they could have increased LVH as identified by ECG or by intraventricular septal or posterior wall thickness. They could also get in if they had resistant hypertension, hypertension despite being on 3 antihypertensive agents, or the second strata was entry through 2 minor criteria, which included a history of myocardial infarction, a GFR between 30 or 60, or evidence of overweight or obesity. Dr. Greg Hundley: And how many subjects did you randomize? Dr. Subodh Verma: So we randomized, of the 318 that we screened, 169 were randomized to receive empagliflozin 10 mg or a placebo. Patients had a baseline cardiac MRI done, and then the exposure was 6 months. They had a follow-up MRI at the end of 6 months. And the primary outcome measure was a 6-month change in left ventricular mass index from baseline to 6 months between the two groups. Dr. Greg Hundley: Very nice. And so , Subodh, can you describe for us now, what did you find? What were your study results? Dr. Subodh Verma: So, first and foremost, what we found in terms of baseline characteristics was that we enrolled a population of people with a mean age of around 60 with a BMI of around 30 kg/m2, predominantly men, about 80% or so were men. These were patients who did not have significant heart failure. The NT-proBNP at baseline was around 50 pg/mL. The eGFR was around 80 mL/minute, and the vast majority of these patients actually had a history of hypertension. Of course, none of them had diabetes by definition. The hemoglobin A1C was around 5.8%. Now what we found was, despite the fact that we went after patients who we thought would be enriched for a baseline increase in LV mass indices, the baseline LV mass index was mildly elevated, was around 63 g/m2. And over the course of 6 months, we did not find any significant difference in terms of LV mass regression between the placebo and empagliflozin groups. In fact, the adjusted treatment effect was minus 0.30 g/m2, which was not statistically significant. No other differences were found in terms of other indices of a remodeling, including left ventricular and diastolic or end systolic volume indices or in terms of left ventricular ejection fraction. There was a 2% increase in ejection fraction, and the p-value for that was 0.07, but really was not statistically significant. Dr. Greg Hundley: And very nice. And realizing that women may have smaller LV masses, any stratified analysis that evaluated effects on men versus women? And then what about, perhaps in the higher quartile versus lower quartile, of age? Dr. Subodh Verma: Right. So, Greg, we actually did look at various subgroups and covariates, including gender, including age. And age or gender did not really influence the overall result that we obtained. There was really a neutral result in empagliflozin, irrespective of these 2 covariates. We also looked at baseline blood pressure, baseline NT-proBNP, LV mass indices, the presence or absence of heart failure, chronic kidney disease. So for the covariates that we have evaluated over a short term of 6 months in this relatively low risk population, we did not find any heterogeneity the result, per se. Dr. Greg Hundley: Very good. Well, Subodh, thank you so much for that beautiful presentation. And listeners, now we're going to turn to our guest editor, Dr. Chris Granger. And Chris is an expert in the field of heart failure. Also, a lot of familiarity with HFpEF, which sounds a little bit, we're looking at precursors. We don't have HFpEF yet, but maybe trying to inhibit this from happening using empagliflozin. How do you put these results in the context with other studies that have emphasized utilizing SGLT2 inhibitors in patients with sort of a preserved ejection fraction and absence of diabetes? Dr. Christopher Granger: Yeah. Well thanks, Greg. And again, congratulations, Subodh, to your study. And I think you framed some of the context here as these drugs, the SGLT2 inhibitors, as being transformative, which I think is exactly right. And it's such a fascinating story. Right? These drugs, which we thought originally, with their cause of glucose spilling in the urine, and a modest decrease in blood glucose, might have a role for modestly improving glucose control in diabetes. And low and behold, they've turned out to be one of the great stories I think in recent, across all of medicine, in terms of their consistent and substantial improving clinical outcomes for patients with heart failure, with diabetes and cardiovascular disease, and now even kidney protection, and much broader implications. And their well tolerated, and they don't have dose titration. So there's some practical appeal to this class of drugs in terms of their benefits, in terms of clinical outcomes. But we're left with having this amazing evidence-based generated without really understanding why are these drugs so effective? And what are they doing? And you've provided, I think, an important piece to the puzzle. We did have the data from patients with diabetes and heart failure, with diabetes and left ventricular hypertrophy, that there is a modest reduce in LV mass with SGLT2 inhibitors. And what you've shown is that for patients that with mild LVH, with risk for LVH, that we simply don't see a substantial reduction in LV mass with the use of these drugs. So I think that provides this evidence that that's not a major cause of benefit, at least in this earlier phase of development of heart failure. And I think it really underscores the fact that there's a lot of work to do still to understand. We know that the renal effects are obvious place that these drugs have such an important benefit. And then the linkage of renal disease and cardiac performance is one of the areas, I think, that's a very exciting aspect of a probable contribution of the mechanism of these drugs. But I think in the end, we're left with still not really understanding why these drugs are so beneficial. But understanding that, I think, will be important, both for opening new avenues of targeting pathways, as well as being able to tell the clinical community, okay, you have these important benefits, but people do want to also know why are we seeing these benefits. Dr. Greg Hundley: Very nice. Well, listeners, we're going to turn back to Dr. Verma here. Subodh, what do you see is the next study to be performed in this sphere of research? Dr. Subodh Verma: Well, first, my thanks to Professor Granger, Chris, for handling this paper and for his very thoughtful comments. And he's absolutely right. We have such wonderful clinical data, and these results, of course, should not in any way take away from the importance of using empagliflozin or other SGLT2 inhibitors in the prevention of heart failure in people with diabetes, or in the treatment of HFpEF or HFrEF. But we're struggling with trying to understand what is the dominant mechanism of action here. And, in the previous precursor to EMPA-HEART 2, we did EMPA-HEART 1 in people with diabetes, and we saw a modest effect that was statistically significant of reduction in LV mass index. And we did not see this, of course, in a lower risk population without diabetes. And that tells me that remodeling may be occurring to a modest effect, it may require a longer time to actually show its benefits, but that this is unlikely a dominant sort of mechanism through which these drugs are working. And I do share Chris's thoughts that one of the key mechanisms of benefit that needs to be further explored is looking at the renal cardiac axes. We know that these drugs are profoundly renal protective, and that the benefits may actually be secondary to improvements in renal hemodynamics, improvements in renal function. And I think that is a population that needs to be, that's a mechanism that needs to be studied further. So I think the next generation of translational mechanistic studies need to really tease out the renal cardiac axes, maybe tease out populations that are at risk but have more significant left ventricular hypertrophy, maybe evaluate patients for a longer duration of treatment, or select people who truly have significant hypertension at baseline. I think those are groups and questions that need further exploration. And, of course, the translational science needs to be also studied in the context of larger completed clinical trials, where biomarkers are currently available and they can be linked, of course, to the outcomes in those trials. So those are some of my thoughts as to where the field could move towards. Dr. Greg Hundley: Very nice. And Chris, do you have anything to add? Dr. Christopher Granger: Subodh, I think that was a great summary. And I might just make a comment on the other end of the spectrum. That is, we have these drugs and the evidence of their benefit, and yet they're grossly underused in the populations that have proven to have benefit. Now it takes some time to educate, to get people familiar with, and get them to integrate these treatments into practice, but there's an enormous opportunity, and I think there is a linkage here. I think when people understand the mechanism, and when they're thoughtful about how these drugs may be working, that that really helps to make the case that the drug should be used, and that people are on board with using them. So I think there's this linkage here, there's the need to both better understand mechanism, and there's the need to have systems of care where these treatments are integrated to provide the benefit that's been so clearly shown in the randomized trials. Dr. Greg Hundley: Very nice. Well, listeners, we want to thank Dr. Subodh Verma, from St. Michael's University in Toronto, and our guest editor, Dr. Chris Granger, from Duke University in Durham, North Carolina, for bringing this paper highlighting that among people with neither diabetes nor significant heart failure but with risk factors for adverse cardiac remodeling, that SGLT2 inhibition with empagliflozin did not, did not, result in a meaningful reduction in LV mass index after 6 months. Well, on behalf of Carolyn, Peder, and myself, we want to wish you a great week, and we will catch you next week on the run. This program is copyright of the American Heart Association 2023. 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.

Chris Granger, CEO of Oak View Group Facilities, joins Jed Hughes for Episode #91. With more than 25 years of experience in the industry, Granger oversees OVG Facilities, OVG Media & Conferences, and the OVG Arena Alliance, a collection of 32 North American venues that provides a platform for booking, content, and sponsorship sales opportunities. Previously Granger was group president of sports and entertainment with Detroit-based Ilitch Holdings. Chris explains his start in the National Basketball Association where he worked in various capacities for the league including 4 years as President of the Sacramento Kings.

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.

In this episode Marcus Mire, CPA sits down with Chris Granger an attorney turned real estate titan with over 100 doors in his current portfolio. Learn the challenges he faced, how he overcame them, and the role cloud technology played along the way.

This week's show features a panel discussion between authors Adrian Wells and Hyeon Chang Kim as they discuss their articles "Improving the Effectiveness of Psychological Interventions for Depression and Anxiety in Cardiac Rehabilitation PATHWAY—A Single-Blind, Parallel, Randomized, Controlled Trial of Group Metacognitive Therapy" and "Associations of Ideal Cardiovascular Health and Its Change During Young Adulthood With Premature Cardiovascular Events: A Nationwide Cohort Study." 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, also your co-host. And Associate Editor, Director of the Pauley Heart Center, VCU Health in Richmond, Virginia. Dr. Carolyn Lam: Greg, we're starting off the month with double features, and these are just so interesting. The first paper talks about psychological interventions for depression and anxiety in cardiac rehabilitation. And the next talks about ideal cardiovascular health and its change during young adulthood and how that relates to premature cardiovascular events. Cool, huh? Dr. Greg Hundley: Absolutely. Well, Carolyn. How about we grab a cup of coffee and start discussing some of the other articles in the issue? And I could go first. Carolyn, the first article that I've got is from Mrs. Elizabeth Jordan from Ohio State University Wexner Medical Center. And it really pertains to cardiomyopathies. And remember, Carolyn, classically, we categorize hypertrophic, dilated, and arrhythmogenic right ventricular cardiomyopathy. And each has a signature genetic theme. Hypertrophic cardiomyopathy and ARVC are largely understood as genetic diseases of sarcomere or desmosome proteins. But in contrast, there are over 250 genes spanning more than 10 gene ontologies that have been implicated in dilated cardiomyopathy. And therefore, it really represents a very complex and diverse genetic architecture. So to clarify this, a systematic curation of evidence to establish the relationship of genes with dilated cardiomyopathy was conducted by an international panel with clinical and scientific expertise in dilated cardiomyopathy genetics. And they evaluated evidence supporting monogenic relationships of genes with idiopathic dilated cardiomyopathy. Dr. Carolyn Lam: Oh, wow. That sounds like a lot of work. And what did they find, Greg? Dr. Greg Hundley: Right, Carolyn. So in the curation of 51 genes, 19 had high evidence. 12 are definitive strong, and seven moderate. And notably, these 19 genes only explain the minority of cases, leaving the remainder of dilated cardiomyopathy genetic architecture really incompletely addressed. And clinical genetic testing panels include most high evidence genes. However also, the panel noted that genes lacking robust evidence are very commonly observed clinically. Dr. Greg Hundley: So Carolyn, the take home message from this international panel is that while dilated cardiomyopathy genetic testing panels include an average of about 60 genes, when curating published evidence for dilated cardiomyopathy, only 19 have really emerged as high levels of evidence. And then in this study, 51 genes were evaluated. And the 19 genes appraised as high evidence were recommended to be routinely used in the genetic evaluation of dilated cardiomyopathy. And one more point. Rare variants from genes without moderate, strong, or definitive evidence should not be used in clinical practice to predict dilated cardiomyopathy risk most importantly when also you're screening at risk family members. Dr. Carolyn Lam: Wow. Very nice. Stunning numbers. Well, my paper is identifying a novel therapeutic target in pulmonary arterial hypertension. Do you want to know what that is? Dr. Greg Hundley: Ah, yes, Carolyn. Very interesting. So what is it? Dr. Carolyn Lam: It's switch-independent 3A. Which is an epigenetic modifier, which is drastically down-regulated in pulmonary arterial hypertension patients and rodent models of pulmonary arterial hypertension. And strongly associated with decreased bone morphogenic protein receptor type two, or BMPR2 expression. So this switch-independent 3A overexpression up-regulated BMPR2 expression by modulating critical epigenetic pathways and decreasing a specific transcription factor binding to the BMPR2 promoter in pulmonary vascular smooth muscle cells. Furthermore, aerosolized lung-targeted gene transfer of adeno-associated virus zero type one and containing switch-independent 3A reversed and prevented pulmonary arterial hypertension phenotype in preclinical animal models. So this beautiful study, from Dr. Hadri from Icahn School of Medicine at Mount Sinai in New York and colleagues, really suggests that switch-independent 3A can be a clinically relevant molecule for the treatment of pulmonary arterial hypertension. Dr. Greg Hundley: Wow, Carolyn. Really nice. Very intricate science for the study of pulmonary hypertension. Well, my next paper actually comes to us from Dr. Joe Hill and colleagues at UT Southwestern Medical Center. And Carolyn, as we know, cardiac hypertrophy is an independent risk factor for heart failure. Of course, the leading cause of morbidity and mortality globally. And the calcineurin NFAT, or nuclear factor of activated T-cells pathway, and the MAP kinase ERK, or extra cellular signal regulated kinase pathway, contributes to the pathogenesis of cardiac hypertrophy as an interdependent network of signaling cascades. However, Carolyn, how these pathways interact really remains unclear. And so Dr. Hill and colleagues engineered a cardiomyocyte-specific ETS2, a member of the E26 transformation specific sequence or ETS domain family knockout mouse, and investigated the role of ETS2 in cardiac hypertrophy. Primary cardiomyocytes were also used to evaluate ETS2 function in cell growth. Dr. Carolyn Lam: Wow. Okay. So what were the results, Greg? Dr. Greg Hundley: Right, Carolyn. Three main findings. First, ETS2 is activated by ERK1/2, or extracellular signal-regulated kinase 1/2, in both hypertrophied murine hearts and in human dilated cardiomyopathy. Second, ETS2 is required for both pressure overload, and calcineurin induced cardiac hypertrophy responses involving signaling cascades distinct from, but interdependent with ERK1/2 signaling. And third, this group discovered that ETS2 synergizes with NFAT to transactivate RCAN1-4, an established downstream target of NFAT, or nuclear factor of activated T-cells. And they identified an MIR-223 as a novel transcriptional target of NFAT ETS2 in cardiomyocytes. Dr. Carolyn Lam: Wow. Wow. That sounds like a lot of detailed work. Could you tell us what the clinical implications are, Greg? Dr. Greg Hundley: You bet, Carolyn. So in aggregate, these findings unveil a previously unrecognized molecular interaction between two conical hypertrophic signaling pathways, MAP kinase-driven hypertrophy, and calcineurin driven hypertrophy. And therefore, as pathological cardiac hypertrophy is an established risk factor for heart failure development, this unveiling of novel signaling mechanisms really is of potential clinical relevance. Dr. Carolyn Lam: Thanks, Greg. Well, let's round up with what else there is in this week's issue. There's a Frontiers paper by Dr. Chris Granger. And it's a big call to action to the cardiology community, to incorporate SGLT2 inhibitors and GLP-1 receptor agonists for cardiovascular and kidney disease risk reduction. There's a Joint Opinion piece from the American Heart Association, World Heart Federation, American College of Cardiology, and European Society of Cardiology on, “The Tobacco Endgame: Eradicating a Worsening Epidemic,” by Dr. Elkind. Dr. Greg Hundley: Oh great, Carolyn. Well, I've got an On My Mind piece from Professor Bhatt. And it's entitled, “Does SGLT1 inhibition Add Benefit to SGLT2 Inhibition in Type 2 Diabetes Mellitus?” And next, Dr. Viskin has an ECG Challenge entitled, “Long QT Syndrome and Torsade de Pointes Ultimately Treated With Quinidine, The Concept of Pseudo Torsade de Pointes.” And then finally, there's a Letter to the Editor by Dr. Lu regarding the article, “Association of Body Mass Index and Age with Morbidity and Mortality in Patients Hospitalized with COVID-19, Results from the American Heart Association COVID-19 Cardiovascular Disease Registry.” Well, Carolyn, I can't wait to get on to this double feature. Dr. Carolyn Lam: Me too. Let's go. Dr. Greg Hundley: Welcome, listeners, to our feature discussion today. And again, we're going to create today a forum, because we have two very interesting papers to present during this timeframe. Our first is going to come to us from Dr. Adrian Wells from University of Manchester. And our second paper will come to us from Dr. Hyeon Chang Kim from Yonsei University. I want to welcome you both, gentlemen. And Adrian, I would like to start with you. Tell us a little bit about the background related to your study. And then what was the hypothesis that you wanted to address? Dr. Adrian Wells: Okay, well thank you for inviting me to take part in this podcast. Following cardiac events, around one in three individuals will develop significant anxiety and depression symptoms. And we know that anxiety and depression can have an impact on prognosis, quality of life, future outcomes. Psychological treatment isn't routinely offered in cardiac rehabilitation for anxiety and depression, despite the fact that we identified that many of our patients felt that they would benefit from a psychological intervention to address these issues. And they felt that their needs were not really being met. So our primary question was, can we improve psychological outcomes in patients with cardiovascular disease? Dr. Greg Hundley: Very nice. And Adrian, what was your study population? And also, what was your study design? Dr. Adrian Wells: So we selected patients who entered cardiac rehabilitation in the UK. So these are patients with acute coronary syndrome, revascularization, stable heart failure, heart transplantation, and so on. And so, a wide group of individuals. We recruited 332 patients, all of whom had had anxiety and depression scores of eight or more. So these were people showing mild to severe levels of psychological distress. We conducted a two arm single blind randomized controlled trial, with 332 patients who were randomly allocated to one of these two conditions. And we assessed anxiety and depression symptoms before treatment at four months and at 12 months. Dr. Greg Hundley: Describe a little bit some of the specifics of your intervention. And then what did you find? Dr. Adrian Wells: We use relatively recent new treatment called metacognitive therapy. And this was delivered in a group format over six sessions. And we trained cardiac rehabilitation staff, nurse consultants, physiotherapists, in the delivery of this intervention. Metacognitive therapy works on helping patients discover unhelpful patterns of thinking, such as worrying and ruminating ,and excessive threat monitoring. And to reduce those patterns of thinking that contribute to anxiety, depression, and poor adaptation following stressful life experiences. Dr. Greg Hundley: And what did you find? Dr. Adrian Wells: Well, what we found was that the addition of metacognitive therapy to treatment to usual cardiac rehabilitation, significantly improved outcomes at four months and 12 months. What was striking about this was that our effect sizes were modest and moderate to large. They seem to be larger than those obtained in other studies or psychological treatments. And of note, the treatment seemed to impact well on both anxiety and depression symptoms. Whereas other types of intervention evaluated in the past have tended to treat the depression, but not so much the anxiety. Dr. Greg Hundley: Very good. So it sounds like a group-based intervention. And I'm assuming maybe participants interacted not only with your staff, but with one another. How would you put your results really in the context with other research that's going on in this space? Dr. Adrian Wells: Well, there have been a number of studies in the past that have looked at individual and group-based treatments, and patient preference for different types of intervention. I think this is the first study to use a clear manualized intervention that's based on the psychological theory of mechanisms that contribute to the maintenance of psychological problems. Obviously, this tended to use more prescriptive interventions like anxiety management, stress management, taking techniques from a range of different sources. So I think there's a difference of conceptual basis to this kind of intervention. And it's something that is highly manualized and structured, and in fact can be delivered by a range of different healthcare professionals. Dr. Greg Hundley: Very nice. And also during cardiovascular rehab. Correct? Dr. Adrian Wells: Absolutely, yeah. During cardiac rehab. One interesting finding... And we were a little concerned that this might adversely affect attendance at cardiac rehab. But we found that the treatment was well tolerated, and it didn't have any negative impact on attendance at these other sessions. Dr. Greg Hundley: Excellent. Well, congratulations on this new finding. Well, listeners, we're next going to turn to Dr. Hyeon Chang Kim from Yonsei University in Korea. And Yong-Chan, could you describe for us also the background related to your study, and the hypothesis that your research wanted to test? Dr. Hyeon Chang Kim: Thank you for inviting me to this wonderful discussion. South Korea is among the countries with the lowest cardiovascular mortality in the world. And the rate is even decreasing. However, cardiovascular risk factor is worsening. Especially in younger generation in Korea. So these young people may not have a very high cardiovascular risk, but I wanted to know the potential impact of worsening cardiovascular risk profile in this younger Korean generation. And furthermore, I wanted to know how much we can lead youth cardiovascular risk by improving their cardiovascular health profile. Dr. Greg Hundley: Very nice. And so tell us about your study design and what was the study population, related to your study? Dr. Hyeon Chang Kim: My study is basically based on the national health checkup program and national health insurance claim database. In Korea, adults over the age of 20 and employed workers of all ages are required to take general health checkup every two years. The participation rate is between 70 and 80%. So we identified three and a half million adults, age 20 to 39 years, who complete the health checkup. And cardiovascular health scores was calculated as the number of ideal cardiovascular health component, which include non-smoking, moderate physical activity three times a week, body mass index below 2030, normal blood pressure, normal cholesterol and normal fasting glucose. So the score can range from zero to six. And higher score meaning better cardiovascular health. Our outcomes were myocardial infarction, stroke, heart failure, and cardiovascular deaths in about 16 years. In addition, we also evaluate the risk of cardiovascular disease. According to two year change in how the vascular health score using repeated health checkup data. Dr. Greg Hundley: Very nice. So evaluating a set of behavioral patterns and risk factors in younger individuals, and then predicting what their longer term adverse cardiovascular outcomes would be. So what did you find? Dr. Hyeon Chang Kim: So even in this relatively low risk population, better cardiovascular health score was associated with significantly lower cardiovascular risk. About 20% reduction per one point higher score. And more importantly, people with improving cardiovascular score over two years showed leading toward cardiovascular risk. Even if their baseline cardiovascular health score was very low. Dr. Greg Hundley: Really unique findings. Tell us about the impact of your results relative to other studies published in this space. And was this also.... This was unique, because it's an Asian population, Dr. Hyeon Chang Kim: Asian population. And we are among the very low risk population. And even in this low risk population, cardiovascular health score was... Fear can be a good predictor of cardiovascular risk. And compared to many Western countries, we have very low cardiovascular risk. And our population was younger than most other studies. So we can provide some evidence that even in the higher risk population, they can do much better, based on our study. Another important thing, we can check the impact of a changing cardiovascular score, even in the younger generation. Dr. Greg Hundley: Very good. And just as a frame of reference for our listeners. Give us some characteristics, if you wouldn't mind, on what really constitutes practically a low risk score, versus what would constitute a high risk score Dr. Hyeon Chang Kim: In this younger Korean population, their cigarette smoking, and their obesity, and physical inactivity are the most common causes of worsening cardiovascular profile. And the behavioral risk factor also can attack the blood glucose and cholesterol blood pressure. So in this younger generation, they're keeping the good behavior. Past behavior is very important and it's beneficial in the very long-term. Dr. Greg Hundley: Very nice, well listeners. We're going to turn to our experts here. Two very interesting studies. And ask them both, what do they think is the next study that needs to be performed in their respective areas of research? So Yong-Chan, we'll start with you. Since we just discussed your paper. What do you think is the next study to be performed really in this sphere of research. Dr. Hyeon Chang Kim: Korea is a relatively low cardiovascular risk, has a very small size, and no racial diversity. But even in this country, disparity and inequality in cardiovascular health is becoming an important issue. So I want to identify subcultural relatively poor cardiovascular health among younger population. And also I want to find ways to improve their cardiovascular score. The conventional approaches, such as education and mass campaign, are less effective oppose this younger adults have a poor socioeconomic status. So, we may need to develop newer target-specific strategies to improve their cardiovascular health. Dr. Greg Hundley: Good. And Dr. Wells, our agent will turn next to you. What do you see is the next area of investigation or research study that needs to be performed in your sphere of interests? Dr. Adrian Wells: Well, I think the next step is to look at rollout of this intervention. Is that feasible, and how acceptable is this to cardiac services? In fact, the National Institute of Health Research have just awarded us some funding to examine feasibility and barriers to implementation in the healthcare system. In addition to that, we're beginning to examine the effects of metacognitive therapy with other health conditions, such as cancer in children and adolescents. Dr. Greg Hundley: Nice. Well listeners, we have had just a wonderful discussion today from both Dr. Adrian Wells from University of Manchester. Who brought to us combining a group-mediated, psychological stress-reducing, anxiety-reducing, intervention to the cardiac rehab sphere. And how impactful that was in reducing both anxiety, and overall depressive symptoms. And then also exciting research from Dr. Hyeon Chang Kim from South Korea. Identifying for us that in Asian population, as well as what we know in other races, those individuals in their twenties to thirties with favorable lifestyle habits, have reduced cardiovascular risk much later in life. Dr. Greg Hundley: Well, on behalf of both Carolyn and myself, we want to wish you a great week. And we'll catch you next week on the run. Dr. Greg Hundley: This program is copyright of the American Heart Association, 2021. 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, visit ahajournals.org.  

Fredrik snackar gränssnitt med Felix Holmgren och Gustav Jansson. Utgångspunkten är att Fredrik har börjat bygga gränssnitt i Apples ramverk Swiftui. Vi börjar med att snacka lite om Apples tidigare lösningar för gränssnittslayout, och Felix berättar om intressanta kopplingar mellan autolayout och, bland annat, föreslagna alternativ till CSS. Gustav berättar lite om Microsofts gränssnittslösningar genom tiderna, och sedan om så kallade immediate mode-gränssnitt. Därifrån kommer vi in på det här med objektorientering, och att många äldre gränssnittslösningar varit väldigt objektorienterade. Är objektorientering över lag på väg ut, och hur kom det sig att objektorientering kändes som nästan det enda rimliga alternativet så länge? Sist men inte minst jämför vi Elm, Swiftui, och React med Redux, och Fredrik börjar dels undra om han missat bitar av Swiftui, dels om inte Swiftui skulle kunna bli mycket mer renodlat och tydligt. Ett stort tack till Cloudnet som sponsrar vår VPS! Har du kommentarer, frågor eller tips? Vi är @kodsnack, @tobiashieta, @oferlund, och @bjoreman på Twitter, har en sida på Facebook och epostas på info@kodsnack.se om du vill skriva längre. Vi läser allt som skickas. Gillar du Kodsnack får du hemskt gärna recensera oss i iTunes! Du kan också stödja podden genom att ge oss en kaffe (eller två!) på Ko-fi, eller handla något i vår butik. Länkar Felix Gustav Felix driver också den eminenta podden The search space Captain it's Wednesday Swiftui Podcast Chapters Appkit Springs and struts Autolayout Constraints Xerox Smalltalk Cassowary En video med autolayout-constraint-tänk Interface builder DSL för constraints via ASCII-art Constraints istället för CSS Hur Swiftui-layouter beräknas Combine Reaktiv programmering - deklarativ och fokuserad på dataströmmar Knockout Reactive Ember Sproutcore Shadow DOM DSL - domänspecifikt språk Hacking with Swift Swift by Sundell Winforms WPF - Windows presentation foundation Deklarativ programmering Metro-gränssnitt, som var inne i Windows 8-trakten Silverlight Visual basic 6 Java Swing Borderlayout QT Opengl Retained mode Immediate mode Immediate mode GUI Treminutersvideo om immediate mode GUI Elm Entity component system Mike Acton snackar prestanda Chris Granger snackar Lighttable Eve Ocaml ML Haskell Redux Enum i swift Abstrakt datatyp Algebraisk datatyp Vue Titlar Ett sidoprojekt till andra sidoprojekt Det går att tänka på Teknologi från Xerox- och Smalltalkvärlden Självklart är detta det bästa sättet Såhär ofta ska det vara en svamp Det var inte autolayout Deklarativt och i XML Det var borderlayout som gällde Du vill rita Ungefär där man ritat det Ett deklarativt UI Bokstavligt talat objekt En objektorienterad programmerare Feta basklasser Konceptuellt extremt enkelt Om det händer någonting Någon liten magi för mycket Dataflöde i en riktning Kaos-React

In this episode, Dr. Jeck sits down with the Chairman of the Fauquier County Board of Supervisors, Chris Granger. The two discuss Mr. Granger's role as a supervisor, his decision-making process, the relationship between the Board of Supervisors and School Board, and much more.

April 1, 2021 ~ The Ilitch Holdings Group President of Sports and Entertainment talks to Paul about Opening Day and says they are doing their best to keep fans safe as they return to the ballpark.

See omnystudio.com/listener for privacy information. See omnystudio.com/listener for privacy information.

The latest health order from the state will allow more fans to be at the Detroit Tigers home opener.  Chris Granger, Group President of Sports & Entertainment for Ilitch Holdings, talked live with WWJ's Mike Campbell.  See omnystudio.com/listener for privacy information.

Wednesday, September 25, 2019 The Cabildo Louisiana State Museum The Louisiana Museum Foundation, Louisiana State Museum, Letters Read, Antenna, and stationer Nancy Sharon Collins bring an intimate, performative evening celebrating our love for history and architecture, and a unique understanding of our relationship with property. A special reading in which professional actors read and interpret contemporary and historic communications surrounding the current exhibit The Baroness de Pontalba & the Rise of Jackson Square at the Louisiana State Museum’s Cabildo. This event weaves the legacy of Don Andrés Almonester (1728–1798), his formidable daughter, Micaela, the Baroness de Pontalba (1795–1874), and specific members of her descendant family into an exploration of our notions of property and property ownership. Special guests include emcee Christopher Kamenstein and Grace Kennedy. About the image: “Spanish Cabildo” by artist Jim Blanchard, 1992. From the exhibition The Baroness de Pontalba & The Rise of Jackson Square at the Cabildo, French Quarter, New Orleans. The drawing was lent by Paul St. Martin and photographed by Advocate staff photographer Chris Granger.

Episode 224: Chris Granger, Group President, Sports And Entertainment, Ilitch Holdings by Yellow Flag Productions, Matt Shepard and Chad Shepard

Kitty O'Neal interviews Bill Herenda on the KFBK Afternoon News on Chris Granger leaving the Sacramento Kings.

Tracy Chou from Pinterest, and Chris Granger and Jamie Brandon from Eve, discuss whether coding is a literacy (or as Granger puts it, a "superpower" ). But as software infuses every industry and much of our lives, do we all really need to start writing code? Or is a less hands-on approach -- educating ourselves about what software can (and can't) do, and the basic architecture behind its creation -- the most useful way to gain software literacy for most people? The views expressed here are those of the individual AH Capital Management, L.L.C. (“a16z”) personnel quoted and are not the views of a16z or its affiliates. Certain information contained in here has been obtained from third-party sources, including from portfolio companies of funds managed by a16z. While taken from sources believed to be reliable, a16z has not independently verified such information and makes no representations about the enduring accuracy of the information or its appropriateness for a given situation. This content is provided for informational purposes only, and should not be relied upon as legal, business, investment, or tax advice. You should consult your own advisers as to those matters. References to any securities or digital assets are for illustrative purposes only, and do not constitute an investment recommendation or offer to provide investment advisory services. Furthermore, this content is not directed at nor intended for use by any investors or prospective investors, and may not under any circumstances be relied upon when making a decision to invest in any fund managed by a16z. (An offering to invest in an a16z fund will be made only by the private placement memorandum, subscription agreement, and other relevant documentation of any such fund and should be read in their entirety.) Any investments or portfolio companies mentioned, referred to, or described are not representative of all investments in vehicles managed by a16z, and there can be no assurance that the investments will be profitable or that other investments made in the future will have similar characteristics or results. A list of investments made by funds managed by Andreessen Horowitz (excluding investments and certain publicly traded cryptocurrencies/ digital assets for which the issuer has not provided permission for a16z to disclose publicly) is available at https://a16z.com/investments/. Charts and graphs provided within are for informational purposes solely and should not be relied upon when making any investment decision. Past performance is not indicative of future results. The content speaks only as of the date indicated. Any projections, estimates, forecasts, targets, prospects, and/or opinions expressed in these materials are subject to change without notice and may differ or be contrary to opinions expressed by others. Please see https://a16z.com/disclosures for additional important information.

During the first segment of the Cowbell Kingdom Podcast, Sacramento Kings president Chris Granger stops in to talk about the new arena district under construction downtown, the Kings quick start and whether the city of Sacramento is in line for an NBA All-Star game.In segment two, Kings rookie guard Nik Stauskas gives us a few minutes before taking on the Houston Rockets on Thursday night.  In segment three, NBC Sports' Aaron Bruski hops on t [...]Learn more about your ad choices. Visit megaphone.fm/adchoices

Ben talks with Chris Granger, creator of Light Table, about building a better IDE and envisioning a world where all programming happens inside a database and anyone can do it. Light Table Toward a Better Programming Aurora StrangeLoop 2013 Demo Exploring Data-Centric, Declarative Programming for the Cloud Chris on Twitter

Recorded November 12th, 2011, second in a series of conversations from Clojure Conj 2011. I had a chance to sit down with Chris Granger on the last night of the Conj.  It’s been fun to watch him over the past months put out a set of really pleasant-to-use and extraordinarily well-documented and well-packaged libraries, and […]