Podcast appearances and mentions of david mcmanus

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Best podcasts about david mcmanus

Latest podcast episodes about david mcmanus

The Tradesman's Support Group Podcast with Joe Doyle
Tradesman's Survival Guide - 2024 - Ep. 2 - David McManus

The Tradesman's Support Group Podcast with Joe Doyle

Play Episode Listen Later Nov 8, 2024 42:14


In this week's instalment of Joe Doyle's Tradesman's Survival Podcast, Joe speaks to David McManus of Premier TimberFrame Homes in Kildare.

Horsepower Happenings
S6E29 Feat David McManus & Katie Hudson W Gary Did Ya Know

Horsepower Happenings

Play Episode Listen Later Sep 17, 2024 93:07


Hear from 2023 Owosso Speedway track Champion, David McManus after winning the last two events of the season - his first of the year. Then, Katie Hudson previews Friday's Katie Hudson Late Model Show Kolton Strong featuring DIRTcar UMP Late Models. Plus, test your racing knowledge with Gary Did Ya Know.

Charity on SermonAudio
Unity, Liberty, & Charity

Charity on SermonAudio

Play Episode Listen Later Jun 23, 2024 47:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: Unity, Liberty, & Charity Subtitle: Letters to the Thessalonians Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday Service Date: 6/23/2024 Length: 47 min.

Anxiety on SermonAudio
Godly Anxiety

Anxiety on SermonAudio

Play Episode Listen Later May 19, 2024 46:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: Godly Anxiety Subtitle: Letters to the Thessalonians Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday Service Date: 5/19/2024 Bible: 1 Thessalonians 2:17-3:4 Length: 46 min.

Ordination on SermonAudio
Elder Ordination Jan 2024

Ordination on SermonAudio

Play Episode Listen Later Jan 23, 2024 7:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: Elder Ordination Jan 2024 Speaker: David McManus Broadcaster: Freedom Bible Church Event: Special Meeting Date: 1/14/2024 Length: 7 min.

When Would We Die?
Episode 17: Up

When Would We Die?

Play Episode Listen Later Jan 14, 2024 45:44


Go up, up and away with Doogie and Tom in their beautiful balloon, as they retrace the steps of Carl and Russell in the beloved Pixar classic. Journalist and ageing specialist, David McManus, explains how they wouldn't be the only OAP's looking for adventure these days (11:01), before hot air ballooning legend Troy Bradley gives them the benefit of his first hand experience flying houses through electrical storms (25:05).

Complaining on SermonAudio
Faithful Complaining

Complaining on SermonAudio

Play Episode Listen Later Oct 22, 2023 41:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: Faithful Complaining Subtitle: Considering Job Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday Service Date: 10/22/2023 Bible: Job 13-14 Length: 41 min.

Voices of UMassMed
UMass Chan experts discuss benefits, concerns of AI in health care

Voices of UMassMed

Play Episode Listen Later Oct 18, 2023 30:38


David McManus, MD'02, MSc and Neil Marya, MD'12, discuss how artificial intelligence will impact the field of medicine and research.

Horsepower Happenings
S5E26 Feat Leah Thirlby, David McManus, Derrick Hilliker

Horsepower Happenings

Play Episode Listen Later Aug 1, 2023 96:11


Let's preview the $35k to win WoodTic/Dan Salay Memorial with Leah Salay. Plus, hear from David McManus after his third win of the season at Owosso Speedway. Also, Derrick Hilliker has found victory lane for the 5th time and we talk about that and so much more.

OKAY, LET'S GO!
Episode 6 - The View, The View, The View w/ David McManus

OKAY, LET'S GO!

Play Episode Listen Later Apr 18, 2023 30:27


David McManus joins me to talk all things HBO Max, Harry Potter, The Phantom of the Opera, McDonalds, The Weeknd, Kelly Ripa, Regis Philbin, Mark Consuelos, Ryan Seacrest, and The View!!! This one is for fans of daytime television. Follow and subscribe if you can! @johnraphael12 on instagram :)

Sowing on SermonAudio
Sowing & Reaping

Sowing on SermonAudio

Play Episode Listen Later Nov 13, 2022 51:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: Sowing & Reaping Subtitle: Galatians Study Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday Service Date: 11/13/2022 Bible: Galatians 6:6-10 Length: 51 min.

Preaching on SermonAudio
The Necessity of Expository Preaching

Preaching on SermonAudio

Play Episode Listen Later Oct 9, 2022 41:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: The Necessity of Expository Preaching Subtitle: Sunday School Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday School Date: 10/9/2022 Length: 41 min.

Elders, Church on SermonAudio
Elder Qualifications

Elders, Church on SermonAudio

Play Episode Listen Later Sep 26, 2022 49:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: Elder Qualifications Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday School Date: 9/25/2022 Bible: 1 Timothy 3:1-7 Length: 49 min.

Mothers on SermonAudio
A Tale of Two Mothers

Mothers on SermonAudio

Play Episode Listen Later Sep 12, 2022 51:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: A Tale of Two Mothers Subtitle: Galatians Study Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday Service Date: 9/11/2022 Bible: Galatians 4:21-31 Length: 51 min.

Mothers on SermonAudio
A Tale of Two Mothers

Mothers on SermonAudio

Play Episode Listen Later Sep 12, 2022 51:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: A Tale of Two Mothers Subtitle: Galatians Study Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday Service Date: 9/11/2022 Bible: Galatians 4:21-31 Length: 51 min.

Highlights from Newstalk Breakfast
Local authorities are owed almost €105 million in unpaid rent

Highlights from Newstalk Breakfast

Play Episode Listen Later Aug 30, 2022 5:58


Local authorities across the State are owed almost €105 million in unpaid rent, with 285 social housing tenants having arrears in excess of €20,000 each. That's according to new figures compiled by The Irish Times, which also reveal that Dublin City Council, the largest local authority, is owed the highest amount of arrears at over 38 million euro. David McManus is a Fine Gael Councillor for Rathfarnham-Templeogue and spoke to Newstalk Breakfast this morning.

Newstalk Breakfast Highlights
Local authorities are owed almost €105 million in unpaid rent

Newstalk Breakfast Highlights

Play Episode Listen Later Aug 30, 2022 5:58


Local authorities across the State are owed almost €105 million in unpaid rent, with 285 social housing tenants having arrears in excess of €20,000 each. That's according to new figures compiled by The Irish Times, which also reveal that Dublin City Council, the largest local authority, is owed the highest amount of arrears at over 38 million euro. David McManus is a Fine Gael Councillor for Rathfarnham-Templeogue and spoke to Newstalk Breakfast this morning.

Fool on SermonAudio
I Pity The Fool

Fool on SermonAudio

Play Episode Listen Later Aug 3, 2022 41:00


A new MP3 sermon from Freedom Bible Church is now available on SermonAudio with the following details: Title: I Pity The Fool Subtitle: Galatians Study Speaker: David McManus Broadcaster: Freedom Bible Church Event: Sunday Service Date: 7/3/2022 Bible: Galatians 3:1-5 Length: 41 min.

The Niall Boylan Show
Sinn Fein Councillor William Carey and Fine Gael Councillor David McManus speak to Niall about social housing rent arrears

The Niall Boylan Show

Play Episode Listen Later Jun 16, 2022 21:49


Sinn Fein Councillor William Carey has accused Fine Gael of engaging in “gutter politics” after Councillor  David McManus suggested that tenants in arrears were responsible for the council failing to refurbish additional housing stock. Both Councillors join Niall on air now See omnystudio.com/listener for privacy information.

Nighttime Talk With Niall Boylan
Sinn Fein Councillor William Carey and Fine Gael Councillor David McManus speak to Niall about social housing rent arrears

Nighttime Talk With Niall Boylan

Play Episode Listen Later Jun 16, 2022 21:49


Sinn Fein Councillor William Carey has accused Fine Gael of engaging in “gutter politics” after Councillor David McManus suggested that tenants in arrears were responsible for the council failing to refurbish additional housing stock. Both Councillors join Niall on air now See omnystudio.com/listener for privacy information.

Horsepower Happenings
S4E18 Feat David McManus & Nate Dussel

Horsepower Happenings

Play Episode Listen Later Jun 7, 2022 72:52


Tonight - hear from pavement modified ace, David McManus after he collects over $5,000 from Birch Run Speedway. Plus, Ohio's Nate Dussel came to Michigan and put on a clinic at I-96 Speedway Friday night. Hear from both drivers plus news and industry insite on the latest episode of Horsepower Happenings.

Elders, Church on SermonAudio
Concerning Elders

Elders, Church on SermonAudio

Play Episode Listen Later May 19, 2022 54:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: Concerning Elders Subtitle: 1 Timothy Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Midweek Service Date: 5/18/2022 Bible: 1 Timothy 5:17-25 Length: 54 min.

Girls on SermonAudio
No Girls Allowed!

Girls on SermonAudio

Play Episode Listen Later Mar 10, 2022 62:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: No Girls Allowed! Subtitle: 1 Timothy Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Midweek Service Date: 3/9/2022 Bible: 1 Timothy 2:8-15 Length: 62 min.

Cardiovascular Digital Health Journal Podcast
The Digital Doctor: Interview with Dr. Robert Wachter

Cardiovascular Digital Health Journal Podcast

Play Episode Listen Later Jan 21, 2022 22:16


Guest Dr. Robert Wachter sits down with host Dr. David McManus to discuss all things digital health. Learn more about Dr. Wachter here: https://profiles.ucsf.edu/robert.wachter Read the journal: https://www.cvdigitalhealthjournal.com/ Follow the Journal: https://twitter.com/CVDH_journal

Optimized Advisor Podcast
Learn From An Optimized Advisor: David McManus, CFP, Cooper McManus

Optimized Advisor Podcast

Play Episode Listen Later Jan 13, 2022 57:14


Scott invited David McManus in studio for a discussion on optimization. David is the Senior Wealth Advisor and Co-Founder of Cooper McManus. David shares his journey, how he sets himself apart from other advisors, how efficiently scaled his business and client reach in a virtual environment and much more. Connect with Scott on LinkedInConnect with David on LinkedInFor more on The Optimized Advisor Podcast click here  For more on Cooper McManus click hereFollow us on LinkedInFollow us on InstagramFollow us on Facebook**This is the Optimized Advisor Podcast, where we focus on optimizing the wellbeing and best practices of insurance and financial professionals. Our objective is to help you optimize your life, optimize your profession, and learn from other optimized advisors. If you have questions or would like to be a featured guest, email us at optimizedadvisor@mailpcwest.com

Fasting on SermonAudio
From Fasting to Feasting

Fasting on SermonAudio

Play Episode Listen Later Sep 9, 2021 51:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: From Fasting to Feasting Subtitle: Zechariah Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Midweek Service Date: 9/8/2021 Bible: Zechariah 8:9-23 Length: 51 min.

Horsepower Happenings
S3E31 Feat David McManus & Johnny VanDoorn

Horsepower Happenings

Play Episode Listen Later Aug 24, 2021 80:59


On this loaded episode, David McManus discusses his dominating season that has his average finish at less than third. Plus, Kyle Crump drops by to talk about his Battle at Berlin victory; and his crew chief, Johnny VanDoorn discusses what it's been like to transition into his roll as a race car builder, rather than a driver. Plus, trackside interviews from all across the state.

Local Voices
055: The Living Wage | Hot School Meals | Cycling, A Sustainable Transport Future?

Local Voices

Play Episode Listen Later May 24, 2021 59:54


#55: On this discussion show, councillors David McManus, Laura Donaghy and Dermot Richardson debate raising the minimum wage to meet the living wage in Ireland, hot school meals for schools in disadvantaged areas, and Cycle South Dublin.To watch this episode of Local Voices on YouTube, click here:https://youtu.be/EZ5N-ETBMik

Celtic Ligers
#117 Patreon Teaser - professional dumb experts

Celtic Ligers

Play Episode Listen Later May 24, 2021 1:55


The Ligers talk about the adults in the room. -David McManus thinking school dinners are like getting the ride. -Larissa Nolan thinking mental health is for my freaking shrink!-Mark Paul thinking woke mobs won't let Blindboy make songs he's made. All here on the patreon.com/celticligersbecome a liger. go on. Get bonus content on Patreon See acast.com/privacy for privacy and opt-out information.

Local Voices
044: Challenging Misinformation | Rezoning the Greenbelt | Crack Cocaine | Wetlands

Local Voices

Play Episode Listen Later Mar 8, 2021 62:14


#44: From the dangers around the dissemination of misinformation to ongoing troubles with drugs, housing and the importance of biodiversity in South Dublin, councillors Mick Duff, Louise Dunne and David McManus discuss some of the biggest issues from the past month.

Benediction on SermonAudio
The God of Peace

Benediction on SermonAudio

Play Episode Listen Later Feb 11, 2021 43:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: The God of Peace Subtitle: Hebrews Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Midweek Service Date: 2/10/2021 Bible: Hebrews 13:18-25 Length: 43 min.

Money on SermonAudio
Marriage & Money

Money on SermonAudio

Play Episode Listen Later Jan 14, 2021 34:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: Marriage & Money Subtitle: Hebrews Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Midweek Service Date: 1/13/2021 Bible: Hebrews 13:4-6 Length: 34 min.

Marriage on SermonAudio
Marriage & Money

Marriage on SermonAudio

Play Episode Listen Later Jan 14, 2021 34:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: Marriage & Money Subtitle: Hebrews Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Midweek Service Date: 1/13/2021 Bible: Hebrews 13:4-6 Length: 34 min.

9/11 Tragedy on SermonAudio

A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: Ground Zero Subtitle: 1 Peter Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Sunday Service Date: 12/13/2020 Bible: 1 Peter 4:17-19 Length: 46 min.

Endurance on SermonAudio
Run With Endurance

Endurance on SermonAudio

Play Episode Listen Later Nov 19, 2020 44:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: Run With Endurance Subtitle: Hebrews Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Midweek Service Date: 11/18/2020 Bible: Hebrews 12:1-3 Length: 44 min.

Oaths and Vows on SermonAudio
Faith & A Foolish Vow

Oaths and Vows on SermonAudio

Play Episode Listen Later Sep 24, 2020 50:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: Faith & A Foolish Vow Subtitle: Hebrews Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Midweek Service Date: 9/23/2020 Bible: Hebrews 11:32; Judges 10:17 Length: 50 min.

Wife, The on SermonAudio
A Word to the Wives

Wife, The on SermonAudio

Play Episode Listen Later Sep 13, 2020 51:00


A new MP3 sermon from Plainfield Bible Church is now available on SermonAudio with the following details: Title: A Word to the Wives Subtitle: 1 Peter Study Speaker: David McManus Broadcaster: Plainfield Bible Church Event: Sunday Service Date: 9/13/2020 Bible: 1 Peter 3:1-6 Length: 51 min.

Discover CircRes
July 2020 Discover CircRes

Discover CircRes

Play Episode Listen Later Jul 16, 2020 21:17


This month on Episode 14 of the Discover CircRes podcast, host Cindy St. Hilaire highlights four featured articles from the July 3 and July 17 issues of Circulation Research. This episode also features an in-depth conversation with Dr. Brenda Ogle and Drs. Molly Kupfer and Wei-Han Lin regarding their study, In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid.     Article highlights:   Wei, et al. Palmitoylation Cycling and Endothelial Maturity   van Ouwerkerk, et al. Functional Variant Elements in Atrial Fibrillation Models   Ibarrola, et al.  Aldosterone in MVP   Sharma, et al. Atherosclerosis Regression Requires Regulatory T Cells   Cynthia St. Hilaire: Hi, welcome to Discover CircRes, the podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Dr. Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. Today I'm going to share with you four articles selected from our July issues of Circulation Research, as well as have a discussion with Dr. Brenda Ogle and the first authors, Molly Kupfer and Wei-Han Lin, regarding their study, In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid. So first, the highlights. The first article I want to share with you is titled, "Endothelial Palmitoylation Cycling Coordinates Vessel Remodeling in Peripheral Artery Disease." The first author is Xiaochao Wei, and the corresponding author is Clay Semenkovich from Washington University, St. Louis. Peripheral artery disease, or PAD for short, is a vascular occlusive disease of the lower extremities. It affects more than 2 million individuals globally, and its prevalence is ever increasing as our population ages. While statin therapy can be useful for combating coronary artery disease in peripheral artery disease patients, it does not prevent or reduce PAD patients' rates of lower extremity amputation. So looking to gain insights into the mechanisms underlying PAD, this team focused on the findings that circulating fibronectin and the dietary saturated fatty acid, palmitate, are associated with peripheral artery disease. They found this interesting as lipid modification proteins has been implicated in infections, premature aging, cancer and diabetes. One such protein modification is palmitoylation, which is the formation of a thioester bond between palmitate sand cysteine. Acyl-protein thioesterase 1, or APT1, is a depalmitoylase enzyme, which removes the fatty acid palmitate from protein. Using mouse models with inactivated endothelial APT1, as well as cell systems in arterial samples from humans with end stage peripheral artery disease, they tested whether deficiencies in palmitoylation cycling promotes endothelial instability, which is a hallmark of chronic arterial occlusive diseases. They discovered that as many as 10% of all proteins are palmitoylated. They found deficiency of APT1 in endothelial cells disrupts vascular homeostasis, in part by altering the intracellular trafficking of the small GTPase R-Ras. Impaired R-Ras membrane trafficking was rescued by modifying the palmitoylated R-Ras molecule to promote dissociation from membranes. These observations identify palmitoylation cycling as a potential therapeutic target in the treatment of peripheral vascular disease. The second article I want to highlight is titled, "Identification of Functional Variant Enhancers Associated with Atrial Fibrillation." The first author is Antoinette van Ouwerkerk, and the corresponding authors are Antoine de Vries and Vincent Christoffels, And they're from UMC Amsterdam. As we heard in our podcast last month with our interview with Dr. David McManus, atrial fibrillation, or AFib, is the most common form of arrhythmia, and is a major risk for heart failure, dementia, and stroke, and sudden death. Genome-wide association studies have revealed more than a hundred genetic loci linked to this condition, and many of these loci are found in non-coding regions, which are enriched for transcription factor binding sites and epigenetic modification sites, suggesting that these loci could potentially have gene regulatory roles. To test this idea, they use the method called self-transcribing active regulatory region sequencing, or STARR-seq, which is a method used to identify the sequences that act as transcriptional enhancers in a direct quantitative and genome-wide manner. They use STARR-seq to screen 12 of the strongest AFib linked regions of the genome, which contain more than 1600 individual aphid linked genetic variance, and they did this in cultured rat atrial monocytes. From this screen, they found approximately 400 regulatory elements, of which 24 exhibited variant-specific differences in regulatory activity. For one of these elements, upstream of the gene HCN4, deletion of the orthologous element in mice caused diminished transcriptional activity of the gene. Moreover, these variant-containing mice had brachycardia and sinus node dysfunction, both components of arrhythmia. This proof of principle study confirms that such a regulatory element screen could provide insight into the consequences of variants associated with AFib, or for that matter, many other diseases. The next article I want to share with you is titled, "A New Role for the Aldosterone/Mineralocorticoid Receptor Pathway in the Development of Mitral Valve Prolapse." The first author is Jaime Ibarrola, and the corresponding author is Natalia López-Andrés, and their work was completed at Sanitaria de Navarra in Pamplona, Spain. Mitral valve prolapse is a condition where blood leaks back into the left atrium of the heart, and it is the most common form of heart valve defects. The underlying pathology includes an overabundance of cells in the valve leaflet, so-called valve interstitial cells, or VICs. These activated VICs overproduce extracellular matrix protein, and the combination of increased numbers of VICs and increased amounts of extracellular matrix proteins contributes to the impairment of the structural integrity of the valve leaflet. The increase in VICs is due to excess proliferation, but also transformation of valve endothelial cells, so the cells that line the leaflet, valve endothelial cells, into mesenchymal like VICs. As a driver of endothelial to mesenchymal transition, aldosterone was suspected to play a role. Aldoesterone increased expression of VIC activation markers in cultured valve endothelial cells and increased production of certain extracellular matrix protein components. Spironolactone, an aldosterone inhibitor, prevented these effects, and importantly, prevented valve remodeling in a mouse model of mitral valve prolapse. The team showed that valve tissue from mitral valve prolapse patients taking aldosterone receptor inhibitors displayed less evidence of VIC activation and lower production of disease-regulated extracellular matrix components, than those not taking the drugs. These exciting results suggest aldosterone antagonists, already used for certain patients with heart failure or high blood pressure, may also benefit those with mitral valve prolapse. The last article I want to share before we switch to our interview, is titled, " Regulatory T Cells License Macrophage Pro-Resolving Functions During Atherosclerosis Regression." The first author is Monika Sharma, and the corresponding author is Kathryn Moore, and they're from New York University. Atherosclerosis is a chronic inflammatory condition characterized by the buildup of fatty deposits in the artery walls, and monocytes and macrophages can infiltrate into these fatty deposits and contribute to the formation of plaque. Cholesterol-lowering drugs, like statins, promote the reduction of low-density lipoproteins in the blood, which can help to slow plaque growth, but they do not reverse disease progression. One possibility for changing the course of the disease is to develop therapies that can reduce plaque inflammation, and therefore, progression. With that goal in mind, this team investigated how the immunosuppressive activity of regulatory T cells, or Tregs, may influence the functions of plaque monocytes and macrophages. Using mouse models in which the disease can be reversed through aggressive lipid lowering, they found that depletion of the Treg population caused an increase in the numbers of monocytes and macrophages in the plaques, and resulted in poorer plaque regression. Indeed, these monocytes and macrophages proliferated more, remained in the plaques longer, and were less likely to adopt an anti-inflammatory pro-plaque resolving M2-like phenotype than plaque macrophages in mice with normal Treg numbers. Together, these results highlight the importance of Tregs for promoting plaque regression, and suggest future therapies aimed at boosting these cells, or indeed, M2 macrophages may enable atherosclerosis remission. Okay, so now we're going to switch over to the interview portion of our podcast. I have with me Dr. Brenda Ogle, who is a professor of biomedical engineering, and first authors Molly Kupfer and Wei-Han Lin, and they're from the University of Minnesota. And today we're going to be discussing their manuscript titled, "In Situ Expansion, Differentiation and Electromechanical Coupling of Human Cardiac Muscle in a 3D Bioprinted, Chambered Organoid." So thank you all for joining me today.   Brenda Ogle: Thank you. Molly Kupfer: Thanks for having us. Wei-Han Lin: Thank you. Cynthia St. Hilaire: Great. I'm glad we can all do this remotely and nice and safe for COVID. So Dr. Ogle, you're the PI of the group, but Molly and Wei-Han, what stages of career are you at? Molly Kupfer: I just recently completed my PhD, so this work is sort of the culmination of that. Cynthia St. Hilaire: Oh, congratulations! Molly Kupfer: Yeah. Thank you. Cynthia St. Hilaire: Well done. Circ Research is a great thesis publication. Congratulations. Molly Kupfer: Thank you. Cynthia St. Hilaire: Wei-Han, how about you? Wei-Han Lin: So I'm a BME PhD student at the University of Minnesota. And I got my master degree in chemical engineering, but in Taiwan, and now I'm working with professor Brenda Ogle on cardiac tissue engineering stuff. Cynthia St. Hilaire: Excellent. So this is a beautiful paper. It's stunning. It has all sorts of wonderful parts, biological, biomechanical, great imaging, and essentially you created a 3D bio-ink that can be used to print and make a living pump, kind of a heart in a dish. And it's something that you're calling this human chambered muscle pump, or ChaMP, which I think is a great name. Can you please describe exactly what that is and why did you want to go about trying to make it? Molly Kupfer: Yeah, it might help if I give a little bit of context to this. So since the beginning, one of the central questions that the lab has been exploring is how do the cells of the heart interact with their environment, or the extracellular matrix, as we call it? We know that these interactions that occur at the cellular level are absolutely critical for cardiac function, both at the tissue and the organ level. And based on years of research studying how the extracellular environment modulates cellular function, we have now sought to apply what we've learned in order to engineer functional human cardiac tissues by recapitulating those very critical interactions in vitro. And actually, back in 2017, we published another study in Circulation Research, where we generated these contractile patches of cardiac tissue using a form of light-based 3D printing that allowed us to fabricate scaffolds with really high resolution micron-level features that were distributed in a way that mimics the native extracellular environment. And what we found is that by organizing the extracellular matrix in that way, we enabled the cells to organize themselves in the scaffold and form connections with each other and with the scaffold itself. And this was critical to achieving synchronous electromechanical function of the tissue as a whole. But these were very small millimeter scale tissues, and so for this new study, we sought to create something on a larger scale where you could incorporate some new geometric features such as chambers and the capacity for perfusion. And as you mentioned, using our knowledge of the interactions between cells and the extracellular matrix, we developed this unique bio-ink that could be used as a vehicle to 3D print these centimeter scale chambered tissue structures that are based on the geometry of the human heart. And so the tissues that resulted from this, the human chambered muscle pumps, or hChaMPs, exhibit thick, contiguous muscularization. They demonstrate electrical connectivity and pump function. And notably, this is the first time that this level of function and muscularization has been achieved in an engineered cardiac tissue of this level of geometric complexity. Cynthia St. Hilaire: So can you maybe talk a little bit about what do you mean by an ink, exactly? Is it actually printed? Is this like a printer that I could buy on Amazon? Obviously there's a huge biological component, but what are the actual technical things that you had to develop to make this chamber happen?  Molly Kupfer: Yes. So we did use an extrusion-based 3D printing, which is similar to probably what people normally think about with 3D printing. Traditionally, it's been with plastics. In this case, we're printing with a bio-ink, which is essentially a formulation of proteins and other materials that we encapsulate the cells in, and then after that, we extrude it from a nozzle in a specific formulation or shape in order to create the structure. Cynthia St. Hilaire: So that's interesting. So in this mix, the cells are already in there as opposed to, I guess, some other things that people tend to call scaffolds where you kind of print that and then seed it?  Molly Kupfer: Mm-hmm (affirmative). And in the example of the paper I discussed from 2017, that was an example where we printed a scaffold and put the cells in. But in this case, for such a large and complex structure, we actually mix the cells in prior to printing, and then we create the structure. Cynthia St. Hilaire: Wow. What's the timeframe of that? Like the cells, you got to digest them and mix things up and then print it. The cells, are they happy?  Molly Kupfer: Yeah, that's a good question. So the actual printing process is quite fast, maybe a couple of minutes for this particular scale. We have to prepare, culture, the cells in advance and we're working with human-induced, pluripotent stem cells, so it takes time to grow them up, and then yes, we do detach them and singularize them, and we then mix them with the components. But overall, the actual printing process is relatively quick. Then it's a matter of maintaining the structure and culturing it and doing the differentiation as we did. And that takes weeks to do over time. But the actual process of making it, initially, is quite quick. Brenda Ogle: Challenging thing about this project was the fact that mature cardiac muscle does not transfer well. Meaning when you move it from a dish to an ink and then print it and ask it to start beating again, it doesn't typically happen. And that is because cardiomyocytes don't proliferate well, or make more of each other, and they also don't move well, or migrate. And so the premise on which most of this paper relies is on printing the stem cells first, letting them expand, sort of like they do with development, and then encouraging them to specify into cardiac cell types. Cynthia St. Hilaire: What's the bigger good that can come out of this? Why do we want to be able to do this in vitro, or even ex vivo heart in a dish? Brenda Ogle: The value is pretty tremendous because, suddenly we have a human model system in which we can perfuse volume, so volume can go in and come out, in which the cells experience those volume metric and fluid-induced forces that we haven't been able to study human cells in this way ever before. In the context of human disease, this is the first time we'll be able to look at onset of a particular disease, what was happening with onset, and then progression. And I think that is what is going to transform this field. Cynthia St. Hilaire: So what was the first one like? I'm thinking back to my graduate school and also my postdoc where I was involved in some disease discovery and I have a very vivid memory of the Western blot that proved the mutation that we found. And I literally ran down the hall holding the film. I'm imagining, maybe I'm projecting too much, but what was seeing that first one beat like? Molly Kupfer: You're not projecting. I feel like that well describes my experience. We had some early experiences where we would start to see beating areas under the microscope, but I think the moment, for me, was, I think there was one night I was working in the lab and I had some plates out, I was looking at stuff under the microscope going through just the mundane lab tasks, and I think I sort of saw it at the corner of my eye in the dish, something was moving. And that was the first time. Like I had watched parts of these things beat under a microscope all the time. I spent years looking at cardiomyocytes under a microscope, but that was the first time, for these hChaMPs, where I could actually see it moving just by my eye. Cynthia St. Hilaire: Wow. Molly Kupfer: And that was a really cool moment. Wei-Han Lin: Yeah. I was mostly working on the printing side, so the first time I realized the heart started beating, it's more like a shock to me, because I'm always printing the models or just the mold. But then really seeing those cells, or the whole structure, start to beat, was quite amazing.   Cynthia St. Hilaire: Could you please tell me a bit about the 3D printing aspect of it? Is it like a shell like the outside of a balloon, or does it have an interior structure that helps dictates where the cell go? Can you explain what the printing is? Wei-Han Lin: So the structure we are printing is derived from MRI image stacks on a real human heart. And the image stack was segmented and reduce the size by 10 times, and then we convert the stack into the STL file, which is the standard operating format. And then we modify the model a little bit to make it into two chambers and with two vessels, and two connected chambers with two openings. And this is the heart we are using for the study. Cynthia St. Hilaire: Got it. So it's got kind of the big picture items of the heart. It's got two tubes going in and it's got two chambers and the fluid can flow between all of those aspects in a specific flow pattern. Wei-Han Lin: Exactly. Cynthia St. Hilaire: You said you have to differentiate them in a dish and you're adding different factors to do that. Do the cells like being in that scaffold, or do they want to seep out of that structure or is there something about the bio-ink that they're happy there? Molly Kupfer: You know, I think this bio-ink was, to a certain extent, optimized or designed such that the cells would be able to continue to attach and grow and remodel. So basically, for the most part, these components are biological materials. Some of them are just proteins. Some of them are proteins that have been modified with photo cross-linkable elements, but they still have these moieties that the cells can attach to. And over time we do see some remodeling and some extracellular matrix gets degraded and some gets deposited. Cynthia St. Hilaire: So have you gone to the next steps of something like single cell seq and trying to see what kind of cells you're getting in this? Or even maybe inputting different, the scaffold is getting one differentiation protocol, but are you possibly able to prime IPS cells such that they're maybe halfway to a vascular cell, or halfway to a cardiomyocyte cell, and then put them in the bio-ink? Brenda Ogle: That's a really interesting idea. I'm going to take that one. Cynthia St. Hilaire: Give me an acknowledgment. Brenda Ogle: So we've been thinking about that, the context of if expansion of IPS cells is the best way, for many cell types, how do we get multiple cell types and organize them? And you can imagine even just printing in specific areas, different cell types. Cynthia St. Hilaire: Oh, sure. Brenda Ogle: But the other thing we've thought about is delivering differentiation factor spatially. So almost printing a cell, but then printing that. depot of a factor, in the area that we wanted or in an arrangement that we want, and then releasing it when we want. And it's challenging for stem cell differentiation, because you really need no release, and then basically zero order release for two or three days, and then no release again. Cynthia St. Hilaire: Right. Brenda Ogle: So it's a challenging drug delivery problem, but we've been thinking a lot about it. Now priming the cells beforehand is another interesting approach. Cynthia St. Hilaire: Well, that's wonderful. I just want to congratulate you all again. Brenda Ogle: Thank you so much for having us. Cynthia St. Hilaire: Yeah, thank you so much. Wei-Han Lin: Thank you so much. Cynthia St. Hilaire:  That's it for our highlights from the July issues of Circulation Research. Thank you so much for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and on Instagram with the handle @CircRes and #discovercircres. Thank you to our guests, Dr. Brenda Ogle, Dr. Molly Kupfer and Wei-Han Lin. This podcast is produced by Rebecca McTavish and Ishara Ratnayake, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy texts for highlighted articles was provided by Ruth Williams. I'm your host Dr. Cindy St. Hilaire, and this is Discover CircRes, you're on the go source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

Discover CircRes
June 2020 Discover Circ Res

Discover CircRes

Play Episode Listen Later Jun 18, 2020 27:53


This month on Episode 13 of the Discover CircRes podcast, host Cindy St. Hilaire highlights three featured articles from the June 5 issue of Circulation Research and gives listeners an inside scoop on the cutting-edge ideas in the June 19th Compendium on Atrial Fibrillation. This episode also features an in-depth conversation with Dr David McManus on emerging technologies for identifying AFib.    Article highlights:   Zhang, et al. ACEI/ARB on COVID-19 in patients with hypertension Sakamoto, et al. ERR Signaling and Cardiac Maturation Xie, et al. CIRP Governs the Heart Rate Response to Stress Cindy St. Hilaire:           Hello and welcome to Discover CircRes, the podcast for the American Heart Association's journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire, from the Vascular Medicine Institute at the University of Pittsburgh. Today, I'm going to share with you three articles selected from the June 5th issue of Circulation Research as well as give you an overview of the Compendium on Atrial Fibrillation also coming out in June. We'll follow that by having a discussion with Dr David McManus regarding his review on the emerging technologies for identifying AFib in the general population. So first, the highlights. The first article I'm sharing with you is titled Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients with Hypertension Hospitalized with COVID-19. The first author is Peng Zhang and the corresponding author is Hongliang Li and they're from Wuhan University in Wuhan, China. Patients with hypertension have increased risk of death from COVID-19. While the high blood pressure itself is likely to contribute to this, concerns have been raised that medications used to treat hypertension, specifically ACE inhibitors and Angiotensin II receptor blockers may worsen coronavirus infection. Research in animals showed that these drugs increased expression of ACE-2, the protein on lung epithelial cells that is used by the virus to gain entry into the host cell where it can then replicate. However, other conflicting evidence has shown that these drugs might reduce lung injury in pneumonia patients, which is also a complication of COVID. To weigh up the benefits and risks of ACE inhibitors and Angiotensin II receptor blockers, Zhang and colleagues performed a retrospective analysis of 1,128 patients with COVID-19 and hypertension who are treated at nine hospitals in Hubei Province, China. Of the patients, 188 took the hypertensive medicine during their hospital stay and 940 did not. The ages, sexes and comorbidities of the two groups were very similar. After 28 days of follow up, 99 of the patients had died, seven from the group taking the hypertensive medications, equivalent to 3.7% and 92 from the group that did not or 9.8%. The team concludes that treatment of hypertension patients with hypertension medications does not increase risk of COVID-19 mortality and may even reduce the threat. However, a much larger sample size would be necessary to fully confirm. The second article I want to highlight is titled A Critical Role For Estrogen Related Receptor Signaling and Cardiac Maturation. The first authors are Tomoya Sakamoto and Timothy Matsuura and the corresponding author is Daniel Kelly from the University of Pennsylvania.  From fetal to postnatal development, the human heart goes through significant changes, including the expansion of mitochondrial numbers, a change in fuel utilization within the mitochondria and replacement of fetal contractile proteins for the adult ones. Further, there is increases in ion uptake and release. Transcription factor estrogen-related receptor was known to drive postnatal mitochondrial biogenesis and now this group has shown that it also drives these developmental changes. They developed a genetic model to knock down expression of estrogen-related receptor in early postnatal mice. When the animals were five weeks old, they performed transcriptomic analysis. In mice lacking estrogen-related receptor, there was a reduction in expression of genes involved in ion channeling in handling, fatty acid oxidation, which is the major metabolic process in the adult heart, as well as adult versions of the contractile proteins. By contrast, expression of genes and coding field contractile proteins and factors, specifically those involved in glycolysis, was upregulated. In heart failure, cardiomyocytes can revert to fetal-like cells. The authors, therefore, suggest that boosting estrogen-related receptor might be a way to counteract such pathology as well as a way to induce and study cardiomyocyte maturation and cultured progenitor cells. The next article I want to share with you is titled Cold-Inducible RNA-Binding Protein Prevents the Excessive Heart Rate Response to Stress by Targeting Phosphodiesterase. The first authors are Duanyang Xie and Li Geng and the corresponding author is Yi-Han Chen and they're from the China Ministry of Education. During a fight-or-flight situation, also known as the acute stress response, the heart rate increases rapidly due to the effects of adrenergic signaling on the cells in the sinoatrial node, which is the heart's pacemaker. Within sinoatrial node cells, levels of the signaling factor, cyclic AMP, ramp up and this, in turn, increases the cell's calcium handling and contraction rate, but excessive or prolonged racing heartbeat can be damaging and it is unclear what keeps the system in check. This group has now shown that cold-induced RNA-binding protein or CIRP puts the brakes on the heart by regulating cyclic AMP levels. The team showed that while baseline rates between wild-type and CIRP-deficient rats were the same, triggering the adrenergic signaling via treatment with isoproterenol caused CRP-deficient rat hearts to beat faster for longer than in the wild-type counterparts. Cardiac tissue from the CIRP-lacking rats showed higher than usual levels of cyclic AMP after isoproterenol treatment. This was due to lower than usual levels of phosphodiesterase, the enzyme that normally degrades cyclical AMP. The team went on to show that CIRP normally binds and stabilizes phosphodiesterase's messenger RNA and sharing a ready supply of the enzyme to restrain cyclic AMP signaling. As well as revealing this crucial control mechanism, the work highlights CIRP as a potential new target for future heart rate lowering medications. The last thing I want to share with you before we switch to our interview is our Atrial Fibrillation Compendium. Atrial fibrillation, or AFib, is a major cause of morbidity and mortality globally. There have been significant advances in the detection, management and treatment of AFib over the past two decades. However, the burden of the disease continues to increase. This Compendium on AFib features articles on epigenetics and transcriptional networks underlying atrial fibrillation, inflammasomes and proteostasis, novel molecular mechanisms associated with atrial fibrillation, emerging technologies with the identification of atrial fibrillation, epidemiology of atrial fibrillation in the 21st century, how will genetics inform the critical care of AFib, how will machine learning inform the clinical care of AFib, population-based screening for AFib, the molecular basis of AFib pathophysiology and therapy, the genetics of AFib in 2020, GWAS genome sequencing, polygenetic risk and beyond, is there hope for animal models of AFib and ablating AFib in 30 minutes, new technologies for safer and more efficient pulmonary vein isolation. Okay. So we're now going to switch over to the interview portion of the podcast. I have with me, Dr David McManus, who is a professor of medicine in the Division of Cardiology and the Department of Medicine at UMass Medical Center in Worcester, Mass and he's also a cardiac electrophysiologist. And today, we're going to be discussing his recent Review on the emerging technologies for identifying atrial fibrillation, also known AFib, So thank you so much for taking the time to speak with me today. David McManus: My pleasure. Thanks for inviting me. Cindy St. Hilaire: Yeah, so before we dig into the review and about the emerging technologies for AFib, can you maybe give me a brief explanation of what is AFib, who gets it and what's the spectrum of disease severity in the patients that do get AFib? David McManus: Sure, so atrial fibrillation is the world's most common sustained heart rhythm problem. It is associated with a number of different health conditions in terms of risk factors. The biggest risk factor for getting this rhythm problem is age, so it's most common in people over the age of 40 and it increases ... in fact, it doubles in terms of the incidents with each decade of life. So as you get into your 80s and 90, it's really quite common. The additional risk factors are kind of common things that you might imagine and a few things you might not, things like diabetes and high blood pressure that are also risk factors forgetting plaque in your heart arteries are also risk factors for AFib, but some other risk factors that are a little more controversial with respect to heart artery disease, things like alcohol consumption, even if it's red wine, which otherwise might seem to have some benefit, is actually a risk factor too for AFib. In fact, in the old days, some doctors used to refer to AFib as holiday heart because of its association with acute alcohol intake around the holidays. So, the fact is that AFib is related to some health behaviors like drinking. It's also related to a condition called sleep apnea or sleep-disordered breathing. Weight is associated with getting AFib. So all these things combined with your genetics, your family history and your age to contribute to getting this disease, so those are the most common risk factors. The question about why it is important to diagnose? It was a disease that people sort of treated like gray hair for a long time. Something that you might not want to have, but is not particularly impactful, but some really important studies, especially in the 70s and 80s, started to establish a link between atrial fibrillation and clot-based strokes and so that is a very strong relationship that exists between people who get AFib and a much higher risk of having a clot form in the heart and traveling to the brain. Cindy St. Hilaire: Which is obviously very dangerous. So how often does AFib go undetected? Because I think that's kind of at the core of using this new technology. Once you get AFib, do you know you have it right away? David McManus: So, that's exactly right. The fact is that we don't truly know, right? Because by definition it's undiagnosed. We don't really know how long your average person goes before they're diagnosed and I think it varies a lot, but it's important to know a couple of things about AFib to sort of talk around the perimeter of this answer and try to kind of hone in a bit.  So first off, some people who develop AFib don't feel it or they have very minimal symptoms or they have symptoms that come and go so quickly. By the time they get in for an evaluation, the arrhythmia is gone so it can be what's called paroxysmal in its early stages, which means it can come and go. The duration of that AFib can be minutes or hours or even in some cases, seconds, and therefore elude a diagnosis. The other thing is symptoms from AFib, when they do exist, are not always the sensation of palpitation, a sensation of an irregularity. Some people just feel short of breath when they go up a flight of stairs and- Cindy St. Hilaire: Which you can associate with age. David McManus:  ... they may attribute that symptom to being older. Yeah. Right. They may just think "I'm getting tired because I'm older," or "I'm out of shape." And so the simple answer is, I guess, I'd start with this statistic. A significant minority of patients with atrial fibrillation present with a stroke as their first clear manifestations, so they come in with stroke. The estimates on that vary considerably, but at least one in five patients who present with a stroke have a first diagnosis of AFib at the time of that stroke and about 5% of patients with AFib overall present with stroke as their first manifestation. Those are two different statistics to kind of come at it different ways and that's what you're trying to prevent. You want to make the diagnosis of AFib before the stroke because we have a lot of really good treatments that can prevent stroke if you know you have it. Cindy St. Hilaire: Right and so I think that gets to this idea of maybe screening patients of a certain age. I don't know what that age cutoff would be. But when you look at the guidelines right now, there is no clear guideline. The US Preventative Task Force says there's no good data to screen patients beforehand. I think the AHA and the ACC just don't have any guidelines regarding screening. But yet in Europe and Australia, they do perform opportunistic screening for AFib patients and this is in the clinic. This is now with ECGs. They screen for patients over 65. So based on this statistic you said that 20% of stroke patients had undetected AFib, why is there not a specific guideline? Where does that come from? David McManus: I think you're spot on that there's a lot of controversy about this right now and that's good because the reason I think it's controversial is there's some emerging technologies and opportunities that didn't exist before. Because pretty clearly, before doing a conventional 12-lead EKG in the office, did not offer sufficient benefit over and above usual care to demonstrate to groups like the US Preventative Service Task Force, which issues the guidance around things like breast cancer screening and colon cancer screening, so they have to weigh costs, financial costs, harms from false-positive tests. And so, the reason there's controversy is because what we had previously was a pretty suboptimal situation for screening. We had intermittent tests, which were of significant costs and they were spaced so far apart and required coming in for clinical care that there was really no benefit to doing them over and above taking someone's pulse in the office. But there's no question that there are groups. There's a group called the AF-SCREEN Group, for example, that is really challenging the research community and clinicians to revisit some of these assumptions about screening, given new technologies and how we might thoughtfully use them in a pharmacy, for example, or in a clinic or at home with commercial technologies to study that. Because, really, to make a recommendation that screening is clearly beneficial, you have to do some kind of a study or studies that show that not only can you diagnose more of the arrhythmia, but that by diagnosing it, you can do something about it and that that action, in this case, anticoagulation, leads to a reduction in stroke and without a significant increase in harm from that treatment and that's somewhat controversial because this is a disease…the technologies that we have now are creating new diseases, right? So in a sense, we've created the new disease, undiagnosed AFib. And so, okay, we found it. Now, is it kind of like cancer where finding it earlier maybe has a different prognosis than finding it later in terms of risk? Some people think so. And in that case, you really have to prove that finding it early and treating that early form with the treatment that you have for the late form works as well and doesn't cause harm. So that's kind of where we are right now is there a number of really big studies going on that are hoping to help inform this more, which is pretty cool. Cindy St. Hilaire: Yeah. And so on that note, my parents got new supplemental insurance. They're both retired and this new insurance came with a nurse that dropped by your house and just kind of did a wellness check. And that nurse came and checked my mom's pulse, asked her how she was feeling and checked it again and said, "You're going to your doctor. You're in AFib," and she had no symptoms of that. She's 69, she's very healthy, she's active. And essentially in the course of a couple of months, she went from what she thought was normal to not being able to take one step up one stair because her AFib got so bad and she obviously saw a cardiologist and they got her on blood thinners. And eventually, after two cardioversions, things stuck and it's now in control, but one of the things that we did was we immediately bought her an at-home KardiaMobile heart monitor. That is essentially what you're reviewing now and I'm wondering if you could maybe give us a little bit of information about this. So, there's multiple devices out there. There's the KardiaMobile. There's also the Apple Watch and the Fitbit that are starting to get these kinds of technologies. And so for us, it was at least reassuring to see her heart rate was something and now it's getting more normal with the medicine. And now even after the cardioversion, it's been a couple of months, she checks it once a day to make sure it's still functioning as it should. So can you tell us a little bit about these and about what this might mean for the future of AFib and clinical management? David McManus: Sure. So you are using an FDA-cleared technology. You've referenced the AliveCor KardiaMobile. It's in a recent survey that the Heart Rhythm Society did. One of the most common ones that's purchased or advised to patients to buy by their cardiologists and healthcare providers and I think it was cleared about 2015. And what it is is it's a credit card-sized device that gets you a 1-lead EKG and it records about 30 seconds. And then that data, it can be transmitted directly to your cardiologist. Cindy St. Hilaire: She actually would bring her phone in and show them, "Look at my last week." David McManus: Yeah, you can do it that way or, like many of my patients are, just constantly emailing them or putting them in their electronic health record, which speaks to a whole other ball of wax. But that is a very valuable tool for people who are at risk for AFib or know they have it and want to monitor themselves for things like recurrences, to check their rhythm, check their rate, so that's an FDA-cleared device. And it also provides an automated read so that she is able to see at the top of the EKG what the computer thinks her heart rhythm is and that is a really nice technology that's been fairly well studied in a variety of different settings, including people like your mom who have had a prior cardioversion, to look for recurrences. So that's one approach that exists, which is for intermittent monitoring. And that's also in essence, the same approach that one of the two tools that an Apple Watch has embedded in it. So the Apple Watch 4 and 5 are also FDA-cleared for similar analysis. So the Apple Watch has a EKG on the bevel of the watch. The thing you turn to change the time, not really in an Apple Watch, but in an old-fashioned watch. And so you can kind of put your finger on it and again, create that same circuit in your body to record a single-lead EKG and that similarly can present a 30-second EKG strip, so it's very similar to what AliveCor's KardioMobile does. Just in the watch. But again, that's an EKG-based approach and those approaches are not the only technologies that are out there. There are a number of other devices that have CE marking designation in Europe. Other devices that are starting to become available in the US and we go through some of the performance of those devices in our review. And generally speaking, the ECG approach, the advantage is it's one of the more accurate approaches to AFib detection, but it does require, at least right now, that you intermittently check yourself.  In contrast, there's a movement afoot, and Apple has a separate  FDA clearance, to use the lens and video camera on the back of the watch, that was previously used to measure your heart rate, to analyze the skin color changes that happen when your blood is flowing in and out of your wrist, to your hand. It looks at that skin color change, records it and analyzes it for irregularity. So it's an essence, like someone checking your pulse and it's called pulse plethysmography and that recording is similar to what other groups are analyzing. For example, there's something called FibriCheck, which is an app that is FDA cleared for AFib detection. But again, you put your finger on the camera of your iPhone or Android and it analyzes the pulse. Cindy St. Hilaire: So a patient has to actively say, "I'm going to check this right now," as opposed to a background assessment? David McManus: Yeah, so just to be clear. The background assessment is the automated sort of pulse check that the Apple Watch is doing and then it can prompt you to perform your own EKG, so that's the difference between kind of an intermittent-check approach versus a more near-continuous ... it's not truly continuous, but it's a near-continuous approach Cindy St. Hilaire: So are there any drawbacks to people more regularly performing these in their kitchen? As a clinician, what are the drawbacks? David McManus: It really is exciting and I think there are a lot of good reasons to pursue this. As you know, I'm sort of an early adopter of this idea and so I definitely would side with you that I think there were a lot of good reasons to be using these technologies. I just want to highlight though that there are a couple of issues. So when commercial technology companies build medical-grade tech intended to diagnose or detect rhythm problems, those rhythm problems come to the clinics in a very different way and from a different type of patient, so they're not necessarily contextualized the same way a workup would happen if you came into the doctor, they prescribed a medical-grade patch monitor or a traditional monitor or did another type of medical test on you. You're kind of on your own. And so when you get the diagnosis or you get the possible diagnosis, you have very little information,  and it can be anxiety-provoking. In many cases, especially in younger people ... in fact, the majority of people who have Apple Watches are at really low risk from having a complication from AFib. So now, you're making an upstream diagnosis and you may not do anything about it other than introduce a word onto their chart. And so, yeah, I do think there's some things that warrant further study and evaluation about some of the unintended downstream consequences of making diagnoses earlier and worrying people about a condition. David McManus: Now, some have argued that an early diagnosis, even if you wouldn't put someone on a blood thinner, as you call it or an anticoagulant ... Like for example, maybe you change your health behaviors, maybe you lose some weight or you get more active or you stopped drinking so much. So I happen to think that early diagnosis is a good thing, but I do think that we don't really have robust care-management systems across the country that can support people who are at home. It's really hard right now for your doctor to, on top of seeing 30 patients in the office, to find the time to respond to your new test that he didn't order or she didn't order. Cindy St. Hilaire: I got this blip on my strips. David McManus: Yeah, what do I do about this? Well, okay, now I got to see you, what tests are ordered, what's the process and I think there's a lot of opportunity for us to, especially in the COVID era, redesign how we're delivering heart care and integrating these technologies become a facilitator as opposed to a burden, so I think there's a lot of interest in incorporating them. But right now, at least, they're kind of separate from your chart, in the electronic chart and your doctor has to sort of find a way of reviewing on your smartphone, in the office, finding extra time to do that. They're not really paid to do that, how do you protect the safety of that information and et cetera, et cetera. So there are all these sort of little, but they seem little, but they're actually kind of important downstream implications. So we talk a little bit about, and this is kind of a unique part of this Review, the clinical actionability of device-detected AFib. There's no debating the fact that AFib is bad, but the real impact of device-detected AFib remained something that we really need to define and so there's a lot of interesting work going on in this area. Cindy St. Hilaire: And so, because we're still all at home because of the COVID epidemic, there's been some things in the news regarding some of these wearable technologies being able to detect or track trends in swaths of patient health. Where do you see this going in terms of either things like COVID and epidemics or even things regarding AFib and we always see those maps from the AHA with hotspots of diabetes, things like that, so how do you think that this kind of technology can help transition the future of medical care, specifically in the US? David McManus: I think it's really exciting because everybody has a smartphone and that crosses age, sex, race, occupation, religion and I think people are increasingly understanding the connections between health behaviors and their heart health. And I think, for example, just using your heat map example, that there's a stroke belt and a diabetes belt and different areas in the United States, also tremendous rural health disparities, that mobile devices have a really remarkable opportunity to help us understand what is going on, what is driving these sort of risks? Is it stress, is it alcohol, food consumption, nutrition, activity, sleep, all the things we talked about? And whether it be AFib or other cardiovascular conditions, these wearable devices and mobile devices and digital technologies allow for quantifying different health behaviors and mood and opinion and activity in ways that our  regular in-person exams that we do, when we see you for an hour or two every 365 days, we just really don't quantify. And I look forward to a time in the near future where your vital signs that are presented for your visit with your doctor over the internet is your activity, your blood pressure from your watch or heart rate from your watch or EKG, your oxygen levels at any of a myriad of other things that these devices can impact or will in the near future. Cindy St. Hilaire: Yeah, I agree. I think it's great. And I think also it helps to empower the patient. David McManus: Oh, for sure. I mean, if done well, it really connects you as a patient to your health more and it also, if done well, could connect you better to your healthcare team. I mean, a lot of people are afraid in the healthcare community of this technology replacing them, but that only will happen if we don't incorporate it as a tool into our relationships with our patients. I think if it's done in that way, it's a facilitator. It actually makes your mom maybe feel more connected to her cardiologist to be able to kind of run that list. Cindy St. Hilaire: Yeah and she understands what she's looking at more, so it's been wonderful. Well, thank you so much. This was an excellent Review; it was really timely and thank you again for the contribution and for taking the time to speak with me today. David McManus: My pleasure and thanks for the invitation and I hope people will read the Review. Cindy St. Hilaire: Great. Wonderful. Well, thank you so much, David. David McManus: Good luck to you and your mom. Cindy St. Hilaire: So that's it for the highlights from our June issues of Circulation Research and our compendium on atrial fibrillation. Thank you for listening. Please check out the Circulation Research Facebook page and follow us on Twitter and Instagram with the handle @CircRes and #DiscoverCircRes. Thank you to our guests, Dr David McManus. This podcast is produced by Rebecca McTavish and Ishara Ratnayaka, edited by Melissa Stoner and supported by the editorial team of Circulation Research. Some of the copy text for highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire And this is Discover CircRes, you're on-the-go source for the most up-to-date and exciting discoveries in basic cardiovascular research.  

98FM's Dublin Talks
Dublin Councillor Calls For BLM Protesters To Lose €350 Covid19 Payments

98FM's Dublin Talks

Play Episode Listen Later Jun 8, 2020 37:16


This morning on Dublin Talks we spoke to Dublin Councillor, David McManus, who wants to see those who participated in the Black Lives Matter march in Dublin lose their €350 Covid-19 payments. We asked listeners if they would agree with this idea and it gathered a very mixed reaction. One caller believes that anyone who has a problem with these marches taking places has "racial intentions". Listen Back Here Now: [audio mp3="https://media.radiocms.net/uploads/2020/06/08122520/200608-Take-Covid-Payment-off-Protesters.mp3"][/audio] TUNE IN TO DUBLIN TALKS LIVE EVERY WEEKDAY MORNING FROM 10-12, ONLY ON 98FM!!!!

Voices of UMassMed
How digital devices play a role in screening patients for disease

Voices of UMassMed

Play Episode Listen Later Nov 15, 2019 26:31


In this Voices of UMassMed podcast episode, David McManus, MD, discusses research into how digital devices can improve patient care and enhance our understanding of disease.

Midnight Radio
Episode 10: Road

Midnight Radio

Play Episode Listen Later Oct 13, 2018 16:20


There is a road and we can’t see the end of it. David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter. Midnight Radio is written by Bobbie Parker. Our original music by Morgan Jackson, and can be purchased along with Morgan’s other work at wedidthetimewarpagain.bandcamp.com. Show cover art is by Em Broude, who can be found at riskystandard.tumblr.com. Transcripts of the show are available on our official website at martletradio.com. Content warnings for this episode: static, feedback, and high-pitched noises; physical violence, discussion of death. Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ “Mic feedback fx short Mid 2″ by chimerical https://freesound.org/people/chimerical/sounds/105980/ “Violently closing wooden door” by SeanSecret https://freesound.org/people/SeanSecret/sounds/440644/ “Microphone being knocked around” by Zamazan https://freesound.org/people/Zamazan/sounds/408311/ “Fumbling with a Box” by SketchComPod https://freesound.org/people/SketchComPod/sounds/256770/ “Static_Radio” by kMoon https://freesound.org/people/kMoon/sounds/90792/ “Crickets in the Woods at Night 001″ by SoundPacks https://freesound.org/people/SoundPacks/sounds/388401/ “Leaves in wind” by Sandermotions https://freesound.org/people/Sandermotions/sounds/276294/ “Forest dry leaves walk” by rempen https://freesound.org/people/rempen/sounds/274833/

Midnight Radio
Episode 9: Ghost

Midnight Radio

Play Episode Listen Later Sep 29, 2018 17:18


AMELIA? ARE YOU THERE, AMELIA, I NEED TO T   David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter.   Midnight Radio is written by Bobbie Parker. Our original music by Morgan Jackson, and can be purchased along with Morgan’s other work at wedidthetimewarpagain.bandcamp.com. Show cover art is by Em Broude, who can be found at riskystandard.tumblr.com.   Transcripts of the show are available on our official website at martletradio.com. Content warnings for this episode: static and feedback (0.00–0.15, 15.29 onward), abuse, xenophobia, homophobia, death, physical violence.   Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ “Mic Signal Tone” by Dnab55 https://freesound.org/people/Dnab55/sounds/149265/ “muffled mic” by supernanify https://freesound.org/people/supernanify/sounds/417684/ “chair scrape” by mredig https://freesound.org/people/mredig/sounds/120560/ “Clatter” by SoundsExciting https://freesound.org/people/SoundsExciting/sounds/204363/ “Unfolding_ripping_paper” by Anton https://freesound.org/people/Anton/sounds/343/

Midnight Radio
Episode 8: Gone

Midnight Radio

Play Episode Listen Later Sep 15, 2018 19:24


A loss is shared, and museums are considered.   David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter.   Midnight Radio is written by Bobbie Parker. Our original music by Morgan Jackson, and can be purchased along with Morgan’s other work at wedidthetimewarpagain.bandcamp.com. Show cover art is by Em Broude, who can be found at riskystandard.tumblr.com.   Transcripts of the show are available on our official website at martletradio.com. Content warnings for this episode: static (0.00–0.15, 18.00-18.35), implied abuse, grief, death.   Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ "Opening folded papers" by Dee151 https://freesound.org/people/Dee151/sounds/243811/ "Door Slam" by FunWithSound https://freesound.org/people/FunWithSound/sounds/361167/ "Radio Tuning" by Dnab55 https://freesound.org/people/Dnab55/sounds/146841/

Midnight Radio
Episode 7: Waters

Midnight Radio

Play Episode Listen Later Sep 1, 2018 21:42


The flood is remembered, and a question is asked.   David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter.   Midnight Radio is written by Bobbie Parker. Our original music by Morgan Jackson, and can be purchased along with Morgan’s other work at wedidthetimewarpagain.bandcamp.com. Show cover art is by Em Broude, who can be found at riskystandard.tumblr.com.   Transcripts of the show are available on our official website at martletradio.com. Content warnings for this episode: static (0.00–0.15), terminal illness, death, grief.   Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ “Applause” by ZyryTSounds https://freesound.org/people/ZyryTSounds/sounds/219241/ "Bell, Counter, A.wav" by InspectorJ https://freesound.org/people/InspectorJ/sounds/415510/ “Unfolding_ripping_paper” by Anton https://freesound.org/people/Anton/sounds/343/

Midnight Radio
Episode 6: Ache

Midnight Radio

Play Episode Listen Later Aug 18, 2018 22:11


Some things return. Others are lost. David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter. Midnight Radio is written by Bobbie Parker. Our original music by Morgan Jackson, and can be purchased along with Morgan’s other work at wedidthetimewarpagain.bandcamp.com. Show cover art is by Em Broude, who can be found at riskystandard.tumblr.com. Transcripts of the show are available on our official website at martletradio.com. Content warnings for this episode: static (0.00–0.15), homophobia, terminal illness, death, grief. Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ “Open letter and reading” by dersuperanton https://freesound.org/people/dersuperanton/sounds/434466/

Midnight Radio
Episode 5: Constellation

Midnight Radio

Play Episode Listen Later Aug 4, 2018 16:34


A strongly-felt absence, and a story written in the stars. David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter. Midnight Radio is written by Bobbie Parker. Original music by Morgan Jackson, who can be found at wedidthetimewarpagain.bandcamp.com. Show cover art by Em Broude, who can be found at riskystandard.tumblr.com. Transcripts of the show can be found at martletradio.tumblr.com. Content warnings for this episode: static (0.00--0.15), smoking. Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/

Midnight Radio
Episode 4: Love

Midnight Radio

Play Episode Listen Later Jul 21, 2018 19:00


A love story, and a ghost story. David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter. Midnight Radio is written by Bobbie Parker. Original music by Morgan Jackson, who can be found at wedidthetimewarpagain.bandcamp.com. Show cover art by Em Broude, who can be found at riskystandard.tumblr.com. Transcripts of the show can be found at martletradio.tumblr.com. Content warnings for this episode: static (0.00--0.15), implied parental abuse, drowning, death. Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ “Paper_Shuffling_Crinkling_Crisp “ by bewagne https://freesound.org/people/bewagne/sounds/187615/ “Sneeze AC 3″ by oldedgar https://freesound.org/people/oldedgar/sounds/130977/ “old fashion radio jingle 2″ by chimerical https://freesound.org/people/chimerical/sounds/105228/

Midnight Radio
Episode 3: Vanish

Midnight Radio

Play Episode Listen Later Jul 7, 2018 19:07


Reflections on what is lost with the passage of time, and a reason for coming back home.   David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter.   Midnight Radio is written by Bobbie Parker. Original music by Morgan Jackson, who can be found at wedidthetimewarpagain.bandcamp.com. Show cover art by Em Broude, who can be found at riskystandard.tumblr.com.   Transcripts of the show can be found at martletradio.tumblr.com. Content warnings for this episode: static (0.00--0.15), discussions of terminal illness, parental abuse, and death.   Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ “Unfolding_ripping_paper” by Anton https://freesound.org/people/Anton/sounds/343/

Midnight Radio
Episode 2: Radio

Midnight Radio

Play Episode Listen Later Jun 23, 2018 17:06


Walking together in the dark, and an explanation.   David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter.   Midnight Radio is written by Bobbie Parker. Original music by Morgan Jackson, who can be found at wedidthetimewarpagain.bandcamp.com. Show cover art by Em Broude, who can be found at riskystandard.tumblr.com.   Transcripts of the show can be found at martletradio.tumblr.com. Content warnings for this episode: static (0.00--0.15), smoking.   Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ “Letter Opening1″ by achase4u https://freesound.org/people/achase4u/sounds/341805/

Midnight Radio
Episode 1: Letter

Midnight Radio

Play Episode Listen Later Jun 9, 2018 16:01


Memories of running away, and an unexpected change in routine.   David McManus is the Announcer. Courtney Dietz is Sybil McIntyre. Cory Ensle is the Presenter.   Midnight Radio is written by Bobbie Parker. Original music by Morgan Jackson, who can be found at wedidthetimewarpagain.bandcamp.com. Show cover art by Em Broude, who can be found at riskystandard.tumblr.com. Transcripts can be found at martletradio.tumblr.com. Content warnings for this episode: static (0.00--0.15)   Sound effects used: “Tuning AM radio” by CGEffex https://freesound.org/people/CGEffex/sounds/98338/ “FM Radio Static” by caculo https://freesound.org/people/caculo/sounds/347039/ ”Old radio switch” by eneibol https://freesound.org/people/eneibol/sounds/369964/ “Opening_Letter” by kmyers1316 https://freesound.org/people/kmyers1316/sounds/344597/ “Paper_Shuffling_Crinkling_Crisp “ by bewagne https://freesound.org/people/bewagne/sounds/187615/ 

The Unshackled Waves
Ep. 63 Interview Show with David McManus from Being Libertarian

The Unshackled Waves

Play Episode Listen Later Jun 19, 2017 56:54


On our interview show this week our guest is Davi…