Podcasts about VUS

Quant franc essas Vus che la lavur che Vus faschais na vegn in di betg surpigliada d'insatgi u meglier ditg d'insatge auter? Pertge tuttina sco l'informatica e la digitalisaziun ils ultims decennis fulla il mument era l'intelligenza artifiziala sia via en noss mund da lavur. Ella avanza pass per pass en ils pli differents champs e surpiglia adina dapli chaussas che nus umans faschevan avant. E quai va davent da sortir chaussas, racoltar e servir en in'ustaria fin a programmar, far translaziuns en las pli differentas linguas, scriver cudeschs u era far musica e films. Procura l'intelligenza artifiziala che nus essan in di forsa tuttas e tuts dischoccupads, perquai ch'i na dovra betg pli nus? U vegnin nus simplamain a far en il futur autras lavurs che l'IA na vegn betg da far? La «Marella» emprova da dar ina u l'autra resposta a questas dumondas prest existenzialas.

If you could listen to just one conversation about Ehlers-Danlos syndromes (EDS), hypermobility spectrum disorders (HSD), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS), what would you need to know? In this listener Q&A episode, producer Aron Korney puts host Dr. Linda Bluestein, the Hypermobility MD, in the hot seat to answer the questions patients ask most about hypermobility, connective tissue disorders, genetic testing, medications, and managing complex chronic illness. Dr. Bluestein explains why EDS, HSD, POTS, and MCAS are whole-body conditions rather than isolated joint disorders, and how connective tissue affects nearly every organ system. She shares why "less is more," why small, consistent improvements create meaningful long-term progress, and how the placebo and nocebo effects can influence healing. The conversation also covers the U.S. Food and Drug Administration (FDA) black box warning for fluoroquinolone antibiotics, including ciprofloxacin, levofloxacin, and moxifloxacin, explaining why people with connective tissue disorders should discuss safer alternatives with their healthcare providers when appropriate. Dr. Bluestein then tackles one of the most confusing topics in EDS: genetic testing. She explains why a negative genetic test does not rule out every rare subtype of EDS, how variants of uncertain significance (VUS) and direct-to-consumer genetic reports can be misleading, and why clinical evaluation remains essential, especially when vascular EDS is suspected. Finally, she discusses how mast cell activation syndrome (MCAS) can amplify pain, migraines, gastrointestinal symptoms, dysautonomia, and other multisystem symptoms, how to obtain accurate laboratory testing, and why she casts a wider diagnostic net when evaluating complex patients. The episode concludes with a simple hypermobility hack that uses vagus nerve activation to help calm a constant fight-or-flight response. Whether you're newly diagnosed with EDS or HSD, wondering if you have POTS or MCAS, trying to understand genetic testing, or looking for practical strategies to improve your health, this episode delivers the essential concepts every patient should know. Takeaways: • Think EDS only affects your joints? Discover why Ehlers-Danlos syndromes (EDS), hypermobility spectrum disorders (HSD), POTS, and mast cell activation syndrome (MCAS) are whole-body conditions that can affect nearly every organ system. • Could doing less actually help you feel better? Learn why "less is more," how stacking small wins leads to meaningful progress, and how the placebo and nocebo effects can influence your symptoms and recovery. • Are antibiotics like ciprofloxacin safe if you have EDS or another connective tissue disorder? Understand the FDA black box warning on fluoroquinolones, the risks of tendon rupture, nerve injury, and aortic complications, and when it's worth asking about alternatives. • Can a negative genetic test still mean you have a rare type of EDS? Learn why clinical features, family history, and red flags often matter as much as laboratory results, especially when vascular EDS is a possibility. • Could mast cell activation syndrome be making your symptoms worse? Discover how MCAS can amplify pain, migraines, gastrointestinal symptoms, and dysautonomia, why testing is often misunderstood, and the biggest mistakes patients should avoid. Go http://www.AquaTru.com now for 20% off (your purifier) using promo code BENDY. Head to http://www.cozyearth.com and use my code BENDY for an exclusive 20% off. Want more Dr. Linda Bluestein, MD? Website: https://www.hypermobilitymd.com/ YouTube: https://www.youtube.com/@bendybodiespodcast Instagram: ⁠⁠⁠⁠https://www.instagram.com/hypermobilitymd/⁠⁠⁠⁠ Facebook: ⁠⁠⁠⁠https://www.facebook.com/BendyBodiesPodcast⁠⁠⁠⁠ X: ⁠⁠⁠⁠https://twitter.com/BluesteinLinda⁠⁠⁠⁠ LinkedIn: ⁠⁠⁠⁠https://www.linkedin.com/in/hypermobilitymd/⁠⁠⁠⁠ Newsletter: ⁠⁠⁠⁠https://hypermobilitymd.substack.com/ Shop my Amazon store ⁠⁠⁠ https://www.amazon.com/shop/hypermobilitymd Dr. Bluestein's Recommended Herbs, Supplements and Care Necessities: https://us.fullscript.com/welcome/hypermobilitymd/store-start Want to learn more about the UVA EDS Center? For Appointments and Questions: RUVAEDSCenter@uvahealth.org UVA EDS: https://www.uvahealth.com/healthy-practice/advancing-care-through-ehlers-danlos-clinic UVA EDS FAQ: https://www.uvahealth.com/support/eds/faq UVA Pediatric Integrative Medicine: https://childrens.uvahealth.com/specialties/integrative-health Thank YOU so much for tuning in. We hope you found this episode informative, inspiring, useful, validating, and enjoyable. Join us on the next episode for YOUR time to level up your knowledge about hypermobility disorders and the people who have them. Join YOUR Bendy Bodies community at ⁠⁠https://www.bendybodiespodcast.com/⁠⁠. YOUR bendy body is our highest priority!⁠⁠ Learn more about Human Content at ⁠⁠⁠http://www.human-content.com⁠⁠⁠ Podcast Advertising/Business Inquiries: ⁠⁠⁠sales@human-content.com⁠⁠⁠ Part of the Human Content Podcast Network FTC: This video is not sponsored. Links are commissionable, meaning I may earn commission from purchases made through links Learn more about your ad choices. Visit megaphone.fm/adchoices

If you could listen to just one conversation about Ehlers-Danlos syndromes (EDS), hypermobility spectrum disorders (HSD), postural orthostatic tachycardia syndrome (POTS), and mast cell activation syndrome (MCAS), what would you need to know? In this listener Q&A episode, producer Aron Korney puts host Dr. Linda Bluestein, the Hypermobility MD, in the hot seat to answer the questions patients ask most about hypermobility, connective tissue disorders, genetic testing, medications, and managing complex chronic illness. Dr. Bluestein explains why EDS, HSD, POTS, and MCAS are whole-body conditions rather than isolated joint disorders, and how connective tissue affects nearly every organ system. She shares why "less is more," why small, consistent improvements create meaningful long-term progress, and how the placebo and nocebo effects can influence healing. The conversation also covers the U.S. Food and Drug Administration (FDA) black box warning for fluoroquinolone antibiotics, including ciprofloxacin, levofloxacin, and moxifloxacin, explaining why people with connective tissue disorders should discuss safer alternatives with their healthcare providers when appropriate. Dr. Bluestein then tackles one of the most confusing topics in EDS: genetic testing. She explains why a negative genetic test does not rule out every rare subtype of EDS, how variants of uncertain significance (VUS) and direct-to-consumer genetic reports can be misleading, and why clinical evaluation remains essential, especially when vascular EDS is suspected. Finally, she discusses how mast cell activation syndrome (MCAS) can amplify pain, migraines, gastrointestinal symptoms, dysautonomia, and other multisystem symptoms, how to obtain accurate laboratory testing, and why she casts a wider diagnostic net when evaluating complex patients. The episode concludes with a simple hypermobility hack that uses vagus nerve activation to help calm a constant fight-or-flight response. Whether you're newly diagnosed with EDS or HSD, wondering if you have POTS or MCAS, trying to understand genetic testing, or looking for practical strategies to improve your health, this episode delivers the essential concepts every patient should know. Takeaways: • Think EDS only affects your joints? Discover why Ehlers-Danlos syndromes (EDS), hypermobility spectrum disorders (HSD), POTS, and mast cell activation syndrome (MCAS) are whole-body conditions that can affect nearly every organ system. • Could doing less actually help you feel better? Learn why "less is more," how stacking small wins leads to meaningful progress, and how the placebo and nocebo effects can influence your symptoms and recovery. • Are antibiotics like ciprofloxacin safe if you have EDS or another connective tissue disorder? Understand the FDA black box warning on fluoroquinolones, the risks of tendon rupture, nerve injury, and aortic complications, and when it's worth asking about alternatives. • Can a negative genetic test still mean you have a rare type of EDS? Learn why clinical features, family history, and red flags often matter as much as laboratory results, especially when vascular EDS is a possibility. • Could mast cell activation syndrome be making your symptoms worse? Discover how MCAS can amplify pain, migraines, gastrointestinal symptoms, and dysautonomia, why testing is often misunderstood, and the biggest mistakes patients should avoid. Go http://www.AquaTru.com now for 20% off (your purifier) using promo code BENDY. Head to http://www.cozyearth.com and use my code BENDY for an exclusive 20% off. Want more Dr. Linda Bluestein, MD? Website: https://www.hypermobilitymd.com/ YouTube: https://www.youtube.com/@bendybodiespodcast Instagram: ⁠⁠⁠⁠https://www.instagram.com/hypermobilitymd/⁠⁠⁠⁠ Facebook: ⁠⁠⁠⁠https://www.facebook.com/BendyBodiesPodcast⁠⁠⁠⁠ X: ⁠⁠⁠⁠https://twitter.com/BluesteinLinda⁠⁠⁠⁠ LinkedIn: ⁠⁠⁠⁠https://www.linkedin.com/in/hypermobilitymd/⁠⁠⁠⁠ Newsletter: ⁠⁠⁠⁠https://hypermobilitymd.substack.com/ Shop my Amazon store ⁠⁠⁠ https://www.amazon.com/shop/hypermobilitymd Dr. Bluestein's Recommended Herbs, Supplements and Care Necessities: https://us.fullscript.com/welcome/hypermobilitymd/store-start Want to learn more about the UVA EDS Center? For Appointments and Questions: RUVAEDSCenter@uvahealth.org UVA EDS: https://www.uvahealth.com/healthy-practice/advancing-care-through-ehlers-danlos-clinic UVA EDS FAQ: https://www.uvahealth.com/support/eds/faq UVA Pediatric Integrative Medicine: https://childrens.uvahealth.com/specialties/integrative-health Thank YOU so much for tuning in. We hope you found this episode informative, inspiring, useful, validating, and enjoyable. Join us on the next episode for YOUR time to level up your knowledge about hypermobility disorders and the people who have them. Join YOUR Bendy Bodies community at ⁠⁠https://www.bendybodiespodcast.com/⁠⁠. YOUR bendy body is our highest priority!⁠⁠ Learn more about Human Content at ⁠⁠⁠http://www.human-content.com⁠⁠⁠ Podcast Advertising/Business Inquiries: ⁠⁠⁠sales@human-content.com⁠⁠⁠ Part of the Human Content Podcast Network FTC: This video is not sponsored. Links are commissionable, meaning I may earn commission from purchases made through links Learn more about your ad choices. Visit megaphone.fm/adchoices

ESSAI COMPLET : Jeep Wrangler 392 MOAB : 470 hp de pur plaisirTORQ | Épisode 579Essai routier complet du Jeep Wrangler 392 MOAB 2026, un véritable Wrangler de performance équipé du légendaire V8 HEMI 6,4 L, développant 470 chevaux et 470 lb-pi de couple, jumelé à une transmission automatique à 8 rapports et à un véritable système 4x4 conçu pour le hors route.Dans cet épisode de TORQ, je prends le volant du Wrangler 392 MOAB 2026 pour découvrir ce que donne un gros V8 atmosphérique dans l'un des véhicules hors route les plus emblématiques au monde. On analyse ses accélérations, sa sonorité, son comportement routier, ses capacités hors route, son confort, sa consommation et son prix canadien de 110 845 $ avant taxes.Ce modèle est notamment équipé de pneus tout-terrain de 35 pouces, de différentiels avant et arrière verrouillables, d'une barre antiroulis avant déconnectable électroniquement, d'un treuil Warn, du toit électrique Sky One-Touch et d'un échappement qui met pleinement en valeur le moteur HEMI.Au programme :Jeep Wrangler 392 MOAB 2026Moteur V8 HEMI 6,4 L470 chevaux et 470 lb-piTransmission automatique 8 vitessesPerformance et accélérationsSystème 4x4 et capacités hors routePneus 35 poucesTreuil WarnConsommation réellePrix au CanadaComparaison avec les autres Wrangler 392Le Wrangler 392 MOAB représente exactement ce que plusieurs amateurs recherchent encore : un gros moteur atmosphérique, une sonorité unique, de vraies performances et des capacités hors route sérieuses.Abonnez-vous pour plus d'essais routiers, de nouvelles automobiles, de pickups, de VUS et de contenu automobile canadien en français.#JeepWrangler #Wrangler392 #V8HEMI

Tge schessas Vus, sch'i naschiss quest onn sulet in uffant en Vossa vischnanca? E quai suenter che l'onn avant èn er be trais naschids. Cunzunt sche Vus sa regurdais anc vi dals onns ch'i deva mintg'onn anc 20 e dapli naschientschas cun be in zic dapli avdants ed avdantas.

Dr. Deb Muth 00:02What if I told you that before a single drop of chemotherapy goes into a cancer patient’s body, we can take a blood sample, grow their actual living cancer cells in a lab, and test 70 different drugs against those cells, all outside the patient’s body, to find out which ones actually work. And what if I told you that the conventional oncology doesn’t routinely use this test? Well, today we’re going to talk about why that matters and we’re going to go through and I’m going to share a story that is very personal to me. It’s about a 38 year old man with a rare complex cancer diagnosis and the precision testing that is helping to keep that cancer from progressing. Stay with me. This is one that is going to change how you think about cancer treatment. Dr. Deb Muth 01:05You guys can put a little ad right in here before we start the next segment here. Hey everybody, welcome back to Let’s Talk Wellness Now. I’m Dr. Deb and today we’re going deep. I mean really deep. It’s some of the most cutting edge cancer testing I have ever seen in clinical practice. Now, normally I don’t talk about cancer. And I would not be sharing this story if it was anyone other than my own family. I do have permission to share and talk about this publicly. So I want to do this. I want to make sure that I share this message. And he is giving his blessing to share this story because we both believe that it can save lives. So his name is Cameron. He’s 38 years old. And he is my son-in-law. And two years ago, he came to me with a small lymph node underneath his arm and a bullseye rash. So of course, being the lime literate person that I am, my first inclination was to say, yeah, this makes sense. You have an enlarged lymph node because you have this bullseye rash. You got bit by the tick. Let’s keep an eye on it. If it doesn’t go away, let me know. So Fast forward a year and a half later, he comes to me and says, mom, what do you think about this? This thing is getting a little bit larger. And I said, yeah, it’s a little larger. Not sure. Let’s keep an eye on it. He wasn’t feeling anything. All his labs looked okay. And then one day he was out chopping wood and he started getting numbness in that arm and he felt it again. And it had exploded in size. And so after some evaluation with my daughter and him, we decided to do a ultrasound. And we thought what was going to come back was a fatty tumor. It felt like one looks like one responded to one. He’s 38 years old. He’s healthy. There’s nothing in our mind that’s ever thinking the result that we’re going to get back. Dr. Deb Muth 03:28Is a possible lymphoma. Needless to say, we were shocked by that ultrasound result. And we go fast forward, we have the biopsy. I requested a total excisional biopsy. I was told by the oncologist that that was old school. They don’t do that that way anymore. And I need to stay out of this. I need to let the experts take care of this because that’s what they do best. And this came from a breast surgeon here in Wisconsin. And so I stepped back for a moment. I let him do his biopsy and what came back was adenocarcinoma of an unknown origin. Had we excised the entire lymph node, we would have had more tissue to work with. I think we could have gotten a better diagnosis. So over the course of the next two and a half, three months, we have some more imaging done. We have some more testing done. They send a pathology out to Mayo Clinic. And what continues to come back is this incongruent test results. If anybody’s ever had this, it’s extremely frustrating. One test shows lymphoma. Now it shows breast cancer. Then the next week it shows estrogen receptor HER2 positive breast cancer. Two weeks later, another test comes back and it says, no, it’s not HER2, it’s triple negative breast cancer. And now it looks like it’s out of the lymph nodes. Now it looks like it’s in the lymph nodes. And we do a PET scan and they can’t find cancer anywhere except in this axilla area. But now we find a lymph node on the right side. So it must have spread.Let’s go ahead and do a biopsy on that. And so they biopsy the right side and the right side comes back with nothing other than tattoo ink. Now, all of this is kind of crazy. I am not a cancer specialist. I want to start by saying that I am not a cancer specialist. What I am sharing today is from a mother-in-law’s perspective, from a medical detective’s perspective, I do know how to do research. I do know how to find answers. And so what I’m going to share with you Dr. Deb Muth 05:54Is totally my opinion and totally my experience. And I’m not telling anybody to do anything different than what their doctors are telling them to do. But I am telling you to ask questions. So I go deep down the rabbit hole and find out that Tattoo Ink can appear like metastatic cancer on a PET scan. And we all know everybody gets tattoos today. They’re all over everyone. And yet we’re not thinking about how this tattoo ink can cause problems for us down the road, not to mention that there are heavy metals in them and it’s a toxin and it’s creating an inflammatory process in your body that your body’s constantly trying to get rid of. So the surgeon says to us, well, yes, that’s normal that that lymph nodes inflamed. It’s normal that there’s tattoo ink in it. The body’s doing what it’s supposed to do. It’s trying to get rid of a toxin. Okay. I will agree with that, but My son-in-law is covered with tattoos everywhere. And why didn’t we mention the tattoo ink that was found in the left axilla? We are only mentioning it in the right axilla. So there’s a lot of controversy, a lot of confusion. Many of you would never know any of this because A, you either don’t look at your lab results. And if you do, you don’t understand what you’re looking at. And that creates a problem for us, right? You don’t know what questions to ask. So we go into the doctor and the doctor tells us you have cancer and we’re going to swoop you in. And in the next two weeks, you’re going to be doing chemotherapy and radiation. And six months from now, we’re going to be doing surgery and there’s no time for questions and you’re scared shitless and you’re just doing what you can to survive. And I get that. And I totally understand that. And I appreciate that. But I’m telling you that If that is your choice, that is your choice. But as you’re doing that, take the time to ask the right questions. When this happened to us, there was a lot of challenging things with the oncology team. Nobody bothered to allow them to be a partner in their care. They dictated their care, but didn’t allow them to be a partner. So, Dr. Deb Muth 08:17Here’s what most oncologists do when patients get a cancer diagnosis. They look at the tumor type, they look at the stage, they look up the NCC guidelines, the National Comprehensive Cancer Network, and they follow the algorithm. Now, I have an enormous respect for conventional oncology. I really do. Working with cancer is probably one of the hardest things in medicine that anyone can do. The advances in this field over the last 10 years have been remarkable. But here’s my issue. Standard treatment assumes your cancer is the same as the cancer in the clinical trial that created the guidelines. It’s assuming that you and your cancer are the exact same as everyone else. You are the unique fingerprint, not the cancer. And this is the problem because your cancer is unique, just as unique as if you had your fingerprint taken, the mutations driving your tumor, the drugs your cancer cells are sensitive to, the metabolic vulnerabilities of your cancer. These are all different from the person sitting next to you in the chemo suite that has the same triple negative breast cancer or HER2 positive breast cancer or prostate cancer or colon cancer that you have. So what do do about that? Well, in my world, in the integrative medicine world, we test precisely, intelligently with the tools that most oncologists have never heard of. Or if they have, they haven’t incorporated it into their treatment modality for a variety of reasons. Either it’s not acceptable by the organization that they work for, they don’t understand it, They’re not going to be able to change their protocol anyway because they have to follow the NCCN protocol. So they don’t do it or they use a portion of it and they don’t do anything outside the protocol. So today I want to cover three things with you, three tools that we used that I think every cancer patient should be asking for when they start treatment or wherever you are in treatment at this point. Dr. Deb Muth 10:44you need to have these tests done. I don’t have any affiliation with any of these companies. I don’t get paid to tell you any of this. So let me just start by saying that I understand the chemistry behind these and how important it is to give you precision cancer treatment. And that’s why I’m talking about them today. The first one we’re going to talk about is the North Star response. This is your cancer surveillance score in the blood. How much cancer is circulating in the blood. The North Star Select, your cancer’s genomic blueprint from a blood draw. And the Datar Cancer Genetic Chemoscale, the live cell drug sensitivity test that tells us which drugs actually kill your cancer. So let’s go. Let’s dive into this. Let me just take a drink here. I’m going to cough a little bit. I apologize. I have this horrible tickle. It just never seems to go away, but that is not for today to discuss. So what is all of this? OK, the North Star response is a test that was developed by a company called Billion to One. And yes, that name is intentional because of the precision involved. It’s a next generation sequencing test, meaning it reads DNA at an incredibly detailed level. And it looks at something called methylated circulating tumor DNA or methylated CT DNA. Now let me break this down in plain English for you, because this can get a little overwhelming. When the cancer cells die or shed, they release tiny fragments of DNA into your bloodstream. We call this cell-free DNA or CFDNA, and it’s hidden within that cell-free DNA. And there are fragments that come from tumor cells. We call those CT DNA or circulating tumor DNA. Here’s what makes North Star’s response different. Rather than just looking for mutations in that tumor DNA, which is what most liquid biopsies do, and a liquid biopsy is just a blood test, Dr. Deb Muth 13:03This test looks at something called methylation patterns. Think of methylation like a dimmer switch on a gene. In healthy cells, certain genes are switched on and off in a very predictable way. In cancer cells, those dimmer switches go haywire. And cancer DNA has a characteristic hypermethylation, meaning switches are turning on and should be off or off and they should be on. And these patterns are essentially a cancer fingerprint in the blood. Now the North Star response scans more than 2000 locations in the genome for these cancer specific methylation patterns. And then it adds them all up into a single number called the tumor methylation score or TMS. So for Cameron, Cameron’s blood which was drawn on April 20th, 2026, his baseline tumor methylation score came back at 13. Now here’s the critical thing, to understand this was his baseline test, his starting point. And the real power of this test is in serial monitoring, meaning we run it again and again and again over time. And if that number goes up, the cancer activity is likely increasing. If it goes down, we’re likely suppressing the tumor activity. And if it stays flat or falls, that’s telling us that the disease is responding. So this is now in the blood. We have an actual fingerprint and every test from here forward will be compared to this number. Now let’s talk a little bit about this because I was not familiar with this test at all. I wasn’t sure what to expect. I wasn’t sure what to do with it. I did not order this test. He’s working with Inveda Medical and they are fabulous over there. I will tell you that from the beginning. This is coming from a practitioner and from a mother-in-law. They were absolutely wonderful to us. So when I saw this North Star, I didn’t know, should it be zero? Should it be a hundred? And when I talked to the doctor, he said, Dr. Deb Muth 15:29This number is actually really good. An average person walking around who’s never been diagnosed with cancer, who doesn’t have cancer, their number will be between 75 and 100. Cameron’s was 13. I think that’s fantastic. But what was the first question that went through my head? It’s probably the same question that you guys are doing. How can he have cancer with a number of 13 when it’s less than the normal average? And if we’re supposed to use this to track what’s happening with his cancer, how are we going to do that once we remove the cancer? Is this number going to go to zero? And it could possibly do that. And we may not be able to use this to track whether or not the disease is actually gone. But what we can do is use this to track over the course of his lifetime to see if the cancer cells are coming back long before we detect them on imaging. And that’s the huge part of this.So this is not a test that just anybody should go out and get because you’re worried about cancer. It is a test that should be done in somebody that is already diagnosed with cancer. So let’s start by making sure we explain that, okay? So imagine if every time your cancer cells are active and they’re shedding and they’re multiplying and they’re fighting back, they’re leaving a signature in your blood not just any signature, but a specific chemical tag that says, cancer’s here. That’s what the North Star Response Test reads. Those tags across thousands of locations and gives us a single score. So we track that score over time like a thermometer for your tumor. If it goes up, we get concerned. If it stays stable or goes down, we celebrate. And we can catch a change in the blood often months before it will show up on a scan. Pretty important when we’re talking about surveilling somebody for cancer returning, when we’re worried about it, and everybody knows the cancer patient is always worried after they get that clean bill health that something’s gonna come back, and most of the time they’re told that there is no way for them to determine that or know that from a blood test. And here is the blood test that can tell us, yes, it can. Dr. Deb Muth 17:51So I would really encourage you guys to talk to your oncologist about this. If you can’t find an oncologist that will do this, talk to an integrative cancer doctor. They will most likely be familiar with it. If not, ask them to find it for you and order it for you. So next, let’s talk about that genetic blueprint because North Star Select is a different test also by billion to one run on the same blood draw, but this one is doing something completely different. This is a comprehensive genomic liquid biopsy. Liquid biopsy just means blood tusks, meaning it’s looking for specific mutations in 84 cancer related genes, all from a blood sample, no biopsy needle, no surgery, just a blood draw. It looks for CNVS, single nucleotide variants, tiny one-letter typos in the DNA code. It looks for indels, small insertions or deletions in the DNA. It looks for copy number changes, the sections of the genomes that are duplicated or deleted. It looks at fusions. So when two genes incorrectly link together to create a dangerous hybrid, MSI status, micro satellite instability, which tells us whether immunotherapy is likely to work. And it has extraordinary sensitivity. It can detect a mutation that represents as little as 0.15 % of cell free DNA in the bloodstream. That is an almost impossibly small signal in the ocean of genetic noise. So what did this show for Cameron? This is where Cameron’s case gets clinically fascinating and where it tells the story of how his cancer is being held in check. Two major mutations were identified as actionable. One was called CRAS G12C. Dr. Deb Muth 20:11And it’s a variant-ELI fraction at 0.1%. Now, CRAS, if you’ve spent any time in integrative oncology, you’ve heard this name. CRAS is one of the most well-known oncogenes in cancer biology. Think of it like an accelerator pedal in the car. In a healthy cell, CRAS pushes the cell to grow when it receives the signal to do so. And then it stops. In cancer, crass gets stuck in the go position, like on the accelerator, foot on the accelerator, to the floor, going as fast as you can around that track, right? But it’s stuck there permanently. It doesn’t turn off and it’s supposed to be turning off. The G12C variant specifically is a mutation at a very precise location. Position 12 of the CRAS protein, where a glycine is replaced by cysteine. And this matters because CRAS G12C is now a drugable target. There are FDA approved drugs specifically designed to lock this mutation into its inactive state, essentially putting a foot on the brake. Now those are drugs like, and I’m gonna slaughter these names, Sordisib, a brand name is Lumacras, and Atacras, the brand name is Crastol. Neither is yet FDA approved for breast cancer, but they are approved for lung and colorectal cancer with CrasG2C. And Cameron’s tests identified 10 active clinical trials within a region that he could potentially qualify for with this mutation. The fact that his CRAS G12C is circulating at only 0.1%. That is a very low fraction. We call that a VAF, V-A-F, very low fraction. And it tells us something important. It means that this mutation is present in a small subclone of the tumor. It’s not the overall tumor burden. So either way, when we identify, we know it’s there. Dr. Deb Muth 22:37We can catch it and we can watch it. Now, here’s another interesting thing that we saw. His TP53 was at 0.23%. This is a tumor suppressor gene, the guardian of genome. And this gene is responsible for telling damaged cells to either repair themselves or self-destruct. And when it mutates as it is here in the position R196Q, that guardian goes off duty. The cell no longer has a reliable mechanism to prevent uncontrolled growth. So TP53 mutations are present in roughly 50 % of all human cancers. And there’s currently no FDA approved drug directly targeting the TP53 but there are clinical implications. TP53 mutant tumors may respond differently to chemotherapy and several investigational approaches, including TP53 vaccines and aurora kinase inhibitors are under active investigation. So we are seeing things happen in this part of cancer right now. Now there’s something called the VUS list and we are watching This is what we’re watching. beyond those two actionable mutations, NORSTAR Select identified what we call variants of an unknown significance, VUS, adenocarcinoma of an unknown significance, ACUP. These are mutations where we don’t yet have enough clinical evidence to determine whether they’re driving cancer or not, but we watch them. So on our mutation list was CDH1, a gene linked to hereditary gastric and lobular breast cancer, CDKN2A, a tumor suppressor cell cycle regulator, CDK12, involved in DNA repair, EGFR, ERBB, this is HER2 receptor, tyrosine kinases. Dr. Deb Muth 24:55I thought this one was pretty interesting since he had an IHC that showed a three plus HER2, but then when we confirmed it with FISH, FISH showed that was negative, but now we’re actually seeing genes expressing this HER2. So is there a HER2? Is there not a HER2? This is really important because if we don’t get these diagnoses right in cancer the first time, people will spend months and years treating the wrong type of cancer with the wrong type of medication. And this may be in part why some people do better than others. If we get it right out of the gate, they do good. If we don’t get it right out of the gate, they don’t do so good. Very important to have the actual genetic makeup of the tumor that’s growing in somebody. Now last, we have something called Notch C1, NRAS and RAF1. These are key pathway components. Now all of these were at very low baffs under 0.5%. These are just whispers, not shouts, but whispers that this cancer is excreting, but your body is listening. We have to be listening. We have to be able to watch these things and monitor these. Now here’s another note of clinical interest. It was an androgen receptor positive cancer. So also detected as a VUS.We know from tissue pathology that Cameron’s tumor was androgen receptor positive. So seeing this in circulation confirms that this AR expression of the cells are present in the bloodstream and that an anti-androgen approach remains worth considering. What that means is suppressing the testosterone. What all of you know I’m about ready to say is that I hate ever suppressing hormones, especially in a 38 year old male. That is not necessarily a good thing. So before we go suppressing hormones willy-nilly, we have to know that it’s the right thing to do. And we have to be able to combat all of the complications that are going to result of that. A 38-year-old male with no testosterone could lead to heart disease down the road, could lead to bone loss, could lead to dementia, Alzheimer’s. Not to mention the sexual side effects that are going to be present. And in a man that is very, very Dr. Deb Muth 27:20Difficult for someone to manage. So you have to be very specific and you want to be very, very diligent about what you’re doing in these cases like this. Now the MSI status was not detected. This tells us that cancer is not a microsatellite instability high, meaning that standard monotherapy may have a lower baseline response of probability and the strategic integration that we’re working with with in Vita could create an immunogenesis genicity becomes even more critical. So immunotherapy is going to be very critical in a cancer case like this and working with somebody that understands that and can carefully navigate that, especially if you have an autoimmune disease like Hashimoto’s or lupus, this is all very, very pristine and has to be looked at very carefully and done very diligently in order for somebody to do this without overstimulating that immune system and causing more problems. So when we looked at the blood and found this DNA fingerprint of the cancer cells circulating in the body, from that, what we see exactly is the genetic switches that are stuck on. They’re stuck on in the wrong position. This tells us which drugs were designed to fix exactly that problem. And it opens the door to clinical trials built for these specific mutations. It also gives us a list of things to watch for over time. And if one of those tiny little signals starts to grow, we know that cancer is gaining a ground in that area. And if it shrinks or disappears, we know we’re winning. This is like, I cannot tell you how exciting this is in the cancer world and the medical world because this is really pristine cancer therapy that we’re dealing with here. And to be able to have this is just so important to life saving events in treating cancer. So. Dr. Deb Muth 29:41Let’s talk about something called the Dittar Chemoscale. This is the battle before the battle. Okay, so I’ve saved the most remarkable test for last, and this is one from a company called Dittar Cancer Genetics. They’re based out of the UK. They are CAP and CLIA certified, which means it meets the rigorous standards required for clinical laboratory testing in the US. And this test is called the ChemoScale. And it is a live cell chemosensitivity assay. So let me explain exactly what that means because it sounds complex, but the concept is actually quite elegant. When we drew the blood from Cameron, the Dittar’s laboratory isolated what are called circulating tumor associated cells or CTACs. And these are actually living cancer cells and they’re associated cells that are traveling through his bloodstream. Excuse me. So let’s think about that for a moment. Real live cancer cells isolated from a blood draw. Those living cancer cells were placed into a lab environment and exposed to over 70 different drugs, both conventional chemotherapy agents and what we call repurposed drugs. I’ll talk more about those in a minute. The lab then measured how many of those cancer cells were killed by each drug expressed as a percentage of cell death. So the scale runs from zero to a hundred and below 25%, that drug doesn’t work well against any type of cancer in that person. Might work great in somebody else, but in that particular person’s cancer that they have, it’s not gonna work so great. Anything that’s 25 to 50 % is intermediate and above 50 % is a high response. And that’s really where Dr. Deb Muth 31:43we want to be. We want to see anything higher than 50 % because that’s a great medication that can be used to kill the cancer. This is not a theoretical test. This is not based on tumor’s genetic sequence and the computer algorithm that predicts the drug response. This is a HIS actual tumor cell being killed or not being killed in real time. That is the difference. So in traditional chemotherapy, we have our protocols. If you have triple negative breast cancer, if you have HER2 positive breast cancer, if you have prostate cancer, if you have colon cancer, here’s the protocol that you’re going to use because that’s the type of cancer you have. That’s what’s been studied. Now, the problem is most of these cancers have mutated over time, especially depending on how long they’ve been in your body, because that’s what they do to try to survive. They have to change so they can survive because your immune system’s constantly trying to kill them. And so this is a really important thing. And if we don’t take an individual into response or into our thought process when we’re creating these protocols, we may give a drug that doesn’t work at all towards that cancer and you just wasted seven cycles of chemotherapy with a drug that never would have worked in the first place or had such low resistance to it that it’s now just created side effects for you but did nothing to the cancer. And then we pull out another drug and we try that. And then we pull out another drug and we try that. Instead of us knowing precisely what we can use and what we can do. And this goes for both the conventional world and the alternative world. In the alternative world of cancer, we use things like IV vitamin C and tumeric and lately ivermectin and fenbendazole and mendendazole and all kinds of other things. And if we are not truly aware that this is going to do anything, we could be wasting somebody’s time and money. So I love that this test is available. I want to walk you through a little bit about what Dr. Deb Muth 34:01we are what we saw in our case, because I think this can make a big impact on people to ask the right questions. So this particular blood test looked at several different drugs. Cameron had sensitivity from 44 % up to 61 % on different medications. Now he was really lucky. The three main drugs that they would use to treat his cancer he had greater than a 50 % response to. So that was great. However, the drugs that were recommended for him to use out of the gate had less than 50 % activity. So he would have had one drug that was really good, one drug that was not so good. And we don’t know what the outcome would have been, right? So I think this is such an incredible, incredible test to have done. This is critical friends. I’m telling you if his oncologist had chosen the two drugs based on the general guidelines for his tumor, his cells would have largely not survived. But because we ran this test, we know. So we know to avoid the drugs that won’t work and we focus on the firepower where it really counts. So I want to also talk about this repurposed drug result because this is where it gets integrated for us. Now, this section is what I want everyone in our community, our Let’s Talk Wellness community, our members to understand. This is where conventional medicine and integrative medicine intersect in a peer-reviewed clinical validated way. So the Dittar test looks at live cancer cells against what they call repurposed drugs, meaning pharmaceuticals and natural compounds that were developed for the purposes, for other purposes, like it could be an antibiotic, it could be an herbal medicine, it could be all kinds of things, vitamins, whatever. But they have demonstrated anti-cancer activity in research. And when we’re talking about integrative medicine, this is a lot of where we get Dr. Deb Muth 36:26The integrative protocols from because these particular drug compounds are known for having anti-cancer benefits. And so that’s how integrative protocols get developed. But again, it could be just like medication, like cancer drugs. If your body doesn’t have a susceptibility to it, then you’re using a product that’s not necessarily going to work. And we all know we cannot take everything that somebody recommends just simply because it has an anti-benefit to whatever it is we’re treating. There’s only so many supplements you can take. There’s only so many things you can do before you get burnt out on taking it. We call it supplement fatigue. And so we want to be very precise with what we’re doing and target this very specific area. So one of the things that showed up really, really well for our case was artemisium, sweet wormwood. It’s an anti-malarial drug that has very potent anti-cancer effects. Now I found this extremely interesting in Cameron’s case because he does have a positive tick-borne illness called Babesia. And this is one of the things that we use to treat Babesia. The other thing I think is very interesting in this case is we are studying how parasites affect cancer these days. And that’s how Ivermectin, Fenbendazole, and Menbendazole have all gotten thrown into the treatment of cancer. And so for this drug or this herb to be sensitive to this type of cancer is really intriguing to me in the world of parasites and how parasites are truly decreasing the body’s immune system and causing cancer to grow. Another thing that worked, showed up really well for him was Valprolac acid. It’s an anti-seizure drug with HDAC inhibitor properties, and this disrupts cancer cell gene expression. There was a soy formula that showed up really well. Naltrexone, you guys have heard me talk about low dose naltrexone, LDN. This actually stimulates an endogenous opioid immune response feeling, and this drug actually showed up really well. Dr. Deb Muth 38:49Something as simple as quercetin. It’s an anti-inflammatory. This is a crass inhibitor in some studies. So this is really important. I’m sure most of you have heard about the benefits of green tea and green tea also actually has anti-angiogenic or anti-cancer benefits to it. Hydroxychloroquine, very popular drug. It’s another anti-malarial drug. So again, now we have two anti-malarial drugs that are susceptible to this type of cancer. And on top of it, he has a positive babesia test. So just saying, you got to connect the dots sometimes. You got to think outside the box sometimes. Metformin is very well known as a anti-proliferative in cancer. We use it to suppress the sugar because sugar feeds cancer. Nobody should be eating sugar if they have cancer. So this one showed up as well. And then CBD, we all know of the benefits of THC, the Rick Simpson oil, and CBD can be tested to see if that is beneficial to a particular cancer cell. This is different than THC. THC works very differently in cancer. CBD is your healthy component of it. It’s the part of the marijuana plant that does not make you high. So very important here. So now let me be very clear, because I always try to be very clear. This is not FDA approved. I’m going to repeat that. This is not FDA approved. This test is a laboratory developed test, not FDA cleared. These results represent in vitro testing, meaning in a lab, not inside the human body. And the results can differ in what we call in vivo, inside the body. And this is why I always say work with a qualified clinician who can interpret these results in full clinical context. But here’s why this matters. We now have evidence, live evidence of a cancer cell that shows sensitivities to compounds that are accessible, relatively safe, and some of which he may already be using, which some of them we were. Dr. Deb Muth 41:13We were already using some of them, which made us sit back and say, this cancer has been in there for two years. If it’s a triple negative breast cancer, it’s supposed to be an aggressive breast cancer that should have spread to a different organ already after two years. It is not, it has stayed in one spot. Also interesting in this case is that there is no breast tumor that they could find anywhere. This was all confined to the axilla into the lymph node. So to have this growing for this period of time with such a small tumor marker number, that 13 that we talked about in the North Star test originally, and to see some mutations, there’s a lot of questions to this particular case. And there are lots of questions to everybody’s cancer case. They are not all straightforward cancer cases. So this is what’s important to understand this fingerprint of these cancer cells so that you can identify exactly, exactly what’s going on and treat it exactly the correct way. Super important. So this kind of information gives us the direction in an integrative protocol. It’s not guessing. This is not eat more tumor, I can hope for the best. This is personalized tumor specific precision guided integrative oncology. It is very precise. There are several countries, several clinics like this around the country that offer this type of therapy. If it’s something that you’re interested in doing, I would encourage you to look at in Vita Medical. Hope for Cancer is another great facility. There are several great facilities around the country. Like I said, that could put together an integrative approach for you if this is something that you are thinking about doing. If you’re looking for answers, if you’re in stage four or stage three and you are not getting the results that you want to get, you want to look at a different approach. You want to do a combo approach of integrative medicine and traditional medicine and alternative medicine. Dr. Deb Muth 43:37I think this is so important to look at and have experts on your team. You know, in our case, Cameron’s cancer is very complex. It’s genomically aggressive in its presentation, yet it’s not progressing to distant areas, which is so wonderful. And I want to be careful here. I can’t tell you with certainty that this is any one thing. Biology is complex. Cancer is adaptive. It’s trying to survive. That’s what it is supposed to do. It is changing its shape. It’s changing its genetic structure. It’s changing everything to try to survive and try to hide against your immune system. Now we are not even close to the finish line in our journey, but what I can tell you is that what the integrative precision approach has done that standard care alone might not do. I can tell you that today and I will share our journey along the way for any of you that are going through this that want to look at a different approach as well because I think it’s important to have this information. So first of all, we know the tumor’s fingerprint. North Star response gives us that TMS score. so we can track it over time. And if the cancer tries to gain ground, we’ll see it in the blood before a scan, we’ll show it. We know the cancer’s genetic vulnerability. We know how to handle the DNA now. We know the watch list of things to look for. And when those signals start to grow, we have a roadmap of how to address it next, how to change it. We know which drugs will automatically work against the tumor cells. We’re not guessing based on a tumor type. We tested the cells. We know how many drugs in the commercial world and in the repurposed world will and will not work. And this is going to guide the treatment protocol that we walk forward with. So we’re not giving him drugs that won’t work or have a low response. Dr. Deb Muth 45:55We’re avoiding them completely and that matters because every ineffective drug is a dose of toxicity with no benefit. There is no lie to this. Chemotherapeutic drugs are toxic. That’s how they kill the cells, but they kill the good cells and the bad cells. And if we can avoid using a drug that’s not going to work, that is so important. And then we’re layering in those repurposed and natural compounds with proven activity against specific cells. This is not complementary fluff. This is biologically active tumor tested precision medicine. Very, very important. So here is what I need you all to know and what I want you to walk away with today. If you or someone you love is facing a cancer diagnosis before treatment starts, before the first infusion goes in, I want you to ask these questions so quick. Go grab something to write with. Pause this if you need to, because this is really, really important for you to do that. And we’re going to take a break for just a second while you guys go and do that. We’re going to give you a word from our sponsor, and then we’re going to come back. And I’m going to give you the four questions that I want you to ask specifically of your medical team so that you have the answers and the ammunition that you need to work with. So we’ll be right back. Dr. Deb Muth 47:29All right, everybody, welcome back. I hope you got your pencil, your paper, your pen, your phone, whatever you’re going to take notes with because this is important. So I’m to give you four questions that I want you to ask your medical team before you get started. Question one, can we do a chemo sensitivity test before we choose a chemotherapy regime? Ask specifically about DATAR, D-A-T-A-R. cancer genetics, Oncostat Plus, or a similar functional chemosensitivity platform. Very, very important to ask those specific things. All right, question two. Can we do a comprehensive liquid biopsy to identify actionable mutations and monitor tumor burden? Ask about North Star Select, Billion to One, Guardian 360, or Foundation One Liquid CDX? I’m gonna say those for you one more time, because I said them kind of fast. North Star Select by Billion to One, Guardian 360 or Foundation One Liquid CDX? Okay, question three. Can we establish a baseline tumor methylation score, TMS, so we have a surveillance marker to track over time? and ask specifically about the North Star Response Test. All right, question four. Is there an integrative oncology center that can layer precision guided natural compounds alongside conventional treatment? Research institutes like Inveda Medical Center, CTA CA Integrative Medicine, or Hope for Cancer, these people are doing integrative medical miracles. Let me tell you, I have researched every one of them. I have spoken to each of them individually before we made our decision of who we were going to work with. They are all fantastic. You want to work with an integrative nurse practitioner who understands oncology. And if you’re working with an integrative practitioner, you want to ask them these same questions about this test so that you can get the best outcome. Dr. Deb Muth 49:56For what you’re dealing with. You are allowed to ask these questions. You are allowed to want more information from that protocol that was designed for the average patient. You’re not average and your cancer is not average either. And your care doesn’t have to be. You do not have to settle for the same thing that the person sitting next to you in the IV suite is dealing with when you both have different cancers excreting different genetic material. This is so incredibly important. want to make sure you understand precision medicine is what changes the lives for people every single day, every single day. So I started this episode by telling you about a 38 year old man with a cancer that baffled conventional medicine and integrative medicine, an occult primary that was not found complex genetic genomic profile, a presentation that in many hands might have resulted in a one size fits all treatment protocol and a prayer. And instead we ran the tests, we mapped the fingerprint, we watched the cells, we guided the protocol, and we are still fighting with precision, with data, with intelligence. This is what Let’s Talk Wellness is all about not giving up. This is what not accepting we don’t know as a final answer and demanding the level of scrutiny and personalization that every cancer patient deserves. So if this episode resonates with you, please share it because somewhere out there, there is a person who is about to get the wrong chemotherapy because no one ran the right test. And maybe, just maybe, that This episode will be the reason someone asks the right question at the right moment. If you’re going through something like this, you need a group, you need somebody to connect with, please join our free Facebook group called Seen At Last. It is where we support one another, we share this information, we share knowledge, and we help people for free support and ask the right questions. Dr. Deb Muth 52:23And if you’re inclined in your heart to pray, pray for Cameron, we could use every ounce of prayer. If you are in a position where you can help support this journey financially, we do have a fund going in free funder. I can post the link below. Every little bit helps. If you have $5, $500, it doesn’t matter. We’re raising money for this treatment. And along the way, I am documenting every step of what we’re going through so I can provide more episodes like this for you guys to share the outcome and share what our journey is like so that it can help the next person along. I really always believe that whatever happens to us happens to us because we’re meant to share it. That’s why I’ve shared my personal journey. I’m sharing his personal journey and we want to help other people. So until next time, I’m Dr. Deb. Keep asking questions, keep advocating, and never ever accept being unseen.The post Episode 274 – Stop Guessing on Chemotherapy: The Live Cell Test Most Doctors Miss first appeared on Let's Talk Wellness Now.

durée : 00:14:04 - Le 13/14 - par : Céline Asselot - Quel accord entre les États-Unis et l'Iran ? Dorothée SCHMID directrice du programme Moyen-Orient à l'IFRI et Karim Emile BITAR, chercheur associé à l'IRIS, spécialiste du Moyen-Orient et de la politique étrangère des États-Unis. - réalisation : Cecilia Arbona, Camille Poux-Jalaguier Vous aimez ce podcast ? Pour écouter tous les épisodes sans limite, rendez-vous sur Radio France

Ford teste le terrain pour un futur Lincoln Bronco ?ÉPISODE 573 | TORQDans cet épisode de TORQ, on parle du nouveau Ford Bronco Filson et de ce qu'il pourrait représenter pour l'avenir de Ford et Lincoln. Est-ce que cette version plus premium, plus luxueuse et plus lifestyle du Bronco est simplement une édition spéciale? Ou est-ce le premier vrai signal d'un futur Lincoln Bronco, un 4x4 de luxe américain capable de rivaliser avec le Land Rover Defender?Le Bronco Filson apporte une approche différente : plus de raffinement, une vibe outdoor haut de gamme, une image plus mature, et un positionnement qui dépasse le simple véhicule hors-route. Avec le succès du Ford Bronco, la montée des SUV d'aventure premium et l'intérêt grandissant pour les véhicules de luxe capables de sortir des sentiers battus, Lincoln pourrait avoir une vraie opportunité.Dans cet épisode, on analyse :Le Ford Bronco FilsonLe potentiel d'un futur Lincoln BroncoLa stratégie de Ford avec les éditions premium du BroncoLe positionnement face au Land Rover DefenderLe marché des 4x4 de luxePourquoi Lincoln pourrait avoir besoin d'un véhicule plus émotionnelLe lien entre Bronco, Filson, luxe, aventure et image lifestyleEst-ce que Ford teste tranquillement le marché avant de lancer un vrai Lincoln Bronco?Est-ce que Lincoln devrait créer son propre 4x4 de luxe?Et surtout, est-ce qu'un Lincoln Bronco pourrait devenir le Defender américain?Abonnez-vous à TORQ pour plus d'actualités automobiles, analyses, essais routiers, trucks, VUS, véhicules hors-route, voitures électriques, performance et industrie automobile canadienne.#LincolnBronco #FordBronco #BroncoFilson

In this episode, reproductive endocrinologist Dr. Natalie Crawford sits down with board-certified breast surgeon Dr. Sangeetha Kaluri to unpack a vital conversation around the rising rates of breast cancer diagnoses in young women. Moving past generic, one-size-fits-all medical advice, they dive deep into the absolute necessity of personalized screening and risk assessments to ensure no woman slips through the cracks. By highlighting how true self-advocacy and early action save lives, this episode serves as a critical blueprint for young women looking to take control of their own breast health and reproductive futures. What You'll Learn: The surprising intersection of the peripartum period and an elevated baseline risk that every postpartum woman needs to understand. Why standard age-based screening guidelines might fail young women, and the specific diagnostic gaps that occur before age 40. The hidden relationship between a customized hereditary cancer gene panel and navigating complex results like variants of unknown significance (VUS). How a specific, free online tool uses your detailed family history and imaging data to completely personalize your preventative screening schedule. The critical timeline linking urgent fertility preservation, chemotherapy, and protecting your ovarian reserve after an unexpected diagnosis. Guest Resources: Instagram: @breasttexas Tiktok: @wildflowerbreastcenter Website: wildflowerbreast.com Host Resources: Order The Fertility Formula! ⁠https://www.nataliecrawfordmd.com/book⁠ Newsletter: nataliecrawfordmd.com/newsletter Instagram: @nataliecrawfordmd Youtube Channel: Natalie Crawford MD Interested in becoming a patient?: Fora Fertility Earn FREE CE/CME: Learn at Pinnacle App This episode is brought to you by The Pinnacle Podcast Network.  Learn more about your ad choices. Visit megaphone.fm/adchoices

Quelle marque auto a la meilleure… et la pire réputation au Québec ?TORQ – Épisode 560Quelle marque automobile a la meilleure réputation au Québec… et laquelle se retrouve au fond du classement? Dans cette vidéo TORQ, on analyse l'étude Léger Réputation 2026 – Québec pour voir quelles marques auto inspirent le plus confiance aux Québécois, lesquelles chutent, et pourquoi la réputation est devenue un enjeu majeur dans l'industrie automobile.On parle de Toyota, Honda, Mazda, Subaru, Hyundai, Nissan, Ford, GM, Chrysler, Tesla et d'autres constructeurs présents dans l'étude. On revient aussi sur l'influence des médias, des réseaux sociaux, de l'image de marque, de l'expérience client et de la perception du public au Québec.Pourquoi certaines marques montent-elles dans l'opinion publique, alors que d'autres s'effondrent? Est-ce une question de fiabilité, de service, de marketing, de scandales, de politique, ou simplement de perception? Cette vidéo te donne un portrait clair, simple et direct de la réputation automobile au Québec en 2026.Abonne-toi à TORQ pour plus d'analyses sur l'actualité automobile, les marques, les trucks, les VUS, les voitures sport, les essais routiers et les grandes tendances de l'industrie auto au Québec et en Amérique du Nord.DÉBLOQUE LE CONTENU VIP :YouTube Membres VIP :https://www.youtube.com/channel/UCbha0iHrKImRyDXbDNO-EJw/joinSpotify Membres VIP :https://podcasters.spotify.com/pod/show/torqpodcast/subscribeFAST WHEELShttps://fastco.ca/Fast-Wheels/HomeASSURAGOhttps://www.assurago.ca/ #AutomobileQuebec #Torq #Media

Ford confirme le nouveau F-150 : grosse surprise pour 2029 ?TORQ – Épisode 559Ford a confirmé que le prochain Ford F-150 de nouvelle génération arrivera d'ici 2029, et ça soulève déjà beaucoup de questions. Dans cette vidéo TORQ, on passe en revue toutes les informations, rumeurs et analyses autour du futur F-150 2029 : date de lancement possible, changements attendus, nouvelles technologies, électrification, versions hybrides, F-150 Lightning, design, capacités, et ce que ça pourrait vouloir dire pour les amateurs de pickup pleine grandeur.Est-ce que Ford prépare une vraie révolution pour son camion le plus important, ou simplement une évolution du F-150 actuel? Est-ce qu'on doit s'attendre à plus de technologie, plus d'électrification, un nouveau style, ou même des changements majeurs dans la façon dont le F-150 est conçu?Dans cette vidéo, je vous donne mon analyse claire et directe sur ce que Ford pourrait préparer avec le F-150 2029, en tenant compte des infos officielles et des rumeurs les plus crédibles qui circulent actuellement.Abonne-toi à TORQ pour plus de contenu sur les pickup, camions, VUS, nouveautés automobiles, industrie auto, Ford, GM, Ram, Toyota, Honda, Nissan, et toute l'actualité automobile vue d'ici.DÉBLOQUE LE CONTENU VIP :YouTube Membres VIP :https://www.youtube.com/channel/UCbha0iHrKImRyDXbDNO-EJw/joinSpotify Membres VIP :https://podcasters.spotify.com/pod/show/torqpodcast/subscribeFAST WHEELShttps://fastco.ca/Fast-Wheels/HomeASSURAGOhttps://www.assurago.ca/ #Pickup #FordF150 #Ford

What is Deja Vu, where does it come from and why do we get it? Deja Vu researchers Dr. Christopher Moulin and Dr. Akira O'Connor have spent their lives trying to answer those questions. In this episode of Profoundly Pointless we look at the latest science surrounding Deja Vu, Jamais Vu and memory. We talk what causes Deja Vu and Jamais Vu, if Deja Vu is connected to past lives and how different types of Vus explains our lives. Then, it's Darth Vader and Scarface against Thanos and Anton Chigurh as we countdown the Top 5 Movie Villain Quotes. 00:00: Introducing Dr. Christopher Moulin and Dr. Akira O'Connor 01:17: What is Deja Vu 02:00: What's Happening During Deja Vu 05:01: How Long Does Deja Vu Last 06:18: How Deja Vu Helps Us 07:28: Jamais Vu Explained 13:29: Other Types of Vus 15:31: Deja Vu and Past Lives 19:10: Pointless 30:11: Top 5 Movie Villain Quotes Learn more about your ad choices. Visit megaphone.fm/adchoices

Nissan élimine 11 modèles… mais le Xterra et la Skyline reviennent ?TORQ – Épisode 556Nissan est en train de faire un énorme ménage dans sa gamme mondiale. Dans cet épisode de TORQ, on parle de la décision de Nissan d'éliminer 11 modèles, de ce que ça pourrait vouloir dire pour l'avenir de la marque, et surtout des nouveaux véhicules qui commencent déjà à faire réagir.On revient sur les rumeurs et indices entourant le retour possible du Nissan Xterra, du Skyline, ainsi que sur la nouvelle direction produit de Nissan et Infiniti. Est-ce qu'on assiste enfin à un vrai recentrage stratégique, ou simplement à une marque qui coupe parce qu'elle n'a plus le choix?On jase aussi du look des nouveaux modèles, du positionnement futur de Nissan, d'Infiniti, et de ce que ces changements pourraient signifier pour les amateurs de VUS, de performance et de véhicules japonais.Penses-tu que Nissan prend enfin les bonnes décisions?Le retour du Xterra t'intéresse plus que celui du Skyline?Dis-moi ça en commentaire.Abonne-toi à TORQ pour plus d'analyses, d'actualités automobiles et d'opinions franches sur l'industrie auto.DÉBLOQUE LE CONTENU VIP :YouTube Membres VIP :https://www.youtube.com/channel/UCbha0iHrKImRyDXbDNO-EJw/joinSpotify Membres VIP :https://podcasters.spotify.com/pod/show/torqpodcast/subscribeFAST WHEELShttps://fastco.ca/Fast-Wheels/HomeASSURAGOhttps://www.assurago.ca/ #Nissan #Xterra #Skyline

In this episode of Liver Lineup, hosts Nancy Reau, MD, and Kimberly Brown, MD, are joined by Saul Karpen, MD, PhD, and Robert Gish, MD, for a practical, clinician-focused discussion on the evolving role of genetic testing in cholestatic liver disease.As genetic panels become more widely used in hepatology, many clinicians are left wondering when to order these tests—and how to interpret the results when they come back. From unexplained cholestasis and AMA-negative PBC to intrahepatic cholestasis of pregnancy and atypical liver enzyme patterns, the conversation explores where genetic testing can add real clinical value.Karpen and Gish break down the basics of modern genetic panels, including how they've evolved over time, what clinicians should look for in results, and how to approach common challenges like variants of uncertain significance (VUS). The discussion also highlights key genes, such as ABCB4 and ABCB11, and explains how genetic findings can influence diagnosis, risk assessment, and treatment decisions.Read more: https://www.hcplive.com/view/liver-lineup-navigating-genetic-testing-in-cholestatic-liver-disease

Hyundai attaque enfin le Bronco et le Wrangler ?!TORQ - Épisode 551Dans cette épisode de TORQ, on parle du Hyundai Boulder Concept, la grosse surprise de Hyundai au Salon de New York 2026. Contrairement à ce que certains pourraient penser, ce n'est pas un pickup, mais bien un VUS off-road qui vise clairement le territoire du Jeep Wrangler et du Ford Bronco. Hyundai présente aussi avec ce concept sa première architecture body-on-frame, ce qui marque un gros changement de direction pour la marque.On décortique ensemble le design, le positionnement, le message derrière ce concept, et surtout la vraie question : est-ce que Hyundai peut vraiment devenir crédible dans le monde du 4x4 sérieux? Parce qu'une chose est sûre, le look frappe fort, mais pour l'instant Hyundai n'a toujours pas confirmé les vraies specs mécaniques du Boulder.Dis-moi en commentaire :Est-ce que le Hyundai Boulder a ce qu'il faut pour rivaliser avec le Bronco et le Wrangler?DÉBLOQUEZ LE CONTENU VIP : YOUTUBE Membres VIP :https://www.youtube.com/channel/UCbha0iHrKImRyDXbDNO-EJw/joinSpotify Membres VIP :https://podcasters.spotify.com/pod/show/torqpodcast/subscribeFAST WHEELS https://fastco.ca/Fast-Wheels/HomeASSURAGOhttps://www.assurago.ca/#JeepWrangler #HyundaiBoulder #Bronco

Autoinflammatory diseases are often considered rare — but, in clinical practice, they may be far more common than we think. In this episode of Around the Rheum, hosts Dr. Daniel Ennis and Dr. Janet Pope speak with Dr. Jason An, a Toronto rheumatologist with expertise in autoinflammatory disorders.Together, they explore how these conditions differ from classic autoimmune disease, why adult rheumatologists should be thinking about them more often, and how to approach diagnosis when the presentation doesn't fit neatly into familiar categories.Dr. An also shares practical strategies for recognizing autoinflammatory patterns, interpreting genetic testing, and using targeted therapies both diagnostically and therapeutically.In this episode we discuss:The evolving definition of autoinflammatory disease and how it differs from autoimmune diseaseWhy these disorders are not just pediatric diseases and may present in adulthoodA practical cytokine-based framework for classifying autoinflammatory diseasesThe four major inflammatory “buckets”:IL-1–mediated diseasesIL-18-mediated diseasesTNF / NF-κB pathway disordersInterferonopathiesClinical pattern recognition in patients with recurrent fevers and systemic inflammationThe role and limitations of genetic testing in autoinflammatory diseaseWhy variants of uncertain significance (VUS) may still be clinically meaningful in adultsUsing targeted therapies as diagnostic tools (colchicine, IL-1 blockade, JAK inhibitors)When rheumatologists should consider referral to an autoinflammatory disease specialistRecommended reading:Dr. An's review on autoinflammatory diseases in The Journal of Rheumatology:https://www.jrheum.org/content/51/9/848Dr. Jason An, MD, MSc is an adult rheumatologist specializing in the diagnosis and treatment of autoinflammatory diseases who works in community practice in the Greater Toronto Area (GTA)Around The Rheum is produced by the CRA Communications Committee. A special thank you to the podcast team, Dr. Dax G. Rumsey (CRA Communications Committee Chair), Dr. Daniel Ennis (Host), Dr. Janet Pope (Host) David McGuffin (exploreproductions.ca), and Erin Stewart (CRA) for leading production.Our theme music was composed by Aaron Fontwell.For more on the work of the Canadian Rheumatology Association, visit rheum.ca

Martin a appris une mauvaise nouvelle à Rémi ce matin… Mike s’en va dans la tête de Kim… pis ça va vite! As-tu déjà gâché une surprise sans le vouloir? Mister fun : Surévalué ou sous-évalué : Le compte en banque de Luc Poirier? La rockstar du jour : Roxette Les débateurs : L’explosion des ventes des VUS et pick-up au Québec… Le mashup : QUAND ALEX WARREN ET JELLY ROLL RENCONTRE DAFT PUNK ET RHYTHM IS A DANCER ET…. LA DÉRAPE DE L’ÉQUIPE UN PEU PLUS TÔT!! Spécial K : Comment Kim s’est fait écoeurer sur ses seins au secondaire? Rémipédia : L’histoire tragique de Blanche Monnier.

In this episode we are talking about uncertainty and risk along with patient preferences for communication. Segment 1: The attitudes of individuals with or at risk of adult-onset genetic conditions on reproductive genetic testing: A systematic review Shanice Allen is a PhD student from the Sheffield Institute for Translational Neuroscience (SITraN) at the University of Sheffield. The aim of her research is exploring the attitudes and experiences of individuals with or at-risk of genetic MND on reproductive genetic testing, and explore how and if clinicians discuss these options with these individuals. This will help us identify any barriers to accessing reproductive services. LinkedIn: https://www.linkedin.com/in/shanice-allen-9a89661a5/   In this segment we discuss: - The attitudes toward reproductive genetic testing in adult-onset genetic conditions. - Experiential knowledge and perceived disease severity in shaping reproductive decision-making. - Ethical themes including guilt, eugenics, and concerns about pregnancy termination. - Findings supporting more tailored, longitudinal genetic counseling approaches.   Segment 2: Assessing patient communication preferences for reclassified variants of uncertain significance in a general genetics clinic Eden Brush, MS, CGC is a pediatric and inpatient genetic counselor in the Division of Clinical Genetics at Columbia University Irving Medical Center. She completed her graduate training at Columbia University as part of the class of 2024. She is passionate about rare disease advocacy, narrative medicine, and disability justice.   In this segment we discuss: - Patient communication preferences for reclassified variants of uncertain significance (VUS) and patient-driven practice insights - Factors that emphasize the utility of shared responsibility, the need for standardized recontact systems, and the importance of equity-focused implementation strategies. - How VUS reclassification type impacted patient-preferred disclosure methods.    Would you like to nominate a JoGC article to be featured in the show? If so, please fill out this nomination submission form here. Multiple entries are encouraged including articles where you, your colleagues, or your friends are authors.   Stay tuned for the next new episode of DNA Dialogues! In the meantime, listen to all our episodes Apple Podcasts, Spotify, streaming on the website, or any other podcast player by searching, “DNA Dialogues”.    For more information about this episode visit dnadialogues.podbean.com, where you can also stream all episodes of the show. Check out the Journal of Genetic Counseling here for articles featured in this episode and others.    Any questions, episode ideas, guest pitches, or comments can be sent into DNADialoguesPodcast@gmail.com.    DNA Dialogues' team includes Jehannine Austin, Naomi Wagner, Khalida Liaquat, Kate Wilson and DNA Today's Kira Dineen. Our logo was designed by Ashlyn Enokian. Our current intern is Stephanie Schofield.

durée : 00:35:17 - L'invité du 13/14 - par : Jérôme CADET - Comment la commune des Ponts-de-Cé, près d'Angers, s'organise pour faire face à une montée des eaux historique ? Nous en discutons en direct avec quatre invités, le maire Jean Paul Pavillon, la ministre Françoise Gatel, le dessinateur Etienne Davodeau, et la chargée de mission Virginie Gaspari. Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

durée : 00:58:55 - Le 13/14 - Comment la commune des Ponts-de-Cé, près d'Angers, s'organise pour faire face à une montée des eaux historique ? Nous en discutons en direct avec quatre invités, le maire Jean Paul Pavillon, la ministre Françoise Gatel, le dessinateur Etienne Davodeau, et la chargée de mission Virginie Gaspari. Vous aimez ce podcast ? Pour écouter tous les autres épisodes sans limite, rendez-vous sur Radio France.

Écoutez le meilleur de La commission du 11 février 2026: Préférez-vous conduire un VUS ou une voiture compacte? Négociations FMSQ: l'impasse monétaire et le spectre des moyens d'action; Les jeunes s’informent de plus en plus sur les réseaux sociaux; Une médaille pour les patineurs canadiens. Voir https://www.cogecomedia.com/vie-privee pour notre politique de vie privée

In this special episode, recorded live at the 2025 Genomics England Research Summit, host Adam Clatworthy is joined by parents, clinicians and researchers to explore the long, uncertain and often emotional journey to a genetic diagnosis. Together, they go behind the science to share what it means to live with uncertainty, how results like variants of uncertain significance (VUS) are experienced by families, and why communication and support matter just as much as genomic testing and research. The panel discuss the challenges families face when a diagnosis remains out of reach, the role of research in refining and revisiting results over time, and how collaboration between researchers, clinicians and participants could help shorten diagnostic journeys in the future. Joining Adam Clatworthy, Vice-Chair for the Participant Panel, on this episode are: Emma Baple – Clinical geneticist and Medical Director, South West Genomic Laboratory Hub  Jamie Ellingford – Lead genomic data scientist, Genomics England  Jo Wright – Member of the Participant Panel and Parent Representative for SWAN UK  Lisa Beaton - Member of the Participant Panel and Parent Representative for SWAN UK  Linked below are the episodes mentioned in the episode:  What is the diagnostic odyssey?  What is a Variant of Uncertain Significance?  Visit the Genomics England Research Summit website, to get your ticket to this years event. You can download the transcript, or read it below. Sharon: Hello, and welcome to Behind the Genes. My name is Sharon Jones and today we're bringing you a special episode recorded live from our Research Summit held in June this year. The episode features a panel conversation hosted by Adam Clatworthy, Vice-Chair of the Participant Panel. Our guests explore navigating the diagnostic odyssey, the often-complex journey to reaching a genetic diagnosis. If you'd like to know more about what the diagnostic odyssey is, check our bitesize explainer episode, ‘What is the Diagnostic Odyssey?' linked in the episode description. In today's episode you may hear our guests refer to ‘VUS' which stands for a variant of uncertain significance. This is when a genetic variant is identified, but its precise impact is not yet known. You can learn more about these in another one of our explainer episodes, “What is a Variant of Uncertain Significance?” And now over to Adam. -- Adam: Welcome, everyone, thanks for joining this session. I'm always really humbled by the lived experiences and the journeys behind the stories that we talk about at these conferences, so I'm really delighted to be hosting this panel session. It's taking us behind the science, it's really focusing on the people behind the data and the lived experiences of all the individuals and the families who are really navigating this system, trying to find answers and really aiming to get a diagnosis – that has to be the end goal. We know it's not the silver bullet, but it has to be the goal so that everyone can get that diagnosis and get that clarity and what this means for their medical care moving forwards.    So, today we're really going to aim to demystify what this diagnostic odyssey is, challenging the way researchers and clinicians often discuss long diagnostic journeys, and we'll really talk about the vital importance of research in improving diagnoses, discussing the challenges that limit the impact of emerging research for families on this odyssey and the opportunities for progress. So, we've got an amazing panel here. Rather than me trying to introduce you, I think it's great if you could just introduce yourselves, and Lisa, I'll start with you. Lisa: Hi, I'm Lisa Beaton and I am the parent of a child with an unknown, thought to be neuromuscular, disease. I joined the patient Participant Panel 2 years ago now and I'm also a Parent Representative for SWAN UK, which stands of Syndromes Without A Name. I have 4 children who have all come with unique and wonderful bits and pieces, but it's our daughter who's the most complicated. Adam:  Thank you. Over to you, Jo. Jo:  Hi, I'm Jo Wright, I am the parent of a child with an undiagnosed genetic condition.  So I've got an 11-year-old daughter. 100,000 Genomes gave us a VUS, which we're still trying to find the research for and sort of what I'll talk about in a bit.  And I've also got a younger daughter. I joined the Participant Panel just back in December. I'm also a Parent Rep for SWAN UK, so Lisa and I have known each other for quite a while through that. Adam:  Thank you, Jo.  And, Jamie, you're going to be covering both the research and the clinician side and you kind of wear 2 hats, so, yeah, over to you. Jamie:  Hi, everyone, so I'm Jamie Ellingford and, as Adam alluded to, I'm fortunate and I get to wear 2 hats. So, one of those hats is that I'm Lead Genomic Data Scientist for Rare Disease at Genomics England and so work as part of a really talented team of scientists and engineers to help develop our bioinformatic pipelines, so computational processes. I work as part of a team of scientists and software engineers to develop the computation pipelines that we apply at Genomics England as part of the National Health Service, so the Genomic Medicine Service that families get referred to and recruited to, and we try to develop and improve those. So that's one of my hats. And the second of those is I am a researcher, I'm an academic at the University of Manchester, and there I work really closely with some of the clinical teams in the North West to try and understand a little bit more about the functional impact of genomic variants on kind of how things happen in a cell. So, we can explore a little bit more about that but essentially, it's to provide a little bit more colour as to the impact that that genomic variant is having. Adam: Great, thank you, Jamie. Over to you, Emma. Emma: My name's Emma Baple, I'm an academic clinical geneticist in Exeter but I'm also the Medical Director of the South West genomic laboratory hub, so that's the Exeter and Bristol Genomics Laboratory. And I wear several other hats, including helping NHS England as the National Specialty Advisor for Genomics. Adam: Thank you all for being here. I think it's really important before we get into the questions just to ground ourselves in like those lived experiences that yourself and Jo and going through. So, Lisa, I'm going to start with you. The term ‘diagnostic odyssey' gets bandied around a lot, we hear about it so many times, but how does that reflect your experience that you've been through and what would you like researchers and clinicians to understand about this journey that you're on, essentially? Lisa: So I think ours is less an odyssey and more of a roller-coaster, and I say that because we sort of first started on a genetic journey, as it were, when my daughter was 9 weeks of age and she's now 16½ – the half's very important – and we still have no answers. And we've sort of come a bit backwards to this because when she was 6 months old Great Ormond Street Hospital felt very strongly that they knew exactly what was wrong with her and it was just a case of kind of confirmation by genetics. And then they sent off for a lot of different myasthenia panel genes, all of which came back negative, and so having been told, “Yes, it's definitely a myasthenia, we just need to know which one it is,” at 4 years of age that was removed and it was all of a sudden like, “Yeah, thanks, sorry.” And that was really hard actually because we felt we'd had somewhere to hang our hat and a cohort of people with very similar issues with their children, and then all of a sudden we were told, “No, no, that's not where you belong” and that was a really isolating experience. I can remember sort of saying to the neuromuscular team, “Well is it still neuromuscular in that case?” and there was a lot of shrugging of shoulders, and it just…  We felt like not only had we only just got on board the life raft, then we'd been chucked out, and we didn't even have a floaty. And in many ways I think I have made peace with the fact that we don't have a genetic diagnosis for our daughter but it doesn't get easier in that she has her own questions and my older children – one getting married in August who's already sort of said to me, you know, “Does this have implications for when we have children?”  And those are all questions I can't answer so that's really hard. Adam:  Thank you, Lisa. Yourself, Jo, how would you describe the odyssey that you're currently experiencing? Jo: So my daughter was about one when I started really noticing that she was having regressions. They were kind of there beforehand but, I really noticed them when she was one, and that's when I went to the GP and then got referred to the paediatrician. So initially we had genetic tests for things like Rett syndrome and Angelman syndrome, which they were all negative, and then we got referred on to the tertiary hospital and then went into 100,000 Genomes. So we enrolled in 100,000 Genomes at the beginning of 2017, and we got our results in April of 2020, so obviously that was quite a fraught time. Getting our results was probably not as you would want to do it because it was kind of over the phone and then a random letter. So, what I was told in that letter was that a variant of uncertain significance had been identified and they wanted to do further research to see if it might be more significant. So we were to be enrolled into another research project called Splicing and Disease, which wasn't active at the time because everything had been put on hold for COVID, but eventually we went into that. So, I didn't know what the gene was at that point, when I eventually got the form for going to get her bloods done…  So that went off and then that came back and the geneticist said, “That gives us some indication that it is significant.” So, since that point it's been trying to find more information and research to be able to make it a diagnosis. There have been 2 sort of key things that have happened towards that but we're still not there. So one of the things is that a research paper came out earlier this year so that's kind of a little bit more evidence, it's not going to give us a diagnosis but it kind of, you know, sits there. And the other thing is that my geneticist said, “Actually, yeah, it looks like it's an important change.”  That's as far as we've got. So we've still got work to do to make it a diagnosis or not.  Obviously if it is a diagnosis, it is still a one-of-a-kind diagnosis, so it doesn't give me a group to join or that kind of thing. But now I've got that research paper that I've read and read, and asked ChatGPT to verify that I've understood it right in some places, you know, with the faith that we put into ChatGPT (laughs), I've got a better understanding and I've got something now that I can look back on, the things that happened when my daughter was one, 2, 3, 4 and her development was all over the place and people thought that I was slightly crazy for the things I was saying, that “Actually, no, I can see what's happening.” So, it's like the picture's starting to come into focus but there's work to do. I haven't got a timeframe on that, I don't know when it's going to come together. And I always say that I'm a prolific stalker of the postman; ever since our first genetic tests you're just constantly waiting for the letters to drop through the door. So a diagnostic odyssey to me is just waiting for random events. Adam: I think what you've both kind of really clearly elaborated on is how you're the ones that are having to navigate this journey, you're the ones that are trying to piece this puzzle together, and the amount of time you're investing, all whilst navigating and looking after your child and trying to cope with the daily lived experience as well. And something you've both touched on that I'd love to draw out more is about how exactly was the information shared with you about the lack of diagnosis or the VUS or what's going on, because in our case you get this bit of paper through the post that has all these numbers and it's written in clinical speak and we had no conversation with the geneticist or the doctors. You see this bit of paper and you're reading it, scared for what the future will hold for your child, but I'd love to know like how were you communicated whilst all this is going on, how did you actually find out the next steps or any kind of future guidance. Lisa: So I think in our case we kept sort of going onto neuromuscular appointments, and I think for probably the first 5 years of my daughter's life I kind of had this very naïve thought that every time we turned up to an appointment it would be ‘the one' and then…   I think it would've been really helpful actually in those initial stages if they had said to us, “Actually, we don't know when this is going to happen, if it's even going to happen, you need to kind of prepare yourself for that.” It sounds fairly obvious to say but you don't know what you don't know. And in some ways we were getting genetic test results back for some really quite horrible things and they would tell us, “Oh it's good news, this mitochondrial disorder hasn't come up,” and so part of you is like, “Yay!” but then another part of you is thinking, “Well if it's not that what is it?” And we've very much kind of danced around and still don't really have an answer to whether it's life-limiting. We know it's potentially life-threatening and we have certain protocols, but even that is tricky. We live in North Yorkshire, and our local hospital are amazing. Every time we go in, if it's anything gastro-related, they say to me, “What's the protocol from Great Ormond Street?” and I say, “We don't have one” (laughs) and that always causes some fun. We try to stay out of hospitals as much as we absolutely can and do what we can at home but, equally, there's a point where, you know, we have to be guided by where we're going with her, with the path, and lots of phone calls backwards and forwards, and then is it going to be a transfer down to Great Ormond Street to manage it. And actually the way I found out that nothing had been found from 100,000 Genomes was in a passing conversation when we had been transferred down to Great Ormond Street and we'd been an inpatient for about 6 weeks and the geneticist said to me, “So obviously with you not having a diagnosis from the 100,000 Genomes…” and I said, “Sorry?  Sorry, what was that?  You've had the information back?”  And she said, “Well, yes, did nobody write to you?” and I said, “No, and clearly by my shock and surprise.” And she was a bit taken aback by that, but it happened yet again 2 years later (laughs) when she said, “Well you know everything's been reanalysed” and I said, “No.”  (Laughs)  And, so that's very much, it still feels an awful lot like I'm doing the heavy lifting because we're under lots of different teams and even when they're working at the same hospital they don't talk to each other. And I do understand that they're specialists within their own right, but nobody is really looking at my daughter holistically, and there are things that kind of interrelate across.    And at one of the talks I attended this morning they were talking about the importance of quality of life, and I think that is something that has to be so much more focused on because it's hard enough living without a diagnosis, but when you're living with a bunch of symptoms that, I think the best way I can describe it is at the moment we've got the spokes of the umbrella but we don't have the wrapper, and we don't know where we're going with it. We can't answer her questions, we can't even necessarily know that we're using the most effective treatments and therapies for her, and she's frustrated by that now, being 16, in her own right, as well as we are. And I'm panicking about the navigation towards Adult Services as well because at the minute at least we have a clinical lead in our amazing local paediatrician but of course once we hit and move into that we won't even have him and that's a really scary place to be, I think. Adam: Jo, is there anything you wanted to add on that in terms of how you've been communicated to whilst all this is going on? Jo: Yeah, so I think part of what makes it difficult is if you're across different hospitals because they're not necessarily going to see the same information. So obviously it was a bit of a different time when I got our results, but I got our results on a virtual appointment with a neurologist in one hospital, in the tertiary hospital, and because he could see the screen because it was the same hospital as genetics, and he said, “Oh you've got this” and then the letter came through later. When I had my next appointment with the neurologist in our primary hospital, or secondary care, whatever it's called, in that hospital, he hadn't seen that, so I'm telling him the results, which isn't ideal, but it happens quite a lot. What I think is quite significant to me is the reaction to that VUS.  I have to give it, the doctors that look after my daughter are brilliant, and I'm not criticising them in any way but their reaction to a VUS is “I'm so grateful for the persistence to get to a diagnosis.” Neurologists are a bit more like “Oh it's a VUS so it might be significant, it might be nothing.” Actually, as a patient, as in a parent, you actually want to know is it significant or not, “Do I look at it or not?” And, I mean, like I said, there were no research papers to look at before anyway until a few months ago so I didn't have anything to look at, but I didn't want to look at it either because you don't want to send yourself off down a path. But I think that collective sort of idea that once someone gets a VUS we need a pathway for it, “What do we do with it, what expectation do we set the patients up with and what is the pathway for actually researching further?” because this is where we really need the research. Adam:  Thank you, Jo. So, Emma, over to you in terms of how best do you think clinicians can actually support patients at navigating this odyssey and what's the difference between an initial diagnosis and a final diagnosis and how do you then communicate that effectively to the patients and their family?   Emma: So I think a key thing for me, and it's come up just now again, is that you need to remember as a doctor that the things you say at critical times in a patient's or parent's journeys they will remember – they'll remember it word for word even though you won't – and thinking about how to do that in the most sensitive, empathetic, calm, not rushed way is absolutely key.   And there are some difficulties with that when you're in a very high-pressure environment but it is absolutely crucial, that when you are communicating information about test results, when you're talking about doing the test in the first place, you're consenting the family, you're explaining what you're trying to do and those conditions, you balance how much information you give people.    So, you were talking earlier about “So you haven't got this diagnosis, you haven't got that diagnosis,” I often think it's…  We're often testing for numerous different conditions at the same time, I couldn't even list them all to the parents of the children or the patient that I'm testing. It's key to try and provide enough information without overwhelming people with so much information and information on specific conditions you are just thinking about as a potential.  Sometimes very low down your list actually but you can test for them.    Because people go home and they use the internet and they look things up and they get very, very worried about things. So, for me it's trying to provide bite-sized amounts of information, give it the time it deserves, and support people through that journey, tell them honestly what you think the chance of finding a diagnosis is. If you think it's unlikely or you think you know, sharing that information with family is helpful.   Around uncertainty, I find that a particular challenge. So, I think we've moved from a time when we used to, in this country, declare every variant we identified with an uncertain significance. Now, if we remember that we've all got 5 million variants in our genome, we've all got hundreds and hundreds… thousands and thousands, in fact, of variants of uncertain significance in our genetic code. And actually, unless you think a variant of uncertain significance genuinely does have a probability of being the cause of a child's or a patient's condition, sharing that information can be quite harmful to people.    We did a really interesting survey once when we were writing the guidelines for reporting variants of uncertain significance a few years ago. We asked the laboratories about their view of variants of uncertain significance and we asked the clinicians, and the scientists said, “We report variants of uncertain significance because the clinicians want them” and the clinicians said, “If the labs put the variant of uncertain significance on the report it must be important.” And of course, if you're a parent, if the doctor's told you the variant is a variant of uncertain significance of course you think it's important.    So, we should only be sharing that information, in my opinion, if it genuinely does have a high likelihood of being important and there are things that we can do. And taking people through that journey with you, with the degree of likelihood, the additional tests you need to do and explaining to them whether or not you think you will ever clarify that, is really, really key because it's very often that they become the diagnosis for the family.  Did I cover everything you think's important, both of you?  Lisa: I think the one thing I would say is that when you are patient- or parent-facing, the first time that you deliver that news to the parent… you may have delivered that piece of news multiple times and none of us sit there expecting you to kind of be overcome with emotion or anything like that but, in the same way that perhaps you would've had some nerves when, particularly if it was a diagnosis of something that was unpleasant, you know, to hold onto that kind of humanity and humility. Because for those patients and parents hearing that news, that is the only time they're ever hearing that, and the impact of that, and also, they're going on about with their day, you don't know what else they're doing, what they're juggling.    We're not asking you all to be responsible for kind of, you know, parcelling us up and whatnot but the way information is imparted to us is literally that thing we are all hanging our hats on, and when we're in this kind of uncertainty, from my personal experience I'm uncomfortable, I like to be able to plan, I'm a planner, I'm a researcher, I like to sort of look it up to the nth degree and that, and sitting in a place without any of that is, it's quite a difficult place to be. And it's not necessarily good news for those parents when a test comes back negative, because if it's not that then what is it, and that also leaves you feeling floundering and very isolated at times.  Adam: Yeah, and you touched upon the danger of like giving too much information or pushing families down a particular route, and then you have to pull them out of it when it's not that.   You talked about the experience you had, you felt like you'd found your home and then it's like, “Well, no, no, sorry, actually we don't think it's that.” And you've invested all of your time and your emotion into being part of that group and then you're kind of taken away again. So it's to the point where you have to be really sure before you then communicate to the families, and obviously in the meantime the families are like, “We just need to know something, we need to know,” and it's that real fine line, isn't it?    But, Jamie, over to you. Just thinking about the evolving nature of genomic diagnosis, what role does research play in refining or confirming a diagnosis over time?  Jamie: So it's really, really difficult actually to be able to kind of pinpoint one or 2 things that we could do as a community of researchers to help that journey, but perhaps I could reflect on a couple of things that I've seen happen over time which we think will improve things. And one of that's going back to the discussion that we've just had about how we classify genetic variants. And so, behind that kind of variant of uncertain significance there is a huge amount of effort and emotion from a scientist's side as well because I think many of the scientists, if not all, realise what impact that's going to have on the families.   And what we've tried to do as a community is to make sure that we are reproducible, and if you were to have your data analysed in the North West of England versus the South West that actually you'd come out with the same answer. And in order to do that we need guidance, we need recommendations, we need things that assist the scientists to actually classify those variants.  And so, what we have at the moment is a 5 point scale which ranges from benign to likely benign, variant of uncertain significance, unlikely pathogenic variant and pathogenic variant. It's objective as to how we classify a variant into one of those groups and so it's not just a gut feeling from a scientist, it's kind of recordable measurable evidence that they can provide to assist that classification.   So in many instances what that does is provide some uncertainty, as we've just heard, because it falls into that zone of variant of uncertain significance but what that also does is provide a framework in which we can generate more evidence to be able to classify it in one direction or another to become likely pathogenic or to become likely benign. And as a research community we're equipped with that understanding –– and not always with the tools but that's a developing area – to be able to do more about it.   What that doesn't mean is that if we generate that evidence that it can translate back into the clinic, and actually that's perhaps an area that we should discuss more. But kind of just generating that evidence isn't always enough and being able to have those routes to be able to translate back that into the hands of the clinicians, the clinical scientists, etc, is another challenge. Adam:  And how do you think we can drive progress in research to deliver these answers faster, to really try and shorten those diagnostic journeys, like what are the recommendations that you would say there? Jamie:  So being able to use the Genomics England data that's in the National Genomic Reference Library, as well as kind of other resources, has really transformed what we can do as researchers because it enables teams across the UK, across the world to work with data that otherwise they wouldn't be able to work with.   Behind that there's an infrastructure where if researchers find something which they think is of interest that can be reported back, it can be curated and analysed by teams at Genomics England and, where appropriate, kind of transferred to the clinical teams that have referred that family. And so having that pathway is great but there's still more that we can do about this. You know, it's reliant on things going through a very kind of fixed system and making sure that clinicians don't lose contact with families – you know, people move, they move locations, etc. And so, I think a lot of it is logistical and making sure that the right information can get to the right people, but it all falls under this kind of umbrella of being able to translate those research findings, where appropriate, into clinical reporting.   Adam:  Thank you. And, Emma, is there anything you would add in terms of like any key challenges that you think need to be overcome just to try and shorten the journeys as much as possible and find the answers to get a diagnosis?  Emma: I think trying to bridge that gap between some of the new technologies and new approaches that we've got that we can access in a research context and bringing those into diagnostics is a key area to try to reduce that diagnostic odyssey, so I really want to see the NHS continuing to support those sorts of initiatives.   We're very lucky, as Jamie said, the National Genomic Research Library has been fundamental for being able to reduce the diagnostic odyssey for large numbers of patients, not just in this country but around the world, and so trying to kind of look at how we might add additional data into the NGRL, use other research opportunities that we have in a more synergistic way with diagnostics I think is probably key to being able to do that.    We are very lucky in this country with the infrastructure that we've got and the fact that everything is so joined up. We're able to provide different opportunities in genomics for patients with rare conditions that aren't so available elsewhere in the world.  Adam: Great, thank you. I think we're it for time, so thank you very much to the panel. And I'd just say that if you do have any further questions for ourselves as participants then we're only too happy to pick those up. Thank you for lasting with us ‘til the end of the day and hope to see you soon.  -- Sharon: A huge thank you to our panel, Adam Clatworthy, Emma Baple, Jo Wright, Lisa Beaton and Jamie Ellingford, for sharing their insights and experiences. Each year at the summit, the Behind the Genes stage hosts podcast style conversations, bringing together researchers, clinicians and participants to discuss key topics in genomics.  If you're interested in attending a future Genomics England Research Summit, keep an eye out on our socials. If you'd like to hear more conversations like this, please like and subscribe to Behind the Genes on your favourite podcast app. Thank you for listening.    I've been your host, Sharon Jones. The podcast was edited by Bill Griffin at Ventoux Digital and produced by Deanna Barac.

Quant franc essas Vus che la lavur che Vus faschais na vegn in di betg surpigliada d'insatgi u meglier ditg d'insatge auter? Pertge tuttina sco l'informatica e la digitalisaziun ils ultims decennis fulla il mument era l'intelligenza artifiziala sia via en noss mund da lavur. Ella avanza pass per pass en ils pli differents champs e surpiglia adina dapli chaussas che nus umans faschevan avant. E quai va davent da sortir chaussas, racoltar e servir en in'ustaria fin a programmar, far translaziuns en las pli differentas linguas, scriver cudeschs u era far musica e films. Procura l'intelligenza artifiziala che nus essan in di forsa tuttas e tuts dischoccupads, perquai ch'i na dovra betg pli nus? U vegnin nus simplamain a far en il futur autras lavurs che l'IA na vegn betg da far? La «Marella» emprova da dar ina u l'autra resposta a questas dumondas prest existenzialas.

Fernand Cuville, Jeune italienne, Vicence, 1918 (c) Archives de la planète Vus de Sirius, les êtres humains sont certainement analogues les uns aux autres. Mais pour nous qui en sommes, pour qui l’unité fondamentale est tellement évidente qu’on n’y prête plus attention et qui avons, de plus, appris à décrypter, avec une extraordinaire acuité, le moindre détail des traits permettant de distinguer un être humain d’un autre, c’est la diversité, la magnifique diversité qui l’emporte. Et pourtant, comment ne pas voir, derrière la variété des photographies et films des Archives de la planète, rassemblés entre 1908 et 1931 sous la direction d’Albert Kahn ; comment ne pas voir un grand album de famille reproduisant les mille facettes de notre humanité commune, un grand album où se dissout la distinction traditionnelle entre anthropologie et ethnologie ? Dans le rassemblement, la conjonction, la juxtaposition de ces dizaines de milliers d’images fixes et animées captées un peu partout dans le monde, on perçoit qu’il n’y a pas, d’un côté, l’unité de l’espèce, et, de l’autre, sa diversité. Le trait fondamental d’homo sapiens, de cet homo parmi les autres ayant progressivement pris la place des autres homo, c’est son incroyable plasticité, sa capacité à se modeler, à adopter des rites, des coutumes, des croyances, des vêtements, des façons indéfiniment différentes d’être au monde pour s’adapter à la diversité des lieux, des climats, des écosystèmes où il a choisi de s’établir, de s’enraciner puis de se perpétuer avant de partir, éventuellement, ailleurs puis ailleurs encore. Son unité, son identité la plus profonde, c’est justement sa faculté d’adaptation et la diversité par laquelle elle se traduit. Et pourtant, quand on regarde les visages, les visages souvent magnifiques de ces femmes et de ces hommes depuis longtemps rendus à la poussière, ces visages qui à la demande du photographe regardaient l’objectif et nous regardent donc, leurs yeux plongés au plus profond des nôtres, quelle proximité et quelle émotion ! De quelque pays qu’ils soient, quel que soit l’âge, le costume et la majesté, c’est toujours un frère ou une soeur, un proche qui nous tend son regard comme un miroir, et de ses yeux nous interroge. Ils sont si différents et cependant si identiques avec leur sourire, leur gêne, leur fierté, leur lassitude, leur joie ou leur indifférence. Quels que soient leurs atours, leurs décorations, leurs bijoux, le panache de leur pose ou de leurs habits, ils sont finalement si transparents, si nus, si faibles, si peu de chose, si déjà disparus. Et si touchants, cependant, d’être là et de se prêter, de se donner en spectacle. Je ne reviens pas, je ne reviens jamais de l’émotion qui me transporte à la vue de mes semblables, de ces êtres qui se savent si petits et si fragiles et qui pourtant, au même moment, se tiennent dignes, radieux et pleins d’espoir face à la vie. Je me demande s’il n’y a pas, là aussi, une définition de l’humanité. Le musée départemental Albert Kahn, récemment refait, est à Boulogne-Billancourt, près d’une boucle de la Seine, sur le site de la propriété d’Albert Kahn. Outre les collections de photographies et de films, on y trouve un jardin, d’une exceptionnelle beauté. L‘image d’illustration a été prise par Fernand Cuville en 1918. On y voit une jeune fille photographiée à Vicence, en Italie. Pas d’autre détail. L’original est un autochrome sur plaque de verre. Elle porte le numéro d’inventaire A 19 398. En illustration musicale, Bayaty, de George Gurdjieff, dans la très jolie version d’Anja Lechner et Vassilis Tsabropoulos, parce que Gurdjieff sut si bien, lui aussi, illustrer, au moins dans son œuvre musicale, l’unité dans la diversité. Cet article Album de famille : le musée Albert Kahn est apparu en premier sur Aldor (le blog).

Dévoilement du Kia Seltos 2027 Le Volvo EX90 quitte le Canada, l’EX30 coupe son prix Un rabais de 15 000 $ pour le Ford Mustang Mach-E Mercedes-Benz GLB 2027 : désormais deux VUS en un Antoine tu peux nous parler de ton périple chez Toyota? Pour de l'information concernant l'utilisation de vos données personnelles - https://omnystudio.com/policies/listener/fr

En actualité : Dévoilement du Kia Seltos 2027 Le Volvo EX90 quitte le Canada, l’EX30 coupe son prix Un rabais de 15 000 $ pour le Ford Mustang Mach-E Mercedes-Benz GLB 2027 : désormais deux VUS en un Antoine tu peux nous parler de ton périple chez Toyota? Cette semaine, Hugues Gonnot nous parle de la Lincoln Continental. Le Guide de l'auto reçoit Terry "Zeke" Maxwell, président et fondateur de SLP Canada. Cette firme montréalaise a été responsable de modifier les Chevrolet Camaro et Pontiac Firebird qui sortaient de l'usine de Boisbriand dans les années 1990. M. Maxwell nous parle de son cheminement, et de son livre récemment publié qui retrace les moments forts de l'entreprise. Louis-Philippe Dubé et Antoine Joubert partagent leurs impressions de conduite au sujet de la Kia EV4 et du Nissan Rogue PHEV.Pour de l'information concernant l'utilisation de vos données personnelles - https://omnystudio.com/policies/listener/fr

Les avez-vous vu (ou vuS) se disputer ? Les avez-vous vus (ou vu) s'embrasser ? L'avez vous vu (ou vue) frapper à la porte ? Ce diable de participe passé à la française rend chèvres les auditeurs de RTL. Heureusement, Muriel Gilbert vient à la rescousse !Hébergé par Audiomeans. Visitez audiomeans.fr/politique-de-confidentialite pour plus d'informations.

Nouveau Honda Pilot 2026 – Plus techno, même V6 : bonne ou mauvaise idée ?TORQ - Épisode 495HONDA PILOT 2026 – beaucoup d'améliorations… mais la mécanique ne bouge pas. Est-ce que Honda joue trop safe ?Aujourd'hui, on regarde de près le nouveau Honda Pilot 2026 :• nouvelle face avant plus massive• écran 12,3'' de série (!), tableau de bord numérique 10,2''• plus d'équipement sur chaque version• plus d'isolant, plus de techno, look retouché… mais toujours le même V6 atmosphérique de 285 chevaux, dans un marché où tout le monde pousse le turbo ou l'hybride.Dans cette vidéo, on analyse :

Le retour d’Allô Police : les vedettes du crime au Québec. Décès du nouveau-né à Longueuil: les derniers développements. Vers une année sombre pour les motocyclistes. Incendie criminel d’un VUS à Montréal. Tour de table entre Isabelle Perron, Alexandre Dubé et Mario Dumont. Regardez aussi cette discussion en vidéo via https://www.qub.ca/videos ou en vous abonnant à QUB télé : https://www.tvaplus.ca/qub ou sur la chaîne YouTube QUB https://www.youtube.com/@qub_radioPour de l'information concernant l'utilisation de vos données personnelles - https://omnystudio.com/policies/listener/fr

Limb-girdle muscular dystrophies (LGMDs) encompass a group of genetically heterogeneous skeletal muscle disorders. There has been an explosion of newly identified LGMD subtypes in the past decade, and results from preclinical studies and early-stage clinical trials of genetic therapies are promising for future disease-specific treatments. In this episode, Gordon Smith, MD, FAAN, speaks with Teerin Liewluck, MD, FAAN, FANA, author of the article “Limb-Girdle Muscular Dystrophies” in the Continuum® October 2025 Muscle and Neuromuscular Junction Disorders issue. Dr. Smith is a Continuum® Audio interviewer and a professor and chair of neurology at Kenneth and Dianne Wright Distinguished Chair in Clinical and Translational Research at Virginia Commonwealth University in Richmond, Virginia. Dr. Liewluck is a professor of neurology at the Division of Neuromuscular Medicine and Muscle Pathology Laboratory at Mayo Clinic College of Medicine in Rochester, Minnesota. Additional Resources Read the article: Limb-Girdle Muscular Dystrophies Subscribe to Continuum®: shop.lww.com/Continuum Earn CME (available only to AAN members): continpub.com/AudioCME Continuum® Aloud (verbatim audio-book style recordings of articles available only to Continuum® subscribers): continpub.com/Aloud More about the American Academy of Neurology: aan.com Social Media facebook.com/continuumcme @ContinuumAAN Host: @gordonsmithMD Guest: @TLiewluck Full episode transcript available here Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast. Dr Smith: This is Dr Gordon Smith with Continuum Audio. Today I'm interviewing Dr Teerin Liewluck, a good friend of mine at the Mayo Clinic, about his article on the limb girdle muscular dystrophies. This article appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders, a topic that is near and dear to my heart. Teerin, welcome to the podcast, and maybe you can introduce yourself to our listeners. Dr Liewluck: Thank you very much, Gordon, and I want to say hi to all the Continuum fans. So, I'm Dr Teerin Liewluck, I'm the professor of neurology at Mayo Clinic in Rochester, Minnesota. So, my practice focus on all aspects of muscle diseases, both acquired and genetic myopathies. Glad to be here. Dr Smith: I just had the great pleasure of seeing you at a seminar in Houston where you talked about this topic. And so, I'm really primed for this conversation, which I'm very excited about. I find this topic a little hard, and I'm hoping I can learn more from you. And I wonder if, as we get started, recognizing many of our listeners are not in practices focused purely on muscle disease, maybe you can provide some context about why this is important for folks doing general neurology or even general neuromuscular medicine? Why do they need to know about this? Dr Liewluck: Yes, certainly. So, I would say limb girdle muscular dystrophy probably the most complex category of subgroup of muscle diseases because, by itself, it includes thirty-four different subtypes, and the number's still expanding. So, each subtype is very rare. But if you group together, it really have significant number of patients, and these patients present with proximal weakness, very high CK, and these are common patients that can show up in the neurology clinic. So, I think it's very important even for general neurologists to pick up what subtle clues that may lead to the diagnosis because if we are able to provide correct diagnosis for the patients, that's very important for patient management. Dr Smith: So, I wonder if maybe we can talk a little bit about the phenotype, Terran. I mean, your article does a great job of going over the great diversity. And you know, I think many of us here, you know, limb girdle muscular dystrophy and we think of limb girdle weakness, but the phenotypic spectrum is bananas, right? Rhabdomyolysis, limb girdle distal myopathy. I mean, when should our listeners suspect LGMD? Dr Liewluck: Yes, I think by the definition to all the LGMD patients will have limb girdle of proximal weakness and very high CK. So, these are common phenotypes among thirty-four different subtypes. But if it did take into details, they have some subtle differences. In the article, what I try to simplify all these different subtypes that we can categorize at least half of them into three main group that each group the underlying defect sharing among those subtypes and also translate into similar muscles and extra muscular manifestations. You will learn that some of the limb girdle muscular dystrophy may present with rhabdomyolysis. And we typically think of this as metabolic myopathies. But if you have a rhabdomyolysis patient, the CK remain elevated even after the acute episode, that's the key that we need to think this could be LGMD. That's for an example. Dr Smith: So, I wonder if maybe we can start there. I was going to go in a different direction, but this is a good transition. It's easy to see the opportunity to get confused between LGMD or, in that case, a metabolic myopathy or other acquired myopathies. And I think particularly adult neurologists are more accustomed to seeing acquired muscle disease. Are there particular clues that, or pearls that adult neurologists seeing patients with muscle disease can use to recognize when they should be thinking about LGMD given the diverse phenotype? Dr Liewluck: Yes. What I always tell the patient is that there are more than a hundred different types of muscle diseases, but we can easily divide into groups: acquired and genetic or hereditary. So, the acquired disease is when you encounter the patients who present with acute or subacute cause of the weakness, relatively rapidly progressive. But on the opposite, if you encounter the patient who present with a much more slowly progressive cause of weakness over several months or years, you may need to think about genetic disease of the muscle with also including limb-girdle muscular dystrophy. The detailed exam to be able to distinguish between each type of muscular dystrophy. For example, if proximal weakness, certainly limb girdle muscular dystrophy. If a patient has facial weakness, scapular winking, so you would think about facial scapular hematoma dystrophy. So, the slowly progressive cause of weakness, proximal pattern of weakness, CK elevation, should be the point when you think about LGMD. Dr Smith: So, I have a question about diagnostic evaluation. I had a meeting with one of my colleagues, Qihua Fan, who's a great peripheral nerve expert, who also does neuromuscular pathology. And we were talking about how the pathology field has changed so much over the last ten years, and we're doing obviously fewer muscle biopsies. Our way of diagnosing them has changed a lot with the evolution of genetic testing. What's your diagnostic approach? Do you go right to genetic testing? Do you do targeted testing based on phenotype? What words of wisdom do you have there? Dr Liewluck: Yes, so, I mean, being a muscle pathologist myself, it is fair to say that the utility of muscle biopsies when you encounter a patient with suspects that limb girdle muscular dystrophy have reduced over the year. For example, we used to have like fifteen, seventeen hundred muscle biopsies a year; now we do only thirteen hundred biopsies a year. Yes, as you pointed out, the first step in my practice if I suspect LGMD is to go with genetic testing. And I would prefer the last gene panel that not only include the LGMD, but also include all other genetic muscle disease as well as the conjunctive myopic syndrome, because the phenotype can be somehow difficult to distinguish in certain patients. Dr Smith: So, do you ever get a muscle biopsy, Teerin? I mean you obviously do; only thirteen hundred. Holy cow, that's a lot. So, let me reframe my question. When do you get a muscle biopsy in these patients? Dr Liewluck: Muscle biopsy still is present in LGMD patients, it's just we don't use it at the first-tier diagnostic test anymore. So, we typically do it in selected cases after the genetic testing in those that came back inconclusive. As you know, you may run into the variant of unknown significance. You may use the muscle biopsy to see, is there any histopathology or abnormal protein Western blot that may further support the heterogenicity of the VUS. So, we still do it, but it typically comes after genetic testing and only in the selected cases that have inconclusive results or negative genetic testing. Dr Smith: I'd like to ask a question regarding serologic testing for autoantibodies. I refer to a really great case in your article. There are several of them, but this is a patient, a FKRP patient, who was originally thought to have dermatomyositis based on a low-titer ME2 antibody. You guys figured out the correct diagnosis. We send a lot of antibody panels out. Wonder if you have any wisdom, pearls, pitfalls, for how to interpret antibody tests in patients with chronic myopathies? We send a lot of them. And that's the sort of population where we need to be thinking about limb-girdle muscular dystrophies. It's a great case for those, which I hope is everyone who read your article in detail. What do you have to say about that? Dr Liewluck: Yes, so myositis antibodies, we already revolutionized a few of muscle diseases. I recall when I finished my fellowship thirteen years ago, so we don't really have much muscle myositis antibodies to check. But now the panel is expanded. But again, the antibodies alone cannot lead to diagnosis. You need to go back to your clinical. You need to make sure the clinical antibodies findings are matched. For example, if the key that- if the myocytes specific antibodies present only at the low positive title, it's more often to be false positive. So, you need to look carefully back in the patient, the group of phenotypes, and when in doubt we need to do muscle biopsies. Now on the opposite end, the other group of the antibody is the one for necrotizing autoimmune myopathy; or, the other name, immune-mediated necrotizing myopathy. This is the new group that we have learned only just recently that some patients may present as a typical presentation. I mean, when even thinking about the whole testing autoimmune myopathy, we think about those that present with some acute rapidly progressive weakness, maybe has history of sudden exposures. But we have some patients that present with very slowly progressive weakness like muscular dystrophies. So now in my practice, if I encounter a patient I suspect LGMD, in addition to doing genetic testing for LGMD, I also test for necrotizing doing with myopathy antibodies at the same time. And we typically get antibody back within what, a week or two, but projected testing would take a few months. Dr Smith: Yeah. And I guess maybe you could talk a little bit about pitfalls and interpretation of genetic tests, right? I think you have another case in your article, and I've certainly seen this, where a patient is misdiagnosed as having a genetic myopathy, LGMD, based on, let's say, just a misinterpretation of the genetic testing, right? So, I think we need to think of it on both sides. And I like the fact that the clinical aspects of diagnosis really are first and foremost most important. But maybe you can talk about wisdom in terms of interpretation of the genetic panel?  Dr Liewluck:Yes. So genetic testing, I think, is a complex issue, particularly for interpretation. And if you're not familiar with this, it's probably best to have your colleagues in genetics that help looking at this together. So, I think the common scenario we encounter is that in those dystrophies that are autosomal recessive, so we expect that the patient needs to have two abnormal copies of the genes to cause the disease. And if patients have only one abnormal copy, they are just a carrier. And commonly we see patients refer to us as much as dystrophy is by having only one abnormal copy. If they are a carrier, they should not have the weakness from that gene abnormality. So, this would be the principle that we really need to adhere. And if you run into those cases, then maybe you need to broaden your differential diagnosis. Dr Smith: I want to go back to the clinical phenomenology, and I've got a admission to make to you, Teerin. And I find it really hard to keep track of these disorders at, you know, thirty-four and climbing a lot of overlap, and it's hard to remember them. And I'm glad that I'm now going to have a Continuum article I can go to and look at the really great tables to sort things out. I'm curious whether you have all these top of mind? Do you have to look at the table too? And how should people who are seeing these patients organize their thoughts about it? I mean, is it important that you memorize all thirty-four plus disorders? How can you group them? What's your overall approach to that? Dr Liewluck: I need to admit that I've not memorize all twenty-four different subtypes, but I think what I triy to do even in my real-life practice is group it all together if you can. For example, I think that the biggest group of these LGMD is what we call alpha-dystroglycanopathies. So, this include already ten different subtypes of recessive LGMD. So alpha-dystroglycan is the core of the dystrophin-associated glycoprotein complex. And it's heavy glycosylated protein. So, the effect in ten different genes can affect the glycosylation or the process of adding sugar chain to this alpha-dystroglycan. And they have similar features in terms of the phenotype. They present with proximal weakness, calf pseudohypertrophy, very high CK, some may have recurrent rhabdomyolysis, and cardiac and rhythmic involvement are very common. This is one major group. Now the second group is the limb-girdle muscular dystrophy due to defective membrane repair, which includes two subtypes is the different and on dopamine five. The common feature in this group is that the weakness can be asymmetric and despite proximal weakness, they can have calf atrophy. On muscle biopsy sometimes you can see a myeloid on the muscle tissues. And the third group is the sarcoglycanopathy, which includes four different subtypes, and the presentation can look like we share. For the rest, sometimes go back to the table. Dr Smith: Thank you for that. And it prompts another question that I always wonder about. Do you have any theories about why such variability in the muscle groups that are involved? I mean, you just brought up dystroglycanopathy, for instance, as something that can cause a very distal predominant myopathy; others do not. Do we at this point now have an understanding given the better genetics that we have on this and work going on in therapeutic development, which I want to get to in a minute, that provides any insight why certain muscle groups are more affected? Dr Liewluck: Very good question, Gordon. And I would say the first question that led me interested in muscle disease---and this happened probably back in 2000 when I just finished medical school---is why, why, why? Why does muscle disease tend to affect proximal muscles? I thought by now, twenty-five years later, we'd have the answer. I don't. I think this, you don't know clearly why muscle diseases, some affect proximal, some affect distal. But the hypothesis is, and probably my personal hypothesis is, that maybe certain proteins may express more in certain muscles and that may affect different phenotypes. But, I mean, dysferlin has very good examples that can confuse us because some patients present with distal weakness, some patients present with proximal weakness, that's by the same gene defect. And in this patient, when we look at the MRI in detail, actually the patterns of fatty replacements in muscle are the same. Even patient who present clinically as a proximal or distal weakness, the imaging studies show the same finding. Bottom line, we don't know. Dr Smith: Yeah, who knew it could be so complex? Teerin, you brought up a really great point that I wanted to ask about, which is muscle MRI scan, right? We're now seeing studies that are doing very broad MR imaging. Do you use some muscle MRI very frequently in your clinical evaluation of these patients? And if so, how? Dr Liewluck: Maybe I don't use it as much as I could, but the most common scenario I use in this setting is when I have the genetic testing come back with the VUS. So, we look at each VUS, each gene in detail. And if anything is suspicious, what I do typically go back to the literature to see if that gene defect in particular has any common pattern of muscle involvement on the MRI. And if there is, I use MRI as one of the two to try to see if I can escalate the pathogenicity of that VUS. Dr Smith: And a VUS is a “Variant of Unknown Significance,” for our listeners. I'm proud that I remember that as a geneticist. These are exciting times in neurology in general, but particularly in an inherited muscle disease. And we're seeing a lot of therapeutic development, a lot going on in Duchenne now. What's the latest in terms of disease-modifying therapeutics and gene therapies in LGMD? Dr Liewluck: Yes. So, there are several precritical and early-phase critical trials for gene therapy for the common lymphoma of muscular dystrophies. For example, the sarcoglycanopathies, and they also have some biochemical therapy that arepossible for the LGMD to FKRP. But there are many things that I expect probably will come into the picture broader or later phase of critical tryouts, and hopefully we have something to offer for the patients similar to patients with Duchenne muscular dystrophy. Dr Smith: What haven't we talked about, I mean, holy cow? There's so much in your article. What's one thing we haven't talked about that our listeners need to hear? Dr Liewluck: Good questions. So, I think we covered all, but often we get patients with proximal weakness and high CK, and they all got labeled as having limb-girdlemuscular dystrophy. What I want to stress is that proximal weakness and high CK is a common feature for muscle diseases, so they need to think broad, need to think about all possibilities. Particularly don't want to miss something treatable. Chronic, slowly progressive cause, as I mentioned earlier, we think more about muscle dystrophy, but at the cranial range, we know that rare patients with necrotic autonomyopathy and present with limb good of weakness at a slowly progressive cost. So, make sure you think about these two when suspecting that LGMD patient diabetic testing has come back inconclusive. Dr Smith: Well, that's very helpful. And fortunately, there's several other articles in this issue of Continuum that help people think through this issue more broadly. Teerin, you certainly don't disappoint. I enjoyed listening to you about a month ago, and I enjoyed reading your article a great deal and enjoy talking to you even more. Thank you very much. Dr Liewluck: Thank you very much, Gordon. Dr Smith: Again, today I've been interviewing Dr Teerin Liewluck about his article on limb-girdle muscular dystrophy, which appears in the October 2025 Continuum issue on muscle and neuromuscular junction disorders. Please be sure to check out Continuum Audio episodes for this and other issues. And thanks to our listeners for joining today. Dr Monteith: This is Dr Teshamae Monteith, Associate Editor of Continuum Audio. If you've enjoyed this episode, you'll love the journal, which is full of in-depth and clinically relevant information important for neurology practitioners. Use the link in the episode notes to learn more and subscribe. AAN members, you can get CME for listening to this interview by completing the evaluation at continpub.com/audioCME. Thank you for listening to Continuum Audio.

Tge schessas Vus, sch'i naschiss quest onn sulet in uffant en Vossa vischnanca? E quai suenter che l'onn avant èn er be trais naschids. Cunzunt sche Vus sa regurdais anc vi dals onns ch'i deva mintg'onn anc 20 e dapli naschientschas cun be in zic dapli avdants ed avdantas. Als Tuatschins e Tuatschinas fa quai bain quitads ed han era ina tscherta tema, manegia l'anteriur scolast ed archivar communal Tarcisi Hendry ch'enconuscha anc fitg bain ils temps sco scolast dals onns 1970 cun gronds classas. Dentant Tujetsch n'è betg l'unica vischnanca en il Grischun che senta il regress d'uffants, il uschenumnà «baby-bust». L'onn passà hai dà uschè paucs uffants sco mai ils ultims 50 onns en il Grischun e la populaziun crescha il mument be pli pervia da la migraziun. Dentant quant alarmanta è la situaziun en il Grischun? Pertge faschain nus adina pli paucs pops e poppas? E tge munta quai per il chantun e las vischnancas? Respostas datti en la Marella.

What genetic tests actually do—and what they don't—so you know when to use them (and when not to). Practical next steps. Chapters below. For step-by-step guides + live Q&A, join the community: https://familybuilding.net/building-your-family-community/ You'll learn: Screening vs diagnostic: what each actually tells you Carrier testing, NIPT, and embryo testing (PGT‑A/M): when it helps vs overkill Limits: false positives/negatives, VUS, and context (why “a result” ≠ a decision) Donor gametes: brief considerations for donor sperm/egg Questions to ask your clinic + first steps this week

Send comments and feedbackWhat are variants of uncertain significance (VUS) in epilepsy genetic testing? How are they defined, and can those definitions change over time? Sharp Waves talks with Dr. Gemma Carvill as part of our genetic testing series.RESOURCESStandards for interpreting variants (American College of Medical Genetics)Gene ReviewsClinVarGeneMatcherGnomadClinGenILAE genetic literacy seriesEpiPred website for STXBP1 (developed by EpiMVP project - will be final by end of July)Think Genetics paper – genetic testing in South Africa projectLink to Sharp Waves episode on genetic testing in LMICs  Sharp Waves episodes are meant for informational purposes only, and not as clinical or medical advice.Let us know how we're doing: podcast@ilae.org.The International League Against Epilepsy is the world's preeminent association of health professionals and scientists, working toward a world where no person's life is limited by epilepsy. Visit us on Facebook, Instagram, and LinkedIn.

durée : 01:18:28 - Les Nuits de France Culture - par : Antoine Dhulster - En 1994, pour "Les Nuits magnétiques", Simon Guibert demandait à des Européens ce que l'Europe représentait pour eux. - réalisation : Virginie Mourthé

Vus de Washington et Moscou, Ukrainiens et Européens sont des empêcheurs de faire la paix entre soi.Hébergé par Ausha. Visitez ausha.co/politique-de-confidentialite pour plus d'informations.

The Katherine Massey Book Club @ The C.O.W.S. hosts the 3rd study session on the late Dr. Maya Angelou's A Song Flung Up To Heaven. This is the 6th autobiography in her 7 book memoir series. We read books 1, I Know Why The Caged Bird Sings, and 4, The Heart of a Woman. Dr. Angelou now reigns as the only author to have three books read on the Katherine Massey Book Club. We're reading this book to hear Dr. Angelou's depiction of the assassinations of Minister Malcolm X and Dr. Martin Luther King Jr. Last week, Dr. Angelou detailed the smells and sounds from her sightseeing tours through the 1965 Watts riots. Oddly, she laments the lack of attention she receives while everyone is focused on the smoldering ruins and shootin' and lootin'. With a reputation as a poet, not a historian, Dr. Angelou is scant on specific details about what's happening during the infamous SoCal battle. The late Wanda Coleman wrote that a few of Dr. Angelou's descriptions of the Watts kerfuffle are factually incorrect. Later, the Wake Forest scholar tells us that she and her "former husband" Vus, who is not named in this book, attempt to reconcile. It fails miserably, and they resume the same toxic, destructive arguments they had on a different continent. We noted that the daily consumption of alcoholic beverages is a theme in both Dr. Angelou memoirs we read this year. Including the infamous Mogen David's "Mad Dog 20/20" - which is a fortified wine that's been banned in parts of Seattle, Washington. #SobrietytWouldBeBest #TheCOWS16Years INVEST in The COWS – http://paypal.me/TheCOWS Cash App: https://cash.app/$TheCOWS CALL IN NUMBER: 605.313.5164 CODE: 564943#

durée : 00:03:19 - Le Billet de Daniel Morin - par : Daniel Morin - Ca fait cher pour un téléphone pas cher, non ?

durée : 00:03:19 - Le Billet de Daniel Morin - par : Daniel Morin - Ca fait cher pour un téléphone pas cher, non ?

The Katherine Massey Book Club @ The C.O.W.S. hosts the 8th and final study session on the late Dr. Maya Angelou's The Heart of A Woman. The acclaimed author, poet, rape victim and Victim of White Supremacy, Dr. Angelou penned a 7-book autobiography series on her life and work. This is book number 4 in the series. Gus T. was inundated with the life and literary work of Dr. Angelou during his recent Golden State sojourn. And it took Gus seeing the documentary film Soundtrack to a Coup d'État three times to accurately write down the title The Heart of a Woman. The extraordinary film on the assassination of Patrice Lumumba is "receipt-heavy," and Andrée Blouin and Dr. Angelou's respective memoirs are just 2 of the many books in the project. Last week, Dr. Angelou describes following her husband Vus to Africa without even an address or hotel reservation once she travels across the planet with her son, Guy. She and Vus have repeated conflicts about money and are nearing a second eviction. Dr. Angelou tells us she fell out of "love" with her care mate at this point. We heard about a lot more parties, dancing and liquor drinking. Dr. Angelou took time to make a distinction between she and the black people born in the United States as opposed to black people born in Africa. She incorrectly tells readers that "black Americans" were the last large group of people enslaved on the planet. Brazil kept black people in formal slavery until 1888, and there are millions more black people in the Portuguese-speaking country than the US. #ImGoinGetMeSomeStuffTonight #SoundtrackToACoupdÉtat #TheCOWS16Years INVEST in The COWS – http://paypal.me/TheCOWS Cash App: https://cash.app/$TheCOWS CALL IN NUMBER: 605.313.5164 CODE: 564943#

Between 5-10% of breast and 20-25% of ovarian cancers are inherited. The majority of hereditary breast and ovarian cancer cases are caused by deleterious mutations (variants) in the BRCA1 and BRCA2 genes, which normally prevent cancer through protecting and repairing our DNA. Genetic testing is used to identify pathogenic BRCA carriers who would subsequently benefit from personalized screening, preventative and management plans. However, its widespread implementation has resulted in a significant increase in findings of variants of uncertain significance (VUS) – DNA sequence variants with uncertain effects on disease risk. VUSs pose a critical clinical challenge as they limit clinicians' ability to effectively interpret genetic test results. For upcoming interviews check out the Grad Chat webpage on Queen’s University School of Graduate Studies & Postdoctoral Affairs website.

The Katherine Massey Book Club @ The C.O.W.S. hosts the 7th study session on the late Dr. Maya Angelou's The Heart of A Woman. This is a rare "double dip" for the book club, as we read I Know Why The Caged Bird Sings in the summer of 2014 just after the transition of the famed author and Wake Forest scholar. Gus T. was inundated with the life and literary work of Dr. Angelou during his recent Golden State sojourn. And it took Gus seeing the documentary film Soundtrack to a Coup d'État three times to accurately write down the title Heart of a Woman. The extraordinary film on the assassination of Patrice Lumumba is "receipt-heavy," and Andrée Blouin and Dr. Angelou's respective memoirs are just 2 of the many books in the project. Last week, Dr. Angelou describes her involvement in the White French convict Jean Genet's play, The Blacks: A Clown Show. This celebrated show featured a cast of renown black thespians and was shown around the world. Dr. Angelou describes how mostly White audiences devoured the play, but continued their dedication to White Supremacy - even to the negro cast as soon as they stepped off the stage. The Suspected Racist director, Sidney Bernstein, shafted Max Roach and Dr. Angelou for their musical labor on the play. This is typical White Racism and the time-honored White tradition of robbing black artists. Bernstein was not ignorant about Racism. After speculating that her husband Vus might be cheating on her, our heroine contemplates poisoning her African care-mate. #AppleEvent #SoundtrackToACoupdÉtat #TheCOWS16Years INVEST in The COWS – http://paypal.me/TheCOWS Cash App: https://cash.app/$TheCOWS CALL IN NUMBER: 605.313.5164 CODE: 564943#

Today, we’re going to talk to Carmen David, who is going to share her experience with an aortic dissection after the delivery of her second daughter, her experiences recovering from that physically and emotionally, how she handled the information of two VUS’s, or Variants of Unknown Significance, and what she’s been doing since her dissection … Read More Read More

Wenn plötzlich alle Grosseltern werden Therese hat sich auf unseren Aufruf hin bei uns gemeldet. Wir wollten Geschichten hören von Menschen, die die Lebensmitte bereits hinter sich haben. Denn wir fragen uns: Wie ist es, kinderfrei zu sein, wenn rund um einen nun alle Grosseltern werden? Welche Déjà-Vus kommen da allenfalls wieder hoch, aus einer […]

Wenn plötzlich alle Grosseltern werden Therese hat sich auf unseren Aufruf hin bei uns gemeldet. Wir wollten Geschichten hören von Menschen, die die Lebensmitte bereits hinter sich haben. Denn wir fragen uns: Wie ist es, kinderfrei zu sein, wenn rund um einen nun alle Grosseltern werden? Welche Déjà-Vus kommen da allenfalls wieder hoch, aus einer […]***** Hat dir diese Folge gefallen? Dann kommentiere sie und abonniere den Podcast überall dort, wo du Podcasts hörst: Apple, Spotify, Deezer, Pocket Cast und Youtube. Du findest uns auch auf Facebook und Instragram. Ein «Like» freut uns ungemein und hilft anderen, «Expectations – geplant und ungeplant kinderfrei» besser zu finden. Gemeinsam mit dir machen wir die leisen Geschichten lauter und machen so den kinderfreien Alltag sichtbar! Expectations bricht Tabus, klärt auf und interviewt geplant und ungeplant Kinderfreie und Expert:innen. Offen und inklusiv, gesellschaftspolitisch relevant. *****

In this episode we’re going to talk to Nancy Billon, who was diagnosed with Vascular Ehlers-Danlos Syndrome (VEDS) with a combination of her medical history and a genetic test that revealed a VUS on COL3A1. 

Erin Langley was tested for VEDS (Vascular Ehlers-Danlos Syndrome) due to some concerning family history, but her results came back as a Variant of Unknown/Uncertain Significance, or VUS. In this episode, she shares her experience with those results and how she’s found support in the meantime. Link to the articles mentioned in the interview: The … Read More Read More

Ms. Charité Ricker, MS, CGC and Dr. Nadine Tung, MD, FASCO share updates from the new ASCO guideline on selection of germline genetic testing panels in patients with cancer. They discuss highlights on family history collection, when and how multigene panel germline genetic testing should be used, which genes are generally recommended for testing, and how germline genetic testing interfaces with somatic genetic testing. Ms. Ricker and Dr. Tung also note the importance of the guideline and the impact of these new recommendations on clinicians and patients with cancer. Read the full guideline, “Selection of Germline Genetic Testing Panels in Patients with Cancer: ASCO Guideline” at www.asco.org/molecular-testing-and-biomarkers-guidelines. TRANSCRIPT GDL 24E13 This guideline, clinical tools, and resources are available at www.asco.org/molecular-testing-and-biomarkers-guidelines. Read the full text of the guideline and review authors' disclosures of potential conflicts of interest in the Journal of Clinical Oncology, https://ascopubs.org/doi/10.1200/JCO.24.00662  Brittany Harvey: Hello and welcome to the ASCO Guidelines Podcast, one of ASCO's podcasts delivering timely information to keep you up to date on the latest changes, challenges and advances in oncology. You can find all the shows, including this one at asco.org/podcasts My name is Brittany Harvey, and today I'm interviewing Dr. Nadine Tung, a medical oncologist from Beth Israel Deaconess Medical Center in Boston, and Ms. Charité Ricker, a cancer genetic counselor with the Norris Comprehensive Cancer Center at the University of Southern California and Los Angeles General Medical Center, co-chairs on, “Selection of Germline Genetic Testing Panels in Patients with Cancer: ASCO Guideline.” Thank you for being here, Ms. Ricker and Dr. Tung. Dr. Nadine Tung: Pleasure.  Ms. Charité Ricker: Thank you. Brittany Harvey: Then, before we discuss this guideline, I'd like to note that ASCO takes great care in the development of its guidelines and ensuring that the ASCO conflict of interest policy is followed for each guideline. The disclosures of potential conflicts of interest for the guideline panel, including Dr. Tung and Ms. Ricker, who have joined us here today, are available online with the publication of the guideline in the Journal of Clinical Oncology, which is linked in the show notes.   So then, to start us off first, Dr. Tung, could you provide us a broad overview of both the purpose and scope of this guideline? Dr. Nadine Tung: Sure. A main impetus for creating the guideline is that oncologists are increasingly being tasked with ordering genetic testing for hereditary cancer risk for their cancer patients. More and more now, they may find themselves sending the test and then seeking guidance from genetic experts to interpret the result. And these panels range from focused tests with just a few genes to comprehensive ones that include over 100 genes. So it can be very overwhelming for an oncologist to be able to understand ordering these tests and explaining them to their patients. So, we believe that it was important to offer some guidance and direction on the use of these multigene panels. Brittany Harvey: Thank you for setting the stage for this guideline and the recommendations that come from it.   So then, Ms. Ricker, this guideline addresses four overarching clinical questions. I'd like to review the recommendations based on each of those questions for our listeners. So starting with that first question, what is the importance of family history collection in the setting of germline multigene panel testing and which elements of family history are the most important? Ms. Charité Ricker: Thanks. As a genetic counselor, this is probably one of my favorite questions. I love the opportunity we have to sit with families and really dig into family history. But family history collection can be overwhelming and a big lift sometimes in busy clinics where genetics is not the focus. So, what we tried to do was to break down the key elements of what components of family history are most relevant to informing which test to do, and also the interpretation of those test results. And I like to think about the key pieces of family history as being the who, what, and when of somebody's family cancer history. Who was diagnosed with cancer within their close relatives? And usually we're most focused on first and second degree relatives. So parents, siblings, grandparents, aunts, and uncles. But sometimes relevant history might go into third degree relatives like cousins or more distant. So the who being who has cancer on both sides of the family? And then the what: what kind of cancer was it? Or where did that cancer begin? And the when: how old was that individual at the time they were diagnosed? Often we ask patients maybe not to fixate on the exact age, but to give us a sense. So was this somebody who was diagnosed young, in their 20s or 30s or older, in their 60s or 70s? Because that at least gives us a ballpark around what might be relevant for understanding the genes that should be included on somebody's test.  When we are thinking about the purpose of this history, as Dr. Tung said, often the range of multigene panels might be from a few very focused genes to a very broad panel. Family history can help us understand if we need to step beyond the very focused genes that might be relevant for the patient's history of cancer and include other genes that might be indicated based on that family history. So I think about the role that family history has at the time of identifying which test to do and then its role when interpreting what those results mean for the patient and their family. Again, Dr. Tung touched on the fact that we are often testing very large panels. However, we still don't know everything. And so a negative genetic test result does not mean that somebody does not have additional cancer risk. And family history becomes our kind of guiding star for understanding if there is still a need to change the cancer screening and prevention management for that individual and their family members. Brittany Harvey: Absolutely. Those are key points to understanding the important role of family history for each individual patient.  So then moving to the next clinical question, Dr. Tung, what does the panel recommend regarding when and how multigene panel germline testing should be used, when germline genetic testing is indicated? Dr. Nadine Tung: Well, anytime multiple genes need to be tested, as Ms. Ricker said, because of the patient's own personal cancer history, or their family history of cancer and close relatives, it's appropriate to consider a multi-gene panel. And in truth, we rarely ever just order one gene these days. Perhaps we do if there's a known gene like a BRCA gene in the family, and a relative just wants to know if they have that. But it's not all that common. And to be clear, as Ms. Ricker is going to cover a bit later, we are recommending that the appropriate minimal panel at least include the genes relevant to the patient's own cancer and the cancers in their relatives.  But it's worth thinking about what are some of the pros and cons of ordering genes beyond that, beyond the patient's own cancer or their relatives? Well, for pros, since a patient's awareness of their family history may be incomplete, testing for a larger number of cancer risk genes does ensure that significant pathogenic variants won't be overlooked. And sometimes, even if the family history is well known, pathogenic variants in important cancer risk genes can be found even when the family history would not have prompted testing for them. But it is important for clinicians to appreciate that bigger isn't necessarily better. Some larger panels may include genes for which management of pathogenic variants is not entirely clear and that can create anxiety or unnecessary screening. And if the clinician receiving the information is not well informed about the significance of the finding, that can lead to unnecessary treatment and sometimes even unnecessary surgeries.   And I'd add one final point that clinicians must have a system for communicating reclassification of these variants, the ones with uncertain significance that we call VUS. Because as the number of genes tested increases, so does the likelihood of encountering these VUS. So I would say those are some of the main points about when to use the panel and when to think about larger or smaller panels. Brittany Harvey: Yes, I appreciate you reviewing both the pros and cons of expanding the genes included in multi-gene panel testing and the importance of variants of uncertain significance.   So then Dr. Tung just touched on this, but speaking of minimal panels and which genes should be included, Ms. Ricker, what are the recommendations on which genes are generally recommended for germline genetic testing? Ms. Charité Ricker: I think this is one of the harder questions that our group took on as we were working on this guideline. I don't think there is a one size fits all and one easy answer to this question. However, we chose to approach it by selecting the more common solid tumors that oncologists see in their clinics and the ones where the role of genetic testing is most well defined, as well as some very rare tumors where they're kind of easy. So we know that all individuals with certain types of cancers, even though they are rare, should merit genetic testing regardless of age of diagnosis, family history.  And so as we approached it, and I really appreciate ASCO's support in helping us develop some tools and tables that hopefully will be important aids for clinicians who are trying to make these decisions, we took the approach of, as Dr. Tung mentioned, selecting kind of a minimal set of recommended genes where most individuals who are informed in this area would agree that if nothing else was done, these genes should be done, but then also acknowledged that there is an expanding understanding about the impact of certain genes on cancer risk, and so then also provided a kind of a next level if somebody wanted to be more expansive, what we would recommend less strongly, but would be reasonable to consider. Then I think the other last piece that the committee felt was important to acknowledge is that given how common, in comparison to some of these genetic conditions that we work with, pathogenic variants in BRCA1 and BRCA2 can be, and also the important clinical impact of those genes along with the genes associated with Lynch syndrome, we felt that those were important to think about in the setting of all cancer patients. So if you're approaching a panel and thinking about what genes to include, looking at that kind of minimally recommended based on the patient's personal and family history, maybe the next level, which might include some additional genes that we have included in kind of the less strongly recommended category for those tumor types. And then consideration of the BRCA1 and 2 genes and genes associated with lynch syndrome, if they weren't already encapsulated by your other personal and family history considerations. Brittany Harvey: Definitely. This was a big lift for the panel to tackle, and the tools and tables that you mentioned are all available online with the publication in the Journal of Clinical Oncology. So listeners who are looking for more specifics on that can definitely refer to those tools and tables there.  Dr. Tung, the last clinical question: which patient should be offered germline genetic testing, who will have or who have previously had somatic genetic testing? Dr. Nadine Tung: Identifying which genes identified through the tumor testing should trigger germline testing is really important for assessing our patients' future risk of cancer and their relatives. So during the development of our guidelines, the ASCO expert panel became aware that the ESMO Precision Medicine Working group had updated their recommendations for this topic, namely germline testing in response to tumor test findings. And these recommendations were based on the Memorial Sloan Kettering IMPACT registry, which consists of nearly 50,000 tumors and paired germline testing. Given the sheer volume of that data and the methods that ESMO used, our group decided to use that as a framework to develop our recommendations. The ASCO guideline provides a list of genes that, if found in the tumor, a pathogenic variant in those genes may prompt germline testing.  And we offered or proposed two different approaches. The first approach, which is broad and perhaps simplest, involves doing germline testing if a pathogenic variant is found in any of the genes listed. But then we offer a conservative approach to test the germline for all highly actionable genes, like BRCA1 and 2, or lynch genes that are found in a tumor, but for less actionable genes, testing the germline only if the pathogenic variant is found in a tumor relevant to that gene. So, for example, ATM, if found in breast cancer or pancreatic cancer, would trigger germline testing with this approach, but not if found in lung cancer, whereas with the permissive first approach, you would simply test the germline if any pathogenic variant is found in any of the genes on the list. This latter, more conservative approach, while less sensitive for identifying every germline pathogenic variant, increases the likelihood that a pathogenic variant found in the tumor will actually be germline. That approach considers the limited resources available, such as genetic counselors, and respects trying not to overwhelm a system already stressed. Brittany Harvey: Thank you for reviewing both of those approaches and to you both for discussing all of the recommendations included in this guideline.   Finally, to wrap us up, in your view, Ms. Ricker, what is the importance of this guideline and how will it impact both clinicians and patients with cancer? Ms. Charité Ricker: I hope that this guideline can open the door for more expansive and appropriate utilization of germline genetic testing. For me, I think about, from both the clinical and patient side, for example, all ovarian cancer patients have had a recommendation for germline genetic testing for many years. Nonetheless, data from multiple research studies has shown us that ovarian cancer patients still are not being tested universally, and this has important implications for their treatment plans and for their family members. And so even in the setting where genetic testing, if I can use the phrase, has been simple in that it didn't require family history, it didn't require even a specific age criteria, it was just broad, testing is not utilized as much as it should be, and then you step into the world of more complex decision making around genetic testing for other tumor types. And so we hope that this provides a framework to simplify that decision making process for providers to increase appropriate utilization.   And then from the patient perspective, I also think about the lack of access of genetic testing in underrepresented communities and minoritized patient populations where there's many barriers that patients face in accessing genetic services. And so if we can help reduce the barriers for this piece of the genetic testing process, my hope is that that opens up better avenues for access to testing, not just for patients with certain tumor types, but for all patients from all communities and backgrounds. Brittany Harvey: Yes, those are key points. We hope that this guideline helps all patients access the appropriate testing to better inform their cancer prevention and treatment.  So I want to thank you both so much for your work on this comprehensive guideline on germline genetic testing and all of the work that you put into it. And thank you for your time today. Ms. Ricker and Dr. Tung,  Dr. Nadine Tung: Thank you. Ms. Charité Ricker: It was a pleasure to be here. Thank you. Brittany Harvey: And thank you to all of our listeners for tuning in to the ASCO Guidelines Podcast. To read the full guideline, go to www.asco.org/molecular-testing-and-biomarkers-guidelines. You can also find many of our guidelines and interactive resources in the free ASCO Guidelines app, available in the Apple App Store or the Google Play Store. If you have enjoyed what you've heard today, please rate and review the podcast and be sure to subscribe so you never miss an episode.    The purpose of this podcast is to educate and to inform. This is not a substitute for professional medical care and is not intended for use in the diagnosis or treatment of individual conditions.   Guests on this podcast express their own opinions, experience, and conclusions. Guest statements on the podcast do not express the opinions of ASCO. The mention of any product, service, organization, activity, or therapy should not be construed as an ASCO endorsement.

durée : 01:18:30 - Les Nuits de France Culture - par : Philippe Garbit - En 1994, pour "Les Nuits magnétiques", Simon Guibert demandait à des Européens ce que l'Europe représentait pour eux.

durée : 01:18:28 - Les Nuits de France Culture - par : Antoine Dhulster - En 1994, pour "Les Nuits magnétiques", Simon Guibert demandait à des Européens ce que l'Europe représentait pour eux. - réalisation : Virginie Mourthé

ICD-11 = LD90.Y #LD90Y https://x.com/cureSYNGAP1/status/1730629792137883800   Adult paper and study https://x.com/AledoNeuro/status/1726206128390848604   AES - Lots of SYNGAP1 incl paper with ciitizen data https://x.com/JillianLMcKee/status/1731420167672942878   RT23 - Science: Repurposing, VUS, Genetic Tx & Biomarkers  - Chow https://x.com/CNSdrughunter/status/1730233903602872424  - VUS https://x.com/CNSdrughunter/status/1730268276989571512  - Genetic Therapies https://x.com/dretico/status/1730298959824875741   FD23 - 60 Families from 16 Countries.  Awesome leadership.   Sign up for Adult Study led by Dr. Andrade, if you loved one is 17 or over please email Ilakkiah.Chandran@uhn.ca    Sign up for NET Study, email KHuba@jcu.edu check out #S10e122 and the #SRFFrazier Release if you are not up to date. (14 so far, ½ returning) https://www.eurekalert.org/news-releases/1006753   Give all three of our podcasts 5 stars everywhere.   https://podcasts.apple.com/us/channel/syngap1-podcasts-by-srf/id6464522917    This is a podcast subscribe! https://podcasts.apple.com/us/podcast/syngap10-weekly-10-minute-updates-on-syngap1/id1560389818 Episode 125 of #Syngap10 - December 6, 2023 #epilepsy #autism #intellectualdisability #id #anxiety #raredisease #epilepsyawareness #autismawareness #rarediseaseresearch #SynGAPResearchFund #CareAboutRare #PatientAdvocacy #GCchat #Neurology #GeneChat