Podcasts about digeorge

Send us a textHow do families navigate the uncharted waters of raising children with congenital heart disease (CHD)? Join us on a groundbreaking episode of Heart to Heart with Anna, where we host our very first live show with a studio audience! With guests like Amanda, Joey, Michael, Ayrton, Regina, Rachel, and Chris, you'll hear raw and honest conversations about everything from recent surgeries to the complexities of living with DiGeorge syndrome and HLHS. The live audience format brings an unscripted, spontaneous energy that's sure to engage and inspire.Ever wondered what it takes to grow a podcast network dedicated to CHD? We share our ambitious plans for the next five years, including launching podcasts in multiple languages such as Spanish, Urdu, and even an African language. You'll laugh along with us as we recount some of the humorous mishaps we've encountered—like losing an internet connection during a live show from a coffee shop! Our journey is a testament to the passion and community effort behind each episode, evolving from personal contacts to listener-generated suggestions.This episode also offers a deep dive into the emotional landscape of CHD families. Special guests Meg Didier and Annie Ulchek, HLHS survivors, discuss the unique challenges they face. We cover a range of sensitive topics such as the role of fathers, the experiences of career moms, and the emotional toll on siblings. Discover how CBD and THC are being used for anxiety and pain management, and meet a father who opens up about the scars left by navigating the challenge of raising a child with a CHD while also parenting two heart-healthy children. We cap off by emphasizing the importance of awareness initiatives like placing AEDs in schools and invite you, our listeners, to contribute your stories and feedback for future projects.Thanks to our newest HUG Patron, Ayrton Beatty and long-standing Patrons: Laura Redfern, Pam Davis, Michael Liben, Nancy Jensen, Alicia Lynch, Deena Barber, Carlee McGuire, Carter & Faye Mayberry, and Frank Jaworski. We appreciate you!Support the showAnna's Buzzsprout Affiliate LinkBaby Blue Sound CollectiveSocial Media Pages:Apple PodcastsFacebookInstagramMeWeTwitterYouTubeWebsite

Send us a textWhat would you do if you suddenly discovered that multiple members of your family were living with an intricate genetic condition? Join us for a heartfelt conversation with Regina Lawrence as she opens up about her family's journey with DiGeorge syndrome (a.k.a. 22q11.2 deletion syndrome). From the moment they learned about Aubrey's diagnosis in utero, to the immediate surgeries that followed her birth, Regina shares the raw, emotional experiences of navigating multiple complex medical needs. Dive into the Lawrence family's world, where resilience is not just a necessity but a way of life.Listen as Regina recounts the unexpected revelation of her husband's diagnosis at age 35 and the impact it had on their family dynamics. Discover how the Lawrences juggle specialized medical care, feeding challenges, and the critical role of American Sign Language and communication tablets in Aubrey's day-to-day life. Learn about Tina, Aubrey's sister, and the family's experiences at Boston Children's Hospital. Regina's advocacy work within the CHD community also offers a passionate perspective on why genetic testing is paramount. This episode promises to leave you with a profound understanding of DiGeorge syndrome and the unbreakable spirit of a family united in their fight.Link to The CHC Podcast: Congenital Heart Conversations: https://tinyurl.com/CHCPodcastAppleThanks to our newest HUG Patron, Ayrton Beatty and long-standing Patrons: Laura Redfern, Pam Davis, Michael Liben, Nancy Jensen, Alicia Lynch, Deena Barber, Carlee McGuire, Carter & Faye Mayberry, and Frank Jaworski. We appreciate you!Support the showAnna's Buzzsprout Affiliate LinkBaby Blue Sound CollectiveSocial Media Pages:Apple PodcastsFacebookInstagramMeWeTwitterYouTubeWebsite

This week we delve into the world of fetal cardiology when we review a recent large, multicenter study on the impact of prental diagnosis of 22.q11 deletion syndrome. How did the prenatally diagnosed patients differ from those diagnosed postnatally in regards to degree of heart disease and postnatal morbidity and mortality? What is the role of cell-free DNA testing in the screening for patients with this deletion syndrome? How do outcomes differ for this syndrome between the US and other countries and why might this be? These are amongst the many questions reviewed with the first author of this week's work, Dr. Lindsay Freud who is the director of fetal cardiology at Toronto Sick Kid's Hospital and also Associate Professor of Pediatrics at the University of Toronto. Also joining the podcast this week are the co-directors of this year's Mount Sinai Imaging Symposium entitled: Conversations in Care - The Single Ventricle. Dr. David Ezon, Dr. Jennifer Cohen, Dr. Kenan Stern and Mount Sinai Technical Director and Echo Lab Manager, Ms. Jen Lie Yau share their thoughts about the upcoming conference. This year's symposium will be taking place on May 4th, 2024 and the faculty are a who's who of important pediatric cardiac specialists from the worlds of imaging, interventional cardiology, sonography, surgery and more. For those interested, you can get more information about this wonderful conference at the following web address:https://mssm.cloud-cme.com/assets/MSSM/data/Single%20Ventricle%20Symposium24G.pdfToday's article link:DOI: 10.1016/j.ajog.2023.09.005

“If you have a question, ask it. You are the parent, you need to know” -  Jessica Siddi-Sewart  How can medical parents use their experiences to promote action and advocacy? As a child life specialist, I know that there is not one "normal" or "best" reaction for a parent when their child receives a medical diagnosis. Today's guest, Jessica Siddi-Sewart and she helps us reflect on the different stages parents go through when facing a medical diagnosis for their child. She is also a mother of three, a paralegal, and a business owner. I had the pleasure of meeting Jessica during our time at the American Academy of Pediatrics Conference this past October and was instantly drawn to her products and knew I wanted her to join me on the Child Life On Call podcast. Her company Puffaluffs Inc. was inspired by a personal experience with one of her sons.  After giving birth at 28 weeks, a NICU stay, and a long and emotional journey to receiving a diagnosis, Jessica still found a way to make meaning and give back. For Jessica's son, it took 12 years and hundreds of doctor appointments to receive a concrete diagnosis: DiGeorge Syndrome. She shares her journey and learned the importance of finding support and resources from families walking through similar challenges.  “It teaches you to pivot. It teaches you, you know, to learn different things and be okay. It is what it is and you will be okay” The resources mentioned in this episode are: Puffaluffs Inc. Diagnosis resources for families with DiGeorge include: https://www.nationwidechildrens.org/conditions/22q-deletion-syndrome https://22q.org/ https://www.maxappeal.org.uk/ About Katie Taylor, CCLS and Child Life On Call: Katie Taylor is the co-founder and CEO of Child Life On Call, a digital platform revolutionizing pediatric healthcare by putting parents at the center of the medical journey. With over 13 years of experience as a certified child life specialist, Katie has made significant contributions to the field of child life and the families she's served with over a decade of working at the bedside. She is an accomplished author, engaging child life and entrepreneurship speaker, and the Child Life On Call Podcast host. Katie's work emphasizes the vital role of child life services in supporting caregivers and enhancing children's medical journeys. Learn 6 Positions to Help Kids Feel Comfortable and Safe During Procedures Instagram | LinkedIn | Amazon   

DiGeorge syndrome… what a complicated condition for such a little area of a single chromosome being affected. The condition's descriptive and preferred name is 22q11.2. This is called a microdeletion. Along with microduplications, microdeletions are collectively known as copy number variants. Copy number variants can lead to disease when the change in copy number of a dose-sensitive gene or genes disrupts the ability of the gene(s) to function and affects the amount of protein produced. Other examples of microdeletion syndromes include Prader- Willi, (which is a deletion on 15q), and Cri du chat syndrome which results from a microdeletion on 5p. In this episode, we will review the varied penetrance of DiGeorge syndrome and review its genetic basis. What are some suggestive features found on prenatal ultrasound? What are the associated abnormalities/phenotypes? And how is this condition managed after birth? And why is this also known as CATCH22. We will answer all of these questions, and more, in this episode.

Today we're going to talk about things you can do over time to help boost your immune system and thymosin alpha 1 (TA1), a peptide therapy used for immune support. Most of us know that there are certain things we can do to limit our exposure to germs that can make us sick. Things like washing our hands with soap and water or hand sanitizer and keeping high-touch areas clean can limit your exposure to germs.  But there are other things we can do over time to boost our immunity and create a stronger immune system.  What works to boost our immune system? A balanced approach to your diet is important. Your meals should include a variety of fruits and vegetables, whole grains, and healthy protein sources (legumes, nuts, fresh fish, low-fat dairy, or lean cuts of meat).  Try to avoid refined sugars, which are usually found in processed foods. These include foods like packaged snacks, candy, soda, and cereals. These foods can increase inflammation and can dampen a strong immune response. They can also leave you feeling tired and have been linked to weight gain, type 2 diabetes, and heart disease. Sometimes it can be difficult to tell if food is processed. But reading the ingredients can help if you're not sure. If any ingredient listed on the label isn't used in kitchens, it's probably processed food. Examples include fructose, high-fructose corn syrup, maltodextrin, and lactose, to name a few. Clinical studies have shown that physical activity affects the immune system. In fact, regular exercise can boost the immune system, provide additional energy, promote restful sleep, and help lower your risk of type 2 diabetes, heart disease, and cancer. It can even help reduce chronic pain and stress, which may help improve your mood.  But how often should you exercise? The American Heart Association recommends weekly 150 minutes of moderate aerobic activity (e.g., water aerobics, dancing, or gardening) or 75 minutes of vigorous aerobic exercise (e.g., running, swimming laps, or jumping rope). It also recommends two days of muscle-strengthening activities like resistance or weight training, yoga, or pilates. It's recommended that older adults should also include balance training in their exercise routines (e.g., tai chi, heel-to-toe walking, or balancing on one leg). These exercises improve coordination and stability and may help prevent falls. Fun fact: Your immune system is activated during sleep. But how much sleep do you need? Individual sleeping requirements vary depending on age, overall health, medications, underlying sleep disorders, and lifestyle. For example, the National Sleep Foundation recommends that adults ages 18 to 60 get 7 or more hours per night while adults 61 to 64 get 7 to 9 hours per night. If you're 65 years and older, getting 7 to 8 hours of sleep per night is recommended. Not getting enough sleep may increase inflammation or decrease your immune response. Lack of sleep can also worsen or lead to chronic diseases like depression, diabetes, high blood pressure, heart disease, stroke, and unintentional weight gain.  Excessive alcohol consumption can weaken the immune system. Alcohol can damage the lining of the gut, causing inflammation, infections, and stomach ulcers.  A heavier body weight can dampen the immune system and increase the risk of infections. This is because there are fewer infection-fighting immune cells, and excess body fat contributes to inflammation.  What peptide may help to enhance immune function? Thymosin alpha 1 (TA1) has been shown to enhance the function of certain immune cells. TA1 has been shown to exhibit antibacterial and antiviral properties, suppress tumor growth, and promote wound and tissue healing.  TA1 is used for clinical conditions where immune support is needed. Zadaxin is a TA1 peptide evaluated and approved in 30 countries for treating hepatitis B & C, HIV, and AIDS. It's also used with chemotherapy for certain lung, liver, and skin cancer patients. In addition, it is used in people with DiGeorge syndrome and has shown promising results in treating Lyme disease.  Currently, the medication is in Phase III trials for treating hepatitis C and Phase II trials for hepatitis B in the United States.  How do I take TA1? The peptide injection is subcutaneous (injected into the fatty tissue) once daily. For viral infections, treatments usually last for 2 weeks. But, depending on what you're treating and how serious your infection is, treatment could last 3 months or more. The dose depends on why you're taking it. What are the possible side effects of TA1? Possible side effects include redness, itching, or swelling at the injection site. As always, you should tell your healthcare provider about any side effects you experience.  Thanks again for listening to The Peptide Podcast, we love having you as part of our community. If you love this podcast, please share it with your friends and family on social media, and have a happy, healthy week! Pro Tips We're huge advocates of using daily collagen peptide supplements in your routine to help with skin, nail, bone, and joint health. But what do you know about peptides for health and wellness? Giving yourself a peptide injection can be scary or confusing. But we've got you covered. Check out 6 tips to make peptide injections easier. And, make sure you have the supplies you'll need. This may include syringes, needles, alcohol pads, and a sharps container.

Check out these links for more details on today's episode:DiGeorge syndrome - Wikipedia Justice for Mary Santinahttps://podcasts.apple.com/us/podcast/marys-voice-the-murder-of-marysantina-collins/id1551568238?i=1000555063972 Defendant pleads guilty to charges in connection with death of Charlotte woman (wbtv.com) Mary Collins: 3 Charged in Death of N.C. Woman Missing Since March (people.com) Woman stabbed 133 times, stuffed in mattress amid COVID lockdown | wcnc.com Mary Collins' story — Her tragic murder - TheNetline Subscribe, follow and review us! It really helps us keep bringing you stories like this!Follow Us: @therealcrimepodcastQuestions? Email Us at Therealcrimepodcast@gmail.comJoin our Patreon! The Real Crime Podcast is creating Stories to detail how wild the Real Estate Industry can be! | PatreonSubscribe, follow and rate us on itunes, spotify, goodpods and whereever you listen!Episode written by Christina Van De WaterEpisode Editing by Christina Van De WaterCo-Hosted by Christina Van De Water & Kristen VarneyHate Ads?? Support the show on patreon. Support the show

$5 Q-BANK: https://www.patreon.com/highyieldfamilymedicine Intro 0:30, Selective IgA deficiency 1:30, Bruton's agammaglobulinemia 3:27, Transient hypogammaglobulinemia 4:47, Hyper IgM syndrome 5:45, Common variable immunodeficiency (CVID) 6:52, Severe combined immunodeficiency (SCID) 8:17, DiGeorge syndrome 10:58, Ataxia telangiectasia 13:21, Wiskott-Aldrich syndrome 14:54, Hyper IgE syndrome 16:02, Leukocyte adhesion deficiency 18:04, Chediak-Higashi syndrome 19:11, Chronic granulomatous disease 20:09,  Complement deficiencies 21:56, Leukemia and lymphoma 23:40, Secondary immunodeficiencies 25:25, Practice questions 27:22

$5 Q-BANK: https://www.patreon.com/highyieldfamilymedicine Intro 0:30, Fetal circulatory system 2:00, Persistent fetal circulation 6:38,  Patent ductus arteriosus 8:02, Differential cyanosis 8:40, CCHD screening 9:24, Common themes 10:39, Non-cyanotic heart defects 13:26,  Ventricular septal defects 14:08, Atrial septal defects 15:35, Eisenmenger syndrome 16:28, Aortic and pulmonary stenosis 17:42, Coarctation of the aorta 18:42, Double aortic arch 19:53, Interrupted aortic arch 21:07, Cyanotic heart defects 21:34,  Tetralogy of Fallot 23:39, Transposition of the great arteries 28:03, Hypoplastic left heart syndrome 29:47, Persistent truncus arteriosus 31:09, Partial and total anomalous pulmonary venous connection 33:01, Scimitar syndrome 35:04, Tricuspid and pulmonary atresia 36:03, Prostaglandin E1 indications 36:31, DiGeorge syndrome 38:08, CHARGE syndrome 38:42, Dextrocardia 39:06, Situs inversus and total situs inversus 39:16, Ebstein anamoly 40:04, Noonan syndrome 40:34, Turner syndrome 41:11, Down syndrome 41:28, Marfan syndrome 40:52, Congenital heart blocks 43:03, Practice questions 43:27

Today we are talking about Thymosin alpha-1 (TA1) and its potential benefits. All this and more in less than 2 minutes.  Before we get into what TA1 is and does, we need to talk about the thymus gland. Your thymus gland is a small gland located in your upper chest behind your breastbone in the lymphatic system. It makes special white blood cells called T-cells.  There are two types of T-cells: killer T cells and helper T cells. Both help your immune system fight disease and infection. Killer T cells destroy cancerous cells and cells infected with a virus. Helper T cells work with the other cells of the immune system to make an immune response. What is Thymosin alpha 1 (TA1)? TA1 is a peptide that's produced naturally by the thymus gland. As we age, our thymus gland shrinks (atrophies), and this affects the production of TA1.  In our bodies, TA1 is known as a natural senolytic, which induces the death of aging cells our thymus makes. Taking TA1 as peptide therapy works by mimicking the body's natural release of TA1 in the thymus gland, which stimulates the production of T cells. It also decreases the production of certain proteins called cytokines that can cause chronic inflammatory or immune responses in some people (e.g., chronic fatigue syndrome and fibromyalgia). Studies have shown that people fighting infection have a lower amount of circulating TA1 than healthy people. What are the BENEFITS?  TA1 is used for clinical conditions where immune support is needed. Zadaxin is a TA1 peptide evaluated and approved in 30 countries for treating hepatitis B & C, HIV, and AIDS. It's also used along with chemotherapy for certain lung, liver, and skin cancer patients. In addition, it is used in people with DiGeorge syndrome. Currently, the medication is in Phase III trials for the treatment of hepatitis C and Phase II trials for hepatitis B in the United States.  Fun fact: TA1 has an Orphan Drug approval by the FDA for several indications. Orphan drugs are medications approved by the FDA for rare conditions that affect fewer than 200,000 people in the U.S. TA1 has also shown promising results in the treatment of Lyme disease.  How do I take TA1? Compared to other peptide therapies, TA1 has a longer half-life of 2 hours, requiring fewer peptide injections. The peptide injection is a subcutaneous injection (injected into the fatty tissue) once every third day. For viral infections, treatments usually last for 2 weeks. But, depending on what you're treating and how serious your infection is, treatment could last 3 months or more. Possible side effects include redness, itching, or swelling at the injection site. Rare cases of increases in liver enzymes have happened. If you have signs of liver injury (nausea or vomiting, yellowing of the skin or eyes (jaundice), or stomach pain tell your healthcare provider right away. As always, you should tell your healthcare provider about any side effects you experience.  You can find more information at pepties.com. That's peptides without the D. Where we are tying all the peptide information together in one easy place. Thanks again for listening to The Peptide Podcast. We love having you as part of our community. If you love this podcast, please share it with your friends and family on social media. And subscribe to our podcast. Have a happy, healthy week! Pro Tips Giving yourself a peptide injection can be scary or confusing. But we've got you covered. Check out 6 tips to make peptide injections easier. And, make sure you have the supplies you'll need. This may include syringes, needles, alcohol pads, and a sharps container. We're huge advocates of using daily collagen peptide supplements in your routine to help with skin, nail, bone, and joint health. They also help with anti-aging. Our favorite collagen peptide powder is Thorne® Collagen Plus. 

He pitched for two iconic franchises ( the Cubs and Red Sox) that play in iconic ballparks (Wrigley Field and Fenway Park). Now Ryan Dempster is pitching for the Marquee Sports Network which televises Chicago Cubs games and creates original programming. His natural and infectious sense of humor seem to be a perfect fit.Then again, Chicago is a perfect fit for this 16 year veteran of 5 teams though he spent more than half his time with the Cubs. “I'm a Cub” exclaimed the seemingly happy go lucky Dempster who started 154 games but was also a closer and during the 2005 season saved 33 of 35 games and the other two were victories!"I just had a little different view on what I wanted to do. To be able to use my time talking about the game-the positives of the game. There are so many great things. Focus on those- the things that guys are doing well, rather than what they're doing wrong," Dempster says on the show."I was always goofing around. If I was more serious, I would have probably been a better player. That's who I am. That's who I've always been. And that's the lens that I always try to look through."But life took a different turn in 2009 when his infant daughter was diagnosed with DiGeorge syndrome, the inability to digest or swallow food. Well, so far so very good as Riley is doing just fine after that harrowing experience. Dempster discusses that, his very interesting career and how he came about doing his now well known Harry Caray impressions.Tell me a story I don't know is now partnering with Sports Media Watch ( sportsmediawatch.com) and please follow on Twitter @paulsen_smw. Tell me a story I don't know is proudly sponsored by Vienna Beef, makers of Chicago's hotdog since 1893! (viennabeef.com). And by Dynamic manufacturing, honor the legacy, pioneer the future (dynamicmanufacutinginc.com). Hear full episodes and make sure to follow us and subscribe at Apple Podcasts, Spotify, Google and wherever you get your podcasts. Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy

He pitched for two iconic franchises ( the Cubs and Red Sox) that play in iconic ballparks (Wrigley Field and Fenway Park). Now Ryan Dempster is pitching for the Marquee Sports Network which televises Chicago Cubs games and creates original programming. His natural and infectious sense of humor seem to be a perfect fit.Then again, Chicago is a perfect fit for this 16 year veteran of 5 teams though he spent more than half his time with the Cubs. “I'm a Cub” exclaimed the seemingly happy go lucky Dempster who started 154 games but was also a closer and during the 2005 season saved 33 of 35 games and the other two were victories!"I just had a little different view on what I wanted to do. To be able to use my time talking about the game-the positives of the game. There are so many great things. Focus on those- the things that guys are doing well, rather than what they're doing wrong," Dempster says on the show."I was always goofing around. If I was more serious, I would have probably been a better player. That's who I am. That's who I've always been. And that's the lens that I always try to look through."But life took a different turn in 2009 when his infant daughter was diagnosed with DiGeorge syndrome, the inability to digest or swallow food. Well, so far so very good as Riley is doing just fine after that harrowing experience. Dempster discusses that, his very interesting career and how he came about doing his now well known Harry Caray impressions.Tell me a story I don't know is now partnering with Sports Media Watch ( sportsmediawatch.com) and please follow on Twitter @paulsen_smw. Tell me a story I don't know is proudly sponsored by Vienna Beef, makers of Chicago's hotdog since 1893! (viennabeef.com). And by Dynamic manufacturing, honor the legacy, pioneer the future (dynamicmanufacutinginc.com). Hear full episodes and make sure to follow us and subscribe at Apple Podcasts, Spotify, Google and wherever you get your podcasts. Advertising Inquiries: https://redcircle.com/brandsPrivacy & Opt-Out: https://redcircle.com/privacy

See all the Healthcasts at https://www.biobalancehealth.com/healthcast-blog/ If you ever wondered if there was something other than anti-cancer chemicals, quarantine or vaccines to help protect you from cancer and viral illness, there is a safe, inexpensive and effective medical treatment.  Why haven't you heard of this wonder drug?  The FDA has blocked the US population from access to this immune stimulator in the middle of a pandemic!  I can't tell you why, except that it gave us a way to improve our immune status without other preventive treatments.  It is not dangerous so you can only imagine your own reasons for this action. ‘In this blog I am going to inform you of this option so your will know about it and possibly help drop the ban on compounding pharmacies from making this communicator protein.  I have included quotes from medical and scientific journals to support my information. At the end of the blog, I will list the sources for my information in case you question my information, you can look it up! “Thymosin alpha 1 is a peptide naturally occurring in the thymus that has long been recognized for modifying, enhancing, and restoring immune function. Thymosin alpha 1 has been utilized in the treatment of immunocompromised states and malignancies, as an enhancer of vaccine response, and as a means of curbing morbidity and mortality in sepsis and numerous infections “, World Journal of Virology 2020 Dec 15; 9: 67-78. This “bit of protein” is called a peptide, and it is just one of thousands of peptide communicators produced by the human body. When we are young and healthy these communicators are all working well in healthy mature adults, but as we age, we lose the ability to produce many of the peptides that keep us healthy, like Thymosin alpha 1. This is the reason that people over 60 get sick and die from infections that don't kill younger people. In the Journal of Virology this information was written in December of 2020, during the Covid Pandemic: Studies have postulated that thymosin alpha 1 could help improve the outcome in severely ill corona virus disease 2019 patients by repairing damage caused by overactivation of lymphocytic immunity and how thymosin alpha 1 could prevent the excessive activation of T cells. …. thymosin alpha 1 deserves further investigation into its antiviral properties and possible repurposing as a treatment against severe acute respiratory syndrome coronavirus-2. What does Thymosin Alpha 1 do? Thymosin alpha-1 (TA1) functions as a stimulator to the thymus gland.  This gland produces white blood cells including but not limited to T-Killer cells and T helper cells (CD4+/CD8+ T cells) those WBCs that kill viruses, bacteria, fungus, and cancer cells.  The thymus gland is located behind the “breastbone” and is largest when we are born and shrinks as we age.  As it gets smaller, our immunity to everything decreases which is why older people get more severe infections and take longer to heal, and why older people need stronger vaccinations than younger people to get the same effect. TA1 has many functions other than increasing the number of T cells, it also increases their killing ability and modulates the T cells, so they respond to both abnormally directed immune responses (autoimmune diseases) and stimulates the activity of T cells against infections. TA1 decreases inflammation and is effective in treating pancreatitis and Hepatitis C. Regarding viruses TA1 decreases viral replication, therefore limits both the infections, communicability, and the severity of all viral infections. For cancer patients this peptide is amazing at limiting both incidence and growth of cancers. It is unparalleled in its activity against cancer recurrence. ..thymosin alpha 1 works via two main mechanisms: Either stimulating the immune system or employing its anti-proliferative activities on tumor cells. The protective action of thymosin alpha 1 against oxidative damage because of its effect on liver superoxide dismutase and glutathione peroxidase has been explored by Armutcu et al [26]. I have given TA1 to patients who have small tumors or failure of cancer treatment, when there is no more treatment left for them, to stimulate their own immune system to kill cancer cells. There are basically 3 other ways to kill cancer.  Surgically remove it, kill it with chemicals that also kill beneficial cells in your body (chemotherapy), or radiate the area of cancer.  However mainstream medicine rarely uses the fourth most effective and least dangerous method of stimulating the natural immune system and preventing and killing cancer. One of the unused methods of killing cancer cells is prescribing TA1 which stimulates your own immune system to kill cancer cells. This fact is rarely discussed by doctors, but it is a fact that everyone produces cancer cells in their bodies daily and when they are young and healthy their own immune system kills those cancer cells. When we are young, cancer is rare because our immune cells are activated by TA1 produced in our own thymus glands.  As we age, our thymus shrinks, our TA1 decreases and some of these abnormal cells are missed and not killed, which allows these cells to grow and proliferate into what we call cancer.  The true cause of cancer is the loss of normal immunity (TA1) to kill cancer cells. Due to the action of thymosin alpha 1 on other cell types, it is used as a therapeutic agent for diseases with evident immune dysfunction [4]. Clinical trials with thymosin alpha 1 for diseases like DiGeorge syndrome, non-small cell lung cancer, hepatocellular carcinoma, hepatitis B and C, HIV, and melanoma have been conducted and yielded promising results.  FDA approved the orphan drug thymalfasin (Zadaxin) for treatment of malignant melanoma, chronic active hepatitis B, DiGeorge anomaly with immune defects, and hepatocellular carcinoma due to its immunomodulatory and anti-tumor effect. These diseases are the ones approved by the FDA for treatment with Thymosin alpha 1, in the form of the pharmaceutical called Thymalfasin, however they have ignored the elephant in the room: Thyomsin alpha 1 is effective against cancer, and preventing cancer recurrence, autoimmune diseases, viruses, parasites and bacterial infections.  Why isn't it used in the US to stimulate our own thymus to act like it did when we were younger?  I can't understand it! When we needed this compounded drug the most—in the middle of a pandemic, the FDA prevented all the compounding pharmacies from making it!  This could have been an answer for those people who could not or would not get vaccinated, but in the beginning of the pandemic, production was shut down! Thymosin alpha 1 works and there is a lot of research to back this up, but it is unattainable in the US since Covid started.  I had several patients with recurrent cancer on this peptide for years before the pandemic, and it prevented a recurrence. These patients got their medication from compounding pharmacies, and it had to be discontinued because no compounding pharmacy was allowed to make it.  Why? Both patients, who had. exhausted their mainstream medical options for their cancer, are now experiencing a recurrence of their cancer without being able to get this drug. With all this proof and knowledge about the power of Thymosin alpha1, to prevent and treat viral illnesses and cancer, why have you never heard of it, especially at a time of pandemic when this peptide could do so much good to prevent and treat the virus that is causing our pandemic, especially for those people with immune dysfunction, cancer, autoimmune diseases, and immune senescence of aging? First, the government enacted an FDA letter to all doctors threatening discipline for doctors and healthcare workers who recommended “unproven” therapies for the Covid virus. Included in this new law, rule, is to silence anyone saying to their patients that Vitamin D (which has now been proven to protect against Covid), Quercetin which has supporting evidence in the medical literature to prevent the recommendation of doctors to patients from suggesting these methods of preventing supplements to our patients. If anyone can explain why our own government is working against us (both patients and doctors who are working to save lives), and using our tax dollars to do it, please tell me. I always thought being a doctor in America meant being able to use any safe and effective means that I know works effectively, to treat my patients.  Doctors were effectively gagged by the FDA letter sent in December 2020, from telling my patients about preventive medicine practices that stimulate the immune system and protect us from infection.  Now I have lost respect for the government who treats us all like we are uneducated and sheep who will follow whatever they tell us. They use the one size fits all in a decade when the practice of medicine is becoming more aware of the individuality of patients especially in the melting pot of the US.  Drugs are ridiculously expensive and unaffordable except for the very rich.  We often use compounding pharmacies for alternatives to this price burden for patients and offer inexpensive alternatives that patients can afford.  I am listing the medical references that support my information.  I don't generally do this but I believe it is important to support my blog. References: World Journal of Virology: Thymosin alpha 1: A comprehensive review of the literature, 2020 Dec 15; 9: 67-78. Regulatory Focus, webpage, FDA Targets Remdesevir , Thymosin Alpha In Compounding ,concerns, posted Feb 24 2021 by Kari Oakes. American Journal Health System Pharmacy. May 15, 2001;58(10):878-885.

In this episode Ben chats with Dr. Val Saini of Brock University. In the first half, Val shares his work translational research specifically in the area of problem behaviour relapse. In the second half we talk about how behaviour analysts can engage in antiracist work through the frame of metacontingencies. Lastly, Ben and Val talk about his work with previous guest, Louis Busch, on behaviour interventions for DiGeorge Syndrome. Correction:  During this episode Ben refers to an article by Rocco Catrone (who will be an upcoming guest). The first author of the article is Dr. Natalia Baires and Ben discusses this article thoroughly with Dr. Baires in episode 26.   Continuing Education Units - This episode counts as 1.5 BACB Learning CEUs: https://cbiconsultants.com/shop   Show Notes: The Behaviour Speak Podcast - Episode 11: https://www.behaviourspeak.com/e/episode-11-the-treatment-of-life-threatening-pica-with-louis-busch-bst-abs-hc-med-bcba     The Behaviour Speak Podcast - Episode 13: https://www.behaviourspeak.com/e/episode-13-behaviour-analysis-and-psychotropic-medication-with-alison-cox-phd-bcba-d   The Behaviour Speak Podcast - Episode 26: https://www.behaviourspeak.com/e/episode-26-smashing-the-patriarchy-a-conversation-about-sexism-and-privilege-in-behaviour-analysis-with-dr-natalia-baires-phd-bcba-d   George Brown College: https://www.georgebrown.ca/programs/autism-and-behavioural-science-program-postgraduate-c405 Wayne Fisher: https://www.abainternational.org/constituents/bios/waynefisher.aspx   Hank Roane: https://www.abainternational.org/constituents/bios/henryroane.aspx   DiGeorge Syndrome: https://www.nhs.uk/conditions/digeorge-syndrome/#:~:text=DiGeorge%20syndrome%20is%20a%20condition,without%20realising%20they%20have%20it       Suggested Articles/Links from Dr. Valdeep Saini on Relapse: Resurgence: https://www.redalyc.org/pdf/593/59341195014.pdf  Renewal: https://doi.org/10.1002/jaba.400   Reinstatement: https://link.springer.com/article/10.1007/s00213-002-1224-x  General overview of all: https://doi.org/10.1037/bar0000119    Articles Referenced: Baires, N. A., Catrone, R., Mayer, B. K. (2021, May 12). On the importance of listening and intercultural communication for actions against racism. PsyArXiv. https://doi.org/10.31234/osf.io/7qa4z  Louis Busch, Valdeep Saini, Sidrah Karim & Roland Jones. (2021). Evaluation and maintenance of behavioral interventions for 22q11.2 deletion syndrome. Developmental Neurorehabilitation. https://doi.org/10.1080/17518423.2021.1960919  Saini, V. & Vance, H. (2020). Systemic racism and cultural selection: A preliminary analysis of metacontingencies. Behavior and Social Issues, 29, 52-63. https://doi.org/10.1007/s42822-020-00040-0  Saini, V., Sullivan, W. E., Baxter, E. L., DeRosa, N. M. & Roane, H. S. (2018). Renewal during functional communication training. Journal of Applied Behavior Analysis, 51, 603-619. https://doi.org/10.1002/jaba.471 

This week Mark is joined by World Series champion and former Chicago Cub Ryan Dempster. Ryan shares his experience playing baseball as a kid in British Columbia, his philosophy on youth sports, his first encounter with Nolan Ryan, the parent as a leader, the importance of failure, and his recipe for being the best version of yourself both on and off the field. Mark shares the 6 most important words a parent can say to their child, and Ryan sheds light on the stigma of mental health in sports and society. They conclude with a challenge to raise money and awareness for DiGeorge syndrome(https://22qfamilyfoundation.org/what-22q/22q-overview). An enlightening and motivating interview with one of baseball's "good guys."For a free 45-minute leadership webinar email mark@elevatedleader.com.

Episode 63: Tumor Markers Basics. George and Harendra discuss with Dr Arreaza the role of tumor markers in the diagnosis and monitoring of different types of cancer.  Introduction: Recent News about COVID-19Written by Hector Arreaza, MD. Participation: George Karaghossian, MS3, and Harendra Ipalawatte, MS3.Before we talk about our topic today, there are three news worth sharing about COVID-19.First, we are all aware of the increased number of patients affected by COVID-19 and increased mortality. Most of the patients who are severely ill or those who require admission are unvaccinated. The cases of breakthrough infections (infections in patients who are fully vaccinated) continues to be rare.Second, CDC has officially recommended COVID-19 vaccination in pregnant women (August 11, 2021)[1].  All people 12 years of age and older is recommended to get vaccinated against COVID-19, including pregnant women. There were 2,500 women who received the mRNA vaccine against COVID-19, and there was not an increased risk for miscarriage. Vaccinated pregnant women (or persons) had a miscarriage rate of 13% (similar to the miscarriage average in general population, which is 11-16%).Third, FDA gave an emergency use authorization for a third dose of mRNA vaccines (Pfizer and Moderna) for certain immunocompromised patients (August 12, 2021)[2]. The third dose of the vaccine (it has to be the same vaccine you received) has to be given at least 28 days apart from your last dose. Patients who may receive a third dose include: Patients who are undergoing active treatment for solid tumor and hematologic malignancies, recipients of solid-organ transplant and taking immunosuppressive therapy, moderate or severe primary immunodeficiency (e.g. DiGeorge syndrome, Wiskott-Aldrich syndrome), patients with advanced or untreated HIV infection, patient who are taking high-dose corticosteroids (i.e. >20 mg prednisone or equivalent per day) and other immunosuppressive medications. If in doubt, consult our oncologists and rheumatologists.Let's switch gear and introduce the topic for today. Given the high mortality and morbidity of cancer, in general, early detection of cancer is one of the most important goals in primary care. Today George and I will discuss the usefulness, pitfalls and will mention some of the most common tumor makers.This is Rio Bravo qWeek, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California. Our program is affiliated with UCLA, and it's sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. Tumor Markers Basics. By George Karaghossian, MS3, Ross University School of Medicine; Harendra Ipalawatte, MS3, Ross University School of Medicine; and Hector Arreaza, MD.   Introduction:Do you remember how we came up with the idea for this topic? We had a patient with an intraabdominal malignancy which appeared to be from the GI tract vs an adnexal mass. We order tumor markers to assist in the diagnosis of the origin of this malignancy.  Definition: Tumor markers are usually proteins or other substances that are produced by cancer cells or non-cancerous cells. Circulating biomarkers and tissue biomarkers are the two types of tumor markers we utilize to track the course of the tumor's growth. Circulating tumor markers are found in bodily fluids such as blood, urine, and stool. Tissue markers are typically found on the actual cancer cells. These markers can help in the assessment of certain cancers. The downside of tumor markers is that they are not always reliable, and they may not be detected in the early stages of cancer[2].  Characteristics of a good screening test: A good screening test must be capable of detecting a high proportion of disease when patients are asymptomatic, tests should be safe, not excessively expensive, lead to improved health outcomes, be widely available, and interventions after a positive test should also be available. Can tumor markers be used for cancer screening?Tumor markers should not be used as a primary tool for cancer screening because they lack sensitivity and specificity. The most definitive tool for diagnosis of cancer therefore is biopsy, thus tumor markers cannot be used to diagnose cancer. Tumor markers can be done in blood, in urine, and in tissue (biopsy). An example of tumor markers in biopsies are estrogen receptor (ER) and progesterone receptor (PR). What are tumor markers good for?Tumor markers may be good indicators of response to cancer therapy. When cancer patients are undergoing therapy for treatment of their cancer, we usually track tumor markers to see if there is downward trend over the course of therapy indicating that the therapy is working.  Tumor markers are also a good tool to monitor early relapse of certain malignancies. After treatment, tumor markers may be measured to see if the cancer is returning after treatment. Some tumor markers also assist in deciding which treatment is best. For example, the example I mentioned before ER and PR are tumor markers that can be used to pick the best treatment for certain breast tumors. Pitfalls of tumor markers. A benign disease can raise some tumor marker levels. Some people without cancer can have high levels of a tumor marker. Tumor marker levels can change over time, and levels may be undetectable until cancer gets worse.  Common tumor markers:PSA (Prostate specific antigen): Elevated in prostate cancer, BPH, DRE (recently showed to be questionable for screening). PSA is one of the most controversial tumor markers when it comes to screening for prostate cancer. Although PSA has been shown to be elevated prostate cancers, it has also been shown to be increased in BPH, prostatitis, digital rectal exams as well as post ejaculation. This tumor marker remains controversial in screening because there is an uncertainty about the outcome of localizing such prostate cancers. According to the American Urological Association they suggest that patients should be given an abundant amount of education about PSA, and they should ultimately decide if they would like this marker to be used as a tool for screening for their prostate cancer. PSA was widely used in the past for prostate cancer screening. It was like the “savior” for men who wanted to avoid digital rectal exam. Well, several years later, PSA increased the number of biopsies and even mortality related to prostate cancer diagnostic tests. The IsoPSA may be a better tool, but it is not ready for prime time yet (listen to episode 60). If you find a PSA higher than 4, refer to urology.ALP (alkaline phosphatase): Elevated in metastasis to bone and liver and Paget's disease of the bone. In Paget's disease, you will not be able to use ALP to tell if the patient has bone cancer or just the progression of the disease, but an incidental elevated ALP can prompt you to investigate and come to a diagnosis of Paget's disease after an extensive work up. ALP is also elevated in many other conditions, for example, obstruction of the biliary tree. AFP (alpha feto-protein): Elevated in hepatocellular carcinoma, yolk sac tumor, neural tube defects, ataxia telangiectasia, mixed germ cell tumors. Beta-hCG (beta human chorionic gonadotropin): Elevated in hydatidiform mole, testicular cancer, mixed germ cell tumors.After treatment of a molar pregnancy, the patient has regular measurements of hCG until it is undetectable. A rise in hCG may prompt additional treatment or work up because there is an increased risk of choriocarcinoma. CA 19-9 - pancreatic adenocarcinoma.CA 19-9: When we think of this tumor marker our minds tend to think about the possibility of pancreatic adenocarcinoma. However, this tumor marker is also associated with other malignancies such as biliary tract cancers and esophageal cancer as well. CA 19-9 has less than 1% PPV, but in the case where pancreatic cancer is already diagnosed, screening with CA 19-9 has a positive predictive value of 97%. Also, there is an 80% and 90% sensitivity and specificity respectively for pancreatic cancer, when already diagnosed. CA 125: Elevated in ovarian carcinoma, and malignant ascites. This tumor marker is often associated with epithelial ovarian cancers, often increased when malignancy is present. CA 125 levels are elevated in 85% of women with malignant type ovarian cancer. However, this marker is insensitive to early stages of ovarian cancer and are not very useful. CA 125 has not shown an increase in survival for women with ovarian malignancies. CEA (Carcinoembryonic antigen): Commonly elevated in colon or pancreatic cancers. Less commonly elevated in gastric cancers, breast cancers, medullary thyroid carcinoma, irritable bowel disease, non-small cell lung carcinoma, increased in smokers.[4]CEA is a tumor marker that is overexpressed in adenocarcinomas especially when it comes to colorectal cancers. When we see elevated CEA values, we tend to think colorectal cancer is imminent however, this is one of the tumor markers that are ultimately one of the most nonspecific. CEA is also elevated in cigarette smoking, PUD, IBD, pancreatitis and medullary thyroid cancers. The American Society of clinical oncology recommends that we monitor CEA levels every two to three months for at least two years with patients for surgical candidates with stage II/III colorectal cancers.  Calcitonin: Elevated in medullary thyroid carcinoma, MEN2A/2B. Some doctors may be tempted to measure calcitonin before initiating a GLP-1 receptor agonist medication, these meds are very popular now for diabetes treatment and obesity. Calcitonin measurement is not recommended before starting treatment. Medullary thyroid carcinoma was demonstrated in mice who received GLP-1 RA, not in humans. MEN2 (multiple endocrine neoplasia type 2) and personal and family history of medullary thyroid cancer are contraindications to GLP-1 RA (exenatide, dulaglutide, semaglutide, those meds that end in -tide). As a reminder, all MEN2 presents with pheochromocytoma and medullary thyroid carcinoma. MEN2A, additionally presents with parathyroid hyperplasia, and MEN2B presents with mucocutaneous neuromas, GI symptoms and muscular hypotonia (marfanoid habitus).  Chromogranin A: Elevated in neuroendocrine tumors (insulinoma, glucagonoma, VIPoma) carcinoid tumor, small cell lung cancer. LDH (lactate dehydrogenase): Elevation indicates tumor invasiveness. This is widely used test for many non-malignant conditions as well, for example hemolytic anemias. CYFRA 21-2: Elevated in lung cancer (non-small cell type), squamous cell lung carcinoma (68% sensitivity, 94% specificity).[3] SMRP (serum soluble mesothelin related peptide): Elevated in mesothelioma. NSE (neuron specific enolase): Elevated in small cell lung cancer, carcinoid, neuroblastoma, also released 2/2 brain injuries. Monoclonal immunoglobulins: Elevated in multiple myeloma, Waldenstrom macroglobulinemia. S-100: Elevated in malignant melanoma. B2 microglobulin: Elevated in multiple myeloma, CLL. Final remarks.George: The biggest challenge we face with these biomarkers is the inconsistency of the results which may be influenced by our collection methods and sample storage[4].  The science community has come a long way over the years in assessing these markers and using them to the best of their abilities, however it remains a subject matter that must be further assessed to make sure our research and data does not result in false and misleading outcomes.Arreaza: For now, use tumor markers with responsibility. Discuss with patients the consequences of elevated tumor markers, as you may end up with more questions than answers. But, we have to be fair and also highlight the role of tumor markers in monitoring response to treatment and cancer recurrence. Also, they may be useful (especially the tissue specific markers in identification of cancers and in the decision on treatments). Conclusion: Now we conclude our episode number 63 “Tumor Markers.” Some of the most common markers were discussed. We hope this information will help you decide when to use tumor makers to evaluate your patients. Remembering which conditions cause elevation for each tumor marker is challenging, but with practice and time, you can master the most common ones. Even without trying, every night you go to bed being a little wiser. Comirnaty®: I want to make sure you know about this. The FDA finally gave official approval to the Pfizer BioNTech COVID-19 vaccine on August 23, 2021. This vaccine now has a brand name: Comirnaty®. It is approved for persons older than 16 years old, however, it continues to be available for children between 12-15 years old. Safety monitoring will continue but so far, this vaccine has a strong evidence of being effective and safe.Thanks for listening to Rio Bravo qWeek. If you have any feedback about this podcast, contact us by email RBresidency@clinicasierravista.org, or visit our website riobravofmrp.org/qweek. This podcast was created with educational purposes only. Visit your primary care physician for additional medical advice. This week we thank Hector Arreaza, Harendra Ipalawatte, and George Karaghossian. Audio edition: Suraj Amrutia. See you next week! _____________________References:New CDC Data: COVID-19 Vaccination Safe for Pregnant People, CDC Online Newsroom, August 11, 2021. https://www.cdc.gov/media/releases/2021/s0811-vaccine-safe-pregnant.html. Talking with Patients Who Are Immunocompromised about an additional dose of an mRNA COVID-19 vaccine, Centers for Disease Control and Prevention, https://www.cdc.gov/vaccines/covid-19/clinical-considerations/immunocompromised-patients.html. Perkins GL, Slater ED, Sanders GK, Prichard JG. Serum tumor markers. Am Fam Physician. 2003 Sep 15;68(6):1075-82. PMID: 14524394. https://www.aafp.org/afp/2003/0915/p1075.html Nagpal M, Singh S, Singh P, Chauhan P, Zaidi MA. Tumor markers: A diagnostic tool. Natl J Maxillofac Surg. 2016;7(1):17-20. doi:10.4103/0975-5950.196135 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5242068/ Wieskopf Bram, et al, CYFRA 21-1 as a biological marker of non-small cell lung cancer. Chest Journal, Clinical Investigations, vol 108, issue 1, P163-169, July 01, 1995, DOI:https://doi.org/10.1378/chest.108.1.163. https://journal.chestnet.org/article/S0012-3692(16)38611-1/fulltext#relatedArticles. Schrohl, Anne-Sofie, et al. Tumor Markers, from laboratory to clinical utility. Molecular and Cellular Proteomics. Journal of Oncological Studies, vol 2, issue 6, P378-387. June 01, 2003. https://www.mcponline.org/article/S1535-9476(20)34451-0/fulltext. Tumor Markers in Common Use. National Cancer Institute. National Institutes of Health. https://www.cancer.gov/about-cancer/diagnosis-staging/diagnosis/tumor-markers-list.

Primera parte: La Administración de Alimentos y Medicamentos (FDA) de EE.UU. El 12 de agosto de 2021. Se pronuncia. Segunda parte: EL Centros para el Control y Prevención de Enfermedades (CDC) de EE.UU. El 18 de agosto de 2021. Se pronuncia. La vacuna Pfizer-BioNTech COVID-19 está actualmente autorizada para uso de emergencia en personas de 12 años o más, y la vacuna Moderna COVID-19 está autorizada para uso de emergencia en personas de 18 años o más. Ambas vacunas se administran como una serie de dos inyecciones: la vacuna Pfizer-BioNTech COVID-19 se administra con tres semanas de diferencia y la vacuna Moderna COVID-19 se administra con un mes de diferencia. Las autorizaciones para estas vacunas se han modificado para permitir que se administre una dosis adicional, o una tercera, al menos 28 días después del régimen de dos dosis de la misma vacuna a personas de 18 años de edad o mayores (12 años o más para Pfizer -BioNTech) que se han sometido a un trasplante de órgano sólido o que son diagnosticados con afecciones que se considera que tienen un nivel equivalente de inmunodepresión. ¿Quién necesita una vacuna COVID-19 adicional? 1-Ha estado recibiendo tratamiento activo contra el cáncer para tumores o cánceres de la sangre. 2-Recibió un trasplante de órgano y está tomando medicamentos para inhibir el sistema inmunológico. 3-Recibió un trasplante de células madre en los últimos 2 años o está tomando medicamentos para inhibir el sistema inmunológico 4-Inmunodeficiencia primaria moderada o grave (como el síndrome de DiGeorge, o el síndrome de Wiskott-Aldrich) 5-Infección por VIH avanzada o no tratada 6-Tratamiento activo con corticosteroides en dosis altas u otros medicamentos que pueden inhibir su respuesta inmunitaria. REFERENCIA. https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-authorizes-additional-vaccine-dose-certain-immunocompromised https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2021-07/07-COVID-Oliver-508.pdf ADAPTACION PARA AUDIO-OYENTES: Medicina en una página. ==================================================== PODCAST CORONAVIRUS. COVID-19 Este es un podcast en el que desde el ojo de la ciencia. Aprenderemos del coronavirus y de la enfermedad covid-19. Recuerden al enemigo es mejor conocerlo. Para acabarlo. Esta es una producción de: Medicina en una página. medicinaenunapagina@gmail.com Dirección y Conducción: John Jarbis García Tamayo. Médico y cirujano, Epidemiólogo y Pedagogo Universitario. Portada: Gracias a Sam Balye por compartir su trabajo (foto-portada) en https://unsplash.com/. Música: https://www.youtube.com/audiolibrary/music?nv=1

美CDC點頭 免疫低下者即將施打第3劑 https://news.cnyes.com/news/id/4703852 美國疾病管制預防中心 (CDC) 周五 (13 日) 採納諮詢委員會建議，同意開始配發第三劑輝瑞和莫德納 疫苗給免疫低下族群，代表可立即展開接種。 美國食品藥物管理局 (FDA) 周四已經同意針對免疫低下的脆弱族群追加劑量，CDC 也在諮詢委員會支持下予以批准，代表可立即開始接種。 CDC 主任 Rochelle Walensky 說：「在 Delta 病毒肆虐的情況下，為免疫不全者追加劑量，有助於避免這些人因染疫受到生命威脅。」 免疫低下者包括接種器官移植、癌症和 HIV 患者，這群人只占美國不到 3% 人口約270萬，卻占了最近已注射兩劑疫苗還住院病例的 44%，凸顯染疫後更容易演變成重症的風險。且這群人打完兩劑的保護力大概僅有59~72%。 根據指引，免疫低下者打完第二劑疫苗的 28 天過後，再打第三劑，而且完成後應該繼續佩戴口罩並遵守社交距離規定。一些小型研究顯示，免疫有缺陷者接種第三劑，不會出現更嚴重或前兩劑不曾發生的副作用，且可以一定程度產生抗體。 CDC 並表示，目前並無數據支持已完整接種嬌生疫苗的免疫低下民眾追加劑量，CDC 和 FDA 正在研究如何提供相關的指引。 追加劑的銷售前景 包括智利、德國和以色列，都已經決定為高齡者和免疫脆弱的族群提供第三劑。市場推估，光靠現行的兩劑疫苗與潛在賣給富國的第三劑，輝瑞、BioNTech 和莫德納在 2021 和 2022 年可望進帳超過 600 億美元。 而在 2023 年，輝瑞和 BioNTech 疫苗部分的營收將超過 66 億美元，莫德納的疫苗營收將達 76 億美元，主力正是第三劑。預料隨著其他藥廠加入這塊市場，年銷售額至少仍能達到 50 億美元。 然而現階段無法確切評估有多少人需要施打加強劑，一切尚待更多數據佐證。一些初期研究顯示，打完疫苗六個月後，人體內的抗體水準減弱，另外，莫德納疫苗效力可能比輝瑞持久。 COVID-19 Vaccines for Moderately to Severely Immunocompromised People https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations/immuno.html Currently, CDC is recommending that moderately to severely immunocompromised people receive an additional dose. This includes people who have: 1.Been receiving active cancer treatment for tumors or cancers of the blood 2.Received an organ transplant and are taking medicine to suppress the immune system 3.Received a stem cell transplant within the last 2 years or are taking medicine to suppress the immune system 4.Moderate or severe primary immunodeficiency (such as DiGeorge syndrome, Wiskott-Aldrich syndrome) 5.Advanced or untreated HIV infection 6.Active treatment with high-dose corticosteroids or other drugs that may suppress your immune response People should talk to their healthcare provider about their medical condition, and whether getting an additional dose is appropriate for them. 美國CDC的疫苗諮詢委員會ACIP開會資料 https://www.cdc.gov/vaccines/acip/meetings/slides-2021-08-13.html 混打疫苗可行嗎？AZ混打輝瑞/BNT AZ混打莫德納等等 https://linshibi.com/?p=39613 給長輩的AZ疫苗懶人包 https://linshibi.com/?p=39590 高端 聯亞 國產疫苗懶人包 第二期結束就緊急授權可行嗎？ https://linshibi.com/?p=39547 新冠快篩懶人包 普篩 抗體快篩 抗原快篩 https://linshibi.com/?p=36564 新冠肺炎疫情下的防疫須知 常見問題解答FAQ https://linshibi.com/?p=35408 新冠疫苗常見問題懶人包 https://linshibi.com/?p=38945 林氏璧醫師的電子名片 https://lit.link/linshibi 歡迎贊助我喝咖啡 https://pay.firstory.me/user/linshibi Powered by Firstory Hosting

The CDC has clarified who is considered immunocompromised enough to receive the third dose of mRNA vaccines. The ACIP of the CDC and the FDA have agreed on appending the Emergency Use Authorization for the mRNA vaccines in individuals who are moderately to severely immunocompromised to receive a third dose booster. This includes people who have: Been receiving active cancer treatment for tumors or cancers of the blood Received an organ transplant and are taking medicine to suppress the immune system Received a stem cell transplant within the last 2 years or are taking medicine to suppress the immune system Moderate or severe primary immunodeficiency (such as DiGeorge syndrome, Wiskott-Aldrich syndrome) Advanced or untreated HIV infection Active treatment with high-dose corticosteroids or other drugs that may suppress your immune response --- Send in a voice message: https://anchor.fm/covidupdates/message

Today we'll be covering T-cell Immunodeficiencies, going along with this month's theme, Immunology. If you haven't listened to our podcast before, each week we have a case-based discussion about a medical topic to help you study for the pediatric medicine board exam. Episodes are released every weekend, and the case is then reviewed and reinforced on social media throughout the week.   Follow the podcast on social media: Facebook- @portablepeds (www.facebook.com/portablepeds) Twitter- @portablepeds (www.twitter.com/portablepeds)   We'd love to hear from you via email at portablepeds@gmail.com!   Also, feel free to visit our website, www.portablepeds.com, for more content.   Today's Case:   A previously healthy 5 year old male presents to the emergency room with 3 days of fever and decreased activity levels. On physical exam, there is cervical lymphadenopathy, evidence of pharyngitis with significant hyperemia, and hepatosplenomegaly present. Initial lab work showed leukopenia with a relative lymphopenia, thrombocytopenia, and significant transaminitis. He was admitted, and further work up revealed an elevated LDH and positive EBV acute infection with significant viral load. Throughout the following two weeks, he developed fulminant liver failure with significant coagulopathy and persistently increasing viremia and eventually passed away due to septicemia. Of the following, which diagnosis is most consistent with this presentation?   Wiskott-Aldrich syndrome X-linked lymphoproliferative syndrome Chronic mucocutaneous candidiasis DiGeorge syndrome Zeta-associated protein 70 (ZAP-70) deficiency   We would like to give an enormous thank you to Zack Goldmann for designing this podcast's logo and accompanying artwork. You can find more of his work at www.zackgoldmann.com.   The intro and outro of this podcast is a public domain song obtained from scottholmesmusic.com.   Intro/Outro- Hotshot by Scott Holmes   Disclaimer: This podcast is intended for healthcare professionals. The information presented is for general educational purposes only and should NOT be used as professional medical advice or for the diagnosis or treatment of medical conditions.   The views and opinions expressed do not represent the views and opinions of our employer or any affiliated institution. Expressed opinions are based on specific facts, under certain conditions, and subject to certain assumptions and should not be used or relied upon for any other purpose, including, but not limited to, the diagnosis or treatment of medical conditions or in any legal proceeding. Full terms and conditions can be found at portablepeds.com.   Thanks for listening! As always, please Rate and Review this podcast on Apple Podcasts, Facebook, or your favorite podcasting platform. Also, Subscribe to get all the latest episodes, and Share this episode with someone you think would enjoy it! Hope to see you real soon!

This episode covers T-cell disorders, such as DiGeorge syndrome, Wiskott-Aldrich syndrome, ataxic telangiectasia and acquired immunodeficiency syndrome.Written notes can be found at https://zerotofinals.com/paediatrics/immunology/tcelldisorders/ or in the immunology section of the Zero to Finals paediatrics book.The audio in the episode was expertly edited by Harry Watchman.

Summary:  DiGeorge syndrome is a genetic condition caused by the deletion of a chunk of genes on chromosome 22 (specifically the q11.2 region). The classic triad of DiGeorge syndrome is cardiac anomalies, underdeveloped thymus gland and hypocalcaemia (secondary to underdevelopment of the parathyroid glands). The phenotype of DiGeorge syndrome is related to abnormal development of the embryonic pharyngeal pouch system, which is responsible for the development of the thymus, parathyroid gland, some facial development including ear development, and some cardiac development. DiGeorge syndrome is classified as either partial or complete, with the distinction being that patients with complete DiGeorge syndrome have profound immune deficiency secondary to a complete absence of the thymus.    You don’t want to miss: A case Explaining the condition to families An overview of the pathophysiology Aetiology Presentation Investigations to consider Complications Treatment and monitoring considerations    Links and resources:   Follow us on Instagram @yourekiddingright.pod Facebook: https://www.facebook.com/yourekiddingrightpod-107273607638323/   Our email is yourekiddingrightpod@gmail.com   Make sure you hit SUBSCRIBE/FOLLOW so you don’t miss out on any pearls of wisdom and RATE if you can to help other people find us!   (This isn’t individual medical advice, please use your own clinical judgement and local guidelines when caring for your patients)

Dr. Charles Scarborough joins the show to discuss the story of his son Jude, and his family's experience with his son's diagnosis with 22q11 deletion syndrome.  In addition to hearing about the Scarborough's personal experience, we talk about the genetic considerations and common clinical manifestations of 22q11.2 deletion syndrome. How do you approach the general diagnostic testing and screening evaluation of a child with 22q11.2 deletion syndrome? We also discuss the impact that genetic and chronic disease has on our pediatric patients and their families. Thanks to Dr. Paul Mann, Dr. Liezl Domingo and Dr. Jacqueline Chan for providing guidance and peer review of the technical material in this episode.  Citation: Hodges, Z. (Host). Scarborough, C. (Host).  Mann, P. (Contributor). Chan, J. (Contributor). Domingo, L. (Contributor).  (2020, Nov 1). Jude's Story/22q11 Deletion Syndrome. (S1:17) [Audio Podcast Episode]. MCG Pediatric Podcast. Medical College of Georgia Augusta.   Links: MCG Pediatric Podcast: https://www.augusta.edu/mcg/pediatrics/residency/podcast.php  Georgia Medicaid Katie Beckett: https://medicaid.georgia.gov/programs/all-programs/tefrakatie-beckett  Clinica La fuente in Cusco, Peru http://www.lafuenteclinica.com/clinic-ingles/  If you would like to donate to Clinica La fuente https://www.mtw.org/projects/details/pe-la-fuente-centro-de-salud-integral    Questions or comments? Contact us by email at mcgpediatricpodcast@augusta.edu    References: Cohen JL, Crowley TB, McGinn DE, et al. 22q and two: 22q11.2 deletion syndrome and coexisting conditions. Am J Med Genet A. 2018;176(10):2203-2214. doi:10.1002/ajmg.a.40494 Campbell IM, Sheppard SE, Crowley TB, et al. What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia. Am J Med Genet A. 2018;176(10):2058-2069. doi:10.1002/ajmg.a.40637 Vorstman JA, Jalali GR, Rappaport EF, Hacker AM, Scott C, Emanuel BS. MLPA: a rapid, reliable, and sensitive method for detection and analysis of abnormalities of 22q. Hum Mutat. 2006;27(8):814-821. doi:10.1002/humu.20330 McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011;90(1):1-18. doi:10.1097/MD.0b013e3182060469 Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome.J Pediatr. 2011;159(2):332-9.e1. doi:10.1016/j.jpeds.2011.02.039

Small business in Orlando is amazing and full of passionate people. This episode features five of those owners, covering pop culture pins, sandwich-themed shirts, acting …

This week we delve into cardiac surgery and genetics as we review a recent large dataset study from Drs. Anita Moon-Grady and Laxmi Ghimire who used the KID database to determine the impact of 22q11.2 deletion syndrome on outcomes of repair of TOF and Truncus. Does this syndrome affect mortality or morbidity? If so, why? Professor Moon-Grady of UCSF and Dr. Ghimire of LRGHealthcare provide many insights in this episode. doi: 10.1007/s00246-020-02333-y.

This week we delve into cardiac surgery and genetics as we review a recent large dataset study from Drs. Anita Moon-Grady and Laxmi Ghimire who used the KID database to determine the impact of 22q11.2 deletion syndrome on outcomes of repair of TOF and Truncus. Does this syndrome affect mortality or morbidity? If so, why? Professor Moon-Grady of UCSF and Dr. Ghimire of LRGHealthcare provide many insights in this episode. doi: 10.1007/s00246-020-02333-y.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.04.29.068932v1?rss=1 Authors: Francisco, A. A., Horsthuis, D. J., Popiel, M., Foxe, J. J., Molholm, S. Abstract: 22q11.2 deletion syndrome (also known as DiGeorge syndrome or velo-cardio-facial syndrome) is characterized by increased vulnerability to neuropsychiatric symptoms, with approximately 30% of individuals with the deletion going on to develop schizophrenia. Clinically, deficits in executive function have been noted in this population, but the underlying neural processes are not well understood. Using a Go/No-Go response inhibition task in conjunction with high-density electrophysiological recordings (EEG), we sought to investigate the behavioral and neural dynamics of inhibition of a prepotent response (a critical component of executive function) in individuals with 22q11.2DS with and without psychotic symptoms, when compared to individuals with idiopathic schizophrenia and age-matched neurotypical controls. Twenty-eight participants diagnosed with 22q11.2DS (14-35 years old; 14 with at least one psychotic symptom), 15 individuals diagnosed with schizophrenia (18-63 years old) and two neurotypical control groups (one age-matched to the 22q11.2DS sample, the other age-matched to the schizophrenia sample) participated in this study. Analyses focused on the N2 and P3 no-go responses and error-related negativity (Ne) and positivity (Pe). Atypical inhibitory processing was shown behaviorally and by significantly reduced P3, Ne, and Pe responses in 22q11.2DS and schizophrenia. Interestingly, whereas P3 was only reduced in the presence of psychotic symptoms, Ne and Pe were equally reduced in schizophrenia and 22q11.2DS, regardless of the presence of symptoms. We argue that while P3 may be a marker of disease severity, Ne and Pe might be candidate markers of risk. Copy rights belong to original authors. Visit the link for more info

Marco DiGeorge visited the studio to discuss the ins and outs, unders and overs of Talk Radio by Eric Bogosian, currently playing at Theater on the Edge. TALK RADIO by Eric BogosianWHERE: Theater on the EdgeWHEN: Until February 16th, 2020TICKETS: theaterontheedge.org

We had our long time friend and actor Elaitheia Quinn on to talk about living the live of an artist and actor and how to stay present in the moment.

Incredibly talented and skilled set designer Samantha DiGeorge of Theater on the Edge visits the show to talk about TOTE’s upcoming production of Talk Radio by Eric Bogosian, her love of set design, and her appreication of hyper-realism on theatrical stages. Her previous design credits include American Buffalo by David Mamet, Superior Donuts by Tracy … Continue reading "21. Samantha DiGeorge (9/23/2019)"

In this episode, Daniel and Stephane present a case they worked on together involving a genetic syndrome and a mysterious symptom complex. What is the next step when Internal Medicine, Rheumatology, Immunology, Infectious Diseases and Hematology cant find the cause of a fever? How could we have solved this one sooner?

Guests: Donna Cutler-Landsman & Anne Lawlor Donna Cutler-Landsman and Anne Lawlor speak with us about 22q and how to raise awareness about this rare disease. Bio: Donna Cutler-Landsman received her bachelor's degree in education and went on to receive a master's degree in counseling psychology from the University of Wisconsin in Madison. She has over 35 years of classroom experience and has been working as an educational consultant and speaker since 1999. The focus of Donna's practice is securing needed services for children with complex exceptional educational needs. Her primary emphasis is complicated medical challenges and genetic syndromes including the 22q11.2 deletion syndrome. She has been assisting schools and parents with understanding this syndrome across the United States and abroad for over 20 years. Donna has presented on educational issues at well over 40 conferences worldwide and is the author of several books and articles on the subject.  The 3rd editions of her book, Educating Children with Velo Cardio Facial Syndrome (also known as 22q11.2 deletion and DiGeorge) is due for publication late 2019. Bio: Anne Lawlor is one of the founding members of the 22q11 Ireland Support Group. The group, set up in 2007, supports Irish families affected by 22q deletion syndrome. 22q11.2 deletion syndrome is caused by small missing piece on the ‘q’ arm of the 22nd chromosome. Children born with 22qDS have complex medical, educational and social care needs over the life-span. Varying effects from the deletion range from congenital heart defects to speech and language problems. Many children with 22q11.2 deletion syndrome have learning disabilities and mental health issues. Dedicated to raising awareness for this poorly understood and under-recognised condition Anne completed a Masters in Management of Community and Voluntary groups and works with 22q11and works with 22q11 Ireland to develop integration across health & social care and education domains.

This is the Immunology chapter from USMLE Step 2 Secrets. Content covered in this episode includes:    [0:42]: Question Dissection: A 29 year old male with a past medical history of HIV infection sees his doctor for ongoing treatment... [4:40] Immunology chapter of S2S including questions like:  - How do you recognize and treat true anaphylaxis? - What usually causes hereditary angioedema?  - How is HIV diagnosed? How long after exposure does the HIV test become positive? - What causes DiGeorge syndrome? How do you recognize it? - Give the classic description of Job-Buckley (hyper-IgE) syndrome.   Get a discount on best selling study resources from Elsevier ITB listeners can get 30% off of books like Netter’s Anatomy Coloring Book, USMLE Step 2 Secrets, Crush Step 1, and many more. Head over to us.elsevierhealth.com/insidetheboards and use the discount code ITB30 at checkout!  ITB Audio Qbank and iOS Beta App The Audio Qbank by InsideTheBoards mobile app has both free and premium features and is available on both Android and iOS.  To get started, first, create a Boardsinsider Account on our website insidetheboards.com Free Features  All of our podcasts in one place organized into playlists for easy studying (also with less ads and exclusive content)  Mindfulness meditations designed specifically for medical students  A monthly offering of high yield content (questions dissections, audio qbank samples) available only on our mobile app.  Premium Features Subscribe to an ITB premium account and get additional features  Access to 500+ audio optimized board style practice questions in our Audio Qbank. The Step 1 version is powered by Exam Circle and the Step 2 Version is powered by OnlineMedEd. New questions added each month.  High Yield Pharmacology (powered by Lecturio) with 100 of the top pharm questions you need to know for both Step 1 and Step 2  Audio Flashcards (coming soon)  Our audio qbank is THE PERFECT companion for studying for the boards on the go. And we're adding content and improving it all the time.   Learn more about the Audio Qbank by InsideTheBoards mobile app here  InsideTheBoards' Other Podcasts InsideTheBoards: The Original Podcast  The flagship podcast from InsideTheBoards' mission is to teach you to "think like a question writer" so you can study smarter, not harder and succeed on the boards. It features high-yield question dissections and interviews with leaders in the medical education world. More than that, its mission is to help students lead better lives inside and outside of medical school, be more confident on their exams, and to encourage balance between their studies and lives. Check it out wherever you listen to podcasts. Or just head over to insidetheboards.com/podcasts.    InsideTheBoards Study Smarter Podcast  Check out the ITB Study Smarter Series Podcast channel. Go to bit.ly/ITBpodcasts or just click here to listen on Apple Podcasts. We're running a USMLE Step 2 Study Smarter Series in the coming months, covering each of the required clerkships and how to study for the shelf exam and the USMLE Step 2 and COMLEX Level 2.  The Medical Mnemonist (an InsideTheBoards Podcast) Check out another InsideTheBoards' original podcast on Apple Podcasts or, for cross platform, on Podbean. This one is focused on accelerated learning techniques and study hacks.  Check out all of ITB's Podcasts on our BRAND NEW Website InsideTheBoards is not affiliated with the NBME, USMLE, COMLEX, NBOME or any professional licensing body. InsideTheBoards and its partners, collaborators, and guests fully adhere to the policies on irregular conduct outlined by the aforementioned credentialing bodies.

A married couple. A sarcastic interviewer. A basement radio station. Drama, comedy. Theater. Okay, it's a regular episode of To a Certain Degree. But we do talk a lot about acting and theater.

Baby Ammon was diagnosed with DiGeorge syndrome and numerous other abnormalities. His parents are grateful he is here despite the difficulties.

On this episode of Film Reverie we spoke with Marco DiGeorge of Truthful Acting Studios in Orlando, Florida. We thoroughly enjoyed this talk with Marco. We actually felt like we got a free lesson in intro to acting. Packed with great information for actors and filmmakers alike.

Evanna was born with DiGeorge syndrome. A 400-day hospital stay wasn't easy for her parents but it strengthened their marriage and love for their daughter.

After learning their son had some markers for a genetic condition in utero, Bijan and Zach were offered to abort one of their twin boys.  They declined the offer and also declined in utero testing. Jackson was diagnosed with 22q11.2 deletion or DiGeorge syndrome.  Three years later, their other son Walker was recently diagnosed with autism. Twins Boys Diagnosed With Two Different Disorders Complications result in abortion advice During her pregnancy, Bijan said, “I was having many complications.”  She explained that Jackson’s fluid was really high and that his umbilical cord wasn’t attached properly.  They were given two options; be put on bedrest and expect a very early delivery, or terminate baby B, Jackson, and continue the pregnancy with baby A. “We both declined immediately, and they were born at 31-weeks gestation.  40 weeks is full-term, 37 for twins.” Bijan said. They also made the decision to decline any in utero testing.   A lengthy hospital stay When the twins were born, Jackson weighed one pound 14 ounces.  He ended up staying in the hospital for 90 days. Bijan said, “He has an underactive thyroid, but they didn’t figure out his thyroid condition for a while.  He was very listless, wasn’t eating properly and wasn’t gaining weight..they kept saying they knew it was a genetic condition but they didn’t know which one.” They were visited by a couple of different geneticists who came by to try and figure out what Jackson had.  They ran a full-scale genetic test on him and were able to receive a diagnosis. DiGeorge syndrome When he was three-months-old, Jackson was diagnosed with 22q11.2 deletion or DiGeorge syndrome.  Meaning that he is missing a small part on his 22nd chromosome. The medical problems associated with this syndrome are: heart defects, poor immune system, cleft palate, difficulties in feeding and gaining weight, and delayed developmental milestones. Jackson was lucky and escaped any heart related conditions. However, he has had several hospital stays due to surgeries and tests that have been run. Reaction following diagnosis “I think for a lot of people, you can’t really believe it at first.  You just expect everything to go perfectly like every parent would. The first day was just denial, I guess..but as the days went on, I grew a little more confident with trust and faith in the whole situation, and I knew it was going to be okay.” Zach shared. Trying to stay positive and being a good support is something that Zach says has been challenging.  He said, “So you just want to be there for him, help him develop and try to be a good dad.” Bijan shared that for her, the challenges have come in watching him go through hard things as an infant.  She said, “In the beginning, it seemed like the cards were going to be stacked against him, and I think that was tough.” Finding happiness in his success Bijan shared that her biggest joy is seeing how far Jackson has come.  She shared, “He still isn’t the typical three year old, but our joys come from his successes and everything that he does do now..he does have such a great personality, and he’s such a great kid.  He’s happy 99.8% of the time, so he’s our whole family’s joy.” Something Zach has found joy in is seeing Jackson smile and hearing him giggle.  He said, “You don’t know what’s going to happen, you never know. Just seeing him smile and looking you in the eye the first time was the biggest joy..I think the biggest joy thus far is his personality and his sense of humor.  That has been greater than I could ever really dreamed of, so we both have a lot to look forward to.” Other son diagnosed with autism Walker, Jackson’s brother, was recently diagnosed with autism.  Upon finding out that diagnosis Zach said, “It was a long stretch of almost three years.  I wasn’t really surprised, I couldn’t really be surprised at that point. All I could really think was, ‘Here we go, let’s just do it.’  We are already there for the boys,

An original MIND Institute/CEDD/CABIL production featuring Kathy Angkustsiri, M.D., providing an overview of the medical issues that are associated with Chromosome 22q11.2 Deletion Syndrome.

The brainchild of Dr. Blythe Corbett of the M.I.N.D. Institute, the SENSE Theatre is a unique theatrical intervention research program designed to improve the social and emotional functioning of children with autism and related neurodevelopmental disorders. Recently coming off their first joint production with the Davis Musical Theatre Company of Disney's "The Jungle Book Kids," Blythe Corbett, Ph.D. sits down to discuss the program. More information about SENSE Theatre can be found at http://www.sensetheatre.com. SENSE Theatre is a 501(c)(3) tax-exempt, non-profit organization.

5.1 Analysis and characterization of the mouse Hic2 gene Like Hic1 and γFBP (chicken), Hic2 cDNA coded five Krüppel-type C2H2 zinc finger domain. Through the sequencing and comparation with different protein sequences from the homolog proteins from different species (HIC1, Hic1, HIC2, γFBP, and Hypothetical protein), Hic2 protein shares more than 80% homology with HIC1 through the BTB/POZ and zinc finger domains, and both proteins have identical GLDLSKK/R motifs. A new part of Hic2 gene coding, exon two, and new exon one deduced full-length Hic2 protein contains 601 amino acids. Hic2 gene has two Exons (240 and 1842 bp), with one Intron (2182 bp). The location of the gene is mouse chromosome 16 (B1, UniGene Cluster Mm.103787 Mus musculus). The human gene HIC2 maps to chromosome 22q11.2, and is a homolog of the HIC1 candidate tumor suppressor gene located at 17p 13.3. (Deltour et al. 2001). Upstream from the TATA box MatInspector predicted different transcription binding sites. Between them Wilms Tumor Suppressor and p53 are most interesting transcription sites for the Hic2 gene. That’s why the Hic2 promoter activity was checked. A 1.2 kb promoter fragment of Hic2 has been characterized in a gene reporter assay system. The peak activity of the Hic2 promoter is associated with the total fragment, the next higher activity is in the fragment which included Wilms Tumor Suppressor and p53 transcription sites. The expression of the mouse Hic2 was investigated by in situ hybridisations (ISHs) of whole mount embryos and paraffin sections. Hic2 expression was detected in restricted territories of the brain, sinus centralis, olfactory bulb, canallis centralis medullae spinalis, embryonic ectoderm (neuroepithelium of neural tube), and small intestine. Because of its expression in the central nervous system, and mapping position of its human homolog HIC2, Hic2 could be involved in some syndromes. Patients with a 22q11 deletion have disrupted brain development which may involve abnormal neural crest cell migration, (Van Amelsvoort et al., 2001). It is now recognized that the 22q11.2 deletion syndrome encompasses the phenotypes previously described as DiGeorge syndrome (DGS) and velocardiofacial syndrome (Shprintzen syndrome),(Thomas and Graham 1997).

Die vorliegende Promotionsarbeit beschäftigt sich vorwiegend mit der Untersuchung von Patienten mit partieller Monosomie 10p. Der Phänotyp dieser Patienten ähnelt häufig dem des DiGeorge-Syndroms. Neben fazialen Dysmorphien und weiteren Nebensymptomen ist die Symptomentrias Herzfehler, T-Zelldefekt und Hypoparathyreoidismus das typische Merkmal dieses Entwicklungsdefektes. Viele Patienten mit einer partiellen Monosomie 10p zeigen diese Symptome, was für einen DiGeorge-Syndrom-Locus auf Chromosom 10p spricht. Der Hauptlocus für das DiGeorge-Syndrom liegt jedoch auf Chromosom 22q11. Mehr als 90 % der DiGeorge-Syndrom-Patienten haben eine Mikrodeletion 22q11. Diese Mikrodeletion zählt mit einer Frequenz von etwa 1/4000 zu den häufigsten Deletionen beim Menschen überhaupt und ist deshalb schon seit langem das Ziel intensiver Forschungstätigkeit. Dennoch ist es erst in der jüngsten Zeit gelungen, zumindest ein Gen aus der Mikrodeletionsregion 22q11 (TBX-1) zu isolieren, welches für den beobachteten Herzfehler verantwortlich sein könnte. Ansonsten sind die molekularen Ursachen dieses Entwicklunsdefektes noch immer weitgehend unbekannt. Die Deletionen auf Chromosom 10p sind sehr selten. Sie sind aber von wissenschaftlichem Interesse, da die molekulare Aufklärung dieser Region zu einem tieferen Verständnis der Pathogenese des DiGeorge-Syndroms und isolierter Fehlbildungen insgesamt beitragen kann. Im ersten Teil der Arbeit wurden 16 Patienten mit partieller Monosomie 10p zytogenetisch und molekulargenetisch untersucht. Elf dieser Patienten zeigten einen DiGeorge-Syndrom ähnlichen Phänotyp, fünf Patienten wurden nicht in das DiGeorge-Syndrom-Krankheitsbild eingeordnet. Die Patienten besaßen terminale und interstitielle Deletionen im Größenbereich von 13-48 cM. Mit Hilfe von FISH mit genomischen YAC-, PAC- und BAC-Sonden wurden die Bruchpunktregionen in den Patienten bestimmt. Bei einigen Patienten, bei denen DNA der Eltern vorlag, konnte auch eine Genotypisierung mit polymorphen Markern aus der Region vorgenommen werden. Mittels zweier Patienten konnte eine Haploinsuffizienzregion (DGCR2) kartiert werden, die für den Herzfehler und den T-Zelldefekt verantwortlich sein sollte. Die Region DGCR2 ist um den Marker D10S585 lokalisiert und besitzt eine minimale Ausdehnung von etwa 300 kb. Eine genaue Genotyp-Phänotyp-Analyse unter Einbeziehung von Patienten aus der Literatur zeigte jedoch, daß der gesamte Phänotyp der partiellen Monosomie 10p nicht mit der Haploinsuffizienz nur einer Region erklärt werden konnte, sondern daß zumindest noch ein zweiter Locus (HDR1) deletiert sein mußte. Dieser Locus war mit dem typischen DiGeorge-Syndrom-Symptom des Hypoparathyreoidismus assoziiert. Zusätzlich kartierten in diesen Locus noch eine sensorineurale Taubheit und Nierendefekte. Patienten mit diesen drei Symptomen leiden an einem HDR-Syndrom. Dieser zweite Haploinsuffizienzlocus HDR1 kartiert etwa 3 Mb distal zur Region DGCR2. Im zweiten Teil der Arbeit wurde sowohl über die Region DGCR2 als auch über die HDR1-Region ein PAC/BAC-Contig etabliert. Ausgewählte Klone aus den Contigs wurden im Rahmen des Humangenomprojekts vom Sanger Centre sequenziert. Der dritte Teil der Arbeit beschäftigte sich mit der molekulargenetischen Untersuchung der beiden Haploinsuffizienzregionen DGCR2 und HDR1. Es konnten 12 EST-Klone in die Region DGCR2 kartiert werden. Bei allen Klonen handelte es sich um Transkripte, die nicht zu funktionellen Proteinen translatiert wurden. Nachdem die genomische Sequenz zugänglich war, konnte eine In-silico-Analyse dieser Region durchgeführt werden. Es handelt sich um eine sehr genarme Region. In die minimale Region DGCR2 kartiert nur das Gen NAPOR, das für ein RNA bindendes Protein kodiert. Es wurde als Kandidatengen für den mit dieser Region assoziierten Herzfehler und T-Zelldefekt näher charakterisiert. Eine Northern-Blot-Hybridisierung zeigte eine Expression in allen aufgetragenen Herzgeweben. Es wurden mindestens sechs verschiedene Transkripte identifiziert, was für die Existenz mehrerer Isoformen des Gens spricht. RNA-in-situ-Hybridisierungen auf Schnitte humaner Embryos und Foeten ergaben eine Genexpression in verschiedenen Geweben beginnend von Embryos des Carnegie-Stadiums C12 bis zu 18 Wochen alten Foeten. Es wurde eine Expression im Thymus vom Carnegie-Stadium C16 an und eine Expression im Herzen bei einem Foetus der 9. Woche beobachtet. Das Expressionsmuster machte NAPOR zu einem guten Kandidatengen für den mit der Haploinsuffizienzregion DGCR2 assoziierten Herzfehler und T-Zelldefekt. Mutationsanalysen in mehr als 100 Patienten ergaben keine Mutationen im NAPOR-Gen. Die meisten untersuchten Patienten besaßen einen DiGeorge-Syndrom ähnlichen Phänotyp waren aber zytogenetisch normal. Besonderer Wert wurde auf die Anwesenheit eines Herzfehlers gelegt. Nur bei etwa 10 % der untersuchten Patienten lag auch eine Thymus-Hypoplasie vor. Ein direkter Beweis für die Beteiligung des NAPOR-Gens am Herzfehler und/oder T-Zelldefekt bei Patienten mit partieller Monosomie 10p steht noch aus. Die HDR1-Region konnte mit Hilfe zweier Mikrodeletionspatienten auf etwa 200 kb eingegrenzt werden. In diese Region kartiert das Gen GATA-3. Mutationsanalysen in zytogenetisch normalen HDR-Patienten zeigten in drei Patienten Mutationen, die zu einem funktionslosen GATA-3-Protein führen. Damit wurde der Beweis erbracht, daß das HDR-Syndrom eine Einzelgenerkrankung ist und daß die Symptome Hypoparathyreoidismus,sensorineurale Taubheit und Nierendefekte bei Patienten mit partieller Monosomie 10p auf eine Haploinsuffizienz des GATA-3-Gens zurückzuführen sind. Zusätzlich zu Patienten mit einer partiellen Monosomie 10p wurden auch zwei Patienten näher charakterisiert, die eine interstitielle Deletion auf dem Chromosom 14q11-q13 aufwiesen. Diese Region war von Interesse, da das Gen PAX-9 dorthin kartiert und homozygote Pax9 -/- Knockout-Mäuse unter anderem eine Thymus-Hypoplasie und einen Hypoparathyreoidismus zeigen. Die Mäuse haben zwei der drei Leitsymptome des DiGeorge-Syndroms und stellen eine Beziehung zum Phänotyp der partiellen Monosomie 10p her. Die Deletionsbruchpunktregionen der beiden Patienten wurden über eine Genotypisierung mit polymorphen Markern identifiziert. Mit Hilfe eines Dosis-Blots und einer FISH-Analyse konnte gezeigt werden, daß beide Patienten für PAX-9 hemizygot waren. Beide Patienten zeigen keine Symptome des DiGeorge-Syndroms, was daraufhin weist, daß beim Menschen eine PAX-9-Haploinsuffizienz nicht zu einem DiGeorge-Syndrom ähnlichen Phänotyp führt. Die in der vorliegenden Arbeit durchgeführten Untersuchungen an Patienten mit partieller Monosomie 10p und an Patienten mit einer interstitiellen Deletion 14q11-q13 lieferten einen Beitrag zur molekulargenetischen Charakterisierung des DiGeorge-Syndroms. Der DiGeorge-Syndrom ähnliche Phänotyp bei vielen Patienten mit einer partiellen Monosomie 10p ist das Resultat eines Contiguous Gene Syndroms, bei dem mindestens zwei unabhängige Regionen (DGCR2 und HDR1) auf Chromosom 10p hemizygot vorliegen müssen. Es wurde gezeigt, daß eine GATA-3-Haploinsuffizienz u.a. zu einem Hypoparathyreoidismus führt, einem der drei Leitsymptome des DiGeorge-Syndroms. Für den mit dem Syndrom assoziierten Herzfehler und T-Zelldefekt wurde mit NAPOR ein gutes Kandidatengen aus der Haploinsuffizienzregion DGCR2 identifiziert und charakterisiert. Eine Haploinsuffizienz des PAX-9-Gens auf Chromosom 14q12 führt zu keinem DiGeorge-Syndrom beim Menschen.