Podcasts about in ms

Multiple Sclerosis (MS) is a complex neurological condition that impacts an estimated 2.8 million people worldwide. This week we explore the science behind MS, treatment options, and the lived experiences of those navigating life with this chronic illness. Multiple Sclerosis (MS) has been called "the disease of 1000 faces" for good reason - it manifests differently in almost every person it affects.  Understanding MS: The Science Behind the Disease Dr. Zied Tayeb, neuroscientist and CEO of MyelinZ, explained the fundamental mechanism of MS in terms anyone can understand: "The brain communicates using electrical signals. These signals travel from one neuron to another through axons, which are protected by myelin sheets that help accelerate the transmission of these signals. In MS, the immune system mistakenly attacks these myelin sheets, leading to demyelination.” This disruption in communication between neurons explains why MS symptoms can vary so dramatically - the location of demyelination determines which functions are affected. "It could be the motor cortex, resulting in mobility issues, or the visual cortex, causing problems with vision," Dr. Tayeb noted. While the exact cause of MS remains unknown, researchers have identified several factors that may contribute to its development. According to our panel, MS is significantly more prevalent in women, who represent approximately 65% of MS patients - possibly due to women's more active immune systems making them more susceptible to autoimmune conditions like MS. Geographic distribution also offers clues, with higher rates in regions farther from the equator such as Canada, northern United States, and parts of Europe (with Denmark having a particularly high prevalence). This pattern has led scientists to investigate a potential link with vitamin D deficiency, though studies remain inconclusive. The Patient Experience: Hassan's Journey Few stories illustrate the unpredictable nature of MS better than that of Hassan Nada, entrepreneur, journalist, and self-described "MS warrior." Hassan's first symptom appeared in 2018 when he suddenly lost vision in his right eye while on holiday in Egypt. "I woke up one day, and out of nowhere, my vision was blurry to the point where I thought I was blind," Hassan recalled. Despite seeing an ophthalmologist, his condition went undiagnosed as MS. His vision eventually returned after treatment with corticosteroids. Four years later, after moving to Luxembourg, Hassan experienced sciatic nerve pain and numbness in his lower body. His general practitioner recognized the connection between his previous episode of optic neuritis and his current symptoms, immediately suspecting MS. "She screamed at me and had me go to the ER right away," Hassan shared. After extensive testing, including MRIs, blood tests, and a spinal fluid sample, the diagnosis was confirmed: Hassan had multiple sclerosis. The emotional impact of this diagnosis was profound. "My life changed from that moment onwards, and I went into complete depression," he admitted. But through the unwavering support of his wife and access to modern treatments, Hassan has found ways to adapt and advocate for others with MS. Treatment Approaches: Managing an Incurable Condition While MS currently has no cure, Dr. Tayeb emphasized that it is treatable. "Notwithstanding the fact that MS is incurable, it is treatable," he stated. "The problem is that every patient is different. The trajectory of the progression, diseases, symptoms are different.” Disease-modifying therapies (DMTs) aim to slow the progression of MS by suppressing or modulating the immune system. These treatments vary widely in their administration methods (pills, injections, infusions) and side effect profiles. Hassan's treatment journey illustrates the often challenging process of finding the right approach. After being diagnosed, he was unable to receive his doctor's first-choice treatment due to having a virus that made it dangerous for him. He then tried a pill-based DMT that, despite its high success rate with other patients, didn't work for him. Finally, he found success with a monthly subcutaneous injection called Kesimpta. "Last week I went to the neurologist office depressed," Hassan shared. "I was like, 'I know it didn't work.' She's like, 'No, it actually worked. There are no new lesions. You can now make long-term plans in life.'" Innovative Approaches: The Brain's Virtual Gym Dr. Tayeb and Samaher Garbaya, co-founders of MyelinZ, are taking a different approach to MS management. Their "virtual gym for the brain" uses neurotechnology to promote neuroplasticity - the brain's ability to form new neural connections. "We're trying to promote neuroplasticity in the brain," Dr. Tayeb explained. Their platform uses games to stimulate specific brain regions while measuring brain activity. Using machine learning, they analyze six different digital biomarkers to create personalized brain exercises. This approach draws inspiration from research showing that activities like playing musical instruments or singing can activate certain brain areas, potentially slowing disease progression by strengthening neural pathways. The Role of Support: Community and Family Multiple speakers emphasized that MS affects not just the individual but their entire support network. Anne Leurs, who manages the Multiple Sclerosis Society in Luxembourg, noted that MS typically appears between ages 20-40 - a critical period when people are building careers, starting families, and establishing their adult lives. "It's a very difficult period, this period of diagnosis," Anne observed. "It's a chronicle disease. This means that you will have to live your life on with this disease.” Hassan's experience underscores the crucial role of support systems. "MS either breaks a couple or it makes them the strongest couple in the world," he remarked. When first diagnosed, he told his wife she should leave. "She's like, 'It's because I love you that I'm not leaving, and we're going to make it out of this stronger than ever.'" Five years later, she remains his "backbone," managing his appointments and ensuring he takes his medications. For those without close family support, community organizations like the Multiple Sclerosis Society provide vital resources, information, and connection. Complementary Approaches: The Mind-Body Connection Mariette Lentz, a Luxembourgish soprano who specializes in the Alexander Technique, offered insights into complementary approaches that can help manage MS symptoms and improve quality of life. The Alexander Technique is "a mental technique" focused on "exploring the relationship between our thoughts and our movement," Mariette explained. While not a therapy or cure, it offers tools to help reduce stress and bring the nervous system to a calmer state - particularly valuable for MS patients who often experience anxiety related to their unpredictable symptoms. This, naturally, is a method that can help us all.  The Daily Reality Hassan painted a vivid picture of what daily life with MS can entail: "Imagine waking up every day of your life with the worst hangover in the world without having to drink.” Despite this challenge, he maintains a positive outlook and has channeled his experience into advocacy work, connecting with MS communities around the world. "I'm disclosing some personal parts of my life in hopes that it's actually going to benefit people," he explained. Looking Forward: Hope in Research and Community While MS remains incurable, advances in treatment options continue to improve outcomes for patients. From traditional DMTs to innovative approaches like brain-computer interfaces and neuroplasticity training, the landscape of MS management is evolving rapidly. As our conversation demonstrated, the combination of cutting-edge medical science, dedicated healthcare professionals, strong personal support systems, and community resources creates a foundation for living well despite MS. For those navigating the complex journey of MS - whether as patients, family members, or healthcare providers - knowledge and community remain powerful tools. By continuing to share stories like Hassan's and insights from experts like Dr. Tayeb, Samaher Garbaya, Anne Leurs, and Mariette Lentz, we can work toward greater understanding and better support for everyone affected by this challenging condition. https://myelinz.com https://www.msweb.lu/wp/

Send us a textEpisode 33 - Season 2Multiple sclerosis (MS)We are well and truly into spring here in the United kingdom, as the sun shines outside Martin & Patrick have another special guest Dominic Shadbolt.Dominic has Multiple sclerosis (MS) and is soon to embark on an extraordinary journey across Canada of some 8,000 KM / 5,000 Miles to raise awareness and money for MS Brain Health initiatives.A coast-to-coast cycling expedition across Canada with the ambitious goal of raising $1 million. This epic ride symbolises resilience, determination, and the power of community, aiming to transform the lives of people living with Multiple Sclerosis and to demonstrate anything is possible with a positive mental attitude.Dominic tells us about his diagnosis with Multiple sclerosis (MS) at the early age of 28, how he deals with this illness day today and his future going forward.This remarkable challenge will commence in Hallifax, Canada on the 1st May this year 2025 and will see Dominic Cycle on his A modified I.C.E. Sprint X modified recumbent cycle solo and un-aided 8,000km to Vancouver on the West Coast, dipping his toe in the water both sides at start and finish.You can check you Dominic's progress and donate to his fundraising event by visiting his website below where more detailed information can be found.https://www.rc4ms.org/Dominic also has his own Youtube channel where you can find out more about both Multiple sclerosis (MS) and his challenge ahead.https://www.youtube.com/channel/UCIpq0cm2wIfKJ6H8xs2AxGAMultiple sclerosis is a disease that causes breakdown of the protective covering of nerves. Multiple sclerosis can cause numbness, weakness, trouble walking, vision changes and other symptoms. It's also known as MS. In MS, the immune system attacks the protective sheath that covers nerve fibers, known as myelin.#HeartTransplant#EbsteinsAnomaly#RareCondition#HealthJourney#LifeChangingDiagnosis#MentalHealth#Vulnerability#SelfCompassion#PostTraumaticGrowth#MedicalMiracle#BBCSports#Inspiration#Cardiology#Surgery#Podcast#Healthcare#HeartHealth#MedicalBreakthrough#EmotionalJourney#SupportSystem#HealthcareHeroes#PatientStories#CardiologyCare#MedicalJourney#LifeLessons#MentalWellness#HealthAwareness#InspirationalTalk#LivingWithIllness#RareDiseaseAwareness#SharingIsCaring#MedicalSupport#BBCReporter#HeartDisease#PodcastInterview#HealthTalk#Empowerment#Wellbeing#HealthPodcast#ChronicIllnessCheck out our new website at www.whostomanddick.comCheck out our website at www.whostomanddick.com

“…the mental, challenges are as great as perhaps the physical ones.“ Peta Hooke interviews Fran, an ambassador for MS Australia. Fran chats about confronting her late diagnosis of multiple sclerosis (MS) and some of the individualised challenges that people with MS face, including heat sensitivity, fatigue, visual impairment and mobility issues.MS is the most common acquired chronic neurological disease and, in Australia, affects three times more women than men. In MS, the body's immune system mistakenly attacks and damages the fatty material – called myelin – around the nerves. This results in a range of symptoms, but no two people experience MS in the same way. For more information about MS, please visit https://hdsunflower.com/au/insights/post/multiple-sclerosis-msFor support please visit https://www.msaustralia.org.au/ or https://www.msplus.org.au/If you are experiencing any issues discussed in this podcast, please contact your healthcare practitioner.The Sunflower Conversations is a Podcast where we explore the experiences of people living with hidden disabilities and what the Sunflower means to them. It's a space to share your experience and to empower and encourage more people to support invisible disabilities.   A big thank you to Peta Hooke for conducting the interviews with compassion and respect and to Sandee Facy for the beautiful Sunflower song. You can follow Peta's I can't stand podcast here and Sandee Facy's music here.If you want to share your experience, get in touch with us by emailing us here. If you enjoyed this podcast, please leave a rating and review. Find out more about the Sunflower by visiting the website hdsunflower.com 

This episode unpacks the rewards of hard work and drive in CRE with Kaylan Knitowski and Justin Walker, Retail Specialists at Franklin Street.The Crexi Podcast explores various aspects of the commercial real estate industry in conversation with top CRE professionals. In each episode, we feature different guests to tap into their wealth of CRE expertise and explore the latest trends and updates from the world of commercial real estate. In this episode, host Ashley Kobovitch sits down with Kaylan and Justin to explore their successful careers in commercial real estate. They share their journeys into the industry, the importance of mentorship, and their strategies for building client relationships.  The conversation covers valuable lessons learned, the impact of macroeconomic factors, and the benefits of leveraging tools like Crexi. They also discuss the role of social media in building a brand, navigating the current market landscape, and preparing for future growth in the retail sector, particularly in the Southeast region. Tune in for insights on maintaining work ethic, overcoming challenges, and the team's vision for the future of Franklin Street's retail investment sales team.Introduction to The Crexi PodcastMeet the Guests: Kaylan Knitowski and Justin WalkerKaylan's Journey into Commercial Real EstateJustin's Path to SuccessMentorship and InfluencesLessons Learned in Real EstateDaily Habits and Work EthicSuccess at Franklin StreetNetworking and Mentoring in Real EstateVision for Franklin Street's Retail Investment Sales TeamThe Power of Social Media in Real EstateOvercoming Imposter SyndromeCurrent State of Commercial Real EstateMacroeconomic Factors Influencing RetailAdvice for Brokers and InvestorsRapid Fire Questions and InsightsParting Words and Contact Information About Kaylan Knitowski:Kaylan Knitowski is a Senior Associate for Franklin Street's Retail Investment Sales Team in Fort Lauderdale. Kaylan transacts throughout the country, and concentrates on value-add, unanchored retail assets, with a particular emphasis on the Southeast region. In Ms. Knitowski's role, she prioritizes cultivating client relationships and identifying off-market acquisition opportunities for key clients. Since entering the commercial real estate field in late 2022, Ms. Knitowski has successfully transacted over $57 million, with an additional $50 million currently under contract.About Justin Walker:Justin Walker leads the team, and serves as the Senior Director for Franklin Street's Retail Investment Sales Team in South Florida, where he plays a pivotal role in driving the growth and success in the retail investment sales sector throughout South Florida and the SouthEast. Mr. Walker has transacted over $100m in his career, throughout the country. If you enjoyed this episode, please subscribe to our newsletter and enjoy the next podcast delivered straight to your inbox. For show notes, past guests, and more CRE content, please check out Crexi's blog. Ready to find your next CRE property? Visit Crexi and immediately browse 500,000+ available commercial properties for sale and lease. Follow Crexi:https://www.crexi.com/​ https://www.crexi.com/instagram​ https://www.crexi.com/facebook​ https://www.crexi.com/twitter​ https://www.crexi.com/linkedin​ https://www.youtube.com/crexi

In Ms. Information, Microbiologist and science communicator Dr Siouxsie Wiles suffers a pandemic backlash.

Intelligence detective Gary Jenkins interviews a mystery and thriller fiction writer, Jode Millman about her research and writing process. In Ms. Millman's recent thriller, Hooker Avenue, she was inspired by a true crime involving sex workers in the Hudson Valley of New York. She also had a personal connection to those crimes. During the late … How to Research and Write Crime Fiction Read More » The post How to Research and Write Crime Fiction appeared first on Gangland Wire.

In this weeks lesson Ms. Hill & Mr. Holland are discussing 2022's "Glorious" directed by Rebekah McKendry and starring Ryan Kwanten and J. K. Simmons. In Ms. Hills "Jenny Dreadfuls" we will be discussing "Out of the Aeons" by H.P. Lovecraft & Hazel Heald https://deepcuts.blog/2020/02/08/out-of-the-aeons-1935-by-hazel-heald-h-p-lovecraft/ https://www.instagram.com/horrorinthehalls/

In this weeks lesson Ms. Hill & Mr. Holland are discussing 2012's The Raven starring John Cusack. In Ms. Hills Spoopy Book Nook we will be discussing Edgar Allen Poe's most famous poem "The Raven" which inspired this film and many others. https://www.instagram.com/horrorinthehalls/

Discussion Topic: Ms.Marvel (show) and The Partition Of India https://en.wikipedia.org/wiki/Partition_of_India https://en.m.wikipedia.org/wiki/Opposition_to_the_partition_of_India#Politicians https://www.foreignaffairs.com/articles/south-asia/2017-10-19/gandhis-role-partition-india?check_logged_in=1&utm_medium=promo_email&utm_source=lo_flows&utm_campaign=registered_user_welcome&utm_term=email_1&utm_content=20220725 In Ms. Marvel they show footage of the riots breaking out and of Ghandi on tv-he fasted to protest the violence https://actionvillageindia.org.uk/unlocked/gandhis-fasts-the-cultural-context-of-fasting-and-in-particular-for-nonviolent-change/ https://en.wikipedia.org/wiki/Ms._Marvel_(TV_series) Kamal means perfection in Persian (thanks Baha'i school!) https://variety.com/2022/tv/news/ms-marvel-finale-kamala-khan-mutants-captain-marvel-1235316482/ Here's some other informative viewing (18) Why was India split into … Continue reading "Marvel does historical fiction now-Episode 239" The post Marvel does historical fiction now-Episode 239 first appeared on Geek Grills.

The Assistant Principal PodcastEpisode X: Tracking Teacher DevelopmentWhy does it always feel like improving teacher quality is an uphill battle? One big reason is that our schools are not structured to facilitate consistent teacher growth. Focusing on helping teachers to grow requires us to focus on the structures that can support growth first. In this episode we look at on important structure, the teacher tracking document. The teacher tracking document helps us to develop and document a coherent and consistent approach to helping individual and groups of teachers grow.Hello colleagues and welcome to the Assistant Principal Podcast. I'm your host Frederick Buskey. The goal of this podcast is to help improve the life and leadership of assistant principals. Today, I will walk us through how to use a teacher tracking document as part of a systems approach to teacher development.After listening to this podcast, you might want to head over to my website, frederickbuskey.com/appodcast, to watch the video. There are several key graphics that go along with today's show that should help you. I will also include images in the show notes. Back in episode one I talked about the six dimensions of organizations. If we think about a three-sided pyramid representing an organization, the pinnacle is the organizational purpose. The three points along the pyramid's base are people, structures, and resources. In the perfect organization, which doesn't exist, the people, structures, and resources are perfectly aligned with the organization's purpose.In the simplest terms, the work of leadership is improving alignment between the purpose, the people, the structures and the resources.Structures include buildings, the arrangement of space within those buildings, but also the rules, policies, expectations, and practices that shape our actions. A block schedule is a structure that is fundamentally different than an 8-period day. They exist for different purposes and if we try and teach during a block the way we did when we had 8 periods, it doesn't work. Our skills need to align with our structures, and both need to be aligned to our purpose. When we ask people to work towards a specific purpose, yet we have structures that aren't aligned with that purpose, it creates a situation in which people feel like they are constantly swimming up stream. Teachers experience this misalignment often: Teachers are expected to plan rich and powerful lessons, yet they have 30-minutes a day to plan. Teachers are expected to use formative assessments to inform their focus, yet we have pacing guides and benchmark tests. Teachers are expected to become masters of pedagogy, yet they work under pressure and expectations that make risk-taking difficult and reflection almost impossible. This misalignment makes it harder for teachers to excel at their core job and it increases pressure and frustration.As assistant principals, you are experiencing a congruent set of circumstances. The purpose of schools is to help young people develop agency over their lives and to become responsible democratic citizens. Or something like that.The roles of the principal and assistant principal are integral structures. School administrators have tow primary functions that are core to the purpose of the school:  Keep everyone safe Create better outcomes for kids However, we don't teach kids and the #1 Influence on student achievement is the classroom teacher. So, the formula is simple:Better teachers = better student learning.Logically then, once we make sure that everyone is safe, our next priority is to focus on teacher development. If better teachers = better student learning then, outside of safety, the most important things we do are the things that help our teacher to continually grow.The challenge is that there is all kinds of stuff that gets in the way.Why does this happen? Because our structures are not aligned to our purpose.What has happened in many schools, is that while the stated purpose of the assistant principal is to contribute to the quality of instruction in the building, the unstated purpose has become to deal with all the issues that come up in day-to-day operations. Our school structures have followed suit: We communicate via email, which demands our constant attention. We carry walkie talkies so we can always be reached. We accept that interrupting what we are working on is part of the job. We use a narrow set of observation practices that are more aligned to accountability than to teacher development. The cumulative impact of these mis-aligned structures and purpose has a profound impact on how we lead: We mistake urgency for purpose in our day-to-day behaviors, so the important purposeful work of teacher development gets displaced by urgent tasks. There are tasks that are both urgent and important- especially those dealing with safety. However, there are many urgent tasks that are less-important or not important. For example, the parent newsletter, school social media posts, or the report to the school board. I can hear you saying “wait, these things are important!” Yes and no. None of these things will improve student learning as much as helping a teacher to get better. The problem is that all these things are urgent, so they feel important, even though – compared to safety and teacher growth, they are not.   The tool that has helped me with this concept is the Eisenhower Matrix. The EM as I affectionately call it has four quadrants. The two upper quadrants are important, and the two lower quadrants are un-important, or less important. The two left quadrants are urgent, and the two right quadrants are not urgent. What tends to happen is that school leaders focus on the two left quadrants – the urgent work, instead of the two upper quadrants – the important work. Teacher development is quadrant 2 work. Quadrant 2 is important but not urgent. This focus on urgency happens for many reasons, and someday I will do a deep dive on the Eisenhower Matrix and break it down. But for now, it is enough to know that there are three large barriers to working in quadrant 2: Mindset. We need to move from prioritizing the urgent to prioritizing the important. Processes. There are many urgent but less-important things that can be systematized and streamlined so that they require less time. Structures. If we build structures into our work that support quadrant two activity, then we are more likely to engage in quadrant 2 activity. This podcast is about one of those structures.  If you are familiar with the flywheel concept, then you'll be familiar with this structural approach to teacher development. If you aren't familiar with the flywheel, I'll give an MVP (minimally viable product) description now. The flywheel is the one thing in your work that, if executed consistently, over time will create momentum in your school and will propel you to the school purpose (better out comes for kids). The flywheel in schools consists of: Providing professional development for teachers Evaluating implementation of the PD focus Using the evaluation results to drive the next step in PD When we do this repeatedly, always using implementation results to inform subsequent growth opportunities, we create positive forward momentum because teachers are consistently getting better. There are two significant challenges with trying to improve your school using the flywheel concept. First, flywheels are hard to get started. It is like pushing a big tire up hill. Until you get to a place where you can build some momentum, every step takes work. Secondly, using a flywheel requires specific structures to be in place. The flywheel structures that work for you may not be identical to the structures I'm sharing. That's fine. What is critical is that you do have a flywheel, that you build the structures to support the flywheel, and that your structures work. We can only have a working flywheel if we have structures in place to support it. There are multiple structures that we need to build, but today we are focusing on just one: the teacher tracking document.  We are starting with the tracking document because, honestly, that is the focus of our APEx work this month. It isn't the best place to start, but it is where we are right now.  As you listen to this podcast it may get a bit complicated, but I encourage you to stick with it and when you watch the video or even just look at the images, it will all make sense. The teacher tracking document is a fundamental component of instructional team meetings. The instructional team meeting is yet another topic I need to cover for you, but it is a set time every week where administrators and instructional support staff meet to analyze data from teacher observations and to use that data to inform the next round of teacher development. When I talk about teacher development, that can take multiple forms. We might be looking at the entire teaching staff, if for example we are emphasizing student engagement strategies. We may be talking about a specific group of teachers such as grade level, topic area, or new teachers. For example, phasing in a new 6th grade ELA curriculum or implementing classroom procedures with four beginning teachers. We might also be talking about the needs of a single teacher. The instruments we use and the data we gather will look different depending on who our focus is on. The data we collect for a school-wide implementation is very different from small-group and individual development. The teacher tracking document is designed to support small groups and individuals. In the weekly instructional leadership team meeting, leaders will discuss what they have seen in weekly observations. They will discuss the implications of that observation data for professional development and plan future PD according to what the data suggests. This PD can be for the whole staff, but using this document we are more likely to focus on groups or individuals. The first time we use the teacher tracking document we need to add some basic information. Before we proceed, I offer you a word of caution. If you do not currently have anything like this in place, please do not try and complete the whole document for your whole staff! You won't be able to do it, will burn multiple hours and, in the end it won't work for you. Start with just one teacher.  This version of the form is not the only or even the “right” way to do it. You might want to change the form by deleting or adding. You might want to use a spreadsheet or data base, or something altogether different. The format is not as important as the purpose – to consistently monitor implementation of professional development. Free to make changes as you see fit. Okay, let's look at the form.The teacher tracking form is a table with 14 columns and a row for each teacher.   The first six columns compose a baseline for the teacher. The information in these columns may change over time, but not week-to-week. Column 1 contains the teacher's name, column 2 their 9-box rating, and columns 3-6 capture their strengths and weaknesses in some key areas. Column 1, the teachers name, is simple enough. Column 2 is the teachers 9-box rating. That's another show, but 9-box is a really handy tool for getting your team onto the same page regarding a teacher's potential versus their performance. 9-box can help guide the type of professional development and the coaching styles that will work best for each teacher. If you don't do 9-box you could substitute your state teacher evaluation rating or some other metric. The importance of column 2 is that it provides guidance on overall performance level of a teacher, and the type of support that is likely to be most helpful for them. The next block of columns, 3-6, relate to key teaching areas. This is an optional section of the tracking chart, but many schools have specific points of emphasis, and these columns allow us to be mindful o how each teacher is doing in those areas.  In my example, column 3 has rows for classroom management, student relationships, curriculum, and pedagogy.  For each of these areas, there is a rating in column 4. You could use your state evaluation instrument here or something else.  Column 5 is the strengths for each area, and  column six is the weaknesses. I like having this block because it helps as a reference point when we are talking about multiple facets of teacher performance and it can help us think more strategically about the most important PD topics for each teacher. You can change the topics in the rows to suit your specific school needs. For example, maybe you are emphasizing literacy across all subject areas, so you want that to be one of your areas. If this seems daunting, then skip it for now. Again, don't feel tied ot the format I have. The critical thing is that you begin tracking teacher performance and documenting your work and commitment related to helping your teachers grow.  Columns 7-11 are for planning the specifics of professional development. Column 7 is for the focus area. For example, classroom procedures. We could be more specific – say, the entering class procedure. More specific is better, but it may take some time to get into the habit of thinking in terms of small incremental changes for the focus area. Column 8 is the goal. The goal should address the impact that the focus will have. For example, implementing an entering class routine should increase available instructional time and decrease student off-task behavior. Column 9 is the A-B step that the next professional development cycle needs to focus on. The concept of A-B is that incremental changes are more likely to lead to success than big changes. An A-B step should be able to be completed in one week or less. “Implement five classroom routines” is not an A-B step. Observing students entering Ms. Smith's and Mr. Garrot's classes once each is an A-B step. Column 10 is for who is responsible for the A-B step. It is common to have more than one person responsible. My teacher is responsible for doing the observations, but maybe I am responsible for letting Ms. Smith and Mr. Garrot know what's going on, or for covering the first 10 minutes of the teacher's class. Column 11 is the type of support being given. This relates to another framework called the cube of development, but for now you can just indicate whether this is an individual or small group form of support. If I am only working with one teacher on the entering class routine, then it is individual coaching. If I am working with three of our first- and second-year teachers, then it could be coaching or group PD. Columns 12-14 constitute the final part of the document, the observations section. This is an essential element because it is where we hold each other accountable for conducting meaningful classroom observations. This mutual accountability is one way that we focus ourselves on the work of quadrant 2. The data we gather from our observations is also what helps us to identify the next A-B step. Column 12 is who will be doing the observation. If more than one of us will be observing, and that is good practice, then we will include multiple names. Column 13 is when. Observations should be scheduled for a specific time and we should know when our colleagues are doing observations so that we can cover those things that will invariably “come up” when someone is scheduled to be in a classroom. Column 14 is where we summarize the data we gather from an observation. Now that we have reviewed the entire tracking sheet, let's talk about implementation.The first consideration is the context. If you are the principal or if your principal is on board, then schedule your instructional leadership team meeting, throw the teacher tracking document from my website into a google doc or other shared platform, and dive right in.If this isn't going to happen right now at the school level, then at least use it yourself. Create your own structures to support your instructional leadership. This will work if you are the assistant principal, instructional coach, or in another teacher support role. An advantage of starting on your own is that you can figure out what works and doesn't work for you and then make changes accordingly. You will still need to schedule an instructional leadership meeting with yourself and adhere to it. Maybe Fridays at 3:30?The first time we use this document we only want to do it for ONE teacher. Not ten, not two, ONE. This is an A-B approach. If something in the format doesn't work or isn't essential for you, you will find out before you invest a lot of time. One teacher.Let's use Ms. Franks as an example. Ms. Franks is a third-year teacher. Her growth as a teacher has been understandably disrupted by the pandemic. Ms. Franks did well pivoting to online instruction her first year and worked hard to build relationships with students. She went beyond expectations in being available to students and in encouraging them to contact her.Ms. Franks did well in her second year when students were on an A-B schedule and class sizes were small. She struggled this fall, along with many other teachers, with the return to full size classrooms and the period of adjustment that saw a large increase in discipline issues. During this time Ms. Franks had referral numbers similar to other teachers, but observations showed high numbers of students off task and Ms. Franks was asking students to be quiet multiple times during each instructional segment.It has become clear that Ms. Franks has not established classroom procedures. Though she has good relationships with students and they are rarely disrespectful, there are often multiple students talking at once, even when Ms. Franks is trying to speak. There are also students frequently moving around the room with no clear purpose and student discussion during group tasks has a high rate of off-task content.  In your conversations with Ms. Franks, she admits that the students are loud but says that is due to the pandemic and expects it will get better soon. She says that she has classroom routines, but that students don't always follow them. She insists that she taught the routines at the beginning of the year.Ms. Franks is committed to group work and wants high levels of student engagement. She is frustrated that students frequently aren't able to demonstrate meaningful outcomes from group work and she wants to improve that area.In her efforts to keep students engaged, Ms. Franks uses lots of activities, some of which she purchases on Teachers Pay Teachers. As designed, most of the activities in her room are engaging, but they often are misaligned to either that standard or the depth of knowledge.You have heard from another teacher that Ms. Franks is discouraged and questioning whether she is cut out for teaching.Now, in the ideal school, every teacher is in the tracking document and receives appropriate PD based on the data. But we know that most schools exist in a real, not ideal world. We also know that administrators, especially assistant principals, may be hard pressed to consistently support even one teacher or one group of teachers. So, if you haven't gone far on the journey of teacher support, then choose just one teacher to work with. If you are only coaching one teacher, then you better choose the right teacher! I did a whole episode of The Assistant Principal Podcast on how to select the right teacher to work with. Look for episode 8 if you haven't listened already. Assuming you aren't going to pause and dial up that episode, here are three reasons why I think Ms. Franks is a good person to coach: She is willing and wants to get better. There is big bang for the buck – she could be much better if we can take care of some little things, AND my life might be easier as referral rates should decrease. She needs help in some areas that I know well enough to be helpful with.   So let's look at how we're going to get Ms. Franks into our tracking document. I first add her name, her 9-box rating, and the ratings, strengths, and weaknesses in four areas: classroom management, where I scored her as 1/4, Student relationships (4/4), curriculum (2/4) and pedagogy (2/4).The ratings should be based on evidence. Those could be formal or informal observations, discussions with Ms. Franks or other instructional leaders, or anecdotal data such as hearing students say how much they like Ms. Franks. If you are working alone, you will drop this information in by yourself. However, a really powerful thing happens when we complete this as a team. It is likely that we will disagree in some places on the ratings we give teachers. Working on the form together enables us to come to consensus and provides for rich discussions on these different teaching areas. It is common for us to observe teachers through our own biases, and when we talk with others it can help us better understand these biases.You may also see through Ms. Frank's ratings – a 1 in classroom management, 2s in curriculum and pedagogy, and a 4 in student relationships, that there appears to be a clear area that we should emphasize, in this case classroom management. So, is classroom management what we will focus on. The clear answer is that it depends.In the situation where a teacher is either oblivious to their needs, or is completely drowning, it is appropriate for us to determine the area of focus. If someone is drowning, we don't ask them whether they would like a blue or brown rope. We look for the most expedient way to get them out of the water. It is the same for a teacher that is crashing and burning.In this case however, Ms. Franks is aware of at least some of her problems and she is not on fire yet – though we can smell smoke. In a situation like this, my preference is to allow teachers to choose the area of focus for these reasons: If the teacher chooses it, the teacher owns the results. If you choose it, you own the results. The teacher will probably be more motivated to work on their own problem than on your problem. The teacher might actually have a better understanding of their needs than we do – ouch! When the teacher chooses, it is crystal clear that we are serving the teacher's needs, not our own. A successful collaboration will build trust, which will lead to more successful collaborations. Finally, an improvement in any area is a win. In Ms. Frank's case, she might achieve better classroom management, or get better outcomes for group work, or align her activities better with her curricular objectives. All these are wins! My first conversation with Ms. Franks is going to be about her perceptions and her priorities. If I already have observation data, I can bring that into the conversation where appropriate. In this situation I am serving Ms. Franks so I want this conversation to be about her and her needs. If she asks for my input, I will give it and point to the data that I'm using as the basis for my thoughts.Let's play with a couple of options for her focus. In terms of needs, classroom management is a priority with needs being “clear structures and reinforcing routines.” Curriculum activities don't align to the standards – that is important, and for pedagogy Ms. Franks has stated that she wants to improve her prompts and procedures for group work. If there were five APs on this show trying to decide what the best area of focus was, we would get at least two different answers, so don't be surprised when Ms. Franks chooses a different area than you would and don't be overly confident that your idea is the best.What is obvious to me is not obvious to you and vice versa. Remember, no matter which one of these things she picks, if we are successful, the kids – and Ms. Franks – will benefit.So, let's imagine that Ms. Franks wants to use better prompts for group work. This isn't what I would have chosen, but it is more important for her to be invested than for me to be right. Remember that columns 7-11 are where we document our specific coaching plan and teacher support.In column 7, I am going to put the focus area. Narrower is better. For Ms. Franks we will put “Use prompts that lead to answers that align to the curricular focus.”Column 8 is our goal. It is helpful to think about impact here – what do we want to happen as a result of our work? Ms. Franks wants students to come up with meaningful answers as a result of group work.Column 9 is our A-B step. This is where it gets complicated. I have gotten tripped up many times. My inclination for Ms. Frank's goal would be to hand her some guidelines on writing good prompts and ask her to try them out, but that probably would not work. Part of the issue is that her group procedures are weak, so even with good prompts she may not get the results she wants. If I simply ask her to try some prompts and they fail, then what?If Ms. Franks doesn't really understand how to create good prompts, then – if group work fails – she won't know whether it is the prompt or something else. So maybe the A-B step is that she reads something on prompts, and that she takes five prompts she has previously used, and thinks about how to change them. In column 10, we record who is responsible for the A-B step. In this case Ms. Franks is responsible for reading, pulling five old prompts, and reflecting. I am responsible for following up with the IC to make sure there is a good reading available.In column 11, I put the type of support being given, in this case coaching. If I was working with three of our new teachers on the same thing, this might be small-group PD instead and that would change the nature of the conversations and tasks.In my example, the “observation” is actually a review of her updated prompts. I reviewed Ms. Franks on March 3rd and noted that the prompts were aligned to the standards and that the type of task was appropriate to the standard. In another week, when we start using new prompts, then I will want to observe what happens in groups with the new prompts and I will schedule times to observe. I have included that in the example, noting that I observed on March 10th and that answers were related to the standards, but that off-task discussion was still high and that a single student did most of the talking.As Ms. Franks and I work through the process, the teacher tracking sheet will get updated with new A-B steps.Okay, I hope this all makes sense. In wrapping up, let's reiterate some key points: Ideally, we use this document as part of an instructional leadership team meeting, but you can use it on your own. There is nothing magical about what I have included and excluded in the chart. Change it to fit your needs. If you are just beginning, use it on just ONE teacher. You can listen to episode 8 of the Assistant principal Podcast to help you decide which teacher. As a general rule of thumb, let the teacher choose the focus area. Break down the desired outcome into incremental, A-B steps. Plan and document your observations. Remember that there is a video on my website, frederickbuskey.com/appodcast, and that there are visuals in the show notes. I may also develop a handout but can't promise that right now.  At this point I have invested about six hours into developing this podcast and you have invested about 30 minutes in listening to it. If you are inspired to try a teacher tracking document, or to take better advantage of something you have in place, then the time that both of us have spent on this is well worth it.However, if this podcast episode didn't help you, then it was a lost opportunity – for both of us.The only way I know whether or not I am hitting the mark is by getting feedback from you. The hardest part of producing a podcast is not knowing how you are doing. Our download numbers are going up each episode, but every episode is different and I can't tell what's working and what's not just from the numbers.Please. Help me make this podcast better. Are these deep, sort of nerdy dives into a specific tool or choice helpful? Would you rather just have interviews of other people? What topics do you really need to hear right now?You can email me at frederick@frederickbuskey.com. I would love to hear from you.If you enjoyed today's show, please subscribe and rate this podcast. This is the only show in world (that I can find) that is devoted to assistant principals. Subscribing and rating will help your colleagues find this series.If you'd like more content tailored towards the needs of assistant principals, you can head over to my website at frederickbuskey.com. You might want to consider looking into APEx, the Assistant Principal Exceleration program. You'll get weekly emails, tools, and be able to participate in monthly group coaching and webinars. I'd love to get to know you through APEx, but no worries if now is not the right time.That wraps up today's show! I'm Frederick Buskey and I hope you'll join me next time for the Assistant Principal Podcast. Links:My email: frederick@frederickbuskey.com The Assistant Principal Podcast website: https://www.frederickbuskey.com/appodcast.html 

Multiple sclerosis (MS) is a disease of the brain and spinal cord (central nervous system), which can cause a disability. In MS , a person's immune system attacks the protective nerve fiber covering and causes communication problems between your brain and the rest of your body to stop. Though this disease has been around for a long time, it doesn't seem to be as diagnosed or even acknowledged in our African community when compared to the common infectious diseases. Such diseases, though rare, are slowly plaquing our community and it is about time we talk about them. Today, our guests speak extensively on MS from living with it to the course of therapy. We hope this episode is as resourceful as it was for us.   Get to meet our guests:   Dr. Leonard Ngarka is a Neurologist who works at Yaounde Central Hospital, Cameroon. He is also a Lecturer at the Faculty of Medicine and Biomedical Sciences, The University of Yaoundé, Cameroon. He will be further educating us on MS and Neuromyelitis Optica.   Contact: Email -  lngarka@yahoo.com   Fuen Beri is the second of four children who live in the United Kingdom (UK). She has been living in the UK since 2005, shortly after high school. She now works for a global consultancy based in the heart of London and her favorite quote is - "no two days are the same." She will be sharing with us her diagnosis with Multiple Sclerosis(MS).   Contact: Email - Fuen.beri@gmail.com Things You Will Learn in This Episode:  [00:01 – 03:00] Introduction Introducing our guests - Dr. Leonard Ngarka & Fuen Beri [03:00 – 17:00] Understanding Multiple sclerosis (MS) The lack of data on multiple sclerosis in Africa Understanding the causes and symptoms of MS The under-reporting of multiple sclerosis in Africa The importance of early detection [17:00 – 43:00] Fuen Ngwa Shares Her Story With MS Early symptoms of MS in childhood Getting misdiagnosed in Cameroon The lack of proper diagnosis in Africa Fuen shares her struggles with MS How she keeps her head up and motivated  [43:00 - 1:06:00] Risks Factors, Prevention & Stigmatization The genetic causing factors Preventive measures we can take How the lack of some important minerals can cause MS The cost of treating MS in Africa Stigmatization of people living with MS [1:06:00 - 1::] Medications, Advice, Mindset & Motivation Dr. Ngarka educates us on some medication used in treating MS Fuen educates us on the mindset and motivation needed General advice with patients living with multiple sclerosis The importance of listening & knowing your body Government need to make drugs accessible and subsidize How to contact Dr. Leonard Ngarka & Fuen Beri [55:00 – 1:00:004] Final Discussions Final words from Dr. Leonard Ngarka Final words from Fuen Beri Final words from Anyoh LEAVE A REVIEW and tell us what you think about the episode so we can continue putting out the best content just for you! Connect with Living African Podcast You can connect with us on Facebook, Instagram, YouTube, Twitter, or send us an email at hello@livingafricanpodcast.com. Check out our website www.livingafricanpodcast.com for more resources and to learn more. You can connect with Anyoh on Facebook (@anyohf), Instagram (@anyohfombad), and Twitter (@anyohfombad).

In this podcast, Episode 102 “The Road to Forgiveness Part 1 – the pathway to mental peace” with host, Nichel Anderson, discussing the pathway to get your state of mind in peace and joyfulness that produces a way to cope with stress, anxiety, and fear that delivers your blissful life purpose. In Ms. Nichel Anderson themed of “Forgiveness” she returns this season in a two part series again discussing this topic that she likes to phrase “forgiveness is earned not given if the person or entity organization hasn't repented. *If you haven't subscribe to the podcast please do and signup to the Ms. Nichel Anderson's eNewsletter.   --- ANNOUNCEMENTS:    Get in the Know and Empowered:  Sign-up Here For Nichel eList Tips Newsletter Stay in the know of Nichel Anderson events and merchandise products at Official Website: NichelAnderson.com   Buy my book:  "Corporate America: Surviving Your Journey Towards Success"   --- Nichel Anderson Career Consultation: Schedule Now --- Check out Nichel Anderson second Podcast Show: "Nichel Anderson Short Stories And Beyond"   NEW Book:  My new collection "It's A New Day" a Motivational Journal highlighting 31 days that Nichel guide you on prompts and activities to focus on and inspire you to focus on things that help your sustainability of mental and joy for another day to live on our journey. available on Amazon.com https://kdp.amazon.com/amazon-dp-action/us/dualbookshelf.marketplacelink/B08HCW2FBZ  NEW Travel Flight Record - its a part of another collection,"The Proactive Traveler" that is a notebook with forms indicated the important data to write down for your record that highlights being organized, proactive, and proficient enough to be on top of key data when contacting the airline, travel agency, especially, with todays world pandemic changes. Available on Amazon.com -  https://www.amazon.com/dp/B08GZLGM3Y   Follow Nichel Anderson on Social Media: twitter.com/nichelanderson facebook.com/nichelandersonfanpage   Thank you! If you like this podcast share it!   -- My Affiliate Links: I personal can refer Podbean as a good distribution platform, after I waited four years using their service and another and decided with Podbean to decide which one for both of my podcast shows. I chose Podbean and their pricing are reasonable along with their investment in seeking new ways to make the platform better as well with metrics that are vital for a podcast host won me over. Consider for yourself as I recently became an affiliate. Disclaimer: the links below will be my affiliate link to promoting Podbean that provides commission for each sign up. I do plan to release a podcast full review of Podbean and another platform of my experience:   Sign up for a podcast unlimited plan https://www.podbean.com/success   Sign up for a podcast business hosting plan https://www.podbean.com/pro/success   Interesting in advertising on Podbean for your business or project sign up here: https://sponsorship.podbean.com/success      

In this podcast, Episode 102 “The Road to Forgiveness Part 1 – the pathway to mental peace” with host, Nichel Anderson, discussing the pathway to get your state of mind in peace and joyfulness that produces a way to cope with stress, anxiety, and fear that delivers your blissful life purpose. In Ms. Nichel Anderson themed of “Forgiveness” she returns this season in a two part series again discussing this topic that she likes to phrase “forgiveness is earned not given if the person or entity organization hasn't repented. *If you haven't subscribe to the podcast please do and signup to the Ms. Nichel Anderson's eNewsletter. ---   ANNOUNCEMENTS:    Get in the Know and Empowered:  Sign-up Here For Nichel eList Tips Newsletter Stay in the know of Nichel Anderson events and merchandise products at Official Website: NichelAnderson.com   Buy my book:  "Corporate America: Surviving Your Journey Towards Success"   --- Nichel Anderson Career Consultation: Schedule Now --- Check out Nichel Anderson second Podcast Show: "Nichel Anderson Short Stories And Beyond"   NEW Book:  My new collection "It's A New Day" a Motivational Journal highlighting 31 days that Nichel guide you on prompts and activities to focus on and inspire you to focus on things that help your sustainability of mental and joy for another day to live on our journey. available on Amazon.com https://kdp.amazon.com/amazon-dp-action/us/dualbookshelf.marketplacelink/B08HCW2FBZ  NEW Travel Flight Record - its a part of another collection,"The Proactive Traveler" that is a notebook with forms indicated the important data to write down for your record that highlights being organized, proactive, and proficient enough to be on top of key data when contacting the airline, travel agency, especially, with todays world pandemic changes. Available on Amazon.com -  https://www.amazon.com/dp/B08GZLGM3Y   Follow Nichel Anderson on Social Media: twitter.com/nichelanderson facebook.com/nichelandersonfanpage   Thank you! If you like this podcast share it!   -- My Affiliate Links: I personal can refer Podbean as a good distribution platform, after I waited four years using their service and another and decided with Podbean to decide which one for both of my podcast shows. I chose Podbean and their pricing are reasonable along with their investment in seeking new ways to make the platform better as well with metrics that are vital for a podcast host won me over. Consider for yourself as I recently became an affiliate. Disclaimer: the links below will be my affiliate link to promoting Podbean that provides commission for each sign up. I do plan to release a podcast full review of Podbean and another platform of my experience:   Sign up for a podcast unlimited plan https://www.podbean.com/success   Sign up for a podcast business hosting plan https://www.podbean.com/pro/success   Interesting in advertising on Podbean for your business or project sign up here: https://sponsorship.podbean.com/success      

“Ransom” reintroduces us to Gerald's little sister, Timberley, who just wants her fair share of sibling time with her older brother. In “Ms. Perfect,” Helga and the girls tear down Lila, the new girl, for being so well-liked – not realizing their vindictiveness is one of the reasons they're not. If you love the show, we'd love for you to leave a review! In the meantime, keep up with us at https://twitter.com/stoopkidzpod and https://www.instagram.com/stoopkidzpod/. All Stoop Kidz show art is created by our own Emily Csuy (https://www.instagram.com/emilycsuy/). Intro music: “Hey Arnold! Theme” by Jim Lang. Intermission music: “Groove Remote” by Jim Lang. Outro music: “Stompin'” by Jim Lang.

From Hollywood legends Brian Grazer and Ron Howard as well as powerhouse producer Lee Daniels comes The Ms. Pat Show, a new sitcom now available on BET+. The Ms. Pat Show is inspired by the life of convicted felon turned stand-up comedian, Patricia Williams, better known as Ms. Pat. The show tells the story of a woman who forged her hustle and resilient spirit on the streets of Atlanta, and now she and her family are adjusting to their new life in conservative middle America (Plainfield, Indiana). In Ms. Pat's memoir Rabbit, she shares her moving story as a single mother of two selling crack in the inner city of Atlanta. At 19, with two toddlers and a new husband, she was handed four more young children from her sister who was struggling with addiction. With her husband's encouragement, she finally decided to get on the straight and narrow, and went to her first open-mic. From the moment she stepped on stage she knew she had found her place. Rabbit was nominated for an NAACP Award for Outstanding Literary Work and Rotten Tomatoes included it on their list of “Books Becoming TV Series We Cannot Wait to See.” Ms. Pat has since become a favorite with audiences and critics alike. Declared by The Washington Post as “unforgiving and darkly hilarious,” and The New York Times as “brutally honest and outrageous,” she's appeared on Netflix's The Degenerates, Larry Charles' Dangerous World of Comedy, Comedy Central's This Is Not Happening, NBC's Last Comic Standing, and Nickelodeon's Mom's Night Out. A favorite guest on podcasts from Joe Rogan, Marc Maron and Bert Kreischer, Ms. Pat now hosts her own popular podcast, The Patdown.

From Hollywood legends Brian Grazer and Ron Howard as well as powerhouse producer Lee Daniels comes The Ms. Pat Show, a new sitcom now available on BET+. The Ms. Pat Show is inspired by the life of convicted felon turned stand-up comedian, Patricia Williams, better known as Ms. Pat. The show tells the story of a woman who forged her hustle and resilient spirit on the streets of Atlanta, and now she and her family are adjusting to their new life in conservative middle America (Plainfield, Indiana). In Ms. Pat's memoir Rabbit, she shares her moving story as a single mother of two selling crack in the inner city of Atlanta. At 19, with two toddlers and a new husband, she was handed four more young children from her sister who was struggling with addiction. With her husband's encouragement, she finally decided to get on the straight and narrow, and went to her first open-mic. From the moment she stepped on stage she knew she had found her place. Rabbit was nominated for an NAACP Award for Outstanding Literary Work and Rotten Tomatoes included it on their list of “Books Becoming TV Series We Cannot Wait to See.” Ms. Pat has since become a favorite with audiences and critics alike. Declared by The Washington Post as “unforgiving and darkly hilarious,” and The New York Times as “brutally honest and outrageous,” she's appeared on Netflix's The Degenerates, Larry Charles' Dangerous World of Comedy, Comedy Central's This Is Not Happening, NBC's Last Comic Standing, and Nickelodeon's Mom's Night Out. A favorite guest on podcasts from Joe Rogan, Marc Maron and Bert Kreischer, Ms. Pat now hosts her own popular podcast, The Patdown.

Season 2 Episode 17: Multiple Sclerosis is a potentially disabling disease of the brain and spinal cord (central nervous system). In MS, the immune system attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between your brain and the rest of your body. Eventually, the disease can cause permanent damage or deterioration of the nerves, resulting in the loss of the ability to walk independently, or at all, loss of muscle use and numbness and tingling of extremities.

Broccoli compound extends lifespan in worm model University of Heidelberg (Germany), February 5 2021.    An article published on January 20, 2021 in Aging reported the findings of a team from the University of Heidelberg in Germany of an association between the intake of the compound sulforaphane derived from broccoli and other Brassicaceae family vegetables and longer survival of the roundworm Caenorhabditiselegans.  “Several studies have described the isolation of natural substances from food plants and characterized them as suitable anti-aging agents; such substances include the phenol resveratrol from grapes and berries, the phenol curcumin from turmeric, the alkaloid berberine found in plants used in traditional Chinese medicine (TCM), the polyphenol chlorogenic acid from coffee and tea, and chlorophyll from green vegetables, among others,” wrote Zhimin Qi and colleagues. “We asked whether sulforaphane may influence the lifespan and health span of C. elegans.” Adding sulforaphane to the worms’ diets increased the lifespan of various strains of C. elegans by an average of 17%. The mechanism of action was attributed to inhibition of abnormal dauer formation protein 2 (DAF-2)-mediated insulin and insulin-like growth factor signaling and its downstream targets, which positively affected other factors. (DAF-2 is part of a metabolic pathway that regulates the rate of aging.) Sulforaphane also increased health span, resulting in a delay in aging-associated physiologic decline. Mobility, appetite and food intake were greater in worms that received sulforaphane, while the accumulation of the aging-associated pigment lipofuscin was reduced. Other experiments revealed that sulforaphane enhanced oxidative stress resistance. "We are the first to report that sulforaphane prolongs the lifespan and increases the health span of C. elegans through the inhibition of DAF- 2/insulin/IGF-1 signaling and the activation of DAF- 16/FOXO nuclear transcription in C. elegans,” the authors announced. “Our study provides a promising hint regarding the suitability of sulforaphane as a new anti-aging drug.”     Oral N-acetylglucosamine may be neuroprotective in demyelinating diseases like MS University of California at Irvine, January 31, 2021   According to news reporting originating in Irvine, California, research stated, “Myelination plays an important role in cognitive development and in demyelinating diseases like multiple sclerosis (MS), where failure of remyelination promotes permanent neuro-axonal damage. Modification of cell surface receptors with branched N-glycans coordinates cell growth and differentiation by controlling glycoprotein clustering, signaling, and endocytosis.” The news reporters obtained a quote from the research from the University of California Irvine, “GlcNAc is a rate-limiting metabolite for N-glycan branching. Here we report that GlcNAc and N-glycan branching trigger oligodendrogenesis from precursor cells by inhibiting platelet-derived growth factor receptor-alpha cell endocytosis. Supplying oral GlcNAc to lactating mice drives primary myelination in newborn pups via secretion in breast milk, whereas genetically blocking N-glycan branching markedly inhibits primary myelination. In adult mice with toxin (cuprizone)-induced demyelination, oral GlcNAc prevents neuro-axonal damage by driving myelin repair. In MS patients, endogenous serum GlcNAc levels inversely correlated with imaging measures of demyelination and microstructural damage.” According to the news reporters, the research concluded: “Our data identify N-glycan branching and GlcNAc as critical regulators of primary myelination and myelin repair and suggest that oral GlcNAc may be neuroprotective in demyelinating diseases like MS.” This research has been peer-reviewed.   Happiness really does come for free: study McGill University (Quebec), February 9, 2021 Economic growth is often prescribed as a sure way of increasing the well-being of people in low-income countries, but a study led by McGill and the Institute of Environmental Sciences and Technologies at the Universitat Autònoma de Barcelona (ICTA-UAB) suggests that there may be good reason to question this assumption. The researchers set out to find out how people rate their subjective well-being in societies where money plays a minimal role, and which are not usually included in global happiness surveys. They found that the majority of people reported remarkably high levels of happiness. This was especially true in the communities with the lowest levels of monetization, where citizens reported a degree of happiness comparable to that found in Scandinavian countries which typically rate highest in the world. The results suggest that high levels of subjective well-being can be achieved with minimal monetization, challenging the perception that economic growth will automatically raise life satisfaction among low-income populations. Measuring happiness To explore how monetization affects people's sense of well-being, the researchers spent time in several small fishing communities, with varying degrees of monetization, in the Solomon Islands and Bangladesh, two very low-income countries. Over a period of a few months, with the help of local translators, they interviewed citizens in both rural and urban areas a number of times. The interviews, which took place both in person and through phone calls at unexpected moments, were designed to elicit information about what constituted happiness for the study subjects, as well as to get a sense of their passing moods, their lifestyle, fishing activities, household income, and level of market integration. In all, the researchers interviewed 678 people, ranging in age between their mid-twenties and early fifties, with an average age of about 37. Almost 85 % of the study participants were male. The disproportionate number of men in the study was due to the fact that cultural norms in Bangladesh made it difficult to interview women. In the Solomon Islands, responses to the study questions from men and women were not significantly different. However, this is not necessarily applicable to the situation in Bangladesh, as men and women's social realities and lifestyles differ so much. Further research will need to address whether gender-related societal norms impact the association found in this study. Early stages of monetization may be detrimental to happiness The researchers found that in the communities where money was in greater use, such as in urban Bangladesh, residents reported lower levels of happiness. "Our study hints at possible ways of achieving happiness that are unrelated to high incomes and material wealth," says Eric Galbraith, a professor in McGill's Department of Earth and Planetary Sciences and the senior author on the study, which was recently published in PLOS One. "This is important, because if we replicate these results elsewhere and can pinpoint the factors that contribute to subjective well-being, it may help us circumvent some of the environmental costs associated with achieving social well-being in the least developed nations." "In less monetized sites, we found that people reported a greater proportion of time spent with family and contact with nature as being responsible for making them happy," explains Sara Miñarro, the lead author on the study who is a Postdoctoral Research Fellow at (ICTA-UAB). "But with increasing monetization, we found that the social and economic factors commonly recognized in industrialized countries played a bigger role. Overall, our findings suggest that monetization, especially in its early stages, may actually be detrimental to happiness." Interestingly, while other research has found that technology and access to information from faraway cultures with different lifestyles may affect people's sense of their own well-being by offering standards to which people compare their own lives, this did not appear to be the case in these communities. "This work adds to a growing realization that important supports for happiness are not in principle related to economic output," adds Chris Barrington-Leigh, a professor in McGill's Bieler School of the Environment. "When people are comfortable, safe, and free to enjoy life within a strong community, they are happy—regardless of whether or not they are making any money."   Depressed moms who breastfeed boost babies' mood, neuroprotection and mutual touch Study first to show EEG patterns shift as a result of feeding method and affectionate touch in depressed and non-depressed moms and babies Florida Atlantic University, February 10, 2021 About 1 in 9 mothers suffers from maternal depression, which can affect the mother-infant bond as well as infant development. Touch plays an important role in an infant's socio-emotional development. Mothers who are depressed are less likely to provide their babies with soothing touch, less able to detect changes in facial expressions, and more likely to have trouble regulating their own emotions. In addition, infants of depressed mothers exhibit similar brain functioning patterns as their depressed mothers, which also are linked to temperament characteristics. Infants of depressed mothers are at a high risk of atypical and potentially dysregulated social interaction. A first-of-its-kind study by researchers at Florida Atlantic University's Charles E. Schmidt College of Science examined the developing mother-infant relationship by studying feeding method (breastfeeding and/or bottle-feeding) and affectionate touch patterns in depressed and non-depressed mother-infant dyads as well examining the infant's electroencephalogram activity (EEG) during development. Affectionate touch was coded during the mother-infant feeding context and included stroking, massaging and caressing initiated by either mother or infant.  For the study, researchers evaluated 113 mothers and their infants and assessed maternal depressive symptoms, feeding and temperament or mood. They collected EEG patterns (asymmetry and left and right activity) from infants at 1 and 3 months old and videotaped mother-infant dyads during feeding to assess affectionate touch patterns in both mother and baby. They specifically focused on alterations in EEG activation patterns in infants across development to determine whether feeding and maternal depression are interactively related to changes in resting frontal EEG asymmetry and power.  Data from EEG activity, published in the journal Neuropsychobiology, revealed that mother-infant affectionate touch differed as a function of mood and feeding method (breastfeeding vs. bottle-feeding), affecting outcomes for infants of depressed mothers compared to non-depressed mothers. Researchers observed a reduction in infant touch toward their mothers only with the infants in the depressed and bottle-fed group. Affectionate touch of mothers and infants varied by depression interacting with feeding type, with breastfeeding having a positive effect on both maternal and infant affectionate touch. Infants of depressed and breastfeeding mothers showed neither behavioral nor brain development dysregulation previously found in infants of depressed mothers.  "We focused on mother-infant affectionate touch patterns during feeding in our study because touch is a form of mutual interaction established in early infancy, used to communicate needs, soothe, and downregulate stress responses, and because mothers and infants spend a significant amount of time feeding across the first three months postpartum," said Nancy Aaron Jones, Ph.D., lead author, an associate professor, and director of the FAU WAVES Emotion Laboratory in the Department of Psychology in the Charles E. Schmidt College of Science, and a member of the FAU Brain Institute. "As experience with maternal mood and feeding pervade the infant's early environment, we chose to examine how these factors interact to affect mother-infant affectionate touch, focusing fastidiously on the key roles of individual variation in temperament and EEG activation patterns."  Asymmetry patterns in certain infant populations, such as those of depressed mothers differ from the asymmetry patterns of typically developing infants and children. While EEG asymmetry measures the balance of the right and left hemisphere activity, infants of depressed mothers exhibit patterns of right frontal asymmetry, due in part to hypoactivation of the left hemisphere within the frontal region. This pattern of brain activation (greater right asymmetry) is similar to the pattern observed in depressed adults and is thought to represent heightened negative affect as well as motor tendencies for withdrawal and inhibited approach behaviors.  In addition to the tactile behavior changes, the infants in this study displayed differential brain activation patterns as a function of maternal depression and feeding group status. Not only were the infants' EEG patterns affected by their mother's depression status, stable breastfeeding experience also interacted with the depression group to impact EEG patterns across early development. Left frontal asymmetry in infants was associated with having a non-depressed mother and infant care experiences in the form of stable breastfeeding. Left frontal activity has been associated with advancing maturation, positive emotions, as well as higher order processing skills. Notably, EEG patterns of infants of depressed mothers showed right frontal asymmetry; however, shifts to greater left frontal activation (left frontal hyperactivation change) were found in those infants with stable breastfeeding experiences.  Analysis from the study also revealed that infant breastfeeding duration and positive temperamental characteristics predicted infant affectionate touch patterns, suggesting that early infant experiences, and more broadly, their underlying neurochemical regulatory processes during feeding could influence the development of infant physiology and behavior, even for infants of depressed mothers.  "Ultimately, our study provides evidence that the sensitive caretaking that occurs, even for mothers with postnatal depression in the context of more predominant breastfeeding, may redirect neurophysiological, temperamental, and socio-emotional risk through dyadic tactile experiences across early development," said Aaron Jones.   Vitamin D supplementation: possible gain in life years combined with cost savings German Cancer Research Center, February 11, 2021 In recent years, three meta-analyses of clinical studies have come to the conclusion that vitamin D supplementation was associated with a reduction in the mortality rate from cancer of around 13 percent. Scientists at the German Cancer Research Center (DKFZ) have now transferred these results to the situation in Germany and calculated: If all Germans over the age of 50 were to take vitamin D supplements, up to 30,000 cancer deaths per year could possibly be avoided and more than 300,000 years of life could be gained - in addition, health care costs could be saved. For several years now, scientists have been investigating the influence of an adequate supply of vitamin D on the prognosis of numerous diseases. The focus is particularly on inflammatory diseases, diabetes, respiratory diseases and cancer.  Three meta-analyses of large clinical studies have been published in recent years on the question of how vitamin D supply affects cancer mortality rates. The studies* came to the same conclusion: cancer mortality is reduced by around 13 percent with vitamin D supplementation - across all cancers. Only methodologically high-quality randomized trials from all parts of the world were included in the meta-analyses. Exactly what biological mechanisms might underlie this is not yet clear. "In many countries around the world, the age-adjusted rate of cancer mortality has fortunately declined over the past decade," says Hermann Brenner, an epidemiologist at the German Cancer Research Center (DKFZ). "However, given the often considerable costs of many new cancer drugs, this success has often come at a high price. Vitamin D, on the other hand, is comparatively inexpensive in the usual daily doses." Vitamin D deficiency is common in the elderly population and especially among cancer patients. Brenner and colleagues now calculated what costs would be incurred by vitamin D supplementation of the entire population of Germany from the age of 50. They contrasted this sum with the potential savings for cancer therapies, which are often associated with costs in the range of several 10,000 euros, particularly in the case of advanced cancers during the last months of patients' lives.  The scientists based this calculation on a daily administration of 1,000 international units of vitamin D at a cost of 25 euros per person per year. In 2016, approximately 36 million people over the age of 50 lived in Germany, resulting in annual supplementation costs of 900 million euros. The researchers took the cost of cancer treatment from the scientific literature, assuming mean additional treatment costs of €40,000 for the last year of life. A 13 percent reduction in cancer mortality in Germany corresponded to approximately 30,000 fewer cancer-related deaths per year, the treatment costs of which amounted to €1.154 billion in the model calculation. Compared with the costs of vitamin supplementation, this model calculates an annual saving of €254 million. The researchers determined the number of years of life lost at the time of cancer death using data from the German Federal Statistical Office. Brenner considers the costs and effort of a routine determination of the individual vitamin D level to be dispensable, since an overdose is not to be feared with a supplementation of 1000 international units. Such a prior testing had not been made in the clinical trials either. "In view of the potentially significant positive effects on cancer mortality - additionally combined with a possible cost saving - we should look for new ways to reduce the widespread vitamin D deficiency in the elderly population in Germany. In some countries, foods have even been enriched with vitamin D for many years - for example, in Finland, where cancer mortality rates are about 20 percent lower than in Germany. Not to mention that there is mounting evidence of other positive health effects of adequate vitamin D supply, such as in lung disease mortality rates," says Brenner, adding, "Finally, we consider vitamin D supplementation so safe that we even recommend it for newborn babies to develop healthy bones." To improve one's vitamin D levels at absolutely no cost, DKFZ's Cancer Information Service recommends spending time outdoors in the sunshine, two to three times a week for about twelve minutes. Face, hands and parts of arms and legs should be uncovered and without sunscreen for this period of time.     Poor fitness linked to weaker brain fiber, higher dementia risk University of Texas Medical Center, February 14, 2021 Scientists have more evidence that exercise improves brain health and could be a lifesaving ingredient that prevents Alzheimer's disease. In particular, a new study from UT Southwestern's O'Donnell Brain Institute suggests that the lower the fitness level, the faster the deterioration of vital nerve fibers in the brain. This deterioration results in cognitive decline, including memory issues characteristic of dementia patients. "This research supports the hypothesis that improving people's fitness may improve their brain health and slow down the aging process," said Dr. Kan Ding, a neurologist from the Peter O'Donnell Jr. Brain Institute who authored the study. White matter The study published in the Journal of Alzheimer's Disease focused on a type of brain tissue called white matter, which is comprised of millions of bundles of nerve fibers used by neurons to communicate across the brain. Dr. Ding's team enrolled older patients at high risk to develop Alzheimer's disease who have early signs of memory loss, or mild cognitive impairment (MCI). The researchers determined that lower fitness levels were associated with weaker white matter, which in turn correlated with lower brain function. Distinctive tactics Unlike previous studies that relied on study participants to assess their own fitness, the new research objectively measured cardiorespiratory fitness with a scientific formula called maximal oxygen uptake. Scientists also used brain imaging to measure the functionality of each patient's white matter. Patients were then given memory and other cognitive tests to measure brain function, allowing scientists to establish strong correlations between exercise, brain health, and cognition. Lingering mysteries The study adds to a growing body of evidence pointing to a simple yet crucial mandate for human health: Exercise regularly. However, the study leaves plenty of unanswered questions about how fitness and Alzheimer's disease are intertwined. For instance, what fitness level is needed to notably reduce the risk of dementia? Is it too late to intervene when patients begin showing symptoms? Some of these topics are already being researched through a five-year national clinical trial led by the O'Donnell Brain Institute. The trial, which includes six medical centers across the country, aims to determine whether regular aerobic exercise and taking specific medications to reduce high blood pressure and cholesterol levels can help preserve brain function. It involves more than 600 older adults at high risk to develop Alzheimer's disease. "Evidence suggests that what is bad for your heart is bad for your brain. We need studies like this to find out how the two are intertwined and hopefully find the right formula to help prevent Alzheimer's disease," said Dr. Rong Zhang of UT Southwestern, who oversees the clinical trial and is Director of the Cerebrovascular Laboratory in the Institute for Exercise and Environmental Medicine at Texas Health Presbyterian Hospital Dallas, where the Dallas arm of the study is being carried out. Prior findings The research builds upon prior investigations linking healthy lifestyles to better brain function, including a 2013 study from Dr. Zhang's team that found neuronal messages are more efficiently relayed in the brains of older adults who exercise. In addition, other teams at the O'Donnell Brain Institute are designing tests for the early detection of patients who will develop dementia, and seeking methods to slow or stop the spread of toxic proteins associated with the disease such as beta-amyloid and tau, which are blamed for destroying certain groups of neurons in the brain. "A lot of work remains to better understand and treat dementia," said Dr. Ding, Assistant Professor of Neurology & Neurotherapeutics. "But, eventually, the hope is that our studies will convince people to exercise more."     A systematic review and meta-analysis of impact of red wine polyphenols on vascular health University of Birmingham (UK), February 4, 2021   According to news reporting originating from Birmingham, United Kingdom, research stated, “Red wine polyphenols (RWP) are plant-based molecules that have been extensively studied in relation to their protective effects on vascular health in both animals and humans. The aim of this review was to quantify and compare the efficacy of RWP and pure resveratrol on outcomes measures of vascular health and function in both animals and humans.” Our news editors obtained a quote from the research from the University of Birmingham, “Comprehensive database searches were carried out through PubMed, Web of Science and OVID for randomised, placebo-controlled studies in both animals and humans. Meta-analyses were carried out on acute and chronic studies of RWP in humans, alongside sub-group analysis where possible. Risk-of-bias assessment was carried out for all included studies based on randomisation, allocation, blinding, outcome data reporting, and other biases. Results 48 animal and 37 human studies were included in data extraction following screening. Significant improvements in measures of blood pressure and vascular function following RWP were seen in 84% and 100% of animal studies, respectively. Human studies indicated significant improvements in systolic blood pressure overall (- 2.6 mmHg, 95% CI: [- 4.8, - 0.4]), with a greater improvement in pure-resveratrol studies alone (- 3.7 mmHg, 95% CI: [- 7.3, - 0.0]). No significant effects of RWP were seen in diastolic blood pressure or flow-mediated dilation (FMD) of the brachial artery.” According to the news editors, the research concluded: “RWP have the potential to improve vascular health in at risk human populations, particularly in regard to lowering systolic blood pressure; however, such benefits are not as prevalent as those observed in animal models.” This research has been peer-reviewed.

Could an injection of your own brain cells be a way to halt multiple sclerosis - MS? That's what researchers in the US are finding in mice with the disease. In MS, the immune system attacks the brain and spinal cord, damaging a material called myelin. An extract of this myelin material, injected into the bloodstream, can permanently deactivate the immune cells that cause MS... Like this podcast? Please help us by supporting the Naked Scientists

Could an injection of your own brain cells be a way to halt multiple sclerosis - MS? That's what researchers in the US are finding in mice with the disease. In MS, the immune system attacks the brain and spinal cord, damaging a material called myelin. An extract of this myelin material, injected into the bloodstream, can permanently deactivate the immune cells that cause MS... Like this podcast? Please help us by supporting the Naked Scientists

The “gospel” is the message of the Gospels. Of the four inspired biographies of Jesus, the Gospel of Mark is active. The motion of Mark’s account of Jesus is fast paced, to the point, and unpacks the convincing reality that He is Lord, King, and Messiah. In MS 1 you will discover who Mark is, why that matters, and how the gospel made its way into hearts then and now. Welcome into the kingdom of forgiveness! CLICK HERE to view the Video.

EP62 Comic book talk about the original Marvel Zombies tpb 1, Marvel Zombies resurrection #3, Ghostbusters Funko Universe one-shot, free comic book day issues. In MS talk we talk about the day in the life of an MSer, myself. --- This episode is sponsored by · Anchor: The easiest way to make a podcast. https://anchor.fm/app --- Send in a voice message: https://anchor.fm/kevin-kleinhans/message Support this podcast: https://anchor.fm/kevin-kleinhans/support

Tune into this episode as co-host, Stephanie Whitehead, and special guests, Tiffany Channer and Aaron Odegard, discuss the importance of joining a professional organization.  If you are a laboratory professional looking to jump start your career or get more involved in your profession, this is the episode for you! Key takeaways: Learn about the personal and professional benefits you will gain from joining professional organizations.  Understand the benefits of being actively involved in a professional organization Learn about volunteer opportunities and committees that support the laboratory profession  Special Guest Bios:Aaron Odegard serves as the current Chair of the ASCP Council of Laboratory Professionals.  He enjoys educating the public, medical laboratory science students and professionals on the topics of antimicrobial resistance and stewardship through many platforms including: classrooms, local and regional meetings, and social media. Aaron can be reached on LinkedIn at “Aaron Odegard”.Tiffany Channer is the assistant administrative director of Laboratories and quality manager at White Plains Hospital (WPH). Prior to joining WPH, Ms. Channer worked for 9 years at Memorial Sloan Kettering Cancer Center (MSKCC) in New York, NY as lead medical technologist III/ safety officer, where she honed her skills in blood banking and transfusion medicine. In Ms. Channer's spare time, she supports her passion for community service, laboratory science, and public health by conducting presentations at local high schools, educating students on the importance of an education and correlating epidemiological theory and statistics into the clinical laboratory setting. Ms. Channer also served as American Society Clinical Pathology (ASCP) / President Emergency Plan for AIDS Relief (PEPFAR) initiative consultant in Swaziland, Africa. Additionally, she has served as the ASCP Chair for the Council of Laboratory Professionals, Patient Champion Advisory Board Member, and Career Ambassador. Tiffany can be reached on LinkedIn at “Tiffany Channer”. Be a Supporter! Listen on Direct Impact Broad Casting, Spotify, Apple Podcast or your favorite podcast platform. Don't forget to subscribe to the show on your phone, tablet or notebook so you never miss an episode! Be sure to leave a comment, and share with a fellow medical laboratory professionals!Be a Guest!  If you have a leadership or laboratory message to share and would like to be a guest on the show, please reach out to us at elaboratetopics@directimpactbroadcasting.com or connect with us on Direct Impact Broadcasting through Social Media.

Do you remember hearing the quote “Don’t judge a book by its cover?” Chronic illnesses, such as Multiple Sclerosis, have symptoms that are like icebergs; you only see what’s on the surface. One of my students recently shared with me her experience as an MS warrior. There are 2.3 million people worldwide that are affected by this disease, according to the National Multiple Sclerosis Society. Multiple sclerosis is an autoimmune disorder that affects the central nervous system and is the most common disabling neurological condition affecting young people. In MS, the immune system attacks the myelin that surrounds nerves and disrupts the electrical signals in our brain and spinal cord. You can think about the nerve as an extension cord where wires are wrapped in a protective coating. If the protective coating is missing or damaged, then the cord will not work properly. Multiple sclerosis is sometimes called the snowflake disease due how it affects individuals differently and uniquely. It

One this episode of The Black, BOLD, and Beautiful Podcast Ms.BBB conducts three different interviews. It was hard catching up with these ladies and gents, but Ms.BBB is grateful each person speaking on this platform, has taken time from their schedules to voice their motivation. Even at the nail salon, on morning walks, and driving from state to state. To stay in the direction of financial stability, this episode will focus on some ways of managing your expenses. In Ms.BBB's opinion, a great way to start budgeting is to focus on your body. Everything starts with you and if you body isn't right, you can't be right. Working out and eating healthy doesn't come easy for everyone. Ms.BBB definitely can relate. Honestly most of it has to do with being Lazy. She called in two friends, Jordan Strong and Alexandria Dior  to speak on their personal journeys with wellness and offer a few tips to motivate the BBB community. The best part is the awesome mix provided by this weeks BBB Artist Spotlight of the week, DJ RNB. All the way from New York, DJ RNB has joined the BBB family and will be catching all the vibes.  

In Ms. Marvel Vol. 2, we ask "Generation Why?", and in Aquaman Vol. 1 our titular hero asks "Who am I?".

Pastor Clarissa sits down and talk with Latrish "The Enlightener" Climons about her journey as a woman in ministry.  Filled with so much wisdom, this young lady shares the many lessons she's learned on the journey, from actually accepting Christ, a moment of rebellion, surrendering to The Spirit's leading, growing in God and learning how to do ministry, the way God has led her.  Today, we will learn that not all ministry is inside the church and you will be blessed as Ms. Latrish shares her journey of Unconventional Ministry. Latrish Climons is a Licensed Master cosmetologist and a licensed Cosmetology Instructor.  Even though Ms.Clinton's had great intentions on not going to school for anything other than cosmetology classes again, she is currently enrolled in MTI Ministry Training Institute in Thomson GA with a clear understanding of why she should not say what she will never do again. Ms. Climons uses all of the education she has obtained to serve as the Owner and master stylist at her first ministry, Salon Divine.  Ms. Climons is currently a member of The Lady Boss Club  and a former member of Grind Chat which they both help build her business, and her personal life. Ms. Climons knows the importance of having a mentor so she takes pride in giving back. She currently serves as assistant vice president with Queendom Motivators of Thomson, Ga., and a Youth Leader at her church InMotion. In Ms. Climons spare time she enjoys inspiring and motivating others, networking, meeting new people, traveling and most of all cultivating the gifts and talents that God has blessed her with.  Ms. Climons initiated her passion for motivating, encouraging and inspiring others by conducting live interviews with people that were willing to share their life experiences/testimonies/expertise with the world to help by changing lives one testimony at a time.”  

Selling Like HotcakesI know you've heard the phrase, “Selling Like Hotcakes”. But how exactly did that phrase come to be?To discover the answer we climb into our Wayback Transport Ship and set our coordinates for Colonial America in the mid and late 1700s. What we know today as pancakes and hotcakes, were known as hoe cakes, Johnnycakes, and flapjacks in the American Colonies. The term, “Pancake” appeared in England as early as the 1400s, but “Hotcakes” is distinctly American and comes from America's Colonial heritage.Let's meet Amelia Simmons who authored what is believed to be the first cookbook in the new world entitled “American Cookery” published in 1796. In Ms. Simmons's cookbook, we see two recipes, one for “Johny Cake or Hoe Cake” and a second for “Indian Slapjack. Ingredients for hoe cakes included milk, “Indian meal”, and molasses. The recipe for “Indian Slapjack” included milk, “Indian meal”, and four eggs.Whether you were a frontiersman, a farmer, or a townsperson, you very likely had eaten and loved these tasty delicacies. Some liked their hoe cakes fried in bear grease, while others preferred lard. Whichever camp you were in, everyone agreed they were delicious.By the early 1800s, hoe cakes were more commonly known as hotcakes. Hotcakes became big sellers at community and church social fundraising events. By 1825, any item that sold well was said to be, “Selling like hotcakes”.The phrase "selling like hotcakes” has flourished as an American saying for 200 plus years and continues to be popular today. If you're curious about exploring more about hotcakes, you'll find the references I used for this podcast in our show notes.If you would like to comment on this or any other episode, email me at CarterMethod@gmail.com. Until our next visit, I'm your host Stephen Carter wishing you blessings in abundance.References: Rebecca Rupp, “Hot off the Griddle, Here's the History of Pancakes”. “National Geographic”; February 27, 2018. https://www.nationalgeographic.com/culture/food/the-plate/2014/05/21/hot-off-the-griddle-heres-the-history-of-pancakes/Matt Soniak, “The Origin of 10 Food Phrases”; “Mental Floss”; October 10, 2010. https://www.mentalfloss.com/article/26034/origins-10-food-phrases.Webb Garrison, “Why You Say It”; Thomas Nelson Publishing. Page 152.Microphone used: BY

On this week's podcast, Just World Educational's president, Helena Cobban, discusses the currently high tensions between the United States and Iran with Amb. Chas W Freeman, Jr., a very distinguished former American diplomatist and the author of a number of very informative books. The most recent of these are collections of his essays on, respectively, US-Chinese relations and US policies in the Middle East.This week's podcast is linked to a column Ms. Cobban wrote that ran May 15 on the Mondoweiss website, under the title “Bolton pushing United States to over-reach in Iran”.In Ms. Cobban's interview with Amb. Freeman, he warns of some of the very dire effects that Pres. Trump's withdrawal from the six-party, 2015 Iran deal has already had on the rule of law internationally and on the continuing erosion of the safeguards the U.S. Constitution always placed on the executive branch's ability to enter willy-nilly into wars of choice. He warns of the dire consequences to be expected if Washington should get into a shooting war with Iran, and he assesses the roles that China, Russia, and the European countries that were also parties to the Iran deal might be able to play in defusing the tentions and de-escalating the conflict.Support the show (http://justworldeducational.org/donate/)

A typical Muslim-American teen saves the world (with the help of her teleporting dog), in our 50th episode, Ms. Marvel Vol. 1: No Normal by G. Willow Wilson. (Transcript) In today’s episode… In Ms. Marvel Vol. 1: No Normal by G. Willow Wilson, Kamala Khan is your average Pakistani-American teenager living in Jersey City. She feels her parents’ expectations of her are too strict, when she’s shown them time and time again that she’s a good, trustworthy daughter. When she decides to ignore their wishes and sneak out to a party, she and the other party-goers are enveloped in a strange green mist. Kamala finds herself with new, unruly transmorphic powers. Can she use her powers to emulate her favorite superheroes, fighting for justice and good to prevail? Or will her parents find out and […] The post Ms. Marvel Vol. 1: No Normal by G. Willow Wilson appeared first on Nouvelle ELA Teaching Resources.

Mindful Mondays-408# February 12th The Strong Within Daily Affirmation Podcast I Say Yes To Great Opportunities   “I imagine that yes is the only living thing.” ~E. E. Cummings That's a pretty powerful quote when you think about it, and usually the simplest things are the most profound. What I heard when I saw that quote is—there is ONLY life in yes. And if No is the opposite of yes, then “no” is lifeless.   But how can that be, because “no” is an answer in helping us describe what we don't want? And I wouldn't disagree with you, but I think there are better ways to focus—then on the word “no.” In my life coaching practice, I talk about focusing on what we want, not on what we don't want. With the law of attraction some people claim that the Universe cannot hear words that focus on lack—so words like “no” or “don't” are ignored by the Universe. However, those words can have power over us…because if we focus on lack we will get more of what we focus upon.   So when we say things like I don't want to be fat, I don't want to be poor, or I don't want to be alone—the universe negates those words we send out—and in this case, it erases the word don't. So the Universe, only hears you saying I want to be fat, I want to be poor, I want to be alone and will continue to send out that energy to you.   That's why E.E. Cummings quote was so profound for me. It reminded me about the power of our word choice, and it got me thinking about babies. Have you ever heard a baby who only says “no.” It makes you really think about how you speak to your children. Kathryn Perrotti Leavitt from American Baby wrote an article about how to discipline your baby better during certain ages in their life rather than by using the word “no.”   “From birth to 15 months you distract the baby from the forbidden toy or activity with a more appropriate one. From ages 12 months and up you utilize modeling by helping the child to do something more appropriate with a forbidden object. So if the child is hitting the kitty, you would show the child how to pet the kitty nicely. And from toddler and up you put their booty in time out.”   I spent a lot of time in time out myself. It helped to calm me down, but it was probably more for my mom so she didn't murder me. In Ms. Leavitt's article, she said something interesting. She said “of course, many of us merely say no when we catch our kids getting into mischief. Your child knows by the tone of your voice that "no" means something different from "I love you," but she doesn't understand the real meaning of the word.”   So we aren't expressing love as much when we take the easier road of saying “no” to our children. And that's what the Universe is trying to teach us as well. There are better ways to get what you want instead of focusing on the lack in your life. And like a baby who is wreaking havoc in your world, it's not because your child is trying to test your patience, but it's what Ms. Leavitt says is that your baby is exploring cause and effect.   And if we are like babies, we are throwing our words and actions around in our lives hoping for them to work someday, never really understanding that the Universe is modeling a way of life for us. It's showing us a better way to focus and live…if only we stop trying to force things from focusing on what's lacking, and instead learn to see the infinite power and abundance in our lives. And Mr. Cummings quote reminded me that when we lean more towards those lacking words that are easier to speak, we aren't being as effective in our lives because those words are essentially lifeless.   I know it seems like I'm being anal when I correct people on how they speak, but when we focus on the power of abundance we allow more abundance in. When we say “yes” we are bringing life to ourselves. It's not that we can't ever say “no,” or “don't,” or “can't”…but maybe we can say better things. Maybe we can pivot away from focusing on why we can't—to how we can, maybe we can focus away from what we don't want—to what we do want, and maybe instead of saying no we can find things that we want to say yes to.   So, let's try a few pivots in our thoughts and speech patterns…instead of saying I don't want to be poor maybe we could say I allow abundance to flow freely and effortlessly into my life. Instead of saying I can't, or it's too hard to lose the weight; maybe we could say I was created healthy and I have the knowledge and wherewithal to let the health that's already within me…out. Now, I know those are wordy affirmations. I was just thinking off the cuff, but what I wanted to display there is by saying “yes,” by focusing on abundance…it takes creativity. It takes a different thought process to not just stop at saying I want something or don't want something, but also to allow ourselves to stop blocking the energy of abundance into our lives.   Because what we want is already within us, we just haven't figured out a way to relax enough, to stop fighting ourselves. We've forgotten that the more we focus on the beliefs of why we can't have something, or don't deserve something, are behaviors that are teaching us about powerlessness in our lives. They are behaviors that teach us to close down instead of open up and allow the great gifts already within us out.   We are doing the equation backwards, hoping to gain something by focusing on our lack of something. Which traps us having to work harder every time thinking that what we want is outside of ourselves. I'm not saying there won't be work involved. What I am saying is that freedom comes from a shift in consciousness; a shift of understanding our power differently—which is to focus less on the physical work and begin working from the inside out.   Because saying yes to life is an easy task, but it's not a simple one. It's a pathway of understanding and seeing how the Universe works. It's a pathway of shutting our eyes off and letting go of our preconceived notions of how we think the physical world works. We've been conditioned to work harder if we aren't getting what we want, but it's not just about working harder…it's about seeing things differently. Working smarter means seeing something more; seeing beyond the physical; and understanding for everytime we say no, can't, don't or any other lacking word that takes our power away we are laying waste to life. But when we are more creative and see abundance by saying yes to the things we want, then we are creating life. And as E.E. Cummings said that he “imagined” yes as the only living thing…we will be purposeful in doing more than imagining…as we deliberately utilize words that have higher vibrational energies that bring life into the world.   Today's Personal Commitment: Have a notepad by your side all day, or keep track on your phone in your notes app. Make a tally mark anytime that you say no, or focus on your lack in some way. The more we become aware of how much we focus on our lack then the more enlightened we'll become. We'll realize that we are more negative than we realized, and that will bring about change. I never thought I was a negative person, I was always saying how happy I was, or trying to brighten someone's day…and then when I did a similar exercise…it really made me aware how I wasn't as deliberate with focusing on happiness and abundance in my life like I thought I was. Which was showing me how I was creating lifelessness rather than life.   Once you become aware of all you are doing negatively, it's not that you need to get rid of it, but it's about knowing that change is only a subtle shift. So instead of getting upset at yourself, think about what a loving parent would do for you—they would model better behavior. So be your own best parent and model better thoughts, actions, and words that focus on your infinite abundance that the Universe has in store for you. What do you have to lose besides your old lifeless ineffective ways?   I Say Yes To Great Opportunities   Thanks for listening.  I'm sending great energy your way as we become Strong Within together, Personal Development Life Coach- Chris O'Hearn Contact info- email: chris@strongwithin.com  phone:865-219-3247     Music by: - Zest by basematic (c) copyright 2011 Licensed under a Creative Commons Attribution (3.0) license. - I Have Often Told You Stories (guitar instrumental) by Ivan Chew (c) copyright 2013 Licensed under a Creative Commons Attribution (3.0) license. Location: Knoxville, Tennessee USA but available worldwide

Abigail Goliber of the Center for Democracy and Technology joins us today to talk about her role as Director of Development and some of the stratgeties she employs to effectively raise money. The Center for Democracy and Technology is a "policy shop" that focuses on keeping the internet "open, innovative, and free" for everyone. As Director of Development, she is usually not the person to do the Ask but does the preliminary work of determining who should be asked and cultivating those relationships -- then the CEO or another person will actually ask for the contribution sometimes doesn't happen for 1-2 years. In Ms. Goliber's fundraising research she uses a process called "LAI" to determine the top 10 people to approach to ask for money and then builds the relationship to make the Ask possible or likely. If you are responsible for fundraising for your organization, you can't afford to miss this episode!  Abigail Goliber is the Director of Development at the Center for Democracy & Technology (CDT), a champion of global online civil liberties and human rights. Prior to joining CDT, Abbie led the development efforts at 501cTECH, a local nonprofit supporting the technology of other nonprofits in the region, and honed her fundraising skills at two international human rights organizations, the RFK Center for Justice & Human Rights and Freedom House. She is fond of dusty vinyl, databases, and her two children.

[intro music]  Host – Dan Keller Hello, and welcome to Episode Fifty-Nine of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller. In our previous podcast, you heard about a group of leading MS researchers and clinicians calling for a big change in improving care for people with MS. The new report, called Brain Health – Time Matters in MS, makes the case for a therapeutic strategy to minimize disease activity. The report advises early diagnosis and treatment, and regular monitoring of disease activity. The report urges patients, physicians, health care payers, and policy makers to support the goal of life-long brain health. In this podcast, another one of the report authors, Dr. Helmut Butzkueven, talks about what the new treatment target means for patients and their doctors in the real world. This is one of our extra podcasts from the big MS meeting in Barcelona talking about ways that evidence from research can be translated now into better MS outcomes But first, here are some new items in the MS Discovery Forum. Every week, MSDF lists the latest scientific papers on MS and related disorders, with links to the abstracts on PubMed. Of more than 110 new studies published last week, we selected three as editor’s picks. MS has been traditionally viewed as a T cell–driven disease, but a new paper from Canadian researchers introduces another villain—a rogue type of B cell in people with MS that may fuel inflammation in two ways. This may be why general B cell depletion seems to work so well in MS and may lead to more targeted treatments. In a new twist on dietary fat and autoimmune disease, German researchers report that certain fats work through gut microbes to exert both good and bad effects. In mice, they found certain fats were protective against inflammatory fats. They have moved on to testing in healthy humans and hope to study the impact in people with MS. A cost-effectiveness study from Spain says do not judge a drug by its price alone. Glatiramer acetate may be more expensive than interferon-beta, but fewer relapses and reduced spasticity may make it more cost effective. Interesting, but you can be sure this fuller economic look will not be the last word on drug costs. [transition music] And now to our interview with Dr. Helmut Butzkueven, who directs the MS services at the Royal Melbourne Hospital and the Box Hill Hospital in Melbourne, Australia. We spoke with him at the recent European Committee for Treatment and Research in MS, or ECTRIMS, meeting in Barcelona about the Brain Health report that was launched at the meeting. The main thrust of the report – aimed at the broad MS community – is that time matters in MS. The report lays out several goals to maximize brain health over the lifetime. A critical one is early intervention. Interviewee – Helmut Butzkueven We know that early disease activity sets up long-term problems. However, early disease activity is often relatively silent to the eye. It’s not silent to the eye of the MRI machine and other monitoring tools that we have. So we would like clinicians and patients, not actually just in early disease, but starting right from the start to have a proactive monitoring approach to jointly assess their disease activity and take action if things are not going well. Interviewer – Dan Keller How much of an emergency is it? If someone finds out they have a cancer diagnosis, they rush to a surgeon, oftentimes. If they find out they have high cholesterol, they might take a year or two to decide to get on a statin. So what’s the time frame we’re talking about here? Dr. Butzkueven I think the appropriate time frame to think about is months, actually. We think that an MRI scan should be performed approximately every 12 months to assess disease activity, to assess how your current treatment is performing. So it’s not seconds or minutes; thankfully, multiple sclerosis isn’t exactly like an acute stroke or a heart attack. But it’s also not a time, particularly early in the disease when you could be setting up these kind of strategies, to just leave people be. We need to, when we first see patients, articulate our monitoring goals. MSDF And how quickly should someone, when they’re referred and there’s a putative diagnosis, get that scan initially? Dr. Butzkueven As soon as possible. I mean, scans are crucial, obviously, for diagnosis – accurate diagnosis, as well as for setting up the monitoring phase, because the first scan can then be compared to the next scan, and so on. MSDF What other goals are there for treatment and management? Dr. Butzkueven The key things that we want to really focus on, apart from what we’ve already discussed which is early diagnosis and articulating a treatment and monitoring plan to maximize brain health, is a joint approach. So for people with MS and doctors to both be empowered to jointly manage the disease. So this includes, of course, increasing consultation time, giving people time to discuss their MS with their managing team. I think this kind of move away from paternalistic medicine, to empowering patients to be part of the management process to self-manage is hugely important. That’s just in step with the modern world. The other thing is more indirect. Across the world, we face huge differences in access to disease-modifying drugs. Some of us living in the United States and Australia in Germany, Switzerland are luckier than others. And we really need to provide evidence to government that disease-modifying drugs are worth funding. MSDF Or else what happens? Dr. Butzkueven Else people, and ultimately governments, incur the costs of markedly worse disability. MSDF To empower patients takes certain knowledge and, I suppose, permissions or rapport with the physician. And to empower the physician, I suppose, takes knowledge, evidence, consult. So are these two different things? Do they move in parallel, but they require different activity? Dr. Butzkueven Yes, they do. Of course they do. To some extent, changing practice in an interaction can come from either side of the interacting party, but certainly patients, on the whole, probably need to be more demanding. They need to have access to evidence, and I’m going to say something controversial, to actually help assess the clinical care that they are receiving. So people should say, for example, if this report, the evidence suggests that perhaps we should be doing something else. What do you think? Physicians, as I said, need to be strongly encouraged to have a priori a specific plan. If you were someone with MS, and we saw you for the first time in our clinic, we should be telling you what the goals are. We should be telling you what our scheme of monitoring is going to be to maximize your outcome, to maximize your brain health. MSDF What kind of a role can longitudinal databases play in changing policy? Dr. Butzkueven They’re really the only source of long-term data. MS is a disease which you’re going to have for decades, once you’re diagnosed with it, and it likely will cause you and your government very significant costs over that time. But those costs can only be measured if we measure those outcomes, and the only way to really measure them is longitudinally. So databases embedded in the real-world healthcare collecting just a minimum of information on as many MS patients as possible can be enormously powerful, doing the sums in the first place, actually understanding how much disability there is; how much can be prevented with appropriate treatment strategies; and, dare I say it, how much money government could save. MSDF MRIs are now a powerful tool. Other medical specialties have had all sorts of invasive measures in the past. You could take biopsies of skin, breast, prostate, liver. You never had an assessment tool this powerful, but now this one is fairly noninvasive. It’s completely noninvasive. What can it tell you? I mean, people look for lesions, but there’s much more to be derived. Dr. Butzkueven Yes, of course. Lesions is still a key outcome, but the other thing is brain shrinkage – brain atrophy. So we, increasingly, understand that people who are experiencing significant brain loss – brain tissue loss – early in their MS will do worse, in the long-term. So here we have another target for monitoring. And people might say, well, I do an MRI scan, but there are no lesion changes reported. There’s no volume changes reported. But this world is changing rapidly. Image recognition analysis tools are advancing very quickly. I predict, within two or three years, routine MRI will actually spit out these metrics for us. At the moment, a lot of reporting, unfortunately, in the world is still what we would call qualitative rather than quantitative. But we’re going to start seeing those numbers, and we need to be ready to act on them. MSDF How much faster does the brain, in an MS patient without treatment, atrophy or lose volume compared to an age-matched control? Dr. Butzkueven So this is a question that I can answer in two ways, I think, to illustrate the concept. I could say it’s five to seven times faster. What I’m talking about there is averages, medians if you like. What I should be saying is that it could be anything. Your trajectory, as an MS patient, could be exactly within the normal range, I mean, sadly – particularly over the age of 30 – all of us lose a bit of brain volume a year: 0.3%, 0.4%. In MS, that could be your trajectory, and that would be fantastic. On the other hand, you could the person losing 3%, 4% – 10 times, 15 times normal. And we could pick that within a year or two, and that is the time to intervene, not when that ultimately results five, six, ten years later in progressive disease. MSDF You’ve made the analogy of managing MS to a new car and its warranty. Can you tell me about that? Dr. Butzkueven I was really just trying to say that plans for keeping things well, keeping things in shape, are quite prominent in society. So this analogy is simple. You buy a new car. What you get with it is a service book. The service book gives you a plan for managing your car. At 6 months, there’ll be a little tire change, oil change; 12 months there’ll be a major service, and so on. And the thing is, as a customer, I mean, you buy the car. It’s already there. It’s the same thing. We want clinicians and patients to demand and to deliver a plan. This is how we’re going monitor your MS to maximize the health of your brain. MSDF So this is your 6 month service. This is your 12 month service. Dr. Butzkueven Exactly. So, for example, in might be we will see you every 6 months, and we’ll do a neurological examination. We might do a particular cognitive test. We will do a repeat MRI scan, ideally on the same machine, once a year. We will be looking for the following: we will take action if things are going badly. If things are going well, then we’re reassured. But we need people with MS to demand this, and we need clinicians to deliver these plans. MSDF I don’t mean to make light of the situation of having the disease, but I think people respond well to something they already know, like a service plan. Dr. Butzkueven Yes, sure. I guess that’s why I’m using that analogy. Maybe we should say we need a service plan for MS. MSDF Is there anything we’ve missed or important to add? Dr. Butzkueven Nothing. We’ve covered the key recommendations of the report: access to early diagnosis, consideration of early treatment, a service plan, empowerment of people with MS to actually have accurate information, and being empowered in shared decision-making, and finally, the health economics situation, powered by clinicians – more and more clinicians – collecting long-term outcomes data on people with MS. MSDF And the Brain Health report is freely available, and we will link to it. I appreciate it. Thank you. Dr. Butzkueven It’s a pleasure. Thank you for talking with me. [transition music] MSDF Thank you for listening to Episode Fifty-Nine of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Carol Cruzan Morton. Heather McDonald curated the MSDF drug database updates. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations. Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances. We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org. For Multiple Sclerosis Discovery, I'm Dan Keller. [outro music]

Special Guest: Singer, Model, and Actress Kristen Henry King  (http://kristenhenryking.com) - Kristen battles with Multiple Sclerosis. She was inspired to write the song IMPERVIOUS chronicling her experience with MS.. listen to the song here on YouTube:https://www.youtube.com/watch?v=ScJit0ET-pw Multiple sclerosis (MS) is a potentially disabling disease of the brain and spinal cord (central nervous system). In MS, the immune system attacks the protective sheath (myelin) that covers nerve fibers and causes communication problems between your brain and the rest of your body.  Signs and symptoms of MS vary widely and depend on the amount of nerve damage and which nerves are affected. Some people with severe MS may lose the ability to walk independently or at all, while others may experience long periods of remission without any new symptoms. There's no cure for multiple sclerosis. However, treatments can help speed recovery from attacks, modify the course of the disease and manage symptoms.

In Ms. Van Horn's kindergarten class, we were all creative. I was part of a circle of 4 and 5 year olds who differed in many ways — not all of us could read or identify colors or numbers. But when it was time to color, draw or build something cool, we all rushed to the play area at full speed. We were all creative.  These days, I'm sure if I could arrange a reunion of my kindergarten classmates, we might all feel differently about our natural creativity. I know because I hear the same uncertainty when I talk with any group of photographers, who I'm sure were all once kindergartners.  My standard question, "what are you struggling with these days?" generates a lot of "I'm just not that creative" responses. Tom Kelley says that's just not true. Tom is an innovation consultant and author of the book, Creative Confidence, and I have fallen for his thesis. We are long past kindergarten, but if we buy in to the premise that anyone can be creative, and I do, how do we go about relearning the steps?  I have six strategies that anyone can use to learn creativity. Listen to the podcast

On this special Q-on-1 podcast edition of T2Q, I chat with author, Lisa Jey Davis!  What was supposed to be a YouTube video is instead a podcast thanks for my sheer genius skills as a videographer (total sarcasm right there).Lisa recently released her newest book entitled, "Ms. Cheevious in Hollywood: My Zany Years Spent Working in Tinsel Town."  The book talks about Lisa and her career working in Hollywood all while doing the single mom thing!"Welcome to the world of Ms. Cheevious. A world where nothing is sacred or predictable. In Ms. Cheeviousland, life is a farce - at least when it's not so damn serious. In this hilarious compilation of stories, Lisa Jey navigates the minefield of her past for tales from her divorce (which unleashed her on an unsuspecting Hollywood), her family, relationships and an enviable turn working in television. Whether she's hiding from an interested suitor in a Vegas casino, her son is mistaken for a homeless guy, her best friend is forced to scrub in to help choose her boobs' implant size, or she's so tipsy, even a strip club turns her away, Lisa Jey always seems to get herself into the most ridiculous situations."Check out my discussion with her on the Talk 2 Q Radio Show!  And check out her book on Amazon!Podcast length: 32 mins.Show No. 473 Hosted on Acast. See acast.com/privacy for more information.

On this special Q-on-1 podcast edition of T2Q, I chat with author, Lisa Jey Davis!  What was supposed to be a YouTube video is instead a podcast thanks for my sheer genius skills as a videographer (total sarcasm right there). Lisa recently released her newest book entitled, "Ms. Cheevious in Hollywood: My Zany Years Spent Working in Tinsel Town."  The book talks about Lisa and her career working in Hollywood all while doing the single mom thing! "Welcome to the world of Ms. Cheevious. A world where nothing is sacred or predictable. In Ms. Cheeviousland, life is a farce - at least when it's not so damn serious. In this hilarious compilation of stories, Lisa Jey navigates the minefield of her past for tales from her divorce (which unleashed her on an unsuspecting Hollywood), her family, relationships and an enviable turn working in television. Whether she's hiding from an interested suitor in a Vegas casino, her son is mistaken for a homeless guy, her best friend is forced to scrub in to help choose her boobs' implant size, or she's so tipsy, even a strip club turns her away, Lisa Jey always seems to get herself into the most ridiculous situations." Check out my discussion with her on the Talk 2 Q Radio Show!  And check out her book on Amazon! Podcast length: 32 mins. Show No. 473 --- Support this podcast: https://anchor.fm/t2q/support

[intro music]   Host – Dan Keller Hello, and welcome to Episode Nine of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s podcast features an interview with researcher Amit Bar-Or about how children with MS can illuminate early mechanisms of the disease. But to begin, here's a brief summary of some of the topics we’ve been covering on the MS Discovery Forum at msdiscovery.org.   According to a Cochrane meta-analysis, interferon-beta and glatiramer acetate are clinically similar treatments for multiple sclerosis. Researchers analyzed five head-to-head clinical trials and found that both drugs did similarly well in improving disability scores and MRI measures in patients with relapsing remitting MS. The researchers were not able to measure quality of life scores for the disease-modifying therapies.   We also published a Research Roundup this week all about social media and the role it plays in science. Social media can sometimes work against the scientific method if patients in a clinical trial are in the habit of oversharing on blogs, Facebook, or Twitter. Patients who discuss their symptoms online might affect the blinding of clinical trials. It’s not all bad, though. We also wrote about some great social media sites for researchers such as ResearchGate, LinkedIn, and even Reddit. We also shared some amusing links on how scientists can improve their communication skills such as the “Up-Goer Five,” a schematic of the Saturn V rocket explained using only the 1000 most commonly used words in English.   Every week we curate research articles on all topics related to multiple sclerosis and highlight our favorites in the “Editors' Pick.” Last week, some of our favorites were a review on oligodendrocytes, a research article about the origin and maturation of B cells, and a review about how the relationship between axons and myelin is involved in demyelination. You can see our weekly picks by going to our website, clicking on the “Papers” tab, and selecting “Editors’ Picks.” In addition to the Editors’ Picks, we link to every MS-related study found in PubMed. Last week was a banner week for MS studies. One hundred four were published, and we linked to them all.   [transition music]   Now to the interview. Dr. Amit Bar-Or is an associate professor of neurology and neurosurgery at McGill University. Some of his work focuses on multiple sclerosis in children and how they can shed light on the origin of the disease.   Interviewer – Dan Keller Welcome, Dr. Bar-Or. Let's talk about pediatric MS and what we can learn from it, especially about treating children but also about what it tells us about the disease, in general. Where does it stand now? What have you found in children?   Interviewee – Amit Bar-Or Well the last few years have seen a substantial increase in the appreciation that MS can occur, does occur in children. Probably one out of every twenty adults with MS will have had an initial episode clinically that manifested in the pediatric age group, which one defines somewhat arbitrarily as 18 in most places. But the presence of MS in children, of course, you can imagine creates a particularly sensitive clinical context with a lot of challenges to both the child and the family and caregivers. So understanding more about pediatric onset MS – for the purpose of better caring for the children – is one important accomplishment of some of the more recent insights that have been gained in the groups that have been studied. The other, of course, is that a challenge that we have, in general, in the MS field is understanding more about what initiates MS. What are the initiating mechanisms? We've learned a fair bit but still have more to learn about the genetics and about the environmental contributions. And we know that in adults with MS one can measure certain abnormalities, for instance, in their immune response, but we really don’t know whether an abnormality that is measured in an adult represents a consequence of dysregulation and an epiphenomena that may be abnormal but is not going to benefit the illness if you treat it, as opposed to an abnormality that is very much involved in mediating the problem. So the children given that at least, on the average, they're going to be closer to the biological onset of the illness could this provide an opportunity to get insights into earlier mechanisms in a context that is less confounded by such epiphenomena of chronicity, of long-standing illness. And so, one is viewing the studies that are ongoing now – in terms of trying to better understand the pediatric MS context – both in terms of the merits of understanding them for their own sake, as well as a potential window into the broader spectrum. One of the first questions that you then need to ask if you're considering whether children can teach you about MS, in general, is whether MS in children is the same illness as MS in adults. Maybe they're different illnesses. And so one of the approaches that has been taken is to say in adults who develop MS as adults the field has identified certain genetic risk factors and certain environmental exposures that are thought to contribute to risk. And one of the first questions that has been asked is do those same risk factors – genetic and environmental – play out in children who develop MS? And the answer is essentially yes. For the same types of genetic contributors that have been identified in adults, one can see them as risk factors for developing MS in children. And the same environmental exposures – which include, for instance, low levels of vitamin D or exposure to a particular virus called Epstein-Barr virus at a certain phase – these again in children have emerged as being risk factors for the development of MS. So one thinks that at least based on that indirect evidence we can think of pediatric onset MS as, indeed, a reflection of the same illness at earlier time points and again reinforcing the value of understanding early mechanisms less encumbered by chronic disease processes.   MSDF What early mechanisms have you been able to discern from looking at the development of MS in children?   Dr. Bar-Or Well, there are a few very interesting observations that have emerged, and they include observations both on the immune system side and on the central nervous system side. So I'll start with the central nervous system side. We have always been challenged with the effort of trying to understand what are the actual targets of injury in multiple sclerosis. Certainly over the years, it's been described as an illness that affects myelin – the myelin making cells or the oligodendrocytes – so people have considered myelin antigens, or potential targets, as important targets in the disease. But much of that thinking has, in fact, been shaped by the most commonly used animal model system, which is experimental autoimmune encephalomyelitis, where you, in fact, inoculate the animal in its periphery with an antigen of the CNS typically a myelin antigen such as MBP or PLP or MOG. The animal has T cells that then get activated in the periphery that can respond to that antigen. They traffic to the central nervous system, identify the antigen, and contribute to an inflammatory injury process. In MS, though, we do not know what the triggering insult is or what they are in terms of the sequence, and we still don't really know what the actual targets of the illness are. This is important because more and more we've appreciated over the last decade or two that in addition to the myelin and the oligodendrocytes there's a very important injury to the neurons and their axons – the neuronal cell bodies and their extensions where they deliver their signals – which are typically wrapped in some cases in myelin, and others remain demyelinated or lacking in myelin. The issue of what the target is could guide both a better insight into initiating mechanisms – and how to deal with them therapeutically – as well as therapies that are designed to try to target very specific immune responses. Because if we knew what the specific antigens were, we might be able to develop approaches to change the immune system in what's called an antigen-specific way. Which means we try to change only the bad guys' cells or enhance the very specific regulatory cells that will control them without impacting the rest of the immune system, which would be conceptually much better in terms of having both benefit without risks of limiting the ability of the immune system to do, for the most part, what it does normally. One study in which we had the opportunity to compare spinal fluids from children presenting with a first episode of what may or may not be MS, and these children are then followed very, very carefully prospectively – meaning forward in time – as part of the Canadian Pediatric Demyelinating Disease Study was to establish over time who, in fact, has MS and who doesn't. And then go back to those early samples from that first clinical event and compare it what's called a proteomic level where we say we don’t know what the differences might be, but let's use a technology that breaks the CSF down – the cerebrospinal fluid down – into all of the components that make the different proteins. And then we have a survey of all of the different protein content and compare between the two. And we anticipated that we would see differences in those typical myelin antigens that the community has thought over the years are the relevant targets. So first surprise was we did not see any differences in those particular previously or traditionally implicated antigens. However, we did see differences in a number of molecules that are referable to a tiny little apparatus that serves an important physiologic function, and that's called the axoglial apparatus. That area is a tiny, tiny area where the glial cell – in this case the oligodendrocyte, the myelinating cell – its membrane dives down and attaches to the axon. That point of contact is part of what forms the axoglial apparatus. And it becomes a very enticing potential target of injury because an injury to that target would be expected to cause, on one hand, injury to the myelinating cell (maybe leading to demyelination) but also could produce an injury to the axon itself perhaps contributing to the axonal and neuronal injury. And again, we now know that both of those injuries are very much part of the MS disease process, or at least part of the consequence of the MS disease process. So this is just one study in children where we may be getting clues in a more refined way to the particular early targets of the disease or those structures involved in early in the disease, which is now guiding some of the thinking about how to followup on that both to better understand and potentially target therapeutically. An example on the immune system side is that there has been the sense in the broad community in MS and in other human autoimmune conditions that certain types of cells – that are called effector cells – may be dysregulated in MS either because they are overly active or insufficiently regulated or both. So either an effector problem, a regulator problem, or a combination of the two. But it's been difficult to identify which of these cell subsets is really involved in the disease as opposed to dysregulated, as I mentioned before, as a consequence of the disease. And the children have provided an opportunity to again look early on. And one study had identified that one of the abnormalities had appeared to involve a failure of normally developing regulatory T cells – this is work by Regitta Walderman (12:20) and Betina Belint at the time – which showed very nicely that in children with MS, as compared to controls, there seems to be a deficiency in the development or the maintenance of regulatory T cells. And in fact, it looked as though cells that normally get educated by an organ that we call the thymus, which is very active particularly in children, seemed to be getting older faster in the kids with MS. And so this raises the interesting question of whether there is a premature senescence or premature aging, in a sense, of certain immune cell populations so that over time their functional capacity is not quite the same, and if this is on the regulatory cell side and you have a diminished capacity for whatever reason you might expect the effector cells to be able to spillover inappropriately and participate in disease. So those are two examples – one of the neurobiological side and one of the immunological side – where children are providing what I would consider very important insights into the overall MS spectrum.   MSDF Let me ask you about the injury to the axoglial complex. Glia provide supporting roles both nutritionally and through other molecules and as well as physically. Do you think this is an injury to the oligodendrocyte – which then impacts the axon – or is it some sort of attack which just hits this area, in general?   Dr. Bar-Or Well this is a great question. And there's an ongoing discussion as to the chicken/egg; what gets injured first? What we do know is that when you look at the available tissue for studying pathology of MS – which, of course, tends to be quite biased to late in the disease where people may die for other reasons and postmortem – we have relatively little insight pathologically in what's happening in patients in early stages of the disease. Fortunately, people who develop MS even through the diagnosis rarely, rarely require a biopsy to get tissue to establish the diagnosis. And in fact, if you're doing a biopsy, it's usually because it's atypical, not typical. So we have several groups who are working hard and making important contributions, including into this earlier event, but there is still a big gap in our understanding of the early events and hence the very difficult to talk about initiating processes. But you bring up the very important context of the neurobiology of MS, which involves the ongoing function and integrity of the brain cells, including the neurons and the different glial cells. Those include the oligodendrocytes which make myelin but also the astrocytes which provide, among other things, important support to the blood-brain barrier and important support to the neurons, as well as the microglial cells which are very crafty cells of the central nervous system that probably performs several different functions. And all of these cells when they get activated or insulted they may fail to provide the normal physiologic protection, or they may even actively contribute to propagating injury. If you injure the oligodendrocyte in the myelin, the axon that is served by that myelin is working harder and may peter out over time. On the other hand, the integrity of the axon is important for the oligodendrocyte to maintain its myelination and its wrapping (15:34). So there's very important crosstalk, and it is very likely that injuring one element sufficiently will result in deterioration of the other regardless of which one you're injuring first. From a therapeutic standpoint, our efforts are to understand this crosstalk better and to understand how to try to establish protection, if not repair, of any one of these elements as part of the overview. It's clear that if you don't have an axon there's nothing to myelinate; if you don't have the myelinating cells you're left with bare axons that don't function or survival as well with the increased demand. And so, we need to have a more complete view so that we can approach not just a single biology at a time but, of course, we also – to understand any given biology – have to develop approaches that will isolate that biology so we can understand it. And one of our challenges is that we do not really have good models of those neurobiological aspects of MS to study. The EAE, for instance, which recapitulates some of the features of MS, has not really been shown to recapitulate those particular features that we're discussing.   MSDF Finally, let me get back to one thing you mentioned that if you can identify the antigens of interest that are either spurring an attack or being targets of an attack the idea would be to find specific ways to approach those antigens. Now we have certain drugs that will deplete B cells, and they show benefit. We have certain drugs that will keep trafficking down cell adhesion molecules, and those seem to have benefit. Is there a focus on any particular antigens at this point and any particular approaches (clonal deletion, any sort of small molecules)? Where's that going?   Dr. Bar-Or Well there are a number, and I probably won't be able to summarize all of them here. But there are generally several different strategies that try to target the immune system in a much more selective way than most of the approved therapies, including the not yet approved B-cell depleting approach which, of course, is more specific than targeting cells beyond B cells but is still depleting quite a few cells. Many of the B cells in the circulation, at least, are depleted. One extension to what you had raised is that it's fascinating to see how different approaches can achieve benefit of decreasing new disease activity, and we need to be able to sit back on a regular basis and integrate the insights from all of the successful, as well as unsuccessful, therapeutic interventions, including those that were not only unsuccessful in limiting new disease activity but the occasion where they increased new disease activity. What would appear initially paradoxical. Understanding all of that will give us very important insights into the disease itself. As far as antigen-specific approaches, one way is if you know what the antigen is – which, of course, we don't really know but we can hypothesize – you can try to develop induction of regulatory cells with that specificity or killing off or creating a state of unresponsiveness, also know as (18:40) of the effector specific cells or a combination of the two. There are different strategies that people have tried to use that are based, for instance, on the requirement of a T cell during activation to have an antigen-presenting cell present the antigen. And the profile of molecules both through contact and through secretion that the T cell can then receive in that environment of interaction with the antigen-presenting cell can often define the response profile, subsequently, of that cell. And if certain molecules such as costimulatory molecules are not present in that interaction or modulated, you might actually shut the cell down – you may not kill it, but it will be unresponsive or hyperresponsive – and that would be one strategy. Another, for instance, is to say well I don't know exactly which particular antigen, but I think it's myelin antigens. Let me get out of a patient's blood their immune cells and stimulate them to a variety of potential antigens, and whatever grows will reflect what grows in that person against the CNS antigens. And use that in a way to modify them so that they cannot cause problems and inject them back into a patient almost like a vaccine with a view that you are now giving that person whatever their T cells were that could respond to myelin, and their immune system now will respond to them and kill them and kill any other such cells that are present in the body leaving the rest of the immune system intact. And will that limit that person's ability to respond to their myelin? That again, is individualized medicine, which is one of the hot areas to pursue in the future, recognizing that if we hang our hat on a single target that may be true for one person but not for others or may be true for a person at some point in their illness but is not the predominant target later on. And so I think that using these kinds of approaches, which recognize the specificity or the selectivity, at least, as potential but also that there are very likely to be differences across individuals and maybe even with the same individual over time. And to try to individualize the therapy that is going to be most suitable for that person at that time.    MSDF Thank you, Dr. Bar-Or.   [transition music]   Thank you for listening to Episode Nine of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]

Aimee Bender is the guest. She is the bestselling author of several books, including The Girl in the Flammable Skirt, The Particular Sadness of Lemon Cake, and The Color Master. The LA Times says "Bender’s work has never been the stuff of manic pixie dream-girl lit. Her fairy tales are dark and wicked, not hipster-precious and faux old-timey. Her sorcery altogether avoids the saccharine, and the thrills and chills of this sometimes sexual, often horror-drenched collection are completely adult. At a time when realism reigns supreme over the literary landscape, one can argue it is absolutely imperative that Aimee Bender be spotlighted for what she is: a vital MVP of modern letters, period…In our world of flash-and-trash insta-Internet-oddities and stranger-than-fiction social-media-bloopers, she will have surpassed the simple feat of inventiveness to own a most dazzlingly urgent relevancy." And The Wall Street Journal says “The fairy-tale elements in her writing, far from seeming outlandish, highlight the everyday nature of her characters’ flaws and struggles. In Ms. Bender’s stories and novels, relationships and mundane activities take on mythic qualities.” Monologue topics: Episode 300, thank you.  Learn more about your ad choices. Visit megaphone.fm/adchoices

[intro music]   Host – Dan Keller Hello, and welcome to Episode Three of Multiple Sclerosis Discovery, the Podcast of the MS Discovery Forum. I’m your host, Dan Keller.   This week’s Podcast features an interview with investigators Daren Austin and Susan Van Meter of the pharmaceutical company GlaxoSmithKline, who will discuss results from the MIRROR trial of ofatumumab, a human monoclonal antibody already FDA approved for leukemia. But to begin, here’s a brief summary of some of the topics we’ve been covering on the MS Discovery Forum at msdiscovery.org.   First, a complementary approach to treating MS. A new study lends support to the prevailing theory that the immune system’s ancient complement system drives persistent axon damage between MS relapses. The complement system consists of proteins that can activate innate and adaptive immune responses, but have a poorly understood role in autoimmune diseases. The new results suggest that anticomplement therapies might help prevent damage to axons. Clinical trials are in the early planning phases, but one of the study’s authors cautions that even if this approach proves valuable, it would be used in addition to and not in place of therapies targeting inflammatory T-cells.   In a second article, we report on a study suggesting that inhibiting a common cytokine called granulocyte macrophage colony stimulating factor – GM-CSF – might be a new therapeutic target to treat MS. Studies have shown an association between the cytokine and MS flares. A newly described class of T helper cells produce GM-CSF, and inhibiting that production might be helpful in preventing flares.   Finally, we’d like to call your attention to our blog series called “MS Patient, Ph.D.” There are numerous blogs and other websites where people with MS talk with other people with MS. And there are also a few, including our own MS Discovery Forum, where MS researchers and clinicians talk with other researchers and clinicians. But we can’t think of any sites where people with MS who have a scientific bent communicate directly with researchers and clinicians. That’s what MS Patient, Ph.D. is all about. It’s a place where two articulate people struggling with MS, both of them Ph.D. biologists, present their points of view about their disease and about the state of MS research. You’ll find some of their opinions provocative and controversial, and we hope you’ll join the discussion. In our two most recent posts, Griselda Zuccarino-Catania discussed the snake oil treatments touted as MS cures and relates that to the recent testimony before the U.S. Senate Committee by Dr. Mehmet Oz. And Emily Willingham discusses conflicting evidence on whether exercise is good or bad for people with MS.   [transition music]   Now, onto the interview. Here at the 2014 annual meeting of the American Academy of Neurology, we caught up with Dr. Daren Austin of GSK in London. He’s presenting the MIRROR study, which is a randomized, placebo-controlled study doing dose-ranging on ofatumumab in subjects with relapsing-remitting multiple sclerosis.   Interviewer – MSDF What led you to implicate B-cells? We often think of T-cells as a target in multiple sclerosis.   Dr. Austin Well, there’d been previous work using other anti-CD20 therapies in immune inflammation diseases that have shown efficacy. Most notably the first was rituximab in rheumatoid arthritis and subsequently rheumatoid looking at multiple sclerosis, so the precedence for anti-CD20 modulation as a target for inflammatory diseases was known before we came to design this study. What wasn’t known before we designed the MIRROR study was how much modulation of B-cells would generate what level of clinical benefit. The primary objective of this study really was to look at how best we could administer ofatumumab, which is an anti-CD20 monoclonal antibody, to modulate B-cells and then modulate clinical disease.   MSDF How’d you go about it? Can you describe the study and also what you found?   Dr. Austin Well, the study was a randomized, double-blind, parallel group study looking at relapsing-remitting multiple sclerosis patients who had to have evidence of disease activity, i.e., they they would be requiring therapy. What we did was we took what we knew about the pharmacology of ofatumumab – and we’d previously conducted both an intravenous study in in multiple sclerosis patients, so we knew the drug could be efficacious in suppressing MRI lesions, and we took what we knew about the clinical pharmacology of ofatumumab; and, namely, that it is an extremely potent depleter of B-cells. We began by by hypothesizing that there was a link between the level of B-cell suppression and the level of MRI lesion suppression. From that we produced some some predictions. And our predictions led us to suggest that extremely low doses given relatively infrequently could be beneficial. We produced a transimulation before we conducted the trial, and we proposed a range of doses and dosing frequencies. So the first dose level was was placebo, the next level was a 3 mg dose that was given once every 12 weeks. The next dose level was 30 mg given once every 12 weeks. The next dose level was 60 mg given once every 12 weeks. And, finally, because we knew that a dose of 200 mg was efficacious over 12 weeks, we gave 60 mg every 4 weeks to give a cumulative dose of 180 mg. So we explored a dose range, a cumulative dose range, of 3 mg to 180 mg, with the primary endpoint being evaluation of MRI lesions at 12 weeks. Placebo patients were then given a 3 mg active dose. All patients were then followed for a further 12 weeks, and we now have the 24-week data. And, again, treatment then ceased and patients were followed-up to see repletion of B-cells.   And what we found in the study was, yes, that ofatumumab is is extremely potent at depleting B-cells. That single 3 mg dose was capable of knocking out about 75% of circulating B-cells, and the 60 mg dose given every 4 weeks depleted almost all patients right down to the undetectable levels, which is had been seen in the past. What we were able to do then is to look at the dose response to dosing of ofatumumab at the 12-week endpoint, and what we found is that at the cumulative dose of 180 mg, we see over 90% suppression of lesions. But we found that there was no incremental benefit in going above doses of about 60 mg, and in fact the dose that generated the half maximum effect from an analysis of the data was predicted to be less than 3 mg; a single 3 mg dose generated half of the maximum benefit.   Having shown that we have got clinical suppression of MRI lesions, we then decided to relay the pharmacology of ofatumumab, which is suppression of B-cells, to the clinical benefit, which is suppression of MRI lesions. And that was the purpose of this abstract, that the analysis that we presented showed quite clearly that there was a very strong relationship between how much you suppress B-cells and how much you suppress MRI lesions. But the surprising thing from this data is that you don’t have to fully deplete all patients to below the limit of quantification to derive benefit. We showed using a variety of analyses that patients that have circulating B-cells of less than 32 to 64 cells per microliter on average over the course of the dosing interval would still derive maximal benefit, i.e., suppression of lesions, to 90%. And that’s intriguing. And the reason it’s intriguing is that the doses that we gave are only acting on peripheral B-cells. There’s been speculation as to where the drug needs to get to give clinical benefit, and that the doses that we give – up to 60 mg doses – the drug can’t penetrate the blood-brain barrier. And, therefore, we know that by modulating peripheral circulating B-cells, we are deriving the maximal benefit in suppression of MRI lesions.   MSDF Is the drug acting on mature B-cells, or in B-cell development which may then migrate into the CNS during development?   Dr. Austin So ofatumumab only binds to the cells that express CD20, so there is some consideration as to where those cells exist. Now it is entirely possible that immature cells maybe sort of enter the periphery not expressing CD20, move to across the blood-brain barrier where they subsequently develop. That is a possibility. And if that is the case, our drug is not capable of reaching those B-cells. Only cells that express CD20 are depleted, so plasmablasts, for example, are not depleted because they do not express CD20. It is just that that population of of of B-cells that are expressing CD20. There’s a lot of hypotheses about how B-cells are working, how they may be producing pathogenic antibodies that may be detrimental. In MS it could be anti-myelin antibodies, for example. But we don’t absolutely know that that is the sole pathogenic mechanism in MS, as in other diseases. It may well be that B-cells are modulating other, say, T-cell activity, which we do not yet know. What we do know from our trial is that modulation of peripheral B-cells gives you benefit, and that’s the principal finding, and that the doses that we modulate at are much, much lower than the oncology doses that have previously been given.   MSDF So you don’t yet know whether you have a direct antibody effect on B-cells, or whether it’s acting possibly through antibody-dependent cellular cytotoxicity.   Dr. Austin We do know that the mechanism of B-cell depletion is through both ADCC and complement-dependent cytotoxicity. That is the primary pharmacology of ofatumumab on cells that express CD20. We do not and cannot say for certain what those B-cells were doing prior to being depleted and how they were driving the pathogenic process, but we have shown that by depleting them to levels of less than 32 cells per microliter, you see suppression of disease activity. One of the important things to say is that the regimens at the every 12-week dosing that we’d selected, there is some evidence that B-cells do start to grow back in at least half of patients, so dosing every 12 weeks pre-dose, there are some circulating B-cells. If we look at immature B-cells, there are lots of immature B-cells but they haven’t yet moved to the to express CD20. So what we see is that the regimens we’ve designed, there is some evidence of of repletion, i.e., that patients are seeing clinical benefit despite having circulating B-cells.   MSDF How does this fit in with the pathogenetic mechanisms of T-cells? Are there interactions in the pathologic process besides the regulatory effect of T-cells themselves?   Dr. Austin The truth is I don’t think we can say. All we can say is that modulation of B-cells circulating in the periphery gives clinical suppression of of MRI lesions, and by implication we believe at the clinical efficacy in multiple sclerosis, and possibly other diseases, although such low doses have not have yet to be tested in other diseases.   MSDF In terms of B-cell repletion, have you also followed new lesions after B-cells come back?   Dr. Austin We have the 24-week data and we have preliminary data out to 48 weeks, and that data won’t be reported yet because we’re still in the process of ana analyzing it. But in the trial we designed, we had individual follow-up to watch patients B-cell replete back up to the lower limit of normal or their baseline, and we are measuring their follow on MRI lesions.   MSDF Working along with Dr. Austin on this project is Dr. Susan Van Meter, the clinical physician involved in the project. Let me ask you, what sort of adverse effects did you see during the trial?   Dr. Van Meter The most common adverse effect that we saw was injection site reactions, and that can include things such as redness at the injection site, nausea, flu-like symptoms. That occurred in most of the patients receiving ofatumumab. It also, very interestingly, occurred in about 15% of patients who received placebo.   MSDF In terms of the more serious and chronic effects, did you see any opportunistic infections or especially progressive multifocal leukoencephalopathy?   Dr. Van Meter So you would certainly worry about infections, especially serious infections. We did not see any cases of PML or other opportunistic infections, and, in fact, no serious infections. As typical for patients with MS, patients did have a variety of infections – urinary tract infections, respiratory infections – but this was seen in all patients including placebo patients, and there was really no evidence of an increased rate of infection in patients receiving ofatumumab.   MSDF What do you see as the potential clinical significance of these findings?   Dr. Van Meter Well, I think it offers another therapy option for patients with MS. Obviously, we have to do further development and show that the benefits that we saw on MRI translate into clinical benefit on relapse rates and disability progression. But we’re offering a subcutaneous dose as opposed to an intravenous dose of medication, and potentially offering a medication that doesn’t completely wipe out one part of your immune system.   MSDF Is there a reason for selecting ofatumumab over rituximab?   Dr. Van Meter Well, I think that would be a clinician choice, to be honest. Rituximab has certainly been studied for multiple sclerosis even though it’s not indicated for multiple sclerosis. There’s another B-cell therapy that will be on the market when we launch, ocrelizumab, and I think it will come down to physician and patient choice.   MSDF Is there anything we’ve missed or that’s important to add?   Dr. Van Meter Well, I think at Glaxo we are very excited about this data; this is new science. Obviously, we need to understand more about it, replicate it. But for the first time, we’ve shown that you don’t need to completely destroy all the B-cells to have effect in multiple sclerosis.   MSDF Very good, I appreciate it. Thank you.   [transition music]   Thank you for listening to Episode Three of Multiple Sclerosis Discovery. This Podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations.   Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.   We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.   [outro music]

Neurofascin (NF) is a cell-adhesion molecule that is found at the nodes of Ranvier. The 186 kDa isoform of neurofascin (NF186) is expressed on the axon in the exposed node, and the 155 kDa isoform (NF155) is expressed on myelinating glia at the paranode. NF186 is essential for clustering of sodium channels to the nodes while NF155 is needed for close paranodal interactions between myelinating glia and axons. The neurofascins are found in both the peripheral and central nervous system (PNS and CNS). NF-specific autoantibodies were identified in serum of multiple sclerosis (MS) patients using a proteomics approach with two-dimensional Western blotting of human myelin glycoproteins. A monoclonal antibody (mAb) specific for NF was shown to induce axonal injury in an animal model of MS, experimental autoimmune encephalomyelitis. This indicated that NF is a relevant autoantibody target in patients with inflammatory diseases of the nervous system (central and peripheral), but actual abundance of anti-NF autoantibodies is unknown. The objectives of the thesis were the following: 1) Develop assays to detect autoantibodies against human NF. 2) Determine the prevalence in patients with MS and with inflammatory diseases of the PNS. 3) Characterize the reactivity by immunoglobulin isotyping, serial dilution, epitope mapping, and staining of nodal structures in tissue sections. 4) Affinity purify anti-NF antibodies from plasma exchange material. 5) Determine possible in vivo effects of anti-NF antibodies in the PNS using a neuritis animal model. First, we expressed the complete human NF155 and NF186 on the surface of stable human cell lines, produced the complete extracellular portion of the NFs in HEK293 cells, and expressed truncated variants of the NFs in E. coli. With these reagents, we set up three antibody detection assays: cell-based assay by flow cytometry, ELISA, and Western blot. These assays were validated using NF-specific monoclonal and polyclonal antibodies, and optimized with a test cohort of serum samples. We screened 687 serum and 48 plasma exchange samples from patients with MS (n = 233), inflammatory diseases in the PNS (n = 294), and controls (n = 208). From serum analysis, we observed low prevalence of anti-NF reactivity (3%) by flow cytometry and/or ELISA despite broad reactivity in almost half of the serum samples analyzed by Western blot. Reactivity observed by flow cytometry and by ELISA were congruent only in the patients with the highest reactivities. The anti-NF antibodies were NF-isoform specific, mainly IgG subclasses, and at high titres in some cases. Using truncated variants of NF fused to super green fluorescence protein (sGFP), we showed that reactivity of anti-NF Abs was largely directed towards the membrane proximal extracellular domains that are unique to each isoform, while the membrane distal immunoglobulin-like domains and fibronectin domains were not recognized. A small proportion (3%; 8/254) of patients with GBS and CIDP showed reactivity to human NF by ELISA. A few showed a particularly high reactivity (up to 1:10 000 dilution) to NF. Two CIDP patients showed a particularly high (up to 1:10 000 dilution) anti-NF155 reactivity by FACS and ELISA, recognized paranodes in tissue sections, and exhibited dominant IgG4 subclass usage. Another CIDP patient who benefited from plasma exchange had a persistent anti-NF155 reactivity by ELISA in serum, and after affinity purification, anti-NF186 and -NF155 reactivity by FACS and ELISA were detected in addition. These antibodies were mainly IgG3, with minor contribution of IgM and IgA. To investigate possible functions of anti-NF antibodies in inflammatory PNS diseases, we injected two different monoclonal antibodies (mAbs) into a P2-peptide induced experimental autoimmune neuritis (EAN) animal model at disease onset. We found that while the anti-NF mAbs prolonged and exacerbated clinical disease in these animals, they could not induce disease on their own. We detected NF-reactivity in a small proportion of MS samples (3%; 7/225) by ELISA and flow cytometry. We obtained follow-up material from two NF-reactive patients and saw a persistent NF reactivity in one of them. To increase detection sensitivity, we affinity purified anti-NF antibodies from plasma exchange material of patients with MS (n = 8). IgG, IgM, and IgA were isolated from most of the samples; they were found to recognize NF155 and to a lower extent NF186 by ELISA and in a few also by flow cytometry. This indicates that low levels of anti-NF antibodies exist in a proportion of MS patients. In conclusion, 3% of serum samples from patients with PNS inflammatory neuropathies (GBS and CIDP) showed reactivity by ELISA and none of the controls. In an animal model of autoimmune peripheral nerve inflammation, we showed, using two anti-NF mAbs, that antibody targeting of NF can enhance and prolong disease course. This suggests that antibodies to NF may be relevant for a small group of patients with peripheral inflammatory neuropathies. In MS patients, 3% showed anti-NF reactivity by flow cytometry and ELISA. Furthermore, low levels of anti-NF antibodies that could be detected by ELISA and flow cytometry after affinity purification were additionally found in some MS patient samples that were unreactive by serum screening. This raises the possibility that low levels of antibodies to NF are present in some MS patients and may contribute to the pathogenesis of this chronic disease.

This study investigated the immunobiology of MOG-induced EAE in the DA rat, an animal model, which reproduces the immunopathology of the type II MS lesion (Lucchinetti et al., 2000). A newly established immunisation protocol results in a highly synchronised biphasic form of EAE, which mimics the disease course of secondary progressive MS, albeit in a strongly abbreviated time course (Figure 3.1.1). This study demonstrates that MOG-specific autoantibodies are responsible for initiating clinical relapse and driving disease progression. On the background of mild, sub-clinical inflammatory activity in the CNS, pathogenic antibodies enter the CNS and mediate demyelination, a process that in turn amplifies the local inflammatory response (Figure 3.1.14 A). It should however be noted that lethal clinical relapses may also occur in the absence of a pathogenic antibody response if an inflammatory lesion develops in a region of the CNS that is particularly sensitive to damage, or where it may perturb vital functions, such as the brain stem. Although antibodies have been shown to amplify the severity of ongoing clinical EAE (Schluesener et al., 1987; Linington et al., 1988; Lassmann et al., 1988), firm evidence for a role in driving relapse and disease progression was missing. This study has now established this principal, which in all probability is relevant to our understanding of the pathogenesis of severe, steroid non-responsive relapses in MS patients. However, this model of EAE is an artificial system, in which the role of antibody is only apparent because of the different kinetics of MOG-specific T and B cell responses. In MS we still have to answer two crucial questions, namely the identity of the autoantigens targeted by the demyelinating antibody response, and the factors that may trigger this response. MOG is the only myelin protein known to initiate a demyelinating antibody response in EAE, and MOG-induced EAE has provided a valuable tool to identify the role of pathogenic autoantibodies in immune mediated demyelination. However, there is a major discrepancy between the proportion of MS patients with pathogenic MOG-specific antibodies in their circulation (5%; Haase et al., 2000) and the frequency of patients with pathological changes suggestive of antibody-mediated pathomechanisms (>50%; Lucchinetti et al., 2000). This discrepancy may in part be accounted for by the absorption of the pathogenic antibodies into the CNS, which will lead to a dramatic reduction of the antibody titre in the periphery, as demonstrated in section 3.1.3.4 of this study. On the other hand, it is unlikely that MOG is the only target autoantigen, which is exposed on the myelin surface and can therefore initiate a demyelinating autoantibody response. The identification of potential targets is a prerequisite to develop diagnostic kits to identify those patients with pathogenic autoantibody responses and then provide an appropriate therapy such as plasma exchange, or immuno-absorption. As demonstrated in this study, DNA vaccination using a plasmid encoding a myelin antigen is one approach to generate high titre autoantibody responses directed against the native protein. The pathogenicity of this antibody response can then be assayed in the same animal by inducing EAE. This method circumvents problems such as purity, yield and denaturation, all of which complicate any study using antigens isolated from the CNS or generated using recombinant technologies. Coupling this approach to a proteomics based analysis of the myelin membrane and reverse genomics to identify candidate gene products provides the means to map out those protein antigens that can be targeted by a demyelinating autoantibody response. The feasibility of this concept is currently being tested in the rat using PLP and MAG as myelin components that may in certain circumstances provoke a pathogenic autoantibody response. Such an analysis will, however, not detect pathogenic antibody responses to glycolipid antigens, which are major target autoantigens in a number of diseases affecting the peripheral nervous system such as Guillain Barré syndrome (GBS). In GBS a pathogenic antibody response to gangliosides appears to be triggered by infections with particular serotypes of Campylobacter jejuni (Fredman, 1998; Willison and O´Hanlon, 1999). In the majority of patients these antibody responses are an acute phenomenon and disappear as the patients recover (Hahn, 1998). It is conceivable that a similar mechanism is responsible for the initiation of severe relapses in some MS patients, if an infection triggers a cross-reactive antibody response to a surface glycolipid epitope. This would induce an episode of acute CNS demyelination that would not be immediately responsive to immunosuppressive therapy, as tissue damage and amplification of the local inflammatory response would be driven by the pre- existing antibody response. Analysis of the autoantibody responses in MS should therefore be extended to examine lipid as well as protein autoantigens. Such studies should also not be restricted to myelin, but also address the question of responses to other structures such as the axon and oligodendrocyte progenitor cells. Such autoantibody responses are however only conditionally pathogenic, in other words their pathogenic potential is only expressed if they can enter the CNS across the blood brain barrier (BBB)(Litzenburger et al., 1998; Bourquin et al., 2000). In EAE the inflammatory insult to the CNS is responsible for the disruption of BBB function and the entry of antibody into the nervous system. MS is characterised by repeated episodes of CNS inflammation but what initiates and maintains this response is unclear. The observation, that DA rats develop a similar, although eventually self-limiting response in the CNS after immunisation with MOG-peptide in CFA provides a model to investigate the immuno-regulatory deficit(s) responsible for chronic CNS inflammation. The disease model is very reproducible with >90% of animals relapsing after peptide immunisation as opposed to