Podcasts about Afferent

Lenny's Podcast: Product | Growth | Career ✓ Claim Key Takeaways Check out the episode pageRead the full notes @ podcastnotes.orgJonny Miller is the founder of Nervous System Mastery, a course that has helped hundreds of founders and tech leaders cultivate calm, reduce nervousness, enhance resilience, and elevate their sense of aliveness. Having personally benefited from Jonny's teachings, I'm especially excited to have him on the show. In this episode, we discuss:• How shifting your focus from the mind to the body can help ease nervousness• The power of breath in changing states• The importance of “interoception”• Specific breathing exercises to both calm and excite your nervous system• The A.P.E. (awareness, posture, and emotion) framework for recognizing body signals• The “feather, brick, dump truck” phenomenon• The concept of emotional debt and how to release it• The competitive advantage of feeling emotions—Jonny's five-week boot camp, Nervous System Mastery, will equip you with evidence-backed protocols to cultivate greater calm and agency over your internal state. Learn to rewire maladaptive stress responses and improve your sleep (use code LENNY for $250 discount). Apply here.—Brought to you by:• Teal—Your personal career growth platform• Vanta—Automate compliance. Simplify security.• Miro—A collaborative visual platform where your best work comes to life—Find the full transcript at: https://www.lennysnewsletter.com/p/managing-nerves-anxiety-and-burnout—Where to find Jonny Miller:• X: https://twitter.com/jonnym1ller• LinkedIn: https://www.linkedin.com/in/jonnym1ller/• Website: https://www.jonnymiller.co/• Podcast: podcast.curioushumans.com • Email: jonny@curioushumans.com• Course: https://nsmastery.com/lenny—Where to find Lenny:• Newsletter: https://www.lennysnewsletter.com• X: https://twitter.com/lennysan• LinkedIn: https://www.linkedin.com/in/lennyrachitsky/—In this episode, we cover:(00:00) Jonny's background(07:19) The bottom-up approach to nervousness and anxiety(09:42) The power of breath in changing states(11:47) The concept of state over story(13:56) Personal experiences with nervousness(15:01) Breathing exercises to calm you down(20:40) The “espresso” breath exercise to give you energy(25:44) Interoception and the A.P.E. framework(34:47) The “feather, brick, dump truck” phenomenon(37:40) Recognizing emotional debt and avoiding burnout(40:47) Using somatic-oriented therapy for healing(45:26) Telltale signs of emotional debt(48:13) The competitive advantage of “feeling the feels”(50:20) Advice for people overwhelmed by stimuli(52:36) The NSDR (non-sleep deep rest) practice for emotional release(55:38) Daily practices for emotional well-being(58:23) Thoughts on meditation(01:01:26) The Body Keeps the Score(01:01:58) Contrarian corner(01:04:43) Lightning round—Jonny's If [This] Then [Breathe] Recipes:• If [overwhelmed], then [hum]• If [anxious], then [breath of calm]• If [lethargic], then [espresso breath]—Referenced:• The Operating Manual for Your Nervous System: https://every.to/p/the-operating-manual-for-your-nervous-system• Afferent vs. Efferent Neurons: https://www.osmosis.org/answers/afferent-vs-efferent-neurons• Insular cortex: https://en.wikipedia.org/wiki/Insular_cortex• Jonny's TED Talk, “The gifts of grief”: https://www.ted.com/talks/jonny_miller_the_gifts_of_grief/details• Humming (Simple Bhramari Pranayama) as a Stress Buster: A Holter-Based Study to Analyze Heart Rate Variability (HRV) Parameters During Bhramari, Physical Activity, Emotional Stress, and Sleep: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182780/• 14-Minute Guided NSDR (non-sleep deep rest) practice: https://www.youtube.com/watch?v=vjXX2c72fYY• Breathing Techniques to Reduce Stress and Anxiety | Dr. Andrew Huberman on the Physiological Sigh: https://www.youtube.com/watch?v=kSZKIupBUuc• Interoception: the hidden sense that shapes well-being: https://www.theguardian.com/science/2021/aug/15/the-hidden-sense-shaping-your-wellbeing-interoception• Exteroception: https://dictionary.apa.org/exteroception• Interoceptive Awareness and ADHD: https://chadd.org/adhd-news/adhd-news-adults/interoceptive-awareness-and-adhd/• Childhood Trauma Affects Stress-Related Interoceptive Accuracy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813623/• The Hour Between Dog and Wolf: How Risk Taking Transforms Us, Body and Mind: https://www.amazon.com/Hour-Between-Dog-Wolf-Transforms/dp/0143123408• Somatic Experiencing: https://www.somaticexperiencing.com/• Hakomi Institute: https://hakomiinstitute.com/• Decisions and Desire (about Antonio Damasio's work): https://hbr.org/2006/01/decisions-and-desire• When enough is enough | Andy Johns (ex-FB, Twitter, Quora): https://www.lennyspodcast.com/when-enough-is-enough-andy-johns-ex-fb-twitter-quora/• What Is Yoga Nidra?: https://health.clevelandclinic.org/what-is-yoga-nidra• Becoming Fully Yourself, What AI Wants, Family Rituals & Rites of Passage, with Kevin Kelly: https://podcast.curioushumans.com/episodes/becoming-fully-yourself-what-ai-wants-rites-of-passage-with-kevin-kelly• Tim Ferriss: https://tim.blog/• The Power of Sensations: Intermediate's Vipassana Body Scan: https://insighttimer.com/carola.ananda/guided-meditations/the-power-of-sensations-intermediates-vipassana-body-scan-meditation• Vipassana Meditation: https://www.dhamma.org/en/index• The Body Keeps the Score: Brain, Mind, and Body in the Healing of Trauma: https://www.amazon.com/Body-Keeps-Score-Healing-Trauma/dp/0670785938• Waking the Tiger: Healing Trauma: https://www.amazon.com/Waking-Tiger-Healing-Peter-Levine/dp/155643233X• Consolations: The Solace, Nourishment and Underlying Meaning of Everyday Words: https://www.themarginalian.org/2015/04/29/david-whyte-consolations-words/• The 15 Commitments of Conscious Leadership: A New Paradigm for Sustainable Success: https://www.amazon.com/15-Commitments-Conscious-Leadership-Sustainable/dp/0990976904/• The Conscious Leadership Group: https://conscious.is/• Recapture the Rapture: Rethinking God, Sex, and Death in a World That's Lost Its Mind: https://www.amazon.com/Recapture-Rapture-Rethinking-Death-World/dp/0062905465• Kubo and the Two Strings on Prime Video: https://www.amazon.com/Kubo-Two-Strings-Charlize-Theron/dp/B01K5BSWX0• Wolfwalkers on AppleTV+: https://tv.apple.com/us/movie/wolfwalkers/umc.cmc.amuoq00hqelfi98j0gvg641x• Scavengers Reign on Max: https://www.max.com/shows/scavengers-reign/50c8ce6d-088c-42d9-9147-d1b19b1289d4• Jerry Colonna on LinkedIn: https://www.linkedin.com/in/jerry-colonna-reboot/• Ra Optics “Sunset” blue-light blockers: https://raoptics.com/collections/night-lenses• Nurosym vagal stimulation device: https://my.nurosym.com/vns1564/• Pulsetto vagal stimulation device: https://pulsetto.tech/new-year/?gc_id=20124962116&h_ad_id=686249897188&gad_source=1• Apollo vagus nerve stimulator: https://apolloneuro.com/products/apollo-wearable—Additional research:• Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging: https://www.sciencedirect.com/science/article/pii/S0306453023003001• Somatic experiencing: using interoception and proprioception as core elements of trauma therapy: https://www.frontiersin.org/articles/10.3389/fpsyg.2015.00093/full• Relationship between interoception and emotion regulation: New evidence from mixed methods: https://www.sciencedirect.com/science/article/abs/pii/S0165032718323723• Out-of-the-blue panic attacks aren't without warning: body sends signals for hour before: https://pubmed.ncbi.nlm.nih.gov/21783179/—Production and marketing by https://penname.co/. For inquiries about sponsoring the podcast, email podcast@lennyrachitsky.com.—Lenny may be an investor in the companies discussed. Get full access to Lenny's Newsletter at www.lennysnewsletter.com/subscribe

Want longer episodes that cover all things human body and medicine?Join us on our other podcast!ApplePodcastSpotifyYouTube Hosted on Acast. See acast.com/privacy for more information.

Want longer episodes that cover all things human body and medicine?Join us on our other podcast!ApplePodcastSpotifyYouTube Hosted on Acast. See acast.com/privacy for more information.

Jonny Miller is the founder of Nervous System Mastery, a course that has helped hundreds of founders and tech leaders cultivate calm, reduce nervousness, enhance resilience, and elevate their sense of aliveness. Having personally benefited from Jonny's teachings, I'm especially excited to have him on the show. In this episode, we discuss:• How shifting your focus from the mind to the body can help ease nervousness• The power of breath in changing states• The importance of “interoception”• Specific breathing exercises to both calm and excite your nervous system• The A.P.E. (awareness, posture, and emotion) framework for recognizing body signals• The “feather, brick, dump truck” phenomenon• The concept of emotional debt and how to release it• The competitive advantage of feeling emotions—Jonny's five-week boot camp, Nervous System Mastery, will equip you with evidence-backed protocols to cultivate greater calm and agency over your internal state. Learn to rewire maladaptive stress responses and improve your sleep (use code LENNY for $250 discount). Apply here.—Brought to you by:• Teal—Your personal career growth platform• Vanta—Automate compliance. Simplify security.• Miro—A collaborative visual platform where your best work comes to life—Find the transcript for this episode and all past episodes at: https://www.lennyspodcast.com/episodes/. Today's transcript will be live by 8 a.m. PT.—Where to find Jonny Miller:• X: https://twitter.com/jonnym1ller• LinkedIn: https://www.linkedin.com/in/jonnym1ller/• Website: https://www.jonnymiller.co/• Podcast: podcast.curioushumans.com • Email: jonny@curioushumans.com• Course: https://nsmastery.com/lenny—Where to find Lenny:• Newsletter: https://www.lennysnewsletter.com• X: https://twitter.com/lennysan• LinkedIn: https://www.linkedin.com/in/lennyrachitsky/—In this episode, we cover:(00:00) Jonny's background(07:19) The bottom-up approach to nervousness and anxiety(09:42) The power of breath in changing states(11:47) The concept of state over story(13:56) Personal experiences with nervousness(15:01) Breathing exercises to calm you down(20:40) The “espresso” breath exercise to give you energy(25:44) Interoception and the A.P.E. framework(34:47) The “feather, brick, dump truck” phenomenon(37:40) Recognizing emotional debt and avoiding burnout(40:47) Using somatic-oriented therapy for healing(45:26) Telltale signs of emotional debt(48:13) The competitive advantage of “feeling the feels”(50:20) Advice for people overwhelmed by stimuli(52:36) The NSDR (non-sleep deep rest) practice for emotional release(55:38) Daily practices for emotional well-being(58:23) Thoughts on meditation(01:01:26) The Body Keeps the Score(01:01:58) Contrarian corner(01:04:43) Lightning round—Jonny's If [This] Then [Breathe] Recipes:• If [overwhelmed], then [hum]• If [anxious], then [breath of calm]• If [lethargic], then [espresso breath]—Referenced:• The Operating Manual for Your Nervous System: https://every.to/p/the-operating-manual-for-your-nervous-system• Afferent vs. Efferent Neurons: https://www.osmosis.org/answers/afferent-vs-efferent-neurons• Insular cortex: https://en.wikipedia.org/wiki/Insular_cortex• Jonny's TED Talk, “The gifts of grief”: https://www.ted.com/talks/jonny_miller_the_gifts_of_grief/details• Humming (Simple Bhramari Pranayama) as a Stress Buster: A Holter-Based Study to Analyze Heart Rate Variability (HRV) Parameters During Bhramari, Physical Activity, Emotional Stress, and Sleep: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10182780/• 14-Minute Guided NSDR (non-sleep deep rest) practice: https://www.youtube.com/watch?v=vjXX2c72fYY• Breathing Techniques to Reduce Stress and Anxiety | Dr. Andrew Huberman on the Physiological Sigh: https://www.youtube.com/watch?v=kSZKIupBUuc• Interoception: the hidden sense that shapes well-being: https://www.theguardian.com/science/2021/aug/15/the-hidden-sense-shaping-your-wellbeing-interoception• Exteroception: https://dictionary.apa.org/exteroception• Interoceptive Awareness and ADHD: https://chadd.org/adhd-news/adhd-news-adults/interoceptive-awareness-and-adhd/• Childhood Trauma Affects Stress-Related Interoceptive Accuracy: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6813623/• The Hour Between Dog and Wolf: How Risk Taking Transforms Us, Body and Mind: https://www.amazon.com/Hour-Between-Dog-Wolf-Transforms/dp/0143123408• Somatic Experiencing: https://www.somaticexperiencing.com/• Hakomi Institute: https://hakomiinstitute.com/• Decisions and Desire (about Antonio Damasio's work): https://hbr.org/2006/01/decisions-and-desire• When enough is enough | Andy Johns (ex-FB, Twitter, Quora): https://www.lennyspodcast.com/when-enough-is-enough-andy-johns-ex-fb-twitter-quora/• What Is Yoga Nidra?: https://health.clevelandclinic.org/what-is-yoga-nidra• Becoming Fully Yourself, What AI Wants, Family Rituals & Rites of Passage, with Kevin Kelly: https://podcast.curioushumans.com/episodes/becoming-fully-yourself-what-ai-wants-rites-of-passage-with-kevin-kelly• Tim Ferriss: https://tim.blog/• The Power of Sensations: Intermediate's Vipassana Body Scan: https://insighttimer.com/carola.ananda/guided-meditations/the-power-of-sensations-intermediates-vipassana-body-scan-meditation• Vipassana Meditation: https://www.dhamma.org/en/index• The Body Keeps the Score: Brain, Mind, and Body in the Healing of Trauma: https://www.amazon.com/Body-Keeps-Score-Healing-Trauma/dp/0670785938• Waking the Tiger: Healing Trauma: https://www.amazon.com/Waking-Tiger-Healing-Peter-Levine/dp/155643233X• Consolations: The Solace, Nourishment and Underlying Meaning of Everyday Words: https://www.themarginalian.org/2015/04/29/david-whyte-consolations-words/• The 15 Commitments of Conscious Leadership: A New Paradigm for Sustainable Success: https://www.amazon.com/15-Commitments-Conscious-Leadership-Sustainable/dp/0990976904/• The Conscious Leadership Group: https://conscious.is/• Recapture the Rapture: Rethinking God, Sex, and Death in a World That's Lost Its Mind: https://www.amazon.com/Recapture-Rapture-Rethinking-Death-World/dp/0062905465• Kubo and the Two Strings on Prime Video: https://www.amazon.com/Kubo-Two-Strings-Charlize-Theron/dp/B01K5BSWX0• Wolfwalkers on AppleTV+: https://tv.apple.com/us/movie/wolfwalkers/umc.cmc.amuoq00hqelfi98j0gvg641x• Scavengers Reign on Max: https://www.max.com/shows/scavengers-reign/50c8ce6d-088c-42d9-9147-d1b19b1289d4• Jerry Colonna on LinkedIn: https://www.linkedin.com/in/jerry-colonna-reboot/• Ra Optics “Sunset” blue-light blockers: https://raoptics.com/collections/night-lenses• Nurosym vagal stimulation device: https://my.nurosym.com/vns1564/• Pulsetto vagal stimulation device: https://pulsetto.tech/new-year/?gc_id=20124962116&h_ad_id=686249897188&gad_source=1• Apollo vagus nerve stimulator: https://apolloneuro.com/products/apollo-wearable—Additional research:• Cellular allostatic load is linked to increased energy expenditure and accelerated biological aging: https://www.sciencedirect.com/science/article/pii/S0306453023003001• Somatic experiencing: using interoception and proprioception as core elements of trauma therapy: https://www.frontiersin.org/articles/10.3389/fpsyg.2015.00093/full• Relationship between interoception and emotion regulation: New evidence from mixed methods: https://www.sciencedirect.com/science/article/abs/pii/S0165032718323723• Out-of-the-blue panic attacks aren't without warning: body sends signals for hour before: https://pubmed.ncbi.nlm.nih.gov/21783179/—Production and marketing by https://penname.co/. For inquiries about sponsoring the podcast, email podcast@lennyrachitsky.com.—Lenny may be an investor in the companies discussed. Get full access to Lenny's Newsletter at www.lennysnewsletter.com/subscribe

Today's topic is an interesting one that comes up a lot in the yoga world. In this episode, hosts Tiffany and Katja talk about the latest research and newest findings on the Polyvagal Theory. They discuss the evolutionary biology that Polyvagal Theory is based around, the neuroanatomy that's involved, and assumptions that have been made about this complex aspect of the body. Listen in to learn about the anatomy of the vagus nerve and how Polyvagal Theory is applied in yoga and therapeutic settings. Show Notes: The emergence of Polyvagal Theory [2:58] Evolutionary biology and dorsal vagus [5:50] Sympathetic nervous system [10:35] Ventral vagus [13:40] Nuances of ventral and dorsal vagus, combinations [15:03] Anatomy of the vagus nerve [17:38] Afferent parts of the vagus nerve (from body to brain) [21:24] Efferent components of vagus (from brain to body) [26:50] How researchers look at cardiac function and Polyvagal Theory [33:01] The role of Polyvagal Theory in yoga and therapeutic settings [37:29] Hypotheses about ventral vagus evolution [43:33] Links Mentioned: Watch this episode on YouTube Polyvagal Resources Doc Connect with Katja Bartsch: Facebook | Instagram | Kalamana Yoga | Yoga Medicine® Online Guest Teacher You can learn more about this episode, and see the full show notes at YogaMedicine.com/podcast-83. And you can find out more about insider tips, online classes or information on our teacher trainings at YogaMedicine.com. To support our work, please leave us a 5 star review with your feedback on iTunes/Apple Podcasts.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.03.547522v1?rss=1 Authors: Bryson, M., Kloefkorn, H., Idlett-Ali, S., Garraway, S. M., Hochman, S., Martin, K. Abstract: Spinal cord injury (SCI) leads to hyperexcitability and dysfunction in spinal sensory processing. As hyperexcitable circuits can become epileptiform we explored whether such activity emerges in a thoracic SCI contusion model of neuropathic pain. Recordings from spinal sensory axons in multiple below-lesion segmental dorsal roots (DRs) demonstrated that SCI facilitated the emergence of spontaneous ectopic burst spiking in afferent axons, which synchronized across multiple adjacent DRs. Burst frequency correlated with behavioral mechanosensitivity. The same bursting events were recruited by afferent stimulation, and timing interactions with ongoing spontaneous bursts revealed that recruitment was limited by a prolonged post-burst refractory period. Ectopic bursting in afferent axons was driven by GABAA receptor activation, presumably via conversion of subthreshold GABAergic interneuronal presynaptic axoaxonic inhibitory actions to suprathreshold spiking. Collectively, the emergence of stereotyped bursting circuitry with hypersynchrony, sensory input activation, post-burst refractory period, and reorganization of connectivity represent defining features of epileptiform network. Indeed, these same features were reproduced in naive animals with the convulsant 4-aminopyridine (4-AP). We conclude that SCI promotes the emergence of epileptiform activity in spinal sensory networks that promote profound corruption of sensory signaling. This includes sensory circuit hypoexcitability during the refractory period and ectopic hyperexcitability during bursting via spiking in afferent axons that propagate bidirectionally via reentrant central and peripheral projections. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.02.526853v1?rss=1 Authors: Zhao, J., Levy, D. Abstract: Cortical spreading depolarization (CSD) is a key pathophysiological event that underlies visual and sensory auras in migraine. CSD further drives the headache phase in migraine by promoting the activation and sensitization of trigeminal meningeal sensory afferents. The factors responsible for this meningeal nociceptive response in the wake of CSD remain poorly understood, but potentially involve the local release of algesic, proinflammatory mediators, including ATP. Here, we used an in vivo extracellular single-unit recording of meningeal afferent activity in combination with topical administration of pharmacological agents in a rat model to explore the role of ATP-P2X receptor signaling in mediating CSD-evoked meningeal afferent activation and sensitization. We found that broad-spectrum inhibition of P2X receptors, P2X7 receptor antagonist, and blockade of the related pannexin1 channel suppressed CSD-evoked afferent mechanical sensitization, but did not affect afferent activation. Pharmacological inhibition of the pronociceptive P2X2,3 ATP receptor did not affect meningeal nociception post-CSD. Finally, we provide evidence supporting the notion that the anti-nociceptive effect mediated by P2X7 is localized to the meningeal and not the cerebral cortex. We propose that meningeal P2X7 and Panx1 signaling, potentially in meningeal macrophages or neutrophils mediates the mechanical sensitization of meningeal afferents, and contributes to migraine pain by exacerbating the headache during normally innocuous physical activities. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.12.23.521695v1?rss=1 Authors: Erdogan, O., Michot, B., Xia, J., Alabdulaaly, L., Yesares Rubi, P., Chiu, I., Gibbs, J. L. Abstract: Dental pulp tissue is densely innervated by afferent fibers of the trigeminal ganglion. When bacteria cause dental decay near the pulpal tissue, a strong neuronal and immune response occur, creating pulpitis, which is associated with severe pain and pulp tissue damage. Neuro-immune interactions have the potential to modulate both the pain and pathological outcome of pulpitis. We first investigated the role of the neuropeptide calcitonin-gene related peptide (CGRP), released from peptidergic sensory afferents, in dental pain and immune responses by using calca knock out (calca-/-) and wild type (calca+/+) mice, in a model of pulpitis by creating a mechanical exposure of the dental pulp horn. While CGRP did not contribute to facial mechanical hypersensitivity, at an early time point, it did contribute to spontaneous pain-like behavior. We also found that CGRP contributed to recruitment of neutrophils and monocytes, while not clearly affecting the progression of pulpal pathology histologically. When we depleted neutrophils and monocytes, we found that there was more sensory afferent loss, tissue damage and deeper spread of bacteria into the pulp tissue, while there was a reduction in facial mechanical hypersensitivity compared to control animals at a later time point. Overall, we showed that there is a crosstalk between peptidergic neurons and neutrophils in the pulp, modulating the pain and inflammatory outcomes of the disease. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.24.517848v1?rss=1 Authors: Winter-Hjelm, N., Tomren, A. B., Sikorski, P., Sandvig, A., Sandvig, I. Abstract: Microfluidic devices interfaced with microelectrode arrays have in recent years emerged as powerful platforms for studying and manipulating in vitro neuronal networks at the micro- and mesoscale. By segregating neuronal populations using microchannels only permissible to axons, neuronal networks can be designed to mimic the highly organized and modular topology of neuronal assemblies in the brain. In vivo, the development of such neuronal assemblies is tightly orchestrated by reciprocal, dynamic structure-function relationships shaped by an interplay between intrinsic neuronal self-organizing properties and spatiotemporally regulated chemical and physical guidance cues. Engineered neuronal networks represent reductionist paradigms that can help recapitulate such dynamics in vitro. However, little is known about how the underlying topological features of such engineered neuronal networks contribute to their functional profile. To start addressing this question, a key parameter is control of afferent or efferent connectivity within the engineered network. In this study, we show that a microfluidic device featuring axon guiding channels with geometrical constraints inspired by a Tesla valve effectively promotes unidirectional axonal outgrowth between neuronal nodes, thereby enabling us to control afferent connectivity. We verified this by applying designer viruses to fluorescently label the neurons to visualise the structure of the networks, combined with extracellular electrophysiological recordings using embedded nanoporous microelectrodes to study the functional dynamics of these networks during maturation. We furthermore show that electrical stimulations of the networks induce signals selectively transmitted in a feedforward fashion between the neuronal populations. This model system has the potential to provide novel insights into the development, topological organization, and neuroplasticity mechanisms of neuronal assemblies at the micro- and mesoscale in healthy and perturbed conditions. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.22.517460v1?rss=1 Authors: Sulkes Cuevas, J. N., Watanabe, M., Uematsu, A., Johansen, J. P. Abstract: The locus coeruleus (LC) is a small region in the pons and the main source of noradrenaline (NA) to the forebrain. While traditional models suggested that all LC-NA neurons project indiscriminately throughout the brain, accumulating evidence indicates that these cells can be heterogeneous based on their anatomical connectivity and behavioral functionality and exhibit distinct coding modes. How LC-NA neuronal subpopulations are endowed with unique functional properties is unclear. Here, we used a viral-genetic approach for mapping anatomical connectivity at different levels of organization based on inputs and outputs of defined cell classes. Specifically, we studied the whole-brain afferent inputs onto two functionally distinct LC-NA neuronal subpopulations which project to amygdala or medial prefrontal cortex (mPFC). We found that the global input distribution is similar for both LC-NA neuronal subpopulations. However, finer analysis demonstrated important differences in inputs from specific brain regions. Moreover, sex related differences were apparent, but only in inputs to amygdala-projecting LC-NA neurons. These findings reveal a cell type and sex specific afferent input organization which could allow for context dependent and target specific control of NA outflow to forebrain structures involved in emotional control and decision making. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.08.515692v1?rss=1 Authors: Trusel, M., Alam, D., Roberts, T. F. Abstract: Birdsong is a complex and volitionally produced skilled behavior that, like speech and language, is dependent on forebrain circuits for its fluent production. The well delineated neural circuits associated with song provide a powerful system in which to study how synaptically linked networks of neurons control a natural and complex behavior. The premotor cortical analog HVC is necessary for song production and for song learning. Although the main input and output pathways of HVC have in most cases been known for decades, we still lack a detailed synaptic wiring diagram of this core circuit. Here we report our progress in building this wiring diagram. HVC has at least three non-overlapping classes of projection neurons and receives input from at least five song associated regions, totaling 15 potential synaptic pathways. Combining optogenetic stimulation of axon terminals from HVCs different afferent pathways with targeted whole-cell patch-clamp recordings of HVC projection neurons, we now provide an initial synaptic connectivity map of 12 of these potential pathways. We report on 435 whole-cell patch-clamp recordings from the 3 classes of HVC projection neurons, examining 4 different input pathways, from NIf, Uva, mMAN, Av, and mapping the polysynaptic and monosynaptic connections in each pathway. We find that the synaptic connectivity of HVCs input-output pathways is complex. Each class of projection neuron receives monosynaptic input from three of the four afferents and all in different combinations. At this stage, only one input pathway, NIf, appears to monosynaptically project onto all three classes of HVC projection neurons. We provide this initial synaptic mapping as an update for the field and will build on this wiring diagram, by updating this bioRxiv manuscript, as more data is collected, and additional pathways are characterized. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.28.514250v1?rss=1 Authors: Ragozzino, F. J., Peterson, B., Karatsoreos, I. N., Peters, J. H. Abstract: Circadian regulation of autonomic reflex pathways pairs physiological function with the daily light cycle. The brainstem nucleus of the solitary tract (NTS) is a key candidate for rhythmic control of the autonomic nervous system. Here we investigated circadian regulation of NTS neurotransmission and synaptic throughput using patch-clamp electrophysiology in brainstem slices from mice. We found that spontaneous quantal glutamate release on to NTS neurons showed strong circadian rhythmicity, with the highest rate of release during the light phase and the lowest in the dark, that were sufficient to drive day / night differences in constitutive postsynaptic action potential firing. In contrast, afferent-evoked action potential throughput was enhanced during the dark and diminished in the light. Afferent-driven synchronous release pathways showed a similar decrease in release probability that did not explain the enhanced synaptic throughput during the night. However, analysis of postsynaptic membrane properties revealed diurnal changes in conductance; which, when coupled with the circadian changes in glutamate release pathways, tuned synaptic throughput between the light and dark phases. These coordinated pre- / postsynaptic changes encode nuanced control over synaptic performance and pair NTS action potential firing and vagal throughput with time of day. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.10.20.513075v1?rss=1 Authors: Yarur, H. E., Casello, S. M., Tsai, V., Enriquez-Traba, J., Kore, R., Wang, H., Arenivar, M., Tejeda, H. Abstract: The medial prefrontal cortex (mPFC) controls emotional behaviors and cognition via connections with limbic excitatory afferents that engage various intra-mPFC inhibitory motifs The mPFC dynorphin (Dyn) / kappa-opioid receptor (KOR) system regulates affect and cognition and is implicated in neuropsychiatric disorders. However, it is unclear how neuropeptides in the mPFC, including the Dyn / KOR system, control excitatory and inhibitory circuit motifs integral in information processing. Here, we provide a circuit-based framework wherein selective KOR expression in mPFC afferents or within mPFC feedforward and feedback inhibitory circuits gates how distinct limbic afferent inputs control mPFC neurons. Dyn/KOR signaling directly decreases the ability of KOR-expressing afferent inputs to drive mPFC cell activity. Dyn/KOR signaling also suppresses afferent-driven recruitment of inhibitory sub-networks via several mechanisms, disinhibiting KOR-negative excitatory afferent control of mPFC ensembles. Thus, the Dyn/KOR system toggles which afferent input controls mPFC circuits, providing mechanistic insights into the role of neuropeptides in shaping mPFC function. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Professor Susan Hillier is a Professor of Neuroscience and Rehabilitation and Dean of Research in Allied Health and Human Performance at the University of South Australia. Her teaching and research interests are broadly in neuroscience and rehabilitation. She has particular interest in the role of afferent stimulation and training using multi-modal feedback. Susan is also trained in Feldenkrais and works clinically at the university private practice. She is especially experienced in Cochrane and other Systematic reviews. We cover most of these topics in this episode! – check out the show notes below. Intro 6.16Proprioception Research 7.15Sensory perception 10.00Feldenkrais training 15.50The Neuroscience Behind Body Image workshops 23.30Afferent Feedback – know what you're doing to make better choices 26.00Clinical Reasoning & Generating new ideas in practice 30.20Supervising PhD students 35.15Obtaining grant funding 37.57Gender discrepancy in research 40.08Systematic reviews 49.06Prof Hillier's Research Gatehttps://www.researchgate.net/profile/Susan-Hillier Uni SA profilehttps://people.unisa.edu.au/susan.hillier

Dr. Guillaume Lamotte. discusses the natural history of afferent baroreflex failure.

In the first segment, Dr. Alex Menze talks with Dr. Clifford Saper about Havana Syndrome and recent attacks on American diplomats. In the second part of the podcast, Dr. Jeff Ratliff discusses the natural history of afferent baroreflex failure with Dr. Guillaume Lamotte.

Podcast 166: Senile Degeneration of afferent mechanoreceptors. This podcast is way more interesting than the title ! join us each month on the Masterclass in Gait https://www.patreon.com/thegaitguys Join at the $40 monthly level and get the masterclass each month, bonus material and the detailed monthly content we only share on Patreon. The Masterclass is a formal LIVE presentation of slides, videos, demos, deep dives on topics you will not hear anywhere but here ! We hit the gait, biomechanics, neurology and orthopedics of all of the gait topics we present. This is not for the weak and timid, this is the deep dive you have been waiting for. Join us while we turn our normal 50 minute presentations into 3.5 hours on a regular basis ! The 40$ Patreon level will give you the Masterclass and also get you the $20, $10, and 5$ Patreon level content. What a deal ! It will not be here forever so lock in now ! Or, you can get less for your money (why would you do that?) and just buy our Monthly $40 Masterclass at our VIMEO on demand page: https://vimeo.com/ondemand/thegaitmasterclass Links to find the podcast: Look for us on Apple Podcasts, Google Play, Podbean, PlayerFM, RADIO and more. Just Google "the gait guys podcast". _______________________________________________________________________________ Our Websites: www.thegaitguys.com Find Exclusive content at: https://www.patreon.com/thegaitguys doctorallen.co summitchiroandrehab.com shawnallen.net Our website is all you need to remember. Everything you want, need and wish for is right there on the site. Interested in our stuff ? Want to buy some of our lectures or our National Shoe Fit program? Click here (thegaitguys.com or thegaitguys.tumblr.com) and you will come to our websites. In the tabs, you will find tabs for STORE, SEMINARS, BOOK etc. We also lecture every 3rd Wednesday of the month on onlineCE.com. We have an extensive catalogued library of our courses there, you can take them any time for a nominal fee (~$20). Our podcast is on iTunes and just about every other podcast harbor site, just google "the gait guys podcast", you will find us. Where to find us, the podcast Links: Apple podcasts: https://itunes.apple.com/us/podcast/the-gait-guys-podcast/id559864138?mt=2 Google Play: https://play.google.com/music/m/Icdfyphojzy3drj2tsxaxuadiue?t=The_Gait_Guys_Podcast Eight-Week Inspiratory Muscle Training Alters Electromyography Activity of the Ankle Muscles During Overhead and Single-Leg Squats: A Randomized Controlled Trial J Appl Biomech. 2020 Oct 12;1-8. doi: 10.1123/jab.2019-0315. Online ahead of print. Behnam Gholami-Borujeni  1 , Ali Yalfani  1 , Leila Ahmadnezhad  1 Why Don't Runners' Knees Fail More Often? Biology suggests that decades of running should invariably blow out your knees. Scientists are trying to understand why that doesn't happen. -suggests that 98% of knees should fail after three decades of running. But they don't, and the big question is why not. One possibility: contrary to the usual view, cartilage adapts to repeated loading. https://www.outsideonline.com/2417356/runners-knee-cartilage-study-2020?utm_medium=social&utm_source=twitter&utm_campaign=onsiteshare Lengthening of the gastrocnemius-soleus complex: an anatomical and biomechanical study in human cadavers Gregory B Firth  1 , Michael McMullan, Terence Chin, Francis Ma, Paulo Selber, Norman Eizenberg, Rory Wolfe, H Kerr Graham.   JBJS Am.: 2013 Aug 21;95(16):1489-96

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.06.138206v1?rss=1 Authors: Meerschaert, K. A., Adelman, P. C., Friedman, R. L., Albers, K. M., Koerber, H. R., Davis, B. M. Abstract: Visceral organs receive neural innervation from sensory ganglia located adjacent to multiple levels of the brainstem and spinal cord. Here we examined whether molecular profiling could be used to identify functional clusters of colon afferents from thoracolumbar (TL), lumbosacral (LS), and nodose ganglia (NG) in the mouse. Profiling of TL and LS bladder afferents was also done. Visceral afferents were back-labeled using retrograde tracers injected into proximal and distal regions of colon or bladder, followed by single cell RT-qPCR and analysis via an automated hierarchical clustering method. Genes were chosen for assay (32 for bladder; 48 for colon) based on their established role in stimulus detection, regulation of sensitivity/function or neuroimmune interaction. A total of 132 colon afferents (from NG, TL and LS) and 128 bladder afferents (from TL and LS) were analyzed. Retrograde labeling from the colon showed NG and TL afferents innervate proximal and distal regions of the colon whereas 98% of LS afferents only project to distal regions. There were clusters of colon and bladder afferents, defined by mRNA profiling, that localized to either TL or LS ganglia. Mixed TL/LS clustering also was found. In addition, transcriptionally, NG colon afferents were almost completely segregated from colon DRG (TL or LS) neurons. These results indicate that populations of primary visceral afferents are functionally ''tuned'' to detect and interact with the internal environment and that information from all levels is integrated at higher (CNS) levels, not only for regulation of homeostatic functions, but for conscious visceral sensations including pain. Copy rights belong to original authors. Visit the link for more info

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.05.18.102913v1?rss=1 Authors: Murphy, C. A., Banks, M. I. Abstract: While their behavioral effects are well-characterized, the mechanisms by which anesthetics induce loss of consciousness are largely unknown. Anesthetics may disrupt integration and propagation of information in corticothalamic networks. Recent studies have shown that isoflurane diminishes synaptic responses of thalamocortical (TC) and corticocortical (CC) afferents in a pathway-specific manner. However, whether the synaptic effects of isoflurane observed in extracellular recordings persist at the cellular level has yet to be explored. Here, we activate TC and CC layer 1 inputs in non-primary mouse neocortex in ex vivo brain slices and explore the degree to which isoflurane modulates synaptic responses in pyramidal cells and in two inhibitory cell populations, somatostatin-positive (SOM+) and parvalbumin-positive (PV+) interneurons. We show that the effects of isoflurane on synaptic responses and intrinsic properties of these cells varies among cell type and by cortical layer. Layer 1 inputs to L4 pyramidal cells were suppressed by isoflurane at both TC and CC synapses, while those to L2/3 pyramidal cells and PV+ interneurons were not. TC inputs to SOM+ cells were rarely observed at all, while CC inputs to SOM+ interneurons were robustly suppressed by isoflurane. These results suggest a mechanism by which isoflurane disrupts integration and propagation of incoming cortical signals. Copy rights belong to original authors. Visit the link for more info

Dr. Megan Seay talks about relative afferent pupillary defects (RAPDs).

Commentary by Dr. Valentin Fuster

Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. We're your co-hosts, I'm Dr Carolyn Lam, Associate Editor from the National Heart Center and Duke National University of Singapore. Dr Greg Hundley:             And I'm Greg Hundley, Associate Editor at the Pauley Heart Center at VCU Health in Richmond, Virginia.                                                 Well Carolyn, did you ever wonder whether cardiovascular drug effects could be investigated through natural variation in the genes for the protein targets? In our feature discussion today, investigators from the British Isles, Germany, and the United States use this approach to explore the potential side effects and repurposing potential of antihypertensive drugs. Sound interesting? Well listeners, we look forward to the results later in our program, but Carolyn, how about we chat about some of the other papers in this issue? Dr Carolyn Lam:                You bet Greg. So, have you ever asked yourself "What is the role of protein glycosylation in regulating LDL metabolism?" Dr Greg Hundley:             That was going through my mind when we were playing basketball just the other night. Dr Carolyn Lam:                Well this is truly a great study from Dr Holleboom at Academic Medical Center Amsterdam and Dr Lefeber from Radboud University Medical Center, both in the Netherlands. And their colleagues will study 29 patients of the two most prevalent types of Type 1 Congenital Disorder of Glycosylation, and these are the ALG6 and PMM2 types. They also study 23 first and second-degree relatives with a heterozygote mutation and measured their plasma cholesterol levels. LDL metabolism was studied in three cell models. They found that patients with type 1 congenital disorder of glycosylation have hypobetalipoproteinemia through increased LDL receptor expression. Carriers of the mutation in glycosylation enzymes affected in this syndrome had decreased LDL cholesterol levels compared to controls, and defects in glycosylation enzymes could play, therefore, an important role in LDL cholesterol metabolism. Dr Greg Hundley:             Boy, this is pretty insightful I think, Carolyn. So, what are the clinical implications? Dr Carolyn Lam:                Well, given that LDL cholesterol was also reduced in a group of clinically unaffected heterozygotes, the authors propose that increasing LDL receptor mediated cholesterol clearance, by targeting N-glycosylation in the LDL pathway, may therefore represent a novel therapeutic strategy to reduce LDL cholesterol, and of course prevent cardiovascular disease. Dr Greg Hundley:             Very interesting work. You know, we just keep learning more and more about LDL. I'm going to switch and jump back with Empagliflozin. And this is a study in diabetic mice that really has an interesting in-vivo imaging component. As an imager, I was really excited about this. The article is from Dr Kengo Kidokoro from Kawasaki Medical School. And we don't often talk about it, but listeners, if you have a chance, there's a very interesting video-enhanced file associated with this article, and if you can download it, it's really just so cool with multiple image clips demonstrating an operative mechanism of SGLT2 inhibition on renal function. And it really gives us an opportunity to revisit renal function.                                                 Quick quiz Carolyn. In diabetic kidney disease, is glomerular hyperfiltration good or bad? Dr Carolyn Lam:                Bad. Dr Greg Hundley:             Yeah, absolutely. So, hyperfiltration is characteristically observed at earlier stages of diabetic kidney disease and involves activation of the renin-angiotensin-aldosterone system at the efferent arteriole and tubuloglomerular feedback mechanisms, especially at the afferent arteriole. So, as they go through this, just picture in your mind that glomerulus and afferent is arriving, and efferent is leaving.                                                 So, SGLT2 upregulation in diabetes is thought to play an important role in TGF signaling by increasing sodium reabsorption at the proximal tubule, thereby decreasing distal delivery to the sodium sensing macula densa at the juxtaglomerular apparatus. This decline in distal sodium delivery is interpreted as a decline in effective circulating volume, leading to inappropriate afferent vasodilation in an effort to preserve intra-glomerular pressure and GFR.                                                 In diabetes, these TGF effects lead to intra-glomerular hypertension and hyperfiltration. You got that quiz right, Carolyn. Which promotes diabetic kidney disease progression and impaired kidney function, ultimately increasing overall cardiovascular risk and mortality. Conversely, blocking SGTL2 pharmacologically reduces renal hyperperfusion and hyperfiltration in animals and humans, which may preserve renal function, thereby reducing risk associated with diabetic kidney disease progression. Dr Carolyn Lam:                You know what, Greg? I kind of had an unfair advantage in this quiz. I work with a lot with the SGLT2 inhibitors, but I just love that you asked us to picture it and look at that video. Anyways, so this article really allows us to review SGLT2 inhibition at the glomerular level, which is truly hot. So, tell us what did they find? Dr Greg Hundley:             So, this is the first report of changes in renal hemodynamic function by SGLT2 inhibition using direct in-vivo visualization techniques in a diabetic animal model. The videos, they're spectacular, and they're excellent so that you can download them for educational purposes. Afferent arteriolar vasoconstriction, and reduced hyperfiltration occurred within a few hours after a single dose of a SGLT2 inhibitor. And Adenosine signaling, through tubuloglomerular feedback, is a key pathway to prevent diabetic hyperfiltration via SGLT2 inhibition.                                                 Clinically, Carolyn, now I know you would ask me about that, so I got ready, this study highlights another potential mechanism for the benefits of SGTL2 inhibition. The SGLT2 inhibitor-related mechanism's responsible for reducing cardiovascular risk in clinical trials may be due to protection against diabetic kidney disease progression, thereby attenuating risk factors for heart failure, such as volume overload and hypertension. Dr Carolyn Lam:                Ah. That is just so cool, and really just so consistent with the clinical data that's emerging too. Thank you, Greg. So, have you ever asked yourself this other question, what role do platelets play in ischemia reperfusion injury? So, I'm not going to quiz you. I'm actually kind and loving and a good person. And so, I will tell you about ischemia reperfusion injury, which is a common complication of cardiovascular disease.                                                 Now, resolution of the detrimental effects of ischemia reperfusion injury generated prothrombotic and proinflammatory responses, is essential to restore homeostasis. Now, although platelets are known to play a crucial role in the integration of thrombosis and inflammation, their role as participants in the resolution of thrombo-inflammation is really under-appreciated. And hence, this other paper that I chose today, and it's from Dr Gavins from Louisiana State University Health Sciences Center Shreveport, and her colleagues, who used pharmacological and genetic approaches, coupled with murine and clinical samples to uncover key concepts underlying this role for platelets. Dr Greg Hundley:             So Carolyn, what did they find? Dr Carolyn Lam:                Well, they found that exacerbation of thrombo-inflammatory responses occurred in ischemia reperfusion injury mouse models of middle cerebral arterial occlusion, as well as lower plasma levels of the anti-inflammatory pro-resolving protein Annexin A1. And this was a lower plasma level of this Annexin A1 among patients with acute ischemic stroke.                                                 Administration of Annexin A1 promoted cerebral protection against thrombo-inflammation and the development of subsequent thrombotic events post-stroke. Annexin A1 was also able to reduce platelet activation and thrombosis, via the suppression of integrins. So, overall, these data reveal a novel multi-faceted role for Annexin A1 to act both as therapeutic and prophylactic drug via its ability to promote endogenous pro-resolving anti-thrombo, anti-inflammatory circuits in the cerebral ischemia reperfusion injury. And collectively, these results further enhance our understanding in the field of platelet and ischemia reperfusion injury biology. Dr Greg Hundley:             Oh wow. So, another important insight from this author group on platelet activation and thrombosis in key clinically relevant syndromes. Well, my last paper is going to be talking about a risk prediction score for life-threatening ventricular tachyarrhythmias. And they're going to study this in laminopathies, and the lead investigator is Dr Karim Wahabi from Cochin Hospital in France.                                                 To estimate the risk of life-threatening ventricular tachyarrhythmia in patients with LMNA mutations, and thus select candidates for implantable cardiac defibrillators, the investigators evaluated 444 patients of about 40 years in age in a derivation sample. And then, 145 patients that are about the same age, 38 years, in a validation sample, for the occurrence of a) sudden cardiac death or b) ICD-treated or hemodynamically unstable ventricular tachyarrhythmias. Dr Carolyn Lam:                Oh. Very important. These laminopathies are really not that uncommon. So what did they find, Greg? Dr Greg Hundley:             Carolyn, predictors of events included male sex, non-missense LMNA mutations, first-degree and higher AV block, non-sustained ventricular tachycardia, and LVEF. The authors developed a new score to estimate the 5-year risk of life-threatening ventricular tachyarrhythmias in patients with LMNA mutations. And compared to the current standard of care, the proposed risk prediction model offered more accurate prediction of life-threatening ventricular tachyarrhythmias, and correctly re-classified almost 30% of the patients in the study.                                                 Nicely, the authors have made this available, and the score can be derived from readily collected clinical and genetic parameters and estimated using an online calculator that's provided in the journal. But, it's https://lmna-risk-vta.fr.                                                 Future prospective studies should focus on the estimation of the clinical benefit conferred by the use of this score in terms of sudden cardiac death prevention. Dr Carolyn Lam:                That is super cool, Greg. But, I am so excited now to move to our feature discussion. Shall we? Dr Greg Hundley:             You bet. Dr Carolyn Lam:                Can we use natural variations in our genes for the protein targets as a way to look at cardiovascular drug effects? Man, this is going to be such an important and exciting discussion, because this is what our feature paper talks about. I am so pleased to have with us our corresponding author, Dr Dipender Gill from Imperial College London, as well as our Associate Editor, Dr Wendy Post from Johns Hopkins.                                                 So, first of all, Dipender, please, could you give us a background on what you did? This is really very novel in approach. Dr Dipender Gill:               It was also a lot of fun to conduct. I think, currently, we're living in an era where there's been a recent explosion in the availability of genetic data, and this really inspired us to think about how we could use that to learn more about commonly prescribed drugs. The implementation of genetics, or genetic variance, to study drug effects isn't entirely novel. It's actually been undertaken for some years now.                                                 Most of the work has been related to lipid lowering drugs, for example, statins, where people can take genetic variance, or versions of genes, corresponding to the drug effect, and study these to investigate what effects these drugs might have, both on the intended target, but also potential side effects. To my knowledge, this hadn't previously been done for anti-hypertensive drugs. But yet, the data for this was available. And therefore, we thought that actually we could very well go ahead and do this, and perhaps find some interesting things. Dr Carolyn Lam:                Oh, that's so interesting thing, Dipender. You know, there was this term in your abstract, and mentioned multiple times, Mendelian randomization. Now, for those of us that don't think about this every day, could you tell us a little bit what that means? Dr Dipender Gill:               Yeah. So, I'll actually give a little bit of background. One of the main limitations of traditional epidemiological research is that any association, it's sometimes difficult to infer causation. They can be confounded by environmental factors, lifestyle factors. In the Mendelian randomization technique, what we do is we use randomly allocated genetic variants to study the effect to an exposure.                                                 So, we select these genetic variants because they are related to the exposure of interest. And because these genes are randomly allocated at conception, they're not subject to confounding from environmental or lifestyle factors. Whether you have a gene or not, is not necessarily related to your lifestyle or your environment. And therefore, the association of these genetic variants with certain outcomes isn't subject to confounding. Dr Carolyn Lam:                That makes so much sense, and I suppose that, not to allow cause and effect to be determined. So please, tell us, in this particular case of the anti-hypertensive drugs, what did you do and what did you find? Dr Dipender Gill:               First, we decided specifically which drugs we wanted to look at, and we thought, actually, let's start off with the most commonly prescribed anti-hypertensive drugs. So, we short-listed these based on recent consensus guidelines, and we looked at ACE inhibitors, beta-blockers, calcium channel blockers, thiazide type diuretics. And then, we went back to various online databases to identify which genes correspond to the target protein of these drugs.                                                 We took these genes, and we then identified genetic variants at their specific genetic loci, their specific region of the genome, and we identified the variants in these regions that were also related to systolic blood pressure. And in this way, we inferred that genetic variants, at the protein coding targets of these genes, that were also related to systolic blood pressure, likely represented the effect of variations in these proteins that also implicated blood pressure, and therefore, could serve as proxies, or instruments, to study the effect of these drug targets.                                                 We then went ahead to validate the selection of these genetic variants by forming Mendelian randomization, and specifically, we checked whether people that have genetic variants that correspond to, say, ACE inhibitor activity, or beta-blocker activity, or calcium channel blocker activity, if they also have correspondingly lower risk of coronary heart disease and stroke, to the same degree that we would observe in randomized control trials against placebo.                                                 And indeed, we found that actually, the results were fairly similar, and this gave us confidence. And studying these genetic variants that mimic the effect of these drugs could be used as a proxy or as a surrogate to study their clinical effect of taking these drugs. So, that was the first phase. Dr Wendy Post:                 Dipender, congratulations to you and our team. This is a really exciting paper, and the editors were especially interested in the novelty, and the potentially impactful findings, especially of the second part of the study, which I think you'll describe briefly next. And that was using an approach that many who are listening may not have heard about too much before called PheWAS, or a phenome wide association study. And maybe you could tell us briefly what you found in that part of the analysis. Dr Dipender Gill:               The first part, it was very cool, because it allowed us to identify versions of genes that corresponded to the effect of these drugs. But in itself, it didn't tell us anything novel. It didn't tell us anything new. So, the real question was, how could we use this new information to make progress towards helping patients? So, we went back and we thought, "So okay." So, we knew that these drugs are used for certain conditions already to prevent heart disease, to prevent stroke.                                                 But, what about their side effects? What about their repurposing potential? How could we use our new approach to study that a little bit more carefully? As you alluded to, when we used this new technique, relatively new technique called phenome wide association study, and we essentially investigated the association of our genetic variants for each respective anti-hypertensive target with all clinically relevant outcomes throughout the phenome, using the UK bio-back cohort, which was the main population used for this PheWAS, this phenome wide association study.                                                 We were actually able to rapidly investigate over 900 disease outcomes, and their association with our genetic risk score for these drugs. And this was very exciting for us, because it allowed us to very rapidly, efficiently, and cost-effectively explore the potential repurposing opportunity and side effects of these very commonly prescribed drugs, which to our mind, offered significant advantage over previous approaches.                                                 We all know that sometimes randomized control trials can be very expensive and time-consuming, and of course, traditional observational research can be limited by reverse causation, assessment-vise confounding. And so, what we were able to do here had several important advantages, and not to mention the efficiency by which it allowed study of these outcomes. Dr Wendy Post:                 Dipender, tell us what you found in your PheWAS study. Dr Dipender Gill:               We identified genetic variants for 3 commonly prescribed anti-hypertensive targets. The first were ACE inhibitors, second, beta blockers, and the third were calcium channel blockers. When performing PheWAS for all of these drug targets, we identified associations with common cardiovascular disease that are related, or implicated in hypertension, specifically hypertension itself, but also circulatory diseases, things like atrial fibrillation, coronary heart disease. They all came up.                                                 And this actually gave us a lot of confidence because that's exactly what we'd expect. We know that these medications prevent or reduce risk of these diseases, and therefore, this served as kind of a positive control that our approach was doing it what it was supposed to do. The novel finding came when we investigated the genetic risk score, or the genetic variants for calcium channel blockers, in this PheWAS approach.                                                 And we actually identified an association which we weren't expecting. We showed that blood pressure reduction through the genetic risk score for calcium channel blockers was an association with an increased risk of diverticulosis, a condition not conventionally thought to be associated with blood pressure. We were very excited and interested by this, and we went on to investigate it further using some other techniques as well. Dr Wendy Post:                 The really impactful part of this, many things, but especially this association with diverticulosis. So, maybe you can briefly summarize what you think the potential clinical implications are, and what the next step should be. Dr Dipender Gill:               The first question we had was whether this was related to blood pressure alone, the effect of calcium channel blockers, or perhaps some other effect of these drugs. We investigated the genetic risk score for systolic blood pressure generally and found that this itself wasn't associated with risk of diverticulosis, which suggested that the effect isn't really mediated by blood pressure alone, but it's some other property of calcium channel blockers.                                                 We know that sometimes calcium channel blockers can be associated with constipation, and it may be through this mechanism that they're having consequent effects on risk of diverticulosis. Other possible mechanisms might be through effects on blood flow, through the vasa recta in the bowel. But, what was very interesting was that we went forward with this finding, and investigated, observed, drug use in the UK bio-bank.                                                 Specifically, we looked at people taking non-dihydropyridine, and dihydropyridine calcium channel blockers at baseline, and found that those taking non-dihydropyridine calcium blockers only were known to have a higher risk of diverticulosis as compared to those taking other anti-hypertensive classes, which further added support for our findings. The interesting point here is that looking at the genetics doesn't allow us to discriminate between these drug classes.                                                 That was only possible with the observed data, and that was because the genes for these drug classes were the same. Dr Carolyn Lam:                Well, congratulations. Wow. I'm just so intrigued listening to all of this. Wendy, I would love if you could help put all of this in context for us. The US, the novel information, and the approach that could potentially go way beyond just anti-hypertensive. Dr Wendy Post:                 So, this is a very exciting new approach to doing genetic studies that can help us to understand potential targets for therapy in the future, and understanding more about causality, which as Dipender explained, can sometimes be confusing, as it may be confounded by environmental factors. So, using these genetic approaches through Mendelian randomization, and what we heard about today, which is PheWAS, or phenome wide association study, we can learn much more about how the potential observational analyses can be related to new discoveries through mechanisms, or potential side effects, as we heard about here of calcium channel blockers.                                                 So, wanted to congratulate Dipender again with his impactful paper here. Dr Carolyn Lam:                Thanks, Wendy. And then if I could, I'm just going to steal minutes here, because this is so interesting. Where do you think the field's going to go next? And Dipender, with these findings of diverticulitis and diverticulosis, what next? How do we apply this? Dr Dipender Gill:               There's 2 main points to cover here. The first is what we do specifically with the findings we got for calcium channel blockers and diverticulosis. I should emphasize that on their own, I don't think that this should currently change practice. But, I think it should inspire and capitalize further research into this association. If we're able to replicate and validate it further, then perhaps there might be some implications for the drugs that we prescribe with patients at risk of diverticulosis.                                                 The second point I wanted to make is more generally, what does this mean for research, and particularly, genetic research. I think we're living in very exciting times, and there's a lot of really great work that's going to come out using these types of approaches. I think 2 areas that we could expand further is what else we can do with our genetic instruments, or our genetic variants that proxied these drugs. How do we look at other targeted refocusing potential? Can we try and explore other side effects? Can we investigate efficacy for other disease outcomes? Specifically, for these anti-hypertensives.                                                 And the other thing is, which other drugs can we identify genetic variants to proxy? We've been thinking about looking at diabetes medicines. There's a variety of other drugs that correspond to specific gene targets, and proteins. And in theory, these could also be studied using genetics. So, there's a lot more work to come out from this. Dr Carolyn Lam:                Thanks so much, both of you, for joining us today. This was just such an exciting discussion.                                                 Thank you for listening to Circulation on the Run. Don't forget to tune in again next week. This program is copyright American Heart Association, 2019.  

Session 11 Today, we discuss a more straightforward, neuro-anatomy question about the glossopharyngeal nerve. As always, we’re joined by Dr. Andrea Paul of Board Vitals. If you’re in the market for QBanks and practice tests for the USMLE/COMLEX, check out Board Vitals. Use the promo code BOARDROUNDS to save 15% on your purchase. [02:00] Question Which of the glands of the options below are innervated by the efferent autonomic fibers of the glossopharyngeal nerve? [02:14] Answer Choices You have to know what the glossopharyngeal nerve and what type of fibers are innervating the glands. Answer choices: (A) Nasal (B) Submandibular (C) Sublingual (D) Parotid (E) Lacrimal [02:45] Thought Process in Answering the Question Glosso refers to the tongue and pharyngeal refers to the pharynx area. So this is somewhere around the mouth. The interesting with glossopharyngeal is that it has a range of effects. Some of the places it touches would surprise you. But first, you can eliminate nasal. But the rest of the choices could be fair game. This specific nerve has a lot of sensory – parasympathetic and motor functions. It's tough to answer so this can be challenging to people. This nerve starts at the medulla and coming out of the jugular foramen. It's traveling through both anteriorly and posteriorly. So it has a branch that goes to the inner ear. Lacrimal refers to the tear ducts so you can get rid of this one too. Now, we're down with three choices. [06:55] Choosing Among the Three First, remember the motor functions. So it's innervating the muscle in the pharynx and then you think through the sensory functions. Glossopharyngeal is sensory to the posterior third of the tongue or the back half of the tongue. If you can remember that section of the tongue, it leads you closer to the location of the gland that may be in that area. It's also going up into the middle ear, the Eustachian tube for sensory function. Anatomically, you start to think more up anterior than sublingual. Think of it as more of in the ear area. So the correct answer here is the Parotid gland, which is the only gland that doesn't receive any autonomic innervations from the facial nerve. So it receives that from the glossopharyngeal nerve. This is the main differentiator. Hence, the exam likes to ask about it. The posterior third of the tongue and the middle ear are things they love to ask about glossopharyngeal. Also, know which muscles are innervated, which is the stylopharyngeus in the pharynx. Also, try to remember the path and the branches. It sends a branch up to the middle ear. There are five other branches. One goes to the stylopharyngeus muscle, one is the pharyngeal branch, one is tonsilar, one is sublingual, and then one goes to the parotid body and sinus. You can draw this to help give you a visualization. Afferent refers to the sensory nerves coming back towards the central nervous system and efferent refers to "going away" for motor function. In terms of understanding parasympathetic vs sympathetic, just remember that most glandular effects are parasympathetic just like most of your organs. [12:24] Board Vitals Check out the QBank and practice tests over at Board Vitals to help you be prepared for your exam. They have over 1,750 questions for USMLE and over 1,500 questions for COMLEX. Get a 1-month, 3-month, or 6-month plan. They all come with a free trial. No credit card required. Use the promo code BOARDROUNDS to save 15% on your purchase. Links: Board Vitals (promo code BOARDROUNDS)

What is the vagus nerve and what are some simple strategies that we can do to activate it? Get a load of some really amazing information from Activate Your Vagus Nerve author, Dr. Navaz Habib. Enjoy! You can find all the info and links about this episode at https://holisticwellness.ca/episode51. Topics Discussed in this Episode: The vagus nerve Some common signs of vagus nerve dysfunction. The effect of stress on the vagus nerve The four major functions of the vagus nerve Strategies and tips to activate the vagus nerve Where sleep and digestion come into play Autoimmune conditions Key Takeaways: If you have poor vagus nerve function, you will experience poor digestion, inflammation, IBS, issues of liver detoxification, even autoimmunity. 12 to 24 hours after you eat a meal, you should be eventually releasing the waste of that meal. Optimally, around 16 hours is the best amount of time. When you don’t have a gallbladder, what’s actually going on is you’re living is going to be extra stressed in being able to push out bile and get toxins out of the body but help to absorb the fats. The four major functions of the vagus nerve: Afferent function Parasympathetic function Motor functions Sensory function to a portion of the ear One of the tools that you can use to see if the vagus nerve isn’t working well is the tone of voice. If you know somebody that has a very monotonous voice and they aren’t able to raise pitch or go up and down with their voice, then that is a sign that the signaling in the vagus nerve is actually quite poor because the muscles aren’t being used correctly. We can actually use auricular acupuncture to treat vagus nerve dysfunction. Gargling is a great tool for activating the vagus nerve. But you have to gargle the right way, up to the point that you tear up. If you’re not able to tear out of our eyes, you’re probably not activating the nuclei inside the brain stem of vagus enough. Heart rate variability is actually a direct sign of vagus nerve function. People that sleep on their right side tend to have higher heart rate variability and tend to be better nose breathers. Action Steps: Monitor your bowel transit time. If it’s too fast or too slow, that’s a sign that the vagus nerve is not doing its job correctly. Get auricular acupuncture treatment to stimulate vagus nerve activity. Practice gargling every morning and evening, in the right way. Make sure that you breathe through your nose, not through your mouth. Try using Breathe Right strips or a mouth tape. Make sure that you chew your food very well and that you’re not eating under stressed circumstances. Go away from the stressful environment of your desk or your work station and get out and do something a little bit different. Be in a calm, relaxed environment. Before you eat, do some humming or chanting or some deep breathing exercises to help activate the vagus nerve.   Navaz said: “What the vagus nerve really is, is the major connection between the gut and all of the organs inside our body directly to our brain. It is the gut-brain axis… It is essentially the controlling pathway by which our body is able to recover, rest, digest, and actually function optimally.” “You are what you eat, digest, absorb, and don’t eliminate… If you’re not absorbing it, it’s not going to get into your body, it’s going to get into your cells, and then it’s not doing the job that it needs to do.”   Thanks for listening!   Important Announcements:   SIGN UP by tonight (March 5th, 2019) to Access the Exclusive Hormone Masterclass.   If you have any questions, connect with me over on Instagram, @holisticwellnessfoodie. And it would mean so much if you would leave us a rating or a review over on iTunes or Spotify or Stitcher, or whichever platform you’re listening to us on. Take a screenshot of your review and email it over to us, and get our FREE 3-Day Hormone Balancing Meal Plan.   Links to things we talk about in the show: Activate Your Vagus Nerve: Unleash Your Body’s Natural Ability to Overcome Gut Sensitivities, Inflammation, Autoimmunity, Brain Fog, Anxiety and Depression by Navaz Habib   Where you can find Dr. Navaz Habib:Dr. Habib’s Instagram (@DrNavazHabib)Dr. Habib's FacebookDr. Habib's Website   Where you can find me: Samantha’s Facebook Samantha’s Instagram Samantha’s Website Samantha’s Twitter Healthy Hormones for Women Private Community on Facebook   How you can work with me: 6 Week Healthy Hormones for Women Intensive - Use the coupon code PODCAST at checkout to save 60%. Healing & Dealing with Hashi’s

Show Sponsors: softscience.com Altrarunning.com Other Gait Guys stuff B. iTunes link: https://itunes.apple.com/us/podcast/the-gait-guys-podcast/id559864138 C. Gait Guys online /download store (National Shoe Fit Certification & more !) http://store.payloadz.com/results/results.aspx?m=80204 D. other web based Gait Guys lectures: Monthly lectures at : www.onlinece.com type in Dr. Waerlop or Dr. Allen, ”Biomechanics” -Our Book: Pedographs and Gait Analysis and Clinical Case Studies Electronic copies available here: -Amazon/Kindle: http://www.amazon.com/Pedographs-Gait-Analysis-Clinical-Studies-ebook/dp/B00AC18M3E -Barnes and Noble / Nook Reader: http://www.barnesandnoble.com/w/pedographs-and-gait-analysis-ivo-waerlop-and-shawn-allen/1112754833?ean=9781466953895 https://itunes.apple.com/us/book/pedographs-and-gait-analysis/id554516085?mt=11 -Hardcopy available from our publisher: http://bookstore.trafford.com/Products/SKU-000155825/Pedographs-and-Gait-Analysis.aspx ________________________ Show Notes: Running helps mice slow cancer growth https://www.sciencedaily.com/releases/2016/02/160216142825.htm The future of Wearables http://readwrite.com/2016/02/19/future-of-wearables mensicus surgery is dead ? http://www.regenexx.com/should-i-have-meniscus-surgery/# Why you should be training your CNS http://www.outsideonline.com/2055066/cross-educate-your-body#article-2055066 The business of insoles http://www.outsideonline.com/2057156/business-insoles-support-system-or-super-rip Altered plantar pressures http://link.springer.com/article/10.1007%2Fs00167-016-4015-3    

Afferent Provider Solutions is the single source for education and life management services healthcare professionals need for their best outcome in life.

Listen to Patrick Decherchi discuss his paper on the use of a poly[N-(2-hydroxypropyl) methacrylamide] hydrogel to repair spinal cord hemisection in rats.

MDS presents the latest research and findings from the field of Movement Disorders. Abstracts of articles from the Society Journal, Movement Disorders, are taken from the August 2013 (Vol. 28, Issue 9) issue.

Enhanced Video PodcastAired date: 9/14/2009 12:00:00 PM Eastern Time

Enhanced Audio PodcastAired date: 9/14/2009 12:00:00 PM Eastern Time

Doctors and patients at the Royal Free Hospital's Pain Clinic and at the Real Health Institute explain how chronic pain works

Doctors and patients at the Royal Free Hospital's Pain Clinic and at the Real Health Institute explain how chronic pain works

Transcript -- Doctors and patients at the Royal Free Hospital's Pain Clinic and at the Real Health Institute explain how chronic pain works

Transcript -- Doctors and patients at the Royal Free Hospital's Pain Clinic and at the Real Health Institute explain how chronic pain works

Enhanced Audio PodcastAired date: 1/8/2007 12:00:00 PM Eastern Time

Enhanced Video PodcastAired date: 1/8/2007 12:00:00 PM Eastern Time Institute: NINDS

Enhanced Audio PodcastAired date: 1/8/2007 12:00:00 PM Eastern Time Institute: NINDS

Enhanced Video PodcastAired date: 1/8/2007 12:00:00 PM Eastern Time